Deaths of profound despair: A retrospective cohort study of mortality among people experiencing homelessness.

INTRODUCTION: The number of people dying while unhoused is increasing nationally. In Santa Clara County (SCC), deaths of unhoused people have almost tripled in 9 years. This is a retrospective cohort study examining mortality trends among unhoused people in SCC. The objective of the study is to characterize mortality outcomes in the unhoused population, and compare these to the SCC general population. MATERIALS AND METHODS: We obtained data from the SCC Medical Examiner-Coroner's Office on unhoused people's deaths that occurred between 2011-2019. We analyzed demographic trends and cause of death, compared to mortality data on the SCC general population obtained from CDC databases. We also compared rates of deaths of despair. RESULTS: There were a total of 974 unhoused deaths in the SCC cohort. The unadjusted mortality rate among unhoused people is higher than the general population, and unhoused mortality has increased over time. The standardized mortality ratio for unhoused people is 3.8, compared to the general population in SCC. The most frequent age of death among unhoused people was between 55-64 years old (31.3%), followed by 45-54 (27.5%), compared to 85+ in the general population (38.3%). Over ninety percent of deaths in the general population were due to illness. In contrast, 38.2% of unhoused deaths were due to substance use, 32.0% illness, 19.0% injury, 4.2% homicide, and 4.1% suicide. The proportion of deaths of despair was 9-fold higher in the unhoused cohort compared to the housed cohort. DISCUSSION: Homelessness has profound impacts on health, as people who are unhoused are dying 20 years younger, with higher rates of injurious, treatable, and preventable causes, than people in the general population. System-level, inter-agency interventions are needed. Local governments need to systematically collect housing status at death to monitor mortality patterns among unhoused people, and adapt public health systems to prevent rising unhoused deaths.

African American Unemployment and the Disparity in Periviable Births.

Periviable infants (i.e., born before 26 complete weeks of gestation) represent fewer than .5% of births in the US but account for 40% of infant mortality and 20% of billed hospital obstetric costs. African American women contribute about 14% of live births in the US, but these include nearly a third of the country's periviable births. Consistent with theory and with periviable births among other race/ethnicity groups, males predominate among African American periviable births in stressed populations. We test the hypothesis that the disparity in periviable male births among African American and non-Hispanic white populations responds to the African American unemployment rate because that indicator not only traces, but also contributes to, the prevalence of stress in the population. We use time-series methods that control for autocorrelation including secular trends, seasonality, and the tendency to remain elevated or depressed after high or low values. The racial disparity in male periviable birth increases by 4.45% for each percentage point increase in the unemployment rate of African Americans above its expected value. We infer that unemployment-a population stressor over which our institutions exercise considerable control-affects the disparity between African American and non-Hispanic white periviable births in the US.

Invisibility as a structural determinant: Mortality outcomes of Asians and Pacific Islanders experiencing homelessness.

Introduction: Asians and Pacific Islanders (APIs) who are experiencing homelessness are situated in a social intersection that has rendered them unrecognized and therefore vulnerable. There has been increasing attention to racial disparities in homelessness, but research into API homelessness is exceedingly rare, despite rapidly growing populations. The purpose of this study is to examine the causes of death among APIs who died while homeless in Santa Clara County (SCC) and compare these causes to other racial groups. Materials and methods: We report on data obtained from the SCC Medical Examiner-Coroner's Office on unhoused people's deaths that occurred between 2011 and 2021 (n = 1,394), including data on deaths of APIs experiencing homelessness (n = 87). Results: APIs comprised 6.2% of total deaths of unhoused people. APIs died less often of causes related to drug/alcohol use than all other racial groups (24.1, compared to 39.3%), and there was a trend toward more API deaths from injuries or illnesses. When APIs were disaggregated into sub-groups (East/Southeast Asian, South Asian, Pacific Islander), there were notable mortality differences in cause of death, age, and sex. Discussion: We argue that invisibility is a structural determinant of health that homeless APIs face. Though relatively small in numbers, APIs who are invisible may experience increased social isolation and, subsequently, specific increased mortality risks. To understand the health outcomes of unhoused APIs, it is essential that researchers and policymakers recognize API homelessness and gather and report disaggregated races and ethnicities.

Food insecurity in older female mice affects food consumption, coping behaviors, and memory.

Food insecurity correlates with poor physical and mental health in older individuals, but has not been studied in a laboratory animal model. This explorative study developed a laboratory mouse model for analyzing the impact of food insecurity on food consumption, stress coping mechanisms, exploratory behavior, and memory. 18-month-old CD-1 female mice were assigned to either the food insecurity exposure condition (31 mice, 8 cages) or the control condition (34 mice, 8 cages) by cage. Over four weeks, the mice that were exposed to food insecurity received varied, unpredictable portions of their baseline food consumption (50%, 75%, 125%, 150% of baseline) for four days, followed by ad libitum access for three days, to approximate the inconsistent access to food observed in households experiencing food insecurity. Behavioral tasks were conducted before and after food insecurity exposure. Mice in the food insecurity exposure condition ate less compared to control mice during food insecurity (two-way ANOVA: group x time interaction: F7,93 = 10.95, P < 0.01) but ate more when given access to high fat food (two-way ANOVA, group x time interaction: F1,14 = 11.14, P < 0.01). Mice exposed to food insecurity increased active escaping behaviors in the forced swim test (repeated measures two-way ANOVA, group x time interaction: F1,63 = 5.40, P = 0.023). Exploratory behaviors were unaffected by food insecurity. Mice exposed to food insecurity showed a reduction in memory (repeated measures two-way ANOVA, group x time interaction: F1,61 = 4.81, P = 0.037). These results suggest that exposure to food insecurity is associated with differences in food consumption patterns, active coping mechanisms, and memory. The behavioral changes associated with food insecurity may inform research on food insecurity's impact on health in elderly humans.

Early life adversity increases the salience of later life stress: an investigation of interactive effects in the PSID.

A large body of evidence has shown that stress throughout life is associated with health trajectories, but the combination of adverse experiences at different stages of the life course is not yet well understood. This study examines the interactions between childhood adversity, adulthood adversity, and adult physical and mental health. Using data from The Childhood Retrospective Circumstances Study (CRCS) supplement to the Panel Study of Income Dynamics (PSID), we created indices of early life adversity (EAI) and adult adversity (AAI). We used logistic regression to examine the effects of EAI and AAI, adjusting for age, sex, race/ethnicity, health behaviors, and childhood health as covariates in all models. We repeated this analysis for the outcomes of fair/poor health, two or more chronic conditions, and psychological distress in adulthood. For all the three outcomes, our findings suggest increasing salience of adult adversity among those who experienced higher levels of early adversity. Individuals with high EAI and high AAI exhibited the highest odds of fair/poor health (OR = 5.71), chronic conditions (OR = 3.06), and psychological distress (OR = 13.08) compared to those with low EAI and low AAI. These findings are consistent with the accumulation of risk or dual risk model of stress and health. Adversity in childhood amplifies the health risks associated with stress in adulthood for multiple health outcomes.

Reproductive suppression and longevity in human birth cohorts.

OBJECTIVES: Reproductive suppression refers to, among other phenomena, the termination of pregnancies in populations exposed to signals of death among young conspecifics. Extending the logic of reproduction suppression to humans has implications for health including that populations exposed to it should exhibit relatively great longevity. No research, however, has tested this prediction. METHODS: We apply time-series methods to vital statistics from Sweden for the years 1751 through 1800 to test if birth cohorts exposed in utero to reproductive suppression exhibited lifespan different from expected. We use the odds of death among Swedes age 1 to 9 years to gauge exposure. As the dependent variable, we use cohort life expectancy. Our methods ensure autocorrelation cannot spuriously induce associations nor reduce the efficiency of our estimates. RESULTS: Our findings imply that reproductive suppression increased the lifespan of 24 annual birth cohorts by at least 1.3 years over the 50-year test period, and that 12 of those cohorts exhibited increases of at least 1.7 years above expected. CONCLUSIONS: The best available data in which to search for evidence of reproductive suppression in humans support the argument that populations subjected to environments dangerous for children yield birth cohorts that exhibit unexpectedly great longevity.

Understanding periviable birth: A microeconomic alternative to the dysregulation narrative.

Periviable infants (i.e., those born in the 20th through 26th weeks of gestation) suffer much morbidity and approximately half die in the first year of life. Attempts to explain and predict these births disproportionately invoke a "dysregulation" narrative. Research inspired by this narrative has not led to efficacious interventions. The clinical community has, therefore, urged novel approaches to the problem. We aim to provoke debate by offering the theory, inferred from microeconomics, that risk tolerant women carry, without cognitive involvement, high risk fetuses farther into pregnancy than do other women. These extended high-risk pregnancies historically ended in stillbirth but modern obstetric practices now convert a fraction to periviable births. We argue that this theory deserves testing because it suggests inexpensive and noninvasive screening for pregnancies that might benefit from the costly and invasive interventions clinical research will likely devise.

Separating the Bruce and Trivers-Willard effects in theory and in human data.

OBJECTIVES: Theories of reproductive suppression predict that natural selection would conserve mechanisms that abort the gestation of offspring otherwise unlikely to thrive in prevailing environments. Research reports evidence among humans of at least two such mechanisms-the Trivers-Willard and Bruce Effects. No literature, however, compares the mechanisms nor estimates their relative contribution to observed characteristics of human birth cohorts. We describe similarities and differences between the Trivers-Willard and Bruce Effects and explore high quality historical data from Sweden to determine which mechanism better describes temporal variation in the ratio of males to females in birth cohorts. METHODS: We measure Trivers-Willard exposures with the death rate among women of reproductive age. We measure Bruce exposures with the death rate among children. We use time-series regression methods to estimate the relative contribution of the Trivers-Willard and Bruce Effects to temporal variation in historical Swedish secondary sex ratio data. RESULTS: We find that the Bruce Effect appears to be a better predictor of the secondary sex ratio than does the Trivers-Willard Effect. CONCLUSIONS: Attempts to identify mechanisms by which reproductive suppression affects fetal loss and characteristics of human birth cohorts should consider the Bruce Effect as an alternative to the Trivers-Willard Effect.

Multifactorial discrimination as a fundamental cause of mental health inequities.

BACKGROUND: The theory of fundamental causes explains why health disparities persist over time, even as risk factors, mechanisms, and diseases change. Using an intersectional framework, we evaluated multifactorial discrimination as a fundamental cause of mental health disparities. METHODS: Using baseline data from the Project STRIDE: Stress, Identity, and Mental Health study, we examined the health effects of discrimination among individuals who self-identified as lesbian, gay, or bisexual. We used logistic and linear regression to assess whether multifactorial discrimination met the four criteria designating a fundamental cause, namely that the cause: 1) influences multiple health outcomes, 2) affects multiple risk factors, 3) involves access to resources that can be leveraged to reduce consequences of disease, and 4) reproduces itself in varied contexts through changing mechanisms. RESULTS: Multifactorial discrimination predicted high depression scores, psychological well-being, and substance use disorder diagnosis. Discrimination was positively associated with risk factors for high depression scores: chronic strain and total number of stressful life events. Discrimination was associated with significantly lower levels of mastery and self-esteem, protective factors for depressive symptomatology. Even after controlling for risk factors, discrimination remained a significant predictor for high depression scores. Among subjects with low depression scores, multifactorial discrimination also predicted anxiety and aggregate mental health scores. CONCLUSIONS: Multifactorial discrimination should be considered a fundamental cause of mental health inequities and may be an important cause of broad health disparities among populations with intersecting social identities.

Twinning in Norway Following the Oslo Massacre: Evidence of a 'Bruce Effect' in Humans.

Emerging theory and empirical work suggest that the 'Bruce Effect', or the increase in spontaneous abortion observed in non-human species when environments become threatening to offspring survival, may also appear in humans. We argue that, if it does, the effect would appear in the odds of twins among male and female live births. We test the hypothesis, implied by our argument, that the odds of a twin among male infants in Norway fell below, while those among females rose above, expected levels among birth cohorts in gestation in July 2011 when a deranged man murdered 77 Norwegians, including many youths. Results support the hypothesis and imply that the Bruce Effect operates in women to autonomically raise the standard of fetal fitness necessary to extend the gestation of twins. This circumstance has implications for using twins to estimate the relative contributions of genes and environment to human responses to exogenous stimuli.

Stress during Adolescence Alters Palatable Food Consumption in a Context-Dependent Manner.

Food consumption and preferences may be shaped by exposure to stressful environments during sensitive periods in development, and even small changes in consumption can have important effects on long term health. Adolescence is increasingly recognized as a sensitive period, in which adverse experiences can alter development, but the specific programming effects that may occur during adolescence remain incompletely understood. The current study seeks to explore the effects of stress during late adolescence on consumption of a palatable, high-fat, high-sugar food in adulthood-under basal conditions, as well following acute stress. Male Long-Evans rats were exposed to a regimen of variable stress for seven days in late adolescence (PND 45-51). During the stress regimen, stressed animals gained significantly less weight than control animals, but weight in adulthood was unaffected by adolescent stress. Palatable food consumption differed between experimental groups, and the direction of effect depended on context; stressed rats ate significantly more palatable food than controls upon first exposure, but ate less following an acute stressor. Leptin levels and exploratory behaviors did not differ between stressed and non-stressed groups, suggesting that other factors regulate preference for a palatable food. Altered food consumption following adolescent stress suggests that rats remain sensitive to stress during late adolescence, and that adult feeding behavior may be affected by previous adverse experiences. Such programming effects highlight adolescence as a period of plasticity, with the potential to shape long term food consumption patterns and preferences.

The influence of early maternal care on perceptual attentional set shifting and stress reactivity in adult rats.

Stress influences a wide variety of outcomes including cognitive processing. In the rat, early life maternal care can influence developing offspring to affect both stress reactivity and cognitive processes in adulthood. The current study assessed if variations in early life maternal care can influence cognitive performance on a task, the ability to switch cognitive sets, dependent on the medial prefrontal cortex. Early in life, offspring was reared under High or Low maternal Licking conditions. As adults, they were trained daily and then tested on an attentional set-shifting task (ASST), which targets cognitive flexibility in rodents. Stress-sensitive behavioral and neural markers were assayed before and after the ASST. High and Low Licking offspring performed equally well on the ASST despite initial, but not later, differences in stress axis functioning. These results suggest that early life maternal care does not impact the accuracy of attentional set-shifting in rats. These findings may be of particular importance for those interested in the relationship between early life experience and adult cognitive function.

Family adversity and autonomic reactivity association with immune changes in HIV-affected school children.

OBJECTIVE: To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. METHODS: Data from 38 HIV-positive and 29 HIV-negative children born to seropositive women were obtained. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity, and enumerative and functional changes in peripheral blood immune parameters. RESULTS: In comparison with children who were HIV-negative, children who were HIV-positive at baseline had fewer CD4(+) T lymphocytes (mean [M] = 916 versus 1206 cells/mm(3) × 10(3); F = 7.8, p = .007), more CD8(+) cells (M = 1046 versus 720 cells/mm(3) × 10(3); F = 7.98, p = .006), and diminished natural killer cell cytotoxicity (M = -0.29 versus 0.41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters after school entry were associated with family stress and preschool entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8(+) cells after school entry or the greatest decrease, depending on reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. CONCLUSIONS: These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV.

A test of maternal human chorionic gonadotropin during pregnancy as an adaptive filter of human gestations.

The risk of abnormalities and morbidity among live births increases with advanced maternal age. Explanations for this elevated morbidity invoke several maternal mechanisms. The relaxed filter stringency (RFS) hypothesis asserts that mothers, nearing the end of their reproductive lifespan, reduce the stringency of a screen of offspring quality in utero based on life-history traits of parity and interbirth interval (IBI). A separate line of research implicates human chorionic gonadotropin (hCG) during pregnancy as a signal of offspring quality. We test the RFS hypothesis directly by examining whether the difference in gestational hCG across consecutive live births varies positively with the mother's number of previous live births but inversely with her most recent IBI. We applied multivariable regression methods to a unique dataset of gestational hCG for over 500 000 live births from 2002 to 2007. The difference in gestational hCG across mothers' consecutive live births varies positively with both mothers' parity and IBI. These associations remain similar among older mothers (35+ years). Findings support the RFS hypothesis for the parity expectation but not for the IBI expectation. Further evidence for the RFS hypothesis among contemporary human gestations would have to invoke screening mechanisms other than hCG.

Natural selection in utero induced by mass layoffs: the hCG evidence.

Evolutionary theory, when coupled with research from epidemiology, demography, and population endocrinology, suggests that contracting economies affect the fitness and health of human populations via natural selection in utero. We know, for example, that fetal death increases more among males than females when the economy unexpectedly contracts; that unexpected economic contraction predicts low secondary sex ratios; and that males from low sex ratio birth cohorts live, on average, longer than those from high sex ratio cohorts. We also know that low levels of human chorionic gonadotropin (i.e., hCG) measured in the serum of pregnant women predict fetal death. We do not, however, know whether male survivors of conception cohorts subjected to contracting economies exhibit, as theory predicts, higher hCG than those from other cohorts. We show, in 71 monthly conception cohorts including nearly two million California births, that they do. We thereby add to the literature suggesting that the economy, a phenomenon over which we collectively exercise at least some control, affects population health. Our findings imply that the effect arises via natural selection - a mechanism we largely ignore when attempting to explain, or alter, how collective choice affects our biology.

The social environment and IL-6 in rats and humans.

Inflammatory cytokine levels predict a wide range of human diseases including depression, cardiovascular disease, type 2 diabetes, autoimmune disease, general morbidity, and mortality. Stress and social experiences throughout the lifecourse have been associated with inflammatory processes. We conducted studies in humans and laboratory rats to examine the effect of early life experience and adult social position in predicting IL-6 levels. Human participants reported family homeownership during their childhood and current subjective social status. Interleukin-6 (IL-6) was measured from oral mucosal transudate. Rats were housed in groups of three, matched for quality of maternal care received. Social status was assessed via competition for resources, and plasma IL-6 was assessed in adulthood. In both humans and rats, we identified an interaction effect; early social experience moderated the effect of adult social status on IL-6 levels. Rats that experienced low levels of maternal care and people with low childhood socioeconomic status represented both the highest and lowest levels of IL-6 in adulthood, depending on their social status as young adults. The predicted interaction held for non-Hispanic people, but did not occur among Hispanic individuals. Adversity early in life may not have a monotonically negative effect on adult health, but may alter biological sensitivity to later social experiences.

The health effects of economic decline.

Political pronouncements and policy statements include much conjecture concerning the health and behavioral effects of economic decline. We both summarize empirical research concerned with those effects and suggest questions for future research priorities. We separate the studies into groups defined by questions asked, mechanisms invoked, and outcomes studied. We conclude that although much research shows that undesirable job and financial experiences increase the risk of psychological and behavioral disorder, many other suspected associations remain poorly studied or unsupported. The intuition that mortality increases when the economy declines, for example, appears wrong. We note that the research informs public health programming by identifying risk factors, such as job loss, made more frequent by economic decline. The promise that the research would identify health costs and benefits of economic policy choices, however, remains unfulfilled and will likely remain so without stronger theory and greater methodological agreement.

Vacuum-cleaner noise and acute stress responses in female C57BL/6 mice (Mus musculus).

Audiogenic stress is a well-documented phenomenon in laboratory rodents. Despite the recommendation in the Guide for the Care and Use of Laboratory Animals to consider noise a concern in the animal facility, only a small body of literature empirically addresses the effects of facility noise on laboratory rodents, particularly mice. The objective of this study was to determine whether facility noise generated by a vacuum cleaner induces an acute stress response in a commonly used strain of laboratory mouse under common housing conditions. In each of 2 experiments, 10 young adult, female C57BL/6Cr mice were exposed for 1 h to noise produced by a vacuum cleaner, and 10 control mice were not. In the first experiment, fecal samples were collected to measure concentrations of fecal corticosterone metabolites just before and 2, 4, 6, 8, 10, 14, 24, and 32 h after noise exposure. In the second experiment, stress-sensitive behavioral tests were performed 2 d before, immediately after, and 24 h after noise exposure. Physiologic and behavioral measurements indicated that vacuum cleaner noise did not cause an acute stress response in the noise-exposed mice but may have affected the diurnal variation of their corticosterone levels. These findings could contribute to the development of best practices in noise-control protocols for animal facilities.