Alzheimer’s Tied to Mutation Harming Immune Response

Alzheimer’s researchers and drug companies have for years concentrated on one hallmark of Alzheimer’s disease: the production of toxic shards of a protein that accumulate in plaques on the brain.

But now, in a surprising coincidence, two groups of researchers working from entirely different starting points have converged on a mutated gene involved in another aspect of Alzheimer’s disease: the immune system’s role in protecting against the disease. The mutation is suspected of interfering with the brain’s ability to prevent the buildup of plaque.

The discovery, researchers say, provides clues to how and why the disease progresses. The gene, known as TREM2, is only the second found to increase Alzheimer’s risk substantially in older people.

“It points very specifically to a potential metabolic pathway that you could intervene in to change the course of Alzheimer’s disease,” said William Thies, chief medical and scientific officer of the Alzheimer’s Association.

Much work remains to be done before scientists understand precisely how the newly discovered gene mutation leads to Alzheimer’s, but already there are some indications from studies in mice. When the gene is not mutated, white blood cells in the brain spring into action, gobbling up and eliminating the plaque-forming toxic protein, beta amyloid. As a result, Alzheimer’s can be staved off or averted.

But when the gene is mutated, the brain’s white blood cells are hobbled, making them less effective in their attack on beta amyloid.

People with the mutated gene have a threefold to fivefold increase in the likelihood of developing Alzheimer’s disease in old age.

The intact gene, says John Hardy of University College London, “is a safety net.” And those with the mutation, he adds, “are living life without a safety net.” Dr. Hardy is lead author of one of the papers.

The discovery also suggests that a new type of drug could be developed to enhance the gene’s activity, perhaps allowing the brain’s white blood cells to do their work.

“The field is in desperate need of new therapeutic agents,” said Alison Goate, an Alzheimer’s researcher at Washington University in St. Louis who contributed data to Dr. Hardy’s study. “This will give us an alternative approach.”

The fact that two research groups converged on the same gene gives experts confidence in the findings. Both studies were published online Wednesday in The New England Journal of Medicine. “Together they make a good case that this really is an Alzheimer’s gene,” said Gerard Schellenberg, an Alzheimer’s researcher at the University of Pennsylvania who was not involved with the work.

The other gene found to raise the odds that a person will get Alzheimer’s, ApoE4, is much more common and confers about the same risk as the mutated version of TREM2. But it is still not clear why ApoE4, discovered in 1993, makes Alzheimer’s more likely.

Because the mutations in the newly discovered gene are rare, occurring in no more than 2 percent of Alzheimer’s patients, it makes no sense to start screening people for them, Dr. Thies said. Instead, the discovery provides new clues to the workings of Alzheimer’s disease.

To find the gene, a research group led by Dr. Kari Stefansson of deCODE Genetics of Iceland started with a simple question.

“We asked, ‘Can we find anything in the genome that separates those who are admitted to nursing homes before the age of 75 and those who are still living at home at 85?’ ” he said.

Scientists searched the genomes of 2,261 Icelanders and zeroed in on TREM2. Mutations in that gene were more common among people with Alzheimer’s, as well as those who did not have an Alzheimer’s diagnosis but who had memory problems and might be on their way to developing Alzheimer’s.

The researchers confirmed their results by looking for the gene in people with and without Alzheimer’s in populations studied at Emory University, as well as in Norway, the Netherlands and Germany.

The TREM2 connection surprised Dr. Stefansson. Although researchers have long noticed that the brain is inflamed in Alzheimer’s patients, he had dismissed inflammation as a major factor in the disease.

“I was of the opinion that the immune system would play a fairly small role, if any, in Alzheimer’s disease,” Dr. Stefansson said. “This discovery cured me of that bias.”

Meanwhile, Dr. Hardy and Rita Guerreiro at University College London, along with Andrew Singleton at the National Institute on Aging, were intrigued by a strange, rare disease. Only a few patients had been identified, but their symptoms were striking. They had crumbling bones and an unusual dementia, sclerosing leukoencephalopathy.

“It’s a weird disease,” Dr. Hardy said.

He saw one patient in her 30s whose brain disease manifested in sexually inappropriate behavior. Also, her bones kept breaking. The disease was caused by mutations that disabled both the copy of TREM2 that she had inherited from her mother and the one from her father.

Eventually the researchers searched for people who had a mutation in just one copy of TREM2. To their surprise, it turned out that these people were likely to have Alzheimer’s disease.

They then asked researchers around the world who had genetic data from people with and without Alzheimer’s to look for TREM2 mutations.

“Sure enough, they had good evidence,” Dr. Hardy said. The mutations occurred in one-half of 1 percent of the general population but in 1 to 2 percent of patients with Alzheimer’s disease.

“That is a big effect,” Dr. Hardy said.

Read More..

Alzheimer’s Tied to Mutation Harming Immune Response

Alzheimer’s researchers and drug companies have for years concentrated on one hallmark of Alzheimer’s disease: the production of toxic shards of a protein that accumulate in plaques on the brain.

But now, in a surprising coincidence, two groups of researchers working from entirely different starting points have converged on a mutated gene involved in another aspect of Alzheimer’s disease: the immune system’s role in protecting against the disease. The mutation is suspected of interfering with the brain’s ability to prevent the buildup of plaque.

The discovery, researchers say, provides clues to how and why the disease progresses. The gene, known as TREM2, is only the second found to increase Alzheimer’s risk substantially in older people.

“It points very specifically to a potential metabolic pathway that you could intervene in to change the course of Alzheimer’s disease,” said William Thies, chief medical and scientific officer of the Alzheimer’s Association.

Much work remains to be done before scientists understand precisely how the newly discovered gene mutation leads to Alzheimer’s, but already there are some indications from studies in mice. When the gene is not mutated, white blood cells in the brain spring into action, gobbling up and eliminating the plaque-forming toxic protein, beta amyloid. As a result, Alzheimer’s can be staved off or averted.

But when the gene is mutated, the brain’s white blood cells are hobbled, making them less effective in their attack on beta amyloid.

People with the mutated gene have a threefold to fivefold increase in the likelihood of developing Alzheimer’s disease in old age.

The intact gene, says John Hardy of University College London, “is a safety net.” And those with the mutation, he adds, “are living life without a safety net.” Dr. Hardy is lead author of one of the papers.

The discovery also suggests that a new type of drug could be developed to enhance the gene’s activity, perhaps allowing the brain’s white blood cells to do their work.

“The field is in desperate need of new therapeutic agents,” said Alison Goate, an Alzheimer’s researcher at Washington University in St. Louis who contributed data to Dr. Hardy’s study. “This will give us an alternative approach.”

The fact that two research groups converged on the same gene gives experts confidence in the findings. Both studies were published online Wednesday in The New England Journal of Medicine. “Together they make a good case that this really is an Alzheimer’s gene,” said Gerard Schellenberg, an Alzheimer’s researcher at the University of Pennsylvania who was not involved with the work.

The other gene found to raise the odds that a person will get Alzheimer’s, ApoE4, is much more common and confers about the same risk as the mutated version of TREM2. But it is still not clear why ApoE4, discovered in 1993, makes Alzheimer’s more likely.

Because the mutations in the newly discovered gene are rare, occurring in no more than 2 percent of Alzheimer’s patients, it makes no sense to start screening people for them, Dr. Thies said. Instead, the discovery provides new clues to the workings of Alzheimer’s disease.

To find the gene, a research group led by Dr. Kari Stefansson of deCODE Genetics of Iceland started with a simple question.

“We asked, ‘Can we find anything in the genome that separates those who are admitted to nursing homes before the age of 75 and those who are still living at home at 85?’ ” he said.

Scientists searched the genomes of 2,261 Icelanders and zeroed in on TREM2. Mutations in that gene were more common among people with Alzheimer’s, as well as those who did not have an Alzheimer’s diagnosis but who had memory problems and might be on their way to developing Alzheimer’s.

The researchers confirmed their results by looking for the gene in people with and without Alzheimer’s in populations studied at Emory University, as well as in Norway, the Netherlands and Germany.

The TREM2 connection surprised Dr. Stefansson. Although researchers have long noticed that the brain is inflamed in Alzheimer’s patients, he had dismissed inflammation as a major factor in the disease.

“I was of the opinion that the immune system would play a fairly small role, if any, in Alzheimer’s disease,” Dr. Stefansson said. “This discovery cured me of that bias.”

Meanwhile, Dr. Hardy and Rita Guerreiro at University College London, along with Andrew Singleton at the National Institute on Aging, were intrigued by a strange, rare disease. Only a few patients had been identified, but their symptoms were striking. They had crumbling bones and an unusual dementia, sclerosing leukoencephalopathy.

“It’s a weird disease,” Dr. Hardy said.

He saw one patient in her 30s whose brain disease manifested in sexually inappropriate behavior. Also, her bones kept breaking. The disease was caused by mutations that disabled both the copy of TREM2 that she had inherited from her mother and the one from her father.

Eventually the researchers searched for people who had a mutation in just one copy of TREM2. To their surprise, it turned out that these people were likely to have Alzheimer’s disease.

They then asked researchers around the world who had genetic data from people with and without Alzheimer’s to look for TREM2 mutations.

“Sure enough, they had good evidence,” Dr. Hardy said. The mutations occurred in one-half of 1 percent of the general population but in 1 to 2 percent of patients with Alzheimer’s disease.

“That is a big effect,” Dr. Hardy said.

Read More..

Obama Meets C.E.O.’s as Fiscal Reckoning Nears

Luke Sharrett for The New York Times

Ursula M. Burns, chief of Xerox, said the president discussed few specifics of a potential agreement but emphasized that “we cannot go over the fiscal cliff.”

WASHINGTON — President Obama extended an olive branch to business leaders Wednesday, seeking their support as he prepared to negotiate with Congressional Republicans over the fiscal impasse in Washington.

If Congress and the president cannot reach a deal to reduce the deficit by January, more than $600 billion in tax increases and spending cuts will go into effect immediately — a prospect many chief executives and others warn could tip the economy back into recession.

Even so, Mr. Obama has some fence-mending to do before he can count on any serious backing from the business community.

“The president brought up that he hadn’t always had the best relationship with business, and he didn’t think he deserved that, but he understood that’s where things were and wanted it to be better,” said David M. Cote, chief executive of Honeywell. He was one of a dozen corporate leaders invited to meet Mr. Obama at the White House for 90 minutes Wednesday afternoon, after the president’s first news conference since the election.

While Mr. Obama did not present a detailed plan at Wednesday’s meeting or reveal what he would propose in terms of new corporate taxes, he strongly reiterated that he would not allow tax cuts for the middle class to expire. The president, according to attendees and aides, said he was committed to a balanced approach of reductions in entitlements and other government spending and increases in revenue.

With time running out, many observers expect the president and Republican leaders in Congress to come up with a short-term compromise that prevents the full slate of tax increases and spending cuts from hitting in January. That would give both sides more time to come up with a far-reaching deal on entitlement spending, even as they work on a broad tax overhaul later next year.

One corporate official briefed on the meeting said that the chief executives came away with a sense that Mr. Obama was poised to present a more formal proposal in the next few days, but that he did not press them for support on particular policies. “It was more of a back and forth,” he said.

The chief executives from some of the country’s biggest and best-known companies, including Procter & Gamble and I.B.M., were not unified on everything, according to one who was interviewed after the meeting.

Many of the executives who described the meeting would speak only on condition of anonymity.

The outreach to business comes as both the White House and corporate America maneuver ahead of the year-end deadline, as well as the beginning of Mr. Obama’s second term. Many executives were put off by what they saw as antibusiness rhetoric coming from the White House in his first term, and many also oppose tax increases on the rich that Mr. Obama favors but would hit them personally.

Both sides have plenty to gain from a better relationship. Business leaders want to buffer their image after the recession and the financial crisis, while Mr. Obama would gain valuable leverage if he could persuade even a few chief executives to come out in favor of higher taxes on people with incomes over $250,000.

Lloyd C. Blankfein, chief executive of Goldman Sachs, publicly endorsed higher tax rates in an opinion article published in The Wall Street Journal on Wednesday.

“I believe that tax increases, especially for the wealthiest, are appropriate, but only if they are joined by serious cuts in discretionary spending and entitlements,” he wrote.

While Mr. Blankfein and other Wall Street leaders have been speaking out about the dangers of the fiscal impasse, only one executive from the financial services industry, Kenneth I. Chenault of American Express, was at Wednesday’s meeting.

Afterward, the corporate leaders seemed pleased with the tone of the meeting but cautious about the prospect of finding common ground with the White House on the budget choices facing Congress and the president.

“I’d say everybody came away feeling pretty good about the whole discussion,” Mr. Cote said. “Now, all of us are C.E.O.’s, so we’ve learned not to confuse words with results. And that’s what we still need to see.”

Ursula M. Burns, chief executive of Xerox, who was also at the meeting, said afterward that it was clear that “we’re going to have to work through some sticking points.” But while “we didn’t get into too many specifics,” she said, it was also made clear that “we cannot go over the fiscal cliff.”

Ms. Burns’s comments about the potentially dire consequences of the fiscal impasse echoed those of other chief executives, including many in the Business Roundtable, which began an ad campaign Tuesday calling on lawmakers to resolve the issue quickly. The Campaign to Fix the Debt, a new group with a $40 million budget and the support of many Fortune 500 chiefs, began its own ad campaign on Monday.

Michael T. Duke, chief executive of Wal-Mart Stores, warned in a statement after the meeting that “before the end of the year, Washington needs to find an agreement to avoid the fiscal cliff.” He said Walmart customers “are working hard to adapt to the ‘new normal,’ but their confidence is still very fragile. They are shopping for Christmas now, and they don’t need uncertainty over a tax increase.”

 

Helene Cooper reported from Washington and Nelson D. Schwartz from New York. Jackie Calmes contributed reporting from Washington.

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White House Supports Top U.S. Commander in Afghanistan

WASHINGTON — Conflicting portrayals of e-mails written by Gen. John R. Allen, the top American and NATO commander in Afghanistan, emerged Tuesday after it was disclosed that the general was under investigation for what the Pentagon called “inappropriate communication” with the woman whose complaint to the F.B.I. set off the scandal involving David H. Petraeus’s extramarital affair.

Defense Secretary Leon E. Panetta and other officials traveling with him to Australia overnight on Monday disclosed the inquiry into General Allen’s e-mails with Jill Kelley, the woman in Tampa, Fla., who was seen by Paula Broadwell, Mr. Petraeus’s lover, as a rival for his attentions.

Mr. Panetta, along with Gen. Martin E. Dempsey, the chairman of the Joint Chiefs of Staff, referred the Allen matter to the Pentagon’s inspector general, according to Mr. Panetta’s aides, after a team of military and civilian lawyers reviewed what defense officials say are thousands of pages of documents, including hundreds of e-mails between General Allen and Ms. Kelley, that the F.B.I. forwarded to the Pentagon.

Associates of General Allen said Tuesday that the e-mails were innocuous. Some of them used terms of endearment, but not in a flirtatious way, the associates said. “If you know Allen, he’s just the kind of guy to respond dutifully to every e-mail he gets — ‘you’re the best,’ ‘you’re a sweetheart,’ that kind of thing,” according to a senior American official who is familiar with the investigation.

Even so, other Pentagon officials briefed on the content of the e-mails said that some of the language did, on initial reading, seem “overly flirtatious” and warranted further inquiry.

The Pentagon’s top lawyer, Jeh Johnson, recommended sending the matter to the inspector general, senior defense officials said. An inappropriate communication could violate military rules.

Senior officials in the Obama administration and lawmakers from both parties expressed shock at what could be a widening scandal into two of the most prominent generals of their generation: Mr. Petraeus, who was the top commander in Iraq and Afghanistan before he retired from the military to become director of the C.I.A., only to resign on Friday because of his affair, and General Allen, who also served in Iraq and now commands 68,000 American troops in Afghanistan.

President Obama, however, voiced support for General Allen through his spokesman on Tuesday. “The president thinks very highly of General Allen,” the spokesman, Jay Carney, said at a White House news briefing. “He has faith in General Allen.”

But the matter has created enough concern that General Allen’s recent nomination to become NATO’s top military officer was delayed at Mr. Panetta’s request, pending the investigation’s outcome.

Aides traveling with Mr. Panetta, reacting to anger from some of General Allen’s associates who said he was being unfairly treated, described Mr. Panetta as having great respect for General Allen. But they said that Mr. Panetta had little choice in referring the matter to the inspector general. General Dempsey informed General Allen of the investigation on Monday from Perth, where he had traveled for a security meeting that Mr. Panetta is also attending.

General Allen, a Marine, succeeded Mr. Petraeus as the top allied commander in Afghanistan in July 2011. He also served as Mr. Petraeus’s deputy when both officers led the military’s Central Command, based in Tampa, from 2008 until 2010.

General Allen’s connection to the scandal appears to have originated with an e-mail he received from an account that was registered under a fake name and has now been linked to Ms. Broadwell, according to a senior American official. The e-mail warned General Allen to be wary of Ms. Kelley and was vaguely threatening. Though he did not know who had written the e-mail, he was concerned and passed it on to Ms. Kelley. She then discussed it with an agent she knew at the F.B.I.’s field office in Tampa, Fla., whose cyber crime unit opened an investigation that eventually linked Ms. Broadwell to General Petraeus.

A senior law enforcement official in Washington said Tuesday that F.B.I. investigators, looking into Ms. Kelley’s complaint about anonymous e-mails she had received, examined all of her e-mails as a routine step. Officials familiar with the investigation said it covers 20,000 to 30,000 page of documents, but Pentagon officials cautioned against making too much of that number, since some might be from e-mail chains, or brief messages printed out on a whole page.

On Monday night, F.B.I. agents searched Ms. Broadwell’s home in Charlotte, N.C., and local television news crews filmed them carrying away boxes of material in what officials said was part of that continuing investigation.

The defense official said that the e-mails between Ms. Kelley and General Allen spanned the years 2010 to 2012.

American officials familiar with the social dynamics at the upper echelons of the Central Command described Ms. Kelley as wealthy socialite who knew “almost every” high- ranking officer serving in Tampa. Her ties were close enough that Mr. Petraeus and General Allen both intervened last September in a messy custody dispute on behalf of Jill Kelley’s twin sister, Natalie Khawam.

A senior official said Ms. Kelley was close to both General Allen and his wife. She would often send e-mails, hundreds over the course of any given year, to the couple about parties or people she had met or trips she was considering. General Allen was never alone with Ms. Kelley,  the official said, and while he may have been “affectionate in a few e-mails with her, there’s nothing he’s embarrassed about or embarrassed to tell his wife about.” 

Eric Schmitt reported from Washington, and Elisabeth Bumiller from Perth, Australia. Matt Rosenberg, Thom Shanker and Ron Nixon contributed reporting from Washington.

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Free Online Courses to Be Evaluated for Possible College Credit

While massive open online courses, or MOOCs, are still in their early days, the race has begun to integrate them into traditional colleges — by making them eligible for transfer credits, and by putting them to use in introductory and remedial courses.

On Tuesday, the American Council on Education, the leading umbrella group for higher education, and Coursera, a Silicon Valley MOOC provider, announced a pilot project to determine whether some free online courses are similar enough to traditional college courses that they should be eligible for credit.

The council’s credit evaluation process will begin early next year, using faculty teams to begin to assess how much students who successfully complete Coursera MOOCs have learned. Students who want to take the free classes for credit would have to pay a fee to take an identity-verified, proctored exam. If the faculty team deems the course worthy of academic credit, students who do well could pay for a transcript to submit to the college of their choice. Colleges are not required to accept those credits, but similar transcripts are already accepted by 2,000 United States colleges and universities for training courses offered by the military or by employers.

Coursera, founded last year by two Stanford computer professors, Daphne Koller and Andrew Ng, has 33 university partners and nearly two million students, who currently can earn certificates of completion, but not academic credit, for their work.

“I feel strongly that degrees are really valuable to people, and having MOOCs allow for credit down the line will increase the number of students with the confidence and wherewithal to complete degrees,” Professor Koller said. “If you’re a random student from another country, what are your chances of being admitted to a university here? But if you can show you’re a motivated student who’s completing five courses and done well on the proctored exam, I think a university would pay attention.”

The project is being watched closely by higher-education experts who expect MOOCs to broaden access to higher education and bring down the costs.

“With the additional benefits of ACE credit recommendation for Coursera courses, students will have an unprecedented opportunity to obtain recognized credentials for their work,” said William G. Bowen, the former president of Princeton University and the Mellon Foundation, and senior adviser to Ithaka, a nonprofit group devoted to digital technologies in higher education.

Also on Tuesday, the Bill and Melinda Gates Foundation announced 13 grants, totaling more than $3 million, for MOOC research. The grants are intended to encourage the development of MOOCs in introductory courses, like developmental math and writing, to see how they might be integrated into community colleges to bolster completion, and to develop a pathway for MOOC transfer credit.

While there is some overlap between the Coursera project and the Gates grants, only four of the nine schools that received grants are putting their MOOCs on Coursera, while the others use different platforms.

The largest grants go to three groups — the American council, Ithaka and the Association of Public and Land-Grant Universities — that will explore the credit issue, consider a possible consortium for collaborating on digital courseware, and research the University of Maryland’s experience with MOOCs.

“It certainly appears that there is potential here, and we ought to kick all the tires and see what we can learn,” said Molly Corbett Broad, the president of the American council.

Read More..

Kidney Donors Given Mandatory Safeguards

ST. LOUIS — Addressing long-held concerns about whether organ donors have adequate protections, the country’s transplant regulators acted late Monday to require that hospitals thoroughly inform living kidney donors of the risks they face, fully evaluate their medical and psychological suitability, and then track their health for two years after donation.

Enactment of the policies by the United Network for Organ Sharing, which manages the transplant system under a federal contract, followed six years of halting development and debate.

Meeting at a St. Louis hotel, the group’s board voted to establish uniform minimum standards for a field long regarded as a medical and ethical Wild West. The organ network, whose initial purpose was to oversee donation from people who had just died, has struggled at times to keep pace with rapid developments in donations from the living.

“There is no question that this is a major development in living donor protection,” said Dr. Christie P. Thomas, a nephrologist at the University of Iowa and the chairman of the network’s living donor committee.

Yet some donor advocates complained that the measures did not go far enough, and argued that the organ network, in its mission to encourage transplants, has a conflict of interest when it comes to safeguarding donors.

Three years ago, the network issued some of the same policies as voluntary guidelines, only to have the Department of Health and Human Services insist they be made mandatory.

Although long-term data on the subject is scarce, few living kidney donors are thought to suffer lasting physical or psychological effects. Kidney donations, known as nephrectomies, are typically done laparoscopically these days through a series of small incisions. The typical patient may spend only a few nights in a hospital and feel largely recovered after several months.

Kidneys are by far the most transplanted organs, and there have been nearly as many living donors as deceased ones over the last decade. What data is available suggests that those with one kidney typically live as long as those with two, and that the risk of a donor dying during the procedure is roughly 3 in 10,000.

But kidney transplants, like all surgery, can sometimes end in catastrophe.

In May at Montefiore Medical Center in the Bronx, a 41-year-old mother of three died when her aorta was accidentally cut during surgery to donate a kidney to her brother. In other recent isolated cases, patients have received donor kidneys infected with undetected H.I.V. or hepatitis C.

Less clear are any longer-term effects on donors. Research conducted by the United Network for Organ Sharing shows that of roughly 70,000 people who donated kidneys between late 1999 and early 2011, 27 died within two years of medical causes that may — or may not — have been related to donation. For a small number of donors, their remaining kidney failed, and they required dialysis or a transplant.

The number of living donors — 5,770 in 2011 — has dropped 10 percent over the last two years, possibly because the struggling economy has made it difficult for prospective donors to take time off from work to recuperate. With the national kidney waiting list now stretching past 94,000 people, and thousands on the list dying each year, transplant officials have said they must improve confidence in the system so more people will donate.

The average age of donors has been rising, posing additional medical risks. And new ethical questions have been raised by the emergence of paired kidney exchanges and transplant chains started by good Samaritans who give an organ to a stranger.

Brad Kornfeld, who donated a kidney to his father in 2004, told the board that it had been impossible to find good information about what to expect, leaving him to search for answers on unreliable Internet chat rooms. He said he had almost backed out.

“If information is power,” said Mr. Kornfeld, a Coloradan who serves on the living donor committee, “the lack of information is crippling.”

Under the policies approved this week, the organ network will require hospitals to collect medical data, including laboratory test results, on most living donors to study lasting effects. Results must be reported at six months, one year and two years.

Similar regulations have been in place since 2000, but they did not require blood and urine testing, and hospitals were allowed to report donors who could not be found as simply lost.

That happened often. In recent years, hospitals have submitted basic clinical information — like whether donors were alive or dead — for only 65 percent of donors and lab data for fewer than 40 percent, according to the organ network. Although the network holds the authority, no hospital has ever been seriously sanctioned for noncompliance.

“It’s time we put some teeth into our policy,” said Jill McMaster, a board member from Tennessee.

By 2015, transplant programs will have to report thorough clinical information on at least 80 percent of donors and lab results on at least 70 percent. The requirements phase in at lower levels for the next two years.

Dr. Stuart M. Flechner of the Cleveland Clinic, the chairman of a coalition of medical societies that made recommendations to the organ network, said 9 of 10 hospitals would currently not meet the new requirement.

Donna Luebke, a kidney donor from Ohio who once served on the organ network’s board, said the new standards would matter only if enforcement were more rigorous. She noted that the organization was dominated by transplant doctors: “UNOS is nothing but the foxes watching the henhouse,” she said.

Another of the new regulations prescribes in detail the medical and psychological screenings that hospitals must conduct for potential donors. It requires automatic exclusion if the potential donor has diabetes, uncontrolled hypertension or H.I.V., among other conditions.

The new policies also require that hospitals appoint an independent advocate to counsel and represent donors, and that donors receive detailed information in advance about medical, psychological and financial risks.

Read More..

Kidney Donors Given Mandatory Safeguards

ST. LOUIS — Addressing long-held concerns about whether organ donors have adequate protections, the country’s transplant regulators acted late Monday to require that hospitals thoroughly inform living kidney donors of the risks they face, fully evaluate their medical and psychological suitability, and then track their health for two years after donation.

Enactment of the policies by the United Network for Organ Sharing, which manages the transplant system under a federal contract, followed six years of halting development and debate.

Meeting at a St. Louis hotel, the group’s board voted to establish uniform minimum standards for a field long regarded as a medical and ethical Wild West. The organ network, whose initial purpose was to oversee donation from people who had just died, has struggled at times to keep pace with rapid developments in donations from the living.

“There is no question that this is a major development in living donor protection,” said Dr. Christie P. Thomas, a nephrologist at the University of Iowa and the chairman of the network’s living donor committee.

Yet some donor advocates complained that the measures did not go far enough, and argued that the organ network, in its mission to encourage transplants, has a conflict of interest when it comes to safeguarding donors.

Three years ago, the network issued some of the same policies as voluntary guidelines, only to have the Department of Health and Human Services insist they be made mandatory.

Although long-term data on the subject is scarce, few living kidney donors are thought to suffer lasting physical or psychological effects. Kidney donations, known as nephrectomies, are typically done laparoscopically these days through a series of small incisions. The typical patient may spend only a few nights in a hospital and feel largely recovered after several months.

Kidneys are by far the most transplanted organs, and there have been nearly as many living donors as deceased ones over the last decade. What data is available suggests that those with one kidney typically live as long as those with two, and that the risk of a donor dying during the procedure is roughly 3 in 10,000.

But kidney transplants, like all surgery, can sometimes end in catastrophe.

In May at Montefiore Medical Center in the Bronx, a 41-year-old mother of three died when her aorta was accidentally cut during surgery to donate a kidney to her brother. In other recent isolated cases, patients have received donor kidneys infected with undetected H.I.V. or hepatitis C.

Less clear are any longer-term effects on donors. Research conducted by the United Network for Organ Sharing shows that of roughly 70,000 people who donated kidneys between late 1999 and early 2011, 27 died within two years of medical causes that may — or may not — have been related to donation. For a small number of donors, their remaining kidney failed, and they required dialysis or a transplant.

The number of living donors — 5,770 in 2011 — has dropped 10 percent over the last two years, possibly because the struggling economy has made it difficult for prospective donors to take time off from work to recuperate. With the national kidney waiting list now stretching past 94,000 people, and thousands on the list dying each year, transplant officials have said they must improve confidence in the system so more people will donate.

The average age of donors has been rising, posing additional medical risks. And new ethical questions have been raised by the emergence of paired kidney exchanges and transplant chains started by good Samaritans who give an organ to a stranger.

Brad Kornfeld, who donated a kidney to his father in 2004, told the board that it had been impossible to find good information about what to expect, leaving him to search for answers on unreliable Internet chat rooms. He said he had almost backed out.

“If information is power,” said Mr. Kornfeld, a Coloradan who serves on the living donor committee, “the lack of information is crippling.”

Under the policies approved this week, the organ network will require hospitals to collect medical data, including laboratory test results, on most living donors to study lasting effects. Results must be reported at six months, one year and two years.

Similar regulations have been in place since 2000, but they did not require blood and urine testing, and hospitals were allowed to report donors who could not be found as simply lost.

That happened often. In recent years, hospitals have submitted basic clinical information — like whether donors were alive or dead — for only 65 percent of donors and lab data for fewer than 40 percent, according to the organ network. Although the network holds the authority, no hospital has ever been seriously sanctioned for noncompliance.

“It’s time we put some teeth into our policy,” said Jill McMaster, a board member from Tennessee.

By 2015, transplant programs will have to report thorough clinical information on at least 80 percent of donors and lab results on at least 70 percent. The requirements phase in at lower levels for the next two years.

Dr. Stuart M. Flechner of the Cleveland Clinic, the chairman of a coalition of medical societies that made recommendations to the organ network, said 9 of 10 hospitals would currently not meet the new requirement.

Donna Luebke, a kidney donor from Ohio who once served on the organ network’s board, said the new standards would matter only if enforcement were more rigorous. She noted that the organization was dominated by transplant doctors: “UNOS is nothing but the foxes watching the henhouse,” she said.

Another of the new regulations prescribes in detail the medical and psychological screenings that hospitals must conduct for potential donors. It requires automatic exclusion if the potential donor has diabetes, uncontrolled hypertension or H.I.V., among other conditions.

The new policies also require that hospitals appoint an independent advocate to counsel and represent donors, and that donors receive detailed information in advance about medical, psychological and financial risks.

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Afghan Warlord Ismail Khan’s Call to Arms Rattles Kabul

Bryan Denton for The New York Times

Supporters of Ismail Khan gathered outside Herat city on Nov. 1.

HERAT, Afghanistan — One of the most powerful mujahedeen commanders in Afghanistan, Ismail Khan, is calling on his followers to reorganize and defend the country against the Taliban as Western militaries withdraw, in a public demonstration of faltering confidence in the national government and the Western-built Afghan National Army.

Mr. Khan is one of the strongest of a group of warlords who defined the country’s recent history in battling the Soviets, the Taliban and one another, and who then were brought into President Hamid Karzai’s cabinet as a symbol of unity. Now, in announcing that he is remobilizing his forces, Mr. Khan has rankled Afghan officials and stoked fears that other regional and factional leaders will follow suit and rearm, weakening support for the government and increasing the likelihood of civil war.

This month, Mr. Khan rallied thousands of his supporters in the desert outside Herat, the cultured western provincial capital and the center of his power base, urging them to coordinate and reactivate their networks. And he has begun enlisting new recruits and organizing district command structures.

“We are responsible for maintaining security in our country and not letting Afghanistan be destroyed again,” Mr. Khan, the minister of energy and water, said at a news conference over the weekend at his office in Kabul. But after facing criticism, he took care not to frame his action as defying the government: “There are parts of the country where the government forces cannot operate, and in such areas the locals should step forward, take arms and defend the country.”

President Karzai and his aides, however, were not greeting it as an altruistic gesture. The governor of Herat Province called Mr. Khan’s reorganization an illegal challenge to the national security forces. And Mr. Karzai’s spokesman, Aimal Faizi, tersely criticized Mr. Khan.

“The remarks by Ismail Khan do not reflect the policies of the Afghan government,” Mr. Faizi said. “The government of Afghanistan and the Afghan people do not want any irresponsible armed grouping outside the legitimate security forces structures.”

In Kabul, Mr. Khan’s provocative actions have played out in the news media and brought a fierce reaction from some members of Parliament, who said the warlords were preparing to take advantage of the American troop withdrawal set for 2014.

“People like Ismail Khan smell blood,” Belqis Roshan, a senator from Farah Province, said in an interview. “They think that as soon as foreign forces leave Afghanistan, once again they will get the chance to start a civil war, and achieve their ominous goals of getting rich and terminating their local rivals.”

Indeed, Mr. Khan’s is not the only voice calling for a renewed alliance of the mujahedeen against the Taliban, and some of the others are just as familiar.

Marshal Muhammad Qasim Fahim, an ethnic Tajik commander who is President Karzai’s first vice president, said in a speech in September, “If the Afghan security forces are not able to wage this war, then call upon the mujahedeen.”

Another prominent mujahedeen fighter, Ahmad Zia Massoud, said in an interview at his home in Kabul that people were worried about what was going to happen after 2014, and he was telling his own followers to make preliminary preparations.

“They don’t want to be disgraced again,” Mr. Massoud said. “Everyone tries to have some sort of Plan B. Some people are on the verge of rearming.”

He pointed out that it was significant that the going market price of Kalashnikov assault rifles had risen to about $1,000, driven up by demand from a price of $300 a decade ago. “Every household wants to have an AK-47 at home,” he said.

“The mujahedeen come here to meet me,” Mr. Massoud added. “They tell me they are preparing. They are trying to find weapons. They come from villages, from the north of Afghanistan, even some people from the suburbs of Kabul, and say they are taking responsibility for providing private security in their neighborhood.”

Habib Zahori and Jawad Sukhanyar contributed reporting from Herat, Afghanistan, and an employee of The New York Times from Kabul.

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Bits Blog: Windows Chief Sinofsky Leaving Microsoft

Steven Sinofsky, the leader of Microsoft‘s Windows business, is leaving the company, just weeks after the company released the biggest overhaul in decades of its flagship product.

Microsoft described the departure of Mr. Sinfosky, a 23-year veteran of the company, as a mutual decision by Mr. Sinofsky and Steven A. Ballmer, the chief executive of the company. Julie Larson-Green, another Microsoft veteran in its Windows division, will take over the leadership of all engineering responsibilities related to Windows. Tami Reller, the chief financial officer of the Windows division, will run business and marketing for the group.

Mr. Sinofsky was seen as one of the most competent managers within Microsoft and earned high marks for helping to improve the quality of its software after the company released Windows Vista, a widely criticized version of the operating system. His name was often floated by people speculating about a possible successor to Mr. Ballmer, who has announced no plans to retire from the company.

But Mr. Sinofsky was also a polarizing figure who alienated many other members of Microsoft’s senior leadership team. For that reason, he was seen by many insiders as an unlikely replacement for Mr. Ballmer.

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‘Dream Team’ of Behavioral Scientists Advised Obama Campaign

Late last year Matthew Barzun, an official with the Obama campaign, called Craig Fox, a psychologist in Los Angeles, and invited him to a political planning meeting in Chicago, according to two people who attended the session.

“He said, ‘Bring the whole group; let’s hear what you have to say,’ ” recalled Dr. Fox, a behavioral economist at the University of California, Los Angeles.

So began an effort by a team of social scientists to help their favored candidate in the 2012 presidential election. Some members of the team had consulted with the Obama campaign in the 2008 cycle, but the meeting in January signaled a different direction.

“The culture of the campaign had changed,” Dr. Fox said. “Before then I felt like we had to sell ourselves; this time there was a real hunger for our ideas.”

This election season the Obama campaign won a reputation for drawing on the tools of social science. The book “Victory Lab,” by Sasha Issenberg, and news reports have portrayed an operation that ran its own experiment and, among other efforts, consulted with the Analyst Institute, a Washington voter research group established in 2007 by union officials and their allies to help Democratic candidates.

Less well known is that the Obama campaign also had a panel of unpaid academic advisers. The group — which calls itself the “consortium of behavioral scientists,” or COBS — provided ideas on how to counter false rumors, like one that President Obama is a Muslim. It suggested how to characterize the Republican opponent, Mitt Romney, in advertisements. It also delivered research-based advice on how to mobilize voters.

“In the way it used research, this was a campaign like no other,” said Todd Rogers, a psychologist at Harvard’s Kennedy School of Government and a former director of the Analyst Institute. “It’s a big change for a culture that historically has relied on consultants, experts and gurulike intuition.”

When asked about the outside psychologists, the Obama campaign would neither confirm nor deny a relationship with them. “This campaign was built on the energy, enthusiasm and ingenuity of thousands of grass-roots supporters and our staff in the states and in Chicago,” said Adam Fetcher, a campaign spokesman. “Throughout the campaign we saw an outpouring of individuals across the country who lent a wide variety of ideas and input to our efforts to get the president re-elected.”

For their part, consortium members said they did nothing more than pass on research-based ideas, in e-mails and conference calls. They said they could talk only in general terms about the research, because they had signed nondisclosure agreements with the campaign.

In addition to Dr. Fox, the consortium included Susan T. Fiske of Princeton University; Samuel L. Popkin of the University of California, San Diego; Robert Cialdini, a professor emeritus at Arizona State University; Richard H. Thaler, a professor of behavioral science and economics at the University of Chicago’s business school; and Michael Morris, a psychologist at Columbia.

“A kind of dream team, in my opinion,” Dr. Fox said.

He said that the ideas the team proposed were “little things that can make a difference” in people’s behavior.

For example, Dr. Fiske’s research has shown that when deciding on a candidate, people generally focus on two elements: competence and warmth. “A candidate wants to make sure to score high on both dimensions,” Dr. Fiske said in an interview. “You can’t just run on the idea that everyone wants to have a beer with you; some people care a whole lot about competence.”

Mr. Romney was recognized as a competent businessman, polling found. But he was often portrayed in opposition ads as distant, unable to relate to the problems of ordinary people.

When it comes to countering rumors, psychologists have found that the best strategy is not to deny the charge (“I am not a flip-flopper”) but to affirm a competing notion. “The denial works in the short term; but in the long term people remember only the association, like ‘Obama and Muslim,’ ” said Dr. Fox, of the persistent false rumor.

The president’s team affirmed that he is a Christian.

At least some of the consortium’s proposals seemed to have found their way into daily operations. Campaign volunteers who knocked on doors last week in swing states like Pennsylvania, Ohio and Nevada did not merely remind people to vote and arrange for rides to the polls. Rather, they worked from a script, using subtle motivational techniques that research has shown can prompt people to take action.

“We used the scripts more as a guide,” said Sarah Weinstein, 18, a Columbia freshman who traveled with a group to Cleveland the weekend before the election. “The actual language we used was invested in the individual person.”

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