Socioeconomic inequalities across life and premature mortality from 1971 to 2016: findings from three British birth cohorts born in 1946, 1958 and 1970

INTRODUCTION: Disadvantaged socioeconomic position (SEP) in early and adult life has been repeatedly associated with premature mortality. However, it is unclear whether these inequalities differ across time, nor if they are consistent across different SEP indicators. METHODS: British birth cohorts born in 1946, 1958 and 1970 were used, and multiple SEP indicators in early and adult life were examined. Deaths were identified via national statistics or notifications. Cox proportional hazard models were used to estimate associations between ridit scored SEP indicators and all-cause mortality risk-from 26 to 43 years (n=40 784), 26 to 58 years (n=35 431) and 26 to 70 years (n=5353). RESULTS: More disadvantaged SEP was associated with higher mortality risk-magnitudes of association were similar across cohort and each SEP indicator. For example, HRs (95% CI) from 26 to 43 years comparing lowest to highest paternal social class were 2.74 (1.02 to 7.32) in 1946c, 1.66 (1.03 to 2.69) in 1958c, and 1.94 (1.20 to 3.15) in 1970c. Paternal social class, adult social class and housing tenure were each independently associated with mortality risk. CONCLUSIONS: Socioeconomic circumstances in early and adult life show persisting associations with premature mortality from 1971 to 2016, reaffirming the need to address socioeconomic factors across life to reduce inequalities in survival to older age

Age of First Overweight and Obesity, COVID-19 and Long COVID in Two British Birth Cohorts

Longer exposure to obesity, and thus a longer period in an inflamed state, may increase susceptibility to infectious diseases and worsen severity. Previous cross-sectional work finds higher BMI is related to worse COVID-19 outcomes, but less is known about associations with BMI across adulthood. To examine this, we used body mass index (BMI) collected through adulthood in the 1958 National Child Development Study (NCDS) and the 1970 British Cohort Study (BCS70). Participants were grouped by the age they were first overweight (> 25 kg/m2) and obese (> 30 kg/m2). Logistic regression was used to assess associations with COVID-19 (self-reported and serology-confirmed), severity (hospital admission and contact with health services) and long-COVID reported at ages 62 (NCDS) and 50 (BCS70). An earlier age of obesity and overweight, compared to those who never became obese or overweight, was associated with increased odds of adverse COVID-19 outcomes, but results were mixed and often underpowered. Those with early exposure to obesity were over twice as likely in NCDS (odds ratio (OR) 2.15, 95% confidence interval (CI) 1.17-4.00) and three times as likely in BCS70 (OR 3.01, 95% CI 1.74-5.22) to have long COVID. In NCDS they were also over four times as likely to be admitted to hospital (OR 4.69, 95% CI 1.64-13.39). Most associations were somewhat explained by contemporaneous BMI or reported health, diabetes or hypertension; however, the association with hospital admission in NCDS remained. An earlier age of obesity onset is related to COVID-19 outcomes in later life, providing evidence of the long-term impact of raised BMI on infectious disease outcomes in midlife

Comparison of the Structural Stability and Dynamic Properties of Recombinant Anthrax Protective Antigen and its 2- Fluorohistidine Labeled Analogue

Protective antigen (PA) is the primary protein antigenic component of both the currently used anthrax vaccine and related recombinant vaccines under development. An analogue of recombinant PA (2-FHis rPA) has been recently shown to block the key steps of pore formation in the process of inducing cytotoxicity in cells, and thus can potentially be used as an antitoxin or a vaccine. This rPA analogue was produced by fermentation to incorporate the unnatural amino acid 2-fluorohistidine (2-FHis). In this study, the effects of 2-FHis labeling on rPA antigen’s conformational stability and dynamic properties were investigated by various biophysical techniques. Temperature/pH stability profiles of rPA and 2-FHis rPA were analyzed by the empirical phase diagram (EPD) approach, and physical stability differences between them were identified. Results showed that rPA and 2-FHis rPA had similar stability at pH 7–8. With decreasing solution pH, however, 2-FHis rPA was found to be more stable. Dynamic sensitive measurements of the two proteins at pH 5 found that 2-FHis rPA was more dynamic and/or differentially hydrated under acidic pH conditions. The biophysical characterization and stability data provide information useful for the potential development of 2-FHis rPA as a more stable rPA vaccine candidate

Psychometric Evaluation and Design of Patient-Centered Communication Measures for Cancer Care Settings

Objective To evaluate the psychometric properties of questions that assess patient perceptions of patient-provider communication and design measures of patient-centered communication (PCC). Methods Participants (adults with colon or rectal cancer living in North Carolina) completed a survey at 2 to 3 months post-diagnosis. The survey included 87 questions in six PCC Functions: Exchanging Information, Fostering Health Relationships, Making Decisions, Responding to Emotions, Enabling Patient Self-Management, and Managing Uncertainty. For each Function we conducted factor analyses, item response theory modeling, and tests for differential item functioning, and assessed reliability and construct validity. Results Participants included 501 respondents; 46% had a high school education or less. Reliability within each Function ranged from 0.90 to 0.96. The PCC-Ca-36 (36-question survey; reliability=0.94) and PCC-Ca-6 (6-question survey; reliability=0.92) measures differentiated between individuals with poor and good health (i.e., known-groups validity) and were highly correlated with the HINTS communication scale (i.e., convergent validity). Conclusion This study provides theory-grounded PCC measures found to be reliable and valid in colorectal cancer patients in North Carolina. Future work should evaluate measure validity over time and in other cancer populations. Practice implications The PCC-Ca-36 and PCC-Ca-6 measures may be used for surveillance, intervention research, and quality improvement initiatives

The Evolution Of LMC X-4 Flares: Evidence For Super-Eddington Radiation Oozing Through Inhomogeneous Polar Cap Accretion Flows ?

We present the results of two extensive Rossi X-ray Timing Explorer observations of large X-ray flaring episodes from the high-mass X-ray binary pulsar LMC X-4. Light curves during the flaring episodes comprise bright peaks embedded in relatively fainter regions, with complex patterns of recurrence and clustering of flares. We identify precursors preceding the flaring activity. Pulse profiles during the flares appear to be simple sinusoids, and pulsed fractions are proportional to the flare intensities. We fit Gaussian functions to flare peaks to estimate the mean full-width-half-maximum to be $\sim$68 s. Significant rapid aperiodic variability exists up to a few hertz during the flares, which is related to the appearance of narrow, spiky peaks in the light curves. While spectral fits and softness ratios show overall spectral softening as the flare intensity increases, the narrow, spiky peaks do not follow this trend. The mean fluence of the flare peaks is (3.1 $\pm$ 2.9) $\times$ 10$^{40}$ ergs in the 2.5--25 keV energy range, with its maximum at $\sim$1.9 $\times$ 10$^{41}$ ergs. The flare peak luminosity reaches up to (2.1 $\pm$ 0.2) $\times$ 10$^{39}$ ergs s$^{-1}$, far above the Eddington luminosity of a neutron star. We discuss possible origins of the flares, and we also propose that inhomogeneous accretion columns onto the neutron star polar caps are responsible for the observed properties.Comment: 39 pages (including figures and tables), accepted for publication in Ap

Post-war (1946-2017) population health change in the United Kingdom: A systematic review

We systematically reviewed the evidence on secular trends in main chronic conditions, disability and self-assessed general health among adults in the United Kingdom, as reported in primary/secondary care databases and population-based surveys. Searches were conducted separately for: (1) trends in age-standardised or age-specific prevalence of major non-communicable diseases, disability, and self-reported general health; (2) trends in health expectancy. The databases searched were MEDLINE, EMBASE/EMBASE Classic and Web of Science (all from 1946/7). The evidence was synthesised narratively. There were 39 studies reporting trends in prevalence of health conditions and 15 studies in health expectancy. We did not find evidence for improvement in the age-standardised or age-specific prevalence of any of the studied major chronic conditions over the last few decades, apart from Alzheimer's disease and other dementias. Both increasing or stable prevalence rates with simultaneous rising life expectancy support the expansion of morbidity theory, meaning that people are expected to spend a greater number of years with chronic condition(s). The evidence on disability—expressed as prevalence or health expectancy—was mixed, but also appeared to support the expansion of morbidity among those aged 65 or over. The evidence on trends in disability for younger age is lacking. Across the studied period (1946–2017), the UK population endured more years with chronic morbidity and disability, which may place a serious strain on the health care system, the economy and the society

Duration of obesity exposure between ages 10 and 40 years and its relationship with cardiometabolic disease risk factors: A cohort study.

BACKGROUND: Individuals with obesity do not represent a homogeneous group in terms of cardiometabolic risk. Using 3 nationally representative British birth cohorts, we investigated whether the duration of obesity was related to heterogeneity in cardiometabolic risk. METHODS AND FINDINGS: We used harmonised body mass index (BMI) and cardiometabolic disease risk factor data from 20,746 participants (49.1% male and 97.2% white British) enrolled in 3 British birth cohort studies: the 1946 National Survey of Health and Development (NSHD), the 1958 National Child Development Study (NCDS), and the 1970 British Cohort Study (BCS70). Within each cohort, individual life course BMI trajectories were created between 10 and 40 years of age, and from these, age of obesity onset, duration spent obese (range 0 to 30 years), and cumulative obesity severity were derived. Obesity duration was examined in relation to a number of cardiometabolic disease risk factors collected in mid-adulthood: systolic (SBP) and diastolic blood pressure (DBP), high-density-lipoprotein cholesterol (HDL-C), and glycated haemoglobin (HbA1c). A greater obesity duration was associated with worse values for all cardiometabolic disease risk factors. The strongest association with obesity duration was for HbA1c: HbA1c levels in those with obesity for <5 years were relatively higher by 5% (95% CI: 4, 6), compared with never obese, increasing to 20% (95% CI: 17, 23) higher in those with obesity for 20 to 30 years. When adjustment was made for obesity severity, the association with obesity duration was largely attenuated for SBP, DBP, and HDL-C. For HbA1c, however, the association with obesity duration persisted, independent of obesity severity. Due to pooling of 3 cohorts and thus the availability of only a limited number harmonised variables across cohorts, our models included adjustment for only a small number of potential confounding variables, meaning there is a possibility of residual confounding. CONCLUSIONS: Given that the obesity epidemic is characterised by a much earlier onset of obesity and consequently a greater lifetime exposure, our findings suggest that health policy recommendations aimed at preventing early obesity onset, and therefore reducing lifetime exposure, may help reduce the risk of diabetes, independently of obesity severity. However, to test the robustness of our observed associations, triangulation of evidence from different epidemiological approaches (e.g., mendelian randomization and negative control studies) should be obtained

Regional trends in birth weight in low- and middle-income countries 2013-2018

Background: Birth weight (BW) is a strong predictor of neonatal outcomes. The purpose of this study was to compare BWs between global regions (south Asia, sub-Saharan Africa, Central America) prospectively and to determine if trends exist in BW over time using the population-based maternal and newborn registry (MNHR) of the Global Network for Women\u27sand Children\u27s Health Research (Global Network).Methods: The MNHR is a prospective observational population-based registryof six research sites participating in the Global Network (2013-2018), within five low- and middle-income countries (Kenya, Zambia, India, Pakistan, and Guatemala) in threeglobal regions (sub-Saharan Af rica, south Asia, Central America). The birth weights were obtained for all infants born during the study period. This was done either by abstracting from the infants\u27 health facility records or from direct measurement by the registry staff for infants born at home. After controlling for demographic characteristics, mixed-effect regression models were utilized to examine regional differences in birth weights over time.Results: The overall BW meanswere higher for the African sites (Zambia and Kenya), 3186 g (SD 463 g) in 2013 and 3149 g (SD 449 g) in 2018, ascompared to Asian sites (Belagavi and Nagpur, India and Pakistan), 2717 g (SD450 g) in 2013 and 2713 g (SD 452 g) in 2018. The Central American site (Guatemala) had a mean BW intermediate between the African and south Asian sites, 2928 g (SD 452) in 2013, and 2874 g (SD 448) in 2018. The low birth weight (LBW) incidence was highest in the south Asian sites (India and Pakistan) and lowest in the African sites (Kenya and Zambia). The size of regional differences varied somewhat over time with slight decreases in the gap in birth weights between the African and Asian sites and slight increases in the gap between the African and Central American sites.Conclusions: Overall, BWmeans by global region did not change significantly over the 5-year study period. From 2013 to 2018, infants enrolled at the African sites demonstrated the highest BW means overall across the entire study period, particularly as compared to Asian sites. The incidence of LBW was highest in the Asian sites (India and Pakistan) compared to the African and Central American sites. Trial registration The study is registered at clinicaltrials.gov. ClinicalTrial.gov Trial Registration: NCT01073475

Gender differences in the distribution of children’s physical activity: evidence from nine countries

Background: Physical activity in childhood is thought to influences health and development. Previous studies have found that boys are typically more active than girls, yet the focus has largely been on differences in average levels or proportions above a threshold rather than the full distribution of activity across all intensities. We thus examined differences in the distribution of physical activity between girls and boys in a multi-national sample of children. // Methods: We used the harmonised International Children Accelerometry Database (ICAD), including waist-worn accelerometry data from 15,461 individuals (Boys: 48.3%) from 9 countries. Employing Generalised Additive Models of Location, Shape, and Scale (GAMLSS) we investigated gender differences in the distribution of individuals, including comparisons of variability (SD) and average physical activity levels (mean and median) and skewness. We conducted this analysis for each activity intensity (Sedentary, Light, and Moderate-to-Vigorous (MVPA)) and a summary measure (counts per minute (CPM)). // Results: Sizable gender differences in the distribution of activity were found for moderate to vigorous activity and counts per minute, with boys having higher average levels (38% higher mean volumes of MVPA, 20% higher CPM), yet substantially more between-person variability (30% higher standard deviation (SD) for MVPA, 17% higher SD for CPM); boys’ distributions were less positively skewed than girls. Conversely, there was little to no difference between girls and boys in the distribution of sedentary or light-intensity activity. // Conclusions: Inequality in activity between girls and boys was driven by MVPA. The higher mean volumes of MVPA in boys occurred alongside greater variability. This suggests a need to consider the underlying distribution of activity in future research; for example, interventions which target gender inequality in MVPA may inadvertently lead to increased inequality within girls

Development of the global network for women\u27s and children\u27s health research\u27s socioeconomic status index for use in the network\u27s sites in low and lower middle-income countries

Background: Socioeconomic status (SES) is an important determinant of health globally and an important explanatory variable to assess causality in epidemiological research. The 10th Sustainable Development Goal is to reduce disparities in SES that impact health outcomes globally. It is easier to study SES in high-income countries because household income is representative of the SES. However, it is well recognized that income is poorly reported in low- and middle- income countries (LMIC) and is an unreliable indicator of SES. Therefore, there is a need for a robust index that will help to discriminate the SES of rural households in a pooled dataset from LMIC.Methods: The study was nested in the population-based Maternal and Neonatal Health Registry of the Global Network for Women\u27s and Children\u27s Health Research which has 7 rural sites in 6 Asian, sub-Saharan African and Central American countries. Pregnant women enrolling in the Registry were asked questions about items such as housing conditions and household assets. The characteristics of the candidate items were evaluated using confirmatory factor analyses and item response theory analyses. Based on the results of these analyses, a final set of items were selected for the SES index.Results: Using data from 49,536 households of pregnant women, we reduced the data collected to a 10-item index. The 10 items were feasible to administer, covered the SES continuum and had good internal reliability and validity. We developed a sum score-based Item Response Theory scoring algorithm which is easy to compute and is highly correlated with scores based on response patterns (r = 0.97), suggesting minimal loss of information with the simplified approach. Scores varied significantly by site (p \u3c 0.001). African sites had lower mean SES scores than the Asian and Central American sites. The SES index demonstrated good internal consistency reliability (Cronbach\u27s alpha = 0.81). Higher SES scores were significantly associated with formal education, more education, having received antenatal care, and facility delivery (p \u3c 0.001).Conclusions: While measuring SES in LMIC is challenging, we have developed a Global Network Socioeconomic Status Index which may be useful for comparisons of SES within and between locations. Next steps include understanding how the index is associated with maternal, perinatal and neonatal mortality. Trial Registration NCT01073475 Socioeconomic status (SES) is an important determinant of health globally, and improving SES is important to reduce disparities in health outcomes. It is easier to study SES in high-income countries because it can be measured by income and what income is spent on, but this concept does not translate easily to low and middle income countries. We developed a questionnaire that includes 10 items to determine SES in low-resource settings that was added to an ongoing Maternal and Neonatal Health Registry that is funded by the National Institutes of Child Health and Human Development\u27s Global Network. The Registry includes sites that collect outcomes of pregnancies in women and their babies in rural areas in 6 countries in South Asia, sub-Saharan Africa and Central America. The Registry is population based and tracks women from early in pregnancy to day 42 post-partum. The questionnaire is easy to administer and has good reliability and validity. Next steps include understanding how the index is associated with maternal, fetal and neonatal mortality