Changes over time in latent patterns of childhood-to-adulthood BMI development in Great Britain: evidence from three cohorts born in 1946, 1958, and 1970.

BACKGROUND: Most studies on secular trends in body mass index (BMI) are cross-sectional and the few longitudinal studies have typically only investigated changes over time in mean BMI trajectories. We aimed to describe how the evolution of the obesity epidemic in Great Britain reflects shifts in the proportion of the population demonstrating different latent patterns of childhood-to-adulthood BMI development. METHODS: We used pooled serial BMI data from 25,655 participants in three British cohorts: the 1946 National Survey of Health and Development (NSHD), 1958 National Child Development Study (NCDS), and 1970 British Cohort Study (BCS). Sex-specific growth mixture models captured latent patterns of BMI development between 11 and 42 years. The classes were characterised in terms of their birth cohort composition. RESULTS: The best models had four classes, broadly similar for both sexes. The 'lowest' class (57% of males; 47% of females) represents the normal weight sub-population, the 'middle' class (16%; 15%) represents the sub-population who likely develop overweight in early/mid-adulthood, and the 'highest' class (6%; 9%) represents those who likely develop obesity in early/mid-adulthood. The remaining class (21%; 29%) reflects a sub-population with rapidly 'increasing' BMI between 11 and 42 years. Both sexes in the 1958 NCDS had greater odds of being in the 'highest' class compared to their peers in the 1946 NSHD but did not have greater odds of being in the 'increasing' class. Conversely, males and females in the 1970 BCS had 2.78 (2.15, 3.60) and 1.87 (1.53, 2.28), respectively, times higher odds of being in the 'increasing' class. CONCLUSIONS: Our results suggest that the obesity epidemic in Great Britain reflects not only an upward shift in BMI trajectories but also a more recent increase in the number of individuals demonstrating more rapid weight gain, from normal weight to overweight, across the second, third, and fourth decades of life

Using Super-Imposition by Translation And Rotation (SITAR) to relate pubertal growth to bone health in later life: the Medical Research Council (MRC) National Survey of Health and Development.

BACKGROUND: To explore associations between pubertal growth and later bone health in a cohort with infrequent measurements, using another cohort with more frequent measurements to support the modelling, data from the Medical Research Council (MRC) National Survey of Health and Development (2-26 years, 4901/30 004 subjects/measurements) and the Avon Longitudinal Study of Parents And Children (ALSPAC) (5-20 years) (10 896/74 120) were related to National Survey of Health and Development (NSHD) bone health outcomes at 60-64 years. METHODS: NSHD data were analysed using Super-Imposition by Translation And Rotation (SITAR) growth curve analysis, either alone or jointly with ALSPAC data. Improved estimation of pubertal growth parameters of size, tempo and velocity was assessed by changes in model fit and correlations with contemporary measures of pubertal timing. Bone outcomes of radius [trabecular volumetric bone mineral density (vBMD) and diaphysis cross-sectional area (CSA)] were regressed on the SITAR parameters, adjusted for current body size. RESULTS: The NSHD SITAR parameters were better estimated in conjunction with ALSPAC, i.e. more strongly correlated with pubertal timing. Trabecular vBMD was associated with early height tempo, whereas diaphysis CSA was related to weight size, early tempo and slow velocity, the bone outcomes being around 15% higher for the better vs worse growth pattern. CONCLUSIONS: By pooling NSHD and ALSPAC data, SITAR more accurately summarized pubertal growth and weight gain in NSHD, and in turn demonstrated notable associations between pubertal timing and later bone outcomes. These associations give insight into the importance of the pubertal period for future skeletal health and osteoporosis risk.NSHD: The authors are grateful to NSHD study members who took part in the clinic data collection for their continuing support. We thank members of the NSHD scientific and data collection teams at the following centres: MRC Unit for Lifelong Health and Ageing; Wellcome Trust (WT) Clinical Research Facility (CRF) Manchester; WTCRF and Medical Physics at the Western General Hospital in Edinburgh; WTCRF and Department of Nuclear Medicine at University Hospital Birmingham; WTCRF and the Department of Nuclear Medicine at University College London Hospital; CRF and the Department of Medical Physics at the University Hospital of Wales; CRF and Twin Research Unit at St Thomas’ Hospital London. ALSPAC: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Oxford Univeristy Press

DNA methylation age and physical and cognitive ageing

Background: DNA methylation (DNAm) age acceleration (AgeAccel) has been shown to be predictive of all-cause mortality but it is unclear what functional aspect/s of ageing it captures. We examine associations between four measures of AgeAccel in adults aged 45-87 years and physical and cognitive performance and their age-related decline. / Methods: AgeAccelHannum, AgeAccelHorvath, AgeAccelPheno and AgeAccelGrim were calculated in the Medical Research Council National Survey of Health and Development (NSHD), National Child Development Study (NCDS) and TwinsUK. Three measures of physical (grip strength, chair rise speed and forced expiratory volume in one second[FEV1]) and two measures of cognitive (episodic memory and mental speed) performance were assessed. / Results: AgeAccelPheno and AgeAccelGrim, but not AgeAccelHannum and AgeAccelHorvath were related to performance in random effects meta-analyses (n=1388-1685). For example, a one year increase in AgeAccelPheno/AgeAccelGrim was associated with a 0.01ml[95%CI:0.01,0.02]/0.03ml[95%CI:0.01,0.05] lower mean FEV1. In NSHD, AgeAccelPheno and AgeAccelGrim at 53 years were associated with age-related decline in performance between 53 and 69 years as tested by linear mixed models (p<0.05). In a subset of NSHD participants(n=482), there was little evidence that change in any AgeAccel measure was associated with change in performance conditional on baseline performance. / Conclusions: We found little evidence to support associations between the first generation of DNAm-based biomarkers of ageing and age-related physical or cognitive performance in mid-life to early old age. However, there was evidence that the second generation biomarkers, AgeAccelPheno and AgeAccelGrim, could act as makers of an individual’s health-span as proposed

Neurocognitive outcomes in neurofibromatosis clinical trials

Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials

Analysis of Nigerians with Apparently Sporadic Parkinson Disease for Mutations in LRRK2, PRKN and ATXN3

Several genetic variations have been associated with Parkinson disease in different populations over the past few years. Although a considerable number of worldwide populations have been screened for these variants, results from Sub-Saharan populations are very scarce in the literature. In the present report we have screened a cohort of Parkinson disease patients (n = 57) and healthy controls (n = 51) from Nigeria for mutations in the genes PRKN, LRRK2 and ATXN3. No pathogenic mutations were found in any of the genes. Hence, common pathogenic mutations in these genes, observed in several different populations, are not a frequent cause of Parkinson disease in Nigeria

A cluster randomized controlled trial of the effectiveness and cost-effectiveness of Intermediate Care Clinics for Diabetes (ICCD) : study protocol for a randomized controlled trial

Background World-wide healthcare systems are faced with an epidemic of type 2 diabetes. In the United Kingdom, clinical care is primarily provided by general practitioners (GPs) rather than hospital specialists. Intermediate care clinics for diabetes (ICCD) potentially provide a model for supporting GPs in their care of people with poorly controlled type 2 diabetes and in their management of cardiovascular risk factors. This study aims to (1) compare patients with type 2 diabetes registered with practices that have access to an ICCD service with those that have access only to usual hospital care; (2) assess the cost-effectiveness of the intervention; and (3) explore the views and experiences of patients, health professionals and other stakeholders. Methods/Design This two-arm cluster randomized controlled trial (with integral economic evaluation and qualitative study) is set in general practices in three UK Primary Care Trusts. Practices are randomized to one of two groups with patients referred to either an ICCD (intervention) or to hospital care (control). Intervention group: GP practices in the intervention arm have the opportunity to refer patients to an ICCD - a multidisciplinary team led by a specialist nurse and a diabetologist. Patients are reviewed and managed in the ICCD for a short period with a goal of improving diabetes and cardiovascular risk factor control and are then referred back to practice. or Control group: Standard GP care, with referral to secondary care as required, but no access to ICCD. Participants are adults aged 18 years or older who have type 2 diabetes that is difficult for their GPs to control. The primary outcome is the proportion of participants reaching three risk factor targets: HbA1c (≤7.0%); blood pressure (<140/80); and cholesterol (<4 mmol/l), at the end of the 18-month intervention period. The main secondary outcomes are the proportion of participants reaching individual risk factor targets and the overall 10-year risks for coronary heart disease(CHD) and stroke assessed by the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Other secondary outcomes include body mass index and waist circumference, use of medication, reported smoking, emotional adjustment, patient satisfaction and views on continuity, costs and health related quality of life. We aimed to randomize 50 practices and recruit 2,555 patients

Ethnic variations in duration of untreated psychosis: report from the CRIS-FEP study

Objectives:  There is inconsistent evidence on the influence of ethnicity on duration of untreated psychosis (DUP). We investigated ethnic differences in DUP in a large epidemiological dataset of first episode psychosis patients in an inner city area of south London, UK. Methods:  We analysed data on 558 first episode psychosis patients at the South London and Maudsley NHS Trust, between 2010 and 2012. We performed multivariable logistic regression to estimate the odds of a short DUP (≤ 6 months) by ethnic group, controlling for confounders. Results:  There was no evidence that ethnicity is associated with duration of untreated psychosis. However, we found evidence that a short DUP was strongly associated with age, living circumstances, and pathways to care variables (involuntary admission, out of office hour contact, accident and emergency referral, criminal justice agency referral and family involvement in help-seeking). Conversely, a long DUP was associated with report of social isolation, living alone, being single and General Practitioner referral. Conclusion:  Our findings suggest that indicators of social isolation were associated with long DUP. Our data also show that pathways into care characteristics play significant role in DUP. Thus, the challenge of tackling the issue of timely access to EI under the new Access and Waiting Time standard for psychosis requires a multilevel approach, including joint working with communities, public awareness of psychosis, less restrictive referral pathways and adequate resourcing of early intervention for psychosis services. These will go a long way in addressing patients’ needs rather than be determined by service structures

Modification of genetic influences on adiposity between 36 and 63 years of age by physical activity and smoking in the 1946 British Birth Cohort Study

Previous studies reporting on the interaction between physical activity and genetic susceptibility on obesity have been cross-sectional and have not considered the potential influences of other lifestyle behaviours. The aim of this study was to examine modification of genetic influences on changes across age in adiposity during mid-adulthood by physical activity and smoking

Resolving confusions about jarrah dieback - don’t forget the plants

The name jarrah dieback has been used for two different disorders, leading to considerable confusion. It was coined in the 1940s to describe the sudden death of groups of jarrah (Eucalyptus marginata) trees in south western Western Australia, which occurred on poorly drained sites, following exceptionally heavy rainfall. In the 1960s these sites were shown to be infested by Phytophthora cinnamomi and jarrah deaths were attributed to it, even though it was only isolated from 5 % of sampled trees. Also the definition of jarrah dieback was expanded to include deaths of many other plants on infested sites, from which P. cinnamomi was more readily isolated. Jarrah trees die from severe water deficiency, indicating problems with water conduction through roots. Xylem vessel diameters vary along roots, being narrow at the root collar, while distally they are larger, providing water storage. Jarrah transpires vigorously during summer, accessing water at depth on sites with deep soil, but being more dependent on internally stored water when root systems are shallower. Following waterlogging, sapwood vessels become blocked with tyloses, reducing both conductivity and potential water storage; such trees may have insufficient water reserves for summer survival. In jarrah P. cinnamomi is unlikely to cause water deficiency because sapwood invasion is rapidly contained in healthy roots. Recent investigations into P. cinnamomi invasion and host responses in other plants show that it can potentially cause a vascular wilt in Banksia spp. and chronic, symptomless infections in herbaceous plants. Susceptibility to waterlogging damage, and/or mortality resulting from infection by P. cinnamomi can only be clarified by detailed knowledge of the hosts and their vulnerabilities. This is essential for making diagnoses, devising management strategies, and avoiding the confusions of the past