Lynn E. Eberly

Sex differences in learning in chimpanzees.

The wild chimpanzees in Gombe National Park, Tanzania, fish for termites with flexible tools that they make out of vegetation, inserting them into the termite mound and then extracting and eating the termites that cling to the tool. Tools may be used in different ways by different chimpanzee communities according to the local chimpanzee culture. Here we describe the results of a four-year longitudinal field study in which we investigated how this cultural behaviour is learned by the communitys offspring. We find that there are distinct sex-based differences, akin to those found in human children, in the way in which young chimpanzees develop their termite-fishing skills.

Depressive Symptoms and Mortality in Men: Results From the Multiple Risk Factor Intervention Trial

Background and Purpose— Depression may be a risk factor for cardiovascular disease (CVD) mortality. We evaluated long-term mortality risk associated with depressive symptoms measured at middle age among men at high risk for coronary heart disease (CHD). Methods— 12 866 men without definite evidence of CHD at study entry but who had above average risk of CHD based on blood pressure, blood cholesterol levels, and/or cigarette smoking were recruited into the Multiple Risk Factor Intervention Trial (MRFIT). Survivors at the end of the trial were followed-up for mortality for an additional 18 years. Men who had completed the Center for Epidemiologic Studies Depression (CES-D) scale near the end of the trial (n=11 216) were used in a prospective analysis of post-trial all-cause and cause-specific mortality during 18-year follow-up after CES-D assessment. Results— Greater depressive symptoms measured at the end of the trial were associated with significantly higher risk of all-cause mortality and for cause-specific death, a higher risk of CVD, and, more specifically, stroke mortality (all P values <0.02) but not CHD mortality (P=0.48) in linear trend analyses. The significant associations were strongest for those reporting the greatest depression: hazard ratio (HR)=1.15 (95% CI, 1.03 to 1.28; P<0.01) for all-cause mortality for those in the highest depressive symptom quintile, HR=1.21 for CVD mortality (95% CI, 1.03 to 1.41; P<0.05), and HR=2.03 for stroke mortality (95% CI, 1.20 to 3.44; P<0.01) compared with those in the lowest quintile. These associations were adjusted for age, intervention group, race, educational attainment, smoking at baseline and visit 6, trial averaged systolic blood pressure, alcohol consumption, and fasting cholesterol, as well as the occurrence of nonfatal cardiovascular events during the trial. Conclusions— Greater depressive symptoms are associated with an increase in the risk of all-cause and, more specifically, CVD mortality in men. Stroke but not CHD was the form of CVD with which depressive symptoms were associated.

Identifiability and convergence issues for Markov chain Monte Carlo fitting of spatial models.

The marked increase in popularity of Bayesian methods in statistical practice over the last decade owes much to the simultaneous development of Markov chain Monte Carlo (MCMC) methods for the evaluation of requisite posterior distributions. However, along with this increase in computing power has come the temptation to fit models larger than the data can readily support, meaning that often the propriety of the posterior distributions for certain parameters depends on the propriety of the associated prior distributions. An important example arises in spatial modelling, wherein separate random effects for capturing unstructured heterogeneity and spatial clustering are of substantive interest, even though only their sum is well identified by the data. Increasing the informative content of the associated prior distributions offers an obvious remedy, but one that hampers parameter interpretability and may also significantly slow the convergence of the MCMC algorithm. In this paper we investigate the relationship among identifiability, Bayesian learning and MCMC convergence rates for a common class of spatial models, in order to provide guidance for prior selection and algorithm tuning. We are able to elucidate the key issues with relatively simple examples, and also illustrate the varying impacts of covariates, outliers and algorithm starting values on the resulting algorithms and posterior distributions.

Increasing Rates of Obesity among HIV-Infected Persons during the HIV Epidemic

Background The prevalence and factors associated with overweight/obesity among human immunodeficiency virus (HIV)-infected persons are unknown. Methods We evaluated prospective data from a U.S. Military HIV Natural History Study (1985–2004) consisting of early diagnosed patients. Statistics included multivariate linear regression and longitudinal linear mixed effects models. Results Of 1682 patients, 2% were underweight, 37% were overweight, and 9% were obese at HIV diagnosis. Multivariate predictors of a higher body mass index (BMI) at diagnosis included more recent year of HIV diagnosis, older age, African American race, and earlier HIV stage (all p<0.05). The majority of patients (62%) gained weight during HIV infection. Multivariate factors associated with a greater increase in BMI during HIV infection included more recent year of diagnosis, lower BMI at diagnosis, higher CD4 count, lower HIV RNA level, lack of AIDS diagnosis, and longer HIV duration (all p<0.05). Nucleoside agents were associated with less weight gain; other drug classes had no significant impact on weight change in the HAART era. Conclusions HIV-infected patients are increasingly overweight/obese at diagnosis and during HIV infection. Weight gain appears to reflect improved health status and mirror trends in the general population. Weight management programs may be important components of HIV care.

Race/Ethnicity, Income, Major Risk Factors, and Cardiovascular Disease Mortality

OBJECTIVES We explored differences between Black and White men for cardiovascular disease (CVD) mortality across major risk factor levels. METHODS Major CVD risk factors were measured among 300,647 White and 20,223 Black men aged 35 to 57 years who were screened for the Multiple Risk Factor Intervention Trial (MRFIT). Hazard ratios for CVD deaths for Black and White men over 25 years of follow-up were calculated for subgroups stratified according to risk factor levels. RESULTS CVD was responsible for 2518 deaths among Black men and 30,772 deaths among White men. The age-adjusted Black-to-White CVD hazard ratio was 1.35 (95% confidence interval [CI]=1.29, 1.40); the risk- and income-adjusted ratio was 1.05 (95% CI=1.01, 1.10). CVD mortality rates were dramatically lower in cases of favorable risk profiles. However, fully adjusted Black-to-White CVD hazard ratios within groups at low, intermediate, high, and very high levels of overall risk were 1.76, 1.20, 1.10, and 0.94, respectively. Similar gradients were evident for individual risk factors. CONCLUSIONS Higher CVD mortality rates among Black men were largely mediated by risk factors and income. These data underscore the need for sustained primordial risk factor prevention among Black men.

Abnormal Amygdala Resting-State Functional Connectivity in Adolescent Depression

IMPORTANCE Major depressive disorder (MDD) frequently emerges during adolescence and can lead to persistent illness, disability, and suicide. The maturational changes that take place in the brain during adolescence underscore the importance of examining neurobiological mechanisms during this time of early illness. However, neural mechanisms of depression in adolescents have been understudied. Research has implicated the amygdala in emotion processing in mood disorders, and adult depression studies have suggested amygdala-frontal connectivity deficits. Resting-state functional magnetic resonance imaging is an advanced tool that can be used to probe neural networks and identify brain-behavior relationships. OBJECTIVE To examine amygdala resting-state functional connectivity (RSFC) in adolescents with and without MDD using resting-state functional magnetic resonance imaging as well as how amygdala RSFC relates to a broad range of symptom dimensions. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional resting-state functional magnetic resonance imaging study was conducted within a depression research program at an academic medical center. Participants included 41 adolescents and young adults aged 12 to 19 years with MDD and 29 healthy adolescents (frequency matched on age and sex) with no psychiatric diagnoses. MAIN OUTCOMES AND MEASURES Using a whole-brain functional connectivity approach, we examined the correlation of spontaneous fluctuation of the blood oxygen level-dependent signal of each voxel in the whole brain with that of the amygdala. RESULTS Adolescents with MDD showed lower positive RSFC between the amygdala and hippocampus, parahippocampus, and brainstem (z >2.3, corrected P < .05); this connectivity was inversely correlated with general depression (R = -.523, P = .01), dysphoria (R = -.455, P = .05), and lassitude (R = -.449, P = .05) and was positively correlated with well-being (R = .470, P = .03). Patients also demonstrated greater (positive) amygdala-precuneus RSFC (z >2.3, corrected P < .05) in contrast to negative amygdala-precuneus RSFC in the adolescents serving as controls. CONCLUSIONS AND RELEVANCE Impaired amygdala-hippocampal/brainstem and amygdala-precuneus RSFC have not previously been highlighted in depression and may be unique to adolescent MDD. These circuits are important for different aspects of memory and self-processing and for modulation of physiologic responses to emotion. The findings suggest potential mechanisms underlying both mood and vegetative symptoms, potentially via impaired processing of memories and visceral signals that spontaneously arise during rest, contributing to the persistent symptoms experienced by adolescents with depression.

Immunogenicity of a Monovalent 2009 Influenza A (H1N1) Vaccine in an Immunocompromised Population: A Prospective Study Comparing HIV-Infected Adults with HIV-Uninfected Adults

BACKGROUND Limited data exist on the immunogenicity of the 2009 influenza A (H1N1) vaccine among immunocompromised persons, including those with human immunodeficiency virus (HIV) infection. METHODS We compared the immunogenicity and tolerability of a single dose of the monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1) between HIV-infected and HIV-uninfected adults 18-50 years of age. The primary end point was an antibody titer of ≥ 1:40 at day 28 after vaccination in those with a prevaccination level of ≤ 1:10, as measured by hemagglutination-inhibition assay. Geometric mean titers, influenza-like illnesses, and tolerability were also evaluated. RESULTS One hundred thirty-one participants were evaluated (65 HIV-infected and 66 HIV-uninfected patients), with a median age of 35 years (interquartile range, 27-42 years). HIV-infected persons had a median CD4 cell count of 581 cells/mm(3) (interquartile range, 476-814 cells/mm(3)) , and 82% were receiving antiretroviral medications. At baseline, 35 patients (27%) had antibody titers of >1:10. HIV-infected patients (29 [56%] of 52), compared with HIV-uninfected persons (35 [80%] of 44), were significantly less likely to develop an antibody response (odds ratio, .20; P = .003). Changes in the median geometric mean titer from baseline to day 28 were also significantly lower in HIV-infected patients than in HIV-uninfected persons (75 vs 153; P = .001). Five influenza-like illnesses occurred (2 cases in HIV-infected persons), but none was attributable to the 2009 influenza H1N1 virus. The vaccine was well tolerated in both groups. CONCLUSIONS Despite high CD4 cell counts and receipt of antiretroviral medications, HIV-infected adults generated significantly poorer antibody responses, compared with HIV-uninfected persons. Future studies evaluating a 2-dose series or more-immunogenic influenza A (H1N1) vaccines among HIV-infected adults are needed (ClinicalTrials.gov NCT00996970).

Personal, Indoor, and Outdoor VOC Exposures in a Probability Sample of Children

As part of the Minnesota Childrens Pesticide Exposure Study we measured volatile organic compound (VOC) concentrations in a probability sample of households with children. The 6-day average concentrations for 10 common VOCs were obtained in urban and nonurban residences twice during this multiphase study: screening-phase indoor measurements were collected in 284 households, and in the intensive-phase matched outdoor (O), indoor (I), and personal (P) measurements were collected in a subset (N=72) of the screened households. Screening-phase households with smokers had significantly higher concentrations of benzene and styrene compared to nonsmoking households; households with an attached garage had significantly higher levels of benzene, chloroform, styrene, and m/p- and o-xylene compared to households without an attached garage; and nonurban residences, which had a greater prevalence of smokers and attached garages, had significantly higher 1,1,1-trichloroethane, styrene, and toluene and significantly lower tetrachloroethylene concentrations compared to urban households. The screening-phase weighted distributions estimate the mean and variability in indoor VOC concentrations for more than 45,000 households with children in the census tracts sampled. Overall, median indoor concentrations of most VOCs measured in this study were similar to or lower than indoor levels measured previously in the United States. Intensive-phase outdoor VOC concentrations were generally lower than other major metropolitan areas, but urban concentrations were significantly higher than nonurban concentrations for all compounds except 1,1,1-trichloroethylene. A consistent pattern of P>I>O was observed for nine of 10 VOCs, with 1,1,1-trichloroethylene (I>P>O) being the only exception to this pattern. For most children, the indoor at-home microevironment was strongly associated with personal exposure after controlling for important covariates, but the ratio of median to upper bound exposures was smaller than that observed in studies of adults. There are relatively little data on VOC exposures in children, so these results are useful for estimating the central tendency and distribution of VOC exposures in locations where children spend a majority of their time.

Human Brain Glycogen Metabolism During and After Hypoglycemia

OBJECTIVE We tested the hypotheses that human brain glycogen is mobilized during hypoglycemia and its content increases above normal levels (“supercompensates”) after hypoglycemia. RESEARCH DESIGN AND METHODS We utilized in vivo 13C nuclear magnetic resonance spectroscopy in conjunction with intravenous infusions of [13C]glucose in healthy volunteers to measure brain glycogen metabolism during and after euglycemic and hypoglycemic clamps. RESULTS After an overnight intravenous infusion of 99% enriched [1-13C]glucose to prelabel glycogen, the rate of label wash-out from [1-13C]glycogen was higher (0.12 ± 0.05 vs. 0.03 ± 0.06 μmol · g−1 · h−1, means ± SD, P < 0.02, n = 5) during a 2-h hyperinsulinemic-hypoglycemic clamp (glucose concentration 57.2 ± 9.7 mg/dl) than during a hyperinsulinemic-euglycemic clamp (95.3 ± 3.3 mg/dl), indicating mobilization of glucose units from glycogen during moderate hypoglycemia. Five additional healthy volunteers received intravenous 25–50% enriched [1-13C]glucose over 22–54 h after undergoing hyperinsulinemic-euglycemic (glucose concentration 92.4 ± 2.3 mg/dl) and hyperinsulinemic-hypoglycemic (52.9 ± 4.8 mg/dl) clamps separated by at least 1 month. Levels of newly synthesized glycogen measured from 4 to 80 h were higher after hypoglycemia than after euglycemia (P ≤ 0.01 for each subject), indicating increased brain glycogen synthesis after moderate hypoglycemia. CONCLUSIONS These data indicate that brain glycogen supports energy metabolism when glucose supply from the blood is inadequate and that its levels rebound to levels higher than normal after a single episode of moderate hypoglycemia in humans.

Smoking and incidence of atrial fibrillation: Results from the Atherosclerosis Risk in Communities (ARIC) Study

BACKGROUND Cigarette smoking increases the risk of coronary heart disease, but whether smoking increases atrial fibrillation (AF) is uncertain. OBJECTIVE The purpose of this study was to determine the association of cigarette smoking with incident AF in a population-based cohort of blacks and whites. METHODS We determined the risk of incident AF through December 2002 in relation to baseline (1987-1989) smoking status and cigarette-years of smoking in over 15,000 participants of the prospective Atherosclerosis Risk in Communities (ARIC) study. RESULTS Over a mean follow-up of 13.1 years, 876 incident AF events were identified. Compared to never smokers, the multivariable-adjusted hazard ratios (HRs) for AF were 1.32 (95% confidence interval [CI] 1.10-1.57) in former smokers, 2.05 (95% CI 1.71-2.47) in current smokers, and 1.58 (95% CI 1.35-1.85) in ever smokers. In the highest tertile of accumulated smoking amount (>675 cigarette-years), the incidence of AF was 2.10 times greater (95% CI 1.74-2.53) than in those who never smoked. Associations were similar by gender, race, type of event (AF and atrial flutter), and when only AF events identified by study exam ECGs were included. Finally, individuals who quit smoking exhibited a trend indicating a slightly lower risk of developing AF (HR 0.88, 95% CI 0.65-1.17) compared to those who continued to smoke. CONCLUSION Smoking was associated with the incidence of AF, with more than a two-fold increased risk of AF attributed to current smoking. In addition, a trend toward a lower incidence of AF appeared among smokers who quit compared to continued smokers.