Obesity-related IL-18 Impairs T-Regulatory Cell Function and Promotes Lung Ischemia-Reperfusion Injury.

Rationale: Primary graft dysfunction (PGD) is a severe form of acute lung injury, leading to increased early morbidity and mortality after lung transplant. Obesity is a major health problem, and recipient obesity is one of the most significant risk factors for developing PGD. Objectives: We hypothesized that T-regulatory cells (Tregs) are able to dampen early ischemia-reperfusion events and thereby decrease the risk of PGD, whereas that action is impaired in obese recipients. Methods: We evaluated Tregs, T cells, and inflammatory markers, plus clinical data, in 79 lung transplant recipients and 41 liver or kidney transplant recipients and studied two groups of mice on a high-fat diet (HFD), which did ("inflammatory" HFD) or did not ("healthy" HFD) develop low-grade inflammation with decreased Treg function. Measurements and Main Results: We identified increased levels of IL-18 as a previously unrecognized mechanism that impairs Tregs' suppressive function in obese individuals. IL-18 decreases levels of FOXP3, the key Treg transcription factor, decreases FOXP3 di- and oligomerization, and increases the ubiquitination and proteasomal degradation of FOXP3. IL-18-treated Tregs or Tregs from obese mice fail to control PGD, whereas IL-18 inhibition ameliorates lung inflammation. The IL-18-driven impairment in Tregs' suppressive function before transplant was associated with an increased risk and severity of PGD in clinical lung transplant recipients. Conclusions: Obesity-related IL-18 induces Treg dysfunction that may contribute to the pathogenesis of PGD. Evaluation of Tregs' suppressive function together with evaluation of IL-18 levels may serve as a screening tool to identify obese individuals with an increased risk of PGD before transplant.

Association Between Educational Attainment and Causes of Death Among White and Black US Adults, 2010-2017.

Importance: There are substantial and increasing educational differences in US adult life expectancy. To reduce social inequalities in mortality, it is important to understand how specific causes of death have contributed to increasing educational differences in adult life expectancy in recent years. Objective: To estimate the relationship of specific causes of death with increasing educational differences in adult life expectancy from 2010 to 2017. Design, Setting, and Participants: Serial cross-sectional study of 4 690 729 deaths recorded in the US National Vital Statistics System in 2010 and 2017. Exposures: Sex, race/ethnicity, and educational attainment. Main Outcomes and Measures: Life expectancy at age 25 years and years of life lost between ages 25 and 84 years by cause of death. Results: The analysis included a total of 2 211 633 deaths in 2010 and 2 479 096 deaths in 2017. Between 2010 and 2017, life expectancy at age 25 significantly declined among white and black non-Hispanic US residents from an expected age at death of 79.34 to 79.15 years (difference, -0.18 [95% CI, -0.23 to -0.14]). Greater decreases were observed among persons with a high school degree or less (white men: -1.05 years [95% CI, -1.15 to -0.94], white women: -1.14 years [95% CI, -1.24 to -1.04], and black men: -0.30 years [95% CI, -0.56 to -0.04]). White adults with some college education but no 4-year college degree experienced similar declines in life expectancy (men: -0.89 years [95% CI, -1.07 to -0.73], women: -0.59 years [95% CI, -0.77 to -0.42]). In contrast, life expectancy at age 25 significantly increased among the college-educated (white men: 0.58 years [95% CI, 0.42 to 0.73], white women: 0.78 years [95% CI, 0.57 to 1.00], and black women: 1.70 years [95% CI, 0.91 to 2.53]). The difference between high- and low-education groups increased from 2010 to 2017, largely because life-years lost to drug use increased among those with a high school degree or less (white men: 0.93 years [95% CI, 0.90 to 0.96], white women: 0.50 years [95% CI, 0.47 to 0.52], black men: 0.75 years [95% CI, 0.71 to 0.79], and black women: 0.28 years [95% CI, 0.25 to 0.31]). Conclusions and Relevance: In this serial cross-sectional study, estimated life expectancy at age 25 years declined overall between 2010 and 2017; however, it declined among persons without a 4-year college degree and increased among college-educated persons. Much of the increasing educational differences in years of life lost may be related to deaths attributed to drug use.

Mortality and kidnapping estimates for the Yazidi population in the area of Mount Sinjar, Iraq, in August 2014: A retrospective household survey.

BACKGROUND: In August 2014, the so-called Islamic State of Iraq and Syria (ISIS) attacked the Yazidi religious minority living in the area of Mount Sinjar in Nineveh governorate, Iraq. We conducted a retrospective household survey to estimate the number and demographic profile of Yazidis killed and kidnapped. METHODS AND FINDINGS: The survey covered the displaced Yazidi population from Sinjar residing in camps in the Kurdistan Region of Iraq. Fieldwork took place between 4 November and 25 December, 2015. A systematic random sample of 1,300 in-camp households were interviewed about the current household composition and any killings and kidnappings of household members by ISIS. Of the 1,300 interviewed households, 988 were Yazidi from Sinjar. Yazidi households contained 6,572 living residents at the time of the survey; 43 killings and 83 kidnappings of household members were reported. We calculated the probability of being killed and kidnapped by dividing the number of reported killings and kidnappings by the number of sampled Yazidis at risk, adjusting for sampling design. To obtain the overall toll of killings and kidnappings, those probabilities were multiplied by the total Yazidi population living in Sinjar at the time of the ISIS attack, estimated at roughly 400,000 by the United Nations and Kurdish officials. The demographic profile of those killed and kidnapped was examined, distinguishing between children and adults and females and males. We estimated that 2.5% of the Yazidi population was either killed or kidnapped over the course of a few days in August 2014, amounting to 9,900 (95% CI 7,000-13,900) people in total. An estimated 3,100 (95% CI 2,100-4,400) Yazidis were killed, with nearly half of them executed-either shot, beheaded, or burned alive-while the rest died on Mount Sinjar from starvation, dehydration, or injuries during the ISIS siege. The estimated number kidnapped is 6,800 (95% CI 4,200-10,800). Escapees recounted the abuses they had suffered, including forced religious conversion, torture, and sex slavery. Over one-third of those reported kidnapped were still missing at the time of the survey. All Yazidis were targeted regardless of age and sex, but children were disproportionately affected. They were as likely as adults to be executed but constituted 93.0% (95% CI 71.9-98.6) of those who died on Mount Sinjar. Moreover, children only accounted for 18.8% (95% CI 8.4-36.9) of those who managed to escape captivity. A sensitivity analysis suggests that the actual toll of killings and kidnappings may be underestimated in our data because of survival bias. The uncertainty associated with inference from a small sample of in-camp households and the reliance on a rough figure of 400,000 for extrapolation to the total Yazidi population of Sinjar at the time of the ISIS attack are the main limitations of this study. CONCLUSIONS: Consistent with other existing evidence, our data provide a clear indication of the severity of the ISIS attack against the Yazidis in terms of both the number and demographic profile of those targeted.

Land cover change and fertility in West-Central Africa: rural livelihoods and the vicious circle model.

The vicious circle argument, rooted in a neo-Malthusian tradition, states that resource scarcity increases the demand for child labor and leads to higher fertility. The rural livelihood framework, on the other hand, contends that households employ multiple strategies, only one of which involves adjusting their fertility levels as a response to environmental pressures. This study provides a unique test of both theories by examining the relationship between land cover change and fertility across hundreds of rural communities in four West-Central African countries. The findings reveal a complex relationship between natural capital and fertility. In communities where natural capital was initially low, a further decline in that capital is associated with both higher fertility preferences and levels. However, we find that fertility preferences and behavior are often discordant, with notable within-community differences in response to decline in natural capital across levels of household wealth.

Trends in Life Expectancy and Lifespan Variation by Educational Attainment: United States, 1990-2010.

The educational gradient in life expectancy is well documented in the United States and in other low-mortality countries. Highly educated Americans, on average, live longer than their low-educated counterparts, who have recently seen declines in adult life expectancy. However, limiting the discussion on lifespan inequality to mean differences alone overlooks other dimensions of inequality and particularly disparities in lifespan variation. The latter represents a unique form of inequality, with higher variation translating into greater uncertainty in the time of death from an individual standpoint, and higher group heterogeneity from a population perspective. Using data from the National Vital Statistics System from 1990 to 2010, this is the first study to document trends in both life expectancy and S25--the standard deviation of age at death above 25--by educational attainment. Among low-educated whites, adult life expectancy declined by 3.1 years for women and by 0.6 years for men. At the same time, S25 increased by about 1.5 years among high school-educated whites of both genders, becoming an increasingly important component of total lifespan inequality. By contrast, college-educated whites benefited from rising life expectancy and record low variation in age at death, consistent with the shifting mortality scenario. Among blacks, adult life expectancy increased, and S25 plateaued or declined in nearly all educational attainment groups, although blacks generally lagged behind whites of the same gender on both measures. Documenting trends in lifespan variation can therefore improve our understanding of lifespan inequality and point to diverging trajectories in adult mortality across socioeconomic strata.

Bisphenol a exposure disrupts genomic imprinting in the mouse.

Exposure to endocrine disruptors is associated with developmental defects. One compound of concern, to which humans are widely exposed, is bisphenol A (BPA). In model organisms, BPA exposure is linked to metabolic disorders, infertility, cancer, and behavior anomalies. Recently, BPA exposure has been linked to DNA methylation changes, indicating that epigenetic mechanisms may be relevant. We investigated effects of exposure on genomic imprinting in the mouse as imprinted genes are regulated by differential DNA methylation and aberrant imprinting disrupts fetal, placental, and postnatal development. Through allele-specific and quantitative real-time PCR analysis, we demonstrated that maternal BPA exposure during late stages of oocyte development and early stages of embryonic development significantly disrupted imprinted gene expression in embryonic day (E) 9.5 and 12.5 embryos and placentas. The affected genes included Snrpn, Ube3a, Igf2, Kcnq1ot1, Cdkn1c, and Ascl2; mutations and aberrant regulation of these genes are associated with imprinting disorders in humans. Furthermore, the majority of affected genes were expressed abnormally in the placenta. DNA methylation studies showed that BPA exposure significantly altered the methylation levels of differentially methylated regions (DMRs) including the Snrpn imprinting control region (ICR) and Igf2 DMR1. Moreover, exposure significantly reduced genome-wide methylation levels in the placenta, but not the embryo. Histological and immunohistochemical examinations revealed that these epigenetic defects were associated with abnormal placental development. In contrast to this early exposure paradigm, exposure outside of the epigenetic reprogramming window did not cause significant imprinting perturbations. Our data suggest that early exposure to common environmental compounds has the potential to disrupt fetal and postnatal health through epigenetic changes in the embryo and abnormal development of the placenta.

Pre-gestational vs gestational exposure to maternal obesity differentially programs the offspring in mice.

AIMS/HYPOTHESIS: Maternal obesity is associated with an increased risk of obesity and impaired glucose homeostasis in offspring. However, it is not known whether a gestational or pre-gestational exposure confers similar risks, and if so, what the underlying mechanisms are. METHODS: We used reciprocal two-cell embryo transfers between mice fed either a control or high-fat diet (HFD) starting at the time of weaning. Gene expression in placenta was assessed by microarray analyses. RESULTS: A pre-gestational exposure to a maternal HFD (HFD/control) impaired fetal and placental growth despite a normal gestational milieu. Expression of imprinted genes and genes regulating vasculogenesis and lipid metabolism was markedly altered in placenta of HFD/control. An exposure to an HFD (control/HFD) only during gestation also resulted in fetal growth restriction and decreased placental weight. Interestingly, only a gestational exposure to an HFD (control/HFD) resulted in obesity and impaired glucose tolerance in adulthood. CONCLUSIONS/INTERPRETATION: An HFD during pregnancy has profound consequences for the offspring later in life. Our data demonstrate that the mechanism underlying this phenomenon is not related to placental dysfunction, intrauterine growth restriction or postnatal weight gain, but rather an inability of the progeny to adapt to the abnormal gestational milieu of an HFD. Thus, the ability to adapt to an adverse intrauterine environment is conferred prior to pregnancy and it is possible that the effects of a maternal HFD may be transmitted to subsequent generations.

Embryonic poly(A)-binding protein (EPAB) is required for oocyte maturation and female fertility in mice.

Gene expression during oocyte maturation and early embryogenesis up to zygotic genome activation requires translational activation of maternally-derived mRNAs. EPAB [embryonic poly(A)-binding protein] is the predominant poly(A)-binding protein during this period in Xenopus, mouse and human. In Xenopus oocytes, ePAB stabilizes maternal mRNAs and promotes their translation. To assess the role of EPAB in mammalian reproduction, we generated Epab-knockout mice. Although Epab(-/-) males and Epab(+/-) of both sexes were fertile, Epab(-/-) female mice were infertile, and could not generate embryos or mature oocytes in vivo or in vitro. Epab(-/-) oocytes failed to achieve translational activation of maternally-stored mRNAs upon stimulation of oocyte maturation, including Ccnb1 (cyclin B1) and Dazl (deleted in azoospermia-like) mRNAs. Microinjection of Epab mRNA into Epab(-/-) germinal vesicle stage oocytes did not rescue maturation, suggesting that EPAB is also required for earlier stages of oogenesis. In addition, late antral follicles in the ovaries of Epab(-/-) mice exhibited impaired cumulus expansion, and a 8-fold decrease in ovulation, associated with a significant down-regulation of mRNAs encoding the EGF (epidermal growth factor)-like growth factors Areg (amphiregulin), Ereg (epiregulin) and Btc (betacellulin), and their downstream regulators, Ptgs2 (prostaglandin synthase 2), Has2 (hyaluronan synthase 2) and Tnfaip6 (tumour necrosis factor α-induced protein 6). The findings from the present study indicate that EPAB is necessary for oogenesis, folliculogenesis and female fertility in mice.

Black and white differences in subjective survival expectations: An evaluation of competing mechanisms.

While black-white inequality in longevity is well documented in the United States, little is known about how individuals from different race/ethnic groups form their own personal survival expectations. Prior research has found that despite having higher mortality, blacks on average report higher survival expectations relative to whites. Using data from the Health and Retirement Study, we examined racial differences in subjective survival expectations across birth cohorts and provide explanatory mechanisms. We find that blacks-men in particular-were overly optimistic about their survival, but this effect had waned with successive birth cohorts. Furthermore, whereas subjective survival expectations and actual survival were correlated among white men, among black men the most optimistic fared worst. Blacks and whites differed not only in their response patterns, but also in how they weighed the different factors (socioeconomic, psychosocial, health, parental longevity) associated with expected survival. Importantly, those who estimated their survival probability with certainty had positive psychosocial characteristics, irrespective of race, but only whites had better health. These findings underscore the importance of group differences in subjective survival expectations as another potential form of inequality. Racial differences in how long individual expect to live may account for differences in social and economic behavior and outcomes, irrespective of actual longevity differentials.

Increasing Education-Based Disparities in Healthy Life Expectancy Among U.S. Non-Hispanic Whites, 2000-2010.

OBJECTIVES: To examine changes in Healthy Life Expectancy (HLE) against the backdrop of rising mortality among less-educated white Americans during the first decade of the twenty-first century. METHODS: This study documented changes in HLE by education among U.S. non-Hispanic whites, using data from the U.S. Multiple Cause of Death public-use files, the Integrated Public Use Microdata Sample (IPUMS) of the 2000 Census and the 2010 American Community Survey, and the Health and Retirement Study (HRS). Changes in HLE were decomposed into contributions from: (i) change in age-specific mortality rates; and (ii) change in disability prevalence, measured via Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL). RESULTS: Between 2000 and 2010, HLE significantly decreased for white men and women with less than 12 years of schooling. In contrast, HLE increased among college-educated white men and women. Declines or stagnation in HLE among less-educated whites reflected increases in disability prevalence over the study period, whereas improvements among the college educated reflected decreases in both age-specific mortality rates and disability prevalence at older ages. DISCUSSION: Differences in HLE between education groups increased among non-Hispanic whites from 2000 to 2010. In fact, education-based differences in HLE were larger than differences in total life expectancy. Thus, the lives of less-educated whites were not only shorter, on average, compared with their college-educated counterparts, but they were also more burdened with disability.

Determination of placental weight using two-dimensional sonography and volumetric mathematic modeling.

An abnormally decreased placental weight has been linked to increased perinatal complications, including intrauterine fetal demise (IUFD) and fetal growth restriction (IUGR). Despite its promise, determining placental weight prenatally using three-dimensional systems is time-consuming and requires expensive technology and expertise. We propose a novel method using two-dimensional sonography that provides an immediate estimation of placental volume. Placental volume was calculated in 29 third-trimester pregnancies using linear measurements of placental width, height, and thickness to calculate the convex-concave shell volume within 24 hours of birth. Data were analyzed to calculate Spearman's rho (r (s)) and significance. There was a significant correlation between estimated placental volume (EPV) and actual placental weight (r (s) = 0.80, P < 0.001). Subgroup analysis of preterm gestations ( N = 14) revealed an even more significant correlation of EPV to actual placental weight (r (s) = 0.89, P < 0.001). Placental weight can be accurately predicted by two-dimensional ultrasound with volumetric calculations. This method is simple, rapid, and accurate, making it practical for routine prenatal care, as well as for high-risk cases with decreased fetal movement and IUGR. Routine EPV surveillance may decrease the rates of perinatal complications and unexpected IUFD.

Different isoforms of the C. elegans FGF receptor are required for attraction and repulsion of the migrating sex myoblasts.

The Caenorhabditis elegans FGF receptor, EGL-15, is alternatively-spliced to yield two major isoforms that differ in their extracellular domains. The EGL-15(5A) isoform is necessary for the gonadal chemoattraction of the migrating sex myoblasts (SMs), while the EGL-15(5B) isoform is required for viability. Here we show that 5A is predominantly expressed in the M lineage, which gives rise to the migrating SMs and their sex muscle descendants, while 5B is predominantly expressed in the hypodermis. Tissue-specific expression, however, explains only part of the functional differences between these two receptor isoforms. 5A can carry out the reciprocal essential function of 5B when expressed in the hypodermis, but 5B is incapable of carrying out SM chemoattraction. Our data, therefore, indicate that the structural differences in these two isoforms contribute to their functional differences. Two lines of evidence indicate that the 5B isoform also plays a role in SM migration, implicating it in the repulsion that is observed when the chemoattraction is compromised. Thus, structural differences in the extracellular domains of these two isoforms can specify either attraction to or repulsion from the gonad.

Stem cells and the pathogenesis of endometriosis.

Endometriosis is a common gynecological disorder that is defined by the presence of endometrial tissue outside the uterine cavity. This disease often results in extensive morbidity, including chronic pelvic pain and infertility. The pathogenesis of endometriosis is likely multifactorial, and extensive investigation has explored the role of genetics, environmental factors, and the immune system in predisposing patients to developing endometriosis. A series of recent publications have described the identification of endometrial stem/progenitor cells. Such cells have long been speculated to function in the cyclic regeneration of the endometrium during the menstrual cycle and in the pathogenesis of several gynecological disorders. This narrative review will (i) examine the evidence for endometrial stem cells, (ii) examine their potential role in the pathogenesis of endometriosis, and (iii) identify important unanswered questions with suggestions for future investigation.

Proteomic profiling of urine identifies specific fragments of SERPINA1 and albumin as biomarkers of preeclampsia.

OBJECTIVE: The cause of preeclampsia remains unknown and the diagnosis can be uncertain. We used proteomic-based analysis of urine to improve disease classification and extend the pathophysiologic understanding of preeclampsia. STUDY DESIGN: Urine samples from 284 women were analyzed by surface-enhanced laser desorption/ionization. In the exploratory phase, 59 samples were used to extract the proteomic fingerprint characteristic of severe preeclampsia requiring mandated delivery and to develop a diagnostic algorithm. In the challenge phase, we sought to prospectively validate the algorithm in 225 women screened for a variety of high- and low-risk conditions, including preeclampsia. Of these, 19 women were followed longitudinally throughout pregnancy. The presence of biomarkers was interpreted relative to clinical classification, need for delivery, and other urine laboratory measures (ratios of protein to creatinine and soluble fms-like tyrosine kinase-1 to placental growth factor). In the translational phase, biomarker identification by tandem mass spectrometry and validation experiments in urine, serum, and placenta were used to identify, quantify, and localize the biomarkers or related proteins. RESULTS: We report that women with preeclampsia appear to present a unique urine proteomic fingerprint that predicts preeclampsia in need of mandated delivery with highest accuracy. This characteristic proteomic profile also has the ability to distinguish preeclampsia from other hypertensive or proteinuric disorders in pregnancy. Pregnant women followed longitudinally who developed preeclampsia displayed abnormal urinary profiles more than 10 weeks before clinical manifestation. Tandem mass spectrometry and de novo sequencing identified the biomarkers as nonrandom cleavage products of SERPINA1 and albumin. Of these, the 21 amino acid C-terminus fragment of SERPINA1 was highly associated with severe forms of preeclampsia requiring early delivery. In preeclampsia, increased and aberrant SERPINA1 immunoreactivity was found in urine, serum, and placenta, in which it localized predominantly to placental villi and placental vascular spaces adherent to the endothelium. In addition, significant perivascular deposits of misfolded SERPINA1 aggregates were exclusively identified in preeclamptic placentae. CONCLUSION: Proteomics-based characterization of urine in preeclampsia identified a proteomic fingerprint composed of SERPINA1 and albumin fragments, which can accurately diagnose preeclampsia and shows promise to discriminate it from other hypertensive proteinuric diseases. These findings provide insight into a novel pathophysiological mechanism of preeclampsia related to SERPINA1 misfolding, which may offer new therapeutic opportunities in the future.

Does the Functional Form of the Association Between Education and Mortality Differ by U.S. Region?

To understand the education-mortality association among U.S. adults, recent studies have documented its national functional form. However, the functional form of education-mortality relationship may vary across geographic contexts. The four U.S. Census regions differ considerably in their social and economic policies, employment opportunities, income levels, and other factors that may affect how education lowers the risk of mortality. Thus, we documented regional differences in the functional form of the education-mortality association and examined the role of employment and income in accounting for regional differences. We used data on non-Hispanic white adults (2,981,672, person years) aged 45-84 in the 2000-2009 National Health Interview Survey, with Linked Mortality File through 2011 (37,598 deaths) and estimated discrete-time hazard models. The functional form of education and adult mortality was best characterized by credentialism in the Midwest, Northeast, and for Western men. For Western women, the association was linear, consistent with the human capital model. In the South, we observed a combination of mechanisms, with mortality risk declining with each year of schooling and a step change with high school graduation, followed by steeper decline thereafter. Our work adds to the increasing body of research that stresses the importance of contexts in shaping the education-mortality relationship.

Educational Differences in the Prevalence of Dementia and Life Expectancy with Dementia: Changes from 2000 to 2010.

Objectives: This article provides the first estimates of educational differences in age-specific prevalence, and changes in prevalence over time, of dementia by education levels in the United States. It also provides information on life expectancy, and changes in life expectancy, with dementia and cognitively healthy life for educational groups. Method: Data on cognition from the 2000 and 2010 Health and Retirement Study are used to classify respondents as having dementia, cognitive impairment without dementia (CIND), or being cognitively intact. Vital statistics data are used to estimate life tables for education groups and the Sullivan method is used to estimate life expectancy by cognitive state. Results: People with more education have lower prevalence of dementia, more years of cognitively healthy life, and fewer years with dementia. Years spent in good cognition increased for most sex-education groups and, conversely, years spent with dementia decreased for some. Mortality reduction was the most important factor in increasing cognitively healthy life. Change in the distribution of educational attainment has played a major role in the reduction of life with dementia in the overall population. Discussion: Differences in the burden of cognitive loss by education point to the significant cost of low social status both to individuals and to society.

Diverging Trends in Cause-Specific Mortality and Life Years Lost by Educational Attainment: Evidence from United States Vital Statistics Data, 1990-2010.

BACKGROUND: Life expectancy at birth in the United States will likely surpass 80 years in the coming decade. Yet recent studies suggest that longevity gains are unevenly shared across age and socioeconomic groups. First, mortality in midlife has risen among non-Hispanic whites. Second, low-educated whites have suffered stalls (men) or declines (women) in adult life expectancy, which is significantly lower than among their college-educated counterparts. Estimating the number of life years lost or gained by age and cause of death, broken down by educational attainment, is crucial in identifying vulnerable populations. METHODS AND FINDINGS: Using U.S. vital statistics data from 1990 to 2010, this study decomposes the change in life expectancy at age 25 by age and cause of death across educational attainment groups, broken down by race and gender. The findings reveal that mortality in midlife increased for white women (and to a lesser extent men) with 12 or fewer years of schooling, accounting for most of the stalls or declines in adult life expectancy observed in those groups. Among blacks, mortality declined in nearly all age and educational attainment groups. Although an educational gradient was found across multiple causes of death, between 60 and 80 percent of the gap in adult life expectancy was explained by cardiovascular diseases, smoking-related diseases, and external causes of death. Furthermore, the number of life years lost to smoking-related, external, and other causes of death increased among low- and high school-educated whites, explaining recent stalls or declines in longevity. CONCLUSIONS: Large segments of the American population-particularly low- and high school-educated whites under age 55-are diverging from their college-educated counterparts and losing additional years of life to smoking-related diseases and external causes of death. If this trend continues, old-age mortality may also increase for these birth cohorts in the coming decades.

Trends and group differences in the association between educational attainment and U.S. adult mortality: implications for understanding education's causal influence.

Has the shape of the association between educational attainment and U.S. adult mortality changed in recent decades? If so, is it changing consistently across demographic groups? What can changes in the shape of the association tell us about the possible mechanisms in play for improving health and lowering mortality risk over the adult life course? This paper develops the argument that societal technological change may have had profound effects on the importance of educational attainment - particularly advanced education - in the U.S. adult population for garnering health advantages and that these changes should be reflected in changes in the functional form of the association between educational attainment and mortality. We review the historical evidence on the changing functional form of the association, drawing on studies based in the United States, to assess whether these changes are consistent with our argument about the role of technological change. We also provide an updated analysis of these functional form patterns and trends, contrasting data from the early 21st Century with data from the late 20th Century. This updated evidence suggests that the shape of the association between educational attainment and U.S. adult mortality appears to be reflecting lower and lower adult mortality for very highly educated Americans compared to their low-educated counterparts in the 21st Century. We draw on this review and updated evidence to reflect on the question whether education's association with adult mortality has become increasingly causal in recent decades, why, and the potential research, policy, and global implications of these changes.

Widowhood and depression: new light on gender differences, selection, and psychological adjustment.

OBJECTIVES: To document short- and long-term trajectories of depressive symptoms following widowhood and to test whether these trajectories vary by gender and anticipatory spousal loss. METHOD: Eight waves of prospective panel data from the Health and Retirement Study, over a 14-year period, are used to evaluate gender differences in depressive symptoms following widowhood in late midlife. Short-term trajectories are modeled using a linear regression of change in Center for Epidemiologic Studies Depression (CES-D) score on duration of widowhood. Long-term trajectories are modeled using a mixed-effects hierarchical linear model of CES-D scores over time. RESULTS: We find no gender differences in bereavement effects on depressive symptoms in either short or long term, net of widowhood duration. When spousal death is anticipated, both men and women return to their prewidowhood levels of depressive symptoms within 24 months of becoming widowed. Across marital groups, the continuously married are better off compared with the widowed even prior to spousal loss, whereas early, long-term widowhood is associated with worse outcomes compared with late widowhood. DISCUSSION: Although men and women do not differ in trajectories of depressive symptoms following widowhood, given similar circumstances, women are distinctly disadvantaged in that they are more likely to become widowed and under less favorable conditions.