Last year, I read The God Particle, Leon Lederman and Dick Teresi’s entertainingly wry flyover of the history of physics and the birth of particle accelerator science. My motivation for slotting this heavy subject into my daily commute was the impending activation of the CERN Large Hadron Collider in Geneva, Switzerland, the most powerful particle accelerator and arguably the most impressive scientific instrument ever built. The LHC was switched on in fall 2008, then promptly suffered technical setbacks that shut it down for over a year. But since the collider was reactivated in November, it has set about its business of breaking physics records left and right, including yesterday’s most powerful particle collision ever at an energy of 7 trillion electron volts.

Despite the excellent, often hilarious writing of Teresi and Lederman, director emeritus of Fermilab in Batavia, Illinois, I still can’t claim to understand everything about high-energy particle physics. My appreciation of the field is mostly aesthetic, inspiring vague awe at the historical lineage from Galileo dropping things off the Tower of Pisa through 17-mile long circular tunnels designed to throw beams of protons at each other to simulate The Big Bang. I’m just a biologist, so I won’t hazard an attempt at explaining the ins and outs of quarks, leptons, antimatter and the Higgs boson. But I’ll do the next best thing, and link to some videos that do a good job of putting these fascinating experiments into context.

The CERN website doesn’t allow its videos to be embedded elsewhere, but here is live footage of their scientists watching yesterday’s record 7 TeV collision and an animation of the actual collision.

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Jet lag is the perennial unwelcome companion of the air traveler, an experience that can make one’s mind feel like it was left back at the airport. That powerful disorientation has made jet lag a topic of interest for scientists, who have looked at changes to a person’s  brain chemistry and physiology after lengthy, intercontinental trips. But unless you’re a serious jetsetter, most of your flights only cross a time zone or two or three, enough to produce a milder form of jet lag’s mind-scramble. Few studies have looked at physiological changes after these more routine flights, until an almost accidental opportunity to do so occurred to a team of researchers studying an unusual subject pool: hundreds of sets of twin brothers.

The Vietnam Era Twin Registry is a pool of military veterans that have been tested in a multitude of studies examining genetic and environmental factors for everything from pathological gambling to cardiovascular disease. In one such study, designed to study different parameters associated with aging, the subjects flew to medical centers in Boston or San Diego for a full day of medical and psychiatric tests. Several scientific papers were published from those results, including one by a team including the University of Chicago assistant professor of psychiatry Kristen Jacobson on the heritability of levels of cortisol, sometimes called the “stress hormone.”

But the researchers in that study realized that there could be an important influence on their data: jet lag. Long-distance flights have previously been shown to throw off a person’s natural cortisol rhythms, the ebb and flow of the hormone normally experienced during a given day. So the researchers in the Vietnam Era study had their participants spit in a vial several times at home, then repeat their spitting during their Boston or San Diego visits. Those salivary samples - used to measure cortisol levels - allowed researchers to look for changes in the hormone before and after air travel for people who are less than frequent fliers.

“A person traveling 5 days a week or repeatedly traveling to Hong Kong on business is not representative of the general population,” Jacobson said. “But we all know how it feels when you’re going to California versus going to DC from Chicago and struggling with waking up. This paper links what we all think to be true about jet-lag with an existing body of research that had shown effects under fairly extreme circumstances and said yeah, this is in fact what’s going on, there are changes in the body even with short-term travel.”

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In the clinic of the future, a person’s genomic information will be a routine part of their medical record, no more exotic than height, weight and family history. The unique genetics of each patient will be employed by the doctor and his computer to custom-tailor treatments for every condition imaginable, from HIV and cancer to allergies and weight gain. Most of the guesswork will be removed, as physicians can prescribe drug doses that maximize effectiveness and minimize side effects for each individual, rather than playing the averages of research results.

Most physicians and scientists agree that this vision of genetic  medicine will become reality…someday. But will gene-based decision-making become a significant part of the clinical world in the coming years, or the coming decades? That was the question that hovered over Translating Genomics into Personalized Therapy, an afternoon symposium at the University of Chicago last Friday. With four speakers from different corners of medicine speaking to an audience spanning several medical and scientific departments, the event was equal parts optimism and caution - a glimpse at both the promise and limitations of genetic medicine.

If the question is “what can genetic information do for me today?,” the answer was “Depends.” Each speaker at Friday’s symposium reported on the current state of genetic research for a different medical problem: HIV/AIDS, breast cancer, psychiatric disease, and blood disorders. And while some fields are on the verge of real, practical use of genetics in the clinic - for diagnosis or determining treatments, or even reprogramming DNA - others are only just beginning to study the potential of genomics.

On one side of the spectrum were blood disorders such as hemophilia and SCID (X-linked severed combined immunodeficiency, aka “bubble boy syndrome”), for which gene therapies are already under investigation. Arthur Nienhuis of St. Jude Children’s Research Hospital talked about efforts to cure these diseases by inserting a new gene into a patient’s DNA, using a lab-designed virus. The first experiments with this gene therapy led to an unexpected severe side effect of leukemia in some patients, but efforts at St. Jude have worked to develop safer means of inserting new genes, Nienhuis said. Researchers are also looking at other virus delivery systems, including one based on a defanged HIV virus, to improve the efficiency of treatments for blood disorders. But Nienhuis admitted that the road to gene therapy for these diseases was much straighter than it would be for other illnessess, since blood disorders are often caused by only a single “broken” gene.

On the other hand, psychiatric disorders have consistently proven themselves difficult to impossible to be traced back to their genetic roots. Margit Burmeister of the University of Michigan described that frustration in her talk, recapping how genetic association studies involving thousands of subjects have failed to reveal likely candidates genes for diseases such as schizophrenia or bipolar depression. Those are illnesses that run in families, but Burmeister reminded us that a familial trait is not necessarily heritable and genetic.

“Going to medical school, speaking Mandarin and Catholicism also run in families,” Burmeister said.

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Expanding the Human Family, One Cave at a Time

A couple weeks back on the blog, Callum Ross debunked a lemur-like creature, Darwinius masillae, purported by some to be a very distant human ancestor. If you were feeling sad about this contraction of the human family circle, you may have been cheered by news this week about the potential debut of a new, more human-like human ancestor. There is no fancy Latin name for this relative yet, because even the authors of the paper announcing its existence are unwilling to declare that an entirely new species has been found. But it’s enough to dream up some not entirely unscientific (and somewhat unsettling) daydreams of a time when what we know today as humans were not the only two-legged tool-using primates on the scene.

The uncertainty surrounding the finding published in Nature by Johannes Krause, Svante Paabo and colleagues is that the discovery was made with a little bit of paleontology and a lot of genetics. The human ancestors or cohabitants we’re more familiar with - like Neanderthals or Homo erectus - were discovered in skeleton form, the classical way scientists learn of extinct creatures. But Krause & company’s fossil findings are limited to a pinky bone discovered in a Siberian cave, dated to 40,000 years ago. Because you can’t tell much anatomically from a pinky bone, the researchers instead harvested DNA from the bone; specifically, mitochondrial DNA (mtDNA), a smaller stretch of genes inherited entirely from one’s mother. When compared to mtDNA from modern humans and Neanderthals, it was dramatically different from both species - roughly twice as different as the gap between humans and Neanderthals.

The authors (and most of the outside scientists I’ve come across online) reason that the most likely explanation for that difference is that the pinky belongs to a very old human-like species, one that may have branched off from modern humans 1 million years ago. There are other theories - Carl Zimmer proposes one alternate theory built on the rather salacious premise of interspecies lovin’ - but analysis from the nucleus DNA of the proposed new species is necessary to decide. In the meantime, it’s fascinating to think about a time when humans sort of like us had to compete with Neanderthals and whatever this new ancestor may have looked like for resources, much like different species of birds will fight over territory and food.

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Orthopedic surgeons are tasked with repairing the architecture of our bodies, setting bones straight when they break and correcting injuries to muscles and joints. It doesn’t take a medical degree to know that, most of the time, those structures lie inside the skin. That means that one of the most important tools available to a modern orthopedic surgeon is the X-ray machine, allowing the surgeon to see the problem and form a plan of action before the patient is on the surgical table.

So how does an orthopedic surgeon work in a tent hospital on the border between Haiti and the Dominican Republic, where the best X-ray device available is one normally used for dogs? You practice “psychic orthopedics,” said Rex Haydon, assistant professor of surgery at the University of Chicago Medical Center. Haydon was one of three surgeons who spoke about the challenges and rewards of aiding medical relief in Haiti in a special session of the Department of Surgery Grand Rounds early Wednesday morning.

Grand Rounds typically feature a physician telling the story of an interesting or unusual patient case, illustrated with X-rays, MRIs and vital signs. I’m guessing this week’s session was the only one this year to feature pictures of collapsed buildings and shower facilities constructed from tarps and buckets. Speaking in order of their time spent in the field hospital established in Fond Parisien, Haiti, Haydon, Kris Alden and Christopher Sullivan each spent more time detailing the unique experience of practicing orthopedic surgery (often without the actual surgery part) in hot, stuffy tents rather than the gritty details of individual cases. Through the three mini-talks, a story formed of how conditions in the camp changed and improved in the weeks following the January earthquake. But there were also common threads through each of the three surgeons’ experiences that depicted the difficulties of providing modern care in a less than modern setting.

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When we chatted with University of Chicago psychiatrists about the proposed changes to the DSM-V - the diagnostic manual for mental disorders - there was one much talked-about piece missing: eating disorders. Many media outlets writing about the DSM-V draft mentioned a change in the chapter on eating disorders that sounds small but could be highly clinically significant, the addition of binge eating disorder as the chapter’s third discrete condition alongside anorexia nervosa and bulimia nervosa. Unlike those two more-established disorders, which can result in dangerous weight loss, binge eating disorder could produce weight gain. Inclusion of binge eating in the chapter on eating disorders thereby could signal a shift toward medically treating overeating, like undereating, as a mental illness.

Daniel Le Grange, professor of psychiatry and behavioral neuroscience and director of the eating disorders center at the University of Chicago Medical Center, said that may be true - researchers and physicians in his field are looking more and more at uncontrollable overeating as a disorder. But binge eating disorder itself is not an entirely new condition; instead, it has long existed in the diagnostic limbo of “eating disorders not otherwise specified,” a catch-all term for less common or less discrete conditions. Still, if the DSM-V draft recommendations are approved, binge eating disorder may receive more attention from doctors and scientists, leading to treatment advances in an area where effective treatments, even for anorexia and bulimia, are relatively new and sometimes lacking in supporting evidence.

In this week’s Dr. FAQ, Le Grange talks about the proposed changes to the DSM-V chapter on eating disorders and binge eating disorder in general. He also explains what treatments are currently used for eating disorders, and what is known about the causes of those conditions (spoiler alert: very little). Finally, Le Grange talks about the eating disorders research being conducted at the University of Chicago, including his work on the Maudsley Approach, a family-based treatment for eating disorders in adolescent patients. Le Grange will be speaking at a conference for families of adolescents with eating disorders in Chicago on April 26th.

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Stem cells are a little like teenagers, full of potential but not sure what they’re going to be when they grow up. It’s that uncertain destiny that makes stem cells so exciting to scientists and physicians, who hope to someday use them for everything from spinal cord repair to organ regeneration. But corralling the uncertain power of stem cells requires learning how to push them toward a desired fate, convincing them to become bone cells or liver cells or neurons. Most laboratories have figured out ways to accomplish this goal with chemicals, exposing stem cells to growth factors and other signals that lead it down a particular developmental path. But there may be another way to play guidance counselor to an indecisive stem cell - changing its physical shape.

This process, called cell patterning, is a primary research focus of Milan Mrksich, professor of chemistry at the University of Chicago. On the surface, cell patterning sounds like a mix of science fiction and Play-Doh art: cells are grown on a plate stamped with a special mold that forces the cells to form a particular shape chosen by the researcher. Those shapes can be as simple as circles or squares of various sizes or as complex as flowers, stars, and pentagons. And far from being mere aesthetic lab trickery, this shape-shifting can have dramatic biological effects upon the cell, its underlying skeleton, and even the expression of particular genes.

In a paper published in PNAS earlier this month, Kristopher Kilian, a postdoctoral fellow in Mrksich’s laboratory, applied the cell patterning technique to a particular type of stem cells. Mesenchymal stem cells, harvested from bone marrow, are the slightly less ambitious cousins of the more-hyped pluripotent embryonic stem cells that can change into virtually any cell type. As multipotent cells, MSCs are generally restricted to one of three career paths: fat cells called adipocytes, bone cells called osteoblasts, or cartilage cells called chondrocytes. But despite being limited, those outcomes are potentially very useful therapeutically should scientists learn how to reliably control the differentiation of these cells.

So Kilian, with colleagues Branmir Bugarija and Bruce Lahn, tested out cell patterning on his supply of MSCs. The first experiments confirmed that size and aspect ratio mattered: when given larger or wider areas to grow, the stem cells preferred to become bone cells instead of fat cells. Kilian then kept the size of the stamp constant, but altered the shape, forcing the cells into either a “flower” with curved edges (top row above) or a “star” with sharp edges (bottom row). Both cell shapes were then grown in the same media - a “cocktail” of signals promoting fat cell or bone cell growth, and fates were chosen.

The results? “Flowers make fat and stars make bone,” Kilian summarized. “The view is that, when you introduce the cocktail, the cells are driven one of two ways…the geometry dictates which path the cell goes toward.”

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We’ve talked a lot over the last several weeks about the University of Chicago Medical Center medical relief efforts in Haiti since the devastating earthquake of January 12th. But most of that discussion has been in the form of photos from the field hospital in Fond Parisien where many of the UChicago volunteers have worked, or in video interviews with those volunteers after they have returned from the still-reeling country. Finally, we now have video from the scene, thanks to Cheryl Reed, senior editor of Medical Center publications, who spent a week with the volunteer team in Fond Parisien earlier this month.

In the documentary posted below, Cheryl’s footage offers a window into the day-to-day life at a field hospital caring for more than 250 patients in tents and with donated supplies. In the weeks following the earthquake, medical needs shifted from trauma surgery to rehabilitation, as thousands of Haitians who received emergency orthopedic surgery for crush injuries needed help recovering from their wounds and procedures. You’ll see some of those patients arriving via helicopter and bus from hospitals in the Dominican Republic, Port-au-Prince, and the US Navy hospital ship USNS Comfort. You’ll also see UChicago volunteers at work - offering physical therapy, surgery and vaccinations - and talking about their experience bringing urgently needed medical care to Haiti in less-than-ideal conditions. The communal, low-tech spirit of the field hospital is best encapsulated by a scene in Part 2, where 40-some volunteers combine to physically move the “operating room” tents so that a new structure can be built for the care of the critically injured. 

If you’d like to learn more about the Medical Center’s continuing efforts in Haiti, visit the project’s web site. You can also read more about Cheryl’s trip, view more of her excellent photography, and listen to a radio interview about the experience at her ChicagoNow blog. 

If you can’t view the videos through YouTube, you can access them here.

fMRI on Trial

Last year, one of the most-followed trials in the Chicago area was the first-degree murder case against Brian Dugan, who was accused of murdering a 10-year-old Naperville girl in 1983. The Dugan trial was interesting for many reasons, most notably for coming at the end of a 26-year process during which two other men were falsely convicted and sentenced to death for the crime. But it wasn’t until I read this week’s issue of Nature that I realized the scientific precedent set during the trial, one that signaled a new intersection of science and law that could be very important in coming decades.

During the sentencing portion of the trial, after Dugan had been convicted of the murder, testimony for both the defense and prosecution was provided by neuroscientists. This occurrence in and of itself is not unusual, as scientific evidence is more and more frequently used to argue whether a criminal suffers from mental illness that contributed to the crime. But as reporter Virginia Hughes summarizes nicely, this courtroom science debate was different, as it hinged upon new evidence for mental illness: an fMRI brain scan.

Through his defense team, Dugan had been volunteered for a study conducted by Kent Kiehl from the University of New Mexico on the brains of psychopaths, people who lack a sense of moral behavior. According to Hughes’ article, Kiehl has conducted fMRI scans - which create a live movie of brain activity - on more than 1,000 criminals over 16 years, including many that used a mobile scanner located at a prison in New Mexico. Dugan, already in police custody for two other murders, was scanned by Kiehl at Northwestern Memorial Hospital during his trial and interviewed by Kiehl for a diagnosis of psychopathy.

But when defense lawyers attempted to introduce the results of the scan and interview into court as a “mitigating factor” that could save him from the death penalty, prosecutors objected. Hughes writes that DuPage County State’s Attorney Joseph Birkett argued in court that the scans would prejudice the jury due to “bright colors and statistical parameters…chosen by the researchers.” A hearing held outside the jury’s presence led the judge in the trial to rule that the results of Dugan’s scan could be discussed, but not shown in the trial. After some more legal oddness unrelated to the brain scans, Dugan was eventually sentenced to death in November 2009.

Though somewhat irrelevant to the details of the case, the role that fMRI scans played in Dugan’s sentencing could open the floodgates of a phenomenon speculated about for quite some time: the use of brain imaging in courtrooms. Hughes’ article does a great job of rounding up scientist opinions about this use - both against and, perhaps surprisingly, for - so I won’t recapitulate those here. But the central argument against brain scan “diagnosis” of mental illness is worth remembering for all brain scan studies - most such research uses average pools of data from multiple subjects that can’t always be applied on an individual basis. As Hughes reports Jonathan Brodie, a psychiatrist from New York University, said in the trial, “If you look at professional basketball players, most of them are tall…but not everyone over six foot six is a basketball player.”

There’s a nice overview of this article and some other research into brain imaging of mental illness by Vaughan Bell at Mind Hacks.

Elsewhere…

In another crossover of science and law enforcement, a PNAS study suggested that the thriving worlds of bacteria present on everyone’s skin (gross but true) could be employed as a forensic tool. Specifically, the authors proposed that by testing the bacteria present on a computer mouse or keyboard, they could identify people who had recently used those devices - a useful police tool for determining who hacked into a system or deleted incriminating data. And as Ars Technica and Wired report, it worked, putting the old-fashioned fingerprint duster on notice.

Science-writing kerfuffle! I normally think that the science writers at UK newspaper The Guardian are some of the best around (and their sportswriters are the best), but boy is this article wrongheaded. I just wrote about epigenetics on the blog recently, and will do so again many times in the future, but nowhere will I ever claim that it proves Darwin wrong, because that’s just, well, wrong. Jerry Coyne, Carl Zimmer, and another Guardian reporter have already torn it to shreds, it’s worth reading like a car accident is worth gaping at.

Should people be allowed to donate their organs to strangers in exchange for money? A recent survey from the University of Pennsylvania said that payment for organ donation would increase supply without drawing disproportionately from the poor, but the University of Chicago’s Lainie Ross criticized their conclusions.

By all accounts, the medical response to January’s devastating earthquake in Haiti has been overwhelming. But what about the situation in Haiti before the earthquake? At the beginning of the year, the small nation boasted the 2nd-highest number of non-governmental organizations, NGOs, per capita, trailing only India. And yet when the 7.0 earthquake struck just 15 miles southwest of Port-au-Prince, not only did buildings crumble, but so too did the infrastructure of the country. The strong NGO presence had done little to help Haiti construct more earthquake-resistant buildings, and most of the medical aid for the hundreds of thousands of injured came from outside Haiti’s borders.

“They were not serious about building a lasting infrastructure,” said Jim Yong Kim, president of Dartmouth College, in a lecture at the University of Chicago on Wednesday. “8,000 NGOs, but I have to say that the execution of those NGOs in this unbelievably beleaguered country was about as poor as I have ever seen.”

Harsh words from Dr. Kim, but as his talk emphasized repeatedly, the time for niceties is over when it comes to delivering health care to the world’s poor. Titled “Why We Can’t Wait: Building a Science of Health Care Delivery,” Kim’s lecture argued that the lack of evidence-based research about how the medical woes of underserved communities can best be addressed squanders billions of dollars and unmeasurable amounts of good intentions each year on unsuccessful efforts.

“What I see a lot of are do-gooders who are very very committed to the notion of themselves going out into the world and doing good, but unfortunately I don’t see very many of those do-gooders committing to truly executing so that their outcomes match their desire to do good,” Kim said. “So much of what we see - and this has never been more true than in Haiti recently - is people who are saying ‘I’m committed to the act of giving, and that’s enough.’”

Kim speaks from experience as the co-founder of Partners in Health, a Boston-based non-profit organization with the mission of bringing health care to poor communities around the world. Through his talk, Kim drew upon case studies of successful projects he oversaw with PIH and the World Health Organization as examples of how an NGO can be effective against a medical problem in a developing country. In one case, Kim and colleagues worked to reduce the price of expensive drugs for multiple drug-resistant tuberculosis - in the face of a WHO stance that the problem was too complicated to address. Later, working with the WHO as the director of their department of HIV/AIDS, Kim launched The 3×5 Initiative, an effort to provide 3 million people in developing countries with anti-retroviral therapy by 2005. Again, Kim said, he met with resistance from organizations that did not want to be pinned down to such a specific goal - and in the end, the 2005 timetable was not met. But so what, Kim seemed to say - they met their goal in 2007, and 3 million people with HIV experienced the “Lazarus Effect” of anti-retroviral treatment.

“It’s the first time in history where rich countries have committed to chronic care for a chronic condition in poor people,” Kim said. “That’s why it’s so important.”

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Genetically identical mice with different DNA methylation produce different tail types. (Photograph courtesy of Emma Whitelaw, University of Sydney, Australia/Wikimedia Commons)

Ah, nature and nurture, those eternal enemies. What once used to be the domain of philosophy and English classes has migrated over the past century to the sphere of science, culminating in the completion of The Human Genome Project in 2003. But far from settling this age-old battle, the HGP may have reinvigorated it. Now that scientists know the roughly 24,000 genes that code for proteins in the human genome, they also know that those genes alone cannot explain the complexity of the human body. Many are now looking for the missing parts of the story in regulatory sequences hidden in “non-coding” DNA, but others are looking at a concept, called epigenetics, where nurture/environmental factors have a chance to make a comeback.

Epigenetics - “upon” genetics, if you’re into word dissection - is the modification of genes without changing their DNA sequence. There are several different epigenetic mechanisms that can modify a gene’s expression, many of which are too complex to tackle in one article. But one epigenetic process is relatively simple at heart - DNA methylation, where the addition of a methyl group to the nucleotide cytosine can effectively silence genes. Those methylated genes can then be handed down to offspring cells or offspring people, a form of non-genetic heritability sometimes known as “cell memory” or “genetic imprinting.” DNA methylation also creates a space for environmental factors, which could presumably change the methylation of genes during a person’s life and thus have dramatic effects upon gene expression.

But is DNA methylation purely a tool for nurture to scramble nature? Not so fast, says Chunyu Liu, assistant professor of psychiatry and behavioral neuroscience at the University of Chicago Medical Center. In a paper published last week in the American Journal of Human Genetics, Liu and colleagues discovered that, for some genes, DNA methylation is under genetic control - that is, genes control the methylation of other genes, and thus their expression.

“Previously, we thought that genetics and epigenetics were two separate things,” Liu said. “When you talk about epigenetics, people think it’s more environmental. Basically, this is the first time we go deep into the genetic components of DNA methylation. I think it’s an important bridge.”

The secret to finding the genes pulling the strings of epigenetics was to think about DNA methylation in a different way: not as a process, but as a genetic trait. Quantitative traits are characteristics determined by multiple genes producing a spectrum of outcomes, as in height or blood pressure. These are all complex traits that are administered by multiple genes, but genetic analysis methods can be used to find particular stretches of DNA important for determining the ultimate outcome.

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As you may have gathered from various television dramas, medical residents work insane hours. A typical shift “on call” often means 30 straight hours on duty at the hospital, mostly spent on the time-intensive process of admitting new patients. People outside the medical profession often ask why such marathon shifts are necessary, and express surprise when limitations on resident work hours are met with resistance from those very residents. The answer lies in the process that occurs at the end of that shift, a process that becomes more frequent every time resident hours are restricted: hand-offs.

In an ideal hand-off, the end-of-shift resident meets with a fresh resident just starting their workday and relays any information they think the new resident might need about patients admitted overnight. That description stresses the word “ideal” - hospitals are not the quietest environment, and distractions and general mayhem can reduce the hand-off process to a few rushed minutes or eliminate it altogether. Thus, important information about how the new resident should deal with any urgent medical issues that should arise in unfamiliar patients can be poorly communicated, or lost entirely.

Thus, limiting resident work hours may lead to fresher residents, but the miscommunication inherent in increased hand-offs are a consequence of those restrictions, said Vineet Arora, an assistant professor of medicine at the University of Chicago Medical Center who researches patient hand-offs.

“You could have concerns about either a tired physician who knows the patient or a well-rested physician that may not know the patient,” Arora said. “The trade-off is between fatigue and familiarity.”

Just how steep a trade-off that can be was revealed by Arora’s latest paper, part of a collaboration with Boaz Keysar, professor of psychology and an expert on communication. Published this month in the journal Pediatrics, the study examined just how much information is successfully passed between pediatric interns (first-year residents) during hand-offs at Comer Children’s Hospital. After the hand-off, each intern was asked separately what they thought were the most important pieces of information passed along about each patient, the rationale for those decisions, and a rating of how they thought the hand-off went.

The results were worrisome, particularly given that hand-off conditions at Comer, with a distraction-free room provided for physicians to discuss patients as shifts change over, far exceed those found at most hospitals. Even in those optimal conditions, Arora and Keysar (with Vivian Chang, and Shiri Lev-Ari, and Michael D’Arcy) found that what the end-of-shift intern judged as the most important piece of information was not successfully communicated to the new intern more than half the time. The rationale for that information - such as why a patient is on a particular antibiotic - also slipped through the cracks in the majority of cases, with the two interns disagreeing on the rationale in 60 percent of the interviews.

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From Rose et al., PNAS, 2010

For the return of Linkage after a week’s dormancy, here’s an interesting paper from the journal Proceedings of the Natural Academy of Sciences - PNAS, in scientific shorthand - a quickfire roundup.

Radioactive Cigarettes

As one of the most popular addictive substances in the world, tobacco has drawn a lot of research attention. Scientists have long sought the mechanisms by which tobacco - whether smoked, chewed or snuffed - affects the brain, creating its powerful dependence in users and the massive profits and public health problems therein. That happens to be the sub-field in which I did my graduate research, but that’s only part of why a paper this week from scientists at Duke and Wake Forest caught my eye. Measuring nicotine concentrations in the brain while a human subject smokes a cigarette? Pretty cool. Doing it with radioactive cigarettes? Extra cool.

Don’t worry - this process isn’t going to turn anybody into some kind of chain-smoking Hulk. The method was a variation on positron emission tomography, more commonly known as PET scans, used regularly by hospitals to obtain high-quality real-time medical images. In a typical PET scan, the patient drinks or is injected with a radioactive tracer, a safe isotope that allows the scanning machine to map internal organs so doctors can find tumors, measure drug metabolism, or observe brain activity.

In this study, researchers gave test subjects cigarettes loaded with radioactive nicotine - a normal carbon on the nicotine was replaced with a radioactive carbon isotope. The substitution allowed them to track the movement of nicotine in real time as a subject smoked, following it along its path from mouth to lungs to brain. When they did this, two surprises were found: 1) Nicotine concentrations in the brain rise gradually over the course of a cigarette, not in spikes corresponding to each “puff,” and 2) Under controlled circumstances, regular smokers actually achieve lower brain nicotine concentrations than casual smokers.

That latter finding has to do, strangely, with the absorption of nicotine from the lungs to blood, which was found to be slower in heavy smokers. But not to be thwarted, the smokers compensate by taking deeper puffs of their cigarettes, the researchers found, offsetting the slower absorption. The main application of that knowledge is to other studies of nicotine in the brain that are trying to simulate the natural concentrations experienced after a cigarette - like my old experiments which tested the effects of nicotine on a slice of rat brain kept alive for several hours in a dish. But for everyone else, at least now you know what a brain on cigarettes looks like, without the use of egg metaphors.

Elsewhere…

I want to link to almost every post Jonah Lehrer makes on his blog (and often do through my twitter account), but this one on creativity, brain hemisphere damage and the effects of marijuana is even a cut above his usual musings. Bonus insight from Vaughan Bell at Mind Hacks, making this a big old jam session of my favorite science bloggers.

Emil Coccaro, chair of psychiatry at the University of Chicago Medical Center, appeared in a Wall Street Journal article about when having a foul temper becomes a psychiatric condition called intermittent explosive disorder. Watch out for an article on Coccaro’s IED research appearing here soon.

We’ve talked a lot here about using DNA sequences as a clinical tool for cancer treatment. This New York Times article suggests that the answers may reside in mitochondrial, rather than nuclear, DNA.

Our own Jerry Coyne blogs about the viral science photo of the week, the all-black king penguin. And talks to the Associated Press about the poor quality of two popular biology textbooks for home-schooled kids.

Speaking of Coyne, science and religion are increasingly antagonistic bedfellows, but this article by Dave Munger in Seed gives a good overview of one scientific DMZ where they can reasonably intersect: the study of why religious beliefs evolved in humans.

At the heart of every trial involving human subjects, there’s a conflict. The investigators design their study to find the most accurate answer to a particular scientific question, be it the efficacy of a new drug or the incidence of disease in a city or state. But the participants in that research likely have different goals: finding a cure for their illness, aiding a good cause (whether its the same cause as the researchers’ or not), or obtaining free medical testing and information. Juggling these competing interests is the mission of institutional review boards, or IRBs, panels of scientists and non-scientists charged with protecting the interests of research subjects in human trials.

But how does an IRB located in the United States make decisions about studies conducted in different countries, with different ethical and cultural standards? That was the central question asked by John Schneider, director of global health programs for the Section of Infectious Diseases at the University of Chicago Medical Center, at this week’s MacLean Center for Clinical Medical Ethics seminar. Schneider’s primary area of research is HIV transmission and prevention in India, a country where attitudes about the disease are profoundly different from those found in the United States. That has a dramatic impact on the researcher-subject (or as Schneider prefers, “researcher-participant”) relationship and raises additional ethics questions about how study results should be handled.

Schneider’s presentation focused on disclosure of HIV test results to study participants, a trickier issue than one might expect. Typically, the medical information obtained from a subject is made anonymous, usually by assigning it a number rather than a name. This process is meant to protect both the privacy of the patient and any bias that might occur when the results are analyzed by a researcher - it’s a conversion of a subject’s complex medical status into pure data.

But say an HIV test comes back positive for a test subject who is unaware that they have the disease? Is the researcher then obligated to inform the subject of the positive test? In the United States, the National Bioethics Advisory Commission says Yes, so long as the test results have “significant implications for a patient’s health concerns” or “a course of action to ameliorate the condition is readily available.” A JAMA paper from 2005 highlighted by Schneider reasoned that “It would be disrespectful to treat research volunteers as conduits for generating scientific data without giving due consideration to their interest in receiving information about themselves derived from their participation in research.”

As a result, the NIH requires results disclosure in any study that employs HIV testing, unless the patient chooses to opt out of receiving those results. But that’s not so simple in India, where the news of HIV infection can be life-or-death for reasons beyond the direct effects of the disease. Schneider, who spends about 3 months a year living in India and conducting research, said he often sees news stories in Indian newspapers about people being thrown out of their homes or committing suicide after learning of an HIV infection.

“Every day or every other day there’s somebody killing themselves based on HIV,” Schneider said. “Someone finds out they’re infected and they’ve infected somebody else in their family, or somebody else in their family is infected and has infected their kids…there’s still a tremendous stigma.”

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No, the blog has not been hijacked by spammers.

Radio silence was necessary yesterday as a I fielded media calls for a new study in the British Medical Journal on the eyebrow-raising subject of “sexually active life expectancy.” Stacy Tessler Lindau, associate professor of obstetrics/gynecology at the University of Chicago Medical Center, and Natalia Gavrilova, senior research associate, coined the term after mining two large aging surveys for information on health and sex in the golden years. That work, as you can see in coverage at CNN, the BBC, Time, the Los Angeles Times, and AOL, struck a chord with media outlets targeting baby boomers moving into their late 50’s and 60’s.

In what may not be surprising news for a culture inundated with erectile dysfunction ads, the sex life of many seniors remains robust, the study showed. But when broken down by gender, the story gets a little more complicated. When calculated from age 30, sexual life expectancy for men is nearly 35 years, while sexual life expectancy for women is closer to 31. Those numbers are fairly close, but there’s a key denominator difference - men, on average, die younger than women, leaving women with a greater percentage of their older years in a sexually inactive state.

If you push the axis for calculating sexually active life expectancy to age 55, the difference is more striking. Once a man reaches double nickels on the odometer, they can expect on average of 15 more years of sexual activity. For women, the figure is much lower, only 10.6 years. By age 75, only 16.8 percent of women were sexually active compared to 38.9% of men. That gap may be in part due to those little-blue-pill ads; Lindau and Gavrilova observed more sexually interested men in the 57-64 age group of a survey conducted in ‘05-06 than in a survey performed 10 years earlier.

“Interest in sex, participation in sex and even the quality of sexual activity were higher for men than women, and this gender gap widened with age,” Lindau told my colleague John Easton. But the study “affirms a positive association between later-life health, sexual partnership and sexual activity.”

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