'Gut Reaction' May Predict Cardiovascular Risk

Higher levels of stomach substance called TMAO linked to heart attack, stroke, study suggests

By Steven Reinberg

HealthDay Reporter

WEDNESDAY, April 24 (HealthDay News) -- A blood test that assesses levels of a compound produced in the stomach appears to be a strong indicator of whether there will be heart trouble down the road, researchers report.

The higher the levels of the compound -- called trimethylamine-N-oxide (TMAO) -- the greater the risk for cardiovascular problems, said the Cleveland Clinic team. Eventually, TMAO could be a target to help prevent or reduce the risk of heart problems, the researchers suggested.

"A new blood test measuring something in the blood that is generated by the bacteria in our gut actually predicted in a strong and powerful way the future risk of heart attack, stroke and death," said lead researcher Dr. Stanley Hazen, from the Clinic's Lerner Research Institute.

Measuring TMAO predicted heart risk better than other blood tests or the usual risk factors, such as high blood pressure, cholesterol and smoking, he noted.

"This is a potentially new target we can go after to prevent heart disease," Hazen said.

In a preclinical study, the researchers found that dietary choline -- found in egg yolks -- is metabolized into TMAO. Carnitine, found in red meat, is another potential source of the compound. According to Hazen, TMAO changes how cholesterol is metabolized. "It's not changing the cholesterol in your blood, it's changing how the cholesterol is being managed," he said.

More specifically, TMAO helps cholesterol attach to blood vessels. It also makes it harder for the liver and the intestines to get rid of cholesterol, he explained.

"This new blood test may help identify people who are most in need of getting preventive cardiology help," Hazen said.

Because TMAO levels seem related to diet -- those who eat the most meat have the highest levels -- Hazen said the test could help people tailor their diets to reduce the risk of cardiovascular problems.

Eating a heart-healthy diet that is low in fats, dairy and sugar -- as recommended by the American Heart Association -- tends to reduce TMAO, Hazen said. Vegetarians have the lowest levels of TMAO, he noted.

In this study, published in the April 25 issue of the New England Journal of Medicine, Hazen's team collected data on TMAO levels from more than 4,000 patients and followed them for three years on average.

As TMAO levels increased so did the risk for heart attack, stroke or heart disease, the investigators found. Those with the highest levels of TMAO had 2.5 times the risk for these outcomes compared to those with the lowest levels of TMAO, the study authors reported.

Dr. Gregg Fonarow, a spokesman for the American Heart Association and professor of cardiovascular medicine and science at the University of California, Los Angeles, said that "there has been increasing interest in the role that intestinal microbial metabolism can play in metabolic and cardiovascular diseases."

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Newborn's Placenta May Predict Autism Risk, Study Suggests

Identifying infants with higher odds could improve treatment, researchers say

By Kathleen Doheny

HealthDay Reporter

THURSDAY, April 25 (HealthDay News) -- Autism risk may be spotted at birth by examining placentas for abnormalities, new research suggests.

"We can look at the placenta at birth and determine the chance of being at risk for autism with extremely high reliability," said Dr. Harvey Kliman, a research scientist at Yale University.

One of 88 U.S. children has an autism spectrum disorder, the umbrella name for complex brain development disorders marked by problems with social interaction and communication, according to the U.S. Centers for Disease Control and Prevention.

The earlier autism is treated, the better the outcome. But children typically aren't diagnosed until behavioral symptoms begin, perhaps at age 2 or 3 years, or even later. Kliman said the children identified as at risk at birth might benefit from early treatment.

For the new study, published online April 25 in the journal Biological Psychiatry, Kliman and his team examined 117 placentas from newborns whose mothers already had one or more children with some form of autism, which put the infant at higher risk for the disorder. The researchers compared those samples with placenta samples from 100 women who already had one or more typically developing children.

During pregnancy, the placenta keeps the unborn baby's blood supply separate from the mother's while providing the baby with oxygen and nutrients. At delivery, the placenta, also called the afterbirth, follows the baby out of the womb.

The placentas from women whose older children had autism were markedly different from the others, Kliman's team found. They zeroed in on abnormal folds and abnormal cell growth in the placenta, known as trophoblast inclusions.

The placentas from the at-risk pregnancies were eight times more likely to have two or more of these abnormal folds than samples from not-at-risk deliveries. Placentas with four or more of the inclusions predicted an infant with at least a 74 percent probability of being at risk for autism, the researchers said.

"There were no [placentas from pregnancies not at risk] that had more than two of the folds," Kliman said.

The study only predicted risk of autism, however, not actual autism. The researchers will continue to follow the children.

The testing can't be done before delivery, Kliman said. "You need enough placenta [to examine]."

But the test could help spot at-risk children much earlier than is now possible, Kliman suggested. "There is no way [currently] to know at birth that your child might have autism," he said. "If you know you have a child who is at risk for autism at birth, you are ahead of the game." Interventions can begin early, when the brain is more open to change.

How the folds in the placenta relate to autism risk isn't clear, Kliman said. He and others speculated that the abnormalities in the placentas and the brains of the children affected with autism are marked by increased cellular growth, which then leads to the unusual folding. "The heads of children with autism are bigger," he said. Their brains grow rapidly early in life.

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Older Adults' Posture May Predict Future Disability

FRIDAY, April 19 (HealthDay News) -- The shape of an older person's spine may predict their future need for home assistance or admission to a nursing home, according to a new Japanese study.

The findings appeared online recently in the Journals of Gerontology Series A: Biological Sciences and Medical Sciences.

The study included more than 800 people aged 65 and older in Japan, who underwent four types of spinal measurement. The researchers found that only one of the measurements was associated with becoming dependent on help for activities of daily living.

These activities include basic self-care tasks such as bathing, feeding, using the toilet, dressing and getting in or out of a bed or chair.

The measurement that predicted the need of assistance is called the "trunk angle of inclination." This is the angle between the true vertical and straight line from the first thoracic vertebra (near the head) to the first sacral vertebra (in the lower spine), the researchers said in a journal news release.

Over four and a half years of follow-up, about 16 percent of the participants became dependent on help for basic daily activities. Those with the greatest angle of spinal inclination were about three and a half times more likely to become dependent on help for basic daily activities than those with the least spinal inclination, the researchers found.

Although the study found an association between spinal angle and future disability in older adults, it did not establish a cause-and-effect relationship.

-- Robert Preidt
Copyright © 2013 HealthDay. All rights reserved. SOURCE: Journals of Gerontology Series A: Biological Sciences and Medical Sciences, news release, April 2013

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Blood Test Might Predict Type 1 Diabetes in Children, Study Finds

Evidence of two autoantibodies signaled a 70 percent risk, researchers say

By Serena Gordon

HealthDay Reporter

TUESDAY, June 18 (HealthDay News) -- A diagnosis of type 1 diabetes often seems to come out of the blue. But German researchers say they can predict who will likely develop the chronic disease.

Blood samples taken from children at increased genetic risk of type 1 diabetes reveal significant "preclinical" clues, the researchers found. The strongest predictor is the presence of two diabetes-related autoantibodies, they reported in the June 18 issue of the Journal of the American Medical Association.

"If you have two or more autoantibodies, it's nearly inevitable that you will develop the disease. Most people -- even physicians -- don't appreciate this risk," said Dr. Jay Skyler, deputy director for clinical research at the Diabetes Research Institute and a professor at the University of Miami Miller School of Medicine. Skyler was not involved in the research.

Nearly 70 percent of youngsters with two diabetes-related autoantibodies developed type 1 diabetes over a 10-year period compared to less than 15 percent of kids with just one autoantibody, the researchers found.

Skyler, co-author of an accompanying journal editorial, said this study highlights the need for effective prevention strategies for type 1 diabetes.

Type 1 diabetes is believed to be an autoimmune disease in which the body's immune system mistakenly destroys the insulin-producing beta cells in the pancreas. Insulin is a hormone needed to turn the carbohydrates from food into fuel for the body.

To survive, people with type 1 diabetes must monitor their food intake and replace the lost insulin through injections or an insulin pump.

Type 1 diabetes can occur at any age, and there's currently no known way to prevent or cure it, according to the JDRF (formerly the Juvenile Diabetes Research Association). And unlike its more common counterpart, type 2 diabetes, the development of type 1 diabetes isn't linked to lifestyle choices.

The current study included children from Colorado, Finland and Germany who were followed from birth for as long as 15 years. Children in the Colorado and Finland study groups were included in the study if they had a specific genotype that indicated a genetic predisposition to developing type 1 diabetes. Children in the German study had to have a parent with type 1 diabetes to be included in the study.

More than 13,000 youngsters were recruited in all. During the study follow-up, the researchers found that nearly 1,100 children -- or about 8 percent of the total group -- developed one or more autoantibodies, which are markers for the destruction of the insulin-producing beta cells in the pancreas.

The vast majority of the children, despite their higher risk, remained free of type 1 diabetes and free of signs that the disease might develop.

"Autoantibodies are a marker for the risk of diabetes. [But] they are just markers; they are not causing the disease," said Dr. Joel Zonszein, director of the Clinical Diabetes Center at Montefiore Medical Center in New York City.

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Blood Tests May Predict COPD Flare-Ups

Signs of chronic inflammation in the blood linked to faster deterioration of lung function

By Brenda Goodman

HealthDay Reporter

TUESDAY, June 11 (HealthDay News) -- People with chronic obstructive pulmonary disease (COPD) who have signs of chronic inflammation in their blood are more likely to have flare-ups of the lung disease than those who do not, a large new study shows.

In addition to the slow, steady deterioration in lung function caused by COPD, patients can have sudden, distressing flare-ups. These so-called "exacerbations" are periods of worsening breathing problems that are typically triggered by infections or air pollution.

Patients who experience frequent flare-ups decline more quickly than those who do not; they also tend to have worse quality of life and poorer survival rates than those whose conditions are more stable, according to background information in the study.

Preventing flare-ups is a major goal of COPD treatment, but these episodes can be difficult to predict.

In a study of more than 61,000 people in Denmark, researchers found that COPD patients who had increased levels of certain proteins and cells in their blood were at greater risk for frequent flare-ups.

These particular proteins and cells -- C-reactive protein, fibrinogen and leukocytes -- increase in response to infections, tissue damage and inflammation.

People with higher levels of all three of these "markers" were more likely to experience frequent flare-ups than those with normal levels. That was true regardless of the stage or severity of their COPD.

But the risk was especially pronounced for patients in the study with the worst breathing problems. Among patients who had the highest grade of COPD symptoms, 24 percent with no elevated markers had frequent flare-ups compared to 62 percent of those who had high levels of all three markers.

Patients with frequent exacerbations had two or more flare-ups each year they were followed for the study.

The study is published in the June 12 issue of the Journal of the American Medical Association.

According to Dr. Elizabeth Regan, who is studying the genetics of COPD at National Jewish Health in Denver, the researchers "give compelling evidence that those are useful tests." Regan was not involved with the study.

"These are tests that are readily available. The practicing physician kind of has them at their fingertips. They're not unusual, they're not high-risk," said Regan. "If I were seeing patients, I'd be strongly attracted to doing it."

The price of each test varies, but in general, they're inexpensive, ranging between $10 and $40. Insurance often covers the cost. The only trouble with doing the tests now, Regan said, is that doctors still don't know exactly how to use the information.

"While these tests look like they're strong predictors, we don't have the next piece of this clearly in place," she noted.

The study wasn't able to prove that inflammation causes COPD exacerbations, or that lowering inflammation with medications could head off future flare-ups, Regan explained.

Other studies currently underway are testing whether antibiotics or newer medications can prevent such attacks, she noted.

Until more is known, the researchers say there is still one good reason for COPD patients to get the blood tests.

"Many patients with COPD aren't very adherent to their inhalation medication. Patients don't like to be sick, so they think 'it's doing well now, so let me stop,'" said study author Dr. Borge Nordestgaard, a clinical professor in the department of diagnostic sciences at the University of Copenhagen in Denmark.

"But if you're one of these patients with high biomarkers, then you should be even better at taking your daily inhalation medication," he said. "That's the best advice at present."

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Breath Test Might Predict Obesity Risk

Title: Breath Test Might Predict Obesity Risk
Category: Health News
Created: 3/26/2013 10:35:00 AM
Last Editorial Review: 3/26/2013 12:00:00 AM

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Breath Test Might Predict Obesity Risk

It works by measuring bacteria balance in the gut, researchers say

By Denise Mann

HealthDay Reporter

TUESDAY, March 26 (HealthDay News) -- A simple breath test may be able to tell if you are overweight or will be in the future, a new study suggests.

According to the findings, results from a standard breath test used to assess bacterial overgrowth in the gut can also tell doctors if you have a high percentage of body fat.

The microbiome, or the trillions of good and bad bugs that line your gut, can get out of balance. When bad bacteria overwhelm good bacteria, symptoms such as bloating, constipation and diarrhea may occur. The new study, appearing in the April issue of the Journal of Clinical Endocrinology & Metabolism, suggests that this scenario may also set someone up for obesity.

For the study, individuals drank a sugary lactulose syrup. Breath samples were then collected every 15 minutes for two hours. Participants also had their body fat measured in two ways. One was body mass index (BMI), which takes height and weight into account. The other method uses low-wattage electrical conductivity, which differentiates between lean and fatty tissue.

Those participants whose breath samples showed higher levels of two gases -- methane and hydrogen -- had higher BMIs and more body fat than participants who had normal breath or a higher concentration of only one of the two gases, the study showed. This pattern suggests that the gut is loaded with a bug called Methanobrevibacter smithii, the researchers explained.

It's possible that when this type of bacteria takes over, people may be more likely to gain weight and accumulate fat, said lead study author Dr. Ruchi Mathur, director of the outpatient diabetes treatment center at Cedars-Sinai Medical Center in Los Angeles.

Although there are other ways to measure body fat and BMI, the researchers suggested that individuals with higher methane and hydrogen content in their breath may be more likely to respond to specific weight loss methods down the line. "Obesity is not a one-size-fits-all disease," Mathur said.

If the study findings are confirmed, certain weight-loss treatments could be matched to people who have this breath pattern. One possibility, for instance, might be that probiotics, which help restore and maintain the natural balance of organisms in the gut, could have a role in treating or preventing obesity.

But the science is not there yet, experts cautioned.

"This is an important study looking at bacteria in the intestine and how they are related to BMI," said Dr. Spyros Mezitis, an endocrinologist at Lenox Hill Hospital in New York City. "The more methane and hydrogen in the breath, the higher the body fat." But, "we need more studies to figure out how bacteria is related to the growing obesity epidemic and what happens if we modify it," Mezitis said.

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Word Tests May Predict Gains for Kids With Autism

Toddlers' brain responses corresponded with later language, thinking and self-care skills

By Mary Elizabeth Dallas

HealthDay Reporter

WEDNESDAY, May 29 (HealthDay News) -- Early brain responses to words may help predict future abilities in children with autism, a new study suggests.

"We showed that a simple measure of how the brain responds to a familiar word taken at 2 years of age was a strong predictor of children's language, social and cognitive abilities ... at 6 years of age," said study co-author Geraldine Dawson, chief science officer at the advocacy group Autism Speaks.

Autism is a neurodevelopmental disorder characterized by impaired communication, difficulty with social interactions and repetitive behaviors. The U.S. Centers for Disease Control and Prevention estimates that one in 88 U.S. children has some form of autism, which can range from mild to severe.

"In this study, we were interested in understanding why some children with autism make rapid progress whereas others progress more slowly," Dawson said. "For example, many children with autism are able to develop spoken language, whereas about 20 percent to 30 percent remain minimally verbal or nonverbal.

"Recent studies have shown that nonverbal children can be helped to develop spoken language if they are given special alternative devices -- such as an iPad or other speech-generating device -- as part of their early intervention program," Dawson added. "But we don't know how to identify which children are likely to need extra help."

The study, published May 29 in the journal PLoS ONE, involved 44 children, all of whom were 2 years old. Twenty-four had autism and 20 did not. The children were asked to listen to a mix of familiar and unfamiliar words while wearing sensors, which measured their brain responses.

The children with autism were divided into two groups based on the level of their social impairment. The brain responses of the children with autism with milder symptoms were similar to the brain responses of the children who did not have autism, the researchers found. These children had a strong response to known words in a specific area of the left side of the brain called the temporal parietal region, which is responsible for language.

This suggests that children with less severe symptoms can process words in much the same way as typically developing children, the study authors said.

Children with more severe social impairments, however, showed brain responses more broadly over the right hemisphere. The researchers said this is not usually seen in healthy children of any age.

The children's language skills, thinking abilities and social and emotional development also were assessed at age 2 and again at ages 4 and 6.

Over time and with intensive treatment, the children with autism improved on the behavioral tests, but individual gains varied widely, the researchers found. The more the autistic children's brain responses resembled those of typically developing children, the greater the improvement in their skills by age 6.

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High Blood Pressure in Pregnancy May Predict Later Ills, Study Says

Title: High Blood Pressure in Pregnancy May Predict Later Ills, Study Says
Category: Health News
Created: 2/11/2013 4:35:00 PM
Last Editorial Review: 2/12/2013 12:00:00 AM

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New Eye Test May Help Predict Risk of Glaucoma

Jan. 4, 2013 -- A new study from Australia may offer a new way of identifying people at risk of glaucoma years before vision loss happens.

Glaucoma is a leading cause of blindness. But because vision damage often occurs gradually, most people with the eye disease do not realize they have it until a good deal of their sight has been lost. If caught early, though, there are medications and procedures that may help treat glaucoma.

In the study, researchers were able to predict who was at increased risk of developing the eye disease with some accuracy by measuring blood vessel thickness in the retinas of study participants using a computer-based imaging tool.

Those with the narrowest vessels at the beginning of the study were four times more likely to have developed glaucoma a decade later.

About 3 million Americans and 60 million people worldwide have glaucoma, and the numbers are projected to rise over the next few decades as the population ages.

The disease involves damage to the optic nerve, which relays images from the retina to the brain.

Early detection is key, but without regular eye exams, most people don’t know they have a problem, says ophthalmologist Andrew Iwach, MD. He is the executive director of the Glaucoma Center of San Francisco and an associate clinical professor of opthalmology at the University of California, San Francisco.

“We call this disease a ‘thief of vision’ because most people with it have no idea that they have lost sight until it is too late to bring it back,” Iwach says.

In the study, researchers from the University of Sydney followed nearly 2,500 adults, aged 49 and older, for 10 years.

None of the participants had glaucoma when they entered the study.

Compared with the group as a whole, those people who were diagnosed with the eye disease during the following decade were older, had higher blood pressure, and were more likely to be female.

The researchers concluded that measuring retinal-vessel narrowing could help identify people at risk for glaucoma. But they added that blood pressure and other factors that can contribute to vessel size would need to be considered.

The study appears in the latest issue of the journal Ophthalmology.

The researchers say that the findings also highlight the importance of having regular eye exams as people age.

The American Optometric Association recommends eye exams for adults aged 18 to 60 every two years, every year for adults 61 and older, or as recommended by their eye doctor.

In addition to glaucoma, regular exams can detect other eye diseases associated with aging, including macular degeneration and cataracts, Iwach says.

Eye surgeon Mark Fromer, MD, of Lenox Hill Hospital in New York City, agrees that having regular eye exams is the best protection against vision loss associated with aging.

“It remains to be seen if this approach will help us identify people at risk for glaucoma sooner,” he says. “We have a number of tools now to help us do that, but we’ve got to get people in our offices to use them.”

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Depression in Elderly May Predict Dementia

Dec. 31, 2012 -- Depression is common among older people who go on to develop Alzheimer’s disease, leading to widespread speculation that it may be one possible cause for age-related dementias.

Now, a new study suggests that rather than being a cause of memory decline, depression in older people may be an early symptom of dementia.

When researchers evaluated 2,000 elderly New Yorkers for depression and then followed them, they found that depression accompanied memory declines but did not necessarily come first.

Having memory problems that are not severe enough to be diagnosed as dementia, but that are more pronounced than the changes associated with normal aging, is known as mild cognitive impairment. Many people with MCI develop dementia, but some do not.

The new research shows that having mild cognitive impairment along with depression doubled the risk of developing full-blown dementia.

But researcher Jose A. Luchsinger, MD, MPH, of Columbia University Medical Center, says depression appears to be a symptom that accompanies age-related memory loss, such as mild cognitive impairment, rather than a separate risk factor for it.

It also means that depression among the elderly should be recognized as a possible early warning sign of age-related memory decline.

The study was published online today in the journal Archives of Neurology.

“When depression and memory complaints occur together in the elderly it is often assumed that the memory problems are caused by the depression,” Luchsinger says. “The thinking is often that by treating the depression the memory problems will go away, but this may not be the case.”

He says older people who are depressed and have memory complaints should be evaluated for mild cognitive impairment or other early signs of dementia.

Neurologist Gayatri Devi, MD, of New York City’s Lenox Hill Hospital, says it makes sense that older people with early memory loss would be more vulnerable to depression.

“Especially in the early stages when people realize that something is not quite right but they don’t really understand what is happening, it is natural to become depressed,” she says.

Devi agrees that depression and memory loss in older patients are too often lumped together instead of being evaluated separately.

“Depression may be related to (memory) decline or it may be totally unrelated,” she says. “From a clinical perspective it is important to understand this. If a patient comes to me in her 70s or 80s with no history of depression and no clear reason for depression, such as the loss of a spouse or a child, I will certainly consider cognitive loss as a possible reason and do the appropriate tests.”

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Perceived stress may predict future coronary heart disease risk

Dec. 17, 2012 — Are you stressed? Results of a new meta-analysis of six studies involving nearly 120,000 people indicate that the answer to that question may help predict one's risk of incident coronary heart disease (CHD) or death from CHD. The study, led by Columbia University Medical Center researchers, was published in a recent issue of the American Journal of Cardiology.

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The six studies included in the analysis were large prospective observational cohort studies in which participants were asked about their perceived stress (e.g., "How stressed do you feel?" or "How often are you stressed?"). Respondents scored either high or low; researchers then followed them for an average of 14 years to compare the number of heart attacks and CHD deaths between the two groups. Results demonstrate that high perceived stress is associated with a 27% increased risk for incident CHD (defined as a new diagnosis or hospitalization) or CHD mortality.

"While it is generally accepted that stress is related to heart disease, this is the first meta-analytic review of the association of perceived stress and incident CHD," said senior author Donald Edmondson, PhD, assistant professor of behavioral medicine at CUMC. "This is the most precise estimate of that relationship, and it gives credence to the widely held belief that general stress is related to heart health. In comparison with traditional cardiovascular risk factors, high stress provides a moderate increase in the risk of CHD -- e.g., the equivalent of a 50 mg/dL increase in LDL cholesterol, a 2.7/1.4 mmHg increase in blood pressure or smoking five more cigarettes per day."

"These findings are significant because they are applicable to nearly everyone," said first author Safiya Richardson, MD, who collaborated with Dr. Edmondson on the paper while attending the Columbia University College of Physicians and Surgeons (she graduated in 2012 and is currently a resident at North Shore Long Island Jewish Health System in Manhasset, New York). "The key takeaway is that how people feel is important for their heart health, so anything they can do to reduce stress may improve their heart health in the future."

Coronary heart disease (CHD), also called coronary artery disease, is a narrowing of the small blood vessels that supply blood and oxygen to the heart. It is caused by a buildup of plaque in the arteries, which can lead to hardening of the arteries, or atherosclerosis. CHD is the leading cause of death in the United States for men and women; more than 385,000 people die each year from CHD.

The researchers did further analysis to try to learn what might underlie the association between stress and CHD. They found that while gender was not a significant factor, age was. The people in the studies were between the ages of 43-74; among older people, the relationship between stress and CHD was stronger.

"While we do not know for certain why there appears to be an association between age and the effect of perceived stress on CHD, we think that stress may be compounding over time. For example, someone who reports high perceived stress at age 60 may also have felt high stress at ages 40 and 50, as well." Dr. Edmondson also noted that older individuals tend to have worse CHD risk factors such as hypertension to begin with, and that stress may interact with those risk factors to produce CHD events.

"The next step is to conduct randomized trials to assess whether broad population-based measures to decrease stress are cost-effective. Further research should look at whether the stress that people report is about actual life circumstances (e.g., moving or caregiving), or about stable personality characteristics (e.g., type A vs. B), said Dr. Edmondson.

"We also need to ask why we found this association between stress and CHD, e.g., what biological components or mechanisms are involved, and what is the role of environment or lifestyle (e.g., diet, alcohol and drug use, exercise), and how best to moderate these factors to lower the risk of CHD," said Dr. Richardson.

The paper is titled, "Meta-Analysis of Perceived Stress and Its Association With Incident Coronary Heart Disease." The other contributors are Jonathan A. Shaffer, Louise Falzon, David Krupka and Karina W. Davidson, all from CUMC's Center for Behavioral Cardiovascular Health.

This research was supported by National Institutes of Health (NIH) grants HL-088117 and CA-156709. It was supported in part by Columbia University's Clinical and Translational Science Awards (CTSA) grant No. UL1RR024156 from the National Center for Advancing Translational Sciences -- National Center for Research Resources/NIH. Dr. Edmondson is supported by NIH grant KM1CA156709.

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