Genetic analyses of the parasitic nematode, Parelaphostrongylus tenuis, in Missouri and Kentucky reveal unexpected levels of diversity and population differentiation.

Wildlife translocations, which involve the introduction of naive hosts into new environments with novel pathogens, invariably pose an increased risk of disease. The meningeal worm Parelaphostrongylus tenuis is a nematode parasite of the white-tailed deer (Odocoileus virginianus), which serves as its primary host and rarely suffers adverse effects from infection. Attempts to restore elk (Cervus canadensis) to the eastern US have been hampered by disease caused by this parasite. Using DNA sequence data from mitochondrial and nuclear genes, we examined the hypothesis that elk translocated within the eastern US could be exposed to novel genetic variants of P. tenuis by detailing the genetic structure among P. tenuis taken from white-tailed deer and elk at a source (Kentucky) and a release site (Missouri). We found high levels of diversity at both mitochondrial and nuclear DNA in Missouri and Kentucky and a high level of differentiation between states. Our results highlight the importance of considering the potential for increased disease risk from exposure to novel strains of parasites in the decision-making process of a reintroduction or restoration.

Do dehydroepiandrosterone, progesterone, and testosterone influence women's depression and anxiety levels? Evidence from hair-based hormonal measures of 2105 rural Indian women.

Depressive and anxiety disorders substantially contribute to the global burden of disease, particularly in poor countries. Higher prevalence rates for both disorders among women indicate sex hormones may be integrated in the pathophysiology of these disorders. The Kshetriya Gramin Financial Services study surveyed a random sample of 4160 households across 876 villages in rural Tamil Nadu, India. An interviewer-administered questionnaire was conducted to quantify depressive (K6-D) and anxiety (K6-A) symptoms. Alongside, hair samples for sex hormone profiling were collected from a subsample of 2105 women aged 18-85 years. Importantly, 5.9%, 14.8%, and 46.3% of samples contained non-detectable hormone levels for dehydroepiandrosterone, progesterone, and testosterone, respectively. Our primary analysis imputes values for the non-detectable sample and we check robustness of results when non-detectable values are dropped. In this cohort of women from rural India, higher depressive symptomatology is associated with lower levels of dehydroepiandrosterone and higher depressive and anxiety symptoms are associated with higher levels of testosterone. Progesterone shows no clear association with either depressive or anxiety symptoms. These results support a potential protective effect of higher endogenous dehydroepiandrosterone levels. An important caveat on the potential negative effect of hair testosterone levels on women's mental health is that the testosterone analysis is sensitive to how non-detectable values are treated.

Co-enrolment of Participants into Multiple Cancer Trials: Benefits and Challenges.

Opportunities to enter patients into more than one clinical trial are not routinely considered in cancer research and experiences with co-enrolment are rarely reported. Potential benefits of allowing appropriate co-enrolment have been identified in other settings but there is a lack of evidence base or guidance to inform these decisions in oncology. Here, we discuss the benefits and challenges associated with co-enrolment based on experiences in the Add-Aspirin trial - a large, multicentre trial recruiting across a number of tumour types, where opportunities to co-enrol patients have been proactively explored and managed. The potential benefits of co-enrolment include: improving recruitment feasibility; increased opportunities for patients to participate in trials; and collection of robust data on combinations of interventions, which will ensure the ongoing relevance of individual trials and provide more cohesive evidence to guide the management of future patients. There are a number of perceived barriers to co-enrolment in terms of scientific, safety and ethical issues, which warrant consideration on a trial-by-trial basis. In many cases, any potential effect on the results of the trials will be negligible - limited by a number of factors, including the overlap in trial cohorts. Participant representatives stress the importance of autonomy to decide about trial enrolment, providing a compelling argument for offering co-enrolment where there are multiple trials that are relevant to a patient and no concerns regarding safety or the integrity of the trials. A number of measures are proposed for managing and monitoring co-enrolment. Ensuring acceptability to (potential) participants is paramount. Opportunities to enter patients into more than one cancer trial should be considered more routinely. Where planned and managed appropriately, co-enrolment can offer a number of benefits in terms of both scientific value and efficiency of study conduct, and will increase the opportunities for patients to participate in, and benefit from, clinical research.

Preliminary results of a feasibility study of the use of information technology for identification of suspected colorectal cancer in primary care: the CREDIBLE study.

BACKGROUND: We report the findings of a feasibility study using information technology to search electronic primary care records and to identify patients with possible colorectal cancer. METHODS: An algorithm to flag up patients meeting National Institute for Health and Care Excellence (NICE) urgent referral criteria for suspected colorectal cancer was developed and incorporated into clinical audit software. This periodically flagged up such patients aged 60 to 79 years. General practitioners (GPs) reviewed flagged-up patients and decided on further clinical management. We report the numbers of patients identified and the numbers that GPs judged to need further review, investigations or referral to secondary care and the final diagnoses. RESULTS: Between January 2012 and March 2014, 19,580 records of patients aged 60 to 79 years were searched in 20 UK general practices, flagging up 809 patients who met urgent referral criteria. The majority of the patients had microcytic anaemia (236 (29%)) or rectal bleeding (205 (25%)). A total of 274 (34%) patients needed further clinical review of their records; 199 (73%) of these were invited for GP consultation, and 116 attended, of whom 42 were referred to secondary care. Colon cancer was diagnosed in 10 out of 809 (1.2%) flagged-up patients and polyps in a further 28 out of 809 (3.5%). CONCLUSIONS: It is technically possible to identify patients with colorectal cancer by searching electronic patient records.

Identifying infants at high-risk for second-hand smoke exposure.

BACKGROUND: To examine the social determinants of infant smoke exposure and whether these associations vary by mothers' smoking status and number of children in the household. METHODS: There were 135 278 mothers from 28 states who participated in the Pregnancy Risk Assessment Monitoring System from 2000 to 2003. RESULTS: Overall 9.9% of mothers reported that her infant was in the same room as someone smoking for 1 or more hours per day. Among smoking households, infants with 1 or 2+ siblings were 25% and 59% more likely to be exposed to 1+ hours of second-hand smoke daily, respectively, than infants with no siblings. CONCLUSION: Infants only a few months old are being exposed to second-hand smoke, particularly infants whose mother smokes and infants with siblings, indicating the importance of surveillance even for this young age group.

Occupational solvent exposure and cognition: does the association vary by level of education?

OBJECTIVE: Chronic occupational solvent exposure is associated with long-term cognitive deficits. Cognitive reserve may protect solvent-exposed workers from cognitive impairment. We tested whether the association between chronic solvent exposure and cognition varied by educational attainment, a proxy for cognitive reserve. METHODS: Data were drawn from a prospective cohort of French national gas and electricity (GAZEL) employees (n = 4,134). Lifetime exposure to 4 solvent types (chlorinated solvents, petroleum solvents, benzene, and nonbenzene aromatic solvents) was assessed using a validated job-exposure matrix. Education was dichotomized at less than secondary school or below. Cognitive impairment was defined as scoring below the 25th percentile on the Digit Symbol Substitution Test at mean age 59 (SD 2.8; 88% of participants were retired at testing). Log-binomial regression was used to model risk ratios (RRs) for poor cognition as predicted by solvent exposure, stratified by education and adjusted for sociodemographic and behavioral factors. RESULTS: Solvent exposure rates were higher among less-educated patients. Within this group, there was a dose-response relationship between lifetime exposure to each solvent type and RR for poor cognition (e.g., for high exposure to benzene, RR = 1.24, 95% confidence interval 1.09-1.41), with significant linear trends (p < 0.05) in 3 out of 4 solvent types. Recency of solvent exposure also predicted worse cognition among less-educated patients. Among those with secondary education or higher, there was no significant or near-significant relationship between any quantification of solvent exposure and cognition. CONCLUSIONS: Solvent exposure is associated with poor cognition only among less-educated individuals. Higher cognitive reserve in the more-educated group may explain this finding.

Racial disparities in job strain among American and immigrant long-term care workers.

BACKGROUND: Nursing homes are occupational settings, with an increasing minority and immigrant workforce where several psychosocial stressors intersect. AIM: This study aimed to examine racial/ethnic differences in job strain between Black (n = 127) and White (n = 110) immigrant and American direct-care workers at nursing homes (total n = 237). METHODS: Cross-sectional study with data collected at four nursing homes in Massachusetts during 2006-2007. We contrasted Black and White workers within higher-skilled occupations such as registered nurses or licensed practical nurses (n = 82) and lower-skilled staff such as certified nursing assistants (CNAs, n = 155). RESULTS: Almost all Black workers (96%) were immigrants. After adjusting for demographic and occupational characteristics, Black employees were more likely to report job strain, compared with Whites [relative risk (RR): 2.9, 95% confidence interval (CI) 1.3 to 6.6]. Analyses stratified by occupation showed that Black CNAs were more likely to report job strain, compared with White CNAs (RR: 3.1, 95% CI: 1.0 to 9.4). Black workers were also more likely to report low control (RR: 2.1, 95% CI: 1.1 to 4.0). Additionally, Black workers earned $2.58 less per hour and worked 7.1 more hours per week on average, controlling for potential confounders. CONCLUSION: Black immigrant workers were 2.9 times more likely to report job strain than White workers, with greater differences among CNAs. These findings may reflect differential organizational or individual characteristics but also interpersonal or institutional racial/ethnic discrimination. Further research should consider the role of race/ethnicity in shaping patterns of occupational stress.

Using self-rated health for analysing social inequalities in health: a risk for underestimating the gap between socioeconomic groups?

BACKGROUND: The use of self-rated health (SRH) for measuring health inequalities could present some limits. The impact of the same disease on SRH could be different according to health expectations people have which are associated with social characteristics. The aim of this study was to analyse the link between physical health status and SRH, according to level of education. METHOD: Data from the National Health and Nutrition Examination Survey for the years 2001-4 were used. Multivariate logistic regression analyses were performed for assessing the relation between health status and SRH according to educational level. RESULTS: The sample consisted of 4661 men and 4593 women. Reporting functional limitation was associated more strongly with poor SRH in higher educated women than in lower educated women (OR, 8.73, 95% CI 5.87 to 12.98 vs OR, 3.97, 95% CI 2.93 to 5.38 respectively), as was reporting respiratory disease (OR, 5.17, 95% CI 3.67 to 7.30 vs OR, 2.60, 95% CI 1.72 to 3.95 respectively), cardiovascular disease (OR, 9.79, 95% CI 6.22 to 15.40 vs OR, 3.34, 95% CI 2.29 to 4.87 respectively) and dental problems (OR, 4.37, 95% CI 3.22 to 5.92 vs OR, 2.58, 95% CI 1.97 to 3.39 respectively). Reporting functional limitation was associated more strongly with poor SRH in higher educated men than in lower educated men (OR, 7.71, 95% CI 5.04 to 11.79 vs OR, 4.87, 95% CI 3.30 to 7.18 respectively), as reporting oral problems (OR, 2.62, 95% CI 1.84 to 3.74 vs OR, 3.63, 95% CI 2.81 to 4.68 respectively). CONCLUSIONS: The impact of health problems on SRH is stronger among better educated individuals. This phenomenon could lead to an underestimate of the health inequalities across socioeconomic groups.

Does childhood schooling affect old age memory or mental status? Using state schooling laws as natural experiments.

BACKGROUND: The association between schooling and old age cognitive outcomes such as memory disorders is well documented but, because of the threat of reverse causation, controversy persists over whether education affects old age cognition. Changes in state compulsory schooling laws (CSL) are treated as natural experiments (instruments) for estimating the effect of education on memory and mental status among the elderly. Changes in CSL predict changes in average years of schooling completed by children who are affected by the new laws. These educational differences are presumably independent of innate individual characteristics such as IQ. METHODS: CSL-induced changes in education were used to obtain instrumental variable (IV) estimates of education's effect on memory (n = 10,694) and mental status (n = 9751) for white, non-Hispanic US-born Health and Retirement Survey participants born between 1900 and 1947 who did not attend college. RESULTS: After adjustment for sex, birth year, state of birth and state characteristics, IV estimates of education's effect on memory were large and statistically significant. IV estimates for mental status had very wide confidence intervals, so it was not possible to draw meaningful conclusions about the effect of education on this outcome. CONCLUSIONS: Increases in mandatory schooling lead to improvements in performance on memory tests many decades after school completion. These analyses condition on individual states, so differences in memory outcomes associated with CSL changes cannot be attributed to differences between states. Although unmeasured state characteristics that changed contemporaneously with CSL might account for these results, unobserved genetic variation is unlikely to do so.

Unemployment as a risk factor for AIDS and death for HIV-infected patients in the era of highly active antiretroviral therapy.

OBJECTIVES: To assess the association between social situation and disease progression among patients diagnosed with HIV infection since the advent of highly active antiretroviral therapy (HAART), taking late testing into account. METHODS: Prospective cohort study of adults diagnosed with HIV since 1996 in six large HIV reference centres in France. Associations between social situation and death, disease progression and treatment initiation were assessed using Cox regression model. Analysis was restricted to 5302 patients (77.9% of the sample) for whom the status at HIV diagnosis (late or not late) was known. RESULTS: 134 people (2.5%) died and 400 presented with a new AIDS defining event (7.5%). In multivariate analysis, probabilities of death (HR 3.75, 95% CI 2.11 to 6.66) and disease progression (HR 1.59, 95% CI 1.17 to 2.15) were higher for non-working patients and for late testers (HR 9.18, 95% CI 4.32 to 19.48 for death) and lower for treated patients (HR 0.18, 95% CI 0.08 to 0.41 for death and HR 0.29, 95% CI 0.20 to 0.42 for disease progression). The probability of receiving antiretroviral treatment was not associated with employment status but was higher for late testers, for those living in a stable relationship and lower for those diagnosed after 2000. CONCLUSION: Among patients diagnosed for HIV infection in the HAART era, poor social situation is an independent risk factor of mortality and morbidity, and is not explained by delayed access to diagnosis or treatment.

Frailty modifies effectiveness of psychosocial intervention in recovery from stroke.

OBJECTIVE: To evaluate the impact of a psychosocial intervention on instrumental activities of daily living, physical performance, cognition and mortality after stroke. DESIGN: A randomized clinical trial. SETTING: Patients were recruited from hospitals and rehabilitation centres; the intervention took place in subjects' homes. SUBJECTS: Two-hundred and ninety-one stroke survivors over age 45. One-hundred and forty-six subjects were assigned to the intervention and 145 subjects were assigned to usual care. INTERVENTION: Up to 16 meetings conducted over six months in the patient's home (approximately weekly for 12 weeks, followed by tri-weekly sessions for another 12 weeks). Sessions lasted approximately 1 hour and included, when possible, the entire support system (stroke survivor, primary caregiver, additional family and friends, and professional caregivers). MAIN OUTCOME MEASURES: Instrumental activities of daily living, physical performance, and cognition were assessed six months post stroke; mortality was assessed at an average of 47 months post stroke. RESULTS: No significant differences in outcomes were observed between the intervention and usual care groups when analysing the total study population. Among non-frail participants (n = 156), subjects randomized to treatment had better scores on instrumental activities of daily living (mean score among treated = 12.4 (standard deviation (SD) = 2.1), mean score among usual care subjects = 11.3 (SD = 2.9), P-value for difference in means = 0.01) and reduced risk of mortality (P = 0.03) than subjects randomized to usual care. CONCLUSION: While there is evidence that the treatment benefited healthier subgroups, results also show evidence that the treatment was not effective, and possibly harmful, in frail subgroups.

Lifelong socioeconomic trajectory and premature mortality (35-65 years) in France: findings from the GAZEL Cohort Study.

BACKGROUND: Studies conducted in the UK and Scandinavia show an inverse association between lifetime socioeconomic position and adult mortality. However, there are virtually no data from other countries and few investigations have examined non-cardiovascular mortality in men and women. METHODS: Lifelong socioeconomic trajectories (father's occupation, own occupation in young adulthood and in mid-life) and premature (< or = 65 years) mortality (all-cause, smoking-related cancer, diseases of the circulatory system and external causes) in the French GAZEL Cohort Study (14,972 men and 5,598 women, followed up between 1990 and 2004) were studied. Hazard ratios (HRs) were estimated using Cox's regression models adjusted for age, marital status, tobacco smoking, alcohol consumption, body mass index, and fruit and vegetable consumption. RESULTS: Men and women who experienced lifelong disadvantage or downward intergenerational mobility were at high risk of dying prematurely compared with those with a favourable trajectory (age-adjusted HRs for all-cause mortality: cumulative disadvantage: HR 1.61, 95% confidence interval (CI) 1.26 to 2.06 in men and HR 1.95, 95% CI 1.10 to 3.47 in women; downward mobility: HR 1.87, 95% CI 1.35 to 2.58 in men and HR 2.05, 95% CI 1.12 to 3.75 in women). Associations were strongest for mortality due to chronic diseases (smoking-related cancers and diseases of the circulatory system). These associations were partly explained by marital status, body mass index, alcohol consumption, cigarette smoking, and fruit and vegetable consumption. CONCLUSIONS: In France, where the leading cause of premature death is cancer, lifelong socioeconomic position is associated with the risk of dying before the age of 65 years. Adult factors seem more relevant than childhood socioeconomic circumstances.

Do psychosocial work factors and social relations exert independent effects on sickness absence? A six year prospective study of the GAZEL cohort.

STUDY OBJECTIVES: The objective of this prospective cohort study was to determine whether psychosocial work characteristics and social relations exert independent effects on the incidence of sickness absence in a population of middle aged French employees over six years of follow up. DESIGN: This study included 9631 men and 3595 women participating in the French GAZEL cohort. Social relations (social networks, personal social support, and social relations satisfaction) were measured in 1994 by self report. Psychosocial work characteristics (decision latitude, psychological demands, and social support at work) were ascertained in 1995. Sickness absence data were collected independently. The authors studied the incidence of short (>7 days), intermediate (7-21 days), and long (>21 days) spells of absence from 1995 to 31 December 2001. Rate ratios associated with psychosocial exposures, adjusted on sociodemographic characteristics, and health behaviours, were calculated by means of log-linear Poisson regression. SETTING: A cohort of 20000 employees of France's national gas and electricity company (the GAZEL study). MAIN RESULTS: Among men and women, levels of decision latitude and personal social support below the median predicted 17% to 24% increases in absence rates. Low satisfaction with social relations and low social support at work lead to a 10% to 26% excess in sick leaves among men. No interactive effects were found between the variables under study. CONCLUSIONS: The quality of the work environment and of social relations affect sickness absence over an extended period of follow up. This study supports the hypothesis of independent, not interactive effects.

Depression, heart rate variability, and acute myocardial infarction.

BACKGROUND: Clinical depression is associated with an increased risk for mortality in patients with a recent myocardial infarction (MI). Reduced heart rate variability (HRV) has been suggested as a possible explanation for this association. The purpose of this study was to determine if depression is associated with reduced HRV in patients with a recent MI. METHODS AND RESULTS: Three hundred eighty acute MI patients with depression and 424 acute MI patients without depression were recruited. All underwent 24-hour ambulatory electrocardiographic monitoring after hospital discharge. In univariate analyses, 4 indices of HRV were significantly lower in patients with depression than in patients without depression. Variables associated with HRV were then compared between patients with and without depression, and potential confounds were identified. These variables (age, sex, diabetes, and present cigarette smoking) were entered into an analysis of covariance model, followed by depression status. In the final model, all but one HRV index (high-frequency power) remained significantly lower in patients with depression than in patients without depression. CONCLUSIONS: We conclude that greater autonomic dysfunction, as reflected by decreased HRV, is a plausible mechanism linking depression to increased cardiac mortality in post-MI patients.

Social ties and mental health.

It is generally agreed that social ties play a beneficial role in the maintenance of psychological well-being. In this targeted review, we highlight four sets of insights that emerge from the literature on social ties and mental health outcomes (defined as stress reactions, psychological well-being, and psychological distress, including depressive symptoms and anxiety). First, the pathways by which social networks and social supports influence mental health can be described by two alternative (although not mutually exclusive) causal models-the main effect model and the stress-buffering model. Second, the protective effects of social ties on mental health are not uniform across groups in society. Gender differences in support derived from social network participation may partly account for the higher prevalence of psychological distress among women compared to men. Social connections may paradoxically increase levels of mental illness symptoms among women with low resources, especially if such connections entail role strain associated with obligations to provide social support to others. Third, egocentric networks are nested within a broader structure of social relationships. The notion of social capital embraces the embeddedness of individual social ties within the broader social structure. Fourth, despite some successes reported in social support interventions to enhance mental health, further work is needed to deepen our understanding of the design, timing, and dose of interventions that work, as well as the characteristics of individuals who benefit the most.

Psychopathology, childhood sexual abuse and other childhood adversities: relative links to subsequent suicidal behaviour in the US.

BACKGROUND: Research shows that psychopathology, child sexual abuse and other childhood adversities are risk factors for suicide. However, few have investigated their joint and independent roles in the pursuit of a reliable, predictive model of suicidal behaviour. METHODS: Data are from the National Comorbidity Survey (N = 5877), a nationally representative study of prevalence, risk factors, and social consequences of psychiatric disorders in the US. Discrete time survival analysis and population attributable risk methodologies were utilized. RESULTS: Among those sexually abused as children, odds of suicide attempts were 2-4 times higher among women and 4-11 times higher among men, compared with those not abused, controlling for other adversities. Odds ratios were reduced but most remained statistically significant after adjusting for lifetime psychiatric illnesses preceding suicide attempts. In the same predictive equation, 79% of serious suicide attempts among women could be attributed to psychiatric disorders while 12% was attributable to rape and 7% to molestation. The highest probability of a first attempt was during early adolescence for those who were sexually abused and had a lifetime disorder, but it was 8-12 years older for those sexually abused without any disorders. CONCLUSIONS: In the US, a strong association exists between child sexual abuse and suicidal behaviour, mediated by psychopathology. There is a substantial proportion of suicide risk attributable to child sexual abuse beyond the presence of psychopathology and other adversities. From a clinical standpoint, abuse survivors represent a high-risk population for suicidal behaviour. Further research into this preventable antecedent of suicide attempts is necessary.

Social relationships, social support, and patterns of cognitive aging in healthy, high-functioning older adults: MacArthur studies of successful aging.

This study examines the relationship of social ties and support to patterns of cognitive aging in the MacArthur Studies of Successful Aging (see L. F. Berkman et al., 1993), a cohort study of 1,189 initially high-functioning older adults. Baseline and longitudinal data provide information on initial levels as well as changes in cognitive performance over a 7.5-year period. Linear regression analyses revealed that participants receiving more emotional support had better baseline performance, as did those who were unmarried and those reporting greater conflict with network members. Greater baseline emotional support was also a significant predictor of better cognitive function at the 7.5-year follow-up, controlling for baseline cognitive function and known sociodemographic, behavioral, psychological, and health status predictors of cognitive aging. The findings suggest the potential value of further research on the role of the social environment in protecting against cognitive declines at older ages.

Living arrangements, social integration, and change in functional health status.

Limited prospective data have examined the association between living arrangements and emotional wellbeing. The authors assessed whether older women living with a spouse were less likely to experience a decline in mental health, vitality, or physical function compared with women living alone or with nonspouse others. The association between living arrangement and 4-year change in functional health status was examined prospectively among 28,324 women aged 60-72 years in the Nurses' Health Study. After adjustment for age, baseline function, comorbid conditions, and health behaviors, women living alone had lower risk of decline in mental health (relative risk (RR) = 0.73, 95 percent confidence interval (CI): 0.65, 0.81) and vitality (RR = 0.72, 95 percent CI: 0.65, 0.80) compared with those living with a spouse. Contact with friends and relatives and level of social engagement were significantly protective against a decline in mental health among women living alone but not among women living with a spouse. These results suggest that women living independently are neither socially isolated nor at increased risk for decline in functional health status. In fact, these women actually fare better on measures of psychologic function than do women living with a spouse.

Long-term outcome of myocardial infarction in women and men: a population perspective.

Because of women's survival advantage, the impact of myocardial infarction (MI) on long-term mortality in women compared with men may be underestimated. The authors examined this issue in a community sample of 2,462 persons aged > or = 65 years living in New Haven, Connecticut, who were free of MI at baseline and were followed for 10 years (1982-1992). By using proportional hazards models with MI hospitalizations and the sex-MI interaction as time-dependent covariables, survival for the MI cases from the date of MI was compared with survival of persons who, at the same follow-up time, were still alive and free of MI. Women survived longer than men mainly in the absence of MI. The multivariable-adjusted hazard ratios of death were 0.53 in the absence and 0.87 in the presence of MI, and MI was associated with a greater risk of death in women (adjusted hazard ratio = 5.9) than in men (adjusted hazard ratio = 3.6) (p = 0.01 for the sex-MI interaction). When out-of-hospital fatal infarctions were considered, the impact of MI on survival in women compared with men increased. In conclusion, in this elderly cohort, when viewed from a population perspective, MI had a greater impact on mortality in women and significantly narrowed women's typical survival advantage over men.