DNA Analysis, More Accessible Than Ever, Opens New Doors

Matt Roth for The New York Times

Sam Bosley of Frederick, Md., going shopping with his daughter, Lillian, 13, who has a malformed brain and severe developmental delays, seizures and vision problems. More Photos »

Debra Sukin and her husband were determined to take no chances with her second pregnancy. Their first child, Jacob, who had a serious genetic disorder, did not babble when he was a year old and had severe developmental delays. So the second time around, Ms. Sukin had what was then the most advanced prenatal testing.

The test found no sign of Angelman syndrome, the rare genetic disorder that had struck Jacob. But as months passed, Eli was not crawling or walking or babbling at ages when other babies were.

“Whatever the milestones were, my son was not meeting them,” Ms. Sukin said.

Desperate to find out what is wrong with Eli, now 8, the Sukins, of The Woodlands, Tex., have become pioneers in a new kind of testing that is proving particularly helpful in diagnosing mysterious neurological illnesses in children. Scientists sequence all of a patient’s genes, systematically searching for disease-causing mutations.

A few years ago, this sort of test was so difficult and expensive that it was generally only available to participants in research projects like those sponsored by the National Institutes of Health. But the price has plunged in just a few years from tens of thousands of dollars to around $7,000 to $9,000 for a family. Baylor College of Medicine and a handful of companies are now offering it. Insurers usually pay.

Demand has soared — at Baylor, for example, scientists analyzed 5 to 10 DNA sequences a month when the program started in November 2011. Now they are doing more than 130 analyses a month. At the National Institutes of Health, which handles about 300 cases a year as part of its research program, demand is so great that the program is expected to ultimately take on 800 to 900 a year.

The test is beginning to transform life for patients and families who have often spent years searching for answers. They can now start the grueling process with DNA sequencing, says Dr. Wendy K. Chung, professor of pediatrics and medicine at Columbia University.

“Most people originally thought of using it as a court of last resort,” Dr. Chung said. “Now we can think of it as a first-line test.”

Even if there is no treatment, there is almost always some benefit to diagnosis, geneticists say. It can give patients and their families the certainty of knowing what is wrong and even a prognosis. It can also ease the processing of medical claims, qualifying for special education services, and learning whether subsequent children might be at risk.

“Imagine the people who drive across the whole country looking for that one neurologist who can help, or scrubbing the whole house with Lysol because they think it might be an allergy,” said Richard A. Gibbs, the director of Baylor College of Medicine’s gene sequencing program. “Those kinds of stories are the rule, not the exception.”

Experts caution that gene sequencing is no panacea. It finds a genetic aberration in only about 25 to 30 percent of cases. About 3 percent of patients end up with better management of their disorder. About 1 percent get a treatment and a major benefit.

“People come to us with huge expectations,” said Dr. William A. Gahl, who directs the N.I.H. program. “They think, ‘You will take my DNA and find the causes and give me a treatment.' ”

“We give the impression that we can do these things because we only publish our successes,” Dr. Gahl said, adding that when patients come to him, “we try to make expectations realistic.”

DNA sequencing was not available when Debra and Steven Sukin began trying to find out what was wrong with Eli. When he was 3, they tried microarray analysis, a genetic test that is nowhere near as sensitive as sequencing. It detected no problems.

“My husband and I looked at each other and said, ‘The good news is that everything is fine; the bad news is that everything is not fine,' ” Ms. Sukin said.

In November 2011, when Eli was 6, Ms. Sukin consulted Dr. Arthur L. Beaudet, a medical geneticist at Baylor.

“Is there a protein missing?” she recalled asking him. “Is there something biochemical we could be missing?”

By now, DNA sequencing had come of age. Dr. Beaudet said that Eli was a great candidate, and it turned out that the new procedure held an answer.

A single DNA base was altered in a gene called CASK, resulting in a disorder so rare that there are fewer than 10 cases in all the world’s medical literature.

“It really became definitive for my husband and me,” Ms. Sukin said. “We would need to do lifelong planning for dependent care for the rest of his life.”

This article has been revised to reflect the following correction:

Correction: February 19, 2013

An earlier version of this article misstated the name of a medicine taken by two teenagers who have a rare gene mutation. The drug is 5-hydroxytryptophan, not 5-hydroxytryptamine.

Read More..

DNA Analysis, More Accessible Than Ever, Opens New Doors

Matt Roth for The New York Times

Sam Bosley of Frederick, Md., going shopping with his daughter, Lillian, 13, who has a malformed brain and severe developmental delays, seizures and vision problems. More Photos »

Debra Sukin and her husband were determined to take no chances with her second pregnancy. Their first child, Jacob, who had a serious genetic disorder, did not babble when he was a year old and had severe developmental delays. So the second time around, Ms. Sukin had what was then the most advanced prenatal testing.

The test found no sign of Angelman syndrome, the rare genetic disorder that had struck Jacob. But as months passed, Eli was not crawling or walking or babbling at ages when other babies were.

“Whatever the milestones were, my son was not meeting them,” Ms. Sukin said.

Desperate to find out what is wrong with Eli, now 8, the Sukins, of The Woodlands, Tex., have become pioneers in a new kind of testing that is proving particularly helpful in diagnosing mysterious neurological illnesses in children. Scientists sequence all of a patient’s genes, systematically searching for disease-causing mutations.

A few years ago, this sort of test was so difficult and expensive that it was generally only available to participants in research projects like those sponsored by the National Institutes of Health. But the price has plunged in just a few years from tens of thousands of dollars to around $7,000 to $9,000 for a family. Baylor College of Medicine and a handful of companies are now offering it. Insurers usually pay.

Demand has soared — at Baylor, for example, scientists analyzed 5 to 10 DNA sequences a month when the program started in November 2011. Now they are doing more than 130 analyses a month. At the National Institutes of Health, which handles about 300 cases a year as part of its research program, demand is so great that the program is expected to ultimately take on 800 to 900 a year.

The test is beginning to transform life for patients and families who have often spent years searching for answers. They can now start the grueling process with DNA sequencing, says Dr. Wendy K. Chung, professor of pediatrics and medicine at Columbia University.

“Most people originally thought of using it as a court of last resort,” Dr. Chung said. “Now we can think of it as a first-line test.”

Even if there is no treatment, there is almost always some benefit to diagnosis, geneticists say. It can give patients and their families the certainty of knowing what is wrong and even a prognosis. It can also ease the processing of medical claims, qualifying for special education services, and learning whether subsequent children might be at risk.

“Imagine the people who drive across the whole country looking for that one neurologist who can help, or scrubbing the whole house with Lysol because they think it might be an allergy,” said Richard A. Gibbs, the director of Baylor College of Medicine’s gene sequencing program. “Those kinds of stories are the rule, not the exception.”

Experts caution that gene sequencing is no panacea. It finds a genetic aberration in only about 25 to 30 percent of cases. About 3 percent of patients end up with better management of their disorder. About 1 percent get a treatment and a major benefit.

“People come to us with huge expectations,” said Dr. William A. Gahl, who directs the N.I.H. program. “They think, ‘You will take my DNA and find the causes and give me a treatment.' ”

“We give the impression that we can do these things because we only publish our successes,” Dr. Gahl said, adding that when patients come to him, “we try to make expectations realistic.”

DNA sequencing was not available when Debra and Steven Sukin began trying to find out what was wrong with Eli. When he was 3, they tried microarray analysis, a genetic test that is nowhere near as sensitive as sequencing. It detected no problems.

“My husband and I looked at each other and said, ‘The good news is that everything is fine; the bad news is that everything is not fine,' ” Ms. Sukin said.

In November 2011, when Eli was 6, Ms. Sukin consulted Dr. Arthur L. Beaudet, a medical geneticist at Baylor.

“Is there a protein missing?” she recalled asking him. “Is there something biochemical we could be missing?”

By now, DNA sequencing had come of age. Dr. Beaudet said that Eli was a great candidate, and it turned out that the new procedure held an answer.

A single DNA base was altered in a gene called CASK, resulting in a disorder so rare that there are fewer than 10 cases in all the world’s medical literature.

“It really became definitive for my husband and me,” Ms. Sukin said. “We would need to do lifelong planning for dependent care for the rest of his life.”

This article has been revised to reflect the following correction:

Correction: February 19, 2013

An earlier version of this article misstated the name of a medicine taken by two teenagers who have a rare gene mutation. The drug is 5-hydroxytryptophan, not 5-hydroxytryptamine.

Read More..

Obama Turns Up Pressure for Deal on Budget Cuts

Seeking to Avoid the Sequester:
The Times’s Michael D. Shear on how President Obama put pressure on Congress to avoid the across-the-board budget cuts.

WASHINGTON — Days away from another fiscal crisis and with Congress on vacation, President Obama began marshaling the powers of the presidency on Tuesday to try to shame Republicans into a compromise that could avoid further self-inflicted job losses and damage to the fragile recovery. But so far, Republicans were declining to engage.

To turn up the pressure on the absent lawmakers, Mr. Obama warned in calamitous terms of the costs to military readiness, domestic investments and vital services if a “meat-cleaver” approach of indiscriminate, across-the-board spending cuts takes effect on March 1. Surrounding him in a White House auditorium were solemn, uniformed emergency responders, invited to illustrate the sort of critical services at risk.

The president plans to keep up the pressure through next week for an alternative deficit-reduction deal that includes both spending cuts and new revenues through closing tax loopholes. He will have daily events underscoring the potential ramifications of the automatic cuts, aides said, and next week will travel outside Washington to take his case to the public, as he did late last year in another fiscal fight on which he prevailed.

In stern tones, Mr. Obama said that the automatic cuts, known in budget terms as a sequester, would “affect our responsibility to respond to threats in unstable parts of the world” and “add thousands of Americans to the unemployment rolls.”

He framed the debate in the way that he hopes will force Republicans into accepting some higher tax revenues, something they so far refuse to do.

“Republicans in Congress face a simple choice,” Mr. Obama said. “Are they willing to compromise to protect vital investments in education and health care and national security and all the jobs that depend on them, or would they rather put hundreds of thousands of jobs and our entire economy at risk just to protect a few special-interest tax loopholes that benefit only the wealthiest Americans and biggest corporations?”

Mr. Obama once again finds himself in a budget showdown with the opposing party, and numerous polls show his position to be more popular than Republican calls for spending cuts only, including cuts in Medicare. Mr. Obama and senior aides hardly disguised their sense of political advantage.

“We are trouncing them,” said one senior administration official about the Republicans.

Still, the president’s leverage might in fact be limited, since by all appearances he seems to want a deal far more than Republicans do. As the leader of the nation, Mr. Obama is eager to see an end to the repeated evidence of Washington dysfunction, or what he referred to again on Tuesday as the cycle of “manufactured crisis.” And with his legacy ultimately at stake, he needs to lift the fiscal uncertainty that since 2011 has held down economic growth.

Despite the risks of an impasse for Republicans, those who control the House have all but forfeited this battle to Mr. Obama and seem poised to let the automatic cuts take effect. Many Republicans, particularly newer members elected with Tea Party support, have pushed party leaders to accept the sequester and lock in the spending cuts rather than compromise. The leaders seem to have decided to wage battle later this spring in the larger fight over the annual federal budget.

Contributing to Republican calculations is the fact that at least in the short term, an impasse over the sequester is not as potentially catastrophic as the threats that loomed in past partisan showdowns, like a full shutdown of government or the nation’s first-ever default on its global debt obligations.

The potential impact is potentially hazardous nonetheless, both economically and politically. As Mr. Obama noted, the prospect of the sequester has already affected military deployments and hiring by military contractors, and threatens layoffs of teachers, air traffic controllers and researchers, among others.

Hours after the president’s remarks, economic forecasters at Macroeconomic Advisers, based in St. Louis, projected that sequestration would reduce the firm’s forecast of growth this year by nearly a quarter, 0.6 percent, and cost roughly 700,000 civilian and military jobs through 2014, with heightened unemployment lingering for several years.

“By far the preferable policy,” the analysis said, “is a credible long-term plan to shrink the deficit more slowly through some combination of revenue increases within broad tax reform” as well as “more carefully considered cuts” in spending programs, including Medicare and Medicaid. That prescription for both long-term spending reductions and revenue increases, as an alternative to immediate deep spending cuts that inhibit job growth, generally tracks Mr. Obama’s approach.

He has proposed $1.5 trillion in spending cuts over 10 years and revenue increases that would build on the roughly $2.5 trillion over the decade that he and Congress have agreed to in the past two years. The total, $4 trillion, is the minimum reduction that many economists say is necessary to stabilize the growth of the nation’s debt at a time when the population is aging and health care costs are rising.

That approach mixing spending cuts and increased revenues got another endorsement on Tuesday when the chairmen of Mr. Obama’s 2010 debt-reduction commission — former Senator Alan K. Simpson, a Republican, and Erskine B. Bowles, a Democrat and former chief of staff to President Bill Clinton — released a revised fiscal plan that would reduce annual deficits by $2.4 trillion in a decade through spending cuts, including in Medicare and Social Security benefits, and an overhaul of the tax system.

But Republicans say they will not consider additional tax increases since Mr. Obama in January won more than $600 billion over 10 years in higher revenues from the wealthiest taxpayers. “The revenue debate is now closed,” Speaker John A. Boehner said in a statement reacting to the president’s remarks.

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Briefs | Middle East: Iran: Rivals Forced to Apologize to Supreme Leader

Rival politicians apologized to Ayatollah Ali Khamenei over the weekend for having been embroiled in an unusually public feud involving secret tapes and a tit-for-tat impeachment. On Sunday, President Mahmoud Ahmadinejad; the Parliament speaker, Ali Larijani; his brother, Sadegh Larijani; the chief of Iran’s judiciary; and all members of Parliament sent letters expressing sorrow and promising renewed allegiance to Ayatollah Khamenei, the supreme leader of Iran. The written apologies, reported by the state-run press, came a day after the ayatollah had criticized both Mr. Ahmadinejad and the Larijanis for letting their own mutual animosity become public, raising speculation of irreparable rifts. The ayatollah had said in a speech that the whole matter “made me feel sad.”

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Rise of Drones in U.S. Spurs Efforts to Limit Uses

Colin Diltz/The Seattle Times, via Associated Press

A Seattle police officer, Jim Britt, with a drone in October. Seattle later banned use of the devices.

They can record video images and produce heat maps. They can be used to track fleeing criminals, stranded hikers — or just as easily, political protesters. And for strapped police departments, they are more affordable than helicopters.

Drones are becoming a darling of law enforcement authorities across the country. But they have given rise to fears of government surveillance, in many cases even before they take to the skies. And that has prompted local and state lawmakers from Seattle to Tallahassee to outline how they can be used by police or to ground them altogether.

Although surveillance technologies have become ubiquitous in American life, like license plate readers or cameras for catching speeders, drones have evoked unusual discomfort in the public consciousness.

“To me, it’s Big Brother in the sky,” said Dave Norris, a city councilman in Charlottesville, Va., which this month became the first city in the country to restrict the use of drones. “I don’t mean to sound conspiratorial about it, but these drones are coming, and we need to put some safeguards in place so they are not abused.”

In Charlottesville, police officers are prohibited from using in criminal cases any evidence obtained by drones, also known as unmanned aerial vehicles. Never mind that the city police department does not have a drone, nor has it suggested buying one. The police are not barred from using drones for other efforts, like search and rescue.

Mr. Norris said the advent of new policing technologies poses new policy dilemmas for his city.

Charlottesville permits the police to install cameras temporarily in areas known for drug dealing, but it has rebuffed a police request to install cameras along its downtown shopping corridor. It has also chosen not to install cameras at traffic lights to intercept speeding cars, as is common elsewhere.

“Drones are capable of taking surveillance to a whole new level,” Mr. Norris said.

Last week, the Seattle Police Department agreed to return its two still-unused drones to the manufacturer after Mayor Michael McGinn answered public protests by banning their use. On Thursday, the Alameda County Board of Supervisors in Oakland, Calif., listened to the county sheriff’s proposal to use federal money to buy a four-pound drone to help his officers track suspected criminals — and then listened to raucous opposition from the antidrone lobby, including a group that uses the Twitter handle @N.O.M.B.Y., short for Not Over My Back Yard.

This week, members of Congress introduced a bill that would prohibit drones from conducting what it called “targeted surveillance” of individuals and property without a warrant.

A federal law enacted last year paved the way for drones to be used commercially and made it easier for government agencies to obtain them. The Department of Homeland Security offered grants to help local law enforcement buy them. Drone manufacturers began to market small, lightweight devices specifically for policing. Drones are already used to monitor movement on the United States’ borders and by a handful of police departments, and emergency services agencies around the country are just beginning to explore their uses.

The Federal Aviation Administration has received about 80 requests, including some from police and other government agencies, for clearance to fly drones, according to a Freedom of Information Act request filed by the Electronic Frontier Foundation, which seeks to limit their use for police surveillance.

Law enforcement authorities say drones can be a cost-effective technology to help with a host of policing efforts, like locating bombs, finding lost children, monitoring weather and wildlife or assisting rescue workers in natural disasters.

“In this time of austerity, we are always looking for sensible and cost-effective methods to improve public safety,” said Capt. Tom Madigan of the Alameda County Sheriff’s Department. “We are not looking at military-grade Predator drones. They are not armed.”

For now, drones for civilian use run on relatively small batteries and fly short distances. In principle, various sensors, including cameras, can be attached to them. But there is no consensus in law on how the data collected can be used, shared or stored.

This article has been revised to reflect the following correction:

Correction: February 18, 2013

An earlier version of this article rendered incorrectly part of the name of the federal department that offered grants to local law enforcement agencies to purchase drones. It is the Department of Homeland Security, not Services.

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Personal Health: Health Effects of Smoking for Women

The title of a recent report on smoking and health might well have paraphrased the popular ad campaign for Virginia Slims, introduced in 1968 by Philip Morris and aimed at young professional women: “You’ve come a long way, baby.”

Today that slogan should include: “. . . toward a shorter life.” Ten years shorter, in fact.

The new report is one of two rather shocking analyses of the hazards of smoking and the benefits of quitting published last month in The New England Journal of Medicine. The data show that “women who smoke like men die like men who smoke,” Dr. Steven A. Schroeder, a professor of health and health care at the University of California, San Francisco, wrote in an accompanying editorial.

That was not always the case. Half a century ago, the risk of death from lung cancer among men who smoked was five times higher than that among women smokers. But by the first decade of this century, that risk had equalized: for both men and women who smoked, the risk of death from lung cancer was 25 times greater than for nonsmokers, Dr. Michael J. Thun of the American Cancer Society and his colleagues reported.

Today, women who smoke are even more likely than men who smoke to die of lung cancer. According to a second study in the same journal, women smokers face a 17.8 times greater risk of dying of lung cancer, than women who do not smoke; men who smoke are at 14.6 times greater risk to die of lung cancer than men who don’t. Women who smoke now face a risk of death from lung cancer that is 50 percent higher than the estimates reported in the 1980s, according to Dr. Prabhat Jha of the Center for Global Health Research in Toronto and his colleagues.

After controlling for age, body weight, education level and alcohol use, the new analysis found something else: men and women who continue to smoke die on average more than 10 years sooner than those who never smoked.

Dramatic progress has been made in reducing the prevalence of smoking, which has fallen in the United States from 42 percent of adults in 1965 (the year after the first surgeon general’s report on smoking and health) to 19 percent in 2010. Yet smoking still results in nearly 200,000 deaths a year among people 35 to 69 years old in this country. A quarter of all deaths in this age group would not occur if smokers had the same risk of death as nonsmokers.

The risks are even greater among men 55 to 74 and women 60 to 74. More than two-thirds of all deaths among current smokers in these age groups are related to smoking. Over all, the death rate from all causes combined in these age groups “is now at least three times as high among current smokers as among those who have never smoked,” Dr. Thun’s team found.

While lung cancer is the most infamous hazard linked to smoking, the habit also raises the risk of death from heart disease, stroke, pulmonary disease and other cancers, including breast cancer.

Furthermore, changes in how cigarettes are manufactured may have increased the dangers of smoking. The use of perforated filters, tobacco blends that are less irritating, and paper that is more porous made it easier to inhale smoke and encouraged deeper inhalation to achieve satisfying blood levels of nicotine.

The result of deeper inhalation, Dr. Thun’s report suggests, has been an increased risk of chronic obstructive pulmonary disease, or C.O.P.D., and a shift in the kind of lung cancer linked to smoking. Among nonsmokers, the risk of death from C.O.P.D. has declined by 45 percent in men and has remained stable in women, but the death rate has more than doubled among smokers.

But there is good news, too: it’s never too late to reap the benefits of quitting. The younger you are when you stop smoking, the greater your chances of living a long and healthy life, according to the findings of Dr. Jha’s international team.

The team analyzed smoking and smoking-cessation histories of 113,752 women and 88,496 men 25 and older and linked them to causes of deaths in these groups through 2006.

Those who quit smoking by age 34 lived 10 years longer on average than those who continued to smoke, giving them a life expectancy comparable to people who never smoked. Smokers who quit between ages 35 and 44 lived nine years longer, and those who quit between 45 and 54 lived six years longer. Even quitting smoking between ages 55 and 64 resulted in a four-year gain in life expectancy.

The researchers emphasized, however, that the numbers do not mean it is safe to smoke until age 40 and then stop. Former smokers who quit by 40 still experienced a 20 percent greater risk of death than nonsmokers. About one in six former smokers who died before the age of 80 would not have died so young if he or she had never smoked, they reported.

Dr. Schroeder believes we can do a lot better to reduce the prevalence of smoking with the tools currently in hand if government agencies, medical insurers and the public cooperate.

Unlike the races, ribbons and fund-raisers for breast cancer, “there’s no public face for lung cancer, even though it kills more women than breast cancer does,” Dr. Schroeder said in an interview. Lung cancer is stigmatized as a disease people bring on themselves, even though many older victims were hooked on nicotine in the 1940s and 1950s, when little was known about the hazards of smoking and doctors appeared in ads assuring the public it was safe to smoke.

Raising taxes on cigarettes can help. The states with the highest prevalence of smoking have the lowest tax rates on cigarettes, Dr. Schroeder said. Also helpful would be prohibiting smoking in more public places like parks and beaches. Some states have criminalized smoking in cars when children are present.

More “countermarketing” of cigarettes is needed, he said, including antismoking public service ads on television and dramatic health warnings on cigarette packs, as is now done in Australia. But two American courts have ruled that the proposed label warnings infringed on the tobacco industry’s right to free speech.

Health insurers, both private and government, could broaden their coverage of stop-smoking aids and better publicize telephone quit lines, and doctors “should do more to stimulate quit attempts,” Dr. Schroeder said.

As Nicola Roxon, a former Australian health minister, put it, “We are killing people by not acting.”

Read More..

Personal Health: Health Effects of Smoking for Women

The title of a recent report on smoking and health might well have paraphrased the popular ad campaign for Virginia Slims, introduced in 1968 by Philip Morris and aimed at young professional women: “You’ve come a long way, baby.”

Today that slogan should include: “. . . toward a shorter life.” Ten years shorter, in fact.

The new report is one of two rather shocking analyses of the hazards of smoking and the benefits of quitting published last month in The New England Journal of Medicine. The data show that “women who smoke like men die like men who smoke,” Dr. Steven A. Schroeder, a professor of health and health care at the University of California, San Francisco, wrote in an accompanying editorial.

That was not always the case. Half a century ago, the risk of death from lung cancer among men who smoked was five times higher than that among women smokers. But by the first decade of this century, that risk had equalized: for both men and women who smoked, the risk of death from lung cancer was 25 times greater than for nonsmokers, Dr. Michael J. Thun of the American Cancer Society and his colleagues reported.

Today, women who smoke are even more likely than men who smoke to die of lung cancer. According to a second study in the same journal, women smokers face a 17.8 times greater risk of dying of lung cancer, than women who do not smoke; men who smoke are at 14.6 times greater risk to die of lung cancer than men who don’t. Women who smoke now face a risk of death from lung cancer that is 50 percent higher than the estimates reported in the 1980s, according to Dr. Prabhat Jha of the Center for Global Health Research in Toronto and his colleagues.

After controlling for age, body weight, education level and alcohol use, the new analysis found something else: men and women who continue to smoke die on average more than 10 years sooner than those who never smoked.

Dramatic progress has been made in reducing the prevalence of smoking, which has fallen in the United States from 42 percent of adults in 1965 (the year after the first surgeon general’s report on smoking and health) to 19 percent in 2010. Yet smoking still results in nearly 200,000 deaths a year among people 35 to 69 years old in this country. A quarter of all deaths in this age group would not occur if smokers had the same risk of death as nonsmokers.

The risks are even greater among men 55 to 74 and women 60 to 74. More than two-thirds of all deaths among current smokers in these age groups are related to smoking. Over all, the death rate from all causes combined in these age groups “is now at least three times as high among current smokers as among those who have never smoked,” Dr. Thun’s team found.

While lung cancer is the most infamous hazard linked to smoking, the habit also raises the risk of death from heart disease, stroke, pulmonary disease and other cancers, including breast cancer.

Furthermore, changes in how cigarettes are manufactured may have increased the dangers of smoking. The use of perforated filters, tobacco blends that are less irritating, and paper that is more porous made it easier to inhale smoke and encouraged deeper inhalation to achieve satisfying blood levels of nicotine.

The result of deeper inhalation, Dr. Thun’s report suggests, has been an increased risk of chronic obstructive pulmonary disease, or C.O.P.D., and a shift in the kind of lung cancer linked to smoking. Among nonsmokers, the risk of death from C.O.P.D. has declined by 45 percent in men and has remained stable in women, but the death rate has more than doubled among smokers.

But there is good news, too: it’s never too late to reap the benefits of quitting. The younger you are when you stop smoking, the greater your chances of living a long and healthy life, according to the findings of Dr. Jha’s international team.

The team analyzed smoking and smoking-cessation histories of 113,752 women and 88,496 men 25 and older and linked them to causes of deaths in these groups through 2006.

Those who quit smoking by age 34 lived 10 years longer on average than those who continued to smoke, giving them a life expectancy comparable to people who never smoked. Smokers who quit between ages 35 and 44 lived nine years longer, and those who quit between 45 and 54 lived six years longer. Even quitting smoking between ages 55 and 64 resulted in a four-year gain in life expectancy.

The researchers emphasized, however, that the numbers do not mean it is safe to smoke until age 40 and then stop. Former smokers who quit by 40 still experienced a 20 percent greater risk of death than nonsmokers. About one in six former smokers who died before the age of 80 would not have died so young if he or she had never smoked, they reported.

Dr. Schroeder believes we can do a lot better to reduce the prevalence of smoking with the tools currently in hand if government agencies, medical insurers and the public cooperate.

Unlike the races, ribbons and fund-raisers for breast cancer, “there’s no public face for lung cancer, even though it kills more women than breast cancer does,” Dr. Schroeder said in an interview. Lung cancer is stigmatized as a disease people bring on themselves, even though many older victims were hooked on nicotine in the 1940s and 1950s, when little was known about the hazards of smoking and doctors appeared in ads assuring the public it was safe to smoke.

Raising taxes on cigarettes can help. The states with the highest prevalence of smoking have the lowest tax rates on cigarettes, Dr. Schroeder said. Also helpful would be prohibiting smoking in more public places like parks and beaches. Some states have criminalized smoking in cars when children are present.

More “countermarketing” of cigarettes is needed, he said, including antismoking public service ads on television and dramatic health warnings on cigarette packs, as is now done in Australia. But two American courts have ruled that the proposed label warnings infringed on the tobacco industry’s right to free speech.

Health insurers, both private and government, could broaden their coverage of stop-smoking aids and better publicize telephone quit lines, and doctors “should do more to stimulate quit attempts,” Dr. Schroeder said.

As Nicola Roxon, a former Australian health minister, put it, “We are killing people by not acting.”

Read More..

DealBook: Reader's Digest Files for Bankruptcy, Again

Executives at Reader’s Digest must be hoping that the magazine’s second trip to bankruptcy court in under four years will be its last.

The magazine’s parent, RDA Holding, filed for Chapter 11 protection late on Sunday in another effort to cut down the debt that has plagued the pocket-size publication for years. The company is hoping to convert about $465 million of its debt into equity held by its creditors.

In a court filing, Reader’s Digest said it held about $1.1 billion in assets and just under $1.2 billion in debt. It has provisionally lined up about $105 million in financing to keep it afloat during the Chapter 11 case.

This week’s filing is the latest effort by the 91-year-old publisher, whose magazine once resided on many American coffee tables, to fix itself in a difficult economic environment.

“After considering a wide range of alternatives, we believe this course of action will most effectively enable us to maintain our momentum in transforming the business and allow us to capitalize on the growing strength and presence of our outstanding brands and products,” Robert E. Guth, the company’s chief executive, said in a statement.

Reader’s Digest last filed for bankruptcy in 2009, emerging a year later under the control of lenders like JPMorgan Chase.

That reorganization substantially cut the publisher’s debt, and afterward the company worked to further shrink its footprint. It jettisoned nonessential publications in a series of deals, including the $180 million sale of Allrecipes.com and the $4.3 million sale of Every Day With Rachael Ray, both to the Meredith Corporation.

Most of the money from those transactions went to pay down a still significant debt burden. But the company remained pressured by what it described in a court filing as steep declines that still bedevil the media industry. Last year, the publisher began negotiating with its lenders, including Wells Fargo, about amending some of its debt obligations. That process eventually led to a “pre-negotiated agreement” with creditors, which will be put into effect by the bankruptcy filing.

This time, Reader’s Digest is hoping to spend even less time in court. Mr. Guth said in a court filing that the publisher aims to emerge from bankruptcy protection in about four months.

The company’s biggest unsecured creditors include firms represented by Luxor Capital. The Federal Trade Commission also contends that it is owed $8.8 million in a settlement claim.

Reader’s Digest is being advised by Evercore Partners and the law firm Weil, Gotshal & Manges.

Reader's Digest bankruptcy petition (2013) by

Declaration by Reader's Digest Chief Executive by

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In Russia, Property Ruined and Spared by Meteor Share Space

CHELYABINSK, Russia — The shock wave from a meteor that exploded above Siberia last week somehow sheared the roof off a brick and steel factory building while leaving a nearby glass facade unscathed.

In some high-rises in this city, the first modern urban community to have felt the breath of a cosmic close encounter, every window blew out on the top floor; elsewhere, the ground floors suffered.

More ominously, reports came in to local news media over the weekend of stranger phenomena: behind unshattered apartment windows, glass jugs were said to explode into shards, dishes to crack, electronics to die. Balconies rattled. One man said a bottle broke right in his hand.

Anna V. Popova was at home with her daughter when she saw the flash, then heard explosions, then found the windows of her enclosed balcony blown in; her neighbor, with identical windows, escaped without property damage.

“A lot of people suffered, not us alone,” Ms. Popova said, but added that there seemed to be randomness in whose property was damaged. “Who are we supposed to blame for all this? Nobody of course.”

Scientists believe the space rock that tore through the atmosphere on Friday morning and blew apart here was the largest to have entered the atmosphere since 1908 and that it was unusual as well for the scale of its effects: more than 1,200 people injured and broad property damage.

Indeed, the event is providing a first indication of the type of structural and infrastructural costs meteors can exact from a highly industrialized society. NASA scientists say a meteor of this size strikes the Earth about once every hundred years.

Shattered glass caused most of the damage and injuries here in Chelyabinsk, a sprawling industrial city of about a million people.

What shattered the glass, scientists say, was both the explosion as the meteor fragmented and the waves of pressure created as it decelerated. Such low-frequency waves — called infrasound — are sometimes detected by cold-war era nuclear blast sensors in remote parts of the Pacific Ocean or Alaska, according to meteor experts.

The waves can bounce off buildings and be stronger in some places than others; they can also resonate with glass, explaining why bottles and dishes might have shattered inside undamaged kitchens, as if crushed by the airy hand of the meteor itself.

“A shock wave is like a ball,” Aleksandr Y. Dudorov, director of the theoretical physics department at Chelyabinsk State University, said in an interview. “Throw a ball into a room and it will bounce from one wall to another.”

Russia has mobilized 24,000 emergency officials to inspect roads, railroads, hospitals, factories and military facilities. Most are undamaged, including 122 sites identified as particularly critical, including nuclear power plants, dams and chemical factories, and a space launching site called Strela.

Also Sunday, Russia’s consumer safety inspection agency, Rospotrebnadzor, released a statement saying the water in Lake Chebarkul, where a hole in the ice appeared on Friday, was not radioactive.

It was unclear why the agency released this finding only Sunday, or whether the tests were conducted to assuage popular concerns or out of any real official uncertainty over what happened on Friday. In any case, the agency said a mobile laboratory quietly dispatched to the lake tested for but did not discover cesium 137 and strontium 90, isotopes created in nuclear explosions.

Infrasound waves have not previously been studied in a cityscape, Richard P. Binzel, a professor of planetary science at the Massachusetts Institute of Technology and an author of a textbook on asteroids and meteorites, said in a telephone interview. But he noted that the apparent randomness of the damage was consistent with the way such waves function.

“A shock wave can be coming from a particular direction, and if you face that direction you are more susceptible,” Dr. Binzel said.

“One building might shadow another, or you may have a street that is optimally aligned to channel the wave, either in a fortunate or unfortunate way.”

Peter Brown, a professor of physics at the University of Western Ontario, wrote in an e-mail that an infrasound wave “is very efficient at traveling long distances,” and that “windows, structures or even glass jars susceptible to resonate at this frequency could be a factor to seemingly random damage at widely disparate locations.”

Dr. Brown studied a similar, though smaller, explosion of a meteor over the Pacific Ocean on Oct. 8, 2009, which also sent out low-frequency waves, though too remote to affect homes or industry.

They were, though, registered by a network of infrasound sensors established to monitor compliance with the international ban on nuclear tests, according to Dr. Brown.

Alekdander V. Anusiyev, the spokesman for the governor of Chelyabinsk region, characterized the damage here as without a discernible pattern. “It is impossible to say more glass broke in one part of the city or another,” he said. “Glass broke everywhere.”

The roof of the zinc factory that collapsed was reinforced with a lattice of steel beams and supported by concrete joists that are now broken, jutting upward with mangled re-bar protruding. Windows on a neighboring house blew in with such force that the frames went with them.

Yet a few yards away on Sverdlovsky Street, the cosmos spared a seemingly vulnerable Hundai dealership, a three-story cube sheathed in glass, with glistening display models inside. Not a window broke.

“People can consider Feb. 15 their second birthday,” the governor of Chelyabinsk, Mikhail Yurevich, told reporters, referring to the day of the meteor strike. “God directed danger away.”

Ellen Barry contributed reporting from Moscow.

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Tech Industry Sets Its Sights on Gambling

Jim Wilson/The New York Times

Cesar Miranda, left, and his brother, Edgar, working on their claw crane game in San Jose, Calif.

SAN FRANCISCO — Look out Las Vegas, here comes FarmVille.

Silicon Valley is betting that online gambling is its next billion-dollar business, with developers across the industry turning casual games into occasions for adults to wager.

At the moment these games are aimed overseas, where attitudes toward gambling are more relaxed and online betting is generally legal, and extremely lucrative. But game companies, from small teams to Facebook and Zynga, have their eye on the ultimate prize: the rich American market, where most types of real-money online wagers have been cleared by the Justice Department.

Two states, Nevada and Delaware, are already laying the groundwork for virtual gambling. Within months they will most likely be joined by New Jersey.

Bills have also been introduced in Mississippi, Iowa, California and other states, driven by the realization that online gambling could bring in streams of tax revenue. In Iowa alone, online gambling proponents estimated that 150,000 residents were playing poker illegally.

Legislative progress, though, is slow. Opponents include an influential casino industry wary of competition and the traditional antigambling factions.

Silicon Valley is hardly discouraged. Companies here believe that online gambling will soon become as simple as buying an e-book or streaming a movie, and that the convenience of being able to bet from your couch, surrounded by virtual friends, will offset the lack of glittering ambience found in a real-world casino. Think you can get a field of corn in FarmVille, the popular Facebook game, to grow faster than your brother-in-law’s? Five bucks says you cannot.

“Gambling in the U.S. is controlled by a few land-based casinos and some powerful Indian casinos,” said Chris Griffin, chief executive of Betable, a London gambling start-up that helps companies negotiate licenses and handle the betting aspects of the business. “What potentially becomes an interesting counterweight is all of a sudden thousands of developers in Silicon Valley making money overseas and wanting to turn their efforts inward and make money in the U.S.”

Betable has set up shop in San Francisco, where 15 studios are now using its back-end platform. “This is the next evolution in games, and kind of ground zero for the developer community,” Mr. Griffin said.

Overseas, online betting is generating an estimated $32 billion in annual revenue — nearly the size of the United States casino market. Juniper Research estimates that betting on mobile devices alone will be a $100 billion worldwide industry by 2017.

“Everyone is really anticipating this becoming a huge business,” said Chris DeWolfe, a co-founder of the pioneering social site Myspace, who is throwing his energies into a gaming studio with a gambling component backed by, among others, the personal investment funds of Jeff Bezos, Amazon’s founder, and Eric E. Schmidt, Google’s executive chairman.

As companies eagerly wait for the American market to open up, they are introducing betting games in Britain, where Apple has tweaked the iPhone software to accommodate them. Facebook began allowing online gambling for British users last summer with Jackpotjoy, a bingo site; deals with other developers followed in December and this month.

Zynga, the company that developed FarmVille, Mafia Wars, Words With Friends and many other popular casual games, is advertising the imminent release of its first betting games in Britain. “All your favorite Zynga game characters will be there, except this time they’ll have real money prizes to offer you,” an ad says. “Play online casino games for pennies and live the dream!”

Mr. DeWolfe’s studio, SGN, is also on the verge of starting its first real-money games in Britain. “Those companies that have a critical mass of users that are interested in playing real-money games are going to be incredibly valuable,” he said.

Mark Pincus, the chief executive of Zynga, said the company was just following the market. “There is no question there is great interest from all kinds of people in games of chance, whether it is for real money or virtual rewards,” he said. Zynga, which has missed revenue expectations in the last year, is making gambling a centerpiece of its new strategy. It has just applied to Nevada for a gambling license.

Casual gaming first blossomed on Facebook’s Web site, where players could readily corral friends into their games. It is now being rethought for mobile devices, so people can play in brief snippets as they wait for a bus or a sandwich.

Some games mimic the slots and poker found in casinos; others emphasize considerably more creativity. The vast majority of casual game players play at no charge. A small number buy virtual objects in the game to speed their play or increase their status.

Tech executives expect an equally small number to play for real money but believe they will bet heavily, making them much more valuable to the gaming companies. By Betable’s estimate, the lifetime value of a casual player is $2 versus $1,800 for a real-money player.

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