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Stanford Medicine

NIH, Research, Science Policy, Stanford News

Shake up research rewards to improve accuracy, says Stanford’s John Ioannidis

Shake up research rewards to improve accuracy, says Stanford's John Ioannidis

currencyLab animals such as mice and rats can be trained to press a particular lever or to exhibit a certain behavior to get a coveted food treat. Ironically the research scientists who carefully record the animals’ behavior really aren’t all that different. Like mice in a maze, researchers in this country are rewarded for specific achievements, such as authoring highly cited papers in big name journals or overseeing large labs pursuing multiple projects. These rewards come in the form of promotions, government grants and prestige among a researcher’s peers.

Unfortunately, the achievements do little to ensure that the resulting research findings are accurate. Stanford study-design expert John Ioannidis, MD, DSci, has repeatedly pointed out serious flaws in much published research (in 2005 he published what was to be one of the most highly-accessed and most highly-cited papers ever in the biomedical field “Why most published research findings are false”).”

Today, Ioannidis published another paper in PLoS Medicine titled “How to make more published research true.” He explores many topics that could be addressed to improve the reproducibility and accuracy of research. But the section that I found most interesting was one in which he argues for innovative, perhaps even disruptive changes to the scientific reward system. He writes:

 The current system does not reward replication—it often even penalizes people who want to rigorously replicate previous work, and it pushes investigators to claim that their work is highly novel and significant. Sharing (data, protocols, analysis codes, etc.) is not incentivized or requested, with some notable exceptions. With lack of supportive resources and with competition (‘‘competitors will steal my data, my ideas, and eventually my funding”) sharing becomes even disincentivized. Other aspects of scientific citizenship, such as high-quality peer review, are not valued.

Instead he proposes a system in which simply publishing a paper has no merit unless the study’s findings are subsequently replicated by other groups. If the results of the paper are successfully translated into clinical applications that benefit patients, additional “currency” units would be awarded. (In the example of the mice in the maze, the currency would be given in the form of yummy food pellets. For researchers, it would be the tangible and intangible benefits accrued by those considered to be successful researchers). In contrast, the publication of a paper that was subsequently refuted or retracted would result in a reduction of currency units for the authors. Peer review and contributions to the training and education of others would also be rewarded.

The concept is really intriguing, and some ideas would really turn the research enterprise in this country on its head. What if a researcher were penalized (fewer pellets for you!) for achieving an administrative position of power… UNLESS he or she also increased the flow of reliable, reproducible research? As described in the manuscript:

[In this case] obtaining grants, awards, or other powers are considered negatively unless one delivers more good-quality science in proportion. Resources and power are seen as opportunities, and researchers need to match their output to the opportunities that they have been offered—the more opportunities, the more the expected (replicated and, hopefully, even translated) output. Academic ranks have no value in this model and may even be eliminated: researchers simply have to maintain a non-negative balance of output versus opportunities. In this deliberately provocative scenario, investigators would be loath to obtain grants or become powerful (in the current sense), because this would be seen as a burden. The potential side effects might be to discourage ambitious grant applications and leadership.

Ioannidis, who co-directs with Steven Goodman, MD, MHS, PhD, the new  Meta-Research Innovation Center at Stanford, or METRICS, is quick to acknowledge that these types of changes would take time, and that the side effects of at least some of them would likely make them impractical or even harmful to the research process. But, he argues, this type of radical thinking might be just what’s needed to shake up the status quo and allow new, useful ideas to rise to the surface.

Previously: Scientists preferentially cite successful studies, new research shows, Re-analyses of clinical trial results rare, but necessary, say Stanford researchers  and John Ioannidis discusses the popularity of his paper examining the reliability of scientific research
Photo by Images Money

Behavioral Science, Mental Health, Public Health, Stanford News

“Every life is touched by suicide:” Stanford psychiatrist on the importance of prevention

in-a-lonely-place-fa873a88-0c57-4b11-8f84-58c09aab94acMost people shy away from talking about suicide. Me too – I have some personal ties to the topic that still stab every time the s-word comes up. Yet after the initial reluctance wears off, that pain from grief and anger and fear turns into a motivational jab. Let’s talk about suicide nonstop. Let’s talk to make it stop.

Laura Roberts, MD, who leads Stanford’s psychiatry department, had the opportunity as editor-in-chief of the journal Academic Psychiatry to focus attention on suicide prevention. And she took it – partnering with the Wisconsin-based Charles E. Kubly Foundation to produce a special package of articles to inform clinicians about the latest efforts to prevent suicide.

Roberts and I spoke recently about the special issue and about suicide prevention:

Why did you want to publish this issue?

Suicide is such an under-recognized phenomenon, and it is an urgent threat to public health. Mental illness affects one in five people. Each year, more than 36,000 people commit suicide in the U.S. That is one person every fifteen minutes. In rough numbers, that’s twice the number of people who die from a violent injury in this country. Really, every life is touched by suicide.

Despite their serious public-health impact and life-threatening nature, illnesses and conditions associated with suicide have received little attention in society. These conditions are poorly understood and so greatly stigmatized. Learning to understand and evaluate people at risk for self-harm is an important element of medical student and resident education — we really wanted to emphasize these topics in this special collection.

New evidence-based models for prevention of suicide are emerging and inspire optimism. Integrating these new models is an exciting challenge for medical educators. Papers in this collection also document the impact of suicide and suicidal behavior among medical students and graduate students. About 350 physicians commit suicide each year in the U.S., and recently two interns in New York City ended their lives shortly after entering residency training. This is devastating.

In our special issue, a systematic review highlights the observation that psychiatry residents commonly experience the death of a patient by suicide, and three articles address coping with suicide professionally. Several articles focus on the development of educational programs that help strengthen suicide prevention, including screening skills and suicide awareness and management. Two articles address the resources and experience of from the Department of Veterans Affairs.

The journal special issue underscores there is much we can do in medical education to foster understanding and strengthen our responses to the phenomenon of suicide. Taken together, the papers also show how important it is that academic leaders better educate other about the prevention and impact of suicide.

What have we learned about preventing suicide?

We have learned a great deal about the prevention of suicide. Population data have shown that certain subgroups are especially vulnerable to suicide, including, for example, older white men who are ill and live alone, Native American youth as they make the transition to adulthood, and people living with serious illnesses that cause great physical and emotional pain. Understanding these larger population patterns has done a lot to help raise awareness of suicide and has allowed for creative interventions to address this problem.

Recently, researchers have been pursuing neurobiological markers that may signal when an individual is most at-risk for attempting suicide. Other studies are connecting other aspects of health — such as healthy sleep and exercise — to protective factors that may help diminish the likelihood of suicide. Such innovative work is very much needed because it will help us understand when a person with latent risk factors for suicide may act on this impulse, or, alternatively, how we can better support and intervene.

Other recent work has focused on psychological and situational factors that may contribute to suicidality among young veterans, and again, this line of inquiry may give us greater understanding on how best to reduce suicide deaths. As you may know, the number of veteran deaths due to suicide have been devastating. The VA has shown immense concern for members of the military and young veterans returning from conflicts around the world. In the course of studying suicide in this population, we have begun to have greater insight into when and whether an individual will act on an impulse to end his life. Three factors appear to be in play: first, a predisposition or vulnerability, for example, the presence of depression or anxiety that increases the general risk of suicide; second, access to a way to end one’s life, such as a gun; and, third an experience or set of experiences that make the individual feel like he is out of place, isn’t part of things, and doesn’t belong — what’s referred to as “thwarted belongingness.”

We are getting parts of the problem figured out, but so much more scientific investigation is needed. Ironically, suicide has been understudied because of concerns that the population is too vulnerable to be included in human research studies and because of the stigma associated with suicide. There have been so many barriers to these studies, and it strikes me as doubly tragic that suicide takes so many lives and yet has been relatively neglected by society and by science. In the Department of Psychiatry and Behavioral Sciences at Stanford, we are working to turn this around.

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Immunology, Infectious Disease, Microbiology, Public Health, Research, Stanford News

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

Paradox: Antibiotics may increase contagion among Salmonella-infected animals

cattleMake no mistake: Antibiotics have worked wonders, increasing human life expectancy as have few other public-health measures (let’s hear it for vaccines, folks). But about 80 percent of all antibiotics used in the United States are given to livestock – chiefly chickens, pigs, and cattle – at low doses, which boosts the animals’ growth rates. A long-raging debate in the public square concerns the possibility that this widespread practice fosters the emergence of antibiotic-resistant bugs.

But a new study led by Stanford bacteriologist Denise Monack, PhD, and just published in Proceedings of the National Academy of Sciences, adds a brand new wrinkle to concerns about the broad administration of antibiotics: the possibility that doing so may, at least  sometimes, actually encourage the spread of disease.

Take salmonella, for example. One strain of this bacterial pathogen, S. typhimurium, is responsible for an estimated 1 million cases of food poisoning, 19,000 hospitalizations and nearly 400 deaths annually in the United States. Upon invading the gut, S. typhimurium produces a potent inflammation-inducing endotoxin known as LPS.

Like its sister strain S. typhi (which  causes close to 200,00o typhoid-fever deaths worldwide per year), S. typhimurium doesn’t mete out its menace equally. While most get very sick, it is the symptom-free few who, by virtue of shedding much higher levels of disease-causing bacteria in their feces, account for the great majority of transmission. (One asymptomatic carrier was the infamous Typhoid Mary, a domestic cook who, early in the 20th century, cheerfully if unknowingly spread her typhoid infection to about 50 others before being forcibly, and tragically, quarantined for much of the rest of her life.)

You might think giving antibiotics to livestock, whence many of our S. typhi-induced food-poisoning outbreaks derive, would kill off the bad bug and stop its spread from farm animals to those of us (including me) who eat them. But maybe not.

From our release on the study:

When the scientists gave oral antibiotics to mice infected with Salmonella typhimurium, a bacterial cause of food poisoning, a small minority — so called “superspreaders” that had been shedding high numbers of salmonella in their feces for weeks — remained healthy; they were unaffected by either the disease or the antibiotic. The rest of the mice got sicker instead of better and, oddly, started shedding like superspreaders. The findings … pose ominous questions about the widespread, routine use of sub-therapeutic doses of antibiotics in livestock.

So, the superspreaders kept on spreading without missing a step, and the others became walking-dead pseudosuperspreaders. A lose-lose scenario all the way around.

“If this holds true for livestock as well – and I think it will – it would have obvious public health implications,” Monack told me. “We need to think about the possibility that we’re not only selecting for antibiotic-resistant microbes, but also impairing the health of our livestock and increasing the spread of contagious pathogens among them and us.”

Previously: Did microbes mess with Typhoid Mary’s macrophages?, Joyride: Brief post-antibiotic sugar spike gives pathogens a lift and What if gut-bacteria communities “remember” past antibiotic exposures?
Photo by Jean-Pierre

Chronic Disease, Health Costs, Infectious Disease, Research

Despite steep price tag, use of hepatitis C drug among prisoners could save money overall

Despite steep price tag, use of hepatitis C drug among prisoners could save money overall

pills-384846_640There’s nothing free about the revolution that’s shaking up hepatitis C treatment. A slew of newer drugs, including sofosbuvir, are nearly eliminating the virus with fewer side effects than the old standbys, pegylated interferon and ribavirin, which had limited effectiveness and caused fatigue, nausea and headaches. But at a cost of $7,000 a week, it seems obvious they are more expensive.

Not necessarily, however, says Jeremy Goldhaber-Fiebert, PhD. Working with colleagues including former Stanford graduate student Shan Liu, PhD, Goldhaber-Fiebert developed a model that examines the overall costs and benefits of treating hepatitis C with sofosbuvir rather than the traditional drugs in prisons. Prisoners are more likely than those in the general population to be infected with hepatitis C, a virus that attacks the liver, because it can be transmitted through intravenous drug use and unclean tattoos.

The researchers found that the high upfront cost saves money in later years by reducing the number of liver transplants and other more invasive treatments needed. In accordance with standard practices, this  study examined the overall societal cost without accounting for the source of the money. For example, the prison system’s are more likely to spend more money upfront, although savings might be recouped by Medicaid or other private insurers several decades later. From our release:

“Overall, sofosbuvir is cost-effective in this population, though its budgetary impact and affordability present appreciable challenges,” said Goldhaber-Fiebert,who is also a faculty member at Stanford’s Center for Health Policy/Center for Primary Care and Outcomes Research, which is part of the university’s Freeman Spogli Institute for International Studies.

Goldhaber-Fiebert called hepatitis C a “public health opportunity.”

“Though often not the focus of health-policy research, HCV-infected inmates are a population that may benefit particularly from a highly effective, short-duration treatment,” he said.

The research appears in this week’s Annals of Internal Medicine.

Previously: Fortune teller: Mice with ‘humanized’ livers predict HCV drug candidate’s behavior in humans, A primer on hepatitis C and For patients with advanced hepatitis C, benefits of new drugs outweigh costs
Photo by stevepb

Cancer, Patient Care, Stanford News

Pioneering cancer nurses guide patients through maze of care

Pioneering cancer nurses guide patients through maze of care

cancer-birminghamLearning you have cancer is a life-changing diagnosis. Even after the initial shock wears off, the gauntlet of medical care necessary to manage the disease can be overwhelming and confusing. At the Stanford Cancer Center, a new program that partners experienced nurses with newly diagnosed cancer patients aims to help the patients navigate the convoluted path their medical care can take.

A recent story in the Stanford Medicine Newsletter profiled Laura Birmingham, RN, (on the left, with cancer patient Sharron Brockman) and Vitale Battaglini, RN, who founded the new program. Birmingham coordinates care for patients with gynecological cancers and Battaglini works with head and neck cancer patients. They are the first people at the Stanford Cancer Center that patients meet and they stay in touch via phone calls, text messages and emails in between patient visits. The staff explained the benefits of a one-on-one program:

“Someone newly diagnosed doesn’t know what to expect, and things that seem basic to us are new to them. Our job is to be their first and main point of contact,” Battaglini said. “It’s a reversal of the traditional nurse’s role: We are the patient’s nurse, not the doctor’s nurse. And what the patient needs depends on that particular patient.”

“Cancer care has become so complex because it involves so many subspecialties,” said Julie Kuznetsov, director of the Cancer Patient Experience, who oversees the new program. “The field continues to evolve with new technologies and specialized expertise. While that means more options and better outcomes, for patients it has become more difficult to put the pieces together to coordinate their care.”

In Birmingham’s words, “Our role is to act as an agent of change in terms of the patient experience.” There are about 18 patients in the program, but that number is expected to grow quickly.

Previously: Stanford researchers examine disparities in use of quality cancer centers and Director of the Stanford Cancer Institute discusses advances in cancer care and research
Photo by Norbert von der Groeben

Immunology, Mental Health, Stanford News

Stanford Medicine magazine traverses the immune system

Stanford Medicine magazine traverses the immune system

cover_fall2014_2If you want to understand the human immune system, try studying humans – not mice. That’s what Mark Davis, PhD, urges in a special report on the immune system in the new issue of Stanford Medicine magazine.

For decades, most research on the immune system has used mice. Davis, director of Stanford’s Institute for Immunology, Transplantation and Infection, launched Stanford’s Human Immune Monitoring Center a few years ago to change the immunology research paradigm.

“Inbred mice have not, in most cases, been a reliable guide for developing treatments for human immunological diseases,” Davis says in the special report, titled “Balancing act: The immune system.”

As the editor of the magazine, I wanted to feature a story that showed how human-focused immunology research plays out. So I was glad to learn that the center is in the midst of its largest study so far – one to figure out the cause of chronic fatigue syndrome. A team led by Stanford professor of infectious diseases José Montoya, MD, is looking for meaningful patterns in the components of blood samples gathered from 200 patients with chronic fatigue syndrome and 400 healthy subjects.

“It’s like dumping a hundred different puzzles on the floor and trying to find two pieces that fit,” Davis says in our story. We also have a video about a patient’s seven-year battle with chronic fatigue, from despair to recovery.

Also covered in this issue:

  • “I can eat it”: on a revolutionary treatment for food allergies
  • “Brain attack”: on the struggle to help children with psychiatric illness caused by a malfunctioning immune system – a condition known as PANS or PANDAS
  • “When bones collide”: on a new view on the cause of osteoarthritis: autoinflammation
  • “My rendezvous with insanity”: a Q&A with Susannah Cahalan, author of Brain on Fire: My Month of Madness, her memoir of surviving an autoimmune attack on her brain
  • “The swashbuckler”: on look back to the early days of molecular biology when Mark Davis cracked one of the greatest mysteries of the immune system

The issue also includes an article on efforts at the VA Palo Alto Health Care System to use peer-support services to help veterans with post-traumatic stress disorder, and a story on the growing concern that biomedical research results are often erroneous and efforts being made to solve the problem.

The issue was funded in part by the Institute for Immunology, Transplantation and Infection.

Previously: Stanford Medicine magazine opens up the world of surgery, Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions and From womb to world: Stanford Medicine Magazine explores new work on having a baby.
Illustration by Jeffrey Decoster

Cancer, Events, Patient Care, Public Health

“Stop skipping dessert:” A Stanford neurosurgeon and cancer patient discusses facing terminal illness

"Stop skipping dessert:" A Stanford neurosurgeon and cancer patient discusses facing terminal illness

terminally_ill

Updated 10-23-14: Dr. Kalanithi spoke about this topic on campus earlier this week; more on the event, and his insights, can be found here.

***

10-20-14: When Paul Kalanithi, MD, a chief resident in neurological surgery at Stanford, was diagnosed at age 36 with stage IV lung cancer he struggled to learn how to live with conviction despite a prognosis of uncertainty. He found comfort in seven words from writer Samuel Beckett, “I can’t go on. I’ll go on.”

That mantra has given Kalanithi the strength to face his own mortality and have tough conversations with his wife and loved ones about the future. Tomorrow evening, he’ll join palliative-care specialist Timothy Quill, MD, for a discussion about end-of-life decision-making. The campus event is free and open to the public; no registration is required.

As a preview to the talk, Kalanithi talked with me about his experience as a patient and about the importance of end-of-life decisions.

How has your prognoses changed the way you talk to patients and their loved ones about grim news?

In large part, the way I talk to patients and their families hasn’t changed, because I had excellent role models in training. I remember witnessing a pediatric neurosurgeon talk parents through the diagnosis of their daughter’s brain tumor. He delivered not just the medical facts, but laid out the emotional terrain as well: the confusion, the fear, the anger and – above all – the need for support from and for each other. I always strove to emulate that model: to educate patients on the medical facts isn’t enough. You have to also find a way to gesture towards the emotional and existential landmarks.

Seeing it from the other side, it’s really hard, as a patient, to ask the tough questions. It’s important for the doctor to help initiate these conversations. I think it’s worth addressing prognosis and quality of life with patients, asking them what they think. My own assumptions about my prognosis were way off base. As a doctor, you can’t provide definite answers, but you can remove misconceptions and refocus patients’ energy.

Finally, I think, if you are the oncologist, it’s important to establish yourself as a go-to for any questions. Patients are bombarded with well-meaning advice, from dietary recommendations to holistic therapy to cutting-edge research. It can easily occupy all a patient’s time, when you ought to also spend time thinking about the priorities in your life. Physicians can also advise patients, as my dad would insist, that they can stop skipping dessert.

What is your advice to patients who are struggling with the certainty of death and the uncertainty of life?

I’ve written a little bit about facing terminal illness in The New York Times and The Paris Review. I found the experience difficult. I still find it difficult. It is a struggle. The problem is not simply learning to accept death. Because even if you do come to terms with finitude, you still wake up each morning and have a whole day to face. Your life keeps going on, whether you are ready for it to or not.

In some ways, having a terminal illness makes you no different from anyone else: Everyone dies. You have to find the balance – neither being overwhelmed by impending death nor completely ignoring it.

You have to find the things that matter to you, in two categories. The first is of ‘the bucket list’ sort. My wife and I always imagined revisiting our honeymoon spot on, say, our 20th wedding anniversary. But I didn’t realize how important to me that was until we decided to go back earlier (on our 7th anniversary, instead, about four months after I was diagnosed).

The second is, as all people should be doing, figuring out how to live true to your values. The tricky part is that, as you go through illness, your values may be constantly changing. So you have to figure out what matters to you, and keep figuring it out. It’s like someone just took away your credit card, and now you really have to budget. You may decide that you want to spend your time working. But two months later, you might feel differently, and say, you really want to learn saxophone, or devote yourself to the church. I think that’s okay – death may be a one-time event, but living with a terminal illness is a process.

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Grand Roundup

Grand Roundup: Week of Oct. 12

Grand Roundup: Week of Oct. 12

The five most-read stories this week on Scope were:

Walking and aging: A historical perspective: An article in The Atlantic this week offered details on recent research into how moderate to vigorous walking can improve mental acuity in aging populations.

How to keep safe while operating on Ebola patients: Two U.S. surgeons with a combined 30 years of working in developing countries have prepared and disseminated well-defined protocols for operating on any patient with the virus or at-risk of having contracting the virus. Stanford surgeon Sherry Wren, MD, and her collaborator discuss this in a San Jose Mercury News op-ed piece.

Healing hands: My experience being treated for bladder cancer: In this Inspire column, an anonymous cancer patient shares his experiences and expresses gratitude for those “whose healing hands, both literally and figuratively, reached out to help me.”

Summer’s child: Stanford researchers use season of birth to estimate cancer risk: Partnering with Lund University, researchers here are using Sweden’s national registries for birth certificates and medical records to track how factors during gestation and soon after birth – called perinatal factors – affect cancer risks.

Stanford experts offer more information about enterovirus-D68: In this Q&A, Yvonne Maldonado, MD, service chief of pediatric infectious disease at Lucile Packard Children’s Hospital Stanford, and Keith Van Haren, MD, a pediatric neurologist, discuss the enterovirus-D68 respiratory illness and neurologic symptoms that might be associated with it.

And still going strong – the most popular post from the past:

Researchers explain how “cooling glove” can improve exercise recovery and performance: The “cooling glove,” a device that helps people cool themselves quickly by using their hand to dissipate heat, was created more than a decade ago by Stanford biologists Dennis Grahn and Craig Heller, PhD. This video demonstrates the device and explains how it can be used to dramatically improve exercise recovery and performance.

 

Stanford News

Weathering heights: Crane operator makes the climb for hospital expansion

image_0.img.320.highMeet  A.J. Barker, second-generation crane operator extraordinaire, who’s currently working on the new Lucile Packard Children’s Hospital Stanford from 16 stories in the air.

In a Stanford Medicine News article, Barker described his workday:

“You have to pay attention at all times,” he said. “There’s no room for error when you are flying iron and sending a load weighing thousands of pounds over to guys who are standing five stories high on beams that are 8 inches wide.”

After climbing up to the cabin, Barker starts each shift with a safety inspection of the equipment on the counter-jib behind the cabin, eyeballing the hoist cable for signs of stress, lubricating the moving parts, and checking the tension on the tower section’s bolts and lattice. He’ll go over the plans with the signalmen for safety and efficiency, and discuss options for flying the loads. The crane operates in all weather, except in very high wind or lightning storms.

Then he stays there for eight to nine hours, “flying iron” at the directions of folks on the ground. Barker, 36, learned from his dad, mastering the basics by the time he was 10. It’s a blend of physics, communication and a lack of fear of heights. “I have the coolest office view, and it changes all the time,” Barker said.

He’s proud to work on the Packard expansion, to construct a building designed to help children and families.

I never knew a person operated cranes from high in the sky. Now, thanks to Barker, I can chat about jib length and admire skilled gingerbread placement.

Previously: A trip down memory lane: Stories from the early days of the School of Medicine. Image of the Week: Digging in at the Stanford Hospital & Clinics groundbreaking and A new chapter for Stanford Hospital 
Photo by L.A. Cicero

History, Medicine and Society, NIH, Public Health

“Don’t go to bed with a malaria mosquito:” exploring World War II medical posters

"Don't go to bed with a malaria mosquito:" exploring World War II medical posters

After exploring Stanford’s collection of historical medical images last week after a tour of the School of Medicine, I got hooked. Hooked on historical medical images — a quirky interest tailor-made for the internet. Turns out the National Institutes of Health’s U.S. National Library of Medicine maintains a massive image library, one that includes some fabulous propaganda posters from World War II, including the lady mosquito with the alluring proboscis (above).

Others in the World War II poster collection focus on venereal diseases, recruiting nurses and doctors, encouraging blood donations and even curbing noise or visiting the dentist.

And that’s just World War II posters. Its Flickr collection is tantalizing, kicking off with a series of medical oddities reminiscent of Philadelphia’s Mütter Museum. It’s quite addictive – just warning you.

Previously: A trip down memory lane: Stories from the early days of the School of Medicine, #ACT4NIH seeks stories to spur research investment and Examining the impact of psychological distress on soldiers’ spinal injuries
Images courtesy of U.S National Library of Medicine

Stanford Medicine Resources: