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Stanford Medicine

Autoimmune Disease, Genetics, NIH, Research, Science

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

Tiny hitchhikers, big health impact: Studying the microbiome to learn about disease

I don’t know about you, but I’m fascinated with the idea of the “microbiome.” If you’re unfamiliar with the term, it describes the millions upon millions of tiny, non-human hitchhikers that live on and in you (think bacteria, viruses, fungi and other microscopic life). Although the exact composition of these molecular roommates can vary from person to person, they aren’t freeloaders. Many are vitally important to your metabolism and health.

We’ve reported here on the Human Microbiome Project, launched in 2007 and supported by the National Institutes of Health’s Common Fund. Phase 2 of the project started last fall, with grants to three groups around the country to study how the composition of a person’s microbiome might affect the onset of diseases such as type 2 diabetes and inflammatory bowel disease, as well as its role in pregnancy and preterm birth. Now the researchers, which include Stanford geneticist Michael Snyder, PhD, have published an article in Cell Host & Microbe detailing what data will be gathered and how it will be shared.

As explained in a release by the National Human Genome Research Institute:

“We’re producing an incredibly rich array of data for the community from the microbiomes and hosts in these cohorts, so that scientists can evaluate for themselves with these freely available data which properties are the most relevant for understanding the role of the microbiome in the human host,” said Lita M. Proctor, Ph.D., program director of the Human Microbiome Project at NIH’s National Human Genome Research Institute (NHGRI).

“The members of the Consortium can take advantage of each other’s expertise in dealing with some very complex science in these projects,” she said. “We’re generating these data as a community resource and we want to describe this resource in enough detail so people can anticipate the data that will be produced, where they can find it and the analyses that will come out of the Consortium’s efforts.”

As I’ve recently blogged, data-sharing among researchers and groups is particularly important for research efficiency and reproducibility. And I’m excited to hear what the project will discover. More from the release:

For years the number of microbial cells on or in each human was thought to outnumber human cells by 10 to 1. This now seems a huge understatement. Dr. Proctor noted that the 10-to-1 estimate was based only on bacterial cells, but the microbiome also includes viruses, protozoa, fungi and other forms of microscopic life. “So if you really look at the entire microbial community, you’re probably looking at more like a 100-to-1 ratio,” she said.

Although thousands of bacterial species may make their homes with human beings, each individual person is host to only about 1,000 species at a time, according to the findings of the Human Microbiome Project’s first phase in 2012.

In addition, judging from the array of common functions of bacterial genes, if the bacteria are healthy, each individual’s particular suite of species appear to come together to perform roughly the same biological functions as another healthy individual. In fact, researchers found that certain bacterial metabolic pathways were always present in healthy people, and that many of those pathways were often lost or altered in people who were ill.

Stanford’s Snyder will join forces with researchers in the laboratory of George Weinstock, PhD, of the Jackson Laboratory for Genomic Medicine in Connecticut to investigate the effect of the microbiome on  the onset of Type 2 diabetes. Snyder may be uniquely positioned to investigate the causes of the condition. In 2012, he made headlines when he performed the first ever ‘omics’ profile of himself (an analysis that involves whole genome DNA sequencing with repeated measurements of the levels of RNA, proteins and metabolites in a person’s blood over time). During the process, he learned that he was on the cusp of developing type 2 diabetes. He was able to halt the progression of the disease with changes in exercise and diet.

Previously: Stanford team awarded NIH Human Microbiome Project grantElite rugby players may have more diverse gut microbiota, study shows and Could gut bacteria play a role in mental health?

Science, Stanford News, Videos

Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz

Carla Shatz

We all know that Carla Shatz, PhD, director of the interdisciplinary institute Stanford Bio-X, is a pioneering scientist — her work in early brain development and in Alzheimer’s disease has earned her many accolades. Now she’s being featured in a videos series celebrating women pioneers in science.

I want to say first that it always rankles a bit when people are celebrated as being “pioneering women in XXX”. That makes it seem like if they weren’t women they wouldn’t have made the pioneer cut. Carla is a pioneer period. And also a woman. And gave a great interview.

One interesting point she made had to do with what she wished she’d known before starting a career in science. She said, “If you really like science and you like research, that is the joy and the easy part. The hard part is managing the teams and the research itself – the people.”

She went on to talk about the people who influenced her (her dad) and her first scientific experiment (it had to do with Siamese cats, and initially didn’t work).

When it comes to women in science, her answer was straightforward. She said we need talented people working on critical problems, and women are half the population. Without them, there are fewer people working on these important questions. She also said that she worries about the diminished funding for science driving the best minds (male and female) into other fields.

Her answer to what gets her up in the morning should help lure at least a few of those potential best minds into a scientific career, even with weak funding. She said:

Every day when I come to work I am so excited to be here and go to my lab and do experiments and be with my students. It’s part of an ongoing mystery. I can hardly wait to see the next part of the mystery that is going to be solved.

The series is sponsored by Scientista, which supports women in math and science, The Scientist magazine, Lab Manager and Mettler Toledo.

Previously: They said “Yes”: The attitude that defines Stanford Bio-X and Pioneers in science
Photo be Steve Fisch

Bioengineering, Research, Stanford News, Technology

Proteins from pond scum revolutionize neuroscience

Proteins from pond scum revolutionize neuroscience

pond scum smallI wrote a story recently about a cool technique called optogenetics, developed by bioengineering professor Karl Deisseroth, MD, PhD. He won the Keio Prize in Medicine, and I thought it might be interesting to talk with some other neuroscientists at Stanford to get their take on the importance of the technology. You know something is truly groundbreaking when each and every person you interview uses the word “revolutionary” to describe it.

Optogenetics is a technique that allows scientists to use light to turn particular nerves on or off. In the process, they’re learning new things about how the brain works and about diseases and mental health conditions like Parkinson’s disease, addiction and depression.

In describing the award, the Keio Prize committee wrote:

By making optogenetics a reality and leading this new field, Dr. Deisseroth has made enormous contributions towards the fundamental understanding of brain functions in health and disease.

One of the things I found most interesting when writing the story came from a piece Deisseroth wrote several years ago in Scientific American in which he stressed the importance of basic research. Optogenetics would not have been a reality without discoveries made in the lowly algae that makes up pond scum.

“The more directed and targeted research becomes, the more likely we are to slow our progress, and the more certain it is that the distant and untraveled realms, where truly disruptive ideas can arise, will be utterly cut off from our common scientific journey,” Deisseroth wrote.

Deisseroth told me that we need to be funding basic, curiosity-driven research along with efforts to make those discoveries relevant. He said that kind of translation is part of the value of  programs like Stanford Bio-X – an interdisciplinary institute founded in 1998 – which puts diverse faculty members side by side to enable that translation from basic science to medical discovery.

Previously: They said “Yes”: The attitude that defines Stanford Bio-X, New York Times profiles Stanford’s Karl Deisseroth and his work in optogenetics, An in-depth look at the career of Stanford’s Karl Deisseroth, “a major name in science”, Lightning strikes twice: Optogenetics pioneer Karl Deisseroth’s newest technique renders tissues transparent, yet structurally intact, The “rock star” work of Stanford’s Karl Deisseroth and Nature Methods names optogenetics its “Method of the Year
Photo by Tim Elliott, Shutterstock photos

Medical Education, Medicine X, Stanford News

Lloyd B. Minor, Stanford medical school’s dean, shares five principles of leadership

Lloyd B. Minor, Stanford medical school's dean, shares five principles of leadership

Dean_MinorOne of the highlights of this past weekend’s Medicine X was a course – “Navigating Complexity and Change: Principles of Leadership” – taught by our own leader, Lloyd B. Minor, MD. I sat in on the thoughtful and robust discussion, which focused on five principles that Minor developed throughout his career as a scientist, surgeon and academic leader. Students in the class were a mix of ePatients, researchers, entrepreneurs, and physicians, including a neuroanesthesiologist at Yale School of Medicine.

The first principle that Minor introduced was listening and learning, which, he said “underlie success in everything.” He went on to say, “I think a lot of leadership problems and failures come about when leaders are not, first and foremost, good listeners.”

Listening to others in the organization articulate their core values and vision provides a cultural context and helps leaders avoid the pitfall of their viewpoint being seen as counter to the organization’s. It also allows leaders to better understand those who disagree with them, he said. Drawing on his recent experience transitioning from provost and senior vice president of academic affairs of Johns Hopkins University to dean of Stanford’s School of Medicine, Minor explained that holding town hall meetings with Stanford faculty, students and staff were crucial in order to engage the community in charting a vision. “Vision is a derivative from listening and learning,” he told the class.

The next principle Minor discussed was building diverse teams. “Successful organizations thrive on diversity, and building diverse teams is one of the most important responsibilities of a leader,” said Minor. He emphasized that racial, gender and socioeconomic diversity, and diversity of viewpoint, are equally essential. Master Class students were advised to identify their weaknesses and surround themselves with individuals who have different backgrounds and cultural contexts and who possess strengths that can compensate for those weaknesses. In addition, if leaders listen and learn from a diverse team that provides constant feedback then they’ll create more opportunities for collaboration.

Once leaders have built diverse teams, the third principle comes into play: empowering teams. “You need to demonstrate the type of team behavior that you want individuals to exemplify to the rest of the organization,” he said. “That will determine how effective those teams are and enable you to be a better leader.” Among Minor’s tenets for empowering teams are: establishing a system of equitable accountability, allowing people to realize and correct their mistakes, establishing incentives, recognizing individuals or teams’ successes, and developing skill sets.

Minor went on to discuss the principle of managing and leading, stressing the point that while management and leadership have different areas of focus, being an effective leader requires one to be capable in management. “There is nothing that will derail leadership faster than poor management,” he explained. Leaders must not only articulate an organization’s vision and core values and build diverse teams to carry out those actions, but respond in a timely fashion, communicate, organize and coordinate.

Minor closed out his talk by touching on transitions. “This is a principle that is often missed and one that often leads to bad consequences for the individual, as well as the organization,” he explained. Leaders need to take time to reflect on both their transition to subsequent roles and the future of the organization. He warned that failing to carve out time to do so could result the erosion of leaders’ physical and mental health and damage the organization. A common mistake that he spoke to students about is when leaders refuse to let go of their former role and try to do the same job in a new position. To make sure Minor himself remembered to abide by this principle during his transition to Stanford, his wife gave him a business card holder for his desk with a quote from Lord Chesterfield that reminds us that in order to “discover new oceans, you must have the courage to lose sight of the shore.”

More news about Stanford Medicine X is available in the Medicine X category. 

Previously: Stanford Medicine X 2014 kicks off todayCountdown to Medicine X: 3D printing takes shapeCountdown to Medicine X: Specially designed apps to enhance attendees’ conference experience and Countdown to Medicine X: How to engage with the “no smartphone” patient
Photo by Stanford Medicine X

Biomed Bites, Research, Science, Stanford News, Videos

Studying the drivers of metastasis to combat cancer

Studying the drivers of metastasis to combat cancer

Today we’re launching Biomed Bites, a weekly series created to highlight some of Stanford Medicine’s most compelling research and introduce readers to promising scientists from across the basic and clinical sciences.

One might not think there’s much of a connection between grapes and cancer cells, but Amato Giaccia, PhD, has found some similarities. “The tumor microenvironment is very analogous to the microenvironment you would have in Napa Valley, where different types of grapes grow in different areas depending on the richness of the soil and the different climate and weather that exist,” explains the Stanford radiation oncologist and cancer biologist in the video above. “In a similar matter, tumors require different environments for them to be able to grow and… metastasize.”

Giaccia and his colleagues study the genetic and epigenetic regulators of metastasis, and their work could lead to the development of therapeutics that inhibit or eradicate the process, which contributes to 90 percent of cancer-related deaths. “Understanding the drivers of metastasis and how to best target them is going to have a major impact on cancer survival and mortality in the future,” Giaccia says.

Learn more about Stanford Medicine’s Biomedical Innovation Initiative and about other faculty leaders who are driving forward biomedical innovation here.

Previously: Cellular culprit identified for invasive bladder cancer, according to Stanford study, Potential anti-cancer therapy starves cancer cells of glucose and Nomadic cells may hold clues to cancer’s spread
Photo in featured entry box by Lee Coursey/Flickr

Health Policy, Public Health, Stanford News

Defining a “public-health emergency” in an age of complex health threats

Defining a “public-health emergency” in an age of complex health threats

MHE_-_KBH_Brandvaesen_-_HAZMAT_3aWhen chemicals used in coal mining were spilled into the Elk River in West Virginia in January, the governor declared a state of emergency the same day. When the H1N1 influenza virus was discovered in 2009, President Obama declared a national public-health emergency. In both cases, people were willing to comply with government orders (don’t drink the water, speed up vaccine production) in order to get an impending health threat under control.

But what happens when the health threat isn’t imminent? Or if it has no clear end-point? In a perspective piece in the most recent issue of the New England Journal of Medicine, Stanford public-health law scholar Michelle Mello, PhD, JD, and her co-authors delve into just such questions. They describe Massachusetts Governor Deval Patrick’s unusual step in March to declare a public-health emergency in order to control the state’s recent opioid-addiction epidemic – 40 people had died from heroin overdoses in four months. The move allowed public-health authorities to take several steps to address the problem, including monitoring prescription use and release funds for addiction treatment. Few states have taken such drastic steps to control drug use problems, though, and it raises questions about what exactly constitutes a public health emergency. In the piece, the authors write:

Patrick’s unusual invocation of emergency public health powers, which are traditionally reserved for infectious disease outbreaks, natural disasters, or acts of terrorism, offers an opportunity to consider some important questions. Should widespread injuries, such as those caused by opiates or motor vehicle crashes, be viewed as public health emergencies? Should chronic health conditions such as hypertension or obesity be similarly categorized? When should normal lawmaking processes, and the typical rights afforded to individuals and entities, be suspended to protect public health?

Although there may be benefits – drawing public attention to an important problem, access to critical funding sources, even mustering military personnel (for example, the National Guard was deployed to deal with the Elk River chemical spill) – there are drawbacks as well. Emergency powers give the government unprecedented leeway, as the authors note, they “sit largely outside the ordinary structures of checks and balances.” The authors go on to describe some of the pitfalls of declaring public-health emergencies:

Most important, concerns about due process are amplified when emergency orders restrict individual freedoms and property rights. The notion that highly coercive measures such as mandatory blood tests, quarantines, or property seizures could be imposed for common threats without democratic procedures and full due process offends our constitutional values. The lack of clear triggering thresholds for terminating emergency powers is particularly troubling, creating the possibility that critical legal protections might be suspended indefinitely.

Government officials rarely invoke public health emergencies, partly due to their out-sized power. The authors note, though that Patrick’s invocation “sets a troubling precedent” for a power that should be used with caution.

Photo by hebster

Cardiovascular Medicine, Research, Science, Stanford News

Scientists preferentially cite successful studies, new research shows

Scientists preferentially cite successful studies, new research shows

Say you’re a medical researcher. You slave over a project for months, even years, and you’re thrilled when a stellar journal agrees to publish it. That’s it, right? Well, no. Now, you need others to spot your work – and cite it in their studies. You can court citations just as you court Twitter followers: by producing high-quality content worthy of a bigger audience.

That said, sometimes bias creeps in. For example, studies by superstar scientists are cited more often than those by their junior colleagues — no surprise there. But now, Stanford medical resident Alex Perino, MD; cardiologist Mintu Turakhia, MD, MAS; and colleagues have shown that studies documenting higher success rates of a certain procedure are more likely to be cited than studies of the same procedure with lower success rates.

“This is an indication that we as clinicians and investigators need to be mindful of how we present the data,” Turakhia told me.

In a study released yesterday in Circulation: Cardiovascular Quality and Outcomes, Perino, Turakhia and other colleagues examined research papers on catheter ablation for atrial fibrillation, a treatment with widely varying success rates. For example, among the examined studies, the success of a single treatment varied between 10 and 92 percent. The variation is perfectly understandable, Turakhia said. Atrial fibrillation, an irregular heart rhythm, can be caused by a variety of underlying conditions and can vary in severity, he explained. The procedure itself, which uses energy to destroy tissue in key areas of the left atrium, can also vary, Turakhia said.

That’s why ablation for atrial fibrillation was an apt treatment to examine. The team included 174 studies with 36,289 patients published since 1990. They found that for every 10 point increase in reported success rate, there was an 18 percent increase in the mean citation count. The citation bias remained significant even when accounting for time since publication, the journal’s impact rating, sample size and study design.

The bias is important when considering the efficacy of new and evolving treatments, Turakhia said: “We just wanted to make sure the totality of evidence is being presented fairly and completely to readers of the medical literature, which may be clinicians, scientists, insurance companies and policy makers. However, in this case, we found that ablation could be perceived to be more effective than the totality of evidence would suggest.”

Turakhia said he hopes this study prompts other researchers to examine bias in other treatments and specialties.

Previously: Re-analyses of clinical trial results rare, but necessary, say Stanford researchers, John Ioannidis discusses the popularity of his paper examining the reliability of scientific research, A discussion on the reliability of scientific research, U.S. effect leads to publication of biased research, says Stanford’s John Ioannidis

Emergency Medicine, Health Policy, In the News, Patient Care, Research, Stanford News

Exploring how the Affordable Care Act has affected number of young adults visiting the ER

Exploring how the Affordable Care Act has affected number of young adults visiting the ER

ER sign - 560

One of the earliest – and most popular – parts of the Affordable Care Act allowed young adults to stay on their parents insurance until their 26th birthday. This week, Stanford researchers led by Tina Hernandez-Boussard, PhD, published a paper in the journal Health Affairs that tracked emergency room visits in California, New York and Florida for two age groups: 19 to 25 year olds – the group affected by the new requirement -  and 26 to 31 year olds for comparison. The researchers examined ER visits for the two years prior to the ACA requirement (2009 and 2010) and one year after the requirement went into effect (2011). Their findings showed that in 2011, 19- to 25-year-olds had slightly fewer ER visits – 2.7 per 1,000 people -compared to the older group.

The researchers calculated that the drop in ER use means more than 60,000 fewer visits for 19- to 26-year-olds across the three states  in 2011. They also found that the  largest relative decreases in ER use were among women and blacks.

post on Washington Post‘s Wonkblog covered the study and discussed further findings:

The researchers had another finding that seems just as important. While the total number of ER visits among the under-26 group was down, about the same number of people still went to the ER. The distinction here is that young adults with chronic conditions, who have greater care needs, probably now had better access to non-ER care settings, so their number of visits to the ER decreased. But the finding also suggests that healthy young adults, who might have shunned health insurance before, still continued to see the ER as a place for seeking out routine care, according to the study. Further, insurance likely makes those ER visits cheaper, which could actually increase how much people use the ER, the researchers wrote.

Hernandez-Boussard and her colleagues concluded in their paper, “As EDs face capacity challenges, it is important to consider how to meet the broad underlying needs of young adults through other channels and ensure the needed availability of these alternative health services.”

Previously: Abraham Verghese on health-law battle: “We’ve worried so much about the process, not the patient”
Photo by Eric Staszczak/KOMU

Mental Health, Research, Stanford News

Study shows benefits of breathing meditation among veterans with PTSD

Study shows benefits of breathing meditation among veterans with PTSD

man meditating - smallEarlier this year, Emma Seppala, PhD, associate director of Stanford’s Center for Compassion and Altruism Research and Education and a research psychologist at the the medical school, wrote on Scope about her work using breathing meditation to help veterans with PTSD. One of her studies, involving 21 male veterans of the Afghanistan and Iraq wars who were taught a set of breathing techniques from the Sudarshan Kriya Yoga practice, has now been published.

A recent Stanford Report article provides more details on the research, which found that the breathing techniques “resulted in reduced PTSD symptoms, anxiety and respiration rate” among study participants. The piece also highlights Seppala’s surprise that the meditation appeared to have a lasting effect:

“It is unusual to find the benefits of a very short intervention – one-week, 21 hours total – lasting one year later,” she said. One year after the study, the participants’ PTSD scores still remained low, suggesting that there had been long-lasting improvement.

When the scientists asked the veterans whether they had continued practicing at home, a few had but most had not. The data showed that whether or not they had practiced at home, it did not hinder meditation’s long-term benefits.

One reason, Seppala suggested, is that Sudarshan Kriya yoga retrained the veterans’ memories.

Before the breathing meditation training, participants reported re-experiencing traumatic memories frequently and intensely, Seppala said. Afterward, they reported that the traumatic memories no longer affected them as strongly or frequently.

The study appears in the in the Journal of Traumatic Stress.

Previously: The remarkable impact of yoga breathing for trauma, The promise of yoga-based treatments to help veterans with PTSD, Using mindfulness therapies to treat veterans’ PTSD, As soldiers return home, demand for psychologists with military experience grows, Stanford and other medical schools to increase training and research for PTSD, combat injuries and Can training soldiers to meditate combat PTSD?
Photo by Sebastien Wiertz

Clinical Trials, Patient Care, Research, Science, Stanford News

Re-analyses of clinical trial results rare, but necessary, say Stanford researchers

Re-analyses of clinical trial results rare, but necessary, say Stanford researchers

The results of large clinical trials are used to make important clinical decisions. But the raw data on which these results are based are rarely made available to other researchers, perhaps due to concerns about intellectual property or giving a leg up to competitors in the field. But a new study by Stanford’s John Ioannidis, MD, DSci, shows that the re-analysis of such data by independent research is critical: About one third of the time it leads to conclusions that differ from those of the original study.

The research was published today in the Journal of the American Medical Association.

Clearly, data sharing is an important step in making sure research is conducted efficiently and renders reproducible results

For the study, Ioannidis and his co-authors surveyed about three decades of research cataloged in the National Library of Medicine’s PubMed database looking for re-analyses of previously published clinical-trial data. They found fewer than 40 studies that met their criteria (reanalyses using the original data to investigate a new hypothesis, or meta-analyses of several studies were not included) and, as I wrote in a release:

Thirteen of the re-analyses (35 percent of the total) came to conclusions that differed from those of the original trial with regard to who could benefit from the tested medication or intervention: Three concluded that the patient population to treat should be different than the one recommended by the original study; one concluded that fewer patients should be treated; and the remaining nine indicated that more patients should be treated.

The differences between the original trial studies and the re-analyses often occurred because the researchers conducting the re-analyses used different statistical or analytical methods, ways of defining outcomes or ways of handling missing data. Some re-analyses also identified errors in the original trial publication, such as the inclusion of patients who should have been excluded from the study.

Clearly, data sharing is an important step in making sure research is conducted efficiently and renders reproducible results – goals shared by the recently launched Meta-Research Innovation Center at Stanford (or METRICS), which Ioannidis co-directs. More from our release:

The fact that researchers conducting re-analyses often came to different conclusions doesn’t indicate the original studies were necessarily biased or deliberately falsified, Ioannidis added. Instead, it emphasizes the importance of making the original data freely available to other researchers to encourage dialogue and consensus, and to discourage a culture of scientific research that rewards scientists only for novel or unexpected results.

“I am very much in favor of data sharing, and believe there should be incentives for independent researchers to conduct these kinds of re-analyses,” said Ioannidis. “They can be extremely insightful.”

Previously: John Ioannidis discusses the popularity of his paper examining the reliability of scientific research, New Stanford center aims to promote research excellence and “U.S. effect” leads to publication of biased research, says Stanford’s John Ioannidis

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