Association between resting heart rate across the life course and all-cause mortality: longitudinal findings from the Medical Research Council (MRC) National Survey of Health and Development (NSHD)

Background: Resting heart rate (RHR) is an independent risk factor for mortality. Nevertheless, it is unclear whether elevations in childhood and mid-adulthood RHR, including changes over time, are associated with mortality later in life. We sought to evaluate the association between RHR across the life course, along with its changes and all-cause mortality. / Methods: We studied 4638 men and women from the Medical Research Council (MRC) National Survey of Health and Development (NSHD) cohort born during 1 week in 1946. RHR was obtained during childhood at ages 6, 7 and 11, and in mid-adulthood at ages 36 and 43. Using multivariable Cox regression, we calculated the HR for incident mortality according to RHR measured at each time point, along with changes in mid-adulthood RHR. / Results: At age 11, those in the top fifth of the RHR distribution (≥97 bpm) had an increased adjusted hazard of 1.42 (95% CI 1.04 to 1.93) for all-cause mortality. A higher adjusted risk (HR, 95% CI 2.17, 1.40 to 3.36) of death was also observed for those in the highest fifth (≥81 bpm) at age 43. For a >25 bpm increased change in the RHR over the course of 7 years (age 36–43), the adjusted hazard was elevated more than threefold (HR, 95% CI 3.26, 1.54 to 6.90). After adjustment, RHR at ages 6, 7 and 36 were not associated with all-cause mortality. / Conclusions: Elevated RHR during childhood and midlife, along with greater changes in mid-adulthood RHR, are associated with an increased risk of all-cause mortality

Psychiatric Disorder Criteria and their Application to Research in Different Racial Groups

BACKGROUND: The advent of standardized classification and assessment of psychiatric disorders, and considerable joint efforts among many countries has led to the reporting of international rates of psychiatric disorders, and inevitably, their comparison between different racial groups. RESULTS: In neurologic diseases with defined genetic etiologies, the same genetic cause has different phenotypes in different racial groups. CONCLUSION: We suggest that genetic differences between races mean that diagnostic criteria refined in one racial group, may not be directly and simply applicable to other racial groups and thus more effort needs to be expended on defining diseases in other groups. Cross-racial confounds (in addition to cultural confounds) make the interpretation of rates in different groups even more hazardous than seems to have been appreciated

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

Novel coronary heart disease risk factors at 60-64 years and life course socioeconomic position: The 1946 British birth cohort.

Social disadvantage across the life course is associated with a greater risk of coronary heart disease (CHD) and with established CHD risk factors, but less is known about whether novel CHD risk factors show the same patterns. The Medical Research Council National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and markers of inflammation (C-reactive protein, interleukin-6), endothelial function (E-selectin, tissue-plasminogen activator), adipocyte function (leptin, adiponectin) and pancreatic beta cell function (proinsulin) measured at 60-64 years. Life course models representing sensitive periods, accumulation of risk and social mobility were compared with a saturated model to ascertain the nature of the relationship between social class across the life course and each of these novel CHD risk factors. For interleukin-6 and leptin, low childhood socioeconomic position alone was associated with high risk factor levels at 60-64 years, while for C-reactive protein and proinsulin, cumulative effects of low socioeconomic position in both childhood and early adulthood were associated with higher (adverse) risk factor levels at 60-64 years. No associations were observed between socioeconomic position at any life period with either endothelial marker or adiponectin. Associations for C-reactive protein, interleukin-6, leptin and proinsulin were reduced considerably by adjustment for body mass index and, to a lesser extent, cigarette smoking. In conclusion, socioeconomic position in early life is an important determinant of several novel CHD risk factors. Body mass index may be an important mediator of these relationships

Run, Jump, Throw and Catch: How proficient are children attending English schools at the Fundamental Motor Skills identified as key within the school curriculum?

This study examined proficiency levels in fundamental motor skills (FMS) in children within Key Stage 1 and 2 of the English school system. Four hundred and ninety-two children aged 6–9 Years old (245 boys, 247 girls) from school Years Two (n = 130), Three (n = 154) and Four (n = 208) participated in this study. FMS for the run, jump, throw and catch were assessed using the Test of Gross Motor Development – 2. The proportion of children who achieved mastery or near mastery of the skills was determined. For the whole sample, 18.5% (n = 91) did not achieve mastery in any of the four skills. A similar proportion (18.7%, n = 92) achieved mastery in all four of the FMS examined in this study. The proportion of children achieving mastery of all four skills was lower for Year Two children (0%) compared to children in years Three (24%) and Four (25%). More boys (25.7%) achieved mastery in all four of the FMS compared to girls (11.7%). Individual behavioural components in skill performance were also examined. The results of the present study highlight that less than one-fifth of children aged 6–9 years old have mastered the four key FMS identified by the physical education (PE) curriculum despite having the developmental potential to become fundamentally competent by six years of age. Fostering positive trajectories of FMS development presents a challenge for PE specialists given the association between FMS mastery in childhood and physical activity, weight status and health.N/

The role of mentorship in protege performance

The role of mentorship on protege performance is a matter of importance to academic, business, and governmental organizations. While the benefits of mentorship for proteges, mentors and their organizations are apparent, the extent to which proteges mimic their mentors' career choices and acquire their mentorship skills is unclear. Here, we investigate one aspect of mentor emulation by studying mentorship fecundity---the number of proteges a mentor trains---with data from the Mathematics Genealogy Project, which tracks the mentorship record of thousands of mathematicians over several centuries. We demonstrate that fecundity among academic mathematicians is correlated with other measures of academic success. We also find that the average fecundity of mentors remains stable over 60 years of recorded mentorship. We further uncover three significant correlations in mentorship fecundity. First, mentors with small mentorship fecundity train proteges that go on to have a 37% larger than expected mentorship fecundity. Second, in the first third of their career, mentors with large fecundity train proteges that go on to have a 29% larger than expected fecundity. Finally, in the last third of their career, mentors with large fecundity train proteges that go on to have a 31% smaller than expected fecundity.Comment: 23 pages double-spaced, 4 figure

Desmocollin switching in colorectal cancer

The desmocollins are members of the desmosomal cadherin family of cell–cell adhesion molecules. They are essential constituents of desmosomes, intercellular junctions that play a critical role in the maintenance of tissue integrity in epithelia and cardiac muscle. In humans, three desmocollins (Dsc1, Dsc2 and Dsc3) have been described. The desmocollins exhibit tissue-specific patterns of expression; only Dsc2 is expressed in normal colonic epithelium. We have found switching between desmocollins in sporadic colorectal adenocarcinoma with a reduction in Dsc2 protein (in 8/16 samples analysed by immunohistochemistry) being accompanied by de novo expression of Dsc1 (16/16) and Dsc3 (7/16). Similar results were obtained by western blotting of a further 16 samples. No change was found in Dsc2 mRNA, but de novo expression of Dscs 1 and 3 was accompanied by increased message levels. Loss of Dsc2 (8/19) and de novo expression of Dsc1 (11/19) and Dsc3 (6/19) was also found in colorectal adenocarcinomas on a background of colitis. The data raise the possibility that switching of desmocollins could play an important role in the development of colorectal cancer

Quantitative nanoscale vortex-imaging using a cryogenic quantum magnetometer

Microscopic studies of superconductors and their vortices play a pivotal role in our understanding of the mechanisms underlying superconductivity. Local measurements of penetration depths or magnetic stray-fields enable access to fundamental aspects of superconductors such as nanoscale variations of superfluid densities or the symmetry of their order parameter. However, experimental tools, which offer quantitative, nanoscale magnetometry and operate over the large range of temperature and magnetic fields relevant to address many outstanding questions in superconductivity, are still missing. Here, we demonstrate quantitative, nanoscale magnetic imaging of Pearl vortices in the cuprate superconductor YBCO, using a scanning quantum sensor in form of a single Nitrogen-Vacancy (NV) electronic spin in diamond. The sensor-to-sample distance of ~10nm we achieve allows us to observe striking deviations from the prevalent monopole approximation in our vortex stray-field images, while we find excellent quantitative agreement with Pearl's analytic model. Our experiments yield a non-invasive and unambiguous determination of the system's local London penetration depth, and are readily extended to higher temperatures and magnetic fields. These results demonstrate the potential of quantitative quantum sensors in benchmarking microscopic models of complex electronic systems and open the door for further exploration of strongly correlated electron physics using scanning NV magnetometry.Comment: Main text (5 pages, 4 figures) plus supplementary material (5 pages, 6 figures). Comments welcome. Further information under http://www.quantum-sensing.c

Stratification of candidate genes for Parkinson's disease using weighted protein-protein interaction network analysis

Background: Genome wide association studies (GWAS) have helped identify large numbers of genetic loci that significantly associate with increased risk of developing diseases. However, translating genetic knowledge into understanding of the molecular mechanisms underpinning disease (i.e. disease-specific impacted biological processes) has to date proved to be a major challenge. This is primarily due to difficulties in confidently defining candidate genes at GWAS-risk loci. The goal of this study was to better characterize candidate genes within GWAS loci using a protein interactome based approach and with Parkinson’s disease (PD) data as a test case. // Results: We applied a recently developed Weighted Protein-Protein Interaction Network Analysis (WPPINA) pipeline as a means to define impacted biological processes, risk pathways and therein key functional players. We used previously established Mendelian forms of PD to identify seed proteins, and to construct a protein network for genetic Parkinson’s and carried out functional enrichment analyses. We isolated PD-specific processes indicating ‘mitochondria stressors mediated cell death’, ‘immune response and signaling’, and ‘waste disposal’ mediated through ‘autophagy’. Merging the resulting protein network with data from Parkinson’s GWAS we confirmed 10 candidate genes previously selected by pure proximity and were able to nominate 17 novel candidate genes for sporadic PD. // Conclusions: With this study, we were able to better characterize the underlying genetic and functional architecture of idiopathic PD, thus validating WPPINA as a robust pipeline for the in silico genetic and functional dissection of complex disorders