Students might sometimes think that their textbook appeared out of thin air, the accumulated knowledge of a field spontaneously forming into a heavy slab of facts and figures. But textbooks are like any other type of book, with flesh-and-blood authors who labor over the words within and make a million tiny decisions to shape the final product. If you try to include everything, the book will likely be too heavy for even the most determined or muscular students to carry. Cut too much out, and your definitive textbook might be scorned as incomplete and elementary.

In writing her new textbook, professor of neurobiology Peggy Mason helped find the happy middle by starting with a very specific audience in mind: the medical students that she has spent 15 years teaching at the Pritzker School of Medicine. Her completed product, simply named “Medical Neurobiology,” is the first designed with aspiring physicians in mind, teaching med students about the broad influence of the central nervous system. Picking a specific target audience helped Mason make the hard choices about what to include and what to leave out, she said - even if the final 660 pages is heavier than she intended.

“I think it’s actually the only textbook completely aimed at the medical students,” Mason said. “I did a few things because of that that no other textbook does.”

For starters, Mason chose not to interpret “medical neurobiology” as simply “neurology.” Only a small percentage of medical students will eventually choose to train as neurologists, but the other 97 percent also need to be familiar with the central nervous system, she said. Knowing the anatomy and function of the brain, spinal cord, and nerve pathways can help everyone from future neonatologists measuring infants’ reflexes to future pulmonologists treating asthma to future geriatricians looking for the warning signs of dementia or motor deficits.

Another important decision came to Mason after a dinner with four medical students who gave her insight into the overwhelming workload of an aspiring doctor.

“All of a sudden I just realized that the immensity of the knowledge base that they need to acquire in two years,” Mason said. “It made me think anew about what we were teaching them, and I decided that as entertaining as it may be for us to talk about the newest, greatest research, it’s a disservice to them. They don’t have the time; they need the body of information that they need clinically and not the extraneous stuff. So I tried to cut out as much as I could.”

Mason kept the page count down by restricting the coverage wherever possible to topics of clinical relevance, leaving out popular neuroscience textbook subjects such as the fundamentals of smell and leech swimming (a common model for the neurobiology of locomotion). Instead, she focused on the anatomical regions where patients are most likely to suffer lesions that cause symptoms, and the neurotransmitter imbalances that cause behavioral changes. Pop-out boxes describe the clinical manifestations physicians are likely to see, such as the pupil constriction and droopy eyelid of Horner syndrome, which indicates damage to a specific pathway from the brain to the eye.

But to really help important neurobiology topics take up permanent residence in the minds of medical students, Mason deployed an armory of inventive examples and metaphors to make the text both enjoyable to read and memorable.

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When the drug ezetimibe was approved in 2002, it was hailed by its makers as a new tool for lowering cholesterol and fighting heart disease in patients. In clinical trials, the drug (marketed by Merck as Zetia) lowered levels of low-density lipoprotein or LDL, the so-called “bad cholesterol” associated with atherosclerosis, the thickening of blood vessels that can lead to stroke and heart attacks. Though LDL was also the target of the highly successful statin drugs, Zetia passed the FDA because it offered an alternative mechanism for reducing cholesterol levels, and soon was making billions of dollars a year for the pharmaceutical company. But as more and more people took the drug and more research was conducted, the scientific data did not match the marketing hype, with large clinical trials failing to find a protective effect against cardiac events and even finding in some cases that it made blood vessels thicker.

Sadly, the story of Zetia is not that unusual. In recent years, other drugs such as Vioxx and Redux have been come under fire when dangerous side effects or underwhelming clinical results became apparent after approval. These high-profile failures (and the inevitable ensuing lawsuits) have threatened to slow drug development, as pharmaceutical companies are understandably nervous about investing big money in a potential dud. Expensive new drugs that offer little to no improvement over pre-existing treatments also cause damage, by needlessly raising health care costs. So what changes can we make to the U.S. health care system to promote the creation of innovative new drugs worth their price tag?

Three authors, including G. Caleb Alexander of the University of Chicago Medical Center, proposed five not-so-easy fixes in a recent issue of Annals of Internal Medicine. Their strategy includes reforms of the FDA’s drug approval process, drug labels, and the payment strategy of insurance companies on the other. For drug companies that may not like the extra squeeze, incentives can be built into the system to sweeten the deal for developing more effective treatments and drugs for currently untreatable diseases. “Despite these challenges, the United States has a long history of successfully improving the safety and value of prescription drugs, and substantial progress can still be made,” the authors write.

1. Raise the Bar

One way to prevent surprises when new drugs are transferred from clinical trials to the real world is to require that higher standards are met before approval. Instead of just demonstrating the drug’s superiority to a placebo treatment, researchers could be required to prove that the new drug is better than the current standard of care. Clinical trials should also be designed to measure effects on clinical outcomes, such as atherosclerosis, rather than physiological measures, such as LDL.

2. Semi-Approval

For an FDA approval process that some already criticize as to slow, these additional requirements could further gum up the works. To allow time for this more thorough review, the authors suggest a more nuanced FDA approval, adding a new “conditional” approval stage where the drug could be available with strings attached. For instance, direct-to-consumer advertising could be restricted while more data is collected on the drug’s effects in a larger, more diverse population.

3. The Patent Carrot for the Regulatory Stick

For the pharmaceutical companies, all of the above is a nightmare that would extend the cost and time it takes to bring a new drug to market. As an olive branch, the paper suggests extending the patent exclusivity for new drugs that meet these most stringent standards, giving the pharmaceutical company more time to collect profits before generics are allowed to reach the market. One suggestion is to start the patent clock when the drug is approved, so that the FDA process does not eat up valuable months and years of exclusivity for the drug’s developer. Such a measure would also ease up the pressure on the regulators, reducing “the tension between the ticking clock of patent protection and drug safety,” the authors write.

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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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Cells are often described as factories, and their product is protein. Thousands of different proteins are built by cellular structures called ribosomes, which translate DNA instructions into chains of amino acids. But in a cell, as in industry, manufacturing is only the first part of the story: products must also be shipped to their final destination. Within the cell, that’s often the membrane, the site where many proteins are deposited to perform their functions. Studying these delivery systems - the postal service of the cell - is an important pursuit of cell biologists.

In the last few years, scientists have discovered that there are actually two separate routes to deliver eukaryotic proteins from the ribosome to the endoplasmic reticulum membrane. For most of these proteins, a system discovered in the 1970s known as the co-translational system does the job. But for a certain type of membrane protein, called ‘tail-anchored’ proteins, a specialized delivery pathway exists - call it the UPS to the rest of the cell’s postal service.

The laboratories of Robert Keenan at the University of Chicago and Ramanujan Hegde of the Medical Research Council in Cambridge have been among the leaders in studying this new pathway, and a paper published today in Nature is the latest and most comprehensive description of its workings.

Tail-anchored proteins make up only 5 percent of the total inventory of membrane proteins, but even that small slice represents hundreds of biologically important products, Keenan said. If you genetically delete one of the components in the trafficking of these proteins to the membrane in mice, it has catastrophic consequences, killing the animal before it is even born.

“These things play all sort of important roles in a variety of different cellular functions,” Keenan said. “If you screw this pathway up, bad things will happen. At that level they are just fundamentally important.”

Previous studies from the Keenan/Hegde collaboration and other laboratories had identified the key components of a tail-anchored protein transport pathway. In yeast, these include a soluble protein called Get3 and two membrane-bound ‘receptor’ proteins, called Get1 and Get2. But until the current paper, nobody had tested whether these three pieces alone were sufficient to ship a protein from ribosome to membrane. To try this, the team (led by postdoctoral researchers Malaiyalam Mariappan and Agnieszka Mateja) created an artificial system that only contained the three Get proteins and a tail-anchored protein for cargo. To their delight, this streamlined system worked, targeting and inserting the proteins in their proper position.

“We have a minimal system, completely purified, that’s only three components plus the substrate,” Keenan said. “Now we can basically do whatever we want. We can make mutants or chemical modifications, and then we can reconstitute the system and ask, does it work? And if it doesn’t work, we can ask where in this process does it actually fail, and why.”

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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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The future of genetic medicine comes in many flavors, from the discovery of the rare mutations responsible for uncommon diseases to the cataloging of variants that may be responsible for common diseases such as high blood pressure and diabetes. A segment from last night’s ABC 7 Chicago news focused on both aspects of this potential, jumping from a young man in Utah with Miller Syndrome to the 1200 Patient Project of the Medical Center’s Mark Ratain and Peter O’Donnell. Results from the project, currently underway, could help physicians customize medical treatments for individual patients, maximizing effectiveness while reducing side effects. As the segment says, if we really are heading toward a future where every patient has their genetic code read as routinely as they receive a doctor’s check-up, such research will be essential for unleashing the power of genetic medicine.

When the media hypes the healthy effects of drinking red wine in moderation, they’re talking about resveratrol, the chemical responsible for wine’s benefits. Scientists have long tested whether isolating that chemical can turn it into a super-pill for good health and long life without the alcoholic “side effects” of its normal route, with mixed results. But a new study featured in the New York Times this morning finds an intriguing benefit of a resveratrol derivative called SRT-1720. Obese mice given the experimental drug lived 30 percent longer - as long as control mice - rather than expiring earlier from obesity-related diseases such as fatty liver and diabetes. As the article states, such a drug may represent “more a moral hazard than an incentive to good health,” seen by some as a way of avoiding the consequences of excess. But with trials of the drug in humans still in their earlier stages, the ethical discussions will have to wait on the science.

Since our piece remembering famed bio-statistician Paul Meier ran last week, two more fine obituaries of the UChicago professor emeritus have appeared. Read the Chicago Tribune take to learn what instrument Meier learned to play at the Old Town School of Folk Music, and the New York Times version for the context of how Meier changed randomization in clinical trials forever.

Living shoulder to shoulder (or even closer, on the subway) in an urban environment feels like a particularly modern phenomenon. But as friend of the blog Tim de Chant explains in his guest blog at Scientific American, human societies have concentrated themselves since even the prehistoric hunter-gatherer days. For more of Tim’s great writing on the science of population density, visit his Per Square Mile blog.

Stress can have all sorts of negative effects on your health, but what about the stress of your spouse or partner? Not Exactly Rocket Science looks at a study in finches that suggests a high-strung life mate could actually shorten your life.

“A pox of this gout! or a gout of this pox! for the one or the other plays the rogue with my great toe.” - Falstaff, Henry IV

Gout was once called “the king of diseases and the disease of kings.” Thanks to that proximity to power, gout has been well documented through history, from the Egyptians to the Greeks to 17th century England, when physician Thomas Sydenham described an outbreak as “The night is passed in torture.” But today, gout has been democratized, afflicting roughly 6 million people in the United States and connected with obesity, heart disease, and alcohol abuse. Fortunately, treatments for gout have kept pace with its numbers, and in this week’s Journal of the American Medical Association, another option has been added to the physician’s arsenal against the rheumatic disorder.

The new treatment, pegloticase, has its origins in an unlikely place for a “royal” disease: an enzyme from the common swine. Unlike humans, most animals can avoid gout thanks to an enzyme called uricase that converts uric acid (high levels of which cause gout) to the harmless and excretable allantoin. Duke University chemists spent decades modifying pig uricase for therapeutic use in humans, adding a protective coating that can keep the enzyme active for days instead of hours. Perfected at last, the treatment showed positive results in its first two major clinical trials, run by researchers at the Medical Center.

“This represents the first effective therapy for a group of patients who previously had no options at all,” said the study’s senior author, Michael Becker, professor of medicine at the University of Chicago. “This is for patients with severe gout, including major disabilities and high levels of pain. Many of these people had dramatic responses within months…as well as reduced levels of pain and disability. The rapidity of these outcomes is unheard of.”

Gout is caused by the gradual accumulation of uric acid, either from over-production or inadequate removal. When levels exceed the saturation point, uric acid forms tiny urate crystals, like thousands of little needles, that deposit in the lining of joints and other tissues. The crystals can cause inflammation, swelling and intense pain, including painful swollen joint nodules known as tophi.

Many patients are treated with medications that block the synthesis of uric acid or help the kidneys remove it. But not everyone with gout finds relief from these medications, or can tolerate their side effects. Three percent of gout patients - about 120,000 to 180,000 Americans - have chronic, disabling disease with no effective therapy.

Those types of patients made up the two parallel trials of pegloticase, conducted at over 50 rheumatology clinics across North America. Patients in the treatment groups were given an intravenous infusion of pegloticase once every two weeks or once every month, and monitored for six months to see if their uric acid levels fell and their symptoms resolved. The results showed an interesting split: although uric acid levels dropped in all patients given the drug, only 42 percent (in the every-two-weeks group) sustained those decreased levels over the entire six months.

Still, helping two out of five patients without any other treatment option is a significant clinical achievement. And in those patients where the drug worked, the magnitude of relief was great, resolving at least one tophi and improving quality of life and physical function. The drug, brought to market under the name Krystexxa, is expected to cost about $60,000 a year.

“People are dramatically helped by the drug,” said rheumatologist John Sundy, director of the Duke Clinical Research Unit and lead author of the study. The drug’s response among patients who have failed common therapies is typically an “all-or-nothing result,” he added, “providing marked relief for those who benefit.”

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By Dianna Douglas

The Affordable Care Act is nearly one and a half years old, but the complexity of its reforms and their gradual roll-out have made it difficult to grade. Different disciplines are still parsing the legislation, attempting to figure out how it will change the future of their field. Experts in the field of Family Planning and Contraceptive Research has been puzzling over an enormous and perhaps unanswerable question: How will health care reform affect the reproductive lives of women and girls?

That was the primary question at the section’s spring conference, “Reproductive Justice and Health Care Reform: the Impact of Reform on the Reproductive Health of Underserved Women and Youth.” The phrase “reproductive justice” connotes the activism to give women and girls of all races and incomes the access to the same choices and education for controlling their reproduction. Panelists argued that some aspects of the bill, particularly the expansion of insurance coverage, would benefit this cause. But there were also warnings about the political resistance, exemplified by Representative John Boehner’s statement that he doesn’t think reproductive health care services are the business of the federal government: “How can you spend hundreds of millions of dollars on contraceptives? How does that stimulate the economy?” he asked in 2009.

Speakers at the conference, which was co-sponsored by UChicago’s Center for the Study of Race, Politics and Culture, posed many unanswered questions about how the Affordable Care Act will affect women and girls in America. Some expressed hope that it could close the gap between black and white and rich and poor in all areas of maternal health, unintended pregnancy, intimate partner violence, and infant mortality.

But Harold Pollack, PhD, professor at the School of Social Service Administration, gave both sides of the story. He argued that the Affordable Care Act is not only health care policy, but it is the defining document of America’s public policy on reproductive health care.

“Near-universal health insurance coverage will reduce disparities in health,” Pollack said. One of the goals of the Affordable Care Act, passed by Congress and enacted by President Obama in 2010, was to stop people from skimping on health care when they couldn’t afford it. If enacted properly, the health care plan would extend reproductive health care to millions of women.

Under the law, Pollack said, insurers can no longer require a referral to see an obstetrician or gynecologist, and must offer women direct access to these specialists. They are required to pay for some preventative services, like screenings for breast and cervical cancers and sexually transmitted infections. Insurers are required to pay for certain vaccines for women. They have to pay for preventive care for children and adolescents, including screenings for pregnancy. And, insurers may be required to pay for contraception and other family planning services.

All of these requirements were designed to improve women’s health across income levels, but basic access to physicians is the key. “When you visit a doctor because your knee hurts, the truth is that she probably won’t do very much for your knee. But you’ll get your blood pressure taken. She’ll ask you about your diet. And she’ll recommend you for other screenings and lifestyle adjustments,” he said. Oregon recently found that poor people with health insurance were healthier than poor people without it.

Pollack’s keynote address was not uniformly cheerful, however. “The bill is vulnerable, and reform is a risk,” he said. The politics around health care reform have become poisonous, he said, and some of the best public policies in the bill are the most under attack.

Pollack lamented that the great benefits of health care reform won’t be enacted for a few years, during which time public opinion on health care reform could sour more dramatically. “Backloading was the sin of this bill,” Pollack said. It takes time for reforms to embed in society, he said and the legal challenges to the bill may stop the process before it can begin.

To keep the Affordable Care Act on track and make the reforms sustainable, Pollack suggested that the people who support the bill should put a human face on it. “Americans are deeply ambivalent about sexuality and reproductive health,” he said. “But even people who disagree with abortion are uncomfortable with making a poor woman carry a baby to term after a rape or if the pregnancy will seriously damage her health.”  The more human and less theoretical the reforms can become, the more likely they are to survive the next few years of budget cutting.

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Muslims are the fastest-growing religious minority in the United States, with over 7 million Americans declaring themselves as followers of Islam and more than 2,000 mosques nationwide. But in spite of the numbers, little data has been collected about American Muslims’ beliefs about health and disease, or their experience in the U.S. health care system. One reason for this also lies within the demographics, as American Muslims are a particularly diverse minority, containing South Asians, Arabs, and African-Americans, as well as both recent immigrants and long-term, multiple-generation natives. With such a wide variety of members from different ethnic, racial, and socioeconomic backgrounds, how does one pin down the health care experience of American Muslims?

The only way, thought Aasim Padela, was to talk to all of them - or at least representatives from each of the major groups in the American Muslim community. For his recent report, “Meeting the Healthcare Needs of American Muslims,” Padela and his colleagues at the Institute for Social Policy & Understanding went to the rich Muslim community of southeastern Michigan, one of the largest Muslim populations in the United States. Reaching out to multiple mosques and holding focus groups with over a hundred participants, the group looked for common denominators of people who share the Islamic faith, but perhaps little else.

“We looked at American Muslims as a conglomerate and asked what was common,” said Padela, assistant professor of medicine and director of the Initiative on Islam and Medicine at the University of Chicago. “We wanted to talk to each of these three large groups, which we know comprise the majority of American Muslims, and look at what’s similar in terms of health care challenges and beliefs. What we found as similar is something we can attribute to their faith.”

The final product was a fascinating piece of medical anthropology, a snapshot of how American Muslims view their own health or illness, the struggles they face in the U.S. health care system, and their solutions for establishing stronger communication between their faith and their medical caretakers. In an environment where physicians are expected to meet their patients halfway on ways to prevent and cure disease, understanding the perspective of a community that is already large, and growing larger, is an important first step toward improved care.

One primary finding of the report describes the “medical narrative” of American Muslims, their views on where disease comes from and the most effective strategy for fighting it off. Many participants in Padela’s focus groups believed that God takes an active role in health and illness, perceiving conditions from a winter flu to breast cancer as divinely ordained.

“Most participants perceived illness through a religious lens as predestined,” the authors wrote, “a trial from God by which one’s sins are removed, an opportunity for spiritual reward, a reminder to improve one’s health, and sometimes a sign of personal failure to follow Islam’s tenets.”

One might think that treating such a patient would be difficult for a physician, faced with a patient that believes they are being religiously challenged through their illness. But Padela said that a closer understanding of Islam refutes these fatalistic notions, and that most Muslims agree that health issues are best confronted with a combination of spiritual and medical healing.

“God also says to take care of your body, and that means you have to go to people in this world,” said Padela, who conducted the research as a Robert Wood Johnson Foundation Clinical Scholar at the University of Michigan. “Doctors are a part of that, but only a part. Imams play a big role in healing, in the sense that they help you understand disease and illness.”

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Medical school isn’t cheap. Today, medical students graduate with an average debt over $155,000, and the need to pay off those mortgage-sized loans drives many a young doctor away from more modestly compensated but sorely needed fields such as primary care and family medicine. To alleviate this financial pressure, many organizations have started scholarships to help with the med school tuition bill, rewarding scholastic achievements and commitments to work in underserved populations. The American Medical Association’s Physicians of Tomorrow program is one such effort, and this week’s announcement of the 2011 recipients [pdf] carried a heavy Pritzker School of Medicine presence.

Two of the 18 (11 percent, but who’s counting) fourth-year medical students receiving the $10,000 scholarship were from the University of Chicago’s medical school. Laura Blinkhorn (left) and Maggie Moore (right) are the two very impressive Pritzker students among the recipients, each with very impressive biographies already built in their young careers. Blinkhorn has done work with South Side neighborhoods as part of the Pritzker Summer Service Partnership, works with the Washington Park Free Children’s Clinic, and is planning to spend 3 months of the next year doing a clinical rotation in the African country of Gabon. Moore volunteered at the Maria Shelter Clinic for Women and Children and the South Side “Girls on the Run” program, and somehow finds time to write poetry about her medical experiences. Because of poems such as “Cadaver Memorial” and a collection called “A Third Year’s Life in Lyrics,” Moore was given the Johnson F. Hammond, MD Scholarships supporting medical journalism by the AMA. Congrats!

New Furniture for Molecular Engineering

When you are building a new house, you’re gonna need some furniture. The same thing goes for building a new research institute - before you can fill it with people, you need somewhere for them to sit. The University of Chicago’s Institute for Molecular Engineering, which was born in December and acquired a leader in March, has this week announced four named professorships made possible by anonymous donations. The funded positions give the institute the power to recruit prominent researchers to help realize the institute’s unique vision blending biology, chemistry, and physics.

“The big job in front of us is to bring together people with expertise in broadly applicable areas of enabling technology, such as synthesis of new materials, biological engineering, new ways of doing computing and quantum information science,” said Matthew Tirrell, the founding Pritzker Director of the Institute for Molecular Engineering and senior scientist at Argonne.

Elsewhere…

The San Diego Union-Tribune Keith Darcé wrote an excellent overview of the Earth Microbiome Project, the global study of the world’s bacterial populations that has previously been featured on the blog. Our own Jack Gilbert is featured (he mentions their current project swabbing bacteria from the animals of the San Diego Zoo), and an interesting hunt for bacteria able to survive in high-salt conditions is also explained.

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Last November, a barrier was broken in the prolific Bollywood film industry of India. A film called Dunno Y featured the first on-screen male-male kiss - a provocative scene in a country that only the year before repealed a law making homosexuality illegal. Many tagged the film as India’s version of Brokeback Mountain, a controversial and progressive step in depicting male-male romance in popular culture that reflected a growing social acceptance of homosexuality. But the full significance of those cultural changes in the South Asian country have yet to be studied, and will require perspectives from law, anthropology, medicine, and more.

Just such a discussion will take place this Saturday morning at the University of Chicago and on the internet in the roundtable event, “Sexual Identity, Health and Stigma in India: Traditional Statuses and Western Influences.” Organized by John Schneider, assistant professor of medicine and epidemiology at the University of Chicago Medical Center and director of Global Health Programs, the discussion will be available worldwide on a webcast broadcast by the UChicago Facebook page, the Global Health Initiative website, and here on ScienceLife (watch this space).

“What I tried to do is bring together scholars from a number of different disciplines to make this a truly interdisciplinary discussion,” Schneider said. “I want it to be like a Sunday morning news program - but smarter - where a topic area is chosen and everybody fires away with their background about it, leaving room for remote viewer input.”

The central topic of whether sexual identity in India is truly shifting can be addressed from any number of angles. There’s the legal status of homosexuality after the 2009 repeal of Section 377 of the Indian Penal Code by the High Court of Mumbai. Or the sexual and mental health consequences after centuries of stigmatization of men having sex with men, including the spread of HIV and other sexually transmitted diseases. Or the pop culture ripples, such as Dunno Y, that may reflect changing attitudes and sexual roles in Indian culture. All of which are set against the backdrop of a country rapidly modernizing and playing an increasingly powerful role in global economy and society.

“I think that India is going through tremendous social and cultural changes as it emerges from what would be, in old terms, a less-developed economy to now becoming something of an economic powerhouse,” said Niranjan Karnik, assistant professor of psychiatry and behavioral neuroscience and another participant in the event. “This has the potential to really change the dynamics of the society and change the way people see themselves and behaviors.”

The participants in the roundtable are all accomplished researchers and experts on India. The keynote speaker, Lawrence Cohen of the University of California, Berkeley, studies medical anthropology in the country, and has written on homosexuality, aging, and organ transplant markets. Philip Kumar and Sanjay Srivastava are researchers based in India studying sexuality and advising the government on health issues related to men who have sex with men. Schneider himself has an extensive project underway in Indian truck drivers, where he is using cell phones in building a network of men who have sex with men to study their behavior and identify potential peer outreach points.

“One of the issues we are looking at is what changes in sex position roles might be occurring over time in India,” Schneider said. “Is a Western identity rubbing off on India, or is it developing a new identity? My work will help address those questions because of the cell phone network data that triangulates often sensitive self-reported data,” Schneider said.

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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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It has been a couple months since the end of the spring quarter, and the with it the end of many of the Medical Center’s weekly lecture series. But a recent batch of videos posted to the website of the MacLean Center for Medical Ethics brought a whiff of the school year to the dog days of summer. The videos feature a selection of the lectures from the third and final segment of the 2010-2011 theme, “Health Disparities: Local, National, Global,” [pdf] and run the gamut of expert perspectives from libertarian law and the insurance industry to black history and medical education. If you are going through lecture withdrawal or want to get excited for next year’s MacLean Center series (“Medical Professionalism and the Future of American Medicine” [pdf]) beginning in late September, enjoy these videos.

The Case for Health Disparities - Richard Epstein, University of Chicago

Richard Epstein’s annual contribution to the seminar series is always a combustible reaction, where the classically conservative law professor’s market economics conflict with the more liberal lean of the regular audience. This year’s topic was especially flammable - after a couple dozen lectures on the struggle to reduce the health care gap in the United States and around the world, here was Epstein arguing for preserving those very same inequities. Beyond the deliberately provocative title, Epstein’s characteristically off-the-cuff speech recommended that health care reformers should choose a different target - instead of minimizing the health care differences between top and bottom, push policies that support growth and innovation for all patients, rich or poor, while encouraging charity instead of coercive giving.

Future Directions for Health Equity - Anne Beal, Aetna Foundation

The Aetna Corporation is in the business of providing health insurance to Americans. The Aetna Foundation is the charitable arm of that company, dispensing grants and funds to research ways of improving the health care system and reducing costs. Researcher and author Anne Beal is the current president of the Aetna Foundation, and focused her talk on reducing costs and inequalities via improving the quality of health care in America. “Giving people the right care at the right time and preventing disease is an amazing way for us to really rein back a lot of these health care costs,” Beal said. [Original Article]

“Without Health and Long Life All Else Fails”: African-Americans and the History of the Elimination of Racial Disparities in Health and Health Care - Vanessa Northington Gamble, George Washington University

Obviously, racial disparities in health care are not a new phenomenon. Efforts to improve the health of African-Americans also didn’t begin with the civil rights movement, though the strategies employed by the disparity-fighters of the segregation era were very different from today.

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Ozzie Rivero (left) stands ready with a cardiogenic flush as Mark Russo, MD, preps the heart for transport

By Dianna Douglas

Ozzie Rivero found out early Tuesday afternoon that a young patient at a community hospital in Chicago had died on life support. The patient’s heart was still beating as a machine filled his lungs with air, but he would never open his eyes again. In their grief, his family was willing to give his organs to others.

The University of Chicago Medical Center had a patient near the same age with the same blood type at the top of the list for a heart.

Ozzie Rivero had to get that heart from a dead patient to a barely living one.

Rivero is a manager of organ procurement, part of the team that coordinates the collection of hearts, lungs, kidneys, livers, and pancreases from deceased donors for transplant at the Medical Center.

The community hospital told Rivero that he could come for the heart in a few hours, when an operating room was available. Maybe 10:30 p.m. At the moment, the ER was crowded with people suffering through the summer heat wave and all the ORs were full.

Two surgeons prepared to perform heart surgery at the same time: Mark Russo, MD, would go to the community hospital with Rivero to remove the heart and Jai Raman, MD, would put the heart into his patient.

A nurse called Raman’s patient and explained that there was a possibility of getting a heart. But only a possibility. Raman’s patient came to the Medical Center, and got ready for surgery.

At 8:30 p.m., the community hospital delayed Rivero - more major trauma cases were in their operating rooms, and the procurement would have to wait until at least midnight.

At 9:30 p.m., the hospital delayed Rivero again, this time until after 1 a.m.

Raman’s patient waited, along with the nurses, anesthesiologists, physician assistants, transporters, and residents who stood ready for one of the most complex surgeries performed at the Medical Center.

At 12:30 a.m., Rivero walked out of the hospital toward a white SUV idling in a cul-de-sac on 58^th Street, the air conditioning on full blast against the swampy night air. “Hey Herb,” he said to the driver as he opened the back and tossed in a duffel bag and a red cooler full of ice.

The car pulled away from the hospital as Rivero’s cellphone rang—it was Operating Room 16, where all the heart transplants happen. They wanted an update. “You can put the patient to sleep,” Rivero said.

Rivero called Raman, who had gone home in the hope of getting a little time with his family before the marathon surgery began. “They’re putting the patient under,” he said. Raman thanked him for the update and prepared to come back in to the hospital.

Many organ procurements are at night, when ORs are otherwise empty and grieving families have gone home. Rivero skips a lot of sleep in his job, and has seen many of his colleagues give up. “The turnover is high when you never get to meet the recipients or see the success stories,” he said. “We don’t meet the guy who got a new life.” The driver dropped Rivero and the surgeon Mark Russo at the community hospital’s emergency room, and waited outside.

The young man lay on a gurney in a large OR, dead from a traumatic head injury. The air conditioning was broken, and the room got hotter with each person who scrubbed in and gathered around his body. Mark Russo changed into scrubs, washed his hands in a steel sink, tied on a hat and face mask, and pushed open the double doors.

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There’s something quaint and charming about a family business, where multiple generations work shoulder to shoulder to keep an enterprise afloat. But when the business in question is academia and the salaries are paid by tax dollars, suddenly keeping it in the family carries the stink of nepotism. In the public universities of Italy, it’s no secret that nepotismo is the rule, not the exception. Despite repeated legislative efforts to reform university hiring, scandals such as the one at University of Bari’s economics department - where a father, two sons, and five grandchildren all work together - remain a perennial problem in Italy.

Stefano Allesina, an assistant professor of evolution & ecology at the University of Chicago, witnessed the damaging effects of these unfair hiring practices as a student in Italy. While pursuing his PhD, Allesina’s advisor told him not to waste his most productive years trying to get a job in Italy - advice he followed in emigrating abroad to the United States. Many of his Italian peers followed similar paths, while those who stayed behind languished in limbo waiting for scarce tenure track positions to open. Frustrated with the broken Italian system, Allesina decided to apply his talents for creating computational models in ecology to measuring the full scope of nepotism in the university system of his home country.

“In Italy, there is an enormous brain drain,” Allesina said. “Italy is losing so many graduate students to other countries, it’s unbelievable. It’s because the hiring is extremely slow, complicated, and not really based on quality…and I think these kind of hiring practices contribute a lot to this brain drain and the fact that Italian universities are not ranked very high internationally.”

In a study published yesterday in PLoS ONE, Allesina used a public directory containing the last names and fields of study for over 61,000 professors to look for systemic signs of nepotistic hiring. With a simple computer model, Allesina detected unusual clustering of last names within disciplines such as law and medicine, far from the random distribution expected with unbiased hiring.

“It’s not a few bad apples, it’s really bad,” Allesina said. “I found that in many disciplines there are much fewer names than you would expect to find at random, indicating a very, very high probability of nepotistic hires.”

The original model worked like a random lottery, repeated one million times. Over the entire dataset, more than 27,000 different last names were represented. For each discipline, Allesina tested whether certain names appeared more than expected at random. So for medicine, where there are 10,783 faculty members with 7,471 different last names, Allesina programmed his computer to test how likely it was to randomly draw only 7,471 names (or fewer) from the total name pool in 10,783 tries.

“It’s very basic, anybody with a laptop can do this analysis,” Allesina said. “I wanted to keep it as coarse-grained and simple as possible. Because then it’s more powerful - if this works, anything else will work. Even this very simplistic analysis can find that some disciplines are above and beyond what one could expect.”

Under this model, the worst offenders were law, medicine, and industrial engineering, all of which showed only a 1-in-1,000 chance of having so few last names by random. On the other end, psychology, demography, and linguistics  each contained a last name distribution close to random, suggesting that hiring was more fair in these fields. Another analysis, which mapped the likelihood of two faculty members in the same field sharing a name by geographic region, found that indicators of nepotism were stronger in the south - a result that would surprise few Italians, Allesina said.

“For an Italian, this is not that surprising,” Allesina said. “It is a narrative of two separate countries, where in the public sector we have more problems in the south.”

A much trickier task than measuring the breadth of nepotism in Italy is finding an effective solution for ending the unfair hiring practices.

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