Predict My Future reveals the answers to one of life's most fundamental questions: what makes us who we are? 43 years ago a New Zealand medical school embarked on a remarkable project—the ultimate nature versus nurture test. They decided to follow every one of the 1,037 babies born in the city of Dunedin between April 1972 and March 1973 for their entire lives. And they have. Those children have... Read More
Predict My Future reveals the answers to one of life's most fundamental questions: what makes us who we are? 43 years ago a New Zealand medical school embarked on a remarkable project—the ultimate nature versus nurture test. They decided to follow every one of the 1,037 babies born in the city of Dunedin between April 1972 and March 1973 for their entire lives. And they have. Those children have become the 1,000 most studied people in the world.
For almost four decades every aspect of their health and development has been monitored—their genes, their growth, their physical well-being, their psychology, their emotional ups and downs, criminal convictions, successes, failures—the lot. The result is the Dunedin Longitudinal Study, the broadest and the most in-depth study of human beings in the world. The project has become the richest and most productive archive of human development anywhere. It is truly unique; the study has retained an unprecedented 96% of its starting participants. It is re-writing the book on what makes us all human. Predict My Future details the study's findings, and explores what they have to say about all our lives. This series has a global audience and is being screened across Europe, and in Australasia, with additional territories in negotiation.
Join us for a screening of the first installment of the four-part documentary in the Connection at SSRI. Lunch will be provided and gourmet cotton candy will be spun on site.
Professor Terrie Moffitt, associate director of the study, will introduce the documentary and stay for a Q&A after the showing.
Please let us know if you can join us. View the invitation and RSVP here. What: Predict My Future
When: Friday, October 28th at noon
Where: The Connection, SSRI, 2nd Floor Gross Hall
The Stochastic Process Model (SPM) represents a general framework for modeling joint evolution of repeatedly measured variables and time-to-event outcomes observed in longitudinal studies, i.e., SPM relates the stochastic dynamics of variables (e.g., physiological or biological measures) with the probabilities of end points (e.g., death or system failure). SPM is applicable for analyses of longitudinal data in many research areas; however, there are no publicly available software tools that implement this methodology. The R-package “stpm” comprises the SPM-methodology and allows for estimating several versions of SPM currently available in the literature including discrete- and continuous-time multidimensional models and a one-dimensional model with time-dependent parameters. Also, the package provides tools for simulation and projection of individual trajectories and hazard functions.
Download and install
“stpm” is available as open source software from the following links: https://cran.r-project.org/web/packages/stpm/ (stable version), http://github.com/izhbannikov/spm (most-recent version)
Contact: firstname.lastname@example.org, email@example.com
Linda Burton, dean of the social sciences and a professor of sociology, examines poverty from a worldwide, interdisciplinary perspective. Contributors discuss the leading theories and conceptual debates regarding poverty, the most salient topics in poverty research and the far-reaching consequences of poverty on the individual and societal level.
The Duke-UNC Social and Biological Determinants of Health Working Group wrapped up the fall semester with their second meeting on December 7th.
We are hoping to re-convene in early 2016 to continue the group’s goal of narrowing down definitional clarity and synthesis across fields.
Social and Biological Determinants of Health Working Group Leadership:
Mike Shanahan (Sociology, UNC/CPC )
Jenny Tung (Evolutionary Anthropology, Duke/DUPRI)
- Dan Belsky (Medicine, Duke/DUPRI)
- Noah Snyder-Mackler (Evolutionary Anthropology, Post-Doc, Duke/DUPRI)
- Susan Alberts (Biology Duke/DUPRI)
- Claire Yang (Sociology, UNC/CPC)
- Kathie Harris (Sociology, UNC/CPC)
- Lauren Gaydosh (Sociology Post-Doc, UNC/CPC)
- Allison Aiello ( Epidemiology, UNC/CPC)
- Lisa McGraw, (Biology, NC State)
- Heather Patisaul, (Biology, NC State)
November 3, 2015, Meeting Summary. The current working group includes membership divided evenly between the social sciences and natural sciences, with representation from Duke, UNC, and NC State and senior faculty, junior faculty, and post-docs. The approaches members use is broad, but we overlap strongly on two shared research interests: social behavior and its health/fitness outcomes. Based on e-mail responses from the working group members and discussion during the meeting, the strongest contribution we think we can make comes first from providing definitional clarity and synthesis across fields, with the possibility, down the road, of collaboratively conducting synthetic analyses. However, the group converged on a more definitional/conceptual synthesis as a primary goal. Meeting Venue: UNC/CPC
To move the dialogue forward, the group decided to roughly separate into the “social science” and “natural science” contingents, and identify “blind spots” in how our fields view the social/biological determinants of health. The goal was to share these blind spots with the other contingent several weeks before the next meeting, so that the other group could evaluate whether an alternative disciplinary perspective could help resolve the issue, drawing on current literature/research (i.e., “I have the perfect paper for you!”). Noah Snyder-Mackler set up a Slack account to promote and track this dialogue
December 7, 2015, Meeting Summary. Jenny Tung provided a summary of key questions that emerged via on-line discussion. The group divided themselves into those in the social sciences fields (Shanahan, Harris, Yang, Gaydosh, Belsky), and those in the natural sciences fields (Tung, Alberts, Snyder-Mackler, Mc Graw, Patisaul) to discuss what each group would like to learn from the other. A discussion based on literature, frameworks and models followed. Key barriers included disconnect in the definition of similar terms (e.g. selection, mediation) or lack of familiarity with constructs belonging to other disciplines (e.g. Niche construction, social isolation). The group determined that discussion will continue on-line via slack, but that a synthetic/definitional paper based on these discussions might be valuable and unprecedented product. Nonetheless all agreed on the need to define and narrow audience and forum for this product. Next meeting to be scheduled in January 2016. The need to reassess both membership and frequency of meetings was also raised. Meeting Venue: Duke University
Joseph Lariscy, a Sociology postdoctoral fellow in DUPRI’s National Institute on Aging-funded training program, has received the Minnesota Population Center's 2014 IPUMS-USA Research Award for the "best published or unpublished work by a graduate student." His paper titled, "Hispanic Older Adult Mortality in the United States: New Estimates and an Assessment of Factors Shaping the Hispanic Paradox" was published in Demography 52:1.
Hispanics make up a rapidly growing proportion of the U.S. older adult population, so a firm grasp of their mortality patterns is paramount for identifying racial/ethnic differences in life chances in the population as a whole. Documentation of Hispanic mortality is also essential for assessing whether the Hispanic paradox—the similarity in death rates between Hispanics and non-Hispanic whites despite Hispanics’ socioeconomic disadvantage—characterizes all adult Hispanics or just some age, gender, nativity, or national-origin subgroups. We estimate age-/sex- and cause-specific mortality rate ratios and life expectancy for foreign-born and U.S.-born Hispanics, foreign-born and U.S.-born Mexican Americans, non-Hispanic blacks, and non-Hispanic whites ages 65 and older using the 1989–2006 National Health Interview Survey Linked Mortality Files. Results affirm that Hispanic mortality estimates are favorable relative to those of blacks and whites, but particularly so for foreign-born Hispanics and smoking-related causes. However, if not for Hispanics’ socioeconomic disadvantage, their mortality levels would be even more favorable.
CAROLINA POPULATION CENTER
400 MEADOWMONT VILLAGE CIRCLE, ROOM 200
SEMINAR: 1:00PM – 5:15PM
The fourth annual Demography ("Days") Daze workshop is a collaboration between the Carolina Population Center (CPC) and DuPRI. This year's events was held May 14 at CPC and included talks on innovations and emerging issues in Population Science.
More info and registration can be found at http://www.cpc.unc.edu/events/demography-daze-2015
The third seminar will focus on Sensitive Periods, Plasticity and Resilience and will feature brief presentations by:
Allison Aiello, Professor of Epidemiology, Gillings School of Global Public Health, Faculty Fellow CPC, the University of North Carolina at Chapel Hill
Jenny Tung, Assistant Professor in the Department of Evolutionary Anthropology and Biology, Faculty Associate DuPRI, Duke University.
An informal discussion will follow.
This collaborative seeks to establish a forum in which scholars from both the social sciences and biological sciences may raise and discuss current progress and challenges in key areas related to social and biological determinants of health, while sharing diverse, expert opinions on major outstanding questions in these key areas.
Join us for a lively discussion and enjoy light refreshments!
Date: Tuesday, April 21, 2015
Time: 5:00-6:30 PM
Venue: Smith Warehouse, Bay 6, Second Floor, Room 271, 114 South Buchanan Street, Durham, NC
*please see website for detailed directions*
Parking: The parking lot on the south side of the Smith Warehouse can be accessed from the Maxwell/Buchanan or Maxwell/Campus Drive intersections. Detailed parking instructions will be emailed to registrants.
Dear DUPRI Colleagues,
I am touching base with you all as we approach the end of the spring semester to bring you up to date on all that has been happening with DUPRI and its affiliated centers this year. DUPRI is a network of cooperating centers that shares staff and spatial resources in association with the Social Science Research Institute (SSRI). The core centers in this network include the Center for Population Health and Aging, the Duke Network Analysis Center, and the Duke Center for Population Research, but each has other affiliated centers as well. Each core center has distinctive intellectual aims and research needs, but many faculty have overlapping memberships across these centers. The bases for these overlapping memberships include common interests in excellence and scientific impact in (1) research on the social bases of physical and mental health across the lifespan and across social contexts; (2) innovative data collection and analysis strategies to enrich our knowledge of lives across time and space; and (3) training and mentorship of the next generation of population scientists.
Much work has been done in the last two years to secure the scaffolding of our networked organization of population scientists. Our primary efforts have been directed at winning university and federally funded support for the DUPRI center infrastructure (principally staffing and programmatic space). The NIA P30 center grant awarded September 2014 to the Center for Population Health and Aging (CPHA) is the first weight-bearing component of this scaffolding. The second to be reviewed at NICHD shortly is the PRC grant proposal for a general population dynamics center called the Duke Population Research Center (DPRC). The third is the Duke Network Analysis Center (DNAC) that is pending award as a NIH R25 center. We have received university support directly from the Dean of Arts & Sciences and the Provost office and indirectly from the Provost through the Social Science Research Institute. This support has come (with more to come conditional on funding) as direct support for staff, programming and new space.
DUPRI also responded to the SSRI $250k Challenge for innovative proposals for data analysis this Spring and has been recognized to move to a second round of discussions with the DUHS to establish a Duke infrastructure to support regular mechanisms for collaboration between population scientists and DUHS through access to medical center databases and collaborations on clinical research projects. This negotiation is in progress. You will be invited to participate in this process, with an initial meeting on Monday April 27th (the announcement has been transmitted to you). This promises to be a long-term signature program for population science at Duke. It will probably take the next half year to develop such an infrastructure, but we have the active attention of Medical Center folks and we ask for your involvement in the months to come.
Currently, we are working to submit a continuation of the NIA supported T32 training grant supporting doctoral and postdoctoral students in the social and economic demography of aging, which we have had for over 25 years. If you have been invited to become involved in this effort (which faces a May 25, 2015 deadline), please respond. If you are interested in being involved, please contact DUPRI.
Finally, woven through all these efforts has been a robust emergent collaboration with UNC-Chapel Hill’s Carolina Population Center. You have probably noticed announcements of jointly sponsored seminars and speakers. NIH funding has already resulted from this collaboration. Our hope is that more collaboration will come in the future.
This has all been possible because Duke has a productive and growing network of scientists making groundbreaking contributions in population studies, not only on human populations but also primate populations, at the ecological, social and molecular levels.
Angela M. O’Rand, Ph.D.
Professor of Sociology and Director of the Duke Population Research Institute and
the Center for Population Health and Aging
Durham NC 27708
Papers or publications submitted should utilize IPUMS-USA, IPUMS-CPS, IPUMS-International or IHIS data to study social, economic, and/or demographic processes. Please submit your work here.
Anatoliy I. Yashin of the Social Science Research Institute has received an award from the National Institutes of Health for a project entitled "Genetics of Changes in Population Pyramids: Implications for Health Forecasting." Total funding will be $2,923,559 over 60 months.
Investigators at the National Science Foundation (NSF) turned up nearly 100 cases of suspected plagiarism in proposals funded by the agency during the fiscal year 2011, all of which are now being investigated. The NSF’s Office of Inspector General (IG), an internal but independent watchdog, used plagiarism detection software to analyze some 8,000 successful funding applications, and flagged 1 to 1.5 percent of cases as suspicious—though it’s not clear what percentage of these are self-plagiarism, in which researchers lift sections from the materials and methods or even introductions of their own previous proposals. Please be careful and not plagiarize in your proposals.
Guidance on Resumption of NIH Extramural Activities Following the Recent Lapse in Appropriations (NOT-OD-14-003) Office of the Director, NIH. This is the latest news we have about operations at NIH after the shutdown. The following topics are covered:
- eRA Systems Availability,
- Rescheduling October Application Due Dates,
- Processing of Applications Submitted During the Shutdown,
- Replacing an Application that was Submitted for an October Due Date,
- Rescheduling Peer Review Meetings,
- Opportunity to “Refresh” Applications that are Reassigned to May 2014 Council,
- Early Stage Investigator Eligibility,
- K99/R00 Eligibility, Payment Management System,
- Award Actions, Financial Operations under a Continuing Resolution.
Ryan Brown, an economics doctoral candidate in DuPRI’s National Institute on Aging-funded training program, has received the Minnesota Population Center's 2012 IPUMS-USA Research Award for the "best published or unpublished work by a graduate student." His paper titled, "On the Long Term Effects of the 1918 U.S. Influenza Pandemic," is based on the Center's U.S. Census microdata series and was unanimously selected by the MPC panel for the recognition.
Brown's as yet unpublished study, written with Economics professor and DUPRI Fellow Duncan Thomas, examines the socioeconomic backgrounds of the cohort of U.S. children who were in utero during the flu pandemic of 1918-1919 and tests a theory that these kids suffered particular hardships, even into old age, as a result of that early-life exposure. The paper shows how challenging a single assumption in a prior analysis can alter its results dramatically.
Brown's paper was not an attempt to challenge the idea that early-life exposures can cause permanent harm, he cautions, but rather a reminder to fellow economists that, "We need to think really hard about how we go about using natural experiments. It's really important to have strong theory behind it, and to take your assumptions very seriously, because they are that, they are assumptions."
In 2006, amid heightened concern over the possibility that a new strain of avian influenza could morph into a global human flu pandemic to rival the Great Influenza, Columbia University economist Douglas Almond published his analysis showing the lifelong disadvantages experienced by the babies born in the U.S. during and just after the 1918-1919 crisis. They had fewer years of education, earned less as adults and had more disability late in life.
Evidence from biology and epidemiology strongly supports the idea that prenatal exposures—whether to exogenous chemicals, disease or other forms of maternal stress—can impact a developing fetus in ways that may harm its health and fitness for a lifetime. And a growing body of research suggests that such developmental deficits can lead to real social and economic losses.
Almond argued that the 1918 pandemic was an ideal natural experiment for identifying these long-term consequences of an early exposure because the flu infected about a third of the U.S. population, including a slightly higher proportion of pregnant women. The pandemic came on suddenly, lasted for a relatively short and clearly defined period, and its spread appeared to be geographically random—no part of the nation was spared.
Brown and Thomas have shown, however, that the fate of being a fetus during the great pandemic was anything but random. They write: "A key assumption underlying [Almond's study] is that the characteristics of the 1919 birth cohort are following the same linear trend as the surrounding birth cohorts."
In fact, the authors remind us, there was still a war going on at the time the flu hit in 1918, and in that era wealth and education made men more eligible for military service, not less so. An exemption from service for sole providers whose absence would cause severe financial hardship was more likely to favor the breadwinners of poorer families than those with ample resources. That meant the men left behind to potentially father children in 1918 were likely of lower socioeconomic status. Together with the fact that higher-status families are more prone and better able to delay childbearing during a period of crisis and uncertainty, Brown and Thomas argue that the family backgrounds of the 1919 birth cohort are a key variable to consider when examining their later-life outcomes.
1918: Red Cross nurses bring food to a Charlotte, NC, family that has just lost its wife and mother to influenza. (Source: U.S. National Archives and Records Administration)
Using data from the IPUMS samples of the 1920 and 1930 U.S. Censuses, they show "that those who were at highest risk of being exposed in utero were born to families of lower socio-economic status relative to the cohorts who were not exposed. Specifically, the fathers that produced a child in 1919 were significantly less likely to be WWI veterans, had jobs that produced less income, had lower socioeconomic status (SES), were older, had more total children, and were less likely to be white than fathers of those who were not at high risk of being exposed to influenza in utero."
As a result, they write of Almond's original analysis, "When including controls for childhood environment, the effect of in utero exposure on adult outcomes becomes small in magnitude and not statistically significant. Conclusions about the deleterious impact of in utero exposure to the influenza pandemic on socio-economic prosperity in adulthood are, at best, premature."
The issue, Brown says, is not that the 1919 cohort was particularly unlucky. On the contrary, "it's that they're just a different set of children, born to less well off parents, and when you compare them to the mixture [of children born before and after the pandemic], it makes them look bad. But when you compare them to a similar group by controlling for the parents' characteristics, it looks like they're doing just as well."
He and Thomas cannot speak to why the exposed cohort appear to be doing as well as the unexposed, and the authors are careful not to imply that being a pandemic baby had no ripple effects. But they conclude on a positive note that their findings at least suggest there is room for mitigating interventions later in life that could offset an early exposure.
Brown was drawn to Almond's paper because it was widely considered the strongest evidence of the potential for prenatal exposures to influence success throughout life. "And the topic itself is one I find incredibly interesting, the idea that things that can happen to us in utero can have such long-lasting and serious effects," he says. "I don't know if everyone is aware that's the case. We think a lot about helping the next generation, but I don't think we think about helping the next generation in utero.... It brings up a lot of interesting questions, so since this was the seminal work, I thought it was worthwhile to think deeply about it."
Brown credits mentoring by Thomas and DUPRI director Seth Sanders with "shaping the economist I am today" and instilling an appreciation for the importance of scientific rigor. Unlike the so-called hard sciences, he says, "We have to deal with a lot of confounding factors that there's no way to control, which does make social science a bit more challenging and brings back the issue of doing your best to look under every rock to make sure the assumptions you're making are valid."
His interest in natural experiments - and in testing their validity for answering specific questions - extends to another ongoing research project to examine the effects of maternal psychological stress on health outcomes for babies in utero during the terrorist attacks of September 11, 2001.
Brown, who will be working on completing his dissertation this summer and hitting the job market in the fall says of his IPUMS-USA Research Award, "Every time your peers say something you've done is worthwhile, and worth checking out, that means a lot. You work really hard on these things, and you really have your head down trying to get it right. It's nice when people you respect as your peers respect what you've done."
"Monkeys don't smoke, and they don't do yoga," says Jenny Tung. But monkeys do experience the kind of psychosocial stress that can drive humans to embrace both of those coping mechanisms. That's why Tung, an Assistant Professor of Evolutionary Anthropology and DuPRI Faculty Associate, believes monkeys are especially useful for shedding light on the ways that persistent stress can undermine human health.
Jenny Tung observing a baboon in Amboseli National Park, Kenya (courtesy Susan Alberts).
In captivity, the rhesus macaques Tung is studying don't have to worry about predators, but they're all the more exposed to the constant harassment of higher-ranking individuals, who have all the power and never let subordinates forget it. For low-ranking animals, the inescapable bullying and lack of control exert the sort of chronic stress shown in the famous Whitehall Study of British civil servants to lead to an early death.
The fact that low status, whether at work or in society in general, greatly raises a human being's chances for heart disease, stroke and a range of other illnesses is well documented but still poorly understood. So Tung is embarking on a five-year study to try to get at some of the underlying mechanisms of those health effects. With a $2.8 million grant from the National Institute of General Medical Sciences, Tung and her collaborators will create new social groups of female macaques at the Yerkes National Primate Research Center in Atlanta, manipulate the animals' social hierarchy and use a range of molecular techniques to profile their gene activity and immune responses.SIGNATURES OF STRESS
In a preliminary project while she was a postdoctoral fellow at the University of Chicago, Tung found significant differences in gene regulation in the immune cells of female macaques depending on their social status—patterns so consistent that an individual's rank could be predicted with 80 percent accuracy based on her gene-expression profile alone. The results of that study, published in April, illustrate how stress-related hormones may signal immune cells to ready themselves for conflict, which the cells would do by raising or lowering the activity of certain genes. In the blood cells Tung examined, the biggest activity changes seen were in genes involved in inflammation and T-cell activation. Those processes help to fight infection, but are also implicated in heart disease and many other degenerative conditions.
Baboons in Amboseli National Park, Kenya.
The study also identified a possible mechanism for the gene-activity changes themselves. Methylation, the sequence of chemical groups along the surface of a DNA strand, constitutes a second "epigenetic" code involved in regulating which genes are activated and when. Tung's team identified clear signatures of rank in methylation changes near DNA regions involved in regulating the immune-related genes. One of Tung's goals in the new project is to explore whether any of the methylation changes associated with stress are long-lasting. There's already evidence that early-life stress can leave a permanent, even heritable, mark on DNA methylation. Noah Snyder-Mackler, a postdoc in Tung's lab who is currently looking at whether published signatures of social stress recapitulate those of aging, will examine the same question for the methylation changes associated with rank in macaques.
"We, like a lot of investigators at DuPRI who come from different directions, are interested in life history, health over the life course," says Tung. "Which is for [non-human primates] 'fitness'… Survival and health and reproduction are really where the rubber meets the road as far as fitness, and how social interactions affect differences in how individuals age over the life course, and how stress accumulates to influence those kinds of outcomes." Tung adds that she sees a lot of potential for cross-disciplinary work in genomics and aging. "We actually have a lot of shared questions, we just come at it from different angles."
A cross-species perspective was central during Tung's postdoc in Yoav Gilad's laboratory at the University of Chicago. Gilad, who is in the Department of Human Genetics, focuses on comparing primate genomes to understand gene-regulatory mechanisms and evolution. And, according to Tung, being around so many people doing human genetics work inspired ideas for getting the most out of the preliminary macaque study, many of which will carry over into the new project. In addition to looking at DNA methylation, the team examined the composition of immune cells in the monkeys' blood, to see whether certain types of cells were increasing or decreasing in response to stress. That also let them account for the possibility that apparent gene activity changes in a given cell type were the result of there being more of that type of cell present. In the new study, Tung and her colleagues will be measuring gene expression through RNA sequencing, which will let them look not just at the level of activity by a particular gene, but also whether its RNA is being "spliced" in alternative versions under different stress conditions.
Finally, Tung and her collaborators want to see how all these gene-activity changes might translate into a direct effect on health by challenging the monkeys' immune systems. Rather than exposing the animals to pathogens, though, the team will draw blood from the 10 highest-ranking and 10 lowest-ranking macaques directly into test tubes laced with antigens that immune cells recognize as parts of viruses or bacteria. This will allow them to capture the sets of genes that respond to a challenge, the magnitude of the response and identify which aspects of immunity (innate, adaptive, etc.) are influenced by dominance-rank effects.GENE-BEHAVIOR DIALOGUE
Tung completed her Ph.D. in Biology at Duke in 2010, under the direction of Gregory Wray and Susan Alberts, and she hopes to continue work she started as a graduate student investigating subtle changes among wild baboons in Kenya's Amboseli National Park. The original population of yellow baboons there is now intermingled with a different subspecies, and Tung, who just returned from Kenya in July, is interested in how that admixture and hybridization affects maturation and mating behavior in the group. The baboon studies with Alberts "focus on longitudinal work, mostly observational, but also genetics," Tung says, "so the data are behavioral and social and demographic, with similarities to the types of data that some of the investigators at DUPRI collect" on people. With non-human primates, though, it's easier to eliminate some of the "noise," she explains.
Rhesus macaques at Yerkes, copyright Yerkes National Primate Research Center."One of the problems with humans is to demonstrate causality. Is the gene expression coming first or the social environment coming first?" Tung says. "We want what we're doing to be relevant to humans, so it's really helpful to do the parallel studies in humans, but doing them in macaques first establishes that social environment seems to have an effect as best we can assess." The social environment for a rhesus macaque is complex but a lot simpler than it is for humans. Especially in modern society, people are "interfacing with a lot of different individuals, depending on the day or time of day or context," according to Tung. So a person might be high-status at work, but berated at home, making it hard to characterize the influence of social status. "The other thing we can do with nonhuman primates is watch them all the time," Tung notes.
In the new experiment, Snyder-Mackler is also interested in seeing whether the low-ranking monkeys adopt any behavioral patterns to help them cope with stress. "Social support is relevant for nonhuman primates, and some of the work my colleagues have done on baboons, for instance, has suggested that survival probabilities are affected by the strength of social bonds," Tung says. "That's mediated by grooming and proximity, also if someone is stressing you out, you should probably get away from them." The macaques at Yerkes will be divided into 10 social groups of five animals each, so it might be hard for an individual to avoid harassment from another of higher rank. For that reason, Tung thinks the investigators might get "a particularly clear signal" of social stress. "In a naturally constituted group, you might have more kin support to help offset that kind of harassment, just by being there or forming coalitions to dissuade that kind of behavior," she says.
If there's a theme to the Tung lab's work, it is adaptation - genetic and behavioral - to changing circumstances. "All of us are interested in the relationship between behavior and social structure and social structure and genes and the genome, and we pursue it in a lot of different ways," Tung says. "I have always worked on primate genetics in the context of evolution, so it's a natural fit. It's the sort of research that bridges between biology and evolution and aspects of behavior and genetics and evolutionary anthropology, so it doesn't seem like a stretch."
Jenny Tung, Ph.D., is Assistant Professor of Evolutionary Anthropology and a DUPRI Faculty Associate.
Jenny Tung, Faculty Associate at DUPRI and an Assistant Professor in the Department of Evolutionary Anthropology, has been awarded a five-year R01 grant from the National Institute of General Medical Sciences totaling $2.8 million to study changes in gene regulation in response to psychosocial stress among rhesus macaques. As a model for the human experience of chronic stress, Tung says the macaques' gene responses may shed light on mechanisms underlying some of the well-documented health effects linked to stress in people.
In a preliminary project while at the University of Chicago, Tung and her colleagues showed significant differences in gene activity in the immune cells of female macaques depending on their rank within the social group—patterns so consistent that an individual's rank could be predicted with 80 percent accuracy based on her gene-expression profile alone. The new work, to be conducted with macaques at the Yerkes National Primate Research Center, will further examine genetic and epigenetic changes linked to rank-associated stresses as well as differences in how the animals' immune systems respond to challenge. Collaborators will include Zachary P. Johnson and Mark E. Wilson at Yerkes and Luis B. Barreiro at the University of Montreal. Tung, who earned her PhD in Biology at Duke in 2010, completed a postdoctoral fellowship in the laboratory of Yoav Gilad in Chicago and recently returned to Duke to form her own lab.
Anatoliy I. Yashin, Scientific Director of the DuPRI Center for Population Health and Aging, received the Mindel C. Sheps Award on May 4, 2012, in San Francisco for his contributions to the methodological foundations of demography. One of the most prestigious international awards in demography, the prize is given biennially by the Population Association of America and the University of North Carolina School of Public Health. The honor is named for Mindel C. Sheps, MD (1913-1973), who became an expert in statistics as well as demographic and biological aspects of fertility through her research on the impact of social factors in public health. It is awarded on the basis of important contributions to knowledge either in the form of a single piece of work or a continuing record of high achievement.
Yashin has a lifetime of accomplishments developing and applying advanced mathematical and statistical methods to understanding the fundamental determinants of aging. The new methods and models he and his colleagues have devised, and the results they generate, continually influence the course of research in the field of aging studies.
Originally trained in radio technology, cybernetics and plasma physics at the Moscow Physical and Technical Institute, Yashin has investigated mathematical aspects of the dynamic mechanisms behind aging, health and mortality at the Institute of Control Sciences in Moscow, and at the International Institute for Applied Systems Analysis in Vienna, the University of Minnesota School of Public Health, the University of Southern Denmark in Odense and the Max Planck Institute for Demographic Research in Rostock, Germany. Yashin's association with Duke University dates back 20 years, through collaborations with eminent Duke population researchers. He joined the CPHA faculty full-time in 2003.
Anatoliy I.Yashin is also a research professor in the Duke University Social Science Research Institute and an adjunct professor in the Duke Cancer Institute. For more detail about the work that has earned him this recognition, see the profile "Seeking the Longevity Equation."
Seeking the Longevity Equation
Whether the secret to long life turns out to be a positive attitude, lucky genes, or highly complex interactions among a multitude of factors over a lifetime, Anatoliy I. Yashin will likely capture those forces at work in a sophisticated mathematical model.
Yashin, the scientific director of DUPRI’s Center for Population Health and Aging, applies advanced mathematics to understanding the complexities of human aging. The new methods and models he has devised, and the results they generate, continually influence the course of research in the field of aging studies.
Indeed, in recent work, Yashin and his team have shown that although long-sought “longevity genes” remain elusive, hosts of genes with very small effects can, together, exert a powerful influence on a person’s healthy lifespan. Moreover, the most relevant genes might differ from one individual to another, depending on conditions in the environment.
Such challenges to conventional wisdom are typical of Yashin’s findings — the result of tackling some of the hottest topics in biology from an unusual direction. Originally trained in plasma physics at the Moscow Physical and Technical Institute, Yashin, in his quest to reveal the dynamic mechanisms behind aging and mortality, continues to come up with ever more creative ways of mining data for insights into what is perhaps the most complex system of all — the human body.HIDDEN HETEROGENEITY
Demographers trying to understand aging have always known that it had to be a complicated and varied process, according to Yashin, and therefore mortality curves for whole populations reveal little about what preserves the health or causes the death of any individual in the group. But since the biology of that process was largely unknown — even to biologists — until fairly recently, population researchers continued trying to draw conclusions about mortality from group data.
Not satisfied with that approach, Yashin argued thirty years ago that to make meaningful predictions about mortality trends among real people required understanding the “Deviant Dynamics of Death in Heterogeneous Populations.” In a 1982 paper with that title, Yashin, then a senior researcher at the Academy of Sciences in Moscow, and his coauthor James W. Vaupel, an associate professor of policy at Duke (now, co-director of the DuPRI CPHA and founding director of the Max Planck Institute for Demographic Research), challenged their fellow demographers to take on this problem."Every individual has his own chances to live long or live short."
In brief, Yashin explains, the issue was that “Every individual has his own chances to live long or live short. It depends on genetic background, individual exposures, conditions, different families, etcetera, so everything influences chances of survival. And since there is a kind of distribution of individuals in the population, this variety of chances of death produced some interesting effects on mortality. If you change the distribution you will change the mortality rate.”
Yashin was drawn early in his career to analyzing healthcare policy questions in the Soviet Union — a line of inquiry that led to multi-year contracts pursuing health-related projects at the International Institute for Applied Systems Analysis in Vienna, where he first met and began collaborating with Vaupel. In 1990 when Vaupel, by then at the University of Minnesota, received a grant from the U.S. National Institutes of Health to study longevity in the oldest old, Yashin joined his friend in Minneapolis.
The pair set out to explore some of the intriguing questions raised by patterns within mortality curves, including the “population compositional influence on mortality rates” they had identified years earlier. Another mystery dated back to an observation in 1825 by Benjamin Gompertz that mortality rates in animals and people seemed to level off and sometimes even slow at advanced ages, hinting there might be something special about those who made it to very old age that allowed them to keep on going.
Vaupel had already devised the concept of individual frailty to describe such an intrinsic quality — whether an aspect of the environment or an inherited predisposition, for example — that would influence a person’s lifespan. To examine this quality in the oldest old more closely, they needed a model that could tease apart the genetic and environmental influences on longevity in individuals. They also needed a lot of data on twins. Yashin and Vaupel began working with Danish registry data, and eventually moved their operation to the University of Southern Denmark, in Odense, to work on determining which aspect of individual frailty — genes or environment — is more important to lifespan.
The correlated frailty model Yashin developed there with PhD student Ivan A. Iachine in 1995 remains widely used today by researchers trying to parse the relative influences of genes and environment. Applied to Scandinavian twins, it offered Yashin and Vaupel the surprising finding that genes were fairly unimportant to longevity — perhaps 25 percent of the picture. Genes, though, could explain about 50 percent of the differences in frailty between individuals. The intriguing result also begged a new set of questions: with or without fortunate genes, what had the very old done, or exposed themselves to, or avoided during their lifetimes that might account for their survival?INTERCONNECTED SYSTEMS
By 1996 Vaupel and Yashin were at the MPIDR in Rostock, Germany, and shifting their focus to the interactions between genes and environment over a lifetime that might shed light on extreme longevity. They realized that longitudinal studies could provide the kind of long-term data on health histories and mortality they would need, but wouldn’t contain everything required to understand the life course of individuals.
“We understood that in order to study aging, we should take into account the wealth of knowledge about aging and lifespan that is accumulated in the field,” Yashin says. “It is not represented in specific data, but people have found connections between phenomena of aging, for example, stress resistance tends to decline with age, which means that the same stress that could be tolerated when we were young could be very dangerous when we're old.” Similarly important, he adds, are adaptive capacity — the body’s ability to adjust its functioning in response to stressors, as well as so-called allostatic load, essentially the burden of chronically making those adjustments.
The quadratic hazard model Yashin developed to incorporate those kinds of unobserved variables, along with longitudinal data, made it possible to analyze a much richer picture of the forces influencing health and lifespan. With this new approach, Yashin and his colleagues have demonstrated the importance of stress and other exposures on how we age and even found evidence for the controversial phenomenon of hormesis — the idea that a little bit of stress, even in the form of a toxin, can produce beneficial effects in the body.
The model also allowed Yashin and his team to show in detail the interactions of various objective biomarkers — such as blood glucose, blood pressure, or weight, with one another, as well as their individual fluctuations over time. Among the important insights these studies revealed is that norms change over a lifetime — for instance, a healthy body mass index for an 80-year-old might be the same BMI that person had at 30, but that is not the ideal at age 15 or 50. Moreover, at the same BMI, the 80-year-old and the 30-year-old have very different states of health, so the biomarker itself is not very informative. The arc of such health measures over the course of that person's life can be very telling, however.
“If you look at the age trajectory of blood pressure,” Yashin explains, “it maxes then declines, and then if we see one individual has a high rate of decline, and another has a slower one, and we know those who have slow decline live longer, then the slope of decline is a kind of risk factor. So when we describe these dynamic changes in terms of mathematical equations, the parameters of these equations not only describe chances of death, they also characterize biological changes in the individual.”
Yashin (third from left)and colleagues at the Max Planck Institute for Demographic Research in Rostock, Germany, 2004.
Yashin calls the original quadratic hazard model, which continued to evolve into the stochastic process models he is applying in many of his current projects, “the kind of methodological breakthrough that allowed us to go further, and to merge together data from different worlds...like population data, demography, longitudinal and some biological and genetic data.” That original model built on a long history of collaboration between Yashin and Duke mathematicians Max Woodbury and Kenneth G. Manton, both innovators who established Duke’s reputation for applying advanced mathematics in population studies. When an opportunity to join the Duke faculty opened up in 2003, Yashin moved to the U.S. with his wife and CPHA colleague, Svetlana V. Ukraintseva, a geneticist who was also studying aging at MPIDR at the time, as well as Konstantin Arbeev, a specialist in statistical modeling. The team now includes Eric Stallard, Kenneth Land, Alexander Kulminski, Igor Akusevich, Irina Kulminskaya and Deqing Wu.
"It was the kind of methodological break through that allowed us to go further, and to merge together data from different worlds."PUTTING THE PIECES TOGETHER
The latest models developed by Yashin’s team enable them to perform aging studies with unprecedented breadth and depth. By adapting the stochastic approach to jointly analyze huge and disparate longitudinal datasets, such as data from the multigeneration Framingham Heart Study, Medicare records and Duke’s own National Long Term Care Survey, the group is continuing to explore the interconnected forces that influence how any one person will age. Their work demands an interdisciplinary approach, Yashin says, “to put all these ideas together.”
The team’s methods can be considered a form of systems biology — a cutting-edge field enabled by modeling techniques borrowed from the physical sciences. And their projects can touch on some of the most fundamental questions in biology. Recent studies have examined, for instance, the relationship between genes involved in aging and those activated in cancer cells, and whether evolutionary trade-offs explain connections between seemingly unrelated diseases — such as the apparent postponement of cancer risk seen in people with a gene variant that raises the risk of developing Alzheimer’s disease.
But their goal remains a very pragmatic one. Discovering how and why the human body ages will help researchers “find the optimal balance between postponing aging and postponing decline,” Yashin says. That, in turn, will help policymakers to predict the population's needs and help individuals to live the longest, happiest and healthiest lives possible.
Anatoliy I. Yashin is Scientific Director of the DUPRI Center for Population Health and Aging, a research professor in the Duke University Social Science Research Institute and an adjunct professor in the Duke Cancer Institute. On May 4, 2012, he received the prestigious Mindel C. Sheps Award from the Population Association of America and the University of North Carolina School of Public Health for outstanding contributions to mathematical demography or demographic methodology.
China as Living Laboratory
In population science, "You want to describe not only what you see, but also what you are missing; not only the appearance but also the reality," says M. Giovanna Merli, Associate Director of the Duke Population Research Institute. Merli has made a specialty of finding hidden populations and uncovering hidden truths about them, all in the world's most populous country, China.
To better understand the realities at the heart of health policy questions, Merli's approach often blends classical demographic methods with a range of modern tools, such as social network modeling. Whether she is simulating the behavior of actual people to gauge its potential to spark an epidemic, or tapping into real-world social networks to characterize an unknown population, Merli's findings frequently challenge widely held assumptions.
In recent work she explores, for instance, whether heterosexual transmission of HIV could lead to the kind of rapid disease spread seen in some other countries and forecast for China. Given that half of HIV infections in China are thought to happen through heterosexual sex, the great majority of those encounters paid, in early 2008 Merli obtained interviews with 550 female sex workers in Shanghai about the details of their clientele and frequency of their contacts.
The women ranged from "high-end" call girls to the lowest-status street walkers, and social network specialist James Moody in Duke's Department of Sociology, a fellow DUPRI Research Associate, used their responses to simulate their web of contacts and interactions. The picture the data painted of China's sex trade showed a network of sex workers, customers, and partners of customers still far too constricted to sustain HIV transmission on the scale it has occurred, for example, in Thailand or parts of Africa."I'm sensitive to the ways that political issues can creep in and interfere with the collection of statistical data"
To Merli, the results illustrate the principle that predictions can't be based on past experience in other places, especially when it comes to China.
Her fascination with that country began with its language. As a teenager in her hometown of Milan, Italy, Merli had already mastered several European languages when she decided to learn Chinese in the Department of East Asian Studies at the University of Venice. China "was just beginning to open up," Merli says, and she ended up living in Shanghai for two years through one of the first student exchange programs between Italy and China.
She has returned many times as a scholar, and finds her time living in China helps in designing studies there. "If you know how the society is organized, you can better foresee potential problems," Merli says. "That's particularly true in China where the political bureaucracy had such a huge role in monitoring and determining outcomes, so I'm sensitive to the ways that political issues can creep in and interfere with the collection of statistical data."SUBTLE AND PROFOUND SHIFTS
China's rising mobility and fast-forward social change can make Merli's work challenging, but not as difficult as some might think in light of her frequent focus on sexual behavior and fertility. China's political history actually makes surveying Chinese on their sexual and reproductive lives easier in some ways, Merli says.
State monitoring of daily life, particularly oversight of the national one-child policy, accustomed citizens to giving officials detailed answers about their intimate lives on a regular basis. As a result, population researchers conducting surveys in China could once routinely get response rates of 95 percent or more. Today, they're nearer to Western norms of about 65 percent. The breakdown of rigid social control in China, particularly in cities, has led its people to "acquire a new sense of privacy," Merli explains. "They don't feel they need to appease local authorities, so they refuse to answer questions. They're pretty much behaving like the U.S. population now."
Merli (right) with an employee at the Shandong Province Rural Family Planning Station, 1995.
Nonetheless, in 2007-2008 Merli and her collaborators at the Fudan University School of Public Health accomplished the first-ever survey of local sexual networks in China. The Shanghai Sexual Behavior and Sexual Networks Survey asked a population-representative sample of 1,600 men and women in that city of 19 million about their sexual activity and partners as well as their reproductive preferences.
Responses to the sexual behavior questions were fed into the network simulations Moody and Merli generated to model potential HIV spread. And Merli used the participants' answers about their reproductive ideals to examine what might happen if China lifted its controversial one-child policy established in 1979.
When the family-size restrictions were first announced, they were only supposed to last a generation. Now more than 30 years later, as scholars and politicians debate whether to rescind the decree, a generation of singleton kids are themselves getting married and making choices about having a family.
In a 2000 study based on early-1990s data, Merli found that birth rates among rural Chinese families were low, but slightly higher than official reports claimed—in part due to underreporting of female babies born to families trying for a son. Merli argued that these girls were likely hidden with the knowledge of local officials charged with enforcing the one-child policy and motivated to meet their quotas. Still, a subsequent examination of the same data set in 2002 showed that in some rural areas, the one-child policy had not only succeeded overall in changing reproductive behavior, but had also started shifting personal preferences toward having fewer children.
In the December 2011 issue of Population, Merli makes the case that based on her more recent Shanghai survey sample, the shift in fertility preferences, at least in Chinese cities, is sincere and grounded in a new individualism and consumerism that have little to do with official fertility policy. Her respondents professed in many cases to be content with a single child or two at most. They often cited reasons like the expense, lifestyle constraints, and career costs of large families that will ring familiar in other nations where fertility rates have fallen naturally as prosperity rose.TOOLS OF THE TRADE
Though the Shanghai residents in the larger sexual-networks survey were selected through standard census-based probability-driven sampling techniques, Merli's sex-worker survey used a recruitment approach gaining popularity for reaching people in the shadowy margins of society. Respondent Driven Sampling relies on an initial group of survey respondents to invite select associates to participate, with the chain of referrals revealing an ever-larger sample of the target population. The U.S. Centers for Disease Control and Prevention has used this method to survey intravenous drug users and men who have sex with men. Other researchers are employing it to assess health risks among street youths and the homeless.
"RDS is widely used now, in fact it's too widely used," says Merli. "It's a very efficient way to quickly and easily sample hidden populations," she explains, "but it also makes claims about population representation based on assumptions that are only now starting to be tested." Indeed, because the technique is becoming so popular in public health research, the National Institutes of Health is sponsoring several studies, including one by Merli and Moody, to evaluate its validity."This is a place where you can take risks in terms of the kinds of studies you take on."
The team will use the Shanghai sex-worker survey data set, as well as data collected for this purpose in the southern Chinese city of Liuzhou, to test assumptions about the respondents' actual underlying social networks and improve estimations in those populations. "What's unique is we're really grounded empirically," Merli says. "We really want to understand how it works on the ground."
Population scientists are getting better answers and asking harder questions, Merli says, in large part thanks to new tools—such as network modeling, econometric methods of determining causality, and new, richer, more complex data sets—borrowed from other disciplines to enhance traditional demography. In turn, she adds, population scientists contribute their own tools and insights to other fields—for instance, by refining how populations examined in public health studies are chosen and how the results are interpreted.
As head of the new DUPRI Development Core, Merli's goal is to offer students the entire toolbox available for studying populations and to train them to take advantage of DuPRI's unique interdisciplinary opportunities. "It's unusual to be so diverse and to have such a welcoming and collaborative group," Merli says of DUPRI. "We are in public policy, economics, sociology, neurosciences, global health." Indeed, that "dynamism" is what Merli says attracted her to Duke four years ago. "This is a place where you can take risks in terms of the kinds of studies you take on," she says.RISKS AND REWARDS
The next project Merli has planned is all about risk. This spring, she hopes to launch a pilot study of Chinese migrant workers in Tanzania. "Of particular interest to me is the negotiation of the Chinese migrants with a very new and challenging disease environment, and the risk [they] take to go to Africa," Merli says. Some are sent by the Chinese government for temporary assignments, but many are migrating on their own. No one knows how many, or whether their willingness to take such a leap will translate into riskier behaviors in their new setting.
The project brings together many threads from Merli's previous work. She'll conduct RDS surveys among the workers, model their social networks, and even use network modeling as a tool to get an estimate of how many Chinese workers might already be in Africa. "It'll be an opportunity to test the claims about RDS in a very different population," she notes. And, of course, if workers' risk tolerance and behavior are changed by their experiences abroad, it would be interesting to see how those who return home contribute to the ongoing social changes there.
Merli considers herself an original scholar whose topic, ultimately, is China. It is a rich "laboratory" for population science, she says. "The very rapid pace of change means you can observe processes that have been seen unfolding elsewhere over decades or centuries, there you can observe them sometimes in just a few years."
M. Giovanna Merli is Associate Professor of Public Policy, Sociology and Global Health in the Sanford School of Public Policy. She teaches core courses in a new population studies cluster that she helped to create for the Sanford Master program, and in the new DUPRI graduate training program in population studies, which she directs. She is also a member of numerous committees charged with developing and refining Duke’s global presence and strategy, including the Duke Kunshan University program in China.
For students who wish to learn more about Training in the Population Sciences at Duke, DUPRI has launched a comprehensive Training website. The site aims to answer any questions prospective students may have regarding courses, grant funding, and conference attendance.
The Duke Population Research Institute (DUPRI) is pleased to announce that it has been awarded a T32 training grant from the National Institute of Aging at the National Institutes of Health. Funding five graduate students and two post-doctoral students who wish to engage in rigorous training in the general fields of social, medical, and economic demography of aging, the program focuses on five substantive areas:
1.Biodemography, including indices and models of aging, vitality, and frailty, 2.Health disparities (by race/ethnicity, sex, socioeconomic status) among the elderly; 3.International comparative studies of the health of aging populations in both developed and developing countries; 4.Important life course transitions (e.g., family changes, work and retirement, morbidity and disability) that relate to the health and well-being of aging persons; and 5.The economics of aging.
This postdoctoral program is administered by DUPRI and is directed by Kenneth C. Land, John Franklin Crowell Professor of Sociology and Demography and Director of the DUPRI Center for Population Health and Aging. Originally awarded to Duke more than 20 years ago, Duke has been able to continually renew this grant. Historically, it has largely trained students in the field of Sociology. With the growth of population sciences on campus, the renewed T32 proposes interdisciplinary training and access to fellowship funds in all departments that have students with an interest in Aging research.
“I am grateful to the Sociology Department for their willingness to expand the program to other departments and I very much believe that all departments will have better scholars as a result of this interdisciplinary training,” says Seth Sanders, Professor of Economics and Public Policy and Director of DUPRI.
With a goal of advancing innovative interdisciplinary demographic and population research, DUPRI is an interdisciplinary research organization bringing together faculty from the biological, economic, mathematical, psychological, statistical, sociological, and policy sciences at Duke. For more information on DUPRI programs and training, please contact DUPRI Training Director, M. Giovanna Merli, Associate Professor of Public Policy and Sociology, at firstname.lastname@example.org
DUPRI offers assistance to faculty associates and affiliates through all stages of the grants process: from proposal development and submission, through research administration responsibilities, to close out activities. For more information or assistance, please contact the Grants staff at email@example.com.