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The Soda-Cancer Link, Debunked

Two years ago, researchers at India’s Tata Memorial Hospital made headlines with their announcement that drinking soda might cause a dramatic rise in the risk of esophageal cancer. But in the January 4 issue of the Journal of the National Cancer Institute, Susan Mayne, a nutritional epidemiologist at the Yale School of Public Health, has put the kibosh on that assertion.

Mayne had been interested in the Indian scientists' research since it was first described at a professional conference in May 2004. Two converging trends had led the Indian researchers to their hypothesis: first, Americans' consumption of sugary carbonated beverages had risen by more than 350 percent over the past few decades; and second, esophageal cancer rates were up by a similar amount during the same time period. Perhaps, the scientists suggested, the carbonation in all those soft drinks was increasing acid reflux, the release of stomach acid back into the esophagus. (Reflux is a known risk factor for this type of cancer.)

Coincidentally, Mayne and her colleagues had just finished an exhaustive study on the health histories and habits of more than 1,000 esophageal and gastric cancer patients, so she decided to examine the data to see if soda drinkers really did show higher cancer rates. Surprisingly, they were actually slightly less likely to develop esophageal cancer than control subjects, and diet-soda drinkers had a 48 percent lower risk of the disease than their counterparts who did not drink diet soda. “It was the opposite of what we expected,” she says.

Mayne isn’t sure why soda drinkers are a lower-risk group, but it may be that they are more likely to belong to groups that already have lower cancer rates: diet-soda drinkers, for instance, may have better exercise habits than non-drinkers.

The research will delight soda consumers—and manufacturers. “When they see these results, people ask me, ‘Have you accepted any funding from the soft drink companies?’” she says. (She has not; her work is funded by the National Cancer Institute and the National Institutes of Health.)

Mayne, however, avoids sugary beverages because of their link with obesity and type II diabetes—just as she did before the study. “I’d never encourage people to go out and drink lots of soda,” she says.


The first legal thriller

Generations of literature students will remember the author of Don Quixote as a soldier at Lepanto, or as a captive in Algiers. But as a civil servant?

In Love and the Law in Cervantes, Sterling Professor of Hispanic and Comparative Literature Roberto González Echeverria suggests that Cervantes’s work as a commissary officer—and ensuing financial conflicts that landed him in prison—contributed to the birth of the modern novel.

For González Echevarría, Golden Age Spain was the first modern state. Royal commissions reformed the judicial and penal systems and assembled massive compilations of existing laws and legislation. Meanwhile, a new royal archive grew up at Simancas to house the avalanche of records produced by a burgeoning bureaucracy.

Cervantes and his audience knew this world well. His readers would have recognized in Don Quixote many scenarios, characters, and even notarial formulas seemingly drawn straight from legal records that, as González Echevarría writes, “inscribe the everyday in all its unwieldy and irregular manifestations.” He sees this legal element in, for example, the infractions of the galley slaves in Don Quixote.

González Echeverria focuses on the interaction of love and the law. “Love leaves a documentary trail only in its transgression,” he writes, and he shows how Cervantes’s legal tales center on issues of marriage, rape, inheritance, and forbidden sexuality—issues that by the early seventeenth century were no longer controlled by the church or local custom, but by the state.

Although González Echevarría has worked on the Spanish Golden Age throughout his career, he is best known as a scholar of Latin American literature. He includes a final chapter on the treatments of Cervantes by Carpentier and Borges: “I discovered to my delight the interest that the great Latin American writers had in Cervantes,” he says.  In studying all of these authors he remains most struck by “the complexity of the relationship between desire and interdiction.” It is a relationship, he adds, that “has left a trail in both law and literature and is at the core of our lives as human beings.”


The prostate test conundrum

More than 15 years ago, scientists identified a protein in the blood that seemed to be reliably linked with the presence of cancer in the prostate. Thus was born a rite of passage for middle-aged men: an annual blood test to look for an increase in prostate-specific antigen (PSA). About half of all American men over age 50 now have the PSA test. With extensive screening, rates of detection of the disease shot up 80 percent. Doctors and patients hoped that finding the cancer early would also increase a man’s chances for survival.

Not so, say the authors of a new Yale study. In the January 9 issue of the Archives of Internal Medicine, John Concato, an associate professor of medicine, and his colleagues report that there was no increase in survival rates for tested men. The study has raised new questions about whether screening makes sense for large numbers of healthy men.

Prostate cancer is the most commonly diagnosed cancer and second most common cause of cancer death among American males. Only lung cancer killed more men than the 30,350 who died of prostate cancer in 2005.

Concato’s team looked at the medical records of more than 70,000 men over 50 treated at ten Veterans Affairs hospitals in New England. They found 501 patients who had been diagnosed with prostate cancer from 1991 to 1995 and had died by 1999. A control group consisted of 501 men (with or without prostate cancer, and matched for age and other factors) who were alive at the time their corresponding “case” patient who died. The study found similar rates of PSA screening among both groups—70 men in the case group who died of prostate cancer versus 65 in the control group. Had screening been effective, there should have been fewer screened patients among the group of men who had died, says Concato.

These near-equal numbers suggested to the researchers that routine testing did nothing to improve either group’s chance of survival. “We should recognize the uncertainty involved in PSA screening,” Concato says. “To date, no credible study has shown a survival benefit from testing.”

Still, many in the medical profession believe in the benefits of screening. Nearly 80 percent of male primary care physicians and 95 percent of male urologists over age 50 have themselves tested. However, an elevated PSA level requires a follow-up biopsy to confirm the presence of cancer, and the biopsy often misses cancerous cells. Moreover, should the presence of cancer be confirmed, pathologists cannot reliably distinguish between more or less aggressive forms of the disease—which often leads to over-treatment of non-lethal cancers. Studies show that more than 50 percent of men who live into old age will develop microscopic amounts of prostate cancer, and most never suffer any ill effects. But prostate cancer therapy can result in incontinence and sexual dysfunction. And it may not even succeed for the more aggressive forms of the disease.

“The public often assumes that even if a screening test isn’t perfect, it’s worth doing because it might find something,” says Concato, the director of the Clinical Epidemiology Unit at the VA Connecticut Health Care System in West Haven. “With PSA screening, it’s not black or white. We don’t know who will or won’t benefit, and there’s a downside to screening that patients should be informed about—rather than automatically having it done.”

Several groups, including the American Cancer Society (ACS), have criticized various aspects of the study, including the small size of the groups compared and the limited follow-up period. “The methodology in this study is clearly quite limited in drawing the conclusion that PSA screening is not helpful,” says Robert Smith, ACS director of screening. “There’s quite a lot of evidence that it is beneficial.”

However, an editorial by Dr. Michael Barry from Massachusetts General Hospital in the January 9 Archives agrees with Concato and states: “We already know that PSA screening has a substantial downside. … The key question is whether early detection and subsequent aggressive treatment of prostate cancers found through PSA screening prevents enough morbidity and mortality to overcome these disadvantages—it will have to work to some degree just to break even.”

Two long-term trials are now under way that, when completed in 2009, should provide more definite answers on the benefits and liabilities of PSA screening. Until then, Concato, who is 47, says, “I personally would not get the test.”


Youth, old age, and roundworms

Why do our bodies decline as we age? Scientists believe the answer is in part genetic, and in the December 23 issue of Science, Yale biologists Michelle Boehm and Frank Slack report on the latest discovery of a gene that influences life span. Boehm and Slack have found tiny bits of RNA that regulate how long a minute roundworm known as Caenorhabditis elegans can live. C. elegans is a mainstay of aging research; the first of its genes linked to aging was identified 20 years ago. C. elegans also shares about 60 percent of its genes with humans, and much of what’s been learned about it has proven true in flies, mice, and our species, says Slack, an associate professor of molecular, cellular, and developmental biology.

In their research, Boehm and Slack worked with a “microRNA” called lin-4. (MicroRNAs are small RNA workhorses that regulate the expression of other genes.) Lin-4 is involved in the timing of developmental milestones, such as organ formation, in C. elegans. Boehm and Slack studied two different mutations in lin-4. One of the mutations caused lin-4 to work harder than usual; when that happened, the worms lived about 15 percent longer than normal. But when lin-4’s function was impaired, the worms' life span was cut in half.

Since lin-4 microRNA is present in humans too, Slack hopes that this work may lead to clinical applications. One possibility is to treat human developmental diseases, such as progeria, a condition that causes children to age prematurely. “And in the future, therapeutic delivery of lin-4 to humans could slow the effects of aging and assist in treating the diseases of old age,” says Boehm.

How such benefits might be delivered remains unknown, but one thing is certain, she says: “You won’t have to eat any worms.”


How green?

The U.S. did not fare well in the Pilot 2006 Environmental Perfor-mance Index (EPI) developed by Yale’s environment school and Columbia’s Earth Institute. The EPI, released in January, ranked 133 countries on 16 key indicators, from drinking water to carbon dioxide emissions. New Zealand was first overall, Niger last. Environment school dean Gus Speth hoped that the U.S. ranking—an ignominious 28th—would be a “wake-up call.”







Protection scheme

In ordinary underwater daylight, a coral reef is travel-poster colorful (top). But under the right kind of light—or to an organism with eyes tuned to a different part of the spectrum—the polyps that build and inhabit a reef glow with a green fluorescence (bottom). This eerie color comes from fluorescent proteins manufactured by most species of reef-building, or hard, corals. Scientists have known about this light show for more than 50 years, but why the animals should invest considerable energy in glowing has remained a mystery.

In a paper under review by the Journal of Morphology, Vincent Pieribone, an associate professor of physiology and neurobiology, and his colleagues offer an explanation. “Fluorescent proteins may be acting as antioxidants and protecting corals from damage by chemicals known as free radicals,” says Pieribone.

Hard corals live in a symbiotic relationship with algae. In exchange for a secure home, the tiny plants provide their host with food. But photosynthesis can also lead to free-radical production. In areas where the water temperature has increased above normal—perhaps due to global warming—free-radical concentration may rise above the corals' ability to cope. The result can be the increasingly common bleached-out reefs that have occurred worldwide as corals, in a desperate effort to survive, eject the algae.

“It’s a big gamble,” says Pieribone. “If the animals aren’t recolonized by algae that are better able to handle the heat, the corals have just committed long-term suicide.”




The Nazis engaged in bioterrorism in Italy during World War II, says Frank Snowden, professor of history. In his new book, The Conquest of Malaria: Italy, 1900-1962, Snowden draws on archival material to show that the Nazis flooded previously drained marshes around Rome with salty water to create conditions under which malaria-carrying mosquitoes could flourish. The strategy did not stop the advance of Allied troops, but it did cause a dramatic increase in malaria rates among Italian citizens returning to the area.

Cell phones may be good for you—at least, in hospitals. Keith Ruskin, an associate professor of anesthesiology and neurosurgery, and his colleagues surveyed more than 4,000 anesthesiologists and found that cell phone use by the doctors resulted in a “reduction in the risk of medical error or injury from communication delay.” The study in the February issue of Anesthesia and Analgesia also showed that newer cell phone technology minimized any risk that wireless signals would interfere with medical equipment such as ventilators and monitors.

A significant number of women with asthma find that the condition worsens during pregnancy. But when Yale researchers monitored a group of 702 pregnant women, they discovered something surprising: expectant mothers carrying girls experienced worse symptoms than those carrying boys. In the February issue of the American Journal of Epidemiology, Michael B. Bracken, the Susan Dwight Bliss Professor of Epidemiology, and his colleagues suggest that the difference may be the result of testosterone secreted by male fetuses; the hormone may make asthma attacks less likely.

In the February issue of Geology, Mark Brandon, professor of geology, and his colleagues proposed an explanation for why the strongest earthquakes occur in subduction zones. These areas just offshore, where one tectonic plate is diving beneath another, sometimes give rise to basins that fill over millions of years with sediment as much as three miles deep. The accumulation may slow down the progress of the plates—until the inexorable forces in the subduction zone cause a rapid and catastrophic movement of the seafloor. (An animated video of the process is available at www.yale.edu/opa/ newsr/06-01-31-03. all.html.)


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