Inverse probability weighting for self-selection bias correction in the investigation of social inequality in mortality.

BACKGROUND: Empirical evaluation of inverse probability weighting (IPW) for self-selection bias correction is inaccessible without the full source population. We aimed to: (i) investigate how self-selection biases frequency and association measures and (ii) assess self-selection bias correction using IPW in a cohort with register linkage. METHODS: The source population included 17 936 individuals invited to the Copenhagen Aging and Midlife Biobank during 2009-11 (ages 49-63 years). Participants counted 7185 (40.1%). Register data were obtained for every invited person from 7 years before invitation to the end of 2020. The association between education and mortality was estimated using Cox regression models among participants, IPW participants and the source population. RESULTS: Participants had higher socioeconomic position and fewer hospital contacts before baseline than the source population. Frequency measures of participants approached those of the source population after IPW. Compared with primary/lower secondary education, upper secondary, short tertiary, bachelor and master/doctoral were associated with reduced risk of death among participants (adjusted hazard ratio [95% CI]: 0.60 [0.46; 0.77], 0.68 [0.42; 1.11], 0.37 [0.25; 0.54], 0.28 [0.18; 0.46], respectively). IPW changed the estimates marginally (0.59 [0.45; 0.77], 0.57 [0.34; 0.93], 0.34 [0.23; 0.50], 0.24 [0.15; 0.39]) but not only towards those of the source population (0.57 [0.51; 0.64], 0.43 [0.32; 0.60], 0.38 [0.32; 0.47], 0.22 [0.16; 0.29]). CONCLUSIONS: Frequency measures of study participants may not reflect the source population in the presence of self-selection, but the impact on association measures can be limited. IPW may be useful for (self-)selection bias correction, but the returned results can still reflect residual or other biases and random errors.

The relationship between self-perceived fatigue, muscle endurance, and circulating markers of inflammation in participants of the Copenhagen aging and Midlife Biobank (CAMB).

BACKGROUND: Fatigue, low muscle endurance, muscle weakness and low-grade inflammation are strongly related to frailty at higher age. When signs of self-perceived fatigue and low muscle endurance are interrelated with low-grade inflammation at midlife, they might be used as early markers for frailty. This study investigated whether the interrelationships among self-perceived fatigue, muscle endurance and inflammation can be observed at midlife. METHODS: A total of 965 participants of the Copenhagen Aging and Midlife Biobank (aged 52 ± 4 years, 536 males, 426 females) were assessed for self-perceived fatigue (20-item multidimensional fatigue inventory), muscle endurance (grip work), circulating markers of inflammation (hsCRP, IL-6, IL-10, TNF-alpha and IFN-γ), daily physical activity (PAS-2), body composition (%body fat assessed by bio-impedance) and self-reported health status. Participants were categorised (correcting for age and gender) according to high fatigue and/or low muscle endurance, differences in inflammatory profile between fatigue categories were assessed by ANCOVA (corrected for PAS-2, %body fat and presence of inflammatory conditions). RESULTS: Overall, muscle endurance, fatigue and inflammatory markers were significantly interrelated. Higher levels of hsCRP (p < 0.001), IL-6 (p < 0.001), IL-10 (p = 0.035) and TNF-alpha (p = 0.028) were observed in participants presenting both low muscle endurance and high fatigue. IFN-γ was highest in those with high fatigue but normal muscle endurance (p = 0.015). CONCLUSIONS: Middle-aged participants with higher fatigue in combination with low muscle endurance show higher levels of inflammation, independently from physical activity, body fat and inflammatory pathology. The underlying mechanisms should be identified and future studies should also investigate whether these individuals show early signs of reduced physiological reserve capacity, which in later life come to full expression by means of frailty.

Educational attainment in young adulthood and self-rated health in midlife - Does allostatic load mediate the association?

This study aimed to examine the extent to which allostatic load (AL), measured in midlife, mediates the association between educational attainment in young adulthood and self-rated health (SRH) in midlife among women and men. The study used data from the Copenhagen Aging and Midlife Biobank (CAMB; n = 5467 participants, aged 48-62 years, 31.5% women). Educational attainment was assessed as years of education. SRH was assessed with one item: 'In general, how would you say your health is?' with response options from "excellent" to "poor". AL mediated 31.7% and 19.7% of the association between educational attainment and SRH in women and men, respectively. We observed that higher educational attainment was associated with better SRH and lower AL in both women and men. Our study showed that AL partly mediates the association between educational attainment in young adulthood and SRH in adulthood among both men and women. This study indicates that educational attainment in young adulthood affects health throughout life. Such knowledge of a potential mediator may be important in breaking the social heritage.

Health, well-being and social relations in a changing neighbourhood: protocol for a prospective, multimethods study of the consequences of large structural changes in an ethnic diverse social housing area in Denmark.

INTRODUCTION: Residential areas constitute an important arena for health, well-being and social relations. Structural interventions such as demolition and area renewal have been used to reduce inequality in health and well-being in disadvantaged areas. However, the effects of larger structural interventions are inconclusive. In a longitudinal perspective, this study aims to analyse how large-scale structural changes in an ethnic diverse social housing area are associated with the residents' health, well-being and social relations. METHODS AND ANALYSIS: In this multimethods study, we examine this aim among middle-aged and older residents in a multiethnic social housing area in a Danish municipality by the inclusion of comprehensive survey (in 2018, 2019 and 2020), register (yearly 2015-2025) and qualitative (2018-2020) data. Municipal Health Profile survey data from 2017 and 2021 will be used for comparison. The area will undergo large structural changes in the built environment during 2018-2021. A 'natural experiment' (n=6000) compares differences in health and social outcomes across the study period between the study area and a similar neighbouring area not undergoing structural changes. Through user engagement in the design of the study, throughout the different phases of the study and in the two co-created interventions embedded in the study design, a focus on empowerment and recognition of the resources and perspectives of residents are encouraged. ETHICS AND DISSEMINATION: The study is registered in the University of Copenhagen's record of biobanks and research projects containing personal data and will be conducted in accordance with the principles of the Helsinki Declaration. Residential and municipal representatives and local non-governmental organisations are engaged in the design and execution of the study to ensure the usefulness, reflexive interpretation of data, and relevance of interventions. Results will be published in international peer-reviewed scientific journals, presented at conferences and as short reports through the use of both written and visual outputs.

Cohort Profile: The Danish Conscription Database(DCD): A cohort of 728,160 men born from 1939 through 1959.

The Danish Conscription Database (DCD) was established to enable studies of the influence of early physical and mental exposures on adverse health and social outcomes from a life-course perspective. In Denmark, all young men are requested to appear before the conscription board when they turn 18 years, to be assessed for military service. The DCD was established by digitizing information from conscription board register cards on the height, weight, educational level, intelligence test score and examination details of Danish conscripts. The DCD contains information on 728,160 men born from 1939 through 1959 and examined by the conscription board from 1957 through 1984. The unique Danish personal identification number of each individual conscript has been traced, and this allows linkage of the DCD to all Danish health and socioeconomic registers. More than 130,000 deaths have been identified in a recent linkage to the Danish Register of Cause of Death. We encourage collaboration, and interested researchers should contact: danishconscriptiondatabase.glostrup-hospital@regionh.dk.

Personality in late midlife: associations with demographic factors and cognitive ability.

OBJECTIVES: To analyze associations in late midlife between sex, age, education and social class, and the Big Five personality traits; to analyze associations between personality traits and cognitive ability in late midlife; and to evaluate how these associations are influenced by demographic factors. METHODS: The study sample comprised 5,397 late midlife participants from three cohorts who had completed the NEO Five-Factor Inventory (NEO-FFI) and a measure of cognitive ability. RESULTS: Associations were demonstrated between the five NEO-FFI personality traits, and all included demographic factors. Cognitive ability and years of education correlated with several NEO-FFI personality traits in analyses adjusting for demographic variables. Cohort differences were observed for Extraversion and Openness. DISCUSSION: Robust sex, educational, and social class differences in personality may contribute to late midlife social gradients in health and early aging. Demographic factors did not fully explain correlations between personality and cognitive ability or cohort differences in personality.

The relationship between cognitive ability and demographic factors in late midlife.

OBJECTIVE: The aim of the article is to analyze associations between sex, age, education, and social class and cognitive ability in late midlife and to evaluate differences in cognitive ability among the three Copenhagen Aging and Midlife Biobank (CAMB) cohorts. METHOD: The sample comprised 5,417 CAMB participants from three cohorts with scores on the Intelligenz-Struktur-Test 2000 R (I-S-T 2000 R). RESULTS: Independent associations of cognitive ability with age, sex, education, and occupational social class were observed. Particularly, strong associations with cognitive ability were obtained for school education, and consistent sex differences were observed with higher cognitive ability in men. Differences in cognitive ability among the three cohorts were small and primarily reflected demographic differences. DISCUSSION: Late-midlife cognitive ability is associated with a number of demographic factors, and demographic differences may contribute to individual differences in health and early aging. In analyses of cognitive ability, the three CAMB cohorts can be combined provided the relevant demographic variables are included as covariates.

Smoking and drinking as risk indicators for tooth loss in middle-aged Danes.

OBJECTIVES: To investigate tobacco and alcohol consumption as risk indicators for missing teeth in late middle-aged Danes. METHOD: In all, 1,517 Copenhagen Aging and Midlife Biobank (CAMB) participants received a clinical oral examination that included number of teeth. Information on smoking, drinking, and various covariates was obtained using self-administered, structured questionnaires. Descriptive statistics and logistic regression (dependent variable: 6+ vs. <6 missing teeth) were used to investigate smoking and drinking in relation to missing teeth. RESULTS: Current smokers, persons who currently or previously smoked >15 tobacco units/day, and persons who had smoked for 27+ years had elevated mean scores of missing teeth and associated odds ratios (OR) compared with never smokers. Relative to nondrinkers, alcohol consumption was associated with reduced odds of missing 6+ teeth. DISCUSSION: Our findings suggest that smoking is positively associated, while alcoholic beverage consumption is inversely related to tooth loss in middle-aged Danes.

Social class differences in physical functions in middle-aged men and women.

OBJECTIVE: The objective of the present study is to analyze gender differences and social class gradients in physical functions; and to study whether the social class gradients in physical functions in midlife differed between men and women. METHOD: This study used traditionally used physical performance tests and we added several tests of vigorous physical functioning (trunk muscle strength and power and sagittal flexibility). We measured reaction time, one-legged balance, sagittal flexibility, jump height, chair rise ability, trunk muscle- and handgrip strength in 5,412 participants aged 50 to 60 years (68.5% men). RESULTS: We found gender differences and social class gradients for all physical performance tests. We did not find an interaction between social class and gender, indicating that the social gradient in physical functions did not differ between men and women. DISCUSSION: Including measures of vigorous physical functioning may add to the existing knowledge on development of functional limitation and poorer functional health later in life.

Social gradient in allostatic load among Danish men and women in late midlife.

OBJECTIVE: The objective of the present study is to describe the prevalence of allostatic load (AL) among Danish men and women in late midlife, and if there is a social gradient in AL. METHOD: A total of 5,420 participants from the Copenhagen Aging and Midlife Biobank (CAMB) aged 48 to 63 years (68.5% men, 31.5% women) underwent a health examination including standardized measures of height, weight, body fat, and blood pressure in 2009-2011. AL (range 0-14) was established by summing the scores of the poorest quartile for each of 14 biological variables related to the metabolic and immune systems. RESULTS: We found a social gradient in AL in late midlife among men and women living in Denmark. DISCUSSION: AL may be a potential biomarker for early aging in countries with a strong social welfare system. It is important for intervention studies to be aware of this type of biological vulnerability already present in late midlife.

Relationships between human vitality and mitochondrial respiratory parameters, reactive oxygen species production and dNTP levels in peripheral blood mononuclear cells.

Low vitality (a component of fatigue) in middle-aged and older adults is an important complaint often identified as a symptom of a disease state or side effect of a treatment. No studies to date have investigated the potential link between dysfunctional mitochondrial ATP production and low vitality. Therefore, we measured a number of cellular parameters related to mitochondrial activity in peripheral blood mononuclear cells (PBMCs) isolated from middle-aged men, and tested for association with vitality. These parameters estimate mitochondrial respiration, reactive oxygen species (ROS) production, and deoxyribonucleotide (dNTP) balance in PBMCs. The population was drawn from the Metropolit cohort of men born in 1953. Vitality level was estimated from the Medical Outcomes Study Short Form 36 (SF-36) vitality scale. We found that vitality score had no association with any of the mitochondrial respiration parameters. However, vitality score was inversely associated with cellular ROS production and cellular deoxythymidine triphosphate (dTTP) levels and positively associated with deoxycytidine triphosphate (dCTP) levels. We conclude that self-reported persistent low vitality is not associated with specific aspects of mitochondrial oxidative phosphorylation capacity in PBMCs, but may have other underlying cellular dysfunctions that contribute to dNTP imbalance and altered ROS production.

Disclosure patterns of mode of conception among mothers and fathers-5-year follow-up of the Copenhagen Multi-centre Psychosocial Infertility (COMPI) cohort.

BACKGROUND: Most studies on disclosure of mode of conception after fertility treatment have focused on donor insemination. We present a large, longitudinal cohort study of fertility patients who conceived through a variety of fertility treatments, including both non-donor and donor techniques. METHODS: A cohort of 2812 women and men (n = 1406 couples) received questionnaires when initiating fertility treatment and at 1-year and 5-year follow-ups. At the 5-year follow up, the response rate was 69.4% and 1036 of the responding participants had at least one child born after fertility treatment. Around 66% of the children were conceived with in vitro fertilization or intrauterine insemination with partners semen, 26% with intracytoplasmic sperm injection, 7% with donor gametes and <1% with other treatments. The parents were asked whether they already had or intended to disclose the conception method to the child and to others. We used logistic regression to identify determinants among women and men for disclosure. RESULTS: Most of the parents had disclosed or intended to disclose the mode of conception to the child, and almost everyone had disclosed to someone else. Not having used donor gametes was a significant determinant of disclosure both to the child and to other people among women and men. Having disclosed to other people was a significant predictor for having disclosed or intending to disclose to the child. Among women, low social class was a significant determinant of disclosure to the child. Among men, satisfaction with the medical treatment was a significant determinant of disclosure to other people. CONCLUSIONS: We found a large majority who had or intended to disclose to the child how he/she was conceived. Non-disclosure was significantly related to the use of donor gametes.

Exposure to bullying at school and depression in adulthood: a study of Danish men born in 1953.

BACKGROUND: Bullying among children is associated with high symptom load and depression. There is little knowledge about long-term consequences of bullying. The aim of the present study is to examine the association between recall of bullying at school and depression in midlife controlling for adult social class and parents' mental health. METHODS: The analyses were based on the 2004 survey among men from the Metropolit 1953 Danish Male Birth Cohort (n = 6094). Information on depression was retrieved by the Major Depression Inventory (MDI) (prevalent depression) and by a measure of first doctor diagnosed depression between the ages 31-51 years (DD). Information on bullying was based on a recall measure of bullying in school categorized into three dimensions: occurrence; intensity; and duration. RESULTS: Compared to subjects who had never been bullied, those exposed to bullying in school were at a significantly increased risk of having been diagnosed with depression between the ages 31-51 years. Long duration and high intensity of bullying were risk factors for both MDI and DD. Inclusion of the possible confounders (SES, parental mental illness) attenuated the associations somewhat, but the associations remained statistically significant. CONCLUSION: The present comparisons of the long-term incidence of depression among middle-aged men who experienced high and low levels of bullying at school might indicate that being bullied at school is a contributing factor in the development of depression. Prospective longitudinal studies are needed to confirm the effect of bullying in school on adult depression.

Inbreeding and population structure in two pairs of cryptic fig wasp species.

We used recently developed microsatellites to directly estimate inbreeding levels in two pairs of coexisting cryptic fig wasp species ('Pegoscapus hoffmeyeri sp. A and sp. B', 'P. gemellus sp. A and sp. B'). Previous tests of Hamilton's local mate competition (LMC) theory in fig wasps have used the number of dead foundresses in a fig fruit to indirectly estimate the relative contribution of each to the common brood and thereby the level of local mate competition. Further, the population level of inbreeding has been indirectly estimated using the distribution of foundress numbers across broods. Our direct genetic estimates confirmed previous assumptions that the species characterized by lower foundress numbers showed higher relative levels of inbreeding. However, there were quantitative differences between the observed level of inbreeding and the expectation based on the distribution of foundress numbers in both pollinator species associated with Ficus obtusifolia. Here, genotype compositions of broods revealed that only 23% of fruits with multiple foundresses actually contained brood from more than one foundress, thus explaining at least part of the underestimate of actual sibmating. Within the four wasp species there was no evidence for genetic differentiation among the wasp populations sampled from different trees across 20 km and from different points in time. Further, no genotypic disequilibrium was detected within any of the species. Although F1 hybrids were observed between the two species pollinating F. obtusifolia, there was no evidence of genetic introgression. Finally, we found that 11% of the sons of allospecifically mated mothers were diploid hybrids suggesting a break down of the sex determination system in hybrids.

Cryptic species of fig-pollinating wasps: implications for the evolution of the fig-wasp mutualism, sex allocation, and precision of adaptation.

Fig-pollinating wasps have provided model systems for developing and testing theories of the evolution of mutualism, sex allocation, and precision of adaptation. With few exceptions, previous studies have assumed one species of pollinator wasp per host fig species. Here we report genetic data demonstrating the coexistence of previously undetected cryptic fig wasp species in at least half of the host fig species surveyed. The substantial mitochondrial sequence differences (4.2-6.1%) imply old divergences ( approximately 1.5-5.1 million years ago) among these species. Furthermore, some cryptic species pairs seem to be sister taxa, whereas others clearly are not, indicating both long-term coexistence on shared hosts and the colonization of novel fig species. These findings undermine the prevalent notion of strict one-to-one specificity between cospeciating figs and their pollinators, thereby challenging existing theory concerning the evolution and stability of mutualisms. Moreover, the incorporation of the genetic information significantly improves the fit of the observed sex ratios to predictions of local mate-competition theory, further strengthening support for sex allocation theory and the precision of adaptation.

The distribution of Wolbachia in fig wasps: correlations with host phylogeny, ecology and population structure.

We surveyed for the presence and identity of Wolbachia in 44 species of chalcid wasps associated with 18 species of Panamanian figs. We used existing detailed knowledge of the population structures of the host wasps, as well as the ecological and evolutionary relationships among them, to explore the relevance of each of these factors to Wolbachia prevalence and mode of transmission. Fifty-nine per cent of these wasp species have Wolbachia infections, the highest proportion reported for any group of insects. Further, neither the presence nor the frequency of Wolbachia within hosts was correlated with the population structure of pollinator hosts. Phylogenetic analyses of wsp sequence data from 70 individuals representing 22 wasp species show that neither the close phylogenetic relationship nor close ecological association among host species is consistently linked to close phylogenetic affinities of the Wolbachia associated with them. Moreover, no genetic variation was detected within any Wolbachia strain from a given host species. Thus, the spread of Wolbachia within host species exceeds the rate of horizontal transmission among species and both exceed the rate of mutation of the wsp gene in Wolbachia. The presence and, in some cases, high frequency of Wolbachia infections within highly inbred species indicate that the Wolbachia either directly increase host fitness or are frequently horizontally transferred within these wasp species. However, the paucity of cospeciation of Wolbachia and their wasp hosts indicates that Wolbachia do not persist within a given host lineage for long time-periods relative to speciation times.