Photo by woodleywonderworks/Wikimedia Commons

It’s a fight all parents are familiar with: the nightly battle to get their children to bed. Kids will try almost any tactic to avoid being tucked in for the night, and even then have long found ways to delay sleep with under-the-cover flashlights. But the deficit of sleep for today’s children and the degree to which that could be harming their short-term and long-term health was underscored last week by a new paper from University of Chicago and University of Louisville researchers. Led by David Gozal, professor and chair of pediatrics, and Karen Spruyt, assistant professor of pediatrics, the study used wristwatch-like activity monitors to objectively measure the sleep of more than 300 children between the ages of 4 and 10 for a week. Their results found that children are sleeping nowhere near the recommended amount of time, and that reduced or irregular sleep increases the risk of childhood obesity.

Like other studies dealing with sleep and weight gain, the research received a flood of media coverage, from sources such as CNN, the New York Times, and Time Magazine. ScienceLife conducted an extended interview with Dr. Gozal to dig deeper into the issues raised by the study, including how sleep deprivation is like an overdrawn bank account, how poor childhood sleep can predispose a child to a lifetime of health problems, and what parents can do to make sure their child is getting adequate rest at night. Here is an edited transcript of that conversation.

Q: What differentiates this study from previous studies of childhood sleep and obesity?

Gozal: Other investigators have conducted studies assessing sleep objectively using an actigraph, but the usual duration of those studies was either one day or three days. There was a study out of China where they actually identified for the first time that kids who slept more during the weekend were somewhat protected from the risk of obesity. Our study set out to look at a US population, to look objectively at both the week and the weekend, and to look at blood correlates of risk. This has never been done, to really look at what impact relatively short sleep or irregular sleep would have on the risk of disease later in life.

Q: What links did the study find between this lack of sleep and obesity?

We found that kids that slept the normally recommended number of hours were actually at the least risk. The kids that slept the least and had irregular sleep schedules were not only at very high risk, over fourfold, of obesity, but also showed a similar increase in metabolic and cardiovascular risk factors. When they tried to compensate during the weekends, the risk was less, but not eliminated. These kids were still at almost a threefold increased risk in obesity, but it’s better than a fourfold increased risk.

Q: The study revealed that he kids (aged 4-10) slept on average about 8 hours a night. Was this a surprise? Is it a concern?

It was a suspected surprise, because in the process of verifying the validity of actigraph recordings in children, we already became fully appraised of the misclassification that parents will assign to the duration of their own children’s sleep. On average, parents tend to overestimate the duration of sleep that their kids get by between 60 and 90 minutes. The moment parents close the door on their children, when they’re a certain age and above, they really don’t know what’s happening. They assume that 15-30 minutes later their kids will be asleep, when in fact it’s not true at all. I remember as a kid myself telling good night to my mom and then taking a little flashlight and book and reading for a long time. Now I’m sure what kids do is pull out their gadgets: phones, computers, mini-TVs, and video games.

The other thing that actually is rather remarkable is that over 80 percent of our kids in our country don’t wake up by themselves, they actually need to be awoken by their parents, which indicates that they still need more sleep, but aren’t getting it. There’s a paper from 1913 which measured and observed that kids of this age would sleep, on average, 10 hours. So the recommendations of all the organizations that are involved in sleep coincide on the need in this age group being 9-1/2 to 10 hours.

I’ve always said you need to look at this as if you were running a bank account. Call it a sleep account. If kids on average have an overdraft every night of two hours of sleep, by the end of the week, after five days of school, they will owe themselves and owe the account about 10 hours. If they continue doing the same during the weekend because they have friends, they want to do all these activities, and sleep is not perceived by the family as important, then they will further owe themselves an additional 4 hours, which gives an overdraft of 14 hours.

Q: So is “catch-up” sleep on the weekend an advisable way to recover from a sleep deficit?

Even if kids are catching up on sleep during the weekend, and let’s say they over-sleep two hours, then they would only reduce the debt of 10 hours accumulated during the week to about 6 hours. In both cases, they’re on overdraft, and long-term their credit history is gone. Also, you must remember, like a real bank account you’re going to pay a penalty every time you are going into overdraft.

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Eodromaeus, or "Dawn Runner" (Copyright Todd Marshall)

While ScienceLife was away at the Science Online 2011 meeting two weeks ago, our friends in the University of Chicago News Office tried to sneak a dinosaur story past us. Eodromaeus, the “dawn runner,” is the latest edition to the dinosaur discovery menagerie of Paul Sereno, professor of organismal biology and anatomy, discovered in the fossil dig site of Argentina known as the “Valley of the Moon.” While only four feet tall and roughly 10-15 pounds, Eodromaeus was (as Chicago Tribune great Bill Mullen puts it) a “nasty looking little critter,” a carnivorous predecessor to the T. Rex in a time (230 million years ago) when dinosaurs were not yet the dominant lifeform on the scene. [You can watch a cool time-lapse movie of the reconstruction of Eodromaeus here, as well as an interview with Sereno about the discovery and its significance for the rise of dinosaurs.]

As the excellent fossil blogger Brian Switek describes at the Smithsonian’s Dinosaur Tracking site, the discovery of Eodromaeus rearranges scientific theories about the early days of dinosaurs. A previous discovery of Sereno’s team in the same area, Eoraptor or “dawn plunderer,” was once thought to be an ancestor of the larger meat-eating dinosaurs that came later. But comparing the teeth of Eoraptor and its neighbor Eodromaeus suggests that the former was actually an omnivore ancestor of the more benevolent sauropods, with Eodromaeus near at the top of the T. Rex family tree.

“We’re looking at the dawn of the dinosaur era where the fork in the road is still very narrow in the divergence of plant eaters from meat eaters,” Sereno told the Tribune. “That is why Eoraptor and Eodromaeus look so much alike.”

But as in Hollywood, your 15 minutes of fame are very short in the world of dinosaurs. In the mere two weeks since Eodromaeus was unveiled, another thunder lizard has stolen the spotlight: the hilarious-looking Linhenykus, the “one-fingered” dinosaur. Seriously, imagine trying not to laugh as one of these ran towards you (bear in mind that they were also small enough to “s[t]and comfortably in the palm of your hand.”). As Switek points out at Dinosaur Tracking, a current theory goes that Linhenykus, and other dinosaurs with one pronounced digit, may have used their comedically short arms to dig for ants and termites.

Nabokov’s Hobby

The research of lepidopterist Vladimir Nabokov never quite got the credit it deserved while he was alive and working as curator of butterflies at Harvard’s Museum of Comparative Zoology. Perhaps it was his outlandish ideas, about butterflies migrating from Asia through Siberia and Alaska and down to South America. Or perhaps it was because he was better known as the experimental novelist responsible for Lolita, Pale Fire, and other books. Catching and studying butterflies was a lifelong hobby for the Russian-born Nabokov, but despite publishing at least one manuscript (pdf, found via Carl Zimmer’s twitter) on the evolution of a group of species known as Polyommatus blues, he was largely ignored by the scientific community as an amateur.

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It is widely acknowledged that racial or ethnic discrimination can negatively affect a person’s health. But how can a scientist measure this impact? The treatment that a person encounters due to the color of their skin, their language, or their country of origin is likely a chronic stimulus, encountered over their entire life rather than during a discrete period of time. How that person perceives or reacts to discrimination may also vary widely from individual to individual - some may shrug it off or internalize the damage, some may grow angry and lash out. Wrapping one’s statistical arms around such a huge variable is nearly impossible.

One way around this problem is to locate a finite period of elevated discrimination against a particular group, and measure the impact of that event upon health. Diane Lauderdale, professor of epidemiology in the Department of Health Studies, found just such an event in the terror attacks of September 11, 2001, and the brief but intense harassment of Arab-Americans that followed. In her talk for the MacLean Center of Clinical Medical Ethics seminar series in January, Lauderdale detailed how she studied a link between post-9/11 discrimination and birth outcomes for a paper in the journal Demography (pdf).

While it might be hard to pin down the discrimination experienced by people of Arabic origin over the course of their lives in the United States, their life in the months after the attacks was undoubtedly more stressful. According to the American-Arab Anti-Discrimination Committee, more than 700 violent incidents were directed toward persons who were perceived to be Arab in the nine weeks after 9/11. But a massive media and government pushback likely limited the duration of this out-of-control hatred, with the director of the ADC commenting in December 2001 that “My impression is that we are rapidly returning to what one would unfortunately call a normal amount of hate crimes.”

Lauderdale chose to focus on pregnant women, who are particularly sensitive to stress. High levels of corticotropin-releasing hormone - a peptide increased by stress - can induce early labor, producing babies that are premature and/or underweight. Lauderdale hypothesized that pregnant Arab-American mothers might have given birth to more low birth weight babies in the six months following 9/11 than they had during the same months in the previous year.

One problem: while Lauderdale had access to the birth certificates of more than 1.5 million children born in California from 2000-2002, the certificates categorized race only by black, white, American Indian, Asian, and Other - no Arabic. Fortunately, previous work by Lauderdale and colleagues had developed an algorithm for predicting a person’s Arab origin using their first and last names. While the algorithm was admittedly imperfect, it was able to create enough of an enriched sample to conduct the comparison, Lauderdale said.

Her analysis found that the births of most groups (white mothers, black mothers, foreign born mothers) were unaffected by the events of 9/11, with virtually no difference in the risk of having a low birth weight baby between the two years. But for the 15,000 Californian women with Arabic names analyzed, there was a small but significant spike in low birth weight babies from October 2001 to March 2002. Children born to those mothers were 34 percent more likely to be underweight than babies born to Arabic mothers from October 2000 to March 2001.

To break the Arabic group down even further, Lauderdale looked at whether each child was given a traditionally Arabic name, potentially a sign of stronger ethnic identity. While the number of Arab names given to newborns did not change before and after 9/11, babies with “traditional” names were more than twice as likely to be born underweight in 01-02 compared to the same months in 00-01. Babies with more “American” names, on the other hand, were almost unperturbed, with only a 16% higher chance of being underweight at birth.

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Since late September, ScienceLife has been posting near-weekly recaps of the annual Maclean Center for Clinical Medical Ethics seminar series. The topic for this academic year, “Health Disparities: Local, National, Global” (pdf), has brought together an all-star cast of physicians, biologists, economists, social scientists and other experts to present research on some of the biggest challenges facing health care in the United States and around the world. Most of the sessions have been videotaped, and the first batch of those videos recently went live on the MacLean Center website. Here’s a digest of the first seven seminars available to watch and the ScienceLife posts that briefly summarized the discussions. The videos have also been added to each post.

Rick Kittles (UIC) - “Race, Biomedical Research, and the Politics of Trust”

Rebuilding Trust, Moving Beyond Race

Kathleen Cagney (UChicago) - “The Neighborhood Context of Health Disparities”

Urban Crime and the Waistline

Robert Sampson (Harvard) - “The Social Reproduction of Health Disparities: Lessons from the Chicago Neighborhood Project”

The Invisible Hand of the Neighborhood

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When you think of a medical instrument, you usually think of a scalpel or forceps. But nine employees of the Medical Center are also proficient in instruments of a musical nature, and are putting those side talents to use for a good cause this weekend.

For the last 11 years, plastic surgeon David Song has led a team of University of Chicago Medical Center employees to the Dominican Republic for two weeks of charity care. Working with Medical Aid for Children in Latin America (MACLA), the team of surgeons, anesthesiologists, nurses, and residents focuses on ear reconstruction, cleft palate surgery, and burn treatment for disfigured residents of Hispaniola (including Haitians and Dominicans) who might otherwise face a life of discrimination and pain.

“A lot of children in the Dominican Republic are born without ears, and they’re ostracized from the community,” said Song, professor and vice chairman of surgery. “Shamanism and voodoo are still practiced in some of these villages near the Haitian border, and a lot of these villagers feel that these children with congenital deformities are really possessed by a demon. They see us as exorcists, when simply it’s reconstructive surgery, and we’re able to reintegrate them back into the village and have them be accepted by their families as normal human beings. That’s really touching for us.”

This Saturday’s “Lend an Ear” fundraiser (pdf), to be held at the International House on the University of Chicago campus, will feature a different type of philanthropy: the debut of the Medical Center band Turnover Time. Named for the medical jargon of the time between procedures in the operating room, the nine members of Turnover Time include surgeons, anesthesiologists, techs, medical students, and residents with serious musical chops. In the video below, you can watch them rehearsing some of the songs from their Saturday setlist, including Coldplay’s “Clocks,” the gospel tune “Oh Happy Day,” and Bonnie Raitt’s “Angel from Montgomery.”

“I knew they were talented, but they blew me away,” Song said of viewing of a Turnover Time rehearsal earlier this month. “It’s an expressive way for them to directly affect our philanthropy and our efforts across the globe and the Western Hemisphere. They’ll have a great time, raise money for a great cause, and it brings the entire Medical Center community together.”

(photo by Wakinnebis/Wikimedia Commons)

At many levels of medicine, it’s important for physicians to make predictions about their patient’s future. Will their disease or condition worsen? Will this treatment or that treatment be more effective in curing them? How much longer does a patient have to live? Such decisions are especially important for pediatricians in the NICU, the neonatal intensive-care unit, where infants born prematurely can be put in incubators and given oxygen for the early days of their life. In the gray area of extremely premature infants born between 22 and 25 weeks of pregnancy, important decisions need to be made by physicians and parents at birth and in the following days about whether to pursue all possible medical interventions for a child that may not survive. Reliable predictions are crucial for these decisions.

William Meadow, professor of pediatrics at the University of Chicago Medical Center, is dedicated to improving the accuracy of that important early-life prognosis. In a recent editorial, Meadow and colleagues from Children’s Memorial Hospital, the Medical College of Wisconsin, and Children’s Mercy Hospital found an unexpected guiding analogy for that effort: the world of sports betting. To illustrate the fluctuating odds of a premature infant’s survival, Meadow chose the competitions on the European football or soccer pitch, where life-or-death stakes are mere hyperbole.

“For premature babies, 24 weekers, we know that many do badly. But which “many” do badly? We need an algorithm to tell us this baby is probably going to do pretty well, this baby is probably going to do pretty badly,” Meadow said. “If we can envision an algorithm like that, then the world would be a better place.”

In sports gambling, the original odds are initially set using all the information available before the game begins. The record of the two teams, relevant statistics, recent streaks and momentum, injured players, and many more factors are part of the calculations of who is the favorite, and by how much. (Betting lines also take into account the influence of a team’s popularity on betting behaviors, but the authors put that factor aside for this analogy.) Similarly, neonatologists use a core set of factors at the time of birth to determine a premature infant’s chances of living, including gestational age, size, steroid levels, and sex. But oddsmaking, in both the sportsbook and the NICU, doesn’t need to end with the initial “betting line.”

“Both in the NICU and in football betting, the pregame odds of a particular outcome only get you so far,” the authors write.

In the boom industry of online sports gambling, the practice of in-game betting has grown more popular. As the game plays out and points go on the scoreboard, gamblers can bet on the eventual winner as odds change in real time. To test how the quality of predictions change as the game progresses, Meadow and colleagues (including his son, Xander Meadow), performed a common-sense experiment, testing how well the score at various intervals of a game predict the final outcome. Originally, they used data from more than 400 baseball games to test the premise. But when the British journal Acta Pediatrica agreed to publish the editorial, they asked that the analysis be repeated in a sport more familiar to their culture.

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Last weekend, I was one of the fortunate 300 who gathered in Research Triangle Park, North Carolina for the 2011 edition of Science Online. The simplest way to describe Science Online is as a science blogging conference, but the real topic on the table was the broad future of science communication, be it through blogs, podcasts, ebooks, twitter, or plain old paper. Through “unconference” sessions led by panels but driven by audience discussion, workshops, field trips to labs and museums, and good old-fashioned bar conversation, scientists, journalists, and scientist-journalists dissected how science can be best defended and explained in a time where mass media coverage is increasingly scant or poor.

I could spill literally thousands of words on what I learned and discovered at Science Online, but for the sake of my audience, I’ll restrict myself to three subjects most relevant to an academic medical center in the new media environment. For more coverage, see the Columbia Journalism Review’s 30,000-foot view, Ed Yong of Not Exactly Rocket Science on the science-blog echo chamber, and Chris Rowan at geology blog Highly Allochthonous on the elephants of the conference. Or you can wade through the over 10,000 tweets sent from and about the conference.

1) Patients Can Blog Too

The majority of the bloggers who attended Science Online cover science through the lens of peer-reviewed research, government policy, or media criticism. Many of these blogs deal with the long-term picture: how will this laboratory study impact medical treatment in 10 years, or how will climate change policy affect our planet’s future. But a corner of the science-writing world is written by people particularly engaged in what science can do for them immediately: patients fighting serious disease.

As a session on “Patient Blogging as Therapy” proved, social media is a natural fit for patients to share information and support. Dave deBronkart, known on the web as e-Patient Dave, called in via Skype to talk about how his own fight against advanced kidney cancer exposed him to the online world of patient engagement, including the technically-primitive but still-functioning listservs of ACOR. Now, having beat his cancer, he’s the hub of an electronic patient advocacy community that includes other panelists like David Seidman (blogging about his kidney disease and need for a transplant) and Alberto Rocca, who started a website for families of children with the rare lung cancer pleuropulmonary blastoma. deBronkart’s motto of “potent information simply portrayed empowers people” was an inspiring reminder of a different way people use blogs or any other media at their disposal to seek knowledge and truth, and the opportunity for online conversations about health that are two-way streets.

2) A Calm Voice in a Shouting Match

But where will patients, of the blogging or non-blogging sort, receive that potent information? The internet is all about easy access to info on virtually any topic, but the quality of that information often leaves much to be desired. Like the search engine TV commercial, a simple search can be easily drowned out by nonsense and falsities - often, in the case of medical advice, dangerous ones. The magnitude of this problem could be read from the beleaguered company accurate medical information kept in the “Defending Science Online” session: evolution and climate change, two other areas where misinformation very noisily tries to shout down evidence-based knowledge.

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Tablets of olanzopine, an atypical antipsychotic drug (from Wikimedia Commons)

If you watch enough football games, you might come away with the impression that today’s most profitable drugs are for erectile dysfunction, cholesterol, and allergies. But far less public attention is paid to one of the most expensive classes of drugs : the antipsychotics, drugs designed to treat certain mental disorders. From 1995 to 2006, the number of doctor visits where antipsychotics were prescribed or continued tripled from 6.2 million to 16.7 million, reflecting a nearly $10 billion chunk of the industry. What’s more, the majority of those prescriptions and dollars result from off-label uses of the drugs to treat illnesses where the clinical evidence of their effectiveness and safety is not crystal clear.

Those astonishing figures come from a new study by University of Chicago and Stanford University researchers, published earlier this month in Pharmacoepidemiology and Drug Safety. In the paper, a team led by G. Caleb Alexander, assistant professor of medicine at the University of Chicago Medical Center, used physician survey data to determine the trends and costs of antipsychotic use from 1995 to 2008. The results portray a corner of the pharmaceutical industry that has evolved at a much faster pace than regulatory agencies and the best scientific evidence can keep up with.

The history of antipsychotic medications stretches back more than 50 years to the first wave of agents, now called the “typical” antipsychotics. These drugs, with names such as haloperidol and chlorpromazine (more commonly known as Thorazine), were originally developed to treat the psychotic symptoms of schizophrenia. The typical antipsychotics led the field until the mid-1990’s, when a new class of “atypical” antipsychotics with a slightly different mechanism began to appear on the market for the treatment of schizophrenia, boasting of fewer motor side effects than the older drugs.

Despite the higher cost of atypical agents - typically 5 to 10 times that of the generic, typical agents - they quickly overtook their predecessors despite unconvincing evidence that they were safer or more effective. Though the atypical agents largely avoided the short-term dyskinesia seen with older antipsychotics, longer-term studies found effects upon weight gain and other metabolic conditions, leading to diabetes in some cases. Furthermore, when directly compared against the typical agents for treatment of symptoms such as mania in bipolar syndrome, atypical drugs were no more effective than the cheaper, older medications.

Alexander’s study shows the magnitude of that turnover: in 1995, 84 percent of antipsychotics used were from the typical group; in 2008, just 7 percent were typical therapies. Furthermore, the shift wasn’t simply a one-for-one replacement. From 2002 to 2006, the overall use of antipsychotics soared, with atypical agents leading the expansion into new uses of the drugs. Ironically, there was a return to using typical agents to treat schizophrenia over the 1995-2008 period studied, while atypical antipsychotics became popular for the treatment of bipolar disorder, depression, and other disorders that were beyond the scope of the original FDA approval.

“We saw remarkable changes over time,” Alexander said. “We know from other prescription drugs that uses change or evolve over time, and one reason is clinical innovation, but there’s also substantial over-use and over-adoption of therapies beyond the evidence base.”

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A male (left) and female (right) splendid fairy-wren in Australia. (photo by Mitchell Walters)

The Friday the 13th and Nightmare on Elm Street movies aren’t typically thought of as mating strategies. But putting on a scary movie is a trick as old as drive-in theaters for encouraging one’s date to jump in fright and snuggle in just a little bit closer. Birds, so far as we know, aren’t into horror movies, but field research published late last year by two University of Chicago researchers suggests that the “scary movie effect” used by humans may also be a mating strategy for some bird species.

Stephen Pruett-Jones, associate professor of ecology and evolution, has been traveling to Australia for more than 20 years to study the splendid fairy-wren, a bird with a very progressive social life. While splendid fairy-wrens are socially monogamous, with males and females forming lifelong pairs, they are sexually promiscuous, mating almost entirely with partners outside of their home relationship. Fairy-wrens also form unusually complex family groups, with young birds sticking around the home territory to help their parents raise offspring rather than flying off to start their own family as soon as possible.

Over the course of studying these unique behaviors, Pruett-Jones and others observed another odd quirk of the splendid fairy-wren. When disturbed by the call or sight of a predator or threat - such as the butcherbird, or a clumsy human researcher - the small, blue males of the species don’t fly away and hide as you might expect, but sing their own distinct call, called Type II song. While a graduate student working with Pruett-Jones, Emma Greig studied the timing of those calls and found that the male fairy-wren responds almost instantaneously to the song of his predator.

“The male begins his Type II call immediately after the butcherbird begins to call, so they’re basically right on top of each other,” Pruett-Jones said. “It sounds like a duet.”

But the purpose of that communication remained mysterious. Was it an alarm call to other fairy-wrens in the area? A display of their bravery and physical fitness to attract mates? Or an effective means of capturing the attention of any females in the area?

The latter theory was tested by another round of field experiments, conducted at Brookfield Conservation Park in South Australia. Using an iPod filled with bird-call audio files, Greig played different songs for female fairy-wrens, using Type I song (a territory-marking call), butcherbird songs, and Type II songs in various combinations. The females responded most strongly when the butcherbird-Type II song combination was played (listen below), as measured by looking in the direction of the call and responding with their own song.

Butcherbird and Male by robmitchum

“We have shown that females do, in fact, become especially attentive after hearing butcherbird calls,” said Greig, currently a postdoctoral researcher at Cornell University. “So, it seems that male fairy-wrens may be singing when they know they will have an attentive audience, and, based on the response of females, this strategy may actually work!”

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A sickle cell (left) and a normal red blood cell (right). From carnegiescience.edu.

In 2006, Rice University football player Dale Lloyd II collapsed during a practice and later died. The cause of death was acute exertional rhabdomyolysis, a sudden breakdown of muscle tissue into the blood brought on by strenuous exercise. But the trigger for Lloyd’s death may have been sickle cell trait, the name for when a person carries one of the two genes required for full-blown sickle cell disease.

People with sickle cell disease form abnormal red blood cells that can lead to chronic pain, hypertension, stroke, and death, while people with sickle cell trait (approximately 2 million in the U.S.) are generally thought to be symptom-free. But Lloyd’s death drew attention to potentially fatal consequences for athletes with sickle cell trait, and a lawsuit filed by the player’s family led to the NCAA mandating testing for all Division I athletes in 2010.

But is screening for sickle cell trait the best preventive measure for college athletes? That was the topic on the table at the first Department of Pediatrics Grand Rounds of 2011 last week, where both the medical and ethical implications of the NCAA’s new policy were considered. Though mandatory sickle cell trait screening has previously been adopted by the military and the National Football League, the NCAA stance could cause a “trickle-down” effect to high schools and youth sports, leading to millions of tests that might cause more harm and expense than good.

At least fifteen NCAA athletes have died from sickle cell trait-related causes in the last 30 years. But given that there have been approximately 2 million total athletes over that time span, that’s only 1 death for every 400,000 people, said Holly Benjamin, associate professor of pediatrics and surgery. Compared to more common, harmful occurrences such as concussions and spinal cord injuries, that’s an exceedingly rare event.

Which is not to say that it shouldn’t be closely monitored. Sickling, the name for a sickle-cell-related attack, can develop after as little as 2 or 3 minutes of strenuous exercise, and can be exacerbated by heat, altitude, and dehydration, Benjamin said. Parents, coaches, and trainers should be vigilant about athletes who suddenly collapse, giving them fluids and oxygen and transporting them to the nearest emergency department.

But while screening athletes for sickle cell trait might improve the response to an athlete’s collapse, preventing that collapse in the first place would be even more beneficial. As a demonstration, Lainie Ross, professor of pediatrics, surgery, and medicine, used the history of sickle cell trait testing in the American military, which has faced similar tragedies and pressure to screen.

After 4 sickle cell trait-related deaths in 1970, a study found that African-American recruits with the gene were 30 times more likely to die during basic training. In response, the Armed Forces considered screening for carriers of the gene and restricting service in those with positive tests. Meanwhile, another study was started to test whether the danger could be reduced by using the wet-bulb globe temperature (WBGT) index, a measure incorporating temperature, humidity and other factors to determine how dangerous conditions are for physical activity. An intervention based around reducing exertion and increasing rest for basic training recruits on days with a high WGBT index was successful not only in completely eliminating deaths related to sickle cell trait, but reduced deaths in non-carriers as well.

“What this shows is that effective intervention does not require the identification of sickle cell trait,” Ross said.

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Two years ago, fear about the the novel H1N1 flu strain spread far more quickly than the virus itself, fueled by equal parts scientific concern about its resemblance to the deadly 1918 flu and media hysteria. In those early days, with a vaccine still months away, scientists were working quickly to develop protections and treatments for the flu for those at high risk of infection and serious illness. As a Chicago Tribune reporter covering the impending pandemic, one of the flu experts I spoke to about these efforts was Patrick Wilson, assistant professor of medicine at the University of Chicago. Wilson, in collaboration with scientists from the CDC and Emory University, was looking at the antibodies produced by the first people exposed to H1N1, to see if they could be used as emergency “vaccines” for health care workers that would be exposed to infected patients.

Though the worldwide pandemic did not measure up to initial concerns, it remained a dangerous and virulent flu, infecting 60 million and hospitalizing more than 250,000 in the United States alone. And while it was not urgently needed, Wilson’s research on the antibodies for H1N1 continued, in order to learn about how the body defended itself against this viral invader. As published this week in the Journal of Experimental Medicine, that project led to a surprising conclusion: the antibodies produced to fight the 2009 H1N1 virus were not only successful in warding off that virus, but might be protective against many different types of influenza - including the historically nasty 1918 strain.

“The result is something like the Holy Grail for flu-vaccine research,” Wilson said. “It demonstrates how to make a single vaccine that could potentially provide immunity to all influenza. The surprise was that such a very different influenza strain, as opposed to the most common strains, could lead us to something so widely applicable.”

When the body reacts to an influenza virus, or any other infectious disease, it creates antibodies that target a specific segment of the invading virus or bacteria to kill or neutralize it. But because influenza viruses are constantly mutating into new forms, antibodies your immune system generated for previous seasons’ strains may not be protective against new strains. Hence, the need for a yearly flu shot, which contains inactivated forms of the viruses that scientists predict will become common in the next season. The vaccine spurs the production of antibodies against those strains, offering protection against infection.

For Wilson and his collaborators, the original idea was to take antibodies from patients exposed to H1N1 in its earliest days and use them to either protect others from infection or treat those who had already been infected. Initial experiments on the antibodies’ power of recognition proved successful - as predicted, many of the antibodies harvested from the white blood cells of H1N1 patients were able to bind the flu strain in an assay. But then, a surprise: when tested with seasonal flu strains from previous years, the antibodies could bind those viruses as well. Researchers threw the last 10 years of seasonal flu, the deadly 1918 virus, and even a dangerous but rare H5N1 avian flu at the antibodies and found they could neutralize them all.

Attacking a virus in a dish is one thing, but the big test would be whether these antibodies could fight infections in the body. Mice were given the antibodies before receiving a dose of the 2009 H1N1 strain, and were found to be protected against the virus as if given a vaccine. When mice were dosed with H1N1 first, then given antibodies as much as 3 days later, the antibodies successfully fought off the infection; by day 12, the antibody-treated mice were free of virus, while the unfortunate control mice all perished by day 7 or 8. The antibodies went on to reign victorious over influenza in further experiments with seasonal flu, the 1918 flu, and avian flu.

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An elephant fish embryo and its yolk (courtesy Andrew Gillis)

Billions of years of evolution has produced an incredible diversity of life - “endless forms most beautiful and wonderful,” as Darwin famously put it. But a fascinating thing about evolution is it has produced such a wide variety of species with a relatively small amount of tools. Many of the roughly 23,000 human genes can be found in species as different as mice and flies, and those genes control embryonic processes that are remarkably similar despite the vastly different outcomes for an insect or a man. But sometimes, finding out just how deep this homology runs requires deep exploration.

Members of Neil Shubin’s laboratory are no strangers to adventure. The search for Tiktaalik, the famous fossil of a transitional species between fish and land-dwellers, took Shubin and his collaborators to remote stretches of the Canadian Arctic. So when J. Andrew Gillis, then a graduate student in Shubin’s laboratory, wanted to study an obscure aquatic relative of sharks with famously hard to acquire eggs, the evolutionary biologist could hardly turn him down.

“I remember when Andrew said ‘I want to get some holocephalans in the lab,’ and I thought ‘yeah, right.’ Everybody’s tried this for years; there’s a long line of people who have always wanted to get holocephalans in the laboratory,” said Shubin, the Robert R. Bensley Professor of organismal biology and anatomy at the University of Chicago. “It’s not like you can buy them at a store, it’s not like you can breed them easily in a lab. They breed on the bottom of the ocean, so you have to find places where the eggs are accessible.”

Holocephalan eggs are prized by evolutionary biologists because of a small but significant anatomical difference from their cousins, the sharks. Both share skeletons made of cartilage and other structural features, but split in terms of appendages called branchial rays, structures that grow outward from the skeletons’ central gill arches. While sharks form several sets of these rays, holocephalans only grow a single set near their head, which eventually forms the support for gill covers. Finding the genetic switch that triggers this anatomical difference, as Gillis, Shubin and colleagues did in a PNAS paper published yesterday, would shed light on the origins of appendage development across the animal kingdom, from fins to wings to limbs.

But first, a scientist needs to leave the safe world of their laboratory in order to find those precious eggs. Gillis’ quest for the embryos of the holocephalan species elephant fish, named for their prominent snout, led him halfway around the world and under the water, on SCUBA expeditions in Australia and New Zealand. Based on anecdotal information collected from local fisherman and marine biologists, Gillis was able to score a precious few eggs to take back to the laboratory for his experiments - but it wasn’t easy.

“Diving for elephant fish eggs was not always a pleasure trip,” said Gillis, now a postdoctoral researcher at the University of Cambridge. “Unfortunately, elephant fish like to lay their eggs in cold, muddy, shark-infested bays, so we spent months seeking out sites like this in southeastern Australia and New Zealand. When you finally find a few eggs in the muck, it feels like winning the lottery.”

Back in the comfort of the laboratory, the mood was still tense, as Gillis had to get all of his experiments working just right so as not to waste the valuable cargo from his expeditions. Previous work by Gillis and Shubin discovered that shark embryos use a gene called sonic hedgehog (Shh) to control the development of branchial arches. The next step was to test whether elephant fish embryos also use this genetic switch to mediate the growth of their less robust appendages.

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The motor symptoms of Parkinson’s disease - tremor, inability to initiate movement, rigidity - result from the loss of neurons that secrete the neurotransmitter dopamine. It therefore follows that the best way to treat these symptoms is by replacing a person’s lost dopamine, the strategy behind the drug levodopa. For the first few years, levodopa (also known as L-dopa) effectively helps people with Parkinson’s move more normally. But the longer the therapy is used, patients are more likely to develop a side effect called dyskinesia: abnormal, involuntary movements that are the opposite of Parkinsonian motor symptoms.

Because this dyskinesia is bad enough to severely affect a patient’s quality of life and gives the primary treatment for Parkinson’s a finite shelf life, neurologists are searching for the cause of drug-induced dyskinesia in order to try and stop it.

“This is probably one of the couple most troublesome aspects of an otherwise good therapy,”  said Un Jung Kang, professor of neurology and director of the Parkinson’s Disease and Movement Disorders Center at the University of Chicago Medical Center.

Logically, many studies have looked for dyskinesia in the dopamine-related areas of the brain, particularly a region called the striatum (pictured above) where dopamine release is necessary for normal control of movement. Investigators examined the striatum to see if repeated exposure to levodopa causes an unwelcome over-reaction that might produce dyskinesia. But an unexpected finding by two University of Chicago labs suggests that an underdog cell type in the striatum may actually be the source of levodopa’s side-effect scourge.

The study, published last month in PNAS, was conducted using a special mouse model of Parkinson’s disease called aphakia mice, previously featured on the blog in a study of levodopa’s beneficial “long duration response.” Thanks to a naturally-occurring mutation, aphakia mice are born blind and specifically lose their dopamine neurons in the same pattern as the brain changes in humans with Parkinson’s. The genetic mouse model allowed researchers in Kang’s laboratory to study dyskinesia in a more natural form than the traditional mouse model of Parkinson’s, which involves killing dopamine neurons in one fell swoop with a neurotoxin.

Previous research discovered that levodopa increases markers of neuronal activity in the striatum, suggesting that replacing dopamine leads to a hyperactive situation that could mediate dyskinesia. Much of the focus has thus been on the medium spiny neurons that make up about 95 percent of the neurons in the striatum, and are also the cells that directly respond to dopamine. But when Yunmin Ding, a research associate in Kang’s lab, looked at repeated administrations of levodopa, he found that different types of cells, called cholinergic interneurons, were stealing the spotlight.

“Before this, the change was thought to be in medium spiny neurons, and that was the focus,” Kang said. “But contrary to his expectation, Yunmin noticed that the cholinergic interneurons were the ones that actually showed this abnormal gene activation and it correlated much better than what people have observed in medium spiny neurons.”

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The late December quiet has given way to a post-holiday flurry of exciting research news, most of which I can’t tell you about until next week. But in the meantime, here’s our first weekly roundup for 2011 of the most interesting science and medical news around the web.

Tears for Fears

Scientists have discovered a multitude of ways by which animals communicate through chemical signals, such as those in the urine that dogs use to mark their territory and the path left by ants to guide their compatriots to food sources. But whether such pheromone signals exist in humans has been much more controversial. Martha McClintock, professor of psychology at the University of Chicago, has published many papers showing evidence for communicative signals in human sweat that can influence menstrual cycling, mood, and brain function in other people. But the behavioral effects of human chemical signals have so far been small, producing nowhere near the sensational effects that marketers of “pheromone” perfumes claim on less than reputable websites.

But another mediator of chemical communication in humans may have been traced this week, in a paper published by Science on the ability of women’s tears to affect sexual interest in males. The Israeli study used a hilarious method of collecting their experimental substance, sitting women down in front of sad movies and catching their tears in test tubes (”We obtained negative-emotion tears from 2 donor women who watched sad movies in isolation,” the authors right in scientist-ese). The fluid was then placed under the nose of male subjects, who viewed pictures of women’s faces and rated their attractiveness. As described by Ed Yong at Not Exactly Rocket Science, the males’ sexual interest decreased when exposed to the tears, as compared to being exposed to a control of saline. Differences in brain activity and testosterone levels were also detected while men sniffed the tears of sadness.

Consulted by the New York Times, McClintock said the study “really broadens the possibilities of where signals are coming from,” but expressed skepticism that the tears’ effect would be restricted to sexual behavior. “I have no doubt that it affected sexuality as they report, but I would be very surprised if it doesn’t turn out to affect other emotions in other contexts. Maybe it’s affecting some deeper, more fundamental psychological process that drives the effect that they’re reporting,” she told the newspaper. Other critics have asked whether the chemical signal lies in the tears themselves, or are collected by the tear from the skin as they roll down a subject’s cheeks. The nature of the chemical still remains to be found, but the evidence suggests another entry in the previously hidden chemical vocabulary of humans.

Fraudulent Science, Human Cost

Last year, the infamous 1998 Lancet paper purporting to show a link between the measles, mumps, rubella vaccine and childhood autism was finally retracted after years of criticism for biased selection of subjects and unethical behavior. But the research, led by Andrew Wakefield, went beyond scientific mistakes to fraudulent falsification of data, a new report from the British Medical Journal released this week discovered. Investigative reporter Brian Deer found that Wakefield, who was being receiving payments from a lawyer seeking to file a lawsuit against vaccine manufacturers before he started the study, changed the timeline of autistic symptoms appearing in patients to make it look more like vaccines were the cause. The article is a rigorous and thorough deconstruction of a scientific fraud that has had concrete consequences for children around the world - in the  12 years since the article was published, measles cases have spiked in England and America as vaccination rates have dropped, and other vaccination-sensitive diseases such as whooping cough have also made a resurgence.

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From Blaxter; Science 24 December 2010

On Christmas morning this year, most people hoped to find an iPad, a puppy, or a luxury car wrapped in a giant red bow under their tree. But geneticists received their present a day early, in the form of two landmark papers published on Christmas Eve in the journal Science. The two extremely dense data sets described in the articles represent new knowledge about gene expression in two seemingly obscure animals: a roundworm and a fruit fly. But the information gained in these massive, multi-institutional projects represents the next important step after the Human Genome Project toward understanding the connection between genes and human health.

Drosophila melanogaster, a species of fruit fly, and Caenorhabditis elegans, a kind of roundworm, are two of the unlikeliest heroes in science. Both are frequently used model organisms used in laboratories around the world, prized for their short reproductive cycle and relatively small, easily manipulated genomes. Much of what we know about the mechanisms of evolution and development have been gained from studies of the fly and the worm, and the Human Genome Project was built on technologies first used on these tiny critters.

Now that scientist are beginning to search beyond the 0.5 percent of DNA that encodes for proteins, Drosophila and C. elegans are once again called upon to be pioneers. The ModENCODE consortium, short for model organism Encycolpedia Of DNA Elements, is building a library of gene expression and interaction in these species to get a better handle on the dynamics of gene function.

“These efforts in model organisms pave the way for similar annotations of the human genome,” said Kevin White, professor of human genetics and ecology & evolution at the University of Chicago, and one of the leaders of the Drosophila side of the modENCODE project.

Figuring out the billions of A, C, G, and T nucleotides that make up an organism’s genome is only the first step in understanding genetic function - the equivalent of a recipe that only lists the ingredients without giving any further instruction. The same set of genes controls the proper development and function of hundreds of different cell types, as different as the specialized cells of the retina and the strong cells of bone and muscle. To accomplish this is a matter of timing, with genetic regulators (themselves moderated by genes) turning on the right genes at the right times.

When you consider that there are 22,000 genes in C. elegans and 17,000 genes in Drosophila, figuring out which genes are turned on when is no modest undertaking. Hence the project is as much computational as biological, as enormous data sets are shaped into networks revealing the intricate genetic choreography cells use to control themselves based on internal and external signals.

“An animal cell behaves as though it contains a tiny computer, assessing the many signals that it receives from its neighborhood and then deciding whether to maintain itself unchanged (its usual fate), grow and divide, or kill itself for the good of the entire cell collective,” Science editor-in-chief Bruce Alberts writes in an accompanying editorial. “Powerful techniques such as those used in these two landmark studies can provide us with lists of all the molecules involved.”

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