Well: Straining to Hear and Fend Off Dementia

At a party the other night, a fund-raiser for a literary magazine, I found myself in conversation with a well-known author whose work I greatly admire. I use the term “conversation” loosely. I couldn’t hear a word he said. But worse, the effort I was making to hear was using up so much brain power that I completely forgot the titles of his books.

A senior moment? Maybe. (I’m 65.) But for me, it’s complicated by the fact that I have severe hearing loss, only somewhat eased by a hearing aid and cochlear implant.

Dr. Frank Lin, an otolaryngologist and epidemiologist at Johns Hopkins School of Medicine, describes this phenomenon as “cognitive load.” Cognitive overload is the way it feels. Essentially, the brain is so preoccupied with translating the sounds into words that it seems to have no processing power left to search through the storerooms of memory for a response.

---

Katherine Bouton speaks about her own experience with hearing loss.

A transcript of this interview can be found here.

---

Over the past few years, Dr. Lin has delivered unwelcome news to those of us with hearing loss. His work looks “at the interface of hearing loss, gerontology and public health,” as he writes on his Web site. The most significant issue is the relation between hearing loss and dementia.

In a 2011 paper in The Archives of Neurology, Dr. Lin and colleagues found a strong association between the two. The researchers looked at 639 subjects, ranging in age at the beginning of the study from 36 to 90 (with the majority between 60 and 80). The subjects were part of the Baltimore Longitudinal Study of Aging. None had cognitive impairment at the beginning of the study, which followed subjects for 18 years; some had hearing loss.

“Compared to individuals with normal hearing, those individuals with a mild, moderate, and severe hearing loss, respectively, had a 2-, 3- and 5-fold increased risk of developing dementia over the course of the study,” Dr. Lin wrote in an e-mail summarizing the results. The worse the hearing loss, the greater the risk of developing dementia. The correlation remained true even when age, diabetes and hypertension — other conditions associated with dementia — were ruled out.

In an interview, Dr. Lin discussed some possible explanations for the association. The first is social isolation, which may come with hearing loss, a known risk factor for dementia. Another possibility is cognitive load, and a third is some pathological process that causes both hearing loss and dementia.

In a study last month, Dr. Lin and colleagues looked at 1,984 older adults beginning in 1997-8, again using a well-established database. Their findings reinforced those of the 2011 study, but also found that those with hearing loss had a “30 to 40 percent faster rate of loss of thinking and memory abilities” over a six-year period compared with people with normal hearing. Again, the worse the hearing loss, the worse the rate of cognitive decline.

Both studies also found, somewhat surprisingly, that hearing aids were “not significantly associated with lower risk” for cognitive impairment. But self-reporting of hearing-aid use is unreliable, and Dr. Lin’s next study will focus specifically on the way hearing aids are used: for how long, how frequently, how well they have been fitted, what kind of counseling the user received, what other technologies they used to supplement hearing-aid use.

What about the notion of a common pathological process? In a recent paper in the journal Neurology, John Gallacher and colleagues at Cardiff University suggested the possibility of a genetic or environmental factor that could be causing both hearing loss and dementia — and perhaps not in that order. In a phenomenon called reverse causation, a degenerative pathology that leads to early dementia might prove to be a cause of hearing loss.

The work of John T. Cacioppo, director of the Social Neuroscience Laboratory at the University of Chicago, also offers a clue to a pathological link. His multidisciplinary studies on isolation have shown that perceived isolation, or loneliness, is “a more important predictor of a variety of adverse health outcomes than is objective social isolation.” Those with hearing loss, who may sit through a dinner party and not hear a word, frequently experience perceived isolation.

Other research, including the Framingham Heart Study, has found an association between hearing loss and another unexpected condition: cardiovascular disease. Again, the evidence suggests a common pathological cause. Dr. David R. Friedland, a professor of otolaryngology at the Medical College of Wisconsin in Milwaukee, hypothesized in a 2009 paper delivered at a conference that low-frequency loss could be an early indication that a patient has vascular problems: the inner ear is “so sensitive to blood flow” that any vascular abnormalities “could be noted earlier here than in other parts of the body.”

A common pathological cause might help explain why hearing aids do not seem to reduce the risk of dementia. But those of us with hearing loss hope that is not the case; common sense suggests that if you don’t have to work so hard to hear, you have greater cognitive power to listen and understand — and remember. And the sense of perceived isolation, another risk for dementia, is reduced.

A critical factor may be the way hearing aids are used. A user must practice to maximize their effectiveness and they may need reprogramming by an audiologist. Additional assistive technologies like looping and FM systems may also be required. And people with progressive hearing loss may need new aids every few years.

Increasingly, people buy hearing aids online or from big-box stores like Costco, making it hard for the user to follow up. In the first year I had hearing aids, I saw my audiologist initially every two weeks for reprocessing and then every three months.

In one study, Dr. Lin and his colleague Wade Chien found that only one in seven adults who could benefit from hearing aids used them. One deterrent is cost ($2,000 to $6,000 per ear), seldom covered by insurance. Another is the stigma of old age.

Hearing loss is a natural part of aging. But for most people with hearing loss, according to the National Institute on Deafness and Other Communication Disorders, the condition begins long before they get old. Almost two-thirds of men with hearing loss began to lose their hearing before age 44. My hearing loss began when I was 30.

Forty-eight million Americans suffer from some degree of hearing loss. If it can be proved in a clinical trial that hearing aids help delay or offset dementia, the benefits would be immeasurable.

“Could we do something to reduce cognitive decline and delay the onset of dementia?” he asked. “It’s hugely important, because by 2050, 1 in 30 Americans will have dementia.

“If we could delay the onset by even one year, the prevalence of dementia drops by 15 percent down the road. You’re talking about billions of dollars in health care savings.”

Should studies establish definitively that correcting hearing loss decreases the potential for early-onset dementia, we might finally overcome the stigma of hearing loss. Get your hearing tested, get it corrected, and enjoy a longer cognitively active life. Establishing the dangers of uncorrected hearing might even convince private insurers and Medicare that covering the cost of hearing aids is a small price to pay to offset the cost of dementia.

---

---

Katherine Bouton is the author of the new book, “Shouting Won’t Help: Why I — and 50 Million Other Americans — Can’t Hear You,” from which this essay is adapted.

---

This post has been revised to reflect the following correction:

Correction: February 12, 2013

An earlier version of this article misstated the location of the Medical College of Wisconsin. It is in Milwaukee, not Madison.

Read More..

Well: Straining to Hear and Fend Off Dementia

At a party the other night, a fund-raiser for a literary magazine, I found myself in conversation with a well-known author whose work I greatly admire. I use the term “conversation” loosely. I couldn’t hear a word he said. But worse, the effort I was making to hear was using up so much brain power that I completely forgot the titles of his books.

A senior moment? Maybe. (I’m 65.) But for me, it’s complicated by the fact that I have severe hearing loss, only somewhat eased by a hearing aid and cochlear implant.

Dr. Frank Lin, an otolaryngologist and epidemiologist at Johns Hopkins School of Medicine, describes this phenomenon as “cognitive load.” Cognitive overload is the way it feels. Essentially, the brain is so preoccupied with translating the sounds into words that it seems to have no processing power left to search through the storerooms of memory for a response.

---

Katherine Bouton speaks about her own experience with hearing loss.

A transcript of this interview can be found here.

---

Over the past few years, Dr. Lin has delivered unwelcome news to those of us with hearing loss. His work looks “at the interface of hearing loss, gerontology and public health,” as he writes on his Web site. The most significant issue is the relation between hearing loss and dementia.

In a 2011 paper in The Archives of Neurology, Dr. Lin and colleagues found a strong association between the two. The researchers looked at 639 subjects, ranging in age at the beginning of the study from 36 to 90 (with the majority between 60 and 80). The subjects were part of the Baltimore Longitudinal Study of Aging. None had cognitive impairment at the beginning of the study, which followed subjects for 18 years; some had hearing loss.

“Compared to individuals with normal hearing, those individuals with a mild, moderate, and severe hearing loss, respectively, had a 2-, 3- and 5-fold increased risk of developing dementia over the course of the study,” Dr. Lin wrote in an e-mail summarizing the results. The worse the hearing loss, the greater the risk of developing dementia. The correlation remained true even when age, diabetes and hypertension — other conditions associated with dementia — were ruled out.

In an interview, Dr. Lin discussed some possible explanations for the association. The first is social isolation, which may come with hearing loss, a known risk factor for dementia. Another possibility is cognitive load, and a third is some pathological process that causes both hearing loss and dementia.

In a study last month, Dr. Lin and colleagues looked at 1,984 older adults beginning in 1997-8, again using a well-established database. Their findings reinforced those of the 2011 study, but also found that those with hearing loss had a “30 to 40 percent faster rate of loss of thinking and memory abilities” over a six-year period compared with people with normal hearing. Again, the worse the hearing loss, the worse the rate of cognitive decline.

Both studies also found, somewhat surprisingly, that hearing aids were “not significantly associated with lower risk” for cognitive impairment. But self-reporting of hearing-aid use is unreliable, and Dr. Lin’s next study will focus specifically on the way hearing aids are used: for how long, how frequently, how well they have been fitted, what kind of counseling the user received, what other technologies they used to supplement hearing-aid use.

What about the notion of a common pathological process? In a recent paper in the journal Neurology, John Gallacher and colleagues at Cardiff University suggested the possibility of a genetic or environmental factor that could be causing both hearing loss and dementia — and perhaps not in that order. In a phenomenon called reverse causation, a degenerative pathology that leads to early dementia might prove to be a cause of hearing loss.

The work of John T. Cacioppo, director of the Social Neuroscience Laboratory at the University of Chicago, also offers a clue to a pathological link. His multidisciplinary studies on isolation have shown that perceived isolation, or loneliness, is “a more important predictor of a variety of adverse health outcomes than is objective social isolation.” Those with hearing loss, who may sit through a dinner party and not hear a word, frequently experience perceived isolation.

Other research, including the Framingham Heart Study, has found an association between hearing loss and another unexpected condition: cardiovascular disease. Again, the evidence suggests a common pathological cause. Dr. David R. Friedland, a professor of otolaryngology at the Medical College of Wisconsin in Milwaukee, hypothesized in a 2009 paper delivered at a conference that low-frequency loss could be an early indication that a patient has vascular problems: the inner ear is “so sensitive to blood flow” that any vascular abnormalities “could be noted earlier here than in other parts of the body.”

A common pathological cause might help explain why hearing aids do not seem to reduce the risk of dementia. But those of us with hearing loss hope that is not the case; common sense suggests that if you don’t have to work so hard to hear, you have greater cognitive power to listen and understand — and remember. And the sense of perceived isolation, another risk for dementia, is reduced.

A critical factor may be the way hearing aids are used. A user must practice to maximize their effectiveness and they may need reprogramming by an audiologist. Additional assistive technologies like looping and FM systems may also be required. And people with progressive hearing loss may need new aids every few years.

Increasingly, people buy hearing aids online or from big-box stores like Costco, making it hard for the user to follow up. In the first year I had hearing aids, I saw my audiologist initially every two weeks for reprocessing and then every three months.

In one study, Dr. Lin and his colleague Wade Chien found that only one in seven adults who could benefit from hearing aids used them. One deterrent is cost ($2,000 to $6,000 per ear), seldom covered by insurance. Another is the stigma of old age.

Hearing loss is a natural part of aging. But for most people with hearing loss, according to the National Institute on Deafness and Other Communication Disorders, the condition begins long before they get old. Almost two-thirds of men with hearing loss began to lose their hearing before age 44. My hearing loss began when I was 30.

Forty-eight million Americans suffer from some degree of hearing loss. If it can be proved in a clinical trial that hearing aids help delay or offset dementia, the benefits would be immeasurable.

“Could we do something to reduce cognitive decline and delay the onset of dementia?” he asked. “It’s hugely important, because by 2050, 1 in 30 Americans will have dementia.

“If we could delay the onset by even one year, the prevalence of dementia drops by 15 percent down the road. You’re talking about billions of dollars in health care savings.”

Should studies establish definitively that correcting hearing loss decreases the potential for early-onset dementia, we might finally overcome the stigma of hearing loss. Get your hearing tested, get it corrected, and enjoy a longer cognitively active life. Establishing the dangers of uncorrected hearing might even convince private insurers and Medicare that covering the cost of hearing aids is a small price to pay to offset the cost of dementia.

---

---

Katherine Bouton is the author of the new book, “Shouting Won’t Help: Why I — and 50 Million Other Americans — Can’t Hear You,” from which this essay is adapted.

---

This post has been revised to reflect the following correction:

Correction: February 12, 2013

An earlier version of this article misstated the location of the Medical College of Wisconsin. It is in Milwaukee, not Madison.

Read More..

WellPoint Hires Joseph Swedish of Trinity Health as C.E.O.

WellPoint, one of the nation’s largest health insurers, announced on Tuesday that it had chosen an experienced hospital executive to lead it through sweeping changes created by the federal health care overhaul law.

Joseph R. Swedish, the 61-year-old chief executive of a major nonprofit Catholic-owned health system, Trinity Health, will become WellPoint’s chief executive on March 25. He will be responsible for leading the company, which operates profit-making Blue Cross plans in 14 states, into a future in which health insurers will sell insurance through state and federal exchanges and to work in new ways with hospitals and doctors.

“It truly is a transformational period,” said Mr. Swedish, who helped build Trinity Health into a $9 billion health system with 47 hospitals in 10 states. He became chief executive at Trinity Health in 2004.

WellPoint “has aggressively examined the marketplace,” he said, and is getting ready to compete for customers in highly regulated exchanges, where it must offer coverage even to people with serious medical conditions. WellPoint also bought a large insurer specializing in Medicaid, Amerigroup, last year, in its effort to adapt to the Affordable Care Act that expands the program.

Mr. Swedish succeeds Angela F. Braly, the former chief whose trouble with regulators and uneven performance led to her departure last August. WellPoint, which has a significant national share in providing insurance to individuals and small businesses, has struggled to prove to investors that it can capitalize on its Blue Cross brand in the new business environment.

“Joe’s background, in concert with our management’s insurance market expertise, creates a team uniquely qualified to manage all facets of our evolving health care system,” Jackie M. Ward, chairwoman of WellPoint’s board, said in a statement.

WellPoint’s decision to name a hospital executive “is a natural choice these days,” said Jaime A. Estupiñán, a partner at Booz & Company, a consulting firm. Given the changing nature of the business, both as a result of the health care law and the pressure to find ways to offer better care at lower cost, large health systems “are the biggest threats to insurers,” he said, and the lines between those systems and traditional insurers are blurring.

While choosing a hospital executive is not completely out of the ordinary, Mr. Swedish’s experience will be helpful as WellPoint works more closely with doctors and hospitals, analysts said.

Read More..

With Pope’s Resignation, Focus Shifts to a Successor

L'Osservatore Romano, via Associated Press

Pope Benedict XVI announcing his resignation on Monday at the Vatican. At left is Msgr. Franco Camaldo, a papal aide.

VATICAN CITY — Pope Benedict XVI’s surprise announcement on Monday that he will resign on Feb. 28 sets the stage for a succession battle that is likely to determine the future course of a church troubled by scandal and declining faith in its traditional strongholds around the world.

Citing advanced years and infirmity, Benedict became the first pope in six centuries to resign. Vatican officials said they hoped to have a new pope in place by Easter, while expressing shock at a decision that some said had been made as long as a year ago.

Saying he had examined his conscience “before God,” Benedict said he felt that he was not up to the challenge of guiding the world’s one billion Catholics. That task will fall to his successor, who will have to contend not only with a Roman Catholic Church marred by the sexual abuse crisis, but also with an increasingly secular Europe and the spread of Protestant evangelical movements in the United States, Latin American and Africa.

The resignation sets up a struggle between the staunchest conservatives, in Benedict’s mold, who advocated a smaller church of more fervent believers, and those who feel the church can broaden its appeal in small but significant ways, like allowing divorced Catholics to receive communion or loosening restrictions on condom use to prevent AIDS. There are no plausible candidates who would move on issues like ending celibacy for priests, or the ordination of women.

Many Vatican watchers suspect the cardinals will choose someone with better management skills and a more personal touch than the bookish Benedict, someone who can extend the church’s reach to new constituencies, particularly to the young people of Europe, for whom the church is now largely irrelevant, and to Latin America and Africa, where evangelical movements are fast encroaching.

“They want somebody who can carry this idea of new evangelization, relighting the missionary fires of the church and actually make it work, not just lay it out in theory,” said John L. Allen, a Vatican expert at the National Catholic Reporter and author of many books on the papacy. Someone who will be “the church’s missionary in chief, a showman and salesman for the Catholic faith, who can take the reins of government more personally into his own hands,” he added.

The other big battle in the church is over the geography of Catholicism, which has spread decisively to the developing world. Today, 42 percent of its adherents come from Latin America, and about 15 percent from Africa, versus only 25 percent from Europe. That has led many in the church to say that the new pope should represent a part of the world where membership is growing quickly, while others say that spiritual vision should be paramount.

But while most of the world’s Catholics live outside Europe, most of the cardinals come from Europe, pointing to a central tension: while the Vatican is a global organization, it is often run like an Italian village.

Under normal circumstances, the cardinals would descend on Rome after the death of the reigning pope. In this case, said the Vatican spokesman, the Rev. Federico Lombardi, the pope will carry out his duties until Feb. 28 at 8 p.m., with a successor probably elected by Easter, which this year falls on March 31. But he said the timing for an election of a new pope is “not an announcement, it’s a hypothesis.”

Already, speculation is rife about who best fills the perceived needs of the church. Cardinal Angelo Scola, the powerful archbishop of Milan, is seen as the strongest Italian contender. A conservative theologian with an interest in bioethics and Catholic-Muslim relations, he is known for his intellect, his background in the same theological tradition as Benedict, his media savvy and his strong ties with the Italian political establishment. Vatican experts laud his popular touch, even if his writings are often opaque.

Cardinal Marc Ouellet, a dogmatic theologian and a Canadian, is widely seen as a favorite of Benedict, who named him head of the Vatican’s influential Congregation for Bishops to help select bishops around the world. Critics in his native Quebec said that he was out of step with the province’s more progressive bishops, but that is not necessarily a drawback in today’s church.

Nicholas Kulish contributed reporting from Berlin, and Alan Cowell from London.

Read More..

Gadgetwise Blog: Speakers With a Big Sound for Big Desks

The British loudspeaker maker KEF, a name well known to audiophiles, has broken out both the high-tech and marketing razzle-dazzle for its desktop X300A speakers.

For starters, it talks about the “Uni-Q driver array,” which joins two speakers in one – a fancy version of a good old coaxial speaker, which puts a woofer for low tones and a tweeter for high tones in the same chassis.

Then it boasts that each speaker has a class AB amplifier, a kind of dual circuit that is used in some higher quality amplifiers and car amps as well. It pumps up to 50 watts to the low frequency speaker and 20 watts to the high.

Neither of these is quite the breakthrough it is made to appear, but you don’t often find either in a speaker built for computers.

The end result is a very solid set of speakers – 16.5  pounds of solid each.

They aren’t for people concerned about desk space. The size of typical bookshelf speakers, they are nearly a foot high, with a roughly 7-by-10-inch footprint.

Nor are they for people concerned about running skeins of cables. Each speaker takes an industrial strength power cord, a USB cable to the computer or player and another cord between the speakers themselves.

With gun-metal-colored cabinets and no grill to obscure (or protect) the speakers, the X300As have a utilitarian look, but alas, not a utilitarian price: They list for $800 a pair.

The price could be excused if the sound were exceptional. Because the speakers can be customized to achieve different sounds, it’s hard to make a blanket assessment. But I’ll try.

After fiddling with the bias and balance controls, the EQ setting and a set of foam stoppers to rein in the bass, I can say the speakers sound very, very good in some cases – “Honky Tonk Woman” was lively, and the cowbell (more cowbell!) was just perfect.

In other cases, they were not as impressive – in the overture for “The Mikado,” the oboes sounded like they had tin cans over them.

But overall, they are a very good pair of speakers if money and desk space are no object.

Read More..

Health Testing on Mice Is Found Misleading in Some Cases

Evan McGlinn for The New York Times

Dr. H. Shaw Warren is one of the authors of a new study that questions the use of laboratory mice as models for all human diseases.

For decades, mice have been the species of choice in the study of human diseases. But now, researchers report evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.

The study’s findings do not mean that mice are useless models for all human diseases. But, its authors said, they do raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.

“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.

The paper, published Monday in Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at a huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, can have something that looks like sepsis in humans, but is very different from the condition in humans.

Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating condition. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.

“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.

“It’s amazing,” said Dr. Richard Wenzel, a former chairman at the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine. “They are absolutely right on.”

Potentially deadly immune responses occur when a person’s immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.

The ramped-up immune system releases its own proteins in such overwhelming amounts that capillaries begin to leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls, and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Vital organs eventually fail.

The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes were being used by white blood cells when responding to these danger signals.

The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.

The group had tried to publish its findings in several papers. One objection, Dr. Davis said, was that the researchers had not shown the same gene response had happened in mice.

“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”

“That started us thinking,” he continued. “Is it the same in the mouse or not?”

The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.

“We were kind of blown away,” Dr. Davis said.

The drug failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that worked in mice by disabling that gene could make the response even more deadly in humans.

Even more surprising, Dr. Warren said, was that different conditions in mice — burns, trauma, sepsis — did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, it might work for all three.

This article has been revised to reflect the following correction:

Correction: February 11, 2013

An earlier version of this article misstated the position of Dr. Richard Wenzel. He is a former chairman of the department of internal medicine at Virginia Commonwealth University. He is not currently the chairman.

Read More..

Health Testing on Mice Is Found Misleading in Some Cases

Evan McGlinn for The New York Times

Dr. H. Shaw Warren is one of the authors of a new study that questions the use of laboratory mice as models for all human diseases.

For decades, mice have been the species of choice in the study of human diseases. But now, researchers report evidence that the mouse model has been totally misleading for at least three major killers — sepsis, burns and trauma. As a result, years and billions of dollars have been wasted following false leads, they say.

The study’s findings do not mean that mice are useless models for all human diseases. But, its authors said, they do raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.

“Our article raises at least the possibility that a parallel situation may be present,” said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.

The paper, published Monday in Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at a huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, can have something that looks like sepsis in humans, but is very different from the condition in humans.

Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating condition. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills one-fourth to one-half of them, and costs the nation $17 billion a year. It is the leading cause of death in intensive-care units.

“This is a game changer,” said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.

“It’s amazing,” said Dr. Richard Wenzel, a former chairman at the department of internal medicine at Virginia Commonwealth University and a former editor of The New England Journal of Medicine. “They are absolutely right on.”

Potentially deadly immune responses occur when a person’s immune system overreacts to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.

The ramped-up immune system releases its own proteins in such overwhelming amounts that capillaries begin to leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls, and vital organs do not get enough blood. Despite efforts, doctors and nurses in an intensive-care unit or an emergency room may be unable to keep up with the leaks, stop the infection or halt the tissue damage. Vital organs eventually fail.

The new study, which took 10 years and involved 39 researchers from across the country, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes were being used by white blood cells when responding to these danger signals.

The researchers found some interesting patterns and accumulated a large, rigorously collected data set that should help move the field forward, said Ronald W. Davis, a genomics expert at Stanford University and a lead author of the new paper. Some patterns seemed to predict who would survive and who would end up in intensive care, clinging to life and, often, dying.

The group had tried to publish its findings in several papers. One objection, Dr. Davis said, was that the researchers had not shown the same gene response had happened in mice.

“They were so used to doing mouse studies that they thought that was how you validate things,” he said. “They are so ingrained in trying to cure mice that they forget we are trying to cure humans.”

“That started us thinking,” he continued. “Is it the same in the mouse or not?”

The group decided to look, expecting to find some similarities. But when the data were analyzed, there were none at all.

“We were kind of blown away,” Dr. Davis said.

The drug failures became clear. For example, often in mice, a gene would be used, while in humans, the comparable gene would be suppressed. A drug that worked in mice by disabling that gene could make the response even more deadly in humans.

Even more surprising, Dr. Warren said, was that different conditions in mice — burns, trauma, sepsis — did not fit the same pattern. Each condition used different groups of genes. In humans, though, similar genes were used in all three conditions. That means, Dr. Warren said, that if researchers can find a drug that works for one of those conditions in people, it might work for all three.

This article has been revised to reflect the following correction:

Correction: February 11, 2013

An earlier version of this article misstated the position of Dr. Richard Wenzel. He is a former chairman of the department of internal medicine at Virginia Commonwealth University. He is not currently the chairman.

Read More..

Media Decoder: A CBS Deal Bolsters Amazon's Challenge to Netflix

Slowly but confidently, Amazon is building a library of television shows and movies to rival that of Netflix, much to the satisfaction of media companies like Time Warner and CBS, whose executives love to see the competition.

Although Amazon will not unveil its own original television shows until the fall at the earliest, it is spending hundreds of millions of dollars to have the exclusive Web rights to shows it can brag about on its Amazon Prime streaming service, like “Downton Abbey,” from PBS, and “Falling Skies,” from TNT.

The latest example came on Monday, when Amazon announced an unusual arrangement with CBS, the country’s most-watched television network, to carry episodes of “Under the Dome” just days after the series makes its debut on TV in June.

“This deal is yet another sign that the streaming marketplace is becoming more and more robust,” said Scott Koondel, the chief content licensing officer for CBS, a position that was created two months ago. “Advances in user-friendly technology from companies like Amazon and Netflix are a boon for premium content owners.”

Amazon has a long way to go to rival Netflix in terms of TV and movie selection. But in some corners of the media business, it is already perceived to be Pepsi to Netflix’s Coke. And many other companies — among them Google, Sony, Intel and a new joint venture between Redbox and Verizon — are trying to come up with a Red Bull or a Snapple they can call their own.

While Netflix has won attention for unveiling a high quality show, “House of Cards,” on its streaming service, “it is increasingly hard to ignore the progress Amazon has made in a relatively short amount of time,” Richard Greenfield, an analyst at BTIG Research, wrote two weeks ago. He predicted that Amazon would quietly spend more than $500 million on video this year.

Amazon declined to comment on that figure. Its nearly two-year-old streaming service, called Prime Instant Video, is bundled as part of its $79 annual Amazon Prime membership, which also provides two-day free shipping and a monthly Kindle e-book rental. The company says it has millions of Amazon Prime subscribers, but it will not disclose the precise number. Netflix has about 27 million streaming subscribers in the United States.

Instant Video started simply enough about two years ago, with relatively cheap acquisitions of older television shows from networks like CBS and nonexclusive rights to older films from studios like Universal. But Amazon’s recent deals have revealed the company’s ambitions.

When Netflix dropped the rights to some cable series like “Pawn Stars” last fall, Amazon swooped in and started streaming them. When Time Warner wanted to sell streams of some of its cable dramas, Amazon bought the exclusive rights to “The Closer” and “Falling Skies,” while Netflix bought “Dallas.”

“This emerging back end for cable originals is a very promising sign,” Jeffrey L. Bewkes, chief executive of Time Warner, told investors last week, “since it should result in production values for cable originals getting even better over time.”

Perhaps its biggest deal yet came last week, when it clinched the rights to past and future seasons of the PBS hit “Downton Abbey.” By July, “Downton” will be gone from Netflix.

Both streaming services mine the data of their users to determine what kinds of shows to license, and what not to. The first two seasons of “Downton” were the “most-streamed TV show on Prime Instant Video,” said Brad Beale, who oversees video acquisitions for Amazon, so it was a “pretty easy decision” to bid for seasons three and four (and five, if it is produced).

“Data is a great proxy for what our customers love,” Mr. Beale added in a telephone interview. “We’re blessed to have a platform that gives us a lot of insight into what our customers love.”

“Under the Dome” — based on the Stephen King novel and produced by Steven Spielberg’s Amblin Television — will be unique because each episode will go onto Amazon four days after its premiere on TV. CBS stands to make more money this way than it now does by streaming shows on CBS.com and attaching ads.

Analysts expect to see more such deals as broadcasters move away from the free online model made popular by Hulu. Hulu has a subscription component as well, but it has not announced any notable licensing deals the way Netflix and Amazon have done. Its owners are at odds over the future of the service, and its founding chief executive, Jason Kilar, will leave later this winter.

Netflix says it expects to compete with Amazon the way HBO and Showtime compete — with TV dramas and comedies of their own. “When it comes to competition, we not only have a superior content offering due to our larger budget, but we are further along the experience curve,” Netflix told investors last month. In other words, Amazon is cheap, off-brand Cola.

While Netflix has four more original series on tap this year, Amazon is trying out test episodes of six comedies and five children’s series. This year, Amazon will stream them and, after hearing from viewers, decide which ones will become series.

Roy Price, the head of Amazon Studios, said the pilot process will ensure quality, just as it does for traditional television networks, and make viewers and producers pay attention to Amazon’s video projects.

“All that matters is being great,” he said. “There’s no great benefit in being good; people don’t change their habits for good.”

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Syrian War Closes In on the Heart of Damascus

Goran Tomasevic/Reuters

Fighters from the Free Syrian Army's Tahrir al Sham brigade look at a Syrian Army base in the Arabeen neighborhood of Damascus.

DAMASCUS, Syria — Unkempt government soldiers, some appearing drunk, have been deployed near a rebel-held railway station in the southern reaches of this tense capital. Office workers on 29th of May Street, in the heart of the city, tell of huddling at their desks, trapped inside for hours by gun battles that sound alarmingly close.

Soldiers have swept through city neighborhoods, making arrests ahead of a threatened rebel advance downtown, even as opposition fighters edge past the city limits, carrying mortars and shelling security buildings. Fighter jets that pounded the suburbs for months have begun to strike Jobar, an outlying neighborhood of Damascus proper, creating the disturbing spectacle of a government’s bombing its own capital.

On Sunday, the government sent tanks there to battle rebels for control of a key ring road.

In this war of murky battlefield reports, it is hard to know whether the rebels’ recent forays past some of the capital’s circle of defenses — in an operation that they have, perhaps immodestly, named the “Battle of Armageddon” — will lead to more lasting gains than earlier offensives did. But travels along the city’s battlefronts in recent days made clear that new lines, psychological as much as geographical, had been crossed.

“I didn’t see my family for more than a year,” a government soldier from a distant province said in a rare outpouring of candor. He was checking drivers’ identifications near the railway station at a checkpoint where hundreds of soldiers arrived last week with tanks and other armored vehicles.

“I am tired and haven’t slept well for a week,” he said, confiding in a traveler who happened to be from his hometown. “I have one wish — to see my family and have a long, long sleep. Then I don’t care if I die.”

For months, this ancient city has been hunched in a defensive crouch as fighting raged in suburbs that curve around the city’s south and east. On the western edge of the city, the palace of the embattled president, Bashar al-Assad, sits on a steep, well-defended ridge.

In between, Damascus, with its walled Old City, grand diagonal avenues and crowded working-class districts, has remained the eye of the storm. People keep going to work, even as electric service grows sporadic and groceries dwindle, even as the road to the airport is often cut off by fighting outside the city, and even as smoke from artillery and airstrikes in suburbs becomes a regular feature on the horizon.

But after rebels took the railway station 10 days ago in a city district called Qadam and attacked Abassiyeen Square on an approach to the city center on Wednesday, a new level of alarm and disorder has suffused the city. Rebels have pushed farther into the capital than at any point since July, when they briefly held part of a southern neighborhood.

Near the Qadam railway station last week, many of the government soldiers, their hair and beards untrimmed, wore disheveled or dirty uniforms and smelled as if they had not had showers in a long time. Some soldiers and security officers even appeared drunk, walking unsteadily with their weapons askew — a shocking sight in Syria, where regimented security forces and smartly uniformed officers have long been presented as a symbol of national pride.

The deployment appeared aimed at stopping the rebels from advancing past Qadam, either across the city’s ring road and toward the downtown or to suburbs to the east to close a gap in the opposition’s front line.

But even stationed here in Damascus, the heart of the government’s power, the soldier at the checkpoint — who was steady on his feet — said he felt vulnerable.

“It is very scary to spend a night and you expect to be shot or slaughtered at any moment,” he said. “We spend our nights counting the minutes until daytime.”

The government has hit back hard, striking Qadam with artillery and airstrikes. It has also made pre-emptive arrests in Midan, the neighboring district, closer to downtown, where rebels gained a temporary foothold in July and which they said was their next target.

Anne Barnard reported from Beirut, Lebanon.

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Reviewing Three Brands of Tax Preparation Software

TAX preparation is moving to the cloud.

The makers of the better-known tax prep programs — TurboTax, H&R Block at Home and TaxAct — say that many customers, particularly younger ones, prefer Web-based programs to old-fashioned, desktop versions. Web-based programs — techies call this cloud computing — reside on remote servers that customers access via their browsers. They offer the convenience of working on a return from any Internet-connected computer and having that return stored on the software makers’ secure servers.

After spending several days running my family’s tax information through Web and desktop offerings, I learned that I’m old-school. For a decade, I’ve completed our return on my Mac desktop, and I prefer that. Desktop programs may be costlier and, in some ways, clunkier — you must buy them on CD or download them — but they also offer more flexibility.

A single purchase, for example, lets you prepare and file multiple returns, as you might want to do if you’re part of a same-sex couple or if you help family members or friends with their taxes. And you can more easily jump back and forth between the tax return and the interviews the programs use to gather information. That lets you check entries as you make them, as my wife, a C.P.A., insists upon. What you lose in convenience, you gain in control.

Each of the tax preparation programs, whether desktop or online, has strengths and shortcomings. TurboTax is the easiest to use, importing lots of financial information with just a few clicks. H&R Block promises the most reassuring help — its staff will represent you at no extra charge if you’re audited. TaxAct offers the best price. A look at each provider’s offerings shows where it excelled and stumbled in preparing my family’s 2012 return.

TurboTax

TurboTax’s maker, Intuit, has its roots in technology, not taxes, and its facility with bits and bytes shows in its wares. Its desktop and online programs make doing taxes as simple as such a time-eating task can be. If you end up cursing come tax time, the target will be the I.R.S., not your software.

I downloaded the desktop version of TurboTax Premier for $89.99 — though I learned later that I could have paid $10 less if I’d bought it on CD at my local Staples. The download took only a few seconds, as did the import of information from our 2011 return. All of the unchanged data from 2011 — names, addresses, federal ID numbers, even descriptions of business expenses — popped into the right places on the 2012 forms. Even the names of the charities we support carried over. The software also imported my wife’s W-2 and all of the information on our investments from Vanguard, T. Rowe Price and Fidelity. All I had to do was key in details for a few local banks and update the amounts we’d given to charity.

The online version of TurboTax, by contrast, didn’t import as much. My attempt to transfer our 2011 return failed, and an import from one of the fund companies went awry. I inherited an I.R.A., and the money is invested in about a half-dozen funds. Instead of creating an entry for a single 1099-R, the program created a half-dozen, which I had to combine.

Otherwise, the online program looked and worked much the same way as the desktop software. I didn’t have to pay to try it because TurboTax, like H&R Block and TaxAct, doesn’t require online users to pay until they file their returns. Had I filed with the online version of TurboTax Premier, I would have paid $49.99 for a single federal return — the price as it was discounted at the time. But TurboTax says it could rise to as much as $74.99, its list price, before April 15.

 

TurboTax upgraded its assistance features for this year’s tax filing season — a welcome improvement. In the past, I’d found some help links hard to locate and navigate. When I wanted to pose a question to a tax expert, I had to dig around. But not anymore. When I had a question about recording tax-exempt interest, I clicked on the help link, and TurboTax offered a choice between a call and an online chat. Within seconds, I was e-chatting with Marilyn G., and she pointed me to the right spot on the return. We were done in less than five minutes, and I paid nothing extra. I’ve had a tougher time buying jeans online. (All three companies also provide extensive tax-law explanations embedded in their programs.)

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