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.

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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.


Figuring Out Fido
To better understand man's best friend, Hungarian scientists are working on computer software that analyzes dog barks. It could help humans recognize basic canine emotions, Hungarian ethologist Csaba Molnar told Reuters. Mr. Molnar and his colleagues at Budapest's ELTE University have tested software which distinguishes the emotional reaction of 14 dogs of the Hungarian Mudi herding breed to six situations: being alone, seeing a ball, fighting, playing, encountering a stranger or going for a walk. "A possible commercial application could be a device for dog-human communication," the scientist added. The iDog, perhaps?



John McCain is looking for deep support from his military brethren to win South Carolina -- the state that ended his presidential bid eight years ago.

Mr. McCain sees a big difference this time. "We were not in a war in 2000," he said here yesterday. "I'm the only one who is really qualified to be commander-in-chief."

After conceding a loss Tuesday night in Michigan's Republican primary, the Arizona senator turned his attention to South Carolina's significant population of active-duty military and veterans.

"I have long admired the deep patriotism of the people of this state," the Navy veteran said in Charleston. "So many of your sons and daughters risk their lives today to keep the rest of us safe, as so many South Carolinians have done in past wars," he said.

The Republican race for president arrives in South Carolina in some disarray. "It is a chessboard extraordinaire," with three candidates having won primaries and no clear leader, said Republican strategist Tony Fabrizio, who isn't affiliated with any campaign.

Mr. McCain is hoping to nose ahead of the pack with a win here Saturday, much of it with the support of the state's sizable military presence. The only one of the major candidates who has served in the military, he upped the ante yesterday by predicting a South Carolina victory, something he declined to do before the Michigan primary.

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"We will win South Carolina," he said at a campaign event in Greenville. His aides say a victory here would propel him through Florida's Jan. 29 contest and into the all-important "Super Tuesday" primaries Feb 5. They aren't saying what it means if he loses.

Mr. McCain lost South Carolina in 2000 after outside groups made what turned out to be wild accusations about the senator's integrity on a host of issues, including his military record. This time Mr. McCain has a rapid-reaction force, including many veterans, to refute such attacks.

That force was put into use Tuesday when a mailer arrived in some South Carolina homes accusing Mr. McCain of distorting his record as a prisoner of war in North Vietnam. Orson Swindle, a close McCain ally and former prisoner of war, dismissed the mailer as coming from "conspiracy-theory people" and saying such attacks on Mr. McCain aren't new. "It's slander, it affects voters, obviously," he said. "It's a bit crazy, too."

The military vote is "very important," senior McCain adviser Steve Schmidt said yesterday. "John McCain speaks the language of the men and women who serve in the military." Mr. Schmidt and other campaign aides said the military vote alone isn't enough to win, but it is a key part of his strategy.

McCain campaign aides are hoping Mr. McCain and his rivals -- Mike Huckabee, Mitt Romney and Fred Thompson -- divide the evangelical vote, leaving the state's sizable population of military and independent voters to Mr. McCain.

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Mr. Huckabee is seen as Mr. McCain's main rival. The Southern Baptist minister has emerged as the favorite of the state's Christian conservatives, especially since he upset Mr. Romney to win the Iowa caucuses. Mr. Romney split the state's party establishment early on with Mr. McCain but has yet to gain traction among rank-and-file Republicans suspicious of his Mormon faith and social-issue flip-flops. Mr. Thompson entered the Republican race late and counted on Christian conservatives' support -- only to see them suddenly flock to Mr. Huckabee amid his Iowa success.

The McCain team has reason for optimism on the military front. Veterans carry heavy weight in South Carolina's Republican politics. They were 14% of the adult population in 2000, according to the Census Bureau, but 27% of voters in the Republican primary, according to exit polls. Though Mr. McCain lost South Carolina to George W. Bush in 2000 by 53% to 42%, he won the veteran vote 48% to 47%, according to exit polls.

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South Carolina is home to 400,000 veterans, according to the Census Bureau. It has high numbers of military personnel stationed in-state and abroad. Almost 29,000 active-duty soldiers claim the state as their legal residence, making up about 1% of its population -- only nine states have a higher percentage. And there are 66,000 soldiers stationed here, constituting about 2% of its adult population, greater than all but eight states.

At campaign stops yesterday, Mr. McCain hammered home his pro-military message about caring for the troops, resolving the Iraq war and improving veterans' health care. He spoke glowingly of the 2,000 South Carolina National Guard and reserve troops who are in Afghanistan and called out veterans in the audience.

And as he often does on the stump, he read a quote from George Washington about the importance of looking after veterans. "The willingness with which our young people are likely to serve in any war, no matter how justified, will be directly proportional as to how they perceived the veterans of earlier wars were treated and appreciated by their country," Mr. McCain said, echoing President Washington.

That message plays well with voters such as Gary Wells, 73 years old, a Greenville resident and veteran who said he served as a Russian linguist in military intelligence in Berlin during the Cold War. He came to a McCain event in Greenville yesterday undecided between Mr. McCain and Mr. Romney. But he liked what Mr. McCain "said about the veterans and the military," particularly the senator's plan to give veterans an insurance card for routine visits to be used at any doctor, rather than having to go to Veterans Administration hospitals, he said. Mr. Wells calls VA hospitals "really horrible."

The Arizona senator made his first stop here after his New Hampshire triumph at the Citadel military college last week. His last major public event before the primary is scheduled to be Friday evening on the decommissioned aircraft carrier U.S.S. Yorktown, in Mount Pleasant, S.C.

Mr. McCain's surrogates also spread the military message yesterday. "Let's make sure the military is well-led by somebody who understands their world," said Republican South Carolina Sen. Lindsey Graham.

Cindy McCain, the senator's wife, talked about their two sons who are serving, one at the Naval Academy, the other in the Marines. At a McCain townhall meeting in Spartanburg, S.C., Mrs. McCain said she supported her husband's run, in part because "it's about my children being safe, my sons particularly, your sons and daughters...that they serve with honor and dignity and come home with dignity."

Veterans and their spouses fill the seats at almost every McCain event, donning blue "Veterans for McCain" stickers. Yet even they acknowledge their ranks are only part of what will make up a McCain victory. "John McCain has a very loyal base among the veterans," said John McGraw, 65, who served in the Navy's River Patrol Force in Vietnam. Speaking before a McCain event yesterday here in Greenville, he said the military vote is "not enough. He has to get other individual Republicans."

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"We hear that phone calls are being made. We will not let it go this time," John McCain told reporters, in reference to calls like those made to South Carolina voters from a group calling itself Vietnam Veterans Against McCain, which accuses the Republican presidential candidate, senator and former prisoner of war of selling out fellow POWs to save himself, the New York Times reports. Another group called Common Sense Issues, which supports rival candidate Mike Huckabee, has begun making what it said were a million automated calls to households in South Carolina telling voters that Mr. McCain "has voted to use unborn babies in medical research," the Times adds. (Mr. Huckabee's campaign says it has no ties to the group.) Burned in the 2000 South Carolina primary by one of the most notorious smear campaigns in recent American politics -- which contributed to his loss to President Bush -- Mr. McCain this time seems more determined to fight back aggressively and is deploying a "Truth Squad" in the state with the help of South Carolina's Republican political establishment.

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The effectiveness of 12 popular antidepressants has been exaggerated by manufacturers' selective publication of favorable results, researchers asserted in a new review of unpublished data that were submitted to the Food and Drug Administration.

As a result, the review concludes, doctors and patients are getting a distorted view of the effectiveness of blockbuster antidepressants like Wyeth's Effexor and Pfizer Inc.'s Zoloft. The review was published in the New England Journal of Medicine.


A review of research submitted to the FDA:
• Of 74 studies reviewed, 38 were judged to be positive by the FDA. All but one were published, researchers said.
• Most of the studies found to have negative or questionable results were not published, researchers found.
Source: The New England Journal of Medicine

Since the overwhelming amount of published data on the drugs show they are effective, doctors unaware of the unpublished data are making inappropriate prescribing decisions that aren't in the best interest of their patients, according to researchers led by Erick Turner, a psychiatrist at Oregon Health & Science University. Sales of antidepressants total about $21 billion a year, according to IMS Health.
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Wyeth and Pfizer declined to comment on the study results. Both companies said they had committed to disclose all study results, although not necessarily in medical journals. GlaxoSmithKline PLC, maker of Wellbutrin and Paxil, said it has posted the results of more than 3,000 trials involving 82 medications on its Web site, and also has filed information on 1,060 continuing trials at a federal government Web site.

Schering-Plough Corp., whose Organon Corp. unit markets Remeron, and Eli Lilly & Co., which makes Prozac, said their study results were indeed published -- not individually, but as part of larger medical articles that combined data from more than one study at a time. The New England Journal study counted a clinical trial as published only if it was the sole subject of an article. "Lilly has a policy that we disclose and publish all the results from our clinical trials, regardless of the outcomes from them," a Lilly spokeswoman said.

Pharmaceutical companies are under no obligation to publish the studies they sponsor and submit to the FDA, nor are the researchers they hire to do the work. The researchers publishing in the New England Journal were able to identify unpublished studies by obtaining and comparing documents filed by the companies with the FDA against databases of medical publications.

"There is no effort on the part of the FDA to withhold or to not post drug review documents," an FDA representative said. For newer drugs, information is posted online "as soon as possible." Older documents aren't always available online and efforts to add those files to the Web are slowed by "a lack of resources," the agency said, acknowledging that there is a backlog in complying with records requests.

A total of 74 studies involving a dozen antidepressants and 12,564 patients were registered with the FDA from 1987 through 2004. The FDA considered 38 of the studies to be positive. All but one of those studies was published, the researchers said.
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The other 36 were found to have negative or questionable results by the FDA. Most of those studies -- 22 out of 36 -- weren't published, the researchers found. Of the 14 that were published, the researchers said at least 11 of those studies mischaracterized the results and presented a negative study as positive.

Five Trials

For example, Pfizer submitted five trials on its drug Zoloft to the FDA, the study says. The drug seemed to work better than the placebo in two of them. In three other trials, the placebo did just as well at reducing indications of depression. Only the two favorable trials were published, researchers found, and Pfizer discusses only the positive results in Zoloft's literature for doctors.

One way of turning the study results upside down is to ignore a negative finding for the "primary outcome" -- the main question the study was designed to answer -- and highlight a positive secondary outcome. In nine of the negative studies that were published, the authors simply omitted any mention of the primary outcome, the researchers said.

The resulting publication bias threatens to skew the medical professional's understanding of how effective a drug is for a particular condition, the researchers say. This is particularly significant as the growing movement toward "evidence-based medicine" depends on analysis of published studies to make treatment decisions.

Colleagues' Questions

Dr. Turner, who once worked at the FDA reviewing data on psychotropic drugs, said the idea for the study was triggered in part by colleagues who questioned the need for further clinical drug trials looking at the effectiveness of antidepressants.
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"There is a view that these drugs are effective all the time," he said. "I would say they only work 40% to 50% of the time," based on his reviews of the research at the FDA, "and they would say, 'What are you talking about? I have never seen a negative study.'" Dr. Turner, said he knew from his time with the agency that there were negative studies that hadn't been published.

The suppression of negative studies isn't a new concern. The tobacco industry was accused of sitting on research that showed nicotine was addictive, for instance. The issue has come up before notably with antidepressants: In 2004, the New York state attorney general sued GlaxoSmithKline for alleged fraud, saying it suppressed studies showing that the antidepressant Paxil was no better than a placebo in treating depression in children. Glaxo denied the charge and eventually settled with the attorney general. The company later posted on its Web site the full reports of all of the studies of Paxil in children.

But publication of negative studies is an issue that cuts across all medical specialties. And it has engendered some strong reactions in the medical-research world: To make it harder to conceal negative study findings, an association of medical journal editors began requiring in 2005 that clinical trials be publicly disclosed at the outset to be considered for publication later. The system isn't foolproof, since manufacturers often run exploratory studies without registering them and can selectively disclose favorable results. The rule only applies to studies intended for publication in a medical journal.

Some studies that don't eventually get published are registered with online trial registries, including the federal government's www.clinicaltrials.gov. Nonetheless, many studies still aren't being registered or reported, says Kay Dickersin, the director of the Center for Clinical Trials at the Johns Hopkins Bloomberg School of Public Health. "We need something more meaningful," she said. "The average person has no idea that www.clinicaltrials.gov is not comprehensive."

The New England Journal study also points to the need for the FDA to disclose more information about the studies it receives, says Robert Hedaya, a professor of clinical psychiatry at Georgetown University Hospital. He said it was "disturbing" that the information on the negative studies wasn't made widely available by the FDA.
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The FDA does post information, including unpublished studies, for some drugs on its Web site, says Dr. Turner. But information that hasn't yet made it online is hard to come by. Dr. Turner said he made public records requests for information not on the Web site more than a year ago, but the requests have gone largely unfulfilled. He said he was able to get some of the FDA's information on unpublished studies from other researchers who acquired it from the agency through their own record requests.

The 'Effect Size'

In this week's study, the researchers found that failing to publish negative findings inflated the reported effectiveness of all 12 of the antidepressants studied, which were approved between 1987 and 2004. The researchers used a measurement called effect size. The larger the effect size, the greater the impact of a treatment.

The average effect size of the antidepressant Zoloft rose 64% by the failure to publish negative or questionable data on the drug, the researchers found.

Parents' Pessimism Affects Children's Investing
Parental attitudes can significantly influence children's decisions to invest. The key is the extent to which parents trust society, according to "Social Capital as Good Culture," a new National Bureau of Economic Research working paper by Luigi Guiso of the European University Institute; Paola Sapienza of the Kellogg School of Management and Luigi Zingales of the University of Chicago.

The economists find that pessimism among parents is passed on to their children as a form of social capital, which is defined as the set of beliefs and values that inspire cooperation in members of a community. Passing on pessimism leads children to avoid investment and prevents them from gaining their own knowledge of society, according to the paper. Allowing pessimistic values to flow from generation to generation until society is stuck at a point the paper deems a "no-trust no-trade equilibrium."

They tested their model using two different samples: the World Value, a survey to determine the correlation between young people's rate of learning and average level of trust in their parents, and the German Socio Economic Panel to link parents' and children's beliefs.

While it doesn't specify how to alter a low trust state, it shows that even a temporary shock to society can alter the perceptions passed from one generation to the next. In a shock that lasts three generations, for example, 19% of families eventually stop investing. If the shock lasts five generations, it drops to 8%.

"This 'temporary' shock is sufficient to induce almost all family lines to have an optimistic prior and always invest. Most interesting, this effect persists forever even after the shock disappears," the researchers conclude.
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The economists sought to prove that lasting effect by demonstrating that the difference in social capital in Northern and Southern Italy today resulted from a period of independence in cities in Northern Italy more than 500 years ago. Italian literature from the 19th century showed that Northern literature was punctuated by intense optimism and faith in others, while Southern literature displayed a sense of mistrust toward the community. Data from the 1990s shows the sentiments persisted long after the "shock." Though 42% of Northerners trusted others, only 25% of Southerners felt the same.

The cycle can change within individuals as well, though. The paper found that as a person ages, trust tends to increase as his life experiences meld with his parents' views. This was based on the finding that parents generally pass conservative versions of their beliefs on to children. It also found that mothers have a stronger influence in passing on personal values and beliefs.

Shifting levels of trust are applicable to second generation Americans also, who often correlate their trust in American society with the level they held in their native countries. This can continue for generations.

"Our model implies also that when transmitting priors, parents should do so in a conservative way, so that the prior they transmit is on average lower than the one they hold," the researchers conclude. "Furthermore, parents that have stronger beliefs about the trustworthiness of others should transmit less conservative priors." -Sara Murray

Telescopes have captured astonishing images of far-away galaxies and other cosmic mysteries. Now, a new book called Touch the Invisible Sky is helping everyone appreciate those pictures, even people who can't see.

This isn't the first book written by Noreen Grice, an astronomer who works at the Museum of Science in Boston. Back in 1984, Grice was a 21-year-old studying astronomy at Boston University. She had a job at the planetarium, and one Saturday, a group of blind people came to the show.

"I didn't know what to do because I didn't know anyone who was blind," says Grice. Her manager told her to just help the people to their seats.

After the show was over, Grice went up to the group.

"I said, 'So how did you like the show?' And there was an uncomfortable pause," she recalls. "And then they said, 'This stunk' and walked away. And that left me speechless because I thought the planetarium was, like, the best place in the world."

The next day, Grice took a bus to a nearby school for the blind. She found its library and looked for astronomy books. They were thick books, printed in Braille.

"But something was missing. I said, 'Where are the pictures? Are there any pictures these books?'"

The librarian explained that it's expensive to translate an image into raised lines and textures that a person can feel with their fingers. So textured images are uncommon in books for the blind. Grice hated the idea that blind people weren't getting the same kind of cool astronomy books she loved as a kid.

"I had grown up in the housing projects outside Boston," says Grice. "People would say, 'you're a project kid, you're not welcome here.' I understood what it meant to be labeled. And I didn't really know how to make astronomy accessible. But I thought, 'I'll try.'"

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Her first book, Touch the Stars, came out in 1990. She used a Braille printer to trace out the constellations. Her next book, Touch the Universe, traced out photos taken by the Hubble Space Telescope. Grice created that one using thin plastic sheets.

"Basically, I was etching them by hand, in my kitchen," she says. "Some were like, really difficult. When you have diffuse gas, that you can hardly see, it is very difficult to apply a texture to it."

Touch the Invisible Sky, her latest book, was written with two co-authors. It's beautiful, designed to be read by both blind people and sighted people.

The book has images taken by telescopes that detect things like radio waves, x-rays and gamma rays — the wavelengths of light that no one can see with the naked eye.

"I think we all have the same thing in common with this book," says Grice. "No human can see these other wavelengths so we're all approaching it together."

There's a real need for more books like this one, says Marc Maurer, president of the National Federation of the Blind.

"Most people think that astronomy is the study of light, and they think therefore that blind people can't do it and would not be interested," he says. "Blind people can do it, and we find it fascinating."

Maurer loved the science textbooks his mom read to him when he was going to school. But a popular science book he could read by himself — there was nothing like that.

"There still are not enough books," he says, explaining that exciting science books with pictures and graphics are a rarity for blind people.

That's one reason why Chelsea Cook, a high school student in Newport News, Virginia, got her family to drive four hours to Baltimore for the new book's unveiling. She says Noreen Grice's astronomy books are "really interesting, you know, the visuals are easy to read, and they're just cool to look at."

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Cook says she has enough vision to see a full moon, but not stars. Still, she wants to study astrochemistry and astrophysics. And she's fascinated by the idea of space exploration.

Her ultimate career goal? To become the first "blind astronaut." It will be "a lot to work towards," she says, "but I think it's possible."

The United States Constitution never uses the word "God" or makes mention of any religion, drawing its sole authority from "We the People." However, Republican presidential candidate Mike Huckabee thinks it's time to put an end to that.

"I have opponents in this race who do not want to change the Constitution," Huckabee told a Michigan audience on Monday. "But I believe it's a lot easier to change the Constitution than it would be to change the word of the living god. And that's what we need to do -- to amend the Constitution so it's in God's standards rather than try to change God's standards so it lines up with some contemporary view."

When Willie Geist reported Huckabee's opinion on MSNBC's Morning Joe, co-host Mika Brzezinski was almost speechless, and even Joe Scarborough couldn't immediately find much to say beyond calling it "interesting,"

Scarborough finally suggested that while he believes "evangelicals should be able to talk politics ... some might find that statement very troubling, that we're going to change the Constitution to be in line with the Bible. And that's all I'm going to say."

Geist further noted of Huckabee that if "someone without his charm," said that, "he'd be dismissed as a crackpot, but he's Mike Huckabee and he's bascially the front-runner."

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If you had to choose between two sets of speaker cables, one costing a few dollars and sounding fine, the other a few thousand dollars but perhaps sounding slightly better, and you chose the second pair, then you would have had a great time last week in Las Vegas.

The city's many goings-on included The Home Entertainment Show, an audiophile trade show held in two small motels off the Strip. Audiophiles, as you probably know, are the hi-fi zealots who think nothing of spending $50,000 on a turntable. I've learned over the years that audiophiles actually come in two varieties: the totally insane and the merely crazy.

The latter have a sense of humor and shrug that theirs is just one of many hobbies -- like wine -- for people with money, expansive vocabularies and the ability to discern differences lost on the rest of us.

By contrast, my interests involve the extent to which beliefs influence perceptions. Scientists have discovered that brain scans of wine drinkers show they physically enjoy a wine more if they think it is expensive. Can audiophiles really hear all the differences they say they can, without being influenced by the brand or price of their equipment?

To find out, Portals became an official exhibitor at T.H.E. Show last week. I set up a room with two sound systems, identical except for one component. Everything except the speakers was hidden behind screens. (A shout-out to Totem Acoustics for the Forest speakers loan and to Magnum Dynalab for the MD-308 amps. They all sounded sensational.)

With the same music playing on both, participants used a remote control to switch between the two, and then tell me which sounded better.

One of the tests compared a high-quality MP3 file from an iPod with a CD on a $3,000 player. Three-quarters of the 24 people taking this test preferred the CD.

That was no surprise. However, when I played .wav files on the iPod -- these are digital but uncompressed files; I was connecting the headphone jack to the amplifier -- 52% of the 21 who took this test preferred the iPod.

That made me smile, not because snooty audiophiles got the "wrong" answer, but because it suggests great sound can come from popular, cheap gear.

I also tested speaker cables, which are controversial even among audiophiles. Some spend tens of thousands of dollars on cabling, while others consider it an absurd waste of money.

Using two identical CD players, I tested a $2,000, eight-foot pair of Sigma Retro Gold cables from Monster Cable, which are as thick as your thumb, against 14-gauge, hardware-store speaker cable. Many audiophiles say they are equally good. I couldn't hear a difference and was a wee bit suspicious that anyone else could. But of the 39 people who took this test, 61% said they preferred the expensive cable.

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That may not be much of a margin for two products with such drastically different prices, but I was struck by how the best-informed people at the show -- like John Atkinson and Michael Fremer of Stereophile Magazine -- easily picked the expensive cable.

Its sound was described as "richer," "crisper" and "more coherent." Like some wines, come to think of it.

In absolute terms, though, the differences weren't great. Mr. Atkinson guesstimated the expensive cables sounded roughly 5% better. Remember, by definition, an audiophile is one who will bear any burden, pay any price, to get even a tiny improvement in sound.

Attendance at the show was disappointing, so I didn't get the numbers of participants I wanted. Even if I had, I'm not sure I would have settled anything. These "A-B" tests have limits, including the fact that differences you might not pick up right away can become more apparent with extended listening.

Skeptics out there might think I've gone all mushy and credulous on them.

Not so.

Consider the thriving audiophile product category of power-line conditioners, said to remove noise and distortions caused by your electrical supply, a problem you may not realize you have. A rep from Audience LLC accepted my invitation for an A-B test of the company's $2,800 AdeptResponse aR6 conditioner.

He picked the system using his conditioner -- the other was plugged into the wall -- two out of three times.

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Note that the aforementioned "merely crazy" audiophiles say that while they might have home setups costing six figures, the rest of us can get splendid sound for under $1,000 by shopping at specialty audio shops, the sort that sell unfamiliar brands.

I can't help you with brands, but my tests suggest you might want to do your ripping as .wav files. While they take up a lot more room than MP3s, falling disk prices make this feasible even for big collections.

As for cables, good ones can cost well under $2,000. I'd still be happy at the hardware store, but you may be the golden-ear sort who can hear a difference. As in "Dirty Harry," you've got to ask yourself, "Do I feel lucky?"

Well, do you?


A cocaine boom in Europe and the continent's strong currency have combined to fuel a thriving industry: euro laundering.

With the euro approaching $1.50 and soaring demand for cocaine in countries like Spain and Italy, Europe has become a far more lucrative place to do business for Latin American drug cartels than in previous years.

To obscure the origins of the funds, and escape government scrutiny in the process, the cartels use a complex system to launder their proceeds -- much of which is landing on U.S. shores.

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In late March, U.S. authorities arrested a man carrying a leather duffel bag who had just landed at Los Angeles International Airport on a flight from Santiago, Chile. Inside the bag was more than $1.9 million in cash, mostly in bundles of €500 and €200 notes.
Authorities are struggling to make a dent in the booming drug trade in Europe. WSJ's Mark Schoofs tags along with Spanish police as they search for clues to the source of cocaine that keeps pouring into the country.

U.S. and Chilean law enforcement officials believe the man was at the end of a money-laundering trail that begins in Europe. Over a period of four and a half years, he and his associates flew to the U.S. from Latin America some 280 times, openly toting more than $244 million worth of euros into the country, according to documents in a case brought by federal authorities in U.S. District Court in New York.

The big bills have become so symbolic of the lush life that they have recently crept into pop culture: The rapper Jay-Z's video for Blue Magic -- the debut single from his new album "American Gangster" -- features a suitcase full of €500 notes and someone thumbing through a stack of them as Jay-Z raps the words, "the kilo business." Hype Williams, director of the music video, said that he and Jay-Z chose euros because they are "more valuable" and because they wanted to "one-up" their hip-hop competitors by showing "the things people are into now."

The wads of euros carried by people like the man arrested at LAX are often the spoils of Europe-bound cocaine shipments -- many of which transit through Africa, law-enforcement officials say.

Consumption of the drug has soared in much of Western Europe, according to a report released last year by the U.N. Office on Drugs and Crime. In Italy, use of the drug rose to 2.1% of the general population in 2005 from 1.1% just four years earlier. In France, it tripled from 2000 to 2005, from 0.2% to 0.6% of the adult population. Cocaine use in England doubled from 1998 to 2006, according to Britain's National Health Service, to 2.4% among adults.

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Some narco-euros are laundered directly in Europe. But officials say the lion's share is routed back to South America as cash and eventually ends up in the U.S.

"This is still a cash business," says Donald Semesky, the Drug Enforcement Administration's head of financial-crimes investigations.

The first step is to convert small bills accumulated from thousands of street sales into €500 notes, which are easy to transport. Obtaining large quantities of these conspicuous notes, though, isn't easy. So drug traffickers turn to specialized criminal rings -- whose members are often involved in banking and real estate -- to gain access to them, says José Manuel Álvarez Luna, chief of the money-laundering section of the Spanish police.

Spain is the center for such aggregation, according to authorities. A high-level Spanish banking official says a disproportionate share of the euro zone's €500 notes, known as Bin Ladens for their scarcity, circulate in Spain.

The purpose of money-laundering is to disguise the criminal origins of ill-gotten gains so the funds appear legitimate. In most cases, laundering also helps criminals escape the notice of tax collectors and law-enforcement officials, boosting the value of their illegal proceeds.

Particularly since 9/11, tightened antilaundering regulations, known by banks as "know your customer" rules, have forced drug cartels to use more circuitous routes to circulate their funds around the globe.

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For starters, the drug cartels do not themselves bring their narco-euros to the U.S. Instead, they usually sell their euros to South American black-market currency brokers or to foreign-exchange houses, known in Spanish as casas de cambio. The casas' business as currency-exchange houses gives them a natural cover for moving large amounts of cash.

But in South America, there are few if any legitimate buyers for the huge sums of euros that the casas obtain -- directly or indirectly -- from the traffickers. So the casas funnel most of the narco-euros, sometimes via middlemen, through a chain of exchange houses in countries like Colombia, Peru, Brazil and Chile, says the DEA's Mr. Semesky.

Often, the drug traffickers will sell their euros for Colombian pesos, and then the euros entering the U.S. no longer belong to the drug cartels but to the casa de cambio. In other cases, says Mr. Semesky, traffickers pay the casas to move funds into one of their U.S. bank accounts. These funds aren't usually intended for withdrawal, but rather to pay various debts. This is achieved by wiring funds to the account of whomever the trafficker wishes to pay.

On a recent night at a bar on Madrid's bustling Gran Vía, a shirtless, tattooed waiter served tables and a buxom drag queen in a nurse's uniform worked the crowd. In the trendy venue was a man in his 30s who talked by cellphone with his dealers. A few minutes later, he stepped outside, leaned into the window of a small car and handed over €60, or about $90. For that sum, he received one gram of cocaine.

Such street sales have surged. Spain now has a larger percentage of its population (3%) using cocaine than the U.S. (2.3%), the previous top per-capita consumer, according to United Nations figures. In the first half of 2007, a kilo of cocaine sold for €33,000, or about $43,900, in Madrid, more than triple the $12,500-$14,600 it fetched in Los Angeles and far more than the $13,000-$26,000 it sold for in New York, according to the Spanish police and the DEA.

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Last year, seven European countries banded together to form the Maritime Analysis and Operations Center-Narcotics, or MAOC-N, an international agency dedicated to stopping drug traffic over the Atlantic. Already, the center is helping to make major busts.

In October, on the high seas off West Africa, Spanish authorities -- acting on a tip from MAOC-N -- seized an aging, cockroach-infested trawler. Called the Opnor, it allegedly had more than three metric tons of cocaine hidden below the floor of its cargo hold. Apparently registered in Panama, the vessel was captained by a grizzled Dutch man in his late 60s and is believed to have been heading toward Senegal.

The boat was following a typical pattern, authorities say. They surmise that, if it hadn't been seized, its cocaine would have been warehoused in West Africa, where crushing poverty, weak law enforcement and, often, rampant corruption make for an ideal way station. The traffickers would have then sent the drugs to Europe by boat, either directly or via North Africa. Increasingly, say Spanish and American authorities, cocaine is also being flown from North Africa in small planes landing in Spain and Portugal on clandestine airstrips.

The traffickers were forced to take those routes because Spanish, Portuguese and British authorities were intercepting boats coming to Europe directly from South America.

Spain is a favorite entry point because of its proximity to Africa, its long coastline and its language, which it shares with Colombia and most other South American countries. Spanish officials say they seized almost 100 metric tons of cocaine in 2005 and 2006. According to United Nations statistics, Spain seized more cocaine than any European nation between 1999 and 2005.

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Authorities suspect that Europe's thriving cocaine business likely provided the euros in the duffel bag of Mauricio Mazza-Alaluf, the man arrested at LAX in March. Along with a cousin, Luis Mazza-Olmos, he ran an exchange house in downtown Santiago, Chile, according to U.S. and Chilean law-enforcement officials.

The probe into the Mazzas began in August 2004, says Christian Caamaño, an investigator for the Investigative Police of Chile. The tip-off was a Peruvian passenger on a flight from Colombia who arrived at the Santiago airport carrying a backpack stuffed with €600,000, according to Mr. Caamaño. Alarmed, Chilean authorities began monitoring such couriers and noticed that they dropped off their bags full of euros at the Mazzas' exchange house.

Later, the Mazzas' routine evolved: A courier from Colombia, allegedly carrying European proceeds, would deliver cash at the Santiago airport to an armored-car service. Personnel would count the money in a parked truck and turn it over to the Mazzas or one of their associates, says Hernán Peñafiel, the lead prosecutor in a parallel case brought in Chile against the Mazzas. One of the Mazzas or their associates would then board a U.S.-bound flight with the money, Mr. Peñafiel says.

Once on U.S. soil, according to authorities, the Mazzas allegedly moved their euros with breathtaking openness. Their main tactic was to dutifully fill out paperwork at customs points and financial institutions, using real family and business names, according to law enforcement officials and court documents from the U.S. case.

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After the Mazzas or their associates cleared customs at Los Angeles International Airport, they would transfer their cash to Associated Foreign Exchange Banknotes Inc., a currency-exchange firm headquartered in Encino, Calif. AFEX Banknotes then converted the euros into dollars and wired the dollars to U.S. bank accounts the Mazzas had opened, according to law-enforcement officials and two AFEX Banknotes employees.

The Mazzas had accounts with at least three banks in the U.S., according to the court documents from the New York case: Israel Discount Bank of New York; Harris Bank in Chicago; and J.P. Morgan Chase in Dearborn, Mich. In opening each account, the Mazzas gave their company's real name and openly described it as a tourism and currency-exchange agency.

The Mazzas proceeded to move huge sums of money through these accounts, according to the court documents, often after receiving faxed instructions, intercepted by Chilean authorities, from people or entities with suspected ties to Colombian traffickers.

In a single year, according to court documents, the Mazzas wired $133 million into the Harris Bank account and $117 million out. At their J.P. Morgan Chase account, they wired $35.5 million in and $34 million out in less than three months, and their IDB checking account recorded more than 2,500 transactions totaling more than $29 million during 2003 and 2005, according to the court documents.

Asked to comment, Harris Bank said in a written statement that it "identified suspicious activity" after conducting its own investigation and "closed the account in accordance with banking regulations." IDB said in a statement that the events outlined in the New York case "occurred under former management" and it no longer maintains accounts for unlicensed money transmitters, including the Mazzas' casa de cambio. Chase declined to comment.

AFEX Banknotes compliance officer Andrew Scherer says his company is "mortified" that it may have helped facilitate illegal activity, but added that it has strong anti-money-laundering policies and has taken "substantive measures" to improve its anti-money-laundering policies in the wake of the Mazza case. He declined to be more specific, citing security concerns.

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When Mr. Mazza-Alaluf landed at LAX on March 31, he didn't attempt to conceal his money. Like he and his associates had done hundreds of times before, he filled out the standard declaration forms, a requirement for passengers entering the U.S. carrying more than $10,000 worth of currency. But this time, he was immediately arrested. The 55-year-old Chilean maintained his innocence.

Mr. Mazza-Alaluf has pleaded not guilty to federal felony charges of conspiracy and operating an unlicensed money-transmitting business. His attorney, Bernard Alan Seidler, calls the charges "a classic case of the government overreaching."

Chilean authorities nabbed members of the Mazza clan and their associates in a coordinated operation. They are now in jail in Santiago, facing money-laundering charges. Their lawyer, Yieninson Yapur, says they are all innocent. In an email sent via Mr. Yapur, Mr. Mazza-Olmos said he is a legitimate businessman and has done nothing illegal.

The U.S. investigation of the Mazza case was conducted by a multi-agency task force based in New York and led by the DEA and the Internal Revenue Service. Officials tout it as an important success. But it's unlikely to significantly restrict the flow of narco-euros gushing out of Europe.

On a recent afternoon, far from the glitz of the night life on Gran Vía, a homeless addict walked around in a northern Madrid shantytown with a syringe hanging out of his forearm.

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Even as police tore down the surrounding shacks to make way for a new development, residents hammered away, rebuilding their wood and cardboard houses. "The demand for cocaine is huge, so knocking these shacks down does nothing," says Gema Bautista, a social worker with Fundación Atenea Grupo GID, which runs a mobile clinic and needle-exchange program. "The shacks just pop up again."


Health insurers are taking a new tack in a bid to improve patient safety and reduce health-care costs: refusing to pay -- or let their patients be billed -- for hospital errors.

Aetna Inc., WellPoint Inc. and other big insurers are moving to ban payments for care resulting from serious errors, including operating on the wrong limb or giving a patient incompatible blood.



The companies are following the lead of the federal Medicare program, which announced last summer that starting this October, it will no longer pay the extra cost of treating bed sores, falls and six other preventable injuries and infections that occur while a patient is in a hospital. The following year, it will add to the list hospital-acquired blood infections, blood clots in legs and lungs, and pneumonia contracted from a ventilator.

Private insurers are looking first at banning reimbursements for only the gravest mistakes. But health-insurance executives say it is only a matter of time before the industry also stops paying for some of the more common and less clear-cut problems that Medicare is tackling, such as hospital-acquired catheter infections or blood poisoning. "I'd rather have the cudgel in place first than push the list too far," says Aetna President Mark Bertolini.

Some hospitals and others are concerned that the new strategy could drive up medical costs in other ways as hospitals absorb or pass on the expense of introducing the safety and screening procedures needed to help avoid mistakes.

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Ultimately, insurers say, the efforts will trigger safety improvements and savings for patients.

Health insurers are taking a new tack in a bid to improve patient safety and reduce health-care costs: refusing to pay -- or let their patients be billed -- for hospital errors.

Aetna Inc., WellPoint Inc. and other big insurers are moving to ban payments for care resulting from serious errors, including operating on the wrong limb or giving a patient incompatible blood.



The companies are following the lead of the federal Medicare program, which announced last summer that starting this October, it will no longer pay the extra cost of treating bed sores, falls and six other preventable injuries and infections that occur while a patient is in a hospital. The following year, it will add to the list hospital-acquired blood infections, blood clots in legs and lungs, and pneumonia contracted from a ventilator.

Private insurers are looking first at banning reimbursements for only the gravest mistakes. But health-insurance executives say it is only a matter of time before the industry also stops paying for some of the more common and less clear-cut problems that Medicare is tackling, such as hospital-acquired catheter infections or blood poisoning. "I'd rather have the cudgel in place first than push the list too far," says Aetna President Mark Bertolini.

Some hospitals and others are concerned that the new strategy could drive up medical costs in other ways as hospitals absorb or pass on the expense of introducing the safety and screening procedures needed to help avoid mistakes.

Ultimately, insurers say, the efforts will trigger safety improvements and savings for patients.

Aetna, the country's third-largest insurer by number of members, is beginning to stipulate in hospital contracts up for renewal that it will no longer pay nor let patients be billed for 28 different "never events." Compiled by the National Quality Forum, a coalition of physicians, employers and policy makers, these mistakes include leaving an instrument in a patient after surgery, the death of a mother in a low-risk pregnancy, allowing a patient to develop bedsores or using contaminated devices. Such errors are so egregious "there can't be any argument that they should ever happen," says Troy Brennan, Aetna's chief medical officer.

WellPoint, the largest insurer, is testing the same approach in Virginia with four errors from the forum's never-events list, including leaving a sponge or other object in a patient after a procedure and performing the wrong procedure. It plans to extend the policy soon to its plans in New England, New York and Georgia. UnitedHealth Group Inc. and Cigna Corp. say they're exploring policies similar to Medicare's. The Blue Cross Blue Shield Association says that its 39 member health plans are looking at approaches similar to Aetna's or working with hospitals on reducing errors.

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The National Quality Forum's so-called never events are rare enough that private insurers say they don't expect to see a big financial savings at first. In Minnesota, where hospitals are required by law to report such errors, 154 never events were reported last year out of nine million hospital admissions. Rather, the idea is to spur more attention to safety and public reporting of mistakes.

"It's not a matter of not paying for them. It's about getting them not to happen in the first place," says Thomas Granatir, director of policy and research at Humana Inc., which is working on a policy similar to Medicare's.

The more common errors offer the biggest potential for savings -- in both lives and money. The Centers for Disease Control and Prevention estimates that patients develop 1.7 million infections in hospitals a year, causing or contributing to as many as 99,000 deaths a year. On average, urinary-tract infections and hospital-acquired pneumonia -- which are on the Medicare list but not on the never-events list -- can add more than $10,000 to a patient's hospital bill. A more serious antibiotic-resistant bloodstream infection can result in more than $100,000 in extra costs. Such common errors total more than $4.5 billion in additional health spending a year, according to the CDC.

Despite growing evidence that hospitals can take steps to reduce infections drastically, until recently, infections typically have been considered an inevitable part of care and billed accordingly. "It's something that no one ever questions when you see it on the bill. But now that Medicare will, maybe that's going to change," says Nora Johnson, director of compliance and education at Medical Billing Advocates of America, a nationwide patient-advocacy network that deciphers hospital and insurance bills for consumers and advocates on behalf of uninsured patients.

As insurers roll out the policy across the country, they say they are structuring their contracts with hospitals so that the hospitals also won't be able to charge patients for care made necessary by medical errors. Given the high rate of medical billing errors, however, consumer advocates advise patients to examine their bills carefully, especially if they are aware of errors or problems that occurred during their stay. People with health insurance should check their bills against the explanation of benefits they receive from the health plan, or press their insurers to make sure they haven't been overcharged.

When it comes to medical errors, some hospitals say they forgive bills or adjust charges on a case-by-case basis. But the complex billing and payment arrangements between hospitals and insurers can make it hard to avoid paying for errors and for patients to know whether they're being charged.

Last January, when Arlene Whitfield, a Los Angeles elementary-school teacher, underwent a hip replacement at Centinela Hospital in Inglewood, Calif., she accidentally received B-positive blood, instead A-positive.

The mistake lengthened her recovery time by two days and she ended up staying in the hospital for a week, for which Centinela billed accordingly. That is because Medicare's hospital billing guidelines require hospitals to document and itemize all the care they provide to a patient, says Von Crockett, the hospital's president and chief executive. "That's different than what we expect to collect and get paid for it," he says. "It's a documentation of what happened to the patient." He says Ms. Whitfield's portion of the bill was forgiven.
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Her health plan, WellPoint's Blue Cross of California, ended up paying for only two days, not because it refused payment for the added stay because of the error, but because before the operation, WellPoint had only authorized a two-day stay and didn't receive a request for an extension. (The average length of a stay for Ms. Whitfield's procedure is 4.6 days.) The insurer says it noted nothing unusual about the claim filed by the hospital, although the bill did list the diagnosis code for an infusion of "mismatched blood."

Spurred by laws requiring more public reporting of errors, some hospitals have adopted their own policies on billing for medical errors. All hospitals in Minnesota and Massachusetts, for example, have pledged not to charge for all or some of the errors on the never-events list.

But others say broader policies, such as Medicare's, could punish hospitals unfairly and force them to absorb the costs of screening each patient for bedsores or infections at the time of admission.


Insurers are refusing to pay for care triggered by some complications they believe hospitals should prevent, including:
Object left in patient after surgery
Letting patient wander or disappear
Administering wrong blood type
Artificially inseminating wrong donor sperm or egg
Allowing patient to fall
Operating on wrong limb
Performing wrong procedure
Using contaminated drugs or devices
Discharging infant to wrong person
Mother's death or serious disability in low-risk delivery
Hospital-acquired bedsores
Patient abduction or sexual assault

Some in the industry worry that hospitals may find ways to turn away or divert patients at greatest risk of developing infections or bedsores. "The concept of not paying for complications that are often a biological inevitability, regardless of safe practice, is discriminatory and could be punitive to those patients at greatest risk," Michael Maves, executive vice president of the American Medical Association, wrote in a June letter to the federal Centers for Medicare and Medicaid Services.

Hospitals have an incentive to invest in reducing infection rates, health-safety advocates argue. Since health plans pick up only so much of the extra cost caused by infections, "hospitals are losing their shirts, too," says former New York Lt. Gov. Betsy McCaughey, who formed the Committee to Reduce Infection Deaths, a national, nonprofit campaign to push hospitals to lower infection rates.

To lower its rate of infection, one hospital, Pitt County Memorial Hospital in Greenville, N.C., in February expanded its screening for methicillin-resistant staph infections to all patients coming into the hospital. By identifying and isolating those with the strain early, it lowered the number of MRSA pneumonia cases related to ventilator use by 67% and MRSA urinary-tract infections by 60% within eight months. In all, the expanded screening has cost nearly $1 million, $800,000 picked up by private and public insurers.

Steve Lawler, the hospital's president, says it has more than recouped its $200,000 investment. Moreover, spending the money to make the hospital safer is a "better return on investment...than some billboard campaign," he says.
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Looking to build on the success of its iPod and iPhone devices, Apple Inc. introduced several new products including an ultra-thin laptop computer, dubbed the Macbook Air, and a much-anticipated online movie rental service.

The new Apple notebook computer's major attribute is its sleek profile: it's about three-quarters of an inch thick and weighs three pounds. The Macbook Air features a full-sized keyboard, a 13-inch screen, a built-in camera, and Wi-Fi and Bluetooth connectivity, all powered by an Intel Corp. dual core chip.

Appearing on stage at the company's Macworld expo, Apple Chief Executive Steve Jobs said the computer, which he called "world's thinnest notebook," will cost $1,799 and is scheduled to ship in about two weeks.

With the MacBook Air, Apple becomes the biggest name in two years to try to revive an industry it arguably began with the introduction of its Newton handheld computer 15 years ago.

Ultramobile notebooks represent about 6% of the 270 million notebooks expected to the sold this year. Sales have of the devices have languished, despite efforts from Lenovo Group, International Business Machines Corp., and two years ago by Microsoft Corp. with its "Origami" ultra mobile device.

Apple may benefit from good timing. Asustek Computer Inc.'s recently introduced Eee PC has topped sales charts at Amazon.com and is usually sold out at retail stores.

"Apple's Newton was ahead of its time,' said Shaw Wu, an analysts with American Technology Research. "The functionality wasn't quite there, battery life, screen technology. Now there are products out there proving there's a market for this."

Investors seemed to be unimpressed by the new products: Apple hares dropped more than 6% Tuesday on the Nasdaq Stock Market.

Apple's CEO also launched the computer maker's much-anticipated online movie rental service and unveiled an updated Apple TV device that will let viewers bypass their computers and rent movies directly from their widescreen TVs.

Apple's Macbook Air

Mr. Jobs said iTunes users can rent new-release movies to watch over their computers, iPods or iPhones for $3.99 for a 30 day period. Older titles will rent for $2.99 for the same time period.

The service has the support of all major Hollywood studios including Walt Disney Co., Time Warner Inc.'s Warner Bros., Paramount, Universal, Sony Pictures, Metro-Goldwyn-Mayer, News Corp.'s Fox, Lionsgate and New Line, Apple said.

Apple's push into the online video market comes after the original Apple TV device stumbled badly with its first effort last year. "We tried. Now were back," he said.

Apple sees the Internet video service as another key element in its effort to put its products at the center of the living room entertainment hub of the future, and at the same time, sell more of its hardware products. This tactic worked before, when the Cupertino, Calif., company created iTunes music store to drive iPod sales.

Mr. Jobs also disclosed Apple had sold more than four million iPhones worldwide in the 200 days since the company's trend-setting smartphone was launched. Mr. Jobs said the iPhone had sold 3.4 million units in the U.S., outstripping even the most optimistic analyst forecasts. Mr. Jobs said Apple now has a 19.5% share of the U.S. smartphone market, second only to Research in Motion Ltd.

Apple also introduced an iPhone software update, available Tuesday, that would include new features that allow users to send texts to multiple addresses, create bookmarks that show up as icons on the home screen. It will cost $20 for iPod Touch customers.


A highly drug-resistant superbug is gaining resistance to more drugs and burrowing deeply into the gay communities of San Francisco and Boston, researchers said.

Sexually active gay men are 13 times as likely to have this strain of the highly resistant bacterium, known as MRSA, or methicillin-resistant staphylococcus aureus.

More worrisome still, the new strain of MRSA called USA300 is growing resistant -- or unresponsive -- to three or even four classes of widely used antibiotics.
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MRSA causes deep and stubborn skin infections and has been called the most common cause of skin infections treated in the nation's emergency rooms. It also more rarely can cause lethal invasive infections such as pneumonia or sepsis (blood poisoning).

Several drug classes that have lost their punch against the worsening strain include families that contain: penicillin, erythromycin, clindamycin, tetracycline and fluoroquinolone drugs such as Cipro, said Binh Diep, researcher at the University of California at San Francisco and first author of the study in the Annals of Internal Medicine.

The toughest strain also now is resistant to mupirocin, a topical antibiotic drug used to clear MRSA from the skin surface and nostrils where the bug is known to colonize even people without an infection.

The study emerged from a retrospective review of charts from 183 patients treated for MRSA at the San Francisco General Hospital's Positive Health Program, an outpatient clinic used by people with HIV, the virus that causes AIDS. An additional 130 patients were studied at Boston's Fenway Community Health clinic.

The review of charts found gay men age 18-35 to be hardest-hit. ZIP Codes around San Francisco's Castro District, a largely gay neighborhood, were heavily affected. Previously, MRSA infections have been documented in sports teams, prison populations, gym-goers and the community at large.

Skin-to-skin contact, including sexual relations, are believed to be major ways the bug spreads from person to person. But Henry "Chip" Chambers, chief of infectious diseases at SF General and a study co-author, said heavy antibiotic use is "the most important factor" that the superbug's toughest strain resides among gay men.

Unlike resistant infections of the past, which thrived mainly in hospitals, MRSA runs rampant through the community and can crop up in people with no recent antibiotic use.

"It's more virulent than standard staph," said Shelley Gordon, an infectious-disease specialist in private practice at California Pacific Medical Center. To avoid using the wrong drug and fueling even more resistance, she urged testing for drug resistance, adding, "doctors in emergency settings have to be hip to this and do cultures."


Worry warts often believe they inherited their tendency to stew from their parents. Biology does play a role, research suggests, but there are things you can do to break the cycle of agonizing.

Researchers at Yale have identified a gene mutation for "rumination" -- the kind of chronic worry in which people obsess over negative thoughts. It's a variation of a gene known as BDNF that's active in the hippocampus, an area of the brain involved in thinking and memory. In a study of 200 mothers and daughters published in the journal Neuroscience Letters last month, the Yale scientists found that those who had been depressed in their youth were more likely to be ruminators and to have this particular variation of BDNF.

The discovery adds to a growing body of evidence that depression involves an inability to control negative thoughts, not just excess emotion, says psychologist Susan Nolen-Hoeksema, one of the Yale investigators. And just because rumination has genetic roots doesn't mean it's inescapable, she says. "People can learn to stop these thought processes and have better emotional health."

Some successful professionals find that worry works for them. Imagining everything that might go wrong, and preparing for it, is known as "defensive pessimism."

"I spend all day thinking of ways to gain an advantage over my adversaries, and I assume they're doing the same thing," says Victor Bushell, a partner at Bushell, Sovak, Ozer & Gulmi LLP. "If that was your job description, wouldn't you be worried?"

Other people use worry as a kind of magical shield -- if they worry that the plane will crash, it won't. It doesn't, ergo, they have to worry on every flight.
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Worrying also seems to be part of some people's personalities. "I've been furrowing my forehead forever -- you could pick me out in kindergarten," says Pam Abramson Grisman, who runs a custom-writing business in Mill Valley, Calif. "These days, I worry about my parenting. Prior to that, it was focused completely on the workplace. Prior to that, it was, 'Am I cool enough to live?' "

But worrying is wearying, she says: "It's like chronic pain, and ultimately it doesn't shield you anymore. It becomes a self-fulfilling prophecy. Then you have a heart attack."

Chronic worry can, in fact, lead to a variety of health issues, including headaches, gastrointestinal problems, high blood pressure, anxiety and depression, studies have shown. Rumination, which focuses more on past events than future what-ifs, has also been linked to binge eating, binge-drinking and self-harm. Ruminators may be subconsciously trying to stop their harmful thoughts, says Dr. Nolen-Hoeksema. "Disengaging is really, really hard -- you see that in their neural activity and in their behavior," she adds. But studies have shown that doing something distracting for just 10 minutes can break the cycle and help people tackle problems more effectively.

Techniques from cognitive-behavioral therapy can also help worriers stop the kind of thinking that just makes them miserable.

"It's all about finding the balance between productive and unproductive worrying," says psychologist Robert L. Leahy, director of the American Institute for Cognitive Therapy in New York City. "Say to yourself, 'Is this worry leading to a To Do list?' If it doesn't lead to some action on your part today, set it aside."

He suggests literally reserving 20 minutes a day to worry. If you can postpone worrying, you are exercising control over it, rather than letting it control you.

And learn to accept some risks. "Worriers feel a tremendous intolerance for uncertainty. They get the idea that worrying can eliminate it. But you can't prepare for everything," Dr. Leahy adds. He also suggests a simple "exposure" technique: Practice saying or writing whatever you fear most, such as, "the plane is going to crash" or "I'm going to lose my job." "Repeat it over and over again slowly, like a zombie, and the fear will begin to subside," he says. Eventually, "you'll just get bored with it."

Wall Street's scramble for foreign funds to shore up the big banks' books continues, with Merrill Lynch this morning announcing $6.6 billion in new investments and Citigroup $12.5 billion -- both relying heavily on cash from Asia and the Middle East.

Merrill said it is issuing convertible, preferred stock as a long-term investment to Korean Investment Corporation, Kuwait Investment Authority, and Mizuho Corporate Bank of Japan. "One of my main priorities over the last several weeks has been to ensure Merrill Lynch's balance sheet is strong, and these transactions make certain that Merrill Lynch is well-capitalized," said John Thain, the former New York Stock Exchange chief picked to lead Merrill last fall as the brokerage giant was reeling from bad bets on mortgage-backed securities. The financial breakdown among the three new investors wasn't immediately clear.

Citigroup's move to get back on what newly installed Chief Executive Vikram Pandit called "our 'front foot'" was bigger in scale and broader in action. Citi's new funds include $6.88 billion from the Government of Singapore Investment Corporation, and money from Capital Research Global Investors; Capital World Investors; the Kuwait Investment Authority; the New Jersey Division of Investment; Prince Alwaleed bin Talal of Saudi Arabia, who's already a big Citi stockholder; and former Citi Chairman and CEO Sanford Weill. After months of saying it wouldn't cut its quarterly dividend, Citi is also doing just that, to 32 cents a share from 54 cents. Citi's investment news came amid its release of quarterly financial results that Mr. Pandit called "clearly unacceptable." Citi posted a net loss of $9.83 billion, or $1.99 per share, on revenue of $7.22 billion -- results that reflected $18.1 billion in write-downs and higher credit costs blamed on Citi's exposure to investments derived from subprime-mortgages. Citi also said that burgeoning losses related to consumer loans had raised its credit costs in the U.S. by $4.1 billion.

A source notably missing from Citi's new list of benefactors was the China Development Bank, a state-owned institution previously expected to invest in Citi that was apparently pulled back by the government. It isn't clear why Beijing nixed the deal, but The Wall Street Journal notes how much political flak such investments by sovereign-wealth funds have been catching in the West, as well as uncertainty about how much bigger the U.S. banks' subprime-related losses can grow. In another announcement today with a much lower profile, the Dubai government-controlled investment firm Istithmar said the political backlash in the U.S. and Europe was too harsh for its tastes, and that it was considering investments in China.
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Talk about a tough spot. While the Fed may be contemplating another rate cut in response to recession worries, its sworn enemy inflation apparently is still stalking the land.

The price of gold, traditionally considered both a safe haven in times of trouble and an important inflation gauge, notched historical highs today, touching $914 an ounce overnight before easing a bit but staying above the $900 psychological barrier. Analysts proffered various rationales for the runup, citing concerns over inflation, the weakening dollar -- gold like oil is denominated using the venerable buck -- and worries that the U.S. economy may be entering recessionary times. Tensions between inflation and recession worries also twisted up the yield curve for bonds early today, with the short side of the curve sinking in response to the looming rate cut by the Federal Reserve. On the other hand, "the long end of the curve is rising [and] that is suggesting that that market is very concerned about inflation," said Lee Olver, fixed-income strategist for SMH Capital this morning.

Shortly after midday, the longer side of the yield curve eased somewhat, suggesting concerns over inflation may be relaxing. But the inflation warning signs this morning likely have many investors wondering what to make of them. Here's one takeaway: Right now, it's good to not to be Fed chief Ben Bernanke, who finds himself having to contend with a mix of price and economic growth data which -- in an a nightmare scenario -- could conceivably coalesce into a stagflationary environment. Still, few see Mr. Bernanke swiveling his white horse to confront the dragon of inflation with recession concerns at their current pitch. Perhaps his best bet for now is to wait for Wednesday's Consumer Price Index reading to filter out of the Labor Department and pray it doesn't fan inflation fears further.

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“That is hot ice, and wondrous strange snow!”
Midsummer Night’s Dream 5.1.59

Rather than in a primordial soup prepared in burning fire and bubbling cauldron, perhaps life originated in ice?

Small amounts of liquid water still exist at -60 degrees F (salt can help maintain liquid water down to -65 degrees F and, under more rare conditions, thin films of liquid water can exist at – 90 degrees F) in an ice field. There are at least one million liquid compartments –- test tubes -- in one cubic yard of sea ice. Sea ice accumulates “pollutants” (ammonia, cyanide, etc.) from the atmosphere and stores and concentrates them in the aforementioned liquid compartments.

The typical assumption is that as the temperature drops, the speed of chemical reactions slows. However, that general tendency does not necessarily apply when chemicals are frozen in ice; when frozen in ice, some reactions increase in speed, especially reactions where small molecules join together to form larger molecules, i.e., e.g., complex polymers. This seemingly counter-intuitive tendency is known as “eutectic freezing.”

Eutectic freezing involves the crystallization of water which necessarily remains unadulterated, i.e., the pollutants are excluded. As such, the pollutants become concentrated in the remaining liquid pockets which, in turn, causes certain pollutant molecules to collide more often which process more than offsets the other slowing effects of cold thus accelerating the reaction(s).

Even more, the structure of ice has a generally regular pattern of positive and negative charges which leads to strong bonding with the liquid water remaining in the compartments. Repeated experiments have established that these electric charges organize the pollutants into chains; further, those shorter chains develop into very long chains IF a single strand of RNA is placed into the compartment to act as a template. ,

Scientists believe cyanide was abundant on primordial Earth more than 2.5 billion years ago. Importantly, cyanide tends to self-assemble into larger molecules and does so efficiently under freezing conditions. Tellingly, cyanide evaporates more quickly than does water so it could only become concentrated in cold temperatures. Cold temperatures also preserve fragile molecules – such as nucleobases – dramatically extending the time they exist thus increasing the opportunity(ies) for further development. Frozen cyanide in the presence of ammonia can form adenine (a nucleotide base).
To state the obvious, the above reasoning has expanded the range of worlds on which to search for extraterrestrial life.

Reference List

Fox, D. (2008, February). Did life begin in ice? Discover. 52-60.

National Public Radio. (2000, March). Analysis: Scientists share results of 25-year experiment of freezing vials of liquid. Retrieved January 11, 2008 from the National Public Radio Home Page: http://www.npr.org/ .

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On the night of April 24, 1944, British air force bombers hammered a former Jesuit college here housing the Bavarian Academy of Science. The 16th-century building crumpled in the inferno. Among the treasures lost, later lamented Anton Spitaler, an Arabic scholar at the academy, was a unique photo archive of ancient manuscripts of the Quran.

The 450 rolls of film had been assembled before the war for a bold venture: a study of the evolution of the Quran, the text Muslims view as the verbatim transcript of God's word. The wartime destruction made the project "outright impossible," Mr. Spitaler wrote in the 1970s.

Mr. Spitaler was lying. The cache of photos survived, and he was sitting on it all along. The truth is only now dribbling out to scholars -- and a Quran research project buried for more than 60 years has risen from the grave.

"He pretended it disappeared. He wanted to be rid of it," says Angelika Neuwirth, a former pupil and protégée of the late Mr. Spitaler. Academics who worked with Mr. Spitaler, a powerful figure in postwar German scholarship who died in 2003, have been left guessing why he squirreled away the unusual trove for so long.

Ms. Neuwirth, a professor of Arabic studies at Berlin's Free University, now is overseeing a revival of the research. The project renews a grand tradition of German Quranic scholarship that was interrupted by the Third Reich. The Nazis purged Jewish experts on ancient Arabic texts and compelled Aryan colleagues to serve the war effort. Middle East scholars worked as intelligence officers, interrogators and linguists. Mr. Spitaler himself served, apparently as a translator, in the German-Arab Infantry Battalion 845, a unit of Arab volunteers to the Nazi cause, according to wartime records.

During the 19th century, Germans pioneered modern scholarship of ancient texts. Their work revolutionized understanding of Christian and Jewish scripture. It also infuriated some of the devout, who resented secular scrutiny of texts believed to contain sacred truths.

The revived Quran venture plays into a very modern debate: how to reconcile Islam with the modern world? Academic quarrying of the Quran has produced bold theories, bitter feuds and even claims of an Islamic Reformation in the making. Applying Western critical methods to Islam's holiest text is a sensitive test of the Muslim community's readiness to both accommodate and absorb thinking outside its own traditions.

"It is very exciting," says Patricia Crone, a scholar at Princeton's Institute for Advanced Study and a pioneer of unorthodox theories about Islam's early years. She says she first heard that the Munich archive had survived when attending a conference in Germany last fall. "Everyone thought it was destroyed."

The Quran is viewed by most Muslims as the unchanging word of God as transmitted to the Prophet Muhammad in the 7th century. The text, they believe, didn't evolve or get edited. The Quran says it is "flawless" and fixed by an "imperishable tablet" in heaven. It starts with a warning: "This book is not to be doubted."

Quranic scholarship often focuses on arcane questions of philology and textual analysis. Experts nonetheless tend to tread warily, mindful of fury directed in recent years at people deemed to have blasphemed Islam's founding document and the Prophet Muhammad.

A scholar in northern Germany writes under the pseudonym of Christoph Luxenberg because, he says, his controversial views on the Quran risk provoking Muslims. He claims that chunks of it were written not in Arabic but in another ancient language, Syriac. The "virgins" promised by the Quran to Islamic martyrs, he asserts, are in fact only "grapes."
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Ms. Neuwirth, the Berlin professor now in charge of the Munich archive, rejects the theories of her more radical colleagues, who ride roughshod, she says, over Islamic scholarship. Her aim, she says, isn't to challenge Islam but to "give the Quran the same attention as the Bible." All the same, she adds: "This is a taboo zone."

Ms. Neuwirth says it's too early to have any idea what her team's close study of the cache of early texts and other manuscripts will reveal. Their project, launched last year at the Berlin-Brandenburg Academy of Science and Humanities, has state funding for 18 years but could take much longer. The earliest manuscripts of the Quran date from around 700 and use a skeletal version of the Arabic script that is difficult to decipher and can be open to divergent readings.

Mystery and misfortune bedeviled the Munich archive from the start. The scholar who launched it perished in an odd climbing accident in 1933. His successor died in a 1941 plane crash. Mr. Spitaler, who inherited the Quran collection and then hid it, fared better. He lived to age 93.

The rolls of film, kept in cigar boxes, plastic trays and an old cookie tin, are now in a safe in Berlin. The photos of the old manuscripts will form the foundation of a computer data base that Ms. Neuwirth's team believes will help tease out the history of Islam's founding text. The result, says Michael Marx, the project's research director, could be the first "critical edition" of the Quran -- an attempt to divine what the original text looked like and to explore overlaps with the Bible and other Christian and Jewish literature.

A group of Tunisians has embarked on a parallel mission, but they want to keep it quiet to avoid angering fellow Muslims, says Moncef Ben Abdeljelil, a scholar involved in the venture. "Silence is sometimes best," he says. Afghan authorities last year arrested an official involved in a vernacular translation of the Quran that was condemned as blasphemous. Its editor went into hiding.

Many Christians, too, dislike secular scholars boring into sacred texts, and dismiss challenges to certain Biblical passages. But most accept that the Bible was written by different people at different times, and that it took centuries of winnowing before the Christian canon was fixed in its current form.

Muslims, by contrast, view the Quran as the literal word of God. Questioning the Quran "is like telling a Christian that Jesus was gay," says Abdou Filali-Ansary, a Moroccan scholar.

Modern approaches to textual analysis developed in the West are viewed in much of the Muslim world as irrelevant, at best. "Only the writings of a practicing Muslim are worthy of our attention," a university professor in Saudi Arabia wrote in a 2003 book. "Muslim views on the Holy Book must remain firm: It is the Word of Allah, constant, immaculate, unalterable and inimitable."

Ms. Neuwirth, the Berlin Quran expert, and Mr. Marx, her research director, have tried to explain the project to the Muslim world in trips to Iran, Turkey, Syria and Morocco. When a German newspaper trumpeted their work last fall on its front page and predicted that it would "overthrow rulers and topple kingdoms," Mr. Marx called Arab television network al-Jazeera and other media to deny any assault on the tenets of Islam.
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Europeans started to study the Quran in the Middle Ages, largely in an effort to debunk it. In the 19th century, faith-driven polemical research gave way to more serious scientific study of old texts. Germans led the way.

Their original focus was the Bible. Priests and rabbis pushed back, but scholars pressed on, challenging traditional views of the Old and New Testaments. Their work undermined faith in the literal truth of scripture and helped birth today's largely secular Europe. Over time, some turned their attention to the Quran, too.

In 1857, a Paris academy offered a prize for the best "critical history" of the Quran. A German, Theodor Nöldeke, won. His entry became the cornerstone of future Western research. Mr. Nöldeke, says Ms. Neuwirth, is "the rock of our church."

The Munich archive began with one of Mr. Nöldeke's protégés, Gotthelf Bergsträsser. As Germany slid towards fascism early last century, he hunted down old copies of the Quran in the Middle East, North Africa and Europe. He took photographs of them with a Leica camera.

In 1933, a few months after Hitler became chancellor, Mr. Bergsträsser, an experienced climber, died in the Bavarian Alps. His body was never given an autopsy; rumors spread of suicide or foul play.

His work was taken up by Otto Pretzl, another German Arabist. He too set off with a Leica. In a 1934 journey to Morocco, he wangled his way into a royal library containing an old copy of the Quran and won over initially suspicious clerics, he said in a handwritten report about his trip.

The Nazis began to use Arabists early in the war when German forces began pushing into regions with large Muslim populations, first North Africa and then the Soviet Union. Scholars were used to broadcast propaganda and to help set up mullah schools for Muslims recruited into the German armed forces.

Mr. Pretzl, the manuscript collector, appears to have worked largely in military intelligence. He interrogated Arabic-speaking soldiers captured in the invasion of France, then, according to some accounts, set off on a mission to stir up an Arab uprising against British troops in Iraq. His plane crashed.

Responsibility for the Quran archive fell to Mr. Spitaler, who had helped collect some of the photos. During the war, Mr. Spitaler served in the command offices in Germany and later as an Arabic linguist in Austria, gaining only a modest military rank, records indicate.

After the war, he returned to academia. Instead of reviving the Quran project, he embarked on a laborious but less-sensitive endeavor, a dictionary of classical Arabic. After nearly half a century of work, definitions were published only for words beginning with two letters of the 28-letter Arabic alphabet.

Mr. Spitaler rarely published papers, but was widely admired for his mastery of Arabic texts. A few scholars, however, judged him overly cautious, unproductive and hostile to unconventional views.

"The whole period after 1945 was poisoned by the Nazis," says Günter Lüling, a scholar who was drummed out of his university in the 1970s after he put forward heterodox theories about the Quran's origins. His doctoral thesis argued that the Quran was lifted in part from Christian hymns. Blackballed by Mr. Spitaler, Mr. Lüling lost his teaching job and launched a fruitless six-year court battle to be reinstated. Feuding over the Quran, he says, "ruined my life."

He wrote books and articles at home, funded by his wife, who took a job in a pharmacy. Asked by a French journal to write a paper on German Arabists, Mr. Lüling went to Berlin to examine wartime records. Germany's prominent postwar Arabic scholars, he says, "were all connected to the Nazis."

Berthold Spuler, for example, translated Yiddish and Hebrew for the Gestapo, says Mr. Lüling. (Mr. Spuler's subsequent teaching career ran into trouble in the 1960s when, during a Hamburg student protest, he shouted that the demonstrators "belong in a concentration camp.") Rudi Paret, who in 1962 produced what became the standard German translation of the Quran, was listed as a member of "The Institute for Research on and Eradication of Jewish Influence on German Church Life." Despite their wartime activities, the subsequent work of such scholars is still highly regarded.

By the mid-1970s, Mr. Spitaler in Munich was nearing retirement at the university there. He began moving boxes into a room set aside for the dictionary project at Bavaria's Academy of Sciences. His last doctoral student in Munich, Kathrin Müller, who was working on the dictionary, says she looked inside one of the boxes and saw old film. She asked Mr. Spitaler what it was but didn't get an answer. The boxes, she now realizes, contained the old Quran archive. "He didn't want to explain anything," she says.

In the early 1980s, when the archive was still thought to be lost, two German scholars traveled to Yemen to examine and help restore a cache of ancient Quran manuscripts. They, too, took pictures. When they tried to get them out of Yemen, authorities seized them, says Gerd-Rüdiger Puin, one of the scholars. German diplomats finally persuaded Yemen to release most of the photos, he says.

Mr. Puin says the manuscripts suggested to him that the Quran "didn't just fall from heaven" but "has a history." When he said so publicly a decade ago, it stirred rage. "Please ensure that these scholars are not given further access to the documents," read one letter to the Yemen Times. "Allah, help us against our enemies."

Berlin Quran expert Ms. Neuwirth, though widely regarded as respectful of Islamic tradition, got sideswiped by Arab suspicion of Western scholars. She was fired from a teaching post in Jordan, she says, for mentioning a radical revisionist scholar during a lecture in Germany.

Around 1990, Ms. Neuwirth met Mr. Spitaler, her old professor, in Berlin. He was in his 80s and growing frail, but remained sharp mentally. He "got sentimental about the old times," recalls Ms. Neuwirth. As they talked, he casually mentioned that he still had the photo archive. He offered to give it to her. "I had heard it didn't exist," she says. She later sent two of her students to Munich to collect the photo cache and bring it to Berlin.
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The news didn't spread beyond a small circle of scholars. When Mr. Spitaler died in 2003, Paul Kunitizsch, a fellow Munich Arabist, wrote an obituary recounting how the archive had been lost, torpedoing the Quran project. Such a venture, he wrote, "now appears totally out of the question" because of "the attitude of the Islamic world to such a project."

Information about the archive's survival has just begun trickling out to the wider scholarly community. Why Mr. Spitaler hid it remains a mystery. His only published mention of the archive's fate was a footnote to an article in a 1975 book on the Quran. Claiming the bulk of the cache had been lost during the war, he wrote cryptically that "drastically changed conditions after 1945" ruled out any rebuilding of the collection.

Ms. Neuwirth, the current guardian of the archive, believes that perhaps Mr. Spitaler was simply "sick of" the time-consuming project and wanted to move on to other work. Mr. Lüling has a less charitable theory: that Mr. Spitaler didn't have the talents needed to make use of the archive himself and wanted to make sure colleagues couldn't outshine him by working on the material.

Mr. Kunitzsch, the obituary author, says he's mystified by Mr. Spitaler's motives. He speculates that his former colleague decided that the Quran manuscript project was simply too ambitious. The task, says Mr. Kunitzsch, grew steadily more sensitive as Muslim hostility towards Western scholars escalated, particularly after the founding of Israel in 1948. "He knew that for Arabs, [the Quran] was a closed matter."

Ms. Müller, Mr. Spitaler's last doctoral student, says the war "was a deep cut for everything" and buried the prewar dreams of many Germans. Another possible factor, she adds, was Mr. Spitaler's own deep religious faith. She opens up a copy of a Quran used by the late professor, a practicing Catholic, until his death. Unlike his other Arabic texts, which are scrawled with notes and underlinings, it has no markings at all.

"Perhaps he had too much respect for holy books," says Ms. Müller.

A new kind of dating agency relies on matching people by their body odour

ONE of life's little mysteries is why particular people fancy each other—or, rather, why they do not when on paper they ought to. One answer is that human consciousness, and thus human thought, is dominated by vision. Beauty is said to be in the eye of the beholder, regardless of the other senses. However, as the multi-billion-dollar perfume industry attests, beauty is in the nose of the beholder, too.

ScientificMatch.com, a Boston-based internet-dating site launched in December, was created to turn this insight into money. Its founder, an engineer (and self-confessed serial dater) called Eric Holzle is drawing on an observation made over a decade ago by Claus Wedekind, a researcher at the University of Bern, in Switzerland.

In his original study Dr Wedekind recruited female volunteers to sniff men's three-day-old T-shirts and rate them for attractiveness. He then analysed the men's and women's DNA, looking in particular at the genes that build a part of the immune system known as the major histocompatability complex (MHC). Dr Wedekind knew, from studies on mice, that besides fending off infection, the MHC has a role in sexual attractiveness. It changes odours in ways the mice can detect (with mice, the odours are in the urine), and that detection is translated into preferences for particular mates. What is true for mice is often true for men, so he had a punt on the idea that the MHC might affect the smell of human sweat, as well.

It did. Women preferred T-shirts from men whose MHC was most different from their own. What was more, women with similar MHCs favoured the use of similar commercial perfumes. This suggests that the role of such perfumes may be to flag up the underlying body scent rather than mask it, as a more traditional view of the aesthetics of body odour might suggest.

That makes evolutionary sense. The children of couples with a wide range of MHC genes, and thus of immune responses, will be better protected from disease. As the previous article suggests, that could be particularly important in a collaborative, group-living species such as humanity. Moreover, comparing MHCs could be a proxy for comparing kinship, and thus help to prevent inbreeding.
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The promise of an MHC-based match is not only that your partner's old laundry will smell better but all sorts of other benefits too. The biological compatibility created by complementary immune systems apparently promises better orgasms, a lower likelihood of cuckoldry, more happiness and so on. Nor are heterosexuals the only ones who can benefit. Gay men and women respond as strongly to MHC-derived smells as straight people do—though, as might be expected, their response is to the smell of people of the same sex, rather than the opposite one.

Indeed, the only people for whom MHC matching might not be expected to work are women on the Pill. Chemical contraception, which mimics pregnancy, messes up the system because of an intriguing twist. When women are pregnant, they prefer the smell of MHCs that are similar to their own. This means they are happier in the company of their relatives, which may, as the previous article also suggests, bring evolutionary benefits of its own.

ScientificMatch.com does not rely entirely on the MHC. Besides sending off a swab taken from the inside of their cheek and a cheque for $1,995, hopeful singles have to answer the usual questionnaire about income, background and details such as whether they would prefer a skiing holiday to one spent sketching. They are not, however, asked whether they wear their T-shirts for three days on the trot.

January 4, 2008, 8:09 am
Breast Cancer Test Errors Cause Faulty Treatment
Posted by Jacob Goldstein

The era of personalized medicine won’t work unless we can also find our way into the era of reliable diagnostic testing. And in the case of breast cancer — one of the diseases with good personalized drugs for certain types of tumors — the diagnostic tests aren’t working very well, the WSJ reports.

As a result, many women who would benefit from drugs such as Genetech’s Herceptin or GlaxoSmithKline’s Tykerb are going without because faulty tests say their tumors wouldn’t respond to the drugs. At the same time, errant tests also cause other women are to take drugs that aren’t right for their type of tumor.

“If we tried to market pregnancy tests with this rate of inaccuracy, they would be taken off the market,” says Allen Gown, chief pathologist of PhenoPath Laboratories in Seattle, told the WSJ. “It means there are a lot of women being treated inappropriately.”

A study published last year and led by Genentech researchers reviewed how well labs performed Her-2 tests, which are used to determine whether a woman should take Herceptin. It found that 14% to 16% of those judged positive for Her-2 were actually negative. Of those judged negative, 18% to 23% were in fact positive.

That sort of high error rate could lead to tighter oversight of labs. The Centers for Medicare and Medicaid Services, the federal agency that regulates the testing sites, is examining tougher quality-control requirements. At the moment, labs have to pass outside proficiency checks on 83 types of tests — a list that was devised 15 years ago and doesn’t include the breast-cancer tests.
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What is the clinical relevance of gene profiling? What is going to happen to the healthcare economic system with the introduction of increasingly expensive new drugs that benefit only a small percentage of patients who receive them? Hence the headlong rush to develop tests to identify molecular predisposing mechansims whose presence still does not guarantee that a drug will be effective for an individual patient. Nor can they, for any patient or even large group of patients, discriminate the potential for clinical activity among different agents of the same class. In the new paradigm of requiring a companion diagnostic as a condition for approval of new targeted therapies, the pressure is so great that the companion diagnostics they’ve approved often have been mostly or totally ineffective at identifying clinical responders (durable and otherwise) to the various therapies. Cancer cells often have many mutations in many different pathways, so even if one route is shut down by a targeted treatment, the cancer cell may be able to use other routes. Targeting one pathway may not be as effective as targeting multiple pathways in a cancer cell. Another challenge is to identify for which patients the targeted treatment will be effective. And tumors can become resistant to a targeted treatment. The drug no longer works, even if it has previously been effective in shrinking a tumor. Drugs are combined with existing ones to target the tumor more effectively. Most cancers cannot be effectively treated with targeted drugs alone. Understanding “targeted” treatments begins with understanding the cancer cell.
Comment by gpawelski - January 4, 2008 at 11:38 am

I am a little confused re my treatment plans. I havw been diagnosed with invasive breast cancer with HER 2 positive along with ER (90%) and PR(40%) positive.

Some one suggested that it is rare to find all three factors positive and suggested to have a retest. Your site is kind of supporting that there could be false positives or negatives in certain case and a second test is advised.

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I am in Toronto, I already have two cycles of CMF chemo. Now waiting for radiation, herceptin and hormone treatment after another surgery at the end of the chemo cycles.

Where do I stand? What do I suggest to my medical team? They seem to be knowing what they are doing. I wonder whether they are aware of your researches and findings.

What is your opinion about supplementary or complementary treatment of Homeopathy?
Where would I see any answers you might be posting?

A friend of mine send me this link from Wall Street Journal.

Thank you,
Confused
Comment by Confused from Toronto, Canada - January 4, 2008 at 11:57 am

I wonder what the reason is for these diagnostic inaccuracies? Is it (a) the equipment that detects the analyte in the blood/tissue sample? (b) is the problem with the analyte (marker)? (c) is it a sample storage/handling issue? (d) maybe its the folks reading the test results???
Comment by The Laughing Cavalier - January 4, 2008 at 12:53 pm

You might want to double check about your understanding…it is triple negative is the rarest not triple positive. I think your treatment seems fine for a triple positive br cancer.
Comment by Reality - January 4, 2008 at 1:37 pm

Gene profiling tests, important in order to identify new therapeutic targets and thereby to develop useful drugs, are still years away from working successfully in predicting treatment response for individual patients. Perhaps this is because they are performed on dead, preserved cells that were never actually exposed to the drugs whose activity they are trying to assess. However, it will never be as effective as the cell culture method, which exists today and is not hampered by the problems associated with gene expression tests. That is because they measure the net effect of all processes within the cancer, acting with and against each other in real time, and it tests living cells actually exposed to drugs and drug combinations of interest.
Comment by gpawelski - January 4, 2008 at 1:42 pm

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http://clearblogs.com/generaljohnbuford/86003/Louis+J+Sheehan%2C+Esquire+11174.html
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Louis J Sheehan Esquire
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statistically valid testing has proven that the women with certain hormone and gene profiles respond differently to different regimens of treatment. Women with certain profiles should NOT receive treatment as it is ineffectively. Gene test cost is around $3000 - but he cost of treatment can be $15000 or more - so the question is - is the balance - of testing vs excessive treatment, right?
Comment by OncoAdmin - January 4, 2008 at 6:41 pm

A new and hitherto unknown atmospheric gas, a combination of oxygen and nitrogen, exists 10 to 25 miles above the Earth's surface, Drs. Arthur Adel and C.O. Lampland of the Lowell Observatory, Flagstaff, Ariz., announced to the American Association for the Advancement of Science at the Indianapolis meeting.

It is nitrogen pentoxide, its molecule consisting of two atoms of nitrogen and five of oxygen. It is probably the rarest of gases of the air, present only in the outer regions where the ultraviolet rays of the sunlight bring oxygen and nitrogen into combination.

Existence of the new gas in the ozone layer of the atmosphere was demonstrated by delicate spectroscopy of the far infrared region of the spectrum. If the new gas existed nearer to Earth in the air around us, it would not be detectable by the most refined chemical and physical methods. Because the nitrogen pentoxide takes out certain portions of the sunlight as it comes through the atmosphere to Earth, its existence could be detected.

The situation of Lowell Observatory high on a mountain in a dry atmosphere contributed to the discovery.
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What use was there for a ball-and-socket jointed bone at the back of a dinosaur's skull?

Charles W. Gilmore, curator of vertebrate paleontology at the U.S. National Museum, would like to know.

At the back of the skull of a hadrosaur, a rooster-crested monster that once lived in Montana, he has found a bone arrangement that has never been found in any other kind of skull. A relatively small, triangular bone bears on its front edge a socket or cup, which fits neatly over a ball-shaped projection on the bone in front of it.

Whatever was the use of this unique skull-joint, it could hardly have been to make room for the hadrosaur's massive brain. For the hadrosaur's brain was anything but massive. It couldn't have weighed more than 2 or 3 ounces. It was enough to see, hear, and probably smell with, but that was about all. But then, very likely a dinosaur never bothered to think—except possibly once in a while about another dinosaur.


1) The bigger the telescope the better, right? So what if your scope is the size of the Earth?
A technique called interferometry combines the light from telescopes that are widely separated, and with it you can make a virtual telescope that’s the same size as the distance between the physical telescopes. If those ’scopes are on opposite sides of the Earth, you get a telescope thousands of miles across. Using this technique, astronomers have made phenomenal measurements, including actually seeing the rotation of the galaxy M33 as well as its physical motion across the sky; something that had never been done before. They have been able to see the effects of the Sun’s motion around the Milky Way’s center, even though a full orbit takes 240 million years!

2) One long-standing mystery in astronomy is an apparent fountain of antimatter streaming out from the center of the Galaxy. What’s causing it? Most astronomers assumed it was coming from the giant supermassive black hole there, but now observations indicate it’s actually being accelerated by binary stars, where one of the two orbiting stars is a neutron star or black hole.
The cloud of antimatter is detected because it gives off gamma rays, which are a very high energy form of light. The gamma rays from the Galactic center are not centered on the center (hmmm, remember to edit that line), but extend a little bit more on the western side. This matches the distribution of the black hole or neutron star binaries. These binaries can generate antimatter when regular matter from the normal (sunlike) star swirls around the denser object.
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3) The most luminous objects in the Universe are, ironically and paradoxically, the faintest.
Huh? 
 Black holes can generate fantastic amounts of light as matter falling in to the hole first forms a disk around it. The disk is hot, and magnetic forces (along with friction and gravity) can make it extremely bright, as bright as billions of stars like the Sun. Supermassive black holes in the centers of galaxies are big, and have proportionately big disks which can outshine the rest of the galaxy in which it sits. We call these active galaxies, and there are different kinds (quasars, blazars, Seyferts) depending on the various characteristics of the galaxy.
It turns out, though, that in many cases our view of these black holes is blocked by tick gas and dust in the galaxy. The folks at the Sloan Digital Sky Survey have figured out a way to detect a fingerprint of these obscured galaxies, and found 887 hidden quasars that were previously unknown, by far the largest such sample ever made. What this means is that we have to be careful in the future about what objects we can and cannot see — astronomers may say "We expect to see XXX of these kind of galaxies and see none, which means our cosmology is wrong," we can take it with a judicious grain of salt.

Space is a dangerous place. Stars explode, black holes gobble up matter… but some violent events are so huge they affect entire galaxies, mayhem on a scale so vast it numbs the mind.
Galaxies are island universes, cities of billions or even hundreds of billions of stars. Some galaxies, like our Milky Way, live pretty much on their own, but others live in vast complexes called clusters. These galaxy clusters may have hundreds or thousands of denizens, all orbiting each other due to their mutual gravity, looking something like bees buzzing around hive.
But there is more there than just the matter we see. Dark matter is there as well; invisible stuff that adds to the gravity of the cluster due to its mass, but gives off no light. However, it betrays its presence in two ways: its gravity changes the motion of the galaxies in the cluster, and it distorts the light from more distant galaxies due to gravitational lensing.
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A team of astronomers has used the Hubble Space Telescope to examine the galaxy cluster Abell 901/902 (they call their project STAGES: Space Telescope A901/902 Galaxy Evolution Survey). They wanted to very carefully map out many aspects of the cluster: how many galaxies it contains, what kinds of galaxies they are (spirals, ellipticals, etc.), and, using lensing, determine where the dark matter is. By making a map of all of these characteristics, they hoped to be able to understand the history of the cluster, since the present configuration of the cluster can provide clues to its past.
For the first time, these cosmic archaeologists were able to map out the dark matter of this cluster, and found four very large concentrations of it scattered throughout Abell 901/902. These clumps of invisible stuff are enormous: they total a stunning 100 trillion times the Sun’s mass, or 500 times the mass of our entire galaxy.
Needless to say, that much mass exerts a powerful gravitational pull. Galaxies round the clumps are falling in toward them, inexorably drawn in by the clumps’ gravity. And as they fall in from the suburbs to the downtown regions, they change. They slam into the thin gas between galaxies, which can blow out the gas inside the galaxies (like leaving you car window open on a highway can air out the inside of the car), for one. But as the galaxies fall in, the inevitably interact with one another, colliding and merging as the make the downhill slide. This distorts the galaxies’ shapes, and that in turn allows the astronomers to determine the past history of the objects.
What’s interesting is that they found that galaxies tend to be more distorted on their way in to the centers of the clusters than they are when they are actually at the center. It appears that as they fall, they have time to interact and merge, changing their shape, but once they aproach the center they are falling so quickly they simply don’t have time to distort much as they pass each. Also, it takes time to settle in at the center, so the galaxies at the center appear to be very old, and have finished their transformation from being unsettled and twisted into more sedate, round, elliptical galaxies. The astronomers also determined that the galaxies at the edge of the cluster still produce stars, but by the time they reach the center that has mostly turned off. Their gas — needed to make stars — gets blown out of the galaxies on the way in, and the mergers trigger vast bursts of star formation, which also uses up the gas.
These discoveries were possible only through the use of Hubble, Spitzer, and other telescopes, each of which unpeeled another layer of the puzzle. I’ll note that for Hubble’s part, this represents the largest area of sky ever observed by the grand dame of space ’scopes; it took 80 separate pointings of Hubble to complete the survey of the cluster, and they mapped the locations and shape of 60,000 galaxies in all, a truly staggering amount.
One last thought: the Milky Way is more or less alone in space, being part of a loose collection of other galaxies. But we are headed toward the Andromeda galaxy, and in a couple of billion years we’ll collide and merge with it. I hope that in this far flung future, some distant astronomers can use our own violent fate to learn a little more about the Universe, too. It only seems fair.
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One of the more amazing aspects of looking into deep, deep space is that the path there is tortured and twisted. Space itself can be distorted by mass; it gets bent, like a road curves as it goes around a hill. And like a truck that must follow that road and steer around the hill, a photon must follow the curve of space.
Imagine a distant galaxy, billions of light years away. It emits light in all directions. One particular photon happens to be emitted almost — but not quite — in our direction. Left on its own, we’d never see it because it would miss the Earth by thousands or millions of light years.
But on its travels, it passes by another massive galaxy. This galaxy warps space, and the photon does what it must do: it follows that curve in pace, and changes direction… and it just so happens that the curve is just right to send it our way.
The intervening galaxy is essentially acting like a lens, bending the light. If the more distant galaxy is exactly behind the lensing galaxy, we see the light from that more distant galaxy distorted into a perfect ring, a circle of light surrounding the lens. We call this an Einstein Ring. If the farther galaxy is off to the side a bit, we see an arc instead of a complete ring. Gravitationally lensed arcs and rings are seen all over the sky, and they can be used to determine the mass of the intervening galaxy! The more mass, the more distorted the light from the farther galaxy. So the Universe has given us a nice method to let us weigh it.
In a surprising twist, astronomers have found a new type of lensed galaxy: a double ring! In a rare alignment, there are two distant galaxies aligned behind an intervening lensing galaxy. They’re like beads on a wire, lined up just right such that both more distant galaxies are lensed by the nearer one. In this case, the lens is about 3 billion light years away, and the other two are 6 and 11 billion light years away, an incredible distance.
This image is amazing, but it is also a powerful scientific tool. It allows us to measure not just the mass of the lensing galaxy, but also the amount of mysterious dark matter nearby. We cannot see the dark matter, but it too bends light, and contributes to the lensings. By observing lenses like this, we can take a sample of dark matter in the Universe, and that’s a crucial first step in understanding it. Even better, these double rings allows us to measure the amount of total mass not just in the nearest galaxy, as is usual, but also in the middle galaxy as well, since it distorts the light from the galaxy behind it (turns out it’s a rather lightweight one billion solar masses; our own Galaxy has more than 100 times that mass, so the middle galaxy is considered a dwarf).
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This is a beautiful happenstance; it gives us a measure of the Universe at two points, with one being for free. In fact, Tommaso Treu, the astronomer at U.C. Santa Barbara who investigated this lens, points out that if we can find as few as 50 of these double rings, we can get a much better idea of the distribution of not just dark matter, but also the even more mysterious dark energy in the Universe. That’s one of the biggest goals of modern astronomy… and we may get a handle on it due to a coincidental ring toss.

Space is a dangerous place. Stars explode, black holes gobble up matter… but some violent events are so huge they affect entire galaxies, mayhem on a scale so vast it numbs the mind.
Galaxies are island universes, cities of billions or even hundreds of billions of stars. Some galaxies, like our Milky Way, live pretty much on their own, but others live in vast complexes called clusters. These galaxy clusters may have hundreds or thousands of denizens, all orbiting each other due to their mutual gravity, looking something like bees buzzing around hive.
But there is more there than just the matter we see. Dark matter is there as well; invisible stuff that adds to the gravity of the cluster due to its mass, but gives off no light. However, it betrays its presence in two ways: its gravity changes the motion of the galaxies in the cluster, and it distorts the light from more distant galaxies due to gravitational lensing.
A team of astronomers has used the Hubble Space Telescope to examine the galaxy cluster Abell 901/902 (they call their project STAGES: Space Telescope A901/902 Galaxy Evolution Survey). They wanted to very carefully map out many aspects of the cluster: how many galaxies it contains, what kinds of galaxies they are (spirals, ellipticals, etc.), and, using lensing, determine where the dark matter is. By making a map of all of these characteristics, they hoped to be able to understand the history of the cluster, since the present configuration of the cluster can provide clues to its past.
For the first time, these cosmic archaeologists were able to map out the dark matter of this cluster, and found four very large concentrations of it scattered throughout Abell 901/902. These clumps of invisible stuff are enormous: they total a stunning 100 trillion times the Sun’s mass, or 500 times the mass of our entire galaxy.
Needless to say, that much mass exerts a powerful gravitational pull. Galaxies round the clumps are falling in toward them, inexorably drawn in by the clumps’ gravity. And as they fall in from the suburbs to the downtown regions, they change. They slam into the thin gas between galaxies, which can blow out the gas inside the galaxies (like leaving you car window open on a highway can air out the inside of the car), for one. But as the galaxies fall in, the inevitably interact with one another, colliding and merging as the make the downhill slide. This distorts the galaxies’ shapes, and that in turn allows the astronomers to determine the past history of the objects.
What’s interesting is that they found that galaxies tend to be more distorted on their way in to the centers of the clusters than they are when they are actually at the center. It appears that as they fall, they have time to interact and merge, changing their shape, but once they aproach the center they are falling so quickly they simply don’t have time to distort much as they pass each. Also, it takes time to settle in at the center, so the galaxies at the center appear to be very old, and have finished their transformation from being unsettled and twisted into more sedate, round, elliptical galaxies. The astronomers also determined that the galaxies at the edge of the cluster still produce stars, but by the time they reach the center that has mostly turned off. Their gas — needed to make stars — gets blown out of the galaxies on the way in, and the mergers trigger vast bursts of star formation, which also uses up the gas.
These discoveries were possible only through the use of Hubble, Spitzer, and other telescopes, each of which unpeeled another layer of the puzzle. I’ll note that for Hubble’s part, this represents the largest area of sky ever observed by the grand dame of space ’scopes; it took 80 separate pointings of Hubble to complete the survey of the cluster, and they mapped the locations and shape of 60,000 galaxies in all, a truly staggering amount.
One last thought: the Milky Way is more or less alone in space, being part of a loose collection of other galaxies. But we are headed toward the Andromeda galaxy, and in a couple of billion years we’ll collide and merge with it. I hope that in this far flung future, some distant astronomers can use our own violent fate to learn a little more about the Universe, too. It only seems fair.
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One of the more amazing aspects of looking into deep, deep space is that the path there is tortured and twisted. Space itself can be distorted by mass; it gets bent, like a road curves as it goes around a hill. And like a truck that must follow that road and steer around the hill, a photon must follow the curve of space.
Imagine a distant galaxy, billions of light years away. It emits light in all directions. One particular photon happens to be emitted almost — but not quite — in our direction. Left on its own, we’d never see it because it would miss the Earth by thousands or millions of light years.
But on its travels, it passes by another massive galaxy. This galaxy warps space, and the photon does what it must do: it follows that curve in pace, and changes direction… and it just so happens that the curve is just right to send it our way.
The intervening galaxy is essentially acting like a lens, bending the light. If the more distant galaxy is exactly behind the lensing galaxy, we see the light from that more distant galaxy distorted into a perfect ring, a circle of light surrounding the lens. We call this an Einstein Ring. If the farther galaxy is off to the side a bit, we see an arc instead of a complete ring. Gravitationally lensed arcs and rings are seen all over the sky, and they can be used to determine the mass of the intervening galaxy! The more mass, the more distorted the light from the farther galaxy. So the Universe has given us a nice method to let us weigh it.
In a surprising twist, astronomers have found a new type of lensed galaxy: a double ring! In a rare alignment, there are two distant galaxies aligned behind an intervening lensing galaxy. They’re like beads on a wire, lined up just right such that both more distant galaxies are lensed by the nearer one. In this case, the lens is about 3 billion light years away, and the other two are 6 and 11 billion light years away, an incredible distance.
This image is amazing, but it is also a powerful scientific tool. It allows us to measure not just the mass of the lensing galaxy, but also the amount of mysterious dark matter nearby. We cannot see the dark matter, but it too bends light, and contributes to the lensings. By observing lenses like this, we can take a sample of dark matter in the Universe, and that’s a crucial first step in understanding it. Even better, these double rings allows us to measure the amount of total mass not just in the nearest galaxy, as is usual, but also in the middle galaxy as well, since it distorts the light from the galaxy behind it (turns out it’s a rather lightweight one billion solar masses; our own Galaxy has more than 100 times that mass, so the middle galaxy is considered a dwarf).
This is a beautiful happenstance; it gives us a measure of the Universe at two points, with one being for free. In fact, Tommaso Treu, the astronomer at U.C. Santa Barbara who investigated this lens, points out that if we can find as few as 50 of these double rings, we can get a much better idea of the distribution of not just dark matter, but also the even more mysterious dark energy in the Universe. That’s one of the biggest goals of modern astronomy… and we may get a handle on it due to a coincidental ring toss.