Recent News from the Center:
Improving the Efficiency of Biomedical Research
PRESS RELEASE: FOR IMMEDIATE RELEASE, January 17, 2014
The Lancet is publishing a new series consisting of commentaries and five articles focusing on biomedical research waste and how to improve research efficiency, dissemination and transparency of new knowledge, and more effective translation of findings into clinical practice . Michael B. Bracken, Susan Dwight Bliss Professor of Epidemiology at Yale University and an author of the series, stated: “While the biomedical research community currently provides a huge amount of benefit to society, it does so in spite of the present high degree of wasted research, this series documents how much more could be accomplished if we substantially improved the efficiency of the research enterprise.”
The first article emphasizes the large amount of dollars spent on research with too little to show for return on the investment. In 2010, US$240 billion dollars were spent on research worldwide. However, many funded research projects do not provide helpful results or information to the medical research communities and their patients. There is a substantial need to improve basic research methods, provide greater transparency for how funding decisions are made in light of existing evidence, and how in-progress research could be made more available to researchers and funders alike. More attention should be paid to asking research questions of interest to patients and users of research. Funding institutions and governments and their advisors are ultimately responsible for reducing monetary waste by making well-informed decisions about which projects to fund or not .
The second article points to the potential for misleading results and biases in research design which can lead to wasting valuable resources. Poor documentation, low statistical precision, disregard for previously conducted studies, and failure to involve statisticians and properly train laboratory staff in research design, are all factors that can lead to inefficient assignment of labor, effort, time and money. Further, the current reward systems, at the institutional level, emphasize quantity over quality and novelty over reproducibility, which can produce an imbalanced picture of how research should be conducted .
The third paper discusses waste arising from overregulation and management of research. Regulators should review other causes of waste in research rather than micromanaging research under the assumption that it is in the best interest of participants and patients. Laws and regulations, particularly related to ethics committees who are overly concerned about low-risk projects, should be streamlined to provide guidance on how research should be done while not impeding research efforts. Efficiency in recruitment, retention, and data monitoring and sharing should be set as priorities. Administrators and managers of healthcare systems should also promote integration of research results into clinical practice .
The fourth article elaborates on the need for better publishing of methods in study protocols. Protocols and detailed study reports are rarely available and when they are provided, the quality of reporting is variable. The authors suggest improvements where funders and institutions should reward researchers who fully disseminate their research protocols, reports, and datasets. Further, they suggest that all health research should have standards for content and that pre-registration of studies be mandatory .
The fifth paper considers waste from incomplete or unusable reports of biomedical research, the current methods and standards for reporting research. Although reporting guidelines such as CONSORT, STARD, PRISMA, and ARRIVE have been developed, these are not followed consistently or widely. The current guidelines aim to organize content and clarify research conducted. More specifically, to outline which research questions were posed and why, what was done to obtain answers, and what the findings may mean. A change in the current system of research rewards is warranted to encourage better reporting as well as developing a funded infrastructure to maintain better reporting practices, and to archive all elements of research for future analysis .
1. Kleinert S, Horton R. How should medical science change? Lancet 2014. Jan 7. pii: S0140-6736(13)62678-1.
2. Chalmers I, Bracken MB, Djulbegovic B, et al. How to increase value and reduce waste when research priorities are set. Lancet 2014; 383(9912): 156-65.
3. Ioannidis JP, Greenland S, Hlatky MA, et al. Increasing value and reducing waste in research design, conduct, and analysis. Lancet 2014; 383(9912): 166-75.
4. Al-Shahi Salman R, Beller E, Kagan J, et al. Increasing value and reducing waste in biomedical research regulation and management. Lancet 2014; 383(9912): 176-85.
5. Chan AW, Song F, Vickers A, et al. Increasing value and reducing waste: addressing inaccessible research. Lancet 2014. Jan 7. pii: S0140-6736(13)62296-5.
6. Glasziou P, Altman DG, Bossuyt P, et al. Reducing waste from incomplete or unusable reports of biomedical research. Lancet 2014. Jan 7. pii: S0140-6736(13)62228-X.
A new Lancet series - Research: increasing value, reducing waste
Published January 8, 2014, The Lancet Online
A new Lancet Series focuses on increasing value and reducing waste in research. The Series documents waste in research from five principal sources — ranging from waste in deciding what research to do, through to waste because of unusable reports of research. In these papers we set out some of the most pressing issues, recommend how to increase value and reduce waste in biomedical research, and propose metrics for stakeholders to monitor the implementation of these recommendations.
Michael B. Bracken, Susan Dwight Bliss Professor of Epidemiology, co-authored the first paper in the series titled 'How to increase valude and reduce waste when research priorities are set' and is part of the The Lancet, Early Online Publication.
An Estimated 8 Million Lives Saved Since Surgeon General’s Tobacco Warning 50 Years Ago, Study Finds
Tuesday, January 7, 2014
By Michael Greenwood
An estimated eight million lives have been saved in the United States as a result of the anti-smoking measures that began 50 years ago this month with the release of the ground-breaking Surgeon General of the United States’ report outlining the deadly consequences of tobacco use.
Published in the Journal of the American Medical Association, the Yale School of Public Health-led analysis used mathematical models to calculate the effect of the seminal report and subsequent anti-smoking measures over the past half century. These cumulative efforts have significantly reshaped public attitudes and behaviors concerning cigarettes and other forms of tobacco.
Theodore R. Holford, professor in the Department of Biostatistics, and six other researchers that are part of the NCI’s Cancer Intervention and Surveillance Modeling Network (CISNET) found that while some 17.6 million Americans have died since 1964 due to smoking-related causes, eight million lives have been saved as a result of increasingly stringent tobacco-control measures that commenced with the report’s January 11, 1964, release.
Of the lives saved, approximately 5.3 million were men and 2.7 million women. The total number of saved lives translates into an estimated 157 million years of life, a mean of 19.6 years for each beneficiary.
“An estimated 31 percent of premature deaths were avoided by this effort, but even more encouraging is the steady progress that was achieved over the past half century, beginning with a modest 11 percent in the first decade to 48 percent of the estimate what we would have seen from 2004-2012 in the absence of tobacco control,” said Holford. “Today, a 40-year-old man can expect on average to live 7.8 years longer than he would have in 1964, and 30 percent of that improvement can be attributed to tobacco control. The gains for women have been slightly less, 5.4 years, but tobacco control accounts for 29 percent of that benefit.”
Using data collected by the National Center for Health Statistics from 1965-2009, the team recreated smoking life history summaries for groups born each year starting in 1890. These were used along with national mortality statistics and studies that followed large populations to calculate mortality rates by smoking status. This allowed them to estimate the impact of alternative scenarios for what might have occurred had the era of tobacco control never happened.
The tobacco warning was released by then-U.S. Surgeon General Luther L. Terry. It is seen by many as a pivotal moment in American public health and as the opening salvo in an ongoing effort to convince people to stop smoking.
Terry convened a committee of specialists who reviewed some 7,000 scientific articles and worked with more than 150 consultants to formulate the report’s findings. It was released on a Saturday in order to generate maximum media coverage in Sunday’s newspapers. Years after its publication, Terry referred to the report’s release as a “bombshell.”
The report has since spawned numerous other efforts at various levels of government to curb smoking. This has included the now-familiar Surgeon General’s warning on the side of cigarette packages, as well as increased taxation, restrictions on advertising, limiting public areas where people can smoke along with programs and products to help people kick their smoking habit.
While the number of smokers in the United States has decreased significantly over the past several decades, there are still an estimated 44 million Americans who smoke, or about 20 percent of the U.S. population.
Today, smoking continues to claims hundreds of thousands of lives annually and is the single largest cause of preventable death in the United States.
“Tobacco control has been a great success story for public health. We have essentially cut in half the number of tobacco-related deaths each year compared to what would have occurred in the absence of this effort. This is very encouraging, but the halfway point also means that there is more to be done,” said Holford.
Researchers from the University of Michigan School of Public Health, Georgetown University and Fred Hutchinson Cancer Research Center co-authored the study.
Related Story at NPR: "50 Years After Landmark Warning, 8 Million Fewer Smoking Deaths"
(click to link to radio edition)
Related Video at NIH (MedLine Plus): "Quitting Saves Lives..."
(click to link to video)
December 16, 2013
Adrienne S. Ettinger, assistant professor in the Department of Chronic Disease Epidemiology, believes many of us are menaced at home not only by lead in paint but also by toxic gases, allergens, and worse.
When Adrienne S. Ettinger started her first job out of graduate school in public health in 1991, there were an estimated 1.7 million American children with high levels of lead in their blood.
Ettinger would know. She went looking for them in inner-city New Jersey, knocking on doors and asking residents to join studies on home cleaning for lead dust — studies that could help protect children living there. She recalls being struck by people’s openness and willingness to participate.
“It was really amazing how these people would let us into their homes and to every detail of their lives,” says Ettinger, assistant professor in the Department of Chronic Disease Epidemiology. “Your home is your safe place.”
Except, of course, when it isn’t. Many of us are menaced at home not only by lead but also by toxic gases, allergens and worse.
Such hazards are Ettinger’s specialty. In a long career as an environmental epidemiologist, she has focused on housing-related hazards, grappling with substances that may be useful in some contexts but also pose insidious threats in and around our own homes. She has found that mothers living near hazardous waste sites have chemical contaminants in their breast milk. She has also played an important role in managing these hazards nationwide by training workers to think beyond individual problems and focus on the whole home.
In some ways, the home environment is getting safer. The last few decades, for example, have seen a drastic decline in the number of American children with high blood lead levels (BLLs). But Ettinger and her fellow epidemiologists say the task is by no means complete — not for lead, and not for a number of other indoor hazards.
And new threats surface all the time.
Lead is a classic example of a double-edged sword. Added to paint, it produced a durable, washable finish; in gasoline, prior to the catalytic convertor, it improved gas mileage and engine efficiency. It is a crucial ingredient of car batteries, makes an excellent radiation shield, and is tremendously useful in building construction.
Yet it is also a notorious neurotoxin, one that does its damage slowly and all but invisibly. Even at low levels, lead exposure can cause learning disabilities or behavior problems that reduce a child’s chances of educational success. And though lead is no longer used in paint or gasoline in the United States, untold tons of it remain in the environment.
Just how to reconcile these realities is a problem that has occupied Ettinger and other researchers for years. The Centers for Disease Control and Prevention’s (CDC) Healthy Homes/Lead Poisoning Prevention Branch (HHLPPB), where Ettinger worked in the mid-1990s, for example, convenes a federal advisory committee of scientists, advocates and health department officials to discuss lead toxicity as well as other home-based threats. It is the members of this committee who set national guidelines for pediatric blood-level testing and recently lowered the limit of concern. Ettinger, meanwhile, recently oversaw the CDC working group that developed guidelines to identify and manage elevated BLLs in pregnant and lactating women.
While blood tests may reveal lead hotspots, practitioners have to strike a careful balance between eliminating lead from the home and mitigating the hazard it poses. Total lead removal is expensive, and the process can disturb lead so that it may do more harm than good if not done properly. In many cases, it’s better to use such interim control strategies as covering painted surfaces and advising residents to control dust in their homes or flush pipes before drinking their water.
“We made a decision as a country in the early 1990s that we were going to make housing lead-safe, not lead-free,” says program head Mary Jean Brown, Sc.D., R.N., who is the former chief of the CDC’s Lead Poisoning Prevention Branch. “That means that for the foreseeable future, we are going to live with this toxin in our midst.”
Statistics suggest that this relatively modest strategy has paid off. A late 1970s survey found that 88 percent of children between ages 1 and 5 had BLLs greater than 10 micrograms per deciliter (mcg/dL). In the late 2000s, less than 1 percent did. And the reduction has been the most pronounced in African-American and poor children, groups with historically higher blood lead levels — which raises issues of environmental justice. Children who have dodged the lead bullet stand a far better chance in life. Today, about half a million American children still have blood lead levels of 10 mcg/dL or higher — a large and tragic number, but a sign of progress nevertheless.
“With lead [abatement], you get an amazing return on your investment, and we know exactly what to do,” says Rebecca Morley, executive director of the National Center for Healthy Housing (NCHH), formerly the National Center for Lead-Safe Housing.
And yet Ettinger cautions that it’s too soon to declare victory.
Although lead was banned from gasoline and paint in the 1970s, some 38 million units of housing still contain aging lead paint, while much of the soil in urban areas is contaminated by decades of lead emissions from the leaded gasoline era.
Lead from both sources can be inhaled or ingested. When a person takes lead into the body, it accumulates in the tissues, mainly in bone where it will remain for decades and can leach out during pregnancy and cross the placenta. In exposed fetuses, as well as in children who chew paint flakes or a lead-coated toy, lead can cause gradual and irreversible brain damage. The work of Ettinger and colleagues has found that pregnancy and breastfeeding can increase the intergenerational risks for exposure to such environmental contaminants as lead, and that those exposed in the womb may be at greatest risk during the first trimester.
Indeed, no blood lead level appears to be safe in children, so the CDC announced in 2012 that a BLL of 5 mcg/dL should trigger a clinical follow-up. Even levels as low as 2 or 3 mcg/dL raise the risk of poor academic performance and attention-deficit disorder.
Amid the new standards, however, the CDC’s lead-fighting resources have been slashed. The HHLPPB’s 2012 budget was cut to just 7 percent of its 2011 budget, forcing it to withdraw financial support for state and local lead-prevention programs. “Unfortunately, the message about our public health success in this area has been communicated as a ‘job well done,’ when in fact the job is far from being done,” says Morley.
To keep up with dwindling resources, tighter standards, and a shift in public attention, public health programs are changing their approach. Although decades of screening children with blood tests have allowed officials to target problem housing, testing doesn’t offer much to the children themselves because the benefits of therapies like chelation are modest at best. The goal now is to prevent childhood lead exposure entirely — primary prevention — which means a shift toward screening houses, not children, for lead contamination. The hope is to nip lead problems in the bud.
A holistic approach
Even as scientists work to prevent lead poisoning, they’re stepping back to look at what else is wrong with our homes. Why stop with lead and pronounce a house “safe” if it also has fire-prone wiring or rampant allergens or excessive use of pesticides?
In the early 2000s, Ettinger, then a Johns Hopkins faculty member, began to work with the NCHH to develop guidelines for what constitutes healthy housing. “Certain toxic exposures, like lead and tobacco, had their own prevention programs, while others, such as mold and pesticides, were emerging as concerns,” she recalls. “Nobody was really taking a holistic look at the home from a health perspective.”
Under that nonprofit’s auspices and with CDC support, Ettinger and colleagues developed curricula in broad healthy housing principles for public health, housing and energy efficiency professionals. Some 20,000 have since been trained across the country. Today’s HHLPPB is similarly holistic. Its goals include not only the elimination of high BLLs in children but also ensuring that a house’s location, design, construction, maintenance and renovation support the residents’ health.
That’s a huge undertaking. Radon gas alone kills 22,000 people a year from lung cancer — more than twice the number killed by drunk drivers. Carbon monoxide and secondhand smoke continue to foul indoor air. Many houses are permeated by asthma triggers like mold, pesticides and cockroach dander. Carpets emit toxic fumes, as do many substances in newly constructed homes — which was demonstrated by some of the post-Katrina FEMA trailers when they offgassed formaldehyde. Children fall through unguarded high-rise windows and elderly people fall down stairwells when handrails are broken or missing.
Despite limited funds, the HHLPPB is working with the Department of Housing and Urban Development on secondhand smoke, allergens, and ventilation, and with the CDC’s Injury Center on home injuries. The branch maintains an advisory board and a national surveillance system, and it works with epidemiologists to respond to reports of lead in consumer products (in recent months, those have included pirate costumes and eye makeup). The HHLPPB also serves as a federal partner to the training center.
Committing to the big picture in environmental epidemiology may go beyond understanding individual hazards; what’s also needed are a cross-disciplinary approach and a search for unconventional solutions. For example, environmental health and perinatal epidemiology are often housed in distinct academic silos, yet many environmental toxins act on the fetus. Yale’s Center for Perinatal, Pediatric and Environmental Epidemiology (CPPEE), combines these academic disciplines. Ettinger’s colleagues at CPPEE, including co-directors Michael B. Bracken, M.P.H. ’70, Ph.D. ’74, and Brian P. Leaderer, M.P.H. ’71, Ph.D. ’75, are studying the effects of household levels of nitrogen dioxide from gas stoves, and such respiratory effects as asthma in children. That broad outlook drew Ettinger, an experienced perinatal researcher, to join the Yale faculty in 2010.
After years of studying fetal exposure to lead, arsenic, and other hazardous substances, Ettinger has recently begun to look at solutions to indoor health hazards from a nutritional angle. The idea is that if engineering fixes are expensive and impractical, eating protective foods or dietary supplements may offer another way to reduce harm. In pregnant women with high bone lead levels, for example, Ettinger has shown that calcium supplements may partially protect the fetus and nursing infant from lead exposure.
Can we look forward to safer homes in the future?
Morley is optimistic, noting that people are getting savvier about their options and that improved transparency is allowing for more choices. “I think that consumers are on to industry,” she says. “It’s going to be in industry’s best interest to adopt some of these practices for marketing differentiation and for liability protection.” Yet the NCHH’s attempts to speed changes are often frustrated. When the nonprofit proposes safety-related updates to building codes before the International Code Council (ICC), Morley says, it meets with opposition — from the National Association of Home Builders.
Indeed, we seem to take two steps forward and one step back with some hazards. Take energy efficiency: though post-1970s homes are more efficient thanks to tighter construction and more seamless insulation, sealing in heat and air conditioning comes at a cost; toxic substances in the air don’t vent as readily and indoor air quality suffers. Mere awareness and the availability of such tests as the one for radon aren’t sufficient to eliminate problems. Ettinger is also concerned about the potential dark side of useful things like Teflon-coated pans, such plasticizers as BPA and phthalates, indoor pesticides and a myriad of personal care products. And despite all we know about lead, it keeps cropping up where we shouldn’t expect to see it any longer. Constant vigilance is in order.
“Twenty years ago my thesis advisor was being interviewed about lead in lipstick, and now it’s in the news again,” Ettinger says. “There’s a lot that still needs to be done.”
Though it can be hard to abate known hazards, the bigger problem according to Ettinger is simply a lack of knowledge. There are hundreds of thousands of synthetic chemicals on the market, and the health effects of the vast majority are unknown. Decision making may be made harder by groups that advocate blanket avoidance of artificial substances, casting an alarmist light on innovation and subtracting nuance from policy discussions. Yet when we do find that a specific chemical causes harm, Ettinger said, manufacturers often react by changing one of its molecules to create a similar but unstudied substance.
“We need well-conducted peer-reviewed research done by scientists in order to answer these questions,” she says.
From a public health perspective, then, it’s important to neither overlook nor oversimplify indoor hazards. Case in point: the two-sided health effects of chlorine in drinking water, which bears some similarities to our relationship with lead. The substance kills harmful bacteria, preventing potentially deadly waterborne illnesses, yet the byproducts of chlorination that we breathe in during a hot shower or consume in drinking water, for example, can themselves be harmful. There is, it seems, no escaping the big picture.
“It’s not a question of right or wrong,” Ettinger says. “It’s about weighing the risks and getting everything in balance.”
This article originally appeared in the Fall 2013 issue of Yale Public Health magazine. The magazine can be viewed here.
Michael B. Bracken Receives 2013 Lilienfeld Award
For immediate release, July 3, 2013
Michael B. Bracken, Susan Dwight Bliss Professor of Epidemiology at the Yale School of Public Health’s Department of Chronic Disease Epidemiology, and Professor of Neurology and Obstetrics, Gynecology and Reproductive Science in the Medical School, has been named recipient of the the 2013 Abraham Lilienfeld Award. The Lilienfeld Award is the highest honor bestowed by the American College of Epidemiology and is given for “outstanding contributions and leadership in the discipline of epidemiology”. Bracken will address the College at its Annual Meeting in September.
Professor Bracken (MPH '70; PhD '74) has been a Yale University faculty member for 42 years and is a sometime Fellow of Green Templeton College, Oxford University. He is the recipient of numerous NIH grants and has published some 400 papers on a broad range of public health and clinical topics. His recent book "Risk Chance and Causation: Investigating the Origins and Treatment of Disease" was released by Yale University Press in June 2013.
Press Release by Michael Greenwood
October 18, 2012
The first comprehensive sequencing study of the protein coding regions of the genome in a family with both asthmatic and non-asthmatic members has identified several variants that may contribute to the potentially debilitating condition.
Scientists at the School of Public Health’s Center for Perinatal, Pediatric and Environmental Epidemiology used a technique that sequenced only the small fraction of the genome that codes for proteins and identified tens of thousands of variants in each subject’s genome. To understand if there were genetic variants found only within this family that contributed to asthma, the investigators focused on novel variants not present in databases containing sequencing data compiled from more than 1,000 subjects, leaving them with hundreds of family-specific variants.
These variants were then examined to see which ones tracked with asthma in this family and 10 of them tracked perfectly. The investigators were then able to narrow this list down to four based on how likely each specific variation would result in a change in the protein for which it coded. Of these, three genes— PDE4DIP, CBLB and KALRN—are of increased interest due to their potential relationship to asthma.
The research comes from the Perinatal Risk of Asthma in Infants of Asthmatic Mothers study, led by Michael B. Bracken, Susan Dwight Bliss Professor of Epidemiology. Andrew DeWan, assistant professor in the Department of Chronic Disease Epidemiology, led the sequencing effort.
The researchers are seeking to determine the extent to which the well-documented increased risk of asthma to children of asthmatic mothers is due to genetic factors and how much is due to factors occurring in the intrauterine and perinatal period, specifically related to the mother’s own asthma status.
While the study does not provide definitive proof that any of these variants contribute to asthma, the work suggests that careful filtering of variants can provide genes for further investigation. Future work will focus on whether or not any of these genes contain family-specific variants tracking with asthma in additional families. If so, it would provide support for the hypothesis that extremely rare variants in a handful to genes may be contributing to asthma, in concert with common variants in several genes.
Previous work from the group has identified common variants in two genes that may be contributing to asthma susceptibility, as well as a rare genetic deletion. Taken together, the research highlights the complex nature of asthma and supports the hypothesis that numerous genetic factors play a role in determining whether or not a child will develop asthma.
The study was published in the journal BMC Medical Genetics and was supported by a grant from the National Institutes of Health.
By Bill Hathaway, May 25, 2012
Women who are depressed during pregnancy are not at higher risk of giving birth prematurely than non-depressed women — but those who take antidepressants during pregnancy seem to be, a new study by Yale researchers shows.
The results, reported May 25 online in the journal Epidemiology, are good news for women who worry that their depression will harm their baby. Researchers also stress that women who take antidepressants during pregnancy should not be overly alarmed.
“Women did not ask to be depressed and yet they worry that their depression may affect their baby,” said Kimberly Yonkers, professor of psychiatry and of obstetrics, gynecology, and reproductive sciences. “This study tells them they should not worry that they are somehow compromising their pregnancy because they are depressed. And when considering whether to take medication for depression, women should understand that the risk of preterm birth is only one of many factors they should weigh.”
The study found that taking serotonin reuptake inhibitors (SRIs) during pregnancy significantly increased risk of what is called a late preterm birth. Late preterm birth is defined as at least 34 weeks after gestation but before 37 weeks. Antidepressant use is not associated with early preterm birth, which is much more dangerous to the baby.
Yonkers said that several previous studies suggested depression itself might lead to premature birth. The Yale team studied almost 3,000 pregnant women, including those who were diagnosed as depressed during their pregnancy. After controlling for numerous variables such as health history, age, drug use, and socio-economic status, they found no association between depression and premature birth.
They did find a significant risk of preterm birth among women who were taking anti-depressants. So should depressed women not take antidepressants?
“A woman should always consult with her doctor, but if she is symptomatic and suffering the use of antidepressants may be indicated,” Yonkers said.
Kathleen Belanger of Yale was senior author of the paper. Megan V. Smith, Nathan Gotman and Haiqun Lin are other Yale-affiliated authors.
The research was funded by grants from the National Institute of Child Health and Human Development of the National Institutes of Health.
New Haven, Connecticut, March 26, 2012
Michelle Bell, an expert on the environment and human health, has received the inaugural Prince Albert II de Monaco/Institut Pasteur Award for outstanding contributions to her field.
Dr. Bell, professor of environmental health at the Yale University's School of Forestry & Environmental Studies (F&ES), was honored by the Institut Pasteur and the Prince Albert II of Monaco Foundation at a scientific symposium on environmental changes and their impact on human health on March 23 in Monaco.
Prince Albert II of Monaco and the Institut Pasteur, a nonprofit research center in Paris dedicated to the prevention and treatment of disease, established the award to honor scientists for their study of how environmental conditions affect public health.
"We are very delighted by this recognition of Michelle and her research, which reflects well on the strength and diversity of work at F&ES," said Dean Peter Crane. "It also extremely gratifying that the Monaco Award recognizes not only the excellence of Michelle's research, but its great practical importance for public health and environmental policy."
Dr. Bell joined Yale in 2004 and was promoted to professor in 2011. Her research investigates how air pollution and extreme weather contribute to mortality and affect health outcomes such as pregnancy, and how climate change could impact human health. Her work integrates epidemiology, atmospheric sciences, environmental engineering and biostatistics, and is global, with studies in the United States, Europe, Asia and South America.
Dr. Bell has conducted several landmark studies of environmental health. In 2004 she led the largest study to date of the health impacts of tropospheric ozone, establishing a clear link between ozone and premature mortality in 95 large U.S. communities covering about 40 percent of the U.S. population over a 14-year period. The study was published in the Journal of the American Medical Association.
In one of the earliest and largest studies on climate change and air pollution, she estimated changes in ozone levels and the subsequent health response under climate change for 50 U.S. cities by linking air quality, meteorological and climate change models.
Dr. Bell has 70 peer-reviewed publications and has received other prestigious awards, including the National Institutes of Health's Outstanding New Environmental Scientist Award in 2006 and the Health Effects Institute's Rosenblith Award in 2004.
The Environmental Protection Agency, World Health Organization and regional environmental agencies have used her results in establishing health-based policies for air pollution, including particulate matter, ozone and carbon monoxide. "I strive for research that is relevant to the medical community and policy makers and that helps address real-world environmental problems," said Bell.
Press Release, National Institutes of Health, Wednesday, March 14, 2012
Embargoed for Release: 4:00 PM ET, March 14, 2012
NIH study examines the impact of tobacco control policies and programs, and the potential for further reduction in lung cancer deaths
Twentieth-century tobacco control programs and policies were responsible for preventing more than 795,000 lung cancer deaths in the United States from 1975 through 2000, according to an analysis funded by the National Cancer Institute (NCI), part of the National Institutes of Health.
If all cigarette smoking in this country had ceased following the release of the first Surgeon General's report on smoking and health in 1964, a total of 2.5 million people would have been spared from death due to lung cancer in the 36 years following that report, according to the analysis. The results of this study were published online March 14, 2012, in the Journal of the National Cancer Institute.
“These findings provide a compelling illustration of the devastating impact of tobacco use in our nation and the enormous benefits of reducing rates of smoking,” said Robert Croyle, Ph.D., director of the Division of Cancer Control and Population Sciences at NCI. “Although great strides have been made, we cannot relax our efforts. The prevention and cessation of tobacco use continue to be vital priorities for the medical, scientific, and public health communities.”
The researchers, part of the NCI-sponsored Cancer Intervention and Surveillance Modeling Network (CISNET), utilized a comparative modeling approach in which they constructed detailed cigarette smoking histories for individuals born from 1890 through 1970, and then related the histories to lung cancer mortality in mathematical models. Using these models, the researchers were able to estimate the impact of changes in smoking patterns resulting from tobacco control activities on lung cancer deaths during the period from 1975 through 2000. Since the 1964 report, tobacco control efforts in the United States have included restrictions on smoking in public places, increases in cigarette excise taxes, limits on underage access to cigarettes, and efforts to increase public awareness of the hazards of smoking.
“This is the first attempt to quantify the impact of changes in smoking behaviors on lung cancer mortality based on detailed reconstruction of cigarette smoking histories,” said lead author Suresh Moolgavkar, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle. “The methods that were developed as a part of this research should prove to be invaluable to other researchers investigating the adverse health impacts of cigarette smoking.”
In the study, the researchers created three scenarios. In the first, called actual tobacco control, they used data on actual smoking behaviors of men and women in the United States. The second, called no tobacco control, predicted smoking behaviors that would have existed if no tobacco control policies were put in place. In the third, called complete tobacco control, the researchers examined the possible outcome if all smoking in the United States had ceased as of 1965, the first full year after the 1964 Surgeon General's Report on Smoking and Health was released.
The difference between lung cancer deaths in the no tobacco control scenario and the numbers of actual lung cancer deaths provided an estimate of the numbers of lung cancer deaths averted as a result of tobacco control activities. This difference is graphically represented in two charts accompanying this release, based on data from Yale University, which created one of the models used in this analysis. The researchers estimated that, without tobacco control programs and policies, an additional 552,000 men and 243,000 women would have died of lung cancer in the period from 1975 through 2000.
Similarly, the difference between the no tobacco control scenario and the complete tobacco control scenario provides an estimate of the lung cancer deaths that could have been avoided if everyone who smoked quit in 1965 and no one started smoking. If tobacco control efforts had been completely successful, an additional 1.7 million lung cancer deaths would have been averted from 1975 through 2000. In total, if all smoking had ceased completely in 1965, as many as 2.5 million fewer people would have died from lung cancer (1.6 million men and 883,000 women).
“An overwhelming majority of lung cancer deaths can be prevented by eliminating cigarette smoking,” said study author Eric Feuer, Ph.D., chief of NCI's Statistical Methodology and Applications Branch. “The progress that has been made by tobacco control programs and policies in reducing lung cancer deaths represents about a third of the progress that could have been made if all cigarette smoking had ceased in 1965. This finding indicates that, while great strides have been made in tobacco control – averting hundreds of thousands of lung cancer deaths in the United States – continued and enhanced efforts have the potential to avert even more deaths.”
The researchers estimations only run through the year 2000 because, for more recent years, sufficiently detailed data were unavailable when the project began. However, it can be inferred that additional lung cancer deaths have been averted since the year 2000, because according to previous research, smoking rates among U.S. adults have continued to fall, dropping from 23.2 percent in 2000 to 20.6 percent in 2008, and leveling off in recent years. Previous research indicates that much of the decrease in smoking rates can be attributed to tobacco control policies. In addition, although beyond the scope of the journal article, rates of other smoking related cancers, and smoking-related diseases, such as cardiovascular and respiratory diseases, have declined due to tobacco control programs and policies.
In 2011, researchers conducting the National Lung Screening Trial (NLST) found that screening heavy smokers with low-dose spiral CT reduced lung cancer mortality by 20 percent, compared to standard chest X-ray (for more information, see the press release on this study). Even with the potential mortality benefits associated with screening, continued implementation of evidence-based tobacco control policies, programs, and services remains a critical approach to reducing the burden of lung cancer, according to the authors.
CISNET is a consortium of NCI-sponsored investigators who use statistical modeling to improve our understanding of cancer control interventions in prevention, screening, and treatment. This modeling approach, which has been validated in several previous studies, can be used to guide public health research and priorities. The network is working on a project to study the efficacy of lung cancer screening for smokers in different age and exposure level groups, based on the results of benefit for spiral CT screening found in the NLST for heavy smokers.
The results discussed in the paper are based on six different models, developed by members of the CISNET network. The centers that created these models include Erasmus Medical Center, The Netherlands; Fred Hutchinson Cancer Research Center, Seattle; Pacific Institute for Research and Evaluation, Calverton, Md.; Rice University-M.D. Anderson Cancer Center, Houston; Massachusetts General Hospital-Harvard Medical School, Boston; and Yale University, New Haven, Conn. More details about the construction of models will be published in a forthcoming special issue of Risk Analysis – An International Journal.
The NCI's Division of Cancer Control and Population Sciences funded the research under grant numbers CA097415, CA097432, CA097450, CA097431, CA097416, CA097337, CA152956, CA126147, and CA133141.
For more information about CISNET, please visit http://cisnet.cancer.gov/index.html For more information about NCI’s Division of Cancer Control and Population Sciences, please visit http://cancercontrol.cancer.gov/. NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at http://www.cancer.gov/ or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).
About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.
New Haven, Connecticut, March 14, 2012
New Haven, Conn. – Quantifying for the first time the impact of anti-smoking measures on lung cancer mortality, a new study based on a Yale mathematical model finds that more than 800,000 lives were saved in the United States over a 25-year period. The authors also write that 2.5 million people who died from smoking-related lung cancer in this same period might have survived if stricter tobacco control measures had been in effect. The study appears online in the Journal of the National Cancer Institute.
Researchers from the Yale School of Public Health and more than a dozen other universities and institutes formed the Cancer Intervention and Surveillance Modeling Network (CISNET) consortium and used various mathematical models, including one developed at Yale, to analyze trends in cigarette smoking and quantify the impact of various tobacco control measures. Detailed cigarette smoking histories were recreated for generations dating back to 1890 and significant events, such as the U.S. Surgeon General’s landmark report in the mid 1960s on the dangers of tobacco use, were factored in.
Using Yale’s mathematical model to calculate smoking rates, the researchers found that gradual changes in smoking behavior over a 25-year period beginning in 1975 resulted in approximately 824,000 fewer lung cancer deaths, 603,000 of which were among men. Models used by other teams produced similar results, showing tobacco control averted about one third of potentially avoidable lung cancer deaths.
“Tobacco-control strategies in the United States have saved hundreds of thousands of lives from lung cancer death,” said co-author Theodore R. Holford, professor of biostatistics at the School of Public health and leader of Yale’s CISNET team. “But there is still much more that needs to be done because globally millions continue to die from lung cancer caused by smoking. Most lung cancer deaths are preventable and the challenge is to find effective ways to reduce cigarette smoking.”
In the years after the Surgeon General’s report, smoking habits started to change, increasingly influenced by measures such as increased taxation on tobacco, public health campaigns and restricting areas where people can smoke.
Still, the authors note, more needs to be done if deaths from lung cancer are to be further curtailed. “The magnitude of what has been achieved by tobacco control should encourage us to redouble efforts to further reduce the cost in life and treasure from cigarette smoking,” Holford said.
While other factors contribute to lung cancer, such as genetic polymorphisms, the vast majority of cases result from smoking. Smoking-related diseases other than lung cancer were not part of the research.
The study was funded by a grant from the National Cancer Institute.
~By Michael Greenwood (203) 737-5151 or email@example.com
New Haven, Connecticut, Tuesday, October 18, 2011
The National Institute of Environmental Health Science awarded the grant to the principal investigators of the project in late July after they began applying for the funding in February 2010. The next step of the project, which began in 2008 with a $3 million grant from NIEHS, is to pinpoint specific sources of air pollution, the principal investigators of the project said.
Michelle Bell, professor of environmental health at the School of Forestry and Environmental Studies and one of the principal investigators said the purpose of the research project is to analyze the components of particulate matter - solid and liquid particles of varying chemical composition - to determine which of these chemical components are most harmful.
Principal investigator Kathleen Belanger, research scientist and lecturer in epidemiology at the School of Public Health, said the project is important because it addresses an issue that affects all pregnant women.
“There are a variety of choices women can make to protect themselves, but they can’t choose not to breathe,” said Belanger.
Bell added that their research particularly focuses on the particle PM 2.5, which gets its name from its size: 2.5 microns.
These smaller particles are potentially more harmful than their larger counterparts because smaller particles can travel deeper into the lungs and cause more damage to a mother and her child, said Belanger.
PM 2.5 particles can contain chemicals such as sulfate, nitrate and metals, each of which can affect the body in harmful ways, said Belanger. She added that researchers hope to discover the relationship between mothers’ PM 2.5 exposure and the effects on her baby, such as pre-term delivery, low birth weight and unusually small size at birth.
Earlier in the course of their project, the team conducted research that involved collecting air samples in filters set up around Connecticut by the Department of Environmental Protection. The team weighed these filters to determine the amount of PM 2.5 present.
Bell and Belanger said their next goal is to determine the chemical components of PM 2.5 in hopes of determining the sources of this pollution.
“Right now there is a regulation treating all PM 2.5 particles as if they have equal toxicity, which we know and they know is not true, but the scientific community does not have enough information to help decision-makers know what types of particles are more harmful,” Bell added.
Belanger said the research team is currently in the process of cataloguing the filters received from the state of Connecticut, adding that they have begun analyzing 500 of 3,000 filters. Both she and Bell said confirming the hazardous nature of chemicals on pregnant women and fetuses would help yield more effective government regulations.
Belanger said in an email that the team would not have been able to conduct this second part of the study without the grant, as its costs would have been too high to cover independently.
“The current funding rates are quite small, so the vast majority of proposals that are submitted do not get funded, including some very outstanding ones, so we felt very fortunate to receive this award,” said Bell.
According to the EPA website, PM 2.5 can cause respiratory problems such as airway irritation, coughing, difficulty breathing and decreased lung function.
~By Liliana Varman
Staff Reporter, Yale Daily News
Folic acid supplements during pregnancy not connected to childhood asthma risk
PRESS RELEASE, New Haven, Connecticut, September 2011
It has been known for 20 years that folic acid (folate) supplements taken during pregnancy reduce the risk of neural tube defects and possibly other congenital malformations.
However, in recent years it has been suggested that folate, an important regulator of a complex set of pathways necessary for fetal development, may also increase the risk of other diseases in exposed children, particularly allergies and asthma.
In a new study by the Yale School of Public Health, 1,499 women were followed from the first trimester of their pregnancy, and their children were followed to age six. No association was found between childhood asthma and the mother’s use of folic acid in pregnancy, the time in pregnancy during which folate was used or the dose administered.
"Public health interventions affecting the diet of entire populations must be most carefully assessed for possible harms," said Michael B. Bracken, the Susan Dwight Bliss Professor of Epidemiology and the study's senior author. "While the current analysis is reassuring, more work studying the safety of higher doses of folate, than were measured in this study, are needed."
Just over half of the mothers in the study used folate in the month before conception and 88 percent in the third month of pregnancy. By age six years, 15 percent of the children had been diagnosed with asthma. This is a higher rate than normally expected because the study focused on mothers at particular risk for having asthma.
The study was conducted at the Yale Center for Perinatal, Pediatric and Environmental Epidemiology. Three visiting scholars, Marit Martinussen, Kari Risnes and Geir Jacobsen, all of whom are from the Norwegian University of Science and Technology in Trondheim, contributed to the study.
The Yale Center is engaged in a broad research program to examine the causes of childhood asthma, which is reaching epidemic proportions in some parts of the world, including indoor and outdoor air pollutants, medication use and other life style factors in pregnancy and early childhood, as well as genetic causes.
The study appears in the current issue of the American Journal of Obstetrics and Gynecology.
~By Michael Greenwood
Yale Researchers Pinpoint Reasons for Dramatic Rise in C-Sections
New Haven, Connecticut, June 2011
In one of the first studies to examine the reasons for the rising number of women delivering their babies by cesarean section, Yale School of Medicine researchers found that while half of the increase was attributable to a rise in repeat cesarean delivery in women with a prior cesarean birth, an equal proportion was due to a rise in first time cesarean delivery. Among these deliveries, factors such as slowly progressing labor and fetal heart rate concerns were the largest contributors.
The U.S. cesarean delivery rate has increased dramatically over the past decade, with some of the highest increases noted in Connecticut and Rhode Island. Much of the previous research on the reasons for this increase is limited to birth certificate data, which does not record the specific indication or reason for cesarean delivery.
Pre-released online and published in the July issue of Obstetrics & Gynecology, the study was led by Yale researcher Jessica Illuzzi, M.D., of the Department of Obstetrics, Gynecology & Reproductive Sciences. Illuzzi and her co-authors analyzed indications for cesarean delivery on prospectively collected data from over 30,000 births at Yale-New Haven Hospital from 2003 to 2009.
"We found that more objective reasons, such as the baby being in a breech position and placenta previa, remained stable over time, while less objective reasons, such as slow progress in labor and concerns about fetal heart tracings contributed large proportions (>50%) to the increasing primary cesarean delivery rate," said Illuzzi.
In addition, suspected large infants, twin pregnancies, and preeclampsia contributed to the increase despite relatively stable rates of these conditions in the population during the seven-year study. "This suggests that the use of cesarean for these indications is increasing," said Illuzzi.
The researchers also examined some of the commonly cited reasons for increasing cesarean rates. "Despite speculation that the decreasing use of forceps and vacuum-assisted vaginal delivery have led to increasing cesarean delivery rates, our data shows that since 2003 the increase in cesarean for labor arrest disorders was manifested in the first stage of labor prior to full dilation when forceps or vacuum are not appropriate." In addition, maternal-choice cesarean births, often cited as another factor, contributed only a small proportion (8%) to the total increase in primary cesarean delivery in the study.
"Elucidating the reasons for the rise in cesarean delivery can help us consider if the benefits of the surgery based on indication appropriately outweigh the known risks, costs and longer recovery time," said Illuzzi.
Yale authors on the study included Emma L Barber, Lisbet S. Lundsberg, Kathleen Belanger, Christian M. Pettker and Edmund Funai.
Citation: Obstetrics & Gynecology doi: 10.1097/AOG.0b013e31821e5f65
— By Karen N. Peart
Prenatal or early life exposure to antibiotics and risk of childhood asthma: a systematic review
Pediatrics 2011. DOI: 10.1542/peds.2008-1536, Publication via eFirst on May 23, 2011
A review conducted by researchers at the Yale School of Public Health has found that antibiotic use in early life may increase the risk of asthma in children. The study estimated that children exposed to antibiotics in their first year of life had a 16% greater likelihood of developing asthma by the age of 18, while those exposed during gestation -- via antibiotics prescribed to their mothers -- had a 24% greater likelihood. However, the authors caution that these conclusions are not definitive, as many studies included in the review were susceptible to several possible sources of bias.
The study, reported in the journal Pediatrics, was a systematic review and meta-analysis of previously published research that has investigated the connection between antibiotic use and childhood asthma, and included 22 publications in its analysis. The authors sought to minimize bias in their analysis by focusing on studies that controlled for a phenomenon known as 'reverse causality', which is an artificial association between an exposure and a disease that occurs when a disease is causative of an exposure, rather than the other way around. Studies of the connection between antibiotics and asthma are particularly sensitive to this type of bias, since antibiotics may be given to treat early symptoms of unrecognized asthma, which can be mistaken for the symptoms of respiratory infections. However, the Yale group found that, even among studies that attempted to control for reverse causality, there was still a significant association between antibiotics and asthma. This conclusion was also supported by their analysis of studies that examined gestational exposure to antibiotics, which avoids the problem of reverse causality, since the antibiotics are prescribed for maternal infections.
Despite their findings, the authors said that additional well-designed studies are needed before a definitive conclusion can be made about the connection between antibiotics and asthma, since it was not possible to completely rule out the effect of reverse causality and other possible biases in many of the studies published to date.
The role of antibiotics in the development of asthma has received significant attention in recent years due to the so-called "hygiene hypothesis", which theorizes that children who grow up in an overly hygienic environment have a low exposure to bacteria and a resulting increased risk of asthma. This could explain why asthma is much more common in industrialized countries compared to non-industrialized countries. Abnormally low levels of bacteria in the gut during the first few years of life, which can be caused by the use of broad-spectrum antibiotics, has been thought to cause permanent imbalances in the immune system, leading to the development of allergic diseases including asthma.
Antibiotics are routinely given to infants to treat respiratory diseases, even though most of these diseases are viral infections that do not respond to antibiotics. Approximately one-third of all infants in the U.S. receive antibiotic prescriptions, and a similar proportion of mothers receive antibiotics during pregnancy. Michael B. Bracken, Ph.D., who led the study, said, "Even if the increased risk of asthma after using antibiotics is small, the fact that the prevalence of antibiotic use is so high means that a large number of children will develop asthma as a result of this exposure. These findings place added emphasis on the need to reduce unnecessary antibiotic prescriptions during pregnancy and early life."
Dr. Bracken is the Susan Dwight Bliss Professor of Epidemiology at the Yale Center for Perinatal, Pediatric, and Environmental Epidemiology (CPPEE). Other investigators were William Murk, a recent graduate from the Yale School of Public Health and lead author of the study, and Kari Risnes, M.D., a pediatrician from the Norwegian University of Science and Technology and a visiting scholar at the CPPEE.
Infant antibiotic use may increase risk of childhood asthma, Yale study shows
Children who receive antibiotics within the first six months of life are at a significantly increased risk of developing asthma and allergy by 6 years of age, new research by the Yale School of Public Health suggests.
New Haven, Connecticut, January 2011
The study followed a large cohort of women and collected data throughout their pregnancies and from their children until their sixth birthday. The researchers found that infants exposed to antibiotics during their first six months of life were up to 52 percent more likely than their peers who did not receive antibiotics to develop childhood asthma and allergies.
While previous studies have also found that antibiotic use may increase the risk of asthma in children, those studies may have been biased because antibiotics are used to treat respiratory tract infections that could themselves be early symptoms of asthma. The Yale study sought to eliminate this bias and concluded that antibiotic use increased risk of childhood asthma even in children not having experienced respiratory tract infections and in children whose asthma is first diagnosed after 3 years of age.
Another controversy from earlier studies has been whether the effect of antibiotic use is different in children who are genetically pre-disposed to asthma. The Yale research was designed to study this since 40 percent of participating mothers had asthma. The findings suggest that the adverse effects of antibiotic use on asthma risk were much stronger in children who did not have any asthmatic parents. The conclusions are reported online in the American Journal of Epidemiology.
The research was done by the Yale Center for Perinatal, Pediatric and Environmental Epidemiology (CPPEE), and led by Michael B. Bracken, the Susan Dwight Bliss Professor of Epidemiology.
Antibiotic use and increased asthma and allergy risk relates to the so-called “hygiene hypothesis,” which may explain why asthma rates have increased in developed countries by children growing up in an apparently overly hygienic environments, Bracken said. Very early microbial exposure, particularly in the intestinal tract, seems necessary for transition to a mature and balanced immune system in childhood. Antibiotic use, especially broad spectrum antibiotics, may alter microbial flora in the gut, thereby causing imbalances in the immune system and a poor allergic response.
A third of U.S. infants are exposed to antibiotics in the first six months of life, most commonly for respiratory tract infections, although the majority of these diseases are viral and do not respond to antibiotics. The use of broad spectrum antibiotics continues to increase.
"The findings from our study should encourage physicians to avoid unnecessary antibiotic use, especially in low-risk children,” said Kari Risnes, a pediatrician from the Norwegian University of Science and Technology, visiting researcher at CPPEE and the study’s lead author. The other investigators were Kathleen Belanger, Ph.D., a research scientist at Yale, and William Murk, a recent YSPH graduate.
Story by Michael Greenwood
Model Devised by YSPH Researchers Estimates Traffic-Related Air Pollution
New Haven, Connecticut, November 2010
An accurate, economical and comparatively easy-to-use method for estimating traffic-related air pollution has been developed in Connecticut by a team of researchers from the Yale School of Public Health.
Epidemiologists routinely measure air quality in and around residential areas to determine how pollution levels from automobiles and other sources affect the health of people and contribute to conditions such as childhood asthma. But existing methods have drawbacks that limit their effectiveness.
The exposure model was devised by the Yale Center for Perinatal, Pediatric and Environmental Epidemiology and avoids the need for more expensive monitoring efforts. It also relies on readily available public information-such as census numbers, land-use records and traffic data-as the basis for a model that predicts residential nitrogen dioxide (NO2) levels. These statistics and other land-use data, elevation readings, wind speed and population density are all applied to a mathematical model that provides a final reading of NO2 concentrations.
"By using detailed spatial data that on some of the major sources of air pollution and factors affecting their dispersion we are able to estimate levels of environmental exposure at a site," said Theodore R. Holford, the Susan Dwight Bliss Professor of Public Health in Biostatistics and one of the paper's authors. "Our approach provides a cost-effective way of measuring exposure that can be used in environmental epidemiology. In addition, it provides a way of understanding the distribution of exposure, which can be important for developing public health policy."
The research team tested and refined the model at 985 Connecticut residences from 2006 to 2009. The environmental and population variables were determined for each of the test sites and NO2 samples were collected using small air samplers placed outside the back door of each home and left in place for a month. A total of 3,140 samples were used to develop the model. Details of the research are published in the December issue of the journal Atmospheric Environment.
The researchers said that the model suggests that approximately 67 percent of the variation in NO2 levels can be explained by traffic volume and types of land use within two kilometers of a residence. Population density, the time of year and a home's elevation are also factors.
The team's model can be recalibrated and easily applied to residential locations in other states and, potentially, to other countries.
The team recently received funding from the National Children's Study and hopes to work with investigators in other states to calibrate the model for use at their sites. In addition, they are studying the use of this approach for other traffic pollutants, such as elemental carbon.
Current scientific evidence links short-term NO2 exposures with a number of adverse effects, including airway inflammation in people who are healthy and increased respiratory symptoms in people with asthma. Also, nitrogen dioxide is a precursor to several other forms of air pollution, including ozone and nitric acid. In addition, studies show a connection between short-term exposure to elevated NO2 concentrations, and increased visits to emergency departments and hospital admissions for respiratory ailments, especially asthma, according the U.S. Environmental Protection Agency.
The principal author on the project was Katherine J. Skene, who earned her M.P.H. at Yale in 2009 and is now a Ph.D. student at the School of Public Health. Other authors on the paper include Brian P. Leaderer, deputy dean and the Susan Dwight Bliss Professor of Epidemiology in Environmental Health, Janneane F. Gent and Kathleen Belanger, both research scientists, and programmer/analyst Lisa A. McKay.
New Haven, Connecticut, September 3, 2010
Yale researchers have identified three genes containing genetic variations that appear to increase a child’s risk of developing asthma.
The study, done by the School of Public Health’s Center for Perinatal, Pediatric and Environmental Epidemiology, used different techniques to identify each of the genes in question. One approach scanned the human genome and identified a genetic change in the PDE11A gene that was more frequent in asthmatic children than non-asthmatic children. This gene was then scanned in other asthma datasets, the majority of which were found to contain at least one genetic change in this gene that was more frequent in asthmatics.
The findings come from the Perinatal Risk of Asthma in Infants of Asthmatic Mothers (PRAM) study, led by Michael B. Bracken, the Susan Dwight Bliss Professor of Epidemiology. The study assessed the extent to which the well-documented increased risk of asthma to children of asthmatic mothers is due to genetic factors and how much is due to factors occurring in the intrauterine and perinatal period, specifically related to the mother’s own asthma status.
“We now believe that increased susceptibility to asthma and other complex human diseases is caused by very large numbers of quite rare genetic changes,” Bracken said. “Each variant only increases risk slightly and many variants are likely needed in an individual to induce clinical disease.”
A second technique used a novel approach to rank candidate genes for asthma. The researchers systematically reviewed the published literature and identified genes previously reported to be associated with asthma. The authors found 251 genes associated with childhood asthma, reported in 469 publications. The top 50 genes were further tested for mutations in the PRAM subjects. One of these genes—RAD50—contained a mutation that was associated with an increased risk of asthma. This gene has previously been implicated in the control of inflammatory responses, suggesting that mutations to this region result in altered immune system functioning that may lead to a predisposition toward asthma.
Finally, the group replicated an association between asthma and missing genetic material in the T-cell receptor γ gene. They were able to demonstrate that this deletion was present in only a small proportion of the cells collected for DNA extraction. This is potentially significant because it suggests that this type of mutation is not inherited and therefore may be caused by environmental factors.
The findings will appear in upcoming issues of the Journal of Allergy and Clinical Immunology, Human Heredity, and Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis. The research was supported with a grant from the National Institutes of Health.
Taken together, these three genes highlight the complex nature of asthma and support the hypothesis that numerous factors play a role in determining whether or not a child will develop asthma, Bracken said.
The other lead investigators were Andrew DeWan, assistant professor of epidemiology, Kyle Walsh, a Ph.D. candidate in public health, and William Murk, a recent YSPH graduate.
~Story by Michael Greenwood
New Haven, Connecticut, March 2010
A research paper by recent YSPH graduate Elizabeth M. Kang on childhood asthma has won the ACOG/Roy M. Pitkin Award by the American College of Obstetricians and Gynecologists.
The winning paper, “Prenatal Exposure to Acetaminophen and Asthma in Children,” was published in 2009 and suggests that acetaminophen use during pregnancy does not increase risk of asthma in children. The drug is widely used for pain relief.
The $5,000 award recognizes outstanding research published in Obstetrics & Gynecology, a leading journal in the field. Each year, a panel of the journal’s former editorial board selects the top four articles of the year.
Kang graduated with an M.P.H. degree in May 2009 and is a former student of Professor Michael B. Bracken, in the division of Chronic Disease Epidemiology. The research formed Kang’s thesis work which was awarded the Dean’s Prize by YSPH. The study focused on a large cohort of women with data collected and housed at the Yale Center for Perinatal, Pediatric and Environmental Epidemiology (CPPEE). The women were followed throughout their pregnancies and their children were followed for six years, in an effort to elucidate the genetic and environmental risk factors for childhood asthma. Kang’s research looked at the association of acetaminophen use in pregnancy and risk of asthma in the children. Her analysis did not support an association and her publication showed that earlier contrary reports may have resulted from residual confounding.
Given that acetaminophen is the drug of choice for pain relief in pregnant women, Kang’s study provides reassurance that antenatal acetaminophen use has limited, if any, effects on asthma development in children.
Kang is currently working at the Food and Drug Administration. Other authors on the paper were Lisbet Lundsberg, Ph.D., M.P.H., and Jessica Illuzzi, M.D., M.S., from the CPPEE.
Yale Increases Participation in Largest Study Ever on How Genes and Environment Affect Children’s Health
New Haven, Conn. — The Yale School of Public Health has received a $10.7 million grant to increase it’s participation in a national study that will follow 100,000 children from before birth to age 21 to understand factors that contribute to their health and development. Last year, Yale was awarded $15 million to start the work in New Haven County. In this additional component, mothers and children from Litchfield County, Connecticut, will join the project.
The study, believed to be the largest of its kind ever undertaken, is a collaboration between the U.S. Department of Health and Human Services and the U.S. Environmental Protection Agency. The goal is to seek information that can be used to prevent and treat some of the nation’s most pressing health problems, including autism, birth defects, diabetes, heart disease, and obesity. Funding is by a special line item in the federal budget and the national study is overseen by the National Institute of Child Health and Human Development.
“The National Children’s Study is poised to identify the early antecedents of a broad array of diseases that affect both children and adults,” said Elias Zerhouni, M.D., director of the National Institutes of Health (NIH). “Such insights will lead to the means to successfully treat and even prevent conditions that to date have defied our best efforts.”
Duane Alexander, M.D., director of the NIH’s National Institute of Child Health and Human Development, said the researchers will examine “not only what children are eating and drinking, but what’s in the air they breathe, what’s in the dust in their homes, and their possible exposures to chemicals from materials used to construct their homes and schools.”
He said the researchers also would analyze blood and other biological samples from study participants to test for exposure to environmental factors and examine whether those factors might influence their health.
Ultimately, there will be 105 study locations in urban and rural areas. The centers were chosen for their strong ability to collect data for the study and to build extensive community networks for recruiting eligible women and newborns, as well as a demonstrated capability to protect the privacy of the information collected on participants. The centers include universities, hospitals, and health departments.
“This important expansion of one of the most important epidemiological studies in the United States today to include mothers and children form Litchfield County is a testament not only to the importance of this landmark study but the expertise of our faculty,” said Paul Cleary, Dean of the School of Public Health.
“I am delighted that Dr. Bracken has been funded to continue and extend his work on this cohort. Prospective studies such as this are critical to our understanding of factors that improve and cause risk to our health,” said medical school Dean Robert J. Alpern.
The Yale Center for Perinatal, Pediatric and Environmental Epidemiology is conducting the study in collaboration with the Departments of Obstetrics and Gynecology, and Pediatrics, under the direction of Michael B. Bracken, principal investigator and Susan Dwight Bliss Professor of Epidemiology, and Kathleen Belanger, Research Scientist in Epidemiology. Other lead investigators are Dr Jessica Illuzzi, Assistant Professor of Obstetrics and Gynecology and Lisbet Lundsberg, Associate Research Scientist in Epidemiology.
The Center currently is studying disease in pregnancy, early infancy and childhood. These studies evaluate genetic, perinatal, and environmental risk factors that lead to early onset and more severe illness in children and young adults. Studies are also being conducted on the causes of preeclampsia, which continues to be a leading cause of morbidity in pregnancy; the relationship between emotional health and pregnancy outcome, and the effects of air pollution on asthmatic symptoms and infant development.
The role that home stoves and heating systems may play in the onset of asthma and its severity has been much studied and debated. Two researchers from the Yale School of Public Health, Kathleen Belanger, Ph.D., and Elizabeth W. Triche, Ph.D., reviewed dozens of unrelated international studies on the topic and found that most research supports a link between indoor combustion sources—fireplaces, woodstoves, kerosene heaters, gas stoves and flued or nonflued gas heaters—and asthma, particularly in children.
The Yale researchers reviewed published studies done in Asia, Europe, Australia and the United States. And while there were some discrepancies in their conclusions, most of the research found that repeated exposure to an indoor combustion source (or sources) appeared to put both adults and children at greater risk of asthma or exacerbated existing symptoms. Indoor combustion produces a variety of gases and particulate matter in a house that residents end up inhaling.
“Exposure to nitrogen dioxide and fine particles in inner city homes can exceed levels allowable in outdoor air by the U.S. Environmental Protection Agency, and the population exposed is the most vulnerable: asthmatics, infants and the elderly,” Belanger said.
In particular, the Yale researchers drew the following conclusions from the research papers surveyed:
- Indoor combustible heating appears to pose a greater risk for asthmatics than exposure to cooking sources.
- Exposure to coal is particularly risky. The effects of wood burning stoves and fireplaces on asthma were less conclusive.
- Nonflued gas heaters in a home pose a significant risk. Removing this type of heating system appears to reduce asthma symptoms in children.
- Differences in asthma symptoms between boys and girls may be related to differences in exposure, or may be due to gender differences in susceptibility.
A factor that could have contributed to the varied results in the different studies could be the characteristics of the combustible appliance in question (including type, age and the frequency and duration of its use) along with the type of home in which it is installed.
Details of the study will appear in the August issue of the journal Immunology and Allergy Clinics of North America.
~ Story by Michael Greenwood
FOR IMMEDIATE RELEASE: July 2008
New Haven, Conn — Women who eat chocolate are at decreased risk of developing preeclampsia, a potentially dangerous complication of pregnancy, a Yale study suggests.
The conclusions are reported in the current issue of the journal Epidemiology.
A team headed by Elizabeth Triche of the Yale Center for Perinatal, Pediatric and Environmental Epidemiology wanted to see if chocolate, particularly dark chocolate which had been previously linked to improved cardiovascular health, might also offer protection to pregnant mothers against preeclampsia. Preeclampsia is a disorder characterized by dangerously high blood pressure and protein in the urine. Pregnant women who suffer from the condition sometimes complain of swelling, sudden weight gain, headaches and vision problems.
The study looked at self-reported chocolate consumption and also at levels of a byproduct of chocolate consumption, called theobromine, in the cord blood of pregnant women. Although the study did not distinguish between dark and other kinds of chocolate, dark chocolate has higher levels of theobromine.
The study of 1,681 women showed that those who reported chocolate consumption of more than five servings a week had a lower risk of developing preeclampsia. Among the 1,346 women with cord blood data available, those with higher theobromine levels had significantly lower risk of developing preeclampsia than those who had low levels of theobromine.
Results were particularly dramatic for women with the highest levels of theobromine. Women who had levels in the top quartile for theobromine were nearly 70 percent less likely to develop preeclampsia than women in the lowest quartile for theobromine. Having the theobromine data available as a more objective measure of chocolate consumption was a strength of the study, Triche said.
Researchers have speculated that the presence of anti-oxidants called flavonoids in dark chocolate may confer cardiovascular benefits.
“This looks promising, but we need to do more research into how much and what type of chocolate is the most beneficial,” Triche said.
Triche also cautioned that the study results do not mean pregnant women can eat all the chocolate they want. Excess consumption of all sweets can lead to weight gain and other health problems, she noted.
Citation: Epidemiology Vol. 19: 459-464 (May 2008)
-Story by Bill Hathaway
FOR IMMEDIATE RELEASE: April 29, 2008
New Haven, Conn. — The Yale School of Public Health has received a $15 million grant to take part in a national study that will follow 100,000 children from before birth to age 21 to understand factors that contribute to their health and development.
The study, believed to be the largest of its kind ever undertaken, is a collaboration between the U.S. Department of Health and Human Services and the U.S. Environmental Protection Agency. The goal is to seek information that can be used to prevent and treat some of the nation’s most pressing health problems, including autism, birth defects, diabetes, heart disease, and obesity. Funding is by the National Institute of Child Health and Human Development.
“The National Children’s Study is poised to identify the early antecedents of a broad array of diseases that affect both children and adults,” said Elias Zerhouni, M.D., director of the National Institutes of Health (NIH). “Such insights will lead to the means to successfully treat and even prevent conditions that to date have defied our best efforts.”
Yale Medical School Dean Robert Alpern, M.D., said, “I am delighted that Yale will serve as one of the study centers in this important cohort of children. Receipt of this award is a tribute to the quality of the investigators and to Yale.”
Duane Alexander, M.D., director of the NIH’s National Institute of Child Health and Human Development, said the researchers will examine “not only what children are eating and drinking, but what’s in the air they breathe, what’s in the dust in their homes, and their possible exposures to chemicals from materials used to construct their homes and schools.”
He said the researchers also would analyze blood and other biological samples from study participants to test for exposure to environmental factors and examine whether those factors might influence their health.
Paul Cleary, dean of the Yale School of Public Health, said, "We are delighted that investigators at the Yale School of Public Health and Yale School of Medicine have been selected for a leadership role in the National Children's Study. This is the largest study of its kind ever undertaken in the world and will provide information about factors affecting the health of children, including behavior patterns, environmental factors, genes, and how all those interact. The data from this path breaking study will provide unprecedented information about how to protect and promote the health of individuals."
In this first phase of funding, 22 study centers were selected to oversee 26 locations. Ultimately, there will be three rounds of funding and 105 study locations in urban and rural areas. The centers were chosen for their strong ability to collect data for the study and to build extensive community networks for recruiting eligible women and newborns, as well as a demonstrated capability to protect the privacy of the information collected on participants. The centers include universities, hospitals, and health departments.
The Yale Center for Perinatal, Pediatric and Environmental Epidemiology will conduct the study in collaboration with the Departments of Obstetrics and Gynecology, and Pediatrics, under the direction of Michael Bracken, principal investigator and professor of epidemiology and public health, and Kathleen Belanger, research scientist.
The center currently is studying asthma, from pregnancy and early infancy to childhood. These studies evaluate genetic, perinatal, and environmental risk factors that lead to early onset and more severe asthma in children and young adults. Studies are also being conducted on the causes of preeclampsia, which continues to be a leading cause of morbidity in pregnancy; the relationship between emotional health and pregnancy outcome, and the effects of air pollution on asthmatic symptoms and infant development.
“Enrolling families in a study that will follow their children for 20 years is both exciting and challenging,” Belanger said. “The support our Center has traditionally received from community hospitals and community based obstetricians and pediatricians makes this study possible.”
-Story by Jackie Weaver
FOR IMMEDIATE RELEASE: October 4, 2007
The British Medical Journal (BMJ) has named the 1992 book, Effective Care of the Newborn Infant, edited by Jack Sinclair, M.D., FAAP, and Yale School of Public Health's Michael B. Bracken, Ph.D., M.P.H., Susan Dwight Bliss Professor of Epidemiology in the Division of Chronic Disease Epidemiology, one of the landmark publications that have influenced how the medical community views evidence-based medicine. Evidence-based medicine has been named as one of the 15 most important medical milestones since 1840.
The most common definition of evidence-based medicine is “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research.” 1Effective Care of the Newborn Infant along with Effective Care in Pregnancy and Childbirth (Chalmers, I., Enkin, M., and Keirse, M, 1989) which was also noted in the article, were two of the first textbooks, both published by Oxford University Press, to use systematic review methods to support the clinical recommendations being made.
“These methods take into account all the valid evidence on a topic and may use meta-analytic techniques to summarize the best data,” states Bracken. “This is quite different from older texts which used ‘expert’ opinion and often produced biased reviews of available evidence.”
Bracken’s primary research interest is the epidemiology of diseases of pregnancy and newborns, emphasizing environmental and genetic risks for causation and iatrogenic factors in patient care. He is the Co-Director of the Yale Center for Perinatal, Pediatric and Environmental Epidemiology, which conducts research in obstetric, perinatal, and neonatal disease. Bracken is an editor of the Cochrane Neonatal Review Group and President of the Society for Epidemiologic Research. Dr. Bracken is also a Fellow of Green College at Oxford University.
BMJ is one of the most influential and widely read medical journals. BMJ has been published since 1840, aiming to produce original scientific studies, articles and papers on the clinical, scientific, social, political, and economic factors affecting health. Please see the January 6, 2007 issue of BMJ for the full articles, Evidence Based Medicine: Increasing, Not Dictating, Choice and Milestones on the Long Road to Knowledge.
-Story by Marcie Foley
1. David L. Sackett, et al. Evidence Based Medicine: What It Is and What It Isn't BMJ 312(7023): 71-72, 1996.
New Haven, Conn. — The intensive and prolonged observation of infants at risk for group B streptococcus (GBS) may not benefit the infant and may heighten parental anxiety, researchers at Yale School of Medicine report in a recent article in Obstetrics & Gynecology.
Current Centers for Disease Control and Prevention (CDC) guidelines recommend at least four hours of antibiotics to treat GBS in pregnant women in labor. About 50 percent of women with GBS are unable to receive the full four hours of treatment due to rapid labor and delivery. The CDC considers their newborns “at risk” for GBS and recommends blood tests and 48 hours of observation in the hospital.
Researchers from Yale School of Medicine’s Departments of Obstetrics, Gynecology & Reproductive Sciences (Ob/Gyn), and Epidemiology and Public Health (EPH) sought evidence to support the CDC guidelines. They conducted a systematic review of all published studies that included the duration of GBS antibiotic treatment of women in the delivery room and the numbers of infants who developed GBS. They calculated risk ratios for GBS colonization or sepsis based on duration of treatment.
“Neither the pharmacologic literature nor the clinical literature provide evidence to support the current CDC guidelines about duration of antibiotic prophylaxis during labor,” said Jessica Illuzzi, M.D., assistant professor in Yale Ob/Gyn who conducted the study with Michael Bracken, the Susan Dwight Bliss Professor of Epidemiology in EPH and Professor of Neurology and Ob/Gyn.
“The current protocol results in large numbers of low risk newborns undergoing invasive, expensive neonatal testing and prolonged observation, despite the lack of evidence that this group of infants is at higher risk for GBS infection,” Illuzzi added.
She said the pharmacologic literature reveals that effective levels of antibiotics are detectable in the fetal bloodstream and amniotic fluid as early as five minutes after treatment begins. The risk of neonatal GBS infection is also significantly reduced after one to two hours of treatment.
“Ultimately, we hope the CDC guidelines will be re-evaluated and revised to reflect the evidence so that resources, invasive testing and prolonged observation are directed to infants truly at risk for GBS disease,” said Illuzzi.
Future research by Illuzzi and Bracken include a possible prospective study to measure the duration of treatment and the spread of GBS among newborns.
Citation: Obstetrics & Gynecology, Vol. 108, No. 5 (November 2006)
Environment School Scientist Receives NIH Award to Study Relationship Between Ozone and Disease
A Yale environment school professor is one of eight scientists to receive an Outstanding New Environmental Scientist (ONES) award from the National Institutes of Health.
Michelle Bell, assistant professor of environmental health at the Yale School of Forestry & Environmental Studies, will receive $500,000 to study the relationship between outdoor concentrations of ozone, a reactive form of oxygen that is a primary component of urban smog, and the incidence of respiratory disease and death in exposed populations.
Bell is one of two Yale University professors to receive a ONES award. Sven-Eric Jordt, assistant professor of pharmacology in the School of Medicine, will study the way in which certain airborne pollutants interact with sensory nerve cells in order to produce eye, nose and throat irritation.
The National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health, awarded grants totalling $3.6 million, which will support the scientists, who are all pursuing careers in environmental health research, over five years.
“The ONES Program is designed to provide a strong foundation for outstanding scientists who are in the early, formative stages of their careers,” said David Schwartz, director of the National Institute of Environmental Health Sciences. “These grants will assist the scientists in launching innovative research programs that focus on human disease and the influence of the environment.”
NIH officials explained in their own announcement that the program is a key element of the NIEHS 2006 Strategic Plan, a five-year blueprint for identifying and funding new research initiatives that will address the diseases and environmental exposures that are likely to have the greatest impact on human health. One of the primary goals of the plan is the recruitment and training of promising young scientists who are prepared to make long-term commitments to environmental health research.
Research supported by the ONES grants will cover a broad range of environmental exposures along with the biological responses they elicit. Each of the awardees will focus on a specific human disease or condition as it relates to a specific environmental exposure. The ultimate goal of the research is to link the effects of these exposures to the cause, moderation or prevention of environmentally-related diseases.
For more information about the NIEHS Strategic Plan, please visit: http://www.niehs.nih.gov/about/od/strategicplan/index.cfm
Michelle L. Bell, Assistant Professor at the Yale School of Forestry & Environmental Studies (Photo: Harold Shapiro)
Department of Public Health Announces Grant Recipients for Biomedical Research into Tobacco-related Illnesses
April 28, 2006
Elizabeth Triche, Ph.D. of Yale University School of Medicine will receive $349, 893 to conduct a cohort study of low-income pregnant women who smoked at least 10 cigarettes per day for at least a year prior to pregnancy. This study will test whether polymorphisms in genes regulating neurotransmitter pathways are related to smoking cessation during pregnancy, and to relapse after pregnancy. Click here for full press release.
Yale Center for Perinatal, Pediatric and Environmental Epidemiology
March 30, 2006
Co-Director of the Center, Professor Michael Bracken, was a member of the National Institutes of Health State of the Science Panel on Cesarean Delivery on Maternal Request (CDMR) as compared to planned vaginal delivery. The panel found insufficient evidence to fully evaluate the benefits and risks of CDMR and recommended that until quality evidence becomes available, any decision to perform a CDMR should be carefully individualized and consistent with ethical principles. A copy of the Panel's report can be viewed by clicking here.
For immediate release
January 30, 2006
A paper in the current issue of the American Journal of Epidemiology reports that mothers with asthma who are carrying a female fetus are more likely to experience worse symptoms of asthma than are mothers carrying a male fetus. This study is one of the first, and is by far the largest study, to investigate the effect of fetal sex on mother’s asthma severity. It is also one of the largest to investigate the effect of fetal sex on any disease of the pregnant mother.
The investigators studied 702 pregnant women throughout southern New England who were trained to assess their lung function, which they did for 10 days at selected points in their pregnancy. Lung function was recorded automatically and a large number of other factors that might influence mother’s asthma severity were also measured.
Asthma severity in mothers with both male and female fetuses worsened until about 30 weeks gestation after which there was an improvement in lung function. However, across pregnancy, mothers with a male fetus had 10% better lung function than mothers of a female fetus. This difference due to sex is potentially important but needs to be placed in the context of other factors which have a greater impact on the severity of mother’s asthma, including: inadequate medical management of asthma symptoms, and whether the mother was a smoker or not.
The mechanism for this effect of fetal sex is unclear. The authors speculate that testosterone, which male fetuses are known to secrete, may relax the mother’s bronchial tissue and inhibit response to histamines. There are other sex-specific factors excreted found in female fetuses that may exacerbate inflammation in mothers but these are all areas needing more research.
Asthma is one of the most common diseases found in pregnancy. Work by these same authors using national data, to appear later in spring of 2006, documents that 8 to 9 percent of all pregnancies are to women with a history of asthma. The principal author of this research is Dr Helen Kwon, now at Columbia University in New York , who completed this work as a doctoral student in Epidemiology at Yale. Her co-authors are Kathleen Belanger, Theodore R Holford and Michael B. Bracken, all from the Yale University School of Medicine.
The Yale Center for Perinatal, Pediatric and Environmental Epidemiology conducts population based research into a broad range of environmental, clinical, behavioral and genetic factors that influence the health of pregnant women, their infants and children. Details can be found at: http://publichealth.yale.edu/cppee/
Kwon HL, Belanger K, Holford TR, Bracken MB. Effect of fetal sex on airway lability in pregnant women with asthma. Am J Epidemiol 2006; 163; 217-221.
July 6, 2005
Michael B. Bracken, Susan Dwight Bliss Professor of Epidemiology, Obstetrics and Gynecology, and Neurology and Co-Director of the Yale Center for Perinatal Pediatric and Environmental Epidemiology, has been elected the next President of the Society for Epidemiologic Research, the largest epidemiological society in the world.
Professor Bracken is a former President of the American College of Epidemiology, and previously served as Head of Chronic Disease Epidemiology in Yale Medical School. Internationally known for his research on the diseases of pregnancy and newborns, and neurological injury, he has published over 275 papers and two books in the scientific literature. Earlier this year Professor Bracken was elected a Fellow of Green College, Oxford University.