Extended Use of Breast Cancer Drug Suggested

The widely prescribed drug tamoxifen already plays a major role in reducing the risk of death from breast cancer. But a new study suggests that women should be taking the drug for twice as long as is now customary, a finding that could upend the standard that has been in place for about 15 years.

In the study, patients who continued taking tamoxifen for 10 years were less likely to have the cancer come back or to die from the disease than women who took the drug for only five years, the current standard of care.

“Certainly, the advice to stop in five years should not stand,” said Prof. Richard Peto, a medical statistician at Oxford University and senior author of the study, which was published in The Lancet on Wednesday and presented at the San Antonio Breast Cancer Symposium.

Breast cancer specialists not involved in the study said the results could have the biggest impact on premenopausal women, who account for a fifth to a quarter of new breast cancer cases. Postmenopausal women tend to take different drugs, but some experts said the results suggest that those drugs might be taken for a longer duration as well.

“We’ve been waiting for this result,” said Dr. Robert W. Carlson, a professor of medicine at Stanford University. “I think it is especially practice-changing in premenopausal women because the results do favor a 10-year regimen.”

Dr. Eric P. Winer, chief of women’s cancers at the Dana-Farber Cancer Institute in Boston, said that even women who completed their five years of tamoxifen months or years ago might consider starting on the drug again.

Tamoxifen blocks the effect of the hormone estrogen, which fuels tumor growth in estrogen receptor-positive cancers that account for about 65 percent of cases in premenopausal women. Some small studies in the 1990s suggested that there was no benefit to using tamoxifen longer than five years, so that has been the standard.

About 227,000 cases of breast cancer are diagnosed each year in the United States, and an estimated 30,000 of them are in premenopausal women with estrogen receptor-positive cancer and prime candidates for tamoxifen. But postmenopausal women also take tamoxifen if they cannot tolerate the alternative drugs, known as aromatase inhibitors.

The new study, known as Atlas, included nearly 7,000 women with ER-positive disease who had completed five years of tamoxifen. They came from about three dozen countries. Half were chosen at random to take the drug another five years, while the others were told to stop.

In the group assigned to take tamoxifen for 10 years, 21.4 percent had a recurrence of breast cancer in the ensuing 10 years, meaning the period 5 to 14 years after their diagnoses. The recurrence rate for those who took only five years of tamoxifen was 25.1 percent.

About 12.2 percent of those in the 10-year treatment group died from breast cancer, compared with 15 percent for those in the control group.

There was virtually no difference in death and recurrence between the two groups during the five years of extra tamoxifen. The difference came in later years, suggesting that tamoxifen has a carry-over effect that lasts long after women stop taking it.

Whether these differences are big enough to cause women to take the drug for twice as long remains to be seen.

“The treatment effect is real, but it’s modest,” said Dr. Paul E. Goss, director of breast cancer research at the Massachusetts General Hospital.

Tamoxifen has side effects, including endometrial cancer, blood clots and hot flashes, which cause many women to stop taking the drug. In the Atlas trial, it appears that roughly 40 percent of the patients assigned to take tamoxifen for the additional five years stopped prematurely.

Some 3.1 percent of those taking the extra five years of tamoxifen got endometrial cancer versus 1.6 percent in the control group. However, only 0.6 percent of those in the longer treatment group died from endometrial cancer or pulmonary blood clots, compared with 0.4 percent in the control group.

“Over all, the benefits of extended tamoxifen seemed to outweigh the risks substantially,” Trevor J. Powles of the Cancer Center London, said in a commentary published by The Lancet.

Dr. Judy E. Garber, director of the Center for Cancer Genetics and Prevention at Dana-Farber, said many women have a love-hate relationship with hormone therapies.

“They don’t feel well on them, but it’s their safety net,” said Dr. Garber, who added that the news would be welcomed by many patients who would like to stay on the drug. “I have patients who agonize about this, people who are coming to the end of their tamoxifen.”

Emily Behrend, who is a few months from finishing her five years on tamoxifen, said she would definitely consider another five years. “If it can keep the cancer away, I’m all for it,” said Ms. Behrend, 39, a single mother in Tomball, Tex. She is taking the antidepressant Effexor to help control the night sweats and hot flashes caused by tamoxifen.

Cost is not considered a huge barrier to taking tamoxifen longer because the drug can be obtained for less than $200 a year.

The results, while answering one question, raise many new ones, including whether even more than 10 years of treatment would be better still.

Perhaps the most important question is what the results mean for postmenopausal women. Even many women who are premenopausal at the time of diagnosis will pass through menopause by the time they finish their first five years of tamoxifen, or will have been pushed into menopause by chemotherapy.

Postmenopausal patients tend to take aromatase inhibitors like anastrozole or letrozole, which are more effective than tamoxifen at preventing breast cancer recurrence, though they do not work for premenopausal women.

Mr. Peto said he thought the results of the Atlas study would “apply to endocrine therapy in general,” meaning that 10 years of an aromatase inhibitor would be better than five years. Other doctors were not so sure.

The Atlas study was paid for by various organizations including the United States Army, the British government and AstraZeneca, which makes the brand-name version of tamoxifen.

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In Inquiry, Drilling Company Chief Quits

LONDON — The chief executive of Saipem, the largest European drilling and engineering contractor for the oil industry, resigned Wednesday evening after an Italian prosecutor’s office said it was investigating possible corruption.

The executive, Pietro Franco Tali, also served as deputy chairman of the company, in which the big Italian oil company Eni has a controlling stake.

A Saipem spokesman, Andrea Pagano Mariano, said the investigation related to contracts on oil and gas projects in Algeria involving the state oil company Sonatrach. He declined to elaborate.

Although Mr. Tali “is in no manner a subject of the prosecutor’s investigation, he felt that his resignation would better enable the company to respond to the prosector’s inquiry,” Saipem said in a statement. The activities were said to have occurred through 2009.

Eni, which has about 43 percent of Saipem’s shares, held an emergency board meeting Wednesday night, according to a news release. In recent days, it said, the board had urged the drilling company’s chairman, Alberto Meomartini, “to take immediate remedial actions in managing the situation.”

Eni’s chief financial officer, Alessandro Bernini, who held the same position at Saipem until 2008, also resigned Wednesday, although he “considers that his actions were right and proper,” according to an Eni release.

An Eni spokeswoman, Erika Mandraffino, said the accusations about Saipem came to Eni’s attention a few days ago. She declined to indicate what the inquiry involves in Algeria, where Saipem has billions of dollars’ worth of oil and gas operations and drilling contracts, and about 2,600 employees.

Saipem’s board named the chief operating officer of Eni’s gas and power division, Umberto Vergine, to replace Mr. Tali as Saipem’s chief.

The company also suspended Pietro Varone, chief operating officer of Saipem’s engineering and construction unit, following a notice of inquiry from the prosecutor related to the same investigation. Saipem’s board also ordered an internal audit using external consultants.

“Saipem believes that its business activities have been conducted in compliance with applicable, internal procedures” and its code of ethics, the company said, and has offered its full cooperation to the prosecutor’s office.

The investigation is a blow to ENI, which under its chief executive, Paolo Scaroni, is working to establish itself as a premier exploration and production company. Earlier on Wednesday, Eni announced a new natural gas discovery off the coast of Mozambique, where the company has become an early leader in staking a position in that country’s promising gas reserves.

Although Eni stresses that Saipem is independently managed, the two companies are closely intertwined.

In an interview on Nov. 19, Mr. Scaroni said that while the company was divesting other noncore assets, he considered Saipem “a major asset.”

He said that Saipem was “managed at arm’s length” because Eni was only “one of the customers” of the engineering company. He said Saipem was the top candidate to build the portion of the proposed South Stream natural gas pipeline from Russia to Eastern and Western Europe, under the Black Sea.

Eni, along with Gazprom, is a crucial backer of the project.

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Cheering U.N. Palestine Vote, New York Synagogue Tests Its Members

Congregation B’nai Jeshurun, a synagogue with several thousand members on the Upper West Side of Manhattan, is known for its charismatic rabbis, its energetic and highly musical worship, and its liberal stances on social causes.

But on Friday, when its rabbis and lay leaders sent out an e-mail enthusiastically supporting the vote by the United Nations to upgrade Palestine to a nonmember observer state, the statement was more than even some of its famously liberal congregants could stomach.

“The vote at the U.N. yesterday is a great moment for us as citizens of the world,” said the e-mail, which was sent to all congregants. “This is an opportunity to celebrate the process that allows a nation to come forward and ask for recognition.”

The statement, at a time when the United Nations’ vote was opposed by the governments of the United States and Israel, as well as by the leadership of many American Jewish organizations, reflected a divide among American Jews and a willingness to break a longstanding taboo by publicly disagreeing with Israel.

Clergy at several Jewish congregations have, in various ways, spoken out sympathetically about the United Nations’ vote.

At B’nai Jeshurun, reaction from congregants was swift. Some, like Allan Ripp, said he and his wife were appalled.

“We are just sort of in a state of shock,” he said. “It’s not as if we don’t support a two-state solution, but to say with such a warm embrace — it is like a high-five to the P.L.O., and that has left us numb.”

Other congregants, however, said it was a bold move that they welcomed.

“I thought it was great; I thought it was very courageous of them,” said Gil Kulick, a congregant. “I think as of late there has been a reluctance to speak out on this issue,” he added, “and that’s why I was really delighted that they chose to take a strong unequivocal stand.”

American Jews have long had a vigorous, and sometimes vitriolic, debate about the positions of the Israeli government and the peace process with the Palestinians. But the tendency has been to keep critical views within the fold, particularly when responding to high-profile actions like the vote supporting an upgrade in Palestinian status in the United Nations.

“In most cases, at most times we impose a kind of discipline upon ourselves — nobody imposes it on us — particularly on a matter that the Israeli government has asked for unanimous support from the Jewish community,” said Samuel Norich, the publisher of The Forward, a Jewish affairs weekly based in New York. “When they speak out, that is rare,” Mr. Norich said of mainstream congregations.

Gary Rosenblatt, the editor and publisher of The Jewish Week, the largest circulation Jewish newspaper in the country, said, “I think the sense of a need for a unified front in the American Jewish community is breaking down.”

In White Plains, a group of synagogues from different branches of Judaism — conservative, reform and reconstructionist — sent an e-mail to congregants after the United Nations’ vote expressing cautious optimism about Palestine’s new status, even as statements from the reform and conservative movements expressed disappointment.

“For their own reasons, most of the American Jewish organizations felt it was necessary to fall into line,” said Lester Bronstein, a rabbi at Bet Am Shalom Synagogue in White Plains and one of the signers of the letter. “I think what we said is indicative of what more and more rabbis believe, and more and more, but in trickles, are able to say it.”

 The rabbis at B’nai Jeshurun — J. Rolando Matalon, Marcelo R. Bronstein and Felicia L. Sol — did not respond to repeated requests this week for comment on why they had sent the e-mail, which was also signed by the president of the synagogue’s board of directors and its executive director. While its gist — that the vote could be a step toward a two-state solution and Middle East peace — was not surprising to congregants, its tone and its timing, so soon after the Gaza conflict, made it stand out, some said.

B’nai Jeshurun, which is not affiliated with any of the major branches of Judaism, worships in an elaborate Moorish-style sanctuary on West 88th Street. The congregation has attracted national attention for its success at energizing a once-struggling synagogue. Some services attract overflow crowds; lectures and events are popular not only among members, but also among young single Jews seeking social connections. During services, congregants are encouraged to express themselves and often clap and even dance to the music, which is played by live musicians with not just a keyboard, but also often with congas, mandolin, flute, guitar or cello.

This article has been revised to reflect the following correction:

Correction: December 4, 2012

An earlier version of this article misspelled the name of the congregation at one point.  It is B’nai Jeshurun, not B’nai Jeshrun,

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Bret Bielema leaves Wisconsin for Arkansas

FAYETTEVILLE, Ark. (AP) — Bret Bielema is taking his brand of power football to Arkansas, leaving Wisconsin after seven seasons.

Arkansas released a statement Tuesday night saying Bielema has agreed to a deal to take over the program reeling following the firing of former coach Bobby Petrino.

A person familiar with the situation, who spoke on the condition of anonymity because the information hasn't been released publicly, says the deal is for six years and $3.2 million annually.

Bielema, Barry Alvarez's hand-picked successor at Wisconsin, was 68-24 with the Badgers, with four double-digit win seasons. He coached Wisconsin to a 17-14 victory over Arkansas in his first season at the Capital One Bowl.

"His tough, aggressive style of play has been successful and will be appealing to student-athletes and Razorback fans," Arkansas athletic director Jeff Long said in a statement. "He not only shares the vision and values for the future of Arkansas football, he embraces them."

Bielema is leaving the Big Ten for the SEC and a Razorbacks program that opened the year with hopes of challenging for a national championship only to get mired in the Petrino scandal before stumbling to a 4-8 finish.

The move was the second stunning hire this year at Arkansas, which brought in John L. Smith as the interim coach after firing Petrino for hiring his mistress to work in the athletic department. Long announced after the season that Smith wouldn't return.

Bielema seems likely to bring a far different approach than what the Razorbacks have become accustomed to. Arkansas continually ranked among the Southeastern Conference's best passing teams under Petrino while Bielema is known for his dominant offensive lines and slew of running backs.

"During my conversation with Jeff (Long), he described the characteristics for the perfect fit to lead this program," Bielema said in a statement. "It was evident we share the same mission, principles and goals."

Wisconsin running back Montee Ball tied Barry Sanders' long-standing single-season record of 39 touchdowns last year, and this year became the FBS career leader in touchdowns. He currently has 82 touchdowns after running for three Saturday night in the Big Ten title game against Nebraska — a 70-31 romp that secured the Badgers third straight trip to the Rose Bowl, where they will play Stanford on Jan. 1.

The 42-year-old Bielema was the defensive coordinator at Wisconsin for two years before being promoted to head coach in 2006. He played for Iowa and started his coaching career there as an assistant under Hayden Fry and later Kirk Ferentz.

"I was very surprised when Bret told me he was taking the offer from Arkansas," said Alvarez, Wisconsin's athletic director and former coach. "He did a great job for us during his seven years as head coach, both on the field and off. I want to thank him for his work and wish him the best at Arkansas."

The Illinois native takes over a program still reeling following the April scandal, one eager for stability and leadership.

"I'm excited about this decision," Arkansas cornerback Tevin Mitchel tweeted.

The Razorbacks improved their win total in four straight seasons under Petrino, including a 21-5 mark in 2010-11, and finished last season ranked No. 5. They had talked openly in the spring about competing for the school's first SEC championship and perhaps a national title.

Then came the April 1 motorcycle accident that led to Petrino's downfall. The married father of four initially lied about being alone during the wreck, later admitting to riding with his mistress — a former Arkansas volleyball player he had hired to work in the athletic department.

Smith, who had been an assistant the last three seasons at Arkansas under Petrino, was chosen by Long to guide a team that returned first-team All-SEC quarterback Tyler Wilson and a host of other key playmakers. The decision was lauded by the Razorbacks, who welcomed the personable Smith back with open arms.

The season hit the skids with a stunning overtime loss to Louisiana-Monroe on Sept. 8, starting a four-game losing streak that dropped Arkansas out of the rankings. The Razorbacks finished with the school's lowest win total since 2005, missing a bowl game for the first time since 2008.

"It's very difficult for me to believe that is not a bowl-eligible team," LSU coach Les Miles said following the Tigers' win over the Razorbacks in the season finale. "Watching the talent there, (it's) very capable."

Arkansas struggled to find its identity in the SEC after leaving the former Southwest Conference in 1992, but it appeared to have finally found just that under Petrino, who was hired after leaving the Atlanta Falcons during the season in 2007.

The Razorbacks turned into an offensive powerhouse under Petrino, leading the league in scoring and total offense last season. After winning 10 games and reaching the school's first BCS bowl game in 2010, losing to Ohio State, Arkansas won 11 games in 2011, capped by a Cotton Bowl win over Kansas State.

Still, Arkansas has yet to win the SEC, losing in the conference championship game three times.

While the country watched closely to see how Arkansas would react following Petrino's dismissal, Smith made headlines of his own throughout the season. The former Michigan State and Louisville coach filed for bankruptcy during the season, revealing $40.7 million in debt he blamed on bad land deals.

He was under far more fire from Arkansas fans for the mounting losses and it will be up to Bielema to turn things around in the loaded SEC West, with Alabama, LSU and now Texas A&M.

Long said during the season that the new coach would be tasked with building on the recent success at the school, which is looking into expanding the 72,000-seat Razorback Stadium and is currently building an 80,000-square-foot football operations center.

"The infrastructure in place at Arkansas shows the commitment from the administration to accomplish our goals together and I am excited to begin to lead this group of student-athletes," Bielema said. "This program will represent the state of Arkansas in a way Razorback fans everywhere will be proud of."

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Software Programs Help Doctors Diagnose, but Can’t Replace Them

SAN FRANCISCO — The man on stage had his audience of 600 mesmerized. Over the course of 45 minutes, the tension grew. Finally, the moment of truth arrived, and the room was silent with anticipation.

At last he spoke. “Lymphoma with secondary hemophagocytic syndrome,” he said. The crowd erupted in applause.

Professionals in every field revere their superstars, and in medicine the best diagnosticians are held in particularly high esteem. Dr. Gurpreet Dhaliwal, 39, a self-effacing associate professor of clinical medicine at the University of California, San Francisco, is considered one of the most skillful clinical diagnosticians in practice today.

The case Dr. Dhaliwal was presented, at a medical  conference last year, began with information that could have described hundreds of diseases: the patient had intermittent fevers, joint pain, and weight and appetite loss.

To observe him at work is like watching Steven Spielberg tackle a script or Rory McIlroy a golf course. He was given new information bit by bit — lab, imaging and biopsy results. Over the course of the session, he drew on an encyclopedic familiarity with thousands of syndromes. He deftly dismissed red herrings while picking up on clues that others might ignore, gradually homing in on the accurate diagnosis.

Just how special is Dr. Dhaliwal’s talent? More to the point, what can he do that a computer cannot? Will a computer ever successfully stand in for a skill that is based not simply on a vast fund of knowledge but also on more intangible factors like intuition?

The history of computer-assisted diagnostics is long and rich. In the 1970s, researchers at the University of Pittsburgh developed software to diagnose complex problems in general internal medicine; the project eventually resulted in a commercial program called Quick Medical Reference. Since the 1980s, Massachusetts General Hospital has been developing and refining DXplain, a program that provides a ranked list of clinical diagnoses from a set of symptoms and laboratory data.

And I.B.M., on the heels of its triumph last year with Watson, the Jeopardy-playing computer, is working on Watson for Healthcare.

In some ways, Dr. Dhaliwal’s diagnostic method is similar to that of another I.B.M. project: the Deep Blue chess program, which in 1996 trounced Garry Kasparov, the world’s best player at the time, to claim an unambiguous victory in the computer’s relentless march into the human domain.

Although lacking consciousness and a human’s intuition, Deep Blue had millions of moves memorized and could analyze as many each second. Dr. Dhaliwal does the diagnostic equivalent, though at human speed.

Since medical school, he has been an insatiable reader of case reports in medical journals, and case conferences from other hospitals. At work he occasionally uses a diagnostic checklist program called Isabel, just to make certain he hasn’t forgotten something. But the program has yet to offer a diagnosis that Dr. Dhaliwal missed.

Dr. Dhaliwal regularly receives cases from physicians who are stumped by a set of symptoms. At medical conferences, he is presented with one vexingly difficult case and is given 45 minutes to solve it. It is a medical high-wire act; doctors in the audience squirm as the set of facts gets more obscure and all the diagnoses they were considering are ruled out. After absorbing and processing scores of details, Dr. Dhaliwal must commit to a diagnosis. More often than not, he is right.

When working on a difficult case in front of an audience, Dr. Dhaliwal puts his entire thought process on display, with the goal of “elevating the stature of thinking,” he said. He believes this is becoming more important because physicians are being assessed on whether they gave the right medicine to a patient, or remembered to order a certain test.

Without such emphasis, physicians and training programs might forget the importance of having smart, thoughtful doctors. “Because in medicine,” Dr. Dhaliwal said, “thinking is our most important procedure.”

He added: “Getting better at diagnosis isn’t about figuring out if someone has one rare disease versus another. Getting better at diagnosis is as important to patient quality and safety as reducing medication errors, or eliminating wrong site surgery.”

Clinical Precision

Dr. Dhaliwal does half his clinical work on the wards of the San Francisco V. A. Medical Center, and the other half in its emergency department, where he often puzzles through multiple mysteries at a time.

One recent afternoon in the E.R., he was treating a 66-year-old man who was mentally unstable and uncooperative. He complained of hip pain, but routine lab work revealed that his kidneys weren’t working and his potassium was rising to a dangerous level, putting him in danger of an arrhythmia that could kill him — perhaps within hours. An ultrasound showed that his bladder was blocked.

There was work to be done: drain the bladder, correct the potassium level. It would have been easy to dismiss the hip pain as a distraction; it didn’t easily fit the picture. But Dr. Dhaliwal’s instinct is to hew to the ancient rule that physicians should try to come to a unifying diagnosis. In the end, everything — including the hip pain — was traced to metastatic prostate cancer.

“Things can shift very quickly in the emergency room,” Dr. Dhaliwal said. “One challenge of this, whether you use a computer or your brain, is deciding what’s signal and what’s noise.” Much of the time, it is his intuition that helps figure out which is which.

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DealBook: Former Goldman Director Gupta to Stay Free Pending His Appeal

A former Goldman Sachs director, Rajat K. Gupta, may remain free on bail while he challenges his insider-trading conviction, a federal appeals court ruled on Tuesday.

In a surprise decision, the United States Court of Appeals for the Second Circuit in Manhattan ruled that Mr. Gupta would not have to report to prison until his appeal is heard, which could take a year. He had been set to start serving his two-year sentence on Jan. 8.

Mr. Gupta, 64, was found guilty in June of leaking Goldman’s boardroom secrets to his friend, the former hedge fund managerRaj Rajaratnam.

Tuesday’s ruling suggested that Mr. Gupta had convinced the judges that he had legitimate issues to argue on appeal. The same federal appeals court had denied a request by Mr. Rajaratnam to remain free on bail pending his appeal. Mr. Rajaratnam is serving an 11-year prison term.

Mr. Gupta’s lawyers are expected to make several arguments. The most significant issue on appeal could be the government’s use of the wiretaps in the trial.

Judge Jed S. Rakoff, the trial court judge, allowed the jury to hear incriminating taped conversations involving Mr. Rajaratnam and his traders. Those conversations suggested Mr. Rajaratnam had a source at Goldman.

“I heard yesterday from somebody who’s on the board of Goldman Sachs that they are going to lose $2 per share,” Mr. Rajaratnam told a colleague on a wiretapped call in October 2008.

Multimedia: Insider Trading

Without the wiretaps, prosecutors would have had to rely on circumstantial evidence — telephone bills and trading records — to prove their case.

Mr. Gupta’s lawyers had argued that because the conversations were between Mr. Rajaratnam and his employees, Judge Rakoff should declare them inadmissible hearsay evidence, meaning that they were too unreliable to be used against Mr. Gupta.

Another issue that Mr. Gupta’s lawyers are expected to raise is that Judge Rakoff erred in limiting testimony by Mr. Gupta’s daughter about her father’s deteriorating relationship with Mr. Rajaratnam.

Mr. Gupta, who lives in Westport, Conn., has been free on $10 million bail since his arrest in October 2011. In addition to a team of lawyers from Kramer Levin Naftalis & Frankel that had represented him, Mr. Gupta hired Seth P. Waxman, an experienced appellate lawyer, to help with his appeal.
Mr. Waxman, a partner at WilmerHale, is a former United States solicitor general who has argued more than 50 cases before the United States Supreme Court.

The court is expected to hear Mr. Gupta’s appeal in the spring.

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U.S. Warns Syria Against Using Chemical Weapons

Narciso Contreras/Associated Press

 A kitchen in a home in Aleppo, Syria showed signs of heavy fighting Sunday.

WASHINGTON — President Obama warned Syria on Monday not to use chemical weapons against its own people, vowing to hold accountable anyone who did, even as American intelligence officials picked up signs that such arms might be deployed in the fighting there.

The White House said it had an “increased concern” that the government of President Bashar al-Assad was preparing to use such weapons, effectively confirming earlier reports of activity at chemical weapons sites. The administration said it would take action if they were used, suggesting even the possibility of military force.

“Today I want to make it absolutely clear to Assad and those under his command: The world is watching,” Mr. Obama said in a speech at the National Defense University in Washington. “The use of chemical weapons is and would be totally unacceptable. If you make the tragic mistake of using these weapons, there will be consequences and you will be held accountable.”

Neither the president nor his aides would specify how it would hold Syrians accountable, but the White House confirmed that contingency plans had been drawn for direct action. The president’s statement amplified similar warnings issued by Secretary of State Hillary Rodham Clinton earlier in the day in Prague, the capital of the Czech Republic, which represents the interests of the United States in Damascus now that the American Embassy there has been closed.

“This is a red line for the United States,” Mrs. Clinton said. “I am not going to telegraph in any specifics what we would do in the event of credible evidence that the Assad regime has resorted to using chemical weapons against their own people. But suffice it to say, we are certainly planning to take action if that eventuality were to occur.”

The sharpening language came as NATO was preparing to buttress its member Turkey against a potential attack from Syria. A plan expected to be endorsed by the alliance’s foreign ministers during two-days of meetings that begin Tuesday in Brussels calls for deploying American, German and Dutch Patriot missile-defense batteries under the operational control of the NATO military command, Western officials said Monday.

Such a move would be the most direct action in the Syrian conflict by the alliance, which has remained cautious about intervention there. But for months, Turkey has expressed concerns about the potential of missile attacks from Syria as relations between the two countries have worsened, and last month Ankara asked for Patriot batteries.

As the United States and its allies tried to forestall the conflict from escalating, the Syrian Foreign Ministry said the government “would not use chemical weapons, if it had them, against its own people under any circumstances.” The statement was reported on Syrian state television and on the Lebanese channel LBC.

Mr. Obama has called for Mr. Assad to step down but has shied away from taking direct action sought by Syrian rebels. With the election over, advisers are considering a more robust response, including possibly providing arms to the rebels and recognizing the opposition as the legitimate representative of the Syrian people.

But Mr. Obama avoided any mention of such actions in his speech. “We will work to support the legitimate aspirations of the Syrian people, engaging with the opposition, providing them with the humanitarian aid and working for a transition to a Syria that’s free of the Assad regime,” he said.

Jay Carney, the president’s press secretary, hinted at possible military action in response to any use of chemical weapons but declined to specify options. “We think it is important to prepare for all scenarios,” he said. “Contingency planning is the responsible thing to do.”

Mrs. Clinton flew from Prague to Brussels for the NATO meeting. A senior NATO official said the alliance would declare its support for Turkey’s request for help and welcome the intention of three allied nations to deploy Patriot missile batteries there. It would then be up to the United States, Germany and the Netherlands to decide how many batteries to deploy and for how long.

Surveys are being conducted of 10 potential sites, mainly in southeastern Turkey, but a senior American official traveling with Mrs. Clinton said it would probably take several weeks to deploy the batteries. Once deployed, they would be under the operational control of NATO’s top military commander, Adm. James. G. Stavridis.

The pending move has prompted speculation that it might be an indirect way of extending protection to forces opposing Mr. Assad in northern Syria by targeting Syrian warplanes operating there. But NATO and American officials were adamant that was not the purpose.

“There is no safe haven,” the American official with Mrs. Clinton said. “There is no de facto cross-border aspect to this.”

Instead, officials said the idea was to discourage Syria from threatening Turkey for supporting Syrian insurgents — and to discourage Turkey from feeling pressured to intervene to head off attacks against it. The Turkish military issued a statement Monday calling the deployment “a measure entirely aimed at defense.”

Peter Baker reported from Washington, and Michael R. Gordon from Brussels.

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Heisman finalists: Manziel, Te'o and Klein

NEW YORK (AP) — Johnny Manziel and Manti Te'o are in position to make Heisman Trophy history.

Manziel, the redshirt freshman quarterback from Texas A&M, and Te'o, Notre Dame's star linebacker, along with Kansas State quarterback Collin Klein, were invited Monday to attend the Heisman presentation ceremony.

Manziel is the favorite to win college football's most famous player of the year award on Saturday night in Manhattan. He would be the first freshman to win the Heisman and the first Texas A&M player since halfback John David Crow won the school's only Heisman in 1957.

"I'm overwhelmed by this tremendous honor of representing Texas A&M, the 12th Man and all my teammates in New York," Manziel said in a statement. "This is a dream come true for me, and I know it's a credit to all my coaches and teammates. I definitely wouldn't be a Heisman finalist without my teammates and coaches."

Three sophomores have won the award (Tim Tebow in 2007, Sam Bradford in 2008 and Mark Ingram in 2009), but the best a first-year player has ever done is second.

Adrian Peterson of Oklahoma finished second to Southern California quarterback Matt Leinart in 2004. Peterson was a true freshman. As a redshirt freshman, Manziel attended A&M last year and practiced with the team but did not play.

Michael Vick of Virginia Tech came in third in 1999 as a redshirt freshman and Herschel Walker was a true freshman for Georgia in 1980 when he finished third in the Heisman balloting.

Nicknamed Johnny Football, Manziel quickly became a national sensation this season, putting up huge numbers in first-year Texas A&M coach Kevin Sumlin's spread offense. He led the 10th-ranked Aggies to a 10-2 record in their first season in the Southeastern Conference.

With a knack for improvisation, Manziel racked up an SEC-record 4,600 yards of total offense, including 1,181 rushing to lead the conference. The 6-foot-1, 200-pound Manziel zoomed to the front of the Heisman race on Nov. 10, when he passed for 253 yards and two touchdowns and ran for 92 yards as the Aggies upset then-No. 1 Alabama 29-24 in Tuscaloosa.

Manziel and Texas A&M will play No. 12 Oklahoma in the Cotton Bowl.

Te'o is trying to become the first defense-only player to win the Heisman. The Fighting Irish have seven Heisman winners, tied for the most with Ohio State and Southern California, but none since Tim Brown in 1987.

Te'o became the face of the No. 1 team in the country and leader of a defense that has been the toughest to score upon in the nation. The senior intercepted seven passes, second-most in the country and tops for a linebacker. He also led the Fighting Irish with 103 tackles, and earlier Monday won the Butkus Award as country's best linebacker.

Te'o and the Irish face No. 2 Alabama in the BCS championship game on Jan. 7 in Miami.

Klein would be the first player from Kansas State to win the Heisman.

"I'm just honored with this opportunity that the Lord has provided me here at K-State," Klein said in a statement. "I'm so proud to represent K-State in this because I feel like my road is very synonymous and in line with the K-State way. It has been a process, it has been a journey. There have been a lot of ups and downs, as well as a lot of hard times and growing pains through it. I'm just very proud to represent the K-State family and our heart and spirit in this environment."

He seemed to be the front-runner for several weeks until Manziel's late push. When Klein threw three interceptions in the Wildcats' late-season loss to Baylor, Manziel moved to the front of the race.

Klein is a multitalented quarterback like Manziel, but with a different approach. The 6-5, 226-pound senior is a bullish runner who scored 22 touchdowns and threw for 15 more, while leading the seventh-ranked Wildcats (11-1) to the Big 12 title. Earlier in the day, Klein won the Johnny Unitas Award given to the top upperclassman quarterback in the nation.

Klein will finish his Kansas State career against No. 5 Oregon in the Fiesta Bowl.

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Global Update: GlaxoSmithKline Tops Access to Medicines Index

Sang Tan/Associated Press

GlaxoSmithKline hung on to its perennial top spot in the new Access to Medicines Index released last week, but its competitors are closing in.

Every two years, the index ranks the world’s top 20 pharmaceutical companies based on how readily they get medicines they hold patents on to the world’s poor, how much research they do on tropical diseases, how ethically they conduct clinical trials in poor countries, and similar issues.

Johnson & Johnson shot up to second place, while AstraZeneca fell to 16th from 7th. AstraZeneca has had major management shake-ups. It did not do less, but the industry is improving so rapidly that others outscored it, the report said.

The index was greeted with skepticism by some drugmakers when it was introduced in 2008. But now 19 of the 20 companies have a board member or subcommittee tracking how well they do at what the index measures, said David Sampson, the chief author.

The one exception was a Japanese company. As before, Japanese drugmakers ranked at or near the index’s bottom, and European companies clustered near the top. Generic companies — most of them Indian — that export to poor countries are ranked separately.

Johnson & Johnson moved up because it created an access team, disclosed more and bought Crucell, a vaccine company.

The foundation that creates the index now has enough money to continue for five more years, said its founder, Wim Leereveld, a former pharmaceutical executive.

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DealBook Column: For Buffett, the Long Run Still Trumps the Quick Return

“If somebody bought Berkshire Hathaway in 1965 and they held it, they made a great investment — and their broker would have starved to death.”

Warren E. Buffett was sitting across from me over lunch at a private club in Midtown Manhattan last week, lamenting the current state of Wall Street, which promotes a trading culture over an investing culture and offers incentives for brokers and traders to generate fees and fast profits.

“The emphasis on trading has increased. Just look at the turnover in all of the stocks,” he said, adding with a smile: “Sales people have forever gotten paid by selling people something. Generally, you pay a doctor for how often he gets you to change prescriptions.”

Mr. Buffett, 82, is famous for investing in companies that he sees as solid operations and essential to the economy, like railroads, utilities and financial companies, and holds his stakes for the long run. The argument that the markets are better off today because of the enormous amount of liquidity in the stock market, a function of quick flipping and electronic trading, is a fallacy, he said.

“You can’t buy 10 percent of the farmland in Nebraska in three years if you set out to do it,” he said. Yet, he pointed out, he was able to buy the equivalent of 10 percent of I.B.M. in six to eight months as a result of the market’s liquidity. “The idea that people look at their holdings in such a way that that kind of volume exists means that to a great extent, it’s a casino game,” he said. Of course, unlike many investors, he plans to hold his stake in I.B.M. for years.

Mr. Buffett was in a reminiscing mood about a bygone era, in part because he was in New York to make the rounds on television to discuss a new book chronicling his 61-year career, which began in 1951 at Buffett-Falk & Company in Omaha. (After lunch, he was going to visit “The Daily Show With Jon Stewart.”)

The book, “Tap Dancing to Work,” by a longtime journalist and good friend of his, Carol Loomis of Fortune magazine, is a compendium of articles that she and others wrote in Fortune that creates a series of narratives spanning the arc of his career.

Ms. Loomis, who first met Mr. Buffett in 1967 — and whose long career is a story unto itself — also came to our lunch. Ms. Loomis may know more about Mr. Buffett than he knows about himself. (“There’s nothing here you’re going to like,” she said, after surveying the various pies when the dessert cart came around. She was right: he took a quick look and asked if they served ice cream. They did.)

As we talked about the “good old days” — he spoke of some of his early friends who were successful hedge fund investors, like Julian Robertson, who founded Tiger Management — it became clear that he was less enamored of the investor class of the next generation.

When I asked, for example, if there were any private equity investors that he admired, he flatly replied: “No.”

When I asked if he followed any hedge fund managers, he struggled to name any, before saying that he liked Seth Klarman, a low-key value investor who runs the Baupost Group, based in Boston.

“They’re not as good as the old ones generally. The field has gotten swamped, so there’s so much money playing and people have been able to raise money by just saying ‘hedge fund,’” he said. “That was not the case earlier on; you really had to have some performance for some time before people would put money with you. It’s a marketing thing.”

For a moment, he paused, and then posited that if he started a hedge fund today, “I’d probably grow faster, because a record now would attract money a lot faster,” speculating that his record of returns would attract billions of dollars from pension funds and others. But he then acknowledged a truism of investing that he knows all too well, as the manager of an enterprise that is now worth some $220 billion: “Then money starts getting self-defeating at a point, too.”

Until 1969, Mr. Buffett operated a private partnership that was akin in some ways to a modern hedge fund, except the fee structure was decidedly different. Instead of charging “2 and 20” — a 2 percent management fee and 20 percent of profits — Mr. Buffett’s investors “keep all of the annual gains up to 6 percent; above that level Buffett takes a one-quarter cut,” Ms. Loomis wrote. However, in 1969, he announced he would shutter his partnership. “This is a market I don’t understand,” he said, according to Ms. Loomis.

He believed that the stock market of 1968 had become wildly overpriced — and he was right. By the end of 1974, the market took a tumble. Instead, he remained the chief executive of Berkshire Hathaway, one of his early investments.

“If you want to make a lot of money and you own a hedge fund or a private equity fund, there’s nothing like 2 and 20 and a lot of leverage,” he said over a lunch of Cobb salad. “If I kept my partnership and owned Berkshire through that, I would have made even more money.”

Mr. Buffett says he now considered himself as much a business manager as an investor. “The main thing I’m doing is trying to build a business, and now we built one. Investing is part of it but it is not the main thing.”

Today, Mr. Buffett is particularly circumspect about the investment strategies that hedge funds employ, like shorting, or betting against, a company’s stock. He used to short companies as part of a hedging strategy when he ran his partnership, but now he says that he and Charlie Munger, his longtime friend and vice chairman of Berkshire, see it as too hard.

“Charlie and I both have talked about it, we probably had a hundred ideas of things that would be good short sales. Probably 95 percent of them at least turned out to be, and I don’t think we would have made a dime out of it if we had been engaged in the activity. It’s too difficult,” he explained, suggesting that the timing of short investments is crucial. “The whole thing about ‘longs’ is, if you know you’re right, you can just keep buying, and the lower it goes, the better you like it, and you can’t do that with shorts.”

One of his big worries these days is about what’s going to happen to all the pension money that is being invested in the markets, often with little success, in part because investors are constantly buying and selling securities on the advice of brokers and advisers, rather than holding them for the long term. “Most institutional investors, whoever is in charge — whether it’s the college treasurer or the trustees of the pension fund of some state — they’re buying what they’re sold.”

Most pension funds probably didn’t buy Berkshire in 1965 and hold it, but if they had, they would have far fewer problems today. At the end of her book, Ms. Loomis notes that when she mentioned Mr. Buffett’s name for the first time in Fortune magazine in 1966 — accidentally spelling Buffett with only one “t” — Berkshire was trading at $22 a share. Today it is almost $133,000 a share.

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