There’s no denying that preventive medical screens do save lives, whether through mammograms, colonoscopies, or prostate exams. But for all the benefits, screening is not a one-size-fits-all practice. In the case of prostate cancer, mortality rates have declined by more than 30 percent in the last 20 years as testing levels of prostate-specific antigen (PSA) became a common clinical screen in older men. But other studies of the benefits of PSA screening have been less decisive, including a large 2009 study that found no difference in cancer-specific mortality over the last 10 years. Why the discrepancy?

One answer is that the benefit of PSA screening changes with age - and the reduced life expectancy that comes with age. Though 1 in 6 men will be diagnosed with prostate cancer at some point in their lives, many older men diagnosed with prostate cancer die of something other than the disease. Screening elderly men who already have serious health problems can therefore do more harm than good, paving the way for invasive procedures, risky treatment, anxiety, and health care costs that may have been unnecessary. As a result, many clinical panels have recommended that PSA screening should only be conducted in men younger than 75 or men with at least 10 years of estimated life expectancy due to old age or health problems.

But recommendations do not always match up with practice. To measure the true screening patterns in the clinical setting, a team including Scott Eggener, assistant professor of surgery at the Medical Center, broke down the numbers from a huge national health survey. The data , published this week in the Journal of Clinical Oncology, showed a quite different shape than many would hope: rather than a bell curve with the highest screening rates appearing in men 55-69 who benefit the most, the curve is an uphill climb to a plateau, with men in their 70s receiving the most tests. Men aged 70 to 79 were screened for PSA at almost twice the rate of men aged 50 to 54.

“Our findings show a high rate of elderly and sometimes ill men being inappropriately screened for prostate cancer,” Eggener told John Easton. “We’re concerned these screenings may prompt cancer treatment among elderly men that ultimately has a very low likelihood of benefiting the patient and paradoxically can cause more harm than good.”

When measured according to life expectancy, the results were not much better. Roughly 750,000 men with an estimated life expectancy of 5 years - half of the recommended 10 years - received PSA screening in the previous year.

“The men most likely to benefit from PSA screening are paradoxically being screened at markedly lower rates than men highly unlikely to benefit,” the authors wrote.

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Field assistant Jared Singer maps a partial elk carcass in Yellowstone National Park. Photo credit: Joshua Miller

Paleontologists often deal with time scales in the hundreds of millions of years, reading the messages of fossils to learn about life on Earth long before humans arrived on the scene. But bones aren’t limited to providing insight on prehistoric ecosystems. The skeletal fragments left behind by animals at their final resting place can be just as valuable as ecological data points when they’re 100 years old as when they are 100 million years old, a new study discovered. The “ghosts” of animals from decades past can give scientists the tools to study more recent ecological changes, due to climate change, invasive species and other threats to global biodiversity.

Yellowstone National Park, established in 1872, was the first of its kind not just in the United States, but in the world. For the past 139 years, the National Parks Service has both protected the western territory and studied it, regularly monitoring the wildlife that lives within its nearly 3,500 square miles of land. So for Joshua Miller, a graduate of the University of Chicago Committee on Evolutionary Biology, the Park offered a perfect testing ground for his study assessing the scientific worth of relatively young bones.

“Yellowstone is phenomenal; it’s one of our nation’s gems,” said Miller, now a postdoctoral researcher at Wright State University. “They have a huge amount of historical data on living populations, so it is a great place to look at the bone record and be able to match up what we see in bones to what we know has happened in the living community.”

Miller’s plan was elegant and simple: take a census of the bones he could find lying on the ground (no digging required) at different locations in Yellowstone, and see how well the story of the bones matches up with historical data on the local living species. Specifically, Miller would look at the bones of large mammals such as elk, bison, and mountain goats, estimating the abundance of each species over the last century by counting their skeletal remains. While a straightforward idea, and building off of work by researchers with similar interests, Miller said he initially received skepticism from Park officials who didn’t believe that a researcher could find enough bones to make estimates about historical animal populations. That assumption was proved untrue almost immediately, he said.

“It turns out everywhere you go, you run into bones,” Miller said. “We went up to the Arctic National Wildlife Refuge [on a later project], landed the plane and right next to the wheel was an antler. Bone accumulations are just rampant.”

In Yellowstone, Miller and his field assistants spent three consecutive summers laboriously analyzing forty different plots of land. The assistants walked slowly over a one kilometer area, planting flags wherever they came across animal remains. Miller, who had spent months at Chicago’s Field Museum looking at specimens and memorizing their bones, would then investigate their discoveries to identify the species. He also estimated how long the bones had been lying there, either based on how weathered the remains were, or by taking a small sample for radiocarbon dating.

Partial elk carcass in Yellowstone National Park. Photo credit: Joshua Miller

Slowly, a unique database of population changes over the history of Yellowstone was built by Miller. He then was able to compare his bone data to population surveys collected the old-fashioned way - by flying over the Park and counting the animals. Excitingly, there were few surprises, as the bone database matched known fluctuations in animal populations within the Park over many decades. For instance, the reintroduction of wolves in 1995 produced a decrease in elk populations, a shift reflected in Miller’s database by the high number of older elk bones contrasting with the lower number of more recent elk bones. The predictability was a good thing - it meant that the bone record was accurately depicting known ecological history in Yellowstone, and could therefore be used as a proxy for studying population changes in regions without historical survey data.

Other discoveries were totally unexpected and made little sense - at least initially.

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Reading The Emperor of All Maladies, Siddhartha Mukherjee’s “biography of cancer” from last year, one is struck by both the long and short history of cancer. Descriptions of breast cancer can be found as long ago as an Egyptian papyrus dated to 2500 BC and ancient Greek histories, and tumors have been found in thousand-year-old mummified remains from Peru. But the idea of cancer as a treatable disease is barely a hundred years old, and as recently as the 1940’s, clinicians could do little more than help patients die from the disease as comfortably as possible. Despite these deep historical roots, Mukherjee chooses to start his book in 1947, with Sidney Farber’s first experiments on chemotherapy for children with leukemia.

From there, the pace of the “war on cancer” (though not known by that phrase until 1971’s National Cancer Act) accelerates rapidly, as chemotherapy, radiation and surgical protocols were improved through scientific inquiry. Progress in understanding and treating cancer no doubt seemed incremental as it was happening, and even today some still question its overall success. But Mukherjee’s skillful portrayal presents an astonishing difference in the experience of cancer patients only 50 years apart - from being hidden in out-of-the way wards because of the hopelessness of their condition, to the ultra-modern cancer centers of today offering targeted treatments that offer the promise of a cure, if not yet a certainty.

But stumbling blocks still exist in the scientific progress against cancer. One place where reinforcements are desperately needed is at the level of clinical cancer trials, where the true benefits of laboratory discoveries are put to the test in a human population. While there is no shortage of ideas for new cancer therapies, clinical trials have struggled due to insufficient accrual of patients. Though 25,000 to 30,000 patients are enrolled in cancer trials each year, they only represent 3 to 5 percent of all U.S. adult cancer patients,  Richard Schilsky, professor of medicine and chief of hematology/oncology, wrote in a commentary for Science Translational Medicine last week.

“Despite various attempts to remedy the accrual problem, such as awareness campaigns, establishment of clinical trial registries, and the development of search engines to match patients to trials, annual enrollment on cooperative group clinical trials has remained essentially unchanged throughout the past decade,” he writes. As a result, “up to 40% of cooperative group phase III trials have failed to complete accrual and closed without achieving study endpoints, wasting the contribution of those patients willing to enroll in the trial.”

There are plenty of barriers against getting cancer patients into appropriate trials, Schilsky says. Many are institutional - physicians outside of the academic world may not have dedicated research staffs than can help coordinate patients, deal with regulations and insurance issues, and fill out the extensive paperwork. To circumvent these issues, some doctors would rather write off-label prescriptions for drugs being tested in a clinical trial, getting the potential benefits of the drug without the logistical commitments. On the other side, patients may not be aware of the trials available to them, or may misunderstand the purpose of a clinical trial.

The new era of molecular medicine could raise some of these obstacles even higher or knock them down, Schilsky writes. In 2001, the drug Gleevec ushered in the age of smarter drugs that directly interfere with the cause of the disease, rather than general features of tumor growth. Testing these types of drugs requires new types of trials, with more biospecimens (blood, tumor tissue, DNA) collected from patients and tighter rules about who is eligible for the experiments. Classifying broad cancers into more specific subtypes may eventually improve treatment effectiveness, but in the short term could make testing those treatments even more difficult.

“The challenge is that many patients may need to be screened if the biomarker used for patient selection is of low prevalence in the tumor type under study,” Schilsky writes.

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llustration by Meike Köhler/Journal of Vertebrate Paleontology

Just in time for Easter, a team of scientists digging on a Spanish island have discovered the fossils of a prehistoric rabbit of unusual size: 26 pounds, more than six times the size of today’s bunnies. Called Nuralagus rex - the “king of the hares” - the big guy definitely did not hop when it lived 5 million years ago. While it might resemble more of a rodent than a rabbit to the untrained eye (and its discoverers originally thought it was a tortoise?), experts in the field are convinced that it’s an ancestral figure in the line. “Really, this is a rather typical rabbit head [albeit large] stuck on an atypical rabbit body,” Brian Kraatz, an expert in rabbit evolution at the Western University of Health Sciences in Pomona, told National Geographic. (Kraatz seems like a funny guy - he also told Discovery News “It’s unclear whether their feet would have been decent good luck charms.”). Oh and before you start writing that giant bunny horror movie script, Brian Switek reminds us that it’s already been done.

Scientists in England find they can change the sexual preference of male mice by deleting genes related to the neurotransmitter serotonin. As you might expect, the study has led to some interesting headlines. For a more thoughtful take, science writer Ed Yong asks whether they are truly affecting sexual preference or whether they are merely making indiscriminately friskier mice.

Are people with strong religious beliefs at higher risk for obesity? A study by our friends at Northwestern University suggest that’s the case, finding a correlation between obesity and attendance at religious activities when other factors (such as age, race, sex, education, and more) are controlled for. One interesting take-home message from, suggested by the Medical Center’s Daniel Sulmasy in a HealthDay News article, is that religious activities might be a good place for potential anti-obesity interventions to take hold. No more donuts after Sunday services, bummer.

A scientific skirmish has erupted over a paper by co-authored by famed biologist E.O. Wilson disputing the existence of kin selection, a extension of Darwin’s theory of natural selection that has helped scientists explain the evolution of everything from homosexuality to child-rearing to altruism. Kin selection is the idea that an individual will help protect and nourish relatives beyond their direct offspring because even nieces, nephews, and cousins share some a significant portion of an individual’s genetic background. As recapped by Carl Zimmer, the current debate began with the publication of Wilson’s paper questioning the evidence of this process by Nature last August, a paper that was roundly criticized by the evolutionary biology community (my favorite quote Zimmer received for his original article: “This paper, far from showing shortcomings in inclusive fitness theory, shows the shortcomings of the authors.” Zing!). This week, Nature published several rebuttals to the original paper - one signed by 137 scientists - and the authors’ re-rebuttal. Jerry Coyne, one of the original critics of the paper on his blog, examines the latest salvos in the argument and what it says about the role of professional reputation in scientific publication.

The nuclear reactor situation in Japan appears to have fortunately become less alarming this week. But just in case you are still concerned about radiation traveling over thousands of miles of Pacific Ocean to the United States, here are reassuring comments from David Grdina, professor of radiation and cellular oncology at the Medical Center, given to Fox Chicago News. Also, to put reports on the amount of radiation being measured from Japan to O’Hare Airport into perspective, keep this awesome chart from science comic xkcd handy.

Imagine if your comfortable existence was suddenly and traumatically disrupted by a disaster. Your home is destroyed, food becomes scarce, and social structures suddenly break down. Even the most civilized people would respond to this situation with desperation, doing whatever it takes to survive in the short-term without the usual considerations for the long term.

Now imagine you are a bacterium, living inside the human gut (this might take a bit more imagination). For as long as you can remember, everything has been cool there - a steady stream of nutrients pass by to feed on, the police force of the body’s immune system does not perceive you as a threat, and a happy society has been established with the thousands of other bacterial species in the area. But suddenly, the world as you know it is shaken. The human in which you have made your home contracts a serious illness, and undergoes surgery and intense antibiotic treatment. Millions of your fellow citizens are killed, the food supply dries up, the immune system declares martial law. Facing this desperate situation, bacteria tend to act just like humans would - they riot.

This pattern of ecological collapse leading to chaos may underlie one of the most difficult problems facing health care today: hospital infections. Since surgeon Joseph Lister discovered in the 1860’s that carbolic acid can be used to sterilize surgical instruments and wounds to reduce infection rates, hospitals have grown obsessed with cleanliness to protect patients from bacterial invasion. Yet even perfect diligence cannot prevent serious infections from occurring in a small population of patients, causing scientists such as John Alverdy, professor of surgery at the Medical Center, to ask: Could the threat of bacterial infection be coming from within?

“It’s a new way of thinking about infection, because we’re already doing already we can - washing our hands, sterilizing the site, giving our patients antibiotics - and yet some of the infections seem to be getting worse,” Alverdy said. “There has to be a strategy change, and I think we’re at the forefront of understanding that.”

Alverdy’s group has spent the last decade studying a member of the gut microbiome (the world of bacteria living inside our digestive system), called Pseudomonas aeruginosa. Most of the time, Pseudomonas is a passive colonizer of the human body, an “accidental pathogen” that we pick up through our diets or other environmental exposure that causes no harm. But when the body is severely stressed by a surgical procedure, illness, chemotherapy, or radiation, Pseudomonas occasionally panics and becomes an extremely dangerous inhabitant. Alerted to the body’s emergency by immune system factors and starved for food, it begins tunneling through the lining of the gut to invade the unfortunate patient’s blood. Once the bacteria goes on the attack, it’s very difficult to treat, giving it the highest mortality rate of any hospital infection.

“I have seen some people postulate that Pseudomonas isn’t a very virulent pathogen, and I say ‘what are you talking about?’,” Alverdy said. “If you provoke it the right way, it will kill everything in its wake. It’s very virulent.”

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Like the rest of campus, the MacLean Center for Clinical Medical Ethics seminar series is on spring break, resuming in early April with a talk from provocative economist Richard Epstein. So now’s a good chance to get caught up on the previous quarter’s seminars, covering topics under the umbrella of health disparities from the biological factors of breast cancer to the relationship between crime and public health to some of the exciting projects from the Urban Health Initiative. Hopefully, the ScienceLife coverage has kept interested readers informed about the valuable contents of this unique seminar series, but if you prefer a more visual experience, the MacLean Center website has posted several of the lectures in video form. Here’s a recap of the Winter Quarter sessions that are currently available for viewing.

Eliminating Global Disparities in Breast Cancer - Olufunmilayo Olopade Jim Fackenthal, University of Chicago

Unfortunately, Dr. Olopade was unable to deliver her talk due to a last-minute conflict, but Jim Fackenthal, research associate assistant professor in her laboratory, was able to provide emergency relief. The disparity in the survival rates of white women and black women in the United States with breast cancer remains wide, and while some of this gap can be explained by socioeconomic factors, biology also plays a role. Fackenthal talks about the evidence for more aggressive and harder to treat forms of breast cancer in women of West African origin here and abroad. The group’s research projects span from laboratory experiments on genetics and epigenetics to blood testing and screening in Nigeria.

Births to Arab-American Women Before and After 9/11: Evidence of Stress Effects - Diane Lauderdale, University of Chicago

The terrorist attacks of September 11, 2001 were stressful for all Americans, but possibly most challenging for Arab-Americans who experienced discrimination in the wake of the events. Lauderdale, a professor of epidemiology, wanted to look at whether one could measure a negative health impact of this discrete period of stress, choosing premature or underweight births as a health outcome potentially sensitive to discrimination. It wasn’t an easy task, as Lauderdale and her collaborators first had to develop an algorithm to find names in California’s birth registry that are likely of Arab origin. But the results of the study were striking, as Lauderdale was able to measure a spike in babies born underweight to Arab-American mothers in the months after 9/11, without any significant changes among other ethnicities.

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Since the time of Linnaeus, scientists have loved classifying the world around them. But while centuries of biologists have worked to collect and categorize the plants and animals of Earth, all that work likely only covers about a minute fraction of our planet’s life. As much as 99 percent of the biodiversity on Earth is smaller than 2 microns - bacteria, viruses, and tiny eukaryotes - and most of these remain to be discovered by humans. There are more microbial cells on earth (1 nonillion, or 1×10^30) than there are stars in the sky, and all of this new life exists in soil, in seawater, and inside animals, plants, and even us.

“You are mostly microbes,” Jack Gilbert told the Institute for Genomics and Systems Biology in a lecture last month. “The world is mostly microbes, and yet we have less of an understanding of how microbes run the universe than we do of the universe itself.”

Gilbert, an assistant professor of evolution and ecology at the University of Chicago, is part of an international project to remedy that shortage of knowledge about the microbial world. The Earth Microbiome Project, a group bringing together scientists from several different institutions, is dedicated to filling in these gaps in the tree of life and, more importantly, figuring out how they may be secretly pulling the strings of Earth’s ecosystems. In his talk, Gilbert rapidly narrated the group’s aims and his own research projects until he ran out of breath, leading an hour-long tour around globe in search of nature’s smallest and most abundant participants.

Classically, microbiology has taken place in cell culture dishes and incubators, as scientists grew bacteria in the laboratory in order to study its identity and function. But the field has benefited greatly in recent years from genetic advances opening up new paths of discovery. As the price of accurately sequencing DNA and its products has exponentially dropped - driven largely by the demand for human genomics - ecologists interested in microbes have borrowed the technology for their own uses. Now, instead of growing bacterial populations in the laboratory, microbiologists can take a genetic sample of whatever environment they wish and use the genes in that sample to reconstruct its microbial denizens. This process is called “metagenomics,” and it is expanding our knowledge of the bacterial world in leaps and bounds, Gilbert said.

“We can take a sample, sequence it, look at the microbial taxa in there, and identify things we couldn’t culture,” Gilbert said. “There are four trillion base pairs of genetic information in a millileter of seawater, in one teaspoon. In a gram of soil, there are about 4 quadrillion base pairs.”

With so much information out there waiting to be discovered, one of the most important questions is where to start. The Earth Microbiome Project is overseeing dozens of projects, each with their own hypotheses and environmental targets. Gilbert outlined just a few: analyzing samples from near the site of the Gulf of Mexico oil spill; comparing soil samples - some as old as 135 years old - from China, France, Australia, and South America; characterizing the microbial communities from the vaginal canals of fertile and infertile pandas in the San Diego Zoo (seriously). Importantly, the procedures used to analyze such widely different samples are being standardized by the project to ensure that comparisons between different research groups and samples are possible.

“The goal of this project is to systematically approach the problem of characterizing microbial life on Earth,” Gilbert said. “We’re reaching a zenith point in our ability to do things individually, and if we want to start generating synthesis of our understandings, we need to start working as a team, as a group, like the physicists do. We want to do the same thing: Come together as a group and say ‘we have a really good idea, a life-changing idea that will change the way we live on this planet, we just need to do it in a systematic and well organized fashion.’”

As a discrete example, Gilbert offered one of his own research projects, conducted before he relocated to Argonne National Laboratory last summer. As senior scientist at Plymouth Marine Laboratory in England, Gilbert and his team studied a section of the English Channel that has been sampled by scientists every week since 1864 - interrupted only by the two World Wars. Since 2000, the team has taken samples suitable for metagenomic analysis, and has methodically characterized what microbes live in this patch of water and how that population changes.

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Photo by Bruce Powell

Yesterday wasn’t just St. Patrick’s Day for fourth-year medical students around the country - it was also Match Day, the tense and celebratory day when aspiring doctors learn the residency program where they will spend their next 3-7 years. At the Pritzker School of Medicine, green-clad students and supporters absolutely packed the hospital’s Billings Auditorium for the big event Thursday morning, cheering their peers as they were called one by one at random to collect their match envelope. In a local tradition, it literally pays to go last, as students throw into an informal prize pot for whoever has to wait and squirm the longest to pick up their envelope (second-to-last gets a Hershey bar as consolation). In the video below, you can see some of that process - including the outcry when the last envelopes are miscounted - followed by the amazing tension-release of the countdown and unison envelope opening.

The numbers from the day are just as exciting as the video. At Pritzker (recently ranked #12 among medical schools by US News and World Report), 110 students were matched in 24 specialties at 46 institutions, including 23 students who will stay with us here at the Medical Center. The most popular specialties for Pritzker students were internal medicine (25% of the class), general surgery (11%), and pediatrics (11%). Nationally, trends continued to shift for the second consecutive year toward primary care specialties such as internal medicine, family medicine, and pediatrics, according to the National Residency Matching Program, a step in the right direction to meet some of the increased demand for primary care doctors expected in the wake of health care reform. MedPageToday’s Kristina Fiore breaks down the numbers.

Podcast 0.3: Transplants, Rock-Paper-Scissors Ecology, and More

We have settled on a name for our young research podcast: Bench to Bedside. However, we are still keeping the training wheels on as we work out the technical kinks and explore the best ways to deliver audio versions of our latest research and medical stories. Please enjoy the third installment of our podcast, featuring a recent coast-to-coast kidney transplant chain that involved the Medical Center, how Rock-Paper-Scissors can explain biodiversity, the fight against indoor air pollution in Nigeria, and the new numbers on the eating disorders epidemic in the United States. As always, we would love to hear feedback on what we’re doing right and wrong at robert.mitchum@uchospitals.edu or dianna.douglas@uchospitals.edu.

Bench to Bedside Episode #0.3 by robmitchum

Elsewhere…

Some people keep ant farms, some people keep multiple flasks of bacteria growing for 13 years (and counting) to study evolution. Ed Yong writes about experiments from Michigan State University that show “tortoise” bacteria can beat out “hare” bacteria over the long run. (And if you’re a science communicator of any sort, do listen to Ed and Carl Zimmer’s “Death to Obfuscation” session from January’s Science Online meeting)

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Electronic health records are a hot topic in the world of medicine, as hospitals implement new computerized systems to meet federal incentives. Proponents of replacing paper records with electronic health records (EHR) in hospitals and other health care settings argue that the update will improve the efficiency of health care, cutting costs and making life easier for patients and doctors. But a less popularized - and probably more immediate - effect of the EHR wave will be felt by clinical researchers, who will suddenly have a flood of medical data where there once was a drought.

This new EHR-enabled world of clinical research was featured in a recent lecture at the Department of Medicine Grand Rounds by Ari Robicsek, visiting from the Medical Center’s partner institution in Evanston, NorthShore University Health System. Robicsek is an infectious disease specialist and a self-described “accidental informaticist,” a physician and researcher who found himself drawn to EHRs as a tool to address important clinical questions. As an early adopter of paperless medical records, NorthShore has had 8 years to build a “data warehouse” that can be used for research projects. While the Medical Center works toward the next phase of its own EHR launch, called Phoenix, Robicsek’s examples were an exciting peek at how the new resource can be used to prevent hospital-acquired infections and make the most significant change to the definition of fever in 140 years.

“These are, I hope, a series of interesting illustrations of the increasingly amazing things that researchers and hospital systems are capable of doing because of the growing informatics resources available to us,” Robicsek said.

A top priority and concern for any hospital is reducing the spread of bacterial such as MRSA, which can infect sick patients with suppressed immune systems during their inpatient stay. In the last decade, hospitals have launched intensive screening programs to find patients who are carrying these bacterial strains as soon as they are admitted to the hospital, so that extra precautions can be taken. However, it’s not cheap to test every single patient, and false positives in the tests create unnecessary expense. Being able to target tests to patients more likely to be colonized by MRSA could save millions of dollars - a shift that Congress has ordered, without offering any help on just how to find those “magical” high-risk patients, Robicsek said.

Sounds like a job for the electronic health record! Because NorthShore has been adding the results of its MRSA screening tests to patients’ electronic records, Robicsek and colleagues were able to quickly comb through the data of more than 23,000 patients to find characteristics that predicted a high chance of carrying the bacteria. Instead of pulling each paper record by hand as in the old days, computer models could be built to find predictors of risk. When tested in a second batch of data (built from more than 26,000 patients), the models published earlier this year could identify the 30 percent of “high-risk” patients who account for the majority of positive MRSA tests. If implemented (as NorthShore plans to do later this year), such models could direct testing to those patients most likely to be an infection risk, rather than testing willy-nilly and racking up giant expenses.

Besides alerting physicians to clinical threats, electronic health records can also help them do more with data they’ve been collecting the old-fashioned way for centuries. Fever might be the most basic biometric, simple enough for Moms to test informally at home with the back of their hand. But the meaning of fever has changed little since Carl Reinhold August Wunderlich established the normal body temperature of humans (roughly 37° Celsius or 98.6° Fahrenheit) in 1871, Robicsek said.

“[Wunderlich] is thought over the course of his career to have taken the temperature of some 25,000 individuals, and it was his monograph on clinical thermometry that caused temperature vigilance to be introduced into routine clinical care,” Robicsek said. “Remarkably, there has been very little subsequent work validating his data…almost nobody has looked at this in the setting of physiological perturbation,” - in other words, asking what is a “normal” fever after a surgery, and when is it a cause for worry.

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For three weeks starting tonight, the attention of sports fans around the country will be on the brackets of the NCAA Basketball Tournament as 68 teams are methodically reduced to one champion. The process is somewhat similar to evolution, as a combination of direct competition and environmental luck (determined by a team’s seeding and the results in other games) helps whittle down the field in a survival of the fittest fashion - no wonder the bracket is initially set by the NCAA Selection Committee. Nature, it turns out, conducts its own tournaments to determine which species in a given ecosystem will live on and which will go extinct. Only in this game, it’s a little harder to keep score.

Rock-Paper-Scissors is best known as a childhood playground game, one that gets old once the players realize that no clear winner will ever emerge. But that indecisive quality attracted researchers Stefano Allesina and Jonathan Levine to the simple game as a potential explanation for one of ecology’s greatest mysteries: biodiversity. The ability of similar species to occupy similar niches within an ecosystem has long baffled ecologists, since evolutionary competition between the species should eventually produce a surviving winner and an extinct loser. But in systems like the Amazon, thousands of species appear to have struck a truce, peacefully co-existing.

Yet what looks like peace on the surface may merely be the result if constant rock-paper-scissors-like tournaments behind the scenes, Allesina and Levine report this week online at Proceedings of the National Academy of Sciences. The game is an example of an intransitive relationship, where none of the three options can achieve total dominance: rock beats scissors, scissors beats paper, and paper beats rock. That kind of relationship has been observed in nature, for trios of lizards or bacterial species. But what about intransitive relationships with more than three participants - the rock-paper-scissors-dynamite and beyond of nature?

“No one had pushed it to the limit and said, instead of three species, what happens if you have 4,000? Nobody knew how,” said Allesina, assistant professor of ecology and evolution at the University of Chicago. “What we were able to do is build the mathematical framework in which you can find out what will happen with any number of species.”

Allesina and Levine built their model to simulate the outcome when different numbers of species compete for various amounts of “limiting factors” with variable success. An example, Allesina said, is a group of tree species competing for multiple resources such as nitrogen, phosphorus, light, and water. Some trees may be better at obtaining nitrogen from the soil, while others may have better access to water or light.

When such a complex model is simulated over time, some weaker species lose and go extinct. But many species remain - some common, some rare, but all balanced in a state of equilibrium. With each additional limiting factor added into the model, more species are able to survive, producing robust biodiversity despite constant competition.

“What we put together shows that when you allow species to compete for multiple resources, and allow different resources to determine which species win, you end up with a complex tournament that allows numerous species to coexist because of the multiple rock-paper-scissors games embedded within,” said Levine, professor of ecology, evolution & marine biology at the University of California, Santa Barbara.

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For some diseases, taking a census is easy. Most people who have cancer are diagnosed with the disease before they die and seek treatment, allowing for the collection of detailed national cancer statistics. But other diseases tend to hide in the shadows, undetected and under-counted due to infrequent diagnosis or an unwillingness of patients to seek treatment. Into this latter group falls the eating disorders: anorexia nervosa, bulimia nervosa, and other conditions. Because many of these patients try to avoid treatment, psychiatrists have long suspected the numbers are skewed because only a subset of people suffering from eating disorders find their way to their clinical practice.

“We only see the tip of the iceberg,” said Daniel Le Grange, professor of psychiatry and director of the University of Chicago Eating Disorders Program. “As clinicians and researchers, we’ve known that in the community there are thousands of people out there with eating disorder behaviors that we never see in our clinics.”

Hard data on the frequency of eating disorders in the broader community has been hard to come by. But a new survey study of over 10,000 adolescents, released last week in the Archives of General Psychiatry, confirmed that the iceberg of eating disorder prevalence among American teens is as broad below the surface as psychiatrists suspected. Almost 6 percent of those surveyed in the study met the criteria for one of the five eating disorders tested at some point in their lifetime, a number extrapolated by some media outlets to 500,000 teens in the United States.

But the total numbers were just one of the eyebrow-raising results of the research. Le Grange, a co-author on the study, sat down with ScienceLife and detailed the most significant findings of this long-awaited census, and discussed its implications for the nature of these diseases and the patients who are slipping through the field’s fingers.

1. The Myth of Rarity

Health care dollars are not infinite, and cynical as it may sound, diseases must compete for research funding and insurance reimbursements. So when conditions such as eating disorders are perceived as rare occurrences, the people who treat and study those conditions face an uphill struggle for attention and support. Thus, the under-reporting of eating disorder prevalence has held the field back from being considered as a priority concern in adolescents. The new numbers - lifetime prevalences of 0.3% for anorexia nervosa, 0.9% for bulimia nervosa, 1.6% for binge-eating disorder, and 3.3% for sub-threshold disorders - lift eating disorders into a higher tier of concern for teenage and adult health.

“The myth has been that eating disorders and especially anorexia nervosa are relatively rare disorders, and we constantly have to argue that they’re not, because that’s what it feels like when we sit in clinical practice and we are inundated by patients,” Le Grange said. “This is robust data to demonstrate that eating disorders are not rare.”

2. A Gender-Blind Illness

In the clinic, psychiatrists see far more girls with eating disorders than boys - a ratio of 9-to-1. But surprisingly, the community survey revealed roughly equal prevalence for anorexia nervosa in males and females, suggesting that boys are not less likely to suffer from the condition, but are much less likely to be diagnosed and treated. Le Grange said he suspects that physician bias may lead them to more quickly consider an eating disorder  when the patient is a she rather than a he.

“We are so convinced that anorexia nervosa is predominantly a female disorder that pediatricians and mental health professionals, when presented with a boy who’s lost weight, do not consider anorexia to be a legitimate  diagnosis,” he said. “When we do see boys in our clinic, they usually have had an extensive preliminary workup, as the clinicians don’t consider an eating disorder…until everything comes back negative.”

3. Effects Beyond Mealtime

Psychiatrists observe that eating disorders don’t typically occur in isolation, as patients often carry “co-morbid” psychiatric issues such as depression or anxiety. The community survey puts a number on this observation, finding that the majority of those that met the criteria of an eating disorder also met the criteria of at least one other psychiatric disorder. Perhaps most alarming was the very high occurrence of suicidal thoughts and attempts in adolescents with eating disorders - more than half of those with bulimia nervosa reported thinking about suicide, and more than a third reported attempts.

Also striking was that these associations were just as common for kids who exhibited “sub-threshold” eating disorders, those did not meet the full criteria for anorexia nervosa or bulimia nervosa. In the DSM-IV, the diagnostic bible of psychiatry, such patients would be lumped into the category of Eating Disorders Not Otherwise Specified (EDNOS). The health risks associated with these patients suggest that EDNOS should not be seen as any less severe an illness, Le Grange said.

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Alien Life & Scientific Skepticism: The Sequel

In a bit of deja vu this week, a new paper stirred up fevered online debate about the existence of aliens among us - and the traditions of scientific publications. This time, ground zero for the debate was not the bacteria of arsenic-laced Mono Lake, but microscopic filaments on a rare group of meteorites collected in Antarctica in the 80’s and 90’s. In a paper published last Friday by the Journal of Cosmology, NASA scientist Richard Hoover argued that these filaments are bacterial fossils, of species that fell to Earth with the meteorite - a conclusion that was breathlessly reported by Fox News with the lede “We are not alone in the universe.”

Panspermia, the idea that life on Earth may have been seeded by alien organisms that arrived on the backs of meteorites, is a seductive idea. But as the old saying goes: once bitten by reports of alien bacteria, twice shy. Far fewer science reporters fell for the meteorite alien bacteria as they had on the arsenic-based bacteria story of last December, perhaps because of a lesson learned or merely because of the lower-profile journal in which the new paper appeared. And while the criticisms over the arsenic study took a few days to seep from science blogs to mainstream media, the travel time was much shorter this time around - Phil Plait’s skepticism on his Bad Astronomer blog was quickly trailed by an AP story that carried a chorus of criticism. Questions about the qualifications and objectivity of the author and the journal soon followed, as the Columbia Journalism Review recaps.

As with the arsenic story, the meteorite episode was almost more fascinating for what it says about modern scientific communication than what it said about science itself. On the surface, the Journal of Cosmology appeared to take some progressive steps for publishing research, including making the article free and open access and soliciting commentaries from “100 experts” on the findings, 24 of which were published soon after the original article. That move would appear to address one of the critiques of the team that published the arsenic bacteria paper, regarding their attitude that criticism was only valid through traditional (and slow) peer-reviewed channels, instead of online discussion that is able to react more immediately.

However, a very thorough, critical commentary by microbiologist Rosie Redfield (who also sounded the first alarm about the arsenic bacteria research) has not been published by the journal, while some very odd commentaries have, such as one concluding “Hoover’s findings are incompatible with the creationist model of life based on biblical Genesis and Aristotelian philosophy.” The journal has also reacted petulantly to criticism, posting an editorial called “Have the terrorists won?” that claims “Only a few crackpots and charlatans have denounced the Hoover study.” So while the latest alien bacterial invasion of Earth’s media is showing some steps in the right direction, it also signals that the growing pains of adapting scientific discussion to a faster media age are still present.

Elsewhere…

Last week, the Medical Center was part of a four-way kidney swap that spanned the country, from the Bronx to California (we should have a video of the event posted next week). Coincidentally, in a New York Times editorial published Sunday, the Medical Center’s Lainie Ross argued that such swaps or “donor chains” were a better option than proposed revisions to the current organ allocation system that would prioritize younger recipients.

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Cooking indoors over firewood and dung is a tough habit to break for billions of poor people around the world. But Sola Olopade, MD, professor of medicine and family medicine, found a way. He wanted to stop women from hunching for hours over open fires inside their houses, cooking with babies strapped to their backs. The air in such houses quickly becomes filled with toxins, and the women and children have a host of bad health consequences.

“It’s the most unclean combustion you can get,” Olopade said in his seminar earlier this month at the MacLean Center for Clinical Medical Ethics. “The women and children have coughs, headaches, runny noses, chest tightness.”

Those are just the health problems he could measure. “I wonder what kind of cognitive dysfunction people develop in spaces where the carbon monoxide is so high.”

Unfortunately, the billions of poor people who cook their daily meals over firewood and dung have few other options. Without electricity, Olopade said, “energy poverty drives people to use whatever they can get their hands on.” But Olopade was determined to see whether education and a little technology could make it less dangerous for people to breathe inside their houses.

Olopade, who is clinical director of the University of Chicago Global Health Initiative, went to two small villages in his native Nigeria, ready to distribute energy-efficient ceramic stoves. He believed the simple stoves could make an enormous improvement in the community’s health. His team measured the air quality inside 100 homes, and found heavy metals, carbon monoxide, and particulate matter more than twenty times the World Health Organization acceptable standards. The researchers also educated the community about the dangers of exposure to smoke from using firewood to cook indoors and the benefit of using the new stoves, handing out brochures about cooking in their native dialect.

“I told them without medical jargon that this was killing people,” Olopade said.

Three months after giving the stoves to the families in the villages, Olopade returned. He took the same air quality measurements, repeated the survey of symptoms and saw a remarkable improvement. Carbon monoxide and particulate matter levels were dramatically lower, much closer to the WHO standards.

“People were very happy with the stoves. They’re very simple. They’re lined with ceramic which retains a lot of heat and promotes more complete combustion of the firewood or biomass fuel,” Olopade explained.

The women were burning the same fuel - cow dung, agricultural waste, and firewood - but the stoves had kept most of the pollutants from pouring into the homes. With this small change, “you can really improve the indoor environment,” Olopade said.

The health benefits were drastic. Before the intervention, many of the children and most of the mothers suffered from dry cough, runny noses, burning eyes, breathing difficulties, chest tightness, headaches and dizziness. All of these health problems plummeted after they started cooking on the clean stoves.

“Just by engaging the community in partnership, educating them on the dangers of exposure to toxic fumes and giving people efficient stoves, without changing their lives much, the change in symptoms is dramatic,” Olopade concluded.

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Late last year, we relayed the announcement of an exciting new academic program here at the University of Chicago, the Institute of Molecular Engineering. At the time, the IME had a future home (sharing the new William Eckhardt Research Center with the Physical Sciences Division) and a vision, but did not yet have a leader. Yesterday, that crucial headpiece was officially put in place, as biomolecular engineering and nanotechnology expert Matthew Tirrell was named the first Pritzker Director of the IME.

Tirrell will come to UChicago from California, where he has spent time at the University of California campuses in Berkeley and Santa Barbara over the last 12 years. His research specialty is the surface properties of polymers, chains of molecules that can be manipulated for building better materials used for everything from energy to technology to medicine. Those versatile aspirations make Tirrell the perfect leader for the IME, where the mission is to bridge disciplines at UChicago and Argonne National Laboratory and bring the tools of biology, chemistry, engineering, and physics to bear on finding solutions to some of science’s most important challenges.

“This isn’t going to be directed narrowly toward one scientific discipline, but at creating an institute that attacks societal problems from a technological viewpoint,” he said in the official announcement. “Many important societal problems in energy or health care or the environment can be addressed by new molecular-level science. When you are trying to solve problems, you need people from different kinds of disciplines. That’s something the Institute for Molecular Engineering can create right from the beginning.”

In his nearly 300 scientific publications, Tirrell has often studied and discussed how the surface properties of polymers are important for the success of biomaterials. Materials “communicate” with their surroundings through their surfaces, and designing new synthetic devices for technological uses requires a firm grasp on this process. As a result, bioengineers have taken inspiration from how natural materials such as mollusk shells and animal tissue solve surface compatibility problems to understand these interactions on a molecular level.

One application of that accumulated knowledge about biomaterials is novel solutions to clinical problems. In a phone interview Monday with ScienceLife about the biomedical goals of the IME, Tirrell talked about how these new technologies will not be merely passive construction materials, but active biological compounds.

“There are going to be ways of using biology not only to make things but also to do things,” Tirrell said. “Therapeutic organisms can be engineered with the tools of modern biology: living devices, if you will, as well as man-made devices.”

One example from Tirrell’s own research career expands upon designing living machines as a sort of multi-functional Swiss Army knife for diagnosing and treating diseases such as cancer and cardiovascular disease. A 2009 paper, published in Proceedings of the National Academy of Sciences, used a self-assembling lipid sphere called a micelle (pictured at right) to target the fatty plaques that form in blood vessels during atherosclerosis. When those plaques rupture, dangerous clots can form and  block blood vessels. To treat those clots, physicians currently prescribe blood thinning drugs that can produce unwelcome side effects, because the drug is not specifically targeted to the clot and acts throughout the body.

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Cells are often described as factories, a metaphor that adequately describes the swarm of specialized tasks constantly underway in each of the human body’s 100 trillion cells. The factory floor of the cell is so busy and complex that scientists are still discovering new machinery responsible for important jobs, with no clear end in sight. The neurons of the brain have been especially difficult to analyze given their role as communicators, ceaselessly sending and receiving chemical messages called neurotransmitters. Many different proteins are needed to release these signals, and when just one is missing, it can cause disaster.

The CLC family is a group of ion channel proteins known by such disasters. When these channels are missing or not working properly, motor disorders such as myotonia can result, suggesting how important their normal function is to the nervous system. Through the use of genetically-modified mice, where the gene for a single protein can be switched off, scientists can determine what a protein’s job is in the cell’s factory. But the process requires working methodically backwards, analyzing the big problems caused by a defective factory and retracing the steps back to where the target protein should have been working.

Yesterday in Nature Neuroscience, the laboratory of Deborah Nelson, professor of neurobiology, pharmacology and cell physiology, reported on one such investigation of a CLC family member. CLC-3 has not been tied as of yet to any human disease, but when it is deleted in mice, there’s no missing the consequences. Without CLC-3, the hippocampus, a region of the brain involved in learning and memory, slowly degenerates over the first months of a mouse’s life until it has completely vanished by the end of their first year. The retinas of the eye also degenerate in CLC-3 knockout mice, causing blindness during their first month of life. What could CLC-3, a humble ion channel that allows chloride ions to pass through its gate when activated, be doing in normal circumstances to avert such neurological catastrophe?

Vladimir Riazanski and Ludmila Deriy, research associates in Nelson’s laboratory, started with a clue about where CLC-3 lives in the cells of the hippocampus. Before they are released, neurotransmitters must be concentrated into packages called synaptic vesicles, sort of like a car being filled up at a gas station. A 2001 study of CLC-3 found that the protein is located on these synaptic vesicles in hippocampal neurons, suggesting a role for the ion channel in this packaging process. Experiments recording electrical activity from hippocampal regions of CLC-3 knockout and normal mice indicated that something was wrong with the transmission of GABA, the inhibitory neurotransmitter, when CLC-3 went missing.

So Riazanski and his collaborators zeroed in on the process of filling vesicles with GABA in the neurons of the hippocampus. By isolating those extremely small vesicles (on the scale of nanometers), the researchers could look very closely at what CLC-3 is doing to package GABA. The vesicles lacking the ion channel acidified more slowly, researchers discovered - a logical result of losing a channel that allows for the influx of acidifying chloride ions. But without acidification, the GABA vesicles can not be filled as efficiently, leaving vesicles with lower amounts of GABA or no GABA at all. It’s as though the gas station inside GABA neurons is missing its attendants - there’s plenty of fuel, but nobody around to properly fill up the vesicles.

Without sufficient inhibitory GABA being released, surrounding neurons can become over-excited to the point of death, Nelson said, which may explain the hippocampal and retinal damage seen in knockout mice.

“This is the first study to show any effect of CLC-3 on inhibitory transmission,” Nelson said. “It’s this loss of GABA transmission that probably contributes to the imbalance between excitatory and inhibitory signals within the mouse hippocampus, and eventually gives rise to excitotoxicity and cellular loss.”

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