Immune cell phenotype and function patterns across the life course in individuals from rural Uganda.

Background: To determine the pattern of immune cell subsets across the life span in rural sub-Saharan Africa (SSA), and to set a reference standard for cell subsets amongst Africans, we characterised the major immune cell subsets in peripheral blood including T cells, B cells, monocytes, NK cells, neutrophils and eosinophils, in individuals aged 3 to 89 years from Uganda. Methods: Immune phenotypes were measured using both conventional flow cytometry in 72 individuals, and full spectrum flow cytometry in 80 individuals. Epstein-Barr virus (EBV) IFN-γ T cell responses were quantified in 332 individuals using an ELISpot assay. Full blood counts of all study participants were also obtained. Results: The percentages of central memory (TCM) and senescent CD4+ and CD8+ T cell subsets, effector memory (TEM) CD8+ T cells and neutrophils increased with increasing age. On the other hand, the percentages of naïve T (TN) and B (BN) cells, atypical B cells (BA), total lymphocytes, eosinophils and basophils decreased with increasing age. There was no change in CD4+ or CD8+ T effector memory RA (TEMRA) cells, exhausted T cells, NK cells and monocytes with age. Higher eosinophil and basophil percentages were observed in males compared to females. T cell function as measured by IFN-γ responses to EBV increased with increasing age, peaking at 31-55 years. Conclusion: The percentages of cell subsets differ between individuals from SSA compared to those elsewhere, perhaps reflecting a different antigenic milieu. These results serve as a reference for normal values in this population.

Effect of PTSD treatment on cardiovascular reactivity during trauma memory recall and correspondence with symptom improvement.

ABSTRACTBackground: Prior research has shown PTSD treatment leads to reductions in cardiovascular reactivity during trauma recall, but the extent to which such reductions are associated with changes in PTSD symptoms is less clear. Moreover, such relationships have not been investigated in a cognitively focused PTSD treatment.Objective: To examine changes in cardiovascular reactivity to the trauma memory in patients receiving cognitive processing therapy (CPT), CPT with a written trauma account, and a written account only condition. We also examined the association of such changes with symptom improvement.Method: 118 women with PTSD secondary to interpersonal violence completed pre- and post-treatment assessments of PTSD symptoms and cardiovascular reactivity during a script-driven imagery task.Results: Results indicated a significant but modest reduction in cardiovascular reactivity in CPT conditions. Changes in cardiovascular reactivity and reexperiencing symptoms were significantly associated among the whole sample. Among individuals with the greatest reactivity to the trauma memory at pretreatment, associations were also seen with changes in total PTSD, numbing, and trauma-related guilt.Conclusions: Results indicate that previous findings on the effect of PTSD treatment on cardiovascular reactivity during trauma recall extend to cognitively oriented treatment. Baseline cardiovascular reactivity may influence the extent to which reductions in PTSD symptoms and reactivity during trauma recall are related.

Cognitive Processing Therapy leads to reduced heart rate reactivity when recalling a trauma memory.Decreases in heart rate reactivity are associated with reduced reexperiencing symptoms.Changes in heart rate reactivity and PTSD symptoms are more closely related among patients with greater pretreatment reactivity.

Associations of recent stressful life events with anxiety symptoms among Chinese adolescents with a consideration of family functioning.

Background: The association between stressful life events (SLEs) and adolescent anxiety symptoms has been extensively studied, but the specific impacts of different SLEs domains remain inconclusive. Moreover, limited research has examined the role of family functioning in these associations.Objective: This study aimed to investigate the associations between various recent SLEs and adolescent anxiety symptoms and explore the role of family functioning.Methods: Data were obtained from the second phase of the Longitudinal Study of Adolescents' Mental and Behavioral Well-being Research in Guangzhou, China. A total of 10,985 students (51.9% boys; mean [SD] age, 15.3 [1.5] years) from forty middle schools participated in the study in 2022 and completed a self-report questionnaire assessing anxiety symptoms, SLEs, and family functioning using the Generalized Anxiety Disorder-7 (GAD-7), Adolescent Self-rating Life Events Checklist (ASLEC; including five subscales: interpersonal stress, academic stress, punishment-related stress, loss-related stress, and adaptation-related stress), and the adapted Chinese version of the Family Assessment Device (FAD), respectively. Linear mixed-effects models were performed and the moderation role of family functioning was also examined.Results: The fully adjusted model revealed that a 1-SD increase in the overall ASLEC score was associated with higher levels of anxiety symptoms (ß = 2.23, 95%CI: 2.15-2.32). Among various SLEs domains, the academic domain shows the most significant association (ß = 2.25, 95%CI: 2.17-2.33). Family functioning exerted an independent protective influence on anxiety symptoms, with each 1-SD increase in FAD scores negatively associated with anxiety symptoms (ß = -2.11, 95%CI: - 2.29 to - 1.93) in the adjusted model. Moreover, family functioning significantly buffered the impacts of overall SLEs and each domain, except for adaptation-related SLEs, on anxiety symptoms.Conclusion: Higher recent SLEs levels were associated with increased anxiety symptoms among adolescents, with academic SLEs showing the greatest association. Positive family functioning had both direct and buffering influences on anxiety symptoms.

Higher levels of recent stressful life events may increase adolescents' anxiety symptoms.Academic stressful life events show the greatest association with anxiety symptoms.Family functioning may be a promising intervention target for adolescent anxiety symptoms.

Implementation of COVID-19 vaccination services in prison in six European countries: translating emergency intervention into routine life-course vaccination.

BACKGROUND: Evidence has shown that the risk of transmission of SARS-CoV-2 is much higher in prisons than in the community. The release of the COVID-19 vaccine and the recommendation by WHO to include prisons among priority settings have led to the inclusion of prisons in national COVID-19 vaccination strategies. Evidence on prison health and healthcare services provision is limited and often focuses on a single country or institution due to the multiple challenges of conducting research in prison settings. The present study was done in the framework of the EU-founded project RISE-Vac. It aimed to analyse the best practices and challenges applied in implementing COVID-19 universal vaccination services during the pandemic to support future expansion of routine life course vaccination services for people living in prison (PLP). METHODS: Two online cross-sectional surveys were designed and piloted: survey1 on prison characteristics and (non-COVID-19) immunisation practices; survey2 on the implementation and coverage of COVID-19 vaccination with open-ended questions for thematic analysis. Each RISE-Vac project partner distributed the questionnaire to one or two prisons in their country. Answers were collected from eight European prisons' directors or medical directors between November 2021-May 2022. RESULTS: According to our findings, the implementation modalities of COVID-19 vaccination services in the surveyed prisons were effective in improving PLP vaccination coverage. Strategies for optimal management of the vaccination campaign included: periodic time slot for PLP vaccination; new staff recruitment and task shifting; distribution of informational material both to PLP and prison staff. Key challenges included continuity of care after release, immunisation information system, and vaccine hesitancy. CONCLUSIONS: To the best of our knowledge, this is the first study describing the implementation of COVID-19 vaccination services in European prisons, suggesting that the expansion of vaccination provision in prison is possible. There is no unique solution that will fit every country but commonalities likely to be important in the design and implementation of future vaccination campaigns targeting PLP emerged. Increased availability of vaccination services in prison is not only possible, but feasible and highly desirable, and can contribute to the reduction of health inequalities.

Life course socioeconomic status, chronic pain, and the mediating role of allostatic load: findings from the midlife in the United States.

Introduction: Low socioeconomic status (SES) has been linked to chronic pain (CP); however, the mechanisms by which SES over the life course influences downstream CP outcomes remain unclear. Methods: This study utilizes data from the Midlife in the United States (MIDUS) survey, a prospective sample of community-dwelling individuals (N=781), to investigate the chain of risk additive model of SES in relation to CP. Additionally, the study examines the mediating role of allostatic load (AL) in the relationship between life course SES and CP. Confirmatory factor analysis was employed to capture the multidimensionality of life course SES and path analysis was used to examine the direct and indirect effects on CP. AL was computed by quartile-based summation and by latent class analysis. Results: Results indicated lower SES in MIDUS 2 was associated with greater high-interference CP odds in MIDUS 3 (OR=1.069, 95% CI=1.006-1.136, P < 0.05) and no association was found between distal SES and levels of CP interference. Similarly, no significant relationship was observed between SES and the number of CP locations. Additionally, no additive effects of SES were found, and AL did not present mediation effects on the association between life course SES and CP. Discussion: The present study emphasizes the importance of directly proximal effects of SES on CP, underscoring the need for equitable distribution of health resources and the implementation of policies focused on diminishing socioeconomic inequalities. Further research is needed to examine alternative pathways by which proximal SES impact CP.

Associations between life course longitudinal growth and hip shapes at ages 60-64 years: evidence from the MRC National Survey of Health and Development.

OBJECTIVE: We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. METHODS: Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested. RESULTS: Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated. CONCLUSION: Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis.

Moving in together in later life: Making spaces into places as a joint endeavor.

BACKGROUND AND OBJECTIVES: We focus on the linkages between relocation, new forms of partner cohabitation, and retirement. What are the patterns and trajectories of moving in with a partner in retirement? How do older adults experience different transitions, place attachment, and placemaking when they move in with a partner? RESEARCH DESIGN AND METHODS: In this qualitative study, 50 persons between 60 and 75 years old were interviewed in Sweden and Germany. For this paper, we focused on nine participants who experienced a relocation with a partner in retirement. Interviews were transcribed and analyzed using a strategy derived from social constructivist Grounded Theory and thematic analysis. RESULTS: Research participants described experiences of several relocations and cohabitation trajectories. In particular, we identified two patterns of relocating with a partner in retirement: moving into a new place with a partner and moving into a partner's pre-existing home, the latter proving more challenging for forming place attachment and for the couple relationship. Relocation experiences appeared to form a joint process in which relationships and retirement were renegotiated. DISCUSSION AND IMPLICATIONS: Using cross-cultural data, this novel study shows an unexpected diversity in housing and cohabitation trajectories among older adults. More research is needed to understand what "aging in the right place" with "the right person" really means and the role of life course trajectories and couple negotiations in such processes. Future research should focus on what comes before and after relocation rather than solely studying the decision-making process that leads up to a move.

"Unlinked lives": Elaboration of a concept and its significance for the life course.

This article introduces the concept of "unlinked lives" and illustrates its significance for scholarship on the life course. There are many lessons to be learned about human interdependence by focusing not on relationships that are formed and then maintained, but instead on relationships that are lost or ended by choice or circumstance, such as through changes in institutional affiliations, social status and positions or places. Unlinked lives carry important social meanings, are embedded in complex social processes, and bring consequences for the wellbeing of individuals, families, and societies. To develop this concept, we put forward nine key propositions related to when and how unlinkings happen as processes, as well as some of the consequences of being unlinked as a status or outcome. The coupling of "unlinked lives" with "linked lives" offers a crucial avenue for advancing life course theories and research, integrating scholarship across multiple life periods and transitions, and bridging the two now-distinct traditions of intellectual inquiry on the life course and on social networks.

Cohort profile: Life-course experiences and pregnancy (LEAP)-A retrospective pregnancy cohort for life-course reproductive health research.

BACKGROUND: Life course factors may be associated with pre-pregnancy body mass index and gestational weight gain; however, collecting information on pre-pregnancy exposures and pregnancy health in the same cohort is challenging. OBJECTIVES: The Life-course Experiences And Pregnancy (LEAP) study aims to identify adolescent and young adult risk factors for pre-pregnancy weight and gestational weight gain (GWG). We built upon an existing cohort study to overcome challenges inherent to studying life course determinants of pregnancy health. POPULATION: Participants in an ongoing prospective cohort study of weight-related health who identified as women. DESIGN: Retrospective cohort study. METHODS: In 2019-2020, 1,252 women participating since adolescence in a cohort study of weight-related health were invited to complete an online reproductive history survey. Participants who reported a live birth were invited to release their prenatal, delivery, and postpartum medical records for validation of survey reports. Descriptive analyses were conducted to assess the characteristics of the overall cohort and the medical record validation subsample, and to describe adolescent and young adult characteristics of those with high (>80th percentile), moderate (20th-80th percentile), and low (<20th percentile) GWG z-score for gestational age and pre-pregnancy weight status. PRELIMINARY RESULTS: Nine hundred seventy-seven women (78%) completed the LEAP survey and 656 reported a live birth. Of these, 379 (58%) agreed to release medical records, and 250 records were abstracted (66% of the 379). Of the 977 survey respondents 769 (79%) reported attempting a pregnancy, and 656 (67%) reported at least one live birth. The validation subsample was similar to the overall cohort. Women with a high GWG had a higher adolescent BMI percentile and prevalence of unhealthy weight control behaviors than those with moderate or low GWG. CONCLUSIONS: LEAP offers a valuable resource for identifying life course factors that may influence the health of pregnant people and their offspring.

Pubertal timing: A life course pathway linking early life risk to adulthood cardiometabolic health.

OBJECTIVE: To evaluate a series of prospective life course models testing whether the timing of pubertal development is a pathway through which prepubertal risk factors may influence adulthood cardiometabolic health. METHODS: Subjects were 655 female participants in the NICHD Study of Early Child Care and Youth Development (SECCYD) and recent SECCYD 30-year follow-up, the Study of Health in Early and Adult Life (SHINE). Prepubertal risk factors included maternal menarcheal age, child race/ethnicity, child health status indicators, and child adversity indicators. Pubertal timing was indexed by breast development onset (Tanner stage [TS] II), pubic hair onset (TS II) and menarcheal age. Adulthood cardiometabolic risk (CMR) was indexed by a composite of waist circumference, systolic blood pressure, diastolic blood pressure, hemoglobin A1c, C-reactive protein, and high-density lipoprotein. RESULTS: Inspection of paths between the prepubertal risk factors, pubertal timing indicators, and adulthood CMR composite showed later breast development onset (-0.173, p < .01), later pubic hair onset (-0.182, p < .01), and later menarche (-0.145, p < .01) each predicted lower adulthood CMR, and each pubertal timing indicator mediated effects of prepubertal risk factors on adulthood CMR. Specifically, the timing of breast development onset and menarche mediated effects of maternal menarcheal age, Black (vs. White), Asian/PI (vs. White), child BMI percentile, and child SES on adulthood CMR (all ps < .05), and the timing of pubic hair onset mediated effects of maternal menarcheal age, Black (vs. White), and child BMI percentile on adulthood CMR (all ps < .10). CONCLUSION: Findings in the current study contribute to the broader literature by identifying pubertal development and its timing as a potentially important pathway through which early life exposures may shape adulthood cardiometabolic health and disease. These findings have important implications for novel opportunities for increased surveillance and potential intervention focusing on pubertal development as a target to improve health more broadly.

Leprosy in Colombia: A look from life experience.

Leprosy continues to be stigmatized, causing harm to fundamental rights, pain and hopelessness in those who have suffered from it and their families. From its relationship with public and mental health, effective strategies must be implemented to reduce stigma and unlearn myths and wrong perceptions, support families, and improve quality of life through early care and detection. This article shows that those affected by leprosy are capable, functional people with much to contribute to society anywhere in the world.

Life course epidemiology and public health.

Life course epidemiology aims to study the effect of exposures on health outcomes across the life course from a social, behavioural, and biological perspective. In this Review, we describe how life course epidemiology changes the way the causes of chronic diseases are understood, with the example of hypertension, breast cancer, and dementia, and how it guides prevention strategies. Life course epidemiology uses complex methods for the analysis of longitudinal, ideally population-based, observational data and takes advantage of new approaches for causal inference. It informs primordial prevention, the prevention of exposure to risk factors, from an eco-social and life course perspective in which health and disease are conceived as the results of complex interactions between biological endowment, health behaviours, social networks, family influences, and socioeconomic conditions across the life course. More broadly, life course epidemiology guides population-based and high-risk prevention strategies for chronic diseases from the prenatal period to old age, contributing to evidence-based and data-informed public health actions. In this Review, we assess the contribution of life course epidemiology to public health and reflect on current and future challenges for this field and its integration into policy making.

Rethinking immunization programs through the life course approach.

The world continues to undergo a profound demographic shift toward increasing longevity -but quality of life is not improving correspondingly. At the same time, countries are taking stock of the negative impacts of the COVID-19 pandemic on national immunization programs. The pandemic exacerbated the declines in vaccination coverage for multiple vaccine-preventable diseases (VPD). To ensure that all persons receive all the vaccines for which they are eligible, it is time to consider how applying a life course approach (LCA) to immunization programs can help reinvigorate and redesign actions for greater vaccine uptake. In this mini review, we present the key concepts and principles of the LCA as applied to national immunization programs. Also, we offer recommendations on how health systems can achieve regional and national goals to ensure all people receive the recommended vaccine doses at every stage of life, thus ensuring the greatest benefits for individuals and societies.

Separating Scarring Effect and Selection of Early-Life Exposures With Genetic Data.

Causal life course research examining consequences of early-life exposures has largely relied on associations between early-life environments and later-life outcomes using exogenous environmental shocks. Nonetheless, even with (quasi-)randomized early-life exposures, these associations may reflect not only causation ("scarring") but also selection (i.e., which members are included in data assessing later life). Investigating this selection and its impacts on estimated effects of early-life conditions has, however, often been ignored because of a lack of pre-exposure data. This study proposes an approach for assessing and correcting selection, separately from scarring, using genetic measurements. Because genetic measurements are determined at the time of conception, any associations with early-life exposures should be interpreted as selection. Using data from the UK Biobank, we find that in utero exposure to a higher area-level infant mortality rate is associated with genetic predispositions correlated with better educational attainment and health. These findings point to the direction and magnitude of selection from this exposure. Corrections for this selection in examinations of effects of exposure on later educational attainment suggest underestimates of 26-74%; effects on other life course outcomes also vary across selection correction methods.

U.S. Fertility in Life Course Context: A Research Note on Using Census-Held Linked Administrative Records for Geographic and Sociodemographic Subgroup Estimation.

Fertility is a life course process that is strongly shaped by geographic and sociodemographic subgroup contexts. In the United States, scholars face a choice: they can situate fertility in a life course perspective using panel data, which is typically representative only at the national level; or they can attend to subnational contexts using rate schedules, which do not include information on life course statuses. The method and data source we introduce here, Census-Held Linked Administrative Records for Fertility Estimation (CLAR-FE), permits both. It derives fertility histories and rate schedules from U.S. Census Bureau-held data for the nation and by state, racial and ethnic subgroups, and the important life course status of parity. We generate three types of rates for 2000-2020 at the national and state levels by race and ethnicity: age-specific rates and both unconditional and conditional parity- and age-specific rates. Where possible, we compare these rates with those produced by the National Center for Health Statistics. Our new rate schedules illuminate state and racial and ethnic differences in transitions to parenthood, providing evidence of the important subgroup heterogeneity that characterizes the United States. CLAR-FE covers nearly the entire U.S. population and is available to researchers on approved projects through the Census Bureau's Federal Statistical Research Data Centers.

How socio-political change is associated with the number of individually reported negative life events: a population-based study using the German reunification 1989/1990 as an example.

BACKGROUND: Socio-political change often leads to disruptions in employment and social networks, which can exacerbate health issues and increase mortality rates. These consequences are likely observed as an increase in negative life events (NLEs), serving as indicators of the broader social and health impacts. Using the German reunification in 1989/1990 as an example, this study investigates changes in reported numbers of NLEs and differences regarding sociodemographic characteristics. METHODS: We used data from the population-based Study of Health in Pomerania (SHIP-START-0, SHIP-Life-Events and Gene-Environment Interaction in Depression; N=1932). Numbers of NLEs in different categories (work/financial, social/interpersonal, illness (own) and illness/death (others)) were measured retrospectively in 5-year intervals (1980-2004) using a semistructured interview. Pre-reunification and post-reunification changes were modelled using piecewise mixed-effects Poisson regressions with the 1990-1994 interval (reunification) as change point. Interactions with age, sex and education were examined. RESULTS: The number of most NLE categories, except social/interpersonal NLEs, increased at reunification. Whereas work/financial NLEs slightly decreased post-reunification, illness-related NLEs continued to increase. Higher numbers of social/interpersonal NLEs were found with younger age. More illness-related NLEs were reported with older age, lower education (illness (own)) and by women (illness/death (others)). However, the majority reported no NLEs at reunification (68.2%-80.7%, varying by category). CONCLUSION: Our findings suggest that although some individuals experience a marked increase in NLEs due to socio-political changes, many remain unaffected, emphasising the need for a differentiated understanding of these effects. This increase in NLEs may partly account for ongoing health and well-being disparities among countries with differing transformation histories.

Cumulative Stress Across the Life Course and Biological Aging in Adulthood.

OBJECTIVE: Psychosocial stressors have been linked with accelerated biological aging in adults; however, few studies have examined stressors across the life course in relation to biological aging. METHODS: In 359 individuals (57% White, 34% Black) from the Child Health and Development Studies Disparities study, economic (income, education, financial strain), social (parent-child relations, caretaker responsibilities) and traumatic (death of a sibling or child, violence exposure) stressors were assessed at multiple time points (birth and ages 9, 15, and 50 years). Experiences of major discrimination were assessed at age 50. Life period stress scores were then assessed as childhood (birth-age 15 years) and adulthood (age 50 years). At age 50 years, participants provided blood samples, and DNA methylation was assessed with the EPIC BeadChip. Epigenetic age was estimated using six epigenetic clocks (Horvath, Hannum, Skin and Blood age, PhenoAge, GrimAge, Dunedin Pace of Aging). Age acceleration was determined using residuals from regressing chronologic age on each of the epigenetic age metrics. Telomere length was assessed using the quantitative polymerase chain reaction-based methods. RESULTS: In linear regression models adjusted for race and gender, total life stress, and childhood and adult stress independently predicted accelerated aging based on GrimAge and faster pace of aging based on the DunedinPace. Associations were attenuated after adjusting for smoking status. In sex-stratified analyses, greater childhood stress was associated with accelerated epigenetic aging among women but not men. No associations were noted with telomere length. CONCLUSIONS: We found that cumulative stressors across the life course were associated with accelerated epigenetic age, with differences by sex (e.g., accelerated among women). Further research of this association in large and diverse samples is needed.

Cognitive ability in early life and risk of depression in adulthood: A systematic review and meta-analysis.

BACKGROUND: There is an established association between cognitive ability and risk of depression, though the direction of this association is unclear. Measuring cognitive ability in childhood, prior to the diagnosis of depression, could help to understand whether childhood cognitive ability is associated with a later diagnosis of depression. This systematic review and meta-analysis explored the association between childhood cognitive ability and risk of depression in adulthood. METHODS: We searched five databases to January 2024. We included studies that assessed cognitive ability in childhood (<18 years) and depression in adulthood. We excluded studies with very specific populations. We pooled each study's most-adjusted correlation coefficient in a random-effects meta-analysis. When studies reported a dichotomous outcome (depression/no depression), we converted the effect size to a correlation coefficient. Subgroup analyses were performed to explore sources of heterogeneity. RESULTS: 18 articles (19 cohorts) were included. There was no association between childhood cognitive ability and depression in adulthood (20 sample populations, N = 45,786, r = -0.04, 95 % CI = -0.09 to 0.01, p = 0.09). Neither age at cognitive assessment, length of follow-up, using a continuous/categorical measure of depression, or sex, significantly influenced the association. We rated most studies as having moderate risk of bias. LIMITATIONS: We limited the literature search to studies written in English. Existing studies were also heterogeneous, often adjusting for a variety of covariates. CONCLUSIONS: Our meta-analysis found no association between childhood cognitive ability and depression in adulthood. Future, longitudinal population-level studies should endeavour to control for potential mediators across the life-course (e.g., demographic and environmental factors).