No abstract

Britain’s oldest birth cohort study, the MRC National Survey of Health and Development (NSHD) provides data to explore life time influences on ageing. The latest data collection was undertaken between 2006 and 2011 when study members were aged 60–64 and consisted of postal and pre-assessment questionnaires to eligible study members, followed by invitation to attend one of six clinical research facilities (CRFs) across the UK for clinical assessments, and dietary diaries and activity monitors in the days following the CRF visit. The option of a home visit for clinical assessments was provided if the study member refused or was unable to attend the CRF. We examined response and attrition, here describing rates overall and for postal and clinical assessment modes of data collection, identifying socioeconomic and health-related predictors of response, and assessing the continued representativeness of the sample. In total, 2,661 (84 % of the target sample) responded. Lower educational attainment, lower childhood cognition and lifelong smoking independently predicted lower likelihood of both overall response and CRF cooperation. At 53 years, not owning one’s home and not being married predicted lower likelihood of overall response whereas manual social class and obesity predicted lower likelihood of CRF cooperation. Providing for collection of biomedical data in the home and use of assessment instruments and modes to retain study members with lower education attainment, lower cognition and poorer health behaviours should be priorities for helping reduce attrition amongst vulnerable ageing study members.

Initial breastfeeding (particularly when exclusive) may be associated with lower blood cholesterol concentrations in later life. Moves to reduce the cholesterol content of formula feeds below those of breast milk should be treated with caution.

Objective: To test the validity of age at menarche self-reported in adulthood and examine whether socioeconomic position, education, experience of gynaecological events and psychological symptoms influence the accuracy of recall. Design: Prospective birth cohort study. Setting: England, Scotland and Wales. Participants: 1050 women from the Medical Research Council National Survey of Health and Development, with two measures of age at menarche, one recorded in adolescence and the other selfreported at age 48 years. Results: By calculating the limits of agreement, k statistic and Pearson's correlation coefficients (r), we found that the validity of age at menarche self-reported in middle age compared with that recorded in adolescence was moderate (k = 0.35, r = 0.66, n = 1050). Validity was improved by categorising age at menarche into three groups: early, normal and late (k = 0.43). Agreement was influenced by educational level and having had a stillbirth or miscarriage. Conclusions: The level of validity shown in this study throws some doubt on whether it is justifiable to use age at menarche self-reported in middle age. It is likely to introduce error and bias, and researchers should be aware of these limitations and use such measures with caution.

Purpose To identify the life course model that best describes the association between life course socioeconomic position (SEP) and cardiovascular (CVD) risk factors [body mass index (BMI), systolic and diastolic blood pressure, total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, glycated haemoglobin] and explore BMI across the life course as mediators of the relationship. Methods The Medical Research Council (MRC) National Survey of Health and Development was used to compare partial F-tests of simpler nested life course SEP models corresponding to critical period, accumulation, and social mobility modes with a saturated model. Then, the chosen life course model for each CVD risk factor was adjusted for BMI at age 53 and lifetime BMI (ages 4, 26, 43, and 53 years). Results Among women, SEP was generally associated with CVD risk factors in a cumulative manner; while childhood critical period was the prominent model for men. Using the best fitting SEP models, adjustment for BMI at age 53 reduced associations for all outcomes in both genders. Further adjustment for lifetime BMI (4, 26, 43 and 53 years) did not substantially alter most associations (except for triglycerides). Conclusion SEP at different points across life influences CVD risk factors differently in men and women.

Edited by Paul E. FraserSignaling events at membranes are often mediated by membrane lipid composition or membrane physical properties. These membrane properties could act either by favoring the membrane binding of downstream effectors or by modulating their activity. Several proteins can sense/generate membrane physical curvature (i.e. shape). However, the modulation of the activity of enzymes by a membrane's shape has not yet been reported. Here, using a cell-free assay with purified diacylglycerol kinase ⑀ (DGK⑀) and liposomes, we studied the activity and acyl-chain specificity of an enzyme of the phosphatidylinositol (PI) cycle, DGK⑀. By systematically varying the model membrane lipid composition and physical properties, we found that DGK⑀ has low activity and lacks acyl-chain specificity in locally flat membranes, regardless of the lipid composition. On the other hand, these enzyme properties were greatly enhanced in membrane structures with a negative Gaussian curvature. We also found that this is not a consequence of preferential binding of the enzyme to those structures, but rather is due to a curvature-mediated allosteric regulation of DGK⑀ activity and acylchain specificity. Moreover, in a fine-tuned interplay between the enzyme and the membrane, DGK⑀ favored the formation of structures with greater Gaussian curvature. DGK⑀ does not bear a regulatory domain, and these findings reveal the importance of membrane curvature in regulating DGK⑀ activity and acyl-chain specificity. Hence, this study highlights that a hierarchic coupling of membrane physical property and lipid composition synergistically regulates membrane signaling events. We propose that this regulatory mechanism of membrane-associated enzyme activity is likely more common than is currently appreciated.

In a longitudinal population cohort we have established a role for polymorphism of IL13 in determining susceptibility to both atopy and asthma.

We attempted to clarify the strength and nature of the association between personality and smoking status in early and middle adulthood, using a longitudinal study design. Data from the Medical Research Council National Survey of Health and Development, based on a stratified sample of all single, legitimate births occurring in England, Wales, and Scotland in one week of March 1946 (N = 5,362), were analyzed using generalized estimating equations methods to account for the correlation between the smoking status variables for the same individual over time. The unadjusted estimates indicated that the odds of being a current smoker increased with higher personality score for both extraversion (p<.0001) and neuroticism (p<.0001) traits. Sex was significantly associated with being a current smoker (p<.0001), with males more likely than females to be current smokers. Current smoking decreased with increasing age (p<.0001). These relationships were maintained in the fully adjusted model. These data indicate that both higher levels of extraversion and higher levels of neuroticism, as measured at age 16, are independently associated with an increased likelihood of subsequently being a current smoker rather than a nonsmoker at all time points, although the observed effect sizes were small. Males also were more likely than females to be current smokers, and increasing age reduced the likelihood of being a current smoker, which is consistent with an attempt by a subset of smokers in the cohort to subsequently stop smoking.