Friday, January 18, 2008

Louis J Sheehan Esquire 30065

Combining a megapowerful magnet, multiple detectors, and carefully tweaked contrast, a new MRI technique developed at the National Institutes of Health (NIH) provides an unprecedented look at the fine structure of the brain. Using an MRI machine equipped with a magnet more than twice as powerful as one in an ordinary device, the researchers created a way to measure the magnetic field changes caused by tissue properties to optimize contrast in the image. They were also able to compensate for the magnetic field fluctuations created by the patients’ breathing. The technique revealed never-before-seen patterns in the white matter and gray matter of the human brain.

Picking up on such differences may help researchers look more deeply into the brain’s subdivisions, allowing them to map it in greater detail. It may also bring about advances in diagnosing diseases like Alz–heimer’s and multiple sclerosis, both of which involve abnormal iron accumulation in the brain. For patients, the new technique may mean that “you could more accurately—and maybe earlier—diagnose a disease,” says NIH physicist Jeff Duyn.
Only eight MRI machines this powerful exist in the United States, and all are housed in research, rather than clinical, settings. Each costs around $5 million, and that’s before the expense of setup—which includes installing 380 tons of shielding material to prevent every metal object in the building from being sucked into the magnet.

Chinese researchers announced (pdf) in March that they had created glass that can be bent into right angles without shattering. But this isn’t glass as we know it: The new glass is opaque, twice as strong as window glass, and made of metal.

As solids, metals have an orderly atomic structure; in liquid metals, the arrangement becomes random, as in glass. To create metallic glass, scientists supercool liquid metals, effectively “freezing” the random array in place. These bulk metallic glasses, or BMG, are two to three times stronger than the crystalline form of the metals.

Superstrong BMG has already been used in the manufacture of high-tech golf clubs and tennis rackets; in 2001, the collector on NASA’s Genesis spacecraft, which caught particles from the solar wind, was made of BMG.
But since the 1980s, when scientists began making BMG, the materials have exhibited a fatal flaw. Paradoxically, the stronger they are, the more vulnerable they are to cracks, says Wei Hua Wang, a physicist who helped develop the new glass at the Chinese Academy of Sciences. A tiny fracture in the original type of BMG spreads quickly and becomes catastrophic.

To create a glass that is both strong and flexible, Wang and his colleagues altered an existing BMG recipe, combining zirconium, copper, nickel, and aluminum. Realizing that small changes in the metal mixture would lead to large variations in brittleness, they sought a combination that would keep cracks from spreading. “The plasticity of the glass is very sensitive to the composition,” Wang explains.

After two years, the scientists produced bendable BMG. It contains hard areas of high density surrounded by soft regions of low density. The result: When a crack begins in one place, it dissipates quickly in the surrounding regions, leaving the whole flexible.

Believe it or not, there are some folks who make a living as professional guinea pigs in tests of experimental drugs. Some question whether testing that relies on frequent lab fliers takes advantage of poor people or compromises the quality of the data.

In a recent issue of the New Yorker, bioethics professor Carl Elliot, from the University of Minnesota, details how early drug safety testing has become more of a business transaction than a scientific endeavor in an article called “Guinea-Pigging.” He’ll also be exploring the topic as part of a book he’s writing on corruption, money and medicine that he expects to be called “White Coat, Black Hat” and to be published next year. We asked Elliot, who is on sabbatical in New Zealand, a few questions via e-mail. Here are the highlights of the long-distance conversation:

How does professional guinea-pigging affect the data on experimental drugs?

What I heard about most often was subjects stretching the truth about their medical histories in order to get into high-paying studies. That seems to be fairly common. I don’t know what kind of impact it has on the results, but it shouldn’t be terribly shocking. We have a safety testing system where subjects don’t have any stake in the results of the study, where they don’t really trust the research sponsors, and where they don’t believe they are going to get access to the drugs that are developed by the studies. If poor people are being asked to test drugs for the benefit of rich people, then we shouldn’t be surprised if the poor people are not always perfectly compliant.

Should we change the system to discourage professional guinea-pigging?

Well, one thing that worries me is the damage that all these studies could be doing to the long-term health of the guinea pigs. They are mostly uninsured, so they are in no position to get regular medical care, and nobody else has any financial interest in monitoring their health.

Payment itself is a real dilemma. New drugs need to be tested for safety, and I can’t imagine that many people will volunteer to test the safety of new drugs for free anymore, especially if it means checking into a testing site for three weeks to undergo invasive medical procedures. But it feels unfair to put the burden on poor people who are driven to volunteer at these testing sites because they can’t get any other kind of work. If we are going to have a payment-based system, we need to make sure that poor subjects are not being exploited.

What changes are needed for safety’s sake?

Apart from watchdog groups like Circare, which operate on a shoestring budget, and investigative reporters, there really are very few people outside the research enterprise watching these studies. Formal oversight has been outsourced to for-profit IRBs [institutional review boards], which are paid by the companies doing the research, and which mainly look at studies on paper. The complaints I often heard about from guinea pigs were conditions on the ground that IRBs have never really thought much about. I don’t think it ever occurred to an IRB to ask SFBC [SFBC International, a company that owned the largest drug-testing site in North America] whether they were testing drugs on undocumented immigrants in a dilapidated motel. Some testing sites have procedures that are not really dangerous, but which are uncomfortable or degrading, like requiring subjects to have a rectal exam whether or not it is relevant to the study. And of course, somebody needs to make sure that researchers who are crooked or incompetent are not allowed to keep doing research.

What can or should be done for participants who are injured or suffer other side effects during a trial?

The very least that can be done is to guarantee that they will get medical care without being stuck with the bill. As things stand now, guinea pigs can’t even count on that. That’s not just a problem with industry studies. Even subjects in federally sponsored trials in universities don’t get that guarantee. Robert Steinbrook published a piece in the New England Journal of Medicine a couple of years ago showing that only 16% of academic health centers in the U.S. provided free care to injured subjects, and none of them compensated subjects for pain and suffering.

Where do you see this process of human subject testing headed?

It’s heading overseas to the developing world. It’s less expensive and the oversight is less rigorous. I think the problems will be the same as here, only more so.

The sequel is out there.

The conspiracy theories will not be.

Ten years after the first film and six years after the show went off the air, The X-Files returns to theaters with Fox Mulder, Dana Scully — and a lot riding on the bet that fans want more of the FBI's paranormal-investigating agents.

The film, which remains without a formal title, will dump the long-running "mythology" plotline — that aliens live among us and are part of a colonizing effort — that made it one of the most popular television shows in the late 1990s but ultimately drove away some viewers who found it too complex and ambiguous.

"We spent a lot of time on (the mythology) and wrapped up a lot of threads" when the show went off the air in 2002, says Chris Carter, creator of the series and director of the new movie. "We want a stand-alone movie, not a mythology conspiracy one."

That will come as welcome news to fans of the show's stand-alone episodes, which included cults, ghosts, psychics and ancient curses.

Carter refuses to divulge any plot points of the movie, but says he wanted to make the film immediately after the show ended. A contractual dispute with 20th Century Fox kept it on the shelf until the case was settled out of court.

He says the delay may turn out to be a blessing.

"There's a whole audience I want to introduce X-Files to," Carter says. "There were kids who couldn't watch it on TV because it was too scary. Now they're in college. I wanted a movie that everyone could go to."

Whether they will could be a test of the show's legacy, says Blair Butler of the G4TV network, which caters to video-game enthusiasts and science-fiction fans.

"At its strongest, it had really creepy stand-alone episodes," she says. "They turned it into a great franchise. But a lot of years have passed. We'll see if it's fallen off the radar."

She says the film could benefit from an ironic twist: the Writers Guild strike.

"I think it could be a sort comfort food for the people who loved how original the show was and aren't seeing original TV now," she says.

But Carter believes they'll be drawn by something else: the show's stars, David Duchovny and Gillian Anderson.

"For me, The X-Files has always been a romance," he says. "They had an intellectual romance that's very rare and restrained compared to so many relationships on TV. I think that's what appealed most to the fans. And they're back."
People have been trying to figure out why we sleep for almost as long as we have been conscious of being awake, tossing and turning in the dark.

After a few restless nights, most of us can't even think straight. We are less able to make sense of problems, make competent moral judgments or retain what we learn, even though studies show our brain cells fire more frenetically to overcome the lack of sleep. Lose too much sleep and we become reckless, emotionally fragile, and more vulnerable to infections and to diabetes, heart disease and obesity, recent research suggests.

We spend a third of our lives asleep, yet no one really knows why. We do know that people simply don't perform as well when they don't sleep enough.
How sleepy are you?
The Epworth Sleepiness Scale can help you rate how likely you are to doze off or fall asleep.
The American Academy of Sleep Medicine and the National Sleep Foundation offer general information about sleep and sleep disorders. The National Institute of Neurological Disorders and Stroke also offers a detailed rundown on the basics of sleep.
New scientific findings about the biology of sleep are highlighted at Sleep Research Online

Bedside Reading
The Society for Neuroscience offers these Brain Briefings on sleep and learning, insomnia and sleep deficits.
For bedside reading about sleep, Stanford University researcher William Dement, founder of the world's first sleep disorder clinic, and science writer Christopher Vaughan outline cures for "a sleep-sick society" in The Promise of Sleep: A Pioneer in Sleep Medicine

Yet scientists probing the purpose of sleep are still largely in the dark. "Why we sleep at all is a strange bastion of the unknown," said sleep psychologist Matthew Walker at the University of California in Berkeley.

One vital function of sleep, researchers argue, may be to help our brains sort, store and consolidate new memories, etching experiences more indelibly into the brain's biochemical archives.

Even a 90-minute nap can significantly improve our ability to master new motor skills and strengthen our memories of what we learn, researchers at the University of Haifa in Israel reported last month in Nature Neuroscience. "Napping is as effective as a night's sleep," said psychologist Sara Mednick at the University of California in San Diego.

Moreover, slumber seems to boost our ability to make sense of new knowledge by allowing the brain to detect connections between things we learn.

In research published last April in the Proceedings of the National Academy of Sciences, Dr. Walker and his collaborators at the Harvard Medical School tested 56 college students and found that their ability to discern the big picture in disparate pieces of information improved measurably after the brain could, during a night's sleep, mull things over.

It is these patterns of meaning -- the distilled essence of knowledge -- that we remember so well. "Sleep helps stabilize memory," said neurologist Jeffrey Ellenbogen, director of the sleep medicine program at Massachusetts General Hospital.

The erratic biorhythms of sleep and behavior are intertwined everywhere in nature. Socially active fruit flies need more sleep than loner flies, and even zebra fish can get insomnia.

Sleep is controlled partly by our genes. The difference between those of us who naturally wake at dawn and night owls who are wide-eyed at midnight may be partly due to variations in a gene named Period3, which affects our biological clock. Variations in that gene also make some people especially sensitive to sleep deprivation, scientists at the U.K.'s University of Surrey recently reported.

How much sleep do you need? And how much do you actually get? Tell us about your sleep habits in an online forum12.

For many of us, though, sleeplessness is a self-inflicted epidemic in which lifestyle overrides basic biology. "In this odd, Western 24-hour-MTV-fast-food generation we have created, we all feel the need to achieve more and more. The one thing that takes a hit is sleep," Dr. Walker said. On average, most people sleep 75 minutes less each night than people did a century ago, sleep surveys record.

Yet, rarely have so many millions of drowsy people been trying so hard to secure some shut-eye, spending billions on sleep aids. By one estimate, pharmacists filled 49 million prescriptions for sleep drugs last year. Even so, we think we sleep more than we actually do, according to Arizona State University scientists. They recorded how long 2,100 volunteers actually slept each night and compared that with how long the people reported they had slept. Most people overestimated their sleep by about 18 minutes, the scientists found.

Psychologists Jeffrey Ellenbogen at Harvard's Mass General Hospital and Matthew Walker at UC/Berkeley found that sleep boosts our ability to make sense of new knowledge by allowing the brain to detect connections and patterns between things we learn. They reported their findings recently in The Proceedings of the National Acemdy of Sciences.

The consequences of too little sleep can be dire. Almost half of all heavy-truck accidents can be traced to driver fatigue, while decisions leading to the Challenger space-shuttle disaster, the Chernobyl nuclear-reactor meltdown and the Exxon Valdez oil spill can be partly linked to people drained of rest by round-the-clock work schedules. Weary doctors make more serious medical errors, while sleepy airport baggage screeners make more security mistakes, researchers reported at the Associated Professional Sleep Societies.

All told, the frayed tempers, short attention spans and fuzzy thinking caused by sleep deprivation may cost $15 billion a year in reduced productivity, the National Commission on Sleep Disorders Research estimated.

The expectation of a nap, however, is by itself enough to measurably lower our blood pressure, researchers at the Liverpool John Moores University in England reported in October in the Journal of Applied Physiology.

Indeed, regular nappers -- working men who took a siesta for 30 minutes or more at least three times a week -- had a 64% lower risk of heart-related death, researchers at the University of Athens reported last February in the Archives of Internal Medicine.

"All of the things we are proving about sleep and the brain are things that your mother already knew decades ago," Dr. Walker said. "We are putting the science and the hard facts behind it."

Scientists have taken a key step toward understanding the cause of prostate cancer, finding that a combination of five gene variants sharply raises the risk of the disease. Added to family history, they accounted for nearly half of all cases in a study of Swedish men.

The discovery is remarkable not just for the big portion of cases it might explain, but also because this relatively new approach -- looking at combos rather than single genes -- may help solve the mystery of many complex diseases.

It also might lead to a blood test to predict who is likely to develop prostate cancer. These men could be closely monitored and perhaps offered hormone-blocking drugs like finasteride to try to prevent the disease.

The Swedish results must be verified in other countries and races, where the gene variants, or markers, may not be as common. Researchers already have plans to look for them in U.S. men. Unfortunately, the markers do not help doctors tell which cancers need treatment and which do not -- they turned out to have nothing to do with the aggressiveness of a tumor, only whether a man is likely to develop one.

The study was led by doctors at Wake Forest University in Winston-Salem, N.C., and involved Johns Hopkins University in Baltimore and the Karolinska Institute in Stockholm. Results were published online by the New England Journal of Medicine.

It involved 2,893 men with prostate cancer and 1,781 similar men who did not have the disease. Sweden was chosen because the population is so ethnically similar and well suited to gene studies.

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