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922 F.2d 156
CAM-FUL INDUSTRIES, INC., Plaintiff-Appellant, Cross-Appellee,v.FIDELITY AND DEPOSIT COMPANY OF MARYLAND, Defendant andThird-Party Plaintiff-Appellee, Cross-Appellant,Adams Electric Corp., Raymond R. Adams, Eleanor Adams andRobert M. Adams, Third-Party Defendants-Appellees,Cross-Appellants.
Nos. 1349, 1566 and 1567, Dockets 90-7113, 90-7169 and 90-7173.
United States Court of Appeals,Second Circuit.
Argued June 8, 1990.Decided Jan. 4, 1991.
Ronald G. Robey (Smith, Currie & Hancock, D. Lee Roberts, Jr., Atlanta, Ga., of counsel), for plaintiff-appellant.
Gerald J. Mathews (Menter, Rudin & Trivelpiece, P.C., Jeffrey A. Dove, of counsel), Syracuse, N.Y., for defendant-appellee Fidelity and Deposit Co. of Maryland, and third-party defendant Adams Elec. Corp.
Before OAKES, Chief Judge, PRATT, Circuit Judge, and JOHN E. SPRIZZO, District Judge, for the Southern District of New York, sitting by designation.
GEORGE C. PRATT, Circuit Judge:
1
This dispute arises out of a public construction project in Syracuse, New York. We are asked primarily to reverse the district court's determination that relieved a surety of responsibility under a payment bond for the claim of an excavation subcontractor who, at the request of the prime contractor, installed wood sheeting that was required by the prime contract, but was beyond the scope of its subcontract. On this issue we reverse and remand for a determination of damages on the wood sheeting claim.
2
We also reverse the district court's sua sponte dismissal after trial, for lack of subject matter jurisdiction, of the reciprocal cross-claims between the third-party defendant prime contractor and the plaintiff subcontractor, and we dispose of other issues as indicated later in this opinion.
I. BACKGROUND
3
In early 1983 the City of Syracuse, New York, requested bids for rehabilitating the main electrical duct bank at the Syracuse Hancock International Airport ("the project"). Adams Electric Corp. ("Adams Electric"), a third-party defendant in this case, submitted the low bid of $590,630. The city's engineer for the project notified Adams Electric that its bid was more than 10 percent below the engineering estimate, and, as required by Federal Aviation Administration regulations, requested Adams Electric to review its bid. After checking with its proposed subcontractors and verifying its figures, Adams Electric, on May 16, 1983, entered into a contract with the city for construction of the project at the bid price.
4
As required by the contract, Adams Electric obtained from defendant Fidelity and Deposit Company of Maryland ("Fidelity") both a performance bond, not here in issue, and the labor and materials payment bond that is the subject of this appeal. Each bond was for the full contract price of $590,630, and each named Fidelity as surety and Adams Electric as principal.
5
Under the payment bond, the principal and the surety were "bound unto City of Syracuse, New York as Obligee, hereinafter called Owner, for the use and benefit of claimants" in the amount of the contract price. The condition of the bond's obligation was that Adams Electric should promptly make payments to all "claimants" for all labor and material used or reasonably required for use in the performance of the prime contract between Adams Electric and the city.
6
As a subcontractor of Adams Electric, plaintiff Cam-Ful Industries, Inc. ("Cam-Ful") qualified under the bond as a "claimant" and was therefore entitled to prompt payment from Adams Electric as principal, or in the event of Adams Electric's default, from Fidelity as surety, for labor and material "used or reasonably required for use in the performance of the Contract". Significantly for purposes of our review of the decision below, the "Contract" to which the bond refers is the prime contract between Adams Electric and the city, not the subcontract between Adams Electric and Cam-Ful.
7
Adams Electric subcontracted to Cam-Ful that part of the project's work that included excavating, protecting, and back-filling the long trench into which the airport's main electrical duct bank was to be placed. Prior to submitting its bid to the city, Robert Adams of Adams Electric met with Robert Bradley of Cam-Ful, and the two men walked the construction site with copies of the plans. At both ends of the trench, and at nine locations along its 3,000 foot length, electrical manholes were to be constructed. These manholes required excavations that were both wider and deeper than the normal trench section.
8
Standard considerations of safety require that whenever an excavation is made in the earth, some consideration be given to preventing the sides of the excavation from falling in during construction. On this project, Adams and Bradley considered two possibilities for that protection: open cut trenching and wood sheeting. With the former technique, the sides of the excavation are sloped back so as to be self-supporting. With the wood sheeting technique, boards are driven into the ground to make a temporary wall along the sides of the excavation. Aided by cross-bracing, the boards then support the sides of the excavation during the work. While more secure, wood sheeting is considerably more expensive than open cut trenching because it requires more materials and labor.
9
In their preliminary discussions of this job, neither Adams nor Bradley was certain as to which type of protection the city's engineer would ultimately require on the project. Later, however, the two men agreed between themselves that wood sheeting would not be needed except in and near the manholes. At one meeting, when Bradley pointed out to Adams that the "typical trench section" shown on the plan appeared to call for wood sheeting, Adams reassured Bradley that it would not be necessary for the entire excavation, but only for the manholes.
10
On the basis of Adams's reassurance, Cam-Ful submitted a subcontractor's proposal to Adams Electric, which Adams Electric relied upon in making its successful bid to the city. Cam-Ful's proposal included wood sheeting for the manholes, but contemplated open cut trenching for the rest of the project.
11
Well after the prime contract had been awarded to Adams Electric, the project's engineer, on July 27, 1983, rejected the proposed excavation plan prepared by Cam-Ful, and indicated that the whole project, not just the manholes, would require wood sheeting. At this point Adams Electric had already signed its contract with the city and had obtained from Fidelity the performance and payment bonds; Adams Electric had not yet, however, executed any contract with Cam-Ful.
12
The district court found that despite the engineer's position on wood sheeting, "Bradley was being encouraged by Adams to continue on the Project"; that Adams suggested "that while tight wood sheeting might be the method of choice at the beginning of the Project, that method would be changed fairly early in the Project"; and that "Adams also suggested that if tight wood sheeting were required throughout the Project, Cam-Ful would be paid for it". The district court further found that "[t]hese conclusions as to Adams' statements prior to the signing of the [sub]contract are uncontroverted".
13
Adams prepared a proposed subcontract, and on August 10, 1983, Bradley signed it after modifying the liquidated damages clause; he then returned the signed, modified subcontract to Adams. Bradley testified that he had modified the subcontract to reflect his understanding of his conversations with Adams regarding wood sheeting. He did this by crossing out the original liquidated damages clause and replacing it with the following language:
14
NO LIQUIDATED DAMAGES AS LONG AS WORK PROGRESSES AS FAST AS POSSIBLE AND ADAMS ELECTRIC DOCUMENTS PROJECT DELAYS BY JACK EASTERLY OF OCWA, WEATHER AND UNFORESEEN CONDITIONS SUCH AS SHEETING ENTIRE TRENCH. (emphasis added)
15
Adams noticed the modification and even spoke with an attorney about it before signing the modified contract. The district court found that Adams had testified "somewhat incredibly, that the modification did not 'raise any doubts' in his mind." It further found that Adams surely understood "that concerns about tight wood sheeting were paramount in Bradley's mind" and that Adams "certainly must have understood that his subcontractor [Cam-Ful] was not prepared or expecting to undertake tight wood sheeting of the entire project." The district court also concluded that "Adams undoubtedly understood that his signature bound him to the terms of the Subcontract." The only conclusion that can be drawn from these findings is that under the subcontract between Cam-Ful and Adams Electric, the price of $154,906 was not intended by either party to include wood sheeting beyond that needed for the manholes.
16
Eventually the project engineer did require that the entire excavation, including the trench, be reinforced with wood sheeting; this work was done, at Adams Electric's request, by Cam-Ful, which now seeks to recover an additional $316,444.97 for that work.
II. PROCEEDINGS BELOW
17
Initially, Cam-Ful commenced arbitration with Adams Electric to resolve their disputes, including Cam-Ful's claim for additional work. While the arbitration was pending, Cam-Ful brought this action in the district court based on the payment bond, and it named Fidelity, the surety on the payment bond, as the only defendant. At a pretrial conference the district court suggested that the issues in the arbitration be brought into this action so that the entire dispute could be resolved in a single forum. The parties then entered into a stipulation withdrawing the arbitration, and providing for Fidelity to make a third-party claim against Adams Electric and its principals, based upon the indemnification agreement given upon issuance of the payment bond.
18
Adams Electric and Cam-Ful then asserted various cross-claims against each other: in addition to the $316,444.97 sought by Cam-Ful for the wood sheeting, Cam-ful also sought additional compensation for extra dewatering and restoration work. Adams Electric raised claims for delays, additional engineering costs, and liquidated damages sought from Adams Electric by the city, as well as for delay and other damages sought from Adams Electric by Hogan, the other subcontractor on the job.
19
The entire matter was tried in a bench trial in the district court. In its final decision, the district court sua sponte raised a question as to its jurisdiction over the cross-claims between Adams Electric and Cam-Ful, (both of which are New York State corporations), and ultimately, the court dismissed the cross-claims for lack of jurisdiction. The district court then denied Cam-Ful's claim against Fidelity on the grounds that Cam-Ful's decision to install the wood sheeting without first notifying the surety constituted a modification of the subcontract, and this modification discharged the surety from liability for that work. In addition, the district court:
20
1. Denied, for failure of proof, the subcontractor's claim for extra work in dewatering the site;
21
2. Denied that part of the subcontractor's claim for extra restoration work that related to installing the wood sheeting, but allowed 15% of the claim relating to other extra restoration work; and
22
3. Allowed the subcontractor's claim for a balance due on the subcontract of $3,525.21.
23
Cam-Ful appeals the judgment; Fidelity and Adams Electric jointly cross-appeal the district court's decision to award Cam-Ful $6,343.65 for additional restoration work. They also cross-appeal the district court's decision that it lacked jurisdiction over Adams Electric's cross-claim against Cam-Ful.
24
We reverse the dismissal of the cross-claims; we reverse the denial of the subcontractor's claim for wood sheeting and of the related claim for restoration work; we affirm the denial of the dewatering claim; we affirm the determination of a balance of $3,525.21 due on the contract, but recognize that the sum may be changed after remand; and we remand for further proceedings.
25
Fidelity originally answered the complaint in 1985 through its attorneys, Hiscock & Barclay. Frequently in construction litigation, when the surety is fully indemnified by the principal, the attorneys for the principal take over defense of any action brought against the surety by a subcontractor. That happened here, and the firm of Menter, Rudin & Trivelpiece, P.C. served an amended answer on behalf of Fidelity. Although on its third-party complaint against Adams Electric, Fidelity was represented by Hiscock & Barclay, the Menter firm represented Adams Electric in its answer to Fidelity's third-party complaint and on the cross-claim against Cam-Ful.
26
Despite the apparent conflict of interest with the Menter firm representing both Fidelity in defense of Cam-Ful's claim, and Adams Electric in defense of Fidelity's third-party claim, there is no real conflict because Fidelity's liability to Cam-Ful is purely derivative from Adams Electric's liability to Cam-Ful, and any judgment to be paid by Fidelity to Cam-Ful would have to be reimbursed by Adams Electric and its guarantors, Raymond, Eleanor, and Robert Adams, under the indemnification agreement which forms the basis for the third-party complaint.
27
Both at trial and on appeal the Menter firm has represented both Fidelity and Adams Electric. All of the issues raised by the complaint, third-party complaint, and the cross-claims were fully litigated before the district court and presented for decision. Not until its final decision did the district court determine that it lacked jurisdiction over the cross-claims.
DISCUSSION
28
A. Jurisdictional Issue.
29
Without question, the district court correctly found there to be no diversity or other independent basis for federal jurisdiction over the cross-claims between Adams Electric and Cam-Ful. We think the district court erred, however, in failing to invoke its ancillary jurisdiction to adjudicate those claims. The district court viewed the cross-claims as "logically independent" of the main federal claim by Cam-Ful against Fidelity. We disagree.
30
Fed.R.Civ.P. 13(g) allows a party to "state as a cross-claim any claim * * * against a co-party arising out of the transaction or occurrence that is the subject matter * * * of the original action." A cross-claim does not need an independent basis for jurisdiction so long as it satisfies the test for ancillary jurisdiction. See 6 Wright, Miller & Kane, Federal Practice and Procedure Sec. 1433 (1990). Under the doctrine of ancillary jurisdiction, the Supreme Court "has identified certain considerations which justified the joining of parties with respect to whom there was no independent basis of federal jurisdiction." Aldinger v. Howard, 427 U.S. 1, 10, 96 S.Ct. 2413, 2418, 49 L.Ed.2d 276 (1976). These considerations--"judicial economy, convenience and fairness to litigants" United Mine Workers of America v. Gibbs, 383 U.S. 715, 726, 86 S.Ct. 1130, 1139, 16 L.Ed.2d 218 (1966)--provide a satisfactory basis for jurisdiction over a nonfederal claim, provided, of course, that the claim satisfies the "common nucleus of operative fact" test set out in Gibbs. See Gibbs, 383 U.S. 715, 725, 86 S.Ct. 1130, 1138, 16 L.Ed.2d 218 (1966).
31
The facts of this case offer a model for a federal court's proper exercise of its ancillary jurisdiction. The two groups of claims, one federal (based on diversity) and one nonfederal, are so tightly interwoven that the federal claims cannot be resolved unless the federal court also addresses the nonfederal claims. Moreover, all the claims arise out of a single construction project--the "common occurrence" requirement of Gibbs. Furthermore, the context in which the nonfederal claim is asserted, a "crucial" element according to the Court, see Owen Equip. & Erection Co. v. Kroger, 437 U.S. 365, 375-76, 98 S.Ct. 2396, 2403-04, 57 L.Ed.2d 274 (1978), also favors an exercise of ancillary jurisdiction in this case, since "ancillary jurisdiction typically involves claims by a defending party haled into court against his will, or by another person whose rights might be irretrievably lost unless he could assert them in an ongoing action in a federal court." Id. at 376, 98 S.Ct. at 2404. Such is the suit in this case.
32
In denying the cross-claims because they did not independently satisfy jurisdictional requirements, the district court failed to give proper weight to the other considerations underlying ancillary jurisdiction. Clearly, "Congress did not intend to confine the jurisdiction of federal courts so inflexibly that they are unable to protect legal rights or effectively to resolve an entire, logically entwined lawsuit." Id. at 377, 98 S.Ct. at 2404. This is such a lawsuit.
33
Cam-Ful was suing on Fidelity's payment bond. As a "claimant" under the bond, Cam-Ful was entitled to recover only to the extent that it (a) had supplied labor and materials for work under the prime contract between Adams Electric and the city, and (b) had not been paid by Adams Electric. Cam-Ful's claim under the bond, therefore, was not only logically related to, but also inherently dependent upon the resolution of the cross-claims between Cam-Ful and Adams Electric. Fidelity's liability to Cam-Ful was derivative in nature and stemmed solely from Adams Electric's liability to Cam-Ful; therefore, resolution of the issues presented by Cam-Ful's complaint against Fidelity, over which there was unquestioned federal diversity jurisdiction, necessarily required determination of the cross-claims between Adams Electric and Cam-Ful.
34
On the remand, therefore, the district court should determine all of the cross-claims that were presented to it and fully briefed by the parties at trial.
35
B. Cam-Ful's Wood Sheeting Claim.
36
We agree with the district court's conclusion that the prime contract permitted the city's engineer to require that wood sheeting be used for the full length of the project. Under the prime contract, Adams Electric was, therefore, bound to provide the wood sheeting. Cam-Ful, however, was not bound to do the work. Its subcontract with Adams Electric was finally executed on August 10, 1983, and was based on Adams's assurances to Bradley, given to induce Cam-ful to execute the subcontract, that if wood sheeting were to be required for areas other than the manholes, Cam-Ful was to be paid for that work by Adams Electric. As a practical matter, if Cam-Ful had refused to do any wood sheeting or if it had refused entirely to enter into the subcontract because of the wood sheeting problem, then Adams Electric would have had to obtain another subcontractor who would, of course, have required reasonable compensation to do the wood sheeting work.
37
Fidelity's payment bond guaranteed payment for all work required by the prime contract, and this included a guarantee of payment for any wood sheeting required on the job. To the extent that Adams Electric may owe Cam-Ful additional money over and above the subcontract price, and if that additional amount is not "paid" as part of the resolution of the cross-obligations between Cam-Ful and Adams Electric, Fidelity will be liable to Cam-Ful under the payment bond.
38
The district court concluded that the understanding reached between Adams Electric and Cam-Ful about the wood sheeting, arrived at after execution of both the prime contract and the payment bond, was a "modification" of the subcontract, even though the subcontract had not yet been executed. The district court also concluded that this new understanding effectively modified the payment bond ex post facto. The court further viewed Cam-Ful's conduct as a failure to reveal to Fidelity facts which materially altered Fidelity's risk on the bond, a failure which precluded Cam-ful from recovering on the bond for its wood sheeting claim.
39
The district court referred to the general rule that discharges a surety from its bond obligation when the contract it has guaranteed has been materially altered. This rule, however, only applies to alterations of the prime contract, which was the situation in both cases upon which the district court relied: United States v. Reliance Insurance Co., 799 F.2d 1382 (9th Cir.1986), and Ramada Development Co. v. U.S. Fidelity & Guarantee Co., 626 F.2d 517 (6th Cir.1980). To the extent that any "modification" or "alteration" took place in this case, however, it occurred at the subcontract level.
40
The district court asserted that Cam-Ful either should have refused to perform the wood sheeting or should have notified Fidelity of the "changed circumstances" between it and Adams Electric. Concluding that Cam-Ful was under an obligation to notify Fidelity of its arrangements with Adams Electric to treat wood sheeting as extra work, the district court also relied on St. Paul Fire & Marine Insurance Co. v. Commodity Credit Corp., 646 F.2d 1064 (5th Cir.1981). That case, however, makes it clear that "as a general rule, the creditor, or obligee, to whom the surety's assurance is given is not bound to disclose to the surety unrequested information concerning the secured transaction." Id. at 1072. Under this general rule Cam-ful would have no obligation to Fidelity, and while the rule has two exceptions, neither applies in this case. See id. at 1073.
41
A surety does not have to pay a claimant who "during negotiations, actively and fraudulently conceals pertinent facts", id., nor is the surety liable if "before the obligation is undertaken, the creditor knew of facts unknown to the surety and which he had reason to believe were not known to the surety, the facts materially increased the obligator's risk and the creditor had adequate time to disclose them but failed in his responsibility." Id. at 1073. See also State v. Peerless Ins. Co., 67 N.Y.2d 845, 848, 501 N.Y.S.2d 651, 653, 492 N.E.2d 779 (1986) (stating that a surety's "guarantee induced by fraudulent misrepresentation or concealment of a material fact is void") (citation omitted). The district court found no evidence of fraud on the part of Cam-Ful, nor was Cam-Ful privy to material information that was unknown to Fidelity before Fidelity undertook its payment bond obligation.
42
At the time that Fidelity agreed to furnish the payment bond for the contract, Cam-Ful was under the impression that wood sheeting would not be required under the prime contract. The bond between Fidelity and Adams Electric was signed on May 16, 1983; Cam-Ful did not sign its subcontract with Adams Electric until August 10, 1983. And even then, based on Adams's assurances, Cam-Ful believed that wood sheeting would not be required on the whole project.
43
The district court concluded that when Cam-Ful finally signed the subcontract, it knew that the project engineer was going to require wood sheeting. While that may be so, it is also true that Cam-Ful did not definitively learn of this requirement until after Fidelity had agreed to act as the surety on the prime contract. It may be that Fidelity was misled by Adams Electric. But even if this were so, the burden of Adams Electric's transgression would not fall on Cam-Ful; rather, in this situation, "the surety bears the burden of making inquiries and informing itself of the relevant state of affairs of the party for whose conduct it has assumed responsibility." Peerless Insurance Co., 67 N.Y.2d at 847, 501 N.Y.S.2d at 652, 492 N.E.2d at 780.
44
In allowing Fidelity to avoid its obligation to Cam-Ful, the district court believed that it was protecting the bidding process. According to the district court, "any other decision under the facts of this case would sanction an undermining of the bidding process and distort the policy behind requiring surety bonds in construction contracts." We disagree. "A surety is one who assumes secondary liability for the performance of an obligation; he agrees to pay if another does not." St. Paul Fire & Marine Ins., 646 F.2d at 1072. Requiring a prime contractor to obtain a payment bond assures subcontractors that they will be paid for their work. The policy behind surety bonds is not to protect a surety from its own laziness or poorly considered decision. "A surety cannot 'rest supinely, close his eyes, and fail to seek important information,' and then seek to avoid liability under the guaranty by claiming he was not supplied with such information." Mohasco Industries, Inc. v. Giffen Industries, Inc., 335 F.Supp. 493, 497 (S.D.N.Y.1971) (citation omitted). See also St. Paul Fire & Marine Ins., 646 F.2d at 1072 ("The law does not favor the indifferent, unseeing surety who fails to help himself.").
45
Cam-Ful did all that it could to avoid confusion about its responsibility: (1) Although the prime contract called for wood sheeting, Adams and Bradley both thought that the requirement probably could be changed; (2) Cam-Ful's price to Adams Electric did not include the cost of wood sheeting and Adams Electric was aware of this; (3) Cam-ful's subcontract with Adams Electric clearly regarded that wood sheeting as an "unforeseen condition" not contemplated by the subcontract; and (4) before commencing the wood sheeting, Cam-Ful was assured by Adams Electric that it would be paid for the work as an "extra". Thus, it was Adams Electric, not Cam-Ful, that took what the district court concluded was a "calculated risk". Adams Electric knew that there was a possibility that the project engineer would insist on wood sheeting; it also knew that Cam-Ful in its subcontract price was undertaking no responsibility to install the wood sheeting. Adams Electric chose to risk the consequences of this potential discrepancy between the prime contract and the subcontract, and it was Adams Electric, not Cam-Ful, with whom Fidelity dealt and whose performance and payments Fidelity guaranteed.
46
Under New York law, it is well established that "[a] compensated, corporate surety * * * is not a favorite of the law and its contract of suretyship will be construed in a manner most favorable to a claimant." Timberline Elec. Supply Corp. v. Insurance Co. of North America, 421 N.Y.S.2d 987, 988, 72 A.D.2d 905, 906 (1979), aff'd, 52 N.Y.2d 793, 436 N.Y.S.2d 707, 417 N.E.2d 1248 (1980). The wood sheeting was required by the prime contract, for which Fidelity issued its payment bond; the sheeting was not required by Cam-Ful's subcontract, and was done by Cam-Ful only after Adams Electric agreed to fully compensate Cam-Ful for the extra work. In deciding to undertake this work, the only "calculated risk" Cam-Ful took was the same risk any subcontractor takes--that it will not be paid by the contractor. This risk is covered by Fidelity's bond, and Cam-Ful is entitled to be paid.
47
Because it disallowed any payment for wood sheeting, the district court did not address the merits of Cam-Ful's claim that the reasonable value of the extra work for installing the wood sheeting amounted to $316,444.97. In its cross-claim against Cam-Ful, Adams Electric contests that figure. On remand, the district court should determine the appropriate amount that Cam-ful should be paid for the "extra" wood sheeting installed beyond what Bradley and Adams originally agreed was required by the subcontract in and near the manhole areas.
48
C. Cam-Ful's Dewatering Claim.
49
After a thorough analysis of the evidence, the district court denied Cam-Ful's dewatering claim, because there was an "absence of creditable proof that a claim was submitted, or from which a determination of damages can be made". This conclusion is not clearly erroneous, and we affirm the district court's denial of this claim.
50
D. Restoration Claim.
51
Cam-Ful sought an additional $42,291 for restoration work not contemplated by the plans and specifications. After analyzing each component of the restoration claim and after excluding those portions that related to areas that had to be restored because wood sheeting was required, the district court allowed 15% of the claim. Except for the disallowance of restoration for the areas of extra wood sheeting, we find no error in the district court's findings or analysis. Since, however, we have determined that the wood sheeting claim is not precluded, the district court, on remand, will have to reexamine the restoration claim and allow an appropriate additional amount for any restoration work required by the extra wood sheeting that Cam-Ful installed for Adams Electric.
52
E. Balance Due on Subcontract.
53
The district court determined that $3,525.21 was the correct balance due from Adams Electric to Cam-Ful on the subcontract. Since on the remand the district court must adjudicate all of the cross-claims between Adams Electric and Cam-Ful and since it must, in addition, determine the amounts owed Cam-Ful on the wood sheeting and restoration claims, a new "balance" will have to be determined. We find no error, however, in the district court's findings as to the makeup of the $3,525.21 found to be due.
IV. CONCLUSION
54
The judgment of the district court is reversed, the cross-claims are reinstated, and the case is remanded for further proceedings. Since the entire action was tried and submitted for decision prior to the district court's concluding that it lacked jurisdiction over the cross-claims, all of the evidence needed to decide the issues in this case has already been presented, and the district court is not required to receive additional evidence or take further argument. It may, however, in its sound discretion take whatever further proceedings, including testimony, briefing, and oral argument, that will assist it in promptly and justly concluding this protracted litigation.
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One- or two-unit internshipTwo options are available for fulfilling the internship requirement: (1) two full-time internships or (2) one full-time internship and one off-campus semester in an approved Albion College program
Senior Capstone (1/4 unit)
All courses for the major must be taken for a numerical grade, except those offered only on a credit/no credit basis.
Completion of a second area of specialization selected from these options: (1) an existing Albion College minor, (2) a College-approved emphasis or concentration, (3) a second major, or (4) an individually designed five-unit focus, determined in collaboration with the Gerstacker Institute director, along with the majority approval of the Gerstacker Internal Advisory Committee and the provost.
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The Albion Advantage. It's the liberal arts. It's career readiness. It's providing you the knowledge, skills, and experiences you'll need to succeed in college, in your career, and in your life.
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2017 Beer University Seminar Stage
3:15 pm - 3:45 PM
Three Blind Beers by What’s on Tap Radio hosts James Simpson and Chad Pilbeam
What's on Tap Radio is a radio show about beer and the culture around it. Heard 3-5p KPRC AM 950 & I heart Radio. Hosted by Beer Guru James Simpson and the Beer Logic Chad Pilbeam. James & Chad will take their show from the studio and perform it live at BrewMasters, interviewing brew masters and testing their expertise with the show staple, "3 Blind Beers." You can join in the fun as James & Chad will turn to the audience for participation and beer related questions for prizes.
What’s on Tap Radio was awarded 3rd place in the North American Guild of Beer Writers awards in the Podcast/Broadcast category at the Great American Beer Festival in Denver.
3:55 pm – 4:25 pm
Women in Craft Beer
Craft Beer—it’s not just a man’s world. Join this powerhouse panel of women in craft beer and see how they are making a mark on the industry.Participants include: Charday VanOrstrand, Galveston Island Brewing; Theresa Hutchings, Fetching Lab; Kristina Fortunato, Karbach Brewing Co.
4:35 pm - 5:05 pm
Houston's Craft Beer History
From the early days, and long before Americans had ever heard the term “craft beer,” settlers in the Bayou City excelled in the art of ales, stouts and lagers. In 1913, it was a Houston brewery that claimed the distinction of “the world’s finest bottled beer” after winning an international competition in Belgium. Hear more from Houston Chronicle Business Editor, TX Beer Blogger and author of “Houston Beer: A Heady History of Brewing in Houston.”
5:15 pm – 5:45 pm
Join Guinness Brewery Brand Ambassador David Schroeder as he guides participants through the evolution of Guinness' 200 years in the U.S. Taste through the current day selections and connect the dots over the past 200 years.
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The global veterinary vaccines market is expected to reach USD 12.6 billion by 2025, according to a new report by Grand View Research, Inc. Rise in the outbreak of livestock diseases, expanding livestock population and increasing zoonotic diseases are driving the market growth. Increasing awareness regarding commercially available vaccines is pushing the adoption globally. However, higher costs associated with storage is challenging the growth and restricting the entry of new players.
This market has emerged to be one of the profitable investment options seeking attention and investments from both government and non-government players. Rise in the number of pet owners and their shifting focus towards healthy animal practices are some other factors propelling the growth of the market. Government intervention in distribution channel on the other hand, is affecting the profitability of the veterinary vaccine manufacturers. The bulk purchase and supply of livestock vaccines by countries such as India and Alaska that have large livestock population are reducing the profit margins of the vaccine manufacturers’ through bulk pricing.
Further Key Findings from the Report Suggest:
Attenuated vaccines emerged as the largest segment as a result of the benefits such as improved effectivity and enhanced long-term prevention
Cattle vaccines accounted for the largest share in the animal type segment owing to the rise in the demand for safe animal products
Companion animal vaccines segment is the fastest growing segment owing to the increase in number of pet owners worldwide
North America dominated the market with the largest share in 2016. Constantly rising awareness regarding animal health and increasing commercialization of animal products are facilitating dominance of the region during the forecast period.
Asia Pacific is projected to witness swift growth during the forecast period owing to the speedy adoption of veterinary vaccines for quality food products and better animal health
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A LAWMAKER on Wednesday pushed for the approval of House Bill 5098, that requires car buyers to present proof that they have parking space for the motor vehicles they acquire.
Nationalist People’s Coalition Rep. Sherwin Gatchalian of Valenzuela filed that bill which provides buyers of new vehicles should have ample car park space in their homes for the said purchase.
Gatchalian filed the bill owing to the observation that illegally parked vehicles are major contributors to the worsening traffic problem in major cities and towns in the country.
He said the purpose of the bill is to lessen congestion, eliminate street parking and to address the problem of pollution. One of the bill’s objectives is to limit the number of vehicles currently using the roads.
The House Committee on Transportation chairman advised Gatchalian to incorporate his proposed bill with the Sustainable Transportation System Bill since both bills are aimed to address similar targets and have similar objectives.
Gatchalian agreed to the proposal.
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First image of a multi-planet system around a sun-like star - MindGods
https://phys.org/news/2020-07-image-multi-planet-sun-like-star.html
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“The two gas giants orbit their host star at distances of 160 and about 320
times the Earth-sun distance. This places these planets much further away from
their star than Jupiter or Saturn, also two gas giants, are from the sun; they
lie at only five and 10 times the Earth-sun distance, respectively. The team
also found the two exoplanets are much heavier than the ones in our solar
system, the inner planet having 14 times Jupiter's mass and the outer one six
times.”
------
uxamanda
Found a larger conversation on this here:
[https://news.ycombinator.com/item?id=23917559](https://news.ycombinator.com/item?id=23917559)
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The present invention relates to an apparatus for sorting coins, in which a plurality of differently sized rectangular coin sorting slots are formed in a coin sorting plate, and a plurality of almost elliptical coin carrying slots are formed in a coin carrying vessel. Each of the coin carrying slots consists of a large arc and a small arc, and therefore, a large coin is settled into the large arc, while a small coin is settled into the small arc of the coin carrying slot. Accordingly, when the coin carrying vessel with the coin carrying slots formed therein revolves, a large coin drops into a large coin sorting slot, while a small coin drops into a small coin sorting slot. Thus the sorted and dropped coins are guided by a plurality of guides respectively, thereby making it possible to sort coins according to their sizes.
Generally, in the commercial transactions and in the financial transactions, large quantities of coins are required at the transaction sites or at the financial organizations. Accordingly, there are the requirements that coins be accurately sorted, and these requirements are being increased day by day. Generally, the conventional coin sorting apparatus, such as disclosed in U.S. Pat. No. 4,275,751, includes: a coin carrying vessel for carrying the coins; and a coin sorting device for sorting the coins thus carried. The coins which are carried by the coin carrying vessel to the coin sorting device are sorted in the following manner. That is, when the coin sorting device revolves together with the coins, if the coins encounters a sorting hole, then the coins are discharged owing to the centrifugal force. The coins which are sorted in this manner are received into receiving vessels respectively according to their sizes. In this apparatus, the coin sorting device which sorts the coins according to their sizes are the principal part.
In the above described conventional coin sorting apparatus, within the passage through which the coins rollingly pass, there are formed a plurality of coin sorting slots having different sizes respectively. Thus when the coins rollingly move through the above mentioned passage, if the coins fall into the coin sorting slots, then these coins are dropped and sorted. That is, a coin orbiting plate has a plurality of differently sized elongate slots, and when the coin orbiting plate revolves, the orbiting coins drop after passing through the elongate slots according to their sizes. The coin sorting apparatus in which the coin sorting slots are formed in the coin passage shows a slow sorting speed. Meanwhile, the coin sorting apparatus in which the coin orbiting plate having the plurality of coin sorting slots shows a low accuracy of the sorting.
The present invention is intended to overcome the above described disadvantages of the conventional techniques.
Therefore it is an object of the present invention to provide an apparatus for sorting coins, in which the sorting speed is high, and the sorting accuracy is also superior.
In achieving the above object, the apparatus for sorting coins according to the present invention is constituted such that the sorting of coins is realized as soon as the coins are carried. Accordingly, the structure of the coin carrying device and the structure of the coin sorting device are different from those of the conventional coin sorting apparatus. The coin carrying device includes a plurality of coin carrying slots, and each of the coin carrying slots consists of: an arcuate portion of a large radius, and an arcuate portion of a small radius. Thus in the large radius arcuate portion, there can be settled a large coin, while a small coin can be settled in the small radius arcuate portion. Further, a plurality of coin sorting slots are formed on a coin sorting plate, and the coin carrying slots revolvingly pass over the coin sorting slots. The coin sorting slots are arranged around the coin sorting plate, and the sizes of the circularly arranged coin sorting slots become larger as advancing clockwise. The first coin sorting slot allows the smallest coins to be dropped through it, while the last coin sorting slots allows the largest coins to be dropped through it. The lower portion of the coins are supported at the round supporting lines until the last moment when the coins are dropped. So as to make sure for the coins to be supported at the round supporting lines, the large or small coins are made to contact with the small radius arcuate portion. As described above, the apparatus of the present invention ensures that the coins are sorted simultaneously with the their carrying. Therefore, the coins are put into the coin carrying vessel at a constant rate, and one coin can be put into each of the coin carrying slots. Accordingly, the thickness of the shell of the coin carrying vessel is made to be same as or smaller than the thickness of the thinnest coin. Even if two or more coins are stacked in one slot, the stacked coins are dropped when the coin carrying slot orbits to be overlapped with the next coin sorting slot.
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The fibroblast growth factor (FGF) family is composed of 22 structurally related polypeptides that bind to 4 receptor tyrosine kinases (FGFR1-4) and one kinase deficient receptor (FGFR5) (Eswarakumar et al (2005) Cytokinc Growth Factor Rev 16, 139-149; Ornitz et al (2001) Genome Biol 2, REVIEWS3005; Sleeman et al (2001) Gene 271, 171-182). FGFs' interaction with FGFR1-4 results in receptor homodimerization and autophosphorylation, recruitment of cytosolic adaptors such as FRS2 and initiation of multiple signaling pathways (Powers et al (2000) Endocr Relat Cancer 7, 165-197; Schlessinger, J. (2004) Science 306, 1506-1507).
FGFs and FGFRs play important roles in development and tissue repair by regulating cell proliferation, migration, chemotaxis, differentiation, morphogenesis and angiogenesis (Ornitz et al (2001) Genome Biol 2, REVIEWS3005; Auguste et al (2003) Cell Tissue Res 314, 157-166; Steiling et al (2003) Curr Opin Biotechnol 14, 533-537). Several FGFs and FGFRs are associated with the pathogenesis of breast, prostate, cervix, stomach and colon cancers (Jeffers et al (2002) Expert Opin Ther Targets 6, 469-482; Mattila et al. (2001) Oncogene 20, 2791-2804; Ruohola et al. (2001) Cancer Res 61, 4229-4237; Marsh et al (1999) Oncogene 18, 1053-1060; Shimokawa et al (2003) Cancer Res 63, 6116-6120; Jang (2001) Cancer Res 61, 3541-3543; Cappellen (1999) Nat Genet 23, 18-20; Gowardhan (2005) Br J Cancer 92, 320-327).
FGF19 is a member of the most distant of the seven subfamilies of the FGFs. FGF19 is a high affinity ligand of FGFR4 (Xie et al (1999) Cytokine 11:729-735). FGF19 is normally secreted by the biliary and intestinal epithelium. FGF19 plays a role in cholesterol homeostasis by repressing hepatic expression of cholesterol-7-α-hydroxylase 1 (Cyp7α1), the rate-limiting enzyme for cholesterol and bile acid synthesis (Gutierrez et al (2006) Arterioscler Thromb Vasc Biol 26, 301-306; Yu et al (2000) J Biol Chem 275, 15482-15489; Holt, J A, et al. (2003) Genes Dev 17(130):158). FGF19 ectopic expression in a transgenic mouse model increases hepatocytes proliferation, promotes hepatocellular dysplasia and results in neoplasia by 10 months of age (Nicholes et al. (2002). Am J Pathol 160, 2295-2307). The mechanism of FGF19 induced hepatocellular carcinoma is thought to involve FGFR4 interaction. Treatment with FGF-19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Fu et al (2004) Endocrinology 145:2594-2603. FGF-19 is also described in, for example, Xie et al. (1999) Cytokine 11:729-735; Harmer et al (2004) Biochemistry 43:629-640; Desnoyer, L R et al, Oncogene (2007):1-13; and Lin, B C et al. (2007) J Biol Chem 282(37):27277-84; Pai, R et al. Cancer Res (2008) 68(13):5086-95.
FGFR4 expression is widely distributed and was reported in developing skeletal muscles, liver, lung, pancreas, adrenal, kidney and brain (Kan et al. (1999) J Biol Chem 274, 15947-15952; Nicholes et al. (2002) Am J Pathol 160, 2295-2307; Ozawa et al. (1996) Brain Res Mol Brain Res 41, 279-288; Stark et al (1991) Development 113, 641-651). FGFR4 amplification was reported in mammary and ovarian adenocarcinomas (Jaakkola et al (1993) Int J Cancer 54, 378-382). FGFR4 mutation and truncation were correlated with the malignancy and in some cases the prognosis of prostate and lung adenocarcinomas, head and neck squamous cell carcinoma, soft tissue sarcoma, astrocytoma and pituitary adenomas (Jaakkola et al (1993) Int J Cancer 54, 378-382; Morimoto (2003) Cancer 98, 2245-2250; Qian (2004) J Clin Endocrinol Metab 89, 1904-1911; Spinola et al. (2005) J Gin Oncol 23, 7307-7311; Streit et al (2004) Int J Cancer 111, 213-217; Wang (1994) Mol Cell Biol 14, 181-188; Yamada (2002) Neurol Res 24, 244-248).
It is clear that there continues to be a need for agents that have clinical attributes that are optimal for development as therapeutic agents. The invention described herein meets this need and provides other benefits.
All references cited herein, including patent applications and publications, are incorporated by reference in their entirety.
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CBD oil contains significant amounts of substances important to human health so knowing the ingredients is the first step to buying CBD oil. Now you need to know what to look for when buying CBD oil online. You want to know the concentration of CBD oil in the product, whether there are any additives in the CBD oil or hemp oil, the type of product best suited to your needs (such as choosing between a capsule or topical) and the reputation of the brand.
Tinctures are ideal for CBD novices, as they’re not always as strong as other CBD product types. If you know how much CBD you require and you’re after a higher concentration, a regular CBD tincture is unlikely to deliver the goods. However, this is beginning to change as companies experiment with higher concentrations. In the meantime, consider a vape oil, paste, or concentrate to enjoy a stronger CBD experience.
CBD Isolate is CBD in its purest form. It is a crystalline CBD that contains pure CBD and CBD alone — nothing else! That’s why it’s called an isolate — it is isolated away from all the other things that the marijuana family usually contains. Isolating the cannabinoid CBD, as separate from all other cannabinoids in the hemp or cannabis plant, is what produces CBD isolate. It’s just pure CBD that you can then use for a variety of other purposes or forms.
Both varieties contain CBD and THC (albeit at different levels), which are the two primary compounds in the Cannabis sativa plant. The Cannabis plant is also very diverse, as it can grow in many different forms. The most common types are Sativa and Indica, but there are more, with each type having dozens – if not hundreds – of different adaptations and different ratios of active compounds, also known as cannabinoids.
This may be a good place to point out that not all CBD products are created equal. The industry is still largely unregulated, and the quality and quantity of CBD in a given product will vary wildly. Third party testing definitely helps to monitor companies’ claims, but it’s still up to you as the consumer to do your homework on the best CBD products.
Disclosure: Some of the links above are affiliate links, meaning, at no additional cost to you, we will earn a commission if you click through and make a purchase. We are a professional review site that may receive compensation from certain companies whose products we review. We test each product thoroughly and give high marks to only the very best. We are independently owned and the opinions expressed here are our own.
There is a tremendous difference between CBD from hemp vs the actual cannabis plant; not addressed the fact that you are discussing CBD from hemp in the beginning of the article is confusing to those who have not been able to do their own research yet. I’ve been trying different CBD products for 2 years now & at first read, I thought you were talking about cannabis.
The statements made regarding these products have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure or prevent any disease. Please consult your health care professional about potential interactions or other possible complications before using any product. The Federal Food, Drug and Cosmetic Act requires this notice.
Colorado Cures is your natural solution to a healthy life with less pain and stress. Our flagship product comes in a variety of options to give you a fully custom experience. Because Colorado Cures is 100% domestically sourced, CBD Plus USA guarantees the premium quality of the product. Wondering if Colorado Cures is right for you? Visit our about page to get more information on CBD products and how they can benefit your life.
I searched a long time for a good cbd product and almost gave up as it felt overwhelming with so many different brands on the market. I tried quite a few but never found a good product that I could afford. I recently was introduced to a new product from this site http://bluedane.myctfocbd.com that came with a 60 day money back guarantee even if you use up the whole bottle so I am trying that out now and have so far been having good results so I would recommend it
Hemp CBD is completely different from cannabis CBD. Hemp also derives from the Cannabis sativa L plant, and while it also contains THC, it contains it in volumes that are less than 0.3% by dry weight. Some governments, including the US, regulate the concentration of THC and permit a specific variety of hemp (called industrial hemp) that is bred with an especially low THC content. This is the reason why, when you type into Google “CBD oil for Sale”, you get hundreds of companies trying to sell you their products – according to most all of them, CBD oil from industrial hemp is 100% legal to sell online and ship to all 50 states.
In order to account for the low CBD content of these hemp plants, manufacturers have to process large volumes of raw material at a time, with the idea of extracting just enough CBD so that they can label their product as a “CBD oil.” While this method is fine in theory, what ultimately ends up happening (unless the manufacturer’s extraction methods are state of the art), is that traces of chemicals cane end up being left over in the final product. These chemicals can potentially contain harsh solvents such as butane, hexane, and propylene glycol, which has been known to break down into carcinogenic (cancer-causing) compounds like formaldehyde and acetaldehyde.
It’s important to research in order to purchase the right product. Always use personal discretion when making purchases both in-person and online. Further, don’t always go for the cheap products but instead be willing to pay the price for a quality product. If you want to reap the benefits of excellent quality, then you have no choice but to pay a substantial amount for it. Also, remember to check labels for any indication of the ingredients that make the product making sure it is hemp oil CBD. Any product that comes without a label or indication of ingredients is illegal and potentially dangerous. Even though no regulation exists, it is always good to take measures to ensure your own safety.
It was a tough choice, but if you are anxious to order quality CBD oil online and want it delivered as fast as possible, then check out PureKana. Apart from investing a huge amount of resources into customer support, it truly feels as if the team at PureKana really cares about delivering high-quality CBD therapy to suffering individuals all across the country.
Tinctures are ideal for CBD novices, as they’re not always as strong as other CBD product types. If you know how much CBD you require and you’re after a higher concentration, a regular CBD tincture is unlikely to deliver the goods. However, this is beginning to change as companies experiment with higher concentrations. In the meantime, consider a vape oil, paste, or concentrate to enjoy a stronger CBD experience.
The endocannabinoid system (ECS) is a group of cannabinoid receptors located in the brain and throughout the central and peripheral nervous systems, consisting of neuromodulatory lipids and their receptors. There are two main types of receptors in the ECS, CB1 and CB2. CB1 receptors are primarily located in the central nervous system and brains of mammals, and CB2 are generally found in the peripheral nervous system. There are two main cannabinoids mammals produce- 2AG and Anandamide. Read more by clicking here
For some, having more than trace amounts of Tetrahydrocannabinol (THC) might not be a big deal, but if you’re being drug tested at work, operating heavy machinery, or fall into a number of other categories, you may want to keep the THC to a bare minimum. In order to qualify as a legal hemp product, CBD oil must contain less than 0.03% THC. Look for CBD oil certified to have low levels of, or zero, THC in them. Many reputable sellers do offer products that have absolutely no THC in them at all, so if you are concerned about keeping even trace amounts of TCH out of your body, it is best to look for those products and sellers.
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# Event 137 - Startup_CGatheringService_Init
###### Version: 0
## Description
None
## Data Dictionary
|Standard Name|Field Name|Type|Description|Sample Value|
|---|---|---|---|---|
|TBD|hr|UInt32|None|`None`|
## Tags
* etw_level_Informational
* etw_keywords_Service
* etw_opcode_Stop
* etw_task_Startup_CGatheringService_Init
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1.Background and Relevant Art
Computer systems and related technology affect many aspects of society. Indeed, the computer system's ability to process information has transformed the way we live and work. Computer systems now commonly perform a host of tasks (e.g., word processing, scheduling, accounting, etc.) that prior to the advent of the computer system were performed manually. More recently, computer systems have been coupled to one another and to other electronic devices to form both wired and wireless computer networks over which the computer systems and other electronic devices can transfer electronic data. Accordingly, the performance of many computing tasks are distributed across a number of different computer systems and/or a number of different computing environments.
In some environments, different components of a distributed application reside and different computer systems and interoperate to implement the functionality of the distributed application. Some distributed applications are relatively simple, perhaps having one component at each of two different computer systems. As such, configuring these components to interoperate is also reasonably simply.
However, other distributed applications can be larger, relatively more complex, and highly inter-connected as well as diverse in their implementations and configurations. For example, a distributed application can have components at tens or event hundreds of different computer systems. The flexibility of configuration models that can be used with each component is also relatively extensive. The combination of the number of components and the complexity of their configuration can lead to challenges when attempting to identify and resolve configuration issues for the distributed application. The challenges can be even more difficult when a distributed application is hosted on a sophisticated server product, which supports powerful configuration features, such as, for example, multi-level configuration hierarchy, configuration locking, and delegation.
Some systems provide little, if any assistance, to an application owner when errors occur. Other systems to produce error messages, providing an application developer at least some information when an error occurs. However, even when they exist, these types of error messages are typically not adequate for resolving errors. For example, these types of errors messages may relate only to small number of (or even a single) component(s) of a distributed application. Thus, an application owner must individually active each component to see runtime errors for the component. Accordingly, troubleshooting multiple inter-connected application components is generally a challenging experience.
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In anticipation of complaints from citizens regarding the Dove Hunting that will commence at dawn tomorrow, I wanted everyone to be aware of a new law passed in the last legislative session. It effectively allows hunting in most of our city on tracts of 10 acres or more. Most of Frisco was not annexed in 1981, so the below bill would apply. SB 734: Sec. 229.002. REGULATION OF DISCHARGE OF WEAPON. A municipality may not apply a regulation relating to the discharge of firearms or other weapons in the extraterritorial jurisdiction of the municipality or in an area annexed by the municipality after September 1, 1981, if the firearm or other weapon is: (1) a shotgun, air rifle or pistol, BB gun, or bow and arrow discharged: (A) on a tract of land of 10 acres or more and more than 150 feet from a residence or occupied building located on another property; and (B) in a manner not reasonably expected to cause a projectile to cross the boundary of the tract; or (2) a center fire or rim fire rifle or pistol of any caliber discharged: (A) on a tract of land of 50 acres or more and more than 300 feet from a residence or occupied building located on another property; and (B) in a manner not reasonably expected to cause a projectile to cross the boundary of the tract.
Yes, I believe the law is not well thought out. Hunting 150 feet from an occupied daycare center is not sound in theory or practice, in my opinion. We experienced that very scenario last year. We experience many complaints every year. Additionally, permitting a high powered rifle within 300 feet of an occupied dwelling is also absurd. I am a hunter as well and have spoken with the author of the law. The purpose of the law was based on complaints from farmers who were annexed into cities but lived miles outside the city. In an urban environment, I think the law is ill-advised. I believe the City Council believes the same, as do the police chiefs surrounding us. Lastly, I am opposed to the state taking away the authority of the local city councils to determine what is best for their community. There is a big difference in urban and rural communities in Texas. I believe the local officials are better-suited to determine what is best for their community.
The Governor signed a bill today that was filed by Senator Shapiro and Representative Paxton that should aide a great deal with this issue. The text of the law is below. Essentially it increases the distance from schools, parks, homes etc. We are hopeful that this will alleviate some of the complaints we receive in the fall. The law effects Collin County and based on the bracketing, I believe it also effects Denton, Fort Bend and Montgomery Counties. The history of the bill can be viewed at: http://www.legis.state.tx.us/BillLookup/History.aspx?LegSess=81R&Bill=SB1742The bill is effective immediately.
Sec. 229.003. REGULATION OF DISCHARGE OF WEAPON BY CERTAIN MUNICIPALITIES. (a) This section applies only to a municipality located wholly or partly in a county: (1) with a population of 450,000 or more; (2) in which all or part of a municipality with a population of one million or more is located; and (3) that is located adjacent to a county with a population of two million or more. (b) Notwithstanding Section 229.002, a municipality may not apply a regulation relating to the discharge of firearms or other weapons in the extraterritorial jurisdiction of the municipality or in an area annexed by the municipality after September 1, 1981, if the firearm or other weapon is: (1) a shotgun, air rifle or pistol, BB gun, or bow and arrow discharged: (A) on a tract of land of 10 acres or more and: (i) more than 1,000 feet from: (a) the property line of a public tract of land, generally accessible by the public, that is routinely used for organized sporting or recreational activities or that has permanent recreational facilities or equipment; and (b) the property line of a school, hospital, or commercial day-care facility; (ii) more than 600 feet from: (a) the property line of a residential subdivision; and (b) the property line of a multifamily residential complex; and (iii) more than 150 feet from a residence or occupied building located on another property; and (B) in a manner not reasonably expected to cause a projectile to cross the boundary of the tract; (2) a center fire or rim fire rifle or pistol of any caliber discharged: (A) on a tract of land of 50 acres or more and: (i) more than 1,000 feet from: (a) the property line of a public tract of land, generally accessible by the public, that is routinely used for organized sporting or recreational activities or that has permanent recreational facilities or equipment; and (b) the property line of a school, hospital, or commercial day-care facility; (ii) more than 600 feet from: (a) the property line of a residential subdivision; and (b) the property line of a multifamily residential complex; and (iii) more than 300 feet from a residence or occupied building located on another property; and (B) in a manner not reasonably expected to cause a projectile to cross the boundary of the tract; or (3) discharged at a sport shooting range, as defined by Section 250.001, in a manner not reasonably expected to cause a projectile to cross the boundary of a tract of land. SECTION 2. This Act takes effect immediately if it receives a vote of two-thirds of all the members elected to each house, as provided by Section 39, Article III, Texas Constitution. If this Act does not receive the vote necessary for immediate effect, this Act takes effect September 1, 2009.
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The Polish version of the Peters et al. Delusions Inventory: factor analysis, reliability and the prevalence of delusion-like experiences in the Polish population.
The study aimed at providing the psychometric properties of Polish version of Peters et al. Delusion Inventory (PPDI) (1999) and assessing the prevalence of delusion-like experiences among healthy subjects in the Polish population. Polish version of PDI was developed on the basis of back translation procedure. The scale was completed by 421 adult subjects. On the basis of the scores, the factor analysis, the reliability of the scale and the frequency of delusion-like experiences in the Polish population were calculated. The Polish version of Peters et al. Delusion Inventory has satisfactory reliability (Cronbach's alpha ranged from 0.084 to 0.87). The examination of scree plot suggests a single factor solution. The participants confirmed the incidence of, on average, 12.5 (SD=6.9), out of 40 different experiences measured using PDI. In the current study the most frequently asserted delusion-like belief is that people say things with double meaning (79.8% of participants), while the least likely beliefs were those similar to delusions observed among psychiatric patients (2.37% of participants). The Polish version of PDI is characterised by good psychometric properties and can be used for delusion-like experiences assessment in non-clinical population. The frequency of delusion-like experiences in the Polish population varies from 2 to 80% depending on their content.
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This application claims the priority benefit under 35 U.S.C. § 119 of Japanese Patent Application No. 2006-006350 filed on Jan. 13, 2006, which is hereby incorporated in its entirety by reference.
1. Field
The presently disclosed subject matter relates to a reflection type optical sensor which optically detects the surface roughness of an object by detecting the reflection of a light beam irradiated onto the surface of the object, and to a method for detecting the surface roughness of a surface to be measured, using the sensor. More particularly, the presently disclosed subject matter relates to a reflection type optical sensor that can function as a media sensor configured to identify the type of paper (such as ordinary paper, glossy paper, recycled paper, coated paper, and an OHP transparency film) for use in a color copier, a color printer, or the like. The disclosed subject matter can also function as a gloss sensor configured to measure the gloss of a painted surface or the like. In addition, the disclosed subject matter can function as a material identification sensor configured to identify types of materials of various components used in an FA field. In addition to these, the presently disclosed subject matter relates to a method for detecting the surface roughness of a surface to be measured.
2. Description of the Related Art
FIG. 1 is a schematic diagram of a conventional reflection type optical sensor 55 configured to include a light projection device 50, a light receiving device 51, a polarizing plate 52, a polarizing beam splitter 53, and a correction light receiving device 54. The light projection device 50 is provided with, as a light source, a light emitting device such as a light emitting diode (LED) or a laser diode, which emits a light beam of a single wavelength. The light receiving device 51 is provided with, as a photoreceptor, a light receiving element such as a photodiode or a phototransistor. The light projection device 50 and the light receiving device 51 are arranged such that the incident angle θ of the optical axis of the light projection device 50 is the same as the reflection angle θ of the optical axis of the light receiving device 51. Here, the incident angle and the reflection angle are determined with respect to the normal to the surface of an object. The light projection device 50 is provided with the polarizing plate 52 disposed on the optical axis of the light projection device 50 in the light irradiating direction. The light receiving device 51 is provided with the polarizing beam splitter 53 disposed on the optical axis of the light receiving device 51 on the light incident side. Furthermore, the correction light receiving device 54 is disposed at a position at which it can receive the light beam that is separated and reflected by the polarizing beam splitter 53.
In the reflection type optical sensor 55 having the above described configuration, the light beam emitted from the light projection device 50 which has a single wavelength is polarized when the light beam passes through the polarizing plate 52. In this case, the polarized light beam has a plane of vibration in a specific direction. This polarized light beam is irradiated onto an object surface 56. Then, the polarized light beam reflected from the object surface 56 is separated by the polarizing beam splitter 53, and the separated light beams are detected by the light receiving device 51 and the correction light receiving device 54, respectively, to produce output signals.
The reflection type optical sensor 55 is configured such that, among the polarized light beams reflected from the surface 56 of the object to be measured, the reflected polarized light beam that has the same plane of vibration as that of the polarized light beam which passed through the polarizing plate 52 is detected by the light receiving device 51 through the polarizing beam splitter 53. Furthermore, the reflected polarized light beam that has a different plane of vibration from that of the polarized light beam which passed through the polarizing plate 52 is detected by the correction light receiving device 54 through the polarizing beam splitter 53.
Therefore, by computing the ratio of the output of the light receiving device 51 based on the amount of the received polarized light beam to the output of the correction light receiving device 54 based on the amount of the received polarized light beam, the surface roughness of the object to be measured can be detected (see, for example, Japanese Patent Laid-Open Publication No. Hei 10-281991).
The reflection type optical sensor as described above is capable of identifying different types of printing media such as ordinary paper, glossy paper, recycled paper, coated paper, and an OHP transparency film. Furthermore, since the detection resolution is very high, the different types of glossy paper which is one of the printing media can be more particularly identified based on the gloss thereof.
However, the above described reflection type optical sensor has polarizing optical elements (the polarizing plate and the polarizing beam splitter) as components. Therefore, a problem exists in that the manufacturing cost associated with multiple elements is high.
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As we know, at present, power generation is a production process of converting, using a power generation device, thermal energy and nuclear energy of petrochemical fuel (such as coal, oil and natural gas) into electrical energy supplied for needs of various departments of national economy and people's life. However, petrochemical fuel can produce large amounts of carbon dioxide, which exacerbates the global greenhouse effect. Besides, nuclear energy faces great challenges of source of raw materials and environmental protection.
Those skilled in the art have begun to use solar energy, wind energy, geothermal energy, water energy (including marine energy) and other clean energies for power generation. However, solar energy and wind energy are seriously affected by climatic conditions, and geothermal energy and water energy (including ocean energy) are subject to harsh geographical conditions as well. Therefore, these energies cannot be popularized on a large scale. Furthermore, long-term development of the ocean energy is prone to result in ecological disasters.
Therefore, a kind of energy which is cheap and can be widely collected is needed. As a result, ubiquitous air, oceans, lakes and rivers come into people's sight. As all the energies on the surface of the earth substantially come from the sun (energy caused by volcanic eruption is relatively weak and can be negligible), the energy of the sun's rays is heating air, oceans, lakes and rivers all the time. If the energy can be extracted for human use, it will no longer have the problem of emissions of carbon dioxide, ecological disasters and the problem of scarcity of resources. Besides, the energy will no longer be subject to climatic conditions and geographical conditions.
For the above reasons, a variety of power generation devices making use of air or liquid have been developed, where air or liquid thermal energy is used to make working fluids having a low boiling point in a vessel be gasified, and then high pressure steam generated is used to drive a generator to generate power through a turbine. However, at present, such devices are basically required to realize liquefaction recycling of the working fluids by means of a refrigeration compressor and a booster pump. The problems lie in that, on one hand, as the refrigeration needs to face enormous liquefaction potential, it is infeasible to use the refrigeration compressor to liquefy the working fluids, and on the other hand, even if there is a ready-made cold source, using the booster pump to make the working fluids back into a high pressure area costs highly. Therefore, the devices have too low overall efficiency and cannot be applied in practice. In addition, such devices have special requirements on working conditions, that is, they require a temperature difference, and the greater temperature difference the better. The devices cannot work in the case of no temperature difference. In view of the above situations, it is necessary to improve the power generation devices, to improve the efficiency of power generation and finally realize all-weather, all-earth and full-time power generation and even provide power under no temperature difference conditions.
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The Deadly Battle at Hicksville
The Deadly Battle at Hicksville is a 1914 American silent short comedy film directed by Marshall Neilan and starring John E. Brennan, Ruth Roland, and Lloyd Hamilton. The film was released by General Film Company on July 31, 1914.
Plot
Cast
John E. Brennan as Jim
Ruth Roland as Dolly - a Southern Belle
Lloyd Hamilton as Dick - Jim's Rival
See also
List of American films of 1914
References
External links
Category:1910s comedy films
Category:American comedy films
Category:American films
Category:1914 films
Category:American black-and-white films
Category:American silent short films
Category:Kalem Company films
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The Steph Effect: How NBA star is inspiring — and complicating — high school basketball
High school guards like Jeremy Roach (left) and Jared Bynum (right) feature the long-range shooting popularized by NBA star Stephen Curry (center) in their games.
From opposite ends of the court, and without so much as glancing at each other, Jared Bynum and Vado Morse launched three-pointer after distant three-pointer, stretched their ranges after each attempt and painted a portrait of basketball evolution.
They were warming up for their teams’ clash in the Interstate Athletic Conference championship inside a Bethesda, Md., gym in late February. Bynum, a senior point guard for Georgetown Prep, took one dribble before launching a 28-foot three from the right wing. It rolled in. Morse, a senior point guard for visiting Bullis, shot from a step inside the center-court logo moments later. That rolled in, too.
The guards were almost completely in sync, their long-range shots arcing through the air one after the other. Then the game started, Morse darted to the right wing, bounced the ball between his legs and buried a three from in front of the Georgetown Prep bench, no closer than 26 feet from the rim.
This is the era of Stephen Curry-inspired point guards, and this is how they play basketball.
“Watching Steph growing up, it sort of made you rethink what was possible,” said Bynum, who is set to play at Saint Joseph’s next season. “The long shooting, the ballhandling, all of that — I think it had a big effect on how a lot of us play.”
Washington-area guards illustrate Curry’s broad effect on high school basketball, as young players across the country are shooting more threes and, more than ever, launching them from well beyond the arc. Curry, the two-time NBA champion, two-time MVP and five-time all-star for the Golden State Warriors at 29 years old, had his major breakout six seasons ago when he made a league-high 272 three-pointers.
The current crop of high school guards were 9, 10, 11 and 12 years old that year — and many were glued to their television screens as Curry shimmied away from defenders, buried threes from unseen distances and turned the world’s best basketball league into his personal playground. In the seasons since, Curry has set the record for threes in a season three times and established himself as one of the best shooters in NBA history.
That all created a new style of play for young players to aim for and a puzzling equation for the coaches tasked with molding their games: how to let kids imitate one of their basketball idols but not take it too far.
“Not a lot of players can shoot like that, but most kids will try,” said Georgetown Prep’s Ryan Eskow, who coaches Bynum. “All the kids nowadays, they practice 29-footers; that’s the fun thing to do. Am I teaching them that? No, it’s on their own time. I don’t want them shooting 35-foot jumpers. But if you take a bad shot and it goes in, it becomes a positive play.”
Warriors guard Stephen Curry is one of the best shooters in NBA history. (Steve Dipaola/AP)
There is a lot for high schoolers to learn from Curry as they map out their basketball dreams. He can shoot from anywhere, yes, but he also dribbles as if the ball were attached to his body by magnet or rope. He passes as if there were no defenders on the court. He is a humble role model, even when he was pressed, daily, to talk about his meteoric ascension from experimental guard to NBA star.
But Curry’s shooting — deep and often coming off the dribble — is what caught on most with this generation of high school guards. The game, at all levels, is following the trends atop the NBA, as Curry and the Warriors have revolutionized basketball with a high volume of threes, endless fast breaks and positionless lineups. It has led to an outpouring of social media hype, two NBA titles in three years and copycat challengers like the Houston Rockets, who are attempting a league-high 42 threes per game this season while owning the NBA’s best record.
This three-point-heavy, space-and-pace era is the only style that current youth players have ever known.
High school coaches and recruiting experts have seen this on the varsity and junior varsity levels, on the AAU circuit in the spring and summer, and even in youth leagues. Damon Handon, who runs the AAU program D.C. Premier, recently went to a 10-and-under game. “Kids were taking deep threes and holding up their follow-through like they were Steph Curry,” he said. “It was crazy.”
“I’m pretty sure that the coaches are being put in a position where they are having to reel some guys back in and make sure that they understand that you got to work on this stuff,” Curry said after the Warriors practiced at Georgetown University last week. “It takes time.”
Eskow and other coaches said if a player is adding range to an already-developed game, it is a positive. If a player is expecting range to be his defining skill, then it becomes a negative. It has become the coaches’ job to teach those players about evolved shot selection, productive training habits and how extending the defense is not just a sign to shoot deeper, but also a chance to drive into the paint and distribute to teammates.
Coaches have to explain that while Curry’s skill set is something to aspire to, his game is built on fundamentals. They have to explain that, while the Warriors have become the NBA’s gold standard and make all those social-media-bound plays, the root of their success is ball movement. They have to take lofty personal goals and temper them into a realistic plan that doesn’t compromise a player’s development or a team’s chemistry.
“At Davidson, when I was there, I didn’t show up on campus doing that,” Curry said of his three-year college career. “I had to kind of work my way up and evolve and prove I could do it consistently and get that buy-in and whatnot, or else I would have been sitting on the bench.”
D.C.-area guards like Bynum, Paul VI sophomore Jeremy Roach and Theodore Roosevelt sophomore Marcus Dockery understand that balance. Bynum expands his range on his own time and counts ballhandling as Curry’s most teachable skill. Roach, who visited Kentucky this fall and is ranked 19th in ESPN’s Class of 2020 rankings, gets instruction in practice from Paul VI Coach Glenn Farello on pull-up, transition threes — the kind of shot that, in a past era, might have landed a player on the bench.
Dockery does late-night push-ups to extend his shooting range — he made more than 70 threes this season — and sees an additional benefit to pulling up from a few (or five) feet behind the line.
“It feels really good to make those long ones,” Dockery said, laughing. “But it also makes you that much closer to being back on defense. I think coach likes that, too.”
“I think the coaches are having to expand the way that they coach. Really, if you’re not, you’re going to fall behind,” said Steve Turner, who coaches at Gonzaga College High in Washington. “When your kids want to play a certain way — maybe like the guys they are imitating on the playground, if it’s Steph or someone else — you have to get them to buy into what you want but also allow them to be the player they want to become.”
Ahead of another game at Georgetown Prep, four nights before Bynum and Morse traded all those warmup threes, more than 40 kids crowded under the same hoop. They were messing around before the teams took the court, fighting for three basketballs that clanged off the rim and into a bevy of outstretched arms.
One of the balls bounced to a 12-year-old standing away from the pack, and he dribbled out well behind the three-point line as his friends watched. He took two dribbles, one more step back, and now stood smack between half court and the top of the three-point arc.
Then he hoisted a jump shot and yelled, “Steph!” in a high-pitched voice.
The ball swished in. A perfect imitation.
“We are in the position that people turn on the TV and watch us play, and we are hopefully pushing the game to the next level and being the mold and the model of how kids want to play coming up,” said Curry, who once modeled his style after point guard Steve Nash and sharpshooter Reggie Miller. “So it is kind of a surreal feeling.”
|
How My Husband's Boyfriend Got His Green Card
Last week, Isabel* got married. Of course, her husband was there. But so was her husband's boyfriend. And her husband's boyfriend's wife.
Confused yet?
Isabel, an immigrant from Latin America, has been living in Miami for the last eight years. She went to school here and has started a promising career. And she has lots of friends -- jet-setting Europeans and American girls who count among the "beautiful people."
When her visa ran out, one of those friends -- her very special friend David* -- agreed to marry her so that she could apply for a resident visa. For David, lending Isabel a hand in marriage wasn't much of a sacrifice. Being gay, David had no intention of marrying another woman, now or any time in the foreseeable future.
As for David's finding some way to marry his gay partner, someone else beat him to it. His gay partner, Manuel,* is also an immigrant from Latin America living in Miami. When he started having visa problems four months ago, he decided to marry Laura.*
Now David, Manuel, Isabel and Laura form an unlikely quartet of marriage under the law: two husbands, two wives, but only one couple. As Isabel describes David, whom she met at work, "he's great at his profession. … He's handsome. … I could have been in love with him," she said. "It's kind of sad that he -- my husband -- is gay."
Cash to Walk Down the Aisle
While the double marriage and sexual preference twist may be unusual, the basic story of marrying to stay in America is nothing new.
According to immigration lawyer Carl Shusterman, what the government calls a "fraudulent spouse profile" -- and he calls a "phony baloney marriage" -- is a relatively common way immigrants evade rules that would otherwise keep them out. Isabel believes that in Miami, it's easy to find American citizens short on cash and ready to offer their hand in marriage for up to $12,000 a hitch.
Shusterman was previously a government immigration officer who investigated suspicious marriages as part of his job. He estimates that 500,000 and 600,000 of the 1 million people who immigrate to the United States each year obtain their green card through marriage. Mixed in with the many legitimate marriages are "fraudulent spouses."
For immigrant brides like Isabel, walking down the aisle is perhaps the easiest step in the process. She and David will go through a series of interviews meant to test whether they married for love or for passport. Immigration agents, on the lookout for any sign of fraudulence, can ask for anything from joint tax filings to the brand of shampoo he or she uses.
If agents get suspicious during the interview, Isabel can get arrested on the spot and subsequently deported. Not only that, her dream of staying in the United States would be washed away forever by section 204c of the Immigration and Nationality Act.
That provision states that any immigrant found to be married for the purpose of evading immigration laws can never be granted a visa and never again allowed into the country.
"You're under a life sentence -- you can never get back in and there's no forgiveness," Shusterman said. "You're better off robbing a liquor store as far as your immigration application is concerned."
Isabel maintains her calm at the forthcoming interview.
"Of course I am afraid they are going to notice that he'll look too gay in the interview," Isabel said. "But I know guys who are much gayer than my husband and could get away with it."
Isabel adds, "If I didn't do this and I just went back to my country, I'd always regret that there was one more thing I could have tried to stay in America, but I didn't do it."
Right Vs. Wrong
"Give me rules that can help me stay," Isabel begs. "I do know that I'm doing a wrong thing but I'm only doing it because there's no right thing to do."
"I've learned so much about a side of things, an ugly side of the coin, that real Americans don't know," she said. "And now I found someone who wants to help me."
Should Isabel be allowed to stay? In helping her, is David harming America? The ethical dilemmas only accumulate.
"What am I doing bad to the United States?" Isabel asks. "I have no criminal record. I want to pay taxes. I want to work legally."
In her opinion, she's not here to take advantage of the United States. "I have so much I can contribute to your country."
|
Objective {#s1}
=========
Wilson's disease is an autosomal recessive metabolic liver disease related to mutation of the copper-transporting ATPase, ATP7B, an intracellular copper transporter mainly expressed in the hepatocytes.[@R01][@R02] Wilson's disease is characterised by excessive copper deposition in the body, primarily in the liver and brain, resulting from inability of the liver to excrete copper in the bile. Cardiac arrhythmias, cardiomyopathy and sudden cardiac death are rare complications but may be seen in children with Wilson's disease due to copper accumulation in the heart tissue.[@R03][@R06] The aims of our study were to determine potential differences in strain and strain rate between patients with Wilson's disease and age-matched controls, and to detect early cardiac dysfunction.
Methods {#s2a}
=======
In this study, 21 patients with Wilson's disease who applied to our hospital's Paediatric Gastroenterology Department between May and October 2013 were included (α = 0.05, 1--β = 0.8, changing ratio = 0.0015). The control group consisted of 20 ageand gender-matched healthy children. Patients with any chronic disease, obesity and hypertension in addition to Wilson's disease or history of drug use that may have affected cardiac function were excluded from the study.
Diagnosis of Wilson's disease was made by the Paediatric Gastroenterology Department, based on the presence of signs of liver or neurological disease and the detection of Kayser-- Fleischer rings, low ceruloplasmin, and elevated levels of urinary and hepatic copper. Liver biopsies were done for all patients and associated histological changes in the liver were confirmed. Before the study, approval of the ethics committee of the Medical School of Inonu University in accordance with Declaration of Helsinki was received.
Age, body weight, height and body surface area were recorded in the patient and control groups. The age at diagnosis of Wilson's disease was also recorded in the patient group. All subjects were evaluated with ECG before echocardiographic evaluation.
All patients and controls were evaluated with two-dimensional (2D) and color-coded conventional transthoracic echocardiography by the same paediatric cardiologist, using the same echocardiography machine (Vivid E9, GE Healthcare, Norway) in the standard precordial positions, according to the American Society of Echocardiography recommendations.[@R07] Left ventricular dimensions, left ventricular wall thickness, end-diastolic and end-systolic volumes, stroke volume, cardiac index, ejection fraction and fractional shortening were measured using M-mode echocardiography in the parasternal long-axis view.
2D strain and strain rate echocardiography were performed by a paediatric cardiologist after the ECG probes of the echocardiography machine (Vivid E9, GE) were adjusted for ECG monitoring. Grey images were obtained from the apical four-, three- and two-chamber, and short-axis view at the papillary muscle position using tissue harmonic imaging with frame rates of 70 per second. All the images that were obtained in the left lateral decubitus position and under ECG monitoring were stored for offline analysis.
2D strain and strain rate measurements were performed using the ECHOPAC software package. As previously described, the endocardial border was traced manually on a single end-diastolic frame and the software automatically tracked the contour on subsequent frames. Tracking accuracy was verified in real time and corrected by adjusting the region of interest or by manually correcting the contour to ensure optimal tracking. If required, region-of-interest width or smoothing functions were changed for optimal tracking. Once the contours were approved by the paediatric cardiologist, the software calculated longitudinal, transverse, radial and global strains for the respective segments. For long-axis strain and strain rate evaluation, the atrioventricular valve closure time was selected manually.
As described, longitudinal and transverse radial strain, and strain rate were assessed from six basal and six mid-ventricular segments of the left ventricle, as recommended by the American Society of Echocardiography ([Figs 1](#F1){ref-type="fig"}[--4](#F4){ref-type="fig"}). This included apical, mid- and basal segments from the four-, two- and three-chamber view of the left ventricle, and anterior, septal and inferior segments from the short-axis view of the left ventricle.
{#F1}
{#F2}
{#F3}
{#F4}
Statistical analysis {#s2b}
====================
SPSS 16.0 was used for statistical analysis. The normality was tested using the Kolmogorov--Smirnov test. The unpaired t-test was used to test for differences between categorical data of the patient and control groups. The ANOVA test was used to evaluate 2D strain and strain rate values of the two groups for each segment. The LD test was applied in the second test to determine the groups that differed significantly. All the results are expressed as mean ± standard deviation; p-values \< 0.05 were considered statistically significant.
Results {#s3a}
=======
The study included 21 patients with Wilson's disease and 20 healthy age-matched children. The patient group consisted of 11 males and 10 females, and the control group, nine males and 11 females. Demographic data of the patient and control groups are shown in [Table 1.](#T1){ref-type="table"} There were no statistically significant differences between the patient and control groups (p \> 0.05). The mean age at diagnosis was 9 ± 2.24 years (5--13) in the patient group. All the subjects had normal sinus rhythm. Wolf--Parkinson--White syndrome was detected in one patient's ECG.
No structural heart disease was detected with conventional 2D colour-coded transthoracic echocardiography. Left ventricular wall thickness (IVSd, IVSs, LPWd, LWPDs), systolic and diastolic diameters (LVIDd, LVIDs), left ventricular diameters normalised to body surface area (LVEDd/m², LVEDs/m²), end-systolic and end-diastolic volumes (ESV, EDV), cardiac output and cardiac index values were within normal limits and statistically similar in the patient and control groups (p \< 0.05). Demographic data, left ventricular wall thickness, dimensions, volumes and systolic function of the patient and control groups are shown [Table 1.](#T1){ref-type="table"}
###### Demographic data of left ventricular wall thickness, dimension, volume and systolic function of Wilson's disease patients and controls
*Patients(n = 21)* *controls (n = 20)*
-------------------------- ----------------------- --------------------- -------
Age (years) 11.04 ± 3 .58 (5--17) 10.53 ± 2.8 (6--16) 0.61
Gender (male/female) 11/10 9/11 0.64
Weight (kg) 38.1 ± 16.04 38.1 ± 16.04 0.84
(14.5--68) (21.4--67)
Height (cm) 141.5 ± 20.2 141.1 ± 14.2 0.93
(100--187) (120--168)
Body surface area (m^3^) 1.21 ± 0.33 1.22 ± 0.25 0.92
(0.63--1.91) (0.9--1.72)
Age of diagnosis 9 ± 2.24 \- \-
(5--13)
IVSd (mm) 7.14 ± 1.10 6.45 ± 1.39 0.85
IVSs (mm) 10.76 ± 1.78 9.7 ± 1.65 0.56
LPWDd (mm) 5.42 ± 1.16 5.2 ± 1.36 0.56
LPWDs (mm) 9.52 ± 2.11 8.8 ± 1.28 0.1
LVIDd (mm) 41.6 ± 6.81 42.1 ± 4.52 0.79
LVEDd/m^2^ (mm/m^2^) 35.5 ± 8.45 35.2 ± 5.16 0.92
LVEDs (mm) 24.8 ± 4.65 26.5 ± 6.09 0.32
LVEDs/m^2^ (mm/m^2^) 21.05 ± 5.08 22.19 ± 4.68 0.46
EDV (ml) 83.38 ± 28.76 79.8 ± 20.41 0.65
ESV (ml ) 24.28 ± 11.89 29.5 ± 20.79 0.32
SV (ml) 60.85 ± 20.53 55.80 ± 13.65 0.36
CI (ml/min) 4.60 ± 1.32 3.98 ± 0.78 0.077
EF (%) 71.76 ± 6.51 69.90 ± 5.33 0.32
FS (%) 40.9 ± 5.62 39.1 ± 4.54 0.26
EDV: end-diastolic volume, ESV: end-systolic volume, SV: stroke volume, CI: cardiac index, EF: ejection fraction, FS: fractional shortening, CI: cardiac index.
Global strain and strain rate {#s3b}
=============================
No statistically significant differences were found between the two groups for global longitudinal/circumferential strain rate, global peak systolic longitudinal/circumferential strain rate, global peak E longitudinal/circumferential strain rate, peak E longitudinal velocity of the left basal point, peak E longitudinal velocity of the right basal point, and peak A longitudinal velocity of the left basal point (cm/s).
While the control group had statistically significantly lower global peak A longitudinal/circumferential strain rates, the patient group had statistically significantly lower peak A longitudinal velocity of the left basal point and peak E longitudinal velocity of the left basal point (p \< 0.05). Global strain and strain rate values of the patients and controls are shown in [Table 2.](#T2){ref-type="table"}
###### Global strain and strain rate values of Wilson's disease patients and controls
*Patients* *Controls*
---------------- ---------------- ---------------- -------
GS (%) --17.30 ± 3.22 --17.11 ± 3.69 0.70
GSRs (1/s) --1.07 ± 0.20 --1.02 ± 0.23 0.17
GSRe (1/s) 1.54 ± 0.40 1.59 ± 0.46 0.35
GSRa (1/s) 0.74 ± 0.44 0.53 ± 0.23 0.02
VEbasL (cm/s) --11.25 ± 2.95 --11.20 ± 2.53 0.91
VESbasR (cm/s) --9.22 ± 3.03 --9.91 ± 3.00 0.16
VAbasL (cm/s) --6.69 ± 2.991 --5.09 ± 1.930 0.001
VAbasR (cm/s) --5.95 ± 2.807 --4.65 ± 2.129 0.002
GS: global peak longitudinal/circumferential strain, GSGRs: global peak systolic longitudinal/circumferential strain rate, GSRe/1s: global peak E longitudinal/ circumferential strain rate, GSRa1/s: global peak A longitudinal/circumferential strain rate, VEbasL: left basal peak E longitudinal velocity, VEbasR: right basal peak E longitudinal velocity point, VAbasL: left basal peak A longitudinal velocity, VAbasR: right basal peak A longitudinal velocity.
Radial strain and strain rate {#s3c}
=============================
No statistically significant differences were found between the two groups for the most negative peak circumferential strain (SLSC peak G), negative systolic peak circumferential strain (SLSC peak S), positive systolic peak circumferential strain (SLSC peak P), end-systolic circumferential strain \[SLSC (ES)\] and end-systolic radial displacement \[DTDR (ES)\] (p \< 0.05).
End-systolic rotation \[ROT (ES)\] was statistically significantly lower in the patient group (p \< 0.05). Segmental analysis showed that rotational strain measurement of the anterior segment was statistically significantly lower (--0.78 ± 3.16) in the patient group (p = 0.019). The lateral segment was also statistically significantly lower in the patient group (--1.17 ± 3.17) (p = 0.14). Radial strain and strain rate measurements of patients and controls are shown in [Table 3.](#T3){ref-type="table"} Radial strain and strain rate values according to the segments are shown in [Table 4.](#T4){ref-type="table"}
###### Radial strain and strain rate measurements of Wilson's disease patients and controls
*Patients (n = 21)* Controls (n = 20)
----------------- --------------------- ------------------- -------
SLSC peak G (%) --16.45 ± 10.74 --16.09 ± 9.85 0.77
SLSC peak S (%) --15.22 ± 11.57 --14.64 ± 11.38 0.67
SLSC peak P (%) 2.60 ± 5.09 2.75 ± 5.46 0.82
SLSC (ES) (%) --14.20 ± 12.41 --13.71 ± 12.89 0.74
STSR (ES) (%) 41.04 ± 18.29 44.92 ± 17.47 0.72
DTDR (ES) (mm) 5.145 ± 2.54 5.01 ± 2.48 0.65
ROT (ES) (°) --4.49 ± 4.53 --2.84 ± 5.06 0.004
SLSC peak G: the most negative peak circumferential strain, SLSC peak S: negative systolic peak circumferential strain, SLSC peak P: positive systolic peak circumferential strain, SLSC (ES): end-systolic circumferential strain, DTDR (ES): end-systolic radial displacement, ROT (ES): end-systolic rotation.
###### Radial strain and strain rate values according to segment
*Strain according to segment* *Patients (n = 21)* *Controls (n = 20*)
------------------------------- --------------------- --------------------- ---------
(mean ± SD) (mean ± SD) p-value
*SLSC peak S (%)*
Anterior --9.55 ± 7.79 --9.71 ± 8.90 0.94
Lateral --3.68 ± 5.75 --4.34 ± 5.76 0.69
Posterior --6.60 ± 8.31 --3.48 ± 8.57 0.21
Inferior --19.95 ± 6.84 --20.01 ± 5.32 0.97
Septal --27.83 ± 6.57 --27.03 ± 4.63 0.64
Anterior septal --23.85 ± 7.69 --23.28 ± 6.11 0.78
*SLSC peak P (%)*
Anterior 2.33 ± 2.89 2.18 ± 2.34 0.84
Lateral 4.31 ± 4.33 5.56 ± 6.30 0.41
Posterior 4.44 ± 6.25 7.37 ± 9.59 0.20
Inferior 1.71 ± 4.20 0.69 ± 0.90 0.29
Septal 1.31 ± 6.10 0.25 ± 0.56 0.44
Anterior 1.48 ± 5.37 0.43 ± 0.984 0.39
*SLSC (ES) (%)*
Anterior --9.21 ± 7.78 --9.50 ± 8.93 0.90
Lateral --1.93 ± 7.40 --2.07 ± 8.98 0.95
Posterior --4.49 ± 10.16 --0.89 ± 12.05 0.26
Inferior --19.28 ± 7.42 --19.77 ± 5.35 0.80
Septal --27.05 ± 7.05 --26.87 ± 4.62 0.91
Anterior septal --23.46 ± 7.80 --23.14 ± 6.03 0.88
*STSR (ES)*
Anterior 42.87 ± 19.56 44.36 ± 16.27 0.78
Lateral 39.94 ± 17.33 41.01 ± 16.22 0.83
Posterior 36.04 ± 15.37 39.35 ± 19.90 0.52
Inferior 38.72 ± 17.77 48.70 ± 19.12 0.06
Septal 43.58 ± 19.31 48.87 ± 16.59 0.32
Anterior septal 45.29 ± 20.14 47.21 ± 16.18 0.72
*DTDR (ES) (mm)*
Anterior 6.70 ± 1.93 6.14 ± 2.10 0.34
Lateral 7.75 ± 1.74 6.98 ± 2.25 0.18
Posterior 6.16 ± 1.55 5.79 ± 2.04 0.48
Inferior 3.34 ± 2.02 3.88 ± 2.23 0.39
Septal 2.70 ± 1.64 3.146 ± 2.16 0.41
Anterior septal 4.22 ± 1.58 4.10 ± 1.78 0.81
*ROT (ES ) (°)*
Anterior --0.78 ± 3.16 1.33 ± 2.72 0.01
Lateral --3.60 ± 3.30 --1.17 ± 3.17 0.01
Posterior --7.04 ± 3.89 --5.48 ± 4.79 0.22
Inferior --8.76 ± 4.34 --7.75 ± 5.36 0.47
Septal --5.07 ± 3.49 --4.13 ± 4.01 0.38
Anterior septal --1.45 ± 3.06 0.13 ± 3.181 0.09
SLSC peak S: negative systolic peak circumferential strain, STSR (ES): end-systolic longitudinal strain, SLSC peak P: positive systolic peak circumferential strain, SLSC (ES): end-systolic circumferential strain, DTDR (ES): end-systolic radial displacement, ROT (ES): end-systolic rotation (°).
Longitudinal and transverse strain and strain rate {#s3d}
==================================================
Four chambers: longitudinal and transverse strain and strain rate measurements are shown in [Table 5.](#T5){ref-type="table"} No statistically significant differences were found between the two groups for the most negative peak longitudinal strain (SLSC peak G), negative systolic peak longitudinal strain (SLSC peak S), positive systolic peak longitudinal strain (SLSC peak P), the most negative peak transverse strain (STSR peak G), end-systolic longitudinal strain \[STSR (ES)\] and end-systolic longitudinal displacement \[DLDC (ES)\].
###### Longitudinal and transverse strain and strain rate values according to segment from the four-chamber view
*Strain according to segment* *Patients (n = 21)* Controls (n = 20)
------------------------------- --------------------- ------------------- -------
SLSC peak G (%)
Basal septal --21.07 ± 2.32 --21.46 ± 2.62 0.57
Mid-septal --20.52 ± 2.20 --20.67 ± 2.17 0.80
Apical septal --17.56 ± 3.72 --18.20 ± 3.70 0.54
Apical lateral --15.56 ± 4.59 --16.91 ± 3.75 0.26
Mid-lateral --14.42 ± 4.35 --15.89 ± 4.24 0.23
Basal lateral --14.10 ± 5.66 --14.07 ± 5.44 0.98
SLSC peak S (%)
Basal septal --20.74 ± 2.50 --21.26 ± 2.67 0.47
Mid-septal --20.40 ± 2.27 --20.56 ± 2.22 0.79
Apical septal --17.04 ± 3.72 --17.57 ± 3.93 0.62
Apical lateral --15.30 ± 4.60 --16.67 ± 3.93 0.26
Mid-lateral --13.96 ± 4.70 --15.58 ± 4.26 0.20
Basal lateral --12.79 ± 6.79 --12.42 ± 7.98 0.86
SLSC peak P (%)
Basal septal 0.29 ± 0.47 0.26 ± 0.41 0.83
Mid-septal 0.07 ± 0.29 0.03 ± 0.09 0.48
Apical septal 0.25 ± 1.29 0.08 ± 0.31 0.53
Apical lateral 0.23 ± 1.20 0.001 ± 0.03 0.35
Mid-lateral 0.38 ± 0.72 0.22 ± 0.55 0.38
Basal lateral 2.76 ± 5.00 3.11 ± 4.03 0.78
STSR peak P (%)
Basal septal 32.31 ± 18.40 37.90 ± 20.18 0.30
Mid-septal 26.00 ± 15.45 31.24 ± 14.79 0.22
Apical septal 21.90 ± 14.32 26.700 ± 11.13 0.19
Apical lateral 19.82 ± 14.28 25.82 ± 14.04 0.14
Mid-lateral 20.38 ± 14.76 27.33 ± 17.61 0.13
Basal lateral 22.64 ± 17.76 31.21 ± 21.17 0.012
STSR peak G (%)
Basal septal --20.53 ± 2.50 --21.12 ± 2.68 0.42
Mid-septal --20.32 ± 2.26 --20.51 ± 2.17 0.76
Apical septal --16.95 ± 3.81 --17.49 ± 3.86 0.61
Apical lateral --15.14 ± 4.72 --16.53 ± 3.90 0.26
Mid-lateral --13.66 ± 5.11 --15.44 ± 4.29 0.18
Basal lateral --11.58 ± 9.45 --12.64 ± 6.89 0.17
SLSC (ES) (%)
Basal septal 28.43 ± 20.12 35.12 ± 21.41 0.25
Mid-septal 23.91 ± 16.32 30.12 ± 15.08 0.16
Apical septal 20.64 ± 14.76 26.02 ± 11.08 0.15
Apical lateral 18.58 ± 14.74 24.56 ± 14.35 0.15
Mid-lateral 17.53 ± 16.27 24.30 ± 18.47 0.17
Basal lateral 16.90 ± 21.08 24.79 ± 22.54 0.69
STSR (ES) (%)
Basal septal 12.14 ± 2.18 12.18 ± 2.69 0.95
Mid-septa 6.64 ± 1.52 6.73 ± 2.23 0.87
Apical septal 1.60 ± 0.74 1.81 ± 1.25 0.45
Apical lateral 2.88 ± 1.32 2.78 ± 0.96 0.77
Basal lateral 11.06 ± 3.50 11.33 ± 2.27 0.66
DLDC (ES) (mm)
Basal septal 1.85 ± 1.74 3.16 ± 1.89 0.014
Mid-septal 1.97 ± 1.34 2.81 ± 1.85 0.06
Apical septal 1.55 ± 1.06 2.01 ± 1.15 0.14
Apical lateral 1.89 ± 0.91 2.05 ± 0.59 0.46
Mid-lateral 3.66 ± 1.26 3.52 ± 1.073 0.66
Basal lateral 5.97 ± 1.77 5.51 ± 1.64 0.35
SLSC peak G: the most negative peak longitudinal strain, SLSC peak S: negative systolic peak longitudinal strain, SLSC peak P: positive systolic peak longitudinal strain, SLSC (ES): end-systolic longitudinal strain, STSR peak P: positive peak transverse strain, STSR peak G: the most negative peak transverse strain, STSR (ES): end-systolic longitudinal strain, DLDC (ES): end-systolic longitudinal displacement.
End-systolic longitudinal strain \[SLSC (ES)\] and positive peak transverse strain (STSR peak P) were statistically significantly lower in the patient group (p \< 0.05). Segmental analysis showed statistically significantly lower levels of end-systolic longitudinal strain \[STSR (ES)\] of the basal lateral (p \< 0.05), and statistically significantly lower levels of end-systolic longitudinal strain \[SLSC (ES)\] of the basal septal segment (p \< 0.05) in the patient group. Longitudinal and transverse strain and strain rate measurements from four and two chambers and the apical longaxis views are shown in [Table 6.](#T6){ref-type="table"}
###### Longitudinal and transverse strain and strain rate values according to segment from the four-chamber view
*Strain according to segment* *Patients (n = 21)* *Controls (n = 20)*
------------------------------- --------------------- --------------------- -------
Four-chamber view
SLSC peak G (%) --17.21 ± 4.82 --17.87 ± 4.55 0.22
SLSC peak S (%) --16.70 ± 5.27 --17.34 ± 5.39 0.29
SLSC peak P (%) 0.66 ± 2.36 0.62 ± 1.99 0.84
STSR peak P (%) 23.84 ± 16.25 30.03 ± 17.05 0.001
STSR peak G (%) --16.36 ± 6.11 --17.29 ± 5.08 0.15
SLSC (ES) (%) 21.00 ± 17.61 27.49 ± 17.75 0.002
STSR (ES) (%) 6.93 ± 4.41 7.05 ± 4.32 0.80
DLDC (ES) (mm) 2.819 ± 2.08 3.180 ± 1.84 0.11
Two-chamber view --
SLSC peak G (%) 18.73 ± 5.44 --17.56 ± 7.24 0.13
SLSC peak S (%) --18.46 ± 5.48 --17.34 ± 7.54 0.16
SLSC peak P (%) 0.38 ± 0.87 0.72 ± 2.03 0.07
STSR peak P (%) 25.55 ± 18.21 31.68 ± 17.63 0.005
STSR peak G (%) --18.32 ± 5.42 --18.32 ± 5.42 0.16
SLSC (ES) (%) 20.46 ± 19.14 29.17 ± 18.67 0.001
STSR (ES) (%) 7.25 ± 5.11 6.72 ± 5.25 0.40
DLDC (ES) (mm) 3.44 ± 2.25 3.35 ± 2.23 0.73
Apical long-axis view (APLAX)
SLSC peak G (%) --17.73 ± 5.92 --17.18 ± 5.36 0.36
SLSC peak S (%) --17.38 ± 5.84 --16.97 ± 5.43 0.49
SLSC peak P (%) 0.62 ± 3.76 0.54 ± 1.18 0.80
STSR peak P (%) 24.15 ± 1.92 26.40 ± 20.12 0.55
STSR peak G (%) --17.21 ± 6.08 --16.84 ± 5.45 0.55
SLSC (ES) (%) 20.02 ± 22.72 23.04 ± 21.12 0.20
STSR (ES) (%) 7.35 ± 5.11 6.85 ± 4.52 0.33
DLDC (ES) (mm) 2.71 ± 2.10 2.68 ± 1.69 0.89
SLSC peak G: the most negative peak longitudinal strain, SLSC peak S: negative systolic peak longitudinal strain, SLSC peak P: positive systolic peak longitudinal strain, SLSC (ES): end-systolic longitudinal strain, STSR peak P: positive peak transverse strain, STSR peak G: the most negative peak transvers strain, STSR (ES): end-systolic longitudinal strain, DLDC (ES): end-systolic longitudinal displacement (mm).
Two chambers: there were no statistically significant differences found between the two groups for the most negative peak longitudinal strain (SLSC peak G), negative systolic peak longitudinal strain (SLSC peak S), positive systolic peak longitudinal strain (SLSC peak P), the most negative peak transverse strain (STSR peak G), end-systolic longitudinal strain \[STSR (ES)\] and end-systolic longitudinal displacement \[DLDC (ES)\].
End-systolic longitudinal strain \[SLSC (ES)\] and positive peak transverse strain (STSR peak P) were statistically significantly lower in the patient group (p \< 0.05). Segmental analysis showed statistically significantly lower values of end-systolic longitudinal strain \[SLSC (ES)\] of the mid-anterior and basal anterior segments (p \< 0.05) in the patient group. The most negative peak longitudinal strain (SLSC peak S) value was --18.00 ± 3.33 in the mid-anterior segment of the patient group and --14.9723 ± 6.23886 in the mid-anterior segment of the control group (p \< 0.05) ([Tables 7](#T7){ref-type="table"}[,8](#T8){ref-type="table"}).
###### Longitudinal and transverse strain and strain rate values according to segment from the apical long-axis view
*Strain according to segment* *Patients (n = 21)* Controls (n = 20)
------------------------------- --------------------- ------------------- --------------
SLSC peak G (%)
Basal inferior --21.80 ± 4.37 --21.14 ± 6.86 0.70
Mid-inferior --21.24 ± 3.56 --20.69 ± 6.95 0.73
Apical inferior --17.40 ± 3.73 --17.65 ± 6.61 0.87
Apical anterior --11.41 ± 4.04 --12.17 ± 5.90 0.62
Mid-anterior --18.00 ± 3.33 --14.97 ± 6.23 0.047
Basal anterior --22.22 ± 5.04 --18.75 ± 7.16 0.06
SLSC peak S (%)
Basal inferior --21.75 ± 0.35 --21.20 ± 6.26 0.73
Mid-inferior --21.18 ± 3.61 --20.62 ± 6.99 0.73
Apical inferior --16.97 ± 3.72 --17.34 ± 7.44 0.83
Apical anterior --10.99 ± 3.97 --11.75 ± 6.44 0.63
Mid-anterior --17.72 ± 3.30 --17.72 ± 3.30 0.06
Basal anterior --21.82 ± 4.94 --18.35 ± 7.63 0.07
SLSC peak P (%)
Basal inferior 0.33 ± 0.49 0.62 ± 1.034 0.23
Mid-inferior 0.06 ± 0.18 0.52 ± 1.98 0.27
Apical inferior 0.46 ± 0.66 1.03 ± 3.14 0.39
Apical anterior 0.65 ±1.11 1.01 ± 2.53 0.55
Mid-anterior 0.20 ± 0.52 0.55 ± 1.67 0.35
Basal anterior 0.61 ± 1.50 0.63 ± 1.18 0.95
STSR peak P (%)
Basal inferior 30.87 ± 12.70 30.60 ± 11.08 0.93
Mid-inferior 24.16 ± 8.65 26.84 ± 9.22 26.84 ± 9.22
Apical inferior 20.89 ± 7.31 26.22 ± 11.44 0.06
Apical anterior 21.55 ± 13.51 29.40 ± 16.40 0.09
Mid-anterior 25.47 ± 23.34 35.20 ± 21.54 0.15
Basal anterior 30.20 ± 30.81 41.83 ± 26.16 0.180
STSR peak G (%)
Basal inferior --21.55 ± 4.19 --20.82 ± 6.76 0.66
Mid-inferior --21.09 ± 3.52 --20.40 ± 7.23 0.68
Apical inferior --16.92 ± 3.72 --17.32 ± 7.19 0.81
Apical anterior --10.92 ± 3.95 --11.73 ± 6.37 0.61
Mid-anterior --17.53 ± 3.26 --14.735 ± 6.58 0.07
Basal anterior --21.61 ± 5.00 --18.36 ± 7.37 0.09
SLSC (ES) (%)
Basal inferior 24.62 ± 16.37 25.58 ± 13.77 0.83
Mid-inferior 21.18 ± 10.41 24.35 ± 11.35 0.33
Apical inferior 19.02 ± 8.22 24.90 ± 12.82 0.07
Apical anterior 18.972 ± 13.33 28.12 ± 17.37 0.05
Mid-anterior 19.41 ± 23.34 33.33 ± 22.37 0.047
Basal anterior 19.51 ± 32.88 38.74 ± 26.77 0.038
STSR (ES) (%)
Basal inferior 13.93 ± 3.22 13.21 ± 4.30 0.53
Mid-inferior 7.70 ± 1.99 7.55 ± 2.58 0.82
Apical inferior 2.06 ± 0.97 2.14 ± 1.27 0.811
Apical anterior 1.67 ± 1.15 1.67 ± 1.83 0.999
Mid-anterior 5.69 ± 1.81 5.24 ± 3.03 0.55
Basal anterior 12.19 ± 2.72 10.50 ± 4.68 0.14
DLDC (ES) (mm)
Basal inferior 4.40 ± 1.88 4.46 ± 2.09 0.91
Mid-inferior 4.07 ± 1.71 3.89 ± 1.83 0.72
Apical inferior 2.49 ± 1.42 2.54 ± 1.30 0.90
Apical anterior 1.42 ± 0.94 1.64 ± 1.04 0.45
Mid-anterior 2.58 ± 1.57 2.5523 ± 1.75 0.94
Basal anterior 5.59 ± 2.74 5.00 ± 2.96 0.48
SLSC peak G: the most negative peak longitudinal strain, SLSC peak S: negative systolic peak longitudinal strain, SLSC peak P: positive systolic peak longitudinal strain, SLSC (ES): end-systolic longitudinal strain, STSR peak P: positive peak transverse strain, STSR peak G: the most negative peak transverse strain, STSR (ES): end-systolic longitudinal strain, DLDC (ES): end-systolic longitudinal displacement.
###### Longitudinal and transverse strain and strain rate values according to segment from the apical long-axis view
*Strain according to segment* *Patients (n = 21)* *Controls (n = 20)*
------------------------------- --------------------- --------------------- --------
SLSCC peak G (%)
Basal anterior septal --19.99 ± 2.75 --18.63 ± 5.80 0.24
0.24 --16.60 ± 11.17 --15.34 ± 5.24 0.58
Mid-posterior --18.27 ± 3.83 --17.08 ± 3.20 0.20
Apical posterior --17.94 ± 4.47 --17.73 ± 4.48 0.86
Apical anterior septal --15.33 ± 5.55 --16.56 ± 6.86 0.46
Mid-anterior septal --18.01 ± 2.58 --17.72 ± 5.69 0.80
SLSC peak S (%)
Basal anterior septal --19.68 ± 3.06 --18.45 ± 5.81 0.31
Basal posterior --16.29 ± 10.74 --15.06 ± 5.42 0.59
Mid-posterior --17.98 ± 4.10 --17.018 ± 3.14 0.32
Apical posterior --17.39 ± 4.56 --17.44 ± 4.80 0.96
Apical anterior septal --14.91 ± 5.32 --16.21 ± 6.88 0.43
Mid-anterior septal --17.82 ± 2.71 --17.64 ± 5.65 0.87
SLSC peak P (%)
Basal anterior septal 0.25 ± 0.81 0.125 ± 0.28 0.42
Basal posterior 2.88 ± 8.90 2.07 ± 2.08 0.64
Mid-posterior 0.16 ± 0.49 0.43 ± 0.69 0.08
Apical posterior 0.15 ± 0.29 0.17 ± 0.42 0.84
Apical anterior septal 0.22 ± 0.36 0.30 ± 0.68 0.61
Mid-anterior septal 0.02 ± 0.06 0.14 ± 0.35 0.07
STSR peak P (%)
Basal anterior septal 21.30 ± 22.17 29.87 ± 24.35 0.16
Basal posterior 35.91 ± 26.93 34.86 ± 25.61 0.88
Mid-posterior 27.98 ± 23.49 27.18 ± 18.86 0.88
Apical posterior 21.76 ± 18.45 21.56 ± 14.17 0.96
Apical anterior septal 19.14 ± 16.83 20.87 ± 13.64 0.67
Mid-anterior septal 18.56 ± 18.17 24.07 ± 19.07 0.26
STSR peak G (%)
Basal anterior septal --19.54 ± 3.04 --18.38 ± 5.85 0.39
Basal posterior --16.04 ± 11.32 --14.81 ± 5.47 0.60
Mid-posterior --17.89 ± 4.14 --16.87 ± 3.17 0.29
Apical posterior --17.19 ± 4.63 --17.30 ± 4.75 0.92
Apical anterior septal --14.66 ± 5.51 --16.09 ± 6.82 0.39
Mid-anterior septal --17.68 ± 2.84 --17.59 ± 5.66 0.93
SLSC (ES) (%)
Basal anterior septal 14.59 ± 24.85 24.53 ± 25.34 0.13
Basal posterior 28.05 ± 27.70 28.55 ± 28.82 0.94
Mid-posterior 24.35 ± 23.59 23.42 ± 21.06 0.87
Apical posterior 20.06 ± 19.09 20.12 ± 14.95 0.99
Apical anterior septal 17.58 ± 17.78 19.77 ± 14.08 0.61
Mid-anterior septal 15.53 ± 20.06 21.84 ± 19.12 0.22
STSR (ES) (%)
Basal anterior septal 10.95 ± 3.58 11.50 ± 3.49 0.55
Basal posterior 13.75 ± 3.59 11.37 ± 2.26 0.004
Mid-posterior 8.81 ± 2.56 7.20 ± 1.59 0.0006
Apical posterior 3.23 ± 1.26 2.27 ± 1.216 0.005
Apical anterior septal 1.28 ± 1.61 2.21 ± 2.46 0.10
Mid-anterior septal 5.55 ± 2.96 6.56 ± 3.34 0.23
DLDC (ES) (mm)
Basal anterior septal 1.77 ± 2.00 2.62 ± 2.11 0.11
Basal posterior 4.91 ± 2.08 3.57 ± 1.57 0.008
Mid-posterior 3.97 ± 1.59 2.95 ± 1.37 0.012
Apical posterior 2.46 ± 1.34 2.24 ± 1.31 0.53
Apical anterior septal 1.56 ± 1.37 2.17 ± 1.55 0.12
Mid-anterior septal 1.55 ± 1.50 2.54 ± 1.81 0.027
SLSC peak G: the most negative peak longitudinal strain, SLSC peak S: negative systolic peak longitudinal strain, SLSC peak P: positive systolic peak longitudinal strain, SLSC (ES): end-systolic longitudinal strain, STSR peak P: positive peak transverse strain, STSR peak G: the most negative peak transverse strain, STSR (ES): end-systolic longitudinal strain, DLDC (ES): end-systolic longitudinal displacement.
Apical long-axis (APLAX): there were no statistically significant differences found between the two groups for the most negative peak longitudinal strain (SLSC peak G), negative systolic peak longitudinal strain (SLSC peak S), positive systolic peak longitudinal strain (SLSC peak P), the most negative peak transverse strain (STSR peak G), end-systolic longitudinal strain \[STSR (ES)\], end-systolic longitudinal displacement \[DLDC(ES)\] end-systolic longitudinal strain \[SLSC (ES)\] and positive peak transverse strain (STSR peak P).
Segmental analysis showed that end-systolic longitudinal strain \[STSR (ES)\] measurements of the basal posterior and mid-posterior segments were statistically significantly lower in the patient group (p \< 0.05). End-systolic longitudinal displacement \[DLDC (ES)\] of the basal posterior, mid-posterior and mid-anterior septal segments were statistically significantly lower in the patient group (p \< 0.05).
Discussion {#s4}
==========
Wilson's disease is an autosomal recessive inherited disease, characterised by excessive copper storage in the body, especially the liver and brain, and also in the heart tissue due to reduced biliary copper excretion secondary to loss of the mutation for copper-transporting ATPase (ATP7B). Wilson's disease, characterised by excessive copper deposition in the body, primarily in the liver and brain, results from an inability of the liver to excrete copper in the bile.[@R01][@R02]
Cardiac involvement of Wilson's disease has not been sufficiently investigated. Electrocardiographic abnormalities, cardiac arrhythmias, cardiomyopathy, autonomic dysfunction and sudden cardiac death are rare complications but may be seen in children with Wilson's disease due to copper accumulation in the heart tissue.[@R03][@R05]
Arat et al. showed increased P-wave dispersion in adults with cardiologically asymptomatic Wilson's disease.[@R06] In another study on adults, electrocardiographic abnormalities, including left ventricular hypertrophy, early repolarisation, biventricular hypertrophy, premature atrial or ventricular contractions, atrial fibrillation, sino-atrial block and Mobitz type 1 atrioventricular block were detected in 34% of the patients.[@R06] Electrocardiographic abnormalities are not uncommon in Wilson's disease and are presumably related to an underlying cardiomyopathy due to deposition of copper in the heart.[@R05]
We previously evaluated 22 children with Wilson's disease with 24-hour ECG monitoring and our study showed that one patient had first-degree atrioventricular block, one had frequent sinus exit block, and four had rare ventricular ectopic beat.[@R08] In our study, all the patients were assessed with ECG before echocardiographic evaluation. Only one patient had Wolf--Parkinson--White pattern, but there were no arrhythmias or ECG abnormalities in any of the patients. We assumed that ECG abnormalities develop over a long period or in untreated patients.
The major pathological findings of the myocardium in Wilson's disease included the presence of interstitial and myocardial fibrosis, focal myocarditis and cardiac hypertrophy, conduction tissue degeneration, and early atherosclerosis due to the toxic effect of copper, leading to mitochondrial injury and lipid peroxidation, which is caused by reactive free oxygen radicals. Hlubocka et al. suggested that cardiac changes seen in Wilson's disease are not only related to copper accumulation but also to free oxygen radicals.[@R09] Therefore echocardiography is an important tool to assess asymptomatic Wilson's patients. In this study, left ventricular wall thickness was increased and left ventricular end-diastolic diameter was decreased in patients with Wilson's disease and the differences were statistically comparable to the results of the control group. Measurement of local and global myocardial function using non-invasive methods is a major aim in clinical cardiology.[@R10] Cardiac systolic function may deteriorate in prolonged disease or in untreated patients.
In our study, systolic function of the left ventricle, wall thickness, left ventricular diameters, volumes, and cardiac index measurements were within normal limits. There were no statistically significant differences between the Wilson's disease patients and the control group for left ventricular systolic function, wall thickness, diameter, volume and cardiac index (p \< 0.05). Our patients were relatively young and the mean age at diagnosis was 9 ± 2.24 years, so their time from diagnosis was relatively short. Cardiac systolic function may deteriorate in the long term or due to serious disease.
Tissue Doppler echocardiography, strain and strain rate echocardiography are relatively novel echocardiographic techniques and important tools to assess asymptomatic patients.[@R11][@R14] Tissue Doppler imaging, which has recently allowed a detailed examination of cardiac function, is widely used to evaluate children with various conditions.[@R14][@R17] Our previous study showed early diastolic dysfunction in patients with Wilson's disease using tissue Doppler echocardiography. Despite its reliability, tissue Doppler echocardiography cannot show regional deformation and regional deformation abnormalities.
Difficulties with angle dependency of tissue Doppler imaging, the effects of preload, and the translational motion of the heart were overcome by strain and strain rate echocardiography, which were then adopted as new models in the assessment of myocardial performance and local deformation properties.[@R13][@R15] Strain imaging, based on speckle tracking, in particular, enabled assessment of myocardial motion and deformation irrespective of angle and geometry, allowing an improved examination of the myocardial mechanics.
Our hospital is a liver transplantation centre, therefore, we aimed to assess a new group of children with Wilson's disease using 2D strain and strain rate echocardiography. Strain and strain rate echocardiography are superior to tissue Doppler echocardiography in the evaluation of regional myocardial function because they are not affected by the translation and stretching of neighbouring myocardial segments.[@R16] 2D strain and strain rate echocardiography also can assess different clinical conditions, such as hypertension, obesity, post exercise, Marfan syndrome, healthy children and infants.[@R15][@R18]
To our knowledge, the literature presents no studies showing early detection of subclinical cardiac dysfunction in children with Wilson's disease using 2D strain and strain rate echocardiography. Our study showed that among the global strain and strain rate parameters, Wilson's disease patients had lower peak A longitudinal velocity of the left basal point (VAbasL) and peak E longitudinal velocity of the left basal (VEbasR) point than those of the control group (p \< 0.05). The patients also had statistically significantly higher global peak A longitudinal/circumferential strain rate (GSRa) (p \< 0.05).
Longitudinal strain and strain rate from the four-chamber view showed that end-systolic longitudinal strain \[SLSC (ES)\] and positive peak transverse strain (STSR peak P) were statistically significantly lower in the patient group (p \< 0.05). Radial strain and strain rate analysis showed that end-systolic rotation \[ROT (ES)\] was statistically significantly lower in the patient group (p \< 0.05). Longitudinal strain and strain rate from the two-chamber view showed that end-systolic longitudinal strain \[SLSC (ES)\] and positive peak transverse strain (STSR peak P) were statistically significantly lower in the patient group (p \< 0.05).
Segmental analysis also showed that rotational strain measurement of the anterior segment of the patient group, end-systolic longitudinal strain \[STSR (ES)\] of the basal lateral (p \< 0.05), mid-anterior and basal anterior segments, and end-systolic longitudinal strain \[SLSC (ES)\] of the basal septal and lateral segments, and the most negative peak longitudinal strain (SLSC peak S) of the mid-anterior segment were statistically significant lower in the patient group (p \< 0.05). Our study showed that in the early stages of Wilson's disease, diastolic dysfunction due to copper accumulation may be heterogenous but in the long term, the heart could be affected globally. Early diastolic dysfunction can be detected using strain and strain rate echocardiography.
Conclusion {#s5}
==========
Cardiac arrhythmias, cardiomyopathy and sudden cardiac death are rare complications but may be seen in children with Wilson's disease due to copper accumulation in the heart tissue. Strain and strain rate echocardiography is a relatively new and useful echocardiographic technique to evaluate cardiac function and cardiac deformation abnormalities. In our study, despite normal systolic function, the patients with Wilson's disease showed diastolic dysfunction and regional deformation abnormalities, especially rotational strain and strain rate abnormalities. We suggest that diastolic dysfunction, and rotational strain and strain rate abnormalities in Wilson's disease may be progressive in untreated patients.
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Chiral NMR discrimination of the diastereoisomeric salts of the H3-antagonist 2-[3-(1H-imidazol-4-ylmethyl)piperidin-1-yl]-1H-benzimidazole.
Diastereomeric salts with optically pure (S)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetic acid (MTPA) were used to discriminate the enantiomers of the chiral H(3)-antagonist 2-[3-(1H-imidazol-4-ylmethyl)piperidin-1-yl]-1H-benzimidazole. Chemical-shift differences (Delta delta) in NMR spectra strongly depend on solvent and stoichiometric ratio. The better observable differentiation occurred for the proton at the 2-position of the imidazole ring.
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Deportes Ovalle
Club Deportes Ovalle is a Chilean football club who currently play in the fourth level of Chilean football, the Tercera División. The club's stadium is the Estadio Municipal de Ovalle.
Their main rivals are Deportes La Serena and Coquimbo Unido.
Honours
Domestic Honours
'Copa ChileSemi-finalists (1): 2008–09
Tercera Division
'''Winners (1): 1993
Players
Current Roster 2015–16
External links
Official Site (in Spanish)
Ovalle
Category:Association football clubs established in 1963
Category:1963 establishments in Chile
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Q:
What is the meaning of 捅破 the serial of 寒夜? E.g. 被我们的学生捅破
The following text is taken from the serial of 寒夜:
一直到有一天 一个偶然的机会
我的心事 或者说是我们的心事
被我们的学生捅破
感情是不能被捅破的
一旦捅破 就如同大坝破堤
汹涌而出
He's talking about his love for the heroine of the series, then explains how the ice was broken.
捅破 is the problem word here. None of the dictionary definitions seem to fit.
Actually, the following line referring to dams and dykes is also a bit cryptic. I thought a dam and a dyke are pretty similar but that doesn't fit if you want to understand the text.
By the way, I'm in the process of transcribing both 新结婚时代 and 寒夜 with the aim of learning all the vocab and using the audio/video to get a feel for it all in context.
Are the transcribed subtitles of any of these two already available somewhere?
A:
捅破 comes from 捅破窗户纸 (poke the window paper). Try googling "捅破窗户纸".
In the past, Chinese used paper instead of glass on their windows until the technology of making glass is imported to China. Window paper can stop the wind, but is much more fragile than glass and can be easily poked. Window paper is not transparent. If you poke a hole on it, you can see the other side.
The two people loved each other, but they are too shy to tell each other. That's like there is a thin piece of paper hiding them from each other. Once it is poked, they can see each other. That is, they know how the other person feels.
捅破窗户纸 is also similar to "break the ice" in English.
A:
Think about that, there's a dam preventing they make a further step for their feelings/relationship. something or someone pokes a little hole on the dam, then the water just flood out...
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Background: I spent my sabbatical from Creighton University working at
the Large Lakes Observatory (LLO), part of the University of Minnesota,
Duluth. Most of the sabbatical (January - August 2010) was spent
in the laboratory of Dr. Liz Minor, a chemistry professor at UMD.
I studied two extraction disks used to collect and concentrate
dissolved
organic matter from natural waters. During the research cruise
pictured below, I was able to use these two different disks at the
various mooring stations that are maintained and operated by
UMD-LLO. These pictures capture some of the activities that took
place during the cruise.
The Blue
Heron is the 86-ft research vessel operated for the Large Lakes
Observatory, University of Minnesota - Duluth. The ship has a
5-person crew and can accommodate six scientists. It can go 20
days or 3000 miles between port calls. Inside the ship on the
main deck level (just forward of the open rear deck in the picture) is
the wet lab where my lab station was located. Forward of
that is the galley and then the bunk area. The upper deck
contained the pilot house and a lower deck features a dry lab, computer
work station for the scientists, and the engine room. Photo by
Bruce
Groehler, UMD photographer.
Standing in front of the Blue Heron at dockside. We had a day to
load
our equipment and set up our lab areas for the cruise.
Lake Superior off the bow of the Blue Heron. The lake has many
moods and personalities, some of which make the ship seem even smaller.
Under all this water lie the remains of nearly 400 commercial ships,
all much larger than the Blue Heron, that have sunk in the past 140
years.
Overview
of
my
project:
1. Water samples were collected from
specific locations and depths.
2. The samples were filtered through a 0.70 um filter to remove
particulate organic matter, leaving dissolved organic matter.
3. This filtered water was then extracted with the specialty disks.
4. I then recorded the UV-vis of the resulting filtrate (on board) and
later, back in the lab, of the material retained on the disks
(retentate).
The ship stopped at a series of seven existing moorings: Here, the
water sampler is being landed on deck after
collecting water at a specified depth.
Water sampler being emptied into various sample containers. Under
the cylinders, note the electronic equipment that detected temperature,
conductivity and depth. Pictured at left are Lindsey
and Annie (from
Virginia Commonwealth University) and Prosper, a graduate
student at UM-D, LLO.
For several experiments, water was filtered through a 0.7 um filter,
our working cut-off between dissolved and particulate
substances. In the picture above, water is being transferred to a soda
canister where is then forced by compressed nitrogen through the glass
fiber filter. The water I studied was filtered in this
way
because I was interested in measuring dissolved organic matter.
Pictured is Hongyu, a graduate student (L) and Dr. Liz Minor, of the
Large Lakes Observatory (LLO) and UM-D Chemistry. My sabbatical
was spent working in her lab at LLO.
Here Hongyu is filtering water late at night. Filtering had to be
done as soon as possible after collection. The air temperature was
about 38 oF (3.5 oC) at night in the middle of the lake -- the same as
the lake! Note
that the life jackets had refective strips so it would be easier to
locate a person overboard in the dark.
Me at my lab station on the Blue Heron with two filter rigs. I
had a porthole to the right in the photo so I had a nice view of the
lake
at all times. The lab was cool because the large door to the deck
was always open. The
purple gloves are intended to keep skin oil away from the water
samples. Lake Superior is an extremely clean lake and oils from
skin would contribute to the amount and type of organic materials
measured.
My cool window in the lab. The gloves didn't make using the laptop
mouse any easier! (Note: the computer was duct-taped to the benchtop.)
Filter rig: In my experiments, I filtered 5 L samples of lake water
through expensive extraction disks manufactured by 3M. The
extraction disk at left looks discolored because it contains all of the
dissolved organic matter that was trapped by the disk.
The label: The "3" refers to this being the third research cruise Dr.
Minor's group has taken to these locations. The "NM" refers to
"Northern Mooring" (in Ontario waters of Lake Superior). The "XC"
refers to the 3M extraction disk I was using, and the hatch marks was
my way of keeping track of how many liters of water I had passed
through the filter rig (I had another way as well). In the picture at
right, the same disk is shown
after the trapped organics were extracted with methanol. This
leaves the disk looking much lighter in color. The extracted
organic materials were analyzed.
Here I am at the UV-vis spectrophotometer that we took with us.
Note how the instrument is tied to the table with cording to prevent it
from sliding off the table in high seas. Note also how I held the
sample bottles upright behind the cord. This prevented tipping,
falling, and rolling. For most of this trip, the seas were
reasonable, although I quickly learned how to use my hip along with my
legs, spread apart, to make a tripod for stability, especially useful
when pouring liquids.
Old Glory on Memorial Day. At left, the water sampler and at
right, the core
sampler (samples the lake floor)
Other
experiments. In the following pictures, some of the other
sampling techniques used
by the other scientists are shown:
Here the core sampler (returns cored samples of the lake floor) is
being lowered into the lake.
Here the core sampler is returning from a visit to the bottom of the
lake
where it collected samples of the lake bottom. The water is so
clear
that one can see the sampler through 30 feet (10 m) of water.
Mud from the core sampler is being removed from the core tubes.
Note the sampler in the background.
This is a sediment trap used as part of a long-term experiment
(months). As sediment slowly sifts to the bottom of the lake, it
is caught in the yellow cone and collected in one of the bottles at the
bottom. Every two weeks, for example, the bottle carousel
advances to a new bottle. The sediment trap is set on one cruise and
collected on another. On this particular cruise, the sediment
trap was
recovered from a mooring damaged during the winter of 2009-10.
A plankton net.
Prosper using a filter rig. Filter rigs are used for a variety of
projects.
The ship and crew.
This is Captain Mike in his pilot house explaining something about the
ship's
capabilities. We were welcomed to visit the pilot house and
Captain Mike was always interested in our projects and how they were
going.
This is a view from on the back deck, looking forward toward the lab
area. Note several differences between this research cruise and
a typical Caribbean cruise. (I never found the pool deck, ballroom, or
the shuffleboard courts, however, the dining was exceptional!)
Just like at home, everybody gathers around the kitchen table (ooops,
galley table)
Kathy, one of the four crew members, served amazingly satisfying and
delicious meals! She and the other crew members had a delightful
sense of humor and were wonderful hosts. (Next time I will do
something with my hair before pictures!)
Here are two bunks. Each had curtains for privacy. My bunk
was the top one and I tried hard not to step on John in the lower bunk
getting in and out of the bunk.
This is a rare photo where some of the crew seem to be relaxing.
Standing is Captain Mike (left), and Justin, the ship's technician
(from the LLO) and Rual
(sitting). The nice weather must have brought them to the
deck.
Flying the colors.
Here I am on deck on a particularly nice morning.
Sonar tracks the lake bottom.
No cruise is complete without a visit to the engine room. Note
the ear protection. Rual was the guide and the tour was
conducted entirely with gestures. The
engine was 775 horsepower, got 2 gallons to the mile and cruised at 9
miles per hour.
The research group.
Our research group on deck. From left: Me, Annie (a collaborator
from Virginia Commonwealth University), Hongyu, Liz and Prosper.
One other scientist, Lindsey, is not pictured here; with sampling at
anytime during 24
hours, it was hard to find everyone awake at the same time. In
this picture I am just getting up (note coffee), while Prosper and
Hungyu are ready for bed after being up all night.
Lake Superior and its incredible beauty.
Out my lab porthole.
Gray seas with a storm approaching.
Sunset over Michigan's Keweenaw Peninsula (known to the locals as the
U-P where the residents call themselves "Yoopers").
Almost home.
At the end of the cruise: Heading into Duluth's shipping canal and
under the Lift Bridge.
Acknowledgments.
My sabbatical has been a great
experience, with the highlight being the research cruise on Lake
Superior. I wish to express my gratitude:
to the Creighton University College of
Arts and Sciences for providing sabbaticals.
to Dr. Liz Minor for hosting me as a visiting professor in her research
lab and for providing an interesting project for me.
to the students in Dr. Minor's group, specifically Brittany, Meg,
Prosper, Hongyu, and Melissa (from Dr. Werne's group) for teaching me
many of the techniques I used.
to the faculty and staff of the Large Lakes Observatory of the
University of Minnesots, Duluth for making me feel most welcomed.
I especially enjoyed lunches with them and the graduate students.
to Dr Josef Werne, whom I've never met, for allowing me to use his
office while he was on sabbatical in Australia.
to the crew of the Blue Heron, Mike, John, Kathy, and Rual, for making
my cruise experience the highlight of my sabbatical.
|
/* ------------------------------------------------------------------
* Copyright (C) 1998-2009 PacketVideo
*
* Licensed under the Apache License, Version 2.0 (the "License");
* you may not use this file except in compliance with the License.
* You may obtain a copy of the License at
*
* http://www.apache.org/licenses/LICENSE-2.0
*
* Unless required by applicable law or agreed to in writing, software
* distributed under the License is distributed on an "AS IS" BASIS,
* WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either
* express or implied.
* See the License for the specific language governing permissions
* and limitations under the License.
* -------------------------------------------------------------------
*/
#ifndef OSCL_CONFIGFILE_LIST_H_INCLUDED
#define OSCL_CONFIGFILE_LIST_H_INCLUDED
#ifndef OSCL_MEM_H_INCLUDED
#include "oscl_mem.h"
#endif
#ifndef OSCL_STRING_CONTAINERS_H_INCLUDED
#include "oscl_string_containers.h"
#endif
#ifndef OSCL_VECTOR_H_INCLUDED
#include "oscl_vector.h"
#endif
#ifndef OSCL_LIBRARY_COMMON_H_INCLUDED
#include "oscl_library_common.h"
#endif
struct OsclUuid;
class PVLogger;
/**
* OsclConfigFileList contains the list of .cfg files found from a given directory
**/
class OsclConfigFileList
{
public:
enum SortType
{
ESortByName = 0,
ENoSort
};
/**
* Default object Constructor function
**/
OSCL_IMPORT_REF OsclConfigFileList();
/**
* Object destructor function
**/
OSCL_IMPORT_REF ~OsclConfigFileList();
/**
* Populate the list for the given directory.
*
* @param aConfigFileDir - directory path of the .cfg files; path can trail with or without delimiter (path prefix, e.g. '\')
* @param aSortType - Define type type of sort, if any, for the config file list. Default is not sorted
*
* @returns OsclLibStatus about whether the config file vector got populated or not
**/
OSCL_IMPORT_REF OsclLibStatus Populate(const OSCL_String& aConfigFileDir,
OsclConfigFileList::SortType aSortType = ENoSort);
/**
* Get the number of config file in the list.
*
* @returns Number of config file in list.
*/
OSCL_IMPORT_REF uint32 Size();
/**
* Returns the n'th element.
* @param n element position to return
* @returns the reference to the config file name stored in the iCfgList vector
*/
OSCL_IMPORT_REF const OSCL_String& GetConfigfileAt(uint32 n);
private:
Oscl_Vector<OSCL_HeapString<OsclMemAllocator>, OsclMemAllocator> iCfgList;
PVLogger* ipLogger;
#if OSCL_LIBRARY_PERF_LOGGING
PVLogger* iDiagnosticsLogger;
uint32 iCfgFileNum;
#endif
/**
* Sort iCfgList by name
*/
void Sort(void);
};
/**
* OsclLibraryUtil is mainly used by test app to setup library search path
**/
class OsclLibraryUtil
{
public:
/**
* static api sets, appends, or unset aDir to system PATH environment as the lib search folder
*
* @param aEnvName - environment name to be set or unset
* @param aEnvValue - environment value of the aEnvName to be set or unset
*
* @returns OsclLibStatus
**/
OSCL_IMPORT_REF static OsclLibStatus SetupLibraryEnv(const char* aEnvName, const char* aEnvValue);
};
#endif //OSCL_LIBRARY_LIST_H_INCLUDED
|
Osaka Travel Guide
Blithe and edgy Osaka is the hyperactive younger brother of Tokyo. The heart of the Kansai region is a busy metropolis of close to 3 million people and a significant, influential player in the global economy. The industrial and business side of Osaka, however, is unlikely to interest casual tourists. What will undoubtedly entice and cajole is a phenomenal range of bustling commercial districts, tantalizing pedestrian restaurant rows, raucous nightlife, sacred shrines, temples and museums. The drum beat in Osaka is fast and feverish but duly enchants visitors anxious to commune with a dynamic urban swath of Honshu island outside of Greater Tokyo.
The food culture of Osaka gets a lot of attention and rightfully so. The de facto kitchen of Japan is awash with culinary innovators and pioneers. As a shopper's Shangri-La, Osaka has specific areas that cater to every interest, from luxury goods and electronics, to fashion and furniture. For those in need of cultural sustenance, Osaka has it in droves. A slew of historic parks and shrines dot the cityscape and compete with niche museums and a notable theater scene for your attention and time.
Osaka’s Top 10
10. Osaka Aquarium, or Kaiyukan, is fun for kids of all ages and is one of the largest in the world.
5. Osaka Science Museum contains a massive Omnimax cinema and one of the top 5 planetariums in the world.
9. Umeda Sky Building is not the tallest high-rise in Osaka but it is the most distinctive. Worth a tour, from the underground market to the skydeck observatory.
4. Osaka Castle sits on a tract of land that covers 15 acres and many important cultural assets.
8. Amerikamura Triangle Park is the place to observe the unique rituals of Japanese youth subcultures.
3. National Museum of Ethnology makes fabulous use of former World Expo ‘70 digs in Suita.
Tempozan Ferris Wheel – This gigantic wheel rates a ride for its breathtaking vistas of the ocean, the city and the mountains.
Osaka Sport
Watch high-voltage sumo wrestling at the Osaka Prefecture Gymnasium.
Cycle or jog around the winding trails of Osaka’s Maishima Jogging Island.
Rent a yacht or dinghy and sail the waters of the Hokko Yacht Harbour.
Go surfing, jet skiin, or play beach volleyball at the Nishikinohama Beach Park.
Catch live football or rugby action in the 20,000-seater Kincho Stadium.
Osaka Local
Osaka proper is home to 2.7 million people. The central part of the city is split between Kita (north) and Minami (south), with Midōsuji boulevard as the major axis. Kita envelops Umeda and Minami is home to the Namba, Shinsaibashi and Dōtonbori districts. The traditional financial and business districts of Osaka, Yodoyabashi and Honmachi, reside between Kita and Minami as well. In all, Osaka has 24 wards (ku).
Asahi-ku has a famous covered shopping street in Sembayashi Shōtengai and points of interest like Shirokita Park and the Osaka Municipal Space of Art.
Chūō-ku is a busy economic, commercial, transport and consulate hub, with landmarks like Osaka Castle, Shinsaibashi-suji arcade, the Amerikamura retail and entertainment precinct and perhaps the most popular tourist pulse point in Osaka, Dōtonbori. The vibrant artery of restaurants and shops, once a seedy red-light strip, is now much more famous as a requisite pilgrimage for global foodies.
Higashisumiyoshi-ku is home to Nagai Park, Nagai Botanical Garden and the Osaka Museum of Natural History.
Ikuno-ku’s Tsuruhashi district is a famous hub for Korean food.
Kita-ku is the ward of Umeda, the downtown or central business district of Osaka and home of Osaka Station, numerous skyscrapers, malls and department stores.
Minato-ku has a few notable points of interest, such as Osaka Aquarium, the Modern Transportation Museum and the vast Port of Osaka.
Naniwa-ku is another commerical hive of activity and home to Nipponbashi (Den Den Town), a major area for electronics and manga. Other important landmarks include Namba Parks, Osaka Prefectural Gymnasium, Shinsekai district and the Osaka Human Rights Museum.
Nishi-ku is home to the Osaka Dome and Utsubo Park.
Suminoe-ku has several impressive attractions, from the Osaka Prefectural Government Sakishima Building to the Osaka Maritime Museum.
Sumiyoshi-ku is the eponymous home of the Sumiyoshi Grand Shrine.
Tennōji-ku contains some remarkable temples and green spaces, such as Shitennō-ji and Tennōji Park and Zoo.
Yodogawa-ku’s Jūsō is a gritty red-light enclave of the city with noisy, unfussy bars and restaurants that local hipsters covet and frequent on weekends.
Osaka Eat & Drink
The Osakan appetite for food and drink is legendary and while the reputation may come with some embellishment, the city is a boon for gourmands. The old proverb "dress (in kimonos) till you drop in Kyoto, eat till you drop in Osaka" is apropos. From iconic bar snacks to Korean, staples like takoyaki and okonomiyaki to luxurious sushi, the culinary scene in Osaka is a tasty patchwork.
Mogami (Shinsaibashisuji 2-2-10, Chūō-ku) is a kushikatsu institution in Osaka.
Osaka is dynamic with or without festivals. Indeed, several conspicuous areas of the city resonate with a carnival-like atmosphere on a near-nightly basis. The event calendar is chock-full, however, for those who want to take in local culture.
Osaka Asian Film Festival showcases cinematic talent from the continent every March.
Tenjin Matsuri has a history of more than 1,000 years and is one of the most venerable annual events in Japan. Held on July 24 and 25, the festival takes place at Tenman Shrine and features theatrical performances, costumed parades, boat processions and fireworks.
Aizen Matsuri is a love, luck and matrimony temple festival held from June 30 to July 2. The festival features colorful processions of girls in traditional yukata summer dress.
Kishiwada Danjiri Matsuri is the most famous cart festival in Japan. Held in Kishiwada city, about one hour south of Umeda by subway and train, the Shinto harvest festival is over 300 years old and features elaborate, boisterous cart parades in September and October.
Tōka-Ebisu is a lively luck and prosperity festival held in January at Imamiya Ebisu Shrine in Naniwa-ku and throughout Osaka. Inherent events and processions lure as many as 1 million people.
Osaka Dome is the home stadium for the Orix Buffaloes of Nippon Professional Baseball’s Pacific League.
Traditional kabuki is on hand at Shin-Kabuki-za and Osaka Shōchiku-za, two of the better theaters in Japan.
The Sumo Spring Grand Tournament takes place in mid-March at Osaka Prefectural Gymnasium.
When To Go
Osaka has a four season humid subtropical climate. Summer swelters with a temperature range of 68°F (20°C) to 91.5°F (33°C). Factor in the humidex and it often feels much warmer on a June or July afternoon. The months of May, June, July and September feature a lot of rain as well, though no time of year is immune from a downpour in Osaka.
Weather-wise, October, November and April stand out for overall comfort, with temperatures between 50°F (10°C) and 73°F (23°C).
What To Miss
Shinsaibashi is Osaka’s crown jewel commercial and retail district and has all the telltale hallmarks of a shopper’s paradise. From the uber youth culture trendsetter Amerikamura to the electronics emporium of Nipponbashi, the Chuo-ku district is decidedly must-see. Few areas, however, highlight just how costly Osaka and, indeed, Japan, can be for international travelers. The city is seldom not at the top of annual expensive city indices and Shinsaibashi shops drive the point home.
Though some guidebooks and locals exhort visitors not to set foot in Shinsekai, Osaka’s early 20th century tribute to New York City and Paris, the old ‘hood is a lot safer than in years past. While urban revivalism has not completely rid the area of poverty and red-light pachinko parlor grime, Shinsekai is worth a walk-through. Preferably in daylight, however.
Osaka has some tourist traps that deserve a pass. Tsūtenkaku is the most conspicuous landmark in Shinsekai but the Eiffel-ish observation tower is not worth the time and effort. Universal Studios Japan is undeniably popular but the amusement park feels counterfeit and lifeless. Much more critical, however, is the fact that it sits on top of a toxic industrial waste site. If you want to have fun with the kids in Osaka, Dōtonbori is a wild, authentic ride.
Spa World, also in Shinsekai, combines the venerable Japanese onsen with the scale of a theme park. The result is not necessarily blissful. A lot of people love the place but more tranquil and genuine thermal resorts reside in Kansai.
Getting Around
Kansai International Airport was built on a man-made island in Osaka Bay in 1994 to alleviate pressure from Osaka-Itami International, which was at capacity and could not logistically expand. The latter now serves as the primary domestic hub for the Kansai region, with up to 20 million passengers a year. Kansai International handles up to 15 million passengers a year, with service to the likes of New York-JFK, San Francisco, Honolulu, Seattle-Tacoma, Beijing-Capital, Hong Kong, Shanghai-Pudong, Busan, Seoul-Incheon, Amsterdam, Frankfurt, Paris-Charles de Gaulle, Cairns, Sydney, Bangkok, Delhi, Hanoi, Jakarta, Kuala Lumpur, Manila and Singapore.
Kansai International connects to Osaka by rapid rail and the trip is fairly easy to navigate. Osaka-Itami has a monorail and suburban rail line to the city but most visitors take the more convenient airport limo bus. Taxis can be prohibitively expensive.
The train is the way to travel in Honshu, Japan and Osaka is duly easy to get to via shinkansen (or a host of other options for Japan Rail Pass holders) from the likes of Hiroshima, Kobe, Kyoto and Tokyo. Moreover, countless bus operators ply routes between every major and minor city in Honshu and the Osaka International Ferry Terminal has regular service to Busan and Shanghai.
Transport in the Keihanshin Osaka-Kobe-Kyoto megalopolis benefits from a high degree of development and sophistication. The Osaka Municipal Subway is one of the busiest metro systems in the world, although with 2.2 million daily passengers, has only a quarter the ridership of the Tokyo subway. The Midosuji Line is the primary conduit in the subway network. In order to negotiate the hodpodge of commuter rail lines and municipal trains throughout Keihanshin and Kansai, consider the five-day consecutive limitless Kintetsu Rail Pass the best bet.
Frenetic Osaka is like the boisterous younger brother of Tokyo - in the eyes of some at least. With a busy population of under 3 million, the notable city of shops, bars and restaurants is an absolute gem. The food culture for one, is unlike any other in Japan. Osaka has a reputation as the nation's kitchen and culinary innovations in the vast city seem to know no limits. From udon noodles to okonomiyaki bars and octopus balls, the endless parade of local treats will cause both eyes and stomach to bulge.
As a shopper's paradise, Osaka has specific areas that cater to every interest, from luxury goods, electronics, fashion, mange and anime and much more. For those in need of cultural substance, Osaka has it in spades. A number of historic parks and shrines dot the cityscape and compete with superb museums and a notable kabuki theater scene for tourist's attention.
Attractions & Activities
Attractions
National Museum of Art
Osaka Science Museum
Osaka International Peace Center
Mitami Shrine
Osaka Castle
Activities
National Bunraku Theater
Cherry Blossom Festival
Golden Week
Shitennoji Temple Doya Doya Festival
Aizen Festival
Restaurant & Nightlife
Restaurants
Kogaryu
Fugetsu
Bar Tachibana
Kani Doraku
Nightlife
Club Quattro
Club Karma
Cinquecento
Covent Garden
Sam and Dave Umeda
Climate
With wet, hot and humid summers and typhoon season in September and October, the best time to visit Osaka may be the mild spring.
Hotels in Osaka
Recommended hotels
Swissotel Nankai Osaka invites savvy travellers to lavish accommodations equipped with state-of-the-art facilities set in the bustling shopping and entertainment hub of Osaka. This luxury hotel... More
“
Family Trip
We're really enjoy our trip. Have really nice view from our room. The staff were helpful. It was very close to Namba station that is what a choice for.
Hotel New Otani Osaka welcomes travellers to an idyllic retreat with lavish spaces set in a convenient city centre location. Located along the riverside in Osaka Business Park, this Osaka hotel... More
“
Centrally located and beautiful hotel
Located within 300 metres of JR Osakajokoen Station and Osaka Business Park Subway Stations, this beautiful hotel was great value for money. Staff were extremely helpful and room was large.
big room in Japan
Hotel Monterey Grasmere Osaka provides modern travellers refined elegance and luxurious accommodations in the heart of bustling Osaka. A trip to this part of Japan is not complete without checking... More
“
Very convenient and great service
The location is very convenient and great service from the staff. Highly recommended to stay in this hotel.
Hilton Osaka hotel welcomes urbane travellers to deluxe accommodations and understated grandeur set in the heart of vibrant Osaka. Tourists at this elegant hotel can travel to Osaka Castle or enjoy... More
“
Very good but...
Excellent service from staff and a generally comfortable room let down by the lack of free wifi in our room (only being available in the ground floor lobby), lack of toothpaste and some other basic...
Prices reflect the lowest "base rate" found over the next 30 days. Rates are subject to change and may not include taxes and fees, hotel service charges, extra person charges, or incidentals, such as room service. Converted rates are provided for your convenience. They are based on today's exchange rate, but the hotel will charge you in the local currency. Taxes may be payable in addition.
|
Progression of mild ureteropelvic junction obstruction in infancy.
Mild and clinically silent ureteropelvic junction obstruction was observed to progress in severity in 2 infants. Diuretic renography was useful in serial evaluation and documentation of progression. The possible mechanism for such progression of obstruction is proposed. Although mild obstruction in the older child and adult can be followed successfully without surgery, it appears that close follow-up of mild obstruction during the first year of life is necessary to detect and assure treatment of progressive obstruction at an optimum age.
|
Patagonia micropuff hoody, Men's medium.
This one is used with minor thread pulls
in chest at logo (photo) and small pink
stain on arm (photo). It ...
238
Good
65.00
Thu December 18, 2014 1:15am
Patagonia Guide Hoody
posted by D.B.AndersonPatagonia Guide hoody size men's small.
Few years old but great shape other than small
nick on elbow (see pic). Zipper works fine but has
one missing tooth. Never has been a ...
|
# Copyright (c) 2019 Intel Corporation
#
# Licensed under the Apache License, Version 2.0 (the "License");
# you may not use this file except in compliance with the License.
# You may obtain a copy of the License at
#
# http://www.apache.org/licenses/LICENSE-2.0
#
# Unless required by applicable law or agreed to in writing, software
# distributed under the License is distributed on an "AS IS" BASIS,
# WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
# See the License for the specific language governing permissions and
# limitations under the License.
description: >-
The "efficientnet-b7-pytorch" model is one of the EfficientNet <https://arxiv.org/abs/1905.11946> models
designed to perform image classification. This model was pretrained in TensorFlow*,
then weights were converted to PyTorch*. All the EfficientNet models have been pretrained
on the ImageNet* image database. For details about this family of models, check
out the EfficientNets for PyTorch repository <https://github.com/rwightman/gen-efficientnet-pytorch>.
The model input is a blob that consists of a single image with the [3x600x600] shape
in the RGB order. Before passing the image blob to the network, do the following:
1. Subtract the RGB mean values as follows: [123.675,116.28,103.53] 2. Divide the
RGB mean values by [58.395,57.12,57.375]
The model output for "efficientnet-b7-pytorch" is the typical object classifier
output for the 1000 different classifications matching those in the ImageNet database.
task_type: classification
files:
- name: model/gen_efficientnet.py
size: 40997
sha256: 8613d48ca74611d3566d8c02cbf7c92aad6b16a708ffcf21183a7014fecdec09
source: https://raw.githubusercontent.com/rwightman/gen-efficientnet-pytorch/a36e2b2cd1bd122a508a6fffeaa7606890f8c882/gen_efficientnet/gen_efficientnet.py
- name: model/efficientnet_builder.py
size: 18446
sha256: 69bb2adc49dc79c8860f36acca910bad6733e23b46ed80551248b90141d5e1b5
source: https://raw.githubusercontent.com/rwightman/gen-efficientnet-pytorch/a36e2b2cd1bd122a508a6fffeaa7606890f8c882/gen_efficientnet/efficientnet_builder.py
- name: model/helpers.py
size: 1097
sha256: 0415f198b8a87cb34c9f9aed79f267043010fbd197e27df805bab9d070da82ed
source: https://raw.githubusercontent.com/rwightman/gen-efficientnet-pytorch/a36e2b2cd1bd122a508a6fffeaa7606890f8c882/gen_efficientnet/helpers.py
- name: model/conv2d_helpers.py
size: 6175
sha256: e6ba7e878dd28c6d0ccc9707205bf6b58bea664d7fee820d7101a6a8e48990a9
source: https://raw.githubusercontent.com/rwightman/gen-efficientnet-pytorch/a36e2b2cd1bd122a508a6fffeaa7606890f8c882/gen_efficientnet/conv2d_helpers.py
- name: model/__init__.py
size: 32
sha256: e0bedda5f5e949b8ace7d4f5cdf80e7e664c0b0a935486b6152078fa61c80c1b
source: https://github.com/rwightman/gen-efficientnet-pytorch/raw/a36e2b2cd1bd122a508a6fffeaa7606890f8c882/gen_efficientnet/__init__.py
- name: tf-efficientnet-b7.pth
size: 266843942
sha256: 076e3472fb198ec7c3091aecc73ff205bcca4a114f5862e2297a4c2720c91826
source: https://github.com/rwightman/pytorch-image-models/releases/download/v0.1-weights/tf_efficientnet_b7_aa-076e3472.pth
postprocessing:
- $type: regex_replace
file: model/conv2d_helpers.py
pattern: '_EXPORTABLE = False'
replacement: '_EXPORTABLE = True'
conversion_to_onnx_args:
- --model-path=$dl_dir
- --model-name=tf_efficientnet_b7
- --import-module=model
- --weights=$dl_dir/tf-efficientnet-b7.pth
- --input-shape=1,3,600,600
- --input-names=data
- --output-names=prob
- --output-file=$conv_dir/efficientnet-b7.onnx
model_optimizer_args:
- --reverse_input_channels
- --input_shape=[1,3,600,600]
- --input=data
- --mean_values=data[123.675,116.28,103.53]
- --scale_values=data[58.395,57.12,57.375]
- --output=prob
- --input_model=$conv_dir/efficientnet-b7.onnx
framework: pytorch
license: https://raw.githubusercontent.com/rwightman/gen-efficientnet-pytorch/a36e2b2cd1bd122a508a6fffeaa7606890f8c882/LICENSE
|
Q:
How to display floating point number from table show as digit format
In my table i have the record value 0.0000009 like this since i run my program i got result like this 9.0E-7. But i need to display 0.0000009 this format.
<?php echo $a=0.0000009; ?>
Kindly guide me
A:
You can use formatting print, %f means that you bind float value, "1" symbols before point, "8" after point:
echo sprintf('%1.8f', 0.00000009);
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Big K (magazine)
Big K was a short-lived multi format magazine published by IPC Magazines Ltd during the 1980s. The design of the magazine was very similar in style to their comic strip publications at the time, 2000ad and Roy of the Rovers and seemed to be aimed squarely at the younger computer user.
The March 1985 issue featured the first episode of the digitally created comic strip Shatter, although as this was the last Big K printed, it was also Shatter's only appearance until a run in Jon Sable: Freelance from issues #25-30 in June 1985.
See also
Computer and Video Games (magazine)
ACE
The Games Machine
Edge
GamesMaster (magazine)
References
Category:Defunct British computer magazines
Category:British video game magazines
Category:Home computer magazines
Category:Magazines established in 1984
Category:Magazines disestablished in 1985
Category:London magazines
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Caregiver Packet Bundle 4
Caregiver Packet Bundle 4
Caregiver Packet Bundle 3
This course covers: How to prevent and respond to emergencies due to food or allergic reactions, Handle, store and dispose of hazardous materials, Maintaining a Commitment to Professionalism and Building Productive Relationships with Families
(7) Preventing and controlling the spread of communicable diseases, including immunizations.
(8) Recognizing and preventing shaken baby syndrome and abusive head trauma;Understanding and using safe sleep practices and preventing sudden infant death syndrome (SIDS); and Understanding early childhood brain development
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DETROIT (Reuters) Ford Motor Company said Thursday that it would cut production through the remainder of 2008 and said it no longer expects to meet a long-held goal of returning to profitability in 2009.
In a statement, Ford said rising prices for commodities, particularly steel, and an accelerating consumer shift from larger trucks and sport utility vehicles would make it impossible to meet the key milestone in its turnaround efforts.
Ford’s chief executive, Alan Mulally, said the company now expects to be “about break-even” in 2009, on a pretax basis and before special items, with strong results from Europe and South America.
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Laira Traction & Rolling Stock Maintenance Depot
Laira T&RSMD is a railway Traction & Rolling Stock Maintenance Depot situated in Plymouth, Devon, England. The depot is operated by Great Western Railway and is mainly concerned with the overhaul and daily servicing of their fleet of High Speed Trains and also the DMUs used on local services. The depot code "LA" is used to identify rolling stock based there.
After sixty years as a steam depot, servicing locomotives used on the Exeter to Plymouth line that runs past the shed as well as local lines, diesels started to arrive in 1958. A diesel depot opened in 1962 and was expanded in 1981 to accommodate the High Speed Trains.
History
Steam shed
Laira was the location of the temporary terminus of the South Devon Railway from 5 May 1848 when a small engine shed would have been provided. With the completion of the line to Plymouth Millbay railway station on 2 April 1849 a new shed was provided there and the facilities at Laira dismantled, although it remained a junction for the branch line to Sutton Harbour which was mixed gauge for the use of the Plymouth and Dartmoor Railway.
The Great Western Railway, which had amalgamated with the South Devon Railway on 1 February 1876, a new engine shed opened at Laira in 1901 on a site inside a triangle of lines formed by the main line, Sutton Harbour branch, and a curve that was mainly used by London and South Western Railway trains to reach their terminus at Plymouth Friary. It was adjacent to the Embankment Road with the estuary of the River Plym just the other side of the road. The shed was a 434 by 181 feet (132 by 55-metre) brick roundhouse with a turntable in the middle. 28 lines radiated from the turntable for stabling locomotives and it was fitted with a 20-ton hoist for lifting locomotives (a 35-ton one was added later).
A small railway station known as Laira Halt was opened on the adjacent main line on 1 June 1904 but closed again on 7 July 1930. The shed at Millbay closed in 1925 and in 1931 a new 210 by 67 feet (64 by 20-metre) four track shed at Laira was brought into use just south of the original roundhouse, funded by a government loan under the Development (Loan Guarantees and Grants) Act 1929. This became known as the "Long Shed" or "New Shed". At the same time the coaling stage was raised and a new 50 ton hoist supplemented the smaller ones in the roundhouse.
Diesel shed
Warship Class diesel-hydraulic locomotives started to appear in 1958 and were at first accommodated in the New Shed alongside steam locomotives until the diesel maintenance depot had been finished. The Laira marshalling yard alongside Embankment Road was closed in 1958 to make room for carriage sidings and a new diesel shed, which was fully opened on 13 March 1962, although parts had been in use since 1960.
Laira was designed for the servicing and heavy maintenance of the diesel-hydraulic locomotives favoured by the Western Region of British Railways (the depot became well known as the final home of the "Western" Class). It also handled the local diesel electric shunter and DMU fleets, although servicing of the latter was done initially at Belmont sidings at Millbay.
The diesel shed was in reinforced concrete and comprised three adjoining buildings. The servicing and maintenance building that covers roads 1–4 is on the western side of the shed; number 1 road is equipped with a wheel lathe and lifting jacks for bogie changes. The central building was the Heavy Maintenance Shed; engines can be removed and repainting undertaken on the two roads, numbers 5 and 6. The final three roads were in the servicing shed on the eastern side of the site, where locomotives could be inspected and refuelled. There were covered fuelling points outside in the yard, supplied by a 45,000 gallon fuel tank. A small group of buildings house stores and a workshop for shed equipment and is situated between the main shed and the curve of the Sutton Harbour branch (now realigned to the west of the shed and known locally as the "Speedway"). Carriage washing takes place south of the shed at Mount Gould, alongside the line to Plymouth Friary.
On 30 September 1981 a new shed, long was built on the site of the old servicing shed that can accommodate the eight coaches and two Class 43 power cars of a High Speed Train set.
Following the withdrawal of steam from the area in 1964, the roundhouse was closed on 13 June 1965 and the area used for additional siding space. This area was later modernised and fenced off in readiness for servicing the Nightstar Channel Tunnel sleeper coaches, but the proposed service from Plymouth to Paris Gare du Nord never materialised.
InterCity Express Programme
When the InterCity Express Programme was released, Laira Traction & Rolling Stock Maintenance Depot was considered for an upgrade to one of the 'IET' maintenance facilities, however a new depot in Swansea and Bristol as well as the purchase of North Pole International Depot from Eurostar which sits adjacent to Old Oak Common Depot meant that Laira T&RSMD was soon declined.
CrossCountry
CrossCountry trains also use Laira Traction & Rolling Stock Maintenance Depot. Unlike Great Western Railway, CrossCountry only use the storage, cleaning and washing facilities within the depot as their HST fleet is maintained at Edinburgh Craigentinny Depot and Neville Hill Depot in Leeds whilst the Voyager and Super Voyager fleet are maintained at Burton Central Rivers and Bristol Barton Hill depots respectively.
In the case of a traction failure, the failed stock is often sent to Laira T&RSMD, unless occurring on an upbound journey, this allows it to be stored and inspected before running to its respective maintenance base.
Allocation
Up to the 1960s Laira had an allocation that consisted of a wide variety of Great Western Railway motive power, including "Castle" Class and "King" Class express passenger locomotives. The following lists give summaries for various years.
During the 1960s and 1970s it was well known for its fleet of "Western" Class diesel-hydraulics. The last of these were withdrawn in 1977, by which time British Rail Class 50 diesel-electric locomotives had taken over many of their duties. These were later given Warship names in the same manner as the first diesel hydraulics. A fleet of DMUs was also stationed here for operating the branch lines in Devon and Cornwall.
In recent years the allocation has solely consisted of Class 43 power cars for High Speed Trains along with some British Rail Class 08 shunting locomotives. The DMUs in Devon and Cornwall were based at Cardiff Canton TMD for several years, but in December 2007 Laira had an allocation of two-car Class 150 and single-car Class 153 DMUs. After a while these were transferred to a reopened Exeter Traction Maintenance Depot.
Shed codes
The following shed codes have been used to identify locomotives allocated to Laira:
Named locomotives
Locomotives named after Laira shed have been:
3338 (3326 from 1912) Laira GWR Bulldog Class 4-4-0 steam locomotive
08641 Laira British Rail Class 08 0-6-0 diesel shunting locomotive
08644 Laira Diesel Depot British Rail Class 08 0-6-0 diesel shunting locomotive
43179 Pride of Laira British Rail Class 43 power car
References
Further reading
External links
Encyclopedia of Plymouth History – Laira Motive Power Depot and Yard
Category:Railway depots in England
Category:Rail transport in Devon
Category:Great Western Railway
Category:Transport in Plymouth
Category:Transport infrastructure completed in 1962
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Highland Park (Meridian, Mississippi)
Highland Park is a historic park in Meridian, Mississippi. Home to a museum honoring Jimmie Rodgers, a Meridian native, the site was listed on the National Register of Historic Places in 1979. The park is also home to the Highland Park Dentzel Carousel and Shelter Building, a National Historic Landmark manufactured around 1896 by Gustav Dentzel of Philadelphia, Pennsylvania. The historic carousel is the only two-row stationary Dentzel menagerie still in existence.
History
The history of Highland Park begins in the late 19th century when the area was used as the Meridian Fair and Livestock Exposition. The organization, which was influenced by World's fairs such as the 1893 Chicago World's Fair and Atlanta's International Cotton Exposition in 1895, was founded in 1904 by big names in Meridian such as Israel Marks, the Threefoot brothers, and the Rothenbergs. They acquired land in west Meridian but never made any plans of what to do with it. When the Fair and Exposition Corporation dissolved in 1906, ownership of the land was transferred to a non-profit trust. After a city Park Association was formed in 1908, the association was tasked with assembling property and developing initial plans for the park.
At the time Highland Park was designed, there was a national trend for streetcar pleasure parks, and electric railway companies wanted to increase their operations by owning or investing in these parks. The Meridian Light and Railway Company followed the national trend, building a rail line beginning at 8th Street and following 34th Avenue until it turned west between 19th and 20th Streets and continuing west into Highland Park. The platform for the streetcar line was located in the northeast corner of the park at the main entrance. A promenade connected the platform with a small pool, a carousel house, a large loveseat, a bronze statue honoring Israel Marks, and a gazebo. A sidewalk extended from the promenade to a dance pavilion, and another sidewalk connected the gazebo with a bandstand. South of this group was a lagoon, alligator pond, footbridge, and greenhouse. In the western section of the park, there were two picnic shelters, a small toilet facility, and a terraced amphitheater. The northern part of the park was originally meant for pedestrians while the southern part was reserved for those with horses.
A downtown monument honoring Frank M. Zehler, a fireman who died on duty in 1901, was relocated to the park in the 1920s from its original location at the intersection of 23rd Avenue and 4th Street in downtown Meridian. In the 1930s, two swimming pools were built on the site of the former dance pavilion, a one-story commercial building was added in the northwest corner of the park, and an arboretum was added by the amphitheater. The pathways in the park were paved in the 1940s, allowing vehicles to travel through the area. A small fighter jet was located in the park between the pools and the promenade in 1972. Also, a Parks and Recreation office, a museum honoring Jimmie Rodgers, a steam locomotive and caboose, children's playground equipment, and the Frank Cochran Center have been added since. Of the original features, all remain except the dance pavilion and greenhouse.
Dentzel carousel
The Highland Park Dentzel Carousel and Shelter Building was manufactured about 1896 for the 1904 St. Louis Exposition by Gustav Dentzel of Philadelphia, Pennsylvania. Meridian bought the carousel in 1909 and installed it in its house in the park. It is the only remaining two-row stationary Dentzel menagerie in the world. As such, it was declared a National Historic Landmark in 1987. Its house, also in the National Historic Landmark listing, is the only remaining original carousel building built from a Dentzel blueprint.
While the carousel building was closed from 1983 to 1984 for major restoration, the carousel animals were removed and placed in various local institutions while funds were raised. From 1984 to 1995, the animals, chariots, and canvas oil paintings of the carousel were restored to their original appearance. The restoration was done by Rosa Ragan of Raleigh, North Carolina, one of the foremost restoration specialists in the country.
Jimmie Rodgers museum
The park houses a Jimmie Rodgers museum honoring the Meridian-born country legend and displaying the original guitar of the so-called "Singing Brakeman," along with other memorabilia of his life and career and various railroading equipment from the steam engine era — Meridian's "golden age". In addition to the museum building itself, which was built in 1976, outside memorials honor the country star, and a vintage steam locomotive is displayed on a small section of railroad track, symbolizing Meridian's strong ties to railroading history. The locomotive is a 1917 Baldwin steam locomotive from the Susquehanna and New York Railroad line. It was later used by the Meridian and Bigbee railroad, who donated it to the city in 1953 as a memorial to all deceased railroaders. The locomotive was moved to the park in 1970.
Arts in the Park
The park hosted the annual Arts in the Park festival from the festival's premiere in 1971 until 2006, when the Meridian Council of Arts decided to move the festival to Bonita Lakes, another location in Meridian. In 2009 the festival was combined with the Threefoot Arts Festival and moved to downtown Meridian to form the Threefoot Festival.
Arts in the Park, held on the first Saturday in April, provides a multi-discipline venue for artists, craftsmen, musicians and performers. Local dance groups, martial arts groups, drama groups, gospel-drama groups, gospel praise dance teams, singers, bands and choral groups perform their art for crowds of people on two separate entertainment stages. The festival features a juried art competition and show as well as a non-competition craft area. Arts in the Park acts as a revenue source for non-profit groups as well as a showcase for the Arts. In general the non-profit groups that take part in Arts in the Park are art organizations, local churches, and various community wide charitable organizations.
See also
List of music museums
References
External links
Highland Park - City of Meridian
Dentzel Carousel - City of Meridian
Jimmie Rodgers Museum
Category:Meridian, Mississippi
Category:Parks in Mississippi
Category:Protected areas of Lauderdale County, Mississippi
Category:Historic districts on the National Register of Historic Places in Mississippi
Category:Mississippi Landmarks
Category:National Register of Historic Places in Lauderdale County, Mississippi
Category:Parks on the National Register of Historic Places in Mississippi
Category:Tourist attractions in Meridian, Mississippi
Category:1909 establishments in Mississippi
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Let me begin by telling you a little story. Some time ago I needed to run a script at work once a day. We had tons of machines ranging from big Unix servers to Linux desktops. Due to various reasons the script could only be run on a desktop machine. However using cron was disabled on desktops. All other machines allowed cron.
I contacted the IT guys and asked them to allow cron on desktop
machines. A long and arduous battle followed. Among the issues said to
me was that allowing cron on desktop machines would be a security
issue (apparently because then people would actually use it).
When I replied that cron is freely usable on all other machines I got
a bunch of other comments, including a "helpful" way to work around my
problem with a complicated combination of xnest and ssh port
forwarding.
All I wanted was to get cron working. Eventually I was told that
"you can code your own cron program with Python really easily, just
run it under screen and you're all set".
End of line!
I had come face to face with the workaround trap. I'm sure
most readers have faced some mutation of this phenomenon where an
obvious problem does not or will not get fixed because you can hack
around it somehow. Workarounds by themselves are not a bad thing.
Problems arise when workarounds prevent the so-called real (or
"correct") solution from emerging. This problem is especially
prevalent on UNIX type systems, which have traditionally had a strong
culture of DIY whenever the basic tools don't do exactly what is
required.
Some examples might illustrate the nature of the workaround trap.
The first one deals with binary relocation and the second one with
email protocols.
Where am I, asked the little program
One of the cool things about OS X is that most programs come in
self-contained bundles. Those can be placed anywhere in the file
system and run. Similarly Windows programs can be installed in any
directory whatsoever. In contrast rpms and debs have hardcoded install
locations and simply will not work anywhere else. At least most of the
time.
There are several reasons for this but one of the main ones is that
there is no standardised way for a UNIX program (or a dynamic library)
to ask where is the file it is being run from. Windows and Mac both
have this feature.
Suppose we have a C program that consists of two different files: a
binary called foo and a user-editable configuration file
called foo.conf. These files are placed somewhere in the
filesystem (say /opt/myprog/foo and
/opt/myprog/foo.conf) spesified by the install system. The
user then runs the program, which begins by reading its conf file.
What filename should it pass to fopen to access its conf
file?
Simply passing foo.conf would try to open the file in
the directory the program was launched from (usually the user's home
directory). Opening the correct file would require some way to know
where the executable file currently resides.
This is where the workaround trap springs into action.
The common solution is that the build system #define:s
a string constant such as INSTALL_PREFIX as the path
where the program will eventually get installed. Then accessing the
data file is simply a matter of string concatenation
(INSTALL_PREFIX + "foo.conf"). This works and is
relatively simple, but the downside is a severe static dependency: the
files must be in the spesified directory or else nothing
works.
You can do all sorts of cool things with relocatable binaries, like
allowing users to install non-official rpms (such as daily
snapshots of Firefox 3) to their own home directories in a safe and
reliable way. But these things will never get explored since there is
no way for a UNIX program to ask where is the file it is currently
being run from.
An oft-repeated wisdom about design is that you have reached
perfection not when there's nothing left to add, but when there's
nothing to remove. Email is one area where this rule has definitely
not been followed.
Have you ever wondered why you need to define both an incoming mail
server and an outgoing mail server? You'd think that a server that can
transport mail in one direction would be smart enough to know how to do it
in the other direction as well. And in fact those server can do that, but
you can not send mail through IMAP.
And why is that, you ask?
Because mail is sent using SMTP. Mail has always been sent using
SMTP. Mail will always be sent using SMTP. To not use SMTP is
unthinkable.
This causes a lot of unnecessary work. Mail client developers have
to code and debug two different protocols instead of one. You need two
different authentication steps, one for incoming mail and one for
outgoing. Basically you need two of everything when one would suffice.
A committee has even developed a way for an SMTP server to communicate
with an IMAP server to retrieve attached files from sender's IMAP
mailbox so that they can be attached to the current outgoing message.
I kid
you not! I hope they patented the hell out of that 5-phase email
sending process of theirs so that no-one will ever have to use it.
There is a simple solution to this mess. The IMAP server shows
clients a virtual folder called, say, OUTBOX. The client composes a
message and writes it to this folder. The IMAP server takes the
message, possibly checks that it is valid and passes it on to an SMTP
server. Mail sent. With 50 percent less cruft, even.
Sounds too simple to be true? Can't possibly work? There must be
some critical thing missing?
The Courier mail server
has had this feature for ages. But should you suggest that this
feature be added to other programs, you'll probably get some blank
stares followed by instructions on how to properly set up an SMTP
server.
Conclusions
Have you ever wondered what Steve Jobs actually does at work?
Looking at his public performances you can clearly see that his most
important task is aggressively seeking and destroying workaround traps
that lie in Apple's products.
Take for example the iPhone. Almost everything it does has been possible for ages. Telephone exchanges have had the support to make
conference calls since the 80s. However I don't personally know a
single person that would have used this feature. Mostly because to get
it working you had to enter long magical keysequences with zero
feedback. Smartphones may have this feature in their menus somewhere. On
the iPhone you just push one button. The same holds true for most of
its other features. Some of those features required changes to
Cingular's telephone exchanges. No-one else was willing to do those
changes because they kept saying "you can already do that by ...".
The free software community does not and can not have one person like
Jobs who would force people to fix needlessly complex systems and
eradicate harmful habits. We must do it ourselves. Therefore I encourage
all readers to think of one example where a complicated and crufty hack is
being widely used today even though creating a more elegant solution would
make everyone's life easier.
Then post it in the comments. Back your assertion with solid
technological facts.
Because the first step to recovery is admitting your problems.
About the author:
Jussi Pakkanen is a long time Linux user. He has had the dubious
pleasure of beating his head against most corners the personal
computing world has managed to build. The doctors are optimistic
that, given time, he may yet become a productive member of society.
If you would like to see your thoughts or experiences with technology published, please consider writing an article for OSNews.
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Article content continued
The unidentified man was rushed to hospital, where he remains in intensive care. But when Lopez went to file an incident report, he was fired for going 500 meters out of his assigned area.
“They didn’t tell me in a bad way. It was more like they were ‘sorry, but rules are rules,’” Lopez said. “I couldn’t believe what was happening.”
His employer, Orlando-based Jeff Ellis & Associates, said the lifeguard broke a company rule and could have put beachgoers in his section of Hallandale Beach in jeopardy.
“We have liability issues and can’t go out of the protected area,” explained a supervisor for the private contractor that supplies lifeguards for Hallandale Beach, a popular destination for Canadian winter holiday makers.
“What he did was his own decision. He knew the company rules and did what he thought he needed to do.”
The rescue was performed about 1,500 feet south of the protective boundaries set by the employer. The unprotected area has signs alerting beachgoers to swim at their own risk.
However, Ms. Ellis conceded Mr. Lopez’s section was not left unpatrolled at any time and his action did not put anyone at risk.
Other lifeguards watched the area during the rescue and were on the phone with 911 operators.
Mr. Lopez became a lifeguard four months ago after passing the company’s requirements, which include swimming and physical exams. The job pays $8.25 an hour.
Two other lifeguards have quit in protest of Mr. Lopez’s firing.
One of them, Szilard Janko, told the newspaper, “What was he supposed to do? Watch a man drown?”
Thursday, Jeff Ellis, the company head, said Mr. Lopez would be offered his job back.
“I am of the opinion that the supervisors acted hastily,” he said.
But the lifeguard said he wasn’t interested.
“They are trying to fix the wrong that they did. I just don’t want to work for that company anymore,” he said.
“It’s not out of spite against the company. After all is said, I really just want to move on and get another job.”
Agence France-Presse, with files from The Associated Press
Find the National Post on Facebook
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This invention relates to methods for embossing a pattern in a piece of glass.
Hot glass is a relatively sticky material that tends to adhere to hot embossing tools. In the manufacture of glass articles, this sticking tendency is controlled by working the hot glass with chilled tools. Fine detail however, cannot be embossed in glass with chilled tools because a skin forms on the surface of the glass, which limits the fineness of the pattern than can be impressed. This skin inhibits the flow of the glass into the small detail of the embossing die.
If the die temperature is increased to permit a greater glass flow, a condition will be reached where the glass will adhere to the tool making the embossing impossible. The adherence of molten glass to mold surfaces has been reduced by vibrating the mold while the glass was in contact with the mold as shown in U.S. Pat. No. 1,482,760 issued on Aug. 9, 1922 to J. A. Milliken. This vibration was heretofore used to eliminate the necessity for cooling the mold between separate molding operations. Carbon and graphite die materials have nonstick properties that permit their utilization in glass forming. However, these materials cannot be employed to emboss fine patterns because the details in the patterns are destroyed by the oxidation of the materials at high temperature.
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-12*z**2 - 8 + z**3 - z**3 + z**3. Let s be g(12). What is s*o(h) - 5*d(h)?
-h**2 + h + 2
Let q(d) = 195*d + 91. Let f(h) = 13*h + 6. Determine 91*f(g) - 6*q(g).
13*g
Let x = 14 - 12. Let m(p) = x - 2 + 5*p + 3. Let h(b) = 14*b + 8. Calculate 4*h(i) - 11*m(i).
i - 1
Let n(h) = h**3 - h**2 + 1. Let a(m) = -m**3 - 6*m**2 - m + 2. Calculate -a(f) + 6*n(f).
7*f**3 + f + 4
Let o(j) = -2*j**2 - 3*j - 7. Let s(l) = 3*l**2 + 4*l + 10. Let q be (-6)/(-4)*(-50)/(-15). Determine q*s(r) + 7*o(r).
r**2 - r + 1
Let q(i) = 7*i - 1. Let p(x) = 6*x - 1. Suppose 0 = 2*h - 3*a - a + 4, -a = -h + 1. What is h*q(n) - 5*p(n)?
-2*n + 1
Let x(d) = -7*d**3 - d**2 + 5*d - 3. Let k(j) = 8*j + 6*j**3 - 3 - 12*j + 6 + j**2. What is 5*k(t) + 4*x(t)?
2*t**3 + t**2 + 3
Let u(w) = 7*w - 4. Let n(q) be the second derivative of -4*q**3/3 + 5*q**2/2 - 7*q. Calculate 6*n(c) + 7*u(c).
c + 2
Let c(p) = -6 + 13*p**2 + 14 + 10*p - 21*p**2. Let t(z) = -z**2 + z + 1. Determine 2*c(u) - 18*t(u).
2*u**2 + 2*u - 2
Let f(g) = 47*g + 1. Let u(m) = 48*m + 2. Give -3*f(z) + 2*u(z).
-45*z + 1
Let n(p) = -25*p**2 + 35. Let s(m) = 2*m**2 - 3. Suppose 5*v + d = -70 + 247, -3*d - 29 = -v. Give v*s(i) + 3*n(i).
-5*i**2
Let z(h) be the third derivative of h**4/8 + h**3/2 - 2*h**2. Let u(o) = 4*o + 4. Give -4*u(s) + 5*z(s).
-s - 1
Let y(j) = j**2 - 1. Let f(t) = t + 5. Let d be f(-4). Let x(u) = -4*u**2 + 2*u + 0 - u**2 + d. What is -x(p) - 3*y(p)?
2*p**2 - 2*p + 2
Let w(q) = 2*q**2 + 5*q - 4. Let s(x) = x**2 - 1. What is 4*s(z) - w(z)?
2*z**2 - 5*z
Let c(n) = 8*n**3 + 7*n - 7. Let y(q) = -4*q**3 - 3*q + 3. Suppose z - 3*z = 14. Determine z*y(m) - 3*c(m).
4*m**3
Let x be (4 - -10)/(-2)*-1. Let z(k) = -6*k**3 + 7*k**2 + 9*k - 8. Let f(n) = -5*n**3 + 6*n**2 + 8*n - 7. Give x*f(r) - 6*z(r).
r**3 + 2*r - 1
Let u(d) = -d**2 + 7*d - 2. Let y(r) = r**2 + 1. What is -u(p) - 3*y(p)?
-2*p**2 - 7*p - 1
Let h(b) = -64*b**2 + 28*b - 28. Let r(n) = 7*n**2 - 3*n + 3. Give 6*h(a) + 56*r(a).
8*a**2
Let p(r) = r - 4. Let m(i) be the third derivative of -3/2*i**3 + 0*i + 0 + 4*i**2 + 1/8*i**4. What is 4*m(n) - 9*p(n)?
3*n
Let j(p) be the first derivative of 2*p**2 - 4*p - 12. Suppose -4*n = -3*k - 6*n - 27, -58 = 5*k - n. Let g(z) = -21*z + 21. Determine k*j(s) - 2*g(s).
-2*s + 2
Let u(r) = r - 3. Let s(i) = i - 4. What is 5*s(o) - 6*u(o)?
-o - 2
Suppose f = 2*o + 14, -3*f + 12 = -0*f + 4*o. Let i(v) = v + 3. Let h(j) = -4*j - 8. Determine f*i(t) + 3*h(t).
-4*t
Let k(d) = d**3 + 2*d**2 + 2*d. Let v(c) = c**3 + 3*c**2 + 3*c. Suppose 0 = 3*l - 4*p + 21, 5 = -l + 2*p - 4. Determine l*v(s) + 4*k(s).
s**3 - s**2 - s
Let h(w) = 4*w**2 + 9*w - 5. Suppose 23*y - 10*y = 39. Let f(n) = -2*n**2 - 4*n + 2. What is y*h(v) + 7*f(v)?
-2*v**2 - v - 1
Let o(d) = -3*d**2 + 3*d. Let i(h) = -2*h**2 - 3*h - 3. Let a(n) = -n**2 - 2*n - 2. Let t(g) = 3*a(g) - 2*i(g). Give o(y) + 5*t(y).
2*y**2 + 3*y
Let z(u) = -5*u**3 + 3*u**2 + 38*u - 2. Let y(t) = t**3 - t**2 - t. Give 3*y(r) + z(r).
-2*r**3 + 35*r - 2
Let f(j) be the third derivative of -j**4/6 + j**3/2 - 36*j**2. Let o(h) = -5*h + 4. Determine 7*f(k) - 6*o(k).
2*k - 3
Let m(w) = w**2 + 15*w - 5. Let p(n) = 2*n**2 + 30*n - 9. Give 7*m(y) - 4*p(y).
-y**2 - 15*y + 1
Let t(c) = -9*c**2 - 11*c. Let l(y) = -13*y**2 - 16*y. What is 5*l(w) - 7*t(w)?
-2*w**2 - 3*w
Let m(a) = -2*a**3 + a**2 - 8*a - 4. Let u(z) = 2*z**3 - z**2 + 7*z + 3. Give 3*m(t) + 4*u(t).
2*t**3 - t**2 + 4*t
Let a be 1/(-3) - (-16)/(-6). Let i(u) = -u**2 - u. Let j(c) be the first derivative of c**3 + c**2 + 13. Determine a*j(z) - 7*i(z).
-2*z**2 + z
Let u(x) be the first derivative of -4*x**3/3 - x**2 - 4*x + 15. Let i(q) = q**2 + 1. What is 3*i(c) + u(c)?
-c**2 - 2*c - 1
Let y(g) = 114*g**3 - 11*g**2 + 11*g + 11. Let f(r) = 28*r**3 - 3*r**2 + 3*r + 3. Give -22*f(x) + 6*y(x).
68*x**3
Let r(g) = -2*g**3 + g**2 - g - 3. Let l(p) = 5*p**3 - 3*p**2 + 3*p + 8. Suppose -d - 12 = -2*t - 5*d, 0 = 2*t - 5*d - 21. Give t*r(q) + 3*l(q).
-q**3 - q**2 + q
Let i(r) = -17*r**3 - 9*r**2 - 4. Let m(y) = -35*y**3 - 23*y**2 - 6. Let q(o) = 12*o**3 + 8*o**2 + 2. Let n(d) = -4*m(d) - 11*q(d). Give -6*i(k) - 13*n(k).
-2*k**3 + 2*k**2 - 2
Let o(m) be the second derivative of 3*m**5/20 - m**4/12 + 2*m**3/3 + 5*m**2/2 - 9*m. Let p(s) = 2*s**3 - s**2 + 2*s + 3. What is -3*o(d) + 5*p(d)?
d**3 - 2*d**2 - 2*d
Suppose -7*g + 28 - 70 = 0. Let h(a) = 19*a. Let u(i) = 9*i. What is g*h(p) + 13*u(p)?
3*p
Suppose -14*l + 30 = -9*l. Let a(p) = -4*p**2 - 2*p + 6. Let c(b) be the first derivative of -7*b**3/3 - 2*b**2 + 11*b + 1. Give l*c(z) - 11*a(z).
2*z**2 - 2*z
Let b(n) = -4*n - 2. Let m(f) = 7*f + 3. Give 5*b(q) + 3*m(q).
q - 1
Let v(q) = 2. Let t(i) = -18*i - 30. Give 2*t(o) + 30*v(o).
-36*o
Let k(v) = -3*v - 4*v - 3*v. Suppose -4*d + 5*b = -7, -d + 17 = -2*d - 5*b. Let p(i) be the first derivative of i**2/2 + 1. Calculate d*k(q) - 18*p(q).
2*q
Let y = -34 + 41. Let c(o) = 3*o**3 + 2*o**2. Let v(k) = -8*k**3 - 7*k**2. Determine y*c(s) + 2*v(s).
5*s**3
Let g(o) = -o**2 + 2*o - 2. Let u(p) = 3*p**2 - 7*p + 7. Let r(b) = -2*b - 10. Let w be r(-7). Suppose -t = 3 + w. Calculate t*g(k) - 2*u(k).
k**2
Let k(q) = 31*q - 13. Let g(a) = 8*a - 3. Give -9*g(o) + 2*k(o).
-10*o + 1
Let a(b) = 4 - 5*b**2 - 4*b - 5 - 2*b**2. Let j(g) = -8*g**2 - 5*g - 1. Give 6*a(h) - 5*j(h).
-2*h**2 + h - 1
Let o(i) = -48*i + 48. Let b(n) = -3*n + 3. Determine -33*b(l) + 2*o(l).
3*l - 3
Let p(y) = 4*y**3 + 2*y**2 + 5*y - 7. Let l(s) = -s**3 - s + 1. Give -5*l(t) - p(t).
t**3 - 2*t**2 + 2
Let h(r) be the first derivative of 3 - r - 3/2*r**2 + r**4 - r**3. Let l(a) = -4 - 13*a**2 - 6*a + 17*a**3 + a - 8*a. Determine 26*h(t) - 6*l(t).
2*t**3 - 2
Suppose -2*g = 6 - 2, -3*g = -5*q + 31. Let o(j) = -3*j**2 + 13. Let a(t) = -2*t**2 + 9. Calculate q*o(z) - 7*a(z).
-z**2 + 2
Let z(y) be the third derivative of 7/6*y**3 + 3/8*y**4 + 0*y + 4*y**2 + 0. Let r(i) = -4*i - 3. Calculate -5*r(v) - 2*z(v).
2*v + 1
Let y(w) = -8*w - 6. Let d(j) = -15*j - 11. Let s be 198/(-30) - 1/((-15)/9). What is s*d(v) + 11*y(v)?
2*v
Let o be (9/6)/(3/(-4)). Let b(k) = -1 + 9*k**2 - 2 - 3 - 3 - k**3. Let l(g) = -g**3 + 4*g**2 - 4. Give o*b(r) + 5*l(r).
-3*r**3 + 2*r**2 - 2
Let a(q) = q**2 + q - 1. Let w(s) = -7*s**2 - 6*s + 13. Give 6*a(y) + w(y).
-y**2 + 7
Let s(f) = -f**2 - 1. Let v(p) = -6*p**2 + p - 10. What is 18*s(m) - 2*v(m)?
-6*m**2 - 2*m + 2
Let o(x) = x**3 - 3. Let h(s) = 1. What is -15*h(p) - 5*o(p)?
-5*p**3
Let a(h) = h**2 + h - 1. Let j(v) = 6*v**2 + 5*v - 5. Let q(i) = -15*a(i) + 3*j(i). Let k(c) = 4*c**2 - c - 1. Determine -2*k(g) + 3*q(g).
g**2 + 2*g + 2
Let f(w) = 1. Let t be 1*2/(-4)*-4. Let s(o) = 7*o + 6. Let i(q) = -q + 1. Let y(g) = -6*i(g) - s(g). Calculate t*y(n) + 22*f(n).
-2*n - 2
Let j(z) be the second derivative of -z**5/20 + z**2/2 + 96*z. Let n(r) = 0 - 6 - 3*r**2 + 5*r**2 + 5*r**3. Give -6*j(m) - n(m).
m**3 - 2*m**2
Let d(b) = -b**2 + 2*b - 3. Let n(h) = 2*h**2 - 2*h + 4. Give -3*d(p) - 2*n(p).
-p**2 - 2*p + 1
Let j be (-2)/(-2 + 3) + -1. Let n = 108 + -115. Let s(v) = -3*v - 2. Let g(f) = f + 1. Determine j*s(t) + n*g(t).
2*t - 1
Let m(f) = -f**2 + 7*f - 4. Let i be m(5). Let z(t) = 5*t - 6. Let p be 22/4*(3 + -1). Suppose -2*y + 1 = p. Let u(k) = 4*k - 5. Determine i*u(g) + y*z(g).
-g
Let i(v) = 11*v - 41. Let z(f) = -4*f + 14. Give 3*i(h) + 8*z(h).
h - 11
Let b(o) = 7*o**3 + o**2 - 8*o + 4. Let u(x) = -2*x**3 + 2*x - 1. Calculate -2*b(g) - 9*u(g).
4*g**3 - 2*g**2 - 2*g + 1
Let o(a) = -a**2 + 7*a + 7. Let p(x) be the third derivative of -x**4/24 - x**3/6 - 8*x**2. Determine -4*o(v) - 28*p(v).
4*v**2
Let w(n) = -31*n**3 + 6*n**2 + 6*n + 6. Let z(r) = 2077*r**3 - 403*r**2 - 403*r - 403. Determine -403*w(l) - 6*z(l).
31*l**3
Let j(v) = 2*v**3 + 4*v**2 + 9*v - 4. Let y(d) = d**3 + d**2 + d - 1. Calculate j(u) - 4*y(u).
-2*u**3 + 5*u
Let r(i) = -14*i + 5. Let y(j) = -j + 1. What is -r(k) + 5*y(k)?
9*k
Let g(o) = o + 4. Suppose q = 5*y, 0 = -3*q + 3*y - 6*y. Let r = q - 1. Let u(t) = -4. Let x(i) = 3. Let l(m) = 2*u(m) + 3*x(m). Calculate r*g(d) + 3*l(d).
-d - 1
Let b(l) = -l**3 + 5*l**2 - 3*l - 3. Let s(m) = -2*m**2 + m + 2. Determine 2*b(a) + 5*s(a).
-2*a**3 - a + 4
Let j(b) = 13*b**3 - 2*b**2 + 3*b - 6. Let v(h) = -14*h**3 + 2*h**2 - 4*h + 7. Give -4*j(c) - 3*v(c).
-10*c**3 + 2*c**2 + 3
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The California Supreme Court ruled on Thursday that San Diego’s six-year-old pension cutbacks were not legally placed on the ballot because city officials failed to negotiate with labor unions before pursuing the measure.
The ruling, which could cost the city millions, overturned an appeals court ruling last year that had upheld the cuts.
The Supreme Court ordered the appeals court to take the case back and evaluate the state labor board’s conclusion that 4,000 employees hired since pensions were eliminated must receive compensation that would make them financially whole.
While the unanimous ruling stopped short of reversing the cuts, it essentially ordered the appeals court to invalidate the ballot measure that imposed those cuts.
The ruling directs the appeals court to enact “an appropriate judicial remedy” for the city’s failure to follow all of the legally required steps before placing the measure on the ballot.
The only way to do that, attorneys for the city’s labor unions said, would be to invalidate the ballot measure and nullify the pension cuts.
The ruling vindicates claims by city labor unions that then-Mayor Jerry Sanders needed to engage in labor negotiations before pushing the Proposition B pension measure onto the ballot in 2012.
The measure, which was approved by more than 65 percent of city voters, replaced guaranteed pensions with 401(k)-style retirement plans for all newly hired city employees except police officers.
Sanders maintained he supported the measure only as a citizen, not as mayor, and therefore negotiations with unions weren’t required.
The Supreme Court disagreed in its ruling, concluding Sanders was obligated to meet with the unions before placing the measure on the ballot because he used his power and influence as mayor to support the measure.
“Sanders supported the signature-gathering campaign,” the court said in the ruling, which was written by Justice Carol Corrigan. “He touted its importance in interviews, in media statements, and at speaking appearances.”
Sanders said by phone on Thursday that his actions were based on legal advice he received, and that he still doesn’t believe he acted improperly. But Sanders also said he should have handled things differently.
“If I had it to do all over again — and if I had better advice — we probably would have done meet and confer (labor negotiations),” he said.
San Diego is the only city in California to discontinue pensions for new hires, so the ruling could have an impact across the state as other city and county governments consider pension cuts and how they can be legally enacted.
Supporters of Proposition B have said they may place a similar measure on a future ballot if the cuts are eventually nullified.
In Thursday’s ruling, the Supreme Court emphasized that it wasn’t taking a position on pension cuts.
“We are not called upon to decide, and express no opinion, on the merits of pension reform or any particular pension reform policy,” the ruling said.
The ruling reinstates a 2015 decision by the state labor board that also concluded the city was legally required to conduct labor negotiations before placing Proposition B on the ballot.
In that decision, the labor board ordered San Diego to make employees hired since 2012 whole by compensating them for the loss of pensions and paying them interest penalties of 7 percent. Estimates of how much that would cost the city have ranged from $20 million to $100 million, depending on a variety of factors.
The labor board, formally known as the Public Employment Relations Board, couldn’t invalidate the ballot measure because that power is reserved for state courts.
When the appeals court overturned that decision last year and ruled the city had acted legally when placing the pension cuts on the ballot, the appellate judges didn’t evaluate the proposal to make employees whole because it seemed unnecessary.
The Supreme Court, however, ordered the appellate court on Thursday to evaluate the proposal to make employees whole and to take judicial steps to reverse Proposition B because the city skipped a key legal step when placing it on the ballot.
Supporters of Proposition B on Thursday issued news releases saying that the Supreme Court’s ruling didn’t invalidate the measure or reverse the pension cuts.
Ann Smith, an attorney for the Municipal Employees Association labor union, said by phone on Thursday that those supporters are misreading the ruling.
“They’re out to lunch,” she said. “The Supreme Court is telling the appeals court you should add the judicial remedy of invalidation because that’s the only outcome that’s consistent with the Supreme Court’s binding conclusion that the city violated the law.”
Courts, however, have typically been reluctant to nullify ballot measures that are citizen’s initiatives.
Mayor Kevin Faulconer issued a new release on Thursday afternoon noting that the ruling leaves Proposition B in place until the appeals court acts.
“San Diego pension reform remains the law of the land and today’s Supreme Court decision keeps Proposition B in full force and effect,” the mayor said. “My administration will work closely with the City Attorney’s Office on the direction provided by the Supreme Court.”
A spokesman for City Attorney Mara Elliott said she wouldn’t be commenting on the ruling on Thursday.
Former Councilman Carl DeMaio, who helped write Proposition B, said he was pleased the Supreme Court didn’t overturn the city’s pension cuts, but added that still might occur.
“Taxpayers must be very concerned by what may happen next,” he said in a news release. “Specifically we are concerned that the Supreme Court ruling opens the door for the lower court to consider a yet-undefined ‘remedy’ for the so-called violation of the city of San Diego’s duty to meet and confer on pension changes before implementing them.”
DeMaio said the remedy could be as small as a fine for not meeting and conferring, or as big as overturning part or all of Proposition B. DeMaio vowed to appeal any remedy prescribed by the appeals court to the Supreme Court.
Based on the labor board proposal that the city make employees whole, the actuary for the city’s pension system estimated in late 2015 that it would cost the city $20.1 million for 1,600 employees hired without pensions at that point. But the number of employees hired without pensions has increased to more than 4,000 since then, more than doubling the city’s potential cost.
In addition, new demographic studies showing the city had been underestimating life expectancies for its retirees prompted city pension officials to significantly increase the projected cost of pensions in 2016.
The labor board recommendation, however, said the city could count against its costs the many millions it has contributed to 401(k)-style retirement plans for those workers.
Because of the particularly strong performance of the stock market since 2012, those retirement plans are worth more than expected. That could make the city’s costs relatively minimal.
Employees would also be required to contribute to pensions created retroactively for them, further reducing the city’s costs.
The state labor board ruling didn’t recommend any changes for a separate element of Proposition B, a five-year freeze on pay raises for city employees that expired June 30. The pay freeze was not part of the labor board ruling because the city’s labor unions agreed to it during negotiations with then-Mayor Bob Filner in 2013.
[email protected] (619) 269-8906 Twitter:@UTDavidGarrick
UPDATES:
This story was updated at 3:40 p.m. with additional information and interviews
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Thursday, December 07, 2017
Community: The Final Chapter
If you filter out from the common, mainstream uses of the word “community” all of the obviously non-community-related ones, such as “international community” (a lame euphemism) or “community relations” (a synonym for “public relations”) or “community center” (a synonym for “neighborhood center”) pretty much all that remains is “retirement community.” There are well over two thousand of them just in the US, with close to a million residents.
In comparison, “intentional communities,” including ecovillages, monasteries, communes, survivalist retreats, kibbutzim, ashrams and so on are rather boutique, being mainly aspirational and ideological rather than practical in nature. But added together they present more or less the entire landscape of “communities” within the developed world. And all of them are degenerate cases.
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Embodiments of the present invention relate to determining whether a configuration for an installed subsystem is suitable for operating the subsystem and to providing to an installed subsystem data for a suitable configuration.
Conventional systems are packaged to facilitate maintenance and upgrades by permitting portions of a system to be removed and replaced with a functionally compatible replacement portion. Such portions may be equivalently referred to as subsystems, system components, replaceable units, or line replaceable units (LRUs). A subsystem may be operated by itself apart from the rest of the system for testing, though such operation may be somewhat different from typical system operation, for example, to facilitate diagnostics, analysis of extreme conditions, measurement, calibration, monitoring of internal signals, debugging, or special purpose tests. The specified performance of a subsystem is typically defined for system level operations and may also be defined at the subsystem level by specifying sequences of inputs and acceptable outputs of the subsystem.
Certifying the performance of a subsystem typically includes ascertaining and recording the identity and configuration of the subsystem, isolating the subsystem from other system components (e.g., to assure performance isn""t masked by other subsystems), conducting tests using instrumentation that has been properly calibrated, recording that each step of a test was performed properly with an acceptable result, and recording that all testing was completed satisfactorily. The time, labor, equipment utilization, and management associated with certifying a subsystem represent a costly investment aimed at assuring proper operation of the system under all system operating conditions.
Conventional subsystem design in electronics and software places emphasis on modular design techniques for decreasing development time. These modules may be circuits, circuit assemblies, memory devices, integrated circuits, application specific integrated circuits, or portions of software handled as a unit during software development processes. Such portions of software may include data or instructions in any form readable by human programmers or machines. Subsystems as a whole, and all internal modules, may be designed to perform according to one or more predefined configurations. Typically, a configuration corresponds to prescribed conditions of signals at an electrical interface of the subsystem or module, or to prescribed contents of a memory device. A configuration may establish an initial operating mode (or set of modes) or may, upon configuration change, establish a different mode (or set of modes) for further operations.
Conventional subsystems have been designed to operate with centralized control of subsystem modules. For example, all hardware and software modules for an airplane cockpit system function such as a collision avoidance system computer for a collision avoidance system have been packaged as a line replaceable unit. Also, a system may be installed in a variety of environments, each characterized by different system operations or operational modes. Consequently, for a given subsystem, all modules that may be necessary or desirable for all system environments have typically been included in the subsystem. As the number of environments and the complexity of the system and subsystem increase, the cost of certification of the subsystem has dramatically increased.
Without systems and methods of the present invention, further development of systems and subsystems may be impeded. Development, operating, and maintenance cost targets and performance reliability goals may not be met using conventional system design as discussed above. Consequently, important systems for assuring safety of personnel and equipment may not implemented to avoid injury, loss of life, and destruction of property.
A system, according to various aspects of the present invention, operates in an aircraft and includes several cooperating subsystems. At least one of the subsystems is coupled to an environment memory having content and a plurality of signature values of respective portions of the content. That subsystem includes a nonvolatile memory, an interface, and a processor. The nonvolatile memory includes content and at least one signature value of the content of the nonvolatile memory. The interface facilitates removal and replacement of the subsystem. The processor has access to the environment memory via the interface. The processor validates the content of the nonvolatile memory with reference to the signature value of the content of the nonvolatile memory, validates the content of the environment memory with reference to at least one signature value of the content of the environment memory, updates the content of the nonvolatile memory in accordance with the content of the environment memory, and performs a program in accordance with the updated content of the nonvolatile memory.
By using signatures stored in environment memory and in nonvolatile memory, the processor may easily recognize that the subsystem has been removed from one system and installed in another system. After updating the content of nonvolatile memory, the program operates in a certified configuration for the system where the subsystem is now installed.
A subsystem, according to various aspects of the present invention, operates in a system in accordance with contents of a system memory that is not part of the subsystem. The system memory includes content and a plurality of signature values of respective portions of the content of the system memory. The subsystem includes a nonvolatile memory, an interface, and a processor. The nonvolatile memory has content and a signature value of the content. The interface facilitates removal and replacement of the subsystem. The processor has access to the system memory via the interface. The processor validates the content of the nonvolatile memory with reference to the signature value of the content of the nonvolatile memory, validates the content of the system memory with reference to at least one signature value of the content of the system memory, updates the content of the nonvolatile memory in accordance with the content of the system memory, and performs an application program in accordance with the updated content of the nonvolatile memory.
A tray, according to various aspects of the present invention, accepts a replaceable subsystem. The tray includes an interface and a memory. The interface facilitates removal and replacement of the subsystem. The memory is coupled to the subsystem via the interface. The memory includes a plurality of signatures, each signature associated with a respective portion of the content of the memory. In one implementation, the memory is housed in the shell of a connector of a cable assembly that connects to the subsystem.
By storing a signature in the memory for each of several portions of content, the identity and certification status of that portion of content may be easily ascertained. Greater flexibility results in defining memory content when the identity of each portion of content is independent of its storage location in memory.
A method, according to various aspects of the present invention, operates a subsystem of an avionics system. The avionics system has a plurality of subsystems. The subsystem is packaged as a replaceable unit for installation via an interface of the subsystem. The subsystem includes a processor and a first memory. The system includes a second memory accessed by the subsystem via the interface. The method is performed by a processor of the subsystem and includes in any order: (a) determining a first calculated signature of a first content of the first memory; (b) comparing the first calculated signature with a first stored signature stored in the first memory to conclude validity of the first content; (c) determining a second calculated signature of the second memory, the second memory comprising a plurality of stored signatures for respective portions of the content of the second memory; (d) comparing the second calculated signature with a second stored signature stored in the second memory to conclude validity of the second content; (e) updating the first content in accordance with the second content in response to determining that the first content is valid and the second content is valid and a difference exists among at least two of the first calculated signature, the second calculated signature, the first stored signature, and the second stored signature; and (f) performing an avionics program in accordance with the updated first content.
By determining validity before performing an avionics program, the avionics program may be performed in a certified configuration.
A method, according to various aspects of the present invention operates a subsystem of an avionics system. The avionics system includes a plurality of subsystems. The subsystem being packaged as a replaceable unit for installation via an interface of the subsystem. The subsystem includes a processor and a first memory. The avionics system includes a second memory accessed by the subsystem via the interface. The method is performed by a processor of the subsystem. The method includes in any order: (a) determining whether first content of the first memory is not complete, determining being with reference to a preferences store of the subsystem; and (b) transferring second content from the second memory to the first memory, the second content being identified by a signature.
Use of a signature simplifies identification of portions of content to assure that a preferred certified configuration of an application program is used by the subsystem.
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Here comes the debt: How media is changing the way we wed
In a world where high-cost weddings have the attention of social media, news coverage, advertising and countless reality TV shows, is the media changing the face of weddings, or simply giving audiences what they want?
Comment
By Chandra Johnson
The Rolla Daily News - Rolla, MO
By Chandra Johnson
Posted Apr. 24, 2014 at 12:01 AM
Updated Apr 24, 2014 at 10:39 PM
By Chandra Johnson
Posted Apr. 24, 2014 at 12:01 AM
Updated Apr 24, 2014 at 10:39 PM
When destination-wedding planner Sandy Malone got married in 2004, there was no Pinterest, no Instagram, Facebook was in its infancy and there were few bridal websites to draw from.
Just a decade later, Malone deals with the media's impact on weddings constantly.
"Pinterest is my worst enemy," Malone said. "They put down the deposit, everything's good to go and then they're on Pinterest, they're on Instagram. (The bride) then sees the need to add more things and do more stuff. My clients are so plugged into social media that they even have their own hashtags for their guests. There are a lot of things that are growing with the expansion in the media that are feeding the wedding industry."
According to TheKnot.com, the average cost of a wedding is now $28,427. Not included in The Knot's study is a new arrival to the wedding scene, unveiled at New York's W Hotel this winter: A social media concierge at the venue. The price for a perfectly Instagrammed, hashtagged and live-tweeted affair is a cool $3,000; evidence that social media may become as valued as a professional photographer or wedding planner to today's couples.
In a world where high-cost weddings have the attention of social media, news coverage, advertising and countless reality TV shows, is the media changing the face of weddings, or simply giving audiences what they want?
Elizabeth Fairbanks-Fletcher with the Society for New Communications Research says the media play a big role in telling us what's normal.
"The Internet specifically makes all that information accessible," Fairbanks-Fletcher said. "The media coverage of celebrity weddings is now the benchmark for individuals planning their own. Advertising can spur the interest, but reality TV and the Internet create renewable engagement. They all work together to continually fan the flames of interest."
The media coverage also fans the flames of a business that nets an estimated $80 billion per year.
"Every time some pop star gets married and it's all over the cover of People Magazine, it inspires more girls to have destination weddings. Just like little girls emulate what they see, so do young women who are watching the stars," Malone said. "People joke about how the funeral business is the one business that's always fine. So is the wedding industry. The only difference is there's a lot more room for potential growth without a plague."
Brad Wilcox, a sociologist and the director of the National Marriage Project, says that it isn't just the weddings that have changed - we've changed, too.
Wilcox says that since the 1970s and the advent of no-fault divorce, Americans look at marriage with less permanency and couples may compensate with an elaborate wedding.
"Because there's not much legal protection anymore because of no-fault divorce, it signals that the couple and their family are financially vested in the marriage," Wilcox said. "In some ways, a big wedding is an exclamation point saying, 'we understand the fragility of marriage and despite everything, we're going to get married.' "
Beyond the media
There's research to support Wilcox's claims. A 2010 Pew Research study found that marriage is less common than it once was. In 2008, 52 percent of American adults were married, down from 72 percent in 1960.
Education and class distinction played a major role as well. In 2008, 48 percent of people without a college degree were married, compared to 64 percent of college graduates. In 1960, a college grad was only 4 percent more likely to marry than someone with a high school diploma or less.
"There's a growing marriage divide in America," Wilcox said. "I think one reason is that over-the-top weddings are a barrier to entry into marriage for the working class and poor Americans."
Elevated ideals, serious consequences
Romanticized ideas of marriage and weddings not only play out in the media, but can also have major consequences for new couples that buy into them.
Mary Claire Allvine is a financial adviser who wrote "The Family CFO," for young couples planning their future. She says the media pressure on couples is real and so are the financial ramifications.
"Anytime you see a wedding whether it's in a movie or it's on a television show, these are enormous, complicated affairs. It causes people to become de-linked from their own value structure," Allvine said. "The 'Today Show' will give someone a fantasy wedding. When you put a label on it of 'reality' presented on a news show and don't say this is a massive trade-off where this couple may never get out of credit card debt."
But the struggle also lies with us, she added. As a bride 13 years ago, Allvine got a firsthand look at the pressure the wedding industry puts on couples when she went into the Macy's bridal boutique. She said she found a staff eager to show her gowns that began at $1,500. Allvine walked out.
"I was 35 years old. If I had been 25 and intimidated by the way they said, 'a lot of girls,' it's harder to do that," Allvine said. "If you or your future partner doesn't say, 'That's out of our reach,' at what point is it not the movies' fault but the fault of your own process?"
The younger the couple, the more vulnerable they can be to the message. Lisa Firestone is a California-based clinical psychologist and director of research at the Glendon Association, a nonprofit organization dedicated to addressing suicide, abuse and troubled relationships.
"You don't see older people who are getting married worrying quite so much about this whole thing," Firestone said. "Younger people have grown up where everything about your life is shown in pictures online. Some young people today have grown up with parents having broken marriages and they may be buying into this romanticized idea of the perfect, forever kind of wedding."
That "forever" kind of wedding portrayed so often in the media is a fantasy that can veil real problems.
"It becomes a very shallow focus when we get into the fantasy of the relationships instead of caring about the real content," Firestone said. "It makes people feel like their relationship isn't good enough if they can't do the big, expensive wedding."
Unfortunately, brides and grooms aren't encountering a lot of moderation in either the media or the retail world.
"What you need is a gaggle of women sitting around saying: 'You would look so good retired someday," Allvine said. "Where's the cheerleading crowd for that?"
Malone, whose Puerto Rico-based wedding business has been the subject of the reality show, "Wedding Island," said the media attention isn't all bad.
"There are a lot of TV shows out there that are setting expectations very high. I don't know that that's bad. There's nothing wrong with young girls dreaming about their weddings," Malone said. "We're looking at an industry that's grown when the economy has consistently gone downhill. People may be giving up their cable TV and Starbucks may be full of people that don't have Wi-Fi at home, but they are not giving up on their weddings."
Balancing fantasy and reality
As weddings continue to fascinate through television and social media, many couples are taking matters into their own hands.
That's what Dana LaRue did when she got engaged and became overwhelmed. LaRue's experiences created one of the most popular DIY wedding blogs on the Internet, which shares innovative and resourceful ways to weddings on a budget.
"The media tries to pressure couples into thinking that they need to spend a certain amount of money on this or that element," LaRue said. "There's a great deal of voyeurism happening with reality television and manufactured celebrity events that are publicized. People seem to have this innate desire to peer into these other worlds whether or not we know they're manufactured."
With a mission of "empowering couples to use their creativity" to "save your money and sanity," LaRue's enterprise straddles the line between wedding extravagance and what the site calls "real weddings," where couples can share details of their day and tips for staying on-budget.
"It's not about being cheap, it's about spending smart," LaRue said. "There's a shift in the way couples today approach the expense of a wedding vs. that old-fashioned mentality of having to spend $20,000-$50,000 on one day of your life."
One piece of advice Malone gives couples? Focus finances toward what's most important. Malone gets all kinds of over-the-top requests from brides-to-be.
"My favorite is the girl that wanted elephant rides on the beach. I actually researched how to rent an elephant," Malone said. "I have to put up a tipi for a wedding in April. They didn't ask me about it, they just said, 'We're shipping you a tipi.' "
LaRue also suggests tailoring tradition to individual needs, no matter how much pressure may be coming from TV or computer screens.
"At the end of the day, it really is up to you what you do or don't include. And if somebody's going to judge you for that, that's their problem, not yours," LaRue said. "It's really about following your own heart."%3Cimg%20src%3D%22http%3A//beacon.deseretconnect.com/beacon.gif%3Fcid%3D164590%26pid%3D46%22%20/%3E
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Intracellular localization of carbonic anhydrase in the frog nephron.
The intracellular distribution of carbonic anhydrase has been studied in the frog nephron by a histochemical method. The study of the detailed intracellular localization was possible by sectioning tissue embedded in plastic (Sorwall, JB-4), before staining essentially according to Hansson. This procedure preserves the intracellular structure well and the resolution is high. For light microscopy sections from 1 to 10 mum were used. For electron microscopy 0.25 mum thick sections were stained and examined in the electron microscope using an accelerating voltage of 100 kV. The highest concentrations of the enzyme seem to be localized to the cell membranes or their immediate neighbourhood. A faint cytoplasmic staining may sometimes be observed. In distal tubule cells the apical part of the cell membrane was heavily stained. Weaker staining was found at the lateral membranes and their infoldings and to some extent the basal parts of the cell membrane. In the canaliculi cells only the lateral and basal parts of the membranes were stained. This latter localization is similar to that in the parietal cells of the mammalian stomach.
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Gastric antral motility in functional dyspepsia. Effect of mental stress and cisapride.
Disordered gastric antral motor activity may be induced by mental stress. The effect of cisapride on these abnormalities has previously not been investigated. Ten healthy subjects and 19 patients with functional dyspepsia (FD) and erosive prepyloric changes participated in the study. Antral motility was recorded with real-time ultrasonography after ingestion of 500 ml meat soup during i) a 4-min rest period, ii) 2.5 min of mental stress, and iii) a 4-min recovery period. Patients and controls were studied after 3 days of treatment with 10 mg cisapride three times daily and placebo in a double-blind crossover design. Mean postprandial amplitude of antral contractions was lower in patients than controls (p < 0.001). Antral amplitude was reduced by mental stress in healthy persons (p < 0.001) but not in patients. Both fasting and postprandial antral areas were larger in FD patients than controls (p < 0.001 and p = 0.02, respectively). Cisapride reduced the fasting (p < 0.001) and the postprandial (p = 0.05) antral area in the FD group but not in controls. The soup meal produced dyspeptic symptoms in 90% of the patients and in only 10% of the controls (p < 0.001). Cisapride had no significant effect on symptoms or antral contractions. Mental stress induced antral hypomotility in healthy subjects but not in patients with FD who had reduced motility at base line. Cisapride reduced the enlarged fasting and postprandial antral areas in the patients but had no effect on amplitudes of antral contractions or symptoms.
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Q:
"Postfix" or "suffix"?
Wikipedia and The Free Dictionary were not much help — is there a practical difference in the semantics of suffix and postfix, except that the latter is more rare?
File name extensions are well known. For example, index.en.xhtml could reasonably be assumed to be the index file of a website directory, in XHTML format, and with primarily English, human-readable contents. I’d normally call the collection of extensions (.en.xhtml in the example) the suffix or postfix, but it’s not obvious which (if any) is technically and/or semantically more accurate.
A:
I think both can be used interchangeably, although the context sometimes determines which word you are more likely to use. For example, in linguistics, an affix after the stem of the word is called a suffix. In computer programming, when an operator appears after the operand, it is known as a postfix operator.
As far as a file extension goes, my intuition would be to go with "suffix", but I believe that "postfix" would be equally valid.
The word "suffix" has been around since 1778. I was unable to uncover a similar etymology for the word "postfix", leading me to guess that it is a modern invention, as "post-x" is a more obvious candidate for being the opposite to "pre-x". In this regard it is very much like prepone in Indian English, except that it has caught on globally.
A:
From a "pure" English standpoint, postfix is essentially a lesser-used synonym for suffix, both in the noun and verb sense (with the verb being the act of adding a suffix). In fact, my dead-tree American Heritage Dictionary, 2nd College Ed. gives these (and only these) definitions of postfix:
n. A suffix.
tr v. To suffix.
More modern definitions of postfix have cropped up, including the adjective used in computing and mathematics, and a medical verb.
I disagree with Roaring Fish's analysis of the n-grams. I believe postfix and suffix are both rising in large part because of their use in computing. Computer programmers typically use postfix only as an adjective and suffix only as a noun. Therefore, the thing that comes after a dot in the name of a file would only be referred to as a suffix (given just these two choices). The use of suffix dwarfs that of postfix even in computing because plenty more people are exposed to file extensions than to mathematical or programming notation.
Finally, I would like to say that for your particular use (denoting the part or parts of a file name following a dot), extension is actually the most common and preferred term. Normally it refers only to the stuff after the last dot, so if you want to specify the collection of extensions, the most clear alternative is to say just that, or something to its effect. (Other possibilities might be stack, string, or series of extensions.)
A:
In linguistics, the term "postfix" is not so widespread in Anglophone linguistics, the more common one being "suffix".
Indeed, there is a difference between a suffix and a postfix. A postfix is whatever comes after the base of a word, be it a suffix or an ending or even an enclitic. Thus, under this interpretation, a postfix is a hyper(o)nym, whereas a suffix is a hyponym.
The term "postfix" is somewhat more common in German and Russian linguistics, cf. Hall 2000:
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package com.xabber.android.ui.adapter.chat;
import android.view.View;
import com.xabber.android.data.database.messagerealm.MessageItem;
public class NoFlexForwardedVH extends ForwardedVH {
public NoFlexForwardedVH(View itemView, MessageClickListener messageListener,
MessageLongClickListener longClickListener, FileListener listener,
int appearance) {
super(itemView, messageListener, longClickListener, listener, appearance);
}
@Override
public void bind(MessageItem messageItem, MessagesAdapter.MessageExtraData extraData, String accountJid) {
super.bind(messageItem, extraData, accountJid);
if (messageText.getText().toString().trim().isEmpty()) messageText.setVisibility(View.GONE);
}
}
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Spread the love
The Trump administration is working hard to stem the spread of Coronavirus while trying to keep the economy moving.
No matter if you believe President Trump is doing the job well, or he could have done better that is fair to debate because they are major issues that will impact millions of Americans.
But what are journalists in the White House press pool asking Trump?
What are the Democrat politicians screaming about after President Trump’s daily Coronavirus Press briefings?
They want to know why he keeps calling it the Wuhan Virus and/or the China virus because they want to claim President Trump is a xenophobic racist.
Responding to a question from Fox News anchor Martha MacCallum about whether former Vice President Joe Biden and others should say “this is a moment to get behind our president”.
Joe Biden’s senior campaign adviser Symone Sanders, immediately launched into her well-rehearsed ‘He’s a Racist’ diatribe about President Trump’s usage of the term “Chinese virus.”
Fox News “The Story with Martha MacCallum” host challenged Symone Sanders to answer, Why the President using the term “Chinese coronavirus” is a “racial slur”?
Symone Sanders fictitiously claimed “It’s something that’s offensive to many Americans,”
What made this exchange so hysterical was the fact that Symone Sanders answer destroyed her own Trump is a racist narrative, while also exposing the liberals attack as nothing more than typical Democrat stupidity.
Symone Sanders Racist Stupidity
Of course, to prove she’s nothing more than Biden’s moronic mouthpiece, Symone Sanders was so excited to call President Trump a racist, she claimed President Trump called the Coronavirus “COVID-19” which Sander’s laughably claimed was a racist slur.
But as Symone Sanders tried to avoid giving a reason why using the name of the originating region most viruses are typically named after is now all of a sudden racist.
Symone Sanders casually mentions the “Ebola Crisis” which, of course, is the name of the African river from which the virus takes its name.
Sanders using “Ebola” completely destroys the Democrats idiocy that Trump is a racist because he called the virus “Wuhan”.
RELATED STORY Trump Trolls Media With ‘Chinese Virus’ Tweet
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239 F.3d 626 (4th Cir. 2001)
CLIFTON E. SPENCER, PETITIONER-APPELLANT,V.ERNEST SUTTON, RESPONDENT-APPELLEE.
No. 99-7007.
U.S. Court of Appeals, Fourth Circuit.
Argued: September 28, 2000.February 07, 2001.
Appeal from the United States District Court for the Eastern District of North Carolina, at Raleigh.
W. Earl Britt, Senior District Judge. (CA-99-46-5-2BR)Argued: Letitia C. Echols, North Carolina Prisoner Legal Services, Inc., Raleigh, North Carolina, for Appellant. Clarence Joe DelForge, III, Assistant Attorney General, North Carolina Department OF Justice, Raleigh, North Carolina, for Appellee.
On Brief: Michael F. Easley, Attorney General, North Carolina Department OF Justice, Raleigh, North Carolina, for Appellee.
Before Luttig and King, Circuit Judges, and Hamilton, Senior Circuit Judge.
1
Affirmed by published opinion. Judge Luttig wrote the majority opinion, in which Senior Judge Hamilton joined. Judge King wrote a dissenting opinion.
OPINION
Luttig, Circuit Judge
2
Clifton Spencer pled no contest to the murder of Stacy Stanton. The district court dismissed Spencer's subsequent petition for a writ of habeas corpus as untimely, and he now appeals. Although for different reasons than those relied upon by the district court, we also conclude that Spencer's petition was untimely. Accordingly, we affirm the judgment of the district court.
I.
3
Stacy Stanton was found dead on her living room floor on February 3, 1990. She was sprawled on her mattress, with over sixteen stab wounds to her body. J.A. 349-52. Based on information that Spencer planned to visit the victim on the night of her murder, police questioned Spencer, who made numerous incriminating statements. J.A. 176-78, 356-62. Spencer was later indicted for first-degree murder, and the prosecutor announced his intention to seek the death penalty. J.A. 196.
4
On January 9, 1991, based on advice from his mother and his attorney, Spencer pled no contest to a charge of second-degree murder, the sentence for which was life imprisonment. Thereafter, Spencer filed a motion for appropriate relief (MAR) in North Carolina state court, in which he raised several claims, including ineffective assistance of counsel. After an evidentiary hearing, the court denied the MAR, and the North Carolina Court of Appeals subsequently denied Spencer's certiorari petition. J.A. 51, 75.
5
Spencer did not pursue further collateral relief for almost three years following the Court of Appeals' June 3, 1994, denial of certiorari. Then, on April 23, 1997, Spencer filed a second MAR in Dare County Superior Court. Based on the statement of a witness who had contacted his attorney in July 1995, nearly two years earlier, Spencer alleged in his second MAR that the state, in violation of Brady v. Maryland, 373 U.S. 83 (1963), had failed to disclose the names of witnesses who made exculpatory statements. J.A. 76-79. The court denied Spencer's second motion for appropriate relief on June 17, 1997. Spencer filed a certiorari petition to the North Carolina Court of Appeals on June 23, 1997, and an evidentiary hearing was ordered. J.A. 97-116.
6
Because Spencer had not filed his second motion for appropriate relief until the day before the one-year limitations period ran on his right to file a federal habeas petition, he was concerned that, due to the time necessary to receive notification of state court action by the ordinary mail, he would not learn of any state court order denying him relief before the remaining day of the federal filing period lapsed. Therefore, Spencer filed a motion in federal court for a fourteen-day extension of the one-year statute of limitations. The district court granted the extension on February 3, 1998. J.A. 124-27.
7
Following the state evidentiary hearing on Spencer's Brady claim, the state court denied Spencer's second MAR on April 24, 1998. J.A. 128-30. On May 6, 1998, Spencer filed a motion for preparation of a transcript, and, on May 13, 1998, a certiorari petition to the North Carolina Court of Appeals together with a motion to amend the petition after receipt of the transcript. J.A. 132-38. Several weeks later, the Court of Appeals dismissed the petition without prejudice to refile after receipt of the transcript. J.A. 193. Spencer eventually received the transcript and, on September 18, 1998, filed a motion for ruling on a claim of newly discovered evidence, which was denied on December 9, 1998. J.A. 140-44, 191.
8
Spencer then filed a certiorari petition to the North Carolina Court of Appeals on December 18, 1998. That court denied the petition on January 13, 1999, thus exhausting Spencer's state remedies. J.A. 192. And, six days later, on January 19, 1999, Spencer filed a petition for a writ of habeas corpus in federal district court pursuant to 28 U.S.C. § 2254, in which he claimed that his counsel was ineffective and that the prosecution failed to disclose exculpatory evidence. J.A. 12-38.
9
The federal district court held that Spencer's habeas petition was untimely because the one-year statute of limitations applicable to habeas petitions in the federal courts was not tolled during the more than fifteen days that elapsed between the various denials of Spencer's claims and the resulting filings of appeal over the course of his pursuit of his second MAR. Thus, reasoned the district court, even though the statute of limitations was equitably tolled for fourteen days, Spencer was still tardy in the filing of his habeas petition. J.A. 406-12, 424-25. This appeal followed.
II.
10
The timeliness of Spencer's habeas petition is governed by the Antiterrorism and Effective Death Penalty Act of 1996 (AEDPA).1 The AEDPA was signed into law on April 24, 1996, and became effective immediately. It provides in relevant part as follows:
11
A 1-year period of limitation shall apply to an application for writ of habeas corpus by a person in custody pursuant to the judgment of a State court. The limitation period shall run from the latest of -
12
(A) the date on which the judgment became final by the conclusion of direct review or the expiration of the time for seeking such review....
13
28 U.S.C. § 2244(d)(1). For prisoners like Spencer, whose criminal convictions preceded enactment of the AEDPA, the limitations period began to run with the AEDPA's effective date on April 24, 1996, and ended on April 24, 1997. Hernandez v. Caldwell, 225 F.3d 435, 439 (4th Cir. 2000).
14
Here, as noted, the district court equitably tolled the AEDPA's oneyear limitations period for fourteen days. The court nonetheless dismissed Spencer's petition as untimely, holding that the statute was not tolled during the days (in excess of 15) between the various state court denials of the claims raised by Spencer in his second motion for relief and his appeals from those denials.
15
If the district court was incorrect in its decision not to toll the statute during the fifteen or more total days between the state denials of Spencer's claims and Spencer's appeals from those denials, then Spencer's habeas petition was timely filed, assuming the court was correct in its decision to equitably toll the statute of limitations for fourteen days. Paradoxically, however, if the district court was incorrect not only in its decision not to toll during the so-called "gaps" between state proceedings, but also in its decision equitably to toll the statute for the fourteen days to accommodate the ordinary mails, then the court was correct in its ultimate conclusion that Spencer's petition was untimely.
16
For the reasons that follow, we hold that the district court actually did err in both of its tolling decisions, and therefore that Spencer had only one day after the final disposition of his second state MAR in which to file his federal habeas petition. Because he filed his habeas petition six days after the state court finally disposed of his motion, his petition was, in fact, untimely.
A.
17
As to the district court's decision not to toll the statute of limitations during the times between a state court's denial of Spencer's claims and Spencer's appeal from that denial, the AEDPA provides as follows:
18
The time during which a properly filed application for State post-conviction or other collateral review with respect to the pertinent judgment or claim is pending shall not be counted toward any period of limitation under this subsection. 28 U.S.C. § 2244(d)(2). The district court held that this provision only authorizes the tolling of the statute during times when an application for relief was literally pending in a state tribunal and does not authorize tolling during times between the denial of a claim by a state court and the appeal from that denial. Although it was entirely reasonable for the district court to have so held, we held subsequent to the district court's decision, in Hernandez v. Caldwell, that the limitations period is tolled from the time an application for state post-conviction or other collateral review is initially filed until it is finally disposed of by the state courts, including during times between denials of claims and appeals. 225 F.3d at 438. Therefore, the district court erred in not tolling the statute of limitations for the entire period from Spencer's initial filing of his second MAR on April 23, 1997, until its final disposition on January 13, 1999.
B.
19
Because the district court erred in not tolling the statute of limitations during the gaps between the various North Carolina state court denials of Spencer's claims and Spencer's appeals from those denials, Spencer's habeas petition was timely filed unless the district court also erred in its decision to toll the statute equitably for fourteen days following the state court's final disposition of Spencer's second motion for appropriate relief. If the court erred in this latter regard as well, then of course Spencer had only one day remaining after the state court's final disposition of his second MAR in which to file his federal habeas petition, and, because he did not file until six days after that disposition, his petition was untimely.
20
"[A]ny invocation of equity to relieve the strict application of a statute of limitations must be guarded and infrequent, lest circumstances of individualized hardship supplant the rules of clearly drafted statutes." Harris v. Hutchinson, 209 F.3d 325, 330 (4th Cir. 2000). For this reason, equitable tolling is available only in "those rare instances where -- due to circumstances external to the party's own conduct -- it would be unconscionable to enforce the limitation period against the party and gross injustice would result." Id. It is appropriate when, but only when, "extraordinary circumstances beyond [the petitioner's] control prevented him from complying with the statutory time limit." Id.
21
The district court equitably tolled the statute of limitations because Spencer waited until the final day of AEDPA's one-year limitations period before filing his second state motion for appropriate relief, thus allowing himself but a single day after the state court's final disposition in which to file his federal habeas petition-- an insufficient amount of time within which for Spencer to receive notice of the decision via the ordinary mail. J.A. 125-26. Even assuming arguendo that an inordinate delay in the delivery of the mail could be so regarded, we do not believe that the ordinary time that it takes to deliver the mail can be regarded as a "circumstance[ ] external to [a] party's own conduct" within the contemplation of the equitable tolling doctrine. Cf. Sandvik v. United States, 177 F.3d 1269 (11th Cir. 1999) (refusing to toll statute where tardiness was due to lawyer's decision to send petition by the ordinary mails). And to accept it as such, effectively would be nothing short of to extend judicially the legislativelyprescribed one-year statute of limitations. Every person knows, or should know, that it can take at least several days to receive mail even from within the same postal jurisdiction, and he can, and may reasonably be required to, adjust his conduct accordingly. Ordinary delivery time is not a "rarity," nor is the charge of knowledge of such to the habeas petitioner "unconscionable."
22
Even were we inclined to recognize equitable tolling to accommodate the time ordinarily necessary to deliver the mail, we would be disinclined to extend the doctrine under the circumstances with which we are presented here. That Spencer had only one day remaining in the limitations period is solely the result of his own strategic decision not to file his MAR until the final day before the one-year federal limitations period expired. Were it not for Spencer's own delay, the time needed for ordinary mail delivery almost certainly would not have affected the timeliness of his habeas petition. Moreover, not only did Spencer wait until the eleventh hour to file his second state motion; he did not file that second motion for almost two years after first learning of the information upon which he now bases his principal claim. J.A. 79 (affidavit of Barbara McGuinness, a witness whose statements the police allegedly withheld in violation of Brady) ("Upon reading about Clifton [Spencer's] case in the Virginian Pilot Newspaper on July 4, 1995, I contacted attorney Edgar Barnes [Spencer's attorney] and told him about the facts stated above."); see also Appellant's Reply Br. at 7 (conceding that Spencer learned of witness information in 1995).2
23
Indeed, it is apparent that Spencer has delayed at every juncture of his post-plea, state and federal proceedings. Although the criminal judgment against Spencer became final when he pled no contest to second-degree murder in January 1991, he waited over a year, until April 1992, to file his first state MAR. After his first MAR was finally disposed of in June 1994, Spencer waited almost three more years -- until April 1997 -- to file his second MAR, pursuing no collateral relief in the meantime, even though he knew the information on which he now bases his Brady claim. He finally filed his federal habeas petition in January 1999 -- eight years after the judgment against him became final, only four of which were consumed with the pursuit of collateral relief in state court. This is not, we are satisfied, a petitioner with a special call on equity.
CONCLUSION
24
Because the district court erred in not tolling the AEDPA's statute of limitations during the times between the various denials of Spencer's claims and his appeals from those denials while he pursued his state court remedies, but also erred in its fourteen-day tolling of the statute in equity, Spencer had only one day following the denial of his second certiorari petition by the North Carolina Court of Appeals in which to file his federal habeas petition. Spencer's filing of his habeas petition six days after the final disposition of his second state MAR, accordingly, was untimely. The judgment of the district court is therefore affirmed.
AFFIRMED
NOTES:
1
The Supreme Court held in Slack v. McDaniel, 529 U.S. 473, 484 (2000), that, [w]hen the district court denies a habeas petition on procedural grounds without reaching the prisoner's underlying constitutional claims, a COA [certificate of appealability] should issue when the prisoner shows, at least, that jurists of reason would find it debatable whether the petition states a valid claim of the denial of a constitutional right and that jurists of reason would find it debatable whether the district court was correct in its procedural ruling. We assume for purposes of this appeal that the requirements of Slack for the issuance of a COA are satisfied.
2
Spencer claims that the police withheld statements taken from witnesses Barbara McGuiness and Dawn Beacham about a protracted public argument between Stacy Stanton, her boyfriend, Mike Brandon, and his mistress, Patty Rowe, on the night before Stanton was killed. J.A. 18. The state court held that the statements given to police were not exculpatory and that Spencer failed to show that discovery of the statements would have caused him to change his plea. J.A. 128-30. While we need not decide the merits of Spencer's Brady claim, the fairest inference based on the transcript of the hearing in state court is that, at most, the two witnesses told police about threats of some kind toward the victim, but not about death threats. J.A. 160, 163, 165, 182-83, 187. Furthermore, the record indicates that Spencer already knew about tension and conflict between the victim and her boyfriend on the night before the murder. J.A. 167-69.
KING, Circuit Judge, dissenting:
25
Because of Spencer's detrimental reliance on the fourteen-day extension granted by the district court's Order of February 3, 1998, he is entitled to invoke the "unique circumstances" exception to the jurisdictional bar his untimely claim would otherwise present. I would therefore vacate the dismissal of Spencer's petition, and I would remand his case for further consideration.
I.
26
The majority correctly concludes that the district court erroneously tolled the AEDPA one-year statute of limitations to account for delays inherent in the delivery of the mail. Ante, at 630. Indeed, an ordinary delay in mail delivery cannot be regarded as a "circumstance[ ] external to [a] party's own conduct" within the meaning of equitable tolling. Ante, at 6. In my view, however, the inquiry should not end there.
A.
27
Spencer's state petition was filed in time to toll the AEDPA oneyear statute of limitations -- exactly one day before it expired. Later recognizing that slow mail delivery might cause the anticipated federal petition to be untimely, Spencer sought and received a fourteenday extension from the district court (providing him, after exhaustion of his state post-conviction remedies, a putative total of fifteen days within which to file his federal petition). Spencer reasonably relied on the extension Order -- and that reliance was fatal. My friend Judge Luttig, in considering Spencer's habitual dilatoriness, has concluded that Spencer does not have "a special call on equity." Ante, at . I respectfully disagree. Had the extension Order not been granted, Spencer could otherwise have filed his petition in a timely manner. His detrimental reliance on the extension Order therefore presents a compelling case for the exercise of our jurisdiction under the "unique circumstances" doctrine.
B.
28
The Supreme Court, for over thirty-five years, has recognized our power to equitably alter jurisdictional deadlines when a litigant has detrimentally relied on a court order or statement. In Thompson v. INS, 375 U.S. 384 (1964) (per curiam), the petitioner filed a naturalization petition with the district court, which was denied on April 18, 1962. Id. at 384. Twelve days later (April 30), the petitioner filed a motion to amend, along with a motion for a new trial. Those motions were, under the applicable rules, two days late. The government did not object, however, and the court specifically held the post-trial motions to be timely. The motions were then denied on October 16, 1962, and a notice of appeal was filed on December 6, 1962. The appeal was therefore filed within sixty days from the denial of the post-trial motions, but not within sixty days from the April 18 denial of the naturalization petition. Id. at 385.
29
The Supreme Court acknowledged that, under a literal application of the rules, Thompson's appeal was untimely because the tardy posttrial motions were ineffective to toll the sixty-day period for filing the appeal. The Court held, however, that since the petitioner "filed the appeal within the assumedly new deadline but beyond the old deadline.... `unique circumstances'" mandated that the appeal be deemed timely. Id. at 387.
30
Given his detrimental reliance on the extension Order, Spencer presents an equally compelling case of "unique circumstances." Indeed, this exception has been used widely by appellate courts to hear otherwise untimely appeals. Wolfsohn v. Hankin, 376 U.S. 203 (1964) (per curiam); Hollins v. Department of Corrections, 191 F.3d 1324, 1326-28 (11th Cir. 1999) (habeas counsel's reliance on court's computerized docket information sheet constituted unique circumstance when final judgment was never shown on the system); Estle v. Country Mut. Ins. Co., 970 F.2d 476, 478 (8th Cir. 1992) (finding notice of appeal timely because the plaintiff was"lulled into inactivity" by district court's erroneously granted extension) (quoting Willis v. Newsome, 747 F.2d 605, 606 (11th Cir. 1984)); Fairley v. Jones, 824 F.2d 440, 442-43 (5th Cir. 1987) (detrimental reliance on magistrate's unauthorized extension of time for filing notice of appeal constituted "unique circumstances justifying our exercise of jurisdiction"); Government of the Virgin Islands v. Gereau, 603 F.2d 438 (3d Cir. 1979) (applying unique circumstances doctrine to jurisdictional deadline for filing motion to reduce prior sentence). See also Myers v. Stephenson, 748 F.2d 202, 205 (4th Cir. 1984) (dicta) ("To the extent Myers' failure to request an extension is attributable to the district court's [erroneous] assurance, he may be entitled to appellate consideration of his claims in spite of his failure to comply fully with [the applicable time limits].").
31
While the validity of the unique circumstances doctrine has been sometimes called into doubt, its vitality continues to be recognized. United States v. Heller, 957 F.2d 26, 28-29 (1st Cir. 1992) (noting that many courts have questioned the doctrine, but that "[t]he Supreme Court [ ] passed up an opportunity to repudiate it" and "courts of appeals generally have continued to assume that the doctrine remains viable."); In re Mouradick, 13 F.3d 326, 329 n.5 (9th Cir. 1994). See also Thurston Motor Lines, Inc. v. Jordan K. Rand, Ltd., 460 U.S. 533, 535 (1983) (per curiam) ("Needless to say, only this Court may overrule one of its precedents. Until that occurs, [Supreme Court precedent] is the law.").
32
Furthermore, proscriptions properly placed on the unique circumstances doctrine have no application here. In this situation, Spencer received specific assurance from the extension Order, unchallenged by the State of North Carolina, that the statute would be tolled for fourteen additional days. Cf. Moore v. South Carolina Labor Bd., 100 F.3d 162, 164 (D.C. Cir. 1996) (doctrine limited to"written court orders or oral rulings made in the course of a hearing"); Hope v. United States, 43 F.3d 1140, 1143-44 (7th Cir. 1994); Heller, 957 F.2d at 30-31. Nor was Spencer's reliance on the extension Order unreasonable. Cf. Feinstein v. Moses, 951 F.2d 16, 19-20 (1st Cir. 1991); Pinion v. Dow Chemical, U.S.A., 928 F.2d 1522, 1532 (11th Cir. 1991); Kraus v. Consolidated Rail Corp., 899 F.2d 1360, 1365-66 (3d Cir. 1990). Moreover, nothing in AEDPA expressly forbade the district court from granting the extension. Cf. Weitz v. Lovelace Health System, Inc., 214 F.3d 1175, 1178-80 (10th Cir. 2000) ("unique circumstances" did not apply because"[u]nlike a situation where some extension of time was permissible, here the rules specifically and directly prohibit courts from granting any extensions").*
33
Spencer's reliance on an explicit and valid court order should not render his habeas corpus petition unreviewable. In the unusual situation presented here, I believe Spencer to be entitled to consideration of his petition. I respectfully dissent.
NOTE:
*
Indeed, we have acknowledged that equitable tolling is available in some situations. Harris v. Hutchinson, 209 F.3d 325, 329-330 (4th Cir. 2000). It is not until today that we have specifically held that district courts are without power to grant an equitable extension under the facts presented here. Thus, Spencer's reliance on the extension Order would not present the problems the Tenth Circuit found determinative in Weitz.
|
Q:
how can i shorten the border-left height property in css
I have made a simple address panel where i have made three panels of each consisting of address,phone number and email.Each panels consist of an icon and an paragraph besides it.I have use vertical align:top and display table property to align them side by side.Then i have given a border-left property to the main div that consist all this divs inside of it.I want to have a design such that the line should go through the icons and and not exceed the top and bottom icon.But the problem is happening here where the main consist all these icons and there are some padding and margin, hence it is crossing over and can't fix it even when i remove margin and padding.I want to have a design such that the icons shouldn't exceed top and bottom icons.And if anyone is suggesting position property,just keep in mind i have a div inside another col-md-6 which has a position absolute.
Here is the HTML part:-
<div class="row">
<div class="col-md-6 col-sm-12">
<h2 class="heading-title">Drop in our office</h2>
<p>Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.</p>
<div class="address-top">
<div class="address-repeat">
<div class="address-left">
<div class="body-widget">
<i class="fa fa-map-marker" aria-hidden="true"></i>
</div>
</div>
<div class="address-right">
<div class="body-widget">
<label>ADDRESS</label>
<p>Huatai Securities (USA)10 Hudson Yards 41FlNY, NY 10001</p>
</div>
</div>
</div>
<div class="address-repeat">
<div class="address-left">
<div class="body-widget">
<i class="fa fa-phone" aria-hidden="true"></i>
</div>
</div>
<div class="address-right">
<div class="body-widget">
<label>LETS TALK</label>
<p>212-763-8166</p>
</div>
</div>
</div>
<div class="address-repeat">
<div class="address-left">
<div class="body-widget">
<i class="fa fa-envelope" aria-hidden="true"></i>
</div>
</div>
<div class="address-right">
<div class="body-widget">
<label>GENERAL SUPPORT</label>
<p>[email protected]</p>
</div>
</div>
</div>
</div>
</div>
Here is the CSS part:-
.address-left, .address-right{
vertical-align: top;
height: 100%;
display: table-cell;
}
.address-left{
width:50px;
box-sizing: border-box;
padding: 20px 0 0 0;
}
.address-right{
width: 200px;
max-width: 100%;
box-sizing: border-box;
padding: 25px 0 0 0;
}
.address-repeat{
width: 100%;
margin: 20px 0 0 -12px;
}
.address-top{
width: 100%;
border-left:2px solid #d5d5d5;
margin: 20px 0 0 10px;
}
#contact-us .address-right p{
color:#5e5e5e;
font-family: 'Montserrat-Regular';
padding: 0;
margin: 0;
letter-spacing: 0.5px;
font-size:14px;
width:200px;
font-weight: lighter;
}
#contact-us label{
font-family: 'HelveticaNeueLTStd-HvCn';
font-size:17px;
color:#343434;
}
#contact-us i{
color:#ffffff;
font-size: 15px;
border-radius:50%;
width:25px;
height:25px;
line-height:23px;
padding:1px 0 0 6px;
background-color:#e70020;
}
A:
You can use ::before pseudo element instead of left-border like this:
.address-left, .address-right{
vertical-align: top;
height: 100%;
display: table-cell;
}
.address-left{
width:50px;
box-sizing: border-box;
padding: 20px 0 0 0;
}
.address-right{
width: 200px;
max-width: 100%;
box-sizing: border-box;
padding: 25px 0 0 0;
}
.address-repeat{
width: 100%;
margin: 20px 0 0 -12px;
}
.address-top{
width: 100%;
margin: 20px 0 0 10px;
position:relative;
}
.address-top::before {
position: absolute;
left: 0;
top: 25px;
height: calc(100% - 50px);
width: 2px;
content: '';
background-color: #d5d5d5;
z-index: -1;
}
#contact-us .address-right p{
color:#5e5e5e;
font-family: 'Montserrat-Regular';
padding: 0;
margin: 0;
letter-spacing: 0.5px;
font-size:14px;
width:200px;
font-weight: lighter;
}
#contact-us label{
font-family: 'HelveticaNeueLTStd-HvCn';
font-size:17px;
color:#343434;
}
#contact-us i{
color:#ffffff;
font-size: 15px;
border-radius:50%;
width:25px;
height:25px;
line-height:23px;
padding:1px 0 0 6px;
background-color:#e70020;
}
<div class="row">
<div class="col-md-6 col-sm-12">
<h2 class="heading-title">Drop in our office</h2>
<p>Lorem ipsum dolor sit amet, consectetur adipiscing elit, sed do eiusmod tempor incididunt ut labore et dolore magna aliqua.</p>
<div class="address-top">
<div class="address-repeat">
<div class="address-left">
<div class="body-widget">
<i class="fa fa-map-marker" aria-hidden="true"></i>
</div>
</div>
<div class="address-right">
<div class="body-widget">
<label>ADDRESS</label>
<p>Huatai Securities (USA)10 Hudson Yards 41FlNY, NY 10001</p>
</div>
</div>
</div>
<div class="address-repeat">
<div class="address-left">
<div class="body-widget">
<i class="fa fa-phone" aria-hidden="true"></i>
</div>
</div>
<div class="address-right">
<div class="body-widget">
<label>LETS TALK</label>
<p>212-763-8166</p>
</div>
</div>
</div>
<div class="address-repeat">
<div class="address-left">
<div class="body-widget">
<i class="fa fa-envelope" aria-hidden="true"></i>
</div>
</div>
<div class="address-right">
<div class="body-widget">
<label>GENERAL SUPPORT</label>
<p>[email protected]</p>
</div>
</div>
</div>
</div>
</div>
</div>
|
/**
* PANDA 3D SOFTWARE
* Copyright (c) Carnegie Mellon University. All rights reserved.
*
* All use of this software is subject to the terms of the revised BSD
* license. You should have received a copy of this license along
* with this source code in a file named "LICENSE."
*
* @file textureImage.h
* @author drose
* @date 2000-11-28
*/
#ifndef TEXTUREIMAGE_H
#define TEXTUREIMAGE_H
#include "pandatoolbase.h"
#include "imageFile.h"
#include "paletteGroups.h"
#include "textureRequest.h"
#include "namable.h"
#include "filename.h"
#include "pnmImage.h"
#include "eggRenderMode.h"
#include "pmap.h"
#include "pset.h"
class SourceTextureImage;
class DestTextureImage;
class TexturePlacement;
class EggFile;
/**
* This represents a single source texture that is referenced by one or more
* egg files. It may be assigned to multiple PaletteGroups, and thus placed
* on multiple PaletteImages (up to one per PaletteGroup).
*
* Since a TextureImage may be referenced by multiple egg files that are each
* assigned to a different set of groups, it tries to maximize sharing between
* egg files and minimize the number of different PaletteGroups it is assigned
* to.
*/
class TextureImage : public ImageFile, public Namable {
public:
TextureImage();
void note_egg_file(EggFile *egg_file);
void assign_groups();
const PaletteGroups &get_groups() const;
TexturePlacement *get_placement(PaletteGroup *group) const;
void force_replace();
void mark_eggs_stale();
void mark_texture_named();
bool is_texture_named() const;
void pre_txa_file();
void post_txa_file();
bool got_txa_file() const;
void determine_placement_size();
bool get_omit() const;
double get_coverage_threshold() const;
int get_margin() const;
bool is_surprise() const;
bool is_used() const;
EggRenderMode::AlphaMode get_alpha_mode() const;
EggTexture::WrapMode get_txa_wrap_u() const;
EggTexture::WrapMode get_txa_wrap_v() const;
SourceTextureImage *get_source(const Filename &filename,
const Filename &alpha_filename,
int alpha_file_channel);
SourceTextureImage *get_preferred_source();
void clear_source_basic_properties();
void copy_unplaced(bool redo_all);
const PNMImage &read_source_image();
void release_source_image();
void set_source_image(const PNMImage &image);
void read_header();
bool is_newer_than(const Filename &reference_filename);
void write_source_pathnames(std::ostream &out, int indent_level = 0) const;
void write_scale_info(std::ostream &out, int indent_level = 0);
private:
typedef pset<EggFile *> EggFiles;
typedef pvector<EggFile *> WorkingEggs;
typedef pmap<std::string, SourceTextureImage *> Sources;
typedef pmap<std::string, DestTextureImage *> Dests;
static int compute_egg_count(PaletteGroup *group,
const WorkingEggs &egg_files);
void assign_to_groups(const PaletteGroups &groups);
void consider_grayscale();
void consider_alpha();
void remove_old_dests(const Dests &a, const Dests &b);
void copy_new_dests(const Dests &a, const Dests &b);
std::string get_source_key(const Filename &filename,
const Filename &alpha_filename,
int alpha_file_channel);
private:
TextureRequest _request;
TextureProperties _pre_txa_properties;
EggRenderMode::AlphaMode _pre_txa_alpha_mode;
SourceTextureImage *_preferred_source;
bool _is_surprise;
bool _ever_read_image;
bool _forced_grayscale;
enum AlphaBits {
// consider_alpha() sets alpha_bits to the union of all of these pixel
// values that might be found in the alpha channel.
AB_one = 0x01,
AB_mid = 0x02,
AB_zero = 0x04,
AB_all = 0x07 // == AB_zero | AB_mid | AB_one
};
int _alpha_bits;
double _mid_pixel_ratio;
bool _is_cutout;
EggRenderMode::AlphaMode _alpha_mode;
EggTexture::WrapMode _txa_wrap_u, _txa_wrap_v;
PaletteGroups _explicitly_assigned_groups;
PaletteGroups _actual_assigned_groups;
EggFiles _egg_files;
typedef pmap<PaletteGroup *, TexturePlacement *> Placement;
Placement _placement;
Sources _sources;
Dests _dests;
bool _read_source_image;
bool _allow_release_source_image;
PNMImage _source_image;
bool _texture_named;
bool _got_txa_file;
// The TypedWritable interface follows.
public:
static void register_with_read_factory();
virtual void write_datagram(BamWriter *writer, Datagram &datagram);
virtual int complete_pointers(TypedWritable **p_list,
BamReader *manager);
protected:
static TypedWritable *make_TextureImage(const FactoryParams ¶ms);
void fillin(DatagramIterator &scan, BamReader *manager);
private:
// These values are only filled in while reading from the bam file; don't
// use them otherwise.
int _num_placement;
int _num_sources;
int _num_dests;
public:
static TypeHandle get_class_type() {
return _type_handle;
}
static void init_type() {
ImageFile::init_type();
Namable::init_type();
register_type(_type_handle, "TextureImage",
ImageFile::get_class_type(),
Namable::get_class_type());
}
virtual TypeHandle get_type() const {
return get_class_type();
}
private:
static TypeHandle _type_handle;
friend class TxaLine;
};
#endif
|
Are anomalies of the caval veins more common in complex congenital heart disease?
Anomalies of the caval veins are considered to be common cardiac malformations. The knowledge of the varieties of the caval venous system is essential for cardiovascular surgery, pacemaker implantation, intensive care medicine or cardiac catheterization. The authors wanted to know, if anomalies of the caval veins are related to the type and complexity of congenital heart disease. The records of 1,631 patients who were catheterized between 1991 and 2003 were reviewed. 92 of these had anomalies of either the superior or inferior caval vein. 23 had simple congenital heart disease, while in 69 this was considered to be complex (p < 0.001). Embryologic considerations are discussed. It could be proven that anomalies of the caval veins are more often related to complex congenital heart disease. Embryologic considerations show at least a coincidence of the development of the caval veins and of congenital heart disease. For clinical work with these patients the knowledge of these anomalies is important.
|
SPINACH SOCCA w/ CARAMELISED PEACH SALAD
Dearest readers,
what a crazy summer ride the last couple of weeks have been. So much stuff going on, got done (… some things are still on the to-do-list), good and bad things happened, I jumped up and down – figurely and emotionally.
My boyfriend and I moved in together. Which led me to tidy.the.F.up! Decluttering for real- and let me tell you it was not easy.
But it feels SO good now. Amazing how free and relieved it makes you feel. And it also opens up some paths to act out in different aspects of life. Like decluttering your relationships or cutting the negative self-talk, minimising the to-do lists, let go, release and simplify. For me it was the perfect end of a summer that wasn’t a ”real” summer. But all the decluttering and organising made me see things in another way.
To let go of expectations and just go with a situation makes life so much easier. Honestly, I expected that with him moving in, my apartment would be too crowded and full, that ”me” space I created was in danger and it would all just be too much. It turned out to be the complete opposite. It feels right and light. I finally let go and opened up my home and heart. Got rid of old clutter, things I didn’t need anymore. I just surrounded myself with things and a person that sparks joy in me!
To declutter the too-often worried voices in my head and the actual tyding-up of my home inspired a balanced, calm + motivated mindset.
And with that I create a warmth in my heart, so that a rainy summer does not bother me at all.
We made the best out if it and tried to get some nourishing and vibrant dinners out on our rooftop balcony as often as possible. It’s the little things, right?
And this salad wrapped up in spinach-socca is a celebration to late-summers-harvest. A simple yet precious dish. Luscious caramelised peaches paired with fresh arugula and pine nuts… Need I say more?
I hope you are at peace with your situation wherever you are right now. Maybe find some peace with that salad/socca combo.
1. In a blender mix the flour, water, spinach, oil, salt and pepper together. Let the dough rest.
2. Heat a pan with a little olive oil, slice the peaches and add them to the pan on medium heat. After 5 minutes add maple syrup and reduce the heat. Let it caramelise.
3. Rinse the arugula, take it to a salad bowl. Add slices of cucumber, pine nuts and basil.
4. Heat a pan on high with a little bit of oil to create a thin layer, add the socca batter and let it bake until it has set and begins to take on colour. Flip around. Repeat with remaining batter, one after the other.
5. Add olive oil, apple cider vinegar, salt + pepper to the salad bowl. Add peaches and some crumbled feta. Carefully stir around.
6. Once the socca are ready, place them on plates and garnish with salad. Wrap it or eat it flat with a fork and knife.
|
AutonomousVmClusterSummary
==========================
.. currentmodule:: oci.database.models
.. autoclass:: AutonomousVmClusterSummary
:show-inheritance:
:special-members: __init__
:members:
:undoc-members:
:inherited-members:
|
Q:
What does “factor out” an ideal mean?
I am studying this article. In proving Theorem 2.14—
Let $R$ be an $\alpha$-ring and $S=R[x,\alpha]$. Then $S$ is $\alpha$-Jacobson if and only if $R$ is $\alpha$-Jacobson
—the author says that:
. . . we can factor out $(P \cap R)S $, which is contained in $P$, and assume that $P \cap R = 0$
(where $P$ is an $\alpha$-prime ideal of $S$).
I don't understand what this “factor out” means. Any help would be great.
A:
It means to consider the quotient. When you do $P/(P\cap R)$, now $P\cap R$ is the zero of the quotient.
|
Q:
sqlite insert statement BAD MOJO
I have a simple problem which probably has a simple solution, but the solution alludes me...
so I have a simple table i.e. phone that has 4 columns, and I want to add one new column. Since SQLite doesn't modify tables I have to drop and create.
phone_old
_id integer primary key autoincrement,
name text not null,
value text
phone
_id integer primary key autoincrement,
name text not null,
itemState text not null,
value text
so I do the following :
1. I rename the old table,
2. I create the new one with the extra field (in my case it's itemState) and
3. I select and insert everything defining a default value for itemstate.
1 ALTER TABLE Phone RENAME TO Phone_OLD;
2 CREATE table Phone(
_id integer primary key autoincrement,
name text not null,
itemState text not null,
value text );
3) INSERT INTO Phone SELECT * , 'Synced' as itemState from Phone_OLD where Phone_OLD. ;
what happends as a result is that the item state (synced) is added as the last field and not in column 3 which is the itemState.
so the column names do not correspond to the row values, meaning the itemstate is added at the end (as the last column in the row and not as position 3 as it's supposed to )
Just putting the itemstate at the end would solve the problem, but since my table creation statements are generated I would have to rewrite a whole bunch of code to do so, and to be hones it pisses me off that this set of queries returns crap..
any ideas?
A:
Sqlite does support appending columns
ALTER TABLE Phone ADD COLUMN [itemState] text not null default ''
|
617 So.2d 1220 (1993)
THREE RIVERS FARM SUPPLY, INC., Plaintiff-Appellant,
v.
Clyde Ray WEBBER, Clerk of Court, et al., Defendant-Appellee.
CONCORDIA BANK AND TRUST COMPANY, Plaintiff-Appellant,
v.
Clyde R. WEBBER, Jr., et al., Defendant-Appellee.
No. 92-299.
Court of Appeal of Louisiana, Third Circuit.
April 14, 1993.
*1221 George Crooks Murray Jr., Vidalia, and Brent Stafford Gore, Ferriday, for Three Rivers Farm Supply, Inc.
Ralph Bisland Shields, III, Vidalia, for Clyde Ray Webber, Clerk of Court etc.
Before GUIDRY, LABORDE, YELVERTON, WOODARD and DECUIR, JJ.
DECUIR, Judge.
In this case, Concordia Bank and Trust Corporation (CBT) appeals a trial court decision finding that two prior judgments in favor of Three Rivers Farm Supply, Inc. prime CBT's mortgage executed by defendants, the Greenes. Finding that the trial court erred, we reverse.
FACTS
This suit involves the ranking of two judgments and a mortgage recorded in the mortgage records of Concordia Parish. On October 15, 1982, a default judgment in suit number 23,057, dated October 14, 1982, was recorded in favor of Three Rivers Farm Supply, Inc. (Three Rivers) and against E & D Greene, for the principal sum of $18,814.83 plus attorney's fees. This judgment was computer indexed under "E" as "E & D Green" and a hand written notation was made under "G" as "Green, D & E."
On February 1, 1983, Three Rivers amended its petition in the original suit number 23,057 to add as defendants Mrs. Emmitt Greene and Dwayne Greene doing business as "E & D Green." On February 15, 1983, various members of the Greene family executed a mortgage in favor of Concordia Bank and Trust Company (CBT), which was recorded in the mortgage records under the letter, "G", for Elzy Dwayne Greene. Thereafter, a default judgment was rendered against the defendants as named in the amended petition of suit number 23,057. This judgment was recorded on March 11, 1983 against Mrs. Emmitt Greene and Dwayne Greene, doing business as "E & D Greene."
On June 12, 1987, CBT requested a mortgage certificate from the Concordia Parish Clerk of Court in various names, including Emmitt Greene, Elzy Dwayne Greene, and Dwayne Greene. The mortgage certificate *1222 by the clerk listed Three Rivers' Judgment recorded October 15, 1982.
CBT filed a mandamus proceeding against Clyde R. Webber, Jr., the Concordia Parish Clerk of Court (Clerk), and Three Rivers in Suit No. 27,699-B, requesting that the Clerk be ordered to delete item 4, the October 1982 judgment from the mortgage certificate. The district court eventually rendered judgment on December 30, 1987 decreeing that the Concordia Bank mortgage primes the judgment, item 4 on the mortgage certificate 6306, against "E & D Greene" in suit number 23,057-B and, making the writ of mandamus peremptory and ordering the deletion of the Judgment from the mortgage certificate.
Three Rivers appealed, and this court, while declining to reach the merits, found CBT should not have used the mandamus proceeding, it being by summary process, and reversed the trial court's judgment and ordered the suit dismissed.
Three Rivers then filed suit number 29,616 for a writ of mandamus to which CBT filed an exception. By agreement of all the parties and to cure the exception, Three Rivers filed a motion to consolidate the two suits and convert them from summary to ordinary proceedings.
The Greene's failed to file an answer and Three Rivers filed a preliminary default against them on June 27, 1991. Thereafter, a final judgment was rendered against these defendants.
On November 14, 1991, a Judgment was signed in the consolidated cases in favor of Three Rivers ordering the Clerk of Court to reinstate the recorded judgment dated October 14, 1982 and the recorded judgment in favor of Three Rivers against Mrs. Emmitt Greene, et al. dated March 10, 1983. This judgment further found that the two aforementioned judgments outrank and prime CBT's mortgage recorded on February 15, 1983 from Ruth Greene, et al. It is from this judgment that CBT appeals.
ASSIGNMENT OF ERROR NUMBER ONE
In this assignment of error, CBT alleges the trial court erred in ordering the Clerk of Court to erase the cancellations and reinstate the October 14, 1982 judgment. In the trial court's written judgment, the trial court ordered the October 14, 1982 judgment reinstated. While the record is clear that this judgment was never actually cancelled, Three Rivers points out that this judgment was noted as cancelled in the Concordia Parish Clerk's index. It is equally clear from the record that CBT does not contest that the judgment is still valid and existing on the clerk's records. For this reason, we find the issue of whether the October 1982 judgment was cancelled moot, and if an error does exist from the trial court's use of the word, `reinstate,' it is harmless. Accordingly, this assignment of error lacks merit.
ASSIGNMENT OF ERROR NUMBER TWO
In this assignment of error, CBT alleges the trial court erred in finding that Three Rivers' judgments outrank and prime CBT's mortgage and in ordering CBT to pay all cost of the proceedings. In addressing this assignment we will discuss the original and amended judgments separately.
RELATION BACK OF AMENDED PETITION
In response to CBT's argument, Three Rivers argues La.C.C.P. art. 1153 applies and the second judgment relates back to the original judgment recorded on October 15, 1982. We disagree.
According to La.C.C.P. art. 1153 when a party files an amended petition, the amendment relates back in time to the first petition if the amendment arises out of the conduct, transaction, or occurrence set forth or attempted to be set forth in the original pleading. The amendment relates back even when the identity of the parties are changed to named corporations where the amendment arises out of the same transaction or occurrence set forth in the original petition. Cortinez v. Handford, 490 So.2d 626 (La.App. 2nd Cir.1986). Furthermore, where there is some factual connexity and some identity of interest between the original and amended proceedings, *1223 the amendment relates to the original file dates. Baker v. Payne and Keller of La., Inc. 390 So.2d 1272 (La.App. 2nd Cir. 1980). However, in this case, the record indicates Three Rivers filed an amended petition to add two defendants, Mrs. Emmitt Greene and Dwayne Green, after the original petition had resulted in a judgment. We find the legislature in enacting La.C.C.P. art. 1153 did not intend for this article to be applied after an original petition has resulted in a final judgment. Therefore, we find La.C.C.P. art. 1153 does not apply to the facts of this case.
EFFECTIVENESS OF RECORDATION OF ORIGINAL JUDGMENT
The rank of a creditor's claim is established by the priority of its registry in the appropriate public record. United Credit Plan of Gretna v. Pullen, 448 So.2d 95 (La.1984). In this case, the initial default judgment against E & D Greene was recorded on October 15, 1982, and indexed under "E" as "E & D Green" and under "G" as "Green, D & E." CBT executed and recorded its mortgage on February 15, 1983, and it was indexed under "G" as "Elzy Dwayne Greene." Three Rivers' amended petition was filed in February 1983, and the final judgment resulting from this petition was recorded on March 11, 1983. This judgment was recorded against Mrs. Emmett Greene and Dwayne Greene, doing business as E & D Greene.
Under the public records doctrine, third person's need only look to the public records to determine adverse claims. See McDuffie v. Walker, 125 La. 152, 51 So. 100 (1909). All persons are held to have constructive notice of the existence and contents of recorded instruments affecting immovable property. Thomas v. Lewis, 475 So.2d 52 (La.App. 2nd Cir.1985); Wells v. Joseph, 234 La. 780, 101 So.2d 667 (1958). Thus, the question becomes: did Three Rivers judgment recorded against E & D Greene, provide sufficient notice to CBT that the judgment affected the same persons as did CBT's mortgage?
We find that Three Rivers' original judgment did not provide sufficient notice. Three Rivers erred when it secured a judgment against E & D Greene, rather than against the parties using their full names. Three Rivers' belated attempt to amend the original petition after judgment, suggests that they recognized this error. Previous cases upholding the use of an initial have involved the use of a full name plus a middle initial. See Succession of Montgomery, 46 So.2d 677 (La.App. Orleans 1950); Tranchina v. Williams, 10 La.App. 656, 120 So. 882 (La.App. Orleans 1929). These cases are readily distinguishable. A full first name provides much more notice than the use of two initials and a surname. Likewise, the use of the ampersand in the present case makes the entry even more misleading to third parties, as the form is seldom used in reference to individuals.
Further in our view, E & D Greene is not a "reasonable variation" of the names Mrs. Emmitt Greene and Dwayne Greene within the purview of La.R.S. 9:2728(A)(2) such as to be effective against third persons. In any event, La.R.S. 9:2728(A)(2) did not become effective until July 16, 1987, and although designated as remedial legislation, it cannot adversely affect the vested rights of CBT. Voelkel v. Harrison, 572 So.2d 724 (La.App. 4th Cir.1990), writ denied, 575 So.2d 391 (La.1991); Ford v. Tilden, 7 La.Ann. 533 (La.1852); Graves v. Hunter, 23 La.Ann. 132 (La.1871).
Since we have found La.C.C.P. art. 1153 inapplicable to the facts of this case, the judgment arising from the amended petition does not relate back to the filing of the original petition. Furthermore, we find that the original judgment was not properly filed so as to be effective as to third parties, either under La.R.S. 9:2728(A)(2) or the prior law. Accordingly, we find the trial court erred. We reverse the trial court's judgment and find that CBT's mortgage primes both the original judgment and the judgment resulting from the amended petition.
DECREE
The trial court's judgment is reversed. All costs of this appeal are to be assessed against Three Rivers Farm Supply, Inc.
REVERSED.
LABORDE, J., dissents and assigns reasons.
*1224 LABORDE, Judge, dissenting.
While I agree with the majority that La.C.C.P. art. 1153 does not apply to the facts of this case, I cannot agree that CBT's mortgage primes Three Rivers' recorded judgment which resulted from the original petition. I believe the first recorded judgment is a valid judgment which provided sufficient notice in the public record to effect third parties. This is particularly true in light of the fact that the Clerk of Court listed this judgment on the 1987 mortgage certificate requested by CBT. In my view, Three Rivers' first judgment primes CBT's mortgage which primes Three Rivers' second judgment. Therefore, I respectfully dissent.
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491 F.Supp. 583 (1980)
Russell M. GIBSON, Plaintiff,
v.
CBS, INC., Defendant.
No. 78 Civ. 0035(MEL).
United States District Court, S. D. New York.
June 24, 1980.
Klein & Vibber, New York City, for plaintiff; Alfred W. Vibber, New York City, of counsel.
Pryor, Cashman, Sherman & Flynn, New York City, for defendant; Stephen F. Huff, Gayle A. Yeomans, New York City, of counsel.
LASKER, District Judge.
Russell M. Gibson sues CBS, Inc. alleging that his copyright[1] in a lecture entitled "I am And Egg" was infringed by the CBS broadcast on September 24, 1975 and June 6, 1976 of a skit entitled "SFX: Egg Cracking" on the Tony Orlando and Dawn Show.
CBS moves pursuant to Rules 12(b)(6) and 56 of the Federal Rules of Civil Procedure for summary judgment dismissing the complaint on the grounds that it fails to state a claim upon which relief may be granted. CBS argues that as a matter of law there is no substantial similarity between the two works and accordingly no copyright infringement.
I. The Principal Works
Gibson's lecture is one half of a typewritten page and is written to be delivered by only one person. It begins with the character announcing "I Am AND [sic] EGG," and goes on to describe the "plight of an egg," from the comfort of lying under a chicken, *584 to being picked up by a "no good farmer ... with his cold hand" who puts him in a "little grey box with eleven strange eggs ... on this little shelf frezzing" [sic] where a light goes on and off. He hears voices saying "I WANT MINE OVER LIGHT" or "ILL [sic] HAVE MINE SCRAMBLED." He remembers his mother's advice to "Make SHORE YOUR SUNNY SIDE UP" [sic] but learns that it is more fun to be scrambled and "swoshed around together" with a female egg. He concludes that "MOTHER WAS WRONG."
The CBS skit, which was performed by Tony Orlando and Anne Meara, is written for two characters, the white and the yolk of one egg, who confront the trauma of anticipated separation. The introduction, performed by an unseen narrator, states the theme:
"One of the most painful experiences in any relationship is separation. When Romeo was separated from Juliet that was painful. Every separation is painful. Even the separation of the white of an egg from the yolk."
As the skit begins, the roof of an egg shell lifts revealing the yolk (Anne) and the white (Tony) who speculate about "what's going on." Tony believes they are a rooster, but Anne disagrees and suggests that they are an oyster or perhaps an egg. Tony expresses surprise at discovering Anne's true color: yellow. From the smell of bread they deduce that they are in a bakery, which upsets Anne because, as she complains to Tony, that is where
"[t]hey rip us apart from each other . . they separate the white from the yolk. Sure, you could end up in icing and I could end up in a hostess Twinkie."
The sight of a man in a "big white hat" and holding an egg beater frightens Anne, who is reassured by Tony:
"Easy does it Yolkie ... We've come through tighter places before you know."
Each speculates about what might have been: Tony had "political ambitions."
"I saw us on Easter day rolling on the White House lawn."
Anne had other dreams:
"I could have been an egg nog at a Howard Cosell party . . . . if only we'd have stayed under mom just a few more days . . . We would have been a chicken."
Anne confesses that she will miss Tony, who stages a fight and accuses her of being "full of cholesterol." At first taken in, Anne responds that he is "all white and runnie and gushie," and that he "take[s] up the whole shell."
Suddenly the man appears again holding a frying pan, causing Anne to comment on the unjustness of being an egg:
"[W]hat is it all for, huh ... 21 days to become an egg ... another two weeks sitting on the shelf with eleven other dummies in a cardboard condominium ... and for what .. for what? ... for this, once over easy with a side of bacon."
The skit concludes as Tony points out that the "most important thing" is not what happens to them, but "Just so long as we can face it together."
II. Substantial Similarity
To prove copyright infringement, a plaintiff must establish that the defendant copied his work. Mazer v. Stein, 347 U.S. 201, 217, 74 S.Ct. 460, 470, 98 L.Ed. 630 (1954); Reyher v. Children's Television Workshop, 533 F.2d 87, 90 (2d Cir.), cert. denied, 429 U.S. 980, 97 S.Ct. 492, 50 L.Ed.2d 588 (1976). "`[I]f there are no similarities, no amount of evidence of access will suffice to prove copying,'" id. (quoting Arnstein v. Porter, 154 F.2d 464, 468 (2d Cir. 1946)). Accordingly, summary judgment would be appropriate if there is no substantial similarity between Gibson's lecture and the CBS skit.
Copyright protection extends only to the expression of an idea, and not to the idea itself. Mazer v. Stein, supra, 347 U.S. 201, 217, 74 S.Ct. 460, 470, 98 L.Ed. 630 (1954); Baker v. Selden, 101 U.S. 99, 102-03 (1879); Reyher v. Children's Television *585 Workshop, supra, 533 F.2d at 90; 17 U.S.C. § 102(b). Although the distinction between an idea and its expression is not always clear, see 3 Nimmer on Copyright § 13.03[A], at 13-18 (1979), past applications of that distinction by the Second Circuit clearly dictate the result here.
In Reyher v. Children's Television Workshop, supra, the court affirmed the dismissal of a copyright action on the grounds that there was no substantial similarity between the principal works. There the theme of plaintiffs' children's book as well as defendants' television show and subsequent magazine publication was that of a lost child who describes his or her mother to a group of strangers as the most beautiful woman in the world. After a search for the mother based on that description proves unfruitful, a homely woman, who turns out to be the mother, is united with the child.
The court held that "[s]ince both [stories] present only the same idea, no infringement as to protected expression occurred," id. at 92-93, even though "both works present the thematic concept that to a lost child, the familiar face of the mother is the most beautiful face, even though the mother is not, in fact, beautiful to most." Id. (footnote omitted). The court stated:
"The overlapping sequences of events concern the lost child finding his or her mother, albeit with some difficulty because of the description given. This similarity of events, however, may be considered scenes a faire, scenes which necessarily result from identical situations. Thus, where a lost child is the protagonist, there is likely to be a reunion with parents. Furthermore, the morals stated by the two stories differ in emphasis . . .. More importantly, however, the two works differ in `total feel.' .. The two stories are not similar in mood, details or characterization."
Id. at 92 (footnote omitted) (emphasis in original).
Similarly, in Nichols v. Universal Pictures Corporation, 45 F.2d 119 (2d Cir. 1930), cert. denied, 282 U.S. 902, 51 S.Ct. 216, 75 L.Ed. 795 (1931), the court found that no more than the idea of plaintiff's play, "Abie's Irish Rose," had been used in defendant's motion picture "The Cohens and the Kellys." Although common to both works were a "quarrel between a Jewish and an Irish father, the marriage of their children, the birth of grandchildren and a reconciliation," the court held that these were ideas, not expressions, and therefore not subject to copyright protection. Id. at 122.
Here, the only similarities between Gibson's lecture and the CBS skit are (1) the use of the literary device of personifying an egg (or its parts) that is, attributing to an egg the powers of speech, sensation and feelings (2) the egg's undergoing certain experiences, such as lying under a chicken or in a box with other eggs in a refrigerator where it is cold and a light goes on and off, and (3) the egg's reacting to the possibility of being scrambled or fried.
The attribution to an egg of the qualities normally possessed by human beings is of course an "idea" and no more. The idea alone is not subject to copyright protection. The other similarities depictions of the experience and reactions of an egg are "scenes a faire," that is:
"sequences of events which necessarily follow from a common theme. `[S]imilarity of expression ... which necessarily results from the fact that the common idea is only capable of expression in more or less stereotyped form will preclude a finding of actionable similarity.'"
Reyher v. Children's Television Workshop, supra, 533 F.2d at 91 (quoting 3 Nimmer on Copyright § 13.03[A] at 13-26 (1979)).
Gibson argues that the similarities do not necessarily follow from the common idea of an egg personified, since an author has a wide choice of events that may occur in the life of an egg. For example, Gibson suggests that instead of lying under a chicken, an egg might be hatched in an incubator, could have been colored and rolled, preserved in a liquid bath, boiled (soft or hard), whipped, used in a souffle, freezed or dried into a powder, or used raw, such as in an *586 eggnog. However, the occurrences that are common to both works, that is, lying under a chicken, sitting in a refrigerator and facing the possibility of being scrambled or fried, are fairly predictable and usual in the life of an egg, while the alternatives Gibson offers do not "necessarily follow" from the "common theme."
Moreover, even if the similarities between the two works be deemed to have "descended so far into the concrete as to invade [his] expression," Reyher, supra, at 91, the similarity would be insufficiently substantial to be actionable in light of the large difference between the two works. The CBS skit treats more events that occur to an egg such as being separated and being used in an icing and a Hostess twinkie, put into a blender and a cake mix, "rolling on the White House lawn" on Easter Day, used in an eggnog for a Howard Cosell party, and hatched into a chicken and subsequently fried than does Gibson's lecture. The theme of separation which is the subject of the CBS skit[2] nowhere appears in the Gibson lecture whose message is that it would be better to be scrambled with a female egg than to be sunnyside up as his mother had advised. The skit focuses on the relationship between the two characters while the lecture is concerned with the reactions of one.
In sum, the only similarities between the plaintiff and defendant's material are the idea of a personified egg and of certain situations that necessarily follow from that idea. There is no substantial similarity between the expressions of the idea in the two works.
The motion for summary judgment is granted and the complaint is dismissed.
It is so ordered.
NOTES
[1] CBS concedes that Gibson's lecture was copyrighted.
[2] Gibson argues that the use of two characters in the CBS skit does not constitute a dissimilarity between that work and his lecture because by the end of the skit they have not yet been separated. While it is true that the ultimate fate of the white and the yolk remains a subject of speculation at the end of the skit, the more important element of the theme of anticipated separation of the two characters markedly distinguishes the skit from the lecture.
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/**
* Copyright (c) Microsoft Corporation. All rights reserved.
* Licensed under the MIT License. See License.txt in the project root for
* license information.
*
* Code generated by Microsoft (R) AutoRest Code Generator.
*/
package com.microsoft.azure.management.cognitiveservices.v2017_04_18;
import rx.Observable;
import com.microsoft.azure.management.cognitiveservices.v2017_04_18.implementation.ResourceSkusInner;
import com.microsoft.azure.arm.model.HasInner;
/**
* Type representing ResourceSkus.
*/
public interface ResourceSkus extends HasInner<ResourceSkusInner> {
/**
* Gets the list of Microsoft.CognitiveServices SKUs available for your Subscription.
*
* @throws IllegalArgumentException thrown if parameters fail the validation
* @return the observable for the request
*/
Observable<ResourceSku> listAsync();
}
|
<?xml version="1.0" encoding="UTF-8" standalone="yes"?>
<!--
DO NOT ALTER OR REMOVE COPYRIGHT NOTICES OR THIS HEADER.
Copyright (c) 2013 Oracle and/or its affiliates. All rights reserved.
Oracle licenses this file to You under the Apache License, Version 2.0
(the "License"); you may not use this file except in compliance with
the License. You may obtain a copy of the License at
http://www.apache.org/licenses/LICENSE-2.0
Unless required by applicable law or agreed to in writing, software
distributed under the License is distributed on an "AS IS" BASIS,
WITHOUT WARRANTIES OR CONDITIONS OF ANY KIND, either express or implied.
See the License for the specific language governing permissions and
limitations under the License.
-->
<project xmlns="http://maven.apache.org/POM/4.0.0" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"
xsi:schemaLocation="http://maven.apache.org/POM/4.0.0 http://maven.apache.org/maven-v4_0_0.xsd">
<modelVersion>4.0.0</modelVersion>
<parent>
<groupId>org.jvnet.jax-ws-commons.test</groupId>
<artifactId>jaxwscommons87</artifactId>
<version>1.0-SNAPSHOT</version>
<relativePath>../pom.xml</relativePath>
</parent>
<artifactId>jaxwscommons87.child</artifactId>
<name>JAX_WS_COMMONS-87-child</name>
<build>
<plugins>
<plugin>
<groupId>org.jvnet.jax-ws-commons</groupId>
<artifactId>jaxws-maven-plugin</artifactId>
<executions>
<execution>
<id>wsimport-handlers</id>
<goals>
<goal>wsimport</goal>
</goals>
<configuration>
<wsdlDirectory>${basedir}/src/main/wsdl/</wsdlDirectory>
<bindingDirectory>${basedir}/src/main/bindings</bindingDirectory>
</configuration>
</execution>
</executions>
</plugin>
</plugins>
</build>
</project>
|
Q:
WPF Canvas, how to add children dynamically with MVVM code behind
Requirement:
To draw one Bitmap Image and rectangle(s) based on the collection of points. The rectangle should exactly fit on the pixels location over the image. There is also some text need to be added inside the rectangle.
The Image will be always only one and the rectangles will be dynamically added.
Current Solution:
Have a canvas with Image Control. Add the the dynamic code under the code behind file ViewImageResult.xaml.cs.
private void DrawResult(int left, int right, int width, int height)
{
Border bord = new Border();
bord.BorderThickness = new Thickness(1);
bord.BorderBrush = Brushes.Red;
bord.Width = width;
bord.Height = height;
_mainCanvas.Children.Add(bord);
Canvas.SetLeft(bord, left);
Canvas.SetTop(bord, right);
}
Issue:
Since i follow MVVM pattern, the collection of points for rectangle is in my ViewModel file ViewImageResultModel.cs. I am not able to add the child rectangle dynamically from the ViewModel file.
A:
ItemsControl is your friend:
<Grid>
<Image Source="..."/>
<ItemsControl ItemsSource="{Binding Points}">
<ItemsControl.ItemsPanel>
<ItemsPanelTemplate>
<Canvas/>
</ItemsPanelTemplate>
</ItemsControl.ItemsPanel>
<ItemsControl.ItemContainerStyle>
<Style>
<Setter Property="Canvas.Left" Value="{Binding X}"/>
<Setter Property="Canvas.Top" Value="{Binding Y}"/>
</Style>
</ItemsControl.ItemContainerStyle>
<ItemsControl.ItemTemplate>
<DataTemplate>
<Border BorderBrush="Red" BorderThickness="1" Width="{Binding Width}" Height="{Binding Height}"/>
</DataTemplate>
</ItemsControl.ItemTemplate>
</ItemsControl>
</Grid>
The above assumes your VM exposes a collection of points via a Points property, and that each point VM has X, Y, Width, and Height properties.
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Thank you. At last, it is clear.
It solved the problem. Excellent suggestion. Thank you!
Thank you. I spent a month trying to figure this one out.
Thank you. It's easy as 123.
Thanks. I had the same problem and couldn't figure it out.
Other:
This is NOT abusive. I pressed this button by accident.It is spam / self promotion.It is offensive or harmful.It does not contain enough information.It contains or requests illegal information.It does not make sense.
"Normally used in the united states non-judicial foreclosure most lenders use the non-judicial foreclosure..."
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He someone you know should immediately call the current lender and see if they have a program for that will prevent the foreclosure all together. I am sure they have many programs available. They must communicate this financial situation to the lender.
The lender does not know about individual financial situations. The banks are willing to work with you.
Depending on the type foreclosure the lender decide to use, Arizona allow both judicial and non-judicial foreclosures.
Each lender have their own procedures as to when to file a foreclosure against a person that is behind in their mortgage payments. Some file foreclosure immediately after one payment, some as long as 3-9 months after missing your first monthly payment.
There are two types of foreclosures normally used in the United States Non-Judicial Foreclosure Most lenders use the non-judicial foreclosure procedure. No courts or lawyers are involved.
Under this procedure normally the lender has the right to sell the property after completing the foreclosure procedure. The lender, under this procedure can not normally sue for a judgment after the sale. You do not have the right to reclaim the house under any circumstance.
Under a non-judicial foreclosure and the lender has decided to foreclose on you they issue a "Notice of Default/Foreclosure" this document is recorded at the county recorders office where the property is located.
You will receive a copy of this notice in the mail as well as one will be delivered to your front door.
At this point you now have 90 days to bring the mortgage current, refinance the mortgage or do what ever you want to do to keep your property. Your lender might entertain the idea of refinancing your mortgage for you at this stage.
Once the 90 day period is over the lender then decides to record a "Notice of Sale" at the county recorders office. You will receive a copy in the mail as well as someone will deliver one to your front door. This notice will have a sale date and place of sale.
Once this document has been recorded you now have 20 days in which to refinance or cure your foreclosure. Most lenders will not entertain the idea of refinancing their own loan once this document has been issued. Some might, but most will not. At this point the lender is interested in you paying the mortgage off or bringing it current.
At the sale if the property is sold to someone, they have to get the property recorded in their name so there is lots of legal work to be done before they officially own the property.
This new owner will contact you when all the legal documents are signed and between the two of you select a time for you to move. You might be required to pay rent for the time you stay there but this is between you and the new buyer.
If the property does not sell then the lender has to get a few legal matters taken care of so they have to wait until the legal matters are completed. This normally take 5-7 business days or less.
If this happens once all the legal matters are taken care of the lender normally hires a real estate agency to take care of their real estate sales.
An agent from the agency will contact you about the date and time of your departure. In some instances they will offer you a sum of cash for you to move.
If you are not required to go to court and has not received documents from a court stating that you must appear. This is probably the procedure being used by your lender.
Judicial Foreclosure
If the lender decide to use the judicial foreclosure procedure you will be issued a summons to appear in court. The court will set the time and date of appearance as well as when you will have to vacate the property.
If the lender use the judicial foreclosure procedure they are allowed by law to file a deficiency judgment against you.
Most lenders, though the law allow them to file for a judgment do not do so. they would just rather sell the property, write any loss off and move on without other legal problems that might cost them money and then would have to collect on the judgment if they won.
On the other hand the law also allow you the right to reclaim your house after the foreclosure procedure has been completed in some instances any where from three months and in some states up to a year.
If you received a document stating that you have to appear in court and a date for you appearance has been set, your lender is probably using this procedure.
This method of foreclosure is used only by a few lenders where both procedures are allowed.
Under either procedure if the bank can not reclaim the entire loan amount from the sale of the property they claim they have a loss. Since this is a loss to them someone had to have a gain. You are the one considered having the gain, therefore the lender would then send you a 1099 indicating the amount of gain you had.
"Resident alien (based on days present in the united states..."
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And if Joel W was being upfront with his information, I think Joel W. is hoping no one actually reads his link just the parts he posted. (in part)
"Individual Taxpayer Identification Number (ITIN)"
**NEW** Posted December 22, 2009
*Moratorium on NEW Acceptance Agents Applications Starting January 1, 2010
"The Internal Revenue Service (IRS) Individual Tax Identification Number (ITIN) Program is announcing a moratorium effective January 1st through April 30th, 2010 on all new Forms 13551, Application to Participate in the IRS Acceptance Agent Program.
During the moratorium, the IRS will not accept or process Forms 13551, Application to Participate in the IRS Acceptance Agent Program. Only amendments to existing, approved agreements will be accepted during the moratorium. The ITIN Program will resume accepting applications during the new 2010 Acceptance Agent Open Season, effective May 1 through August 31, 2010."
"What is an ITIN?
An Individual Taxpayer Identification Number (ITIN) is a tax processing number issued by the Internal Revenue Service. It is a nine-digit number that always begins with the number 9 and has a range of 70-88 in the fourth and fifth digit, example 9XX-70-XXXX.
IRS issues ITINs to individuals who are required to have a U.S. taxpayer identification number but who do not have, and are not eligible to obtain a Social Security Number (SSN) from the Social Security Administration (SSA).
ITINs are issued regardless of immigration status because both resident and nonresident aliens may have a U.S. filing or reporting requirement under the Internal Revenue Code.
Individuals must have a filing requirement and file a valid federal income tax return to receive an ITIN, unless they meet an exception.
What is an ITIN used for?
ITINs are for federal tax reporting only, and are not intended to serve any other purpose. An ITIN does not authorize work in the U.S. or provide eligibility for Social Security benefits or the Earned Income Tax Credit. ITINs are not valid identification outside the tax system.
IRS issues ITINs to help individuals comply with the U.S. tax laws, and to provide a means to efficiently process and account for tax returns and payments for those not eligible for Social Security Numbers.
Who needs an ITIN?
IRS issues ITINs to foreign nationals and others who have federal tax reporting or filing requirements and do not qualify for SSNs. A non-resident alien individual not eligible for a SSN, who is required to file a U.S. tax return only to claim a refund of tax under the provisions of a U.S. tax treaty, needs an ITIN.
Examples of individuals who need ITINs include:
* Non-resident alien filing a U.S. tax return and not eligible for a SSN
* U.S. resident alien (based on days present in the United States) filing a U.S. tax return and not eligible for a SSN
* Dependent or spouse of a U.S. citizen/resident alien
* Dependent or spouse of a non-resident alien visa holder
How do I know if I need an ITIN?
If you do not have a SSN and are not eligible to obtain a SSN, but you have a requirement to furnish a federal tax identification number or file a federal income tax return, you must apply for an ITIN.
If you have an application for a SSN pending, do not file Form W-7. Complete Form W-7 only if the Social Security Administration (SSA) notifies you that a SSN cannot be issued.
To obtain a SSN, see Form SS-5, Application for a Social Security Card. To get Form SS-5 or to find out if you are eligible to obtain an SSN, go to Social Security Administration Website or contact a SSA office. By law, an alien individual cannot have both an ITIN and a SSN.
IRS processes returns showing SSNs or ITINs in the blanks where tax forms request SSNs. IRS no longer accepts, and will not process, forms showing "SSA205c," "applied for," "NRA," blanks, etc.
Are ITINs valid for identification?
No. ITINs are not valid identification outside the tax system. Since ITINs are strictly for tax processing, IRS does not apply the same standards as agencies that provide genuine identity certification.
ITIN applicants are not required to apply in person, and IRS does not further validate the authenticity of identity documents. ITINs do not prove identity outside the Federal tax system, and should not be offered or accepted as identification for non-tax purposes.
Are ITINs valid for work purposes?
No. ITINs are for federal income tax purposes only. Getting an ITIN does not change your immigration status or your right to work in the United States."
http://www.irs.gov/individuals/article/0…;
Edit:
I did my research, I read your link and what you posted. I do not see a question about "the base of the economic collapse" Just like when I questioned your fifty foot wall and the fifty one foot ladder postings is that why you are now again defending what you say?
"Notice the Chief said I left after the previous post."
Like your selective posting, you are adding words and ideas to mine that are not there. I invite you to show where I said you left.
"When the foreclosure is over then it is necessary..."
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It depends. If you are targeting a foreclosed property then you have to depend a lot on the bank with which the foreclosed property is associated. After commencement of the process, it generally takes around three to six months to wind up the entire thing. It is completely a legal process where the court is highly involved. When the foreclosure is over then it is necessary that the bank transfers the power of attorney to the buyer of the property and this paper transfer takes around three to six weeks time usually.
Keegan.
"Basically this all procedure of foreclosure rely upon the laws and principles..."
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This question How long to foreclosures take to close, holds much importance in the procedure of foreclosure. Basically this all procedure of foreclosure rely upon the laws and principles of company or bank performing the foreclosure of any property. Mostly banks start foreclosure after 3 nonpayments. It issues the notice to warn the customer about nonpayments, if customer doesn`t react on that notice then bank has to perform auction or foreclosure.
"The answer of this question how long to foreclosures take to close is..."
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I agree with my friend ! the answer of this question How long to foreclosures take to close is, it all depends on law of foreclosure.Bank in fact starts its procedure after 3 or 4 missed payments of mortgage and then warn the person to pay mortgage if person is unable to pay mortgage then bank will take the action and it will be completed within few months. and it also depends on their will either they allow person to live in it or not.thank you.
Usually it`s 3 months of non-payment and they start the proceeding and you have another 3 months before you have to leave. You still need to call and let them know what`s going on. There`s nothing to be embarrassed about because everyone has been late on a bill at least once. For me, it`s been more than once! I`m not sure why the bank is so pushy... maybe they are being a little antsy because the failing economy and forclosures are putting a crunch on them as well. I actually just saw a news article where all the banks in Florida have boats filling their parking lot because everyone is walking away from their loan. It`s just a financial crisis right now in the US of A.
"Foreclosure process is initialized after 90 -..."
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Banks take on foreclosure process from 6 months to 2 years, it depends on your state and your lender.
foreclosure process is initialized after 90 - 120 days from the date your payment is considered late, and this will happen when you miss your next payment and your grace period (usually 15 days) has been expired.
It`s highly recommended to contact with your lender as soon as you know that you are going to miss your next mortgage payment, so that you might get other payment plans.
"A foreclosure process starts after 90 -120 days..."
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Banks foreclosure process might take from 6 months to 2 years, depending on your state laws and your lender.
A foreclosure process starts after 90 -120 days from the date you miss your payment and your grace period expires (usually 15 days).
As soon as you know you will not be able to pay your next mortgage payment, it`s recommended to contact your lender, so that you might get a longer grace period or you might reschedule your payments.
"Generally the foreclosure process takes time from 12 -18 months..."
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The mortgage company foreclosures on the person, depends upon the state where the person live. Generally the foreclosure process takes time from 12 -18 months. They start by sending the notice to the person after 90 days. After that the bank provides a deadline to him so that he pay the loan off. If he is unable to pay, he is taken to the court. The judge will issue the judgement against him for forclosure.
Tim Doubtson.
"About 210 to 270 days in judicial foreclosure..."
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The time taken by the wells fargo depends on the place where the person live. The rules varies from state to state as every state has their own rules. Generally, they take action after 90 days in non- judicial foreclosureand it takes about 210 to 270 days in judicial foreclosure. The person should get more details from the local legal officer.
Jack Powell.
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I don't find EJ interesting now - he is a supporting character to Nicole and I don't like it. At least when he was in Sami's orbit he wasn't supporting her character his character was actually driving the storyline somewhat. But with Nicole he is just there ... he is supporting her drama.
I too am losing interest in any one particular pairing. My other board I frequent used to have multiple posts every day. Some of the posts became quite passionate discussions about who should be with whom but now the board is deathly quiet. I see it as an big indicator that no one else is interested in the story lines either. If anyone was interested they would want to talk about them and no ones talking. :shrug:
I donno. I don't want the evil EJ of late 2006-spring 2007, but I want him to be grey. Roger Thorpe grey. Doing bad, bad things, but nothing that isn't redeemable. Make him HUMAN. Soaps can't seem to do that anymore, though. They're either vile, soulless murderers or neutered, whitewashed pussies who revert back when the writers are bored, and so on.
I want him back to bad, not evil, and totally devoted to sAmi.
I honestly think any chance they've had with the majority of the viewers backing EJami again has been seriously damaged. They keep screwing it up with poor writing and poor direction and inconsistency about the feelings of the characters, and if they try to bring them back together, it'll be like the frequent recasting of Shelle to have Shelle just to have that couple................fewer and fewer people will care each time it happens.
Right now, based on boards, there seems to be little support for Sami. It's hard to root for a character to go back to a couple when you're tired of the character. Right now, I just want Sami to go to a cloistered convent.
I do realize there are still people who want EJami...I just think there are a lot more people now who are losing interest. If nothing else, they seem to want a break from Sami. I just don't think they can do it right. IF they go back to EJami, it will probably need to be after a long break from the Sami Shriek Show. Sami offscreen for a while, EJ alone, given time to re-develop the character and KEEP it a certain personality, and re-introduce Sami a little later. But, I also don't think the show has the luxury of time to redo it correctly.
Now, they still can try to salvage EJole somehow. I don't think they will, though, but it's not too late if they woke up. Give it another month or so of stupid decisions, and more people will start to quit caring about EJole, too. Frankly, I think if it weren't for the professionalism and dedication of the two actors involved overcoming this crap, EJole would have sunk as soon as Nicole bought that fake stomach. I realize for some, it has. But, I think AZ and JS's acting is still saving it and making it intriguing. I assume so. I need to watch and find out and FF the other shit. :D
I like AZ and JS. I just really don't like them together romantically. When they were snarky back and forth, they were great, but romantically I don't think they spark. They're kinda boring together to me. It doesn't look natural.
I think Ari can play a heroine type role or the Vivian-like villainous, but of all the unmarried characters, she's the one I'd like the writers to write a good love story for and find an actor she does have great romantic chemistry with (she's good with anybody but why not go for great?). Not to stereotype stories, but she could be the Steve in a Steve/Kayla type of story. I'd love for her to find someone she truly loves who can love her back, and I'd like to see them showing that love, overcoming human mistakes, sacrificing for each other, etc. Maybe I'm too set on a soap being about love, but even during Days' most fanciful plots, I watched for love between characters. Maybe once there is more direction and JS is into it, I could go for Ejole, but they just never really attracted me thus far. I loved them much more when they were friendly antagonists.
This is not a pro-ejami post. I'd rather EJ find someone else too. I used to like Ejami for a multitude of reasons, but I'm so tired of Sami as she is portrayed now. I wish they'd send her offscreen for a bit and let her calm down.
My love for Ejami has dimmed a little, but it's still there. One of the biggest reasons I loved them is because they were different. They weren't the 'next (insert supercouple here)' and I no clue where the storyline was headed. I had my hopes and my theories but I didn't KNOW. It was fun to be in the dark. I had to rush home so I could actually watch to see what was going to happen.
Now, I know what's gonna happen long before it happens. I'm watching Elvis Wells DiMera turn into Austin Reed, and that's not a good thing. Sami's reverted to always whining all the time.
And it's not just Ejami, it's everything. Phil and Stephanie? :sleep2: Know where it's going and who's gonna be the bump. Poor old Lucas and Chloe? :sleep2: Know where it's going. Sami and Rafe? :sleep2: Pretty sure where it might go. Steve and Kayla? They'll probably be around to give dating advice. :sleep2: EJ is gonna be played for a fool by both Nicole and Sami. :sleep2:
My love for Ejami has dimmed a little, but it's still there. One of the biggest reasons I loved them is because they were different. They weren't the 'next (insert supercouple here)' and I no clue where the storyline was headed. I had my hopes and my theories but I didn't KNOW. It was fun to be in the dark. I had to rush home so I could actually watch to see what was going to happen.
Now, I know what's gonna happen long before it happens. I'm watching Elvis Wells DiMera turn into Austin Reed, and that's not a good thing. Sami's reverted to always whining all the time.
And it's not just Ejami, it's everything. Phil and Stephanie? :sleep2: Know where it's going and who's gonna be the bump. Poor old Lucas and Chloe? :sleep2: Know where it's going. Sami and Rafe? :sleep2: Pretty sure where it might go. Steve and Kayla? They'll probably be around to give dating advice. :sleep2: EJ is gonna be played for a fool by both Nicole and Sami. :sleep2:
I used to love Ejami. I remember all those times before we found out who he was and what he was up to. He seemed so gray. I loved that he turned out to be little Elvis. It made sense that he was so evil because he was Stefano's son. I always felt like he had been groomed to be Stefano's bad guy (similar to John being his pawn) and never realized that doing whatever was asked for 'Family' was wrong. I loved that Sami made him think differently. I've always loved the idea of his feelings for her changing him. It's one of my favorite themes. I loved Kayla turning Steve good, and while J&M worked kinda reversed with her finding out he had been Stefano's mercenary, I loved that her love saved him. I never got tired of hearing that from him. I guess I was hoping the same from Sami. I knew Sami was no Marlena, but I liked the idea of her paying for all the evil she'd done and being redeemed herself while redeeming Ej.
I really don't care anymore because I now dislike Sami so much, but it's why I originally did love Ejami. I just don't care about any younger couple anymore.
Now, they still can try to salvage EJole somehow. I don't think they will, though, but it's not too late if they woke up. Give it another month or so of stupid decisions, and more people will start to quit caring about EJole, too. Frankly, I think if it weren't for the professionalism and dedication of the two actors involved overcoming this crap, EJole would have sunk as soon as Nicole bought that fake stomach. I realize for some, it has. But, I think AZ and JS's acting is still saving it and making it intriguing. I assume so. I need to watch and find out and FF the other shit. :D
Yup. the writing is shit, but the attraction to Ejole for me is 1) the actors' chemistry and their exceptional talent and 2) I know how amazing they could be together if the tptb could write them as the powerful, dangerous, and sexy characters/couple that I want to see.
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The effects of a cytokine suppressive anti-inflammatory drug on the output of prostaglandin E(2) and interleukin-1 beta from human fetal membranes.
Fetal membranes are a primary source of prostaglandins and pro-inflammatory cytokines implicated in human parturition, so the inhibition of inflammatory pathways may be of benefit in pregnancies complicated by premature labour. We have therefore investigated the effects of a cytokine-suppressant anti-inflammatory drug (CSAID) on the output of prostaglandin E(2) (PGE(2)) and interleukin (IL)-1 beta from human fetal membranes in vitro. Bacterial endotoxin increased the expression of mRNA for IL-1 beta and type-2 cyclo-oxygenase (COX-2), and there were corresponding increases in the output of IL-1 beta protein and PGE(2). The CSAID decreased IL-1 beta protein, COX-2 expression and PGE(2) output, but not mRNA for IL-1 beta, indicating a post-translational effect on the production of IL-1 beta and a transcriptional affect on COX-2, with an overall reduction in PGE(2). These findings are consistent with the effects of CSAIDs in other systems, and indicate that they are of possible use in premature labour.
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T3 Featherweight 2 Pink Chrome Hair Dryer
Description
The premium styling tool creates a luxurious drying experience, combining Tourmaline® with an Ion Generator that work in synergy to emit negative ions and infrared heat, effectively combating frizz and static while infusing brilliant shine.
Clinically proven to dry faster than regular dryers, it features innovative SoftAire™ technology that increases air volume and speed without causing excess damage for a smooth, sleek finish. Featuring variable heat settings and a 2.5” barrel brush for the perfect, voluminous blow out as well as a wide concentrator nozzle for focused drying. Achieve professional, gorgeous locks in less time and with reduced damage.
Lightweight: The new weight-balanced design for even greater comfort weighs just 675 grams (1.5lbs).
2 Year Warranty
Product Details
Brand:
T3
Directions:
Rough dry hair until it is 80% dry. Divide hair into 3-4 inch sections. Place the included barrel brush underneath the first section at the roots and pull down, directing the airflow at the brush. When you reach the ends, roll hair back up to your head and hold. Continue styling this way until the section is dry. Release and move on to the next section. Finish with the Cool Shot to set your style.
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You will receive an email to confirm when your item has been sent.
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Q:
Is there a shorthand syntax for list that allows symbols in Chicken Scheme?
When I write:
'(1 2 3)
I get a list:
(1 2 3)
When I write:
'some-symbol
I get:
some-symbol
When I write:
'('some-symbol)
I get:
((quote some-symbol))
I can of course write:
(list 'some-symbol)
and I get:
(some-symbol)
which is the desired output. Is it correct that I cannot quote a symbol in a list like:
'(some-symbol)
Is there some other shorthand for the list operator that I am missing?
A:
Quote will quote the entire s-expression that follows. So, in that sense,
'(some-symbol)
will actually be a quoted list containing the symbol you're looking for.
The quote sign is a shorthand for (quote ...), so
'(some-symbol)
is equivalent to
(quote (some-symbol))
|
Q:
universal python library for internalization and translation
I need to internationalize and translate python application. I look forward for some dictionary collection resides in additional resource files that could be switched runtime and used smoothly inside python code.
I've searched stackoverflow.com for similar tools but find only platform-specific libraries, e.g. for pylons, for django and so on.
Is there any general ready for use library?
A:
Babel provides such tools:
A collection of tools for internationalizing Python applications
Babel is composed of two major parts:
tools to build and work with gettext message catalogs
a Python interface to the CLDR (Common Locale Data Repository), providing access to various locale display names, localized number and date formatting, etc.
So it helps you translate strings and provide localized float, currency, dates and other information based on a current locale:
>>> locale = Locale('es')
>>> month_names = locale.months['format']['wide'].items()
>>> month_names.sort()
>>> for idx, name in month_names:
... print name
enero
febrero
marzo
abril
mayo
junio
julio
agosto
septiembre
octubre
noviembre
diciembre
>>> format_decimal(1.2345, locale='en_US')
u'1.234'
>>> format_decimal(1.2345, locale='sv_SE')
u'1,234'
>>> format_decimal(12345, locale='de_DE')
u'12.345'
It builds on top of the default gettext library to do translations, giving you tools to extract messages from a variety of source files (python, templates, etc), including a plugin-system for other packages to provide additional extractors.
|
Q:
Pandas Pivot Table Sort Index Level 1 Not "Sticking"
I know this is a lot, but I really cannot pinpoint what is causing the problem.
Most of this code is just to demonstrate what I'm doing, but the short end of it is:
After reordering columns in a multi-indexed data frame (via
transposing and other methods), calling columns.levels returns the
original sorted levels instead of the new ones.
Given the following:
#Original data frame
import pandas as pd
df = pd.DataFrame(
{'Year':[2012,2012,2012,2012,2012,2012,2013,2013,2013,2013,2013,2013,2014,2014,2014,2014,2014,2014],
'Type':['A','A','B','B','C','C','A','A','B','B','C','C','A','A','B','B','C','C'],
'Org':['a','c','a','b','a','c','a','b','a','c','a','c','a','b','a','c','a','b'],
'Enr':[3,5,3,6,6,4,7,89,5,3,7,34,4,64,3,6,7,44]
})
df.head()
Enr Org Type Year
0 3 a A 2012
1 5 c A 2012
2 3 a B 2012
3 6 b B 2012
4 6 a C 2012
#Pivoted
dfp=df.pivot_table(df,index=['Year'],columns=['Type','Org'],aggfunc=np.sum)\
.sortlevel(ascending=True).sort_index(axis=1)
dfp
Enr
Type A B C
Org a b c a b c a b c
Year
2012 3.0 NaN 5.0 3.0 6.0 NaN 6.0 NaN 4.0
2013 7.0 89.0 NaN 5.0 NaN 3.0 7.0 NaN 34.0
2014 4.0 64.0 NaN 3.0 NaN 6.0 7.0 44.0 NaN
#Transposed
f=dfp.T
Year 2012 2013 2014
Type Org
Enr A a 3.0 7.0 4.0
b NaN 89.0 64.0
c 5.0 NaN NaN
B a 3.0 5.0 3.0
b 6.0 NaN NaN
c NaN 3.0 6.0
C a 6.0 7.0 7.0
b NaN NaN 44.0
c 4.0 34.0 NaN
#Sort level 2 by last column and transpose back
ab2=f.groupby(level=1)[f.columns[-1]].transform(sum)
ab3=pd.concat([f,ab2],axis=1)
ab4=ab3.sort_values([ab3.columns[-1]],ascending=[0])
ab4=ab4.drop(ab4.columns[-1],axis=1,inplace=False)
g=ab4.T
g
Enr
Type A C B
Org a b c a b c a b c
Year
2012 3.0 NaN 5.0 6.0 NaN 4.0 3.0 6.0 NaN
2013 7.0 89.0 NaN 7.0 NaN 34.0 5.0 NaN 3.0
2014 4.0 64.0 NaN 7.0 44.0 NaN 3.0 NaN 6.0
I know this was a lot, but I really cannot pinpoint what is causing the problem.
If you do:
g.Enr.columns.levels
The result is:
FrozenList([['A', 'B', 'C'], ['a', 'b', 'c']])
My question is: Why is it not:
FrozenList([['A', 'C', 'B'], ['a', 'b', 'c']]) ?
I really need it to be the second one.
Thanks in advance!
A:
A MultiIndex stores itself as a set of levels, which are the distinct possible values, and labels, which are integer codes for the actual labels used. Changing the column order is just a reshuffling of the codes, not changing the actual levels.
If you want the levels by the order in which they first appear you could do something like this.
In [61]: c = g.Enr.columns
In [62]: [c.levels[i].take(pd.unique(c.labels[i]))
...: for i in range(len(c.levels))]
Out[62]:
[Index([u'A', u'C', u'B'], dtype='object', name=u'Type'),
Index([u'a', u'b', u'c'], dtype='object', name=u'Org')]
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---
abstract: |
In this paper we present a theorem that generalizes Sawyer’s classic result about mixed weighted inequalities to the multilinear context. Let $\vec{w}=(w_1,...,w_m)$ and $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}$, the main result of the paper sentences that under different conditions on the weights we can obtain $$\Bigg\| \frac{T(\vec f\,)(x)}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})} \leq C \ \prod_{i=1}^m{\|f_i\|_{L^1(w_i)}},$$ where $T$ is a multilinear Calderón-Zygmund operator. To obtain this result we first prove it for the $m$-fold product of the Hardy-Littlewood maximal operator $M$, and also for $\mathcal{M}(\vec{f})(x)$: the multi(sub)linear maximal function introduced in [@LOPTT].
As an application we also prove a vector-valued extension to the mixed weighted weak-type inequalities of multilinear Calderón-Zygmund operators.
address:
- 'BCAM, Basque Center for Applied Mathematics, Mazarredo, 14. 48009 Bilbao Basque Country, Spain'
- |
Departamento de Matemática\
Universidad Nacional del Sur\
Bahía Blanca, 8000, Argentina
- |
Departamento de Matemática\
Universidad Nacional del Sur\
Bahía Blanca, 8000, Argentina
author:
- Kangwei Li
- 'Sheldy J. Ombrosi'
- 'M. Belén Picardi'
title: 'Weighted mixed weak-type inequalities for multilinear operators'
---
[^1]
Introduction
============
In 1985, E. Sawyer [@S] proved the following mixed weak-type inequality:
\[sawyer\] If $u,v \in A_1$, then there is a constant $C$ such that for all $t>0$, $$uv\Big(\Big\{ x \in \mathbb{R} :\; \frac{M(fv)(x)}{v(x)} \; > t \Big\}\Big)
\; \leq \; \frac{C}{t} \int_{\mathbb{R}} |f(x)|u(x)v(x)\,dx.$$
In the same work E. Sawyer conjectured that the previous theorem is valid if the maximal operator is replaced by the Hilbert transform. In 2005, D. Cruz-Uribe, J. M. Martell and C. Pérez [@CMP] extended this result to $\mathbb{R}^n$. Furthermore, they proved it for Calderón-Zygmund operators, solving this Sawyer’s conjecture.
\[cmpteo\] If $u,v \in A_1$, or $u\in A_{1}$ and $uv\in A_{\infty}$, then there is a constant $C$ such that for all $t>0$, $$uv\Bigg(\Big\{ x \in \mathbb{R}^n :\; \frac{|T(fv)(x)|}{v(x)} \; > t \Big\}\Bigg)
\; \leq \; \frac{C}{t} \int_{\mathbb{R}^n} |f(x)|u(x)v(x)\,dx,$$ where $T$ is Hardy-Littlewood maximal function or any Calderón-Zygmund operator.
Quantitative estimates of these mixed weighted results can be found in [@OPR]. Moreover, it was conjectured in [@CMP] that the conclusion of the previous theorem still holds if a weaker and more general hypothesis is satisfied. That is, if we have the following conditions on the weights, $u\in A_{1}$ and $v\in A_{\infty}$. Recently, in [@LOP] the first two authors and C. Pérez solved such conjecture. Namely, the following theorem was proved, which constitutes the more difficult case of this class of mixed weighted inequalities.
\[LOPinf\] Let $T$ be a Calderón-Zygmund operator or the Hardy-Littlewood maximal operator and let $u\in A_1$ and $v\in A_{\infty}$. Then there is a finite constant $C$ depending on the $A_1$ constant of $u$ and the $A_{\infty}$ constant of $v$ such that $$\label{a1ainf}
\ \Big\| \frac{T(fv)}{v}\Big\|_{L^{1, \infty}(uv)} \leq C \|f\|_{L^1(uv)}.$$
On the other hand, the study of multilinear Calderón-Zygmund theory started in the seventies with the works of R. Coifman and Y. Meyer ([@CoMe1] and [@CoMe2]). However, a systematic treatment of this topic appears later with works of L. Grafakos and R. Torres [@GraTor1; @GraTor2]. We recall the definition of a multilinear Calderón-Zygmund operator: let $T:S({\mathbb R}^n)\times\dots\times S({\mathbb R}^n)\to
S'({\mathbb R}^n)$ be a multilinear operator initially defined on the $m$-fold product of Schwartz spaces and taking values into the space of tempered distributions; we say that $T$ is an $m$-linear Calderón-Zygmund operator if, for some $1\le q_1, \dots, q_m<\infty$ and $\frac{1}{m} \leq p < \infty$ satisfying $\frac{1}{p}=\frac{1}{q_1}+\dots+\frac{1}{q_m}$, it extends to a bounded multilinear operator from $L^{q_1}\times\dots\times L^{q_m}$ to $L^p$, and if there exists a function $K$ defined off the diagonal $x=y_1=\dots=y_m$ in $({\mathbb
R}^n)^{m+1}$ satisfying the appropriate decay and smoothness conditions (see Page 5 in [@LOPTT] ) and such that $$T(f_1,\dots,f_m)(x) =\int_{\mathbb R^n} \cdots \int_{\mathbb R^n}
K(x,y_1,\dots,y_m) \prod_{i=1}^m f_i(y_i)\, dy_1\cdots dy_m$$ for all $ x \notin \cap_{i=1}^{m} \supp f_{i}$. Related to weighted estimates for these operators, the first result was obtained in [@GraTor2] (see also [@PerTor]) where the authors proved that, if $1 < q_1, \dots, q_m < \infty$ and $w$ is a weight in the Muckenhoupt $A_{q_0}$ class for $q_0=\min\{q_1, \dots, q_m\}$, an $m$-linear Calderón-Zygmund operator $T$ maps $L^{q_1}(w)\times\dots\times L^{q_m}(w)$ into $L^p(w)$. In [@LOPTT] Lerner et. al, developed the appropriate class of multiple weights for $m$-linear Calderón-Zygmund operators. Now, we recall some of those results in [@LOPTT] that will be useful for us along this paper. Let $1\le q_1, \dots , q_{m}<\infty$ and $\frac{1}{m} \leq p < \infty$ be such that $\frac{1}{p}=\frac{1}{q_1}+\dots+\frac{1}{q_m}$. We say that $\vec w=(w_1,\dots,w_m)$ satisfies the *multilinear $A_{\q}$ condition* if $$\label{multiap}
\sup_{Q}\Big(\frac{1}{|Q|}\int_Q\nu_{\vec
w}\Big)^{1/p}\prod_{i=1}^m\Big(\frac{1}{|Q|}\int_Q
w_i^{1-q'_i}\Big)^{1/q'_i}<\infty$$ where the supremum is taken over all cubes $Q$ (when $q_i=1$, $\Big(\frac{1}{|Q|}\int_Q w_i^{1-q'_i}\Big)^{1/q'_i}$ is understood as $\displaystyle(\inf_Q w_i)^{-1}$). Now, if $\vec w$ satisfies the $A_{\q}$ condition and $1<q_1,\dots,q_m<\infty$, then an $m$-linear Calderón-Zygmund operator $T$ maps $L^{q_1}(w_1)\times \dots \times L^{q_m}(w_m) $ into $ L^{p}(\nu_{\vec w})$. If at least one $q_i=1$, then $T$ maps $L^{q_1}(w_1)\times \dots \times L^{q_m}(w_m) $ into $ L^{p,\infty}(\nu_{\vec w})$. It is shown that $\prod_{i=1}^m A_{q_i} \subseteq A_{\q}$ and that this inclusion is strict. Moreover, if $T$ is the $m$-linear Riesz transform, it was proved in [@LOPTT] that $A_{\q}$ is a necessary condition for such weighted estimate of $T$.
One of the key points in [@LOPTT] was the introduction of the multi(sub)linear maximal function $\mathcal{M}$ defined by $$\mathcal M(\vec f\,)(x)=\sup_{Q\ni x
}\prod_{i=1}^m\frac{1}{|Q|}\int_Q|f_i(y_i)|dy_i,$$ where $\vec{f}=(f_1,...,f_m)$ and the supremum is taken over all cubes $Q$ containing $x$.
This maximal operator is smaller than the product $\prod_{i=1}^m Mf_i$, which was the auxiliary operator used previously to estimate multilinear singular integral operators.
The aim of this paper is to obtain mixed weighted estimates that generalize Theorem \[LOPinf\] to the multilinear context. We will investigate both $\prod_{i=1}^m Mf_i$ and $\mathcal{M}(\vec f)$ under different assumptions. Then by an extrapolation theorem we can also prove mixed weighted inequalities for multilinear Calderón-Zygmund operators.
The first result of this paper is the following:
\[main\] Let $w_1,...,w_m \in A_1$ and $v\in A_{\infty}$. Denote $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}$. Then, $$\Bigg\| \frac{\prod_{i=1}^m Mf_i}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})} \leq C \prod_{i=1}^m{\|f_i\|_{L^{1}(w_i)}}.$$
The particular case in which the weight $v=1$ in the theorem above was proved in [@LOPTT] (See Theorem 3.12 there). Adding a non-constant function $v$ in the distribution function makes the proof more complicated. However, benefits from Theorem \[LOPinf\] and the ideas in [@LOPTT] allow us to obtain the result. It is obvious that the conclusion in Theorem \[main\] also holds for the maximal operator $\mathcal M$.
We will see below that as a consequence of Theorem \[main\], we can obtain the same result for multilinear Calderón-Zygmund operators. However, we know that $\prod_{i=1}^m Mf_i$ is too big to estimate multilinear Calderón-Zygmund operators. In fact, it was proved in [@LOPTT] that the condition $w_1,...,w_m \in A_1$ is stronger than $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$. And since the last condition characterizes the weak type of a multilinear Calderón-Zygmund operator $T$ from $L^{1}(w_{1})\times \dots \times L^{1}(w_{m})$ into $L^{1/m,\infty}(\nu)$, it is natural to ask if it is possible to relax the hypothesis $w_1,...,w_m \in A_1$ in Theorem \[main\] if we put $T$ or $\mathcal M $ instead of $\prod_{i=1}^m Mf_i$. The next theorem gives a partially positive answer.
\[Max\]
Let $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$, $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}$ and $v$ be a weight satisfying $\nu v^{\frac 1m}\in A_\infty$. Then there is a constant $C$ such that $$\label{se111}
\Bigg\| \frac{\mathcal M(\vec f\,)(x)}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})} \leq C \ \prod_{i=1}^m{\|f_i\|_{L^1(w_i)}}.$$
So holds for either $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$ and $\nu v^{\frac 1m}\in A_\infty$ or (as a consequence of Theorem \[main\]) if the weights $w_i \in A_1$ for $i=1,...,m$ and $v \in A_\infty$. These conditions are independent. However, we believe that there is a unified condition that contains both such that holds. That is:
\[con1\] Let $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$, $v^{1/m}\in A_{\infty}$ and $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}$. Then there is a constant $C$ such that $$\Bigg\| \frac{\mathcal M(\vec f\,)(x)}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})} \leq C \ \prod_{i=1}^m{\|f_i\|_{L^1(w_i)}}$$
In general, under the hypothesis of Theorem \[Max\] the estimate does not hold if $\mathcal M(\vec f)$ is replaced by $\prod_{i=1}^m Mf_i$ even in the case that $v(x)=1$. This fact was proved in Remark 7.5 in [@LOPTT].
The following (extrapolation) theorem allows us to reduce the problem of multilinear Calderón-Zygmund operators to the multilinear maximal function, exactly as in the linear case. Actually, the theorem below was essentially obtained in [@OmPe], which is a combination of Theorem 1.5 and some observations in Section 2.2 there. However, for the sake of completeness we will give a complete proof in Appendix A .
\[extension\] Let $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$, $v^{1/m}\in A_{\infty}$ and $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}$. Then $$\Bigg\| \frac{T(\vec{f})}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})} \leq C \ \Bigg\| \frac{\mathcal{M}(\vec{f})}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})}$$ where $C$ is a constant and $T$ is a multilinear Calderón-Zygmund operator.
Now, as a consequence of Theorems \[main\], \[Max\] and \[extension\] we obtain the main result of this paper:
\[muczo\] Let $T$ be a multilinear Calderón-Zygmund operator, $\vec{w}=(w_1,...,w_m)$ and $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}$. Suppose that $\vec{w} \in A_{\vec{1}}$ and $\nu v^{\frac 1m}\in A_\infty$ or $w_1,...,w_m \in A_1$ and $v \in A_\infty$. Then there is a constant $C$ such that $$\label{se}
\Bigg\| \frac{T(\vec f\,)(x)}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})} \leq C \ \prod_{i=1}^m{\|f_i\|_{L^1(w_i)}}$$
Recall the definition of $RH_{\infty}$:
\[RHinf\] We denote by $RH_{\infty}$ the class of weights $w$ such that for all cube $Q$, there exists a constant $C$, which is independent of $Q$, such that $$\mathop{\textup{ess}\, \sup}_{x\in Q} \ w(x) \leq \frac{C}{|Q|} \ \int_Q {w(x) dx}.$$
Since if $u \in A_1$ and $v\in RH_{\infty}$, then $uv^{\frac 1m}\in A_{\infty}$ (see Lemma \[pesos\] below), we have a direct corollary of Theorem \[muczo\].
Let $\vec{w}=(w_1,...,w_m)\in A_{\vec{1}}$ and let $v\in RH_{\infty}$. Then there is a constant $C$ such that $$\Bigg\| \frac{T(\vec f\,)(x)}{v}\Bigg\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})} \leq C \ \prod_{i=1}^m{\|f_i\|_{L^1(w_i)}}$$
The article is organized as follows. In Section 2 we prove Theorem \[main\]. The proof of Theorem \[Max\] is presented in Section 3. In Section 4 as an application of Theorem \[muczo\] we obtain a vector-valued extension of the mixed weighted inequalities obtained for multilinear Calderón-Zygmund operators. The last Section is the Appendix A where we give a complete proof of Theorem \[extension\].
Proof of Theorem \[main\]
=========================
First, we need the following Lemma.
\[pesos\]
(a) \[a\] $w\in A_{\infty}$ if and only if $w=w_1w_2$, where $w_1\in A_1$ and $w_2 \in RH_{\infty}$.
(b) \[b\] If $w\in A_1$, then $w^{-1} \in RH_{\infty}$.
(c) \[c\] If $u,v \in RH_{\infty}$, then $uv\in RH_{\infty}$.
(d) \[Ainf\] If $w\in A_{\infty}$ and $u\in RH_{\infty}$, then $wu\in A_{\infty}$.
(e) \[d\] If $w \in RH_{\infty}$, then $w^{s}\in RH_{\infty}$ for any $s>0$.
All these properties of $A_p$ classes of Muckenhoupt are well known. The first three can be found in [@CUN] or [@GCRF] for instance. However, as far as we know, and are not written specifically in any place, so in the following paragraph we present a simple argument for them.
Proof of (\[Ainf\]): Since $w\in A_{\infty}$, by (\[a\]), $w=w_1w_2$, where $w_1\in A_1$ and $w_2\in RH_{\infty}$. By (\[c\]), $w_2u\in RH_{\infty}$. Then, $wu=(w_1w_2)u=w_1(w_2u)$. Now, by (\[a\]), $wu\in A_{\infty}$.
Proof of (\[d\]): If $s\ge 1$, this is just by Hölder’s inequality, so we only need to consider the case $s<1$. Since $w\in RH_\infty\subset A_\infty$, then $$\frac 1{|Q|}\int_Q w \le C_{s,w} \Big(\frac 1{|Q|}\int_Q w^s\Big)^{\frac 1s}.$$ By definition, our claim follows immediately.
**Proof of Theorem \[main\] :** The main idea of this proof is to reduce the problem to the linear case and then apply Theorem \[LOPinf\]. We define $$E=\{ x: v(x)< \prod_{i=1}^m{Mf_i}(x) \leq 2v(x) \}$$ Let $\tilde{v_i}=\prod_{j=1, j\neq i}^m{(Mf_j)}^{-1}$ and let $v_i=v\tilde{v_i}$. Observe that $v\in A_{\infty}$ and $\tilde{v_i}\in RH_{\infty}$. By Lemma \[pesos\] (\[Ainf\]), $v_i\in A_{\infty}$. In order to prove the theorem it is enough to show that $$v^{\frac{1}{m} }\nu (E)\leq C \prod_{i=1}^{m}\|f_i\|_{L^1(w_i)}.$$ By Hölder’s inequality and Theorem \[LOPinf\], we have $$\begin{aligned}
v^\frac{1}{m} \nu (E) & \leq {\int_E{\big(\prod_{i=1}^{m} Mf_i \ w_i\big)^{\frac{1}{m}}}}\leq \prod_{i=1}^{m}{\Big( \int_E{Mf_i \ w_i} \Big) ^{\frac{1}{m}}}\leq 2 \ \prod_{i=1}^{m}\Big( \int_E {v_i \ w_i}\Big)^{\frac{1}{m}} \\
&\leq 2 \ \prod_{i=1}^{m}\Big( \int_{\{ x : Mf_i >v_i\}} {v_i \ w_i}\Big)^{\frac{1}{m}}\leq C \ \prod_{i=1}^{m}{\|f_i\|_{L^1(w_i)}^{\frac 1m}},\end{aligned}$$ where in the last inequality we have used Theorem \[LOPinf\] since $w_i\in A_1$ and $v_i\in A_{\infty}$.
Proof of Theorem \[Max\]
========================
We follow the strategy of [@LOP]. So we only need to consider the dyadic multilinear maximal functions. First, recall that if $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$, then $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}\in A_1$ (see Theorem 3.6 in [@LOPTT]). On the other hand, since $\nu \in A_1$ it is not difficult to check that the hypothesis $\nu v^{\frac 1m}\in A_\infty$ implies that $v^{\frac 1m}\in A_\infty$.
We shall prove $$\nu v^{\frac 1m}\Big(\Big\{x: 1<\frac{\mathcal M_d(f_1,\cdots,f_m)(x)}{v(x)}\le 2\Big\}\Big)\le C \Big(\prod_{i=1}^m\int_{\mathbb R^n} |f_i|w_i\Big)^{\frac 1m}$$ Without loss of generality, we can assume $f_i\ge 0$, $i=1,\cdots,m$. Let $$E_k:=\Big\{x: 1<\frac{\mathcal M_d(f_1,\cdots,f_m)(x)}{v(x)}\le 2, \,a^{mk}<v(x)\le a^{m(k+1)}\Big\},$$ where $a>2^{n}$. Again, define $$\Omega_k=\{\mathcal M_d(f_1,\cdots,f_m)> a^{mk}\}$$ and let $\{I_j^k\}_j$ be the collection of maximal dyadic cubes in $\Omega_k$. Then by maximality, $a^{mk}<\prod_{i=1}^m \langle f_i\rangle_{I_j^k}\le 2^{mn}a^{mk}$. Splitting the collection $\{I_j^k\}_j$ to $$\mathcal Q_{l,k}=\{I_j^k: a^{k+l}\le\langle v^{\frac 1m}\rangle_{I_j^k}< a^{k+l+1}\}, \quad l\in \mathbb Z.$$ Then we have $$\begin{aligned}
\sum_{k\in \mathbb Z}\nu v^{\frac 1m}(E_k)&=\sum_{k\in \mathbb Z}\nu v^{\frac 1m}(E_k\cap\Omega_k)= \sum_{k\in \mathbb Z}\sum_{j}\nu v^{\frac 1m}(E_k\cap I_{j}^k)
\\
&\le \sum_{k\in \mathbb Z}\sum_{l\ge 0}\sum_{I_j^k\in \mathcal Q_{l,k}} a^{k+1}\nu(E_k\cap I_j^k)
\\
&= \sum_{k\in \mathbb Z}\sum_{l\ge 0}\sum_{I_j^k\in \Gamma_{l,k}} a^{k+1}\nu(E_k\cap I_j^k),\end{aligned}$$ where $$\Gamma_{l,k}=\{I_{j}^k\in \mathcal Q_{l,k}: |I_j^k\cap \{x: a^k<v^{\frac 1m}\le a^{k+1}\}|>0\}.$$ From now on, we shall deal with the case $l=-1$ and $l \ge 0$ separately. By monotone convergence theorem, it suffices to give a uniform estimate for $$\sum_{k\ge N} \sum_{l\ge 0}\sum_{I_j^k\in \Gamma_{l,k}} a^{k+1}\nu(E_k\cap I_j^k),$$ where $N<0$. We have the following two lemmas. The proofs are essentially given in [@LOP].
$\Gamma=\cup_{ l\in \mathbb Z}\cup_{k\ge N}\Gamma_{l,k}$ is sparse.
For $l\ge 0$ and $I_j^k\in \Gamma_{l,k}$, there exist constants $c_1$ and $c_2$ depending on $\nu,v$ such that $$\nu(E_k\cap I_j^k)\le c_1 e^{- c_2 l} \nu(I_j^k).$$
We also have the following lemma.
\[rh\] If $w_1 w_2 \in A_\infty$, then for any cube $Q$, we have $$\langle w_1 w_2 \rangle_Q \le C([w_1 w_2]_{A_\infty}) \langle w_1 \rangle_Q \langle w_2 \rangle_{Q}.$$
let $E_1=\{x\in Q: w_1(x)> 4\langle w_1\rangle_{Q}\}$ and $E_2=\{x\in Q: w_2(x)> 4\langle w_2\rangle_{Q}\}$. Then by Chebyshev, it is easy to see that $E:=Q\setminus (E_1\cup E_2)$ satisfies $|E|\ge \frac 12|Q|$. Since $w_1w_2\in A_\infty$, we have $$\begin{aligned}
w_1w_2(Q)&\le c([w_1 w_2]_{A_\infty}) w_1w_2(E)\le 16 c([w_1 w_2]_{A_\infty}) \langle w_1\rangle_{Q} \langle w_2\rangle_{Q} |E| \\
&\le 16 c([w_1 w_2]_{A_\infty}) \langle w_1\rangle_{Q} \langle w_2\rangle_{Q} |Q|.\end{aligned}$$
With this lemma, we can also obtain the exponential decay for $l <0$.
For $l< 0$ and $I_j^k\in \Gamma_{l,k}$, there exists a constant $c_1$ depending on $\nu,v$ such that $$\nu(E_k\cap I_j^k)\le c_1 a^{l} \nu(I_j^k).$$
By Lemma \[rh\], we have $$\nu v^{\frac 1m}(I_j^k)\le C_{\nu,v} \langle \nu\rangle_{I_j^k} \langle v^{\frac 1m}\rangle_{I_j^k} |I_j^k|\le C_{\nu,v} a^{k+l} \nu(I_j^k).$$ On the other hand, $$\nu v^{\frac 1m}(I_j^k) \ge a^k \nu(E_k \cap I_j^k).$$ Therefore $$\nu(E_k\cap I_j^k)\le C_{\nu,v} a^{l} \nu(I_j^k).$$
Now fix $l$, form the principal cubes for $\cup_{k\ge N}\Gamma_{l,k}$: let $\mathcal P_0^l$ be the maximal cubes in $\cup_{k\ge N}\Gamma_{l,k}$, then for $m\ge 0$, if $I_s^t\in \mathcal P_m^l$, we say $I_j^k\in \mathcal P_{m+1}^l$ if $I_j^k$ is maximal (in the sense of inclusion) in $ \mathcal D(I_s^t)$ such that $$\langle \nu \rangle_{I_{j}^k}> 2 \langle \nu \rangle_{I_s^t}$$ Denote $\mathcal P^l=\cup_{m\ge 0}\mathcal P_m^l$ and $\pi(Q)$ is the minimal principal cube which contains $Q$. We have $$\begin{aligned}
\sum_k\sum_{l\in \mathbb Z}\sum_{I_j^k\in \Gamma_{l,k}}a^{k+1}\nu(E_k\cap I_j^k)
& \le \sum_{l\in \mathbb Z}c_1 e^{- c_2 |l|} a^{1-l} \sum_k\sum_{I_j^k\in \Gamma_{l,k}} \langle v^{\frac 1m}\rangle_{I_j^k} \nu(I_j^k)\\
&\le\sum_{l\in \mathbb Z}2c_1 e^{- c_2 |l|}a^{1-l} \sum_{I_s^t\in \mathcal P^l} \langle \nu\rangle_{I_s^t} \sum_{k,j:\pi(I_j^k)=I_s^t} v^{\frac 1m}(I_j^k)\\
&{\lesssim_n} \sum_{l\in \mathbb Z}c_1 e^{- c_2 |l|} a^{-l} [v^{\frac 1m}]_{A_\infty}\sum_{I_s^t\in \mathcal P^l} \langle \nu\rangle_{I_s^t} v^{\frac 1m}(I_s^t)\\
&= \sum_{l\in \mathbb Z}c_1 e^{- c_2 |l|} a^{-l} [v^{\frac 1m}]_{A_\infty}\int_{\mathbb R^n} v^{\frac 1m}\sum_{I_s^t\in \mathcal P^l} \langle \nu\rangle_{I_s^t}\chi^{}_{I_s^t}\\
&\lesssim \sum_{l\in \mathbb Z}c_1 e^{- c_2 |l|} a^{-l} [v^{\frac 1m}]_{A_\infty}[\nu]_{A_1}\sum_{Q\in \mathcal P^l_*} \nu v^{\frac 1m}(Q),\end{aligned}$$ where in the last step we have used the stopping criteria, i.e., $$\sum_{I_s^t\in \mathcal P^l} \langle \nu\rangle_{I_s^t}\chi^{}_{I_s^t}\le 2[\nu]_{A_1} \nu(x), \,\, a.e. \,\,x\in \mathop\cup_{s,t: I_s^t\in \mathcal P^l} I_s^t$$ and $\mathcal P^l_*$ is the collection of maximal cubes (in the sense of inclusion) in $\mathcal P^l$. For fixed $Q\in \mathcal P^l_*$, by Lemma \[rh\] $$\begin{aligned}
\nu v^{\frac 1m}(Q)&\le C_{\nu,v} \langle \nu\rangle_{Q} \langle v^{\frac 1m}\rangle_{Q} |Q| \lesssim_n a^{l}C_{\nu,v} u(Q)\prod_{i=1}^m \langle f_i\rangle_{Q}^{\frac 1m}\\
&\le a^{l}C_{\nu,v}[\vec w]_{A_{\vec 1}} \prod_{i=1}^m (\int_Q f_i w_i)^{\frac 1m}.\end{aligned}$$ By the disjointness of $Q$ and Hölder’s inequality, we obtain $$\sum_{Q\in \mathcal P^l_*} \nu v^{\frac 1m}(Q)\lesssim a^{l}C_{\nu,v}[\vec w]_{A_{\vec 1}} \prod_{i=1}^m \|f_i\|_{L^1(w_i)}^{\frac 1m},$$ and we conclude the proof.
A vector-valued extension of Theorem \[muczo\]
==============================================
Recently in [@CMO] D. Carando, M. Mazzitelli and the second author obtained a generalization of the Marcinkiewicz-Zygmund inequalities to the context of multilinear operators. In the particular case of paraproducts, Marcinkiewicz-Zygmund inequalities were obtained by C. Benea and C. Muscalu in [@BM] and [@BM2]. The results in [@CMO] extend the previous ones in [@GM] and [@BPV].
The following theorem is one of the results in [@CMO].
\[CMO\] Let $0<p, q_1, \dots, q_m < r<2$ or $r=2$ and $0<p, q_1, \dots, q_m < \infty$ and, for each $1 \leq i \leq m$, consider $\{f^i_{k_i}\}_{k_i} \subset L^{q_i}(\mu_i)$. And Let $S$ be a multilinear operator such that $S\colon L^{q_1}(\mu_1) \times \cdots \times L^{q_m}(\mu_m) \to L^{p,\infty}(\nu)$, then, there exists a constant $C>0$ such that
$$\label{weak MZ multilineal p,q>0}
\left\| \left( \sum_{k_1, \dots, k_m} |S(f^1_{k_1}, \dots, f^m_{k_m})|^r \right)^{\frac{1}{r}} \right\|_{L^{p, \infty}(\nu)} \leq C \|S\|_{weak} \prod_{i=1}^m \left\| \left( \sum_{k_i} |f^i_{k_i}|^{r} \right)^{\frac{1}{r}} \right\|_{L^{q_i}(\mu_i)}.$$
As a consequence of this theorem and Theorem \[main\] we obtain the following mixed weighted vector valued inequality for a multilinear Calderón-Zygmund operator $T$.
\[ext vec\] Let $S(\vec{f})=\frac{T(\vec{f})}{v}$, where $T$ is a Calderón-Zygmund operator. Let $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$ and $v\in RH_{\infty}$, or $w_1,...,w_m\in A_1$ and $v\in A_{\infty}$. Let $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}$ and let $1<r\leq 2$. For each $1 \leq i \leq m$, consider $\{f^i_{k_i}\}_{k_i} \subset L^{1}(w_i)$. Then, there exists a constant $C>0$ such that
$$\label{ext vect}
\left\| \left( \sum_{k_1, \dots, k_m} |S(f^1_{k_1}, \dots, f^m_{k_m})|^r \right)^{\frac{1}{r}} \right\|_{L^{\frac{1}{m}, \infty}(\nu v^{\frac{1}{m}})} \leq C \prod_{i=1}^m \left\| \left( \sum_{k_i} |f^i_{k_i}|^{r} \right)^{\frac{1}{r}} \right\|_{L^{1}(w_i)}.$$
Observe that $S$ satisfies $S\colon L^{1}(w_1) \times \cdots \times L^{1}(w_m) \to L^{\frac{1}{m},\infty}(\nu v^{\frac{1}{m}})$, so we are under the hypothesis of Theorem \[CMO\].
Appendix A. Proof of Theorem \[extension\]
==========================================
First, as we mentioned before, that if $\vec{w}=(w_1,...,w_m) \in A_{\vec{1}}$ then $\nu = w_1^\frac{1}{m}...w_m^\frac{1}{m}\in A_1$. We will follow the ideas of [@OmPe Theorem 1.5], and these ideas are based in previous one in [@CMP]. Define the operator $S$ by
$$Sf(x)=\frac{M(f\nu )(x)}{\nu (x)}$$ when $\nu (x) \neq 0$ and $Sf(x)=0$ when $\nu (x)=0$. (Since $\nu \in A_1$, $\nu > 0$ a.e.).
Since $\nu \in A_1$, $S$ is bounded on $L^{\infty }(\nu v^{\frac{1}{m}})$ with constant $C=[\nu ]_{A_1}$, that is, $$\| Sf\| _{L^{\infty }(\nu v^{\frac{1}{m}})} \leq [\nu ]_{A_1} \| f\| _{L^{\infty }(\nu v^{\frac{1}{m}})}.$$ We will now show that $S$ is bounded on $L^{p_0}(\nu v^{\frac{1}{m}})$ for some $1<p_0<\infty $. Observe that
$$\int_{\mathbb{R}_n} Sf(x)^{p_0} \ \nu (x) \ v^{\frac{1}{m}}(x) \ dx = \int_{\mathbb{R}_n} M(f\nu )(x)^{p_0} \ \nu (x) ^{1-p_0} \ v^{\frac{1}{m}}(x) \ dx.$$ Since $v^{1/m}\in A_{\infty}$, $v^{\frac{1}{m}}\in A_t$ for some $t>1$ large. Then by the $A_p$ factorization theorem there exist $v_1,v_2\in A_1$ such that $v^{\frac{1}{m}}=v_1v_2^{1-t}$; hence, $$\nu^{1-p_0}v^\frac{1}{m}=v_1(\nu v_2^{\frac{t-1}{p_0-1}}).$$ By Lemma 2.3 in [@CMP] there exists $0<\e <1$, depending only on $[\nu]_{A_1}$, such that $\nu v_2^{\e} \in A_1$ for all $v_2\in A_1$ and $0<\e <\e_0$. Thus, if we let $$p_0=\frac{2(t-1)}{\e_0}+1,$$ then $\nu v^{\frac{1}{m}}\in A_{p_0}$.
By Muckenhoupt’s theorem, $M$ is bounded on $L^{p_0}(\nu ^{1-p_0} v^{\frac{1}{m}})$ and therefore $S$ is bounded on $L^{p_0}(\nu v^{\frac{1}{m}})$ with some constant $C_0$. Thus by Marcinkiewicz interpolation in the scale of Lorentz spaces, $S$ is bounded on $L^{q,1}(\nu v^{\frac{1}{m}})$ for all $p_0<q<\infty $. In particular, by [@CMP Proposition A.1],
$$\| Sf\| _{L^{q,1}(\nu v^{\frac{1}{m}})} \leq 2^{\frac{1}{q}} \Bigg( C_0 \Big(\frac{1}{p_0} - \frac{1}{q}\Big)+ C_1 \Bigg) \|f\|_{L^{q,1}(\nu v^{\frac{1}{m}})}.$$ Thus, for all $q\geq 2p_0$ we have that $\| Sf\| _{L^{q,1}(\nu v^{\frac{1}{m}})} \leq K_0 \|f\|_{L^{q,1}(\nu v^{\frac{1}{m}})}$ with $K_0=4p_0 \big( C_0 + C_1 \big).$ We emphasize that the constant $K_0$ is valid for every $q\geq 2p_0$.
Again by [@CMP Lemma 2.3], for every weight $W_1 \in A_1$ with $[W_1]_{A_1}\leq 2K_0$ there exists $0<\tilde{\e_0} <1$ (that depends only on $K_0$) such that $W_1 W_2^{\e} \in A_1$ for all $W_2 \in A_1$ and $0<\e < \tilde{\e_0}$.
Fix $0<\e < min\{ \tilde{\e_0}, \frac{1}{2p_0} \}$ and let $r=(\frac{1}{\e})'$. Then $r'>2p_0$ and so $S$ is bounded on $L^{r',1}(\nu v^{\frac{1}{m}})$ with constant bounded by $K_0$. Now apply the Rubio de Francia algorithm to define the operator $\mathcal{R}$ on $h\in L^{r',1}(\nu v^{\frac{1}{m}})$, $h\geq 0$, by $$\mathcal{R} h(x)=\sum_{k=0}^{\infty} {\frac{S^kh(x)}{2^kK_0^k}}.$$
It follows immediately from this definition that:
- $h(x) \leq \mathcal{R} h(x)$;
- $\| \mathcal{R} h\| _{L^{r',1}(\nu v^{\frac{1}{m}})} \leq 2 \| h\|_{L^{r',1}(\nu v^{\frac{1}{m}})}$;
- $S(\mathcal{R} h)(x)\leq 2 K_0 \mathcal{R} h(x)$.
In particular, it follows from the last item and the definition of $S$ that $\mathcal{R} h \ \nu \in A_1$ with $[\mathcal{R} h \ \nu]_{A_1} \leq 2K_0.$ Let $W_1=\mathcal{R} h \ \nu$ and $W_2=v_1\in A_1$. Then $W_1W_2^{\e}\in A_1$. Hence, $\mathcal{R} h \ \nu \ v^{\frac{1}{mr'}} \in A_1 \subset A_{\infty}$.
Then, $$\begin{split}
\Big\| \frac{T(\vec{f})}{v}\Big\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})}^\frac{1}{mr}
& = \sup_{\lambda>0} \ \lambda^{\frac{1}{mr}} \Big(\nu v^\frac{1}{m} \ \{ x\in {\mathbb{R}}^n:\Big|\frac{T(\vec{f)}(x)}{v(x)}\Big|>\lambda \}\Big)^{\frac{1}{r}}\\
& = \sup_{\lambda>0} \ \lambda^{\frac{1}{mr}} \Big(\nu v^\frac{1}{m} \ \{ x\in {\mathbb{R}}^n:\Big|\frac{T(\vec{f)}(x)}{v(x)}\Big|^{\frac{1}{mr}}>\lambda^{\frac{1}{mr}} \}\Big)^{\frac{1}{r}} \\
& = \sup_{t>0} \ t \ \Big(\nu v^\frac{1}{m} \ \{ x\in {\mathbb{R}}^n:\Big|\frac{T(\vec{f)}(x)}{v(x)}\Big|^{\frac{1}{mr}}>t\}\Big)^{\frac{1}{r}} \\
& = \Big\| \Big(\frac{T(\vec{f})}{v}\Big)^\frac{1}{mr}\Big\|_{L^{r, \infty}(\nu v^\frac{1}{m})}\\
& = \sup_{h \in L^{r',1}(\nu v^\frac{1}{m}) \ : \ \|h\|_{L^{r',1}(\nu v^\frac{1}{m})}=1} \Big| \int_{{\mathbb{R}}^n} \Big| \frac{T(\vec{f})(x)}{v(x)} \Big|^{\frac{1}{mr}} \ h(x) \ \nu(x) \ v^\frac{1}{m}(x) \ dx \Big| \\
& = \sup_{h \in L^{r',1}(\nu v^\frac{1}{m}) \ : \ \|h\|_{L^{r',1}(\nu v^\frac{1}{m})}=1} \Big| \int_{{\mathbb{R}}^n} |T(\vec{f})(x)|^{\frac{1}{mr}} \ h(x) \ \nu(x) \ v^\frac{1}{mr'}(x) \ dx \Big|.
\end{split}$$ Before finishing we recall the following fact, which was proved in [@LOPTT] (see Corollary 3.8 there), if $w\in A_{\infty}$ and $s>0$ then
$$\int_{{\mathbb{R}}^n} |T(\vec{f})(x)|^{s} \ w(x)dx \leq C \int_{{\mathbb{R}}^n} \mathcal{M}(\vec{f})(x)^{s} \ w(x) dx.$$
From the definition of $\mathcal{R}h(x)$, the last inequality and Hölder’s inequality
$$\begin{split}
\int_{{\mathbb{R}}^n} |T(\vec{f})(x)|^{\frac{1}{mr}} \ h(x) \ \nu(x) \ v^\frac{1}{mr'}(x) \ dx
& \leq \int_{{\mathbb{R}}^n} |T(\vec{f})(x)|^{\frac{1}{mr}} \ \mathcal{R}h(x) \ \nu(x) \ v^\frac{1}{mr'}(x) \ dx \\
& \leq \int_{{\mathbb{R}}^n} \mathcal{M}(\vec{f})(x)^{\frac{1}{mr}} \ \mathcal{R}h(x) \ \nu(x) \ v^\frac{1}{mr'}(x) \ dx \\
& = C \int_{{\mathbb{R}}^n} \Big( \frac{\mathcal{M}(\vec{f})(x)}{v(x)} \Big)^{\frac{1}{mr}} \ \mathcal{R}h(x) \ \nu(x) \ v^\frac{1}{m}(x) \ dx \\
& \leq C \ \Big\| \Big(\frac{\mathcal{M}(\vec{f})}{v}\Big)^\frac{1}{mr} \Big\|_{L^{r, \infty}(\nu v^\frac{1}{m})} \ \Big\| \mathcal{R}h \Big\|_{L^{r', 1}(\nu v^\frac{1}{m})} \\
& \leq 2 \ C \ \Big\| \frac{\mathcal{M}(\vec{f})}{v} \Big\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})}^\frac{1}{mr} \ \Big\| h \Big\|_{L^{r', 1}(\nu v^\frac{1}{m})} \\
& = 2 \ C \ \Big\| \frac{\mathcal{M}(\vec{f})}{v} \Big\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})}^\frac{1}{mr}.
\end{split}$$
\
So we have that $$\Big\| \frac{T(\vec{f})}{v}\Big\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})}^\frac{1}{mr} \leq C \ \Big\| \frac{\mathcal{M}(\vec{f})}{v}\Big\|_{L^{\frac{1}{m}, \infty}(\nu v^\frac{1}{m})}^\frac{1}{mr}.$$
[2]{}
C. Benea and C. Muscalu, *Multiple vector valued inequalities via the helicoidal method*. Anal. PDE, 9: 1931–1988, 2016.
C. Benea and C. Muscalu, *Quasi-Banach valued inequalities via the helicoidal method*. Preprint, arXiv: 1609.01090.
F. Bombal, D. Pérez-García and I. Villanueva, *Multilinear extensions of Grothendieck’s theorem.* Quart. J. Math., 55(4): 441–450, 2004.
D. Carando, M. Mazzitelli and S. Ombrosi, *Multilinear Marcinkiewicz-Zygmund inequalities*, arXiv:1611.08284 (2016).
R.R. Coifman and Y. Meyer, *On commutators of singular integrals and bilinear singular integrals*, Trans. Amer. Math. Soc. 212 (1975), 315Ð331.
R.R. Coifman and Y. Meyer, *Commutateurs dÕintégrales singulires et opérateurs multilíneaires*, Ann. Inst. Fourier (Grenoble) 28 (1978), no. 3, 177Ð202.
D. Cruz-Uribe, J.M. Martell and C. Pérez, *Weighted weak-type inequalities and a conjecture of Sawyer* Int. Math. Res. Not., 30 (2005), 1849-1871.
D. Cruz-Uribe and C. J. Neugebauer, *The structure of the reverse Hšlder classes* Trans. Amer. Math. Soc. 347 (1995), 2941-2960
J. García-Cuerva and J.L. Rubio de Francia, *Weighted norm inequalities and related topics*. North-Holland Math. Stud. 116, North-Holland, 1985.
L. Grafakos and J.M. Martell, *Extrapolation of weighted norm inequalities for multivariable operators and applications*. J. Geom. Anal., 14(1): 19–46, 2004.
L. Grafakos and R.H. Torres, *Multilinear Calderón-Zygmund theory*, Adv. Math. 165 (2002), no.1, 124Ð164.
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A. Lerner, S. Ombrosi, C. Pérez, R. H. Torres and R. Trujillo-Gonzales, *New maximal functions and multiple weights for the multilinear Calderón-Zygmund theory* Adv. Math., 220 (2009) no. 4, 1222-1264.
K. Li, S. Ombrosi and C. Pérez, *Proof of an extension of E. Sawyer’s conjecture about weighted mixed weak-type estimates*, arXiv:1703.01530 (2017).
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E. Sawyer, *A weighted weak type inequality for the maximal function* Proc. Amer. Math. Soc. 93 (1985), 610-614.
[^1]: K.L. is supported by Juan de la Cierva-Formación 2015 FJCI-2015-24547, the Basque Government through the BERC 2014-2017 program and Spanish Ministry of Economy and Competitiveness MINECO: BCAM Severo Ochoa excellence accreditation SEV-2013-0323. S. O. and B. P. are supported by CONICET PIP 11220130100329CO, Argentina.
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//---------------------------------------------------------------------
// <copyright file="TypeFunctionHelper.cs" company="Microsoft">
// Copyright (C) Microsoft Corporation. All rights reserved. See License.txt in the project root for license information.
// </copyright>
//---------------------------------------------------------------------
namespace Microsoft.Test.OData.Services.ODataWCFService.BuiltInFunctionHelper
{
using System;
using Microsoft.OData.Edm;
public class TypeFunctionHelper
{
public static TOut TypeCastFunction<TOut, TIn>(TIn instance)
{
if (instance == null)
{
throw new ArgumentNullException("Cast input");
}
try
{
if (typeof(IConvertible).IsAssignableFrom(instance.GetType()) &&
typeof(IConvertible).IsAssignableFrom(typeof(TOut)) &&
!typeof(TOut).IsEnum)
{
return (TOut)Convert.ChangeType(instance, typeof(TOut));
}
else if (typeof(TOut).IsEnum && typeof(TIn) == typeof(string))
{
//Convert string to enum;
var enumValue = Enum.Parse(typeof(TOut), instance.ToString(), true);
return (TOut)enumValue;
}
else
{
return (TOut)(object)instance;
}
}
catch (Exception ex)
{
throw new InvalidCastException(string.Format("Can't convert type {0} to type {1}", instance.GetType(), typeof(TOut)), ex);
}
}
}
}
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The present invention relates generally to gas turbine engines, and, more specifically, to noise reduction therein.
In an aircraft turbofan gas turbine engine, air is compressed, mixed with fuel, and ignited for generating hot combustion gases which flow downstream through turbine stages and are discharged as a jet with corresponding thrust. The turbines power a compressor, and also power a fan which produces a majority of the propulsion thrust for powering an aircraft in flight.
The propulsion air and jet exhaust are two sources of engine noise. The reduction thereof is an environmental objective and is typically accomplished using various techniques including higher bypass ratio turbofans, acoustic liners inside the engine ducts and fan nacelle, and exhaust mixers.
A principal source of fan noise is the interaction between the fan rotor blades and stator vanes or struts downstream therefrom. The fan has a rotational speed N and effects a blade passing frequency (BPF) which is the product of the rotational speed N and the number B of rotor blades. The fan air generates spinning mode noise produced by rotating pressure fields and wakes caused by the rotor blade, and the interaction thereof with the adjacent stator vanes. This noise is emitted from the engine both upstream through the inlet of the fan duct and downstream through the duct outlet.
The spinning mode noise occurs at discrete frequencies including the fundamental blade passing frequency BPF, which is also a first harmonic, and higher order frequencies or harmonics thereof.
In order to ensure the decay of spinning mode noise, it is known to select the number of vanes to be greater than or equal to twice the product of the number of blades and the blade passing frequency harmonic number. For example, decay of the first harmonic spinning mode noise may be achieved using a number of vanes greater than or equal to twice the number of blades. Higher harmonic noise decay requires even a greater number of vanes which is impractical to implement in a turbofan engine.
Notwithstanding the various techniques available for reducing fan and jet noise in a turbofan engine, residual noise is still significant.
Accordingly, it is desired to further reduce fan and jet noise in an improved manner.
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Zymographical techniques for detection of matrix metalloproteinases.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases associated with extracellular matrix degradation, cellular migration, tissue remodeling, and angiogenesis. The activity of MMPs is regulated by the tissue inhibitors of metalloproteinases (TIMPs). Zymography and reverse zymography are useful to detect MMPs and TIMPs activities from various samples, for example vitreous, retina, plasma, and so on. Sample proteins are separated in substrate containing polyacrylamide gel by electrophoresis. The gel is incubated and then stained with Coomassie Blue. MMPs' activities are detected as clear bands.
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Heart transplantation for end-stage cardiomyopathy caused by an occult pheochromocytoma.
Dilated cardiomyopathy has been found in patients with pheochromocytoma. The cardiomyopathy and resultant congestive heart failure can be progressive and fatal, or reversible, if the source of the excess catecholamines is removed. Histologic and autopsy studies revealed a characteristic focal myocarditis and contraction band necrosis, indicating that the circulating catecholamine excess secreted by the pheochromocytoma is the cause of the cardiomyopathy.
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Q:
Why is my voltage lower than expected?
I'm designing a voltage measurement device and I i'm testing it and the front end voltage divider and it has a much lower voltage than expected. Circuit is below.
simulate this circuit – Schematic created using CircuitLab
So I put in 5V (real world) input across R1 (10Meg) and R2 (10Meg) I only see 384.6mV between them?? I expect to see 2.5V. What have I done wrong and how do I fix it?
p.s dont simulate the schematic its just representation
UPDATE---------
Thank you for the input, I have found the issue and its a novice mistake which took me awhile to find. I've updated the schematic. See im using R2 and R9 to attenuate the input voltage, but I did not take into account the OFF resistance of M1 and M2, which I have measured to be 0.9Mohm, so obviously most of my voltage is being dropped in R9 and M2.
A:
The opamp has maximum Ibias of 4 nanoAmps.
What Rin does your Digital Volt Meter have?
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Disposition of methylenedioxymethamphetamine and three metabolites in the brains of different rat strains and their possible roles in acute serotonin depletion.
3,4-Methylenedioxymethamphetamine (MDMA) affects both dopamine and serotonin (5-HT) systems. One of its acute actions is to cause a reversible fall in steady-state brain 5-HT concentrations. To investigate the chemical basis of this acute effect, the brain levels of the parent compound and three major metabolites, 3,4- 3,4-methylenedioxyamphetamine (MDA), 3,4-dihydroxymethamphetamine (DHMA) and 6-hydroxy-3,4-methylenedioxymethamphetamine (6-OHMDMA), were monitored, together with 5-HT levels, over a period of 6 hr in male Sprague-Dawley (SD) rats. The temporal relationships between drug concentrations of both stereoisomers and depletions were evaluated first. There was no correlation between the concentrations of the compounds measured and the extent of 5-HT depletion. Brain levels of MDMA and MDA were higher than plasma levels and exhibited a stereoselectivity in that (-)-MDMA and (+)-MDA levels were higher than those of enantiomers. The relationship between the dose of ((+)-MDMA and reduction in 5-HT levels was next investigated in SD male, SD female, and Dark Agouti (DA) female rats. These animals exhibit different capabilities of MDMA metabolism. There is a lower level of MDA, the N-demethylated metabolite of MDMA, in female SD rats than in males. Female DA rats are deficient in CYP2D isozymes, one of the enzymes responsible for demethylenation of MDMA to DHMA at pharmacological concentrations of substrate. there was a significant accuulation of MDMA in the brain and plasma of DA rats, but their 5-HT depletion was somewhat attenuated. The results indicated that MDMA ++ was apparently not the single, causative agent for the acute 5-HT depletion, which may also involve a metabolite formed by CYP2D.
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1. Field of the Invention
The present invention relates to stripping electrical wires and more particularly, to a spiral stripping electrical wire. The invention relates also to the fabrication of the spiral stripping electrical wire.
2. Description of the Related Art
The outer insulative material of an electric wire or cable is formed by means of extrusion coating. During extrusion, the conductor is extruded with the polymer out of the hole of the die at the same time.
The insulator of an electric wire or cable is made in one single color. There are some electric wires and cables that the insulator extruded from two different colors of plastics. The double color design is for easy identification. Further, the double color design also adds to beauty, thus enhancing market competivity.
FIG. 1 is a sectional view of a conventional double color electric wire extrusion device. According to this design, the extrusion device 80 comprises a main flow passage 81 and an auxiliary flow passage 82. During extrusion, the screw rod (not shown) squeezes a first insulative material 92 in the main flow passage 81 axially forwards (along the electric wire extruding direction), and simultaneously squeezes a second insulative material 93 in the second flow passage 83 perpendicularly into the first insulative material 92 in the main flow passage 81, enabling the first insulative material 92 and the second insulative material 93 to be extruded with a conductor 94 out of a die hole 83 to form an electric wire 90 having an insulative coating layer 91. FIG. 2 illustrates the outer appearance of an electric wire 90 made by means of the aforesaid extrusion device 80.
In the aforesaid extrusion device 80, the second insulative material 93 is squeezed into the first insulative material 92 from a fixed point, therefore the second insulative material 93 forms a strip in the first insulative material 92. The strip of the second insulative material 93 provides the insulator of the finished electric wire a second color for identification. To have a breakthrough in visual effect in a double color electric wire, a wire twister may be used to twist a double color electric wire spirally, changing the straight strip into a spiral strip. However, because the electric wire is flexible, it will return from the spirally deformed shape to its former straight strip shape or become not apparent in twisted shape when the external force is disappeared. For once and for all, it is not the cleaver way to change a double color electric wire into a spiral stripping design by twisting.
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Pulmonary Infections in Pregnancy.
Pregnant women experience physiological and immunological changes that increase the risk or severity of certain pulmonary infections. These changes also affect drug disposition, which impacts treatment choices. In this article, we review the available data on (1) the physiological and immunological changes that specifically impact tuberculosis, influenza, and varicella pneumonia; (2) active and latent tuberculosis management, including drug monitoring and maternal–infant outcomes; (3) the treatment and prevention of influenza; and (4) the diagnosis and management of varicella pneumonia. Clinical trials often exclude pregnant women, but there is a consensus that treating pregnant women for tuberculosis, influenza, and varicella pneumonia improves outcomes for both the woman and her child.
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The Neural Correlates of Similarity- and Rule-based Generalization.
The idea that there are multiple learning systems has become increasingly influential in recent years, with many studies providing evidence that there is both a quick, similarity-based or feature-based system and a more effortful rule-based system. A smaller number of imaging studies have also examined whether neurally dissociable learning systems are detectable. We further investigate this by employing for the first time in an imaging study a combined positive and negative patterning procedure originally developed by Shanks and Darby [Shanks, D. R., & Darby, R. J. Feature- and rule-based generalization in human associative learning. Journal of Experimental Psychology: Animal Behavior Processes, 24, 405-415, 1998]. Unlike previous related studies employing other procedures, rule generalization in the Shanks-Darby task is beyond any simple non-rule-based (e.g., associative) account. We found that rule- and similarity-based generalization evoked common activation in diverse regions including the pFC and the bilateral parietal and occipital lobes indicating that both strategies likely share a range of common processes. No differences between strategies were identified in whole-brain comparisons, but exploratory analyses indicated that rule-based generalization led to greater activation in the right middle frontal cortex than similarity-based generalization. Conversely, the similarity group activated the anterior medial frontal lobe and right inferior parietal lobes more than the rule group did. The implications of these results are discussed.
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"Sync:" "Vayger :)" "Ah, the T-7 chip." "Digital gold." "Sweet." "Not this time, guys." "What's your hurry, handsome?" "Relax!" "I've gotcha!" "Scratch three losers." "Did you see that?" "Amazing!" "Terrific!" "Who are those guys?" "Magma, Freon and the 2-D Man." "Who is this terrific trio?" "Tonight we got the exclusive inside story." "Several months ago in the Beywritch Research Center prize winning physicist Dr. Mike Morgan, his fiance Merry Michels and lab assistent Stevard Low, were accidently exposed to dangerous levels of radiation during a partical fusion experiment." "We warn viewers, that the tape we're about to show, may be to intense for children." "Turn it up." "Cool." "The results." "There bodies underwent dramatic changes." "Now, these heros have promised to use there incredible abilities, to clean up Gotham." "The government has speared no expense in establishing there new base of operation." "The Trio tower." "United in there war of crime, here comes the Terrific Trio." "Looks like, I'll be having more time to do my homework now." "We'll see." "Wait, just a little more time." "That's all I'm asking." "Hope you have better luck." "This is Gordon." "Finally." "Someone with a real line of credit." "No deals, until I know, the hostages are safe." "Sweetheart, I've already been through this with your cub scouts." "I'm lookin' at my foreign account right now and still no donations." "Better hurry, love." "Telefon's over in 5 minutes." "Should we go in?" "We can't take the chance." "That's counselor Green's family in there." "Guess who?" "Hey!" "What's the matter, boys?" "Cold feet?" "Wrong door, Einstein." "Move in!" "Let's go!" "Let's go!" "Freeze!" "Been there, done that." "Don't let 'em hurt me!" "We'll take it from here." "Right." "Hey, that's police property." "You tell 'em." "You saw the way, she looked at me." "We're freaks." "Michael, please." "I can't even hold you in my arms anymore." "It's hard for all of us." "I can imagine, my dear." "You would have to imagine, if you'd been there." "Yeah, I'm still trying to figure out that budget meeting, you went to that night." "What are you implying?" "Calm down, Mike." "It's not like he knew, this was going to happen." "Marry, you know, how much I care for you." "All of you and we're doing everything we can, to find a cure." "You should let me help." "Michael, you can't even touch a test tube without melting it." "Better you stay here, where you can do some real good." "How are they?" "Angry, frustrated, confused." "You promised, you could control them." "Give them time." "It's a big adjustment." "I hope your right, Dr. Hodges." "'Cus heaven help us, if you're not." "Hey, Magma underwear." "Shway." "Yeah, it's great to finally have clean holesome heroes, that kids can look up to." "Those guys are twips." "Batman rips." "You think?" "Big time!" "How about an ice cream?" "My treat." "Sure." "What's the catch?" "These are the Trio's latest DNA scans." "Has anyone seen this?" "No, sir." "Run them again." "We've gotta be absolutely certain." "Yes, sir." "General Norman." "We've got a problem." "I don't know, why you even bothered to send me out." "With a Terrific Trio around, there's not even a purse snatcher in site." "Hold on." "I'm picking up a hot spot on the infrared." "A fire." "Or a weenie roast." "I'll check it out." "What is it?" "It ain't Smokey the Bear." "Magma." "Working solo tonight?" "Out of my way." "How about showing a fellow civil servent some profesional courtesy." "And I thought, he was one of the good guys." "I can't believe you broke into the lab." "Why would you take such a risk?" "I had to know the truth." "But, Hodges said..." "Hodges lied." "See for yourself." "We'll be like this forever." "No." "It's worse then that." "What happened?" "We're under attack!" "It's general Norman!" "We've been double crossed!" "Hit 'em hard!" "Don't let 'em get away!" "Now, the army's attacking." "I thought they were the good guys too." "McGinnis, get out of there now!" "Fire!" "Terry!" "Fire!" "After 'em!" "Stand back!" "They're heading for the hanger!" "I see them!" "Let's take them down, major!" "This is Eagle One." "Target has been eliminated." "Station your men at all the entrances." "I want that tower secured." "You heard the general." "Those freaks ar history." "I don't think so." "The car was just a decoy?" "See for yourself." "It's not ovet yet." "I know they were your friends, Dr. Hodges." "But you, yourself, said, there condition was deteriorating and eventually they would have become dangerously psychotic." "Hello, Howard." "We have to talk." "We've been reviewing the data on the particle fusion experiment." "According to your notes, you knew about the danger." "No!" "I had no idea, this would happen!" "Just a freak accident?" "Yes." "One in a million." "Wait!" "Wha..." "What are you doing?" "Finishing, what we started." "But, you can't." "Why not?" "You'll kill us all!" "Once it reaches critical mass, the radiation can't be contained!" "Then you knew all along." "Yes." "That's why you weren't there that night." "Yes and you're not suppose to be either." "What?" "Michael had it all." "The brains, the success, your affection." "I figured, with him out of the way, I'd have a chance." "You figured wrong." "Please, turn it off." "No." "But the whole city will become a hot zone." "You're crazy." "I believe, your words were, dangerously psychotic." "We are, what you made us." "Party's over." "Finish it." "Now!" "No!" "Michael!" "I gotta shut that thing off!" "Thousands of people will die!" "Ma..." "Dr. Morgan." "You can't let that happen." "You're a hero, remember?" "No." "I'm an accident." "Where heroes, they make a choice." "I never did." "No." "You're staying for this." "Satisfied?" "No." "You don't understand." "I was there friend." "Right." "Sync:" "Vayger :)"
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439-441 SPENCER STELIZABETH, NJ07202
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Property Description for 439-441 SPENCER ST, ELIZABETH NJ 07202
This very well kept brick colonial home located in the Peterstown, Elizabeth, has spacious bedrooms, one with double closets, 2 1/2 full bathrooms ,a full basement with so much potential! Once inside you'll see that it is very spacious, with 11 closets throughout the home! 1 Car Detached Garage! Easy Show and Easy Close!
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Intermediary Nodes or proxies are important and necessary in many deployments of various application layer protocols such as e.g. Hypertext Transfer Protocol (HTTP), Hypertext Transfer Protocol Secure (HTTPS), Message Session Relay Protocol (MSRP), Session Initiation Protocol (SIP), Constrained Application Protocol (CoAP), etc. One of the most important use cases are HTTP proxies which are universally deployed in e.g. enterprises, operator networks, hotels, and airports. Another example is MSRP proxies which are abundant in MSRP deployments.
Intermediary Nodes, which may alternatively be referred to as intermediate nodes, perform services, such as e.g. traffic optimization, caching, antivirus protection, downlink content screening and filtering in e.g. schools, uplink content screening and filtering in enterprises, and message storage in the case of messaging protocols, such as e.g. MSRP.
There exist solutions for the Secure Real-time Transport Protocol (SRTP), such as e.g. in WO2010/003713 A1. However, these known solutions are not applicable for the mentioned scenario, since these solutions target another trust model where the proxy is simply not trusted to access content at all. Thus, in these solutions the proxy will not gain any access to desired content. Secondly, the aforementioned SRTP solutions use tunnel-in-tunnel and multiplexing mechanisms with additional (in our case unwanted) overhead. Thirdly, these types of solutions are SRTP-specific and do not work with TLS.
Known 3GPP IMS related mechanisms as disclosed in 3GPP TS 33.828, by which an IMS network may add/replace a Client offer for e2e security with a “hop-by-hop” security, do not offer any control or consent from the endpoints. Also, they are tightly integrated with IMS protocols (SIP, SRTP) and do not work for TLS.
Many of these application layer protocols are protected with Transport Layer Security (TLS), or Datagram Transport Layer Security (DTLS), since they can provide strong security and represent “standard” ways to protect TCP or UDP traffic implemented in most Clients and Servers. In most cases TLS or DTLS is setup before the application protocol is used. With TLS, we hereby mean all versions of TLS and its derivatives like DTLS.
When the communication is not protected with TLS, an Intermediary Node may in most cases insert itself into the communication path, i.e. by interposing itself it can potentially eavesdrop, inject, or modify traffic between sender and receiver, causing what can be referred to as “traffic intervention”. When TLS is used, each Intermediary Node has only three choices, let the Client setup TLS end-to-end with the Server, break the TLS security model, or attempt to block the traffic.
Common to the three options is that in most cases the Client and the Server are not aware that there is any Intermediary Node in the communication path. If an Intermediary Node has “silently” broken the TLS (end-to-end) security model, how does the TLS Client/Server know that their traffic is not subject to unauthorized access?
Furthermore, one or more “friendly” Intermediary Nodes in the communication path still have no way of making their presence known to the TLS Client or TLS Server even if it wants to. As neither the Client nor the Server is aware of the Intermediary Node/s and their identities, they cannot include them in its communication, meaning the Intermediary Node/s must either resort to block the traffic, i.e. disabling the Client/Server communication, or it can let the traffic pass, but then it cannot fulfil the service as intended.
Even though we have referred to TLS Clients and TLS Servers above, it will be evident from the following text that corresponding, intermediary related problems can be relevant also in scenarios where TLS is, not used, or at least initially not used.
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Power 100: The Most Powerful People in New York Real Estate
Two years ago, in the months before the fall of Lehman Brothers, when New York’s economic lily was still contentedly gilded, crafting a list of real estate’s biggest machers was pretty easy: Moguls X, Y and Z had done deals A, B and C, and the business of real estate ticked along.
Then came the bust, and the list was notable more for who had fallen off than for who had stayed on. Last year’s tally was demarcated by government—President Obama was No. 1—and by those adapting to survive. The phrase “money on the sidelines” made numerous appearances.
This year, the list, like the industry it chronicles, is very much in motion. Pinning down who is up, if anybody, and who is down the most changes by the day. This represents our take on the most powerful people in New York real estate right now.
As usual, the list remains arctic white and terminally male. (How does this keep happening in the world’s most diverse city? Even the suites of Wall Street—and of the White House—claim more diversity.) There are 12 women—the most ever—with CBRE tristate chief and REBNY chair Mary Ann Tighe the highest ranked at No. 7, and the chair of City Planning, Amanda Burden, in a distant second at No. 34. Nonwhites? Governor Paterson (No. 55), who, dear reader, will likely not make it next year, and Korean-American developer Young Woo (No. 94)—and that’s just about it.
Brokers, the middlemen (and, on occasion, middlewomen) of the city’s deals, are less represented than landlords and investors—there has just been less work to go around. Brokerages themselves are amply represented, in the form of their chief executives or chairs. These include residential ones like Pam Liebman (No. 66) of the Corcoran Group; Howard Lorber and Dottie Herman (No. 63) of Prudential Douglas Elliman; and an engorging number on the commercial side, including the boys from Newmark Knight Frank (No. 26), Peter Riguardi from Jones Lang LaSalle (No. 27) and Mitchell Steir and Michael Colacino from Studley (No. 28).
Institutionally, the same names showed up as in previous years, such as Lee Bollinger (No. 90) of Columbia; John Sexton (No. 78) of N.Y.U.; Timothy Dolan (No. 76) of the Roman Catholic Archdiocese; and James Cooper (No. 79), the Episcopalian rector of Hudson Square–controlling Trinity Church.
The No. 1 spot, supplanting the president, belongs to Stephen Ross, chairman of Related Companies. His firm seems to be everywhere about New York, particularly on the far West Side. There are train tracks there now, slightly below ground level, in an area to be avoided after dark—or in broadest daylight. But Mr. Ross envisions 13 towers on two platforms producing 5,000 apartments and 6 million square feet of office and retail space—a city within a city, 50 percent bigger than Rockefeller Center.
That’s some change right there. Vision, too.
A final few notes on the list. There are 138 names amid the 100 slots. Of those, more than 25 percent are new; the rest are returnees. If someone made the list last year, that ranking is next to their entry in parentheses. The list was chosen by The Observer, and is subjective. Feedback can be given in the comments section below.
|
:man_page: mongoc_stream_flush
mongoc_stream_flush()
=====================
Synopsis
--------
.. code-block:: c
int
mongoc_stream_flush (mongoc_stream_t *stream);
Parameters
----------
* ``stream``: A :symbol:`mongoc_stream_t`.
This function shall flush any buffered bytes in the underlying stream to the physical transport. It mimics the API and semantics of ``fflush()``, forcing a write of user space buffered data.
Not all stream implementations may implement this feature.
Returns
-------
0 is returned on success, otherwise ``-1`` and ``errno`` is set.
|
Q:
Help optimize this query with a huge IN statement
I have an insert that uses a condition checking for a NOT IN. There are about 230k rows in the NOT IN subquery.
INSERT INTO Validate.ItemError (ItemId, ErrorId, DateCreated)
(
SELECT ItemId, 10, GetUTCDate()
FROM Validate.Item
INNER JOIN Refresh.Company
ON Validate.Item.IMCompanyId = Refresh.Company.IMCompanyId
WHERE Refresh.Company.CompanyId = 14
AND
(
IMAccountId IS NULL OR NOT IMAccountId IN
(
SELECT RA.IMAccountId
FROM Refresh.Account RA
INNER JOIN Refresh.BalancePool BP
ON RA.BalancePoolId = BP.BalancePoolId
WHERE BP.CompanyId = 14
)
)
)
When I run this as-is it takes about 30+ minutes (yikes!). The number of values in the Validate.Item table could be anywhere from 150 rows to over 200k, so you can see how this might be a pain.
There are indices on all the relevant fields in the tables, and none are excessively fragmented.
My first thought was to do this in pieces, and throw it into a WHILE loop:
DECLARE @StartId int, @EndId int, @MaxId int
SELECT @MaxId = MAX(AccountId) FROM Refresh.Account
SET @StartId = 1
SET @EndId = 1000
WHILE (@StartId < @MaxId)
BEGIN
INSERT INTO Validate.ItemError (ItemId, ErrorId, DateCreated)
(
SELECT ItemId, 10, GetUTCDate()
FROM Validate.Item
INNER JOIN Refresh.Company
ON Validate.Item.IMCompanyId = Refresh.Company.IMCompanyId
WHERE Refresh.Company.CompanyId = 14
AND
(
IMAccountId IS NULL
OR NOT IMAccountId IN
(
SELECT RA.IMAccountId
FROM Refresh.Account RA
INNER JOIN Refresh.BalancePool BP
ON RA.BalancePoolId = BP.BalancePoolId
WHERE BP.CompanyId = 14
AND RA.AccountId BETWEEN @StartId AND @EndId
)
)
)
SET @StartId = @StartId + 1000
SET @EndId = @EndId + 1000
END
Doing it this way nets me a time of about a minute per loop; multiply that by 230 times and we have an even more ridiculous number.
Please tell me you guys have a better idea how to optimize this. Without this one query, the entire process only takes 8 seconds; it's just the sheer size of the Refresh.Account table that throws everything into chaos.
TIA!
Valkyrie
A:
Does using NOT EXISTS help here?
(SELECT ItemId, 10, GetUTCDate()
FROM Validate.Item INNER JOIN Refresh.Company ON
Validate.Item.IMCompanyId = Refresh.Company.IMCompanyId
WHERE Refresh.Company.CompanyId = 14
AND (IMAccountId IS NULL OR NOT EXISTS (SELECT TOP 1 RA.IMAccountId FROM
Refresh.Account RA INNER JOIN Refresh.BalancePool BP
ON RA.BalancePoolId = BP.BalancePoolId WHERE BP.CompanyId = 14 AND
RA.IMAcccountID = Validate.Item.IMAccountId)))
I am not sure, if the query is correct.
But, I am using NOT EXISTS along with TOP 1 inside the subquery.
Also, the subquery limits the record by adding an additional AND RA.IMAcccountID = Validate.Item.IMAccountId.
EDIT: I hope you get the idea of what I am trying to do.
Instead of checking it against all rows inside Refresh.Account, I am limiting the rows and trying to find atleast 1 matching row with matching IMAccountID - which should not be existing as per your original query (that uses NOT IN ...).
|
Q:
Problems with r+ mode in fopen()
I was trying out the various modes of opening a file in C. I am stuck a little at the modes of r+, w+ and a+.
#include <stdio.h>
#include <stdlib.h>
#include <string.h>
int main(void)
{
.....
/* make a file with something in it */
if( (fp = fopen( filename, "w" )) )
{
fprintf( fp, "abcd" );
fclose( fp );
}
/* see how r+ works */
if( (fp = fopen( filename, "r+" )) )
{
int c = 0;
/* read something */
c = fgetc( fp );
printf( "c is %c\n", c );
/* write something */
fseek( fp, -1, SEEK_CUR );
fputc( 'x', fp );
fflush(fp);
/* read something */
c = fgetc( fp );
printf( "c is %c\n", c );
/* rewind and show the whole thing */
rewind( fp );
while( (c = fgetc( fp )) != EOF )
{
printf( "c is %c\n", c );
}
fclose(fp);
}
return 0;
}
This gives me the following output -
c is a
c is b
c is x
c is b
c is c
c is d
Even if I remove the fflush() here -
/* write something */
fseek( fp, -1, SEEK_CUR );
fputc( 'x', fp );
//fflush(fp);
it gives me the same output. So how come I am able to write without fflush() on the output stream?(Am I right that fputc() writes on the output stream?) Also, can I use fflush() instead of fseek() in the above code snippet?
A:
Per C11 7.21.5.3.7:
When a file is opened with update mode ... output shall not be
directly followed by input without an intervening call to the fflush
function or to a file positioning function (fseek, fsetpos or
rewind) and input shall not be directly followed by output without
an intervening call to a file positioning function, unless the input
operation encounters end-of-file.
The fact that you get the same input without your fflush() call is not guaranteed by the standard (although some implementations, including glibc, allow it, so it's not all that surprising to see it work here).
For your other question, no, you can't use fflush() instead of fseek() here, because your fseek() comes before an output operation, not an input operation. fflush() is only meaningful for output streams, and for update streams where the most recent operation was not input.
|
Wesley was walking his dog around the harbour area in Bray. It was after 10pm, and he noticed that a swan seemed to be lying awkwardly on the large flood defence rocks, where the river flows into the harbour. A scattering of swan feathers could be seen on other rocks nearby. He guessed that the swan had been involved in some sort of struggle, and he could tell from the way that it was lying that the bird was in trouble. He felt that he needed to help, but he had no experience of handling swans, so he didn't know what he should do. He did what most people would do these days: he went looking for help using his smartphone.
He contacted the local forum on Facebook, where people post any "happenings" around the town that might be relevant to residents. Did anyone know what he could do to get the help he needed? Within a few minutes, he started to get responses from local people. The most promising idea was to call the Kildare Animal Foundation Wildlife Unit, which he did at once. They answered immediately, and promised to send some volunteers to help. Within twenty minutes, two women arrived, and they took on the challenge of rescuing the swan.
They clambered over the wet slippery rocks, through the river and into the darkness towards the beleaguered bird. There was initially some hope that the swan was just trapped, and perhaps he could be freed and released. However they soon discovered that it was far worse than this. The swan needed to be brought back to shore to be looked after. They summoned Wesley to help, and the three of them carried the swan ashore using a coat as a stretcher.
Crossing the river over the rocks carrying the heavy bird was not easy, and they were all up to their waists in water at one stage. They worked as a team and eventually reached dry land. At this stage, in the light of street lamps, they could see that the swan had terrible injuries, and he was not going to survive. The next task was to find a vet to help them.
As it happens, I am the honorary vet for the swans in Bray Harbour. I received a message around 11pm about what was going on, and I arranged to meet the volunteers.
As Wesley and the volunteers wrapped the swan in a towel to bring him up to see me, they noticed that the entire flock of swans had gathered around them. At the front of the flock there was a couple and a solo swan; could this have been the lifelong mate of the injured bird? This was a very moving moment and it felt like a "send-off" from the flock.
Twenty minutes later, I met up with the volunteers, and when I examined the swan, I was horrified by his injuries. He had lacerations and bite marks all along the right side of his body, and worst of all, his right wing was completely absent. I had never heard of a swan actually having a wing torn off by a dog, but this is what seemed to have happened. The bird was now semi-conscious: if they had not rescued him, he would have died a prolonged and painful death out on the rocks by himself. As it was, I could tell that there was no hope of him surviving, even with intensive treatment, so I gave him a injection of euthanasia solution directly into the vein. His trembling body relaxed and stilled as the life ebbed out of him. We had helped him in the only way possible at this stage of his crisis.
Everyone involved in this incident was left traumatised: the death of this swan had been the consequence of human negligence and lack of responsibility by a dog owner. Given the severity of the swan's injuries, the attacking dog must have had blood around his mouth, and the owner must have seen this. It was so disturbing to think that some dog owner had chosen to leave this swan to die on his own instead of trying to help
The incident highlights the need for greater responsibility and care for our wildlife and especially the need to keep dogs on a leash when they are near swans. There are noticeboards and signs in the Bray Harbour area stating these facts, along with phone numbers for people to call if they find swans in trouble, but the word needs to go out to a wider audience. Under Irish law, you are obliged to keep your dog under effective control at all times. And that means that it is illegal to allow your dog to chase and attack swans.
There was an unexpected post-script to this sad story: I had noticed that the swan had a metal ring on one leg. I noted the number, and sent a message to the people who run the database of ringed birds. A few days later, they responded by sending me the background details of the unfortunate creature.
The swan had been caught and ringed in September 2017 at Bray Harbour. After ringing, when his biometrics were being recorded, he was noted to have only one wing. The wound was old and it was presumed that he had been attacked and treated, then released. But who would release a swan with only one wing? The swan was monitored for a few weeks, and it was noticed that every time a dog ran at the flock all the others would fly to safety, while this bird would stand its ground, because he was unable to fly away. He had done well to survive for so long, but tragically, on that dark night, some uncontrolled dog had got the better of him. He was a fine bird, and he had been a hero. Not to be forgotten.
Wicklow People
|
1. Introduction: Circadian Rhythms and Their Molecular Mechanisms {#sec1-ijms-18-00938}
=================================================================
The function of the body is subject to different biological rhythms, the circadian one being keyed to a cycle of a 24-h day corresponding approximately to the 24-h light/dark cycle of the Earth's rotation. In fact, the range of the internal clock period for healthy adults is 24 h and 11 ± 16 min but it is set back to a 24-h cycle each day by exposure to morning light and to external clocks \[[@B1-ijms-18-00938]\]. This rhythm regulates most of our biological and behavioral functions. Its dysregulation leads to sleep disorders and major physiological disturbances. In psychiatric disorders, sleep problems (especially reduced total sleep with insomnia, longer sleep latency, nocturnal and early morning awakenings) are highly prevalent symptoms. Insomnia is the most frequent sleep problem reported in psychiatric disorders \[[@B2-ijms-18-00938]\]. In autism, a prevalence of insomnia from 50% to 80% has been reported \[[@B3-ijms-18-00938],[@B4-ijms-18-00938],[@B5-ijms-18-00938],[@B6-ijms-18-00938]\] compared to 9--50% in age-matched typically developing children \[[@B7-ijms-18-00938],[@B8-ijms-18-00938],[@B9-ijms-18-00938],[@B10-ijms-18-00938],[@B11-ijms-18-00938]\]. However, the interpretation of these results has to take into consideration the high prevalence of insomnia (30%) in typically developing individuals \[[@B12-ijms-18-00938],[@B13-ijms-18-00938],[@B14-ijms-18-00938]\]. It is noteworthy that sleep disorders are not specific to autism spectrum disorder (ASD) given that they are observed in ASD individuals with intellectual disability (ID), ID individuals without ASD, and individuals with brain injury as well as ID, suggesting a possible overlap between ASD and ID. Concerning schizophrenia, a genome-wide association study (GWAS) shows genetic correlations between sleep disorders and schizophrenia and between the late evening chronotype and risk of schizophrenia \[[@B15-ijms-18-00938]\]. No rigorous study of prevalence of sleep disorders was conducted in bipolar spectrum disorder and depression-related disorders but altered patterns of clock genes were reported in these disorders \[[@B16-ijms-18-00938],[@B17-ijms-18-00938]\]. Conversely, high rates of sleep problems and mental disorders have been reported in shift workers, including insomnia, fatigue, anxiety and depression \[[@B18-ijms-18-00938],[@B19-ijms-18-00938],[@B20-ijms-18-00938],[@B21-ijms-18-00938],[@B22-ijms-18-00938],[@B23-ijms-18-00938],[@B24-ijms-18-00938]\]. It is noteworthy that altered patterns of clock genes were also reported in shift workers \[[@B25-ijms-18-00938],[@B26-ijms-18-00938],[@B27-ijms-18-00938]\].
The objective of this article is an attempt to clarify the relationships between psychiatric disorders, altered expression of clock genes and endogenous circadian rhythm disturbances (especially altered sleep--wake rhythms). Is the disruption of circadian rhythms, and therefore of sleep--wake rhythms, a prerequisite for the genesis of psychiatric disorders? What roles do the clock genes play in the disruption of endogenous circadian rhythms? After describing the molecular mechanisms of circadian rhythms, their relationships with psychiatric disorders are discussed, focusing in particular on bipolar disorder, anxiety, depression, attention deficit disorder, schizophrenia and autism spectrum disorder (a rich literature review on this topic was available for these psychiatric disorders, which was not the case for other disorders such as addictions or dementia).
1.1. Daily and Circadian Rhythms {#sec1dot1-ijms-18-00938}
--------------------------------
There are different categories of physiological rhythms with different time scales, such as ultradian, tidal, circadian, lunar, and seasonal rhythms. A daily rhythm is a regular and predictable phenomenon which is defined as a series of significant physiological changes over 24 h. The biological rhythm consists of two components: the first is exogenous and modulated by environmental factors such as light--dark alternations, sleep--wake, hot--cold, and seasonal change \[[@B28-ijms-18-00938],[@B29-ijms-18-00938],[@B30-ijms-18-00938],[@B31-ijms-18-00938]\]; the second is endogenous and linked to genetic factors (studies in identical twins showed that they had identical biological rhythms \[[@B32-ijms-18-00938]\]). Homologous genes involved in the animal's activity--rest cycle have been described in humans. It has been observed that the individual tendency to get up and go to bed more or less early was associated with a polymorphism of the *circadian locomotor output cycles kaput* (*Clock*) gene. Socio-ecological exogenous factors modulate rhythms and are called synchronizers. Endogenous factors, genetic by nature, underpin the internal biological clock which is responsible for an internal time synchronization coordinating the circadian variations of biochemical, physiological and behavioral parameters.
Circadian rhythms are the best known biological rhythms at the molecular level. The alternation of activity and rest over a period of 24 h (or rest-activity cycle) was observed in drosophila, fish and mammals including rodents (rats, mice, hamsters) and humans. In mammals, this circadian rhythm is generated by a master central clock, mainly reset by ambient light, and is located in the suprachiasmatic nuclei (SCN) of the hypothalamus \[[@B33-ijms-18-00938],[@B34-ijms-18-00938]\]. Circadian regulation of all biological functions is processed through direct or indirect signals (cyclic hormone production) between the suprachiasmatic nuclei and different body structures (brain regions, organs). The body has peripheral clocks located in each organ (heart, lung, liver, muscles, kidneys, retina, etc.) that optimize the function of each organ according to the environmental context allowing therefore adaptation of the organism to environmental changes. Thus, the circadian clocks network has an adaptive function \[[@B35-ijms-18-00938]\]. Both central and peripheral clocks are detectable though both cyclic gene expression and rhythmic physiological processes. These peripheral clocks work independently but must be re-synchronized continuously through the brain's master clock acting as a real conductor. Furthermore, the neurohormone melatonin is involved in the synchronization (i.e., adjustment of the timing of existing oscillations) of peripheral oscillators; the nocturnal synthesis and release of melatonin by the pineal gland are controlled by the SCN master clock and inhibited by light exposure \[[@B36-ijms-18-00938]\].
1.2. Clock Genes {#sec1dot2-ijms-18-00938}
----------------
The first gene known as being responsible for the circadian rhythm was found in drosophila; it is the *period* (*Per*) gene \[[@B37-ijms-18-00938]\]. Subsequent research has highlighted another gene involved in the circadian rhythm: the *timeless* (*Tim*) gene \[[@B38-ijms-18-00938],[@B39-ijms-18-00938],[@B40-ijms-18-00938],[@B41-ijms-18-00938]\].
Chemical mutagenesis performed in mammals such as mice allowed identification of the first clock genes: the *Clock* gene \[[@B42-ijms-18-00938]\] (or *Npas2* in neuronal tissue), whose mutation was responsible for a lengthened rest--activity cycle. Other clock genes were then identified in the circadian regulation of the mouse: the *brain and muscle ARNT-like protein 1* (*Bmal1*) gene as a *Clock* partner, *Per1* and *Per2* genes, and *cryptochrome-1* (*Cry1*) and *Cry2* genes (genes encoding proteins involved in blue light reception in non-mammalian species).
The role of melatonin on the circadian oscillatory rhythms, and in particular as a neuroendocrine synchronizer of molecular oscillatory systems has been documented \[[@B36-ijms-18-00938],[@B43-ijms-18-00938],[@B44-ijms-18-00938],[@B45-ijms-18-00938],[@B46-ijms-18-00938]\]. Studies in animal models showed that melatonin is involved in the regulation of circadian expression of several clock genes, such as *Per1*, *Per2*, *Bmal1*, *reverse erythroblastosis virus* (*REV-ERBα*), *Clock* and *Cry1*, in both central and peripheral melatonin target tissues. For example, in rat and mouse models, it has been shown that melatonin induces rhythmic expression of *Per1*, *Bmal1*, *Clock* and *Cry1* in the pituitary (*pars tuberalis*) \[[@B47-ijms-18-00938],[@B48-ijms-18-00938]\]. It is noteworthy that *Per1* expression is undetectable in melatonin-deficient mice \[[@B49-ijms-18-00938],[@B50-ijms-18-00938]\] and pinealectomy abolishes rhythmic expression of *Per1* in the *Pars tuberalis* (PT) and desynchronizes *Per1* and *Per2* expression in the SCN \[[@B51-ijms-18-00938],[@B52-ijms-18-00938]\]. Moreover, melatonin synchronizes circadian oscillations in the cardiovascular system by influencing circadian rhythmic expression of both *Per1* and *Bmal1* in the rat heart \[[@B53-ijms-18-00938]\]. In the pituitary of sheep, melatonin stimulates *Cry1* expression and suppresses other clock genes expression \[[@B54-ijms-18-00938]\]. These effects are probably mediated by melatonin (MT) receptors, such as the MT1 receptors. Indeed, in the *pars tuberalis* of MT1 knockout mice, expression of *Per1*, *Bmal1*, *Clock* and *Cry1* was dramatically reduced but not changed in MT2 knockout mice \[[@B54-ijms-18-00938]\]. Furthermore, in the hypothalamic SCN of rats, melatonin treatment induces phase advance of the nuclear receptor *REV-ERBα* expression \[[@B55-ijms-18-00938]\]. In adipose tissue, melatonin synchronizes metabolic and hormonal function \[[@B56-ijms-18-00938]\] by regulating *Per2*, *Clock* and *REV-ERBα* \[[@B57-ijms-18-00938]\] (*REV-ERBα* is required for the daily balance of carbohydrate and lipid metabolism \[[@B58-ijms-18-00938]\]). Finally, melatonin regulates oscillation of *Clock* genes in healthy and cancerous human breast epithelial cells \[[@B59-ijms-18-00938]\] and induces a shift in the 24-h oscillatory expression of *Per2* and *Bmal1* in cultured fetal adrenal gland \[[@B60-ijms-18-00938]\]. Taken together, these studies underline the major role of melatonin in the regulation of clock genes expression allowing the synchronization of central and peripheral oscillators.
In humans, homologues of *Clock*, *Bmal1*, *Per* and *Cry* were identified. The *Clock* gene, the only cloned circadian rhythm gene, is located on chromosome 4 \[[@B61-ijms-18-00938]\]. There are other clock genes involved in circadian regulation, such as *retinoic acid receptor-related orphan receptor* (*ROR*)*-A* and *ROR-B*, *REV-ERB*, and *casein kinase-1* (*Ck1*)ε and *Ck1δ*, which control transcription of *Bmal1* gene. Additionally, the *albumin-D-site-binding protein* (*Dbp*) is also a circadian clock-controlled gene, involved in the circadian transcriptional regulation of several metabolic enzymes and some transcription factors. Some studies \[[@B25-ijms-18-00938],[@B26-ijms-18-00938],[@B27-ijms-18-00938]\] report altered expression of certain clock genes in cases of shift workers (*Per1* and *Per2*), and free-running/constant conditions (*Per1*). However, most of the clock genes are affected in case of sleep-deprivation studies \[[@B62-ijms-18-00938],[@B63-ijms-18-00938]\], highlighting the interaction between clock genes and sleep reported by Franken et al. \[[@B64-ijms-18-00938],[@B65-ijms-18-00938]\]. Indeed, clock genes contribute to the homeostatic aspect of sleep regulation and mutations in some clock genes modify the markers of sleep homeostasis and an increase in homeostatic sleep drive alters clock genes expression in the forebrain \[[@B64-ijms-18-00938]\]. It is noteworthy that the expression of clock genes is ubiquitous in humans (central nervous system, spleen, thymus, intestine, heart, lung, etc.), but also in animals (clock genes are found in most cell types among vertebrates).
1.3. Molecular Working of the Cellular Circadian Clock {#sec1dot3-ijms-18-00938}
------------------------------------------------------
The discoveries of the different clock genes led to the proposal of a molecular clock model based on a feedback loop running over 24 h \[[@B66-ijms-18-00938]\]. The molecular mechanisms underlying the circadian rhythms are rather similar regardless of the species. They include enhancer elements, repressor elements and control loops involving phosphorylation-dephosphorylation, methylation, acetylation reactions and the specific protein dimerization \[[@B67-ijms-18-00938],[@B68-ijms-18-00938]\]. In mammals, this molecular circadian system is present in the hypothalamic central clock, the suprachiasmatic nuclei, and in secondary clocks within the brain and peripheral organs. Light perceived by the retina leads to changes in transcription of certain genes of the circadian rhythm in the master clock and shows the ability of the body to adjust to a change in the cycle of the photoperiodic environment. This master clock synchronizes multiple peripheral circadian oscillators via mechanisms that remain to be better ascertained.
The molecular loop of the circadian clock seems to imply in a general way two types of mechanisms: transcriptional (transcriptional regulation of genes at the DNA level, i.e., their copy in the form of RNA messenger) and post-transcriptional (regulating steps downstream of the transcription) (see [Figure 1](#ijms-18-00938-f001){ref-type="fig"} \[[@B69-ijms-18-00938]\]).
Transcriptional mechanisms: these mechanisms can be summarized by autoregulatory feedback loops. The first is a primary negative feedback loop: they rely on a pair of positive elements and a pair of negative elements. In mammals, the positive elements are two proteins, CLOCK and BMAL1 transcription factors which heterodimerize each other. The two negative elements are also two proteins, PERIOD (PER) and CRYPTOCHROME (CRY). In a neuron of the suprachiasmatic nucleus, there is little PER and CRY in the morning. The CLOCK--BMAL1 complex activates maximally the transcription of *Per* and *Cry* genes. However, the PER and CRY proteins do not accumulate immediately due to their instability, which allows the cycle not to be interrupted prematurely. Following interactions with other proteins they are gradually stabilized during the day, then they heterodimerize and finally migrate into the nucleus \[[@B70-ijms-18-00938]\], where they inhibit the transcriptional activity of the CLOCK--BMAL1 heterodimer and thus their own transcription \[[@B71-ijms-18-00938],[@B72-ijms-18-00938]\]. The *Per* and *Cry* genes being less and less active, the PER and CRY proteins are less and less produced. Their amount reaches a maximum at the beginning of night, and then decreases. At the same time, the CLOCK--BMAL1 heterodimer gradually regains its activity during the night. Thus, the molecular mechanism of the clock consists principally in a feedback loop comprising a positive component (with the CLOCK--BMAL1 heterodimer) and a negative component (with the PER--CRY heterodimer). A complete cycle of this loop lasts about 24 h. CLOCK and BMAL1 heterodimers are also involved in a daily transcription of many clock-controlled genes (CCGs) in different peripheral tissues \[[@B73-ijms-18-00938],[@B74-ijms-18-00938],[@B75-ijms-18-00938]\]. In addition to the primary feedback loop, another regulatory feedback loop is formed by the orphan nuclear receptors REV-ERBα and RORα. In the nucleus, REV-ERBα competes with RORα for binding to the ROR-responsive element (RORE) in the *Bmal1* promoter. Whereas RORα activates transcription of *Bmal1*, REV-ERBα represses it. Consequently, the cyclic expression of *Bmal1* is achieved by both positive and negative regulation of RORs and REV-ERBs, respectively. This secondary feedback loop is called the "stabilizing loop".
Post-transcriptional mechanisms: the proper functioning of the circadian loop requires that PER and CRY proteins disappear in due course, once they have served their purpose. As long as they inhibit the activity of positive elements (CLOCK and BMAL1), a new cycle cannot start. Several post-transcriptional processes thus affect the ability of PER and CRY to act on CLOCK and BMAL1. The most studied aspect is the modification of these proteins by phosphorylation and dephosphorylation. Several kinase proteins include PER and/or CRY among their targets, and each one of the two proteins can be phosphorylated on many distinct sites. They accelerate or slow down their transfer to the proteasome. Proteins to be degraded are "marked" by ubiquitin. Post-transcriptional regulations of the clock proteins of the main molecular loop make it possible to ensure intracellular traffic, functionality and degradation of clock proteins which are crucial for the functioning of the molecular loop over 24 h \[[@B76-ijms-18-00938]\].
2. Relationships between Circadian Rhythms and Psychiatric Disorders {#sec2-ijms-18-00938}
====================================================================
Several hypotheses can be raised regarding the relationships between the development of psychiatric disorders and problems of circadian rhythms, including altered sleep--wake rhythms: (1)First, sleep problems may lead to cognitive impairments due to the effects of sleep deprivation and fatigue on learning and attention capacities, long-term memory, language development and emotions \[[@B77-ijms-18-00938],[@B78-ijms-18-00938],[@B79-ijms-18-00938],[@B80-ijms-18-00938],[@B81-ijms-18-00938],[@B82-ijms-18-00938]\];(2)Recent studies in cognitive and developmental psychology have highlighted the importance of rhythmicity and synchrony of motor, emotional, and inter-personal rhythms in early development of social communication; the synchronization of rhythms allows tuning and adaptation to the external environment \[[@B83-ijms-18-00938]\]. Impaired circadian rhythms with an absence of synchronization of the circadian clocks network might alter the functioning of motor, emotional and interpersonal rhythms, leading to social communication impairments and vulnerability to psychiatric disorders with social communication deficit such as ASD or schizophrenia (for a review of literature on the importance of rhythmicity and synchrony of motor, emotional, and inter-personal rhythms in early development of social communication, see \[[@B83-ijms-18-00938],[@B84-ijms-18-00938]\]). In addition, circadian rhythms involve sequences of continuities/discontinuities that might be important for typical fetal and child development in order to provide a secure environment (through stable and predictable regularities) but also variations allowing the individual to adapt to changes. Impaired circadian rhythms with no, little or irregular variability might lead to anxiety and difficulties in adapting to changes associated with restricted and repetitive interests observed in some psychiatric disorders described in this article such as ASD, schizophrenia and anxiety disorder;(3)Clock genes control critical periods of brain development \[[@B85-ijms-18-00938]\] and therefore, abnormal expression of clock genes might participate to neurodevelopmental disorders such as psychiatric disorders. It is noteworthy that only a few days of circadian rhythm impairments may impact the maturation and specialization of some brain structures at specific developmental periods; these abnormalities can alter the temporal organization of brain maturation and development \[[@B86-ijms-18-00938]\];(4)Circadian rhythm impairments may alter transcriptional and splicing regulation of Parvalbumin (PV) neurons, knowing that PV knockout mice (PV−/−) or heterozygous (PV+/−) mice showed autism behavioral phenotype \[[@B87-ijms-18-00938]\]. More generally, circadian rhythm impairments may affect gene expression involved in synapse formation and brain maturation;(5)Also, clock-controlled genes (CCGs) may have pleiotropic effects outside the molecular clock and have therefore more widespread impact on cognition, mood, and reward-related behaviors \[[@B88-ijms-18-00938]\];(6)Finally, circadian rhythm impairments (provoked or not by sleep problems) may also alter the adaptation of the individual to his/her environment and therefore his/her state of homeostasis. In this perspective, psychiatric disorders might reflect a loss of synchronization between the external environment's rhythms and the individual's internal rhythms, leading to major problems of adaptation for the individual and the appearance of psychiatric disorders. Single-nucleotide polymorphisms (SNPs) in core circadian clock genes have been associated with autism spectrum disorder \[[@B89-ijms-18-00938]\], attention deficit hyperactivity disorder \[[@B90-ijms-18-00938],[@B91-ijms-18-00938]\], anxiety disorder \[[@B92-ijms-18-00938]\], major depressive disorder \[[@B93-ijms-18-00938],[@B94-ijms-18-00938],[@B95-ijms-18-00938]\], bipolar disorder \[[@B95-ijms-18-00938],[@B96-ijms-18-00938],[@B97-ijms-18-00938]\] and schizophrenia \[[@B98-ijms-18-00938],[@B99-ijms-18-00938],[@B100-ijms-18-00938],[@B101-ijms-18-00938]\]. However, the causal relationship for these associations remains to be better ascertained. Circadian clock genes may affect specific aspects of psychiatric disorders through circadian control or through distinct regulation of downstream effectors.
The suprachiasmatic nuclei (SCN) coordinate the rhythms of other brain regions and peripheral organs like a pacemaker \[[@B102-ijms-18-00938]\]. The sleep--wake cycle is the most documented example of the activity of the SCN, but endocrine, metabolic and immunological activities are also conducted by the SCN. For example, the glucocorticoids are regulated by the circadian cycle and affect the circadian rhythms of the amygdala \[[@B103-ijms-18-00938],[@B104-ijms-18-00938]\]. Also, they regulate directly the clock genes \[[@B105-ijms-18-00938],[@B106-ijms-18-00938]\].
We will explore the current state of research on this subject through five psychiatric disorders: bipolar disorder, anxiety and depression, attention deficit disorder, schizophrenia, and autism spectrum disorders.
2.1. Bipolar Spectrum Disorder {#sec2dot1-ijms-18-00938}
------------------------------
The mechanisms underlying the association between alterations in circadian rhythms and mood disorders are still unclear. However, current scientific studies provide food for thought. According to Jackson et al. \[[@B107-ijms-18-00938]\], sleep disorder is the most common prodrome of mania and one of the six most common prodromes of depression in bipolar disorder (bipolar type I disorder is defined as an isolated manic episode, and bipolar type II disorder is defined as manic and depressive episodes) \[[@B108-ijms-18-00938]\]. Between mood episodes, the sleep--wake cycle remains disrupted in patients with bipolar disorder who have some difficulty falling asleep and frequent night awakenings \[[@B109-ijms-18-00938]\]. These patients have a significantly more eventide sleep pattern than control subjects, in other words, they go to bed later and have more difficulty getting up early compared to healthy controls \[[@B110-ijms-18-00938]\].
McClung \[[@B111-ijms-18-00938]\] studied the involvement of the *Clock* gene in manic episodes in mice. She compared *Clock* mutant mice to mice with a normal *Clock* gene. Mice in which the gene had been modified had mania-like behavior. Those mice were hyperactive, less anxious and less depressed. They slept less and showed greater brain activity in response to sugar water, cocaine and a mild electrical stimulation of the brain. When researchers added lithium in their water, these mice did not show their manic behavior anymore and started to act like the mice with a normal *Clock* gene. A lithium salt treatment could affect circadian rhythms by modulating the expression of clock genes \[[@B112-ijms-18-00938],[@B113-ijms-18-00938],[@B114-ijms-18-00938],[@B115-ijms-18-00938]\]. Indeed, lithium salts might inhibit the expression of *glycogen synthase kinase 3β (GSK-3β)* gene \[[@B116-ijms-18-00938]\], a gene involved in the brain's biological clock \[[@B117-ijms-18-00938]\]. Kaladchibachi demonstrated that both genetic and pharmacological reduction of *GSK-3* activity in mice have a specific effect on the circadian transcriptional oscillation consisting of *mPer2* period lengthening, indicating a delay in phase \[[@B116-ijms-18-00938]\]. Moreover, it has been shown that *GSK-3β* is rhythmically expressed in the SCN and liver of mice, and that it undergoes a daily cycle in phosphorylation in vivo. Lithium chloride treatment inhibits the *GSK-3β* expression and results in a phase delay of *Clock* gene expression in fibroblasts \[[@B118-ijms-18-00938]\]. Bipolar spectrum disorder has been associated with variations in the *Clock* gene. A single-nucleotide polymorphism (SNP) in the 3-flanking region of the *Clock* gene (3111 T to C) is associated with a higher recurrence rate of bipolar episodes \[[@B16-ijms-18-00938]\]. This SNP was also associated in bipolar disorder and/or antidepressant treatment with sleep problems (insomnia and decreased need for sleep) \[[@B17-ijms-18-00938],[@B119-ijms-18-00938]\]. Some studies reported other clock genes associated with bipolar disorder (such as *Bmal1* and *Per3)* \[[@B96-ijms-18-00938]\]. Furthermore, a SNP in *Bmal1* and a SNP in *Tim* have also been identified as having a link with bipolar disorder \[[@B99-ijms-18-00938]\]. One South Indian study showed that the occurrence of the five repeat alleles of *Per3* may be a risk factor for bipolar disorder onset in this ethnic group \[[@B120-ijms-18-00938]\]. The coding region of *Per3* gene contains a variable number tandem-repeat (VNTR) polymorphisms which has been associated with diurnal preference, sleep structure and sleep homeostasis in healthy individuals. In a homogeneous sample of patients with bipolar type I disorder (occurrence of one or more manic episodes or mixed episodes), they observed that *Per3* VNTR influenced age of onset: earlier onset in homozygote carriers of *Per35* variant, later onset in homozygotes for *Per34*, and intermediate onset in heterozygotes. Sjöholm et al. \[[@B121-ijms-18-00938]\] studied four single-nucleotide polymorphisms (SNPs) of *Cry2* gene in a cohort of bipolar patients, some with fast cycles. They observed that *Cry2* is associated with rapid cycling in bipolar disorder patients. Rapid cycling in bipolar disorder is defined according to the 5th version of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as four or more mood episodes in any combination or order within any year in the course of the illness. The A allele of rs10838524 (*Cry2* SNP) was significantly overrepresented among bipolar disorder cases with rapid cycling compared to controls. There was a significant trend in the association between the A allele of rs10838524 and rapid cycling (*p* = 0.0076) and this allele increased the risk for rapid cycling both in a homozygote and a heterozygote form (that is dominant model) compared to controls. Two closely related clock genes, retinoid-related orphan receptors α (*RORA*) and β (*RORB*) are involved in a number of pathways including neurogenesis, stress response, and modulation of circadian rhythms. A study reports that four intronic *RORB* SNPs showed positive associations with the pediatric bipolar phenotype and suggests that clock genes in general and *RORB* in particular may be important candidates for further investigation in the search for the molecular basis of bipolar disorder \[[@B122-ijms-18-00938]\]. Further studies are necessary to better assess the role of *RORB* in bipolar spectrum disorder and explore if this gene is particularly relevant for this disorder compared to other clock genes.
Several genetic studies suggest that certain polymorphisms of clock genes are more common in bipolar disorder than in the general population \[[@B123-ijms-18-00938],[@B124-ijms-18-00938]\]. The clock genes might therefore be viewed as genetic vulnerability factors to bipolar disorder \[[@B125-ijms-18-00938]\]. These results need to be examined further.
The litterature review on clock genes and bipolar spectrum disorder is presented in [Table 1](#ijms-18-00938-t001){ref-type="table"}.
2.2. Anxiety and Depression-Related Disorders {#sec2dot2-ijms-18-00938}
---------------------------------------------
### 2.2.1. Anxiety Disorder {#sec2dot2dot1-ijms-18-00938}
A team of French researchers has evaluated a range of behaviors associated with psychiatric illnesses in mice in which two genes of the circadian clock, *Cry1* and *Cry2*, were investigated \[[@B126-ijms-18-00938]\]. Their work highlighted the causal relationship between the disruption of encoding genes for cryptochrome proteins 1 and 2 (*Cry1* and *Cry2*) and behaviors associated with anxiety. Mice deficient for CRY 1 and 2 proteins show behavioral alterations characterized among other things by an abnormally high level of anxiety. These results indicate clearly that in addition to their critical roles in regulating the molecular clock; these proteins are directly involved in the control of emotional states.
### 2.2.2. Major Depressive Disorder (MDD) {#sec2dot2dot2-ijms-18-00938}
Sleep problems, in particular insomnia or hyperinsomnia, are parts of depression criteria and have been hypothesized to be under genetic control. Major depressive disorder, as well as seasonal affective disorder (winter depression and summer depression) and bipolar type I disorder provide excellent models for studying the molecular mechanisms of mood disorder. An important study published in 2013 first demonstrated dysfunctioning clock genes in brains from depressed humans compared to healthy controls \[[@B127-ijms-18-00938]\]. Involvement of the clock genes in depression is also evident from several genetic studies. It has been reported that polymorphisms of clock genes appear in depressed patients \[[@B93-ijms-18-00938],[@B128-ijms-18-00938],[@B129-ijms-18-00938],[@B130-ijms-18-00938],[@B131-ijms-18-00938],[@B132-ijms-18-00938]\].
Several SNPs in the *Clock* gene (T3111C, 3117 G to T, 3125 A to G) has been reported \[[@B127-ijms-18-00938],[@B128-ijms-18-00938],[@B133-ijms-18-00938]\] to be associated with major depression and sleep disturbances (but some studies did not found any association between T3111C and sleep problems; \[[@B134-ijms-18-00938],[@B135-ijms-18-00938]\]). More precisely, the two rare SNPs (3117 G to T and 3125 A to G) were associated with alternating phases of good sleep and insomnia over the course of a few days \[[@B133-ijms-18-00938]\].
A Swedish team, Lavebratt et al. \[[@B94-ijms-18-00938]\] reported in healthy controls a marked diurnal variation in *Cry2* mRNA levels; total sleep deprivation induced a 2.0-fold increase in *Cry2* mRNA levels. In patients with depressive state of bipolar disorder, sleep deprivation induced significantly decreased *Cry2* mRNA expression compared with healthy controls. In addition, *Cry2* mRNA levels were found to be lowered in blood mononuclear cells from depressed patients with bipolar disorder after total sleep deprivation in comparison to healthy controls, and *Cry2* gene variation was associated with winter depression in both Swedish and Finnish patients \[[@B94-ijms-18-00938]\]. Deletion of *Cry2* gene lengthened the circadian period by approximately 48 min. This study \[[@B94-ijms-18-00938]\] suggests that a *Cry2* locus is associated with vulnerability for depression, and that mechanisms of action involve dysregulation of *Cry2* expression. Associations between the gene *Cry2* and winter depression, but also dysthymia and bipolar type I disorder as seen previously, support the view that the *Cry2* gene has a role in mood disorders.
Shi et al. \[[@B132-ijms-18-00938]\] found genetic polymorphisms in circadian genes, especially *Clock* and *Per3*, in major depressive disorder individuals. Authors propose that the impact of the *Clock* and *Per3* SNPs on transcription and/or expression may not be on the core circadian oscillator in humans, but on global output transcriptional pathways, that are mediated sex-dependently by the circadian system.
The litterature review on clock genes and depression related disorders is presented in [Table 2](#ijms-18-00938-t002){ref-type="table"}.
### 2.2.3. Familial Advanced Sleep Phase Syndrome (FASPS) {#sec2dot2dot3-ijms-18-00938}
A good example of an abnormal circadian system in humans is the familial advanced sleep phase syndrome (FASPS), described in three families by Jones et al. \[[@B136-ijms-18-00938]\]. FASPS is often associated with depression and anxiety. Affected individuals have a lead of a few hours of their sleep patterns and rhythms of temperature and melatonin, and a shorter period than healthy individuals in constant conditions. The joint efforts of several laboratories of the University of Utah in Salt Lake City have recently led to the description of *Per2* mutation in one of those families affected by FASPS. The mutation caused a substitution of serine by glycine in the *Per2* gene at position 662 \[[@B137-ijms-18-00938]\]; this serine that can normally be phosphorylated by casein kinase Iε (CKIε). Inhibiting the action of CKIε accelerates the clock, which is indeed what is observed in FASPS patients. FASPS are also to be caused by a T44A missense mutation in human CK1δ, which causes hypophosphorylation of *Per2* \[[@B138-ijms-18-00938],[@B139-ijms-18-00938]\]. Transgenic mice over-expressing the *hPer2* mutation exhibit shorter free-running periods, mimicking FASPS \[[@B140-ijms-18-00938]\], and their phenotype is sensitive to CK1δ: increased dosage of CK1δ shortens their period further.
Recently, a team has identified a new mutation in the *hCry2* gene associated with FASPS. The mutation leads to replacement of an alanine residue at position 260 with a threonine. In mice, the *Cry2* mutation causes a shortened circadian period and reduced phase-shift to early--night light pulse associated with phase-advanced behavioral rhythms in the light-dark cycle \[[@B141-ijms-18-00938]\].
### 2.2.4. Seasonal Affective Disorder (SAD) and Delayed Sleep Phase Syndrome (DSPS) {#sec2dot2dot4-ijms-18-00938}
Environmental changes like the seasons can be associated with depressive episodes in the inability of the circadian clock to adjust appropriately. Seasonal affective disorder (SAD) is defined as recurrent depressive disorder characterized by a seasonal pattern with, generally, an appearance in the fall or winter, apart from triggering external factor, and spontaneous disappearance in the spring or summer, even in the absence of treatment. SAD affects about 5% of the general population \[[@B142-ijms-18-00938]\]. Lewy evokes the idea of a "phase delay of the endogenous circadian oscillator in relation to sleep-wake rhythm" \[[@B143-ijms-18-00938]\], the equivalent of a delayed sleep phase syndrome (DSPS), as the cause of SAD. Genetic variants in *Npas2*, *Per2*, and *Bmal1* have been found to combine with the development of SAD \[[@B93-ijms-18-00938],[@B144-ijms-18-00938]\].
Iwase et al. \[[@B145-ijms-18-00938]\] reported that the SNP T3111C in the *Clock* gene was associated with morning or evening preference for activity and its frequency was decreased in DSPS. Futures studies are required to investigate the possible contribution of T3111C to DSPS susceptibility.
2.3. Attention Deficit Hyperactivity Disorder (ADHD) {#sec2dot3-ijms-18-00938}
----------------------------------------------------
Many sleep disorders are associated with attention deficit hyperactivity disorder (ADHD), both in adults and children. In particular, the following sleep problems occurring at sleep--wake transition were observed: bed-time refusal, delayed sleep-onset, and early awakenings \[[@B148-ijms-18-00938]\]. Differences in sleep problems were found as a function of ADHD subtype: children with ADHD inattentive type (ADHD-I) had the fewest sleep problems and did not differ from controls, children with ADHD combined type (ADHD-C) had more sleep problems than controls and children with ADHD-I. Daytime sleepiness was greatest in ADHD-I and was associated with sleeping more (not less) than normal \[[@B149-ijms-18-00938]\].
Several studies reported genetic associations between polymorphism (rs1801260) at the 3′-untranslated region (3′-UTR) of the *Clock* gene and psychiatric disorders \[[@B17-ijms-18-00938],[@B90-ijms-18-00938]\] (see [Table 3](#ijms-18-00938-t003){ref-type="table"}). Concerning the association between the rs1801260 polymorphism and ADHD, Kissling et al. \[[@B90-ijms-18-00938]\] found at least one T-mutation being the risk allele in Caucasians of western European origin and German background.
Xu et al. \[[@B91-ijms-18-00938]\] conducted a study which investigated a previously reported discovery of an association between a single nucleotide polymorphism in the 3′-UTR region of the *Clock* gene (rs1801260) in two independent samples of ADHD probands from UK and Taiwan (aged 5 to 15). They found a significant over-transmission of the T allele of rs1801260 SNP, which is associated as a risk allele for delayed sleep phase syndrome \[[@B145-ijms-18-00938]\] in ADHD cases in the Taiwanese population. No association was observed between this polymorphism and ADHD in the UK sample. However, they did find evidence for increased transmission of the T allele of rs1801260 in the Taiwanese samples. Their findings support the hypothesis that genetic variation in the 3′-UTR region of *Clock* gene might be a risk factor for the development of ADHD, particularly in the Taiwanese sample studied. Therefore, more functional polymorphisms of this region should be investigated in other independent studies using larger samples.
2.4. Schizophrenia {#sec2dot4-ijms-18-00938}
------------------
Schizophrenia is often associated with sleep alterations \[[@B88-ijms-18-00938],[@B150-ijms-18-00938]\], observed also in untreated patients \[[@B151-ijms-18-00938]\]. Patients with schizophrenia have a desynchronization between the sleep--wake rhythms and melatonin profiles \[[@B88-ijms-18-00938],[@B152-ijms-18-00938],[@B153-ijms-18-00938]\], the rhythms of body temperature \[[@B154-ijms-18-00938]\], and serum levels of tryptophan and prolactin \[[@B155-ijms-18-00938]\]. These anomalies suggest strongly disturbed circadian rhythms in these patients \[[@B156-ijms-18-00938]\]. Studies of polymorphisms of clock genes or alterations in the regulation of these genes in schizophrenia are rare. The litterature review on clock genes and schizophrenia is presented in [Table 4](#ijms-18-00938-t004){ref-type="table"}.
The expression of *Per1* mRNA in the temporal lobe in individuals with schizophrenia decreases significantly compared with age-matched healthy controls \[[@B98-ijms-18-00938]\]. Another study suggested that *Per3* but not *Per2* abnormalities were associated with schizophrenia \[[@B99-ijms-18-00938]\]. In a sample of 145 Japanese individuals with schizophrenia compared with healthy controls, it was reported that the T3111C polymorphism of the *Clock* gene presented a transmission bias. The T3111C polymorphism of the *Clock* gene might be associated with aberrant dopaminergic transmission in the suprachiasmatic nucleus, which is presumably involved in the pathophysiology of schizophrenia \[[@B157-ijms-18-00938]\]. More recently, two studies focused on white blood cells and fibroblast from smaller samples: Sun et al. \[[@B100-ijms-18-00938]\] reported altered expressions of *Per1*, *Per2*, *Per3* and *Npas2* in white blood cells in individuals with schizophrenia. Indeed, compared with healthy controls, schizophrenia patients presented disruptions in diurnal rhythms of the expression of *Per1*, *Per3*, and *Npas2*, accompanied by a delayed phase in the expression of *Per2* and by a decreasing in *Per3* and *Npas2* expression. Johansson et al. \[[@B101-ijms-18-00938]\] reported a loss of rhythmic expression of *Cry1* and *Per2* in fibroblasts from individuals with schizophrenia compared to cells from healthy controls.
To date, the associations between clock genes and schizophrenia are not clear.
2.5. Autism Spectrum Disorder (ASD) {#sec2dot5-ijms-18-00938}
-----------------------------------
Surveys of parents show that the prevalence of sleep problems in ASD is 50%--80% compared to 9%--50% in age-matched typically developing children \[[@B7-ijms-18-00938],[@B8-ijms-18-00938],[@B9-ijms-18-00938],[@B10-ijms-18-00938],[@B11-ijms-18-00938],[@B12-ijms-18-00938],[@B13-ijms-18-00938],[@B14-ijms-18-00938]\]. Recent results showing abnormal melatonin secretion in ASD children may change the initial disregard of these disorders and suggest a possible key role of the clock and circadian regulations in ASD. Several independent groups detected abnormal melatonin levels in ASD \[[@B158-ijms-18-00938],[@B159-ijms-18-00938],[@B160-ijms-18-00938],[@B161-ijms-18-00938],[@B162-ijms-18-00938],[@B163-ijms-18-00938]\]. These studies conducted on independent autism samples and using different methodologies indicate that abnormally low melatonin level is a frequent trait in ASD. More precisely decreased nocturnal as well as diurnal levels have been reported in individuals with ASD; trial studies support therapeutic benefits of melatonin use in ASD \[[@B83-ijms-18-00938],[@B84-ijms-18-00938],[@B161-ijms-18-00938]\]. Nevertheless, both the underlying cause of this anomaly and its relationship with ASD (cause or consequence?) remain still unexplained.
Many studies have advocated a genetic etiology for autism \[[@B164-ijms-18-00938]\] involving in particular synaptic genes related to synaptic cell adhesion molecules NLGN3, NLGN4, and NRXN1 and a postsynaptic scaffolding protein SHANK3. This protein complex is crucial for the maintenance of functional synapses as well as the adequate balance between neuronal excitation and inhibition. Among the factors that could modulate this pathway there are genes controlling circadian rhythms. However, no direct association has been reported between clock genes and NLGN3, NLGN4, NRXN1 and SHANK3 in humans, but epistasis mechanisms cannot be ruled out. SHANK3 expression is modulated by melatonin concentration and the modulation is brain structure-dependent \[[@B165-ijms-18-00938]\]. Concerning relationships between sleep disorders and NLGN3, NLGN4, NRXN1 and SHANK3 could be a pleiotropic effect on sleep of genes associated with brain disorganization. It is noteworthy that possible interplay of synaptic and clock genes may increase the risk of ASD \[[@B166-ijms-18-00938]\]. The involvement of clock genes in ASD was first suggested by Wimpory et al. \[[@B167-ijms-18-00938]\] who stated the hypothesis that anomalies in clock genes operating as timing genes in high frequency oscillator systems may underline timing deficits that could be important in the development of autism spectrum disorder, notably in autistic communication impairment. To test this hypothesis, Nicholas et al. \[[@B89-ijms-18-00938]\] screened single-nucleotide polymorphisms in 11 clock/clock-related genes in 110 individuals with ASD and their parents. A significant allelic association was detected for *Per1* and *Npas2*. It should be noted that it was a small population and results were not significant after correction for multiple testing. However, the association between *clock* genes and ASD was confirmed by a more recent study \[[@B168-ijms-18-00938]\] reporting also mutations in other circadian clock genes (*Per2*, *Per3*, *Clock*, *Bmal1*, *Tim*, *Cry1*, *Cry2*, *Dbp* and *Ck1ε*) in ASD patients. Taken together, these findings suggest that the circadian rhythm abnormalities observed in ASD may be linked to abnormalities of the circadian clock genes. Finally, it is noteworthy that clock genes are related to the protein association network described in ASD by Roubertoux and Tordjman \[[@B169-ijms-18-00938]\] either through direct gene × gene interactions or protein × protein interactions.
The litterature review on clock genes and autism spectrum disorder is presented in [Table 5](#ijms-18-00938-t005){ref-type="table"}.
3. Conclusions {#sec3-ijms-18-00938}
==============
Circadian clocks enable organisms to anticipate temporal organization of biological functions in relation to periodic changes of the environment, and to adapt consequently their behavior. The genes *Clock*, *Per*, *Cry* and *Bmal1* are currently the major clock genes identified in humans as being involved in the rhythmicity and timing of biological rhythms at the molecular level. Their alteration involves changes to the 24-h rhythm through poor synchronization between the endogenous circadian rhythms and the sleep-wake cycle, and act especially on sleep disorders. These are often early symptoms of altered sleep--wake rhythms at the onset of psychiatric disorders, especially for mood disorders. Furthermore, impairments in the four major clock genes (*Clock*, *Per*, *Cry* and *Bmal1*) were found for bipolar disorder, depression-related disorders, autism spectrum disorder, and impairments in some of these major clock genes were also reported for schizophrenia (*Clock*, *Per* and *Cry*), anxiety disorder (*Cry*) and attention deficit hyperactivity disorder (*Clock*). In addition, other *clock* genes were associated with these psychiatric disorders, such as *Npas2* (winter depression, autism spectrum disorder and schizophrenia), *RORA* and *RORB* (bipolar disorder) or *Tim*, *Dbp* and *Ck1ε* (autism spectrum disorder). The associations of identical clock genes with these different psychiatric disorders suggest that they may share similar pathways and etiopathogenic mechanisms. It highlights the interest and need to study these mental disorders through a transnosographic and multidimensional approach focusing on depression, anxiety and stress responses.
The cascading effects resulting from altered clock genes, poorly understood so far, could participate in sleep problems and the emergence of symptoms present in certain psychiatric disorders through, as discussed in the article, impaired regulation of circadian rhythms and emotional states with neurodevelopmental effects (including impaired control of the temporal organization of brain maturation, neurogenesis, synapses formation/functioning and brain specialization at specific developmental periods). Inversely, sleep problems can alter the expression of clock genes and contribute, as seen in this article, to the development of psychiatric disorders through cognitive effects of sleep deprivation and fatigue. More generally, alteration of clock genes (directly or indirectly through sleep problems) might lead to desynchronized and abnormal circadian rhythms (including sleep/wake rhythm but also other circadian rhythms such as neuroendocrine or body temperature rhythms) impairing in turn the synchronization between external and internal rhythms and therefore the adaptation of the individual to his/her internal and external environment with the development of psychiatric disorders. Future studies are required to better ascertain the underlying mechanisms of the relationships between clock genes, sleep disturbances and psychiatric disorders. Further research may open interesting perspectives with promising avenues for early detection and therapeutic intervention in psychiatric disorders.
Annaëlle Charrier, Bertrand Olliac, Pierre Roubertoux and Sylvie Tordjman wrote the paper.
The authors declare no conflict of interest.
![Model of the mammalian cell-autonomous oscillator (based on Lowrey and Takahashi, 2011) \[[@B69-ijms-18-00938]\]. The transcriptional activators *circadian locomotor output cycles kaput* (CLOCK) and *brain and muscle ARNT-like protein 1* (BMAL1) stimulate the expression of *cryptochrome-1* (*Cry*) and *period* (*Per*) genes. The protein products of these genes are associated in the cytoplasm to form dimers that go into the core. There, they serve two functions: first, the repression of their own transcription, via the inhibition of CLOCK--BMAL1; and second, the activation of *Bmal1* gene, by a mechanism that remains to be discovered. These proteins are thus two regulating loops, one negative and the other positive. CLOCK and BMAL1 activate also the so-called clock-controlled genes (CCG) whose products transmit the rhythm information to the rest of the body via the output channels of the clock. Some proteins modulate the progression of control loops. Thus, casein kinase Iε (CKIε) can phosphorylate PER proteins, which destabilizes them and prevents their translocation into the nucleus.](ijms-18-00938-g001){#ijms-18-00938-f001}
ijms-18-00938-t001_Table 1
######
Clock genes and bipolar spectrum disorder. RORα: retinoid-related orphan receptors α; RORβ: retinoid-related orphan receptors β.
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Studies Measure Individuals with Psychiatric Disorder and/or Organisms Models (*n*) Controls (*n*) Results
------------------------------------------------ ------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------- ---------------------------------- ---------------------------------------------------------------------------------------------------------------------------------
Kaladchibachi et al. \[[@B116-ijms-18-00938]\] Cyclical expression of clock genes (*Per2*) Mouse embryonic fibroblasts (MEFs) \- Genetic depletion of glycogen synthase kinase 3 (GSK3) activity results in a significant delay in the cycling period of *Per2.*
McGrath et al. \[[@B122-ijms-18-00938]\] Genotyping and analysis of 312 single-nucleotide polymorphisms (SNPs) in *RORA* and 43 SNPs in *RORB* Bipolar disorder (BD) children (*n* = 305) Healthy parents (*n* = 306)\ Four intronic *RORB* SNPs showed positive associations with the pediatric bipolar phenotype.
Healthy individuals (*n* = 140)
Lavebratt et al. \[[@B94-ijms-18-00938]\] Assessment of *Cry2* gene expression before and after one night of sleep deprivation BD individuals (*n* = 13) Healthy individuals (*n* = 8) *Cry2* mRNA levels are reduced and unresponsive to sleep deprivation in depressed patients with bipolar disorder.
Sjöholm et al. \[[@B121-ijms-18-00938]\] Analysis of four *Cry2* single-nucleotide polymorphisms BD individuals in Sweden (*n* = 577);\ Healthy individuals (*n* = 1044) Association between the circadian gene *Cry2* and rapid cycling in bipolar disorder.
BD type I (*n* = 497);\
BD type II (*n* = 60);\
BD with rapid cycling (*n* = 155)
Karthikeyan et al. \[[@B120-ijms-18-00938]\] Genotyping and analysis of *Per3* in blood samples Bipolar type I disorder individuals in South India (*n* = 311) Healthy individuals (*n* = 346) The occurrence of the five repeat allele of *Per3* may be a risk factor for bipolar type I disorder onset in this ethnic group.
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ijms-18-00938-t002_Table 2
######
Clock genes and depression related disorders.
Studies Measure Individuals with Psychiatric Disorder (*n*) Controls (*n*) Results
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Takimoto et al. \[[@B146-ijms-18-00938]\] Daily variation of melatonin and cortisol, and daily expression of clock genes (*Per*, *Bmal1* and *Clock)* in whole blood cells Individuals with circadian rhythm sleep disorder (*n* = 1) Healthy male individuals (*n* = 12) The peak phase of *Per1*, *Per2*, and *Per3* appeared in the early morning, whereas that of *Bmal1* and *Clock* appeared in the midnight hours in healthy male individuals.
Partonen et al. \[[@B93-ijms-18-00938]\] Analysis of sequence variations (single-nucleotide polymorphisms) in three core clock genes: *Per2*, *Bmal*, and *Npas2* Depressed individuals (*n* = 189) Healthy individuals (*n* = 189) Variations in the three circadian clock genes *Per2*, *Bmal*, and *Npas2* are associated with winter depression.
Utge et al. \[[@B147-ijms-18-00938]\] Analysis of 113 single-nucleotide polymorphisms of 18 genes of the circadian system Depressed individuals (*n* = 384) Healthy individuals (*n* = 1270) Significant association between *Tim* variants and depression with fatigue in females, and association to depression with early morning awakening in males.
Lavebratt et al. \[[@B94-ijms-18-00938]\] Genotyping of single nucleotide polymorphism of the *Cry2* gene Depressed individuals with bipolar disorder (*n* = 204) Healthy individuals (*n* = 2017) The *Cry2* gene was significantly associated with winter depression in both samples.
Kovanen et al. \[[@B130-ijms-18-00938]\] Genotyping of 48 single-nucleotide polymorphisms in *Cry1* and *Cry2* gene Individuals with dysthymia (*n* = 136) Healthy individuals (*n* = 3871) Four *Cry2* genetic variants (rs10838524, rs7121611, rs7945565, rs1401419) are significantly associated with dysthymia.
Hua et al. \[[@B131-ijms-18-00938]\] Genotyping of single nucleotide polymorphisms (SNPs) of *Cry1* rs2287161, *Cry2* rs10838524 and *Tef (thyrotroph embryonic factor)* rs738499 Chinese individuals with major depressive disorder (MDD) (*n* = 105) Chinese healthy individuals (*n* = 485) The polymorphisms of *Cry1* rs2287161and *Tef* rs738499 are associated to major depressive disorder.
Shi et al. \[[@B132-ijms-18-00938]\] Genotyping of 32 genetic variants from eight clock genes Major depressive disorder individuals (*n* = 592) Healthy individuals (*n* = 776) Genetic polymorphisms in circadian genes, especially *Clock* and *Per3*, influence risk of developing depression in a sex- and stress-dependent manner.
ijms-18-00938-t003_Table 3
######
Clock genes and attention deficit hyperactivity disorder (ADHD).
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Studies Measure Individuals with Psychiatric Disorder (*n*) Controls (*n*) Results
------------------------------------------ ----------------------------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------- ----------------------------------------------- ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Kissling et al. \[[@B90-ijms-18-00938]\] Analysis of polymorphism (rs1801260) at the 3'-untranslated region of the *Clock* gene ADHD individuals (*n* = 143) Healthy individuals (*n* = 143) Significant association (*p* \< 0.001) between genotype and ADHD-scores of the adult ADHD assessments, and the rs1801260 polymorphism with at least one T-mutation is the risk allele.
Xu et al. \[[@B91-ijms-18-00938]\] Analysis of polymorphism (rs1801260) at the 3'-untranslated region of the *Clock* gene in ADHD using within-family transmission disequilibrium test Two clinical ADHD samples:\ Both parents or mother alone or father alone\ Increased transmission of the T allele of the rs1801260 polymorphism in Tawainese samples.
United Kingdom (UK) sample: (*n* = 180);\ UK sample: (*n* = 296);\
Taiwan sample: (*n* = 212) Taiwan sample: (*n* = 326)
---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
ijms-18-00938-t004_Table 4
######
Clock genes and schizophrenia. REV-ERBα: reverse erythroblastosis virus; Dbp: albumin-D-site-binding protein.
Studies Measure Individuals with Psychiatric Disorder (*n*) Controls (*n*) Results
-------------------------------------------- ------------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------- --------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Takao et al. \[[@B157-ijms-18-00938]\] Analysis of 3111C single nucleotide polymorphism of the *Clock* gene Individuals with schizophrenia (*n* = 145) Healthy individuals (*n* = 128) Individuals with schizophrenia had a significantly higher frequency of the C allele compared to controls.
Sun et al. \[[@B100-ijms-18-00938]\] Relative expression of clock gene mRNA: *Per1*, *Per2* and *Per3* in blood samples Individuals with schizophrenia (*n* = 13) Healthy controls (*n* = 15) Individuals with schizophrenia presented disruptions in diurnal rhythms of the expression of *Per1*, *Per3*, and *Npas2 c*ompared with healthy controls, accompanied by a delayed phase in the expression of *Per2* and by a decrease in *Per3* and *Npas2* expression.
Johansson et al. \[[@B101-ijms-18-00938]\] Analysis of *Clock*, *Bmal1*, Per1, *Per2*, *Cry1*, *Cry2*, *REV-ERBα* and *Dbp* in fibroblasts from skin samples Individuals with chronic schizophrenia under neuroleptic medication (*n* = 11) Healthy individuals (*n* = 11) Loss of rhythmic expression of *Cry1* and *Per2* in fibroblasts from individuals with schizophrenia compared to cells from healthy controls.
ijms-18-00938-t005_Table 5
######
Clock genes and autism spectrum disorder (ASD).
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Studies Measure Individuals with Psychiatric Disorder (*n*) Controls (*n*) Results
------------------------------------------ --------------------------------------------------------------------------------------------------------- ---------------------------------------------------- -------------------------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Nicholas et al. \[[@B89-ijms-18-00938]\] Screening of eleven clock/clock-related genes High-functioning ASD individuals (*n* = 110) Healthy parents (*n* = 220) Significant association for two single-nucleotide polymorphisms in *Per1* and in *Npas2*.
Yang et al. \[[@B168-ijms-18-00938]\] Direct sequencing analysis of the coding regions of 18 canonical clock genes and clock-controlled genes ASD individuals with sleep disorders (*n* = 14);\ Healthy individuals (*n* = 23) Mutations in circadian-relevant genes (specifically *Per1*, *Per2*, *Per3*, *Clock*, *Npas2*, *Bmal1*, *Tim*, *Cry1*, *Cry2*, *Dbp* and *Ck1ε*) affecting gene function are more frequent in individuals with ASD than in controls.
ASD individuals without sleep disorders (*n* = 14)
--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
|
Background
==========
Increasingly, the concept \"health-related quality of life\" (HRQL) has attracted attention in research within the medical and caring sciences \[[@B1]\]. There are many definitions of HRQL, but they can be summarized as referring to a multidimensional psychological construct, which encompasses physical, psychological, social, and functional areas of life, and the impact of health and illness on these aspects \[[@B1],[@B2]\]. In studies, measures of HRQL are often used to evaluate the outcome of different treatments and the relative burden of various diseases \[[@B3]\]. However, when assessing HRQL in diverse clinical groups, it is of utmost importance to have validated normative data for the general population at hand, in order to make meaningful comparisons. The lack of normative data, and well-validated instruments, is an even greater problem when assessing HRQL in adolescents and young adults \[[@B4],[@B5]\]. Historically, these groups have been overlooked to a large extent, as quality of life research has almost exclusively focused on adults \[[@B6]\]. Moreover, studies of general populations that do include a young sample often report data lumped together into large age groups, making it difficult to distinguish information about HRQL in adolescence and young adulthood. Recently, efforts have been made to further develop and validate generic instruments specifically aimed at measuring HRQL in children and adolescents, such as KIDSCREEN and PedsQL \[[@B7]-[@B9]\]. Studies show promising results, and add valuable information to the research field. However, it is also useful to be able to include a wider age range in the same sample, avoiding the creation of a gap between the measuring of HRQL in adolescence and adulthood. With this as a starting point, the present study will focus on the Short Form 36 (SF-36) and the Hospital Anxiety and Depression Scale (HADS) used in a young sample (aged 13--23) of the general Swedish population, providing norms and investigating the influence of demographic variables and different methods of administration.
Research has shown that the administration methods influence the way people respond to health status measures. People tend to rate their health and well-being, measured by the SF-36, significantly more favourable in telephone interviews than in questionnaires distributed by mail \[[@B10],[@B11]\]. One explanation for this finding is the difference in perceived anonymity between the two methods \[[@B10]\]. Given this, there is a need for normative data for the two most common modes of administration -- telephone interview and postal questionnaire -- respectively, in order to provide trustworthy comparison data for future studies.
Additionally, demographic variables such as age and gender have been reported as being of importance, both for HRQL in general \[[@B12]\], and for the specific instruments being examined, and will therefore be taken into consideration in the present study. Lower self-evaluated HRQL as measured by the SF-36 is associated with both increasing age \[[@B13],[@B14]\], and being female \[[@B13]\]. Regarding the age effect, the decline is more marked in the scales reflecting physical health, but has also been detected in the mental health scales \[[@B13]\]. The fact that females report lower scores on the SF-36 has also been replicated in one of the few studies on adolescents \[[@B15]\]. Regarding the HADS, a multitude of studies demonstrate that women score higher on the anxiety subscale, while gender differences are generally not demonstrated in the depression subscale \[[@B16]\]. However, in a study of adolescents by White et al., gender differences exist for both subscales, but there are no significant effects due to age \[[@B17]\].
Regarding the SF-36, normative values for the Swedish population are in existence, reported in the Swedish SF-36 Manual and Interpretation Guide \[[@B18]\]. The youngest group included was aged 15--24 (n = 1451, response rate roughly 70%, 50% females and 50% males). Most of the participants came from a small town (Skellefteå). However, these norms were obtained by postal questionnaire only, and may therefore not be suitable for comparison in studies using telephone interviews. Furthermore, no values are presented for early adolescence (13--14-year-olds). An additional reason for obtaining new values is that almost 15 years have passed since these population studies were performed, implying that the values could have changed.
No previous study has investigated the effect of method of administration, age, and gender on how adolescents and young adults rate HRQL, anxiety, and depression. The main aim of this study is to provide normative data for the SF-36 and the HADS for adolescents and young adults in the Swedish general population (aged 13--23), taking these three factors into consideration. Norms will be presented by method of administration -- telephone interview and postal questionnaire -- and the potential effect of survey mode will be examined. Additionally, whether gender and age influence the scores on the SF-36 and the HADS will be explored, by survey mode.
Methods
=======
Participants
------------
The sample was randomly chosen by Statistics Sweden from their register of the total population. The target population included all individuals covered by civil registration between 13 and 23 years of age, living in three public healthcare regions in Sweden: South, Uppsala/Örebro (Middle) and North. These areas were chosen in order to ensure proper representation by including participants from geographically diverse areas. The sample was stratified with proportional allocation regarding gender (an equal amount of males and females), age group (young adolescents: 13--15 years; older adolescents: 16--19 years; and young adults: 20--23 years), and public healthcare region. The stratification regarding geographical area was included to be able to explore any possible occurrences of systematic differences due to region. This was tested by one-way ANOVA, which did not indicate such differences. Within each stratum the participants were randomized according to the two methods of administration, telephone interview and postal questionnaire. The selected eligible sample consisted of 840 individuals who were invited to participate, 391 of whom were approached through telephone interview and 449 by a postal questionnaire.
Questionnaires
--------------
### The Short Form 36 (version 1.0)
The SF-36 was developed by an American research group, led by John Ware \[[@B19]\]. It was designed to provide an instrument for the self-evaluation of HRQL which summarized the essence of conceptions of health. Efforts were made to ask as few questions as possible without omitting valuable information, with the aim of simplifying participation and improving the cost effectiveness of data collection. The questionnaire consists of 36 items measuring eight dimensions of life quality: Physical Functioning (PF); Role Physical (RP), which refers to role limitations due to physical difficulties; Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Emotional (RE), which refers to role limitations due to emotional difficulties, and Mental Health (MH). In addition, one single item determines perceived differences in state of health over the past year. Verbal response choices vary from two to six.
Based upon the eight scales, two summary scales have been constructed for physical and mental health respectively \[[@B20]\]. The Physical Component Summary (PCS), is primarily a comprehensive measure of PF, RP, BP and GH, whereas the Mental Component Summary (MCS) mainly encompasses VT, SF, RE and MH. However, the two summaries somewhat overlap, and especially the VT, GH, and SF scales have noteworthy correlations with both components.
The SF-36 has been extensively validated in an American context \[[@B21],[@B22]\], and Swedish studies have shown similar results for data completeness, scaling assumptions, reliability, construct validity and criterion validity \[[@B13],[@B18],[@B23]\]. The SF-36 is described as adequate from early adolescence, and the Swedish manual presents normative data for people aged from 15 to 75+ \[[@B18]\]. Notwithstanding, a very limited amount of studies has focused on adolescents, and most of these principally concern clinical groups. One of the few studies that has come to our attention where the SF-36 has been used with the aim to explore adolescents\' self-assessment of HRQL is performed by Goodman et al. (1997). This study investigates how gender and social class affect perceptions of health among 16-year-olds \[[@B15]\].
### The Hospital Anxiety and Depression Scale
The HADS is a brief self-report screening scale, developed by Zigmond and Snaith (1983) \[[@B24]\], to investigate the prevalence of emotional distress among patients at general medical out-patient clinics. One of the main motives for developing the HADS was the perceived need of a brief questionnaire, which was easy to administer, while still being a source of discriminating information about emotional disorders. Therefore, the scale focuses on the two aspects of psychological health which were considered to have the most relevance, i.e., anxiety and depression. To measure these two dimensions, the scale contains two subscales, one for anxiety and one for depression, each consisting of 7 items (range 0--21). To lessen the possible effects of physical illnesses, no items relating to symptoms that might stem from a somatic condition, such as dizziness and loss of appetite, were included.
There are two ways of interpreting the HADS scores; either by comparing an individual\'s score to normative values obtained from a sample of the general population, or by using cut-off scores that indicate different levels of clinically relevant distress \[[@B25]\]. Snaith and Zigmond have identified three cut-off levels: a score between 8 and 10 indicate a mild case, 11--14 a moderate case, and 15 or above, a severe case \[[@B25],[@B26]\].
The HADS has been used extensively, and is perceived as performing well when studying aspects of disease and quality of life in clinical as well as general populations \[[@B16]\]. One study of the general population, carried out by Lisspers et al. (1997), concerns psychometric data for a Swedish sample \[[@B27]\]. However, of importance for the present study is that the youngest age group included in their sample consisted of 30--39-year-olds.
The HADS was originally developed for people aged between 16 and 65 \[[@B24]\]. Only one study focusing explicitly on using the HADS in a population sample of adolescents has come to our attention, namely that by White et al. (1999), which aimed at validating the HADS for use with adolescents (aged 12--16) \[[@B17]\]. The study concluded that the HADS is reliable, and has adequate sensitivity and specificity, and is therefore useful for screening adolescents.
Procedure
---------
The study was approved by the regional ethical review board at the Faculty of Medicine, Uppsala University, Uppsala. The data was collected by Statistics Sweden between March and May 2005.
### Telephone interview
After completing an organized training programme, five interviewers performed the telephone interviews. All potential participants received a letter containing information about the study. For those under 18, a separate information letter was addressed to the parents. Potential participants were contacted over the telephone by one of the interviewers within a week after the information letter was mailed. Provided that the respondent agreed to participate, and that parental consent was obtained for those under 18, a time was either booked for the interview, or in some cases the interview was conducted directly. The interviewer read the two questionnaires (the SF-36 version 1.0 and the HADS) aloud to the respondent, and recorded his or her responses. As a form of compensation, all participants received a cinema ticket by mail.
### Postal questionnaire
Potential participants received a letter containing the two questionnaires (the SF-36 version 1.0 and the HADS) and information about the study, as well as a stamped and addressed envelope. In order to obtain parental consent, a separate information letter was addressed to the parents if the potential participant was under the age of 18. Those who did not return the questionnaires within two weeks were sent a reminder. Shortly after their participation, all participants received a cinema ticket by mail, as a form of compensation.
Statistical analyses
--------------------
All statistical analyses were conducted using the Statistical Package for the Social Sciences (SPSS) version 14.0 (SPSS Inc, Chicago, IL).
The SF-36 was scored by coding raw scores for each question, and recalibrating, summing, and transforming them into a scale from 0 (worst possible HRQL) to 100 (best possible HRQL), following the standard SF-36 scoring algorithms \[[@B18]\]. Two summary scores, a Physical Component Summary (PCS), and a Mental Component Summary (MCS), are standardized to a mean of 50, with a score above 50 representing better than average function and below 50 poorer than average function. Missing values were substituted if half or more of the items within a subscale were responded to; that is, a person-specific mean score was calculated based on the existing answers. When a HADS questionnaire was partially incomplete, the scale values were estimated by assuming that the missing item(s) had a value equal to the average of those in existence, provided that no more than three items of a subscale were missing.
Sample characteristics are presented descriptively (frequencies and percentages). In order to provide normative data for the SF-36 and the HADS, score distributions are demonstrated. Apart from means and standard deviations, medians, and 1^st^and 3^rd^quartiles are presented, as scores were not normally distributed. Regarding the HADS, those percentages of the sample classified as being mild, moderate or severe cases, as indicated by Snaith and Zigmond\'s criteria \[[@B26]\], are also presented. All of these descriptive analyses were computed by method of administration. Cronbach\'s alpha coefficients were calculated to estimate the internal consistency reliability of each SF-36 and HADS subscale. According to the generally accepted standard, the alpha coefficient should not fall below 0.70 \[[@B28]\]. In order to make a gender comparison, independent t-test was calculated for the two modes of administration respectively. To evaluate the differences between the three age groups, one-way ANOVA was conducted, followed by the Tukey HSD post-hoc test. Again, the statistical analysis was performed by the two survey modes respectively. P-values ≤ .05 were considered statistically significant.
Results
=======
Sample characteristics
----------------------
Sample demographic characteristics and the response rate are presented in Table [1](#T1){ref-type="table"}. The overall response rate was 69.6% (telephone interview 76.7% and postal questionnaire 63.5%). Only 0.8 % of the addresses of those selected for the telephone interview, and 0.7 % of those selected for the postal questionnaire were impossible to find. It was only possible to record the reasons for non-participation among those randomized for the telephone interview. These reasons were: hindered from participating due to illness or language difficulties (2.1%), impossible to reach (9.2%), and not wishing to participate (11.3%). Teenagers whose parents did not give their consent were included as not wanting to participate (n = 7).
######
Sample demographic characteristics and response rate, by method of administration and in total
**Telephone** **Mail** **Total**
----------------- --------------- ---------- ----------- ------- ----- ------
Approached 391 \- 449 \- 840 \-
Response rate \- 76.7 \- 63.5% \- 69.6
Participated 300 \- 285 \- 585 \-
Gender
Male 147 49 130 45.6 277 47.4
Female 153 51 155 54.4 308 52.6
Age
13--15 89 29.7 91 31.9 180 30.8
16--19 119 39.7 110 38.6 229 39.1
20--23 92 30.7 84 29.5 176 30.1
Region
South 98 32.7 99 34.7 197 33.7
Uppsala/Örebro 138 46 126 44.2 264 45.1
North 64 21.3 60 21.1 124 21.2
Normative data for the SF-36 and the HADS for the general Swedish population ages 13--23
----------------------------------------------------------------------------------------
Important features of score distributions and estimates of reliability are presented for the HADS in Table [2](#T2){ref-type="table"}, and for the SF-36 in Table [3](#T3){ref-type="table"}, divided by method of administration. Distributions were skewed, with more subjects giving favourable response choices. The median exceeded the mean for all SF-36 scales, and fell below the mean for the two HADS scales, as expected for relatively healthy general populations. Cronbach\'s alpha exceeded .70 in all the scales measured by the postal questionnaire, but in the telephone interview mode, three subscales fell below α .70; namely Bodily Pain and Social Functioning in the SF-36, and Depression in the HADS.
######
Descriptive statistics, Cronbach\'s α, and score distributions for the HADS, by method of administration
**Anxiety** **Depression**
-------------------- ------------- ---------------- ------- -------
Mean 4.66 5.31 2.52 2.96
SD 3.35 4.14 2.27 3.14
α .75 .83 .54 .78
Quartile 1 2.00 2.00 1.00 1.00
Median 4.00 5.00 2.00 2.00
Quartile 3 6.00 8.00 3.00 4.00
Range 0--19 0--20 0--14 0--18
\% Ceiling 0.0 0.0 0.0 0.0
\% Floor 6.0 10.4 14.3 19.3
\% Case
Mild (8--10) 10.7 16.1 2.3 3.9
Moderate (11--14) 4.7 9.1 1.7 2.1
Severe (≥15) 1.7 2.5 0.0 1.4
######
Descriptive statistics, Cronbach\'s α, and score distributions for the SF-36, by method of administration.
--------------------------------------------------------------------------------------------------------------------------
**Telephone**\ **PF** **RP** **BP** **GH** **VT** **SF** **RE** **MH** **PCS** **MCS**
**(n = 300)**
-------------------- --------- -------- --------- --------- --------- -------- -------- --------- ------------ -----------
Mean 97.9 89.9 85.4 82.6 69.4 93.3 86.7 80.7 54.7 48.7
SD 7.8 22.8 18.6 15.9 18.5 14.2 27.7 15.0 5.0 9.2
α .86 .75 .62 .71 .81 .67 .75 .82 \- \-
Quartile 1 100 100 72 75 60 87.5 100 76 52.6 45.4
Median 100 100 100 87 75 100 100 84 55.7 51.3
Quartile 3 100 100 100 95 85 100 100 92 57.7 54.9
Range 0--100 0--100 22--100 15--100 10--100 0--100 0--100 20--100 31.2--69.4 5.1--64.8
\% Ceiling 82.7 78.7 54.0 13.0 2.7 72.3 77.7 5.7 \- \-
\% Floor 0.3 2.3 0.0 0.0 0.0 0.3 5.0 0.0 \- \-
**Mail**\ **PF** **RP** **BP** **GH** **VT** **SF** **RE** **MH** **PCS** **MCS**
**(n = 277--285)**
Mean 94.8 86.6 81.6 79.6 64.3 88.2 81.1 76.3 53.7 46.2
SD 13.7 25.9 21.1 18.7 21.6 18.9 32.5 18.9 6.6 11.8
α .91 .77 .79 .80 .84 .84 .78 .85 \- \-
Quartile 1 95 75 72 67 50 75 66.7 68 50.7 42.5
Median 100 100 84 82 66 100 100 80 55.2 50.4
Quartile 3 100 100 100 97 80 100 100 92 57.7 54.1
Range 10--100 0--100 10--100 20--100 0--100 0--100 0--100 16--100 27.7--69.4 2.7--64.8
\% Ceiling 69.5 71.6 42.8 18.2 3.5 57.5 69.5 9.1 \- \-
\% Floor 0.0 3.9 0.0 0.0 0.4 0.4 8.4 0.0 \- \-
--------------------------------------------------------------------------------------------------------------------------
Comparison regarding gender
---------------------------
In both methods of administration, males and females differed from each other regarding the scores of the SF-36 and the HADS on a number of subscales, see Table [4](#T4){ref-type="table"}. In the telephone interview, significant differences could be detected in five of the SF-36 scales and in the HADS Anxiety scale. Correspondingly, in the mail survey, the same differences were detected with the addition of Bodily Pain and Social Functioning. All the differences were due to the males reporting higher HRQL as measured by the SF-36, and lower levels of symptoms of anxiety as measured by the HADS.
######
SF-36 scores and HADS scores by method of administration and gender
**SF-36 and HADS scales** **Telephone M (SD)** **Mail M (SD)**
---------------------------- ---------------------- ------------------- ------------- -------------------
Physical functioning 98.0 (9.5) 97.7 (5.7) 95.4 (13.7) 94.3 (13.8)
Role-Physical 91.8 (19.0) 88.0 (25.8) 86.6 (26.9) 86.6 (25.1)
Bodily Pain 86.7 (17.6) 84.2 (19.4) 84.4 (19.9) 79.4 (21.8)\*
General Health 84.9 (14.3) 80.5 (17.2)\* 83.6 (17.0) 76.3 (19.3)\*\*\*
Vitality 74.0 (17.2) 65.0 (18.6)\*\*\* 68.5 (19.1) 60.7 (22.9)\*\*
Social Functioning 94.5 (14.7) 92.2 (13.6) 93.0 (13.0) 84.2 (21.9)\*\*\*
Role-Emotional 89.9 (24.9) 83.6 (29.9)\* 90.4 (24.7) 73.3 (36.1)\*\*\*
Mental Health 83.7 (13.8) 77.9 (15.6)\*\*\* 81.2 (15.0) 72.1 (20.8)\*\*\*
Physical Component Summary 54.9 (4.6) 54.6 (5.4) 53.5 (6.5) 53.9 (6.7)
Mental Component Summary 50.5 (8.7) 47.1 (9.4)\*\*\* 49.7 (8.4) 43.4 (13.3)\*\*\*
Anxiety 3.82 (2.88) 5.48 (3.57)\*\*\* 4.17 (3.51) 6.27 (4.39)\*\*\*
Depression 2.53 (2.07) 2.51 (2.46) 2.85 (2.82) 3.06 (3.39)
\* p \< .05; \*\* p = .01; \*\*\* p = .001
Comparison regarding age group
------------------------------
No significant differences were detected between the group of older adolescents (16--19 years old) and the group of young adults (20--23 years old). However, the group of young adolescents (13--15 years old) differed significantly from the two other groups on a number of subscales, in both methods of administration, see Table [5](#T5){ref-type="table"}. In the telephone interview mode, there were differences in four SF-36 scales. With reference to the postal questionnaire, the differences were more numerous regarding the SF-36, and both of the HADS scales also differed. All differences derived from the fact that the youngest age group reported higher HRQL as measured by the SF-36, and lower levels of symptoms of emotional distress as measured by the HADS. However, it should be noted, that in the telephone interview mode, the youngest age group (13--15 years) only differed from the 20--23-year-olds and not from the 16--19-year-olds in Social Functioning and Mental Component Summary, and differed only from the 16--19-year-olds and not from the 20--23-year-olds regarding Role-Emotional subscale scores.
######
SF-36 scores and HADS scores by method of administration and age group
**SF-36 and HADS scales** **Telephone M (SD)** **Mail M (SD)**
---------------------------- ---------------------- ----------------- ------------- ---------- ------------- ------------- ------------- -------------
Physical Functioning 98.9 (3.6) 97.5 (10.0) 97.2 (7.5) 1.27 93.4 (18.4) 94.2 (12.8) 96.8 (7.7) 1.37
Role-Physical 92.4 (19.0) 88.7 (23.2) 89.1 (25.5) 0.77 90.1 (22.3) 83.3 (28.6) 87.2 (25.6) 1.69
Bodily Pain 87.8 (17.9) 84.5 (18.5) 84.4 (19.3) 1.06 89.9 (14.5) 78.2 (22.6) 77.4 (22.6) 10.75\*\*\*
General Health 84.7 (14.3) 81.4 (17.1) 82.2 (15.7) 1.16 89.2 (12.5) 75.0 (21.0) 75.4 (17.0) 19.64\*\*\*
Vitality 74.3 (14.8) 67.9 (20.0) 66.6 (18.9) 4.68\*\* 76.4 (16.7) 58.7 (22.0) 58.8 (20.5) 23.96\*\*\*
Social Functioning 96.5 (9.4) 92.3 (14.7) 91.6 (16.7) 3.26\* 95.9 (8.4) 85.0 (19.7) 84.2 (23.1) 11.72\*\*\*
Role-Emotional 92.9 (22.2) 83.5 (30.0) 85.0 (28.7) 3.25\* 91.6 (22.9) 76.7 (35.1) 75.8 (35.2) 7.05\*\*\*
Mental Health 83.1 (13.2) 80.4 (14.7) 78.9 (16.8) 1.81 84.6 (14.0) 73.6 (20.1) 71.0 (19.0) 14.14\*\*\*
Physical Component Summary 55.1 (3.7) 54.5 (5.5) 54.6 (5.5) 0.46 54.4 (6.2) 52.9 (7.0) 54.0 (6.6) 1.26
Mental Component Summary 50.9 (7.5) 48.0 (9.3) 47.6 (10.3) 3.55\* 51.8 (6.8) 44.2 (12.5) 43.0 (13.2) 16.27\*\*\*
Anxiety 4.63 (2.85) 4.60 (3.25) 4.78 (3.90) 0.09 3.47 (3.61) 6.14 (4.08) 6.19 (4.17) 14.05\*\*\*
Depression 2.26 (2.22) 2.59 (1.83) 2.68 (2.78) 0.89 1.99 (2.69) 3.34 (3.23) 3.53 (3.26) 6.83\*\*\*
\* p \< .05; \*\* p = .01; \*\*\* p = .001
Normative data for the SF-36 and the HADS by age, gender, and method of administration
--------------------------------------------------------------------------------------
As all the three factors age, gender, and method of administration were found to significantly affect the reports of HRQL, anxiety, and depression, normative values are in addition presented divided by the three variables simultaneously, see Table [6](#T6){ref-type="table"}. Numerically, the most \"best values\" within each subscale (reflecting the highest HRQL or the lowest level of emotional distress) are found among the male 13--15-year olds in the mail mode, while the most \"worst values\" within each subscale (reflecting the lowest HRQL or the highest level of emotional distress) are reported by the female 20--23-year olds in the mail mode.
######
SF-36 scores and HADS scores by age, gender, and method of administration
**SF-36 and HADS scales** **Telephone M (SD)** **Mail M (SD)**
---------------------------- ---------------------- ----------------- ------------- ------------- ------------- -------------
Physical Functioning
Male 99.4 (2.2) 97.6 (13.3) 97.2 (7.9) 93.6 (17.2) 95.7 (13.4) 96.9 (8.1)
Female 98.4 (4.5) 97.5 (5.4) 97.3 (7.1) 93.3 (19.7) 93.1 (12.3) 96.7 (7.6)
Role-Physical
Male 93.8 (16.3) 91.2 (19.8) 90.8 (20.7) 89.8 (23.7) 81.4 (29.2) 89.6 (27.0)
Female 91.1 (21.4) 86.3 (25.9) 87.5 (29.7) 90.4 (21.0) 84.8 (28.2) 85.4 (24.6)
Bodily Pain
Male 86.9 (18.3) 87.0 (18.1) 86.3 (16.7) 93.5 (14.0) 77.9 (20.7) 81.9 (21.1)
Female 88.8 (17.7) 82.1 (18.6) 82.4 (21.6) 86.4 (14.2) 78.4 (24.1) 74.0 (23.3)
General Health
Male 86.8 (11.7) 85.1 (14.9) 82.9 (15.3) 92.5 (9.7) 79.8 (19.4) 78.1 (16.6)
Female 82.7 (16.4) 78.0 (18.3) 81.6 (16.2) 86.2 (14.1) 71.1 (21.7) 73.3 (17.2)
Vitality
Male 78.2 (12.1) 75.5 (18.9) 68.3 (18.0) 78.9 (14.0) 61.2 (22.0) 65.8 (14.6)
Female 70.6 (16.4) 60.0 (18.4) 65.0 (19.7) 74.0 (18.8) 56.6 (21.9) 53.5 (22.8)
Social Functioning
Male 97.7 (6.2) 93.4 (17.1) 92.6 (17.0) 96.9 (8.1) 90.6 (15.4) 91.7 (13.4)
Female 95.3 (11.7) 91.3 (12.3) 90.5 (16.5) 95.0 (8.6) 80.5 (21.6) 78.6 (27.2)
Role-Emotional
Male 95.5 (18.5) 88.9 (26.2) 85.9 (28.1) 95.5 (18.5) 86.4 (28.8) 89.8 (25.0)
Female 90.4 (25.2) 78.5 (32.6) 84.1 (29.6) 87.8 (26.2) 68.9 (37.9) 65.3 (38.3)
Mental Health
Male 86.8 (9.4) 84.1 (14.4) 80.2 (16.1) 87.0 (12.8) 78.9 (15.3) 77.2 (15.4)
Female 79.5 (15.4) 76.9 (14.2) 77.7 (17.6) 82.2 (14.9) 69.4 (22.6) 66.3 (20.2)
Physical Component Summary
Male 55.0 (2.9) 54.8 (5.5) 54.9 (4.8) 54.6 (6.2) 52.4 (6.1) 53.7 (7.2)
Female 55.3 (4.3) 54.2 (5.5) 54.3 (6.2) 54.1 (6.2) 53.3 (7.6) 54.3 (6.2)
Mental Component Summary
Male 52.7 (4.5) 50.5 (9.7) 48.3 (10.0) 53.3 (5.1) 47.9 (9.3) 48.0 (9.3)
Female 49.1 (9.2) 45.7 (8.3) 47.0 (10.6) 50.5 (7.9) 41.3 (13.8) 39.1 (14.4)
Anxiety
Male 3.59 (2.37) 3.79 (3.12) 4.07 (3.04) 2.34 (2.58) 5.17 (3.58) 5.08 (3.60)
Female 5.64 (2.93) 5.34 (3.22) 5.50 (4.52) 4.58 (4.12) 7.00 (4.29) 6.96 (4.42)
Depression
Male 2.32 (1.91) 2.49 (1.74) 2.78 (2.55) 1.82 (2.29) 3.76 (3.30) 2.89 (2.28)
Female 2.20 (2.51) 2.68 (1.92) 2.59 (3.02) 2.15 (3.04) 3.00 (3.15) 4.02 (3.79)
Discussion
==========
Normative data for the SF-36 and the HADS have been obtained from a large and stratified sample of the general population of adolescents and young adults in Sweden. It should form an important basis of comparison for future studies of these age groups, both of clinical groups and of the general population.
When assessing HRQL in adolescents, the question is raised whether to use questionnaires specifically designed for children and adolescents or instruments like the SF-36 and the HADS that are mainly developed for adults. Both approaches are entailed with several advantages and disadvantages, some of which are broached by Eiser and Morse in an exhaustive systematic review \[[@B29]\]. It can be questioned whether the domains considered in adult measures are appropriate to determine quality of life in children, and whether they have the same meaning for children as for adults. On the other hand, employing well-known and recognized questionnaires for adults has the benefit of drawing on established knowledge. It also makes it possible to investigate a sample of both adolescents and adults using the same questionnaires, something which is crucial for evaluating changes in quality of life across the life span and longitudinal follow-up.
In line with findings from the overwhelming majority of research about HRQL, the males reported higher scores than the females \[[@B5],[@B15],[@B17],[@B30]\]. The salient differences in the SF-36 were mainly associated with mental and emotional aspects of health, whereas few differences were found in the subscales more closely connected to physical health. Regarding the HADS, females reported a higher degree of anxiety, but no significant differences could be detected in the depression subscale. This is also in accordance with most of the research where the HADS is used \[[@B16]\], but differs from the previously mentioned study on adolescents by White et al. \[[@B17]\], where gender differences were identified in both subscales.
Although the systematic difference in subjective well-being between males and females is a common finding, very few explanations or interpretations have been presented as to why this is the case. One researcher who does focus on this matter is Helen Sweeting, who reviews findings on gender differences in health among children and adolescents \[[@B31]\]. She concludes that girls in no way suffer from worse health than boys during childhood, but that these differences emerge in early-mid adolescence. Furthermore, she calls attention to the role that psychological factors play when it comes to physical illnesses: \"It is \[\...\] possible that the excess in physical complaints among females which begins in adolescence arises, at least in part, as a direct result of the relative lowering in their psychological well-being at this age\" (p. 88). That attention should be directed towards the psychological factors seems to be a feasible conclusion also of the present study. It may be that girls experience greater, and/or different, stressors than boys do from adolescence and onwards, when the differing cultural expectations of the two genders become more evident. In any event, more research is needed that not only establishes the existence of gender differences in self-evaluated health and well-being, but also further investigates what these differences entail and what consequences they involve.
In some respects, the group of young adolescents (13--15 years old) reported higher HRQL and less emotional distress than the older participants. It appears as if increasing age is also connected to a decrease in HRQL among adolescents and young adults. This too is in agreement with previous research \[[@B5],[@B32]\]. As other researchers have pointed out, these differences make sense and are consistent with the augmented levels of stress that the transition from childhood to adulthood involves \[[@B32],[@B33]\]. It is not surprising that both internal and external stressors associated with this time in life, such as striving for autonomy and forming a mature self-image, as well as forming relationships and achieving at school or professionally, are mirrored in the assessment of HRQL.
A strong point of the present study is that the normative data is presented according to survey mode -- telephone interview or postal questionnaire. It is evident that the choice of administration method has a decisive influence on the data that will be obtained. Apart from the statistical difference between the two modes of data collection, a central matter is whether this difference is sufficiently large to have any clinical importance. No minimal clinically important difference standards have been established for the SF-36. However, studies of the score profiles of various clinically defined patient groups have suggested that a 3--5 point change in scale scores may represent a clinically important difference \[[@B34]-[@B36]\]. Although this change may be considered small, it could at least partly cloud the impact of an intervention evaluated with an initial interview and a postal follow-up questionnaire, especially since interventions seldom can be expected to be a complete success. Therefore, it is strongly recommended to use the same mode of administration when comparing groups or changes over time.
It is of interest that different groups seem to respond to the mode of administration in diverse ways and to varying degrees, which is also something that researchers should take into account when planning the design of future studies. Both gender and age were shown to have an impact on how people responded to the two methods of administration. Males and females alike tended to report better scores in the telephone interview compared to the postal questionnaire, but the difference was more marked among the females. Contrary to both adults in general and the two older age groups, the youngest age group did not evaluate their HRQL more positively when interviewed over the telephone than when filling in a postal questionnaire. This finding is surprising, and we feel that more research is needed to understand why the youngest respondents react differently to survey mode. One explanation could be that the young adolescents do not follow the rules of social desirability to the same extent, and consequently feel no need to adjust their responses according to expectations.
There are some methodological limitations which should be mentioned. To minimize the risk of possible regional differences, the participants were stratified regarding three geographical areas. However, the regions chosen are vast and encompass small towns and big cities as well as rural areas. Differences due to these circumstances might exist but not come to light in this design. Additionally, there was a difference in response rate between males and females, resulting in more females than males responding to the mail-administered questionnaires. As females generally seem to report worse HRQL, this might have had some influence on the result.
Conclusion
==========
In conclusion, the study provides pertinent and valuable information about measuring HRQL in adolescents and young adults, a field which has been the subject of little research. In addition, the study presents current normative data for the SF-36 and the HADS for this age group. Furthermore, attention is being directed towards matters that should be investigated further, such as what factors underlie the gender difference which seems to appear in adolescence, and what makes young adolescents respond differently to survey mode used. Most of all, the results stress the importance of taking age, gender, and method of administration into consideration, both when planning studies and when comparing results from different groups, studies, or over time.
Competing interests
===================
The author(s) declare that they have no competing interests.
Authors\' contributions
=======================
AJ wrote the manuscript and conducted the analysis of the data. LW participated in data analysis and revised the manuscript critically. LvE conceived of the design of the study, participated in the analysis of the data and revised the manuscript critically.
|
Room Lighting: Using Lighting in a Bedroom
Room lighting is an issue in numerous American homes that is best drawn closer from both a sensible and an imaginative perspective. The utilization of lighting in a room can be part into three expansive goals. These are to give light, to improve the room style and to be advantageous to utilize. We will move toward every one of these both coherently and imaginatively.
Room Lighting: Let There be Light
The major reason for room lighting is to give light. Some lighting is utilized uniquely for its creative properties, however not in the room. Individuals need light to dress and uncover by, for applying beauty care products, to peruse with and on a very basic level just to not be uninformed. So the lighting in a room must be viable. Having built up that, it would then be able to be utilized for its improving properties.
There are a few distinct kinds of room lighting accessible, each expected for an alternate reason. Among these are:
Roof lights: for general space lighting. The most well-known sorts are utilized as a solitary light with a lampshade, or gathering of lights contained in a roof lighting unit. A crystal fixture is an outrageous case of the last mentioned, yet the central reason for existing is to light the whole room. In certain homes that is the main accessible lighting in the room.
Table lights: these frequently come two by two, one on every night represent a twofold bed. Their essential capacity is to give light to perusing by, albeit once more, in a couple of rooms, this is just wellspring of lighting.
Spotlights: spotlights are utilized for coordinated lighting; to a dresser for instance. They are not a methods for general space lighting and are seldom utilized for perusing.
Mirror lights: these are regularly appended to a mirror – the top or the sides – and give light to applying beautifying agents and other such employments.
There are different types of room lighting to be discovered, for example, divider lights which again are a type of room lighting. Be that as it may, those above are by a wide margin the most well-known types of lighting in a room.
Utilizing Lighting in a Bedroom as Decorative Accents
Having accomplished its essential capacity, every one of the above can likewise be utilized beautifully. The shades are accessible in a practically boundless scope of shapes, sizes, plans and hues. In any room, the lights will in all likelihood adjust to a specific beautifying topic, regardless of whether that is only a shading plan.
In a couple of cases the lights themselves will be hued, extending from pinks and reds to golden and blues. Regularly such lights will be utilized as a highlight in a specific zone of the room, as opposed to as the primary methods for giving light. They will either match or appear differently in relation to the general room stylistic theme, or be utilized as a shaded embellishing accent.
The Convenience of a Bedroom Lighting System
One issue with a solitary light in a room is its bother. Except if fitted with two switches, the room will be in dimness, either before they are turned on or after they have been turned off. Numerous individuals use lights on their end tables or on the divider over their headboard. They would then be able to at present have light when the primary light is stifled.
Another answer for this is an infrared-worked light switch. This is worked by a remote control, and can be utilized once you are sleeping to turn off the lights. This is the most advantageous approach to control your room lighting.
Outline
When picking lighting in a room, you should take every one of the above components into thought. You may not intentionally do as such, however you will probably have every one of the primary three factors at the top of the priority list. The vast majority will ensure they have satisfactory lighting in their room and will either coordinate that to their stylistic layout or pick something other than what’s expected as a complexity.
They will likewise ensure that their room lighting can be stifled from their bed. In saying that, it is astonishing what number of individuals still need to stroll to the entryway to switch of the light, and afterward bumble back to their bed in obscurity. Try not to leave that alone you. There is no compelling reason to rework – just supplant your light switch with a remotely enacted one.
|
Q:
Adding music into LibGDX isn't working. Get an error saying that newMusic isn't a method Has anyone else had this problem lately?
intro = new Audio.newMusic(Gdx.files.internal("core/assets/OpenSong.mp3"));
In the javadocs this is how it says to do it
https://libgdx.badlogicgames.com/ci/nightlies/docs/api/com/badlogic/gdx/audio/Music.html
https://libgdx.badlogicgames.com/ci/nightlies/docs/api/com/badlogic/gdx/Audio.html#newMusic-com.badlogic.gdx.files.FileHandle-
Here: https://www.gamefromscratch.com/post/2013/11/19/LibGDX-Tutorial-8-Audio.aspx they used a lowercase audio instead of uppercase but when changing it to lower case that didn't work either.
It's as if audio/Audio just don't have that method.
A:
Your code should import the class com.badlogic.gdx.Gdx and then you can use
intro = Gfx.audio.newMusic(Gdx.files.internal("core/assets/OpenSong.mp3"));
Alternatively you can write
// where all the import statements live
import static com.badlogic.gdx.Gdx.audio;
// where you try to load the music
intro = audio.newMusic(Gdx.files.internal("core/assets/OpenSong.mp3"));
Your code tries to create a new Audio instance (this will not work, since Audio is just an interface - you would need to create an implementation for it).
Just replacing new Audio with audio will also not work (unless you statically import com.badlogic.gdx.Gdx.audio, as in the second example) - audio alone would mean a field or local variable audio.
|
In the ongoing debate about gun control, Senate Majority Leader Harry Reid, D-Nev., has said that a vote on gun control legislation will be soon. However, a group of Republican senators have vowed to block the vote with a filibuster attempt.
Easter weekend is upon us and with it comes colored eggs, bunnies and loads of candy. If at any point during the Easter egg hunts you need a break, here are five alternative non-Easter activities going on in Utah.
Easter weekend is upon us and with it comes colored eggs, bunnies and loads of candy. If at any point during the Easter egg hunts you need a break, here are five alternative non-Easter activities going on in Utah.
The Utah legislature has granted $10 million to further the science, technology, engineering and math education, or STEM, throughout the state in an effort to prepare Utah students for high tech careers.
The Utah legislature has granted $10 million to further the science, technology, engineering and math education, or STEM, throughout the state in an effort to prepare Utah students for high tech careers.
Forty years ago, the last 2,500 U.S. combat troops were withdrawn from South Vietnam, ending the war. Decades later, post-traumatic stress disorder, suicide and homelessness still plague many Vietnam veterans.
Forty years ago, the last 2,500 U.S. combat troops were withdrawn from South Vietnam, ending the war. Decades later, post-traumatic stress disorder, suicide and homelessness still plague many Vietnam veterans.
The obvious injuries to 4-year-old Ethan Stacy did not cause his death. Instead his death was classified a homicide due to a combination of drug toxicity, scalding injuries and aspiration pneumonia, Utah deputy chief medical examiner Edward Leis testified Friday.
The obvious injuries to 4-year-old Ethan Stacy did not cause his death. Instead his death was classified a homicide due to a combination of drug toxicity, scalding injuries and aspiration pneumonia, Utah deputy chief medical examiner Edward Leis testified Friday.
How much salt is in your diet? It may be a necessity for your scrambled eggs but some new studies say that over 2.3 million people worldwide died from cardiovascular disease (CVD) deaths in 2010 from eating too much salt.
It's no secret that being a professional athlete takes talent, skill and hard work.
But for one Park City freestyle skier, it's more than that — it's a constant drive to succeed even in the face of adversity.
Funeral services were held Friday for a 13-year-old girl who died unexpectedly in her Kaysville home Monday morning from unknown causes. When her best friend heard the bad news, she decided to honor the teen by working to complete her bucket list.
Funeral services were held Friday for a 13-year-old girl who died unexpectedly in her Kaysville home Monday morning from unknown causes. When her best friend heard the bad news, she decided to honor the teen by working to complete her bucket list.
|
Best Boyfriend EVER:
The next collection he found that I was looking for was Maybelline's Holiday Gilded in Gold collection. Normally, I do not use their Color Tattoos, but the fact that the ones in this display are matte and limited edition, I just had to have them, so he picked all three up for me as well.
The few that he purchased for me:
A few of both the Revlon Lacquer Balms in Vivacious, Provacateur & Enticing, Revlon Matte Balms in Standout, Shameless, Sultry & Showly, as well as the three color Tattoos in Matte Brown, Just Beige, and Nude Pink.
One thing I would like to note is that 6 of the 10 matte Revlon Matte Balm shades only have one for each display, such as Shameless (the purple) & Standout (deep red), so they may be harder to find. I was lucky enough to have my boyfriend be able to go look for these everyday & for them to put them up when he was there.
I cannot wait until I get to see him later on this week so that I can see these in person! & I will definitely try them out when I have the time to if I am not loaded up with homework this weekend so I can have swatches & review up for you guys! :) Like I have mentioned before, I appreciate my boyfriend SO much and for him to understand and be so helpful with this makeup obsession of mine is amazing! I seriously do not know what I would do without him because he seriously is the best I have ever had.
Do you think you will be picking up some of these new Holiday Collection items?
Since NouveauCheap has mentioned that these had landed, I HAD to look for them. Although I spent all weekend hunting, they were nowhere to be found. When it's the weekdays, I have no car, so I have no access to stalk products & normally by the time it's weekend, the things I want are sold out. Well, my boyfriend is the sweetest ever! Knowing that I have been looking for these & after showing him pictures while I was hunting over the weekend, he ended up going to look for them for me himself so I would not miss out on them. This morning when he told me they had it in & I was SO excited!Here's some display pictures:Revlon's new Lacquer Balms & Matte Balms. My boyfriend had a full display, but he took the picture after he took the ones that he was going to buy for me, which is why it's not full, but he did good! I like how half the display itself is glossy, and the other half is matte!
|
import { Component, render, rerender } from 'inferno';
describe('Error recovery', () => {
let container;
beforeEach(function () {
container = document.createElement('div');
document.body.appendChild(container);
});
afterEach(function () {
render(null, container);
container.innerHTML = '';
document.body.removeChild(container);
});
it('Should be possible to render again if user land code crashes in CWM', () => {
class Crasher extends Component {
constructor(props, context) {
super(props, context);
this.state = {
value: 1
};
}
componentWillMount() {
if (this.props.crash) {
throw Error('test');
}
this.setState({
value: 2
});
}
render() {
return <div>{this.state.value}</div>;
}
}
try {
render(<Crasher crash={true} />, container);
} catch (ex) {
expect(ex.message).toBe('test');
}
render(<Crasher crash={false} />, container);
expect(container.firstChild.innerHTML).toBe('2');
});
it('Should be possible to render again if user land code crashes in ComponentWillUnmount', () => {
class Crasher extends Component {
constructor(props, context) {
super(props, context);
this.state = {
value: 1
};
}
componentWillUnmount() {
if (this.props.crash) {
throw Error('test');
}
}
render() {
return <div>{this.state.value}</div>;
}
}
render(<Crasher crash={true} />, container);
expect(container.firstChild.innerHTML).toBe('1');
try {
render(null, container);
} catch (ex) {
expect(ex.message).toBe('test');
}
// No change as it crashed
expect(container.firstChild.innerHTML).toBe('1');
// Try update
render(<Crasher crash={false} />, container);
expect(container.firstChild.innerHTML).toBe('1');
// Should not crash now
render(null, container);
expect(container.innerHTML).toBe('');
});
/*
* THROW ERROR IN
*
* last node - render - willMount, didMount, willUpdate, didUpdate, constructor, cwrp
* mid node - render - willMount, didMount, willUpdate, didUpdate, constructor, cwrp
* first node - render - willMount, didMount, willUpdate, didUpdate, constructor, cwrp
*
* force keyed? force non keyed?
*/
describe('Error recovery from user land errors', () => {
['last', 'mid', 'first'].forEach((location) => {
['render', 'constructor', 'DidMount', 'WillMount', 'WillReceiveProps', 'shouldUpdate', 'WillUpdate', 'DidUpdate', 'getChildContext'].forEach(
(crashLocation) => {
it('Should recover from subtree crash in ' + location + ' of children when crash happens in components ' + crashLocation, () => {
class Crasher extends Component {
constructor(props, context) {
super(props, context);
this.state = {
value: ''
};
if (props.crash && crashLocation === 'constructor') {
throw Error('test');
}
}
componentWillMount() {
this.setState({
value: 'mounted'
});
if (this.props.crash && crashLocation === 'WillMount') {
throw Error('test');
}
}
componentWillReceiveProps(props) {
if (props.crash && crashLocation === 'WillReceiveProps') {
throw Error('test');
}
}
componentDidMount() {
if (this.props.crash && crashLocation === 'DidMount') {
throw Error('test');
}
}
shouldComponentUpdate(props) {
if (props.crash && crashLocation === 'shouldUpdate') {
throw Error('test');
}
}
componentWillUpdate() {
if (this.props.crash && crashLocation === 'WillUpdate') {
throw Error('test');
}
}
componentDidUpdate() {
if (this.props.crash && crashLocation === 'DidUpdate') {
throw Error('test');
}
}
// Unmount hook is still an issue
// componentWillUnmount() {
// if (this.props.crash && crashLocation === 'WillUnmount') {
// throw Error('test');
// }
// }
getChildContext() {
if (this.props.crash && crashLocation === 'getChildContext') {
throw Error('test');
}
return {};
}
render() {
if (this.props.crash && crashLocation === 'render') {
throw Error('test');
}
return <div>{this.state.value}</div>;
}
}
function TreeOfCrashers({ suffle, crash }) {
let arr = [];
if (location === 'first') {
arr.push(<Crasher crash={crash} />);
}
if (suffle) {
arr.push(<span>1</span>);
if (location === 'mid') {
arr.push(<Crasher crash={crash} />);
}
arr.push(<Crasher crash={false} />);
} else {
if (location === 'mid') {
arr.push(<Crasher crash={crash} />);
}
arr.push(<Crasher crash={false} />);
}
if (location === 'last') {
arr.push(<Crasher crash={crash} />);
}
return <div>{arr}</div>;
}
render(<TreeOfCrashers crash={false} />, container);
try {
render(<TreeOfCrashers suffle={true} crash={true} />, container);
} catch (ex) {
// do nothing
}
render(<TreeOfCrashers crash={false} />, container);
expect(container.firstChild.innerHTML).toBe('<div>mounted</div><div>mounted</div>');
});
}
);
});
['last', 'mid', 'first'].forEach((location) => {
['render', 'constructor', 'DidMount', 'WillMount', 'WillReceiveProps', 'shouldUpdate', 'WillUpdate', 'DidUpdate', 'getChildContext'].forEach(
(crashLocation) => {
it('Should recover from subtree crash in NON-KEYED ' + location + ' of children when crash happens in components ' + crashLocation, () => {
class Crasher extends Component {
constructor(props, context) {
super(props, context);
this.state = {
value: ''
};
if (props.crash && crashLocation === 'constructor') {
throw Error('test');
}
}
componentWillMount() {
this.setState({
value: 'mounted'
});
if (this.props.crash && crashLocation === 'WillMount') {
throw Error('test');
}
}
componentWillReceiveProps(props) {
if (props.crash && crashLocation === 'WillReceiveProps') {
throw Error('test');
}
}
componentDidMount() {
if (this.props.crash && crashLocation === 'DidMount') {
throw Error('test');
}
}
shouldComponentUpdate(props) {
if (props.crash && crashLocation === 'shouldUpdate') {
throw Error('test');
}
}
componentWillUpdate() {
if (this.props.crash && crashLocation === 'WillUpdate') {
throw Error('test');
}
}
componentDidUpdate() {
if (this.props.crash && crashLocation === 'DidUpdate') {
throw Error('test');
}
}
// Unmount hook is still an issue
// componentWillUnmount() {
// if (this.props.crash && crashLocation === 'WillUnmount') {
// throw Error('test');
// }
// }
getChildContext() {
if (this.props.crash && crashLocation === 'getChildContext') {
throw Error('test');
}
return {};
}
render() {
if (this.props.crash && crashLocation === 'render') {
throw Error('test');
}
return <div>{this.state.value}</div>;
}
}
function TreeOfCrashers({ suffle, crash }) {
let arr = [];
if (location === 'first') {
arr.push(<Crasher crash={crash} />);
}
if (suffle) {
arr.push(<span>1</span>);
if (location === 'mid') {
arr.push(<Crasher crash={crash} />);
}
arr.push(<Crasher crash={false} />);
} else {
if (location === 'mid') {
arr.push(<Crasher crash={crash} />);
}
arr.push(<Crasher crash={false} />);
}
if (location === 'last') {
arr.push(<Crasher crash={crash} />);
}
return <div $HasNonKeyedChildren>{arr}</div>;
}
render(<TreeOfCrashers crash={false} />, container);
try {
render(<TreeOfCrashers suffle={true} crash={true} />, container);
} catch (ex) {
// do nothing
}
render(<TreeOfCrashers crash={false} />, container);
expect(container.firstChild.innerHTML).toBe('<div>mounted</div><div>mounted</div>');
});
}
);
});
['last', 'mid', 'first'].forEach((location) => {
['render', 'constructor', 'DidMount', 'WillMount', 'WillReceiveProps', 'shouldUpdate', 'WillUpdate', 'DidUpdate', 'getChildContext'].forEach(
(crashLocation) => {
it('Should recover from subtree crash in NON-KEYED ' + location + ' of children when crash happens in components ' + crashLocation, () => {
class Crasher extends Component {
constructor(props, context) {
super(props, context);
this.state = {
value: ''
};
if (props.crash && crashLocation === 'constructor') {
throw Error('test');
}
}
componentWillMount() {
this.setState({
value: 'mounted'
});
if (this.props.crash && crashLocation === 'WillMount') {
throw Error('test');
}
}
componentWillReceiveProps(props) {
if (props.crash && crashLocation === 'WillReceiveProps') {
throw Error('test');
}
}
componentDidMount() {
if (this.props.crash && crashLocation === 'DidMount') {
throw Error('test');
}
}
shouldComponentUpdate(props) {
if (props.crash && crashLocation === 'shouldUpdate') {
throw Error('test');
}
}
componentWillUpdate() {
if (this.props.crash && crashLocation === 'WillUpdate') {
throw Error('test');
}
}
componentDidUpdate() {
if (this.props.crash && crashLocation === 'DidUpdate') {
throw Error('test');
}
}
// Unmount hook is still an issue
// componentWillUnmount() {
// if (this.props.crash && crashLocation === 'WillUnmount') {
// throw Error('test');
// }
// }
getChildContext() {
if (this.props.crash && crashLocation === 'getChildContext') {
throw Error('test');
}
return {};
}
render() {
if (this.props.crash && crashLocation === 'render') {
throw Error('test');
}
return <div>{this.state.value}</div>;
}
}
function TreeOfCrashers({ suffle, crash }) {
let arr = [];
if (location === 'first') {
arr.push(<Crasher key="first" crash={crash} />);
}
if (suffle) {
arr.push(<span key="span">1</span>);
if (location === 'mid') {
arr.push(<Crasher key="mid" crash={crash} />);
}
arr.push(<Crasher key="false-suffle" crash={false} />);
} else {
if (location === 'mid') {
arr.push(<Crasher key="mid" crash={crash} />);
}
arr.push(<Crasher key="true-suffle" crash={false} />);
}
if (location === 'last') {
arr.push(<Crasher key="last" crash={crash} />);
}
return <div $HasKeyedChildren>{arr}</div>;
}
render(<TreeOfCrashers crash={false} />, container);
try {
render(<TreeOfCrashers suffle={true} crash={true} />, container);
} catch (ex) {
// do nothing
}
render(<TreeOfCrashers crash={false} />, container);
expect(container.firstChild.innerHTML).toBe('<div>mounted</div><div>mounted</div>');
});
}
);
});
describe('Error in child component', () => {
it('Should not block future updates', (done) => {
let parentInstance = null;
let childCrasherInstance = null;
class BadComponent extends Component {
constructor(props) {
super(props);
}
componentWillMount() {
throw 'Oops!';
}
render() {
return 1;
}
}
class ChildCrasher extends Component {
constructor(props) {
super(props);
this.state = {
fail: false
};
childCrasherInstance = this; // For the sake of test
}
render() {
if (!this.state.fail) {
return null;
}
return <BadComponent />;
}
}
class Parent extends Component {
constructor(props) {
super(props);
parentInstance = this; // For the sake of test
}
render() {
return (
<div>
<ChildCrasher />
</div>
);
}
}
render(<Parent />, container);
expect(container.innerHTML).toBe('<div></div>');
expect(() => {
childCrasherInstance.setState({
fail: true
});
rerender();
}).toThrow('Oops!');
// Recover from it
childCrasherInstance.setState({
fail: false
});
setTimeout(function () {
expect(container.innerHTML).toBe('<div></div>');
done();
}, 10);
});
it('Should not block future updates - variation 2', () => {
let parentInstance = null;
let childCrasherInstance = null;
class BadComponent extends Component {
constructor(props) {
super(props);
throw 'Oops!';
}
render() {
return <div>Ok</div>;
}
}
class ChildCrasher extends Component {
constructor(props) {
super(props);
childCrasherInstance = this; // For the sake of test
}
render() {
if (!this.props.fail) {
return null;
}
return (
<div>
<span>1</span>
<BadComponent />
</div>
);
}
}
class Parent extends Component {
constructor(props) {
super(props);
this.state = {
nodes: false
};
parentInstance = this; // For the sake of test
}
render() {
return (
<div>
<span>1</span>
{this.nodes ? <div>2</div> : null}
<ChildCrasher fail={this.props.fail} />
</div>
);
}
}
expect(() => render(<Parent fail={true} />, container)).toThrow('Oops!');
expect(() => render(<Parent fail={true} />, container)).toThrow('Oops!');
parentInstance.setState({
nodes: true
});
rerender();
expect(container.innerHTML).toEqual('');
render(<Parent fail={false} />, container);
expect(() => render(<Parent fail={true} />, container)).toThrow('Oops!');
expect(() => {
parentInstance.setState({
nodes: false
});
rerender();
}).toThrow('Oops!');
expect(() => {
parentInstance.setState({
nodes: true
});
rerender();
}).toThrow('Oops!');
});
});
});
});
|
Q:
Parse the executing file path
Possible Duplicate:
Retrieving python module path
python, path of script
I have a Python file, and I would like to parse the path when this file is executed. If I run myPython.py like this:
python ~/Documents/Project/myPython.py
I would like to know the path "~/Documents/Project/" in the file myPython.py.
A:
sys.argv[0] is the path of your script as executed by Python. You can use os.path.dirname() to get just the directory name from that:
import sys, os
print os.dirname(sys.argv[0])
It is OS-dependent if it is the full path entered on the command line; Mac OS X and Linux both include the path.
The path can, however, differ based on how Python invoked it. An alternative is to use __file__, and you can make the path absolute by using os.path.abspath() and os.path.expanduser() to cover all variations:
print os.path.dirname(os.path.abspath(os.path.expanduser(__file__)))
|
Introduction
============
Cures for age-related diseases such as cardiovascular disease, diabetes mellitus, Alzheimer's disease, and cancer, are increasingly unlikely to come from historic pharmaceutical industry models of therapeutic innovation and development. While the standard model of drug R&D utilized by pharmaceuticals has produced effective treatments to manage such diseases as hypertension, asthma, and arthritis, highly variable and increasingly more complex diseases such as cancer will require much more personalized approaches to patient treatment. The future of medicine, fueled by growth in complex biological data, lack of innovation in current pipelines, and political pressure, has therefore been shifting toward personalized medicine ([@B30]). Personalized medicine, as defined by the National Academies Press, is "the ability to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not" ([@B30]). Specifically in personalized medicine, there has been an increasing focus on the barriers to widespread adoption ([@B4]). The current literature highlights cost-effectiveness, efficacy, reimbursement, and regulation ([@B12]; [@B20]) as the key concerns for adoption of current personalized medicines, but an aspect of personalized medicine that has recently come into the spotlight as an inseparable aspect of precision medicine is the role of companion diagnostics.
Companion diagnostics (CDx) are a critical component in advancing personalized medicine. Companion diagnostics were officially defined in 2014 by the Food and Drug Administration (FDA; Silver Springs, MD, USA) as "a medical device, often an *in vitro* device, which provides information that is essential for the safe and effective use of a corresponding drug or biological product" ([@B7]). Biomarker based stratification assays designed to identify responsive patient subpopulations and detect patients more likely to experience adverse effects are becoming increasingly important to securing market share for high efficacy, high cost therapeutics ([@B2]; [@B46]).
From a pharmaceutical development viewpoint, CDxs can contribute to the successful approval and market launch of high-risk but high benefit therapeutics. The success of Herceptin (Trastuzumab; Roche, Basel, Switzerland), a monoclonal antibody (mAb) that blocks the growth of malignant tumor cells, relies on the ability of a CDx to accurately identify the subpopulation (22%) of patients with HER2-positive early breast cancer ([@B45])^.^ Failure to stratify the patient population will result in both costly interventions and unnecessary exposure to increased cardiotoxicities for patients who cannot benefit from the drug.
Herceptin was groundbreaking as the first targeted therapy to address the underlying causes of a predominantly age-related disease, and its CDx, HercepTest (Dako, Glostrup, Denmark), was the first CDx to enter clinical practice in 1998 \["[@B22]"\]. However, few companion diagnostics/treatment (CDx/Rx) pairs have been approved for the market since Herceptin's breakthrough ([@B27]; [@B12]). There have been a limited total of 23 approved CDx for 11 personalized therapies and seven primary indications in the past 17 years ([@B6]). The rates of technological development and clinical adoption of CDxs has been arguably limited relative to the extent of public and private investment.
Limited progress could be due to a number of reasons. There are numerous scientific challenges to the discovery and production of companion diagnostics and corresponding therapeutics ([@B14]). Equally important to the advancement of personalized therapies, however, are significant regulatory and economic challenges ([@B13]; [@B17]; [@B27]).
Regulation for CDx and Rx is intrinsically connected, and this relationship may or may not be reflected in the economic incentives and disincentives driving innovation and development of CDx/Rx pairs. The FDA recently released the "*In Vitro* Companion Diagnostic Devices: Guidance for Industry and Food and Drug Administration Staff" on July 31st, 2014, suggesting that companion diagnostics and corresponding therapeutics be co-developed and evaluated concurrently ([@B24]).
This suggested regulatory link between companion diagnostics and their corresponding drugs can influence economic factors and affect the rate of market approval and adoption ([@B25]; [@B46]). Specifically, the collaboration between two typically independent industries potentially presents challenges in aligning incentives between diagnostic developers and pharmaceutical manufacturers ([@B9]; [@B28]). **Figure [1](#F1){ref-type="fig"}** shows the regulatory framework that underpins co-development. To date, the regulatory landscape for market approval and price determinations of CDx/Rx pairs is relatively unexamined and lacking quantitative analysis necessary for changes and improvements.
{#F1}
Therefore, it is important to analyze current, publically available data for companion diagnostics and corresponding therapeutics to identify drivers, limitations, and areas for more research in the current landscape. A systematic analysis and numerical data will identify factors affecting the CDx/Rx pair market and provide more information to assess the impact of future regulatory and policy changes in facilitating or limiting the development of companion diagnostics. This paper provides a data driven analysis of the CDx/Rx market by statistically analyzing and discussing factors that may incentivize, restrict, or create uncertainty in the development and adoption of companion diagnostics.
Materials and Methods {#s1}
=====================
Inclusion Criteria
------------------
A systematic analysis was conducted with methodology set in **Figure [2](#F2){ref-type="fig"}**. Seven sets of personalized therapies were selected for analysis based on a series of case studies of personalized medicines and their CDx published in [@B33]. These cases describe a number of indications over a period of 15 years; although not a comprehensive list, they represent a number of leading examples of successful stratification of therapeutics. While there are 23 FDA approved CDx for 11 personalized therapeutics, the availability of established, validated, and publically accessible data, along with the existence of robust prior research, limits the number of CDx/Rx pair available for examination to the seven personalized therapeutics presented in previous literature ([@B33]). The majority of CDx/Rx pairs presented were in the field of oncology, such as Herceptin, Xalkori, Zelboraf (vemurafenib; Roche, Basel, Switzerland), and Vectibix (Panitumumab; Amben, CA, USA). Oncology contributes a large proportion of CDx/Rx due to its inherently highly stratified populations and extensive investment in biomarker discovery, but the development of companion diagnostics is not limited to oncological indications. Therefore, final list of CDx/Rx pairs attempts to capture multiple primary indications, including CDx/Rx pairs beyond those on the "List of FDA Approved Companion Diagnostics" ([@B6]) to include the three highly personalized therapeutics and unofficial companion diagnostics examined in [@B33]: Ziagen (abacavir sulfate; Viiv Healthcare, Brentford, UK), Selzentry (Maraviroc; Viiv Healthcare, Brentford, UK), and Kalydeco (Vertex, Cambridge, MA, USA). All three additional CDx/Rx pairs address indications (cystic fibrosis and HIV) in which specific mutations and tropisms are known at time of diagnosis and extensive prior literature is available to support their classification as personalized therapeutics ([@B33]).
{#F2}
**Table [1](#T1){ref-type="table"}** shows the finalized table of companion and pseudo-companion diagnostic and therapeutic pairs that meet the requirements of a large clinical database, pre-existing research, long duration on market, robust data, and US market approval.
######
Select list of FDA approved personalized therapeutic/CDx pairs.
Primary indication Drug (pharma) CDx/approved year (diagnostic company) Assay
------------------------------------ ----------------------------------------- ---------------------------------------------------------------------------------- -----------------
Breast cancer Herceptin (Roche, Basel, Switzerland) HercepTest/1998 (Dako, Glostrup, Denmark) SemiqIHC
SPOT-light HER-2 CISH Kit/2008 (Life Technologies, South San Francisco, CA, USA) CISH
Bond Oracle Her2 INC System/2012 (Leica Biosystem, Nussloch, Germany) SemiqIHC
PATHVYSION HER-2 DNA Probe Kit/2013 (Abbott, IL, USA) FISH DNA Probe
HER2 FISH PharmDx Kit/2005 (Dako) qFISH
INFORM HER2 Dual ISH/2011 (Roche) CISH
Melanoma Zelboraf (Roche) COB AS 4800 BRAF V600 Mutation Test/2013 (Roche) RT-PCR
Non-small cell lung cancer Xalkori (Pfizer, NY, USA) Lysis ALK Break Apart FISH Probe Kit/2013 (Abbott) FISH
Colorectal Cancer Vectibix (Amgen, CA, USA) Therascreen KRAS RGQ PCR Kit/2011 (Qiagen, Venlo, The Netherlands) PCR
The cobas KRAS Mutation Test/2013 (Roche) RT-PCR
EGFR PharmDx Kit/2003 (Dako) qlHC
Cystic fibrosis Kalydeco (Vertex, MA, USA) Unbranded laboratory test used during (1989) Clinical trials
Human immunodeficiency virus (HIV) Ziagen (Viiv Healthcare, Brentford, UK) LDTs at time of development (2007)
Human immunodeficiency virus (HIV) Selzentry (Viiv Healthcare) Trofile Test/2008 (Labcorp, NC, USA) qPCR
Selection of data was based on availability of data, robust prior research, large clinical database, and US market approval.
SemiqIHC, semiquantitative immunohistochemistry; CISH, chromogenic in situ hybridization; FISH, fluorescence in situ hybridization; qFISH, quantitative fluorescence in situ hybridization; RT-PCR, real-time polymerase chain reaction; qPCR, quantitative polymerase chain reaction.
A list of feasible factors impacting the companion diagnostic industry available for systematic assessment was determined from a preliminary overview of existing research ([@B45]) for each of the seven personalized therapeutics in **Table [1](#T1){ref-type="table"}**.
Nine factors were analyzed that could influence companion diagnostic development and adoption: CDx price, CDx sensitivity, price of drug standardized per course of treatment, duration of drug treatment, years on the market for drug (measured from year of FDA approval to year of patent expiration, or predicted patent expiration for drugs most likely to receive extended protection), drug efficacy, total current population of patients in specific indication, subpopulation of patient population (calculated with the percentage of total patient population predicted to have the specific mutation or biomarker expression), and response rate of patient subpopulation to drug after selection with companion diagnostic.
Factors impacting both the companion diagnostic manufacturers (price of CDx, sensitivity, total patient population) and pharmaceutical therapy development and adoption (drug prices, effectiveness, patient subpopulation, response rate) were included as factors for CDx market analysis because of the unique regulatory dependency of CDx and personalized therapeutic. The factor "price of drug" was standardized as the total cost for one course of complete treatment. "Drug efficacy" was based on the percentage reported in clinical trials of the drug to either decrease tumor size or reach a standard endpoint such cell count and forced expiratory volume in 1 s. Factors fell into two categories -- those relating to the CDx (CDx price, CDx sensitivity) solely and those relating to the therapeutic and treatment (drug price, duration of treatment, years the drug has been on market, drug effectiveness, total patient population, treatable subpopulation, response rate).
Data Collection and Statistical Analysis
----------------------------------------
Data in each category for each therapy was individually obtained from eighty distinct sources, ranging from literature searches in PubMed, personal correspondence with diagnostic and pharmaceutical company representatives, current articles in prominent news journals, government dockets, annual reports, patent filings, Internet searches, and published regulatory agency documents, to official FDA released drug labels. Data for factors in the therapeutic market was applied to each CDx. For example, the numerical value for total population of patients with breast cancer was identical for each of Herceptin's six FDA approved CDx.
Statistical analysis was conducted using JMP. The relationship between two factors was determined by Spearman's Rho, a non-parametric tool to determine correlation for data without a Gaussian distribution. Significant relationships were determined by *t*-test on regression, with a null hypothesis that the regression is zero. Results were considered significant if *p* \< 0.05. Relationships for all possible pairs of factors were tested in order to preserve an unbiased analysis. Statistical analysis was supplemented with detailed case studies examining competition within the CDx landscape in the two CDx/Rx pairs with multiple FDA approved CDx at the time of this assessment (Herceptin with six CDx and Vectibix with three CDx).
Results
=======
Statistical analysis for 36 hypotheses resulted in two significant relationships and 34 non-significant relationships. **Table [2](#T2){ref-type="table"}** shows the nine by nine matrix of factor pairs with calculated *r*- and *p*-values. Further analysis focuses on possible interpretations of insignificant and significant relationships for companion diagnostics, with less focus on relationships for the therapeutic market.
######
Correlation (*r*) and significance (*p*) values for financial and product factors affecting the market for companion diagnostic/therapeutic (CDx/Rx) pairs.
CDx price CDx sensitivity Drug price (treatment) Duration of treatment Drug years on market Drug effective-ness Total patient population Treatable subpopulation Response rate
------------------------------ ----------- ------------------ ------------------------ ----------------------- ---------------------- --------------------- -------------------------- ------------------------- ---------------
**CDx price** 1 **[-0.78]{.ul}** 0.18 0.31 -0.54 -0.26 0.25 -0.25 0.07
0 **[0.04]{.ul}** 0.7 0.5 0.22 0.57 0.59 0.59 0.88
**CDx sensitivity** 1 0.18 -0.44 -0.04 -0.32 0.2 -0.14 -0.14
0 0.7 0.33 0.94 0.48 0.67 0.76 0.76
**Drug price (treatment)** 1 0.55 0.51 -0.71 -0.31 -0.36 0.46
0 0.2 0.25 0.07 0.5 0.43 0.29
**Duration of treatment** 1 -0.49 -0.29 -0.13 -0.04 0.45
0 0.27 0.53 0.78 0.94 0.31
**Drug years on market** 1 0.29 -0.3 -0.21 0.11
0 0.53 0.51 0.66 0.81
**Drug effectiveness** 1 0.41 0.29 0.18
0 0.36 0.53 0.7
**Total patient population** 1 **[0.88]{.ul}** 0.11
0 **[0.01]{.ul}** 0.82
**Treatable subpopulation** 1 0.29
0 0.53
**Response rate** 1
0
Thirty-six factors were statistically analyzed using Spearman's rank test on JMP. Relationships were significant if p \< 0.05. Significant relationships are bolded and underlined. Gray box is correlation while white box is significance.
Relationships Affecting Companion Diagnostics
---------------------------------------------
The factors that relate to the companion diagnostic have a significant relationship between themselves: the CDx price has a significant relationship with the CDx sensitivity. **Figure [3A](#F3){ref-type="fig"}** shows this relationship graphically, with rho calculated as a Spearman's rank correlation that standardizes outliers as opposed to a Pearson's correlation for Gaussian distributions (*r* = -0.78, *p* = 0.04). One explanation for the price of CDx increasing with increasing sensitivity is that a CDx which can more accurately stratify the patient population into correct respondent groups might take longer to develop, or utilize more expensive technology, and therefore be priced higher to offset the higher costs of development.
{#F3}
The factors that relate solely to the companion diagnostic (CDx price, CDx sensitivity) do not have significant relationships to factors relating to the therapeutic or treatment (drug price for treatment, years on market for drug, drug efficacy, population measurements, and response rates to drug). One may expect a significant relationship to exist between the factors affecting companion diagnostics and the therapeutic or treatment because of their interconnected nature and regulatory co-development. For instance, it may be expected that companion diagnostics would follow the same pricing curve as their corresponding therapeutic, because there are costs involved in meeting regulatory standards ([@B36]). A high risk, high benefit therapeutic such as Zelboraf will be priced to reflect the time, cost, and production of larger clinical trials, more advanced technology, and longer development time and because the companion diagnostic used during clinical trials for Zelboraf faces a similar regulatory pathway, it might be expected to be priced accordingly. However, there is no significant relationship between CDx price and the drug price for a complete course of treatment (*r* = 0.18, *p* = 0.7, **Figure [3B](#F3){ref-type="fig"}**). Zelboraf costs approximately \$56,400 per treatment ([@B10]) with a CDx priced at \$401, while Vectibix costs \$68,000 per treatment ([@B35]) -- more than Zelboraf -- but with a CDx priced lower than \$401, at \$385 ([@B37]). In another instance, it may be expected that CDx price will have a relationship with the treatable subpopulation because the treatable population is a representation of the full market size that a CDx could penetrate. However, market size, measured by the total patient population, does not statistically have a significant relationship with the price of a CDx (*r* = 0.25, *p* = 0.59, **Figure [3C](#F3){ref-type="fig"}**). The lack of significant relationships raises more research questions and limitations are further discussed in Section "Limitations."
Competition
-----------
Examining competition in two case studies of Herceptin and Vectibix revealed that as the number of CDx for one therapeutic increases, sensitivity improves. Since the approval of the first companion diagnostic, there have been a growing number of companion diagnostics each year, with an expanding range of pricing and more diverse test types (**Figures [4](#F4){ref-type="fig"}** and **[5](#F5){ref-type="fig"}**). In the case study of Herceptin, the price range of companion diagnostics heightened with the expansion of testing methods, and accordingly, sensitivity increased as technology improved through the years (**Figure [6](#F6){ref-type="fig"}**).
{#F4}
{#F5}
{#F6}
In the case study of Vectibix, the companion diagnostic followed a unique developmental pathway that ultimately led to better identification of the patient population that responded positively to anti-EGFR therapy. Originally, overexpression of EGFR was discovered as a biomarker for colorectal cancer and enlisted in clinical trials for an anti-EGFR mAb, Erbitux. Following the model of Herceptin, patients enrolled in Erbitux clinical studies had to demonstrate immunohistochemistry (IHC) evidence of positive EGFR expression, leading to the co-development of Dako's EGFR pharmDx^TM^ test \[[@B22]\].
In 2007, following the model set by Herceptin and HER2, Erbitux and its companion diagnostic were co-approved. However, unlike the smooth success of Herceptin, subsequent studies post-drug approval failed to support the correlation between EGFR overexpression and response to either Erbitux, or a second anti-EGFR drug in development, Vectibix ([@B11]; [@B41]). In a parallel set of studies, a better predictor of response to Erbitux and Vectibix started emerging. Pivotal studies conducted on the clinical utility of a *KRAS* mutation status confirmed the *KRAS* gene as an accurate predictor of non-responsive individuals to anti-EGFR therapy ([@B31]). The FDA acknowledged the evidence base for KRAS presence as a marker for patients who would achieve no benefit from anti-EGFR therapy and issued a label update for the entire class of drugs, recommending KRAS testing as part of colorectal cancer patient management ([@B1]).
Subsequent approval of Vectibix and corresponding companion diagnostic, Qiagen's (Venlo, The Netherlands) therascreen KRAS RGQ PCR kit, followed ([@B38]). Two years later, Roche developed the cobas^®^, KRAS Mutation kit; a companion diagnostic comparable to Qiagen's therascreen, but one that produces faster results, but at a higher price ([@B23]).
Discussion
==========
Quantitatively assessing the relationship between factors affecting the market for companion diagnostics and corresponding therapeutics reveals that the regulatory codependence of CDx/Rx pairs is not reflected in their economic landscape. With CDx/Rx development, the two separate industries (diagnostic and pharmaceutical) form a relationship in which FDA approval, reimbursement, and prescription of the therapeutic is dependent on accurate stratification of the patient population, and the regulatory approval and utility of the companion diagnostic relies on approval of the therapeutic. Data shows that factors pertaining to the therapeutic do not likewise influence the price or sensitivity of the CDx. It appears that the companion diagnostics market is governed by a different set of drivers than the pharmaceutical market because there is no significant relationship between economic factors for the two industries.
The economic independence of CDx and therapeutic may disincentivize development of companion diagnostics. Personalized medicine is inherently a disruptive innovation and incentives to develop more personalized therapeutics may be economic, as seen through high prices of personalized medicines in oncology. However, the push toward greater investment in CDx seems to be solely regulatory, because CDx do not share in the same high prices and multiple doses as their expensive corresponding therapeutics experience. Pricing for CDx would indicate that diagnostic tests are valued as utility, much like a needle that is used to inject a serum, and not as an integral part of the therapeutic itself ([@B43]). However, unlike the needle, which is universal and non-specific, the CDx can direct a physician toward a specific course of treatment and is as important to a treatment as the drug itself. While companion diagnostics are clinical tools that can help physicians decide the course of patient treatment, their pricing practices are independent of the pricing practices for their corresponding therapeutic, and this economic discrepancy might be a currently overlooked barrier in the race to develop more personalized therapeutics.
In context, there are also many other barriers to the development and adoption of companion diagnostics. Reimbursement uncertainty continues to create challenges ([@B5]). Current reimbursement for companion diagnostics relies on a complex system of CPT code stacking, private health plan policies, evidence of clinical utility, and cost of both the diagnostic and the treatment ([@B18]; [@B44]). Having a wide range for the 'price' of a companion diagnostic indicates a lack of standardization in the charges different providers and insurers receive (**Figure [5](#F5){ref-type="fig"}**) and could create an unwillingness to adopt complex therapies that require not one, but two different payments -- one for the initial companion diagnostic, and one for the following drug treatment.
Coverage and reimbursement for high-risk, high-reward personalized treatments are often decided on a health plan level and the existence of 100s of different insurance plans along with a national payer system for low-income, disabled, and elderly Americans leads to fragmentation in access to life-saving therapies ([@B39]). Skepticism of the efficacy of companion diagnostics to predict responses to therapy and uncertainty on the necessity of a companion diagnostic slows reimbursement and creates challenges to the widespread implementation of existing personalized therapies ([@B19]).
Additionally, the dominance of late stage competition and lack of early stage competition within companion diagnostics creates barriers to the innovation and development of the companion diagnostics market ([@B2]). Uncertainties in evaluating the utility of an assay when clinical activity of the therapeutic or the relationship of the biomarker to the mechanism of action of the therapeutic being developed are major scientific challenges for multiple companion diagnostics to be developed at once ([@B43]). The high risk nature of CDx development incentivizes publicly listed diagnostic companies to gravitate toward close-to-market products capable of generating revenues in the short term to satisfy the investment community instead of encouraging early stage technologies that might deliver products far in the future ([@B15]).
The large upfront investment with low certainty in returns for diagnostics does not encourage competition to occur between companion diagnostics for a singular therapeutic before an initial CDx reaches market. Competition can act as a positive force to stabilize prices, and increase innovation ([@B3]), and while companion diagnostics market does not currently offer a viable space for competition, it has the potential to.
The predictive power of biomarkers varies between indications and therapies ([@B43]), possibly opening up space for more biomarkers with stronger analytical power to enter into consideration for a therapeutics' clinical trials. The presence of some biomarkers, such as a particular gene mutation in a CF mutation panel, or the detection of a KRAS mutation status, allows for straightforward stratification of patients into dichotomous populations -- a group that will respond to a therapeutic and one that will not ([@B8]). The presence of other genes, such as HER2 or ALK (anaplastic lymphoma kinase), is measured on a more continuous scale and requires multiple runs and expert interpretation before subsequent delineation into one particular treatment therapy ([@B40]).
As seen in the case of Vectibix, for which clinicians began with an EGFR-positive companion diagnostic, then added a KRAS-negative companion diagnostic, a single test may not be sufficient to correctly identify patient response levels. Well-planned incremental evaluations of CDx/Tx pairs across phase I, II, and III studies would ideally increase the efficiency of the drug development process and response to therapeutic ([@B43]; [@B28]).
The inherent complexity of biomarker development and the even more uncertain nature of drug development, innovation models that encourage open competition during early stages might work to increase success rates of therapeutics through clinical trials and lower attrition values ([@B16]). With the structure of co-development, competing development of diagnostic methods is currently limited to established contracts and investments from pharmaceutical companies, but advances in technology and risk sharing models might propel a more independent model for competition in the future.
Limitations
-----------
This study has a number of limitations (**Table [3](#T3){ref-type="table"}**). The main limitation of this study is the maturity of the market and therefore the small amount of robust, publically available data published for each companion diagnostic and therapeutic. A young industry has a large number of variations that make direct comparisons difficult. For instance, the point of stratification for one personalized therapeutic is not necessarily the same as the point of stratification of another personalized therapeutic. Some companion diagnostics (Herceptin, Zelboraf, Xalkori) followed a co-development model and received simultaneous CDx/Rx approval from the FDA.
######
Abbreviated list of limitations.
---------------------------------------------------------------------------------------
Limitations
---------------------------------------------------------------------------------------
• Recently approved CDx/Rx pairs\
• Small amount of robust, publically available data\
• Young market has a large number of variations\
∘ Different entrance points for CDx (co-developed, individually adopted)\
∘ Different classification as tests (FDA approved vs. LDT)\
• Wide range of pricing for CDx\
• Different endpoints for efficacy measures of therapeutics in different indications\
• Rapidly changing regulatory and policy landscape\
• Quickly developing technological advances
---------------------------------------------------------------------------------------
Select limitations are detailed in limitations section.
Other diagnostics (Vectibix, Ziagen, Selzentry, Kalydeco) were classified as laboratory-developed tests (LDTs) at their conception and received FDA approval after drug approval, or were adopted into clinical practice without FDA review ([@B29]; [@B26]). Given that LDTs undergo a less rigorous clinical review through the Clinical Laboratory Improvement Amendment (CLIA) regulatory pathway, they may have lower cost requirements, leading to acute cost differences ([@B32]).
There are also two factors, CDx price and drug efficacy, with notable caveats and limitations. The factor 'CDx price' has many contributing sources. There are multiple types of price determinant for companion diagnostics, with a wide range of pricing (**Figure [6](#F6){ref-type="fig"}**). The lower boundary of the pricing range is attributed to Medicare National Limitation Amounts published in the 2014 Clinical Laboratory Fee Schedule ([@B34]) while the upper boundary is generally attributable to company list prices and hospital billings for outpatient, non-insured individuals. Price variation also stems from the segmented nature of Medicare reimbursement; while Medicare is a major payer of high-risk, high-benefit therapies, reimbursement differs depending on region and individual contracts.
Further fragmentation occurs on a providers level with various hospitals stacking CPT codes in a multitude of ways ([@B19]). Other forms of price determination within the ranges in **Figure [6](#F6){ref-type="fig"}** include private insurance, hospital billings, and quotes from individual diagnostic companies. Private insurance often takes example from Medicare limits, and each has individual coverage policies that conditionally cover treatments based on specific situations. Hospitals have opaque pricing policies and differ within regions. Companies typically sell in bulk, rendering prices for individual companion diagnostic tests difficult to determine.
Due to these limitations, no one measure of price is appropriate to represent the complexities in CDx price. Therefore, for the purposes of this analysis, the price of the CDx is defined as the price most associated with the specific companion diagnostic in published, pre-existing literature, and is usually obtained as a measure of the cost of testing equipment and compensation for labor and interpretation.
Therapeutic 'efficacy' is defined in the context of medical interventions as "the performance of an intervention under ideal and controlled circumstances" ([@B42]). Requirements for an efficacy trial include obtaining a readily available form of the drug, recommending the drug to the identified target population, and adhering to the drug prescription. The selected personalized therapeutics in **Table [1](#T1){ref-type="table"}** address different indications and have different endpoints -- oncology generally has endpoints of tumor reduction or disease free progression, cystic fibrosis has an endpoint of FEV (forced expiratory volume), and HIV has endpoints of response rate or percentage of HIV infected RNA. It is hard to find equivalent measures of endpoints and clinical utility across different indications due to the varied nature of disease and mechanisms of action of therapeutics. Despite the different measures of clinical endpoints, the clinical trials for the personalized therapeutics meets the requirements for efficacy trials with equal access, targeted populations, and high adherence rates. Therefore, data for drug efficacy was appropriated from published clinical trial information on patents, labels, and official FDA recommendations.
Additionally, unclear standards for clinical utility, rapid advances in technology, uncertainty in relative efficiency and cost-effectiveness of CDx, and differences inherent to different indications create a variegated landscape for companion diagnostics ([@B43]; [@B21]; [@B12]; [@B33]).Given the rapidly evolving regulations involved in the development of companion diagnostics and the number of contracts, investments, and new therapeutics in the drug development pipeline, this assessment should be considered a snapshot of a quickly evolving system. There are many complexities in the technological development and adoption of companion diagnostics, and further research will be needed as the landscape evolves.
Conclusion
==========
The market for companion diagnostic development and adoption is complex and difficult to navigate. Where there is regulatory pressure to co-develop companion diagnostics for the approval of personalized therapeutics, there is a lack of parallel economic collaboration to develop companion diagnostics. Factors that pertain to the therapeutics market, such as market size and response rate do not drive the CDx market. The discrepancy between the factors for the therapeutic/treatment and the factors for companion diagnostics despite similar regulatory standards, along with an uncertain reimbursement structure and limited opportunities for early stage competition shows that there is a misalignment in economic incentives that could potentially discourage the development companion diagnostics, for unspecified therapeutics. Further research will be needed as the landscape for companion diagnostics evolves.
Author Contributions
====================
All authors were responsible for conception and design of the experiment, revised the work critically for important intellectual content, approved the final manuscript and agree to be accountable for all aspects of the work. DL and JS collected and analyzed the data and wrote the manuscript.
Conflict of Interest Statement
==============================
The content outlined herein represents the individual opinions of the authors and may not necessarily represent the viewpoints of their employers. David A. Brindley is a stockholder in Translation Ventures Ltd. (Charlbury, Oxfordshire, UK) and IP Asset Ventures Ltd. (Oxford, Oxfordshire, UK), companies that, amongst other services, provide cell therapy biomanufacturing, regulatory and financial advice to pharmaceutical clients. James A. Smith is a consultant of IP Asset Ventures Ltd. David A. Brindley is subject to the CFA Institute's Codes, Standards and Guidelines, and as such, must stress that this chapter is provided for academic interest only and must not be construed in any way as an investment recommendation. Additionally, at time of publication, David A. Brindley and the organizations with which he is affiliated, may or may not have agreed and/or pending funding commitments from the organizations named herein.
We wish to express our sincere thanks to the following organizations that have contributed to the CASMI Translational Stem Cell Consortium (CTSCC) as funding and events partners, without whom the consortium and the benefits it will bring to stem cell translation would be constrained: GE Healthcare, CCRM, Sartorius Stedim Biotech (formerly TAP Biosystems), Lonza, CIRM, SENS Research Foundation, UK Cell Therapy Catapult, NIH Centre for Regenerative Medicine, NYSCF, ThermoFisher Scientific, Eisai, Medipost (US), Medipost (Korea), Celgene, Roche, and Oxford Biomedica. DB gratefully acknowledges personal funding from the Oxford Musculoskeletal NIHR BRU, the Said Foundation and the SENS Research Foundation. DL and JS gratefully acknowledges support from the SENS Research Foundation and CASMI Translational Stem Cell Consortium (CTSCC). JS gratefully ackknowledges the support of the UK Medical Research Council and Prof Andrew Carr (University of Oxford).
[^1]: Edited by: *Alex Zhavoronkov, The Biogerontology Research Foundation, USA*
[^2]: Reviewed by: *Barbara Prainsack, King's College London, UK; Pamela Pinzani, University of Florence, Italy*
[^3]: ^†^Present address: *David A. Brindley, Department of Paediatrics, Oxford University Level 2, Children's Hospital, John Radcliffe Headington, Oxford, OX3 9DU, England*
[^4]: ^‡^*Joint Senior Authors*
[^5]: This article was submitted to Genetics of Aging, a section of the journal Frontiers in Genetics
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1930–31 Chicago Black Hawks season
The 1930–31 Chicago Black Hawks season was the team's fifth season in the NHL, and they were coming off a surprising season, in which they finished over .500 for the first time in team history, and making the playoffs after a two-year absence. The Hawks would go on to lose to the Montreal Canadiens in the first round. Prior to the season, Chicago would name former team captain and player-coach Dick Irvin as the head coach. The team responded with a club record 24 wins and 51 points, and finished in second place in the American Division, and make the playoffs for the 2nd straight season.
Regular season
Chicago was led offensively once again by Johnny Gottselig, who scored a club high 20 goals and 32 points, and by Tom Cook, who was the team leader in assists with 14, and finished 2nd in team scoring with 29 points. Frank Ingram would have a big season, scoring a career high 17 goals.
In goal, Chuck Gardiner would play in every game, and he would break the Hawks record for wins (24), shutouts (12) and GAA (1.73). The Hawks finished with the 2nd fewest goals against in the league.
Season standings
Record vs. opponents
Schedule and results
Playoffs
The Hawks would open the playoffs in a two-game total-goals series against the Toronto Maple Leafs, and for the first time in team history, the Black Hawks won the series by a score of 4–3. Next up was a two-game total-goals series against the New York Rangers, and Chuck Gardiner would shine by shutting New York out in both games, as the Hawks won the series by a 3–0 score and earn a berth in the Stanley Cup Finals against the Montreal Canadiens. The Hawks would lose the first game of the best-of-five series, but then would win two in a row in overtime to take a 2–1 series lead. Montreal would respond with a 4–2 victory in game four, and then the Canadiens would put away the Black Hawks with a 2–0 win in the fifth and deciding game, ending the Black Hawks dream of winning the championship one win short.
Chicago Black Hawks 3, Toronto Maple Leafs 2
Chicago Black Hawks 3, New York Rangers 0
Montreal Canadiens 3, Chicago Black Hawks 2
Player statistics
Scoring leaders
Goaltending
Playoff stats
Scoring leaders
Goaltending
References
SHRP Sports
The Internet Hockey Database
National Hockey League Guide & Record Book 2007
Category:Chicago Blackhawks seasons
Chicago
Chicago
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[Tuberculosis in 0-14 year-olds in Cuba (1994-2003)].
Tuberculosis in infants and children is a sign of continuous transmission. The present article describes the distribution and the trend in incidence rates of new tuberculosis cases in 0-15-year-olds in Cuba. Incidence rates and their trend were estimated by provinces and age groups for the 1994-2003 period. Distribution and overall variation percentages, annual average rates, and rates and percentages according to classification were determined. The incidence rate decreased from 0.76 x 10(5) in 1994 to 0.31 in 2003 (59.2% of the overall reduction and 6.6% of the annual average reduction). The highest rate (1.06 x 10(5)) was found in 1995 (26 cases). In almost all provinces, the incidence trend decreased, except in the City of Havana, Sancti Spíritus, Santiago de Cuba, and the Isle of Youth. Childhood tuberculosis was mainly pulmonary (69.6%). Among the affected population, the highest percentages were found in the groups aged 10-14 years (35.6%) and 1-4 years (35.2%). Tuberculosis is infrequent and is extremely uncommon in infants. Notification is low throughout the country and the overall trend shows a steady decrease.
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Tags:
In 2015, the Mental Health Act Code of Practice called on mental health services to reduce restrictive interventions. These practices include the use of restraint, seclusion and rapid tranquilisation. They also include wider practices: for example, preventing a patient from accessing outdoor space.
State of care in mental health services 2014-2017 found that there is variation in the way staff are using restrictive practices when responding to challenging behaviour. The report highlighted concerns that care for some patients is overly restrictive.
As a result the CQC identified 5 NHS mental health trusts where we've seen effective ways of reducing the use of restrictive practices. We asked the trusts about the work they were doing, and what was working well for their staff and the people who use their services.
The resource shares examples of good practice on the following topics:
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