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After a troublesome 2018, the cryptocurrency market is expected to mature in 2019. It is the hope of many that 2019 will see cryptocurrencies establish within the financial markets. For any cryptocurrency investor, the focus should be on digital assets that are future centered.
At the moment, the crypto market has not yet recovered even though we have some projects ongoing. The industry is witnessing the emergence of many ICOs, scammy projects, volatility, and failure of many cryptocurrency startups.
Despite these shortcomings, we’ve put up a list with 10 cryptocurrencies under $10 that might be profitable in 2019 and even after. You should note that this article is not investment advice – its just a list of promising cryptocurrencies based on the unbiased opinion of our writers. Please do your own research if you’d like to invest in these cryptocurrencies.
Most Promising Cryptocurrencies for 2019 & 2020
Ripple (XRP)
Ripple’s XRP is among the most promising cryptocurrencies of 2019. In terms of market capitalization, XRP is the third after Bitcoin and Etherehum. For starters, developers of XRP intended to use the platform to conduct cross border transactions between individuals and bank instantly at reduced costs.
Despite a turbulent 2018, Ripple towered in the crypto market by entering strategic partnerships with leading global financial institutions like banks. This development spurred the mass adoption of the XRP. Ripple has a bright future based on its plan to shun away from ICOs. Without ICOs, Ripple is free from strict regulations by the SEC. At the moment, Ripple has a value of $0.243 and we believe that until the end of 2020 Ripple has the potential to reach $0.4-$0.5 easily.
TRON (TRX)
In 2018, Tron managed to survive the volatile cryptocurrency market. One of the factors that led to Tron’s excellent performance was the foundation’s move to enter different partnerships. Additionally, Tron achieved some development milestones last year. Tron is a decentralized marketplace that allows individuals to host, store, consume and share content based on their terms. The platform has no role for third parties. Developers seek to revolutionise the internet.
Acquisition of BitTorrent and launch of Project Atlas are the latest development at Tron. At the moment, Tron is ahead of other cryptocurrencies in terms of processing power and speed. The Tron platform can run more than 2,000 payments within a second – at least they claim so . The TRX token has a value of $0.0153 at the time or writing. A decent price for 2019&2020 that we feel confident about is a $0.07- $0.09 if the market conditions are favourable. This Tron price prediction is based mostly on the past evolution, the important news of 2019 and how their ecosystem is growing daily. Tron is among the most promising cryptocurrencies, mostly because of its team & partnerships – there are other cryptocurrencies with a better technology though.
Cardano (ADA)
Among all blockchain projects, Cardano is the only platform that is guided by academic research alongside a scientific philosophy. The system allows development of dApps and deployment of smart contracts. This is an advantage compared to peers. With Cardano, smart contracts are initiated on differences places when payments take place.
This feature is not available among other peers. This capability elevates Cardano to the list of best cryptos of 2019. By the time of writing, Cardano’s ADA token was retailing at $0.038. We believe that 2019 will be a good year for Cardano, especially with their future roadmap. Even though Cardano was at one moment worth $1, we think the price there was a bit overvalued. A more possible price for 2019 or 2020for Cardano would be a $0.09 – $0.15. Again, this Cardano price prediction depends on the market evolution.
Cardano is anothing promising cryptocurrency created by the co-founder of Ethereum, Charles Hoskinson. His vision alongside with the experience gathered while working at ethereum makes Cardano one of the most promising crypto of the future years to come.
IOTA (MIOTA)
Its popularity is based on the Internet of Things phenomenon. IOTA is also a unique crypto project that uses “The Tangle” instead of the normal blockchain. Developers of IOTA put in place systems that will execute faster payments on the level of machine-to-machine.
This model is enough for IOTA to be one of the most promising cryptocurrencies in 2019 and above. The MIOTA token current value stands at $0.22884. One factor that needs to be taken into consideration when we’re talking about the IOTA’s future is the fact that the tangle is already tested in partnership with Bosch. If the results there could be good, we can expect a IOTA price above $1 for 2020.
Also, IOTA still have a big road ahead of it. They need to gain more partners and more usage for the cryptocurrency before regaining their top 10 place.Right now, IOTA is a promising cryptocurrency but it might still fail if the team doesn’t prove their value – as any other cryptocurrency. We though IOTA deserved a place on our most promising cryptocurrencies list as the project has a different approach to solving IoT problems.
Binance Coin (BNB)
Binance is among the most successful cryptocurrency trading platforms despite joining the market in mid-2017. Apart from providing a trading platform, Binance also released its token dubbed BNB. By the time of writing, Binance Coin sits on the #8 spot with a value of $16.78.
BNB has a fixed supply, an indicator that the token demand is set to skyrocket as Binance trading platform grows. Most of the Binance coins will be burned by the team in the future so
Binance Coin (BNB) can easily reach a $20 value this year ( again ), especially with their launchpad launching more IEOs and accepting only BNB there.Even if there won’t be any more IEOs – Binance already created an ecosystem of usage for their cryptocurrency. Therefore, we believe BNB is one of the most promising cryptocurrencies for 2020 and above.
Basic Attention Token (BAT)
BAT came into existence alongside the Brave browser. The browser works on the Chromium system, and it aims to enhance the privacy and security of users online. It protects users from harmful malware and blocks ads by default. The Brave browser is gaining popularity due to its business model. With more users, BAT is expected to increase in demand, making it useful crypto to invest in.
The token is ranked 29th on CoinMarketCap and is valued at $0.219. The price of BAT depends 90% of the evolution of Brave Browser. Therefore, more users using it could probably increase in value. For the moment, we think the BAT Token will have a price of $0.40 maximum in 2019 and it can go above $0.60 in 202. BAT remains one of the most promising cryptocurrencies mostly for its amazing use case as the fuel for Brave Browser.
NEO (NEO)
Developers of NEO want to make it an alternative for the transfer of non-digital assets. In 2018, the crypto project made headlines due to its business approach. It strikes some similarities with Ethereum, but it differs with other systems due to some aspects.
The NEO token is not divisible, it uses a two-tier payment system, and it also uses smart contracts. Crypto experts predict NEO to have a significant effect in the market in 2019. The token value stands at $10.86 at the moment of writing. Many people are expecting the psychological price of $20 or over it.
The NEO Price Prediction that we have in mind depends on many factors. But most importantly – if they will gain more partners or strike a few huge partnerships. We believe that NEO could reach a $25 price in 2020- but not regain its glory from where it was $100.However, NEO remains one of the promising cryptocurrencies for 2019 and above.
0X (ZRX)
0X is an open protocol that permits trading of ERC-20 tokens directly on the Ethereum system. The 0X protocol is also used to build many decentralized exchanges that mushroomed in 2018. Decentralized exchanges are vital due to the volatile crypto market alongside privacy concerns.
0X is showing its seriousness in the market by achieving essential milestones. This reason makes 0X token a key competitor in the best crypto for 2019. The token value stands at $0.249. The 0x cryptocurrency was pretty quite in 2018 – with their most important news about them being the Coinbase listing. The news spiked the cryptocurrency to ~$1. ZRX token could easily regain that price in 2019 if the market conditions are favorable. Otherwise, we believe it will stand a long period between $0.2 – $0.7.Even like this, its a promising cryptocurrency with probably a great future ahead – if the team will continue to do the same great work.
VeChain (VET)
The VeChain Foundation created VeChain Thor on the Ethereum smart contract to service enterprise customers. For beginners, VeChain Tho is a blockchain-as-a-service and a double token.
Developers focus on availing Internet of Things solutions.VeChain Thor uses two crypto tokens: VET and VTHO. VET is VeChain Thor’s native cryptocurrency while VTHO is meant to pay for tokenized transactions.
VeChain is a platform to consider because it is a secure, enterprise-grade blockchain that services the entire supply chain on both ends. Plus, VeChain have a model that should work pretty well in the society that we live in. A society that now cares more than before what products are they ordering, who made them,etc. VET’s value is only $0.0057 due to the high number of circulating supply. With more partners and a higher adoption, VET could reach a price of $0.02 – $0.05 until the end of 2020.
Litecoin (LTC)
Bitcoin’s little brother, Litecoin, is another promising cryptocurrency that might surge in the future years. In 2019, Litecoin grew from the minimum value of ~$30 to $134 in June. The pump was a reaction to the long expected Litecoin block halving – which took place in August 2019. Since the top value of $134 – Litecoin decreased to $50.
Even though Litecoin’s currently at a low value and its pump for 2019 already settled, we believe that Litecoin have a good future ahead. On 18th November 2019, Litecoin daily transactions spiked breaking new yearly highs. This is proving that Litecoin’s on the right track to gain a place in the top 5 cryptocurrencies – where it belong. More over, the team are working on Litecoin Core 0.18.1 which is improving day by day.
We don’t really know where is Litecoin going to be in the future, but the fact that the team is working on the updates regularly and the community is growing day by day is a good sign. For 2020, a good litecoin price prediction would be a $80-$90. If you’re interested in purchasing litecoin, you can chose from the best litecoin wallets that we’ve tested.
Conclusion
After a disappointing 2018, many expect the cryptocurrency market to bounce back in 2019. It is worth noting that cryptocurrencies come with unique risks that you should pay attention to before any investment. Despite the token you choose, always know it is risky and spending some time to research will give you value for your money.
Image Source: lhe.io |
Q:
Titanium Studio app crashes while swiping the tabs?
I am developing android app using Titanium Studio 3.2.1, I have tabs to change the screens while I am moving one tab to other tab I am getting below error,
**[ERROR] : SpannableStringBuilder: SPAN_EXCLUSIVE_EXCLUSIVE spans cannot have a zero length**
what is this mean? why I am getting this?
and my issue is I able to move tabs one time only, again I am trying to return to the tabs app getting crash.
will any one please suggest me out to out of this issue?
I gone thorough this link but I am didn't understand what I have to do, I am new to titanium?
http://smorgasbork.com/component/content/article/38-titanium-mobile/140-titanium-mobile-dynamic-tabgroups-on-android
Thanks in Advance.
A:
I did this, I run my app using Titanium SDK as 3.1.3 in MAC OS, it is running fine without crashing.
but still have some doubts in titanium studio.
Why not in Titanium SDK : 3.2.1 ?
Why not in Windows OS.?
Any ways my answer will helps for someone
Thanks
|
Friday 17 September 2010
Russell, Caxton Hall Press Conf., July 9 1955 - Associated Press, 1955An account of the 1955 Manifesto by Bertrand Russell and Albert Einstein, which was crucial in shaping public opinion against nuclear war.
Today there is universal public knowledge about the dreadful effects of nuclear war; but it wasn't always this way. The philosopher Bertrand Russell and the physicist Albert Einstein were two leading figures in the creation of public understanding of, and opposition to, nuclear war. The last public act of Einstein's life was to sign a world-changing manifesto against nuclear war.
Nuclear Weapons: Cold War SecrecyIn the years following World War 2, the USA and the USSR raced to develop ever more powerful nuclear weapons. The development was carried out in secret and covered by disinformation. Scientists working outside the military were able to deduce what was being developed (see Joseph Rotblat's "detective work" on the Bikini Atoll H-bomb test), but to speak out was professionally dangerous: in the US it could lead to blacklisting as a Communist, and in the USSR it could lead to the gulag.
Under these circumstances, Bertrand Russell, then in his 80s, wrote (11 February 1955) to Einstein saying:
"In common with every other thinking person, I am profoundly disquieted by the armaments race in nuclear weapons. [...] I think that eminent men of science ought to do something dramatic to bring home to the public and governments the disasters that may occur. Do you think it would be possible to get, say, six men of the very highest scientific repute, headed by yourself, to make a very solemn statement about the imperative necessity of avoiding war?"
Einstein replied five days later: "I agree with every word in your letter of February 11. Something must be done in this matter, something that will make an impression on the general public as well as on political leaders."
The Manifesto Takes ShapeIn the following weeks Russell worked with Einstein to draw up a text. Einstein wrote to his colleagues to enlist their support (including to former scientific adversaries: one letter written by Einstein, on March 2, begins: "Dear Niels Bohr, Don't frown like that! This is not about our old physics controversy, but about a matter on which we are in complete agreement."
However, Einstein's health was failing. He wrote to Russell saying "It seems to me that, to avoid any confusion, you should regard yourself as the dictator of the enterprise and give orders." Einstein signs off: "Awaiting orders, I am, with warmest regards and in admiration."
Russell's last letter to Einstein was dated 5 April 1955. It contained a draft of the declaration and a list of proposed signatories. A few days later, Russell was flying from Rome to Paris for a conference on world government, when the pilot announced the news of Einstein's death. Russell wrote in his autobiography: "I felt shattered, not only for the obvious reasons, but because I saw my plan falling through without his support."
Einstein's Last Public ActOn arriving in his hotel room in Paris, Russell found a short letter waiting for him. It was dated April 11 and read:
Dear Bertrand Russell,
Thank you for your letter of April 5th.
I am gladly willing to sign your excellent statement.
I also agree with your choice of the prospective signers.
With kind regards,
Albert Einstein
The manifesto was released to the press on July 9, 1955. It calls not just for a reduction of nuclear weapons, but for humanity to find a way to avoid war in general, since "in any future world war nuclear weapons would certainly be used." It was signed by ten scientists of global renown; but it was Einstein, and his death, that gave it the greatest power. Russell described it as "the last public act of Einstein's life."
The Manifesto in RetrospectThe Russell-Einstein Manifesto marked a crucial moment in the development of public consciousness about nuclear war. The fame and authority of those who signed it outmatched the efforts of governments to suppress knowledge, and led to the "Pugwash" movement of scientists against nuclear weapons, as well as being a significant moment in the development of CND.
Further Reading
See the McMaster University archive on the Russell-Einstein Manifesto.
18th National Children’s Science Congress (NCSC) Guide teacher workshop on 16th July -2010.----------Vanakkam. National Children’s Science Congress - NCSC is conducted every year by National Council for Science and Technology Communication –NCSTC, Dept., of Science and Technology (DST) Govt. of India for the children in the age group of 10 to 17 years from all over the country. TamilNadu Science Forum – TNSF is the TamilNadu State coordinator of NCSC for the past 18 years.NCSC is conducted for students in the age group of 10 to 13 years (juniors) and 14 to 17years (seniors). Student groups comprising 3 to 5 students do research projects during their free time for 2-3 months on a topic related to the focal theme under the guidance of a Guide teacher. This year’s focal theme is “Land Resources: Use for prosperity; Save for posterity”.To enlighten the guide teachers on the focal theme, Tamil Nadu Science Forum, North Chennai District is organising a workshop for them. The Guide teacher workshop for NCSC 2010 will be held on 16th July 2010 from 9.30am to 5pm at, ICF Silver Jubilee matriculation higher Secondary School, (opp. ICF stadium, Kambar Arangam bus stop), ICF, Chennai - 38. We request you to send 2 or 3 teachers who have interest in guiding your students in doing NCSC projects, for this guide teacher workshop. Please inform the list of participants in advance to us. Thanking you.
Mr. DhanaSekar, NCSC Chennai (North) District Academic Coordinator Secretary, briefed the instructions for the judges. 25group of students projects were submitted enthusiastically by the Child Scientists in 3 halls.In the afternoon session “Meet the Scientist” program was held. Mr. A.Ravindran Former State Co-Ordinator, “Pasumai Niraintha Ulagathile” The Environment Awareness Radio Programme of Tamilnadu pollution Control Board have participated in the event. In the valedictory function, “Thappattam” cultural program by Child Scientists from Arunodhaya Children Federation was well received by audience. Prof. M.p. Jaganatha Bose, Professor, Zoological Dept, Sir Thiyagaraya College,Chennai, Prof Madhivanan ,Professor, Zoological Dept, Nandanam Govt College, Chennai,TNSF Dist EC member ,Mr. Balu.Thandapani Dist Revenue Officer (redt), A.Ravindran, Environmentist, Mr.Udayan NCSC State Task Force Member felicitated the Child Scientists. 4 Projects from Chennai North were selected for State level NCSC to be held at pudhukottai from november 27 to 29, 2009. Mrs.Prema and Mrs.Arivukkarasi have sung Science songs. Mr. Chandra Sekar , Dist Execute member proposed Vote of thanks.This one day NCSC District Congress was elaborately organized by Mrs. Themozhi Selvi NCSC Chennai (North) District Coordinator , Mr. DhanaSekar, NCSC Mr. Semmal, Chennai North District President of TNSF, Mr. Arun, Chennai North Chennai North District Secretary of TNSF.
Sunday 11 October 2009
Think Diwali, and the first thing that comes to your mind are firecrackers. There’s been growing alarm at the long term ill effects of the fireworks on the environment, apart from the noise pollution and the streets littered with paper and the contaminated air that we breathe. What steps can we take to ensure that this Diwali and subsequent Diwalis are eco-friendly and safe?
WE CAN HAVE A CRACKERS SHOW FOR 2 HOURS IN A COMMON PLACE WHERE PEOPLE CAN SEE AND ENJOY THE CRACKERS, INSTEAD OF EACH DOING AT THEIR HOME IN A SMALL WAY AND MAKING THE WHOLE CITY DUSTY WITH PAPER
IF IN A COMMON PLACE
(1)THE SOUND WILL BE ONLY FOR A PARTICULAR TIME
(2) THE PAPER DUST WILL BE ONLY IN ONE PLACE
(3) THE COST OF DIVALI CELEBRATIONS CAN BE REDUCED
(4) NO NEIGHBOURS ENVY
(5) ONLY A LITTLE OF AIR AND SOUND POLLUTION
(6) CAN BE HAD IN A PLACE FAR FROM HOSPITALS
(7) SAFE MEASURES CAN BE ENSURED IN THAT PLACE
(8) MONITERING OF THE SAFETY OF THE PEOPLE IS EASY
(9) ENJOYMENT CAN BE SHARED BY ALL AT THE SAME PLACE
(10) A GET-TOGETHER IS EASY
Friday 9 October 2009
About Me
Tamil Nadu Science Forum (TNSF) is a People’s Science movement, promoting Literacy, Gender Equality, Scientific Awareness, World Peace, etc for Better and Progressive India and Tamil Nadu. It was started in 1980 as a Forum for scientists with the Motto ‘Science for People, Science for Nation, Science for Self- reliance’. Now, it has grown into a people’s movement and has a membership of 12000 including scientists, Farmers, Teachers, students and Women - people from almost every walk of life. We got National and State Govt. awards for Science Popularization & Promotion of Environmental Awareness. |
Posttransurethral prostatic resection hyponatremic syndrome: case report and review of the literature.
Hyponatremia is a potentially life-threatening complication of transurethral prostatic (TURP) resection. The post-TURP syndrome, although well-recognized by urologists, is not discussed in recent clinical reviews on hyponatremia. We present a case report and review of the literature of this striking clinical syndrome. |
An Exploration of Myths, Barriers, and Strategies for Improving Diversity Among STS Members.
Diversity within health care organizations has many proven benefits, yet women and other groups remain underrepresented in cardiothoracic surgery. We sought to explore responses from a Society of Thoracic Surgeons (STS) survey to identify myths and barriers for informing organizational strategies in the STS and cardiothoracic surgery. We performed a qualitative review of narrative survey responses within three domains surrounding diversity in cardiothoracic surgery: myths, barriers, and strategies for improvement. Common diversity myths included diversity as a pipeline problem (24%), diversity equated to exclusivity (21%), and diversity not supporting meritocracy (18%). The most frequent barrier code was perceived prejudice (22%). Suggested strategies toward improvement were culture change prioritizing diversity (22%) and training the leaders (14%). Notably, 15% of response codes reflected the belief that disparities do not exist; thus, the issue should not be prioritized by the organization. The results do not necessarily reflect the beliefs of most of the STS membership; nonetheless, they provide important insight critical to guide any efforts toward eliminating disparities within cardiothoracic surgery and improving the care of our patients. |
Amy Traub
Melding the Middle
“What will happen if we do it right,” Senator Chuck Schumer informed journalist and Atlantic Monthly editor Joshua Green, “is that there’ll be an alliance between the middle class and the poor, as opposed to the alliance between the middle class and the rich [that held for the past 28 years]. Everything we’re talking about is the work of an active, strong government, and if it works, it will wed the middle class to the Democrats for a generation.”
Schumer’s partisan political analysis is spot on: whichever party speaks most convincingly to the American middle class wins elections. And his sense that the nation’s middle class and the poor – those striving to attain a middle-class standard of living – share common interests is a point the Drum Major Institute has argued for years. But Schumer’s policy prescriptions (mostly an array of tax cuts and credits) don’t quite add up to the type of epochal class alliance he describes. The problem may lie with how the Senator defines the middle class – and in turn, contributes to a political dialogue that impacts how middle-class Americans understand their own political interests.
While the nation’s median household income is $48,000 a year, the figure is significantly higher when the elderly, young workers and recent college grads are excluded. So, according to Schumer and his advisors at the inside-the-beltway think tank Third Way, the middle class really lives in the range of $60,000 to $100,000 a year. Policies like Pell Grants, the Earned Income Tax Credit, and an increased minimum wage mean very little to this group. Instead, according to Schumer, middle-class families need an array of tax cuts: from buying a first home to affording college. “A lot of the things he’s calling for are not really radical,” insists Third Way’s Jim Kessler.
But neither are they the stuff of an alliance – electoral or otherwise – between the poor and middle class.
The problem may lie with those pesky income statistics. Simply equating “middle class” with “middle income” says little about the ways middle-class Americans actually live. The Third Way’s canonical $60,000 to $100,000 a year family may find their middle-class status precarious if they are struggling with heavy medical debts because they cannot secure health coverage for a chronically ill child. And what they – like their low-income counterparts coping with the same problem – need is more than a tax cut.
To consider policies that really unite the middle class with low-income families, it makes sense to consider their common aspirations. At its core, a middle-class standard of living means secure jobs that support a family; a safe and stable home; access to affordable health care; retirement security; time off for vacation, illness, and major life events; opportunities to save and avoid crippling debt; and the ability to provide a good education, including a college education, for one’s children. Middle-class households – increasingly squeezed by rising costs and stagnating wages even before the current economic downturn – aim to hold onto these staples while low-income households aim to attain them. And many of the same policies can do both – both strengthening the existing middle class and expanding it to include more working Americans.
Consider proposals to increase federal investment in voluntary preschool programs available to all youngsters. High quality preschool education has repeatedly been shown to benefit children’s language and cognitive skills. One study suggests that, over time, the benefits of investment in early childhood education may be as high as $12.90 for every dollar invested (others have found a lower, but still substantial payoff). Indeed, investing in preschool may be one of the most cost-effective ways to help children from low-income households get the beginning they need to succeed academically and attain a middle-class standard of living themselves as adults. But while preschool’s benefits are most pronounced for children from low-income households, many middle-class families also choose to send their 3- and 4-year-olds to private preschools. And they pay dearly for it. One recent report found that middle-income families may pay as much as 30% of their income for early education. These households would welcome the option of a free or low-cost public alternative of sufficiently high quality. Federal support for universal preschool programs is the type of policy with the potential to genuinely bring together both the current and aspiring middle class.
Thinking about the poor and middle class in terms of their common aspirations – rather than income categories that divide them – is the key to forming an enduring policy alliance between those who want to stay middle class during tough economic times and those still striving to join their ranks. At his best, such as when he aims to regulate a reckless mortgage lending industry that has devastated both low-income families striving for homeownership and their middle-class counterparts, Schumer seems to recognize this. His hoped-for alliance might be all the more enduring if he considered it explicitly.
All comments, ideas and thoughts on DMI Blog are property of their authors. Reasonable excerpts are permitted on other sites and blogs; otherwise reproduction without the author's permission is strictly prohibited. View our comment policy here.
All opinions expressed on the DMI Blog website are solely those of their authors, and do not necessarily reflect those of the Drum Major Institute for Public Policy. |
508 S.E.2d 347 (1998)
28 Va. App. 688
Elsie Naomi Boyd (McKinney) HORN
v.
Clyde J. HORN.
Record No. 2654-97-3.
Court of Appeals of Virginia, Salem.
December 22, 1998.
*348 Susan E.F. Henderson (Henderson & Fuda, on brief), Bluefield, for appellant.
Robert M. Galumbeck (Dudley, Galumbeck & Simmons, on brief), Bluefield, for appellee.
Present: FITZPATRICK, C.J., and COLEMAN and ELDER, JJ.
FITZPATRICK, Chief Judge.
Elsie Naomi Boyd (McKinney) Horn (wife) appeals the trial court's divorce and equitable distribution decree. Because this order is interlocutory in nature and thus not appealable, we dismiss the appeal.[1]
I.
In its decree entered October 9, 1997, the trial court granted the parties a divorce. On *349 the issue of the equitable distribution of the parties' business property, the court found as follows:
Dana Coal Company, Inc., although the stock in same was solely owned by [wife] at the time of the marriage of the parties, and remains solely owned by [wife] at this time, has been transmuted into marital property by the investment of marital funds, marital property and the personal efforts of the parties in the said company during the marriage. The Court finds that there remains no identifiable portion of the asset which may continue to be classified as separate property, as a result of the investment of marital funds, marital property and the personal efforts of the parties in the operation of the business since the marriage of the parties.
Accordingly, the trial court classified Dana Coal and the remaining businesses as marital property subject to equitable distribution and set the valuation date of the marital estate as the time of the parties' separation.
Although the trial court granted the divorce and determined the classification of property owned by the parties, it retained jurisdiction to value and distribute the various property.[2] The court found that:
[a]dditional evidence must be taken with regard to the value of the marital estate; and, further, this Court finds that matters currently pending before the United States Bankruptcy Court for the Western District of Virginia, Abingdon Division, may affect the valuation of, individual ownership and distribution of such property, specifically as same relates to McHorn Construction Company, Inc. and Dana Coal Company, Inc.; and, that as a result of same, and upon motion of [husband], further matters concerning the equitable distribution of the marital estate, including valuation thereof and the manner in which the distribution of the estate shall be made, must be continued upon the docket of this Court because such action is clearly necessary and the Court will, therefore, retain jurisdiction concerning same.
Accordingly, the court ordered that the equitable distribution, value and manner of distribution "shall be determined at a later date for the reasons previously set forth, herein." The matter was continued on the docket of the trial court. No final valuation of the property or monetary award was entered.
II.
This Court has appellate jurisdiction over final decrees of a circuit court in domestic relations matters arising under Titles 16.1 or 20, and any interlocutory decree or order involving the granting, dissolving, or denying of an injunction or "adjudicating the principles of a cause." Code § 17.1-405(3)(f) and (4), recodifying § 17-116.05(3)(f) and (4). A final decree is one "which disposes of the whole subject, gives all the relief that is contemplated, and leaves nothing to be done by the court." Erikson v. Erikson, 19 Va. App. 389, 390, 451 S.E.2d 711, 712 (1994) (quotations omitted).
In the instant case, the decree is far from final. Only the first step in the equitable distribution scheme has been completed. The parties' property has been classified but *350 has not been valued or divided and no monetary award has been made. The trial court specifically retained jurisdiction to consider further valuation and distribution of the marital property. The court acknowledged that the valuation of Dana Coal and McHorn Construction, two of the included assets, was dependent upon the outcome of a bankruptcy proceeding.
Unless the trial court's decree constituted an interlocutory decree that "adjudicates the principles of the cause," we do not have jurisdiction to consider an appeal of the equitable distribution of property.
An interlocutory decree adjudicates the principles of a cause where "`the rules or methods by which the rights of the parties are to be finally worked out have been so far determined that it is only necessary to apply those rules or methods to the facts of the case in order to ascertain the relative rights of the parties, with regard to the subject matter of the suit.'"
Moreno v. Moreno, 24 Va.App. 227, 231, 481 S.E.2d 482, 485 (1997) (quoting Pinkard v. Pinkard, 12 Va.App. 848, 851, 407 S.E.2d 339, 341 (1991) (quoting Lee v. Lee, 142 Va. 244, 252-53, 128 S.E. 524, 527 (1925))).
An interlocutory decree that adjudicates the principles of a cause is one which must "determine the rights of the parties" and "would of necessity affect the final order in the case." Erikson, 19 Va.App. at 391, 451 S.E.2d at 713. An interlocutory order that adjudicates the principles "must respond to the chief object of the suit," id., which, in an equitable distribution proceeding is to classify the property, value the marital estate, and distribute the estate accordingly. "[T]he mere possibility that an interlocutory decree may affect the final decision in the trial does not necessitate an immediate appeal." Id. (quotations omitted).
The trial court's decree, while classifying the marital property, did not value the property and did not actually determine the manner in which the distribution of marital assets would be accomplished. Although the court's ruling may affect the ultimate decision as to the distribution of Dana Coal and McHorn Construction, the valuation of this property also significantly affects the parties' property rights. See Webb v. Webb, 13 Va.App. 681, 682-83, 414 S.E.2d 612, 613 (1992) (dismissing an appeal because the parties' rights may still be determined through equitable distribution proceedings). We hold the decree is interlocutory and does not adjudicate the principles of the cause. Accordingly, we are without jurisdiction to entertain the appeal.
Dismissed.
NOTES
[1] On appeal, wife argues that the court erred: (1) in classifying a corporation solely owned by wife as marital property; (2) in finding that wife committed waste with regard to the parties' marital property; and (3) in setting the valuation date for the marital estate as of the time of separation. Because of the procedural posture of the case, we do not reach the merits of these claims.
[2] We initially note that the trial court did not retain jurisdiction pursuant to Code § 20-107.3(K), which grants a trial court continuing jurisdiction in various enumerated situations, none of which apply here. Code § 20-107.3(K) provides:
The court shall have the continuing authority and jurisdiction to make any additional orders necessary to effectuate and enforce any order entered pursuant to this section, including the authority to:
1. Order a date certain for transfer or division of any jointly owned property under subsection C or payment of any monetary award under subsection D;
2. Punish as contempt of court any willful failure of a party to comply with the provisions of any order made by the court under this section;
3. Appoint a special commissioner to transfer any property under subsection C where a party refuses to comply with the order of the court to transfer such property; and
4. Modify any order entered in a case filed on or after July 1, 1982, intended to affect or divide any pension, profit-sharing or deferred compensation plan or retirement benefits pursuant to the United States Internal Revenue Code or other applicable federal laws, only for the purpose of establishing or maintaining the order as a qualified domestic relations order or to revise or conform its terms so as to effectuate the expressed intent of the order.
|
[A new sustained-release formulation of trazodone for treatment of minor psychopathological depression. A controlled study].
In a controlled study the activity and tolerance of two formulations of trazodone (traditional and controlled-release) were compared in a group of 30 geriatric patients with minor anxious-depressive manifestations. The results showed a better activity with the controlled-release formulation (a single dose administered in the evening) on sleep disturbances as far as their effects on the psychopathological picture is concerned or on tolerance. |
Wwp2 targets SRG3, a scaffold protein of the SWI/SNF-like BAF complex, for ubiquitination and degradation.
SRG3 plays essential roles both in early mouse embryogenesis and in extra-embryonic vascular development. As one of the core components of the SWI/SNF-like BAF complex, SRG3 serves as the scaffold protein and its protein level controls the stability of the BAF complex, which controls diverse physiological processes through transcriptional regulation. However, little is known about how the protein level of SRG3 is regulated in mammalian cells. Previously, we identified a murine ubiquitin ligase (Wwp2) and demonstrated that it interacts with pluripotency-associated key transcription factor Oct4 and RNA polymerase II large subunit Rpb1, promoting their ubiquitination and degradation. Here, we report that Wwp2 acts as a ubiquitin ligase of SRG3. Our results show that Wwp2 and SRG3 form protein complexes and co-localize in the nucleus in mammalian cells. The interaction is mediated through the WW domain of Wwp2 and the PPPY motif of SRG3, respectively. Importantly, Wwp2 promotes ubiquitination and degradation of SRG3 through the ubiquitin-proteasome system. The expression of a catalytically inactive mutant of Wwp2 abolishes SRG3 ubiquitination. Collectively, our study opens up a new avenue to understand how the protein level of SRG3 is regulated in mammalian cells. |
Recognizing a problem that has long plagued Silicon Valley technology companies, on June 4, 2013, President Barack Obama issued executive actions and legislative recommendations "to protect innovators from frivolous litigation and ensure the highest-quality patents in our system." The announcement by the White House describes patent assertion entities (PAEs) as companies that, in the president's words, "don't actually produce anything themselves" and that instead "essentially leverage and hijack somebody else's idea and see if they can extort some money out of them." Notably, the announcement refers to these entities as "patent trolls" and refers to the operating companies accused of infringement as "innovators." While the announcement is sure to have a positive impact on the national dialogue regarding this problem and may spur legislative action, it will not have an immediate impact on patent-troll litigation.
The White House's initiatives generally are aimed at the following goals: improving patent quality, increasing transparency in the patent system, curbing the most egregious lawsuits, improving the processes at the International Trade Commission (ITC), and education and outreach. The announcement follows increased congressional activity introducing bills targeting PAEs and President Obama's comments regarding PAEs during a recent Fireside Hangout. The current state of affairs, proposed changes, and the likely impact of these initiatives are discussed below.
Executive Actions
Making "Real Party-in-Interest" the New Default: The United States Patent and Trademark Office (PTO) will put rules in place requiring patent applicants and owners to provide information regarding patent ownership when involved in PTO proceedings, including designation of the "ultimate parent entity" owning a patent. Today, PAEs often operate through shell companies that prevent defendants from knowing who the real parties-in-interest are and the extent of the patent portfolios they control. These shell companies are also sometimes used to avoid personal jurisdiction and to defeat declaratory judgment jurisdiction. Though it frequently is possible to determine who is behind a PAE through research, these new rules should result in greater transparency and hinder abusive PAE tactics, including repeat actions by the same patent owners.
Tightening Functional Claiming: The PTO will apply greater scrutiny to functional claiming and develop strategies to improve claim clarity. PAEs frequently have used patents with overly broad claims—particularly in the case of software patents—to allege infringement by wide swaths of products far afield from that to which the patent was intended to apply. These battles typically play out in costly claim construction proceedings more than a year into litigation. New rules limiting functional claims to actual disclosures in patent specifications and their equivalents could prevent over-claiming and, in the long term, address the patent thicket plaguing software innovation.
Empowering Downstream Users: The PTO will provide new educational materials. PAEs increasingly have targeted retailers, consumers, and end-users for doing nothing more than using off-the-shelf products in their intended manner in an effort to obtain multiple settlements in lieu of a single settlement with a product's manufacturer and to establish favorable licensing frameworks to use in future litigation. The PTO's outreach efforts may increase public knowledge regarding PAE activity, particularly for the most unsophisticated of targets, enabling them to better understand their options prior to acquiescing to a costly license.
Expanding Dedicated Outreach and Study: The PTO is announcing an expansion of its outreach efforts, including six months of high-profile events across the country to develop new ideas and consensus around updates to patent policies and laws. The PTO also is enlisting distinguished academic experts to develop more robust data and research on the issues bearing on abusive litigation.
Strengthening Enforcement Process of Exclusion Orders: An interagency review of Customs and Border Protection (CBP) and International Trade Commission (ITC) procedures for evaluating the scope of exclusion orders will take place to ensure that the process and standards for exclusion-order enforcement are transparent, effective, and efficient. ITC practitioners long have recognized the need for an improved process to make the ITC's unique remedy more effective once it has been issued. Today, if the ITC determines that a violation of the statute has occurred, it issues an exclusion order. But an ex parte proceeding before Customs or a lengthy ITC enforcement proceeding are the only options should questions regarding the scope and enforcement of that exclusion order arise once it is in force.
Legislative Recommendations
Requiring Patentees and Applicants to Disclose the "Real Party-in-Interest": In addition to the executive action discussed above, the White House recommends legislation that would require filing updated ownership information when sending demand letters, filing an infringement suit, or seeking PTO review, and proposes sanctions for noncompliance. The impact of this legislation would be similar to, but more robust than, that discussed above.
Permitting More Discretion in Awarding Fees to Prevailing Parties in Patent Cases: Proposed legislation would provide district courts with greater discretion to award attorneys' fees under 35 U.S.C. § 285 as a sanction for abusive court filings, similar to the legal standard that applies in copyright cases. Though the Federal Circuit recently has awarded sanctions for the maintenance of infringement litigation following claim construction that indicated no objective basis on which to proceed, the standard remains that attorneys' fees are awarded in only "exceptional" cases—that is, when a case has been found to involve subjective bad faith and be objectively baseless. The proposed legislation may help curb abusive litigation practices by PAEs. It is, however, unlikely to help innovators with limited resources, as in order to eventually recover fees, a litigant first must be able to litigate a case through judgment and prevail.
Expanding the USPTO's Transitional Program: The White House recommendations would expand the PTO's transitional program for covered business method (CBM) patents to include a broader category of computer-enabled patents and to permit a wider range of challengers to petition for review of issued patents. The recommendations would provide a mechanism for challenging a broader category of patents and would enable the PTO to weed out bad CBM patents even absent litigation in district courts.
Protecting Off-the-Shelf Use by Consumers and Businesses: The White House recommends legislation affording end-users better legal protection against liability for using an off-the-shelf product for its intended use. Such legislation would stay judicial proceedings against end-users when an infringement suit also has been brought against a vendor, retailer, or manufacturer. PAEs increasingly have targeted consumers and end-users. Although stays can be obtained under current law, the law has not been consistently applied. Such legislation should enable more efficient resolution of patent litigation and may better protect consumers and small businesses from abusive patent litigation.
Changing the ITC Standard for Obtaining an Injunction: Proposed legislation would subject the ITC to the four-factor test for injunctions set forth in eBay Inc. v. MercExchange, 547 U.S. 388 (2006). Though the ITC does take into account certain public interest factors, exclusion orders are not subject to the eBay test used for injunctions in district courts. Such legislation would make the standards applied at the ITC and district courts consistent and would curb potential abuse of the ITC and its unique remedy by PAEs.
Using Demand-Letter Transparency to Help Curb Abusive Suits: This proposed legislation would incentivize public filing of demand letters in a way that makes them accessible and searchable by the public. There is currently no easily accessible, searchable repository of demand letters, and PAE activities are often secret. The White House's recommendation should provide more transparency and greater information about PAE activities, allowing for coordinated defense and attacks on the validity of suspect patents earlier in the process.
Ensuring the ITC Has Adequate Flexibility in Hiring Qualified Administrative Law Judges (ALJs): Proposed legislation would give the ITC flexibility in hiring ALJs. The ITC thus far has been constrained by the Administrative Procedures Act. New legislation may enable the ITC to hire qualified ALJs more easily to fulfill increased demand for Section 337 investigations.
For more information on patent litigation or related matters, please contact Stefani Shanberg, James Yoon, or another member of Wilson Sonsini Goodrich & Rosati's intellectual property litigation and counseling practice.
DISCLAIMER: Because of the generality of this update, the information provided herein may not be applicable in all situations and should not be acted upon without specific legal advice based on particular situations.
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Generally, it is old to provide a sidepocket mandrel for use in a well tubing which has an orienting sleeve for aligning a kickover tool for inserting or removing flow control devices from the sidepocket of the mandrel in which a deflector guide is positioned in the mandrel above the pocket and in which the pocket and guide are positioned internally of the mandrel body as best seen in U.S. Pat. No. 4,106,563. It is desirable that the guide rails of the deflector guide be positioned, as shown in FIG. 2 of that patent, in mating coaction with the inside walls of the body. However, the desired flush fitting of the side rails against the inside of the mandrel body is frequently not obtained and gaps occur between the sides of the rails and the mandrel body into which a wireline on which well tools are moved through the well bore may catch. Obviously, this is undesirable and defeats one of the purposes of the deflector guide which is to prevent objects from becoming caught in sidepocket mandrels. The present invention is directed to an improved sidepocket mandrel and method of manufacture which reduces the problems found in the prior art devices. |
Fatty acyl CoA esters as regulators of cell metabolism.
Long chain fatty acyl CoA esters have the ability to interact with certain proteins and thereby serve as effectors in cell metabolism. In particular, they can displace nucleotides from specific nucleotide dependent or binding proteins and interfere with their action. The ADP/ATP carrier and uncoupling protein are two examples where the interplay of nucleotide and acyl CoA binding to the proteins regulate their function. Other proteins such as glucokinase can be considered in this group. In certain tissues like liver they are affected during fasting and insulin deficiency, and when serum fatty acids and liver acyl CoA levels are elevated. More recently, an acyl CoA binding protein in E. coli has been found to be a transcription factor for gene regulation of fatty acid metabolism enzymes. There appears to be some consensus in the amino acid sequence for acyl CoA binding sites on these proteins which serve a variety of important roles in cellular metabolism. |
Development of method of semantic description of works of projects and selection of suitable performers
In article presented the definition of semantic description and management and describes the language of formal problem statements and requirements that are on them. The elements of the semantic description of knowledge on the prepared project. The method of choice with the artists are required to perform design work skills.
Keywords:
qualifications of personnel, elements semantic description of works of project, description is property of objects of concepts, function of choice of precedents, degree of closeness, choice of performers |
namespace kri.sound
import OpenTK.Audio.OpenAL
public class Source:
public final handle as uint
public node as kri.Node = null
public def constructor():
handle = AL.GenSource()
def destructor():
kri.Help.safeKill({ AL.DeleteSource(handle) })
public Relative as bool:
set: AL.Source( handle, ALSourceb.SourceRelative, value )
public Looping as bool:
set: AL.Source( handle, ALSourceb.Looping, value )
public Streaming as bool:
set:
type = (ALSourceType.Static, ALSourceType.Streaming)[value]
AL.Source( handle, ALSourcei.SourceType, cast(int,type) )
public Position as OpenTK.Vector3:
set: AL.Source( handle, ALSource3f.Position, value )
public Velocity as OpenTK.Vector3:
set: AL.Source( handle, ALSource3f.Velocity, value )
public Direction as OpenTK.Vector3:
set: AL.Source( handle, ALSource3f.Direction, value )
public SecOffset as single:
set: AL.Source( handle, ALSourcef.SecOffset, value )
public def init(buf as Buffer) as void:
AL.Source( handle, ALSourcei.Buffer, buf.handle )
public def play() as void:
AL.SourcePlay(handle)
public def stop() as void:
AL.SourceStop(handle)
|
uppose -5*f = p - 10, -p - 8*f = -11*f - g. Calculate the lowest common multiple of 50 and p.
50
Let x(m) = 311*m. Let l be x(-4). Let k = l + 15029/12. Calculate the common denominator of k and (-17 - -43)*6/(-8).
12
Let i be (-26930)/11 + 22/121. Find the common denominator of -3 - (4900/i - 8/(-36)) and 19/20.
340
Let c be ((-3)/6)/(28/8 + -3). Let f be (-3 - c)*9/(-6). Suppose -15 = 5*k, 2*s - 52 = -f*s + 4*k. Calculate the smallest common multiple of s and 7.
56
Let m = 2785 - 2773. What is the smallest common multiple of m and 120?
120
Let d(k) = 2*k**3 + 6*k**2 - 44*k - 18. What is the smallest common multiple of 930 and d(-6)?
930
Let s(p) = 3*p**3 - 123*p**2 + 39*p**2 + 42*p**2 + 7*p - 6 + 41*p**2. Calculate the smallest common multiple of 54 and s(1).
54
Calculate the common denominator of (325/(-240))/(4/(8 + 8)) and 157/6318.
12636
Let d = 30 + -12. Let s = 829 - 2453/3. Find the common denominator of ((-2)/d)/(20/(-3930)) and s.
6
What is the common denominator of ((-4)/(-6))/(3332/(-42)) and 117/748?
5236
Let l = -567613/5 + 95351959/840. Let d = -67/7 - l. What is the common denominator of 22/3 and d?
24
Let m = -1/267 - 263/1068. Find the common denominator of (-61 + 2)/((-16)/(-1)) and m.
16
Let h = 47482/27 + -1759. Let p = 247/189 - h. Calculate the common denominator of 31/37 and p.
259
What is the common denominator of -37/2 and 24/((-4416)/(-2540)) - 12?
46
Suppose -22 = 2*q - 5*x, -5*x + 31 = -5*q + 6. What is the common denominator of 1/48 and q - 0 - 852/180?
240
Let j(m) = 5*m**3 + 2*m**2 + 14*m - 21. Let c be j(3). Suppose 9*i = -3*r + 12*i + 102, -5*r = -i - c. Calculate the smallest common multiple of r and 70.
70
Let p(l) = 9*l + 218. Let i be p(-24). Suppose -2*c - 6*j = -7*j - 107, i*j = 5*c - 266. What is the smallest common multiple of c and 32?
416
Let t = 5974 + -5150. Calculate the lowest common multiple of 8 and t.
824
Let p(r) = 14*r - 88. Let i(u) = -2. Let m(a) = -4*i(a) + p(a). Calculate the lowest common multiple of m(13) and 12.
204
Let h be ((-4)/(-3))/(32/(-48)). Let d be 2/((-2)/2932*h). Let i = d + -20639/14. Calculate the common denominator of -53/8 and i.
56
Let g = 93 + -82. Find the common denominator of 109/20 and g/(-154)*2114/36.
180
Let y be 8/(-83484)*(-1507314)/40. Let g = 212962/4487265 + -55/1161. Let v = g + y. Find the common denominator of 41/9 and v.
18
Let i(t) = 2*t**2 - 2*t - 4. Suppose -4*h + 3*r - 2*r + 8 = 0, -3*h + 3*r = 3. Calculate the least common multiple of i(h) and 71.
568
Suppose -b - 4*b + 135 = 0. Let f(h) = -5*h**3 - 63*h**2 + 477*h - 21. Calculate the least common multiple of b and f(-18).
1269
Let k be 3*3/9 + -4 + 0. Calculate the common denominator of 87/10 and (35/2 - k)/(-2 + 1).
10
Suppose -k + 8 = k. Calculate the smallest common multiple of 64 and 17802/559 + k/(-78)*-3.
64
Let f = 411/5 - 83. What is the common denominator of f and (-3249)/(-456)*24/15?
5
Let w = 6253/2384 - 9/149. Let t = w + -65/48. What is the common denominator of -137/60 and t?
120
Let y = 19963 + -19953. What is the least common multiple of y and 20366?
101830
Let f = -5 + 17. Calculate the smallest common multiple of 1634 and f.
9804
Let c(x) = -x**3 - 2*x**2 - 4*x + 2. Let p be c(-7). Let g be 3 + (16899/138)/(p/(-10)). Let q = 2/1265 - g. What is the common denominator of q and 9/2?
22
What is the lowest common multiple of 104 and ((-160)/10 - -12)*(-63)/2?
6552
Let f = 757 + -751. What is the common denominator of -33 and f/21 - (-1210)/(-13937)?
181
Suppose -4*y + 9*n - 10*n + 90 = 0, 3*y - 64 = n. Let x = 42 - y. Suppose 0 = 3*m - 2*r - 6, -3*r = 2*m - 2 - 2. What is the lowest common multiple of x and m?
20
Let u = -1521 + 2200. What is the smallest common multiple of 485 and u?
3395
Let i be (5/(-2))/(-4 + (-27)/(-6)). Let y be 3/(-1) - (9545/156)/i. Let n = y - 21/52. Calculate the common denominator of -65/8 and n.
24
Suppose -13*a + 3777 = -a + 2301. Calculate the smallest common multiple of 738 and a.
738
Suppose -2*a - 7*a = 27. Find the common denominator of 137/90 and (-15)/a + ((-129)/54 - -3).
90
Let q = 41465/6 + -2404769/348. Let a = -350245 - -1400989/4. What is the common denominator of q and a?
116
Let u = 312 - 225. What is the common denominator of 97/258 and (20/15)/(10/u)?
1290
Let g = -759 - -734. What is the common denominator of 101/20 and (1/g)/(30/7275)?
20
Let n(o) = -o**3 + o**2 - 4*o + 310. Calculate the least common multiple of n(0) and 6.
930
Calculate the common denominator of 193/(-12) + 13*102/221 and ((-2)/69)/(36/(-135)).
276
Calculate the common denominator of (0 + (-267)/18)/(65/15 - 5) and (-2)/4 - 395/(-90).
36
Calculate the common denominator of 97/36 and (2 + 31/36)/(1266/(-18)).
7596
Let z(w) = -w**2 - 21*w + 30. Let o be z(-23). What is the common denominator of 131/24 and (-508)/o*9/(405/(-10))?
72
Let h = 4235 + -3407. Calculate the least common multiple of h and 12.
828
Let y = 1075897 - 6941687467/6452. Find the common denominator of 1/5 and y.
32260
Let n be (1*-1)/(1/6335). Let a = 8406105 - 100949237/12. Let h = n - a. Calculate the common denominator of h and -1/6.
12
Let u be 3 + -4 + 4 + 201983/(-20). Let y = -30420 - -20318. Let x = u - y. Find the common denominator of x and -19/260.
260
Suppose 42317*m - 42362*m = -3150. Let u(c) = 27*c**3 + c**2 - c + 1. Calculate the least common multiple of u(1) and m.
140
Suppose 54 = -0*k + 3*k - 5*m, 3*k - 4*m = 54. Suppose -k*w + 192 = -2*w. Calculate the lowest common multiple of 4 and w.
12
Let f be (-52)/1 + -1 - 1. Calculate the common denominator of 55/(-150)*f/4 and (-14)/(-112)*692/15.
60
Let w = 602 - 600. Calculate the common denominator of 47/9 and (w - 1362/675)*2730/(-80).
450
Let z = -2064/23 + 83227/920. Let o = -86 + 428/5. What is the common denominator of o and z?
40
Let t be (2/(-7))/((-2)/7). What is the least common multiple of 88 and t/((-6)/30) - -69?
704
Suppose 42 = 2*c + y, c - 24 + 3 = 5*y. Suppose -25*i + c*i = -40. What is the lowest common multiple of 50 and i?
50
Let t = -1684841/285 + 29563/5. Let h = -242/67 + 14071/1206. Calculate the common denominator of t and h.
342
Let a(s) be the third derivative of s**6/120 - s**5/10 - s**4/4 + 10*s**3/3 + 10*s**2 + 3. Let v = 97 - 88. Calculate the lowest common multiple of a(7) and v.
27
Suppose -12 = -2*w - 2*a, 5*w - 4*w - 2*a = 3. Suppose u - 3*d - 8 - 9 = 0, -4*u = w*d. Let x = -2 + 3. What is the least common multiple of x and u?
5
Let q be -106*(-6)/28 + 10/35. Suppose -j + m = -q, 0 = j - 4*j - 5*m + 109. Calculate the lowest common multiple of 3 and j.
84
Let l = 1809 + -3694. Let o = -49027/26 - l. What is the common denominator of 151/42 and o?
546
Let y(m) = -m + 4. Let v be y(-2). Suppose 2*h - 4 - 22 = -p, 2*h - 4*p = v. Calculate the smallest common multiple of h and 7.
77
Suppose -299*g = 13*g - 6864. Calculate the smallest common multiple of 8679 and g.
17358
Calculate the smallest common multiple of 411 and (-104)/364 + 0 + 4162/14.
40689
Let u(m) = -3*m**3 - 3*m**2. Let y be u(3). Find the common denominator of 3*304/(-384)*(-3)/(-6) and (-37)/(-1)*3/y.
144
Let m(s) be the third derivative of 2*s**4/3 - 3*s**3 - 3*s**2. Let u be m(-9). Find the common denominator of -11/12 and (8 - 5) + u/64.
96
Let d = 4273 + -12857/3. Find the common denominator of d and 29/293.
879
Suppose 85*z = -74*z + 7*z + 1064. Calculate the smallest common multiple of z and 5873.
5873
Suppose -3*w + h - 123 = 0, 0 = -4*w + w + 3*h - 117. Find the common denominator of (-23)/(-20) + 4 + 180/w and -85/44.
1540
Let t(z) = 27*z + 81. Let u(g) = 5*g + 16. Let c(p) = -2*t(p) + 11*u(p). What is the least common multiple of 14 and c(-4)?
70
Let j be ((-2)/4)/((-11)/66). Calculate the common denominator of (-6)/(-10) - 17/((-39015)/1258) and 1/((-99)/(-24) - j).
27
Suppose -60*o = -50*o - 37*o + 162. Calculate the smallest common multiple of o and 246.
246
Let d(g) = g**3 + 4*g**2 - g - 7. Let p be 1/(-6) - (-306)/(-108). Let y = 138 + -134. Calculate the smallest common multiple of d(p) and y.
20
Let a = 1226 - 386. Suppose -16*d = -4*d + a. Let c = d - -86. Calculate the least common multiple of c and 22.
176
Let y = -1300 + 6376. What is the least common multiple of y and 12?
5076
Suppose -1153*i + 6000 = -1103*i. |
We believe that Electronic Voice Phenomena (EVP) is so important to the research and understanding of paranormal activity; that it had to be reflected in our name. Also listening for the (spirit voices) as they occur in "real time" through the digital audio recorder allows the investigator to determine quickly how intense the paranormal activity may be.
Brad, Allan and I have never been to a haunted location that did not have EVP present, during the investigation. Spirit orbs are also present in our video recordings and digital photography. Our experience shows us that EVP and spirit orbs can be detected in most hauntings. Everyone is welcome to contact us and share their experience or beliefs. |
Tuna’s on a roll! It seems the LA Galaxy attacker has settled into the Mexican National Team with ease: The on-loan Manchester City midfielder scored Mexico’s opening tally in their 5-1 CONCACAF Nations League victory over Bermuda Friday night.
Hirving “Chucky” Lozano escaps the challenges of two opponents before gliding into the final third unimpeded and playing a pleasantly timed through ball for Antuna who easily rounds the keeper with a single touch before passing into an empty net. Tuna now has six goals in eight appearances for El Tri. (Additionally Antuna has six goals and five assists in MLS, picking up his production since the arrival of Cristian Pavon)
Antuna thriving at the national team level bodes well for the Galaxy organization, who would love to see Uriel return next season while he continues to develop and refine his game.
On the flip side, that transfer fee is steadily riding. |
Capsular hyaluronic acid-mediated adhesion of Pasteurella multocida to turkey air sac macrophages.
Serogroup A strains of Pasteurella multocida, the major cause of fowl cholera, are resistant to phagocytosis in nonimmunized birds. Adherence studies with a capsulated strain of P. multocida (serotype A:3) and turkey air sac macrophages in culture showed that the bacteria were capable of adhering in large numbers to the macrophages but were not internalized. A noncapsulated variant of the bacteria (serotype -:3) showed little or no adherence and was not internalized. These data indicated that the adhesive properties were caused by the presence of a capsule on the bacteria. The role of capsular hyaluronic acid in adherence to macrophages was investigated. Depolymerization of the bacterial capsule with hyaluronidase increased phagocytosis by macrophage cultures, and addition of hyaluronic acid to the macrophages inhibited bacterial adherence. Additionally, exposure of macrophages to chondroitin sulfate B, an anionic polysaccharide similar to hyaluronic acid, did not affect the adhesive properties and resistance to phagocytosis of capsulated organisms. Treatment of macrophages with sodium metaperiodate or trypsin suppressed bacterial binding. Collectively, these data indicate that P. multocida adhesion to air sac macrophages, but not internalization, is mediated by capsular hyaluronic acid and suggest that recognition of this bacterial polysaccharide is a result of a specific glycoprotein receptor. |
<?php
namespace Concrete\Core\User\PersistentAuthentication;
use Concrete\Core\Config\Repository\Repository;
use Concrete\Core\Cookie\CookieJar;
class CookieService
{
/**
* The name of the cookie to be used to remember the currently logged in user.
*
* @var string
*/
const COOKIE_NAME = 'ccmAuthUserHash';
/**
* @var \Concrete\Core\Cookie\CookieJar
*/
protected $cookieJar;
/**
* @var \Concrete\Core\Config\Repository\Repository
*/
protected $config;
/**
* Initialize the instance.
*
* @param \Concrete\Core\Cookie\CookieJar $cookieJar
* @param \Concrete\Core\Config\Repository\Repository $config
*/
public function __construct(CookieJar $cookieJar, Repository $config)
{
$this->cookieJar = $cookieJar;
$this->config = $config;
}
/**
* Get the authentication data corrently contained in the cookie jar.
*
* @return \Concrete\Core\User\PersistentAuthentication\CookieValue|null
*/
public function getCookie()
{
if (!$this->cookieJar->has(static::COOKIE_NAME)) {
return null;
}
$rawValue = $this->cookieJar->get(static::COOKIE_NAME);
return $this->unserializeCookieValue($rawValue);
}
/**
* Set (or delete) the authentication cookie.
*
* @param \Concrete\Core\User\PersistentAuthentication\CookieValue|null $value
*/
public function setCookie(CookieValue $value = null)
{
if ($value === null) {
$this->deleteCookie();
return;
}
$this->cookieJar->getResponseCookies()->addCookie(
// $name
static::COOKIE_NAME,
// $value
$this->serializeCookieValue($value),
// $expire
time() + (int) $this->config->get('concrete.session.remember_me.lifetime'),
// $path
DIR_REL . '/',
// $domain
$this->config->get('concrete.session.cookie.cookie_domain'),
// $secure
$this->config->get('concrete.session.cookie.cookie_secure'),
// $httpOnly
$this->config->get('concrete.session.cookie.cookie_httponly'),
// $raw
$this->config->get('concrete.session.cookie.cookie_raw'),
// $sameSite
$this->config->get('concrete.session.cookie.cookie_samesite')
);
}
/**
* Delete the authentication cookie.
*/
public function deleteCookie()
{
$this->cookieJar->getResponseCookies()->clear(static::COOKIE_NAME);
}
/**
* @param \Concrete\Core\User\PersistentAuthentication\CookieValue $value
*
* @return string
*/
protected function serializeCookieValue(CookieValue $value)
{
return implode(':', [$value->getUserID(), $value->getAuthenticationTypeHandle(), $value->getToken()]);
}
/**
* @param string|mixed $rawValue
*
* @return \Concrete\Core\User\PersistentAuthentication\CookieValue|null
*/
protected function unserializeCookieValue($rawValue)
{
if (!is_string($rawValue)) {
return null;
}
$chunks = explode(':', $rawValue);
if (count($chunks) !== 3) {
return null;
}
list($userID, $authenticationTypeHandle, $token) = $chunks;
if (($userID = (int) $userID) < 1 || $authenticationTypeHandle === '') {
return null;
}
return new CookieValue($userID, $authenticationTypeHandle, $token);
}
}
|
Warren Counters GOP Rep. Who Called Her “Darth Vader”: “I’m More of A Princess Leia Type”
When Republican representative Blaine Luetkemeyer of Missouri attacked Senator Elizabeth Warren for her strong stance on finance reform and her dogged determination to hold Wall Street accountable, the Senator hit back with a challenge.
Luetkemeyer said that Warren was the “Darth Vader of the financial services world,” and said that someone should “find a way to neuter” the senator. The representative’s comments drew strong condemnation from his colleagues, but when Senator Warren was asked to respond, she ignored the personal insults and challenged the Representative to put up his political dukes and fight it out over financial regulations.
“Look, if Wall Street and their buddies in the Republican party want to launch an assault on financial regulations and they want to say ‘let’s roll back Dodd-Frank’ all I can say is ‘let’s have that fight,’” she said. “I’m ready. You can make it with words or anything else you want, but I am not backing down.”
Then, on Thursday evening, the Senator followed up with a letter to her supporters in which she responded to Luetkemeyer’s Star Wars-themed insults with her own “force”-ful response.
“My first thought was Really? I’ve always seen myself more as a Princess Leia-type (as a senator and Resistance general who, unlike the guys, is never even remotely tempted by the dark side). Clearly the Force is not strong with Congressman Luetkemeyer (maybe he’s a Trekkie).”
Warren then doubled down on her previous challenge to Luetkemeyer, charging that the Missouri representative was attacking Warren for her big name and his own financial crony backers.
This exchange teaches us two things: 1. That politicians can be massive nerds, and 2. Elizabeth Warren is not a lady you wanna mess with.
Sydney Robinson is a political writer for the Ring of Fire Network. She has also appeared in political news videos for Ring of Fire. Sydney has a degree in English Literature from the University of West Florida, and has an active interest in politics, social justice, and environmental issues. She would love to hear from you on Twitter
@SydneyMkay or via email at [email protected] |
Not my pictures
At a conference in Japan, a Dell laptop suddenly exploded into flames, and lucky for its owner the fiery blast occurred while the PC was sitting on a table and not in his lap. An onlooker reported that the notebook continued to burn, producing several more explosions over the course of about five minutes. |
Q:
Como fazer um formulário que aceite upload de foto e salve no banco de dados
Criei um banco de dados chamado Form e tabela com as seguintes informações
contatos (id int A.I, nome varchar(30), idade int(2), foto(blob)
Fiz aquele formulário padrão:
<!DOCTYPE html>
<html>
<head>
<meta charset="utf-8">
<title>JS Bin</title>
</head>
<body>
<form name="CadastroAlunos" type="text" method="post" enctype="multipart/form-data" action="upload.php">
Nome: <input type="text" name="NomeAluno"></br>
Idade: <input type="text" name="IdadeAluno"></br>
Foto: <input type="file" name="image" /></br>
<input type="submit" value="Enviar" name="envia" />
</form>
</body>
</html>
UPLOAD.PHP
<?php
include_once 'conexao.php';
$nome = $_POST['NomeAluno'];
$idade = $_POST['IdadeAluno'];
$foto = $_FILES['image'];
move_uploaded_file ( string $foto , string $novoDestino );
$sql = "INSERT INTO contatos (nome, idade, foto) values ('$nome', '$idade', $novoDestino");
?>
Como faço para gravar a foto junto com as de mais informações do formulário?
A:
Utilize o tipo BLOB para a coluna foto que receberá o conteúdo do input type="file".
Seu código PHP para inserção no banco ficaria mais ou menos assim:
<?php
include_once 'conexao.php';
$nome = $_POST['NomeAluno'];
$idade = $_POST['IdadeAluno'];
$imagem = $_FILES['image']['tmp_name'];
$tamanho = $_FILES['image']['size'];
//$tipo = $_FILES['image']['type'];
//$nomeImagem = $_FILES['image']['name'];
if ( $imagem != "none" ) {
$fp = fopen($imagem, "rb");
$conteudo = fread($fp, $tamanho);
$conteudo = addslashes($conteudo);
fclose($fp);
$sql = "INSERT INTO contatos (nome, idade, foto) values ('$nome', '$idade', '$conteudo')";
mysqli_query($conexao, $sql) or die("Algo deu errado ao inserir o registro. Tente novamente.");
echo 'Registro inserido com sucesso!';
//header('Location: index.php');
if(mysqli_affected_rows($conexao) > 0)
print "A imagem foi salva na base de dados.";
else
print "Não foi possível salvar a imagem na base de dados.";
} else
print "Não foi possível carregar a imagem.";
?>
|
Q:
Vec of Bundle as a Module parameter
I'm writing a Wishbone Intercon module to make the address decoding automatically.
I have two Bundle classes that describe Wishbone master and Wishbone slave interface.
class WbMaster (val dwidth: Int,
val awidth: Int) extends Bundle {
val adr_o = Output(UInt(awidth.W))
//...
val cyc_o = Output(Bool())
}
// Wishbone slave interface
class WbSlave (val dwidth: Int,
val awidth: Int) extends Bundle {
val adr_i = Input(UInt(awidth.W))
//...
val cyc_i = Input(Bool())
}
I want to pass these Bundle as parameter to my module Wishbone like following:
class WbInterconOneMaster(val awbm: WbMaster,
val awbs: Vec(WbSlave)) extends Module {
val io = IO(new Bundle{
val wbm = Flipped(new WbMaster(awbm.dwidth, awbm.awidth))
val wbs = Vec(?)
})
}
The objective is to permit a variable number of wishbone slaves and let the module doing the plumbing. Like following:
val spi2Wb = Module(new Spi2Wb(dwidth, awidth))
val wbMdio1 = Module(new MdioWb(mainFreq, targetFreq))
val wbMdio2 = Module(new MdioWb(mainFreq, targetFreq))
val slavesVec = Vec(Seq(wbMdio1, wbMdio2))
val wbIntercon = Module(new WbIntercon(spi2Wb.io.wbm, slavesVec))
The question is multiple:
is it the right way to do it ?
How to declare the Vec() in module parameters ?
I tryied this but does not work:
// Wishbone Intercone with one master and several slaves
// data bus is same size as master
class WbInterconOneMaster(val awbm: WbMaster,
val awbs: Vec[Seq[WbSlave]]) extends Module {
val io = IO(new Bundle{
val wbm = Flipped(new WbMaster(awbm.dwidth, awbm.awidth))
val wbs = Vec.fill(awbs.size){awbs.map(_.cloneType())}
})
}
A:
I found a solution with MixedVec (experimental) module. I simply pass a Seq of WbSlave Bundle as a module parameter and I made a MixedVec (WbSlave can have different parameters in fact):
class WbInterconOneMaster(val awbm: WbMaster,
val awbs: Seq[WbSlave]) extends Module {
val io = IO(new Bundle{
val wbm = Flipped(new WbMaster(awbm.dwidth, awbm.awidth))
val wbs = MixedVec(awbs.map{i => new WbSlave(i.dwidth, i.awidth)})
})
io.wbm.dat_i := 0.U
io.wbm.ack_i := 0.U
for(i <- 0 until io.wbs.size){
io.wbs(i).dat_o := 0.U
io.wbs(i).ack_o := 0.U
}
}
That compile in the testbench.
|
/**
* PLUNKER VERSION (based on systemjs.config.js in angular.io)
* System configuration for Angular 2 samples
* Adjust as necessary for your application needs.
*/
(function(global) {
var ngVer = '@2.3.0'; // lock in the angular package version; do not let it float to current!
var routerVer = '@3.3.0'; // lock router version
var formsVer = '@2.3.0'; // lock forms version
//map tells the System loader where to look for things
var map = {
'app': 'app',
'@angular': 'https://npmcdn.com/@angular', // sufficient if we didn't pin the version
'@angular/router': 'https://npmcdn.com/@angular/router' + routerVer,
'@angular/forms': 'https://npmcdn.com/@angular/forms' + formsVer,
'angular2-in-memory-web-api': 'https://npmcdn.com/angular2-in-memory-web-api', // get latest
'rxjs': 'https://npmcdn.com/[email protected]',
'ts': 'https://npmcdn.com/[email protected]/lib/plugin.js',
'typescript': 'https://npmcdn.com/[email protected]/lib/typescript.js',
};
//packages tells the System loader how to load when no filename and/or no extension
var packages = {
'app': { main: 'main.ts', defaultExtension: 'ts' },
'rxjs': { defaultExtension: 'js' },
'angular2-in-memory-web-api': { main: 'index.js', defaultExtension: 'js' },
};
var ngPackageNames = [
'common',
'compiler',
'core',
'http',
'platform-browser',
'platform-browser-dynamic',
'upgrade',
];
// Add map entries for each angular package
// only because we're pinning the version with `ngVer`.
ngPackageNames.forEach(function(pkgName) {
map['@angular/'+pkgName] = 'https://npmcdn.com/@angular/' + pkgName + ngVer;
});
// Add package entries for angular packages
ngPackageNames.concat(['forms', 'router', 'router-deprecated']).forEach(function(pkgName) {
// Bundled (~40 requests):
packages['@angular/'+pkgName] = { main: '/bundles/' + pkgName + '.umd.js', defaultExtension: 'js' };
// Individual files (~300 requests):
//packages['@angular/'+pkgName] = { main: 'index.js', defaultExtension: 'js' };
});
var config = {
// DEMO ONLY! REAL CODE SHOULD NOT TRANSPILE IN THE BROWSER
transpiler: 'ts',
typescriptOptions: {
tsconfig: true
},
meta: {
'typescript': {
"exports": "ts"
}
},
map: map,
packages: packages
};
System.config(config);
})(this);
/*
Copyright 2016 Google Inc. All Rights Reserved.
Use of this source code is governed by an MIT-style license that
can be found in the LICENSE file at http://angular.io/license
*/ |
package com.daasuu.mp4compose.filter;
import com.daasuu.mp4compose.utils.GlUtils;
/**
* Created by sudamasayuki on 2017/11/14.
*/
public class GlGrayScaleComposeFilter extends GlComposeFilter {
private static final String FRAGMENT_SHADER =
"#extension GL_OES_EGL_image_external : require\n" +
"precision mediump float;\n" +
"varying vec2 vTextureCoord;\n" +
"uniform samplerExternalOES sTexture;\n" +
"const highp vec3 weight = vec3(0.2125, 0.7154, 0.0721);\n" +
"void main() {\n" +
"float luminance = dot(texture2D(sTexture, vTextureCoord).rgb, weight);\n" +
"gl_FragColor = vec4(vec3(luminance), 1.0);\n" +
"}";
public GlGrayScaleComposeFilter() {
super(GlUtils.DEFAULT_VERTEX_SHADER, FRAGMENT_SHADER);
}
}
|
import BoardPlugin from '../../plugins/board-plugin.js';
const Random = Phaser.Math.Between;
class Demo extends Phaser.Scene {
constructor() {
super({
key: 'examples'
})
}
preload() {}
create() {
var board = this.rexBoard.add.board({
grid: getHexagonGrid(this),
// grid: getQuadGrid(this),
width: 8,
height: 8
});
var rexBoardAdd = this.rexBoard.add;
board
.forEachTileXY(function (tileXY, board) {
rexBoardAdd.shape(board, tileXY.x, tileXY.y, 0, Random(0, 0xffffff));
}, this)
.destroy();
}
update() {}
}
var getQuadGrid = function (scene) {
var grid = scene.rexBoard.add.quadGrid({
x: 400,
y: 100,
cellWidth: 100,
cellHeight: 50,
type: 1
});
return grid;
}
var getHexagonGrid = function (scene) {
var staggeraxis = 'x';
var staggerindex = 'odd';
var grid = scene.rexBoard.add.hexagonGrid({
x: 100,
y: 100,
size: 30,
staggeraxis: staggeraxis,
staggerindex: staggerindex
})
return grid;
};
var config = {
type: Phaser.AUTO,
parent: 'phaser-example',
width: 800,
height: 600,
scale: {
mode: Phaser.Scale.FIT,
autoCenter: Phaser.Scale.CENTER_BOTH,
},
scene: Demo,
plugins: {
scene: [{
key: 'rexBoard',
plugin: BoardPlugin,
mapping: 'rexBoard'
}]
}
};
var game = new Phaser.Game(config); |
Six youth criminals are chosen to participate in a social experiment, named "Guesthouse Objectivity" (Pensionatet Sakligheten), where they are assigned to live together in an apartment while...
See more »
Special Effects
Other Companies
Storyline
Six youth criminals are chosen to participate in a social experiment, named "Guesthouse Objectivity" (Pensionatet Sakligheten), where they are assigned to live together in an apartment while being supervised by two forgiving social workers.
Written by Ulf Kjell Gür
Additional Details
Did You Know?
On Dec 5 1963, the producer SF sent the film to the National Cinema Agency (NCA) for review. The Agency found itself apparently not able to assess the issue. Therefore the National Film Review Council was consulted. On Dec 28, NCA announced their decision; "The film's public viewing in Sweden is prohibited".
See more » |
The invention relates to a method and a device for encoding a score of semantic and spatial similarity between concepts of an ontology stored in hierarchically numbered trellis form.
An ontology, in the context of the subject of the invention, should be understood to be a set of knowledge of facts and rules conveying information relating to an area of knowledge, of a technical and/or non-technical nature.
This information is translated by predicates, logical information-conveying entities, forming a relationship for at least one fact from the area of knowledge, the arguments of these predicates being able to be instantiated by particular values of these facts. A predicate (for example: Flight, and Country are two predicates useful in the area of knowledge of a traveller) can be instantiated by instances (example: 714/Sydney” is one instance of Flight, “France” an instance of Country).
Implicit information, obtained by saturating the knowledge areas of the ontology (rules, disjunctions, inclusions, definitions) can be calculated by a reasoner, defined for a language or a determined description logic, such as the ALN description logic which can be used to express object classes, concepts, based on constructors associated with the letters A: Top (universal concept), Bottom (empty concept), for All (universal restriction on certain properties associated with certain concepts) and Not; L: And (logical And between several concepts) and N: At least and At most (cardinality restriction on certain concepts).
A concept is a unary predicate, which accepts only one argument, with which it is possible to construct logic description formulae.
With reference to FIG. 1, an ontology of concepts can be represented in trellis form. A trellis is a partial order relation for which any pair of elements (e1, e2) of the trellis has a higher element eS and a common lower element el (e1<eS and e2<eS; e1>eI and e2>eI). The order is said to be partial, because it is not defined for all the pairs of elements: with reference to the higher element eS=T, defined as the universal concept, and the lower element el=⊥, defined as the empty concept, certain elements in the direction of the abovementioned order relation are said to be smaller than others, B<C, but some elements are not comparable to others, B ? H or A ? F. An element or concept can have several higher and lower elements.
The abovementioned trellis structure is richer than a conventional tree structure, which does not allow an element or concept to have multiple parents.
An ontology which no longer contains implicit information is called a saturated ontology, in which any information is accessible in, at most, one forward linkage step. A forward linkage step or saturation step, consists in replacing, by rewriting, the left part of a rule, called condition or body, by its right part, called conclusion or head of the rule.
The exemplary trellis of concepts of FIG. 1a is described in description logic, as represented in the abovementioned figure, according to the relationship of order of subsumption, or generalization, between two concepts which comprises all the instances of the inclusion relation ⊂ between primitive concepts. This relation between two elements e1 and e2 is reduced for two primitive concepts to checking the existence of an instance of the inclusion relation e1⊂e2 or e2⊂e1. On the other hand, determining whether a defined concept generalizes another involves complex calculations on the description logic expressions.
Thus, with reference to FIG. 1,
A is the child of B and E−B is the parent of A and F−B, E, H, A, F and I are the descendents of C−B, E, C and D are the generalizers of A; T designates the universal concept; ⊥ designates the empty concept. The trellis represented in FIG. 1 incorporates two defined concepts H: =C∩G and I where H subsumes I. After these two adjunctions C, D and G subsume H and therefore I.
A process of calculating and encoding a score of semantic proximity between two concepts has been described in the thesis by Alain Bidault, Université de Paris-Sud, France, thesis entitled “Affinement de requêtes posées à un médiateur” (refining requests put to a mediator), order number 6932, July 2002.
Calculating and encoding such a proximity score is also facilitated by a process of completely numbering a trellis of concepts, which is the subject of the prior French patent application FR 05 07326 entitled “Procédé et système de codage sous forme d'un treillis d'une hièrarchie de concepts appartenant à une ontologie” (Method and system of encoding in trellis form a hierarchy of concepts belonging to an ontology), filed in the name of the applicant on Jul. 8, 2005, publicly accessible online at the Internet address:
http://priorart.ip.com/search.jsp?searchType=freetextSe arch, prior to the date of filing of the present patent application.
Such a numbering process was defined for concepts appearing in description logic in a trellis of concepts. The relationships of this trellis take the form Concept 1⊂Concept 2 where the sign ⊂designates the subsumption relation between two concepts. The empty concept ⊥ and the universal concept T do not appear explicitly in the hierarchy, but are assumed present as specializing and generalizing the most specialized concepts and the most general concepts.
The abovementioned numbering process is noteworthy in that it consists in assigning each concept an identifier consisting of one or more paths, each path consisting of a series of integers. Each path is unique on the trellis of concepts and corresponds to the existence of a succession of arcs oriented between the concept concerned and the universal concept T. T and ⊥ have no identifier.
A numbering of the trellis represented in FIG. 1 according to the abovementioned process is expressed:
D(“1”); G(“2”); C(“11”); B(“111”); E (“112”); A(“1111”, “1121”); F(“1112”, “1122”); H(“21”, “113”); I(“211”, “1131”).
It can be seen in FIG. 1 that, for the concept A, there are two routes for reaching the universal concept: ABCD and AECD,which justifies the presence of two paths in the identifier of the concept A, one route being defined as the course of a path.
A determined concept has characteristics, some of which are defined. The defined characteristics correspond to the occurrences or courses of the arcs forming a route between the determined concept concerned and the universal concept T. Each path of the identifier corresponds to a main component of the concept. The number of characteristics of a concept NC is linked to the depth Ph of the hierarchy and to the number K of paths (main components of its identifier), NC=K×Ph. The undefined characteristics are the other characteristics. The characteristics are taken into account globally over the whole of the identifier of the concept or for each of its paths taken separately.
In the example of FIG. 1, a hierarchy of depth Ph=4, the concept I(“211”, “1131”) has K=2 main components, NC=2×4=8 characteristics, of which 3+4=7 are defined and 8−7=1 is undefined.
To proceed with calculating the paths, each node of the trellis representing a concept, the numbering process consists in assigning each node or concept an identifier, which inherits all the paths of its parents, to which, for example, the character or integer 1 for the first child of a parent node p is added to each of the paths of the parent nodes p, and so on for any successive child node of the parent node p.
The abovementioned numbering process is drawn from the topological sorting on an oriented graph. An oriented graph is a non-symmetrical binary relation in which each element of the relation is represented by a node in the graph and in which each occurrence of the relation R(“n1”, “n2”) reveals, on the graph, an arc oriented from the node “n1” to the node “n2”. The topology sorting algorithm makes it possible to apply a processing operation to a node once all its antecedents have been processed. By analogy, a concept of the trellis is numbered once all its parent concepts have been numbered. To keep the information relative to the hierarchy, a child concept Cf inherits all the paths of the identifier of each of its parent concepts Cp extended to the right, for example, by a new character or integer number. The added character or integer number is the same for all the paths from one and the same parent to one of its children.
To guarantee that a path is associated with only a single concept of the hierarchy, the added character or integer is different for each of its children.
With reference to FIG. 1, the concept A has inherited the path “111” from its parent concept B and the path “112” from its parent concept E that it has extended with the character or integer 1, which could have been different depending on the rank of the child concept A for example. The set of the extended paths, obtained from all the parent concepts of the child concept Cf constitutes the identifier of the latter.
Thus, it is possible to find: all the generalizers and the descendents of a determined concept by working through the identifier of this concept and the list of the concepts; the maximum and minimum numbers of arcs that separate each concept from the universal concept T and, consequently, its depth in the trellis.
The numbering process also makes it possible to easily perform a subsumption test between two concepts, even though a subsumption test is a complex calculation in an ontology described in description logic which makes it possible to determine whether the instances of a concept are included or not in those of another concept, by being based on the definition of the concepts. This test, facilitated in a saturated ontology, becomes very simple thanks to the numbering process.
In practice, with reference to FIG. 1, the concept C(“11”) subsumes the concept A(“1111”, “1121”) because the path of the identifier of C is identified with, at least, one path of the identifier of A, here by prefixing one of the paths of the identifier of A.
The numbering process also makes it possible to determine their smallest common generalizers, ppcg. The set of common generalizers ξgc of two concepts C1 and C2 contains all the concepts which subsume both C1 and C2. ppcg is the greatest subset d′=ξgc (ξgc=ppcg U ξremainder) such that no concept of the ppcg subsumes another concept of the ppcg and that no concept of the ppcg subsumes a concept of the remaining set ξremainder.
The ppcg of two concepts can be directly accessible in a saturated ontology and it is easy to extend the calculation of the ppcg from 2 to n concepts. The simplicity of the calculation of the ppcg based on the numbering is all the more appreciable.
With reference to FIG. 1, the ppcg of A(“1111”, “1121”) and F(“1112”, “1122”) is the set of the concepts associated with the paths “111” and “112”, namely the concepts B and E.
The ppcg of the concepts A, F and H is restricted to the ppcg of (“111”, “112”) with (“21”, “113”), namely the concept C(“11”). However, the concepts D and G have no ppcg, apart from the universal concept T.
For a more detailed description of the above notions, reference can usefully be made to the abovementioned French patent application 05 07526.
The abovementioned numbering method also makes it possible to calculate and encode a score of semantic proximity between two concepts, as described in the abovementioned thesis by Alain Bidault.
The abovementioned encoded score is of interest only in a classification to order the concepts relative to a central or reference concept. The closer the concept is to the head of the classification obtained, the closer it is to the reference concept. To calculate and encode the abovementioned score, it is necessary to be able to determine, for two given concepts, the ppcg given by the common defined characteristics of the latter, and their separation in terms of numbers of arcs with respect to this ppcg.
With reference to FIG. 1, the concepts A(“1111”, “1112”) and F(“1112”, “1122”) are both at 2 times 1 arc from their ppcg (“111”, “112”).
The semantic convergence of two concepts favours the descendents, which have all the defined characteristics of their ancestors, orders these descendents according to their depth, the children are closer than the other descendents, and assigns a same score to the descendents located on the same stratum or level of descendence. In practice, a parent concept makes no distinction between its child concepts, just as a grandparent concept makes none with its child concepts, nor with its grandchild concepts, and so on.
The semantic convergence score of a concept C1 centred on a concept C2 is calculated in several phases which are detailed below: 1) determination of the common characteristics: a count is made of the number of defined characteristics of each path from the ppcg on each path of the central concept C2. The paths of the concept C1 are converged with the paths of the ppcg, so that they have a maximum number of common characteristics. The size of the common part is denoted Tpc. 2) each number of characteristics is enriched by the undefined characteristics of a path of the central concept C2: in practice, by definition, the central concept C2 has its undefined characteristics in common with each of its generalizers, therefore with the ppcg. This number is then standardized over the depth of the hierarchy to obtain a proximity ratio value PR:(Tpc+Ph−|path of C2|)/Ph=PR. 3) each defined characteristic of the concept C1 absent from the ppcg is taken into account to penalize the proximity ratio PR, which makes it possible to take account of the separation from C1 to the ppcg. The penalty value retained is 0.002. The proximity score on a path PN satisfies the relation:PN=PR−0.002|other characteristics of C1|. 4) any proximity score on a negative path PN is considered as zero. 5) the semantic proximity score SPN is the average of the scores on a path PNi: SPN= PNi. With reference to the hierarchy of concepts represented in FIG. 1, of depth Ph=4, the semantic proximity score of the concept C1=A(“1111”, “1121”) centred on the concept C2=I(“211”, “1311”) is calculated below: ppcg on “211”=T and ppcg on “1131”=C(“11”); length of the common characteristics 0 and 2; proximity ratios: PR1+(0+4−3)/4=1/4 and PR2=(2+4−4) 4=1/2; scores on a path: PN1=¼−(0.002×4)=0.242 and PN2=1/2−0.002×2=0.496; semantic proximity score of C1 centred on C2: SPN=(0.242+0.496)/2=0.369.
The semantic proximity score of each concept of the hierarchy of concepts represented in FIG. 1, centred on the concept I is given in the table T1 below.
TABLE T1IAverage (((3 + 4 − 3)/4) − 0, ((4 + 4 − 4)/4 − 0) = 1HAverage (((2 + 4 − 3)/4) − 0, ((3 + 4 − 4)/4 − 0) = 0.75CAverage (((0 + 4 − 3)/4) − 0.004, ((2 + 4 − 4)/4 − 0) = 0.373BAverage (((0 + 4 − 3)/4) − 0.006, ((2 + 4 − 4)/4 − 0.002) = 0.371EAverage (((0 + 4 − 3)/4) − 0.006, ((2 + 4 − 4)/4 − 0.002) = 0.371AAverage (((0 + 4 − 3)/4) − 0.008, ((2 + 4 − 4)/4 − 0.004) = 0.369FAverage (((0 + 4 − 3)/4) − 0.008, ((2 + 4 − 4)/4 − 0.004) = 0.369GAverage (((1 + 4 − 3)/4) − 0,0 = 0.25DAverage (((0 + 4 − 3)/4) − 0.002, ((1 + 4 − 4)/4 − 0) = 0.249
The abovementioned semantic proximity score does not represent a distance, for example in number of arcs, between two concepts C1 and C2, because, to take account of the semantic constraints, the calculation of this score is not symmetrical but oriented to C1 or C2. For a more detailed explanation of this choice, reference can usefully be made to the abovementioned thesis.
The abovementioned numbering process does not give access to the other information of the ontology that can appear in a saturated version of the ontology. Thus, neither the exclusion constraints, nor the defined rules on the n-ary predicates, nor the typing constraints are taken into account.
Furthermore, there is currently no simple and cheap to implement way of calculating and encoding concept proximity scores that is representative both of the semantic proximity and of the spatial proximity of these concepts.
In the currently known techniques, the distance scores mainly favour the semantic aspect, which is very important for reasoning on a request, but they do not significantly take into account the spatial convergence of the concepts, within the graph of concepts, which is necessary for a better representation of the ontology. Calculating and encoding spatial distance scores currently entail expensive courses through the various concepts of the ontology. |
Understanding identity integration: Theoretical, methodological, and applied issues.
Identity integration is one of the foundational theoretical concepts in Erikson's (1968) theory of lifespan development. However, the topic is understudied relative to its theoretical and practical importance. The extant research is limited in quantity and scope, and there is considerable heterogeneity in how identity integration is conceptualized and measured. Accordingly, the purpose of this paper is to 1) provide a conceptual discussion of different forms of identity integration 2) highlight the different methodological approaches represented in the literature, and 3) detail the implications of integration for psychological functioning. In particular, we provide a conceptual and methodological discussion of four forms of integration: two that are widely recognized, contextual integration and temporal integration, and two that have received less attention, ego integration and person-society integration. We see this paper as filling a need in the literature for those interested in how complex identity processes are related to psychological functioning. |
Activation of the skeletal muscle Ca2+ release channel by the triazine dyes cibacron blue F3A-G and reactive red 120.
Vesicle-45Ca2+ ion flux and planar lipid bilayer single-channel measurements have shown that the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (SR) is activated by micromolar concentrations of Cibacron Blue F3A-G (Reactive Blue 2) and Reactive Red 120. Cibacron Blue increased the 45Ca2+ efflux rate from heavy SR vesicles by apparently interacting with both the adenine nucleotide and caffeine activating sites of the channel. Dye-induced 45Ca2+ release was inhibited by Mg2+ and ruthenium red. In single channel recordings with the purified channel protein complex, Cibacron Blue increased the open time of the Ca2+ release channel without an apparent change in the conductance of the main and subconductance states of the channel. |
McCoy was a perfect 4-for-4 Friday night when going for the 10 points she needed to reach 1,000 for her career.
McCoy’s game-high 21 points put her career total at 1,011 and it more importantly sparked Cranford to a more-than-convincing 59-39 Union County Conference-Watchung Division victory over Scotch Plains.
A four-year starter who will continue playing in college next year at Division 3 Case Western Reserve, McCoy made all four of her shots in the first quarter to exactly get to 1,000. With seven points already produced on her first three shots, McCoy’s second 3-pointer – from the top of the key right before the first quarter buzzer – sealed the deal.
“When she hit that shot she said, ‘that was it?’ Before the game started we talked about how excited we were for her,” Cranford sixth-year head coach Jackie Dyer said.
McCoy was the second player under Dyer’s tutelage to reach and pass 1,000 career points. Present Lafayatte College freshman player Morgan Miller was the first. Miller did so last year in a 61-44 conference-crossover home win over Scotch Plains, scoring a tied for team-high 15 points to exactly reach 1,000. Miller scored points 999 and 1,000 on a late third quarter drive through the lane.
Friday night against Scotch Plains, Cranford jumped out to a quick 7-0 lead, with senior guard Jenna Goeller scoring the game’s first five points right before McCoy scored inside.
Scotch Plains, behind four points from junior guard Madison Maisel and three from senior guard Taylor Sebolao, came back to tie the game at 9-9.
In Thursday night’s 60-50 Watchung Division home setback to Linden, Sebolao – also a four-year starter – reached and passed 1,000 career points after pouring in 19 to give her 1,003. Against Cranford, Sebolao paced Scotch Plains with 15 points, 11 of those coming in the second half.
McCoy’s second shot was a 3-pointer from the top of the key that give Cranford its second lead at 12-9.
Maisel then hit her second 3-pointer to tie the game again at 12-12.
With 30 seconds left in the first quarter, McCoy gave the Cougars the lead for good at 14-12 when her third shot – a one-hander in the lane – swished through the net.
Cranford got the ball back and McCoy stepped up right in front of the 3-point line once more. She let go of her fourth shot and – again – didn’t miss, giving the Cougars a 17-12 lead going into the second quarter.
McCoy had 15 points at the half – making 6-of-7 first half shots that included three 2-pointers and three 3s – as Cranford led 32-20 at intermission.
“We didn’t force anything and just did what we were supposed to do,” Dyer said. “Jess didn’t let it (going for 1,000 points) get her nervous and she played her game.”
In the game’s first minute alone – when Cranford produced its opening 7-0 lead to prompt a Scotch Plains timeout – McCoy already had two points, one assist, one steal and two rebounds, one on both offense and defense.
McCoy came to play and didn’t let going for 1,000 points become a distraction at all to her or her team’s performance.
McCoy, who is not only Cranford’s leading scorer with a 14-point average, but also – again – leads the team in rebounds with an average of eight, had seven rebounds and one blocked shot in the first half.
“Jess has always been a big scorer, but a silent scorer,” Dyer said. “This year when she gets into the rhythm of scoring, when she scores her first basket, she gets going and usually gets everyone else going.
“She’s also been our leading rebounder since she was a freshman.”
Cranford improved to 8-3 overall with its second straight win and is now 5-2 in the Watchung Division. The Cougars bounced back from a rare three-game losing streak by defeating Union 49-38 at home in Watchung Division play Thursday. Union entered the game 7-3 and on a three-game winning streak that included a 51-39 division home win over Governor Livingston.
“We kind of hit a little bump in the road,” said Dyer, with Cranford going from 6-0 to 6-3 after division road losses to Roselle Catholic and Linden and a non-conference home setback to North Hunterdon in between. “I’m very proud that the girls didn’t let it get the best of them.”
Bouncing back to beat a red-hot Union team and limiting the Farmers to under 40 points was a solid way to snap the losing streak.
“Against Union our defense was phenomenal and it carried over against Scotch Plains,” Dyer said.
Scotch Plains lost for the third straight time to slip to 5-5 overall and 2-5 in the Watchung Division. The teams are scheduled to play their second division game against each other on Feb. 5 at 7 p.m. at Cranford’s Martin Gymnasium.
NOTES: Cranford played without junior forward Carly Maucione, who was out with a leg injury, while Scotch Plains was without starter Katie Harper, a junior guard who had to sit out a suspension after being ejected from Thursday’s game against Linden. |
Harold Thomas Martin III
#REDIRECT Harold T. Martin III |
2003 A 3D host-immune-tumor system
Recent advances in oncology lead to promote the role of the tumor micro-environment in tumor growth [1] . In fact, mathematical cancer model taking into account normal (healthy) cells - thus the micro-environment - interacting with immune and tumor cells are not numerous. There is one proposed by Owen and Sherratt [2] which remains mainly focused on tumor–macrophage interactions, the normal cells being only considered for their ability to colonize the site studied. One of the most interesting models seems to be the model proposed by Lisette De Pillis and Ami Radunskaya [3] which
incorporates host,immune and tumor cells to reproduce certain qualitative aspects as oscillations in tumor size(Jeff’s phenomenon) [4] or tumor dormancy [5]. This model is rather generic in the sense that it is not specific to a given type of cancer. It is indeed based on quite common interactions between host, immune and tumor cells.The model is
where x designates the normalized population of host cells, y being the
population of effector immune cells and z the population of tumor cells. Tumor cells compete for resources with the two other populations of cells. From that point of view, they are the ``generalist’’ competitors while the two others are ``specific competitors’’.
This model produces a chaotic attractor for the set of parameter values as
follows [6] |
The City of Plattsburgh is one step closer to getting a makeover in its downtown.
City officials recently submitted plans to New York State for it’s revitalization project; Plattsburgh secured $10-million from the state.
Some of the work proposed includes turning the Durkee Street parking lot into a multi-use building and park.
The plans have been in the making for nearly 20 years.
“You know we started this process looking at 15 plans over 18 years all of those plans had merits and things that still hold true but we never had the support or push from the state so to varying degrees we were unable to carry them out but now we have this wonderful opportunity,” said Community Development Director Paul DeDominicas.
The approval process is being described as speedy– if the plans are approved, construction should begin this summer. |
{-# LANGUAGE OverloadedStrings #-}
{-# LANGUAGE QuasiQuotes #-}
module DrawingTests
( tests
, testDrawing
, testLineChartSpace
) where
import Control.Lens
import Data.ByteString.Lazy (ByteString)
import Test.Tasty (testGroup, TestTree)
import Test.Tasty.HUnit (testCase)
import Text.RawString.QQ
import Text.XML
import Codec.Xlsx
import Codec.Xlsx.Types.Internal
import Codec.Xlsx.Writer.Internal
import Common
import Diff
tests :: TestTree
tests =
testGroup
"Drawing tests"
[ testCase "correct drawing parsing" $
[testDrawing] @==? parseBS testDrawingFile
, testCase "write . read == id for Drawings" $
[testDrawing] @==? parseBS testWrittenDrawing
, testCase "correct chart parsing" $
[testLineChartSpace] @==? parseBS testLineChartFile
, testCase "parse . render == id for line Charts" $
[testLineChartSpace] @==? parseBS (renderChartSpace testLineChartSpace)
, testCase "parse . render == id for area Charts" $
[testAreaChartSpace] @==? parseBS (renderChartSpace testAreaChartSpace)
, testCase "parse . render == id for bar Charts" $
[testBarChartSpace] @==? parseBS (renderChartSpace testBarChartSpace)
, testCase "parse . render == id for pie Charts" $
[testPieChartSpace] @==? parseBS (renderChartSpace testPieChartSpace)
, testCase "parse . render == id for scatter Charts" $
[testScatterChartSpace] @==? parseBS (renderChartSpace testScatterChartSpace)
]
testDrawing :: UnresolvedDrawing
testDrawing = Drawing [anchor1, anchor2]
where
anchor1 =
Anchor
{_anchAnchoring = anchoring1, _anchObject = pic, _anchClientData = def}
anchoring1 =
TwoCellAnchor
{ tcaFrom = unqMarker (0, 0) (0, 0)
, tcaTo = unqMarker (12, 320760) (33, 38160)
, tcaEditAs = EditAsAbsolute
}
pic =
Picture
{ _picMacro = Nothing
, _picPublished = False
, _picNonVisual = nonVis1
, _picBlipFill = bfProps
, _picShapeProperties = shProps
}
nonVis1 =
PicNonVisual $
NonVisualDrawingProperties
{ _nvdpId = DrawingElementId 0
, _nvdpName = "Picture 1"
, _nvdpDescription = Just ""
, _nvdpHidden = False
, _nvdpTitle = Nothing
}
bfProps =
BlipFillProperties
{_bfpImageInfo = Just (RefId "rId1"), _bfpFillMode = Just FillStretch}
shProps =
ShapeProperties
{ _spXfrm = Just trnsfrm
, _spGeometry = Just PresetGeometry
, _spFill = Nothing
, _spOutline = Just $ def {_lnFill = Just NoFill}
}
trnsfrm =
Transform2D
{ _trRot = Angle 0
, _trFlipH = False
, _trFlipV = False
, _trOffset = Just (unqPoint2D 0 0)
, _trExtents =
Just
(PositiveSize2D
(PositiveCoordinate 10074240)
(PositiveCoordinate 5402520))
}
anchor2 =
Anchor
{ _anchAnchoring = anchoring2
, _anchObject = graphic
, _anchClientData = def
}
anchoring2 =
TwoCellAnchor
{ tcaFrom = unqMarker (0, 87840) (21, 131040)
, tcaTo = unqMarker (7, 580320) (38, 132480)
, tcaEditAs = EditAsOneCell
}
graphic =
Graphic
{ _grNonVisual = nonVis2
, _grChartSpace = RefId "rId2"
, _grTransform = transform
}
nonVis2 =
GraphNonVisual $
NonVisualDrawingProperties
{ _nvdpId = DrawingElementId 1
, _nvdpName = ""
, _nvdpDescription = Nothing
, _nvdpHidden = False
, _nvdpTitle = Nothing
}
transform =
Transform2D
{ _trRot = Angle 0
, _trFlipH = False
, _trFlipV = False
, _trOffset = Just (unqPoint2D 0 0)
, _trExtents =
Just
(PositiveSize2D
(PositiveCoordinate 10074240)
(PositiveCoordinate 5402520))
}
testDrawingFile :: ByteString
testDrawingFile = [r|
<?xml version="1.0" encoding="UTF-8" standalone="yes"?>
<xdr:wsDr xmlns:xdr="http://schemas.openxmlformats.org/drawingml/2006/spreadsheetDrawing" xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" xmlns:r="http://schemas.openxmlformats.org/officeDocument/2006/relationships">
<xdr:twoCellAnchor editAs="absolute">
<xdr:from>
<xdr:col>0</xdr:col><xdr:colOff>0</xdr:colOff>
<xdr:row>0</xdr:row><xdr:rowOff>0</xdr:rowOff>
</xdr:from>
<xdr:to>
<xdr:col>12</xdr:col><xdr:colOff>320760</xdr:colOff>
<xdr:row>33</xdr:row><xdr:rowOff>38160</xdr:rowOff>
</xdr:to>
<xdr:pic>
<xdr:nvPicPr><xdr:cNvPr id="0" name="Picture 1" descr=""/><xdr:cNvPicPr/></xdr:nvPicPr>
<xdr:blipFill><a:blip r:embed="rId1"></a:blip><a:stretch/></xdr:blipFill>
<xdr:spPr>
<a:xfrm><a:off x="0" y="0"/><a:ext cx="10074240" cy="5402520"/></a:xfrm>
<a:prstGeom prst="rect"><a:avLst/></a:prstGeom><a:ln><a:noFill/></a:ln>
</xdr:spPr>
</xdr:pic>
<xdr:clientData/>
</xdr:twoCellAnchor>
<xdr:twoCellAnchor editAs="oneCell">
<xdr:from>
<xdr:col>0</xdr:col><xdr:colOff>87840</xdr:colOff>
<xdr:row>21</xdr:row><xdr:rowOff>131040</xdr:rowOff>
</xdr:from>
<xdr:to>
<xdr:col>7</xdr:col><xdr:colOff>580320</xdr:colOff>
<xdr:row>38</xdr:row><xdr:rowOff>132480</xdr:rowOff>
</xdr:to>
<xdr:graphicFrame>
<xdr:nvGraphicFramePr><xdr:cNvPr id="1" name=""/><xdr:cNvGraphicFramePr/></xdr:nvGraphicFramePr>
<xdr:xfrm><a:off x="0" y="0"/><a:ext cx="10074240" cy="5402520"/></xdr:xfrm>
<a:graphic>
<a:graphicData uri="http://schemas.openxmlformats.org/drawingml/2006/chart">
<c:chart xmlns:c="http://schemas.openxmlformats.org/drawingml/2006/chart" r:id="rId2"/>
</a:graphicData>
</a:graphic>
</xdr:graphicFrame>
<xdr:clientData/>
</xdr:twoCellAnchor>
</xdr:wsDr>
|]
testWrittenDrawing :: ByteString
testWrittenDrawing = renderLBS def $ toDocument testDrawing
testLineChartFile :: ByteString
testLineChartFile = [r|
<?xml version="1.0" encoding="UTF-8" standalone="yes"?>
<c:chartSpace xmlns:c="http://schemas.openxmlformats.org/drawingml/2006/chart" xmlns:a="http://schemas.openxmlformats.org/drawingml/2006/main" xmlns:r="http://schemas.openxmlformats.org/officeDocument/2006/relationships">
<c:chart>
<c:title>
<c:tx><c:rich><a:bodyPr rot="0" anchor="b"/><a:p><a:r><a:t>Line chart title</a:t></a:r></a:p></c:rich></c:tx>
</c:title>
<c:plotArea>
<c:lineChart>
<c:grouping val="standard"/>
<c:ser>
<c:idx val="0"/><c:order val="0"/>
<c:tx><c:strRef><c:f>Sheet1!$A$1</c:f></c:strRef></c:tx>
<c:spPr>
<a:solidFill><a:srgbClr val="0000FF"/></a:solidFill>
<a:ln w="28800"><a:solidFill><a:srgbClr val="0000FF"/></a:solidFill></a:ln>
</c:spPr>
<c:marker><c:symbol val="none"/></c:marker>
<c:val><c:numRef><c:f>Sheet1!$B$1:$D$1</c:f></c:numRef></c:val>
<c:smooth val="0"/>
</c:ser>
<c:ser>
<c:idx val="1"/><c:order val="1"/>
<c:tx><c:strRef><c:f>Sheet1!$A$2</c:f></c:strRef></c:tx>
<c:spPr>
<a:solidFill><a:srgbClr val="FF0000"/></a:solidFill>
<a:ln w="28800"><a:solidFill><a:srgbClr val="FF0000"/></a:solidFill></a:ln>
</c:spPr>
<c:marker><c:symbol val="none"/></c:marker>
<c:val><c:numRef><c:f>Sheet1!$B$2:$D$2</c:f></c:numRef></c:val>
<c:smooth val="0"/>
</c:ser>
<c:marker val="0"/>
<c:smooth val="0"/>
</c:lineChart>
</c:plotArea>
<c:plotVisOnly val="1"/>
<c:dispBlanksAs val="gap"/>
</c:chart>
</c:chartSpace>
|]
oneChartChartSpace :: Chart -> ChartSpace
oneChartChartSpace chart =
ChartSpace
{ _chspTitle = Just $ ChartTitle (Just titleBody)
, _chspCharts = [chart]
, _chspLegend = Nothing
, _chspPlotVisOnly = Just True
, _chspDispBlanksAs = Just DispBlanksAsGap
}
where
titleBody =
TextBody
{ _txbdRotation = Angle 0
, _txbdSpcFirstLastPara = False
, _txbdVertOverflow = TextVertOverflow
, _txbdVertical = TextVerticalHorz
, _txbdWrap = TextWrapSquare
, _txbdAnchor = TextAnchoringBottom
, _txbdAnchorCenter = False
, _txbdParagraphs =
[TextParagraph Nothing [RegularRun Nothing "Line chart title"]]
}
renderChartSpace :: ChartSpace -> ByteString
renderChartSpace = renderLBS def {rsNamespaces = nss} . toDocument
where
nss =
[ ("c", "http://schemas.openxmlformats.org/drawingml/2006/chart")
, ("a", "http://schemas.openxmlformats.org/drawingml/2006/main")
]
testLineChartSpace :: ChartSpace
testLineChartSpace = oneChartChartSpace lineChart
where
lineChart =
LineChart
{ _lnchGrouping = StandardGrouping
, _lnchSeries = series
, _lnchMarker = Just False
, _lnchSmooth = Just False
}
series =
[ LineSeries
{ _lnserShared =
Series
{ _serTx = Just $ Formula "Sheet1!$A$1"
, _serShapeProperties = Just $ rgbShape "0000FF"
}
, _lnserMarker = Just markerNone
, _lnserDataLblProps = Nothing
, _lnserVal = Just $ Formula "Sheet1!$B$1:$D$1"
, _lnserSmooth = Just False
}
, LineSeries
{ _lnserShared =
Series
{ _serTx = Just $ Formula "Sheet1!$A$2"
, _serShapeProperties = Just $ rgbShape "FF0000"
}
, _lnserMarker = Just markerNone
, _lnserDataLblProps = Nothing
, _lnserVal = Just $ Formula "Sheet1!$B$2:$D$2"
, _lnserSmooth = Just False
}
]
rgbShape color =
def
{ _spFill = Just $ solidRgb color
, _spOutline =
Just $
LineProperties {_lnFill = Just $ solidRgb color, _lnWidth = 28800}
}
markerNone =
DataMarker {_dmrkSymbol = Just DataMarkerNone, _dmrkSize = Nothing}
testAreaChartSpace :: ChartSpace
testAreaChartSpace = oneChartChartSpace areaChart
where
areaChart =
AreaChart {_archGrouping = Just StandardGrouping, _archSeries = series}
series =
[ AreaSeries
{ _arserShared =
Series
{ _serTx = Just $ Formula "Sheet1!$A$1"
, _serShapeProperties =
Just $
def
{ _spFill = Just $ solidRgb "000088"
, _spOutline = Just $ def {_lnFill = Just NoFill}
}
}
, _arserDataLblProps = Nothing
, _arserVal = Just $ Formula "Sheet1!$B$1:$D$1"
}
]
testBarChartSpace :: ChartSpace
testBarChartSpace =
oneChartChartSpace
BarChart
{ _brchDirection = DirectionColumn
, _brchGrouping = Just BarStandardGrouping
, _brchSeries =
[ BarSeries
{ _brserShared =
Series
{ _serTx = Just $ Formula "Sheet1!$A$1"
, _serShapeProperties =
Just $
def
{ _spFill = Just $ solidRgb "000088"
, _spOutline = Just $ def {_lnFill = Just NoFill}
}
}
, _brserDataLblProps = Nothing
, _brserVal = Just $ Formula "Sheet1!$B$1:$D$1"
}
]
}
testPieChartSpace :: ChartSpace
testPieChartSpace =
oneChartChartSpace
PieChart
{ _pichSeries =
[ PieSeries
{ _piserShared =
Series
{ _serTx = Just $ Formula "Sheet1!$A$1"
, _serShapeProperties = Nothing
}
, _piserDataPoints =
[ def & dpShapeProperties ?~ solidFill "000088"
, def & dpShapeProperties ?~ solidFill "008800"
, def & dpShapeProperties ?~ solidFill "880000"
]
, _piserDataLblProps = Nothing
, _piserVal = Just $ Formula "Sheet1!$B$1:$D$1"
}
]
}
where
solidFill color = def & spFill ?~ solidRgb color
testScatterChartSpace :: ChartSpace
testScatterChartSpace =
oneChartChartSpace
ScatterChart
{ _scchStyle = ScatterMarker
, _scchSeries =
[ ScatterSeries
{ _scserShared =
Series
{ _serTx = Just $ Formula "Sheet1!$A$2"
, _serShapeProperties =
Just $ def {_spOutline = Just $ def {_lnFill = Just NoFill}}
}
, _scserMarker = Just $ DataMarker (Just DataMarkerSquare) Nothing
, _scserDataLblProps = Nothing
, _scserXVal = Just $ Formula "Sheet1!$B$1:$D$1"
, _scserYVal = Just $ Formula "Sheet1!$B$2:$D$2"
, _scserSmooth = Nothing
}
]
}
|
Q:
Crystal Reports.FormulaException: This field name is not known
I've completed my search of similarly titled posts and nothing seems to relate to my problem.
I'm using Oracle, so I have to create an XML Strongly Typed DataSet which I have done. I have used that DataSet as the DataExplorer's Source for report data.
My DataSet contains fields that are primarily for the Page Header, as the fields in the Details sections are related to the fields in the Page Header, so I have added columns to the dataset that are repeated for each detail row, but contain data for the page header. (I've done this before)
My problem is that when I want to suppress an ITextObject Label in the PageHeader using a value in one of the PageHeader fields (if {dataset.fieldName} = " " then true else false) I get this error;
CrystalDecisions.CrystalReports.Engine.FormulaException: This field name is not known.
Details: errorKind
If I don't include the formulas, the report prints fine, but all ITextObject labels are present, regardless of data, and I get the paging/sections that I want, but I can't seem to set suppress formulas using any field that isn't the one related to the IFieldObject.
I'm using
WIN2008
VS2010
CR4VS2010 13.0.4
and I can't update as it's not owned by my company.
I've done the following:
repaired VS2010
remove and reinstall CR
install CR Runtime (32bit 13.0.4)
removed the formulas and re run the report (works fine)
TL;DR: I want to use an IFieldObject in a Suppress formula for an ITextObject as well as the Suppress formula for an entire section, but am getting the above error.
A:
Thanks again for the reply, @heringer. I found the problem was related to the database I was connecting to. It's not visible in the application as the connection string is stored in the application configuration file, there are 3 database versions, only one of which was updated with the new datafield names. I was inadvertently connecting to another database that had not yet received the update, due to an untimely check-in of the app.config file. It was, of course, the last thing I looked for because I couldn't conceive of me trying to develop something new in a non-dev database!. Case Closed.
|
© Pascal Rossignol/Reuters
About the author
Feargus O'Sullivan is a contributing writer to CityLab, covering Europe. His writing focuses on housing, gentrification and social change, infrastructure, urban policy, and national cultures. He has previously contributed to The Guardian, The Times, The Financial Times, and Next City, among other publications.
France may have a tradition of boisterous protest, but this weekend's mass demonstrations against gas tax increases have still managed to take the country by surprise.On Saturday and Sunday, at least 280,000 protesters took to the streets in urban, suburban, and rural communities across the country, burning cars, blockading highways and fuel depots, and engaging in battles with police and motorists as they demonstrated against planned rises in gas and diesel taxes. So far, over 400 people have been injured in the Gilets Jaunes (Yellow Vests) movement - so named because the protesters are wearing the high-viz vests that French drivers are obliged to carry in case of emergencies. On Saturday, one was even killed after being run over by a panicked driver. The movement shows no signs of letting up, however, with protests continuing Monday and more major protest days planned for later in the month.It's not just the protests' fierceness and geographic spread that have taken the country by surprise - French media reported. Having organized themselves via social media since May (when the movement was sparked by an online petition ), the Yellow Vests have arrived somewhat out of the blue.There is also no clear media consensus as to what they are protesting beyond the cost of gas. To some observers, the protesters are primarily angry about what they see as President Emmanuel Macron's apparent indifference toward tough conditions for working people. To others, the movement is evidence of a middle-class backlash. Meanwhile, it's not automatically easy to say whether the protest cleaves more to the left or the right.The core issue that the Yellow Vests have rallied around is clear enough, at least. Earlier this year, Macron announced tax increases on fuel, due to be introduced in January. If the plans go ahead, gas taxes will rise by €0.029 per liter ($0.12 a gallon) and taxes on diesel - a fuel once heavily promoted in France that is now being proactively phased out - will rise to €0.065 a liter ($0.24 a gallon). These taxes come on the heels of already steep rises in fuel costs over the past few years,The tax rises appear to fit within a pro-Green agenda espoused by Macron's government, in a country where attitudes to road transit and carbon emissions are changing fast. Macron has already pledged to ban all gasoline-fueled cars by 2040, and it seems that local authorities are getting on board with the changes needed to meet that goal. This month, most of the Paris region pledged to start phasing out all but the newest diesel and gas-fueled vehicles.A cross-party consensus seems to be developing on these issues, but in protesting the government's planned tax rises, the Gilets Jaunes have avoided an explicitly anti-Green stance. They have pointed out that, while the rises are being presented partly as a form of carbon tax promoting a shift toward cleaner energy sources, only 20 percent of the tax actually goes toward supporting the country's transition to cleaner energy. The fact that France's fuel taxes are not the highest in Europe , and are actually lower than Germany's, doesn't change the widely felt impression that drivers are being squeezed by a government that is not entirely practicing what it preaches.Given the scale of the protests and the speed at which the movement has grown, there's still likely more powering the anger of the Gilets Jaunes than just the cost of fuel alone. The group doesn't seem to be an obvious worker's group. It has gained the support of both leftist presidential hopeful Jean-Luc Mélenchon and some representatives of the right-wing Republican Party, for example, but has not yet been endorsed by any of France's labor unions, or by truck drivers . And while the protesters have grouped around a single issue, there seems a risk that the movement's lack of explicit politics could place it at risk of being highjacked. Already people taking part in some protests have engaged in ugly racist and homophobic abuse against passers-by that, while still atypical of the demonstrations as a whole, suggest |
There are many examples of medical devices having distal portions for inserting into subjects' bodies. For example, the distal portion of an endoscope is advanced into a body lumen (such as the gastrointestinal tract) in order to visualize and/or record an image from inside the lumen. A colonoscope is an endoscope, a distal portion of which is inserted into the colon for visualizing and/or recording an image of the colon.
PCT Publication WO 05/065044 to Cabiri et al., describes apparatus for use with a biologically compatible fluid pressure source. The apparatus includes an elongate carrier, adapted to be inserted through a proximal opening of a body lumen, and a piston head coupled to a distal portion of the carrier. The piston head is adapted to form a pressure seal with a wall of the lumen after the carrier has been inserted into the lumen, and to be advanced distally through the body lumen in response to pressure from the fluid pressure source. The apparatus is configured to facilitate distal advancement of the piston head by facilitating passage of fluid out of the lumen from a site within the lumen distal to the piston head. The apparatus additionally includes an optical system, coupled to the carrier in a vicinity of the distal portion, the optical system having distal and proximal ends.
U.S. Pat. No. 4,306,446 to Fukuda describes apparatus for estimating the locality of a leaking spot in a pipeline which conveys a fluid, the apparatus comprising: a pair of detectors located on the pipeline at positions spaced from each other by a certain distance and adapted to detect pressures and pressure gradients at the respective positions; and an operating unit adapted to calculate the locality of a leaking spot on the basis of the pressure gradients and mean pressures as obtained by memory-holding the pressures.
U.S. Pat. No. 5,660,198 to Maclaren, describes a control system for monitoring and regulating fluid pressure at a remote and/or potentially hazardous location along the length of a fluid flow conduit, without requiring a pressure sensor device at the remote site. The control system comprises a controller responsive to fluid pressure and flow rate readings taken at a convenient and/or safe location along the length of the flow conduit, to derive fluid pressure at the remote site. The controller provides a display of the derived pressure and/or operates a control valve at the safe site to regulate the pressure at the remote site. |
Q:
Getting the top length of a key in Python
Possible Duplicate:
Find longest (string) key in dictionary
Without folding. Example:
from functools import reduce
dict = {'t1': 'test1', 'test2': 't2'}
print(len(reduce(lambda x, y: x if len(x) >= len(y) else y, dict.keys())))
Is there any way to get the longest key's length in a a dictionary (preferably in one line)? There's nothing wrong with folding but I'm just interested if there's another way to do it in Python 3.
A:
You can simply do
max(map(len, my_dict))
This will take the lengths of all keys and extract the maximum of these lengths.
To get the longest key itself, use
max(my_dict, key=len)
|
P53 (Pro72Arg) polymorphism associated with the risk of oral squamous cell carcinoma in gutka, niswar and manpuri addicted patients of Pakistan.
The chewing habit of paan, chhaliya, and tobacco is common in the traditional culture of Pakistan. Currently, niswar, gutka and manpuri are also commercially available in the Pakistani market. Epidemiologic evidences and increased rate of oral squamous cell carcinoma (OSCC) cases may indicate a direct relationship of these chewing habits with oral carcinogenesis. The p53 gene has been known to be a tumor suppressor gene that is found mutated in common human cancers. The p53 gene contains a single nucleotide polymorphism at codon 72 of exon 4 which encodes either proline (Pro) or arginine (Arg). The aim of the present study was to investigate association of p53 gene codon 72 polymorphism with patients of oral squamous cell carcinoma consuming these carcinogenic chewable materials. Blood and tissue samples of 260 OSCC patients were collected with informed consent from the local hospitals of Karachi. The patients were compared with controls of similar age and sex. The exon 4 of p53 gene was examined by PCR-SSCP. The tumor samples showing mobility shift were purified and sequenced. The C>G missense mutation at nucleotide position 215 of the coding sequence was identified which substitutes proline with arginine at codon 72 of p53 protein. When the data for CCC72CGC polymorphism was analyzed statistically, a significant difference was observed between OSCC and control samples. The Pro allelic frequencies were significantly higher in OSCC patients as compare to controls. The current study indicated the Pro form of p53 codon 72 increases the risk of developing OSCC in Pakistani population. The risk ratio for Pro allele was 1.5004 (95% confidence interval: 1.2559 to 1.7924) and odds ratio of Pro allele was 2.389 (95% confidence interval: 1.5591 to 2.8137) in comparison with the Arg and Pro alleles in the OSCC group. These evidences suggest that there may be specific genetic targets with these chewing ingredients that are responsible for causing OSCC. The p53 codon 72 polymorphism is associated with OSCC at somatic cell level but the polymorphism was not associated at inherited level. |
There hasn't been a lack of strange things turning up in the Ashley Madison data leak. One of the latest discoveries comes from Trend Micro, which found bogus Ashley Madison profiles that used email addresses the company created solely for collecting spam samples. |
Sell my home fast: find a realtor
If you are on a mission to sell my home fast, find a realtor who specializes in marketing quick sales as he or she will have the experience you need.
Selling your home can be a long and drawn out process. Inspections, appraisals and house showings are all components of the process. If you want to sell your home fast and find a realtor, you must research your options carefully. You should also consider the status of the current market in order to find the best realtor who can help you complete the home sale.
Home sales take an average of eight months. If you want to speed up the process search for a realtor who specializes in quick sales and creative marketing. You need a listing agent who knows how to price a house to sell quickly and advertise it as a quick sale.
When you want to sell a home fast, half of the process is choosing a real estate agent who fits your needs and personality. Shop around. Make sure that the person you hire is a member of the National Association of Realtors (NAR). Realtors differ from real estate agents in that they must be official members of the NAR and must follow the organization's strict ethics and codes when working with a client. Set up consultations with a few chosen realtors to determine if your working styles are similar. If you want to sell your home fast, you and your chosen realtor must be able to work together swiftly and efficiently. A realtor who does not mesh well with your standards will slow down your home-selling process.
After hiring a realtor, you must get your home ready for visitors. A large part of selling a home involves the use of visuals. If your home is not particularly eye-catching, you may have trouble selling it. Most home buyers will not submit an offer if your home seems to need a lot of work. Clearing clutter from your home is one of the most important steps. Each room should give off an aura of cleanliness and serenity when a potential buyer walks in. If you need help, hire a professional organizer to help you remove clutter and stage your home. When you want to sell a home fast, find a realtor who is honest about the look and feel of your home. He or she knows what buyers want to see.
To talk with prospective realtors today, go to RealtyNow. A professional will provide home values and tips to get your home ready to sell. |
[[Image:Annunciation.jpg|right|frame|The Annunciation to the Theotokos]]
[[Image:Annunciation.jpg|right|frame|The Annunciation to the Theotokos]]
−
The '''Annunciation''' (or ''Evangelismos'' in Greek) to the [[Theotokos]] is one of the [[Great Feasts]] of the [[Orthodox Church]], celebrated on [[March 25]]. Greeks also celebrate [[Greek Independence Day]] this day. This is one of only two days during [[Great Lent|Lent]], the other being [[Palm Sunday]], when fish is permitted.
+
The '''Annunciation''' (or ''Evangelismos'' in Greek) to the [[Theotokos]] is one of the [[Great Feasts]] of the [[Orthodox Church]], celebrated on [[March 25]]. Greeks also celebrate Greek Independence Day this day. This is one of only two days during [[Great Lent|Lent]], the other being [[Palm Sunday]], when fish is permitted.
−
According to the [[Gospel of Luke]] 1:26-38, the [[Archangel Gabriel]] appeared to [[Theotokos|Mary]] to announce to her that she would conceive and bear a son, even though she "knew no man." According to holy tradition Mary had come home to her parents when she was only fifteen when she was visited by Gabriel.
+
According to the [[Gospel of Luke]] 1:26-38, the [[Archangel Gabriel]] appeared to Mary to announce to her that she would conceive and bear a son, even though she "knew no man." According to holy tradition Mary had come home to her parents when she was only fifteen when she was visited by Gabriel.
−
This date was selected by the [[Church Fathers]] to be exactly nine months ahead of [[Nativity|Christmas]], indicating that Christ was conceived in perfection at that time "of the [[Holy Spirit]] and the [[Theotokos|Virgin Mary]]," as stated in the [[Nicene-Constantinopolitan Creed]].
+
This date was selected by the [[Church Fathers]] to be exactly nine months ahead of the [[Nativity]] of Our Lord (or vice-versa?), indicating that Christ was conceived in perfection at that time "of the [[Holy Spirit]] and the Virgin Mary," as stated in the [[Nicene-Constantinopolitan Creed]].
Many men and women in Greece are named for this event and celebrate their [[name day]] on this date.
Many men and women in Greece are named for this event and celebrate their [[name day]] on this date.
Line 13:
Line 13:
==Celebration of the feast==
==Celebration of the feast==
−
The feast of the Annunciation normally falls during the season of [[Great Lent]], but it is still a joyous day. Many lessen their [[fast]] with fish on this day.
+
The feast of the Annunciation normally falls during the season of [[Great Lent]], but it is still a joyous day. The [[fast]] is lessened, with fish allowed on this day.
−
In some traditions, if the feast comes on a weekday of Lent, the [[Divine Liturgy]] of the feast is served in the evening with [[Vespers]]. When this happens, the fasting rules for the [[Liturgy of the Presanctified Gifts]] are followed. The Divine Liturgy of the Annunciation is the only celebration of the [[Eucharist]]ic liturgy of Saint John Chrysostom allowed on a weekday of Great Lent.
+
If the feast comes on a weekday of Lent, the [[Divine Liturgy]] of the feast is served in the evening with [[Vespers]] (in some traditions). When this happens, the fasting rules for the [[Liturgy of the Presanctified Gifts]] are followed. The Divine Liturgy of the Annunciation is the only celebration of the [[Eucharist]]ic liturgy of Saint John Chrysostom allowed on a weekday of Great Lent.
−
If the feast falls on the same day as [[Pascha]], the resultant festival is called [[Kyriopascha]] and is celebrated with special [[rubrics]].
+
If the feast falls on the same day as [[Pascha]], the resultant festival is called [[Kyriopascha]] and is celebrated with special [[rubrics]]. Presently, Kyriopascha is possible only among the churches that observe the old style or traditional [[Julian calendar]] or the [[Gregorian calendar]] (that is, [[Finland]] and [[Estonia]]).
== Greek traditions ==
== Greek traditions ==
−
Many people make a [[pilgrimage]] as a special tribute to the [[Theotokos]] on the island of Tinos. Thousands of pilgrims jam the docks and city streets to visit the [[Church of Evangelistria (Tinos, Greece)]] that safeguards a miraculous healing [[icon]] of the [[Theotokos]]. Revealed in a vision, it was found buried in a field in 1823, and the church was built to house it. Pilgrims bring items of precious metals and other gifts to leave at the church. On [[August 15]] ([[Dormition]] of the Theotokos) and [[March 25]] the icon is carried through town in a grand procession.
+
Many people make a [[pilgrimage]] as a special tribute to the Theotokos on the island of Tinos. Thousands of pilgrims jam the docks and city streets to visit the [[Church of Evangelistria (Tinos, Greece)]] that safeguards a miraculous healing [[icon]] of the Theotokos. Revealed in a vision, it was found buried in a field in 1823, and the church was built to house it. Pilgrims bring items of precious metals and other gifts to leave at the church. On [[August 15]] ([[Dormition]] of the Theotokos) and [[March 25]] the icon is carried through town in a grand procession.
== Hymns ==
== Hymns ==
Line 33:
Line 33:
[[Kontakion]] (Tone 8)
[[Kontakion]] (Tone 8)
−
:To thee, the Champion Leader, I thy servant offer thanks of victory; O Theotokos, thou who hast delivered me from terror. But as thou that hast that power invincible, O Theotokos, thou alone can set me free; from all forms of danger free me and deliver me, that I may cry unto thee: "Rejoice, O Bride without bridegroom!"
According to the Gospel of Luke 1:26-38, the Archangel Gabriel appeared to Mary to announce to her that she would conceive and bear a son, even though she "knew no man." According to holy tradition Mary had come home to her parents when she was only fifteen when she was visited by Gabriel.
Contents
Celebration of the feast
The feast of the Annunciation normally falls during the season of Great Lent, but it is still a joyous day. The fast is lessened, with fish allowed on this day.
If the feast comes on a weekday of Lent, the Divine Liturgy of the feast is served in the evening with Vespers (in some traditions). When this happens, the fasting rules for the Liturgy of the Presanctified Gifts are followed. The Divine Liturgy of the Annunciation is the only celebration of the Eucharistic liturgy of Saint John Chrysostom allowed on a weekday of Great Lent.
Greek traditions
Many people make a pilgrimage as a special tribute to the Theotokos on the island of Tinos. Thousands of pilgrims jam the docks and city streets to visit the Church of Evangelistria (Tinos, Greece) that safeguards a miraculous healing icon of the Theotokos. Revealed in a vision, it was found buried in a field in 1823, and the church was built to house it. Pilgrims bring items of precious metals and other gifts to leave at the church. On August 15 (Dormition of the Theotokos) and March 25 the icon is carried through town in a grand procession. |
Neuropsychological deficits in withdrawn cocaine-dependent males.
Previous research suggests that cocaine abuse may result in neuropsychological deficits. To examine this further, we compared cocaine-withdrawn patients (N = 35) to normal controls (N = 17) on tasks of attention, concentration, perceptual-motor speed, and cognitive flexibility. The withdrawn cocaine patients performed significantly worse on Arithmetic, Grooved Peg Board Dominant and Non-Dominant, and Trails B tests. These findings suggest that withdrawn cocaine-dependent patients have more neuropsychological impairment than normal controls. |
992 A.2d 1002 (2010)
William J. NYE
v.
Paul G. BROUSSEAU et al.
No. 2009-20-Appeal.
Supreme Court of Rhode Island.
April 29, 2010.
*1004 Charles D. Blackman, Esq., Providence, for Plaintiff.
Bruce E. Vealey, Esq., for Defendant.
Present: SUTTELL, C.J., GOLDBERG, FLAHERTY, and ROBINSON, JJ.
OPINION
Justice FLAHERTY, for the Court.
"Good fences make good neighbours."[1]
William J. Nye appeals from a Superior Court judgment that fixed the boundary dividing his property from that of his neighbors, the defendants, Paul G. Brousseau and Susan J. Brousseau, enjoined Nye from trespassing on the Brousseaus' property, and awarded the Brousseaus damages on the basis of breach of contract. This case came before the Court for oral argument on April 8, 2010, pursuant to an order directing the parties to appear and show cause why the issues raised in this appeal should not summarily be decided. After hearing the parties' arguments and considering the memoranda they submitted, we are satisfied that cause has not been shown, and we proceed to decide this appeal without further briefing or argument. For the reasons set forth in this opinion, we affirm the Superior Court's judgment in part and vacate it in part.
I
Facts and Travel
Nye's parents, now deceased, purchased the property at 251 Tiffany Avenue, Warwick, *1005 Rhode Island in 1964. Nye himself resided at that address during his childhood, until 1977. As an adult, he resumed living at 251 Tiffany Avenue in 1992, until the present. He purchased the property from his father's estate in March 2003.
Between 1964 and 1966, Nye's mother planted evergreen bushes, known as Japanese yews, in a row extending from the northern to the southern end of the property and on the western edge of 251 Tiffany Avenue, abutting the next-door property of 265 Tiffany Avenue. The bushes are located adjacent to the properties' respective driveways. Over the years, the yews grew to be quite tall, at times reaching in excess of fifteen feet.
In 1979, Paul and V. Tang Lintereur purchased the property at 265 Tiffany Avenue. According to an affidavit signed by the Lintereurs, the couple did not consider themselves to be the owners of these bushes when they lived at that address and "did not consider the boundary bushes to be part of [their] former property." Rather, they "always believed [that the Nyes] owned the boundary bushes." According to Nye, he, too, "always considered the land to the east of the evergreen * * * to be our land."
In 2003, the Lintereurs sold the property at 265 Tiffany Avenue to the Brousseaus. In September or October 2003, Mr. Brousseau asked Nye if he could trim and remove bushes to improve his visibility while he exited and entered his driveway. Nye said that he appreciated that Brousseau asked for his permission before trimming the bushes, and so he assented to Brousseau's pruning and removal of those bushes that obscured the view from the Brousseaus' driveway. Later, in the spring of 2004, Brousseau discussed trimming the bushes again to shorten them, and Nye again agreed. Soon after, the pair discussed removing debris from the corner of their respective properties, extracting stumps from between their garages, and replacing a couple of defoliated yews with arborvitae shrubbery.
According to Brousseau, Nye assumed that the boundary between their properties "was somewhere near the bushes in a north-south direction," but that Nye thought that a survey should be conducted. Brousseau testified that he expressed his concern about the expense of a survey, and so Nye agreed to contribute half of the cost of the survey.[2] According to Nye, he "was being generous" when he agreed to pay half the survey's cost.
In early September 2005, Nye and Brousseau again discussed the maintenance of the row of bushes. During this conversation, they agreed to remove the bushes at the properties' southern end and replace them with arborvitae. Brousseau cut and removed the bushes, leaving several stumps near the adjacent driveways. Nye assisted Brousseau in removing one of the stumps, but Brousseau decided to hire a professional to remove the remaining stumps.
Sometime later, Brousseau broached the topic of extending his retaining wall, which, according to Brousseau, prompted Nye to again suggest that a survey be conducted before any extension was initiated. Brousseau agreed to have a survey conducted, and he hired a surveyor who completed the survey in November 2005. The surveyor discovered a granite boundary marker in the southeastern corner of the Brousseaus' property and placed a metal stake in a portion of Nye's driveway. *1006 The surveyor concluded that a portion of Nye's driveway and a portion of the southernmost bushes were actually on the Brousseaus' property. Brousseau provided Nye with a copy of the survey, but Nye disputed its accuracy and declined to reimburse the Brousseaus for any portion of the survey's cost. Nye maintained that "[i]t was [the Brousseaus'] project" and "it wasn't my survey." According to Nye, no agreement existed "as to payment."
Nye and Brousseau also disputed the placement of trash and recycling bins in the vicinity of what each perceived to be the boundary between their properties. Brousseau asked Nye to remove his trash cans, but, according to Brousseau, Nye refused. On one occasion, Brousseau moved Nye's trash cans to "the other side of the survey line," but Nye moved them back because they were damaging the grass. Nye also said that he showed Brousseau the affidavit from the Lintereurs memorializing their belief as to the location of the boundary, but Brousseau did not see any significance in that document. The men exchanged words, and Brousseau described himself as "emotional" at that time. According to Brousseau, Nye then informed him that he was going to have his own survey conducted.
Later, at the end of June 2006, Nye again contacted the Warwick police in connection with the dispute about the proper location of the trash and recycling containers. Brousseau showed the responding police officer a copy of the survey indicating that he owned the land in question, and the officer talked to Nye and departed. As a result, Nye moved his trash cans.
On August 14, 2006, Brousseau trimmed the remaining yews.[3] According to Brousseau, he placed the branches that he cut on the side of his driveway. Nye took issue with this work because he said that he had refused Brousseau's request to cut those bushes. In response, Nye contacted the Warwick Police Department "to make a record of the event." An officer came and talked to both parties, and, according to Nye, "that was basically the end of it."
Nye filed a pro se complaint against the Brousseaus in Superior Court on August 9, 2006, in which he alleged that he had requested that the Brousseaus obtain a survey of their property and asserted that he "contest[ed] the location of the disputed boundary." He claimed that "the boundary * * * between the Nye real estate and the Brousseau real estate is a line, which follows a row of bushes." He alleged that before the survey was completed, the Brousseaus did not believe that the area included within their surveyed boundary was part of their property. Nye further alleged that the Brousseaus are "liable in trespass for traveling in, and beyond, the disputed area, and for moving [his] recycling bins." He claimed that the parties "and former owners and users of both properties have demonstrated mutual acquiescence regarding their respect of [Nye's] asserted boundary." He sought a temporary restraining order and permanent injunctive relief to prevent the Brousseaus "from trespass of the asserted boundary line," "[a]n order declaring the true boundary line," and "[a]ny other such equitable relief as the Court may allow."
As part of their answer to Nye's complaint, the Brousseaus raised two counterclaims. First, they sought a declaratory judgment that the boundary line dividing the two properties was as determined in the survey conducted in November 2005. Second, they sought a temporary restraining order and injunction preventing Nye from entering their property, placing his *1007 personal property upon it, or parking motor vehicles on their property. For both counts of the counterclaim, the Brousseaus also requested that they "be granted such other and further relief as [the Superior Court] shall deem appropriate and the circumstances of the case may require."
A nonjury trial was held before a justice of the Superior Court on June 16, 17, 19, and 30, 2008, and July 7, 2008. Nye represented himself during these proceedings, while the Brousseaus were represented by counsel.[4] Nye called several witnesses, including his brother, a landscape arborist who testified about the value of the shrubbery, the Brousseaus' surveyor, who was under subpoena, and himself. The trial justice allowed video recordings of the Lintereurs' depositions into evidence. At the close of plaintiff's case, the Brousseaus moved for judgment as a matter of law. In response to defendants' motion, Nye argued to the trial justice that the boundary should run along the edge of the bushes' trunks so that each trunk is entirely on his property, but he acknowledged that that was the "ideal location" and that a boundary running through the center of the trunks was "a possible solution." The trial justice denied the motion because he wished to hear testimony from the Brousseaus, as well.
The trial justice's decision was entered on September 23, 2008. He issued an injunction preventing the Brousseaus "from passing onto Mr. Nye's property." He also ruled that because Nye "demonstrated that at the time of the August 2006 trimming, he was in possession of one-half of the shrubs near the border," Brousseau converted Nye's portion of ownership in the shrubbery when he undertook "his significant trimming" on August 14, 2006. Taking into consideration the positive effects that Brousseau's trimming had on the shrubbery, the trial justice set the value of the damage from the trimming of the nine shrubs at $2,200, and he awarded Nye damages in the amount of $1,100, reflecting his one-half ownership of the shrubbery.
With respect to the boundary question, the trial justice ruled that the row of shrubbery was "sufficiently obvious to command notice of [Nye's] claim of ownership." Therefore, because Nye "demonstrated that the row of shrubbery has existed for a sufficient period of time," the shrubbery represented the boundary between the properties under the doctrine of title by acquiescence. The trial justice found that
"[t]he new boundary shall run from the granite bound, which is the northernmost border of the two properties, southward until the northernmost yew, then turning and running along the centerline of the yews to the southernmost yew, then turning slightly eastward and running directly to the point which is the edge of Mr. Nye's paved driveway at its intersection with Tiffany Avenue."
However, the trial justice went on to say, "Any property interest clarified, confirmed or conveyed to Mr. Nye by this Decision shall be invalid until it is set forth in a Judgment, duly approved by the Court and sufficiently describing this line." He directed Nye to prepare a survey description for inclusion in the final judgment.
Acknowledging that the Brousseaus "prayed for an award of any other relief that the Court may deem equitable and just," the trial justice ruled that "[t]he Brousseaus established that Mr. Nye breached an agreement to pay for one-half of the cost of the surveyor's bill" and "[a]n *1008 award of costs for the [Brousseaus] is most appropriate here." Therefore, in recognition of the value of this survey to Nye in preparation for and during the trial proceedings, the trial justice ruled that the Brousseaus were to "be awarded one-half of the cost of the survey as Mr. Nye originally agreed." Finally, he enjoined Nye from entering the Brousseaus' "real estate without the consent of either Mr. or Mrs. Brousseau."[5]
Nye filed a motion to amend the decision on September 29, 2008, which the trial justice denied. Final judgment was entered on October 29, 2008. To comply with the trial justice's decision, Nye prepared and submitted an order with an attached surveyor's description of the new boundary line to the Superior Court on November 12, 2008. This legal description of the border was reflected in the amended final judgment that was entered on April 30, 2009.[6] Nye timely appealed to this Court.
II
Issues on Appeal
Nye raises three issues on appeal. First, he argues that, although the trial justice correctly ruled that the doctrine of acquiescence applied, he "erred in fixing the boundary between the two properties through the center of the trunks of the first and last bushes, rather than with reference to where the bushes were before the Brousseaus removed them in 2004, and by not locating the bushes entirely on the Nye property." Second, he contends that the trial justice erred when he issued an injunction preventing him from entering the Brousseaus' property without their consent. Third, he argues that the trial justice erred when he entered judgment in favor of the Brousseaus on an "unasserted" breach-of-contract claim.
III
Standard of Review
We "will not disturb the findings of a trial justice sitting without a jury in a civil matter `unless such findings are clearly erroneous or unless the trial justice misconceived or overlooked material evidence or unless the decision fails to do substantial justice between the parties.'" Union Station Associates v. Rossi, 862 A.2d 185, 193 (R.I.2004) (quoting Harris v. Town of Lincoln, 668 A.2d 321, 326 (R.I. 1995)). This is so because "[t]he task of determining the credibility of witnesses is peculiarly the function of the trial justice when sitting without a jury." Houde v. State, 973 A.2d 493, 498 (R.I.2009) (quoting McEntee v. Davis, 861 A.2d 459, 464 (R.I. 2004)). This Court also applies a deferential standard of review to the trial justice's "resolution of mixed questions of law and fact, as well as the inferences and conclusions drawn from the testimony and evidence * * *." Id. (quoting Narragansett Electric Co. v. Carbone, 898 A.2d 87, 97 (R.I.2006)). However, we review questions of law de novo. Id. (citing Fleet National Bank v. 175 Post Road, LLC, 851 A.2d 267, 273 (R.I.2004)).
IV
Discussion
A
Boundary Determination
Under the doctrine of acquiescence, "even when there has been no express *1009 agreement, adjoining landowners are `precluded from denying a boundary line recognized by both owners for a length of time equal to that prescribed by the statute of limitations barring a right of reentry.'" Acampora v. Pearson, 899 A.2d 459, 464 (R.I.2006) (quoting Locke v. O'Brien, 610 A.2d 552, 556 (R.I.1992)); see also O'Donnell v. Penney, 17 R.I. 164, 167, 20 A. 305, 306 (1890) (recognizing doctrine of acquiescence for the first time in Rhode Island). "A determination of acquiescence is a mixed question of law and fact." Acampora, 899 A.2d at 462 (citing Locke, 610 A.2d at 556). Specifically, "[a]lthough, `the issue of what constitute[s] the boundaries of a parcel of land is a question of law, the determination of where such boundaries are is a question of fact.'" Norton v. Courtemanche, 798 A.2d 925, 932 (R.I.2002) (quoting Rosa v. Oliveira, 115 R.I. 277, 279, 342 A.2d 601, 602 (1975)); see DeCosta v. DeCosta, 819 A.2d 1261, 1265 (R.I.2003) (vesting title in the entirety of the shrubbery that served as a boundary under the doctrine of acquiescence in the party who "located and planted the shrubbery," but remanding for a declaration of "where the hedgerow originally was located") (emphasis added).
Nye does not find fault with the trial justice's determination that the yews and arborvitae constituted the boundary between his and the Brousseaus' property under the doctrine of acquiescence. Consequently, he does not challenge certain findings of fact that the trial justice made in the context of determining this mixed question of law and fact, such as "whether the boundary is sufficiently obvious to command notice." Acampora, 899 A.2d at 465. He does, however, challenge "where" the trial justice determined the boundary to be. Nye argues that the proper boundary should hug the outside edge of the trunks of the shrubs so that the entire circumference of the trunks rests on his property. Because this is a question of fact, we afford deference to the trial justice's finding on this issue. Applying that standard of review, and after careful review of the record, it is our opinion that the trial justice did not misconceive or overlook material evidence when he determined that the boundary should bisect the trunks of the bushes.
In making findings of fact to support his decision, the trial justice considered the testimony of the witnesses and made several credibility determinations. He found that Nye "used the driveway and land up to the shrubbery." Additionally, the trial justice found that the shrubs "were rarely maintained." He perceived Nye's testimony to be "obviously self-serving," but "credible." As for Mr. Brousseau, the trial justice found him to be "highly credible." The trial justice acknowledged the Lintereurs' deposition testimony that they "`assumed' that the shrubbery was the border" and also that Nye's father never objected to "Mr. Lintereur trimming the bushes."
Nye asserts that "there was certainly not any evidence to suggest that the Lintereurs or the Brousseaus exercised dominion and control of the property up to the centerline of the bushesas though someone occasionally crawled under the bushes up to the centerline. People do not do that." However, there was no evidence that Nye exercised complete dominion of the entirety of the shrubbery to support his contention that he is entitled to a boundary determination that places the shrubbery completely on his property. For example, Nye did not maintain the bushes on the Brousseaus' side of the property; in fact, he rarely maintained the shrubbery at all. In addition, the Lintereurs and Brousseaus both trimmed the shrubbery that faced their property.
*1010 An authoritative treatise has said that mutual acceptance of the boundary line "is an objective test, without regard to what either party knew or thought." 9 Richard R. Powell, Powell on Real Property § 68.05[6][a] at 68-29, 68-30 (Michael Allen Wolf ed. 2000). Therefore, although Nye insists that he always believed that the shrubbery belonged to his family and the Lintereurs' affidavit contains the statement that they "always believed [that the Nyes] owned the boundary bushes," the trial justice's boundary determination is consistent with an objective factual determination of the location of the boundary. Based on the actions of the parties and the former owners of the respective properties in maintaining each side of the shrubbery, we cannot say that the trial justice's resolution of where the boundary runs was clearly wrong.
B
Injunction Against Nye
"A party seeking injunctive relief `must demonstrate that it stands to suffer some irreparable harm that is presently threatened or imminent and for which no adequate legal remedy exists to restore that plaintiff to its rightful position.'" National Lumber & Building Materials Co. v. Langevin, 798 A.2d 429, 434 (R.I.2002) (quoting Fund for Community Progress v. United Way of Southeastern New England, 695 A.2d 517, 521 (R.I. 1997)). "Irreparable injury must be either `presently threatened' or `imminent'; injuries that are prospective only and might never occur cannot form the basis of a permanent injunction." Id. (quoting Rhode Island Turnpike & Bridge Authority v. Cohen, 433 A.2d 179, 182 (R.I.1981)). Nye argues that there is no support for the permanent injunction imposed on him because "[t]here was no evidence that [he] ha[d] ever trespassed on the Brousseau property beyond the point that the Court agreed had become part of the Nye property." Therefore, he maintains that he presents no actual threat of imminent irreparable injury. We agree with Nye that the injunction against him is unnecessary.
"When reviewing the grant or denial of a permanent injunction, we will reverse the lower court on appeal only `when it can be shown that the trial justice misapplied the law, misconceived or overlooked material evidence or made factual findings that were clearly wrong.'" Holden v. Salvadore, 964 A.2d 508, 512-13 (R.I.2009) (quoting Renaissance Development Corp. v. Universal Properties Group. Inc., 821 A.2d 233, 236 (R.I.2003)). Currently, the amended final judgment reflects the boundary description as submitted by Nye in accordance with the trial justice's decision. Whatever imminent injury that the trial justice may have perceived at the time that he issued the injunction does not exist at this time, because the portion of the property that the Brousseaus challenged now belongs to Nye. This has been the case since the trial justice approved Nye's legal description of the boundary in accordance with the decision and incorporated it into the amended final judgment. As a result, there no longer is any imminent threat that Nye will trespass on the Brousseaus' property. Thus, we hold that the permanent injunction that continues to be in force against Nye is no longer called for, and that it should have been vacated when the trial justice approved Nye's submitted legal description of the boundary.
C
Damages for Breach of Agreement
Finally, Nye argues that the trial justice erred when he awarded the Brousseaus damages based on his finding that *1011 Nye breached the parties' agreement that they would share the cost of the survey. He maintains that he "was not on notice that this relief was within the realm of possibility" by the language of the counterclaim and that as a result he "did not argue his side of the story on this apparent non-issue." Although Nye did argue that there was no agreement about payment of the cost of the survey, maintaining that he was simply being "generous" in his offer to pay half the cost, and this statement was part of the evidence during the trial, we hold that the boilerplate language of the Brousseaus' counterclaim was not a sufficient basis for the trial justice's award in their favor for monetary damages.
In count one of their counterclaim, the Brousseaus alleged that the survey completed for their property on November 15, 2005, "delineate[d] the boundary lines of the parties' respective properties," and requested that they "be granted such other and further relief as [the Superior Court] shall deem appropriate and the circumstances of the case may require." The trial justice determined that an award of damages in favor of the Brousseaus for half the cost of the survey was appropriate in light of the circumstances of the case because Nye "met with [the surveyor], subpoenaed [the surveyor] for trial, and had [the surveyor] wait for several days to testify." He further found that the "survey was used as the basis for [the landscape arborist] to prepare his report."
Essentially, Nye argues before this Court that the trial justice erroneously awarded these damages sua sponte. We agree; "[o]ur caselaw consistently has mandated that when a trial justice considers and rules on an issue sua sponte, the parties must be afforded notice of the issue and allowed an opportunity to present evidence and argue against it." Catucci v. Pacheco, 866 A.2d 509, 515 (R.I.2005) (citing Vargas Manufacturing Co. v. Friedman, 661 A.2d 48, 55 (R.I.1995)) (holding that the trial justice erred when he sua sponte added additional defendants as parties "at the close of plaintiff's case" and defendants "were not prepared to offer any witnesses or otherwise defend"). In short, "a party should not be granted relief that it did not request." Providence Journal Co. v. Convention Center Authority, 824 A.2d 1246, 1248 (R.I.2003) (holding that the trial justice erred when she ordered unrequested redactions of certain information from several contracts) (citing Direct Action for Rights and Equality v. Gannon, 713 A.2d 218, 225 (R.I.1998); Vargas Manufacturing Co., 661 A.2d at 55, and Santos v. Santos, 568 A.2d 1010, 1011 (R.I.1990)); see Vargas Manufacturing Co., 661 A.2d at 54-55 (holding that the trial justice erred when he awarded punitive damages for threats amounting to the crime of extortion although the defendants mentioned and requested only punitive damages for knowing, intentional, and willful misrepresentations).
This Court has noted that "[a]ppellate courts are especially hesitant to read a particular claim into a complaint's general boilerplate prayer for relief." Bandoni v. State, 715 A.2d 580, 596 (R.I.1998) (citing Thomas R.W. v. Massachusetts Department of Education, 130 F.3d 477, 480 (1st Cir.1997)). In Bandoni, this Court viewed consideration of an award of declaratory and injunctive relief as "inappropriate" because it was not sought in the complaint, despite the complaint's general language that "prayed for monetary damages and `all such other relief deemed meet and just by this Honorable Court.'" Id. at 596. We characterized the complaint's "general boilerplate language [as] superfluous and simply insufficient to support any claim upon which other relief may be granted." Id. at 597.
*1012 Here, the similarly general boilerplate language in the Brousseaus' counterclaim cannot support an award of damages for breach of agreement. The Brousseaus' counterclaim was restricted to seeking declaratory and injunctive relief; nowhere does it allege the breach of an agreement to share the cost of a surveyor, nor does it request monetary damages. See Bandoni, 715 A.2d at 596-97. In addition, the Brousseaus were free to file a motion under Rule 15 of the Superior Court Rules of Civil Procedure to conform the pleadings to the evidence at trial regarding the alleged agreement between the parties to share the expense of the survey, but they did not do so. Therefore, we hold that the trial justice erroneously granted the Brousseaus relief that they did not request when he awarded them damages for a portion of the surveyor's fees. See Providence Journal Co., 824 A.2d at 1248.
IV
Conclusion
We affirm the Superior Court judgment in part and vacate the judgment in part. The record in this case shall be remanded to that court.
Justice Indeglia took no part in the consideration or decision of this appeal.
NOTES
[1] Robert Frost, "Mending Wall," North of Boston (1914), quoted in The Oxford Dictionary of Modern Quotations 86 (Tony Augarde ed. 1991).
[2] Nye also said that Brousseau asked him to pay only a quarter of the cost of the survey because the surveyor would be surveying the entirety of the Brousseaus' lot, most of which had nothing to do with the boundary issue.
[3] Currently, seven of the original Japanese yews and two stumps remain.
[4] Counsel filed an entry of appearance in Superior Court on behalf of Nye on December 22, 2008. That attorney represents Nye before this Court.
[5] The trial justice also enjoined Mr. Brousseau from entering "Mr. Nye's real estate without the consent of Mr. Nye."
[6] In an order that was entered on December 4, 2008, the trial justice appears to have denied Nye's filed survey map as insufficient to comply with the decision's requirement that he submit a survey description.
|
Nasdaq paying $10 million for botching Facebook IPO
Reporters covered the IPO for Facebook last May at Nasdaq in New York. Computer glitches at Nasdaq delayed trading and threw the launch into chaos.
WASHINGTON — Nasdaq has agreed to pay a $10 million penalty to settle federal civil charges after regulators said its systems and decisions disrupted Facebook’s public stock offering last year.
The Securities and Exchange Commission said Wednesday that the penalty is the largest ever imposed against an exchange. Nasdaq also has had to pay $62 million in reimbursements to investment firms that lost money because of the problems.
Facebook launched its initial public offering on May 18, 2012, amid great fanfare. But computer glitches at Nasdaq delayed the start of trading and threw the launch into chaos. The technical problems kept many investors from buying shares that morning, selling them later in the day or even knowing whether their orders went through. Some said they were left holding shares they didn’t want.
The SEC says a design flaw in Nasdaq’s systems was to blame and Nasdaq officials then made a series of “ill-fated decisions.”
Nasdaq neither admitted nor denied wrongdoing.
Robert Greifeld, the CEO of the exchange’s parent Nasdaq OMX Group Inc., called the settlement an “important step forward.”
In a letter to customers made public Wednesday, Greifeld said Nasdaq has carefully reviewed the Facebook disruption over the past year and put new technical safeguards in place.
The exchange has taken steps such as creating new executive positions within its technology division, and setting up teams to monitor and test trading systems, Greifeld said.
In addition to its namesake stock exchange, Nasdaq OMX also operates other exchanges and clearinghouses in the U.S. and abroad.
The Facebook IPO was widely anticipated and one of the largest in history. The social network was valued at more than $100 billion when it went public for $38 a share.
Nasdaq violated market rules by being poorly prepared for the launch, the SEC said. Exchanges have an obligation to ensure that their systems and contingency plans are strong enough to manage an IPO without disrupting the market.
The SEC said Nasdaq officials believed they had fixed the design flaw by removing a few lines of computer code and opted not to delay the start of trading in Facebook. But they failed to understand the root cause of the problem, the SEC said.
The $10 million penalty had been expected. Nasdaq said last month that it might have to pay that amount to resolve the matter with regulators.
In its administrative order issued Wednesday, the SEC also censured Nasdaq. Censure brings the possibility of a stiffer sanction if the alleged violation is repeated. |
Sphingosine-1-phosphate lyase in immunity and cancer: silencing the siren.
Sphingosine-1-phosphate (S1P) is a bioactive lipid that promotes cell survival, proliferation and migration, platelet aggregation, mediates ischemic preconditioning, and is essential for angiogenesis and lymphocyte trafficking. Sphingosine-1-phosphate lyase (SPL) is the enzyme responsible for the irreversible degradation of S1P and is, thus, in a strategic position to regulate these same processes by removing available S1P signaling pools, that is, silencing the siren. In fact, recent studies have implicated SPL in the regulation of immunity, cancer surveillance and other physiological processes. Here, we summarize the current understanding of SPL function and regulation, and discuss how SPL might facilitate cancer chemoprevention and serve as a target for modulation of immune responses in transplantation settings and in the treatment of autoimmune disease. |
Oakton, VA Real Estate
As is true with many areas in Fairfax County, Oakton has roots in the Civil War. Hunter Mill Road, which is a major artery through Oakton to this day, served as a key travel way or both Confederate and Union forces. Soldiers involved in both battles at Manassas, Antietam and Gettysburg used Hunter Mill. Another major road, Waple’s Mill, took its name from a mill built by Henry Maple shortly after the end of the Civil War, and it was in near continuous use until the 1920’s. Oakton is right in the heart of Fairfax County, with Vienna to the east, Reston to the north, Fairfax to the west and Fairfax City to the south.
Quality of Life:
Rated #36 Best Place to Live by CNN Money Magazine. Oakton benefits from the incredible public park system run by the Fairfax County Park Authority, with Difficult Run Stream Valley Park as well as Oak Marr Park, Golf and Rec Center. Oak Marr sports a tidy 9-hole par golf course and full driving range, miniature golf for the kids and a rec center, complete with an indoor Olympic pool, diving complex, racquetball courts and a fitness center. Oakton’s tree-lined streets feature single-family detached homes that are among Northern Virginia’s finest, along with high-end townhouse communities.
Getting Around:
Busy Route 123 anchors Oakton’s south end, while most of Oakton’s arteries are winding two-land affairs. It’s easy to hop onto I-66, a major east-west commuting highway or onto the Dulles Toll Road/Access Road to head to the airport on into the District.
Airports:
Ronald Reagan National Airport: <20 miles
Washington-Dulles International Airport: < 14 miles
Baltimore-Washington International Airport: < 56 miles |
Q:
Exception (nullreferenceexception) on datagridview - C#
My code is always entering the exception, does not matter if I try to "treat" the cell with NULL using IF/ELSE clauses.
My catch System.Exception error is:
"Object reference not set to an instance of an object"
Situation:
If I enter a NULL value on the Datagrid, an error will occur and the rest of the data is not saved.
private void ExportToExcel()
{
// Creating a Excel object.
Microsoft.Office.Interop.Excel._Application excel = new Microsoft.Office.Interop.Excel.Application();
Microsoft.Office.Interop.Excel._Workbook workbook = excel.Workbooks.Add(Type.Missing);
Microsoft.Office.Interop.Excel._Worksheet worksheet = null;
try
{
worksheet = workbook.ActiveSheet;
worksheet.Name = "ExportedFromDatGrid";
int cellRowIndex = 1;
int cellColumnIndex = 1;
//Loop through each row and read value from each column.
for (int i = -1; i < dataGridView1.Rows.Count - 1; i++)
{
for (int j = 0; j < dataGridView1.Columns.Count; j++)
{
// Excel index starts from 1,1. As first Row would have the Column headers, adding a condition check.
if (cellRowIndex == 1)
{
worksheet.Cells[cellRowIndex, cellColumnIndex] = dataGridView1.Columns[j].HeaderText;
}
else
{
if (dataGridView1.Rows[i].Cells[j].Value.ToString() != null)
{
worksheet.Cells[cellRowIndex, cellColumnIndex] = dataGridView1.Rows[i].Cells[j].Value.ToString();
}
else
{
worksheet.Cells[cellRowIndex, cellColumnIndex] = String.Empty;
}
// working:
//worksheet.Cells[cellRowIndex, cellColumnIndex] = dataGridView1.Rows[i].Cells[j].Value.ToString();
}
cellColumnIndex++;
}
cellColumnIndex = 1;
cellRowIndex++;
}
//Getting the location and file name of the excel to save from user.
SaveFileDialog saveDialog = new SaveFileDialog();
saveDialog.Filter = "Excel files (*.xlsx)|*.xlsx|All files (*.*)|*.*";
saveDialog.FilterIndex = 2;
if (saveDialog.ShowDialog() == System.Windows.Forms.DialogResult.OK)
{
workbook.SaveAs(saveDialog.FileName);
MessageBox.Show("Export Successful");
}
}
catch (System.Exception ex)
{
MessageBox.Show(ex.Message);
}
finally
{
excel.Quit();
workbook = null;
excel = null;
}
} // end ExportToExcel
A:
if (dataGridView1.Rows[i].Cells[j].Value.ToString() != null)
Don't call ToString() here, if your value is null you'll get a NullReferenceException. Simply test Value itself.
if (dataGridView1.Rows[i].Cells[j].Value != null)
In fact, in your case you could shorten it to
worksheet.Cells[cellRowIndex, cellColumnIndex]=dataGridView1.Rows[i].Cells[j].Value?.ToString() ?? "";
?. being the null conditional operator and ?? being the null coalescing operator.
|
The Trump administration has reportedly rejected several U.S. embassies’ requests to fly the rainbow pride flag in June, LGBTQ pride month. Meanwhile, some US diplomats have been finding ways to defy, or at least get around, the Trump administration's policy.
From hanging the rainbow-colored flag on the facades of buildings (U.S. missions in Seoul and Chennai, India, for example) to rainbow-colored lights in New Delhi, embassies from around the world are choosing to honor the LGBTQ+ community in its own way.
The United States Embassy in New Delhi is lit up in #Pride colors to celebrate #PrideMonth. #LGBTPrideMonth pic.twitter.com/v6gxzAps8a — U.S. Embassy India (@USAndIndia) June 4, 2019
"Some embassies got playful with the display of Trump's statement," The Washington Post report read. "In Brasilia, for example, the statement is topped by a photo of two hands holding five Play-Doh letters in rainbow colors: L-G-B-T-Q."
“This is a category one insurrection,” said one diplomat, who expressed his views on the condition of anonymity for the fear of being fired.
Under State Department policy, embassies that want to fly the flag on their flagpoles are expected to obtain permission from Washington, reports the NBC. No embassy that has made the request has been granted permission as of now apart from being allowed to display the flag inside the embassy.
Incidentally, President Donald Trump became the first Republican president to acknowledge the LGBT celebration of Pride Month.
As we celebrate LGBT Pride Month and recognize the outstanding contributions LGBT people have made to our great Nation, let us also stand in solidarity with the many LGBT people who live in dozens of countries worldwide that punish, imprison, or even execute individuals.... — Donald J. Trump (@realDonaldTrump) 31 May 2019
....on the basis of their sexual orientation. My Administration has launched a global campaign to decriminalize homosexuality and invite all nations to join us in this effort! — Donald J. Trump (@realDonaldTrump) 31 May 2019
“As we celebrate LGBT Pride Month and recognize the outstanding contributions LGBT people have made to our great Nation, let us also stand in solidarity with the many LGBT people who live in dozens of countries worldwide that punish, imprison, or even execute individuals on the basis of their sexual orientation,” he wrote in a series of tweets.
But many consider this show of support as hogwash and that it's mere words over action. Many see this as an attempt to portray himself as supportive of LGBTQ people as he gears up for the 2020 re-election campaign.
The news comes as pride celebrations are taking place in Washington. Unfortunately, things turned awry during the Parade when pedestrians, were left injured as people began "running for their lives" after hearing a noise akin to gunshot
Twitter
Rumours stated hat an active shooter has infiltrated among the parade participants, leaving scores into a sense of frenzy.
.@CapitalPrideDC #PrideDc #DCPride - There is NO Active Shooter at Dupont Circle. There are injuries from people running from what they thought were gunshots. But there is NO ACTIVE SHOOTER at Dupont Circle. @DCPoliceDept @DC_HSEMA — Deputy Mayor Donahue (@SafeDC) 9 June 2019
"As the officers were going to the scene, there was a crowd of people going away from it and some of the individuals in the crowd said there was a man with a gun and that someone had fired a shot," said Guillermo Rivera, a commander with the Metropolitan Police Department.
The parade has ended. The Block Party on 15th And P St. is still happening as well as City Winery. The police asks that everyone on Dupont Circle evacuates. Be safe. The police is on site and the threat has been contained. — Capital Pride (@CapitalPrideDC) 9 June 2019
Mayor Muriel Bowser also posted a statement, claiming that she has been briefed by the police and there were "no shots fired."
With inputs from Washington Post & NBC |
Introduction
============
Human cytomegalovirus (CMV) is a ubiquitous beta-herpes virus that leads to congenital infection in 0.4% to 2.3% of all newborns.[@b1-ijwh-2-023] The risk of intrauterine transmission after primary CMV infection during pregnancy approaches 40%, with an increased risk of adverse fetal effects if infection occurs during the first half of pregnancy.[@b2-ijwh-2-023] Of congenitally infected infants, approximately 10% are symptomatic at birth. Of the remaining 90% of infants who are asymptomatic at birth, 10%--15% will subsequently manifest evidence of permanent sequelae.[@b3-ijwh-2-023] Congenital CMV is a significant cause of neurodevelopmental disability, including sensorineural hearing loss (SNHL) and intellectual disability (previously referred to as "mental retardation"). More children suffer from long-term sequelae as a result of congenital CMV infection than Down syndrome or fetal alcohol syndrome.[@b4-ijwh-2-023] In this review, current concepts regarding the epidemiology, pathogenesis, and prevention of CMV infection are summarized, with an emphasis on strategies designed to improve awareness of the risk of CMV among women of childbearing age.
Epidemiology
============
CMV is found worldwide, with the rate of seropositivity affected by geographic, socioeconomic, and ethnic background.[@b2-ijwh-2-023],[@b3-ijwh-2-023] In developed countries, the prevalence of CMV seropositivity is 40% to 60% in individuals of middle to upper socioeconomic status and ∼80% among those of lower socioeconomic status.[@b3-ijwh-2-023] By comparison, virtually individuals in developing countries have been infected by CMV in early childhood.[@b3-ijwh-2-023] In the United States, the seroprevalence of CMV is higher among non-Hispanic blacks and Mexican Americans than among non-Hispanic whites.[@b5-ijwh-2-023]
Congenital CMV infection can occur as the result of a primary CMV infection, reinfection with a new strain of CMV, or reactivation of a latent infection.[@b6-ijwh-2-023],[@b7-ijwh-2-023] Maternal immunity to CMV provides some protection against vertical transmission of the virus. If a primary CMV infection occurs in the period just prior to conception, the risk of transmission is 8.7%.[@b8-ijwh-2-023] Primary maternal CMV infection occurring in the first, second, and third trimester results in congenital infection in approximately 25%, 50%, and 75% of fetuses, respectively.[@b9-ijwh-2-023] In contrast, the risk of CMV transmission to the fetus after a recurrent maternal infection is only 0.15 to 2%.[@b10-ijwh-2-023],[@b11-ijwh-2-023] Fowler et al demonstrated a 69% reduction in the risk of congenital CMV infection in future pregnancies in women who were seropositive for CMV when compared to seronegative women.[@b12-ijwh-2-023] However, despite the risk reduction preconception immunity affords, over 60% of infants with congenital CMV infection are born to mothers with immunity to CMV prior to pregnancy, reflecting the high rate of CMV seropositivity in the population.[@b13-ijwh-2-023] In populations with high maternal CMV seropositivity, the incidence of congenital CMV infection is greater than in populations of lower maternal seroprevalence.[@b1-ijwh-2-023]
It has generally been believed that the fetuses of pregnant women with preconception immunity to CMV are somewhat protected against the most significant neurodevelopmental sequelae of congenital CMV infection. A study comparing women with preconception immunity to CMV to those who acquired primary CMV infection in pregnancy showed that the women with preconception immunity have a significant reduction in transmission of CMV to the fetus, as well as decreased severity of disease in infected infants.[@b11-ijwh-2-023] In that study, 25% of the infants whose mother had a primary infection had at least one sequela, compared with 8% when the infection was recurrent. However, subsequent studies have not demonstrated the same degree of protection conferred by preconception immunity in congenitally infected infants. Boppana et al studied infants with symptomatic congenital CMV infection as the result of both primary and recurrent maternal infection and found no difference in the severity of clinical findings between the two groups.[@b14-ijwh-2-023]
Pathogenesis
============
CMV is a linear double-stranded DNA virus, and its genome is comprised of over 250 kilobase pairs. The three distinct regions of the CMV virus include the capsid containing the viral genome; the tegument layer containing phosphoproteins; and an outer lipid envelope containing glycoproteins. The capsid, which comprises 162 capsomere subunits arranged in icosahedral symmetry, houses the viral genome.[@b15-ijwh-2-023] The capsid is surrounded by the tegument of the CMV virion. A large number of proteins are located in the tegument. These tegument proteins, including phosphoprotein 65 (pp65), are some of the most immunogenic proteins in the virion, and are the immunodominant targets of T-lymphocytes responses to CMV.[@b16-ijwh-2-023],[@b17-ijwh-2-023] Surrounding the tegument is the envelope, which contains an as yet incompletely defined number of virally encoded glycoproteins. The most abundant glycoproteins include gB complex, gM/gN complex, and gH/gL/gO complex. Seropositive individuals typically mount a neutralizing antibody response directed against these glycoproteins making these protein products potentially useful subunit vaccine candidates.[@b18-ijwh-2-023]--[@b20-ijwh-2-023]
CMV is a complex virus that appears to employ multiple strategies to evade the host immune system.[@b21-ijwh-2-023] A healthy, immunocompetent individual can control CMV infection, but only at great expense to the host immune system: remarkably, approximately 10% of both the CD4^+^ and CD8^+^ memory compartments in blood are specific for CMV-encoded proteins.[@b22-ijwh-2-023] The chronic, persistent nature of CMV, characterized by frequent episodes of asymptomatic reactivation and shedding, probably contributes to the ability of the virus to cause congenital infection even in women with long-standing preconception immunity.
Congenital and postnatal transmission
=====================================
Children as source of CMV
-------------------------
Daycare centers are a significant source of CMV infection. Children less than three years of age with postnatally acquired CMV infection have been demonstrated to excrete CMV in their urine and saliva for 6 to 42 months.[@b23-ijwh-2-023] Children enrolled in daycare become infected with CMV between 15 and 70% of the time.[@b24-ijwh-2-023] Seronegative mothers with children in group daycare are at significant risk of acquiring CMV infection, with at least 50% of them seroconverting within 1 year of their child's CMV infection.[@b25-ijwh-2-023]
Breast-feeding
--------------
CMV is excreted in the breast milk of seropositive women.[@b26-ijwh-2-023] The risk of CMV transmission in infants breast-fed by seropositive women shedding virus in their breast milk has been reported to be 58% to 69%.[@b27-ijwh-2-023],[@b28-ijwh-2-023] CMV infection acquired in the postnatal period in healthy term infants typically is asymptomatic, only rarely producing any morbidity. There is no evidence that acquisition of CMV via breast milk leads to any adverse neurodevelopmental sequelae. In a study of CMV transmission through breast-feeding, all of the infants who acquired CMV infection had normal neurodevelopment at a mean follow-up of 51 months.[@b28-ijwh-2-023]
While the safety of breast-feeding has been established in term infants in women shedding CMV virus, controversy exists on the safety of breast-feeding low birth weight, premature infants. Studies in low birth weight and very low birth weight preterm infants yield conflicting results with respect to the risk of developing symptomatic infection following breast milk acquisition of CMV.[@b29-ijwh-2-023] A recent study of early postnatal CMV infection in preterm infants in an highly immune population demonstrated that symptomatic CMV infection was rare.[@b30-ijwh-2-023] Efforts to reduce the infectivity of breast milk from seropositive mothers has included freezing breast milk at −20 °C, Holder pasteurization, and short-term pasteurization.[@b31-ijwh-2-023] Of these methods, freeze-thaw is the best studied approach, and the technique most likely to retain the salutary immunological properties of breast milk. While freezing breast milk does lower the incidence of postnatally acquired CMV infection, it does not entirely eliminate the risk.[@b32-ijwh-2-023] It remains unclear whether interventions designed to interrupt breast milk transmission of CMV to low birth weight, premature babies improve either short-term or long-term outcomes for these infants.
Other
-----
CMV can also be transmitted through close non-sexual contact, sexual activity, blood transfusions, and organ transplantation.[@b4-ijwh-2-023] Two methods are currently employed to decrease the risks of CMV transmission through blood transfusion, including utilizing leukocyte-reduced and CMV-negative blood products. Although leukocyte reduction has dramatically reduced the risk of transfusion-associated CMV infection, reports in the literature are conflicting about whether this intervention completely eliminates any risk of transmission.[@b33-ijwh-2-023],[@b34-ijwh-2-023] A recent survey of the American Association of Blood Bank (AABB) physician members showed that 65% of those responding felt both leukocyte-reduced and CMV-negative blood components were equivalent in their ability to prevent transfusion transmission of CMV.[@b35-ijwh-2-023] However, despite the AABB survey results on attitudes toward leukocyte reduced blood products, fetuses and neonates are more likely to receive CMV-negative blood products compared to other groups receiving transfusions.[@b35-ijwh-2-023]
Clinical manifestations
=======================
Maternal CMV
------------
Most CMV infections are subclinical in healthy immunocompetent hosts.[@b1-ijwh-2-023] When present, clinical symptoms of primary CMV infection include flu-like syndrome, fever, myalgias, pharyngitis, weakness, and fatigue. Laboratory abnormalities can include elevated liver transaminases and lymphocytosis. Most studies have shown that pregnancy does not appear to affect the clinical course of CMV infection. A more recent look at primary CMV infection in pregnancy by Nigro et al demonstrated substantially higher rate of symptoms associated with CMV infection than previously reported.[@b36-ijwh-2-023] In a cohort study, 32 women (31%) diagnosed with primary CMV experienced either persistent fever or a flu-like illness.[@b36-ijwh-2-023] Practitioners should have a high index of suspicion when caring for at risk pregnant women with undiagnosed illness or fever.
Congenital CMV
--------------
Only 10% of congenitally infected fetuses are symptomatic at birth. Clinical symptoms include microcephaly, growth restriction, hepatosplenomegaly, chorioretinitis, jaundice, petechiae, hearing impairment, thrombocytopenia, hyperbilirubinemia, and anemia.[@b13-ijwh-2-023],[@b37-ijwh-2-023] The risk for neurologic sequelae is increased when infection occurs in the first trimester.[@b38-ijwh-2-023] The majority of infants with symptomatic congenital CMV infection at birth have evidence of central nervous system (CNS) impairment. In a study of 106 infants with symptomatic congenital CMV infection, 68% of infants had at least one clinical finding suggestive of neurologic impairment.[@b37-ijwh-2-023] It was reported in the early 1980s that infants with symptomatic congenital CMV infection at birth have a 91% chance of developing long-term sequelae from the infection, and a 29% death rate, although advances in neonatal intensive care make mortality much less likely today.[@b39-ijwh-2-023] Of infants with asymptomatic congenital CMV infection at birth, 10% to 15% will go on to develop symptoms, typically manifested as SNHL.
Congenital CMV infection is the most common non-genetic cause of SNHL in children. In the DECIBEL study, 23% of children with profound SNHL had congenital CMV infection.[@b40-ijwh-2-023] Permanent hearing loss occurs in approximately 14% of children with congenital CMV infection.[@b41-ijwh-2-023] SNHL from congenital CMV can present later in childhood. Approximately 6% to 23% of children with congenital CMV infection who are asymptomatic at birth will subsequently develop hearing loss.[@b42-ijwh-2-023] However, symptomatic infection at birth appears to be much more likely than asymptomatic infection to be associated with delayed SNHL, with a reported rate of delayed-onset hearing loss in symptomatic newborns of 33.7%.[@b43-ijwh-2-023]
Diagnosis
=========
Diagnosis of maternal infection
-------------------------------
Diagnosis of maternal primary CMV infection can be challenging. Maternal primary CMV infection is confirmed if there is documented IgG seroconversion; however, most women do not have a baseline pre-pregnancy serology for comparison. A second method to diagnose primary CMV infection is to test for CMV-specific IgM, which is an indicator of recent or active CMV infection. Several problems exist with CMV IgM as a screening test. First, CMV IgM can be present for up to 9 months after a primary infection.[@b2-ijwh-2-023] Second, CMV IgM can be produced in both recurrent infections, as well as following reactivation of infection; thus, the finding of IgM antibodies does not allow discrimination of the timing of infection.[@b44-ijwh-2-023] Third, there is discordance among commercially available kits for CMV IgM, as well as false positive results.[@b45-ijwh-2-023] The AxSYM CMV IgM assay is very sensitive when compared to other commercial assays.[@b46-ijwh-2-023] A highly sensitive IgM assay can identify more pregnancies at risk.
In pregnant women with CMV-specific IgM, anti-CMV IgG avidity testing can be utilized to differentiate primary CMV infection from reactivation of latent infection or reinfection.[@b44-ijwh-2-023] Low avidity indices are indicative of an acute or recent primary CMV infection, and persist for approximately 18 to 20 weeks.[@b44-ijwh-2-023] Lazzarotto et al demonstrated that if the CMV IgG avidity index is performed prior to 18 weeks gestation, it has 100% sensitivity for detecting pregnancies at risk for transmitting CMV to the fetus, however the sensitivity is decreased to only 62.5% if the test is performed after 20 weeks gestation.[@b47-ijwh-2-023] Additionally, a recent CMV infection can be excluded if a high avidity is demonstrated in the first 12 to 16 weeks of pregnancy. If high avidity antibodies are present in the first trimester, a pregnancy is unlikely to result in symptomatic congenital transmission. In pregnancies where primary maternal infection is confirmed, further evaluation is directed toward determining if the fetus is infected (see [Figure 1](#f1-ijwh-2-023){ref-type="fig"}).
Diagnosis of fetal infection
----------------------------
Ultrasound can detect anomalies associated with CMV congenital infection, although many of the findings are non-specific. Prenatal ultrasonographic findings of congenital CMV infection include intrauterine growth restriction (IUGR), microcephaly, ventriculomegaly, periventricular calcifications, echogenic bowel, hydramnios, hydrops, pleural effusion, and placental enlargement.[@b48-ijwh-2-023] The sensitivity of ultrasound to detect congenital CMV infection is poor given that the majority of congenitally infected infants are asymptomatic. In a study of 600 pregnant women with primary CMV infection, abnormal ultrasound findings were detected in 51/600 (8.5%) of those pregnancies and in 23/154 (14.9%) fetuses with documented congenital infection.[@b48-ijwh-2-023] The positive predictive value of an abnormal ultrasound predicting symptomatic congenital infection in women with primary CMV infection was only 35.3% when fetal infection status was unknown, compared to 78.3% when congenital CMV infection was confirmed.[@b48-ijwh-2-023]
Fetal infection can be diagnosed by documenting the presence of CMV in the amniotic fluid (AF), most typically demonstrated by PCR analysis (below). Amniocentesis should be offered to women with documented seroconversion, serologic studies suggestive of a primary CMV infection, or abnormal ultrasound findings consistent with congenital CMV infection. The drawback of definitive testing is the risk associated with invasive diagnostic testing. The risk of procedure-related pregnancy loss has been demonstrated to be approximately 1/300 to 1/500.[@b49-ijwh-2-023],[@b50-ijwh-2-023] The risk of iatrogenic vertical CMV transmission through amniocentesis is minimal.[@b51-ijwh-2-023]
The timing of diagnostic testing is important. Amniocentesis for fetal diagnosis of congenital CMV infection should be performed after 21 to 23 weeks gestation, and at least 6 weeks after documentation of primary maternal infection, as earlier testing can lead to false negative results.[@b52-ijwh-2-023],[@b53-ijwh-2-023] In cases where maternal seroconversion occurs in the first trimester, the interval between seroconversion and testing of the AF may need to be increased.[@b52-ijwh-2-023] The timing of diagnostic testing is due to the fact that CMV is excreted through the fetal urine at detectable levels 6 to 9 weeks after maternal infection, and fetal urination is increased after 20 to 21 weeks gestation. When testing AF ≥ 6 weeks after maternal infection and ≥ 23 weeks gestation the sensitivity of prenatal diagnosis of congenital CMV infection increased from 45% to 55% to 95.5%.[@b52-ijwh-2-023]
AF can be evaluated with CMV viral culture and CMV polymerase chain reaction (PCR). The drawback of viral culture is that it can yield false negative results, and it requires a lengthy period of time to grow the virus in the laboratory (up to 6 weeks). PCR of the AF to detect CMV has a sensitivity and specificity of 90% to 98% and 92% to 98%, respectively.[@b54-ijwh-2-023] Studies attempting to determine the threshold of CMV viral load that is predictive of symptomatic congenital infection and/or sequelae have yielded conflicting results. Lazzarotto et al demonstrated that if the AF viral load is ≥10^3^ copies/mL the risk for congenital infection is 100%, and that the presence of viral load of ≥10^5^ copies/mL is predictive of symptomatic congenital infection.[@b55-ijwh-2-023] Additionally, Lazzarotto et al found that an AF PCR level of \<500 copies/mL is unlikely to be associated with symptomatic congenital infection.[@b54-ijwh-2-023] Other studies have not demonstrated clear viral load cut-offs correlating with fetal outcomes.[@b56-ijwh-2-023],[@b57-ijwh-2-023] While the viral load is generally greater in symptomatic infections when compared to asymptomatic infections, considerable overlap exists.[@b54-ijwh-2-023],[@b56-ijwh-2-023] The analysis of viral load by PCR is also fraught with uncertainty given that there are a great number of PCR assays, differing in primer sequence, method of PCR, and technique for quantification. If the AF CMV PCR and viral culture are negative, then congenital CMV infection is unlikely.
Counseling women with primary CMV infection accurately in pregnancy is important. Guerra et al demonstrated that accurate interpretation and counseling of women with positive CMV screening can decrease the rate of termination of pregnancy.[@b58-ijwh-2-023] Women with no evidence of CMV infection in the AF are likely to have an uninfected neonate. Women with CMV present in the AF should be counseled that there is a 10% risk of symptomatic congenital infection and a 90% chance of an asymptomatic congenital infection at birth. However, if the primary maternal CMV infection occurred in early pregnancy, the risk of an infected fetus demonstrating symptoms at birth is increased to between 20% and 30%.[@b38-ijwh-2-023],[@b59-ijwh-2-023] Fetuses with documented congenital CMV infection and ultrasound abnormalities have a poor prognosis, especially if cerebral abnormalities are detected.[@b60-ijwh-2-023]
Postnatal diagnosis of congenital infection
-------------------------------------------
In the evaluation of a newborn infant with possible congenital CMV, care must be taken to *not* rely on antibody titers in the infant (so-called "TORCH" titers) because these are seldom of value in establishing the diagnosis of congenital CMV. The finding of CMV antibodies in an infant may simply reflect transplacental transfer of IgG, and IgM assays are fraught with the same issues regarding sensitivity and specificity in the newborn as they are in the mother.[@b44-ijwh-2-023],[@b45-ijwh-2-023] The most important diagnostic studies in the evaluation of suspected CMV disease are virologic studies, not serologic studies, including viral culture and PCR. CMV may be cultured from virtually any body fluid or organ system. Blood, urine, saliva, cerebrospinal fluid, bronchoalveolar lavage fluid, and tissues from biopsy specimens are all appropriate specimens for culture. The specimen is inoculated on to human cells (usually human foreskin fibroblasts) and the cell culture is monitored for the development of the characteristic CMV-associated cytopathic effect. CMV may grow slowly in culture, requiring up to 6 weeks of incubation. Culture identification is enhanced by centrifugation techniques, followed by monoclonal-antibody detection, referred to as the "shell-vial" assay. PCR amplification of CMV DNA from clinical specimens is a useful adjunct to culture techniques, and in recent years is increasingly being employed in place of viral culture for diagnosis of CMV infection.[@b54-ijwh-2-023] The information derived from PCR not only helps establish the diagnosis of CMV infection, but quantitative data may be of value in establishing prognosis, since there is evidence that infants with higher viral loads may portend an increased risk of development of SNHL; these infants, accordingly, may be more likely than infants with low viral load to benefit from antiviral therapy with ganciclovir.[@b61-ijwh-2-023]
CMV screening
=============
Maternal CMV screening
----------------------
Routine maternal screening for CMV infection is controversial. Currently neither the American College of Obstetricians and Gynecologists (ACOG) nor the Centers for Disease Control and Prevention (CDC) recommend routine serologic screening for CMV infection in pregnancy.[@b62-ijwh-2-023],[@b63-ijwh-2-023] Several problems exist with routine maternal serologic screening for CMV. First, if maternal immunity to CMV is documented, it does not rule out the possibility of congenital CMV infection through infection with a new CMV strain or reactivation of maternal CMV. Second, diagnosis of an in *utero* CMV infection does not necessarily predict symptomatic disease or sequelae in the infant upon completion of the pregnancy. Third, there is no established, evidence-based treatment available for fetal CMV infection in the pregnant patient. Finally, maternal screening may produce undue anxiety, particularly if screening is performed without adequate counseling to educate the patient about the implications of a positive or negative screening test.
Another consideration in developing a CMV screening program is the cost-effectiveness of such measures. Cahill et al evaluated the cost-effectiveness of 3 screening strategies and found that universal screening for primary maternal CMV infection would be cost effective if treatment of affected pregnancies with CMV specific hyperimmune globulin (HIG) would result in a minimum of a 47% reduction in symptomatic CMV disease.[@b64-ijwh-2-023] Further studies with randomized controlled trials are needed to evaluate treatment options, including CMV HIG, to determine a screening program's ability to reduce morbidity of congenital CMV disease.
Until evidence-based treatment is available, efforts should be made on emphasizing preventative measures to all women who are attempting pregnancy, or who are currently pregnant. Screening of pregnant women should be limited to instances where there is a clinical suspicion of an active CMV infection, either due to maternal symptoms, or ultrasonographic abnormalities suggesting fetal anomalies or maldevelopment.
Neonatal CMV screening
----------------------
Newborn screening (NBS) for endocrine and metabolic disorders has been successfully performed through collection and analysis of dried blood spot (DBS) specimens. Universal newborn hearing screening (UNHS) is currently employed and has been demonstrated to have a positive effect on language outcomes among children with permanent bilateral hearing loss.[@b65-ijwh-2-023]
Congenital CMV infection is a known cause of SNHL; however, UNHS will miss up to 75% of cases of CMV-associated SNHL, since, as noted, hearing loss may be late-onset. This observation provides support for the concept of universal screening for congenital CMV.
Utilization of NBS for diagnosis of congenital CMV infection is currently being debated. NBS for CMV can be justified based the much higher incidence of congenital CMV infection than many other disorders included in NBS program, and its association with SNHL. The potential benefit of NBS for congenital CMV derives from the opportunity to identify children who require close surveillance, including audiological evaluation and neurodevelopmental assessment. Early intervention programs for SNHL and developmental concerns can then be instituted, if required. Since the majority of cases of SNHL associated with congenital CMV occur post-natally, as already noted, a normal NHS does not provide complete reassurance in an infant with congenital infection, and serial audiological evaluation is required. Additionally, screening could identify children who may benefit from antiviral treatment to prevent hearing loss.
Prior to the implementation of universal CMV screening, a sensitive, reliable, and cost effective screening test for CMV needs to be optimized needs to be established. CMV testing can be performed utilizing urine, saliva, or DBS. Viral culture of the urine has long been the gold standard laboratory test for the diagnosis of CMV infection in newborns. Given the time-consuming and costliness of viral culture, PCR has been increasingly utilized to detect CMV virus. PCR of DBS has recently been reported by a number of investigators as a useful technique for detecting congenital CMV infection. One objection to the use of DBS as the sole test for detecting congenital CMV is that the viral load in blood may often be lower than in saliva or urine, or that DNAemia may be absent altogether in a congenitally infected baby. This may make detection of DNA in the DBS relatively insensitive compared to urine or saliva in making the diagnosis of congenital CMV.[@b66-ijwh-2-023] There have been many studies evaluating varying methods for CMV DNA detection by PCR with a wide range of sensitivities reported.[@b67-ijwh-2-023]--[@b69-ijwh-2-023] Continued work toward identification of the optimal screening test is necessary.
Another hurdle in the development of a NBS program for CMV is the creation and oversight of programs to carry out screening. Two of the options that have been posed for congenital CMV NBS are 1) hospital-based program utilizing urine, saliva, or DBS specimens and 2) state NBS program using DBS.[@b70-ijwh-2-023]
Before universal NBS for congenital CMV can become standard practice, a reliable and sensitive screening test needs to be identified, mechanisms for implementation of this screening test must be validated, and a plan for how to longitudinally monitor children indentified with congenital CMV through screening needs to be identified.
Prevention
==========
Prevention of CMV transmission in women of childbearing age is of utmost importance in order to reduce the rate of congenital infection. Both the CDC workgroup and ACOG recommend education on hygienic practices to prevent CMV viral transmission.[@b62-ijwh-2-023],[@b71-ijwh-2-023] Hygienic strategies are important in preventing CMV transmission given that the saliva and urine of infected children are significant sources of CMV infection among women who are pregnant.[@b25-ijwh-2-023] Preventative strategies include washing hands whenever there is contact with a child's saliva or urine, not sharing food, utensils, or cups, and not kissing a child on the mouth or cheek.[@b4-ijwh-2-023],[@b72-ijwh-2-023]
Education of women about the implications of acquiring CMV infection, particularly during pregnancy, is vital. A survey of women in 2005 showed that only 14% of women knew what CMV was, but reported that following preventative measures for preventing an infection that could harm an unborn baby would generally be acceptable.[@b73-ijwh-2-023] The effectiveness of educating pregnant women on methods to prevent CMV transmission has been demonstrated.[@b74-ijwh-2-023]--[@b76-ijwh-2-023] In a study where seronegative mothers with a child in group day care were instructed on measures to prevent CMV transmission, pregnant mothers had a significantly lower rate of CMV infection when compared to non-pregnant mothers attempting conception.[@b75-ijwh-2-023] Additionally, Vauloup-Fellous et al recently demonstrated a lower CMV seroconversion rate after counseling pregnant women on hygienic measures.[@b76-ijwh-2-023],[@b77-ijwh-2-023]
Despite the demonstrated success of education of pregnant women on hygienic measures to prevent CMV transmission, obstetricans are not providing uniform, appropriate counseling. A recent survey of the ACOG Collaborative Ambulatory Research Network (CARN) members revealed that less than half counseled their patients on methods to prevent CMV transmission and the importance of prevention of transmission.[@b63-ijwh-2-023] Additionally, results of the survey of the ACOG CARN members and a survey of physicians in the Netherlands demonstrated gaps in their knowledge of CMV transmission.[@b63-ijwh-2-023],[@b78-ijwh-2-023] Continued education of providers on CMV infection and prevention is important in order for accurate counseling of pregnant women.
Effective strategies to increase awareness of CMV and the methods to prevent its transmission are needed. Additionally, a systematic means to measure the success of these programs is required. Recently, Bate and Cannon have proposed a plan to identify effective behavioral interventions for prevention of congenital CMV based on a social marketing model.[@b79-ijwh-2-023] This paper provides a framework to identify and evaluate behavioral interventions aimed at encouraging pregnant women to follow preventative measures.[@b79-ijwh-2-023] Identification of effective means to educate pregnant women on CMV would allow for more focused use of resources, and could result in a reduction in CMV transmission.
Therapy
=======
Antiviral
---------
Antiviral agents currently licensed for the treatment of CMV infections include ganciclovir and its prodrugs valganciclovir, foscarnet, and cidofovir. Although there has been significant experience with the use of ganciclovir in the infected newborn (reviewed below), none of these agents have been formally approved by the US Food and Drug Administration (FDA) specifically for the treatment or prevention of CMV infections during pregnancy or for congenital CMV.[@b80-ijwh-2-023] There has been concern reported regarding the safety of treatment with antiviral medications in pregnancy. A case report of use of oral ganciclovir in a liver transplant patient in pregnancy did not show any evidence of teratogenicity.[@b81-ijwh-2-023] Ganciclovir has been demonstrated to cross the placenta, and therefore could in theory, be utilized to treat *in utero* congenital CMV infection.[@b82-ijwh-2-023] An observational study of 20 women with 21 fetuses with confirmed *in utero* CMV infection treated with oral valacyclovir demonstrated placental transfer of the drug, with therapeutic concentrations in the AF and a reductions of viral load in the fetal blood.[@b83-ijwh-2-023] There have been several case reports of treatment of congenital CMV infection *in utero* with oral, parenteral, or intra-amniotic ganciclovir with varying degrees of success.[@b84-ijwh-2-023]--[@b88-ijwh-2-023] Although it is probably safe, prenatal treatment of fetal CMV infection with ganciclovir is currently not supported by the available data; further study with a randomized controlled trial is needed.
Despite a lack of formal FDA approval, there is good evidence supporting the treatment of congenital CMV infection with ganciclovir, based upon its demonstrated impact on SNHL outcomes. A randomized, controlled trial of 100 neonates with symptomatic congenital CMV infection treated with intravenous ganciclovir at a dose of 6 mg/kg every 12 hours for 6 weeks showed prevention of deterioration of hearing at 6 months.[@b89-ijwh-2-023] In a retrospective review of 9 children with symptomatic congenital CMV, none had progression of hearing loss following prolonged ganciclovir therapy.[@b90-ijwh-2-023] In another study, children with asymptomatic congenital CMV infection were treated with ganciclovir versus observation and followed over time.[@b91-ijwh-2-023] No children in the ganciclovir group had SNHL, while 11.1% in the observation group demonstrated evidence of SNHL over time. Valganciclovir has been more recently studied for the postnatal treatment of symptomatic congenital CMV, and is an attractive alternative to ganciclovir, because it can be administered orally.[@b92-ijwh-2-023] A trial is currently in progress comparing treatment with valganciclovir for 6 weeks versus 6 months, with the goal of examining whether prolonged therapy further improves neurodevelopmental outcomes, including SNHL.[@b92-ijwh-2-023]
Passive immunization
--------------------
Immunoglobulin therapy has been used to treat several conditions in pregnancy and is generally well tolerated. The mechanisms by which immuoglobulins act to treat many pregnancy-related conditions remain largely unknown. Treatment of a variety of viral infections with immunoglobulin has been valuable in disease control. Theoretical mechanisms include direct neutralization of virus particles; facilitation of antibody-directed natural killer cell activity; antibody-dependent cellular cytotoxicity; and blocking of viral entry at the cell surface.[@b93-ijwh-2-023]
Passive immunization with hyper-immune globulin (CMV HIG) has been studied for the *in utero* treatment and prevention of congenital CMV infection. CMV HIG is a pooled, high-titer immunoglobulin preparation derived from donors with high levels of CMV antibody. Improved perinatal outcomes after treatment of congenital CMV infection was first demonstrated in animal models.[@b94-ijwh-2-023],[@b95-ijwh-2-023] Nigro and colleagues completed a prospective study of CMV HIG for the treatment of pregnant women with primary CMV infection, including some women with confirmed fetal CMV infection.[@b96-ijwh-2-023] The women were enrolled in the "therapy" group if they had an amniocentesis and confirmed congenital CMV infection, as evidenced by a positive PCR in the AF, or the "prevention" group if they did not have an amniocentesis. In the therapy group only 1/31 of the treated mothers delivered an infant with congenital CMV disease, compared to 7/14 mothers who were not treated with HIG. In the prevention group 6/37 mothers receiving HIG delivered infants with congenital CMV, compared to 19/47 mothers who did not receive treatment. Overall, there was a statistically significant reduction of risk for congenital CMV infection in the HIG therapy group, and a reduction in CMV infection in the HIG prevention group. In a subsequent study by Nigro and colleagues, 3 fetuses treated with HIG had resolution of their ultrasonographically detected cerebral abnormalities; in contrast 2 untreated fetuses had persistence of their cerebral abnormalities.[@b97-ijwh-2-023]
In addition to fetal effects, CMV HIG has been demonstrated to affect the placenta. In pregnancies treated with HIG there has been demonstration of significant reductions in placental thickness.[@b97-ijwh-2-023],[@b98-ijwh-2-023] The reduction in placental thickness observed following HIG treatment suggests that improved fetal outcomes are mediated, at least in part, through improved placental health and function, and not (only) through the salutary effect of immune globulin present in the fetal circulation.[@b99-ijwh-2-023]
The mechanisms by which HIG works for the treatment and prevention of congenital CMV may be due to the virus neutralizing effect. Nigro et al demonstrated that women in the treatment group had significantly higher levels of CMV specific IgG concentration and IgG avidity after HIG treatment when compared to the untreated group.[@b96-ijwh-2-023] Symptomatic CMV disease may be secondary to inflammation in response to CMV infection.[@b100-ijwh-2-023],[@b101-ijwh-2-023] The immunomodulatory effects of HIG may decrease the inflammation, and subsequent tissue damage from CMV. Randomized controlled trials of HIG for treatment and prevention of congenital CMV infection are needed. Until such data are available, clinicians could give consideration to treatment with CMV HIG in pregnant patients with confirmed fetal CMV infection.
Vaccines
========
Live attenuated virus vaccines
------------------------------
It has been over three decades since the first live CMV vaccine candidate was tested in humans.[@b102-ijwh-2-023] A subsequent live attenuated CMV vaccine candidate, the Towne strain, was found to have a good safety profile and was immunogenic.[@b103-ijwh-2-023] A clinical trial of the Towne strain CMV vaccine in kidney transplant patients showed that the vaccine did not prevent CMV infection, but it did reduce the severity of CMV disease when compared to placebo controls.[@b104-ijwh-2-023] However, the Towne vaccine failed to prevent CMV infection in seronegative women who had children attending group day care when it was tested in a placebo-controlled trial.[@b105-ijwh-2-023] The lack of efficacy in this study was attributed to the decreased neutralizing titers produced after Towne vaccination when compared to infection by wild type virus. In addition, the laboratory-adapted Towne strain of CMV has genomic deletions which may affect the immunogenicity of the vaccine. With the goal of improving the immunogenicity of live, attenuated CMV vaccines, 4 "chimeric" vaccines were created which represented hybrids of the Towne strain and the less attenuated Toledo strain of CMV, and tested in a phase one study; these vaccines were all well tolerated, although immunogenicity was difficult to assess.[@b106-ijwh-2-023] Additional study of the chimeric vaccines need to be performed in seronegative controls.
Subunit vaccines
================
### Purified recombinant glycoprotein B
Additional vaccine approaches are currently being developed with the goal of inducing a potent virus-neutralizing antibody response.[@b107-ijwh-2-023] The CMV envelope glycoprotein B (gB) has been the most studied subunit vaccine candidate for this purpose, since it is a target of neutralizing antibody in all CMV-seropositive individuals. Animal models of gB vaccine have shown its ability to prevent congenital CMV infection and disease.[@b108-ijwh-2-023],[@b109-ijwh-2-023] Results of a phase II, placebo-controlled, randomized, double-blind trial of the recombinant CMV envelope gB with MF59 adjuvant were recently published.[@b110-ijwh-2-023] In this study, three doses of the CMV vaccine or placebo were administered at 0, 1, and 6 months to healthy women within 12 months postpartum. Women in the vaccine group were less likely to become infected with CMV than the placebo group (*P* = 0.02) with 18/225 women becoming infected with CMV in the vaccine group, compared to 31/216 in the placebo group.
### DNA vaccines
DNA vaccines have been studied in both animal models and humans. In the guinea pig model gB DNA vaccination administered prior to conception offered some protection against congenital CMV transmission in the liveborn pups.[@b111-ijwh-2-023] A phase I study of a bivalent CMV DNA vaccine demonstrated safety and immunogenicity of the DNA vaccine.[@b112-ijwh-2-023] The effect of immune priming with a CMV DNA vaccine encoding pp65, IE1, and gB was tested by administering the Towne strain after vaccination and evaluating the immune response.[@b113-ijwh-2-023] There was a significant decrease in time to pp65 T-cell and gB antibody response in DNA primed subjects when compared to control subjects who were administered Towne strain only. DNA vaccines are currently being evaluated in the hematopoietic stem cell transplantation population toward the goal of reducing CMV disease in these individuals.[@b114-ijwh-2-023]
### Vector systems
Vector systems utilize non-replicating vectors to express gene products of interest. Two examples of vector systems utilized in CMV vaccine development are the modified vaccinia virus Ankara (MVA) and an alphavirus vector based on an attenuated variant of Venezuelan equine encephalitis virus. MVA utilizes a highly attenuated poxvirus vector. The MVA vector system can express gB, as well as the cell-mediated immunity targets pp65, and IE1.[@b115-ijwh-2-023] The alphavirus vector system produces virus-like replicon particles (VRP) that can express gB, pp65 and IE1.[@b116-ijwh-2-023] The alphavirus vector system has been studied in the in the guinea pig model and was found to induce both humoral and cellular immunity and improve pregnancy outomes.[@b117-ijwh-2-023]
Future prospects
================
Recent advances in the understanding of CMV-cell interactions have lead to new insights into potential glycoprotein targets for vaccination. Recently, a new glycoprotein complex, including the gene products of the UL128-131 region of the viral genome, has been characterized. These proteins are necessary for CMV entry into epithelial cells.[@b118-ijwh-2-023],[@b119-ijwh-2-023] The live, attenuated Towne vaccine and the gB-based protein subunit vaccine are less effective than natural infection in inducing antibodies capable of neutralizing CMV infection in epithelial cells. Future optimization of CMV vaccines may require improvement in the humoral response to virally encoded proteins important in epithelial cell entry, particularly in view of the fact that most CMV infections are acquired at mucosal surfaces.[@b120-ijwh-2-023]
Conclusion
==========
CMV remains a significant public health concern. The neurologic disability from congenital CMV infection can be devastating. Antiviral drugs administered postnatally appear to decrease the severity of SNHL. CMV HIG has shown promising results for *in utero* treatment of fetal CMV infection, and possible prevention of congenital transmission, although randomized, blinded, controlled trials are lacking. CMV vaccine development continues to be a major public health priority. Until an effective CMV vaccine is licensed, education of young women regarding hygienic and behavioral approaches that can help prevent CMV transmission is essential. Obstetricians can lead the way in ensuring that appropriate counseling about the risks of CMV becomes a mainstay of prenatal care.
**Disclosures**
The authors report no conflicts of interest in this work. Supported by NIH R01HD044864 and HD038416.
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Extra Rage Comics
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I did this by making sure the comics would play to all the fucktards who go “aww” and upvote something that isn’t funny.
WELL BY GOD, I’ve got something you’re going to HATE. This is designed for all the little trolls out there, who are now going to RUSH to f7u12 spamposting and spamvoting up horrific comics which will possibly ruin the seriousness which has taken over this CANCEROUS and HIDEOUS scar upon the internet and possibly the worst abscess in COMIC HISTORY. |
We offer speedy registration service. We can meet you anywhere, anytime, to write your policy. If it is more convenient for you to meet us at your home or place of employment, just let us know.
As brokers with availability to a wide number of companies, Roche Insurance Agency is able to obtain the lowest possible rate for the best possible coverage for all of your insurance needs. Our staff is here to serve you, the customer, and answer any questions or concerns you may have.
Whether you have a question about your existing coverages or you are looking for a quote to compare with your current policy, we are happy to help. Please e-mail us or call and speak to one of our qualified Roche Insurance Agency representatives today.
Call or e-mail us now to join the Roche Insurance team and experience the difference!
If you are interested in hearing more information about our services or would like to start a policy with Roche Insurance Agency, simply call, fax, or email us. Or stop by our office at 426 Massachusetts Avenue in Boston's South End. We will gladly answer any questions you may have about any type of insurance you are interested in and what your options are. Once you've decided to join the Roche Insurance team, we will arrange for a time and place that is convenient to you to meet and complete the necesary paperwork. We look forward to meeting you!
If you have additional questions regarding your current policy or would like these issues explained in detail, just call us toll free at 1-888-546-7786 or e-mail us at [email protected]. |
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I always love finding out what beauty products my girlfriends are loving so I thought I would share my everyday favourites with you too. Enjoy!
I am still loving the Becca First Light Primer (you can find my review right here). As I mentioned in my review, it gives the skin a natural, dewy glow. I think it’s always important to start off with a great base which will help the rest of your makeup apply easier and last longer.
Speaking of bases, I have been using Youngblood Loose Natural Mineral Foundationfor over a year now and I could not speak more highly about it. Before this, my skin was breaking out a lot. It wasn’t until I booked an appointment to see a dermatologist where I found out that the liquid foundation I was using was clogging my pores. In comparison, this Youngblood mineral foundation provides a buildable coverage which feels lightweight and comfortable on the skin.
To help conceal any darkness under my eyes, I use Urban Decay Naked Skin Colour Correcting Fluid in Peach. Before this, I was opting for a lighter concealer but instead of brightening, it was leaving a grey cast under my eyes. Not ideal. The peach tone in this fluid actually corrects any blue-hued dark circles, which helps keep my under eyes looking nice and bright. For general concealing, I use the Nars Radiant Creamy Concealer. I find it is long lasting and has a creamy consistency which is easy to blend into the skin.
For my cheeks, I use the Nars Orgasm Blushwhich I am sure every one of you has heard about. It has been a staple in my makeup collection for years now and I don’t see it disappearing anytime soon. Orgasm is a peachy-pink shade with a shimmer finish, perfect for everyday wear. Next, I use the Hourglass Ambient Lighting Bronzer and the Becca Shimmering Skin Perfector in Opal. Together, these products help me achieve a bronzed, glowing complexion.
And finally, I have left my favourite until last, my Yves Saint Laurent Rouge Volupte Shine Oil in Stick. There’s no denying that it’s a splurge purchase but I think it’s worth every penny. The lipstick has a creamy formula which is hydrating on the lips and it smells amazing, what more could you want? I have the shade #44 which is a beautiful pinky nude.
Feel free to share your favourite beauty bits in the comments, I always love finding new products to try! |
[Compilation of Yan ke zheng zong yuan ji qi wei (Orthodox Ophthalmology: Revealing the Mystery of Eye Disease) and its academic achievements].
As an ophthalmic monograph compiled to systemize and elaborate the Yuan ji qi wei (Revealing the Mystery of Eye Disease) written to explore the gist of the original author, a valuable edition of the original Yuan ji qi wei. SHI Shi-de made reviews and comments to each eye disease included in the first volume of Yuan ji qi wei, followed by the rhymes on the etiology, manifestations, treatment and prescriptions written by his son SHI Guang, and rearranged and systemized the whole text made by his little brother SHI Shi-qi for better memory and popularization. He stressed the significant position of Yuan ji qi wei. The achievements of the Yan ke zheng zong yuan ji qi wei can be summarized into 4 points: the "18 disease" of eye disease is the guidelines for the differential diagnosis of ophthalmic diseases; Shi's annotation developed the essence of Ni's theory; SHI Guang's rhymes facilitated the spread of Ni's theory; the "hints for prescription" being the standards for the treatment of eye disease. |
A general population survey on patterns of benzodiazepine use and dependence in Lebanon.
In Lebanon, benzodiazepines are often available without medical prescription. We aimed to carry out the first community-based pharmaco-epidemiological study on benzodiazepine consumption in the Middle East Area. The prevalence of past-month benzodiazepine use was assessed in a 1000-subject randomized sample from the Lebanese community, and risk factors were studied in a group of 496 current users. Benzodiazepine use during the past month was found in 9.6% of subjects. Four variables were significantly associated with use: age higher than 45 years, female sex, cigarette smoking and the existence of a recent life event. Benzodiazepine dependence was found in 50.2% of users. Benzodiazepine use in Lebanon is particularly high, and can be related to well-known factors such as female sex and age, but other potent specific variables, such as war stress or the lack of control on drug access, can be hypothesized. |
/**
* 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.network.v2019_09_01;
import com.microsoft.azure.arm.collection.SupportsCreating;
import com.microsoft.azure.arm.resources.collection.SupportsDeletingByResourceGroup;
import com.microsoft.azure.arm.resources.collection.SupportsBatchDeletion;
import com.microsoft.azure.arm.resources.collection.SupportsGettingByResourceGroup;
import rx.Observable;
import com.microsoft.azure.management.network.v2019_09_01.implementation.DdosCustomPoliciesInner;
import com.microsoft.azure.arm.model.HasInner;
/**
* Type representing DdosCustomPolicies.
*/
public interface DdosCustomPolicies extends SupportsCreating<DdosCustomPolicy.DefinitionStages.Blank>, SupportsDeletingByResourceGroup, SupportsBatchDeletion, SupportsGettingByResourceGroup<DdosCustomPolicy>, HasInner<DdosCustomPoliciesInner> {
}
|
1. Field of the Invention
The invention is directed to purified and isolated polypeptides, the nucleic acids encoding the polypeptides, and processes for production of recombinant forms of the polypeptides. This invention is also directed to antibodies that specifically recognize the polypeptides, compositions containing the polypeptides, and to the use of these materials in various assays. In particular, the polypeptides, the nucleic acids encoding the polypeptides, and the antibodies are useful for the detection of human B cell lymphomas, enhancing the production of interferon γ (IFN-γ), enhancing the growth of NK cells, treating viral infections and tumors, and enhancing the activity of cytotoxic T lymphocytes (CTLs).
2. Description of Related Art
1. Lymphomas
The malignant lymphomas represent multiple diseases with diverse morphologic and clinical expressions. Morphologic classification schemes have been shown to be useful in delineating natural history, prognosis, and response to therapy. However, in some instances, distinctive morphologic entities may be very closely related clinically or biologically or both, whereas other diseases that share morphologic similarities may be clinically and biologically quite distinct. Thus, immunological methods have become essential tools for the diagnosis and classification of certain human tumors, particularly for leukemias and lymphomas.
More particularly, some patients carrying malignancies have been found to produce antibodies against tumor-associated or other malignant cell-associated surface determinants as well as against a variety of differentiation and other non-tumor antigens. Several very sensitive immunological procedures have been developed for the detection of such antibodies.
A variety of other markers of hematopoietic malignancies allows clinically valuable categorizations, which are not possible by morphological or histochemical parameters. These markers can also be detected using immunological procedures. One of the main advantages of these procedures over other methods for the measurement of tumor-associated markers is their high level of sensitivity, with the ability often to detect a substance at nanogram or even picogram levels. In addition, immunological tests afford the ability to discriminate among substances with closely related structures and thereby to identify tumor-associated analogs found in normal, nonmalignant states.
Many tumor-associated markers have been detected in the sera or other body fluids of patients with malignancies. A few of these markers have been sufficiently restricted to tumor-bearing individuals to aid in detection or differential diagnosis (or both) of malignant disease. However, most markers have been found to lack sufficient specificity for such applications, with an appreciable frequency of elevated marker levels in patients with nonmalignant diseases (i.e., false positive results).
In addition, malignant lymphomas are usually an admixture of a neoplastic element and normal elements or both. A cell suspension prepared from a malignant lymphoma will consist of a mixture of benign and malignant cells, and the malignant cells may not necessarily be in the majority. To determine the phenotype of malignant cells, it is necessary to identify those markers associated with neoplastic cells.
It should be evident that there exists a need in the art for the identification of additional cell surface markers associated with malignant conditions. In particular, there is a continuing need for cell surface markers associated with malignant lymphomas. The identification of specific cell surface markers associated with malignant lymphomas will aid the detection of malignancies associated with these markers.
2. NK Cells
One of the major types of circulating mononuclear cells is that of the natural killer, or NK, cell (M. Manoussaka et al., Journal of Immunology 158:112-119, 1997). NK cells are a cell type derived from bone marrow precursors (O. Haller et al., Journal of Experimental Medicine 145:1411-1420, 1977). NK cells appear to be closely related to T cells and the two cell types share many cell surface markers (M. Manoussaka et al., 1997). Although NK cells are cytotoxic cells as are some T cells, unlike T cells, NK cells do not express the T-cell receptor or CD3 components (P. Scott and G. Trinichieri, Current Opinion in Immunology 7:34-40, 1995; G. Trinichieri, Adv. Immunology 47:187-376, 1989). NK cells commonly express CD16 and CD56 antigens (K. Oshimi, International Journal of Hematology 63:279-290, 1996). Similar to cytotoxic T lymphocytes (CTL), NK cells are capable of exerting a cytotoxic effect by lysing a variety of cell types (G. Trinichieri, 1989). NK cells are capable of exerting cytotoxicity in a non-MHC restricted fashion (E. Ciccione et al., J. Exp. Med. 172:47, 1990; A. Moretta et al., J. Exp. Med. 172:1589, 1990; and E. Ciccione et al., J. Exp. Med. 175:709).
NK cells mediate some of their functions through the secretion of cytokines, such as interferon γ (IFNγ), granulocyte-macrophage colony-stimulating factors (GM-CSFs), tumor necrosis factor α (TNF-α), macrophage colony-stimulating factor (M-CSF), interleukin-3 (IL-3), and IL-8 (P. Scott and G. Trinichieri, 1995).
Cytokines including IL-2, IL-12, TNF-α and IL-1 can induce NK cells to produce cytokines (P. Scott and G. Trinichieri, 1995). IFNγ and IL-2 are strong inducers of NK cell cytotoxic activity (G. Trinichieri et al., Journal of Experimental Medicine 160:1147-1169, 1984; G. Trinichieri and D. Santoli, Journal of Experimental Medicine 147:1314-1333, 1977). NK cells can be stimulated and expanded in the presence of IL-2 (K. Oshimi, International Journal of Hematology 63:279-290, 1996). IL-12 has been shown to induce cytokine production from T and NK cells, and augment NK cell-mediated cytotoxicity (M. Kobayashi et al., Journal of Experimental Medicine 170:827-846, 1989).
NK cells can lyse a variety of cell types, including normal stem cells, infected cells, and transformed cells (D. See et al., Scand. J. Immunol. 46:217-224, 1997). Cells that lack MHC class I are susceptible to NK cell-mediated lysis (H. Reyburn et al., Immunol. Rev. 155:119-125, 1997). The lysis of cells occurs through the action of cytoplasmic granules containing proteases, nucleases, and perforin (D. See et al., 1997). Antibodies directed against CD2 and CD11a inhibit the cytotoxic effect of NK cells (O. Ramos et al., J. Immunol. 142:4100-4104, 1989; C. Scott et al., J. Immunol. 142:4105-4112, 1989). NK cells can also lyse cells by antibody-dependent cellular cytotoxicity (D. See et al., 1997).
NK cells have been shown to destroy both extracellular protozoa and the cells infected by protozoa (T. Scharton-Kersten and A. Sher, Current Opinion in Immunology 9:44-51, 1997). In most instances, cytotoxic activity appears to be dependent upon lymphokine activation (T. Scharton-Kersten and A. Sher, 1997).
NK cells have been implicated as mediators of host defenses against infection in humans with varicella zoster, herpes simplex, cytomegalovirus, Epstein-Barr virus, hepatitis B, and hepatitis C viruses (D. See et al., 1997). Many viruses induce NK cell cytotoxicity, including herpesvirus and cytomegalovirus (C. Biron, Current Opinion in Immunology 9:24-34, 1997). The induction of NK cell activity is a result of the induction of IFN-γ by viral infection, and NK cells are important in the early defense against many viral infections (C. Biron, 1997). The NK1+CD3− population of NK cells is the subset activated by viral infection (C. Biron, 1997). The response of NK cells to viral infection involves direct cytotoxicity and production of various cytokines such as IFN-γ and TNF-α (C. Biron, 1997).
A number of human lymphoproliferative disorders of NK cells are known. These include NK cell-lineage granular lymphocyte proliferative disorder (NK-GLPD), NK cell lymphoma, and acute leukemia of NK cell lineage (K. Oshimi, International Journal of Hematology 63:279-290, 1996). Most patients with aggressive type NK-GLPD die of the disease (K. Oshimi, 1996). NK cell lymphoma is resistant to combination chemotherapy (K. Oshimi, 1996).
NK cells activated with IL-2 have been shown to have activity against human leukemia cells (L. Silla et al., Journal of Hematotherapy 4:269-279, 1995). Furthermore, NK cells appear to have a role in the treatment of chronic myeloid leukemia (K. Oshimi, 1996).
NK cells are involved in both the resistance to and control of cancer spread (T. Whiteside and R. Herberman, Current Opinion in Immunology 7:704-710, 1995). Furthermore, the presence and activation of NK cells may be outcome determinative; low or non-existent NK activity is associated with a high frequency of viral disease and cancer (T. Whiteside and R. Herberman, 1995).
In view of the important role that NK and T cells play in vivo, in host defenses, tumor cell surveillance, and autoimmune diseases, there exists a need in the art for polypeptides suitable for the in vivo and in vitro enhancement of NK and T cell activity.
3. Interferon γ
The production of IFNγ is a function of T cells and NK cells, and IFN-γ activates antiviral immune reactions (E. De Maeyer and J. De Maeyer-Guignard, in The Cytokine Handbook, A. W. Thompson (ed.), Academic Press, 1994, pp. 265-288). IFN-γ preferentially inhibits Th2 proliferation, but not Th1 proliferation (T. F. Gajewski and F. W. Fitch, J. Immunology 140:4245-4252, 1988). IFN-γ also plays an important role in macrophage activation and promotes proliferation of activated B cells (De Maeyer and De Maeyer-Guignard). These, and other effects of IFN-γ, indicate that increased in vivo levels of IFNγ production serve as a general immune modulator.
IFN-γ has been used clinically in treating chronic granulomatous disease, atopic dermatitis, systemic achlerosis, lepratmatous leprosy, common warts, hepatitis B infection, myelogenous leukemia, and metastatic melanoma (J. Mordenti et al., in Therapeutic Proteins, A. H. C. Kung et al. (eds.), W.H. Freeman and Co., 1993, pp. 187-199). In view of the important role that IFN-γ plays, in vivo, in immune modulation, there exists a need in the art for polypeptides suitable for the enhancement of in vivo and in vitro IFN-γ levels.
4. Cytotoxic T Lymphocytes
CTLs are an important in vivo defense against viral, and bacterial, and cancerous diseases, in that they lyse target cells bearing foreign antigens (G. Berke, in Fundamental Immunology, W. E. Paul (ed.) Raven Press Ltd., 1989, pp. 735-764. In view of the important role that CTLs plays, in vivo, in the immune response to infections and tumor surveillance, there exists a need in the art for polypeptides suitable for the enhancement of in vivo and in vitro CTL activity. |
Basic fibroblast growth factor increases regional myocardial blood flow and salvages myocardium in the infarct border zone in a rabbit model of acute myocardial infarction.
Basic fibroblast growth factor (bFGF) has been shown by some to promote angiogenesis and myocardial salvage in experimentally induced acute myocardial infarction. Although these findings have spurred much clinical interest, they are not universally observed, and the true efficacy of bFGF remains unclear. The authors used a rabbit model of acute myocardial infarction to further elucidate the effects of bFGF on acutely infarcted myocardium containing few collaterals. Myocardial infarction was evoked by ligation of the left coronary artery. Prior to ligation, either 100 microg of bFGF (bFGF group; n = 15) or physiological saline (control group; n = 22) was injected into the myocardium supplied by the ligated artery. With use of nonradioactive colored microspheres, regional blood flow (Qm) was measured before, immediately after, and 4 weeks after coronary artery ligation. Infarct and border zone sizes were measured in cross-sectional slices of the resected hearts, and the amount of viable myocardium (myocardium score) and the extent of fibrosis were histologically determined in each area. Four weeks after ligation, Qm values in the infarcted area did not significantly differ between the bFGF and control groups (0.54 +/- 0.36 vs 0.48 +/- 0.30 mL/min/g); in the border zone, Qm tended to be higher in the bFGF group (3.39 +/- 2.68 vs 1.47 +/- 0.80 mL/min/g), but the difference was not significant; finally in the noninfarcted area, Qm was significantly (p < 0.05) higher in the bFGF group (6.06 +/- 3.85 vs 2.09 +/- 0.82 mL/min/g). There was no significant difference in the amount of viable myocardium or the extent of fibrosis in the infarcted areas of the two groups. In the border zone, however, the amount of viable myocardium was significantly (p < 0.005) larger in the bFGF group (61.8 +/- 8.5% vs 35.8 +/- 20.3% of the visual field). Likewise, as graded on a scale from 0 to 5, the extent of fibrosis was significantly (p < 0.005) less in the bFGF group (2.1 +/- 0.5 vs 3.3 +/- 0.8). In conclusion, injection of bFGF into acutely infarcted myocardium increased blood flow to the noninfarcted area and salvaged the myocardium in the border zone. |
Roku cracked 10 million in total units sold last September. Apple is up to 25 million Apple TV units sold, and more than half of those are the current 3rd-gen model. I would hardly call that "roundly trounced".
Plus, Netflix + Hulu Plus + HBO Now + AirPlay will be compelling enough for plenty of people over the next 3 months. (Might be a different case come the holidays, though.)
The people interested in GoT and nothing else will probably continue pirating. HBO is counting on that group being very, very small -- especially given the sheer number of shows (True Detective, The Wire, Treme, Boardwalk Empire, etc.) that many will likely find binge-worthy. That's HBO Now's value proposal.
And it's only a hassle to sign up and then cancel if you're dealing with a cable company. It wasn't nearly as bad when I did it with DishWorld and Hulu Plus.
It's also a blatant supply chain-emptying move by Tim Cook. He's trying to clear out Apple TVs, possibly to introduce a new product later this year. That said, it's a move that seems likely to work out for Apple.
I feel a strange urge to play devil's advocate on this one -- which I know is usually a bad idea on this site, but follow me on this...
Yes, people who just want to watch Game of Thrones and either refuse to pay or don't want to watch any other HBO shows will continue seeding torrents. That's not going away.
But...
1.) Apple TV has already sold 25 million Apple TV units to date, and based loosely on the sales figures listed on Wikipedia, more than half those units appear to be the 3rd-generation model, which has not been jailbroken. That's a pretty big installed base, and lowering the price on Apple TV ensures that base will grow. (It's a blatant supply chain-emptying move by Tim Cook, yes, but most potential buyers won't care that much.)
2.) Having more than one set-top box connected to a TV isn't so far-fetched these days. I have both an Apple TV and a Roku 3. They do have some different uses -- the Roku has Amazon Prime, Sling TV, and DIAL streaming, while the Apple TV has a superior podcast interface and AirPlay for certain iPad apps I like to use. I used to have a Chromecast as well. Given how cheap all these STBs and streaming sticks are now, it's not so odd for cord-cutters to buy and use more than one.
3.) HBO Now's value proposal goes beyond GoT. Think of all those other HBO series and movies that people might not have seen yet -- The Wire, True Detective, Veep, Treme, Boardwalk Empire, etc. That's a lot of binge-watching for not that much money. Sure, you can pirate all of them, but for $15/month, you can stream the whole kit and caboodle and not have to look at those soul-sucking porn ads. (Or maybe I'm the only guy who's grown weary of computer-animated tits. You tell me.) Netflix streaming traffic overtook torrent traffic FOUR YEARS AGO. That proved people will pay for convenience. This is what HBO Now is offering, and it *will* be compelling to many who only use torrents because HBO hadn't otherwise made it convenient. Does Apple exclusivity lessen that convenience for a few months? Sure, but the installed Apple TV base and the relatively low cost of entry *will* attract customers.
4.) This is a long play for HBO, and for its parent company, Time Warner, which licensed its Turner Broadcasting channels to Sling TV. By Labor Day, *all* those channels will be available on a *lot* of STBs and streaming sticks. Apple exclusivity is just a temporary move to help keep Comcast off its back for a while.
Also, apropos of nothing:
5.) At least one market research group (Parks Associates) has predicted that as many as 7 million people will get rid of cable TV once HBO Now becomes available. I don't think it will be quite that high all at once, but let's revisit that figure a year from now and see how close they got.
6.) None of this takes into account HBO Go password-sharing, which is also likely to rise with the premier of GoT season 5 -- especially if cable companies still try to offer customers 3 months of free HBO. That might already be putting a dent in piracy without anyone examining it too closely. It's certainly a reason why HBO Now exists in any form. If the market wasn't there, HBO wouldn't bother.
ESPN and TNT show a ton of NBA games, including most of the playoffs. ESPN also shows a lot of college basketball, and TBS/TNT will air a huge chunk of the NCAA Tournament, including the Final this year. So if you like hoops but hate your cable company, this might work. (And there have been studies showing basketball fans skew younger than other sports, so this falls in line with Dish's target market here.)
If you're a hockey fan, forget it. There's no way Dish and Comcast come to terms here, especially if Charlie Ergen gets on Capitol Hill and starts screaming about data caps being uncompetitive.
After I got on Twitter and bemoaned the lack of competition among ISPs in my city, he told me I was misguided, because there was plenty of competition provided by WISPs out there. Never mind the fact that:
1. A bit of Googling failed to uncover an WISPs in the Raleigh-Durham area, and2. I live in an apartment, so even if a WISP existed, I couldn't put up an antenna to use it.
So what, I'm supposed to move into a house in another city to conform to Brett Glass' little Wyoming fantasy world? Right. When I challenged him to find a WISP, any WISP, here in the Triangle, he offered no help and just told me I was delusional and there was no hope for me.
Brett Glass has no clue what the vast majority of consumers have to go through in this country with their internet access. I blocked him on Twitter. You should, too.
Now that ESPN is valued at more than one-third of the entire Walt Disney Company, Disney is simply focusing fewer resources on copyright protection and more resources on simply keeping the cable bundle intact, so that they can continue to collect $70/year from people who don't care about sports but gotta have their Mad Men fix.
1.) The Comcast-NBCU merger practically prevents NBC from withholding its programming from other services, but even if it didn't, if Dish wants to settle on similar terms with NBC, Comcast can't afford to be viewed as a holdout. Any appearance that Comcast abusing their market position could convince regulators to block the buyout of TWC.
2.) Should Dish get this IPTV service off the ground, Charlie Ergen could go in front of the press (and Congress) and claim that Comcast's data caps are anti-competitive, because they prevent Comcast Internet customers from using Dish. That could force Comcast to concede on data caps to get the TWC acquisition through.
3.) In terms of the marketplace, Dish has a long-term partnership with Frontier Communications to be the TV portion of their "triple play" package, but Frontier can't offer that package to apartment dwellers who can't put up a satellite dish. If Dish gets this IPTV service working, that changes, and those renters who hate Comcast and TWC can have a legit alternative for TV service.
I don't know about you, but I'm okay with losing Auto-hop if it means either putting the kibosh on data caps, blocking the Comcast-TWC merger, or costing either of them a large number of customers.
Just because the guy who wrote YMCA decides that he doesn't want whoever the Village People are now to perform the song anymore, the whole concept of a song's copyright reverting back to the creator is suddenly a "dumb idea"?
I don't buy that. Think about all the songs that the major labels currently "own" that they're practically hoarding in a vault somewhere and not promoting at all. Musicians have far more avenues for promoting their compositions in 2013 than they did in 1978. Why shouldn't those musicians take those songs back and do something new with them? Why should the labels be allowed to keep those songs locked up in perpetuity?
One guy who doesn't get the concept does not invalidate the concept. Give the art back to the artists.
tl;dr : Because their current deal with cable & satellite carriers calls for a 6.5% carriage fee increase every year, ESPN's annual carriage fee income will continue to increase between now and 2020 -- unless the annual number of cord cutters increases by 50%, year over year. And that rate of cord cutting seems rather unlikely at the moment.
Also, if ESPN became a premium channel, the network would need 40.7 million subscribers at $14.95/month, or 30.5 million subscribers at $19.95/month, to make as much as it makes now in annual carriage fees -- about $7.3 billion -- from ESPN, ESPN2, ESPNU, and ESPNEWS. And it probably couldn't get away with selling $3.3 billion in ads if it went premium.
So yeah, big media really isn't going to change until we all stop giving it so much money.
Team doctors are paid by team OWNERS, not players. There's a long history of team doctors bending rules to get players back on the field/court/ice too quickly. If Derrick Rose thinks the advice he's getting will hurt his career in the long-term (he's only 24), then I'm giving him a pass.
Besides, these Bulls are not beating the Heat with or without Derrick Rose, so why pin the blame solely on him?
I was just thinking the same thing, especially given Fox's 9-year, $10-billion deal with the NFL that goes into effect next March. Pretty sure Roger Goodell would remind Chase Carey of a few 11-figure cancellation fees in that contract if Fox shuts down its broadcast network. The NFL wants as many eyeballs as possible.
The NBA, on the other hand, makes all its money from ESPN and Turner. If ABC disappears, I'm not sure the NBA would miss it that much, save for Xmas-day hoops and the Finals. |
1. Introduction {#sec1-cancers-12-02264}
===============
Acute lymphoblastic leukemia (ALL) is the most frequent neoplastic disorder in children, which was virtually incurable before the 1960-ies. Nowadays, about 90% of children with ALL experience long-term survival in high-income countries using risk-tailored combined chemotherapy. 'BFM ALL Intercontinental' (ALLIC) is a network of national groups and single centers of the international Berlin-Frankfurt-Münster Study Group (iBFM-SG) with restricted resources. ALLIC members do not have a regular access to the most advanced molecular technologies required from participants of most recent ALL clinical trials \[[@B1-cancers-12-02264],[@B2-cancers-12-02264],[@B3-cancers-12-02264]\]. Yet, the ALL IC-BFM 2002 clinical trial demonstrated successful co-operation of the participating groups resulting in competent event-free survival (EFS) and overall survival (OS) rates which exceeded historical results of the members \[[@B4-cancers-12-02264]\]. Toxic mortality in ALL IC-BFM 2002 was higher than in parallel clinical trials of the Children's Oncology Group (COG) and other BFM consortia. This fact highlights the need for the identification of potent biomarkers allowing precise stratification of risk groups of pediatric ALL. A broad spectrum of chromosomal abnormalities, submicroscopic structural genetic alterations and sequence mutations gained a role as prognostic and predictive biomarkers in childhood ALL, in addition to conventional risk factors, such as age, sex, initial white blood cell count (WBC), and response-to-treatment measures \[[@B5-cancers-12-02264],[@B6-cancers-12-02264],[@B7-cancers-12-02264],[@B8-cancers-12-02264]\]. Cell surface and intracellular (cytoplasmic; cy) proteins of leukemic cells may provide additional prognostic biomarkers \[[@B9-cancers-12-02264],[@B10-cancers-12-02264]\]. Identification of novel leukemia-associated protein biomarkers to be detected by flow cytometry (FC) is of special interest for ALLIC members \[[@B11-cancers-12-02264]\]. FC is an economic, powerful, and user-friendly method. Recently, next generation flow cytometry was shown to reach the sensitivity and specificity of advanced molecular technologies in the detection of minimal residual disease (MRD) \[[@B12-cancers-12-02264]\]. The consortium developed a multiparameter FC-based MRD detection method as a pilot project of ALL IC-BFM 2002 \[[@B13-cancers-12-02264]\]. Result of mid-induction, day 15 bone marrow (BM) FC-MRD was incorporated in the risk assessment approach of the next ALLIC clinical trial, ALL IC-BFM 2009 (EuDract: 2010-019722-13, unpublished data) \[[@B14-cancers-12-02264]\]. ALLIC FC laboratories became members of the International BFM Flow-network \[[@B8-cancers-12-02264],[@B15-cancers-12-02264]\].
Presence and Role of FXIII-A in Different Cell Types
----------------------------------------------------
FXIII is a pro-transglutaminase circulating in plasma as a tetramer of subunit A and B (FXIII-A~2~B~2~). FXIII-A but not FXIII-B is present physiologically as a dimer, FXIII-A~2~ in several types of cells, such as megakaryocytes, platelets, monocytes/macrophages, dendritic cells, mast cells, sebocytes, preadipocytes, osteoblasts, chondrocytes, and cornea cells. Excellent reviews summarized the functions of FXIII in health and disease \[[@B16-cancers-12-02264],[@B17-cancers-12-02264],[@B18-cancers-12-02264]\]. In addition to normal cells, FXIII-A is present in transformed cells of benign and malignant neoplastic conditions, such as hamartomas of tuberous sclerosis, juvenile xanthogranuloma, dermatofibroma, other fibrovascular tumors, anaplastic hemangiopericytoma, clear cell carcinomas (CCC), biphenotypic sinonasal sarcoma, myeloid leukemias of the monoblast/monocyte and megakaryocyte lineages, and acute promyelocytic leukemia (APL) \[[@B19-cancers-12-02264],[@B20-cancers-12-02264],[@B21-cancers-12-02264],[@B22-cancers-12-02264],[@B23-cancers-12-02264],[@B24-cancers-12-02264],[@B25-cancers-12-02264],[@B26-cancers-12-02264],[@B27-cancers-12-02264]\]. Our group was the first to identify leukemic lymphoblasts of patients with BCP-ALL as a previously unknown expression site for FXIII-A. FXIII-A expression was only observed in B-cell progenitor (BCP) lymphoblasts and neither in mature normal and leukemic B-cells, nor in normal BM B-cell precursors. Immunophenotypic markers of FXIII-A positive BCP lymphoblasts did not differ from FXIII-A negative BCP lymphoblasts \[[@B28-cancers-12-02264]\].
In contrast to the role of FXIII in circulation, little is known about the function of the FXIII-A~2~. The role of FXIII-A~2~ was demonstrated in cytoskeletal remodeling and in the complex processes of phagocytosis, chemotaxis and cell adhesion. Translocation of FXIII-A~2~ from the cytoplasm to the nucleus was demonstrated, where the enzyme may react with as yet unidentified substrates \[[@B16-cancers-12-02264],[@B18-cancers-12-02264],[@B29-cancers-12-02264]\]. FXIII-A~2~ expression in CCC cells was implicated in the pathogenesis of thromboembolic complications \[[@B25-cancers-12-02264]\]. In neoplastic fibroblasts preferentially expressing FXIII-A~2~ as compared with normal fibroblasts, FXIII-A~2~ was suggested to support cell proliferation \[[@B23-cancers-12-02264],[@B30-cancers-12-02264]\].
Previously, our group described that FXIII-A was expressed in leukemic BCP lymphoblasts in addition to known expression sites. In a retrospective single-center cohort of children with ALL treated with the ALL IC-BFM 2002 protocol, expression of FXIII-A was correlated with statistically significant survival advantage \[[@B31-cancers-12-02264]\]. According to the observations of on one of our further study, FXIII-A expression intensity at the protein level seemed an important marker to stratify better the BCP-ALL. Using oligonucleotide microarray analysis and RT-Q-PCR method, we have also demonstrated that the intensity of expression of the FXIII-A~1~ gene (*F13A1*) at the mRNA level correlated with the three characteristic FXIII-A protein expression groups defined by FC, i.e., FXIII-A-negative, -dim, and --bright. The three different FXIII-A expression groups, i.e., FXIII-A-negative, -dim, and --bright, defined three distinct gene expression signatures. The differentially expressed genes had biologically and clinically relevant functions and were associated with leukemia and other forms of cancer. Moreover, gene expression profile of FXIII-A-negative samples exhibited an almost complete overlap with that of samples classified as belonging to the 'B-other' genetic category. These data suggested that the three different FXIII-A expression profiles defined by FC might characterize novel subgroups of pediatric BCP-ALL \[[@B32-cancers-12-02264]\]. Similar associations between expression intensity of biomarkers both at the mRNA and protein levels and clinical relevance have been observed to exist in T-ALL and in AML \[[@B33-cancers-12-02264],[@B34-cancers-12-02264]\].
Our aim was to investigate the association of FXIII-A expression pattern on survival figures and correlations with known clinical and genetic prognostic factors in a multi-center study within the frames of the prospective ALL IC-BFM 2009 clinical trial. We also wanted to identify cases characterized by adverse risk so that these can be more closely monitored not only by widely used methods but also the examination of FXIII-A pattern.
2. Results {#sec2-cancers-12-02264}
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2.1. Clinical Significance of Different Expression Patterns of FXIII-A by B-Cell Progenitor (BCP) Lymphoblasts {#sec2dot1-cancers-12-02264}
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We observed three different staining patterns of FXIII-A expression in terms of positivity of leukemic lymphoblasts: a negative pattern, a dim pattern, and a bright pattern ([Figure 1](#cancers-12-02264-f001){ref-type="fig"}) \[[@B35-cancers-12-02264]\]. In case of the negative expression pattern, leukemic lymphoblasts overlapped with residual normal lymphocytes. In bright cases, the leukemic blast cell population separated almost completely from residual normal lymphocytes. In case of dim samples, leukemic lymphoblasts appeared as a broad but homogenous group with a partial overlap with residual normal lymphocytes on FC dot-plots. The histogram analysis of FXIII-A dim expression cases showed that the leukemic cell population exhibited a single group with a continuously increasing fluorescence intensity and excluded the existence of two distinct subpopulations, i.e., a negative and a bright one with respect to FXIII-A expression. Of the analyzed 408 cases, there were 137 negative, 189 dim, and 82 FXIII-A bright samples.
In 36 patients, FXIII-A expression was evaluated in parallel at diagnosis and in the day 15 BM sample. We excluded patients of the Flow Low-risk (FLR) category because exact ratio of FXIII-A positive lymphoblasts below 0.1% could not be estimated due to the cytoplasmic expression of FXIII-A. The percentage of FXIII-A positive leukemic lymphoblasts of patients with Flow Medium- risk (FMR) and Flow High-risk (FHR) categories was significantly lower in Day 15 than in Day 0 samples (*p* \< 0.001) \[[@B14-cancers-12-02264]\]. FXIII-A expression of FXIII-A negative de novo cases did not change significantly by Day 15. Of the de novo FXIII-A negative cases, none surpassed the cut-off value of 20% for FXIII-A positivity by Day 15 ([Figure 2](#cancers-12-02264-f002){ref-type="fig"}).
We investigated the association of FXIII-A expression pattern at diagnosis on the EFS and OS of patients using Kaplan-Meier survival analysis. EFS and OS of patients with FXIII-A positive BCP-ALL were not significantly different from that of patients with FXIII-A negative BCP-ALL ([Figure S1](#app1-cancers-12-02264){ref-type="app"}). Investigating the three different FXIII-A expression patterns separately, a significant EFS advantage of the FXIII-A dim group was demonstrated when compared both with the FXIII-A negative (*p* = 0.012), and with the FXIII-A bright group (*p* = 0.001) ([Figure 3](#cancers-12-02264-f003){ref-type="fig"}a). The 5-year EFS of patients with dim, negative, and bright FXIII-A expression was 93%, 70%, and 61%, respectively. The 5-year OS of the FXIII-A dim group (95%) was significantly higher than that of the FXIII-A negative group (88%; *p* = 0.044). The difference between the 5-year OS of the FXIII-A dim and the FXIII-A bright group (87%) was not significant ([Figure 3](#cancers-12-02264-f003){ref-type="fig"}b).
The impact of categorical variables representing known risk factors on the two pairs of groups, i.e., the FXIII-A dim vs. FXIII-A negative groups and the FXIII-A dim vs. FXIII-A bright groups, was analyzed with the multivariable Cox regression model. Categorical variables, such as FXIII-A expression pattern, age, prednisone response, distribution of genetic risk categories, and distribution of the "B-other" genetic subgroup had significant effects on 5-year EFS and 5-year OS figures of the dim vs. negative FXIII-A groups. The effect of ALL BFM-IC 2009 risk groups was significant on the 5-year OS. In the multivariate analysis model, only genetic risk category (good vs. intermediate) remained significant ([Table 1](#cancers-12-02264-t001){ref-type="table"}). Significant differences between survival figures of the dim vs. bright FXIII-A groups were seen in case of FXIII-A expression pattern, ALL BFM-IC 2009 risk categories (BFM-HR vs. BFM-IR) and the genetic risk categories. In the multivariate Cox analysis, FXIII-A expression pattern and genetic risk categories remained significant ([Table 2](#cancers-12-02264-t002){ref-type="table"}). FXIII-A negative and bright group associated with adverse outcome. Comparing the two groups, the prednisone response and genetic risk categories differed significantly. Poor prednisone response was more frequent in FXIII-A negative group, while the presence of patients with high-risk genetic alterations was higher in FXIII-A bright group ([Table 3](#cancers-12-02264-t003){ref-type="table"}).
Copy number alteration (CNA) was investigated in 59 patients, 20 with negative, 26 with dim, and 13 with bright FXIII-A expression pattern. Poor prognostic CNA were detected in a slightly higher ratio (7/20) in the negative FXIII-A group than in the dim (4/26), and the bright FXIII-A (1/13) groups ([Table S2](#app1-cancers-12-02264){ref-type="app"}). The differences were not significant.
2.2. Correlation of FXIII-A Expression Patterns with Conventional Clinical, Minimal Residual Disease (MRD), and Genetic Risk Factors {#sec2dot2-cancers-12-02264}
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Relationships between the FXIII-A expression patterns and other known risk factors were investigated with Pearson's Chi square test and multinomial logistic regression models. The different FXIII-A expression patterns did not correlate significantly with either risk stratification according to ALL BFM-IC 2009 or FC MRD risk categories. The intermediate genetic risk category was significantly more prevalent in the FXIII-A negative group than in the FXIII-A dim or bright group (*p* = 0.009 and *p* = 0.039, respectively). Correlation between negative and positive FXIII-A expression patterns and the "B-other" subgroup was equally strong (*p* = 0.008 FXIII-A negative and dim group; *p* = 0.004 FXIII-A negative and bright group).
Patients with FXIII-A dim or bright lymphoblasts had lower chance for having "B-other" alteration (OR: 0.49 and 0.36, respectively). This association persisted after adjusting for categorical variables, as sex, age, and WBC ([Table 4](#cancers-12-02264-t004){ref-type="table"}). iAMP21 was also significantly more (*p* = 0.029) prevalent in the FXIII-A negative group as compared with the two other FXIII-A expression groups. Other recurrent genetic aberrations showed a similar distribution within the three FXIII-A expression groups.
3. Discussion {#sec3-cancers-12-02264}
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In this study we investigated the potential usefulness of FXIII-A as a risk-associated biomarker in BCP-ALL of children treated within the frames of the ALL BFM-IC 2009 clinical trial. In a previous small-scale, single-center, retrospective study we observed a survival advantage of children with FXIII-A positive (≥20%) vs. FXIII-A negative BCP-ALL treated with the ALL BFM-IC 2002 protocol \[[@B31-cancers-12-02264]\]. The strength of the present study was that four national groups, belonging to two different childhood ALL treatment consortia (Polish, Hungarian, Slovak, and Austrian) investigated FXIII-A expression by quality-controlled multiparameter FC and delivered clinically relevant data of patients participating in this multi-center, prospective clinical trial. The high number of cases included in this study enabled the more detailed examination of FXIII-A expression patterns.
In a recent publication, our group investigated the gene expression profile of the three different expression types of FXIII-A in BCP-ALL. The three groups had unique gene expression signatures according to FXIII-A expression pattern. The gene expression pattern of the FXIII-A negative subgroup overlapped with the gene expression profile of the "B-other" genetic subgroup \[[@B32-cancers-12-02264]\].
The effect of FXIII-A expression in the leukemic cell population on survival was studied in patients with APL and conflicting results were reported \[[@B29-cancers-12-02264],[@B36-cancers-12-02264]\]. The two groups applied different methods, i.e., FC and immunohistochemistry to detect manifestation of FXIII-A in leukemic promyelocytes. However, neither of the two groups made a distinction between bright and dim expression pattern of FXIII-A in APL cells, only patients with FXIII-A positive and negative expression patterns were compared which might explain the opposite conclusions of the two investigations.
Most children with BCP-ALL displayed a dim FXIII-A expression. This subpopulation had a superior outcome over both the bright and the negative FXIII-A groups according to the univariate Kaplan-Meier analysis. The inferior survival chances of the FXIII-A negative subgroup were explained by the significantly higher prevalence of patients with intermediate genetic risk group, and, within this group, patients belonging to the "B-other" category, compared with the FXIII-A positive group. Patients with "B-other" BCP-ALL were shown to have a higher risk for relapse \[[@B7-cancers-12-02264],[@B32-cancers-12-02264]\]. We also demonstrated the significant prognostic value of the "B-other" genetic category on EFS and OS of patients with negative vs. dim FXIII-A expression by the multivariable Cox regression analysis \[[@B37-cancers-12-02264]\]. We observed a trend of association of poor prognostic CNAs with FXIII-A negativity; however, probably because of the small sample size of the multiplex ligation dependent probe amplification (MLPA) investigation, the difference was not statistically significant.
Comparing the expression of FXIII-A of leukemic lymphoblasts on Day 0 and Day 15, a significant decrease was detected in the ratio of FXIII-A positive lymphoblasts of BM samples by day 15, while FXIII-A expression did not appear on originally FXIII-A negative lymphoblasts. Complemented with the results of ES and OS, this finding suggested a preferential clearance of FXIII-A positive blast cells over negative ones.
Multivariate Cox analysis showed significant impacts of the presence of high-risk and intermediate-risk genetic alterations on survival figures of patients with bright FXIII-A expression as compared with that of the dim FXIII-A group. In the univariate Cox regression analysis there was a significant association between the dismal EFS and OS of the bright FXIII-A expression group and the BFM-HR category. These results suggest that unfavorable genetic alterations may supersede the beneficial effect of FXIII-A expression in children with BCP-ALL.
In a previous study, results suggested that not even the lowest possible MRD cut-off was associated with the best overall survival for all patients \[[@B38-cancers-12-02264]\]. Therefore, novel markers, such as FXIII-A expression pattern may gain importance in achieving optimal stratification of patients. By improving risk stratification, the new biomarkers may contribute to developing a more refined risk-adjusted, or even personalized treatment.
There were several limitations of this study. Of note, survival rates of the present study do not represent either the total ALL BFM-IC 2009 study population, or any of the patient subpopulations of the participating national groups. First, only children with BCP-ALL were investigated. Second, FXIII-A labeling and measurement was performed on the basis of the availability of the anti-FXIII-A monoclonal antibody. Third, patients of the Polish group were not randomized. Fourth, a substantial number of patients were enrolled within the last four years in the study which may alter ultimate 5-year EFS and OS figures. Yet, follow-up times were sufficient to demonstrate statistically significant differences between groups with different FXIII-A expression patterns. A complete genetic diagnosis was available only from 214/317 patients and copy number alterations by MLPA was investigated on a small subset of patients.
4. Materials and Methods {#sec4-cancers-12-02264}
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4.1. Study Cohort {#sec4dot1-cancers-12-02264}
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Diagnostic BM samples and clinical data were collected from 408 children with BCP-ALL treated by the Polish (188), Hungarian (114), and Slovak (13) groups of the ALL IC consortium and by the Austrian (93) group of the AIEOP-BFM consortium between 2011 and 2018. Patients with Down-syndrome, t(9;22), and infants were excluded. Patients were unselected for FXIII-A labeling. In a subset of 36 children treated at the Debrecen Center (Hungary), diagnostic and day 15 BM samples were studied in parallel for FXIII-A labeling. Of the 408 patients 310 had a complete genetic test. Results of these patients were included in the regression analyses. Of these patients, six patients in Hungary, eight patients in Poland, and two patients in Slovakia underwent allogenic haematopoietic stem cell transplantation. In a subset of 59 children treated at the Debrecen and Budapest Centers (Hungary), multiplex ligation dependent probe amplification (MLPA) assay was performed to investigate copy number alterations (CNA).
Polish, Hungarian, and Slovak patients were treated according to ALL IC-BFM 2009 protocol, while Austrian patients were treated according to AIEOP-BFM 2009. Due to the difference in the applied treatment protocols, the data from the Vienna cases were used only in the analysis of the association between the initial variables and FXIII-A expression; the association of FXIII-A expression on survival was examined exclusively by comparing data of patients treated with the same protocol. Among the ALLIC cohort of patients, i.e., patients from Hungary, Poland, and Slovakia there were 21 relapses. Relapsed ALL patients were treated according to ALL-REZ BFM 2002 protocol/clinical trial (ClinicalTrials.gov identifier:NCT00114348) \[[@B39-cancers-12-02264],[@B40-cancers-12-02264]\]. Risk estimation at diagnosis and evaluation of prednisone response in day 8 peripheral blood (PB) samples were retained from ALL IC-BFM 2002 \[[@B4-cancers-12-02264]\]. Low hypodiploidy (chromosome number \<45), and iAMP21 were considered as high-risk (BFM-HR) features in ALL IC-BFM 2009 in addition to ALL IC-BFM 2002. Evaluation of mid-induction (day 15) BM samples was based on FC-MRD analysis. An MRD load by FC \<0.1% was considered as FLR, FC-MRD between 0.1% and \<10% was considered as FMR, and FC-MRD ≥10% was considered as FHR. Only patients stratified into the standard-risk (BFM-SR) group according to conventional risk factors and having FLR status remained in the BFM-SR group. Patients with FMR and FHR status were upgraded into the intermediate-risk (BFM-IR) group, and into the BFM-HR group, respectively. Patients of the BFM-IR group based on conventional risk factors but displaying an FHR status, were upgraded into the BFM-HR group. ALL BFM-IC 2009 accepted a risk estimation based on morphologic evaluation of day 15 BM samples in the lack of an FC-MRD analysis. However, FC-MRD analysis was performed in every case in the present study.
Standard treatment arms of ALL IC-BFM 2009 were identical with that of ALL IC-BFM 2002 \[[@B4-cancers-12-02264]\]. Patients in Hungarian and Slovak centers were randomized. Patients with BFM-IR and BFM-HR disease received either standard early intensification as in ALL BFM-IC 2002, or an "augmented" early intensification, applied previously by BFM and Children's Cancer (CCG) groups \[[@B4-cancers-12-02264],[@B41-cancers-12-02264],[@B42-cancers-12-02264]\]. Patients with IR BCP-ALL were randomized to receive either 2 g/m^2^ methotrexate (Mtx) as in ALL BFM-IC 2002 or 5 g/m^2^ Mtx, as in ALL-BFM 86 in consolidation \[[@B43-cancers-12-02264]\]. The Polish group did not perform randomization: patients of the BFM-IR group received standard and patients of the BFM-HR group received augmented early intensification. Patients with IR BCP-ALL received 2 g/m^2^ Mtx. Initial clinical characterization and risk stratification of study patients are shown in [Table S1](#app1-cancers-12-02264){ref-type="app"}.
The study was approved by the Scientific Research Ethical Committee of the Medical Research Council of Hungary (no 43033-1/2014/EUK(423/2014)) and was performed according to the 2008 Declaration of Helsinki. Written informed consent was obtained from legal guardians of participating patients.
4.2. Immunophenotype Analysis {#sec4dot2-cancers-12-02264}
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FC investigations were performed as described \[[@B13-cancers-12-02264],[@B28-cancers-12-02264],[@B31-cancers-12-02264]\]. Briefly, samples were analyzed by 5--8 color labeling procedure using FacsCantoII (Becton Dickinson, Franklin Lakes, NJ, USA) and Navios and FC-500 (Beckman Coulter, Brea, CA, USA) flow cytometers. Lineage assignment was determined according to EGIL criteria \[[@B44-cancers-12-02264]\]. Surface and ic staining was performed according to standard protocols, with the ALLIC-2009 suggested panel of monoclonal antibodies. Generation and fluorescent isotihocyanate (FITC) labeling of mouse monoclonal antibody against FXIII-A was carried out as previously described \[[@B45-cancers-12-02264]\]. To examine the sensitivity of FXIII-A determination, the percentage of FXIII-A expression in residual lymphoblasts was analyzed in three parallel serial dilutions (10×, 100×, 1000×). The percentage of FXIII-A expression in residual lymphoblasts could be clearly assessed when the percentage of lymphoblasts was above 0.04% ([Figure 4](#cancers-12-02264-f004){ref-type="fig"}).
Each center used the same tube to assess FXIII-A labeling: FXIII-A (FITC)--CD10(PE)--CD45(PerCP-Cy5.5)--CD19(APC). The threshold of positivity was set to 20% positive leukemic cells for a certain immunophenotype marker. To examine the significance of the FXIII-A expression in more detail, three groups were defined: BCP-ALL with FXIII-A negative blasts (\<20% FXIII-A positive lymphoblasts; FXIII-A negative group), BCP-ALL with FXIIII-A dim positive expression (20--79% FXIII-A positive lymphoblasts; FXIII-A dim group), and BCP-ALL with FXIII-A bright positive expression (≥80% FXIII-A positive lymphoblasts; FXIII-A bright group). To determine FXIII-A expression of leukemic cells, normal residual lymphocytes served as a negative control \[[@B19-cancers-12-02264],[@B28-cancers-12-02264]\]. FC data were analyzed by FACSDiva (Becton Dickinson, Franklin Lakes, NJ, USA) or Kaluza (Beckman Coulter, Brea, CA, USA) software. Flow cytometers were controlled applying Cytometer Setup&Tracking (Becton Dickinson, Franklin Lakes, NJ, USA) or Flow Check Pro (Beckman Coulter, Brea, CA, USA) fluorescent microbeads. All laboratories participated in the UK-NEQAS Leukocyte Immunophenotyping MRD program and in the ALLIC Annual Ring Trials successfully.
4.3. Genetic Investigations {#sec4dot3-cancers-12-02264}
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The unstimulated 24 h cultures of BM were subjected to cytogenetic analysis using standard protocol. Subsequently fluorescence in situ hybridization (FISH) was performed on cells from the same BM samples according to manufacturer's recommendations using commercially available probe sets (*BCR-ABL, ETV6-RUNX1, MLL)* (MetaSystems, Altlussheim, Germany). The low-risk group was formed of patients with t(12;21)/*ETV6/RUNX1* or high hyperdiploidy (51--65 chromosome), while the high-risk group was made up of patients with *MLL* translocations, iAMP21, complex karyotype, near haploidy (chromosome number 23--29), and low hypodiploidy (chromosome \<45). Finally, an intermediate-risk group was established from patients with t(1;19) and all other genetic subgroups not fitting in the low- and high-risk categories, including the "B-other" subgroup \[[@B5-cancers-12-02264],[@B6-cancers-12-02264]\].
Genomic DNA was extracted from BM samples using QIAamp DNA Blood Mini Kit (QIAGEN, Hilden, Germany). SALSA MLPA P335-B2 ALL-IKZF1 probe mix was used to perform MLPA analysis (MRC-Holland, Amsterdam, The Netherlands). The kit includes probes for *IKZF1, CDKN2A/B, PAX5, EBF1, ETV6, BTG1, RB1* genes and the *PAR1* region (*CRLF 2, CSF2RA, IL3RA*). No deletion of *IKZF1, CDKN2A/B, PAR1, BTG1, EBF1, PAX5, ETV6*, or *RB1*, isolated deletions of *ETV6, PAX5,* or *BTG1, ETV6* deletions with a single additional deletion of *BTG1, PAX5*, or *CDKN2A/B* were considered as good; single deletions of *CDKN2A/B*, and combined deletions of *CDKN2A/B/PAX5* were considered as intermediate; and any deletion of *IKZF1, PAR1, EBF1*, or *RB1,* and all other CNA profiles not mentioned above were considered as poor prognostic factors according to CNA \[[@B46-cancers-12-02264],[@B47-cancers-12-02264],[@B48-cancers-12-02264],[@B49-cancers-12-02264]\].
4.4. Statistical Analysis {#sec4dot4-cancers-12-02264}
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Normal distribution was tested by the Shapiro-Wilk test. To compare two groups, we used paired Student's t-test for parametric and Wilcoxon test for non-parametric data. Where there were more than two groups, data were analyzed by the Kruskal-Wallis test. Dunn's multiple comparison test was applied as post hoc test. The initial parameters of patients, such as age and WBC count, were transformed to categorical variables on the basis of their prognostic impact.
Dichotomous categorical variables were compared using Pearson's Chi square test and multinomial logistic regression to analyse multiple variables. *p*-values \<0.05 were considered as significant. Survival analysis was carried out by the Kaplan-Meier survival estimator. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazard model analysis. The end point of event-free analysis was defined as the time elapsed between the diagnosis of ALL and the first relapse or death. Statistical analysis and the creation of figures were performed using STATA/IC 14.2 (College Station, TX, USA), SPSS 20.0 (Chicago, IL, USA) and GraphPad Prism 6.0 (San Diego, CA, USA) statistical programs.
5. Conclusions {#sec5-cancers-12-02264}
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The intracellular marker, FXIII-A has three different expression patterns in leukemic BCP lymphoblasts as determined by FC, i.e., FXIII-A bright positive, dim positive and FXIII-A negative expression. Our previous study showed that the three different staining patterns were associated with three distinct gene expression signatures. In the present study we demonstrated statistically significant and clinically meaningful differences in children with BCP-ALL according to FXIII-A expression pattern by FC which can be incorporated in the risk estimation strategy of a new ALL BFM-IC clinical trial. FXIII-A expression status of leukemic lymphoblasts can be easily and accurately determined by FC. FXIII-A negative expression pattern was a prognostic indicator of dismal survival in children with BCP-ALL due to the significant association between the FXIII-A negative expression pattern and the "B-other" genetic category. Similar associations between expression intensity of biomarkers both at the mRNA and protein levels and clinical relevance have been observed to exist in T-ALL and in AML. Patients with FXIII-A negative BCP lymphoblasts should be extensively investigated with sophisticated genetic and molecular methods so as to provide these patients an optimal risk-adjusted treatment.
Authors are grateful to the past president and the president of iBFM-SG, Martin Schrappe and Andrea Biondi, the past chairman and the chairman of the iBFM ALL Committee, Ajay Vora, and Kjeld Schmiegelow and the principle investigator of the ALL BFM-IC 2009 clinical trial, Myriam Campbell for consultation and support. Authors express their appreciation to all members of the Hungarian, Polish, and Slovak ALLIC 2009 centers and the Austrian AIEOP-BFM 2009 center for collecting informed consents, data, and samples from study patients. Publication costs of the article were covered by the "Leukémiás Gyermekekért" ("For Children with Leukemia") Foundation.
The following are available online at <https://www.mdpi.com/2072-6694/12/8/2264/s1>, Figure S1: Event-free and overall survival of children with B-cell precursor acute lymphoblastic leukemia (ALL) of FXIII-A positive and negative groups, Table S1: Initial clinical characterization and risk stratification of study patients, Table S2: Distribution of copy number alterations (CNA) according to FXIII-A expression patterns.
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Click here for additional data file.
Conceptualization, B.K., K.G., H.Z., J.K., M.D., G.T.K. and C.K.; methodology, B.K., A.U., Ł.S., G.B., P.J., P.S., E.S., J.R.K.; A.K., M.D., A.S., K.N., O.A.H., J.K. and Z.H. software, A.C.N., B.K. and K.G.; validation, J.K., M.D. and C.K.; formal analysis, B.K., K.G. and A.C.N.; investigation, B.K., K.G., A.U., Ł.S., G.B., P.J., P.S., E.S., J.R.K.; A.K., M.D., A.S.,K.N., O.A.H., J.K., K.G., J.M., R.S., Á.V., I.S., L.G.T., G.T.K., T.S. and C.K.; resources, B.K., A.U., Ł.S., G.B., P.J., P.S., E.S., J.R.K.; A.K., M.D., A.S., K.N., O.A.H., J.K., Z.H. and C.K.; data curation, B.K., K.G., A.U., Ł.S., G.B., P.J., P.S., E.S., J.R.K.; A.K., M.D., A.S., A.A., K.N., O.A.H., J.K., K.G., J.M., R.S., Á.V., I.S., L.G.T., G.T.K., T.S. and C.K.; writing---original draft preparation, B.K., K.G., Z.H. and C.K.; writing---review and editing, B.K., K.G., A.U., Ł.S., G.B., P.J., P.S., E.S., J.R.K.; A.K., M.D., A.S., A.A., K.N., O.A.H., J.K., K.G., J.M., R.S., Á.V., I.S., L.G.T., G.T.K., T.S. and C.K.; visualization, B.K. and K.G.; supervision, C.K.; project administration, C.K.; funding acquisition, C.K., S.L and T.S. All authors have read and agreed to the published version of the manuscript.
This research funded by the Hungarian National Scientific Research Fund "OTKA K108885" grant. Ł.S. and T.S. were supported by STRATEGMED3/304586/5/NCBR/2017 Person ALL grant of the Polish National Center for Research and Development.
The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
FXIII-A
coagulation factor XIII subunit A
BCP
B-cell progenitor
ALL
acute lymphoblastic leukemia
BFM ALL-IC 2009
Berlin-Frankfurt-Münster inter-Continental 2009 clinical trial
iBFM-SG
international Berlin-Frankfurt-Münster Study Group
EFS
event-free survival
OS
overall survival
COG
Children's Oncology Group
WBC
white blood cell count
ic
Intracellular
FC
flow cytometry
MRD
minimal residual disease
BM
bone marrow
MLPA
multiplex ligation dependent probe amplification
CNA
copy number alterations
AIEOP-BFM 2009
International Collaborative Treatment Protocol For Children And Adolescents With Acute Lymphoblastic Leukemia clinical trial
cyFXIII-A
cytoplasmic coagulation factor XIII subunit A
PB
peripheral blood
HR
high-risk
IR
intermediate risk
SR
standard risk
FLR
flow low-risk
FMR
flow medium-risk
FHR
flow high-risk
BFM-HR
BFM-high risk
BFM-SR
BFM standrard risk
BFM-IR
BFM intermediate risk
CCG
Children's cancer group
Mtx
Methotrexate
FITC
fluorescent isotihocyanate
FISH
fluorescence in situ hybridization
CI
cinfidence intervals
HR
Hazard-ratio
CCC
clear cell carcinomas
APL
acute promyelocytic leukemia
PGR
prednisone good response
PPR
prednisone poor response
OR
Odds ratio
NA
not available
N
Number
{#cancers-12-02264-f001}
{#cancers-12-02264-f002}
{#cancers-12-02264-f003}
{#cancers-12-02264-f004}
cancers-12-02264-t001_Table 1
######
Association of categorical variables on event-free survival (EFS) and OS of the FXIII-A negative vs. dim groups by univariate and multivariate Cox regression analysis
Variables Event-Free Survival Overall Survival
--------------------------------- --------------------------- ------------------ ------------- ------------- ------------- -------------
**Univariate Analysis**
FXIII-A expression pattern
FXIII-A negative 2.91 1.17--7.21 **0.021** 2.63 0.88--7.84 0.084
FXIII-A dim 0.34 0.14--0.85 0.38 0.13--1.14
Age
1--5 years 0.39 0.17--0.92 **0.032** 0.24 0.08--0.71 **0.010**
≥6 years 2.56 1.10--6.05 4.20 1.41--12.56
WBC
\<20,000 0.69 0.29--1.66 0.407 0.60 0.21--1.71 0.334
≥20,000 1.45 0.60--3.51 1.69 0.58--4.86
Sex
Male 1.53 0.62--3.79 0.360 1.87 0.59--6.00 0.291
Female 0.65 0.26--1.62 0.54 0.17--1.71
prednisone response
PGR 0.27 0.09--0.73 **0.010** 0.15 0.05--0.45 **0.001**
PPR 3.75 1.37--10.24 6.71 2.25--20.03
FC risk categories
FLR/FMR 1.43 0.40--5.13 0.581 1.18 0.25--5.54 0.838
FLR/FHR 3.37 0.78--14.58 0.104 3.40 0.62--18.56 0.158
ALLIC BFM 2009 classification
BFM-HR/BFM-SR 0.12 0.01--0.95 **0.044** 0.00
BFM-HR/BFM-IR 0.41 0.16--1.05 0.063 0.32 0.11--0.92 **0.035**
Genetic risk categories
good/intermediate 7.12 2.07--24.73 **0.002** 13.8 1.77--107.9 **0.012**
good/high 23.7 4.72--119.3 **\<0.001** 63.1 6.50--613.3 **\<0.001**
B-other
Recurrent genetic abnormalities 0.26 0.10--0.68 **0.006** 0.27 0.08--0.86 **0.027**
B-other 3.82 1.48--9.86 3.71 1.16--11.85
**Multivariate Analysis**
FXIII negative 2.29 0.85--6.20 0.102 1.70 0.51--5.71 0.390
Genetic risk categories
good/intermediate 5.78 1.63--20.52 **0.007** 10.0 1.24--81.4 **0.031**
good/high 17.4 2.88--104.8 **0.002** 30.5 2.63--353.4 **0.006**
*p* \< 0.05 values were considered statistically significant, such *p* values are marked in bold.
cancers-12-02264-t002_Table 2
######
Association of categorical variables on event-free survival (EFS) and OS of the FXIII-A dim vs. bright groups by univariate and multivariate Cox regression analysis.
Variables Event-Free Survival Overall Survival
--------------------------------- --------------------------- ------------------ ----------- ------------- ------------- -----------
**Univariate Analysis**
FXIII-A expression pattern
FXIII-A dim 0.24 0.09--0.64 **0.004** 0.32 0.09--1.04 0.057
FXIII-A bright 4.10 1.56--10.78 3.17 0.97--10.38
Age
1--5 years 0.52 0.19--1.37 0.186 0.32 0.10--1.05 0.060
≥6 years 1.92 0.73--5.06 3.13 0.96--10.28
WBC
\<20,000 0.67 0.26--1.76 0.417 0.56 0.17--1.84 0.341
≥20,000 1.49 0.57--3.92 1.78 0.54--5.83
Sex
Male 1.43 0.53--3.86 0.483 2.08 0.55--7.86 0.278
Female 0.70 0.26--1.90 0.48 0.18--1.81
prednisone response
PGR 0.34 0.08--1.47 0.146 0.43 0.06--3.41 0.427
PPR 1.43 0.53--3.86 2.08 0.55--7.86
FC risk categories
FLR/FMR 0.90 0.27--2.83 0.857 1.33 0.24--5.54 0.863
FLR/FHR 1.25 0.23--6.81 0.801 2,59 0.36--18.43 0.342
ALLIC BFM 2009 classification
BFM-HR/BFM-SR 0.39 0.098--1.59 0.192 0.17 0.02--1.49 0.110
BFM-HR/BFM-IR 0.27 0.09--0.78 **0.015** 0.21 0.06--0.73 **0.014**
Genetic risk categories
good/intermediate 2.08 0.75--5.74 0.051 3.68 0.92--14.73 **0.065**
good/high 4.86 0.99--23.76 0.157 9.65 1.59--58.42 **0.014**
B-other
Recurrent genetic abnormalities 0.55 0.21--1.44 0.225 0.41 0.12--1.33 0.137
B-other 1.80 0.70--4.78 2.46 0.75--8.07
**Multivariate Analysis**
FXIII-A bright 3.92 1.41--10.84 **0.009** 3.90 0.99--15.31 **0.051**
Genetic risk categories
good/intermediate 2.69 0.84--8.55 0.095 6.07 1.17--31.65 **0.032**
good/high 3.56 0.70--18.03 0.124 7.67 1.21--48.64 **0.031**
*p* \< 0.05 values were considered statistically significant, such *p* values are marked in bold.
cancers-12-02264-t003_Table 3
######
Association of categorical variables on event-free survival (EFS) and OS of the FXIII-A negative vs. bright groups by univariate and multivariate Cox regression analysis.
Variables Event-Free Survival Overall Survival
--------------------------------- --------------------------- ------------------ ----------- ------------- ------------- -----------
**Univariate Analysis**
FXIII-A expression pattern
FXIII-A negative 0.66 0.29--1.51 0.323 0.80 0.28--2.24 0.665
FXIII-A bright 1.52 0.66--3.47 1.26 0.45--3.54
Age
1--5 years 0.52 0.24--1.17 0.116 0.36 0.13--1.02 0.056
≥6 years 1.90 0.85--4.24 2.75 0.98--7.72
WBC
\<20,000 0.49 0.21--1.13 0.093 0.68 0.23--1.98 0.477
≥ 20,000 2.06 0.89--4.76 1.48 0.50--4.32
Sex
Male 1.21 0.53--2.78 0.647 1.43 0.49--4.17 0.518
Female 0.82 0.36--1.89 0.70 0.24--2.05
prednisone response
PGR 0.36 0.13--0.96 **0.041** 0.28 0.09--0.87 **0.028**
PPR 2.81 1.04--7.58 3.61 1.15--11.35
FC risk categories
FLR/FMR 2.48 0.72--8.56 0.150 1.90 0.41--8.80 0.411
FLR/FHR 3.29 0.77--13.9 0.106 3.53 0.65--19.28 0.145
ALLIC BFM 2009 classification
BFM-HR/BFM-SR 0.21 0.05--0.97 **0.045** 0.15 0.02--1.22 0.076
BFM-HR/BFM-IR 0.47 0.20--1.11 0.085 0.37 0.13--1.04 0.060
Genetic risk categories
good/intermediate 2.14 0.89--5.17 0.091 2.50 0.75--8.30 0.135
good/high 6.48 1.69--24.84 **0.006** 10.5 2.33--47.2 **0.002**
B-other
Recurrent genetic abnormalities 0.61 0.27--1.36 0.228 0.66 0.24--1.81 0.413
B-other 1.64 0.73--3.67 1.53 0.55--4.21
**Multivariate Analysis**
FXIII-A bright 0.54 0.22--1.34 0.108 0.59 0.19--1.88 0.3751
Genetic risk categories
good/intermediate 2.33 0.87--6.22 0.091 2.63 0.68--10.25 0.164
good/high 4.55 1.14--18.15 **0.032** 7.44 1.54--36.00 **0.013**
*p* \< 0.05 values were considered statistically significant, such *p* values are marked in bold.
cancers-12-02264-t004_Table 4
######
Correlation of FXIII-A expression patterns with conventional clinical and "B-other" subgroup by multinomial logistic regression analysis.
FXIII-A Expression Patterns *p* Value OR 95% CI
----------------------------- ----------- ---------- ---------- ----------
FXIII-A dim
"B-other" subgroup **0.009** **0.49** **0.28** **0.84**
Sex **0.851** **1.05** **0.61** **1.81**
Age **0.197** **0.69** **0.39** **1.21**
WBC **0.093** **1.69** **0.92** **3.10**
FXIII-A bright
"B-other" subgroup **0.004** **0.35** **0.18** **0.71**
Sex **0.726** **0.89** **0.46** **1.72**
Age **0.581** **0.82** **0.41** **1.64**
WBC **0.393** **1.38** **0.66** **2.92**
*p* \< 0.05 values were considered statistically significant, such *p* values are marked in bold.
|
Jason Momoa is letting loose.
The "Aquaman" star appeared in a commercial during Super Bowl LIV in which he was seen getting comfortable at home.
As he talked about being able to relax -- thanks to Rocket Mortgage, of course -- Momoa, 40, walked around his home and peeled his muscles off as if they were fake.
BILLY RAY CYRUS 'KEEPS IT REAL' IN SUPER BOWL COMMERCIAL, TALKS KOBE BRYANT'S LEGACY
"What does home mean to me?" he said in the ad. "It's my sanctuary. It's the one place I can let my guard down. It's where I can just kick back and be totally comfortable in my own skin."
He first removed fake muscles from his arms, revealing scrawny twig-like limbs beneath.
CHRISSY TEIGEN, JOHN LEGEND SUPER BOWL LIV AD HAS HELICOPTER EDITED OUT IN WAKE OF KOBE BRYANT DEATH
He then reached up his shirt and removed his chest, shoulder and abdomen muscles before relaxing on the couch, happy to be feeling more like himself.
"That feels pretty darn good," said Momoa, smiling.
He then reaches up and removes a toupe, revealing a balding scalp beneath.
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The ad ended with a shot of the actor attempting to lift a weightless barbell with wife Lisa Bonet spotting him, and easily lifting the bar when he struggles to do so. |
I feel like it’s not necessary to say much about this jumpsuit. It is clearly gorgeous! As soon as I saw it on Tobi’s website I thought: I need to have it! Haha And I honestly don’t feel like that very often. Even though I’m a personal style blogger and have a lot of clothes, I feel like is becoming harder and harder to fall in love for a garment. It’s like I have worn so many clothes and now need some pieces more different and audacious.But I have always loved jumpsuits and I especially love how they make my legs look longer. I think it’s a great trick for those who are unhappy with their height and want to look a little taller. And the look is easily elevated with the help of the deep cleavage and side cuts in the waist area. |
Mexico’s most famous drug lord, Joaquin “El Chapo” Guzman Loera, regularly paid $5,000 to have girls as young as 13-years-old drugged and brought to him for sexual intercourse, court records allege.
Officials disclosed the accusations in a series of documents that were unsealed late this week under orders of U.S. District Judge Brian Cogan as prosecutors in the case sought to limit the type of questions that could be asked of witnesses during Guzman’s trial. El Chapo is currently being tried on multiple drug trafficking and money laundering conspiracies that could lead to several life sentences.
One of the newly unsealed court briefs dealt with the testimony of Alex Cifuentes, a close associate of El Chapo and one of the prosecutions main witnesses. The document was first discovered by Alan Feuer from the New York Times.
Under judicial order prosecutors in the Chapo case have just unsealed several docs.
One revelation: Alex Cifuentes, Chapo’s personal secretary, had a procuress send Chapo pics of 13-year-old girls. Young girls could be bought for sex at $5000 a piece. Sometimes they were drugged. pic.twitter.com/jFs4Fyp76W — Alan Feuer (@alanfeuer) February 2, 2019
The court brief mentioned that Cifuentes would have his staff get girls as young as 13-years-old through an intermediary for sex. The drug lords would receive photographs of the girls and, for a fee of $5,000, the girls would be drugged and brought to El Chapo for sex.
El Chapo Underage Girls Docs by on Scribd
“The defendant (El Chapo) would call the youngest of the girls his ‘vitamins’ because he believed that sexual activity with young girls gave him life,” the court document revealed.
El Chapo’s trial has uncovered the vast level of corruption that reached every aspect of Mexico’s government. As reported by Breitbart News, money from El Chapo’s cartel allegedly touched two former Mexican presidents –Enrique Pena Nieto and Felipe Calderon — and the 2006 failed campaign of current Mexican President Andres Manuel Lopez Obrador (AMLO). The Sinaloa Cartel also bribed numerous Mexican military generals and had them fight his rivals. Former Mexican president Vicente Fox has not been named as having taken a bribe, but testimony unmasked his chief bodyguard as an employee of El Chapo’s cartel.
Ildefonso Ortiz is an award-winning journalist with Breitbart Texas. He co-founded the Cartel Chronicles project with Brandon Darby and Stephen K. Bannon. You can follow him on Twitter and on Facebook . He can be contacted at [email protected] . |
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Sam Hinkie caught trying to make several trades out of spite
Philadelphia, PA – 76ers staff and executive had to forcibly break the door down of Sam Hinkie’s office Thursday evening, as the general manager reportedly tried to trade several members of the current roster for next to nothing.
Behind the barricaded door to his office, 76ers executives could hear Hinkie having a discussion with the Los Angeles Lakers that would have sent Jahlil Okafor to the west coast for Nick Young and a second round pick in return.
Hinkie is reportedly “not pleased” with the hiring of Jerry Colangelo, as several pundits think the move to bring on Colangelo will signal the end of Hinkie’s employment with the Sixers.
Josh Harris, owner of the 76ers, said Hinkie “really freaked the fuck out this afternoon. Just freaked right the fuck out.”
His unsteady mental condition was on full display when team employees finally broke into his office.
“This is the new process, do you hear me?! THIS IS THE NEW PROCESS!” Hinkie screamed, as he was forcibly dragged from his office, still clutching his cell phone in his meaty, pasty hand.
“You’re going to regret this, you hear me, you will regret it. YOU’RE ALL GOING TO DIE!”
Several NBA front office executives reportedly took calls from Hinkie and thought they were being prank called, as the GM desperately tried to trade off the remaining team assets for next to nothing.
One GM said Hinkie offered him “Nerlens Noel for one of our popcorn making machines and an extra crate of nets. If I had thought he was serious, I wouldn’t have hung up on him.”
League officials had to step in Thursday morning and nullify a trade Hinkie had worked out with the Utah Jazz that would have sent Okafor and a 2016 first round pick for the team’s mascot, the Jazz Bear. |
Translational or post-translational processes affect differentially the accumulation of isocitrate lyase and malate synthase proteins and enzyme activities in embryos and seedlings of Brassica napus.
We have analyzed the accumulation of the glyoxylate cycle enzymes isocitrate lyase and malate synthase in embryos and seedlings of Brassica napus L. The two enzyme activities and proteins begin to accumulate during late embryogeny, reach maximal levels in seedlings, and are not detected in young leaves of mature plants. We showed previously that mRNAs encoding the two enzymes exhibit similar qualitative patterns of accumulation during development and that the two mRNAs accumulate to different levels in both embryos and seedlings (L. Comai et al., 1989, Plant Cell 1, 293-300). In this report, we show that the relative accumulation of the proteins and activities do not correspond to these mRNA levels. In embryos and seedlings, the specific activities of isocitrate lyase and malate synthase are approximately constant. By contrast, the ratio of malate synthase protein to mRNA is 14-fold higher than that of isocitrate lyase. Differences in the translational efficiencies of the two mRNAs in vitro do not appear to account for the discrepancy between mRNA and protein levels. Our results suggest that translational and/or post-translational processes affect differentially the accumulation of the proteins. |
Filling out its roster after trading Roger Mason Jr., the Miami Heat signed forward DeAndre Liggins to a 10-day contract Tuesday.
Liggins will be available for the Heat’s home game against the New York Knicks on Thursday. Previously drafted by the Oklahoma City Thunder, Liggins most recently played for the Heat’s D-League affiliate, the Sioux Falls Skyforce. He averaged 14.5 points, 7.5 rebounds, 4.8 assists and 2.54 steals per game for Sioux Falls.
“I’m going to try to do my job to stay as long as I can,” Liggins said after practice Tuesday at AmericanAirlines Arena.
The Heat can re-sign Liggins after 10 days, or sign another free agent to take his place. This is Liggins’ third NBA team. He played 17 games for the Orlando Magic during the 2011-12 season, and then played 39 games for the Oklahoma City Thunder last season. Liggins was released by the Thunder in September of 2013 after being charged with domestic abuse in the presence of a minor, a felony.
“We all make mistakes, unfortunately,” Liggins said. “I learned from it, I moved past it and I’m ready to get back on track.” |
Transcriptional control by E2F.
Considerable evidence suggests that the E2F/DRTF1 family of transcription factors (hereafter referred to as 'E2F') plays a critical role in cell growth control. For example, the ability of several small DNA tumour viruses, such as SV40, adenovirus and human papillomavirus, to transform certain cells is tightly linked to their ability to deregulate E2F. Furthermore, E2F appears to directly regulate the transcription of a diverse set of genes implicated in DNA replication and cell growth control. Finally, a number of known cell cycle regulators, some of which are commonly mutated in human tumours, appear to exert their effects, at least in part, by altering E2F activity. Among these are pRb, p53, cdk-2, cdk-4 and certain cyclins. |
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[Treatment of severe uveitis with cyclosporin A].
The results of a treatment with ciclosporin A in 4 patients with severe uveitis (2 cases with Behçet's disease, 2 cases Vogt-Koyanagi-Harada disease) are presented. Ciclosporin A produced a rapid regression of exudates in the ocular fundus and of the inflammatory signs at the anterior segment in the 4 cases. However, at the same time, side effects including the deterioration of the hepatorenal function developed. Interruption of the treatment with ciclosporin A led to the development of inflammation at the anterior and posterior segments in cases 2 and 4. |
Optimization of transient transfection into human myeloid cell lines using a luciferase reporter gene.
Leukemic cell lines such as HL-60, U937, and KG-1 provide an excellent model for studying human myeloid differentiation. These cells can be induced to differentiate from their immature state to form cells resembling more morphologically and functionally mature monocytes, macrophages, and granulocytes. During differentiation, expression of gene products such as myeloperoxidase and the integrin cell surface antigen CD11b is decreased or increased, respectively. Thus, these cell lines constitute an excellent model system in which to study the regulation of such differentially expressed genes. However, these myeloid cell lines are refractory to transfection by calcium phosphate or diethylaminoethyl (DEAE) dextran. Here we have optimized the transient transfection of myeloid cell lines using electroporation and the firefly luciferase reporter gene driven by viral promoters. The luciferase assay is extremely sensitive; transcription that is not detectable by Northern blot or run-on assays can be measured with this system. The system can be used in combination with the inducing agent 12-o-tetradecanoylphorbol-13-acetate (TPA), thus allowing analysis of developmentally regulated genes in these cells. Preliminary results suggest that this system can be applied to study the promoter for the myeloid specific gene, CD11b. |
For many aspiring female footballers, their journeys have been cut short due to a lack of development pathways.
But for 17-year-old Kiana Lee, an opportunity with the Optus Crows Cup means her dreams of playing for the Adelaide Crows are now within reach.
Kiana played her first game of football as a six-year-old for the Rosewater Football Club, where she went on to play over 100 games.
She picked up several awards along the way and was named in the Woodville-West Torrens Football Club Under-15 talent squad.
“At my first training with Rosewater, I was the only girl there,” Kiana said.
“Back then I didn’t have anything to reach towards because AFLW didn’t exist, so I was playing for fun.”
Like many girls her age, Kiana stopped playing when she turned 14 because she was no longer eligible to be part of the boys’ league.
However, her passion for football was reignited in 2016, when Crows AFLW players Chelsea Randall and Anne Hatchard visited her school, Henley High, and ran a football session.
From there, Kiana joined her school team for the Optus Crows Cup and has never looked back.
Her football career has only continued to build since then and in 2018, she was selected in the South Australian Under-18 state football team and named in Woodville-West Torrens Football Club inaugural SANFLW team.
“The best thing about SANFLW is that the level of competition and skill is completely different to local league,” Kiana said.
“I was one of the younger girls in the team and my teammates were so inclusive which made my bond with them really close and trainings were a lot of fun.
“The coaching staff were incredible, I learnt so much from all of them.”
Kiana ended up playing all 10 games for the Eagles and she finished the season as their best first year player, leading goal kicker and placed third in the best and fairest.
She was also named in the Central Allies squad to play in early July on the Gold Coast.
Kiana played in her fourth Optus Crows Cup match on Thursday, June 13 on Adelaide Oval, in a curtain raiser to Adelaide’s Round 13 clash with Richmond.
With an AFLW contract in her sights, Kiana is grateful that opportunities like the Optus Crows Cup have given her a pathway back to AFL.
“When I found out I had to stop playing at the age of 14, I was devastated,” she said.
“Knowing that I now have a pathway to follow and a dream to play AFLW, it is a surreal feeling.
“Football is in my blood, and I will keep working hard to reach my goal of playing AFLW.
“I cannot wait to see what the future holds for women’s footy.”
Our Crows Cup program would not be possible without Principal Partner Optus, who proudly support grassroots footy. |
A transconductance amplifier is an amplifier for supplying output current in proportion to input voltage, and has stable gain in general. In other words, when varying input voltage over a predetermined operating input range, the ratio between output current and input voltage is stable, that is, the output current is linear with respect to the input voltage.
As a transconductance amplifier with good linearity between input voltage and output current over a predetermined operating input range, one using a differential pair composed of source grounded MOS transistors as shown in FIG. 1 is known (see Non-Patent Document 1, for example). The transconductance amplifier as shown in FIG. 1 comprises a differential pair composed of source grounded MOS transistors 111 and 112; a MOS transistor 113 with its source terminal connected to a drain terminal of the MOS transistor 111; a MOS transistor 114 with its source terminal connected to a drain terminal of the MOS transistor 112, and its gate terminal connected to a gate terminal of the MOS transistor 113; a voltage generating circuit 100 for outputting tuning voltage Vctrl to be supplied (good?) to the gate terminals of the MOS transistors 113 and 114; a voltage generator for outputting common voltage Vcm for generating voltages Vip and Vin to be input to the differential pair; and a differential pair input voltage generating circuit 120 which receives input voltage Vinput and the common voltage Vcm to supply the voltage Vip to the gate terminal of the MOS transistor 111 and the voltage Vin to the gate terminal of the MOS transistor 112. The transistor size (the ratio between channel width and channel length) of the individual MOS transistors, and the tuning voltage Vctrl and the common voltage Vcm are controlled so as to operate the MOS transistors 111 and 112 constituting the differential pair in triode region, and the MOS transistors 113 and 114 in saturation region. In addition, the voltages Vip and Vin satisfy the relationshipVin=2×Vcm−Vip,and the difference between Vip and Vin is determined by Vinput.
In such a configuration, when Vip−Vin is seen as input voltage and Ip−In as output current, the circuit as shown in FIG. 1 functions as a transconductance amplifier. FIG. 2 illustrates the transconductance Gm obtained by differentiating the output current by the input voltage. The transconductance Gm is constant near Vip−Vin=0, and it can be seen that the output current is proportional to the input voltage. In addition to the good linearity between the input voltage and the output current, tuning of the transconductance Gm is possible by controlling the tuning voltage Vctrl. The transconductances Gm under different tuning voltage conditions are shown wherein the tuning voltage Vctrl is varied from a middle level to a small and large level.
In a conventional transconductance amplifier as shown in FIG. 1, however, the linearity between input voltage and output current of the transconductance amplifier deteriorates when the tuning voltage Vctrl is varied for the purpose of tuning transconductance. Assume that the range in which transconductance Gm is constant before tuning (when the Vctrl is middle in the example of FIG. 2) is the operating input range when using the transconductance amplifier. Then, increased tuning voltage Vctrl diminishes the transconductance Gm near the upper limit and lower limit of the operating input range, thereby narrowing the range in which the transconductance Gm is constant. Hence, it would become impossible to supply output current in proportion to input voltage. From a different point of view, to achieve tuning with the linearity between input voltage and output current maintained over the entire operating input range, the range in which the tuning voltage Vctrl is variable for tuning the transconductance is narrowed.
The present invention is directed to the foregoing problem, and an object of the present invention is to provide a transconductance amplifier capable of tuning transconductance in a broader range with the linearity between input voltage and output current maintained over a predetermined operating input range.
Non-Patent Document 1: Chun-Sup Kim, “A CMOS 4× Speed DVD Read Channel IC,” IEEE Journal of Solid-State Circuits, vol. 33, No. 8, August 1998. |
Introduction {#S0001}
============
Appreciation for the importance of professionalism in the practice of medicine is ubiquitous \[[1](#CIT0001),[2](#CIT0002)\]. Medical school faculty face the challenge of defining the behaviors through which student professionalism is judged and the standards of performance to which learners are held. Ideally, students should learn about professional behavior expectations, see those behaviors reinforced by role models in a supportive environment, have their behaviors measured appropriately, and receive guidance when they struggle \[[3](#CIT0003)\]. Because learning environments are often not ideal, professionalism lapses can go unnoticed, undocumented, and unaddressed. Previous work supports a relationship between medical school performance and future unprofessional behavior \[[4](#CIT0004),[5](#CIT0005)\]. Less is known about prospectively identifying learners at highest risk of repetitive problems while in medical school.
Characterizing a learner's professional attributes does not lend itself to a single point-in-time measurement. Better longitudinal assessments are needed \[[6](#CIT0006)\]. It is especially useful to identify students most at risk of serious or repeated deficiencies at the earliest possible time and to distinguish them from students who experience isolated transgressions. While objective structured clinical exams, multiple mini-interviews, and other techniques hold promise for identifying some at-risk behaviors, longitudinal tools and techniques are needed that can be used across the training continuum \[[7](#CIT0007),[8](#CIT0008)\]. A variety of processes are used throughout North American medical schools to identify or track professionalism issues, including incident-based reports, courses on professionalism, and peer assessment \[[9](#CIT0009)\]. Interpreting the growing literature on professionalism is complicated by various classification systems used to group types of behaviors deemed as unprofessional \[[10](#CIT0010),[11](#CIT0011)\].
Our medical school is a large (230 students/year) institution functioning as part of a public, multidisciplinary health science campus. The curriculum follows a conventional '2 + 2'-year sequence but differs from many schools in its heavy emphasis on small-group problem-based learning. The early concern note (ECN) in our school, modeled after similar initiatives at other institutions \[[12](#CIT0012)\], has been used for 17 years as part of a comprehensive approach to creating a professional environment. Initially intended for course and clerkship directors, its use has been expanded so that any faculty or staff member who has contact with a medical student may report on his or her behavior. The ECN instrument focuses on representative behaviors ([Table 1](#T0001)) developed through a school-wide consensus-building process. Three major categories of physician performance are represented---integrity and reliability; motivation and insight; and compassion and respect.10.1080/10872981.2018.1485432-T0001Table 1.Early concern note behaviors (modeled after Papadakis \[[12](#CIT0012)\]).Integrity and personal responsibility ● Fails to fulfill responsibilities reliably ● Misrepresents or falsifies actions and/or information ● Fails to accept responsibility for actions ● Fails to respect patient confidentiality ● Uses his/her professional position to take advantage of a patientMotivation to pursuit of excellence and insight for self-improvement ● Inadequate personal commitment to honoring the needs of patients ● Resistant or defensive in accepting criticism ● Unaware of his/her limits ● Resists changes based on feedback ● Seeks minimally acceptable level of effortPersonal interactions of compassion and respect ● Inadequate rapport or empathy ● Fails to function and interact appropriately ● Insensitive to the needs, feelings, and wishes of others ● Uses demeaning or disrespectful language about others ● Abusive of arrogant under stress ● Fails to maintain professional appearance and attire
The principles guiding the use of ECNs may be more important than the words on a reporting form \[[13](#CIT0013)\]. At our institution, the ECN is designed to be a supportive 'early-warning' device that serves several educational functions: a trigger for counseling students who exhibit problematic behavior, a longitudinal tracking system of such behaviors, and the basis for a graded (progressive) program of counseling and intervention. Faculty, staff, and students are educated about the purpose of the ECN each year. Faculty and staff are encouraged to use it to report behaviors of concern, including events they may deem insufficient to impact official evaluations or grades. The program operates as follows: Upon receipt of a student's first ECN, a copy is sent to the student with a reminder of the purpose of the ECN process and instructions to review the report prior to meeting with the project's director. A first ECN results in a confidential discussion with the student and informal counseling is provided, but no punitive measures result. The first ECN is not part of the student's academic record and is not shared with any other parties, including faculty who may encounter the student in a future course or clerkship.A second ECN results in a confidential discussion between the student and a larger group of education deans. Additional counseling is provided, with attention to commonalities that may appear between the two ECNs. As is the case for a first ECN, no punitive measures result, and the ECN is not part of the academic record. Exceptions to confidentiality of first and second ECNs occur when the student is felt to be a danger to him-/her-self or others.A third (or subsequent) ECN results in the student appearing before the school's academic progress committee and the student is subject to official action, ranging from mandatory counseling to academic consequences, up to and including dismissal. These actions (and ECNs) become part of both the academic record and the student's Medical Student Performance Evaluation letter sent to postgraduate training programs.
Our approach to addressing recipients of three or more ECNs developed over time and reflects our concern with this limited group of students. Early observations demonstrated that students with one or two ECNs during enrollment have academic outcomes indistinguishable from students without an ECN. Prospectively identifying the subgroup of students who will progress to three or more ECNs remained a challenge. Previous authors have suggested that student maturity, insight, propensity for reflection, or receptiveness to feedback might be related to future behavior \[[14](#CIT0014)--[16](#CIT0016)\]. The receipt of an ECN may be characterized as a 'stressful' event which asks a student to reflect on behavioral change and accept or reject counseling and feedback.
Our previous work failed to find an association between the specific ECN behavior reported (e.g., attendance problem and poor group interaction) and progression to additional ECNs. We hypothesized that student response to being confronted with an ECN would better identify students at-risk. To study this, we classified students based on their response to the ECN and tracked students' receipt of subsequent reports. Additionally, we tracked academic performance during the study period.
Materials and methods {#S0002}
=====================
ECNs are submitted electronically. The person submitting the report notes that the category(ies) of behavior and provides a detailed description of behavior(s) triggering the report. Beginning in 2010, student response to receipt of an ECN was documented. Responses were classified based on (1) whether (or not) the student recognized and acknowledged his or her behavior as inappropriate and (2) whether (or not) the student accepted responsibility for the behavior.
This report includes data on students receiving a first ECN during a seven-year period (October 2010 through December 2017), any subsequent ECNs, and academic performance history.
The study used a correlational design. Classification of student responses was performed by one of the authors (MA) immediately after meeting with each student. [Table 2](#T0002) summarizes the four classifications and sample student comments. Each meeting began by providing the student another copy of the ECN and asking the student 'what would you like to tell me about this report?' Students were placed in classification (class) 1 only if they spontaneously (without further prompting) volunteered that they recognized their behavior was inappropriate and accepted responsibility for their actions. Students were placed in class 2 if, after prompting during the discussion, they ultimately acknowledged that the behavior was inappropriate and accepted responsibility. Class 3 represented students who, after discussion, were able to recognize their errors, but deflected personal responsibility to others, agreeing reluctantly to comply. Class 4 included students who demonstrated neither recognition nor acceptance of responsibility. Reliability of classifying student reactions was assessed by a secondary review of a subset (*n* = 24) of ECNs across all four response classes by two additional independent raters. These raters, blinded to student identity and the original classification, received the ECN and a written summary of the corresponding student responses. Level of agreement across raters was compared and demonstrated 92% interrater agreement. Academic performance was assessed by review of student transcripts; frequency of adverse academic events (defined as required course and clerkship grades of less than 'Pass') was recorded for each student.10.1080/10872981.2018.1485432-T0002Table 2.Classification of student response to an early concern note. Class 1Class 2Class 3Class 4RecognitionSpontaneously recognized that behavior was inappropriateRecognized error when brought to their attentionReceptive to recognizing inappropriate nature of their behavior after discussionRemained resistant to recognizing inappropriate action or denied it occurredResponsibilitySpontaneously accepted\
responsibilityAccepted responsibility when described to themRemained resistant to accepting responsibility but agreed to comply anywayRejected responsibilitySample comment'I forgot to make a note of that schedule change; I'm sorry I missed it and embarrassed I messed up.''I had no idea they took attendance at orientation so seriously. It won't happen again.''I realize the course wants it done a certain way. I still think it's unnecessary, but I'll do what they say.''The course is blowing it way out of proportion. I spoke my mind and they are taking it out of context.'
We used Fisher's exact test to determine whether there were differences in the proportion of students with repeat ECNs based on the classification of student reactions. Significance was defined as a difference measured at the *p* \< 0.05 level.
Data for this study were derived from information collected as a part of the school's standard educational practices. This study was approved by the University of Texas Medical Branch Institutional Review Board. Permission for use of curriculum data was obtained from the School of Medicine Curriculum Committee \[[17](#CIT0017)\].
Results {#S0003}
=======
Since inception of the ECN program at our institution in 2000, over 700 ECNs have been submitted. The study period includes data from 459 ECNs submitted on 344 students, specifying 644 behaviors. The ECNs, which could report behaviors in more than one category, included issues of integrity and personal responsibility (418 behaviors; 65% of the total), motivation to the pursuit of excellence and insight for self-improvement (125; 19%), and personal interactions of compassion and respect (101; 16%). Nearly equal numbers of ECNs were received by Year 1 and 2 students (237; 52%) and Year 3 and 4 students (222; 48%), and the distribution of reported behaviors across the three categories was similar for pre-clerkship (Year 1 and 2) and clinical (Year 3 and 4) students. Most submissions (289; 63%) were from course and clerkship directors or other faculty, with the remainder coming from staff members (most often the course and clerkship coordinator staff). The majority of ECNs (263; 57%) reported behaviors directly observed; the others (196; 43%) represented behaviors reported to the submitter by a third party (typically to course or clerkship personnel from a person working directly with a student).
Classification of student responses to ECNs and frequency of progression to subsequent ECNs are summarized in [Tables 3](#T0003) and [4](#T0004). [Table 3](#T0003) sorts student responses after a first ECN and frequency of progression to subsequent ECNs; [Table 4](#T0004) represents the responses of students after a second ECN and the frequency of receipt of additional (third or greater) ECNs.10.1080/10872981.2018.1485432-T0003Table 3.Classification of *student responses following receipt of a first ECN* and rate of progression to subsequent ECNs.ECN recipients grouped by response to first ECN *n* = 344 *Knew they erred*\
Class 1\
*n* (%)*Naive*\
Class 2\
*n* (%)*Resistant but able to Adapt*\
Class 3\
*n* (%)*Unable to adapt*\
Class 4\
*n* (%)ECN \#1162 (47.1)78 (22.7)70 (20.3)34 (9.9) {#ILG0001}{#ILG0002}{#ILG0003}{#ILG0004}Progressed to\
second ECN23 of 162 (14.2)15 of 78 (19.2)^a^25 of 70 (35.7)^b^20 of 34 (58.8)^c^ {#ILG0005}{#ILG0006}{#ILG0007}{#ILG0008}Progressed to\
third ECN2 of 162 (1.2)1 of 78 (1.3)†13 of 70 (18.6)††5 of 34 (14.7)†††[^1][^2][^3][^4][^5][^6][^7][^8]10.1080/10872981.2018.1485432-T0004Table 4.Classification of *student responses following receipt of a second ECN* and rate of progression to subsequent ECNs.ECN recipients grouped by response to second ECN\
*n* = 83 *Knew they erred*\
Class 1\
*n* (%)*Naive*\
Class 2\
*n* (%)*Resistant but able to adapt*\
Class 3\
*n* (%)*Unable to adapt*\
Class 4\
*n* (%)ECN \#211 (13.3)15 (18.1)25 (30.1)32 (38.6) {#ILG0009}{#ILG0010}{#ILG0011}{#ILG0012}Progressed to\
third ECN0 of 11 (0.0)2 of 15 (13.3)\*6 of 25 (24.0)\*\*13 of 32 (40.6)\*\*\*[^9][^10][^11][^12]
A total of 240 (70%) first-ECN students had responses placed in class 1 or 2. These students might be conceptually viewed as individuals who spontaneously knew that they erred (class 1) or were initially naive about professional expectations (class 2). The common feature across the two groups is that they appeared to have no intent to violate professional norms. These two groups progressed to a second ECN at low rates (14% and 19%, respectively).
A total of 104 (30%) first-ECN students had responses placed in class 3 or 4, which appears to represent students more challenged by professional expectations. As shown in [Table 3](#T0003), the subset of students in class 3 (initially disagreed but expressed willingness to adapt) represented 20% of the study population, and these students progressed to a second ECN at a statistically significant higher rate than class 2 (36% vs. 19%). The 10% of students in class 4 (remained resistant to recognizing the behavior or accepting responsibility) progressed at an even higher rate (59%). The findings were similar for progression of these students to a third ECN. The response classifications for students after receiving a second ECN ([Table 4](#T0004)) reached statistical significance for classes 1 and 2 combined compared to classes 3 and 4 combined. Neither year of medical school nor category of behavior (integrity, motivation, and interactions) differed across students in the four classes. Behaviors reported by third parties were not different from those directly reported, most likely because the third parties (course/clerkship personnel) were merely conduits for ECN submission by the faculty who directly observed the behavior.
Adverse academic events are relatively uncommon in the general student population, representing 1.3% of preclinical course grades and 2.2% of clerkship grades in academic year 2016--2017. In contrast, such events were recorded by 15 of 21 (71%) of students with three or more ECNs, primarily based on performance on traditional academic measures of knowledge such as multiple-choice-question examinations. Of those 15 students, 6 have been dismissed for a range of academic and professional deficiencies. Most (40/52; 77%) of the ECNs received by those 15 students occurred outside the courses during which an academic deficiency was reported. No pattern was discernable whether ECNs occurred prior to or after a student's academic difficulty.
Discussion {#S0004}
==========
At our institution, most students complete their studies without a report of unprofessional behavior. The vast majority of ECNs that are submitted represent students who receive only one or two ECNs during their medical school career---students whose academic outcomes are indistinguishable from students without an ECN. Yet, some students progress to additional reports, and this subgroup was the focus of this report.
Our findings support our hypothesis that student reaction to a report of unprofessional behavior identifies individuals with a high risk of subsequent professional lapses. In our student population, those classified as having insight into their behavior and no recognizable intent to behave in an unprofessional manner (classes 1 and 2) progressed to a subsequent ECN at a statistically lower rate than those who might be seen as more challenged by professional expectations (classes 3 and 4). Such reactions can be a reflection of the student's maturity, insight, and adaptability to the professional challenges faced by all physicians, making these relevant skills to cultivate \[[16](#CIT0016)\]. Students with diminished capacity to adapt to behavioral expectations or to accept responsibility for them appear to be at highest risk of future reports of unprofessional behavior, reinforcing the importance of insight in professional performance \[[18](#CIT0018)--[20](#CIT0020)\].
Not all ECNs necessarily reflect a student's underlying character. The observed behaviors triggering an ECN at our institution often reflected a range of underlying problems. For example, 'a pattern of frequently arriving late' has included underlying factors as diverse as failure to set a wake-up alarm, sleep disturbance from a newborn child at home, ignorance (or dismissal) of professional norms, declining interest in medicine as a career, depression, burnout, or substance abuse \[[21](#CIT0021),[22](#CIT0022)\]. In such cases, the behavior might represent a transient, self-limited, or treatable condition or provide an opportunity to educate the student. Thus, the value of an ECN does not always lie in remediation, but in recognition of the student's unique situation, bringing unacceptable behavior to his/her attention, and support toward resolution. The non-specificity of behaviors that bring a student to attention might also explain why the offending actions observed during the dominantly classroom-based Years 1 and 2 did not differ from the behaviors observed during the dominantly clinical Years 3 and 4.
It is important to note that while students with responses in classes 1 and 2 progressed to subsequent ECNs at a lower rate than students in classes 3 and 4, the progression rate was not zero. This suggests that refraining from unprofessional behavior requires more than just recognition, good intentions, and insight. It is possible that some students in classes 1 and 2 are well intentioned but nevertheless struggle with issues of impulsivity, immaturity, ongoing personal challenges, or other contributions to subsequent lapses. More work is needed to explore such factors.
Ideally, students would receive direct feedback on their behavior (and other skills) from those with whom they work. The value of early-warning-systems such as ECNs and similar programs at other institutions derives in part from two phenomena \[[23](#CIT0023)\]. First, there are limits to relying solely on direct feedback to students from those with whom they interact. Faculty, whether in classroom or clinical settings, often have limited scope of direct observation or may be hesitant to report isolated events either from insecurity, desire to avoid labeling a student, discomfort with confrontation, or fear of damaging the teacher--learner relationship \[[24](#CIT0024),[25](#CIT0025)\]. Those who work transiently with learners may also hesitate to report isolated events but would feel more comfortable in doing so if they knew such behavior represented a pattern. Second, sharing performance information across courses is not routine, and if 'isolated events' go unreported, no pattern is ever detected \[[26](#CIT0026)\]. Strengths of a graded-response ECN process include the ability to maintain a supportive and counseling-dominant environment until a pattern is recognized that justifies stronger action \[[27](#CIT0027)\]. In this respect, our ECN program reflects the tiered approach of Hickson et al. with licensed physicians that emphasizes progression from a 'cup of coffee' conversation to more formal, structured intervention when warranted \[[28](#CIT0028)\].
Threats to reliability of any classification process can exist if students respond with what they think is the right answer during the meeting. Such a phenomenon would result in misclassification from a higher class (3 or 4) to a lower one. This may have contributed to the finding that some students in the low-risk classifications (1 and 2) progressed to subsequent ECNs.
Our work supports the premise that ECNs can be a practical, objective and easy-to-implement reporting, and classification strategy. It additionally demonstrates the importance of student responses to an ECN. A process that identifies students at increased risk of repetitive problematic behaviors at the time of their first ECN creates an opportunity to intervene or interrupt patterns of behavior \[[27](#CIT0027),[29](#CIT0029)\]. Several students in our study group were dismissed in part or in whole because of unprofessional behavior, so the ramifications of allowing problematic behaviors to go unrecognized or uncorrected can be substantial. Since this population may also be at higher risk for problems after graduation, interventions tailored to a student's individual needs, including more intense observation, feedback, counseling, or leaves of absence, appear justified \[[30](#CIT0030),[31](#CIT0031)\].
Most students in this study appeared to have had no conscious intent to be unprofessional, a gratifying result. It is possible that their low rate of progression may reflect personal growth, professional identity development, or simply the impact of students seeing that their behaviors were actually noticed, rather than the counseling provided through this program \[[23](#CIT0023)\]. But since students in class 2 were clearly surprised by the professionalism norm they violated, the ECN can serve an educational function as well.
Any ECN system has limitations. Like all screening instruments, its sensitivity exceeds its specificity, and adjunctive information is needed to more clearly isolate the subset of students identified in the screening process most likely to benefit from intervention. Incorporating student reactions to ECN reports may provide that information and improve specificity. It is also reasonable to speculate that some of the reactions displayed by students in class 3 might actually be normal adaptive behavior. For example, when faced with a required task in life one deems unpleasant or unnecessary (such as navigating a poorly designed electronic medical record system), compliance 'just to avoid sanctions' (preferably with feedback to the designers) may be a learned functional or productively adaptive response. Yet, the rate of progression to subsequent ECNs in this group (36%) suggests this represents a high-risk group.
It is not clear why students with three or more ECNs were also more likely to experience adverse academic events. It is possible that they had additional underlying skill deficiencies that impacted their broader performance or that the same behavioral issues resulting in ECNs were deleterious to their academic preparation, such as rule-following or attention to clinical responsibilities. A small number of students acknowledged facing substantial personal challenges (life stressors, substance abuse, and/or mental health problems) with impacts ranging from mild distraction to substantial impairment, but they were not otherwise distinguishable by the ECN process. However, it seems clear that academic failures alone cannot be used as a reliable early warning system.
Cautions to the generalizability of these findings are warranted. At our institution, the ECN system does not operate in isolation. It is part of a broader initiative addressing professionalism which includes a Professionalism Charter for all faculty, students, and employees, frequent workshops on the subject, a biennial professionalism symposium, and support from leadership. A range of reporting opportunities for undesired behaviors is provided, including both formal and informal (and anonymous) options. This environment may mean our students and faculty are more sensitized or receptive to the program. Additionally, results are from a single school and student response classifications were judgments of a single author, a practice chosen to minimize exposure of confidential information and to maximize consistency of interpretation of student responses. However, classifications were purposefully designed to limited subjectivity; for example, class 1 was used only when the student's initial response unambiguously acknowledged the inappropriateness of the behavior and acceptance of responsibility without qualification. Class 2 was used only when such acknowledgements were forthcoming by the end of the meeting. While re-review of a subset of blinded classifications by independent raters was included to strengthen the reliability of such judgments, misclassification may have occurred. Work to examine generalizability of this approach across raters and institutions is needed. A small number of classifications were based on a telephone or videoconference interview of the student rather than an in-person interview because of geographic separation between the parties. Absence of in-person interaction may have influenced the judgments being made. Finally, the follow-up period in the study did not extend through the entire medical school career of all students, so the number of subsequent ECNs or adverse academic events may be incomplete.
This analysis did not examine impact on future practice. While such results are powerful reflections of the impact of professional behavior on patient care and a physician's career, medical schools also need surrogate measures which allow them to identify as early as possible, among all students who misstep, that critical subpopulation at highest risk of additional problems while enrolled \[[17](#CIT0017),[23](#CIT0023),[32](#CIT0032)\]. Using professionalism reports like ECNs as a screening method in the way described offers schools another tool to help identify those students most in need of assistance. If the value of this approach to the use of ECNs is verified, they could also (with appropriate safeguards) become part of a 'feed-forward' system designed to alert future courses that additional attention to these skills in such students is appropriate. Examples of safeguards used at our institution include requiring student permission for such a process and providing information only to course directors who could select assignments tailored to the student's needs---not to faculty who directly grade the student.
Acknowledgments
===============
The authors gratefully acknowledge the valuable editorial review assistance of Era Buck, PhD, and Christine Ford, MA.
Disclosure statement {#S0005}
====================
The authors report no conflict of interest.
Previous presentations {#S0006}
======================
Abstracts of earlier versions of this work were presented at the 124th Annual Meeting of the Association of American Medical Colleges. Philadelphia, PA. November 2013.Association of Medical Education in Europe annual meeting. Glasgow, Scotland. August 2015.Learn, Serve, Lead meeting of the Association of American Medical Colleges. Boston, MA. November 2017.
Data availability statement {#S0007}
===========================
None.
Ethics review {#S0008}
=============
This work was reviewed and approved by the Institutional Review Board of the University of Texas Medical Branch IRB \# 16-0369. Permission for use of curriculum data was obtained from the School of Medicine Curriculum Committee.
[^1]: ^a^FET = 0.2646 (nonsignificant) compared to class 1.
[^2]: ^b^FET = 0.0273 (*p* \< 0.05) compared to class 2.
[^3]: ^c^FET = 0.0349 (*p* \< 0.05) compared to class 3 and \<0.0001 (*p* \< 0.05) compared to class 2.
[^4]: FET \< 0.0001 (*p* \< 0.05) for combined class 1 + 2 compared to combined class 3 + 4.
[^5]: †FET = 1 (nonsignificant) compared to class 1.
[^6]: ††FET = 0.0003 (*p* \< 0.05) compared to class 2.
[^7]: †††FET = 0.7845 (nonsignificant) compared to class 3 and 0.0096 (*p* \< 0.05) compared to class 2.
[^8]: FET \< 0.0001 (*p* \< 0.05) for combined class 1 + 2 compared to combined class 3 + 4.
[^9]: \*FET = 0.4923 (nonsignificant) compared to class 1.
[^10]: \*\*FET = 0.6857 (nonsignificant) compared to class 2.
[^11]: \*\*\*FET = 0.2597 (nonsignificant) compared to class 3 and 0.0944 (nonsignificant) compared to class 2.
[^12]: FET = 0.0142 (*p* \< 0.05) for combined class 1 + 2 compared to combined class 3 + 4.
|
community medics
If you’ve ever picked up the phone to call 9-1-1, you or someone else probably needed help. Badly. And you probably assumed that after dialing those three numbers, help would come screeching around the corner, lights and sirens blaring.
If you’ve ever picked up the phone to call 9-1-1, you or someone else probably needed help. Badly. And you probably assumed that after dialing those three numbers, help would come screeching around the corner, lights and sirens blaring.
Well, the residents of East and West Oakland say that depends on where you live. In this special hour-long KALW documentary, “The Race to an Emergency” host Martina Castro and reporter Ali Budner trace the path of a 9-1-1 call in Oakland: from the dispatchers to the emergency responders. And they consider how geography and demographics figure into a crisis that has been brewing in Oakland for decades.
Click the player to listen to the hour-long documentary. For more information, links to sources, photos and data maps, please visit the documentary website, www.theracetoanemergency.org.
Listen
Listening...
/
56:00
Note: This piece first aired on October 8th, 2013. To see the original post and hear the audio from that airing, click HERE.
The story behind the country's real first ambulance system carries themes of race and class. It was created in the late 1960s. Up until then, police would take patients to the hospital in wagons that weren't equipped with gurneys or medical equipment. |
Unifying Ambiance Set
Fills the air with a comforting atmosphere.
Bring about a sense of well-being with the comforting combination of lavender, eucalyptus and peppermint oils. Disperse pure essential oil with an elegant aroma diffuser, inspired by the ripening lotus bud of the east. |
Monthly Archives: August 2017
Brian and I made it to Midway and spent the night while the girls stayed home! We enjoyed dinner and atv-ing! It was so much fun. Zermat resort30 miles of beautiful mountain exploring
Then when we came over we finally took our bikes out for the first time. Elsie really did like it. I think we might need another trailer because this one is only made for two. Although, Molly preferred to ride in the trailer instead of riding her own bike- which meant Elsie had to ride on Mollys lap 😂. poor Brian, he was pulling about 70lbs of babies. 🚴🏻🏋🏼
I know I know it’s only preschool, but we are preparing to go back the week after next. Kate and I are practicing saying goodbye to each other without tears. Molly is planning her outfits and deciding what new and old friends she will play with (yes, she is still 4 not 14). And Elsie and I are imagining all the possibilities to do together with the two hours of freedom twice a week without the older sissies. 🏖.
We had a wonderful time at AG. I think everyone in the family had a great time. I loved all the activities and the opportunity to enjoy them while not having to worry about my small girls. Everything was taken care of. Some of the highlights for me were hiking, archery, shooting, slip n slide, playing with my camera, laser tag, ropes course, napping, matching t-shirts, Molly’s talent, 9 square, swimming, and exceeding my “steps” goal every day by thousands. Brian loved the archery because he was so great at it. Molly loved her camp group and swimming. I hope we can do it again in a few years.
Now, we are going to need a few days to recover and heal the ear infections we brought home and catch up on some lost sleep. |
Jonah Simms is getting a mom and dad!
Superstore will introduce Jonah's parents in the NBC workplace comedy's current fourth season, ET exclusively reveals.
Fred Melamed (A Serious Man, In a World...) will play Jonah's father, Richard, while Meagen Fay (Grace and Frankie, La La Land) will portray his mother, Marilyn. They will appear in the seventh episode, titled "New Initiative," which is slated to air in mid-November.
ET exclusively debuts the first photos of Melamed and Fay, alongside Superstore stars America Ferrera and Ben Feldman, in the Cloud 9 store. See the gang all together in the pics below.
NBC
NBC
"We’re going to meet his parents and we’re going to find out more about him and what really is going on in his life, or what his family believed to have been going on in his life and what his whole situation was when they show up in episode [seven]," Feldman told ET. "I’m really excited. I’ve wanted family for Jonah for a long time."
Added creator Justin Spitzer: "We’ll have a big episode when they come into the store and we’ll get to see his family’s reaction working there."
Feldman also expressed optimism that Jonah's sometimes mentioned-never seen brothers would eventually drop by at some point down the line, sharing a storyline idea he's positive won't ever come to fruition.
"I want the brothers to come in too. I was talking to a friend of mine, Darren Criss, a long time ago. He was like, 'You have multiple brothers on the show. The greatest thing would be if your brothers all hated each other and the only person that they talked to was you, and so you never saw more than one brother in a room with you and then I just played all the brothers,'" Feldman shared, chuckling at the thought. "I would love that. That would, of course, never happen."
While it took three seasons for Superstore to bring in members of Jonah's family, the show introduced Amy's parents -- Ron and Connie, played by Ugly Betty's Tony Plana and Marlene Forte, respectively-- in the second season.
Superstore airs Thursdays at 8 p.m. ET/PT on NBC.
RELATED CONTENT:
'Superstore' Creator, Ben Feldman Break Down Amy & Jonah's 'Scandalous' New Secret (Exclusive)
'Superstore': Ben Feldman Promises Answers to Amy & Jonah's Racy Hookup in Season 4 Premiere (Exclusive)
'Superstore': First Look at the Slick New Season 4 Poster (Exclusive) |
Biathlon World Championships 2015 – Women's mass start
The Women's mass start event of the Biathlon World Championships 2015 was held on 15 March 2015. 30 athletes participated over a course of 12.5 km.
Results
The race was started at 14:30 EET.
References
Women's mass start
Category:2015 in Finnish women's sport |
Ahead of the eagerly-awaited release of Doctor Who - The War Doctor 1: Only The Monstrous this Monday 14th December, Big Finish is pleased to reveal details of the War Doctor's next epic battle...
Available in February 2016, Doctor Who - The War Doctor 2: Infernal Devices continues the legendary conflict of the Time War. John Hurt reprises his role as The War Doctor – the secret regeneration of the Doctor, who has abandoned his peaceful code to wage war against the Daleks (Nicholas Briggs).
The War Doctor will again be joined by Cardinal Ollistra (Jacqueline Pearce), who sends the Time Lord to investigate an initiative that could change the course of the War – but at what cost?
Also featuring in the box set are David Warner, Jamie Newall, Zoë Tapper, Robert Hands, Oliver Dimsdale, Laura Harding, Barnaby Kay, Jaye Griffiths, Tim Bentinck and Tracy Wiles.
The three stories included in Doctor Who - The War Doctor 2: Infernal Devices are:
Legion of the Lost by John Dorney
In a time of war, every means of victory must be explored. In the Time War, the unthinkable must be thought, and neither side can afford to be squeamish about their methods.
When the destruction of an obscene weapon leads to the Time Lord once known as the Doctor uncovering a secret Gallifreyan initiative, he cannot believe what is being considered.
Should victory be sought at any cost? Or are there worse possibilities than losing to the Daleks..?
A Thing of Guile by Phil Mulryne
The Daleks are developing a secret weapon on Asteroid Theta 12. It is imperative that their plans are uncovered.
Cardinal Ollistra has her hands full studying the range of ancient and mysterious armaments the universe has to offer, but she makes it a personal mission to investigate the Dalek project.
On this dangerous assignment, there is one particular Time Lord she wants at her side - and he will be accompanying her whether he wants to or not.
The Neverwhen by Matt Fitton
On an isolated world ravaged by battle, time itself has become a weapon, laying waste to all who live and die there. Arms and technology are in a state of flux – and it seems that everlasting war is their only option.
The arrival of one battered Type Forty TARDIS inside this nightmare offers hope to the combatants trapped within.
But when he discovers the truth, the horrors of the Neverwhen will shock even the War Doctor…
Doctor Who - The War Doctor 2: Infernal Devices can be pre-ordered today for just £20 on CD or Download.
You can also order this release as part of the Time War Saga bundle. The bundle contains all four box sets from the War Doctor series, along with the five-disc prequel Doctor Who - The Eighth Doctor: The Time War starring Paul McGann. And remember, when you when you buy any of these titles on CD directly from Big Finish, you will also unlock access to a digital copy for download on day of release.The War Doctor's Battles will continue in Doctor Who - The War Doctor 3: Agents of Chaos in September 2016.
The first box-set in the series, Doctor Who: The War Doctor 1: Only The Monstrous will be released this Monday the 14th December 2015. Pre-order now, and you will qualify for free UK delivery. Check out the trailer below! |
Articles by Kristof Phillips
Philadelphia’s Out-of-School Time (OST) Initiative continues to build on past programs and improve the quality of OST for children by increasing participation from non-city funded programs. Mayor Jim Kenney’s administration sees improving OST programing as a […]
All along Bustleton Avenue are businesses built by foreign-born people who came to the U.S. in pursuit of a better life. Yet many highly educated and skilled immigrants are underemployed in Northeast Philadelphia and the […]
Northeast Philadelphia has become a home for small immigrant businesses. Shopping centers along Bustleton Avenue feature many thriving businesses owned by immigrants from all over the world. With his restaurant not even two months old, […]
While 15-year-old Natalie Dove awaits to defend her No. 1 junior women’s boxing ranking in the amateurs, she is focusing on her bigger dream: Winning the 2020 Olympic gold medal for her gym and country. […]
South Philadelphia is not the only the neighborhood to get Philly’s famous steak sandwich. Hidden within the Northeast’s sprawling landscape of mini shopping malls you can find five cheesesteaks that rival their South Philly brethren, like, […] |
Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells.
Vasopressin-dependent translocation of aquaporin-2 (AQP2) between intracellular vesicles and the plasma membrane has been demonstrated in vivo and in vitro. Furthermore, the vasopressin-induced increase in apical membrane water permeability of renal principal cells is dependent on a rise in intracellular adenosine 3',5'-cyclic monophosphate and activation of protein kinase A (PKA). To determine whether trafficking of AQP2 is dependent on PKA phosphorylation, we first examined the effect of the PKA-inhibitor N-(2[[3-(4-bromophenyl)-2-propenyl]-amino]-ethyl)-5-isoquinolinesulfonam ide (H-89) on AQP2 translocation in transfected LLC-PK1 cells. Vasopressin-induced membrane insertion of AQP2 was completely inhibited by pretreatment of the cells for 60 min with H-89. This reagent also caused a dense accumulation of AQP2 in the Golgi region. Next, LLC-PK1 cells were stably transfected with AQP2 cDNA in which the PKA phosphorylation site, Ser256, was replaced with alanine (S256A). S256A-AQP2 was not phosphorylated in vitro by PKA, and S256A-AQP2 was mainly localized to intracellular vesicles in the basal condition, similar to wild-type AQP2. However, after stimulation with vasopressin or forskolin, the cellular distribution of S256A-AQP2 remained unchanged. In addition, the usual vasopressin-induced increase in endocytosis seen in AQP2-transfected cells was not observed in S256A-AQP2-transfected cells. These results demonstrate that the Ser256 PKA phosphorylation site is possibly involved in the vasopressin-induced trafficking of AQP2 from intracellular vesicles to the plasma membrane and in the subsequent stimulation of endocytosis. |
“Dissatisfaction with democracy within developed countries is at its highest level in almost 25 years,” say researchers at the University of Cambridge. “The UK and the United States had particularly high levels of discontent.”
No wonder. Certainly, America is a severely divided country. “Severely divided societies are short on community,” and “community is a prerequisite for majority rule,” argues Donald L. Horowitz, a scholar of democracy, at Duke University.
Having studied “constitutional engineering” in divided societies like South Africa, Horowitz has concluded that, “In societies severely divided by ethnicity, race, religion, language, or any other form of ascriptive affiliation, ethnic divisions make democracy difficult, because they tend to produce ethnic parties and ethnic voting. An ethnic party with a majority of votes and seats can dominate minority groups, seemingly in perpetuity.” (Journal of Democracy, April 2014.)
The Democratic Party has morphed into such a political organ. It’s responding to the fact that minorities in the U.S. will soon form a majority. This rising majority, as polling trends indicate, will speak in one political voice, for most immigrants to the United States are not from Europe and Canada, but from Latin America and Asia, south and east. And this cohort of immigrants is reliably progressive: It votes Democratic.
Likewise, the poor and the unskilled are well-represented among our country’s immigrant intake. It’s the way we roll. Poor immigrants favor the rearranging of the income curve in their new home.
The policy establishment preaches well-meaning pieties. All these energetically imported, fractious minorities, claims our ruling Idiocracy, will relinquish race and tribe as unifying principles, and adopt our U.S. constitutional design and “our values.”
Democrats know better. Oh, the founding population, they expect, will naively hitch its existential survival to a political dispensation called liberal democracy.
The duped, historic majority of the U.S. will willingly cede political and institutional dominance in return for the constitutional safeguards—for the abstractions—offered by democracy. This, Democrats know only too well.
Moreover, being pushover-passive on matters domestic, Caucasian America is generally pro-immigration, the more exotic and culturally incongruent, the better. It makes for a warm and fuzzy feeling about The Self. But while Americans don’t see race; the people they’re importing see nothing but race.
Take Indian Americans. They’re a relatively new addition to the United States’ top-down, state-planned, multicultural mess of pottage. Most Indian-Americans have “arrived in America over the past two decades.” But they are highly aggressive politically and reliably Democrat.
By the Economist’s telling, “Capitol Hill, for example, is crammed with staff and interns of Indian-American heritage. They also appear to be ‘over-represented’ in academia, the media and other influential posts.” And, it is their indisputable habit to deploy and grow “informal networks, as well-connected Indian-Americans find jobs for each other’s offspring.”
Caste and ethnicity: It’s what the scrupulously candid English magazine is here hinting at, ever so genteelly. As many in the corporate world know all too well—once an individual of South-Asian descent gets into a position of power, he is inclined to hire others of the same persuasion, talent be damned. Meek Anglo-Americans, on the other hand, hire by talent, not by tribe. Honky just doesn’t have that screw-or-be-screwed DNA to do battle with the Other’s flinty duplicity.
This mercenary, extractive approach to politics prevails among the immigrants being imported at a furious rate by the immigration-industrial-complex. Asians, aforementioned, are especially primed to seek, and aggressively extract, advantage from positions of power.
Take Sen. Kamala Harris. Although she “rarely mentioned the Indian side of her family while campaigning,” the erstwhile presidential candidate’s mother migrated to California from Chennai, in southern India. Angry, anti-white, and highly receptive to theories that blacken the West and porcelainize the undeveloped world—Kamala and her kind cannot be trusted to relinquish race as an organizing principle, in favor of a complete commitment to a constitutional design, in the America she and her progeny hope to inherit.
What about that seething Somali, Ilhan Omar, the representative from Minnesota? Who will be the loser in her brave, new, tribal America?
In the context of democracy and its discontents, Anglo-American elites and policy makers have courted and engineered their own demise. No other group expresses such incontinent exhilaration at the prospects of turning their historic populations into minorities.
“The United States has more immigrants than any other country in the world,” states Pew Research. “Immigrants and their U.S.-born children now number approximately 89.4 million people, or 28 percent of the overall U.S. population,” says the American Community Survey (ACS). According to the Migration Policy Institute, “One in seven U.S. residents is foreign born.”
As stated, the foreign-born are, for the most, from alien, often-hostile cultures.
“A century ago, more than 80 percent of [America’s] foreign-born population came from Europe; now the figure is only 10 percent. … America is becoming less European,” bewailed the Economist in one issue, inexplicably.
“Inexplicably,” because this (superb) news magazine usually glorifies the ethnic transformation of European societies through exotic immigration.
Confusion born of contradiction peaks in the next issue, where Robert Guest, of the same open-borders Economist, lectures and laments that, “The simplest way to make the world richer is to allow more people to move. Yet the politics of migration has never been more toxic.”
D’oh! While extolling endless migration to the West, the very same, Nov. 16-22 issue of the magazine depicts a world beset by unrest:
“It is hard to keep up with the protest movements under way around the world. … only the global unrest of the late 1960s was similar in scope.”
After much dissembling, it is eventually conceded that the global unrest is engulfing “well-functioning democracies” big time, too.
ORDER IT NOW
In fact, “a related phenomenon [in the unrest equation] is the weakening of the bargain at the heart of Western-style democracy—that losers, who may represent a majority of the popular vote, will accept rule by the winners until the next election. The millions on the streets do not accept the patience that trade-off demands.” [Emphasis added]
“A weakening of the bargain at the heart of Western-style democracy”? I wonder why?
Because flooding Western democracies with non-Western people has created societies without social capital, societies that share no enduring bonds other than the quest to extract as much power and possessions possible from the political process.
Western nation-states are now imperiled entities. Their central authorities have worked to erode delicate sectarian and ethnic balance within, and thus hope for lasting comity among disparate communities.
By using their police powers to swamp their already fructuous populations with alien nations—where are the referenda on mass immigration?—governments have undermined exiting ethnic balance in Western democracies, and, with it, the fellow feeling so essential to democracy’s endurance.
Consider: Before Comrade Ted Kennedy’s coup of 1965, America was, by and large, a biracial nation. To quote author Ann Coulter, “From 1620 to 1970, the U.S. was demographically stable. … The country was about 85 percent to 90 percent white, almost entirely British, German, French and Dutch, and 10 percent to 15 percent African American.” In other words, America was largely a biracial compact; never a multicultural “nation of immigrants.”
Blacks and whites were only just beginning to come to terms with each other and with a shared, painful past.
Arguably, by opening the floodgates to mass, Third-World immigrants, the government of the day forever upset the teetering bi-racial balance within America.
Ilana Mercer has been writing a weekly, paleolibertarian column since 1999. She’s the author of Into the Cannibal’s Pot: Lessons for America From Post-Apartheid South Africa (2011) & The Trump Revolution: The Donald’s Creative Destruction Deconstructed” (June, 2016). She’s on Twitter, Facebook & Gab. Latest on YouTube: “How Democracy Made Us Dumb. |
Rainbow trout liver microsomal lipid peroxidation. The effect of purified glutathione peroxidase, glutathione S-transferase and other factors.
Glutathione peroxidase (glutathione: hydrogen-peroxide oxidoreductase, EC 1.11.1.9) was purified approximately 600-fold from rainbow trout liver soluble fraction and its activity in the NADPH microsomal lipid peroxidation system tested. The enzyme has an approximate molecular weight of 100 000, contains four subunits and four atoms of selenium per mol protein. No selenium-independent glutathione peroxidase activity could be attributed to glutathione S-transferase (EC 2.5.1.18) in trout liver. Glutathione peroxidase together with glutathione (GSH) did not provide any additional protection in the in vitro liver microsomal lipid peroxidation system over and above that provided by GSH alone. Microsomal lipid peroxidation was, however, reduced by a partially purified glutathione S-transferase together with GSH. The protection provided by dialysed liver cytosol in this system was not GSH-dependent, showing that other factors in addition to glutathione S-transferase are involved. Of other possible factors, vitamin E reduced lipid peroxidation in this system. Concentrations of vitamin E in microsomes before and after peroxidation in vitro indicated that protective cytosolic factor(s) act prior to the termination of the free radical chain reactions effected by vitamin E. A GSH-dependent protective factor was present in microsomal protein, malondialdehyde formation in the in vitro microsomal system being markedly reduced in the presence of 5 mM GSH but not significantly lowered by 1 mM GSH. |
Voltaire — To learn who rules over you, simply find out who you are not allowed to criticize
Sunday, April 14, 2013
A variation in the gene ABCA7 causes the risk of late-onset Alzheimer's disease to double in African-Americans
The research, the largest analysis yet to establish genetic risk linked to late-onset Azheimer's disease in African-Americans, was undertaken by the Alzheimer's Disease Genetics Consortium and led by scientists from Columbia University Medical Center. "Our findings strongly suggest that ABCA7 is a definitive genetic risk factor for Alzheimer's disease among African-Americans," said Richard Mayeux, MD, MS, professor and chair of Neurology at CUMC. "Until now, data on the genetics of Alzheimer's in this patient population have been extremely limited." The ABCA7 gene plays a part in the production of lipids and cholesterol, which indicates that lipid metabolism might be a more crucial pathway for the disease in African-American individuals than in whites. It is more common for African-Americans to experience lipid and cholesterol imbalances - which ultimately result in heart attacks, strokes, and vascular disease. Therefore, the researchers explained that treatments that lower cholesterol and vascular disease could possibly be a successful way to decrease or delay Alzheimer's among this group of people. The experts aimed to look for genetic variants in African-Americans, who generally have an increased incidence of late-onset Alzheimer's, compared to whites residing in the same community. Alzheimer's affects approximately 5 million people aged 65 and older in the United States, and 90% of all cases of the disease are reported to be the late-onset form. Christiane Reitz, MD, PhD, first author and assistant professor of neurology, said: "ABCA7 is the first major gene implicated in late-onset Alzheimer's among African Americans, and it has an effect on disease risk comparable to that of APOE-e4 - which has been known for two decades to be a major genetic risk factor in whites. Both genes raise the risk of Alzheimer's in this population twofold." The importance of the role of APOE-e4 in African-Americans had been unclear due to conflicting results from prior, smaller investigations. "Based on these results, we now know that both APOE-e4 and ABCA7 are major genetic risk factors for African-Americans, whereas for whites, only one of the two - APOE-e4 - confers a similar degree of risk," said Dr. Mayeux, who is also co-director of the Taub Institute for Research on Alzheimer's Disease and the Aging Brain and the Gertrude H. Sergievsky Center at CUMC. Many other genes that had recently been associated with the disease in white people were also shown in this report to have a role in African-Americans. Dr. Reitz, who is a member of both the Sergievsky Center and the Taub Institute, explained: "Because they cross ethnic groups, the likelihood increases that these genes are very important in the development of Alzheimer's. And that gives us clues in our search for the cellular pathways associated with the disease. These findings suggest that the genetic underpinnings of Alzheimer's disease may vary among different populations - and so should not be treated homogeneously." |
Distraint
Distraint or distress is "the seizure of someone’s property in order to obtain payment of rent or other money owed", especially in common law countries. Distraint is the act or process "whereby a person (the distrainor), traditionally even without prior court approval, seizes the personal property of another located upon the distrainor's land in satisfaction of a claim, as a pledge for performance of a duty, or in reparation of an injury." Distraint typically involves the seizure of goods (chattels) belonging to the tenant by the landlord to sell the goods for the payment of the rent. In the past, distress was often carried out without court approval. Today, some kind of court action is usually required,inappropriate tertiary source the main exception being certain tax authorities, such as HM Revenue and Customs in the United Kingdom and, in the United States, the Internal Revenue Service—agencies that retain the legal power to levy assets (by either seizure or distraint) without a court order.
History
Article 61 of the Magna Carta extended the law of distraint to the monarch's properties. In England in 1267 the Statute of Marlborough was passed making distraint unlawful without a court order.
Chapter 1 (Distress, or Unlawful Distress) of the Statute of Marlborough 1267 provided that: all persons "as well of high as of low estate" were to receive justice in the King's court. No individual was to be entitled to seek "revenge or distress of his own authority" against his neighbour for any damage or injury suffered without first obtaining an award from the court.
Distress in this context was (and still is) a summary remedy designed to secure performance of an obligation or settlement of an outstanding debt. First, it was the bedrock of the notion that all citizens, irrespective of rank, were entitled to seek civil justice through the King's court or courts. Secondly, it laid down a prohibition on individuals taking the law into their own hands and seeking remedies (revenge or distress) without the court's sanction. That prohibition was reinforced with criminal penalties.
Procedure
The goods are held for a given amount of time, and if the rent is not paid, they may be sold. The actual seizure of the goods may be carried out by the landlord, the landlord's agent, or an officer of the government, a bailiff or sheriff officer in the United Kingdom or a sheriff or marshal in the United States.
Certain goods are protected against distraint – these are called "privileged goods". Such goods include, for example, goods belonging to the state, fixtures, goods delivered to the tenant or debtor for business purposes, the goods of a guest, perishable goods (e.g. food), livestock, gas, water, electricity, and tools of the tenant's trade.
Forced entry is usually not permitted by the distraint officer, but in the UK, in the event of entry being refused to the HMRC distraint officer, HM Revenue and Customs can apply for a break open warrant under Section 61(2) of the Taxes Management Act 1970. This permits forced entry to the debtor's premises by the HMRC distraint officer. Any additional costs incurred from obtaining the warrant are passed onto the debtor and added to the debt to be collected by distraint.
Also in the UK, forced entry is also permitted if the distress warrant is for amounts of a criminal nature; court fines for instance. The use of forced entry for these purposes is covered in the Domestic Violence, Crime and Victims Act 2004.
Execution of fines and judgment debts in the United Kingdom and abolition of non-bailiff, non-warrant distraint
In the United Kingdom the proposals which have been implemented to reduce the area to post-warrant executions by registered court bailiffs (enforcement officers) gained serious traction in the late 20th century.
In post-warrant execution and former civil distress concerns were regularly expressed that certain instances of distraint/distress violate human rights, such as Article 8 of the European Convention on Human Rights, the right to respect for private life. The Lord Chancellor's Department (now the Ministry of Justice) in May 2001 issued Enforcement Review Consultation Paper No. 5: Distress for Rent, which spurred the abolition of distraint for residential leases and reduced it to peaceable re-entry, that is closing down of commercial premises and no taking of goods, by authorised, registered bailiffs ("Enforcement Officers") in commercial property subject to safeguards — to ensure compliance with the Human Rights Act 1998.
It was thought that distraint would be abolished in the UK when the Tribunals, Courts and Enforcement Act 2007, s.71 came into force, replacing it, solely for leases on commercial property, by a statutory system of Commercial Rent Arrears Recovery (CRAR) (the Tribunals, Courts and Enforcement Act 2007 received Royal Assent July 2007 but no date for implementation was published. A Commencement Order of 2012 followed which brings into force sections 93 and 94 of the Act (on 1 October 2012 and 17 May 2012 respectively), which amend the Charging Orders Act 1979.)
Bailiffs must provide evidence of their identification upon request by the debtor, as a well as sight of the warrant providing them with authority to enter. They must also legally give the debtor an enforcement notice seven days before they visit. In contrast, private sector debt collectors can chase a debtor to pay what is owed to a creditor, but they cannot levy distress. Debt collectors are not allowed to pretend to be a bailiff. Debtors can also check the register of certificated bailiffs if they are unsure about whether a bailiff is certificated or not.
Distraint in the United States
Distraint was adopted into the United States common law from England, and it has recently been challenged as a possible violation of due process rights under the Fourteenth Amendment. In decisions like Luria Bros. and Co. v. Allen, 672 F.2d 347 (3d Cir. 1982), however, the courts have upheld the rule because, as a landlord's self-help remedy, distraint involves no state action and thus cannot violate due process rights. In the case of distraint by the federal government for collection of taxes, the power of administrative levy by distraint (distress) dates back to the year 1791, according to the U.S. Supreme Court.
Distraint in Sweden
In Sweden, distraint (Swedish:Utmätning) is performed by the Swedish Enforcement Authority. Bank assets and similar are taken first, but if needed the Enforcement Authority can visit people's homes, assisted by the police. Goods needed for an acceptable standard of living are protected, like clothes, TV-sets and stoves. Protected items that are expensive can be replaced with cheaper, and excess items can be taken. Goods found in the home, but belonging to others, e.g. to the girlfriend, can also be taken unless it is proven who it belongs to. Homes can be forcibly sold (Swedish: exekutiv auktion), and everyone living there might be evicted.
See also
Attachment (law)
Collection agency
Conversion (law)
Foreclosure
Quia Emptores
Repossession
Self-help (law)
Sequestration (law)
Tax levies
Theft
Warrant sale
Notes
External links
Category:Judicial remedies
Category:Landlord–tenant law |
Accordin' to the Romanian researcher Cornel Dan Niculae ("The Unseen war" - 2nd volume), the canadian company "Gabriel Resources" owns the license to exploit the resources of Rosia Montana/ The Red Montana, a region located in the Western Carpathians (Apuseni).
The financial investment was given by the Washington branch of the "Rothschild Bank".
(Previously, durin' the XVIII-XIXth centuries, the owner of the gold mines from Rosia Montana was a jewish named David Albert.)
Another canadian company, "The Gold Corporation", got involved by foundin' the romanian branch, named "Rosia Montana Gold Corporation SRL".
The name beyond these companies is Vasile Frank-Timis, a "romanian-british-canadian"... jewish, who sponsored a lot of the Secret Services (SIE,SRI etc.) actions, next to
this Ovidiu Tender.
There are rumours that the shadow-name beyond these is, in fact, the jewish billionaire Marc Rich.
"The Independent" (january 2004) was noticin' that Frank Timis' phantom-firm "Balcan Petroleum" was founded in july 2003 by David Garnell, director of the british company "Inktrend Ltd.", founded by Stephen Roman, ex-director of "Gabriel Resources", which was founded by Frank Timis especially/with the purpose to exploit the biggest gold mine from all over Europe - Rosia Montana, Romania.
David Garnell is also economic-director of another canadian company, named "European Goldfields", also founded by Frank Timis as off-shore.
"Deva Gold SRL", located in Certej (Hunedoara, Romania) is owned by "European Goldfields", the company who's got to exploit several gold-rich regions of Transilvania.
("International Goldfields" came as a branch of the australian
company "Carpathians Investment PTY Ltd.", owned by the very same Frank Timis and his sister, Iona Majdik.
2
"International Goldfields" got an exploatation area over 2.500 km , between the cities Deva, Lugoj and Otelul Rosu.
"Esmeralda Ltd.", part of this hydra extended all over Romania is responsable for the echologykal disaster from Baia Mare, right after the scandal involvin' Romania and Hungary its name bein' changed to "Eurogold Ltd." - which controls "Transgold" and "Explorer", another couple of these inter-related companies.)
As hard as it seems to believe, all these names and facts mean almost nothin', comparin' to the real drama...
It's just the surface of the entiredeal, a labyrinth ment to mentain disinformation, a cover-up element - may I say...
Among all these, the former ministry of culture Razvan Theodorescu (also a jewish ethnyk) approved the systematik destruction of the archeologykal artefacts in Rosia Montana.
This info brings us
right in the middle of the "Rosia Montana affair".
Let's get it on !" (D 12 & Eminem - Fight music)
.......
"The fact is that in Rosia Montana an ancient underground, presentin' a few odd qualyties, got discovered. In short time, a french (or, a french-speakin' ) team came in the area and tried to get in. It was very hard, 'cause of the unbreakable "energy shield" of the subterranean. But, "yadda- yadda- yadda" (have you seen that Seinfeld episode ?) they got in, somehow...
And, "blah-blah-blah"..., they tried to remove the hole containment of tha cave in France. Or, it was just a hoax, 'cause in the end all they did was to destroy everythin' within.
Then out of the sudden, durin' 2005, Radu Cinamar revealed the discovery of an underground, estimated to be 55.000 years old (atlantean), somewhere in the Carpathyans.
The hole Cianamar' s version can be found in the book named "Future with a cranium" / "Viitor cu cap de mort". |
Inverness Tickets
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Inverness Tickets
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Inverness Football Club
The Inverness Football Club is the hottest football team in the Scottish highlands. Inverness football tickets are hard to come by as the stadium only holds 7,000 people, but these tickets are well worth the effort. You are better off to get them online as you can expect to pay a lot less than if you try to buy them on the street and they are often sold out at the stadium. People hold onto these items like gold. This football club has been moving up the ranks in the Scottish Premier League since being formed in 1994. Inverness plays a tough game to a packed stadium and the Inverness Football Club is looking very good this season. The most famous player on the Inverness football team is Dennis Wyness who has scored over 100 goals. If you want good Scottish football action, get your Inverness football tickets right here at Worldticketshop.com - Your Ticket to Fun! |
Last Minute Prediction for Post-Poll in Assam
As the counting date is approaching, political leaders, workers and analysts have gone for last minute prediction and speculation on various parties’ performance in the two phases of Assam election in Northeast India. The pertinent question that arises, whether any party can get sufficient seats in the Legislative Assembly to form the government at Dispur. The counting of votes are due on Friday, 13th of 2011. If a single party cannot manage the required number of elected representatives, what are the other options?
Finally who can make a natural and sustainable ally to whom? Who can not or should not go for alliance with whom? All have been continuously discussed in public forum, media column and television talk shows. Assam this time witnessed a peaceful elections where nearly two crore electorates exercised their franchises without any fear and favouritism to any particular party. The overall percentage of voting was recorded as high as 76 percent.
This time no major political alliances were observed in the pre-poll scenario. Parties like Indian National Congress, Bharatiya Janata Party and All India United Democratic Front contested the election without pre-poll allies. Even the ruling ally of the Congress in Assam, Bodoland People’s Front contested all the constituencies in Bodo dominated areas separately. Only the main opposition party Asom Gana Parishad had pre-poll alliances with some ethnic parties like Bodo People’s Progressive Front, Gana Shakti and Autonomous State Demand Committee. Earlier the AGP had managed to unite its break away factions under one leadership.
The AGP leaders are now thinking of inviting the BJP to form an alliance. In fact, senior AGP leaders like CM Patowary and PK Mahanta have urged the political parties to come forward to prevent the Congress from attaining power for consecutive third time in Assam. The State BJP leaders have shown interest in the alliance, though the others like AIUDF and Left parties have put few conditions. Senior BJP leader Vijay Goel, who is in-charge of Assam, made an official statement that they are open to post-poll engagement with the AGP to ‘keep the ruling Congress out of power’ in the State. Mr Goel even claimed that his party would get sufficient seats this time to make deal with the AGP to form the government. He however clarified that the BJP would not go for any alliance with the AIUDF and Left parties.
The same was reverted by the AIUDF leader Aditya Langthasa that his party would not support any alliance with the BJP in its fold. The Congress, which is not confident this time, has opened the door to the minority dominated AIUDF. The party has reiterated its ongoing understanding with the BPF chief Hagrama Mohilary. But at least in one occasion Mr Mohilary hinted that they might think of supporting the AGP-BJP alliance at Dispur (if not the Congress). So both the AIUDF and BPF may get the opportunity to be the kingmaker this time, as no major parties are expecting single majority (64 MLAs) in the intensely contested polls. |
Tuesday, May 24, 2011
UNICEF’s equity-based approach to achieving the Millennium Development Goals aims to reach the poorest and most vulnerable children and families with cost-effective interventions for sustainable progress. Here is one in a series of stories that make the case for equity.
By Tanya Turkovich
POCOATA, Bolivia, 23 May 2011 – It takes money to make money. Just ask Pilar Rueda, 38, a Quechua mother of two from this remote rural town in the Bolivian department of Potosí. She and much of her community have lifted themselves out of extreme poverty through ‘Bancos Comunales’ – Communal Banks – an innovative project developed by UNICEF.
VIDEO: 6 May 2011 - UNICEF correspondent Thomas Nybo reports on a community banking initiative that extends credit and empowers women in Bolivia's rural indigenous communities. Watch in RealPlayer The project extends credit to indigenous people, mainly women, in 13 remote municipalities of northern Potosí. Normally, it is almost impossible for the population in these areas to get loans for small, income-generating ventures. But unlike the microcredit schemes of traditional banks, which charge high interest rates, the Bancos Comunales project offers very low rates and is entirely directed and driven by the community.
The project now comprises an association of some 70 communal banks in Potosí. Besides extending loans, it trains participants in microcredit financing, gender equality, leadership and basic rights.
Increased income and opportunities
“This store just used to have a couple of things,” Ms. Rueda says about the shop she owns and operates with her family. “Now it has so many products and provides us with a good source of income.”
And she has not stopped there. After an initial loan from Bancos Comunales allowed Ms. Rueda to increase the stock and revenue from her store, she purchased and started using an ice cream maker for additional income. She also began knitting and painting textiles to sell in the shop.
“Women can now do business. They don't depend on the men anymore,” notes Ms. Rueda. “So now mothers can buy whatever their children need.” As a result, she adds, “Men are feeling proud of their women.”
Ms. Rueda has always been an industrious worker. Now she has become a community leader and savvy businesswoman. Access to credit and information about women’s and children’s rights has expanded opportunities for her and for her children. Although Ms. Rueda never had the chance for a secondary education, for example, her son is in college and she has enough money to buy the supplies that keep her daughter in school.
Breaking the cycle of poverty
Ms. Rueda’s family and other Bancos Comunales beneficiaries live in South America’s poorest country. Out of Bolivia’s population of 9.1 million, nearly 6 million – half of them children – are in impoverished households.
In rural areas, almost two-thirds of the population is considered extremely poor. They do not have enough money to cover their basic necessities, food and health care, much less education. Moreover, the rural population is primarily indigenous, historically the most disadvantaged group in Bolivia and other countries in the region.
In fact, the profile of an indigenous, impoverished girl living in a rural area is a precise picture of social exclusion and inequality in Bolivia. Progress and prosperity have passed these girls by – and are likely to pass by their children.
Yet schemes such as Bancos Comunales are based on the conviction that when governments and international aid organizations invest in meeting the essential needs of the poor, the intergenerational cycle of poverty can be broken. To that end, the banking initiative serves disenfranchised and socially excluded families who live at least 70 km from the nearest paved road and 175 km from the nearest city, and who survive primarily on farming.
An equity-based approach
UNICEF Bolivia Chief of Policy Claudio Santibanez explains that the initiative is unique in that it focuses on improving child rights through women’s empowerment. In addition, it takes an equity-based approach to human development by targeting the poorest of the poor.
“Unlike other microfinance initiatives, communal banks are created in the most extremely poor communities and thus have a strong equity approach,” says Mr. Santibanez. “They engage with a socially vulnerable population that otherwise would be excluded from financial markets.”
Because local residents own the communal banks, money and capital stay in the community. Combined with training in agricultural and trade techniques, this provides food security and a sustainable economic base even for the poorest families.
At the same time, Mr. Santibanez points out, Bancos Comunales trains women in understanding and advocating for their rights and those of their children. “Providing access to micro-loans jointly with other initiatives that empower communities on protecting their children’s rights is a strong combination,” he says.
How loans are structured
To achieve its aims, the Bancos Comunales project offers loans of up to 3,000 bolivianos (about $425) at an interest rate of 2 per cent. Three-quarters of the interest goes toward increasing the communal bank’s reserves, while the rest goes into a savings account for the borrower. This amount is returned once he or she has finished paying the loan, usually within 12 months.
Borrowers must begin repayments a month after the loan is provided. If they are late, it is the community that pressures neighbours to meet their obligations. Social pressure and reputation are still powerful forces in the rural Andes.
Even though some loan repayments have been delayed, the organizers of the communal banking association report that only a few borrowers have defaulted.
Empowered women
While the project loans money to both women and men, women have – by design – taken an increasingly prominent role. This is especially significant in a culture where women are often not in charge of household decision-making and are not generally the primary earners.
Women involved in Bancos Comunales express a strong commitment to helping their children achieve better lives than they’ve had. To that end, they use the income from their businesses to enhance child health and education.
Loan recipient Vilma Huaype lives with her husband and two children in Jarana, about an hour’s walk from Pocoata. Like Ms. Rueda, she has improved her family’s situation through direct access to financial resources. She has also gained new status in the community as the bank treasurer, and has more say in the household than she did before.
Ms. Huaype’s store, once stocked with meagre supplies, has grown into a thriving business. “I have taken advantage of this opportunity for my family,” she says, “so we do not have to remain poor.” |
Q:
why some of my html content is getting removed after adding some php code?
after adding some PHP code the code below that is getting removed. if I remove the PHP part then it is working fine. even in the source code the below HTML code is not showing
<div class="row data">
<div class="row info">
<div class="datatitle">Education</div>
</div>
<div class="grad-fetch row">
<?php
session_start();
$hostname = "127.0.0.1";
$username = "root";
$db_password = "";
$db_name = "resume";
$conn = mysqli_connect($hostname, $username, $db_password, $db_name);
if(!$conn){
die("connection failed : ".mysqli_connect_error());
}
/* $sql = graduation(degree_status ,college ,start_year ,end_year ,degree ,stream ,performence_scale ,performence_marks)*/
$sql = 'SELECT * FROM graduation ';
$result = mysqli_query($conn, $sql);
if (!$result) {
die("Error: " . $sql . "<br>" . mysqli_error($conn));
}
while ($row=mysqli_fetch_array($result)) {
$deg= $row['degree'];
$str= $row['stream'];
$str_yr= $row['start_year'];
$end_yr= $row['end_year'];
$clg= $row['college'];
$prf_scl= $row['performence_scale'];
$prf_mrk= $row['performence_marks'];
}
?>
</div class="row">
<h5>
<?php
echo $deg;
echo $str;
echo $str_yr;
echo $end_yr;
?>
</h5>
<div>
<?php
echo $clg;
?>
</div>
<div>
<?php
echo $prf_scl;
echo $prf_mrk;
?>
</div>
<div>
<?php
exit;
mysqli_close($conn);
?>
</div>
<div class="row dialouge"><h4>Tell us bit about your education</h4></div>
<div class="col userinfo">
<div class="row discipline" data-toggle="modal" data-target="#graduation-modal" id="grad">Graduation
<i class="fa fa-plus education-fa-plus fa-x" aria-hidden="true"></i>
</div>
<div class="row discipline" data-toggle="modal" data-target="#hs-modal">XII(Higer Secondary)
<i class="fa fa-plus education-fa-plus fa-x" aria-hidden="true"></i>
</div>
<div class="button-container">
<a href="student.php" class="previous">PREVIOUS</a>
</div>
</div>
if I'm not adding the PHP code then the all the contents are showing but after adding the below part is not showing. I don't understand what is wrong here
A:
<?php
exit;
mysqli_close($conn);
?>
You need to remove exit from your code as it will stop the execution right there.
|
Power for Living explores the intersection of faith, culture and relationships
Categories
Authors
My fee is $100 an hour. I have a limited amount of spaces that I reserve for a discount. Contact me further if you have questions.
At this time, I do not take insurance. If you'd like to know more about the pros and cons of mental health insurance, please read the following article: http://www.jamartin.com/documents_Reimbursement.html. You might find it in your best interest not to use your insurance for mental health purposes.
For further help and information, please contact me at 720-201-5030
I included a paragraph below from the article. Pay special attention to point #1.
The conduct of psychotherapy is, under this system, determined by the terms of the contracts binding the providers and the company that manages utilization. Typically, these contracts set providers’ fees and make a number requirements of providers, including the following: (1) Providers are generally required to submit detailed confidential information about the client’s problems, history, current functioning and the course of treatment to these case managers and other employees of these intermediary companies for evaluation and review. (2) They are generally required to abide by the intermediary company’s final decision concerning whether treatment is in fact necessary. (3) They are generally required to refrain from informing clients about alternative treatment options that may contradict the decisions of the intermediary company. (4) They are generally required to absolve the intermediary company of any legal or ethical responsibility in the event that the client believes that he or she has been harmed by failure to obtain adequate treatment. Therapists are at risk for firing, cancellation of their contracts, or even legal action if they fail to deliver contracted psychotherapy services in a consistent and cost-effective way. |
Madrona K-8 School is a school servicing grades PK to 8 and is located in the district of "Seattle Public Schools" in Seattle, WA.
There are a total of 299 students and 22 teachers at Madrona K-8 School, for a student to teacher ratio of 14 to 1.
There are a total of 147 free lunch students and 15 reduced lunch students.
Madrona K-8 School has an average proficiency test score (in mathematics and languages) of 39.5%,
which is 18% lower than the Washington average.
Academics
Students/Teachers
Students
299
Teachers
22.3
Student/Teacher ratio
14:1
Free lunch
147
Reduced lunch
15
Advanced Placement
AP enrollment
n/a
Taking some courses
n/a
Taking some courses (not tests)
n/a
Passing some courses
n/a
Passing no courses
n/a
Advanced placement (AP) is a program that offers high school students the ability to take college level courses and exams.
These programs were created to be at the same level of most first year university courses. If the students were successful in the AP programs, they could potentially receive advanced placement, credit or exemptions when they go on to university.
At Madrona K-8 School, there are a total of n/a students enrolled in advanced placement courses, with n/a taking some courses.
Proficiency in mathematics comparison
Proficiency in languages comparison
Proficiency in mathematics by grade
Grade
Proficiency
All
40-44%
3
40-59%
4
< 50%
5
21-39%
6
21-39%
7
60-79%
8
30-39%
High School
n/a
Proficiency in languages by grade
Grade
Proficiency
All
35-39%
3
40-59%
4
< 50%
5
21-39%
6
60-79%
7
40-59%
8
30-39%
High School
n/a
The proficiency in math and languages tables represent the percentage of students that scored at or above the proficiency level on their standardized state assessment tests. Although these tests are standardized within each state, the tests may vary from state to state. Comparing the results of one state to another may not always be an accurate or fair comparison.
AreaVibes 250 for $2,500 Short Essay Scholarship
At AreaVibes, we believe that education is the key to our children’s future. To show our support and to contribute to the nation’s future generation of students, we are offering educational scholarship awards. |
Emil Szolomajer
Emil Attila Szolomajer (born 24 January 1974) is a Romanian former football goalkeeper. In his career Szolomajer played for teams such as: Baia Mare, CSM Reşiţa or Universitatea Cluj. After retirement he started to work as a goalkeeping coach.
Trivia
In Liga I, Szolomajer played 10 games for FC Baia Mare during the 1994-95 season, one of them as a substitute. In those 10 games, the opponents scored 40 goals against FC Baia Mare.
External links
Category:1974 births
Category:Living people
Category:People from Sighetu Marmației
Category:Romanian footballers
Category:Association football goalkeepers
Category:Liga I players
Category:Liga II players
Category:CS Minaur Baia Mare (football) players
Category:CSM Reșița players
Category:FC Universitatea Cluj players
Category:ACS Sticla Arieșul Turda players
Category:CSM Câmpia Turzii players |
On November 3, 1987 at approximately 8:30 p.m., defendants were stopped for speeding by two New Jersey State Troopers on Route 539 in Plumstead, New Jersey.
*fn1"
At the time, the defendants were traveling in a Volkswagen pickup truck owned and driven by Middleton. As soon as the defendants noticed the flashing lights of the police cruiser behind them, they pulled to the side of the road and stopped. As the Troopers approached the pickup on foot, they both claim to have seen in the bed of the truck at least two cardboard boxes stamped "Supply and Service Division . . . WHSE J2535, Bay 1 Knox Street, Fort Bragg, North Carolina 23307" and containing what appeared to be several new suitcases. How the Troopers were able to observe these boxes is a matter of contentious debate between the parties. Defendants claim that the entire bed of the pickup, which was filled with cardboard shipping boxes, was covered by a securely fastened tarpaulin. Defendant Middleton claims to have seen in his side-view mirror one of the Troopers use his flashlight to lift the tarp and peer underneath. The Troopers, on the other hand, assert that the front driver's-side corner of the bed was exposed, with the boxes in plain view.
*fn2"
Upon request, Middleton provided a valid drivers license and vehicle registration, but when the Troopers -- who were aware that three military installations (none of them Fort Bragg, however) were in the immediate vicinity -- asked defendants about the boxes, they apparently gave evasive and inconsistent answers. In addition, defendants were "extraordinarily nervous," were acting "very suspicious" and defendant Myers, who was sitting in the passenger seat, continually glanced toward the rear of the truck. As a result, the Trooper standing by the passenger side door, ostensibly fearing for his safety and that of his partner, reached back and lifted part of the tarpaulin to ensure that neither a confederate nor a weapon was hidden underneath. It was at this point that a box containing empty pistol holsters was discovered. Defendants were then asked to exit the vehicle, and after being frisked they were questioned about the origins of the holsters and the contents of the rest of the boxes. Defendant Myers claimed that the goods were his and that he had gotten them from a friend. When pressed further, however, neither defendant provided explanations that satisfied the Troopers. One of the Troopers then searched the cab of the truck and found a large pair of bolt-cutters and a second valid drivers license for Middleton from a different state. When defendants could not provide satisfactory explanations for the existence of these items either, they were placed under arrest and charged with obstruction pursuant to N.J. Stat. Ann. § 2C:29-1.
Following the arrest, the tarpaulin was fully removed from the bed of the truck, revealing at least twenty boxes filled with assorted military items. Defendants and their truck were taken to the Fort Dix police barracks where a full inventory search of the truck was conducted. Among the items seized were holsters, assault vests, assault belts and canteens. Defendants were released on bail on the obstruction charge the next day, but the truck and its contents were retained. Upon further investigation the police determined that the military items in the truck had been stolen from the Lakehurst Naval Air Center and it was at this point that the defendants were charged with theft of government property.
The government concedes that the burden is on them to establish the reasonableness of a warrantless search, United States v. Williams, 604 F.2d 1102 (8th Cir. 1979), by a preponderance of the evidence, United States v. Matlock, 415 U.S. 164, 177, 39 L. Ed. 2d 242, 94 S. Ct. 988 (1974). They go on to argue that the initial stop and "unintrusive" questioning were justified under Terry v. Ohio, 392 U.S. 1, 20 L. Ed. 2d 889, 88 S. Ct. 1868 (1968), and from there the information the Troopers gathered "'quickly matured . . . into the requisite probable cause to believe that the automobile contained contraband.'" Government's Brief at 8 (quoting United States v. Rickus, 737 F.2d 360, 366 (3d Cir. 1984)). Once probable cause existed, the government continues, the automobile exception to the warrant requirement established by Carroll v. United States, 267 U.S. 132, 69 L. Ed. 543, 45 S. Ct. 280 (1925), permitted the search of the pickup. While the government's legal argument has merit, it does not mesh with the facts of this case as they developed at the suppression hearing.
First, of course, it is uncontroverted that the initial stop of the truck -- for speeding and for a defective tail light -- was lawful. The issue thus becomes whether it was lawful to effectively "stop" the defendants again, by keeping them on the scene for purposes not related to the traffic infractions.
The stop and detention of a person or of a moving vehicle -- even for a brief period -- is considered a "seizure" within the meaning of the fourth amendment. United States v. Montgomery, 182 U.S. App. D.C. 426, 561 F.2d 875, 878 (D.C. Cir. 1977) (citing United States v. Brignoni-Ponce, 422 U.S. 873, 878-82, 45 L. Ed. 2d 607, 95 S. Ct. 2574 (1975)); cf. Terry v. Ohio, 392 U.S. 1, 16-19, 20 L. Ed. 2d 889, 88 S. Ct. 1868 (1968); Brown v. Texas, 443 U.S. 47, 50, 61 L. Ed. 2d 357, 99 S. Ct. 2637 (1978). While a fourth amendment seizure normally requires a warrant, or at least probable cause, the Supreme Court has held on countless occasions that the stop of a person or vehicle may be accomplished in certain circumstances without a warrant and even without probable cause to believe the person is or has been engaged in criminal activity. As the Court stated in Brown v. Texas :
We have recognized that in some circumstances an officer may detain a suspect briefly for questioning although he does not have "probable cause" to believe that the suspect is involved in criminal activity, as is required for a traditional arrest. United States v. Brignoni-Ponce, [422 U.S.] at 880-881. See Terry v. Ohio, [392 U.S.] at 25-26. However, we have required the officers to have a reasonable suspicion, based on objective facts, that the individual is involved in criminal activity.
Brown v. Texas, 443 U.S. at 51 (emphasis added) (citations omitted). The requisite reasonable suspicion must be objectively gauged. In Brown, for example, the Court held that two men seen walking away from each other in an alley in an area with a high incidence of drug traffic did not objectively present the level of "reasonable suspicion" necessary to allow a stop and brief questioning of one of the men. In United States v. Montgomery, the D.C. Circuit came to the same conclusion, based on the fact that the police had observed the defendant driving through a mostly residential area at about 6:00 p.m. on a Friday evening. A few minutes after their initial sighting, the officers again saw defendant in the same general area, and when they followed him he appeared to be watching them in his rear-view mirror. The court held:
This may have been reason for an officer to become suspicious enough to keep an eye on defendant. But it can hardly be deemed to be an objective indicator of reasonable suspicion of criminal conduct.
561 F.2d at 879.
The government relies heavily on the Third Circuit's decision in United States v. Rickus, 737 F.2d 360 (3d Cir. 1984), to defend the detention of defendants in this case. In Rickus, the police officer observed the defendants' car at 3:30 a.m. driving past the closed stores of a deserted business district at twenty miles below the posted speed limit. The officer then followed the car as it turned into a residential area that had recently been plagued by a dozen unsolved nighttime burglaries. The officer followed the car for several minutes as it continued to travel extremely slowly, at one point stopping momentarily in front of a residence. Finally, the officer stopped the car. The Court, speaking through Judge Hunter, held that "this stop was an entirely proper 'intermediate response' of the type approved in Terry." Id. at 366.
In determining where the instant case falls along this "reasonable suspicion" spectrum, this court will accept the Troopers' version of the facts; specifically that at least two boxes with the apparent military address were in plain view as they approached the truck.
*fn4"
Given the fact that the boxes were stamped with what appeared to be the address of a military base, and given the proximity of three military bases to where defendants were stopped, this court finds that the Troopers had the requisite "reasonable suspicion" to transfer the stop for speeding into a Terry investigative stop. This finding, however, far from ends the inquiry, as the government must demonstrate something more than this "reasonable suspicion" of criminal activity to justify the subsequent search of the truck, a burden it does not meet.
C. The Search
It is clear that once the box containing the pistol holsters was discovered in the bed of the truck, the Troopers had probable cause to believe that the vehicle contained the fruits of a crime and could search the rest of the truck pursuant to the automobile exception to the warrant requirement as developed by the Supreme Court in Carroll v. United States, 267 U.S. 132, 69 L. Ed. 543, 45 S. Ct. 280 (1925). However, this court finds that the Troopers did not have the requisite probable cause required by Carroll before the holsters were recovered and thus could not rely on the automobile exception to search for them. The testimony of the Troopers demonstrates that immediately prior to the lifting of the tarp and the discovery of the holsters, the Troopers knew the following: two boxes with military addresses and containing luggage were in the bed of the truck; other boxes were also apparently in the bed, but covered by a tarp; the defendants were acting "extraordinarily nervous" and were evasive and inconsistent in their answers to questions; and defendant Myers kept glancing towards the rear of the truck. The court finds the following facts to be relevant as well: the defendants were only driving 10 miles per hour over the speed limit;
*fn5"
they stopped as soon as they were signaled to by the police; the driver produced a valid license and registration on request; while the Troopers noted that these defendants seemed more nervous than normal, they also acknowledged that all drivers are nervous when stopped by the police; a private citizen has no obligation to give non-evasive or logically consistent answers to a police officer;
*fn6"
none of the military bases in the area had reported any thefts to the police and the Troopers did not first try to ascertain if any thefts had indeed taken place;
*fn7"
and there are just too many innocent explanations for why the defendants were in possession of two boxes bearing military addresses. In light of the above-enumerated factors, this court finds that the Troopers did not have the requisite probable cause to search beneath the tarpaulin in the back of the truck.
However, the government claims in its brief, and one of the Troopers testified at the hearing, that he feared for his safety and thus lifted the tarp to ensure that a confederate or a weapon was not hidden underneath. This argument, while legally sound, also does not fit the facts of this case.
In Terry v. Ohio, 392 U.S. 1, 20 L. Ed. 2d 889, 88 S. Ct. 1868 (1968), the Supreme Court recognized the need to allow police officers who have made investigatory stops of individuals to protect themselves. The Court held that when the officer has a reasonable belief
that the individual whose suspicious behavior he is investigating at close range is armed and presently dangerous to the officer or to others, it would appear to be clearly unreasonable to deny the officer the power to take necessary measures to determine whether the person is in fact carrying a weapon and to neutralize the threat of physical harm.
392 U.S. at 24. This "frisk" rationale has been extended by the Court to cover individuals seated in a car whom the officer reasonably believes to be armed, see Adams v. Williams, 407 U.S. 143, 32 L. Ed. 2d 612, 92 S. Ct. 1921 (1972), and to those areas in the passenger compartment of an automobile where a weapon could be hidden when the officer reasonably believes that an occupant poses a danger. See Michigan v. Long, 463 U.S. 1032, 77 L. Ed. 2d 1201, 103 S. Ct. 3469 (1982). While this court recognizes the "protective sweep" doctrine expressed in these decisions, it cannot extend it to cover the Troopers' actions in this situation.
First, the operative phrase in all the above cases is "reasonably believes to be armed." There is absolutely no evidence in the record before this court to demonstrate that the Troopers could have had a reasonable belief -- before the holsters were found -- that either of the defendants were armed. Indeed, most of the defendants' actions were more consistent with those of disgruntled motorists than of armed criminals. The court is sympathetic to the dangers confronting police officers as they deal with the unknown, but it is not clear how these defendants posed any more of a danger to the Troopers than any other motorist stopped for a traffic violation. The cases cited above are all distinguishable in that they involved officers who had reliable information that the suspect was armed, see Adams, 407 U.S. 143, 32 L. Ed. 2d 612, 92 S. Ct. 1921, or who had already observed a weapon within the suspect's reach. See Long, 463 U.S. 1032, 77 L. Ed. 2d 1201, 103 S. Ct. 3469.
Second, it seems clear from the record that the Trooper's search of the truck bed for a weapon or a confederate was simply a pretext for a search for evidence of some crime. The testimony of the Troopers themselves reveals that defendants were seated in the truck with one officer standing behind each door, near the front of the truck bed. In addition, one of the Troopers testified that the rear window of the cab was made of solid glass. Therefore, it seems physically impossible to this court that either of the defendants could have reached out the side windows and past the Troopers, both of whom were armed, and into the truck bed for a weapon. If the Troopers were really concerned that either defendant might produce a weapon, the most logical place to search would have been the cab of the truck. This was not done, however, according to the Troopers' own testimony, until the defendants had exited the truck and were sitting by the side of the road. Even more telling is the fact that, once the Trooper did look under the tarp, he only examined one corner of the truck bed, ending his "protective sweep" as soon as the holsters were discovered.
Because it was the discovery of the holsters that led the police to search the cab of the pickup and later to search the entire truck bed, all evidence discovered must be suppressed as the fruit of an illegal search. See Wong Sun v. United States, 371 U.S. 471, 484, 9 L. Ed. 2d 441, 83 S. Ct. 407 (1962).
The court recognizes that its holding means that there are certain cases where the police may have a "reasonable suspicion" of criminal activity that does not rise to the level of probable cause and, thus, they may have to release suspects who, it is later discovered, were carrying the fruits or instrumentalities of a crime. This does not trouble the court however, as such a result is necessary to ensure that some of our more precious freedoms are not trampled upon. In addition, we note that the Troopers could have taken the simple step of releasing the defendants and then following them while they attempted to contact the nearby military bases for information regarding the two boxes they had seen in plain view. No such attempt was made.
D. The Arrest
This court also feels compelled to comment on the legality of the arrest of the defendants for obstruction under N.J. Stat. Ann. § 2C:29-1. The government conceded in its brief that the arrest may not be "technically sustainable" and this court could not agree more. The statute states in pertinent part:
a. A person commits an offense if he purposely obstructs, impairs or perverts the administration of law . . . by means of intimidation, force, violence or physical interference or obstacle, or by means of any independently unlawful act.
N.J. Stat. Ann. § 2C:29-1 (emphasis added). It is clear from the plain language of the statute that it in no way applies to the defendants' actions in this case. Indeed, any statute that did proscribe "inconsistent" and "evasive" answers would run squarely up against the fifth amendment to the United States Constitution.
Curiously, counsel for the government, after reciting the statute to the court, tried to fit the defendants' actions under the category of "obstacle." However, a careful look at the structure of the statute and a quick nod to Strunk and White reveals that the "obstacle" must be "physical," not simply verbal. This court finds, therefore, that defendants' arrest was purely pretextual; effectuated for the sole purpose of seizing their truck and its contents pending further investigation.
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build.xml.data.CRC32=0efc30b9
build.xml.script.CRC32=d1f1ecca
[email protected]
# This file is used by a NetBeans-based IDE to track changes in generated files such as build-impl.xml.
# Do not edit this file. You may delete it but then the IDE will never regenerate such files for you.
nbproject/build-impl.xml.data.CRC32=0efc30b9
nbproject/build-impl.xml.script.CRC32=fe180a9d
nbproject/[email protected]
|
/*
* Copyright (C) 2012 The Guava Authors
*
* 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.
*/
package com.google.common.reflect;
import static com.google.common.base.Preconditions.checkNotNull;
import com.google.common.annotations.Beta;
import com.google.common.collect.ImmutableList;
import com.google.errorprone.annotations.CanIgnoreReturnValue;
import java.lang.annotation.Annotation;
import java.lang.reflect.AccessibleObject;
import java.lang.reflect.AnnotatedType;
import java.lang.reflect.Constructor;
import java.lang.reflect.GenericDeclaration;
import java.lang.reflect.InvocationTargetException;
import java.lang.reflect.Member;
import java.lang.reflect.Method;
import java.lang.reflect.Modifier;
import java.lang.reflect.Type;
import java.lang.reflect.TypeVariable;
import java.util.Arrays;
import org.checkerframework.checker.nullness.qual.Nullable;
/**
* Wrapper around either a {@link Method} or a {@link Constructor}. Convenience API is provided to
* make common reflective operation easier to deal with, such as {@link #isPublic}, {@link
* #getParameters} etc.
*
* <p>In addition to convenience methods, {@link TypeToken#method} and {@link TypeToken#constructor}
* will resolve the type parameters of the method or constructor in the context of the owner type,
* which may be a subtype of the declaring class. For example:
*
* <pre>{@code
* Method getMethod = List.class.getMethod("get", int.class);
* Invokable<List<String>, ?> invokable = new TypeToken<List<String>>() {}.method(getMethod);
* assertEquals(TypeToken.of(String.class), invokable.getReturnType()); // Not Object.class!
* assertEquals(new TypeToken<List<String>>() {}, invokable.getOwnerType());
* }</pre>
*
* @param <T> the type that owns this method or constructor.
* @param <R> the return type of (or supertype thereof) the method or the declaring type of the
* constructor.
* @author Ben Yu
* @since 14.0
*/
@Beta
public abstract class Invokable<T, R> extends Element implements GenericDeclaration {
<M extends AccessibleObject & Member> Invokable(M member) {
super(member);
}
/** Returns {@link Invokable} of {@code method}. */
public static Invokable<?, Object> from(Method method) {
return new MethodInvokable<>(method);
}
/** Returns {@link Invokable} of {@code constructor}. */
public static <T> Invokable<T, T> from(Constructor<T> constructor) {
return new ConstructorInvokable<T>(constructor);
}
/**
* Returns {@code true} if this is an overridable method. Constructors, private, static or final
* methods, or methods declared by final classes are not overridable.
*/
public abstract boolean isOverridable();
/** Returns {@code true} if this was declared to take a variable number of arguments. */
public abstract boolean isVarArgs();
/**
* Invokes with {@code receiver} as 'this' and {@code args} passed to the underlying method and
* returns the return value; or calls the underlying constructor with {@code args} and returns the
* constructed instance.
*
* @throws IllegalAccessException if this {@code Constructor} object enforces Java language access
* control and the underlying method or constructor is inaccessible.
* @throws IllegalArgumentException if the number of actual and formal parameters differ; if an
* unwrapping conversion for primitive arguments fails; or if, after possible unwrapping, a
* parameter value cannot be converted to the corresponding formal parameter type by a method
* invocation conversion.
* @throws InvocationTargetException if the underlying method or constructor throws an exception.
*/
// All subclasses are owned by us and we'll make sure to get the R type right.
@SuppressWarnings("unchecked")
@CanIgnoreReturnValue
public final R invoke(@Nullable T receiver, Object... args)
throws InvocationTargetException, IllegalAccessException {
return (R) invokeInternal(receiver, checkNotNull(args));
}
/** Returns the return type of this {@code Invokable}. */
// All subclasses are owned by us and we'll make sure to get the R type right.
@SuppressWarnings("unchecked")
public final TypeToken<? extends R> getReturnType() {
return (TypeToken<? extends R>) TypeToken.of(getGenericReturnType());
}
/**
* Returns all declared parameters of this {@code Invokable}. Note that if this is a constructor
* of a non-static inner class, unlike {@link Constructor#getParameterTypes}, the hidden {@code
* this} parameter of the enclosing class is excluded from the returned parameters.
*/
public final ImmutableList<Parameter> getParameters() {
Type[] parameterTypes = getGenericParameterTypes();
Annotation[][] annotations = getParameterAnnotations();
AnnotatedType[] annotatedTypes = getAnnotatedParameterTypes();
ImmutableList.Builder<Parameter> builder = ImmutableList.builder();
for (int i = 0; i < parameterTypes.length; i++) {
builder.add(
new Parameter(
this, i, TypeToken.of(parameterTypes[i]), annotations[i], annotatedTypes[i]));
}
return builder.build();
}
/** Returns all declared exception types of this {@code Invokable}. */
public final ImmutableList<TypeToken<? extends Throwable>> getExceptionTypes() {
ImmutableList.Builder<TypeToken<? extends Throwable>> builder = ImmutableList.builder();
for (Type type : getGenericExceptionTypes()) {
// getGenericExceptionTypes() will never return a type that's not exception
@SuppressWarnings("unchecked")
TypeToken<? extends Throwable> exceptionType =
(TypeToken<? extends Throwable>) TypeToken.of(type);
builder.add(exceptionType);
}
return builder.build();
}
/**
* Explicitly specifies the return type of this {@code Invokable}. For example:
*
* <pre>{@code
* Method factoryMethod = Person.class.getMethod("create");
* Invokable<?, Person> factory = Invokable.of(getNameMethod).returning(Person.class);
* }</pre>
*/
public final <R1 extends R> Invokable<T, R1> returning(Class<R1> returnType) {
return returning(TypeToken.of(returnType));
}
/** Explicitly specifies the return type of this {@code Invokable}. */
public final <R1 extends R> Invokable<T, R1> returning(TypeToken<R1> returnType) {
if (!returnType.isSupertypeOf(getReturnType())) {
throw new IllegalArgumentException(
"Invokable is known to return " + getReturnType() + ", not " + returnType);
}
@SuppressWarnings("unchecked") // guarded by previous check
Invokable<T, R1> specialized = (Invokable<T, R1>) this;
return specialized;
}
@SuppressWarnings("unchecked") // The declaring class is T's raw class, or one of its supertypes.
@Override
public final Class<? super T> getDeclaringClass() {
return (Class<? super T>) super.getDeclaringClass();
}
/** Returns the type of {@code T}. */
// Overridden in TypeToken#method() and TypeToken#constructor()
@SuppressWarnings("unchecked") // The declaring class is T.
@Override
public TypeToken<T> getOwnerType() {
return (TypeToken<T>) TypeToken.of(getDeclaringClass());
}
abstract Object invokeInternal(@Nullable Object receiver, Object[] args)
throws InvocationTargetException, IllegalAccessException;
abstract Type[] getGenericParameterTypes();
abstract AnnotatedType[] getAnnotatedParameterTypes();
/** This should never return a type that's not a subtype of Throwable. */
abstract Type[] getGenericExceptionTypes();
abstract Annotation[][] getParameterAnnotations();
abstract Type getGenericReturnType();
public abstract AnnotatedType getAnnotatedReturnType();
static class MethodInvokable<T> extends Invokable<T, Object> {
final Method method;
MethodInvokable(Method method) {
super(method);
this.method = method;
}
@Override
final Object invokeInternal(@Nullable Object receiver, Object[] args)
throws InvocationTargetException, IllegalAccessException {
return method.invoke(receiver, args);
}
@Override
Type getGenericReturnType() {
return method.getGenericReturnType();
}
@Override
Type[] getGenericParameterTypes() {
return method.getGenericParameterTypes();
}
@Override
AnnotatedType[] getAnnotatedParameterTypes() {
return method.getAnnotatedParameterTypes();
}
@Override
public AnnotatedType getAnnotatedReturnType() {
return method.getAnnotatedReturnType();
}
@Override
Type[] getGenericExceptionTypes() {
return method.getGenericExceptionTypes();
}
@Override
final Annotation[][] getParameterAnnotations() {
return method.getParameterAnnotations();
}
@Override
public final TypeVariable<?>[] getTypeParameters() {
return method.getTypeParameters();
}
@Override
public final boolean isOverridable() {
return !(isFinal()
|| isPrivate()
|| isStatic()
|| Modifier.isFinal(getDeclaringClass().getModifiers()));
}
@Override
public final boolean isVarArgs() {
return method.isVarArgs();
}
}
static class ConstructorInvokable<T> extends Invokable<T, T> {
final Constructor<?> constructor;
ConstructorInvokable(Constructor<?> constructor) {
super(constructor);
this.constructor = constructor;
}
@Override
final Object invokeInternal(@Nullable Object receiver, Object[] args)
throws InvocationTargetException, IllegalAccessException {
try {
return constructor.newInstance(args);
} catch (InstantiationException e) {
throw new RuntimeException(constructor + " failed.", e);
}
}
/**
* If the class is parameterized, such as {@link java.util.ArrayList ArrayList}, this returns
* {@code ArrayList<E>}.
*/
@Override
Type getGenericReturnType() {
Class<?> declaringClass = getDeclaringClass();
TypeVariable<?>[] typeParams = declaringClass.getTypeParameters();
if (typeParams.length > 0) {
return Types.newParameterizedType(declaringClass, typeParams);
} else {
return declaringClass;
}
}
@Override
Type[] getGenericParameterTypes() {
Type[] types = constructor.getGenericParameterTypes();
if (types.length > 0 && mayNeedHiddenThis()) {
Class<?>[] rawParamTypes = constructor.getParameterTypes();
if (types.length == rawParamTypes.length
&& rawParamTypes[0] == getDeclaringClass().getEnclosingClass()) {
// first parameter is the hidden 'this'
return Arrays.copyOfRange(types, 1, types.length);
}
}
return types;
}
@Override
AnnotatedType[] getAnnotatedParameterTypes() {
return constructor.getAnnotatedParameterTypes();
}
@Override
public AnnotatedType getAnnotatedReturnType() {
return constructor.getAnnotatedReturnType();
}
@Override
Type[] getGenericExceptionTypes() {
return constructor.getGenericExceptionTypes();
}
@Override
final Annotation[][] getParameterAnnotations() {
return constructor.getParameterAnnotations();
}
/**
* {@inheritDoc}
*
* <p>{@code [<E>]} will be returned for ArrayList's constructor. When both the class and the
* constructor have type parameters, the class parameters are prepended before those of the
* constructor's. This is an arbitrary rule since no existing language spec mandates one way or
* the other. From the declaration syntax, the class type parameter appears first, but the call
* syntax may show up in opposite order such as {@code new <A>Foo<B>()}.
*/
@Override
public final TypeVariable<?>[] getTypeParameters() {
TypeVariable<?>[] declaredByClass = getDeclaringClass().getTypeParameters();
TypeVariable<?>[] declaredByConstructor = constructor.getTypeParameters();
TypeVariable<?>[] result =
new TypeVariable<?>[declaredByClass.length + declaredByConstructor.length];
System.arraycopy(declaredByClass, 0, result, 0, declaredByClass.length);
System.arraycopy(
declaredByConstructor, 0, result, declaredByClass.length, declaredByConstructor.length);
return result;
}
@Override
public final boolean isOverridable() {
return false;
}
@Override
public final boolean isVarArgs() {
return constructor.isVarArgs();
}
private boolean mayNeedHiddenThis() {
Class<?> declaringClass = constructor.getDeclaringClass();
if (declaringClass.getEnclosingConstructor() != null) {
// Enclosed in a constructor, needs hidden this
return true;
}
Method enclosingMethod = declaringClass.getEnclosingMethod();
if (enclosingMethod != null) {
// Enclosed in a method, if it's not static, must need hidden this.
return !Modifier.isStatic(enclosingMethod.getModifiers());
} else {
// Strictly, this doesn't necessarily indicate a hidden 'this' in the case of
// static initializer. But there seems no way to tell in that case. :(
// This may cause issues when an anonymous class is created inside a static initializer,
// and the class's constructor's first parameter happens to be the enclosing class.
// In such case, we may mistakenly think that the class is within a non-static context
// and the first parameter is the hidden 'this'.
return declaringClass.getEnclosingClass() != null
&& !Modifier.isStatic(declaringClass.getModifiers());
}
}
}
}
|
The assault came a day after Bahrain declared a three-month state of emergency and handed wide powers to the armed forces, as it moved to quell weeks of demonstrations by mainly Shiite protesters a day after the arrival... |
Background
==========
In the setting of acute myocardial infarction (AMI), the aim of reperfusion and pharmacologic therapies is to salvage areas of ischemic, but reversibly injured myocardium within the area-at-risk (AAR). The current histopathologic reference standard requires administration of microspheres, destructive sectioning of the heart, the use of tissue stains, and digital photography to delineate the AAR, infarction, and to calculate salvage. We evaluated a newly developed CMR protocol that potentially provides non-destructive, high-resolution, ex-vivo assessment of the AAR simultaneous with infarction.
Methods
=======
Four canines underwent 50-minute occlusion of the LAD coronary followed by reperfusion. Imaging was performed 5-days post-AMI. The main goal of the protocol was to create 3 distinct myocardial gadolinium concentrations delineating viable AAR, infarcted AAR and remote myocardium. This was achieved by (1) injecting gadolinium (0.3-0.4mmol/kg) in-vivo to differentially accumulate in infarction, (2) providing a wait time to allow washout of gadolinium from viable myocardium, (3) injecting another dose of gadolinium prior to sacrifice using the same process as if administering microspheres for determining the AAR by pathology. For validation purposes, microspheres (2-8μm, ThermoScientific) were mixed with gadolinium in this step. Finally, (4) the heart was extracted and ex-vivo 3-dimensional-delayed-enhancement-CMR imaging was performed. The heart was sectioned into short-axis slices and photographed under UV-light to delineate the AAR (absence of microspheres) and after staining with triphenyltetrazoliumchloride to delineate infarction. Histopathology and ex-vivo-CMR images were analyzed by 2 blinded observers.
Results
=======
Figure [1](#F1){ref-type="fig"} shows histopathology of a subendocardial-AMI with transmural AAR. On the matched delayed-enhancement-CMR image, 3 distinct image intensities are present: (1) myocardium with lowest signal matches location and shape of the viable AAR by microspheres, (2) region with highest signal matches infarction on pathology and (3) remote zone with intermediate signal.
{#F1}
On an animal basis, ex-vivo-CMR AAR was similar to that by microspheres (33%±7 vs. 35%±6 respectively, p=0.4). On a slice basis (n=27), there was a strong linear correlation between the ex-vivo-CMR and microsphere-defined AAR (r=0.98, slope=0.96±0.04, p\<00001). Similarly, CMR infarct size matched that by triphenyltetrazoliumchloride (r=0.97, p\<0.0001). Calculated CMR salvage was also highly correlated with that of histopathology (r=0.92, p\<0.0001).
Conclusions
===========
We developed a new CMR protocol that provides high-resolution, ex-vivo images of the AAR simultaneous with infarction in the same 3-dimensional dataset. This can serve as an alternative to histopathology as a truth standard measurement of the AAR and salvage that is non-destructive, allows for multiplanar reconstruction and is automatically registered with the spatial map of infarction.
Funding
=======
Funded in part by 5R01HL064726-07.
|
Q:
Repository or DAO: read data from multiple tables
We have a class in which we have methods:
find: select + multiple joins in order to filter data
add: insert in multiple table
update: update in multiple table
delete: delete in multiple table
check: multiple select + multiple joins in order to check something
Is it a Repository or a DAO?
A:
TL;DR;
This looks more like Repository to me; personally.
There is a good part of controversy between Repository and DAO among purists. Many developers use terms DAO and Repository interchangeably. I personally do not put myself deep in that debate. I prefer to focus on my application needs instead.
Following is very rough description of some of the patterns used in Data Access Layer:
Unit Of Work:
Handle database connection and transactions.
Additionally handle cache, batch queries, tracking etc.
Please refer this answer.
Repository:
May use UnitOfWork; not always.
Not per table, it is per aggregate root.
Returns Domain Object; NOT Object State (Entity/POCO).
Please refer this answer. Also, this other answer for few more terms.
DAO (Data Access Objects):
Tightly bound to database instead of Business Logic.
Mostly 1:1 mapping with tables.
Each action is transaction.
Returns Object State (Entity/POCO).
CQRS (Command Query Responsibility Segregation):
Use a different model to write (INSERT, UPDATE, DELETE) data than the model you use to read (SELECT) data.
Write operations are covered under Command.
Read operations are covered under Query.
Each layer can be optimized independently for specific needs.
Query Object:
Accept queries as an object in parameter of method.
Data Mapper:
Map POCO/Entity classes with database row and vice versa.
ORMs (Object Relational Mappers) are based on this pattern.
Active Record:
Properties and Methods related to instance are in same class.
Mapping happens in same class.
Acts on single record.
|
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