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Health Policy, NIH, Research, Science Policy, Stanford News

NIH tries to reduce the gray in the grant pool

NIH tries to reduce the gray in the grant pool

This 45-second animation vividly illustrates the funding crisis that young scientists face as they work to launch their research careers: For the last three decades, large NIH grants have increasingly been awarded to older investigators.

“The average age of first-time, R01-funded investigators who have PhDs remains 42, even after seven years of policies at NIH to increase the numbers of new and early-stage investigators,” said Robin Barr, director of the NIH’s Division of Extramural Activities, in a recent editorial on the NIH website.

But there is hope on the horizon, as the NIH rolls out a series of funding mechanisms that aim to give new investigators a leg up. I recently wrote about one such program, the KL2 mentored career development award, and an inspirational Stanford physician-researcher, Rita Hamad, MD, MPH, who is taking full advantage of it.

Hamad is interested in studying the cause-and-effect relationships between poverty and health. The KL2 program helps Hamad’s research through salary support, mentoring, pilot grants and tuition subsidies. In just two years, she has produced actionable data that can be used by policymakers and by health-care providers to improve the overall health of populations, including a study exploring the impact of the earned-income tax credit on child health in the United States. It will be published this fall in the American Journal of Epidemiology.

Previously:NIH funding mechanism “totally broken,” says Stanford researcher, NIH director on scaring young scientists with budget cuts: “If they go away, they won’t come back” and Sequestration hits the NIH – fewer new grants, smaller budgets
Animation by the NIH

Imaging, Neuroscience, NIH, Research, Videos

Video reconstruction reveals stunning detail within a tiny section of brain

Video reconstruction reveals stunning detail within a tiny section of brain

Important discoveries in science are often called “big” breakthroughs, yet much of the information that makes these “aha” moments possible is found in the most diminutive of details. So it seems fitting that our first glimpse into the inner workings of the mammalian cerebral cortex arises from a tidbit of brain no bigger than a grain of sand.

For the first time, researchers have created a digital reconstruction of part of a mammalian cerebral cortex — the “rind” of the brain, about two to three dimes thick, that plays a central role in functions like memory, thought, language and consciousness.

This digitized rendering was created by NIH grantee Jeff Lichtman, MD, PhD, and his colleagues as part of the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Francis Collins, MD, PhD, director of the National Institutes of Health, offers more details on how the film was made over on the NIH Director’s blog.

Previously: Exercise and your brain: Stanford research highlighted on NIH Director’s blogProcess that creates transparent brain named one of year’s top scientific discoveries and How CLARITY offers an unprecedented 3-D view of the brain’s neural structure

Big data, Cardiovascular Medicine, Health Policy, NIH, Precision health, Public Health

The diagnostic odyssey

The diagnostic odyssey

Sick-girl-christian-krohg-1881Imagine developing some odd symptoms, like a rash and an ache. You go to the doctor and she shrugs it off and says they are probably unrelated and to come back if the rash doesn’t go away. Two months later, the rash is gone but the ache is worse. You go back and she sends you to physical therapy and suggests a specialist. A month later, neither has identified a problem. The physical therapist suspects you aren’t doing the exercises and the specialist suggests you see a psychiatrist about depression. The rash is back, too. And you are tired all the time.

For some people this frustrating and scary lack of diagnosis and care can go on for years. Sometimes, doctors have overlooked a common disease that just manifests oddly. But often, the patient has a rare disease their doctors have never heard of, let alone seen.

Yesterday, NIH launched a new Undiagnosed Diseases Network, consisting of seven major medical centers where select patients with no diagnosis can go — at no cost — for the best diagnostic facilities available. Together, the seven centers, one of which is at Stanford Medicine, magnify that network of expertise to consider patients’ cases.

Euan Ashley, MRCP, DPhil, associate professor of cardiovascular medicine and of genetics at Stanford Medicine, is co-chair of the UDN steering committee. Recently, he spoke to me for a Q&A about the new network, which is open for business. And more information on the Stanford Center for Undiagnosed Diseases can be found here.

Previously: NIH network designed to diagnose, develop possible treatments for rare, unidentified diseases and Using crowdsourcing to diagnose medical mysteries
Photo by Christian Krohg, 1881, from Wikimedia Commons

Cardiovascular Medicine, Chronic Disease, Health and Fitness, NIH, Research, Stroke

NIH-funded study shows effectiveness of intensive blood pressure management

NIH-funded study shows effectiveness of intensive blood pressure management

blood pressure reading2This morning the National Institutes of Health announced that it halted a clinical trial on high blood pressure in order to share the results publicly right away. According to the initial study findings, managing high blood pressure so it falls below a specific blood pressure target significantly reduces rates of cardiovascular disease and lowers risk of mortality.

The Systolic Blood Pressure Intervention Trial, commonly called SPRINT, is the largest known study of its kind to examine how holding systolic blood pressure below the currently recommended level affects cardiovascular and kidney diseases.

For this trial, nearly 100 medical centers in the United States and Puerto Rico, including Stanford, recruited more than 9,300 participants age 50 and older for a study that involved carefully adjusting the amount or type of blood pressure medication to achieve a target systolic pressure of 120 millimeters of mercury (mm Hg).

As outlined in an NIH press release, the researchers found that reducing systolic pressure to 120 mm Hg or less, reduced rates of stroke, heart attacks, heart failure and other cardiovascular events by almost a third and reduced the risk of death by almost a quarter, compared to the target systolic pressure of 140 mm Hg.

“SPRINT addressed a fundamental question faced by internal medicine physicians, nephrologists, cardiologists and other specialists – that is, how low should our blood pressure target be?” said Glenn Chertow, MD, MPH, principal investigator for the Stanford site.

Although researchers have known for some time that lowering patients’ blood pressure can improve survival rates and reduce their chances of having a stroke, heart disease or a kidney-related event, studies that link these benefits to a specific blood pressure were lacking. This is why the SPRINT study is so important.

“Before today there was no evidence from randomized clinical trials to demonstrate that lowering systolic blood pressure toward or below 120 mmHg was safe and effective,” Chertow told me yesterday afternoon.

“Adoption of the approach learned from SPRINT could change medical practice and materially improve the public health,” Chertow continued. “We’re proud to have participated” in the study.

Previously: The importance of knowing your blood pressure level in preventing hypertensionUltra-thin flexible device offers non-invasive method of monitoring heart health, blood pressureAsk Stanford Med: Stanford interventional cardiologist taking questions on heart health and High-quality chocolate linked to lower risk of heart failure
Photo by World Bank Photo Collection

Genetics, In the News, NIH, Science, Technology

The quest to unravel complex DNA structures gets a boost from new technology and NIH funding

The quest to unravel complex DNA structures gets a boost from new technology and NIH funding

5232013153_7808b471a2_zIf you’ve ever tried folding a map, packing an overnight bag or coiling a string of holiday lights, you know that the way you arrange an object affects how much space it takes up and how easy it is to use in the future. This same principle is true of DNA.

As a recent article in Science News explains, the way a DNA double helix is folded, packed and coiled is known to have a big effect on how much space it requires and how easy it is to access the information stored within. But, until recently, researchers lacked the technology to fully explore these four-dimensional DNA structures.

Now, new technology and last year’s launch of the National Institutes of Health‘s five-year, $120 million, 4D Nucleome project is helping researchers reveal the complex architecture of DNA. William Greenleaf, PhD, assistant professor of genetics at Stanford, discusses the significance of a genome‘s arrangement in the Science News article:

Like the genetic text within it, the genome’s shape holds specific instructions. “The way it’s compacted forms this sort of physical memory of what the cell should be doing,” Greenleaf says.

Loops of DNA that aren’t needed by a particular cell are tucked away from the biological machinery that reads genetic blueprints, leaving only relevant genes accessible to produce proteins. Studies have shown that sections of the genome that are shoved toward the edges of a nucleus are often read less than centrally located DNA. Such specialized arrangements allow cells as diverse as brain cells, skin cells and immune cells to perform different jobs, even though each contains the same genome. “In different cell types, there are very large changes to the regions that are being used,” Greenleaf says.

Much more remains to be understood about how a genome’s shape directs its activity. Future maps might zero in on functionally interesting regions of the genome, Greenleaf says. But he cautions there is also a benefit to unbiased, general exploration. Focusing on one location in the nucleome might lead researchers to miss important structural information elsewhere, he says.

Previously: DNA origami: How our genomes foldPacked and ready to go: The link between DNA folding and disease and DNA architecture fascinates Stanford researcher – and dictates biological outcomes
Photo by: Kate Ter Haar

Medical Education, Microbiology, NIH, Public Health, Research, Videos

Investigating the human microbiome: “We’re only just beginning and there is so much more to explore”

Investigating the human microbiome: "We’re only just beginning and there is so much more to explore"

The more scientists learn about the body’s community of bacteria, the more they believe that the human microbiome plays an important role in our overall health. For example, research published earlier this week suggests that a specific pattern of high bacterial diversity in the vagina during pregnancy increases a woman’s risk of giving birth prematurely.

Despite these and other insightful findings, researchers have a long way to go to understand the composition of our internal microbial ecosystems. As Keisha Findley, a postdoctoral fellow at the National Human Genome Research Institute says in the above video, “We’re only just beginning and there is so much more to explore.”

Findley and colleagues are working to survey all of the fungi and bacteria living on healthy human skin and develop a baseline to determine how these microbial communities may influence skin conditions such as acne, athlete’s foot, skin ulcers and eczema. Watch the LabTV video above to learn more about her work.

Previously: Drugs for bugs: Industry seeks small molecules to target, tweak and tune up our gut microbes, A look at our disappearing microbes, Exploring the microbes that inhabit our bodies and Diverse microbes discovered in healthy lungs shed new light on cystic fibrosis
Via NIH Director’s Blog

Behavioral Science, Mental Health, NIH, Public Health, Research

Developing certain skills may help you cultivate a positive outlook

34835574_9e61cfe6bb_zMany of us have heard that having a positive outlook on life can improve our mental and physical health. Yet, if you’re like me, you’ve noticed that it can be hard to focus on the bright side of things when you’re feeling anything but positive.

That’s why I was drawn to this article in the National Institutes of Health (NIH) newsletter. It discusses several NIH-funded studies on the topic and explains what it means to have a positive outlook and how a positive mood can affect your health. The really helpful information, from my perspective, is it also explains how developing certain skills, like meditation and self-reflection, can make you can feel more positive more often. From the NIH story:

Having a positive outlook doesn’t mean you never feel negative emotions, such as sadness or anger, says Dr. Barbara L. Fredrickson, a psychologist and expert on emotional wellness at the University of North Carolina, Chapel Hill. “All emotions—whether positive or negative—are adaptive in the right circumstances. The key seems to be finding a balance between the two,” she says.

The research teams used a variety of techniques to learn about the underlying mechanisms of positive and negative emotions and what it is that enables people to bounce back from difficult times.

Among those who appear more resilient and better able to hold on to positive emotions are people who’ve practiced various forms of meditation. In fact, growing evidence suggests that several techniques—including meditation, cognitive therapy (a type of psychotherapy), and self-reflection (thinking about the things you find important)—can help people develop the skills needed to make positive, healthful changes.

“Research points to the importance of certain kinds of training that can alter brain circuits in a way that will promote positive responses,” Davidson says. “It’s led us to conclude that well-being can be considered as a life skill. If you practice, you can actually get better at it.”

Previously: Navigating a rare genetic disorder with a positive attitudePromoting healthy eating and a positive body image on college campusesWhen life gives you lemons: Study suggests the benefits of a positive outlook are context dependent and The power of positive moods in improving cognitive function among older adults
Photo by: premasagar

Cancer, Health Policy, NIH, Public Health

Draining the cancer swamp

Draining the cancer swamp

4011473415_46405053bd_zThere’s an old adage that applies to many difficult situations that we face in life: When you’re up to your armpits in alligators, it’s difficult to remind yourself that you should have drained the swamp.

I’ve come to view cancer as a vicious predator lurking in dark waters, eager to attack one out of two of us in our lifetimes. Cancer is the second most common cause of death in the United States.

Looking at the current national funding model for cancer research, I wonder if society has lost track of a vital goal: preventing cancer, not just treating it. Wouldn’t it be better if we prevented cancer in the first place? Cancer prevention would reduce the devastating physical, psychological, emotional, social and economic burden placed on patients, their families and their friends.

As he stepped down from the role of Director of the National Cancer Institute, Harold Varmus, MD, spoke about the deep complexity of cancer and the tremendous amount of basic research that needs to be done. While recognizing the need for clinical testing, he also called for more pioneering discoveries into who gets cancer, where and why.

The financial constraints facing scientific research force us to make difficult choices. Right now, our current health-care model prioritizes “identifiable individuals” over “statistical individuals.” Identifiable individuals are those real persons in distress who have been diagnosed with cancer. They need treatment, and we are highly motivated to help cure them. The cost of doing so, however, is high: The average monthly cost of cancer treatment has more than doubled to $10,000 over the last decade. Of course, we are willing to pay the costs – these victims are our mothers, our fathers, our sons and our daughters.

Statistical individuals are those who may be at risk, but they may not know it. They may never know that scientific research “rescued” them from a devastating disease. Through prevention measures enacted by individuals themselves (e.g., getting more exercise, avoiding tobacco use) or by society (e.g., limiting chemical exposures in the environment, banning the use of tanning beds for minors), these individuals may be able to escape the scourge of cancer.

When making choices about where to invest limited dollars, it is so much easier to say “no” to statistical people rather than real people.

I don’t advocate taking money away from cancer treatment, but I do advocate a greater investment of federal dollars in research that leads to reducing the incidence of cancer in the healthy population. By tracking and analyzing patterns and trends of cancer, we can identify potential risk factors and inform individuals and communities about positive changes they can make toward living cancer-free lives.

It is estimated that over 50 percent of the 585,720 cancer deaths in the U.S. in 2014 were related to preventable causes. As such, federal dollars directed toward statistical individuals will save both money and lives.

We need to drain the swamp. Our ultimate societal goal shouldn’t be to treat cancer more effectively, but to prevent it altogether. We need to intervene as early as possible in the trajectory of cancer. By doing so, we will greatly reduce the extent and depth of human suffering.

Donna Randall, PhD, is chief executive officer of the Cancer Prevention Institute of California.

Photo by William Warby

NIH, Pregnancy, Research, Technology, Women's Health

Scientists create a placenta-on-a-chip to safely study process and pitfalls of pregnancy

Scientists create a placenta-on-a-chip to safely study process and pitfalls of pregnancy

2798127284_487b56b9cf_zThese days it seems that just about anything can be recreated on a microchip. But still, I did a double-take when I read about the new way that scientists are using technology to study pregnancy: They’ve created a “placenta-on-a-chip.”

A functioning placenta is critical for a healthy pregnancy because it regulates the flow of nutrients, oxygen and waste products between the mother and fetus. It also controls the fetus’ exposure to bacteria, viruses and other harmful substances. Researchers would like to learn more about how the placenta acts as a “crossing guard” and how it can regulate the body’s traffic so well. Yet, studying the placenta is hard to do because it’s highly variable, and tinkering with the placenta is risky for the fetus.

To overcome these challenges, an interdisciplinary team led by a University of Pennsylvania researcher created a two-chambered microchip that mimics the structure and function of the human placenta. The study was published online in the Journal of Maternal-Fetal and Neonatal Medicine and is reported on in this National Institutes of Health press release:

The device consists of a semi-permeable membrane between two tiny chambers, one filled with maternal cells derived from a delivered placenta and the other filled with fetal cells derived from an umbilical cord.

After designing the structure of the model, the researchers tested its function by evaluating the transfer of glucose (a substance made by the body when converting carbohydrates to energy) from the maternal compartment to the fetal compartment. The successful transfer of glucose in the device mirrored what occurs in the body.

As Roberto Romero, MD, chief of the perinatology research branch at the NIH’s National Institute of Child Health and Human Development, explains in the press release, this new technology could help researchers explore how the placenta works, and what happens when it fails, in ways that couldn’t be safely done before. This, the researchers say, could lead to more successful pregnancies.

Previously: NIH puts focus on the placenta, the “fascinating” and “least understood” organPlacenta: the video game, The placenta sacrifices itself to keep baby healthy in case of starvation, research showsThe placenta sacrifices itself to keep baby healthy in case of starvation, research shows and Program focuses on the treatment of placental disorders
Photo by Jack Fussell

NIH, Obesity, Public Health, Research

Capturing the metabolic signature of obesity

Capturing the metabolic signature of obesity

scale_weightWorldwide obesity rates have more than doubled since 1980, and today the majority of the global population live in areas where being overweight kills more people than being underweight, according to data from the World Health Organization. But new research that provides a comprehensive view of the metabolic signature that may correlate with obesity could help scientists develop more effective ways to manage and prevent obesity, and it offer insights into how variability in genes, environment, metabolism and lifestyle affect our health individually.

As reported today on the NIH Director’s Blog:

The new analysis uncovered changes to 29 molecular metabolites, or biomarkers, that correlated with obesity in 1,880 people from the United States. Most of those biomarkers—25 to be exact—also turned up in the urine of obese people from the other side of the Atlantic, offering confirmation that the findings represent a shared metabolic signature of obesity.

Several of the biomarkers are byproducts of what a person eats, which may reflect differences in the diets of obese and non-obese people. For example, urine from obese people was more likely to contain a metabolite that comes from eating red meat, while thinner folks were more likely to have a metabolite indicative of citrus fruit consumption.

However, not all of the biomarkers were directly related to food. Some appeared to stem from widespread changes in kidney function, skeletal muscle, and metabolism that may occur as a person packs on extra pounds. And, intriguingly, nine of the biomarkers significantly associated with obesity weren’t even produced by the human body, but rather by the trillions of microbes that live inside our guts. Those microbial partners play important roles in the breakdown of essential vitamins, amino acids, and protein. In fact, recent research findings suggest that a significant portion of obesity risk may be explained by the activity of gut microbes. This discovery adds to mounting evidence, spurred in recent years by the NIH-funded Human Microbiome Project, for the intricate and essential role of microbes—collectively known as the microbiome—in many aspects of our health.

The piece goes on to say that the findings also “raise the intriguing possibility that people might one day be able to visit their health-care providers, receive a blood or urine test, and leave with precise, individualized information regarding their risk” for obesity and other health issues.

Previously: Childx speaker Matthew Gillman discusses obesity prevention, Discussing how obesity and addiction share common neurochemistry, Stanford team awarded NIH Human Microbiome Project grant and Obesity is a disease – so now what?
Photo by Matthew

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