As another year comes to a close we’d like to look back at the fascinating research breakthroughs and inspiring patient stories from 2011. ScienceLife ran 168 posts this year, and while we wish we could highlight all of them, here are a handful of our favorites from each month.

January

Patrick Wilson found out that the H1N1 virus could end up helping us fight all types of flu. Stephen Pruett-Jones studied how some male birds mimic the sounds of predators to pick up the ladies (with an audio clip). We interviewed David Gozal about his study on the link between childhood obesity and lack of sleep, and took a look at NCAA regulations mandating sickle cell testing for athletes.

February

Harold Pollack gave a lecture on why violent crime in urban, minority communities should be considered a public health epidemic. Siri Atma Greeley studied the actual medical benefit of widespread genetic testing. Stacy Lindau wanted to know why so few women get help for sexual problems after surviving cancer. We talked to Bana Jabri about the causes of celiac disease, and Sliman Bensmaïa showed us how the brain processes the basic elements of touch very much like it handles visual information.

March

Sola Olopade educated women in Nigeria about using clean-burning stoves to prevent indoor pollution. Stefano Allesina and Jonathan Levine looked at how rock-paper-scissors helps explain evolution. Joshua Miller went to Yellowstone Park to see what stories the ghostly bones of animals can tell, and Scott Eggener questioned the wisdom of indiscriminate prostate cancer screening.

Photo by Gerald Waddell

Andrea King studied the wide range of responses to drinking alcohol, and why it can be fun for some people and a bummer for others. Cheryl Reed took a ride in a helicopter with our UCAN nurses. Kamal Sharma looked at the genes that control animals’ gait, and Ningqi Hou studied how urban environments can dictate how much exercise people get.

May

Daniel McGehee looked at the long-term effects of nicotine on the brain. Habibul Ahsan went to Bangladesh to study the health impacts of accidental exposure to arsenic in drinking water. The brain’s overlooked supporting cells got their due at a conference on neuroscience, and we remembered a landmark discovery about a once popular drug taken during pregnancy that we now know can cause cancer.

June

As we headed into summer, Diana Lauderdale used Google to track MRSA. We learned about an extraordinary transplant where a man received a new heart, liver AND kidney. Daniel Geynisman gave us the rundown on whether or not cell phones are killing us (they’re not, as long as you don’t use them in the car), and some UChicago undergrads studied what happens to gorillas on the birth control pill.

July

We spoke to Donald Jensen and Andrew Aronsohn about the new outlook for patients with hepatitis C. Igor Schneider made a time machine to find the genetic switch for limb development. Farr Curlin led a study about the benefits of addressing spiritual needs alongside medical care, and Adam Cifu looked at the phenomenon of scientific study reversals.

August

Stefano Allesina dug into the long, shady history of nepotism in academia in Italy. John Schneider talked about his work addressing sexual health and stigma in India. Michael Becker discovered a new treatment for the Royal Disease, and we had the rare chance to name check a Spiderman villain in a post.

September

Martha McClintock and Suzanne Conzen studied the connection between social isolation, stress and breast cancer. Gallego Romero traveled to India to search for the origins of lactose intolerance. Stephanie Dulawa developed a mouse model for OCD, and Paul Vezina looked at a different kind of obsession, compulsive gambling.

October

Arshiya Baig started a pilot project to help people learn about life with diabetes through pictures. Manyuan Long found that some of the youngest genes are in the brain. Jens Ludwig and Stacy Lindau published a landmark study about the connection between neighborhood poverty and health, and Issam Awad studied a rare brain disease that soon could be treated with a drug instead of surgery.

November

Cathy Pfister and Tim Wootton figured out how to use seashells to track climate change over the years. Lianne Kurina found a link between loneliness and sleep quality. Shantanu Nundy, Monica Peek and Marshall Chin developed a program to send text message reminders to people with diabetes, and Pan Chen looked at the links between childhood abuse and aggressive behavior in adults.

December

Inbal Ben-Ami Bartal, Jean Decety and Peggy Mason discovered that rats can show empathy for their fellow rats in distress. Maciej Lesniak performed a scary but amazing brain surgery on a patient who was awake. Cathryn Nagler searched for the source of food allergies within our bodies, while Stafano Guandalini uncovered the challenges in educating doctors about one of those allergies, celiac disease.

Whew. Hope you were able to click through at least a few of those. We look forward to another great year of research in 2012. We’re taking a break next week, but we’ll be back on January 5. Happy holidays!

Have you ever cheated on a test by glancing over at someone else’s work? Or relied on a fellow student to carry the load on a group project while you coast along with minimal effort? While few will admit to these forms of cheating, they have long been fixtures of the classroom. However, a lazy individual benefiting from the hard work of a colleague is not a trick exclusive to humans. In a recent study of bacterial infections in plants, the laboratory of evolutionary biologist Joy Bergelson demonstrated that these unsavory practices can also be found in pathogens - and that may be a good thing for us.

In the bacterial world, the goal is survival. What we perceive as an infection is merely colonization for the bacterial population, who are establishing a new home where they can happily feed off the host’s nutrients and reproduce. Bacteria build and release virulence factors to achieve this settlement and evade immune system defenses. But because these factors spread out, benefiting an individual bacterium’s neighbors as well as itself, a sneaky bacterium can get by without producing its own virulence factors. In laboratory dish experiments, scientists observed that bacteria engineered without the ability to release factors can still thrive so long as they are paired with normal, pathogenic partners.

Though scientists described this “cooperator-cheater model” in the artificial environment of the dish, nobody had yet observed it in a natural setting. For a study published in September by the journal Ecology Letters, a team led by postdoctoral fellow Luke Barrett discovered the model in action within the cells of the popular genetic model plant Arabidopsis thaliana.

“We’re showing that cheating actually happens in nature, and that the cheaters persist,” Bergelson said. “You can make cheaters that do well in the lab, and you can show that these systems may be stable in theory, but to show that it is actually happening in nature is novel.”

Recently, researchers discovered that Arabidopsis carried two strains of the bacteria Pseudomonas syringae, a common plant pathogen. While one strain had all the normal pathogenic activity, another was a kind of bacterial pacifist, with a broken system for secreting virulence factors. Surprisingly, these two strains appear with almost equal frequency in Arabidopsis, suggesting that the non-pathogenic strains are far more successful in nature than previously thought.

To test the nature of this relationship, researchers took the two natural strains and experimentally infected plants with only one or the other. When grown alone, the “cheater” strain was not nearly as successful without its more aggressive partner around to unwittingly “donate” virulence factors. Additional modeling suggested that the more aggressive the virulent strain, the more likely it was that cheaters would be found nearby eager to exploit the hard work of their pathogenic peers. The cheater strains are also harder for the host immune system to spot, since the machinery that produces and releases virulence factors is a frequent target of those defenses.

“When you go into the field, it’s kind of a curiosity: why would non-pathogenic cheaters be almost as common as pathogens inside the host?” Bergelson said. “It turns out that the cheaters can do really well as long as they’re with the pathogenic variety, and they don’t pay the price of having to actually make a secretion system or effectors. They also don’t run any risk of being recognized because it is the presence of secreted effectors that causes the recognition events in the first place. So, these non-pathogens have some good things going for them.”

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By Dianna Douglas

The goal of World AIDS Day 2011 is not to make the public aware of the disease. That was the goal in 1988, back when the international health threat was still new, infections were rising every year, and there was no hope of a treatment in sight. This year, World AIDS Day marks the sunset of the public panic about the virus. The stated goal this year is “getting to zero” — or bringing the number of AIDS-related deaths and new HIV infections down to zero and ending all discrimination against people living with the virus.

The University of Chicago has various ways of reaching that goal here in Chicago. There’s the STI/HIV Intervention Network (SHINE) based at the School of Social Service Administration, which brings interventions to neglected groups such as men who have sex with men, people in the criminal justice system, minority youth, and young couples. There’s also the Medical Center’s Living Positively program, in which HIV-positive young people act as advocates to their peers who are at risk.

Now, in honor of World AIDS Day, the Medical Center is trying an innovative approach to this public health issue. Instead of doing what he calls the “typical academic thing for World AIDS Day” — a panel of researchers talking about AIDS in Africa in an auditorium full of other researchers — John Schneider, MD, MPH, has organized a ball. “This year, we want to collaborate and fully engage with the community,” he said. In gay culture, a ball is where people dress in drag to show off their moves, a lot like a fashion show. The community he hopes to reach with this ball is the young GLBTQ (gay, lesbian, bisexual, transgender, and queer) minorities who have the highest HIV infection rates in the city.

While the tide may have turned in the AIDS epidemic, the infection rates of several groups remain stubbornly high. Around 22,000 people in Chicago live with HIV or AIDS, and the infection rates among African Americans and gay men are particularly sobering. Since 2005, 57 percent of new HIV infections in men have been a result of men having sex with infected men. Among African Americans, the HIV infection rate since 2005 is more than double the general population’s infection rate.

A partnership with the young people striking a pose at underground balls may seem unusual, but it may also be the best way to reach Chicago’s most vulnerable populations. “We know where the epidemic is, and we have the tools to take care of it. What is needed now is hard work using traditional case-finding methods to reach these vulnerable groups with health services,” Schneider said.

The ball tradition, subject of the award-winning documentary Paris is Burning, has long been a safe place for young black gay and transgendered people to express their creativity and build communities. The World AIDS Day mini-ball will celebrate the support that the members of this subculture offered each other during the worst days of the AIDS epidemic in the 1980s and ’90s.

“These are the people most impacted by AIDS in the United States,” said Keith Green, MSW, co-director for the Chicago Black Gay Men’s Caucus and a co-sponsor for the event.

Everyone at the ball will see their peers promoting safe sex and healthy behavior.

Contestants — many of whom are gay, transgender or bisexual — will compete against one another in the lobby of the School of Social Service Administration this Friday night. Participants will display their dance skills, costumes and attitude in a variety of events, similar to a runway show. In some events, they will be judged on the “realness” of their drag. In others, on the beauty of their clothing and overall style. Each of the seven walk competition categories has a cash prize for the winner.

“Every category requires the creative integration of the AIDS ribbon, the color red, or latex,” said Matt Richards, outreach program manager for pediatric infectious diseases at the University of Chicago Medical Center.

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By Meghan Sullivan

What is it about viruses that so easily captures our attention? With the teeth mostly taken out of bacterial infections by the advent of penicillin and parasites a rare and mostly exotic concern, viruses remain one nemesis that we often struggle to treat. Unlike complex bacteria and parasites, viruses are little more than genetic material wrapped up in a vessel designed to take its blue prints to the next host. Once in a host, viruses inject their genetic material into cells and take over the cellular machinery to carry out their lifecycles. Imagine terrorists sneaking into a Ford factory and using the assembly lines to crank out WMDs. Infected cells eventually die, but not before triggering immune responses (coughing, sneezing, etc) that aide their spread to the next host.

Taken starkly, viruses execute an elegant life cycle. If the aim of life is to pass on one’s genetic material, viruses have succeeded by reducing themselves to only genetic material, relying on other organisms for the messy business of replicating and spreading. The only way to make the process more streamlined would be to cut out the effort of budding, replicating, and finding its next host.

Which, it seems, viruses have also done.

Called human endogenous retroviruses (HERVs), some viruses have slipped their genetic material into our genome, inserting themselves between host genes or in the long stretches of inaptly named “junk” DNA. Over the course of evolution, these genetic stowaways were passed down to the host’s offspring right alongside genes for blue eyes and attached earlobes. Millions of years later, we find remnants of the viruses encountered by our ancestors written in our DNA like graffiti in a bathroom stall. HERVs comprise as much as 8% of the human genome and some may have integrated into our genomes as long ago as 60-70 million years ago.

Considering the vast changes our genome has undergone in the past 70 million years (by comparison, the human-chimpanzee split occurred only 6 million years ago) it makes sense that the HERVs fossilized in our genome have also been changing. HERVs, like the rest of our genome, acquire DNA mutations at a low but consistent rate. Scientists are able to estimate when a HERV integrated - and by extension, when it was last infectious - by comparing mutations in long terminal repeat (LTR) sequences, stretches of DNA that flank the viral genes like book ends. At the time of integration, these regions are identical, but the longer the HERV has been in the genome, the more mutations the LTRs acquire. By comparing the differences in LTRs flanking HERVs, scientists can estimate how long a HERV has been in the genome.

Previously, the youngest HERVs were estimated to be 800,000 years old. For a recent paper in the journal PLoS ONE that explored how recently HERVs were actually circulating as viruses, Aashish Jha, a University of Chicago graduate student in the Department of Human Genetics and former member of Douglas Nixon’s lab at UCSF, looked for recent integrations into the human genome. Using a genome browser at UCSC, Jha and colleagues tracked all the human-specific, full-length HERVs at a particular place in the human genome. Interestingly, one HERV called k106 didn’t fit the normal timeline.

“It looked interesting because it did not have any mutations in its LTRs,” Jha said.

This was an unusual find, as the age of most HERVs insures at least a few mutations that would aid in dating it. Using genetic information from 51 ethnically diverse individuals, Jha and colleagues were able to estimate that the k106 HERV integrated between 92 and 100 thousand years ago, making it one of the youngest HERVs ever identified.

“This time period is exactly the time modern humans were emerging,” Jha pointed out, “So someone was infected and, given that it was a small population size, it rapidly became fixed in the genome. Then humans moved out of Africa…so even though the virus is new we find it fixed in every human population.”

Having identified this recently integrated, human-specific HERV, it’s possible to gain insight on the ways HERVs have affected the course of our development. LTRs flanking HERVs contain signals that control when and where genes are turned on and off. Placing these viral signals in front of host genes could impact how and when they are expressed and, in some cases, lend an advantage to the individuals possessing it.

“There are multiple ways they [affect evolution],” Jha said.

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The University of Chicago can fill a couple of classrooms with all of the Nobel Laureates affiliated with the school, from Milton Friedman to Saul Bellow to Barack Obama. After Monday, a third room might have to be opened up, as Pritzker School of Medicine graduate Bruce Beutler became the 86th member of the exclusive club. Beutler, who graduated from our medical school in 1981, was honored with this year’s Nobel Prize in Physiology or Medicine, along with Jules Hoffman and Ralph Steinman. The three scientists were credited with advancements in the field of immunology that have paved the way for new strategies fighting infections, cancer, and other diseases.

“I thought it was possible, but nobody can count on winning the Nobel Prize, so I’m just ecstatic,” Beutler, now at University of Texas Southwestern Medical Center, told the Chicago Tribune.

In the confusing calculus of the Nobel, Beutler and Hoffman split half of the total award for research on the innate immune system, known as the first line of the body’s defenses against infectious invaders. In the late 1990’s both scientists’ laboratories were looking for immune receptors that respond to signals on the surface of bacteria - Hoffman looking in fruit flies with genetic mutations, Beutler in mice. Within two years of each other, Hoffman discovered a fly mutant named “Toll” involved in the response to an infection, and Beutler found a similar gene in mice for a receptor (named, appropriately, the “Toll-like receptor”) that binds to lipopolysaccharide (LPS), a signal on the surface of bacterial cells.

These findings opened the floodgates to learning about new players in the innate immune system, including the discovery of a dozen more Toll-like receptors that recognize various pathogen signals - what some call “the eyes of the immune system.” Clinically, mutations in these genes can lead to either increased susceptibility to infection (if the innate immune system is too weak) or autoimmune and inflammatory disorders (if the innate immune system is too strong). Drugs that target this system might therefore be promising for the treatment of many different diseases.

“I think the most hopeful line or realm is in inflammatory and autoimmune disease,” Beutler told the Nobel website. “Inflammation is something that evolved to cope with infection, and when we speak of sterile inflammatory diseases like rheumatoid arthritis and autoimmune diseases like lupus, probably some of the same pathways are utilized. It may very well be that by blocking TLR signalling you’ll have very specific therapies for those kinds of diseases.”

Beutler said that he received the news in bed, waking up in the middle of the night and reading an e-mail on his cell phone.

“I was a little bit disbelieving, so I went downstairs to look at my laptop,” Beutler said. “I went to Google News and saw my name there, so I knew it was real.”

At the University of Chicago Medical Center campus, the news quickly spread among former colleagues and teachers of Beutler, as well as scientists that who work in his field.

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Since the Roe v. Wade decision of 1973, abortion has been a woman’s legal right (with ever-changing state-specific restrictions) in the United States. But one factor often trumps the legal status of abortion: access. Though abortion training is required for medical residents studying to become obstetrician-gynecologists, physicians are not required to perform the procedure or even to refer a patient to a ob-gyn who will. That voluntary basis can create pockets of the country where access to an abortion provider is a larger obstacle than any legislation.

As a window into these access issues, a team led by Debra Stulberg, assistant professor of family medicine, conducted a survey of more than 1,000 Ob-Gyn physicians on their experience regarding abortion requests and providing the procedure. Their answers, published in Obstetrics & Gynecology, reflected how commonly ob-gyns are approached for the procedure - 97% of respondents said they had encountered patients seeking abortions. However, only 1 in 7 (14.4%) of those surveyed said that they had provided abortions themselves.

The data collected from other question on the survey allowed Stulberg and her colleagues to paint a picture of who was more or less likely to provide an abortion. Some of the results were unsurprising: female ob-gyns were more like to perform the procedure than men, those with strong religious beliefs were less likely to provide abortions, and those who worked at Catholic hospitals were very unlikely to provide the option to their patients. Geographically, ob-gyns from the Northeastern, Western, and urban regions of the United States were more likely to have performed an abortion, while those from the South, Midwest, and rural areas were less likely. That could contribute to large areas of the country where there are limited options for women seeking abortion - regions that happen to be where abortion providers commonly experience harassment, the authors note.

Breaking down the responses by age also reveals an interesting U-shaped curve. The most likely age group to provide abortions was ob-gyns 35 years or younger. But the second most likely were those aged 56-65 years old - the generation that was in medical school around the time of the Roe v. Wade decision. As that age group heads toward retirement, the number of abortion providers could drop even lower, the authors speculate, should the younger generation not pick up the slack. For responses to this data from both sides of this always polarized issue, see U.S. News & World Report. More coverage can be found at the Los Angeles Times, NPR, and the State Column.

Our New Facebook Home

Thanks to the hard work of our colleague Matt Wood, the Medical Center has a new Facebook page! The page will be updated daily with articles and videos about Medical Center care and research, including the occasional article from this here blog. If you are so inclined, please visit the page and click the all-important Like button.

Elsewhere…

It sounds counter-intuitive: burning the smooth muscle of the lung to improve symptoms for people suffering from severe asthma. But bronchial thermoplasty is a promising new procedure, and has worked for patients like swimmer Stephanie Manikas, featured in this CBS Early Show piece from Thursday. Manikas’ physician, the Medical Center’s Kyle Hogarth, has previously explained the procedure as part of ScienceLife’s Dr. FAQ series.

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The 2009 H1N1 pandemic, better known as the season of swine flu, was not like other flu seasons of recent vintage. A typical seasonal strain of influenza is most deadly at the extremities of age, with the highest mortality rates in the very young and very old. One of the reasons why experts were concerned about the 2009 flu was that it went off-script, killing mostly people in their twenties and thirties. Influenza researchers speculated on why the normally vulnerable elderly appeared to have the advantage against this particular pandemic. But it wasn’t until a recent study by University of Chicago and Stanford scientists looking at the failure of flu vaccines in older adults that the source of this advantage revealed itself.

In a typical season, senior citizens are among the priority groups for receiving the flu vaccine, due to their increased risk of severe symptoms. Yet the success rate of the standard influenza vaccine is reduced in those above 65 years of age, falling from 90 percent efficacy to as low as 17 percent. Most have attributed this decline to a general principle called “immunosenescence,” the weakening of a person’s immune system as they grow older. Since vaccines work by stimulating the production of antibodies against an inactivated flu strain to protect against the real virus, is the deficiency in the aged a matter of antibody quantity, quality, or both?

A multi-institutional team led by co-first authors Meghan Sullivan of UChicago and Sanae Sasaki of Stanford developed a new assay to test this question for a recent article in The Journal of Clinical Investigation. Two groups of volunteers - one aged 18-30, one aged 70-100 - received the seasonal flu vaccine in the winter of 2007-08, and researchers took blood samples from them seven days later, when vaccine-induced antibody production is at its peak. Scientists could then measure the number of antibody-secreting cells, called plasmablasts, and antibodies circulating in the blood of the volunteers. They could also run experiments testing how well those immune defenses bind different strains of influenza, the first step in fighting off a virus.

Their first experiments replicated the clinical data - even in a test tube, younger volunteers (or at least their antibodies) are much more likely to respond to the influenza strains included in the vaccine than samples from older subjects. Subsequent experiments revealed that the immune systems of elderly subjects were at a numerical disadvantage, with significantly fewer plasmablasts observed in serum compared to the samples from their younger counterparts.

“It had been appreciated before that there are fewer immune cells in older people, but this is the first time showing that fewer antibody secreting cells are raised in response to vaccination,” said Sullivan, a graduate student in the laboratory of Patrick Wilson (and a contributor to ScienceLife).

But surprisingly, that was where the immune deficits in older patients started and ended. Though there were fewer plasmablasts in older subjects, each produced the same number of antibodies as those of the young. What’s more, when the antibodies from young and old were compared for their ability to bind the viral strains targeted by the vaccine, they were nearly identical. So the failure rate of vaccines in elderly can be explained by the lower quantity of antibody “factories,” rather than a defect in the quality of the antibodies themselves.

“We would think that antibody activity would be decreased in older people, but in fact the ability to bind is basically identical,” Sullivan said. “The antibody secreting cells are the weak point; elderly people are just not making enough.”

Amid the media storm surrounding the rapid spread of swine flu in 2009, the research team used the same samples to test another idea. One theory for why senior citizens were protected against that particular H1N1 strain was that they may have been exposed to a similar influenza that circulated before 1950. With their blood samples, the researchers could compare how the antibodies of their old and young subjects responded to the 2009 H1N1, which neither group had been vaccinated against two years prior. In this competition, the senior citizens were the surprise winners - antibodies from older subjects (especially those older than 78) were more responsive to the H1N1 virus than those from younger volunteers.

The result suggests something off an immune system trade-off in the elderly. Though they may have a harder time producing sufficient antibodies to fight off the flu, the antibodies they do produce are able to attack a more diverse range of influenza strains.

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By John Easton

Let’s start with a statistic: almost 2,000 citations a year. One paper by Paul Meier, the Ralph and Mary Otis Isham Distinguished Service Professor emeritus of statistics, pharmacological and physiological sciences, medicine, and the college, has been cited more often, by a wide margin, than any other paper in the field. At last count it was the fifth most cited research paper of all time, in any field. With about 34,000 citations to date, Kaplan, E. L., and Meier, P. (1958), “Nonparametric Estimation from Incomplete Observations,” has been cited by another scientific publication about once, on average, for every day of Meier’s long life—he was born in 1924—and still counting.

Sadly, however, that ratio can only increase. Citation counting will continue, but the numbering of days stopped on Sunday, August 7th, when Professor Meier, a world-class statistician who made “extraordinary contributions to statistics and to society,” according to Columbia University - and everyone else - passed away peacefully at his Manhattan home.

The Kaplan-Meier estimator is used ubiquitously in medical studies to estimate and depict the fraction of patients living for a certain amount of time after treatment. This is not as simple as it sounds. Survival curves are complicated by the uncooperative way in which research subjects often behave. Some leave a study part of the way through. Others elect not to die before the study ends. These are known as “censored observations.” The Kaplan-Meier estimate is a simple way to compute the survival curve despite such troublesome behavior.

There was almost a Kaplan estimator and a Meier estimator. Each had submitted a separate manuscript to the Journal of the American Statistical Association, but the editor recommended that their papers be combined into one. It took them four years. “At one place he solved a problem that I couldn’t solve,” Meier later recalled in an interview [pdf]. “Other places I solved problems he couldn’t.” Finally published in 1958, it was only cited 25 times over the next ten years. Then, boosted by statisticians’ increased computing power, it caught on. It has since been applied to data from clinical trials of therapies for every disease from cancer to cardiology to concussion.

Friends and colleagues point out that this was only one of Meier’s fundamental contributions. He published many more studies, was a persistent and outspoken advocate for randomization in clinical studies, helped design some of the 20th Century’s most important clinical trials and trained many of the leaders in the field.

“Paul was a friend and colleague as well as one of the most influential statisticians of an important era,” recalled Stephen Stigler, the current chair of statistics at the University of Chicago. “He left an indelible mark on us, and through his research on the world’s clinic analytical practice. He will be missed and cannot be replaced.”

“I have been so fortunate and privileged to know this truly great, wonderful, helpful, kind man who was always so generous with his skills and wise advice,” said toxoplasmosis expert Rima McLeod, professor of ophthalmology and visual sciences at the University. “He is one of the founding fathers and giants of statistics in the past century. He was at the same time simply a modest, helpful, supportive and warm colleague who only let you know how special he was by the quality and content of what he said and wrote.”

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Most people turn to Google to search for news on Justin Bieber, baseball scores, and who got kicked off Top Chef last night. But users of the search engine also turn to Google for medical advice, typing in symptoms and conditions as a sort of pre-screening tool before making the call to the doctor’s office. These health-related searches inspired the creation of Google Flu Trends, an official tool of the website that estimates influenza incidence and spread via the dynamics of searches for flu symptoms, medications, and other related terms. With some complicated mathematics, Google developed a formula predicting flu activity that closely matched actual surveillance data, an achievement deemed worthy of publication in Nature.

The success of Google Flu Trends have prompted scientists to wonder if other diseases can be similarly watched by tracking search engine data. But while everyone knows about the flu (even if it is often mistakenly blamed for illnesses caused by other bugs), more obscure diseases might not be as easily captured by such a strategy. Take the case of methicillin-resistant Staphylococcus aureus, the medical mouthful better known as MRSA. Though MRSA is the most common cause of human infections, with 94,000 cases in 2005, it isn’t usually part of the layperson’s medical vocabulary. But because the CDC surveillance system for MRSA only covers 9 sites, a team of researchers from the University of Chicago and the University of Colorado set out to see if Google searches would suffice as a higher resolution alarm system for public health observers.

“If we had a comprehensive, linked electronic-health-records system that researchers had access to, we wouldn’t need it,” senior author Diane Lauderdale, professor of epidemiology, told Wired. “There are systems like that in Scandinavian countries, where you can analyze disease factors in all kinds of ways. But you can’t do that in the U.S.”

As reported in Emerging Infectious Diseases, Lauderdale, Vanja Dukic and Michael David measured the frequency of Google searches for “MRSA” and “staph” (because many news stories refer to the bacteria as drug-resistant or antibiotic-resistant staph) between 2004 and 2008. The group also charted appearances by MRSA in the media, to control for the influence of the news upon searches, and used data from a consortium of hospitals to serve as a measure for MRSA hospitalizations over the time period. Other challenges, such as the frequent mis-spelling of “mersa” and the infrequent correct spelling of “methicillin” were also taken into account.

The data showed a steady rise in the number of searches for MRSA, staph, and even “mersa” that mirrored the increase in hospitalizations for MRSA over that same time period. Surprisingly, media reports about the drug-resistant bacteria were not very influential on the number of searches, except for the coverage of a 2007 CDC report that MRSA caused nearly 19,000 deaths in the year 2005 - which prompted a spike of Googling. As such, the team was able to create a model using the Google queries that predicted the rate of MRSA hospitalization with considerable accuracy, as reflected by the red and pink lines in the graph above.

Interestingly, Google searches for MRSA steadily increased at the same time as one group of MRSA infections declined. A study published last year examining the rates of hospital-acquired or health care-associated MRSA cases found a reduction from 2005 to 2008 as medical facilities stepped up preventative measures against the bacteria. The Google trend may thus reflect increases in the more alarming community-acquired form of MRSA, as spotlighted in Maryn McKenna’s Superbug. With a new prediction model, public health experts can keep an eye on the search engine trends to try to pinpoint outbreaks, even on a local level, before patients begin arriving in hospital emergency rooms with severe infections.

“If we knew the rate was two or three times higher in one city than another, that could be an influence on public health campaigns,” said Lauderdale in Wired.

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Dukic VM, David MZ, Lauderdale DS. Internet queries and methicillin-resistant Staphylococcus aureus surveillance. Emerg Infect Dis. 2011 Jun

TED Comes to Campus

This weekend, the students of the University of Chicago are putting together a local edition of the renowned TED conference called TEDxUChicago. The theme, “Reinventing the Life of the Mind,” nicely blends the goals of TED and the University, the idea-sharing mission of the conference sutured to the intellectual spirit of our campus. Among the talks taking place at the Reynolds Club this Sunday are a few UChicago scientists: paleontologist and educator Paul Sereno (speaking on the topic of “Art In Science”), psychologist and child language expert Susan Goldin-Meadow (”What Our Hands Can Tell Us About Our Minds”), and student speaking contest winner Bruno Cabral (“The Life of the Mind Lived Through Noise”), an undergraduate working in the laboratory of psychologist Howard Nusbaum. Other speakers include Mark Inglis, the first double amputee to climb Mount Everest, Jonathan Greenblatt, the former CEO of GOOD magazine, and cybernetics expert Kevin Warwick giving probably the talk with the coolest title: “The Last Remaining Hurdles to Cyborg Technology.” Tickets are still for sale on the TEDxUChicago website, but if you can’t make it down to Hyde Park, the talks will be webcast live at the UChicago Facebook page.

The Rules of Language

Last week, the Joseph P. Kennedy Intellectual and Developmental Diabetes Research Center held a symposium called “Variations in Language Learning,” a series of talks about how languages are acquired by children, adults, and cultures. Elissa Newport, a professor of brain & cognitive sciences and linguistics at the University of Rochester, presented fascinating data on the concept of “statistical learning,” the theory that the brain uses mathematical tricks to learn the arcane rules of a new language. To test this idea, Newport and her colleagues played a made-up language of nonsense syllables for 20 minutes (!) to volunteers, showing that combinations of syllables that show up more frequently (such as “dutaba” or “babupu”) are eventually perceived as “words” by the listener. The researchers also went on to show that children are better at this “statistical learning” than adults when confronted with a new language, offering an explanation for why languages are easier to pick up when learned at a younger age.

The idea of a universal foundation for learning and developing language echoes the “universal grammar” theories of Noam Chomsky and others, if peripherally so - Newport’s experiments showing that the same statistical learning can be used for tones and visual sequences implies that it’s a universal learning mechanism, not specific to language. But a new phylogenetic analysis of the world’s languages appearing in Nature this week argues against innate rules for language, demonstrating deep grammatical differences between “families” of languages go against the idea of a universal human grammar. Most linguists seem skeptical or underwhelmed about the result, and the debate smacks of a false dichotomy, with the truth about language development less a battle between cognition and culture than a combination of the two forces. Discover, the LA Times’ Amina Khan, and Ars Technica’s John Timmer all weigh in on the study.

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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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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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The immune system is designed to protect the body against foreign invaders, neutralizing disease and infection. But organisms are all too happy to invite invasions several times a day through a seemingly innocuous act: eating. When food enters the digestive system, it has to be dealt with by the immune system just like everything else that finds its way into the body. Under normal circumstances, the immune defenses recognize that food is not a threat and lay down their arms. But in the case of food allergies or digestive disorders, certain types of food are treated as dangerous enemies, with unpleasant consequences for the person.

Celiac disease is one such disorder, where patients suffer painful symptoms after consuming gluten, a dietary protein found in wheat, barley, and rye. Rather than building up a tolerance to the protein that allows for untroubled digestion, the immune system treats gluten as a threat and activates its defensive weapons, including inflammatory factors that attack the lining of the small intestine. As a result, an innocent piece of bread for most people can be absolute misery for one of the 3 million Americans with celiac disease, causing abdominal pain, diarrhea, vomiting, and more serious chronic symptoms.

So far, the best treatment for celiac disease is plain old avoidance - a gluten-free diet to prevent digestive symptoms. Because the immune system is so complex, researchers have struggled to find the exact components responsible for the intolerance to gluten. But clues abound from patients treated at clinics such as the University of Chicago Celiac Disease Center, including unusually high levels of an immune factor called interleukin-15 in the patients’ intestines. That clue was the starting point for a new study published last week in Nature and led by Bana Jabri, associate professor of medicine at the Medical Center, that tracks down two triggers of celiac disease that may prove crucial to better treatments.

Interleukins are the messengers of the immune system, carrying signals that instruct the body’s defensive force to ramp up or stand down, depending on their context. In the gut, interleukin-15, or IL-15, was found by Jabri and colleagues to inhibit the activity of regulatory T cells, peacekeepers that block the immune response on targets that are considered non-threatening. After repeated exposure to gluten, most people build up a tolerance to the protein and are able to digest the nutrients in grains and breads without trouble. But for people with celiac disease, elevated IL-15 may interfere with this cease fire.

The researchers further tested their theory by engineering mice that over-expressed IL-15 in their digestive systems. When these mice were fed a protein found in eggs, another common food allergy trigger, the result was inflammation instead of tolerance - as is seen in celiac disease with gluten. Conversely, blocking IL-15 activity restored the normal response in the mice.

“We found that having elevated levels of IL-15 in the gut could initiate all the early stages of celiac disease in those who were genetically susceptible, and that blocking IL-15 could prevent the disease in our mouse model,” Jabri told John Easton.

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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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