World Briefing | Africa: South Africa’s President Gives a Biting Critique of Pets





President Jacob Zuma, left, said in a speech that the idea of having a pet was part of “white culture” and that people should focus on family welfare, the newspaper The Star reported Thursday. The president’s office sought to clarify the remarks, saying that he was encouraging “the previously oppressed African majority” to uphold its own culture. It also suggested the way in which the comments were reported, rather than the comments themselves, was divisive.




During his speech on Wednesday to a crowd in KwaZulu-Natal, Mr. Zuma’s home province, the president said that people who loved dogs more than people had a “lack of humanity” and that some people were trying in vain to “emulate whiteness,” The Star reported. In a statement, the South African presidency said that Mr. Zuma was trying to “decolonize the African mind post-liberation” and enable people to take pride in their heritage and not feel pressure to adopt customs of minority cultures. Animals can be cared for, was the message, but not at the expense of people.


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Stomach bug knocks Nadal from Australian Open


MADRID (AP) — Rafael Nadal will miss the Australian Open because of a stomach virus, further delaying his comeback after being sidelined since June.


The Spaniard also will skip the preceding Qatar Open. The Australian Open, the year's first Grand Slam tournament, begins Jan. 14. The virus kept Nadal from making his return at Abu Dhabi this week.


Nadal said Friday his withdrawals had nothing to do with the tendinitis in his left knee, which forced him to take a break last summer following his second-round loss at Wimbledon to then 100th-ranked Lukas Rosol. Nadal also missed the London Olympics.


"My knee is much better and the rehabilitation process has gone well as predicted by the doctors," Nadal said in a statement. "But this virus didn't allow me to practice this past week, and therefore I am sorry to announce that I will not play in Doha and the Australian Open."


The former No. 1 player hopes to return at Acapulco, Mexico, starting Feb. 27. However, he did not rule out playing an earlier tournament if his recovery went well enough.


"I always said that my return to competition will be when I am in the right conditions to play," he said. "And after all this time away from the courts I'd rather not accelerate the comeback and prefer to do things well."


Nadal, ranked No. 4, won the Australian Open in 2009. Last year, he lost to top-ranked Novak Djokovic in a title match that lasted 5 hours, 53 minutes, the longest recorded Grand Slam final.


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Well: Spinach Recipes for Health

Spinach goes well with all kinds of foods. It’s also a green that is easy to find year-round. As Martha Rose Shulman writes in this week’s Recipes for Health:

Spinach has remained a part of my holiday ritual. I love the convenience of bagged spinach, but I prefer the richness of the lush bunches I get at the farmers’ market. I don’t mind stemming and washing it, but if you are pressed for time the bagged spinach is a godsend, especially if you live in a cold climate and don’t have access to farmers’ market spinach in December.

Below are five new ways to add spinach to your meal. And for more spinach recipes, see “Making Spinach the Star of the Meal.”


Spinach and Millet Timbale With Tomato Sauce
A timbale is a molded custard, somewhat similar to a quiche without a crust.


Garlic Soup With Spinach
A quick and easy soup that is a great way to use any leftover turkey stock from Thanksgiving.


Penne With Mushroom Ragout and Spinach
This is a delicious meal no matter what variety of mushrooms you have on hand.


Spinach Gnocchi
A considerably lighter version of the classic gnocchi made with spinach and ricotta.


Spinach, Sardine and Rice Gratin
This classic Provençal gratin is a good way to work fish that is high in omega-3s into your diet.

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Amid Fiscal Stalemate, How to Handle Tax Rate Uncertainty



So we’re left with no idea how much we’ll be paying in federal income taxes in 2013, and a wide range of possibilities for taxes on investments and estates and tax deductions for mortgage interest and charitable contributions. Plenty of people will spend the next several days feeling helpless, with one eye on the stock market and the other on Washington.


For all the uncertainty, though, there are a few things we do know about how things will change next year. For example, new taxes, some of which will help pay for Medicare, will affect a few million affluent households.


We also know that in all likelihood, whatever happens in Washington in the coming days or weeks won’t come close to solving the problem that tends to clear the room when you say it aloud: We are not collecting enough money to pay for the promises we’ve made to one another. It isn’t just Medicare, either. Many states have steadfastly refused to set aside the trillions of dollars they will need to cover benefits for public workers once they retire.


As for what you should do about all of this, the answer, for now, is probably nothing. In the short term, stock prices may decline and the economy may get the hiccups, but it’s foolish for amateurs to try to alter their investment portfolios to take advantage of the situation. Leave that to the hedge funds, and watch how many of them get it wrong.


In the long term, however, prepare to make the kind of attitude adjustment that can take a while to embrace. A decade or two from now, most of us will probably be paying more in taxes or getting fewer services from the government than we do now. Once that happens, you’ll need to earn more, save more, live on less or take better advantage of legal tax avoidance strategies.


In fact, you may want to try to do all of these things in the next couple of years, just to see which ones you can accomplish with the least amount of pain.


Here is what we do know will happen in 2013. First, there is a new tax of 0.9 percent on wages, other compensation and self-employment income above $200,000, if you’re single, or $250,000, if you’re married and filing your taxes jointly. This is on top of the existing Medicare tax.


Second, there is a new tax of 3.8 percent on investment earnings, including interest, dividends and capital gains, in addition to whatever the capital gains tax ends up being. It applies to single people with modified adjusted gross income of $200,000, or $250,000 for married couples filing jointly.


There is still some time to maneuver around the second tax. If you have winning investments you were planning to sell soon anyway, say for a down payment on a house, you might as well do it by Monday. That way, you can avoid the new tax if you’re certain you’ll be in the qualifying income category next year.


A few other changes: For now, you can generally take a tax deduction only for unreimbursed medical expenses that exceed 7.5 percent of your adjusted gross income. That floor will rise to 10 percent next year, except for people 65 and over, who won’t be subject to it until 2017.


Also, if you save money in a flexible spending account for health care expenses, 2013 will bring a $2,500 cap on what you can set aside each year while avoiding income taxes. Many people routinely saved $5,000 in the past.


Sometime in the next few weeks, we’ll presumably learn more about the new tax rates on income, capital gains, dividends and estates. A solution may come in stages, with a temporary patch now and the promise of a longer-term deal later.


But this is only the beginning, and if you want to read the Stephen King version of our collective fiscal story, there are a few sources to consult. You could start with the radical centrists at Third Way, a research group, who are the best splashers of cold water that I’ve read on the topic of the federal budget. They present some truly scary data while attempting to persuade Democrats to accept cuts to Medicare and other programs.


In 2010, for instance, 11,712 people turned 25 each day, while just 6,670 turned 65. By 2030, 12,499 people will be turning 25 each day, but the number turning 65 will jump to 10,948. The 65-year-olds in 2030 will probably live longer than the people who turned 65 in 2010, and keeping them alive could cost a lot more.


The Pew Center on the States, using the states’ own actuarial data, estimates that there is a $1.38 trillion dollar gap between what governments have set aside to pay for public employees’ pensions and retiree health care costs and their actual obligations. Robert Novy-Marx, an assistant professor at the University of Rochester’s Simon Graduate School of Business, and Joshua D. Rauh, a professor at the Stanford Graduate School of Business, believe the shortfall in pension financing alone is actually $3 trillion to $4 trillion.


If states were to try to fill the gap solely by raising taxes, Mr. Novy-Marx and Mr. Rauh estimate that the cost per household in 2011 would have been $2,250 in New York, $2,000 in New Jersey and $1,994 in California — and we’d need to pay that amount every year for 30 years, with adjustments for inflation. Happy New Year!


These numbers boggle the mind, which is why you’re not seeing them in the newsletters that state legislators send to your home. Instead, lawmakers are trying to change the benefits promised to public employees. But even minor changes have led to lawsuits that could take a decade to resolve. By then, the obligations will probably have grown much larger.


Read enough of these reality checks, and a hazy sort of reckoning starts to take shape. It’s not clear how high taxes will go or how many services — from retiree health care to garbage removal — we may someday need to pay more for, or cover ourselves. But it’s going to cost you more money one way or the other, unless you’re in a truly low tax bracket.


That brings us to those legal tax avoidance maneuvers, which often benefit people who can save. Flexible spending accounts for medical costs will still save you hundreds of dollars in taxes each year, even with a $2,500 cap. A health savings account, the kind that pairs up with a high-deductible health insurance policy, can grow into a sizable pile if you save the money and use it in retirement instead of to pay out-of-pocket medical expenses now. And the fact that the affluent can still avoid capital gains taxes, and get an income tax break in many states, on hundreds of thousands of dollars of college savings via 529 plans is a minor miracle.


There is also the Roth individual retirement account, where even the low-six-figure set can put away money on which they’ve already paid income taxes, leave it there for decades in stocks and bonds, and pull it out without paying a dime of capital gains or other taxes.


That’s the story — for now, at least. In 30 or 40 years, if things are really grim, might the federal government try to tax withdrawals from Roth accounts with enormous balances? As we’re learning now, most great tax deals, like the mortgage interest deduction for beach houses and the tax-free health insurance benefits that many of us get from our employers, may not last forever.


We don’t have much control over what will happen in Washington or our state capitals next year, or 10 years from now. But most of us can probably find ways to earn a little more, save a little extra or spend a little less. Pick just one of those options, make it your New Year’s resolution and see if it helps you feel more in control of your financial destiny by this time next year.


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Temple Run was downloaded more than 2.5 million times on Christmas Day









Title Post: Temple Run was downloaded more than 2.5 million times on Christmas Day
Rating:
100%

based on 99998 ratings.
5 user reviews.
Author: Fluser SeoLink
Thanks for visiting the blog, If any criticism and suggestions please leave a comment




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McElroy has concussion, Sanchez to start for Jets


FLORHAM PARK, N.J. (AP) — Greg McElroy has a concussion and will be replaced by Mark Sanchez as the New York Jets' starting quarterback in the season finale at Buffalo on Sunday.


Coach Rex Ryan says Thursday that McElroy, preparing to make his second NFL start in place of the benched Sanchez, was lifting weights and had headaches. He went to the team's training staff and then revealed he was suffering concussion-like symptoms after being sacked 11 times in the Jets' 27-17 loss to San Diego last Sunday.


Ryan says he chose to start Sanchez over Tim Tebow because the team has just two practices and a walkthrough to prepare before the game and he feels "more comfortable" with Sanchez. Sanchez was benched after turning the ball over five times at Tennessee on Dec. 17.


___


Online: http://pro32.ap.org/poll and http://twitter.com/AP_NFL


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New York’s Mental Health System Thrashed by Services Lost to Storm


Marcus Yam for The New York Times


Dr. Richard Rosenthal, physician in chief of behavioral services for Continuum hospitals, at St. Luke’s-Roosevelt Hospital Center.







When a young woman in the grip of paranoid delusions threatened a neighbor with a meat cleaver one Saturday last month, the police took her by ambulance to the nearest psychiatric emergency room. Or rather, they took her to Beth Israel Medical Center, the only comprehensive psychiatric E.R. functioning in Lower Manhattan since Hurricane Sandy shrank and strained New York’s mental health resources.




The case was one of 9,548 “emotionally disturbed person” calls that the Police Department answered in November, and one of the 2,848 that resulted in transportation to a hospital, a small increase over a year earlier.


But the woman was discharged within hours, to the shock of the mental health professionals who had called the police. It took four more days, and strong protests from her psychiatrist and caseworkers, to get her admitted for two weeks of inpatient treatment, said Tony Lee, who works for Community Access, a nonprofit agency that provides supportive housing to people with mental illness, managing the Lower East Side apartment building where she lives.


Psychiatric hospital admission is always a judgment call. But in the city, according to hospital records and interviews with psychiatrists and veteran advocates of community care, the odds of securing mental health treatment in a crisis have worsened significantly since the hurricane. The storm’s surge knocked out several of the city’s largest psychiatric hospitals, disrupted outpatient services and flooded scores of coastal nursing homes and “adult homes” where many mentally ill people had found housing of last resort.


One of the most affected hospitals, Beth Israel, recorded a 69 percent spike in psychiatric emergency room cases last month, with its inpatient slots overflowing. Instead of admitting more than one out of three such cases, as it did in November 2011, it admitted only one out of four of the 691 emergency arrivals this November, records show. Capacity was so overtaxed that ambulances had to be diverted to other hospitals 15 times in the month, almost double the rate last year, in periods typically lasting for eight hours, officials said.


Dr. Richard Rosenthal, physician in chief of behavioral services for Continuum Health Partners, Beth Israel’s parent organization, said he was proud of how much Continuum’s hospitals had done to handle psychiatric overflow since storm damage shuttered Bellevue Hospital Center, the city’s flagship public hospital; NYU Langone Medical Center; and the Veterans Affairs Hospital. But these days, he said, as he walks on Amsterdam Avenue between Continuum’s Roosevelt hospital on West 59th Street and its St. Luke’s hospital on West 114th Street, he notices more mentally ill people in the streets than he has seen in years.


“When you have the most vulnerable folks, all you need is one chink in the system and you lose them,” Dr. Rosenthal said. “Whether they lost their housing, or the outpatient services they usually go to were closed and they were lost to follow-up, they have become disconnected, with predictable results.”


Similar patterns are playing out in Brooklyn, where Maimonides Medical Center has been overwhelmed with mental health emergencies from the Coney Island vicinity since Coney Island Hospital, one of the city’s largest acute care psychiatric hospitals, suspended operations, hospital officials said.


“Triage has reached a different level: You have to get sicker to get in,” said Dr. Andrew Kolodny, the chairman of psychiatry at Maimonides, citing a 56 percent increase in psychiatric emergency room visits there from Oct. 26 to Dec. 7, compared with the same period last year, and a 24 percent rise in admissions. The increase in admissions was possible only with emergency permission from the state to exceed licensed limits.


“Not only is there decreased capacity, because Bellevue and Coney Island are off line,” Dr. Kolodny added, “but there’s increased demand because the storm or the loss of their residence has been a stressor for mental illness.”


The storm battered a mental health system that still relies heavily on private nursing homes and substandard adult homes to house people with mental illness. Such institutions have a sordid history of neglect and exploitation, and the courts have repeatedly found that their overuse by the state isolated thousands of people in violation of the Americans With Disabilities Act.


Plans are under way to increase supportive housing — dwellings where mentally ill people can live relatively independently, with support services. But even before Hurricane Sandy, the expansion fell far short of demand.


The storm underscored the fragility of the system. Many disabled evacuees who were sent first to makeshift school shelters lost access to the psychiatric medications that kept their symptoms at bay, Dr. Kolodny said. Even those lucky enough to have the drugs they need are at greater risk of relapse as they experience crowded living conditions. “If they’re now sleeping in a gym with 100 people, that can tip them over the edge and start making them really paranoid,” he said.


On Staten Island, where the chief of psychiatry at Richmond University Medical Center says psychiatric resources have been stretched to the limit, clergy members report that mentally ill people transferred to a large adult home in New Brighton from one that was washed away in Far Rockaway, Queens, are now showing up at church rectories, begging for socks and underwear.


“It’s heartbreaking, because they just found us by chance,” said Margaret Moschetto, a missionary at the Church of Assumption-St. Paul in New Brighton. “They were just walking around the neighborhood. They really didn’t know where they were.”


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As Fiscal Deadline Looms, Path to Deal Remains Unclear


Alex Wong/Getty Images


House Republican leaders called on the Senate to act on fiscal legislation, which focused new attention on Senator Mitch McConnell, right.







WASHINGTON — With just five days left to make a deal, President Obama and members of the Senate were set to return to Washington on Thursday with no clear path out of their fiscal morass even as the Treasury Department warned that the government will soon be unable to pay its bills unless Congress acts.




Treasury Secretary Timothy F. Geithner, adding to the building tension over how to handle a year-end pileup of threatened tax increases and spending cuts, formally notified Congress on Wednesday that the government would hit its statutory borrowing limit on Monday, raising anew the threat of a federal default as the two parties remained in a standoff.


Mr. Geithner wrote that he would take “extraordinary measures” to keep the government afloat but said that with so much uncertainty over the shape of the tax code and future government spending he did not know how long the Treasury could shuffle accounts before the government could no longer pay its creditors.


For months, President Obama, members of Congress of both parties and top economists have warned that the nation’s fragile economy could be swept back into recession if the two parties did not come to a post-election compromise on January’s combination of tax increases and across-the-board spending cuts.


Yet with days left before the fiscal punch lands, both sides are exhibiting little sense of urgency, and new public statements Wednesday appeared to be designed more to ensure the other side is blamed rather than to foster progress toward a deal.


After a high-level telephone conference call, House Republican leaders called on the Senate to act but opened the door to bringing to the House floor any last-minute legislation the Senate could produce.


“The House will take this action on whatever the Senate can pass, but the Senate first must act,” said the statement issued on behalf of Speaker John A. Boehner and his three top lieutenants.


But Senator Harry Reid, the majority leader, instead called on House Republicans to pass an existing Senate measure that would prevent tax increases on household income up to $250,000. “The Senate has already rejected House Republicans’ Tea Party bills, and no further legislation can move through the Senate until Republicans drop their knee-jerk obstruction,” he said in a statement.


Senators will return to the Capitol on Thursday evening with nothing yet to consider. The series of votes waiting for them are unrelated to the fiscal deadline. The House will be gaveled into session at 2 p.m., but since Mr. Boehner has not called the members back to Washington, it will most likely be gaveled back into recess shortly thereafter.


The shift to the Senate has focused new attention on Senator Mitch McConnell of Kentucky, the Republican leader and a deal-making veteran. Democrats say they need assurances from Mr. McConnell that he will not use procedural tactics to delay any potential bill for an interim solution to avert the fiscal crisis.


But Don Stewart, a spokesman for Mr. McConnell, said no one from the White House or from Mr. Reid’s office has reached out to begin negotiations. Democrats say that Mr. McConnell knows full well what they are proposing: the same Senate bill that passed in July extending all the expiring Bush-era income tax cuts on incomes below $250,000, setting the tax rate on dividends and capital gains at 20 percent, and stopping the alternative minimum tax from rising to hit more middle class taxpayers. Onto that, Democrats would like to add an extension of expiring unemployment benefits and a delay in across-the-board spending cuts while negotiations on a broader deficit reduction plan slips into next year.


Democrats now suggest that Republicans are content to wait until after the January deadline. On Jan. 3, Mr. Boehner is likely to be re-elected speaker for the 113th Congress. After that roll call, he may feel less pressure from his right flank against a deal.


For its part, the Senate may simply be out of time. Without unanimous agreement, Mr. Reid would have to take procedural steps to begin considering a bill. He could then be forced to press for another vote to cut off debate before final passage. If forced to jump through those hoops, the 112th Congress could expire before final votes could be cast.


“I think there’s some chance that we get a deal done in the early weeks of January, which technically means you’re going over the cliff,” Representative Jim Himes, Democrat of Connecticut, said on CNBC on Wednesday.


Lawmakers from both parties say Mr. McConnell could be the key to a resolution. He has played the role of adjudicator for Congressional Republicans before, during last year’s fight over a payroll tax extension and the battle between Democrats and Republicans over how, or if, to pay for an emergency disaster financing bill.


With days to spare, Mr. McConnell must decide whether to allow on the Senate floor the Democrats’ bill to extend expiring tax cuts. If passed without a filibuster, that legislation could force the House speaker’s hand and quiet his raucous Republican conference. Or Mr. McConnell, who is up for re-election in 2014 and would like to avoid a primary fight, could stand back quietly and hope that Mr. Boehner and Mr. Obama somehow manage to put together a deal that saves him the trouble.


If Mr. McConnell cannot come to the rescue, there is another hope: Starbucks. Howard Schultz, the company’s chief executive officer, asked baristas who work in Washington-area Starbucks to scrawl “Come Together” on coffee cups for the rest of the week to generate enthusiasm for a compromise.


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Syrian General Defects in a Public Broadcast


Aref Heretani/Reuters.


Mannequins were set up to confuse snipers loyal to Syrian President Bashar al-Assad in the old city of Aleppo on Sunday.







Syria’s embattled leadership suffered a new setback on Wednesday with the publicly broadcast defection of its military police chief, the highest-ranking officer to abandon President Bashar al-Assad since the uprising against him began nearly two years ago.




The defector, Maj. Gen. Abdul Azia Jassem al-Shallal, announced his move in a video broadcast by Al Arabiya, saying that he had taken the step because of what he called the Syrian military’s deviation from “its fundamental mission to protect the nation and transformation into gangs of killing and destruction.”


Al Arabiya, a Saudi-owned pan-Arab broadcaster heavily critical of the Syrian government, said General Shallal had made the video on Tuesday somewhere on the Turkish-Syrian border, implying that he was now inside Turkey, where other Syrian military defectors have sought refuge in the conflict. Many have regrouped there to join the Free Syrian Army, the main insurgent force fighting Mr. Assad.


Reading from a prepared statement while sitting at a desk, dressed in a camouflage uniform with red epaulets, the general did not specify in his message when he had decided to defect but said that he had been “waiting for the right circumstances to do so.” He also said “there are other high-ranking officers who want to defect, but the situation is not suitable for them to declare defection.”


General Shallal’s statement came as Syrian insurgents were claiming new territorial gains against Mr. Assad in the northern and central parts of the country and as a special envoy from the United Nations and the Arab League was visiting Damascus as part of an effort to reach a political settlement that would halt the conflict, the most violent of the Arab Spring revolutions that began in the winter of 2010-2011. More than 40,000 people have been killed since protests against Mr. Assad began in March 2011.


There has been speculation that the special envoy, Lakhdar Brahimi, presented Mr. Assad with proposals for relinquishing his authority and possibly leaving the country. But Mr. Assad, whose Alawite minority has ruled Syria for more than four decades, has consistently said he will not leave the country, even as his control over it seems to be slipping further away.


Dozens of lower-ranking Syrian military officers and hundreds of soldiers have fled Syria over the past two years, but General Shallal, the head of the military police division of the Syrian Army, is the highest-ranking military defector so far. He outranked Brig. Gen. Manaf Tlass, a boyhood friend of Mr. Assad’s, who fled last July. General Tlass is now believed to be living in France.


Among civilians who have abandoned Mr. Assad, the highest-ranking defector so far has been the prime minister, Riyad Farid Hijab, who fled to Jordan on Aug. 6. In the past few weeks, unconfirmed reports also have abounded about the possible defection of Syria’s Foreign Ministry spokesman, Jihad Makdissi, a smooth-talking English speaker who had numerous foreign contacts and who disappeared from public view in early December. The Lebanese television channel Al Manar, which is sympathetic to Mr. Assad, said Mr. Makdissi had been fired.


The Guardian reported this week that Mr. Makdissi had fled to the United States and was cooperating with American intelligence. Officials in Washington have not responded to requests for comment on that report.


In Lebanon, Syria’s interior minister, Mohammed al-Shaar, who had been recovering at a Beirut hospital from wounds said to have been received in a Dec. 12 suicide bombing attack outside his offices in Damascus, was on his way back to the Syrian capital on Wednesday. The Associated Press quoted Beirut airport officials as saying the minister flew home on a private jet.


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James leads Heat over Thunder in Finals rematch


MIAMI (AP) — Kevin Durant and Russell Westbrook combined to score 54 points, more than any set of teammates had managed in a game against Miami all season.


Oklahoma City needed them to score at least three more.


That didn't happen, and an NBA Finals rematch went just as last year's title series did — to the Heat.


LeBron James had 29 points, nine assists and eight rebounds, Dwyane Wade scored 21, and the Heat survived a frantic finish to beat the Thunder 103-97 on Tuesday night, a game where Durant and Westbrook both missed potential tying 3-pointers in the final seconds.


"A great game to play," Thunder coach Scott Brooks said, "and a great game to coach."


For the Heat, it was just a little greater.


Mario Chalmers scored a season-high 20 for the Heat, who were 19 for 19 from the foul line, the second-best effort in franchise history behind only a 30-for-30 game in Boston on March 24, 1993. Chris Bosh added 16 points for Miami, which has beaten the Thunder five straight times dating to last June's title series.


"Felt a little bit like a different month," Heat coach Erik Spoelstra said. "Regardless of what your script is coming into the game, when you play this team, it's not going to go according to script. They're too good."


It's the first losing streak of the season for the Thunder, who had been 4-0 after losses. Serge Ibaka and Kevin Martin each scored 15 for Oklahoma City.


The game had a little of everything — a fast start by the reigning champions, a one-handed dunk by James on an offensive rebound that will be added to his copious highlight reel, a scrum after a hard foul that led to double-technicals on Wade and Ibaka early in the fourth, an easy rally by the Thunder from an early double-digit deficit, and even workout partners in Durant and James barking back and forth in the final minutes.


Such was the intensity that James slumped over the scorer's table with 1:08 left, exhausted.


"I'm tired as hell right now," James said — and that was more than an hour after the game ended.


With good reason. On an emotional day, there was a wild finish.


Wade lost the ball on an ill-advised, behind-the-back dribble, and the turnover set up Durant for a two-handed dunk that got the Thunder within 96-95 with 44.1 seconds remaining.


Needing a stop on the next trip, the Thunder instead forgot to play defense. Kendrick Perkins and Ibaka both were confused on the ensuing Miami possession, and Bosh was left alone to take a pass from James and throw down a dunk that restored Miami's three-point edge.


"We went over and helped," Durant said. "We just needed to help on the backside. There was miscommunication but we still had a chance to go into overtime."


Two chances, actually.


Oklahoma City got within one when Durant made a jumper over James, but no closer. Ray Allen's two free throws with 15.6 seconds left made it 100-97, and Miami's last three points came from the line. Durant missed a 3-pointer that James contested, Westbrook wound up with a second chance that Wade defended, and the Thunder guard smacked a nearby table arguing that he was fouled.


"Part of the game," Westbrook said.


While the stars were stars, the Heat got help from one unexpected source. Chalmers was making everything, even unintended plays. Allen lost possession on what looked to be a pass to no one, but Chalmers picked up the bouncing ball on the right wing, whirled and made a 3-pointer — putting Miami up 86-79 with 8:14 left.


In the end, that cushion was necessary.


"I got going early," Chalmers said, "and I stuck with it."


The Heat came out flying, opening a quick 13-2 lead after making six of their first seven shots. About all that didn't go right for the Heat early on was James committing a foul, the first time he was called for a personal since Dec. 8.


It happened 4:03 into the game — 254 minutes and 7 seconds of on-court time since his last one — when James fouled Ibaka on a dunk attempt.


Chalmers had 12 points, matching his season high, in the opening quarter alone, and that was also Miami's lead after his layup for a 15-3 edge. When Durant headed to the bench after being called for his second personal, plus a technical, with 2:08 left in the first, the Heat led 27-16.


But even with Durant out, Oklahoma City scored the last eight points of the quarter, six coming from the line. The Thunder shot 17 of the game's first 18 free throws and finished with a 38-19 edge in tries from the stripe.


The Heat were held to two points in the first 5:05 of the third, and the Thunder grabbed the lead for the first time. Durant connected on a baseline jumper while falling out of bounds and getting fouled by James. The resulting free throw gave Oklahoma City a 58-56 edge.


With that, the back-and-forth began, and Miami found a way.


"Both teams really played up to the billing," Wade said. "An excellent basketball game."


NOTES: James scored at least 20 points for the 30th straight regular-season game and 46th overall. ... Wade is 7-1 on Christmas, and James has won six straight on the holiday. ... Miami's Mike Miller became the 48th active player to reach 10,000 points. ... The Thunder have used the same starting lineup for all 27 games. ... James passed Bernard King for 39th on the NBA career scoring list. ... Attendance was 20,300, the largest crowd for a Heat home game since they moved into AmericanAirlines Arena.


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No Easy Route If Assad Opts to Go, or Stay





BEIRUT, Lebanon — President Bashar al-Assad of Syria sits in his mountaintop palace as the tide of war licks at the cliffs below.




Explosions bloom over the Damascus suburbs. His country is plunging deeper into chaos. The United Nations’ top envoy for the Syrian crisis, Lakhdar Brahimi, met with Mr. Assad in the palace on Monday in an urgent effort to resolve the nearly two-year-old conflict.


How Mr. Assad might respond to Mr. Brahimi’s entreaty depends on his psychology, shaped by a strong sense of mission inherited from his iron-fisted father and predecessor, Hafez al-Assad; his closest advisers, whom supporters describe as a hard-line politburo of his father’s gray-haired security men; and Mr. Assad’s assessment, known only to himself, about what awaits him if he stays — victory, or death at the hands of his people.


From his hilltop, Mr. Assad can gaze toward several possible futures.


East of the palace lies the airport and a possible dash to exile, a route that some say Mr. Assad’s mother and wife may have already taken. But the way is blocked, not just by bands of rebels, but by a belief that supporters say Mr. Assad shares with his advisers that fleeing would betray both his country and his father’s legacy.


He can stay in Damascus and cling to — even die for — his father’s aspirations, to impose a secular Syrian order and act as a pan-Arab leader on a regional and global stage.


Or he can head north to the coastal mountain heartland of his minority Alawite sect, ceding the rest of the country to the uprising led by the Sunni Muslim majority. That would mean a dramatic comedown: reverting to the smaller stature of his grandfather, a tribal leader of a marginalized minority concerned mainly with its own survival.


Mr. Brahimi was closemouthed about the details of his meeting, but has warned in recent weeks that without a political solution, Syria faces the collapse of the state and years of civil war that could dwarf the destruction already caused by the conflict that has taken more than 40,000 lives.


A Damascus-based diplomat said Monday that Mr. Assad, despite official denials, was “totally aware” that he must leave and was “looking for a way out,” though the timetable is unclear.


“More importantly,” said the diplomat, who is currently outside Syria but whose responsibilities include the country, “powerful people in the upper circle of the ruling elite in Damascus are feeling that an exit must be found.”


Yet others close to Mr. Assad and his circle say any retreat would clash with his deep-seated sense of himself, and with the wishes of increasingly empowered security officials, whom one friend of the president’s has come to see as “hotheads.”


Mr. Assad believes he is “defending his country, his people, and his regime and himself” against Islamic extremism and Western interference, said Joseph Abu Fadel, a Lebanese political analyst who supports Mr. Assad and met with government officials last week in Damascus.


Analysts in Russia, one of Syria’s staunchest allies, say that as rebels try to encircle Damascus and cut off escape routes to the coast, the mood in the palace is one of panic, evinced by the erratic use of weapons: Scud missiles better used against an army than an insurgency, naval mines dropped from the air instead of laid at sea.


But even if Mr. Assad wanted to flee, it is unclear if the top generals would let him out alive, Russian analysts say, since they believe that if they lay down arms they — and their disproportionately Alawite families — will die in vengeance killings, and need him to rally troops.


“If he can fly out of Damascus,” Semyon A. Bagdasarov, a Middle East expert in Moscow, said — at this, he laughed dryly — “there is also the understanding of responsibility before the people. A person who has betrayed several million of those closest to him.”


Many Syrians still share Mr. Assad’s belief that he is protecting the Syrian state, which helps explain how he has held on this long. At a lavish lunch hosted by a Lebanese politician outside Beirut in September, prominent Syrian backers of Mr. Assad — Alawites, Sunnis and Christians — spoke of the president, over copious glasses of Johnnie Walker scotch, as the bulwark of a multicultural, modern Syria.


Reporting was contributed by Kareem Fahim and David D. Kirkpatrick from Beirut, Ellen Barry from Moscow, Sebnem Arsu from Istanbul, Rick Gladstone from New York, and an employee of The New York Times from Tartus, Syria.



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Pagano back to coach Colts after cancer treatment


INDIANAPOLIS (AP) — Chuck Pagano stepped to the podium Monday, hugged his team owner, thanked his family for its support and wiped a tear from his eye.


He might, finally, turn out the lights in his office, too.


Nearly three months to the day after being diagnosed with leukemia, the Colts' first-year coach returned to a team eager to reunite with a boss healthy enough to go back to work.


"I told you my best day of my life was July 1, 1989," Pagano said, referring to his wedding date. "Today was No. 2. Getting to pull up, drive in, get out of my car, the key fob still worked. I was beginning to question whether it would or not. When I asked for Bruce to take over, I asked for him to kick some you-know-what and to do great. Damn Bruce, you had to go and win nine games? Tough act to follow. Tough act to follow. Best in the history of the NFL. That's what I have to come back to."


The comment turned tears into the laughter everyone expected on such a festive occasion.


For Pagano and the Colts, Monday morning was as precious as anyone could have imagined when Pagano took an indefinite leave to face the biggest opponent of his life, cancer.


In his absence, all the Colts was win nine of 12 games, make a historic turnaround and clinch a playoff spot all before Sunday's regular-season finale against Houston, which they pegged as the day they hoped to have Pagano back. If all goes well at practice this week, Pagano will be on the sideline for the first time since a Week 3 loss to Jacksonville.


Pagano endured three rounds of chemotherapy to put his cancer in remission.


That Pagano's return came less than 24 hours after Indy (10-5) locked up the No. 5 seed in the AFC and the day before Christmas seemed fitting, too.


"I know Chuck is ready for this challenge. In speaking to his doctor multiple times, I know that the time is right for him to grab the reins, get the head coaching cap on and begin the journey," owner Jim Irsay said. "It's been a miraculous story. It really is a book. It's a fairytale. It's a Hollywood script. It's all those things but it's real."


The reality is that he's returning to a vastly different team than the one he turned over to Arians, his long-time friend and first assistant coaching hire.


Back then, the Colts were 1-2 and most of the so-called experts had written them off as one of the league's worst teams. Now, they're ready to show the football world that they can be just as successful under Pagano as they were under Arians, who tied the NFL record for wins after a midseason coaching change.


Pagano also has changed.


The neatly-trimmed salt-and-pepper hair and trademark goatee that were missing in November have slowly returned, and the thinner man who appeared to be catching his breath during a postgame speech in early November, looked and sounded as good as ever Monday.


He repeatedly thanked fans for their prayers and letters, the organization and his family for their unwavering help and promised to provide comfort and support to other people who are facing similar fights. During one poignant moment that nearly brought out tears again, Pagano even recounted a letter sent to him by a 9-year-old child who suggested he suck on ice chips and strawberry Popsicles in the hospital and advised him to be nice to the nurses regardless of how he felt — and he never even paused.


"I feel great, my weight is back, my energy is back and again, it's just a blessing to be back here," Pagano said.


In the minds of Colts players and coaches, Pagano never really left.


He continually watched practice tape and game film on his computer, used phone calls and text messages to regularly communicate with players and occasionally delivered a pregame or postgame speech to his team.


"He texted me and called me so much, it was like he was standing there in my face every day," said receiver Reggie Wayne, who has been friends with Pagano since the two were working together at the University of Miami.


But the Colts found plenty of other ways to keep Pagano's battle in the forefront.


They began a fundraising campaign for leukemia research, calling it Chuckstrong. Players had stickers with the initials CP on their locker room nameplates, and Arians wore an orange ribbon on his baseball cap during games. Orange is the symbolic color for leukemia. At one point, nearly three dozen players shaved their heads to show their ailing coach they were with him.


That's not all.


Arians and first-year general manager Ryan Grigson decided to leave the lights on in Pagano's office until he returned. Pagano noted the team even installed plastic clips to make sure those lights were not mistakenly turned off while he was gone. Those clips were removed when Pagano arrived Monday morning.


And Arians said nobody sat in the front seat of the team bus.


"He's always been our head coach," Arians said.


So after getting medical clearance from his oncologist, Dr. Larry Cripe, to return with no restrictions, Pagano couldn't wait to get to the office Monday morning.


Arians arrived at 7 a.m., three hours early for the scheduled team meeting. By then, Pagano had already driven past the inflatable Colts player with the words "Welcome Back Chuck" printed on its chest and was back in his office preparing for the Texans.


Players showed up a couple of hours later, and when the torch was passed from Arians back to Pagano, players gave their returning coach a standing ovation that Wayne said was well-deserved.


All Pagano wants to do now is emulate the success Arians and his players have had this season.


"I asked him (Arians) if he would lead this team and this ballclub and this organization and take over the reins," Pagano said. "What a masterful, masterful job you did Bruce. You carried the torch and all you went out and did was win nine ballgames. You got us our 10th win yesterday and you got us into the playoffs. You did it with dignity and you did it with class. You're everything that I always knew you were and more."


___


Online: http://pro32.ap.org/poll and http://twitter.com/AP_NFL


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Despite Billions in Aid, Reconstruction in Haiti Stalls




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Colts recovering coach returns to team facility


INDIANAPOLIS (AP) — Chuck Pagano was back at work Monday morning.


Three months after taking an indefinite leave to battle leukemia, the Colts' coach was scheduled to meet with players, coaches and reporters as he retook the reins from interim coach Bruce Arians.


When Pagano arrived at the team headquarters, he drove past an inflatable Colts player to the side of the driveway with a simple message across the chest "Welcome Back Chuck." The sign usually reads "Beat," plus whichever team the Colts play next.


Indianapolis (10-5) has been waiting months for this day, and last week Arians called Pagano's impending return the best Christmas gift the team could get.


Pagano began the first of three rounds of chemotherapy Sept. 26, after the team completed its final practice during a bye week.


When the Colts returned to their practice facility Oct. 1, they were told Pagano had cancer and was taking an indefinite leave.


Arians, a prostate cancer survivor, immediately established the goal: Play long enough so Pagano could return to the sideline this season.


If all goes well at practice this week, Pagano will likely be on the sideline calling the shots Sunday against AFC South champion Houston in the regular-season finale. It would be the first time Pagano has been making game-day decisions since Jacksonville scored a last-minute touchdown on an 80-yard TD pass in Week 3, handing Indy it's only home loss this season.


Under Arians, the Colts did better than anyone expected.


When players arrived at training camp in August, they handed out T-shirts that showed where the so-called experts figured they would finish this season: The NFL's worst team again.


But with Sunday's 20-13 victory at Kansas City, Indy clinched its first playoff spot of the post-Peyton Manning era and Arians tied the league record for most wins after a midseason coaching change (nine). Indy is the fourth team in league history to win two or fewer games one season and 10 or more the next and became the second team in league history to lose 14 or more games one season and win 10 or more the next — joining the 2008 Miami Dolphins.


Pagano was never far from the Colts' thoughts while he was out.


He was in contact with players and coaches primarily through phone calls and text messages, watched tapes of practices and games on his computer, attended three home games and sometimes showed up at the team complex. He occasionally gave pregame or postgame speeches throughout his recovery.


On Nov. 5, Pagano's oncologist, Dr. Larry Cripe, said the illness was in complete remission, though Pagano still had to complete two more rounds of chemotherapy. The last round ended the first week of December. Last Thursday, Cripe said he gave Pagano medical clearance to return to the team. Cripe said he was putting no restrictions on what Pagano could do, only that he advised Pagano, as he does with other patients, to scale things back if necessary.


___


Online: http://pro32.ap.org/poll and http://twitter.com/AP_NFL


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N.Y.U. and Others Offer Shorter Courses Through Medical School





Training to become a doctor takes so long that just the time invested has become, to many, emblematic of the gravity and prestige of the profession.




But now one of the nation’s premier medical schools, New York University, and a few others around the United States are challenging that equation by offering a small percentage of students the chance to finish early, in three years instead of the traditional four.


Administrators at N.Y.U. say they can make the change without compromising quality, by eliminating redundancies in their science curriculum, getting students into clinical training more quickly and adding some extra class time in the summer.


Not only, they say, will those doctors be able to hang out their shingles to practice earlier, but they will save a quarter of the cost of medical school — $49,560 a year in tuition and fees at N.Y.U., and even more when room, board, books, supplies and other expenses are added in.


“We’re confident that our three-year students are going to get the same depth and core knowledge, that we’re not going to turn it into a trade school,” said Dr. Steven Abramson, vice dean for education, faculty and academic affairs at N.Y.U. School of Medicine.


At this point, the effort involves a small number of students at three medical schools: about 16 incoming students at N.Y.U., or about 10 percent of next year’s entering class; 9 at Texas Tech Health Science Center School of Medicine; and even fewer, for now, at Mercer University School of Medicine’s campus in Savannah, Ga. A similar trial at Louisiana State University has been delayed because of budget constraints.


But Dr. Steven Berk, the dean at Texas Tech, said that 10 or 15 other schools across the country had expressed interest in what his university was doing, and the deans of all three schools say that if the approach works, they will extend the option to larger numbers of students.


“You’re going to see this kind of three-year pathway become very prominent across the country,” Dr. Abramson predicted.


The deans say that getting students out the door more quickly will accomplish several goals. By speeding up production of physicians, they say, it could eventually dampen a looming doctor shortage, although the number of doctors would not increase unless the schools enrolled more students in the future.


The three-year program would also curtail student debt, which now averages $150,000 by graduation, and by doing so, persuade more students to go into shortage areas like pediatrics and internal medicine, rather than more lucrative specialties like dermatology.


The idea was supported by Dr. Ezekiel J. Emanuel, a former health adviser to President Obama, and a colleague, Victor R. Fuchs. In an editorial in the Journal of the American Medical Association in March, they said there was “substantial waste” in the nation’s medical education. “Years of training have been added without evidence that they enhance clinical skills or the quality of care,” they wrote. They suggested that the 14 years of college, medical school, residency and fellowship that it now takes to train a subspecialty physician could be reduced by 30 percent, to 10 years.


That opinion, however, is not universally held. Other experts say that a three-year medical program would deprive students of the time they need to delve deeply into their subjects, to consolidate their learning and to reach the level of maturity they need to begin practicing, while adding even more pressure to a stressful academic environment.


“The downside is that you are really tired,” said Dr. Dan Hunt, co-secretary of the Liaison Committee on Medical Education, the accrediting agency for medical schools in the United States and Canada. But because accreditation standards do not dictate the fine points of curriculum, the committee has approved N.Y.U.’s proposal, which exceeds by five weeks its requirement that schools provide at least 130 weeks of medical education.


The medical school is going ahead with its three-year program despite the damage from Hurricane Sandy, which forced NYU Langone Medical Center to evacuate more than 300 patients at the height of the storm and temporarily shut down three of its four main teaching hospitals.


Dr. Abramson of N.Y.U. said that postgraduate training, which typically includes three years in a hospital residency, and often fellowships after that, made it unnecessary to try to cram everything into the medical school years. Students in the three-year program will have to take eight weeks of class before entering medical school, and stay in the top half of their class academically. Those who do not meet the standards will revert to the four-year program.


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IHT Rendezvous: Adding More Bricks to the Great Firewall of China

HONG KONG — China appears to have reinforced its Internet firewall in recent days, blocking some of the leading services that allow people on the mainland to access forbidden sites like Twitter, Facebook and YouTube.

International business transactions also are being affected, Internet analysts said. The New York Times Web site remains 100 percent blocked on the mainland, along with the Chinese-language edition of The Times and Rendezvous.

At least three foreign companies — Astrill, WiTopia and StrongVPN — have apologized to customers whose virtual private networks, or VPNs, have been slowed or disabled. VPNs are used to circumvent the Communist government’s firewall. The companies, meanwhile, were suggesting some work-arounds.

The daily newspaper Global Times, affiliated with the Communist Party, acknowledged the firewall had been “upgraded,” but it also warned that foreign providers of VPN services were operating illegally.

China blocks online searches of politically sensitive terms, smothers embarrassing news events, blocks online messages from dissidents and simply deletes any microblog posts that it dislikes.

The firewall also blocks countless Web sites that are openly available to users elsewhere around the world — from pornography sites and commercial come-ons to news reporting, political activism and religious proselytizing. Users on the mainland thus have to use VPNs to reach the banned sites.

Liu Xiao Ming, the Chinese ambassador to Britain, told the BBC on Friday that there was “a misconception about the Internet and development in China.”

“In fact, the Chinese are very much open in terms of the Internet,” he said, quoted in an article in The South China Morning Post. “In fact, we have the most number of Internet users in China today.”

An estimated 600 million Chinese have access to the Internet.

Foreign businesses also use VPNs not only to safeguard their transactions but also to keep government censors and rival companies from seeing their corporate communications.

Global Times quoted an anonymous executive at a foreign technology company operating in China who said the lack of a VPN would damage the firm’s operations.

Josh Ong, China editor of the tech monitoring site The Next Web, said in an interview with the Voice of America that international companies were reporting disruptions in their corporate VPN services.

“A lot of companies have a general policy that they must use their own proxy network in order to transfer data, especially into and out of China,” Mr. Ong said. “So you are looking at banks or e-commerce companies, anyone who is transferring very sensitive information, a lot of them use corporate VPNs.”

Mr. Ong suggested that the tightening of the firewall could be tied to the recent leadership change in the Chinese Communist Party.

“It is certainly possible that some of it is just a general flexing of might, kind of coming in with a strong arm to really show who’s in control,” he said. “But there is definitely something intentional happening when these VPN services are being restricted.”

As Bill Bishop wrote recently on DealBook, China’s management of the Internet “has not been encouraging for those who want to believe the leadership will push reforms.”

“I have lived in Beijing since 2005, and these have been the most draconian few days of Internet restrictions I have experienced,” he said last month.

“Indiscriminate blocking of major parts of the global Internet is not going to help China in its quest to internationalize the renminbi and make it a reserve currency,” Bill said. “Internet controls at the level of the last few days may also deter foreign firms from moving their regional headquarters to China.”

Barbara Demick of The Los Angeles Times bureau in Beijing offered this cautionary tweet:

My colleagues Sharon LaFraniere and David Barboza wrote about similar concerns over China’s Internet censorship last year, and they spoke to Duncan Clark, chairman of BDA China, an investment and strategy consultancy based in Beijing.

“It has been double the guard, and double the guard, and you never hear proclamations about things being relaxed,” said Mr. Clark, a 17-year resident of China. “We have never seen this level of control in the time I have been here, and I have been here since the beginning of the Internet.”

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UK paper suing Lance Armstrong over libel case


LONDON (AP) — Lance Armstrong is being sued for more than $1.5 million by a British newspaper over the settlement of a libel action, which followed doping allegations against the cyclist that it published.


The Sunday Times paid Armstrong 300,000 pounds (now about $485,000) in 2006 to settle a case after it reprinted claims from a book in 2004 that he took performance-enhancing drugs.


The U.S. Anti-Doping Agency concluded this year that Armstrong led a massive doping program on his teams. Armstrong was stripped of his seven Tour de France titles and banned from cycling for life.


The Sunday Times announced in an article in its latest edition that it has issued legal papers against Armstrong.


"It is clear that the proceedings were baseless and fraudulent," the paper said in a letter to Armstrong's lawyers. "Your representations that you had never taken performance enhancing drugs were deliberately false."


The paper, which is owned by Rupert Murdoch's News Corp., said its total claim against Armstrong is "likely to exceed" 1 million pounds ($1.6 million).


"The Sunday Times is now demanding a return of the settlement payment plus interest, as well as its costs in defending the case," the paper said.


Read More..

Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..

Genetic Gamble : Drugs Aim to Make Several Types of Cancer Self-Destruct


C.J. Gunther for The New York Times


Dr. Donald Bergstrom is a cancer specialist at Sanofi, one of three companies working on a drug to restore a tendency of damaged cells to self-destruct.







For the first time ever, three pharmaceutical companies are poised to test whether new drugs can work against a wide range of cancers independently of where they originated — breast, prostate, liver, lung. The drugs go after an aberration involving a cancer gene fundamental to tumor growth. Many scientists see this as the beginning of a new genetic age in cancer research.




Great uncertainties remain, but such drugs could mean new treatments for rare, neglected cancers, as well as common ones. Merck, Roche and Sanofi are racing to develop their own versions of a drug they hope will restore a mechanism that normally makes badly damaged cells self-destruct and could potentially be used against half of all cancers.


No pharmaceutical company has ever conducted a major clinical trial of a drug in patients who have many different kinds of cancer, researchers and federal regulators say. “This is a taste of the future in cancer drug development,” said Dr. Otis Webb Brawley, the chief medical and scientific officer of the American Cancer Society. “I expect the organ from which the cancer came from will be less important in the future and the molecular target more important,” he added.


And this has major implications for cancer philanthropy, experts say. Advocacy groups should shift from fund-raising for particular cancers to pushing for research aimed at many kinds of cancer at once, Dr. Brawley said. John Walter, the chief executive officer of the Leukemia and Lymphoma Society, concurred, saying that by pooling forces “our strength can be leveraged.”


At the heart of this search for new cancer drugs are patients like Joe Bellino, who was a post office clerk until his cancer made him too sick to work. Seven years ago, he went into the hospital for hernia surgery, only to learn he had liposarcoma, a rare cancer of fat cells. A large tumor was wrapped around a cord that connects the testicle to the abdomen. “I was shocked,” he said in an interview this summer.


Companies have long ignored liposarcoma, seeing no market for drugs to treat a cancer that strikes so few. But it is ideal for testing Sanofi’s drug because the tumors nearly always have the exact genetic problem the drug was meant to attack — a fusion of two large proteins. If the drug works, it should bring these raging cancers to a halt. Then Sanofi would test the drug on a broad range of cancers with a similar genetic alteration. But if the drug fails against liposarcoma, Sanofi will reluctantly admit defeat.


“For us, this is a go/no-go situation,” said Laurent Debussche, a Sanofi scientist who leads the company’s research on the drug.


The genetic alteration the drug targets has tantalized researchers for decades. Normal healthy cells have a mechanism that tells them to die if their DNA is too badly damaged to repair. Cancer cells have grotesquely damaged DNA, so ordinarily they would self-destruct. A protein known as p53 that Dr. Gary Gilliland of Merck calls the cell’s angel of death normally sets things in motion. But cancer cells disable p53, either directly, with a mutation, or indirectly, by attaching the p53 protein to another cellular protein that blocks it. The dream of cancer researchers has long been to reanimate p53 in cancer cells so they will die on their own.


The p53 story began in earnest about 20 years ago. Excitement ran so high that, in 1993, Science magazine anointed it Molecule of the Year and put it on the cover. An editorial held out the possibility of “a cure of a terrible killer in the not too distant future.”


Companies began chasing a drug to restore p53 in cells where it was disabled by mutations. But while scientists know how to block genes, they have not figured out how to add or restore them. Researchers tried gene therapy, adding good copies of the p53 gene to cancer cells. That did not work.


Then, instead of going after mutated p53 genes, they went after half of cancers that used the alternative route to disable p53, blocking it by attaching it to a protein known as MDM2. When the two proteins stick together, the p53 protein no longer functions. Maybe, researchers thought, they could find a molecule to wedge itself between the two proteins and pry them apart.


The problem was that both proteins are huge and cling tightly to each other. Drug molecules are typically tiny. How could they find one that could separate these two bruisers, like a referee at a boxing match?


In 1996, researchers at Roche noticed a small pocket between the behemoths where a tiny molecule might slip in and pry them apart. It took six years, but Roche found such a molecule and named it Nutlin because the lab was in Nutley, N.J.


But Nutlins did not work as drugs because they were not absorbed into the body.


Roche, Merck and Sanofi persevered, testing thousands of molecules.


At Sanofi, the stubborn scientist leading the way, Dr. Debussche, maintained an obsession with p53 for two decades. Finally, in 2009, his team, together with Shaomeng Wang at the University of Michigan and a biotech company, Ascenta Therapeutics, found a promising compound.


The company tested the drug by pumping it each day into the stomachs of mice with sarcoma.


Read More..