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..

Gadgetwise Blog: A Patch that Monitors the Body

The International Consumer Electronics Show had its share of activity measuring devices, from tiny clips that hang on a pocket to lanyards and wristbands that convert a phone into a private coach.

But BodyMedia is taking a different approach with the Vue Patch, a disposable monitor in a stick-on patch like a large Band-Aid. Once glued on, the Vue will collect data on activity level, sleep patterns and calories burned day and night for week.

The sensor comes in a palm-size adhesive strip made to be worn on the arm.

The Vue is 5 mm thick – a hair thicker than two nickels stacked together — so it can be worn comfortably under clothes. It is considerably smaller and less bulky than BodyMedia’s current monitors, the Link and Core, which are worn on an armband.

The Vue sticks on using a hydrocolloid polymer adhesive, a gel-like substance that is used in bandages for sensitive injuries like skin grafts and burns because it doesn’t damage tender tissue when removed.

The Vue, which is due in the second half of 2013, will share its information by USB. Once a week of recording is over, you remove the patch, open it and get the sensor out. There is already an update planned that will use Bluetooth to share information while the patch is still on.

The final price is not determined, but the company said it should be less than $100.

Read More..

Cardinal Dolan a Dark Horse to Succeed Pope



But suddenly, he found himself in even more rarefied company, with his name mentioned alongside those of more long-serving cardinals as a potential next pope, even though, by all accounts, his chances are slim.


The news on Monday of Pope Benedict XVI’s resignation came as a surprise to Cardinal Dolan, as it did to most of the world. But within hours, his life was already changed. As he continued to go about his regular business as archbishop, he found himself even more in the spotlight to which he has become accustomed, facing a glare that will quite likely continue at least through the conclave in Rome next month.


On Monday, when he dedicated a chapel in Rockland County and attended a prayer meeting in the Bronx, he also ricocheted between media appearances, beginning at 7 a.m. on “Today,” the NBC show, then holding a news conference, writing an op-ed, and granting interviews to ABC and CBS. He was still talking to reporters as night fell, holding an impromptu news conference outside the New York Athletic Club on Central Park South before going inside for a fund-raiser. Both Mayor Michael R. Bloomberg and Gov. Andrew M. Cuomo fielded questions from reporters about the possibility that Cardinal Dolan could become pope; on late-night television, Stephen Colbert offered his endorsement (what he called a “Colbert bump”) for Cardinal Dolan for pope.


Through it all, the cardinal approached the speculation about “Pope Dolan” with his typical self-deprecating humor. Asked what he would do if he found himself among the finalists, he said, “I’ll tell them they have the wrong guy.”


“Don’t bet your lunch money on that one,” he added of his steep odds. “Bet on the Mets.”


On Tuesday, Cardinal Dolan’s schedule returned to a relative normal, as he headed to Camden, N.J., to attend the installation of his former deputy, Dennis J. Sullivan, as bishop. On Wednesday, he plans to visit the bread line at the Church of St. Francis of Assisi in Manhattan in the morning, bestow ashes on the faithful for Ash Wednesday at St. Patrick’s Cathedral at noon, and then attend a wake on Staten Island.


“Honestly, we could do nothing but media — all day, every day — at this point,” said his spokesman, Joseph Zwilling. “He understands the value of it, he likes to do it. But he knows that as archbishop of New York, he’s got a lot of other things he has to attend to.”


The likelihood of Cardinal Dolan becoming the next pope is low, many observers say. “I would put him in the — what’s less than a dark horse?”  category, said Christopher M. Bellitto, a papal historian at Kean University in New Jersey.


“He is arguably going to be, if he is not already, the voice and face of the American church, though whether he can translate that to higher office is another matter,” Professor Bellitto said.


The Rev. Thomas J. Reese, a senior fellow at the Woodstock Theological Center at Georgetown University, put Cardinal Dolan’s odds at “100 to 1.” But, he added, “Anything can happen.”


Cardinal Dolan is considered an unlikely pope for several reasons. Most obviously, he is a citizen of the United States, and the College of Cardinals has been reluctant to choose a pope from a superpower. This year, some Vatican watchers believe the cardinals might choose someone from North America as a compromise between taking the historic step to electing a pope from the developing world and the more conventional choice of someone from Europe. But even if that is the case, Cardinal Marc Ouellet, a Canadian who heads the influential Congregation for Bishops in Rome, seems “a more logical choice,” Professor Bellitto said.


Also, although Cardinal Dolan once served as the rector of the Pontifical North American College in Rome, a seminary for priests, he has never worked at the Vatican, which has often been a credential of a future pope. And, while Cardinal Dolan speaks Italian well enough to converse and deliver speeches, his Spanish is much more basic; many candidates for pope speak multiple languages.


But Cardinal Dolan has strengths as well. He “left an enormously positive impression when he was in Rome last February for the consistory, when he became a cardinal,” said John L. Allen Jr., the senior correspondent for The National Catholic Reporter. For the first time in memory, Italian newspapers were raising the possibility of an American pope, charmed by the “backslapping, baby-kissing, beer-swilling freak-of-nature that is Cardinal Dolan,” Mr. Allen said.


“I think he is a long shot, probably a remote possibility,” Mr. Allen added, “but I do think he will be in the conversation. And that, in and of itself, is something of a novelty for an American cardinal.”


Cardinal Dolan said that, when he first heard about Pope Benedict’s resignation Monday morning, he was in the middle of reading one of the pope’s books on the life of Christ. “That’s how much of my day he is,” he recalled that evening. “So I haven’t really thought to the next one, but I will sure miss him.”


He said he expected to be headed to Rome for the conclave as early as the beginning of March, but like everyone else, was still waiting to hear the exact date. “ ’Cause first of all, I’m a rookie,” Cardinal Dolan said, and also because the church itself is still working out how to handle the rare circumstance of a pope stepping down. “So what will happen now?” he wondered aloud. “I don’t know.”


Read More..

Dow Ends Above 14,000 For Year’s Highest Close


The Dow Jones industrial average rose to its highest close of the year Tuesday, putting it within 1 percent of its record. Stocks gained after two big consumer brands posted impressive quarterly results.


The Dow closed up 47.46 points, or 0.34 percent, to 14,018.70 Tuesday. That is 146 points from its record close of 14,164.53 set in October 2007. The Standard & Poor’s 500-stock index gained 2.42 points, or 0.16 percent, to 1,519.43, also close to its record.


In a day of quiet trading, stocks were driven higher by the beauty products maker Avon and the luxury clothing and accessories company Michael Kors, whose results impressed investors. Consumer spending accounts for 70 percent of economic activity in the United States.


Financial and home-building stocks, led by the Bank of America and the Masco Corporation, which reported some of the day’s biggest gains, also lifted the averages.


The Dow has logged its best January in almost two decades after lawmakers reached a last-minute deal to avoid sweeping tax increases and spending cuts. Investors are also becoming more optimistic that the housing market is recovering and that hiring is picking up.


The Dow has advanced 7 percent this year and the S.& P. 500 is up 6.6 percent.


The 30-member Dow has closed above 14,000 twice this month. Before February, the index closed above that level just nine times in its history. The first time was in July 2007; the rest were in October of that year.


Shares of Avon rose $3.51, or 20 percent, to $20.79 after the company posted a fourth-quarter loss that was not as bad as analysts expected. The company also hopes to save $400 million by slashing costs. Michael Kors rose $5, or 9 percent, to $62 after reporting earnings that beat analysts’ predictions.


Bank of America was the biggest gainer on the Dow, adding 38 cents, or 3.25 percent, to $12.24. Stocks gaining in the index outnumbered those falling by a ratio of more than four to one.


About 70 percent of companies in the S.& P. 500 have reported earnings for the fourth quarter. Analysts are projecting that earnings will rise 6.4 percent for the period, an improvement from the 2.4 percent growth reported in the third quarter, according to S.& P. Capital IQ.


Investors may have become too optimistic about the outlook for stocks, said Uri Landesman, president of the hedge fund Platinum Partners.


“The market is priced for perfection,” Mr. Landesman said. “The odds of a disappointment are very, very high.”


Mr. Landesman predicts that the S.& P. 500 will climb past its record and rise as high as 1,600 by April before then slumping as low as 1,300 as company earnings start to disappoint investors. The record close for the S.& P. 500 is 1,565, reached in October 2007.


Investors were expected to be watching closely Tuesday night when President Obama delivered his annual State of the Union address. Mr. Obama was expected to focus on the economy, including job creation.


A decline in bond prices since the beginning of the year has also slowed. The Treasury’s 10-year note fell 4/32 to 96 28/32 on Tuesday and the yield rose to 1.98 percent from 1.96 percent late Monday. The yield was 1.71 percent at the beginning of the year.


In other trading Tuesday, the Nasdaq composite index was down 5.51 points, or 0.17 percent, to 3,186.49.


Among other stocks making big moves:


Coca-Cola, the beverage company, fell $1.05, or 2.7 percent, to $37.56 after reporting fourth-quarter revenue that fell short of analysts’ forecasts.


Masco, a home improvement and building product company, rose $2.22, or nearly 13 percent, to $20.01 after reporting earnings that beat analysts’ expectations, helped by strong demand in North America.


Dun & Bradstreet, a provider of credit and business data, fell $6.60, or 7.7 percent, to $78.68 after the company reported a fourth-quarter profit that was below market expectations.


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..

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.

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Rabbi David Hartman, 81, Champion of an Adaptive Judaism





JERUSALEM — Rabbi David Hartman, an American-born Jewish philosopher who promoted a liberal brand of Orthodoxy and created a study center that expressed his commitment to pluralism by bringing together leaders from all strains of Judaism, died on Sunday at his home here. He was 81.




His son Donniel said the death came after a long illness.


Rabbi Hartman, who was a professor at Hebrew University for more than 20 years, was a leading advocate of the idea that Jews are partners with God in a covenant, and that they should therefore adapt religious observance to modern values in a multicultural world.


A charismatic teacher and prolific author, he encouraged students to question tradition and urged people of different backgrounds and ideologies to pore over Jewish texts together, a practice more common in his native United States than his adopted country.


“At the center of his thinking was a kind of counter-religious idea, where religious life is a life of affirmation, not a life of denial,” said Moshe Halbertal, a professor of philosophy at Hebrew University and Rabbi Hartman’s former son-in-law. “If human life is not denied by the force of revelation, but it’s actually a participant in revelation, then human life has to come to its full fledge, with its moral convictions, with its encounter with the world.”


The Shalom Hartman Institute, which Rabbi Hartman founded in his father’s name in 1976, has become a theological and cultural landmark, particularly for the thousands of Diaspora Jews who attend conferences or spend summers studying there. With an annual budget of $18 million and a staff of 125, the institute has sponsored two Jerusalem high schools, runs a research center, opened a branch in Manhattan and trained more than 1,000 Israeli military officers. In the last year, according to the institute, more than 5,000 people across North America participated in a Hartman learning series called iEngage.


But Rabbi Hartman’s progressive, universalistic approach was embraced more in the United States than in Israel, where some challenged his status as Orthodox and shunned his open-mindedness as heresy. He received honorary doctorates in the United States but — to his painful regret, people close to him said — not the coveted Israel Prize.


In recent years he had been critical of the growing influence of the ultra-Orthodox on public life. He described as “insane” an ultra-Orthodox boycott of a military ceremony in which women sang.


“What is happening today with religion is more dangerous than what’s happening with the Arabs — the Arabs want to kill my body, the Jews are killing my soul,” Rabbi Hartman said in a 2011 interview with the Israeli daily Yediot Aharanot. “I want to return the Torah to the Labor Party, to the entire people of Israel. I don’t want religion to be the private property of certain people. I don’t want the length of the sidelocks to be the determining factor.”


David Hartman was born on Sept. 11, 1931, in the Brownsville section of Brooklyn, one of six children of Shalom and Batya Hartman, Hasidim who had moved to New York from Israel. Donniel Hartman said that the family was poor — Shalom peddled sheets and pillowcases door to door — but that the four boys became rabbis and the two girls married rabbis.


Rabbi Hartman was ordained by Rabbi Joseph B. Soloveitchik, perhaps the most important Orthodox thinker of the 20th century, and received a doctorate of philosophy from McGill University in Montreal. He was a pulpit rabbi in the Bronx and Montreal before moving to Israel in 1971 as part of a generation of Zionists inspired by the Israeli victory in the Arab-Israeli war of 1967.


Rabbi Hartman published several books in English and Hebrew, including two about his own spiritual evolution. He was an adviser to Ehud Olmert, the former prime minister; Teddy Kollek, the longtime mayor of Jerusalem; and Zevulun Hammer, Israel’s education minister from 1977 to 1984.


“He was a public philosopher for the Jewish people,” said Michael J. Sandel, a professor of political philosophy at Harvard who has written about Rabbi Hartman’s work. “As Maimonides drew Aristotle into conversation with Moses and Rabbi Akiva, so Hartman renovated Jewish thought by bringing the liberal sensibilities to bear on Talmudic argument.”


Besides his son Donniel, who replaced him as president of the Hartman Institute, Rabbi Hartman is survived by four other children, including a daughter, Tova, who helped found Shira Hadasha, a feminist Orthodox congregation in Jerusalem; 16 grandchildren and six great-grandchildren. He is also survived by his former wife, Barbara; the couple had married twice and were divorced twice.


Yedidia Z. Stern, a law professor and vice president of the Israel Democracy Institute, said Rabbi Hartman’s charisma and curiosity were apparent even a few weeks before his death, during a Sabbath meal at Donniel Hartman’s home.


“He was ignoring the adults at the table; he was talking to my kids,” Professor Stern said. “He was asking them about school: Do they like the curriculum, what do they think should be different? Even when he was very sick, you can see the life coming out.”


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U.S. Markets Edge Back From Recent Rally


The stock market drifted lower in thin trading on Monday, pulling the Standard & Poor’s 500-stock index back from a five-year high.


With little in the way of market-moving news, the S.& P. 500 slipped 0.92 of a point to close at 1,517.01. Last week, the broad-market index edged up slightly to its highest level since November 2007.


Seven of the 10 industry groups within the S.& P. 500 dropped.


Now, with major indexes near record highs, many think the stock market’s six-week rally is ready for a pause.


“The consensus seems to be that we’re due for a correction,” said Brian Gendreau, market strategist at the Cetera Financial Group. “If you compound the increase we’ve had so far, this year would be the best year ever for stocks. And nobody thinks that that’s going to happen.”


The best year ever for stocks? For the S.& P. 500 index that was 1933, when the index rebounded 46 percent in the middle of the Great Depression.


Among other stock indexes on Monday, the Dow Jones industrial average dropped 21.73 points to 13,971.24. The UnitedHealth Group led the Dow lower, losing 62 cents to $57.12.


The Nasdaq composite fell 1.87 points to 3,192.00.


Trading volume was light, with 2.6 billion shares trading on the New York Stock Exchange. That stands in contrast to a two-month moving average of 3.4 billion.


Solid earnings reports have helped feed the rally in recent weeks. Of the 342 companies in the S.& P. index that reported results through last week, two out of every three have beaten Wall Street’s earnings estimates, according to research from Goldman Sachs.


Mr. Gendreau gave three reasons he believed that stocks still had room to run. Even after the market’s recent surge, he said, the typical stock looks fairly priced when compared to underlying earnings. Corporations keep finding ways to increase profits, which helps push stock prices higher. And Americans looking for places to put their savings have few attractive alternatives.


“I’ll go out on a limb and say that I think earnings growth, attractive valuations and pent-up demand will add up to a fairly strong year for equities,” Mr. Gendreau said.


Apple’s stock gained $4.95, to $479.93, after The New York Times reported that the technology giant was developing a wristwatchlike device — in essence a smart watch — that would run the same operating system used for iPhones and iPads.


The stock market raced to a stunning start this year. The Dow and the S.& P. 500 have already gained more than 6 percent for the year. The Nasdaq is up 5.7 percent.


Among the companies in the news on Monday, the Danish drug maker Novo Nordisk dropped 14 percent after the Food and Drug Administration refused to approve the company’s proposed diabetes treatments until it received more data, which the drug maker said it could not supply this year. Novo Nordisk’s depositary receipts lost $26.89, to $165.40.


Loews fell 34 cents, to $43.51, after it reported on Monday that it lost $32 million in its fourth quarter, hurt by insurance losses from Hurricane Sandy and sliding prices for natural gas. Loews, a holding company with dealings in insurance, oil and gas and hotels, is largely controlled by the Tisch family of New York.


Carnival, the cruise-ship operator, slipped 29 cents to $38.72 after an engine room fire over the weekend left its cruise ship Triumph stranded in the Gulf of Mexico.


In the bond market, interest rates showed little change. The price of the 10-year Treasury note fell 4/32, to 97, while its yield rose to 1.96 percent, from 1.95 percent late Friday.


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