Area-level and family-level socioeconomic position and body composition trajectories: longitudinal analysis of the UK Millennium Cohort Study

Background: Inequalities in the trajectories of body composition in childhood and adolescence have been infrequently studied. Despite the importance of environmental factors in obesity development, little research has looked at area-level socioeconomic position, independent of family socioeconomic position. We aimed to assess how inequalities in body composition develop with age. Methods: The Millennium Cohort Study is a longitudinal study of 19 243 families who had a child born between 2000 and 2002 in the UK. Multilevel growth curve models were applied to examine change in fat mass index (FMI), fat free mass index (FFMI; using the Benn index), and fat mass to fat free mass ratio (FM:FFM), measured using Bioelectrical Impedance Analysis, from ages 7 years to 17 years by the Index of Multiple Deprivation (IMD) and household income at baseline. Findings: Inequalities in FMI and FM:FFM ratio are evident at age 7 years and widen with age. At age 17 years, adolescents in the most disadvantaged IMD group had FMI 0·57 kg/mB (B=Benn parameter; 95% CI 0·43 to 0·70) higher and FM:FFM ratio 0·037 (95% CI 0·026 to 0·047) higher compared with the most advantaged group. Disadvantaged socioeconomic position is associated with higher FFMI but is reversed in adolescence after adjustment for FMI. Inequalities were greater in girls at age 7 years (mean FMI 0·22 kg/mB; 95% CI 0·13 to 0·32) compared with boys of the same age (0·05 kg/mB; –0·04 to 0·15, p=0·3), but widen fastest in boys, especially for FMI, in which there was over an 11 times increase in the inequality from age 7 years of 0·05kg/mB (95% CI –0·04 to 0·15) to 0·62 kg/mB at 17 years (0·42 to 0·82). Inequalities for the IMD were similar to income, and persisted at age 17 years independent of family socioeconomic position. Interpretation: Childhood and adolescence is an important period to address inequalities in body composition, as they emerge and widen. Policies should consider FFM as well as FM, and inequalities in the environment. Funding: Medical Research Council, Economic and Social Research Council

Using the Gene Ontology to Annotate Key Players in Parkinson's Disease

The Gene Ontology (GO) is widely recognised as the gold standard bioinformatics resource for summarizing functional knowledge of gene products in a consistent and computable, information-rich language. GO describes cellular and organismal processes across all species, yet until now there has been a considerable gene annotation deficit within the neurological and immunological domains, both of which are relevant to Parkinson's disease. Here we introduce the Parkinson's disease GO Annotation Project, funded by Parkinson's UK and supported by the GO Consortium, which is addressing this deficit by providing GO annotation to Parkinson's-relevant human gene products, principally through expert literature curation. We discuss the steps taken to prioritise proteins, publications and cellular processes for annotation, examples of how GO annotations capture Parkinson's-relevant information, and the advantages that a topic-focused annotation approach offers to users. Building on the existing GO resource, this project collates a vast amount of Parkinson's-relevant literature into a set of high-quality annotations to be utilized by the research community

Socioeconomic position and body composition in childhood in high- and middle-income countries: a systematic review and narrative synthesis

BACKGROUND: The relation between socioeconomic position (SEP) and obesity measured by body mass index (BMI), a measure of weight for height, has been extensively reviewed in children, showing consistent associations between disadvantaged SEP and higher BMI in high-income countries (HICs) and lower BMI in middle-income countries (MICs). Fat mass (FM), a more accurate measure of adiposity, and fat-free mass (FFM) are not captured by BMI, but have been shown to track from childhood to adulthood, and be important for cardiovascular health and functional outcomes in later life. It is not clear whether body composition is associated with SEP. We systematically reviewed the association between SEP and body composition in childhood. METHODS: A systematic review was carried out following PRISMA guidelines. The protocol was pre-registered with PROSPERO (CRD42019119937). Original studies in the English language, which examined the association between SEP and body composition in childhood, were included. An electronic search of three databases was conducted. Two independent reviewers carried out screening, data extraction and quality assessment. Due to heterogeneity in results, a narrative synthesis was conducted. Heterogeneity in findings according to SEP, sex, body composition measure and country income level was investigated. RESULTS: 50 papers were included, the majority from HICs. No papers were from low-income countries. Disadvantage in childhood was associated with greater FM and lower FFM in HICs, but with lower FM and lower FFM in MICs. When measures of FFM indexed to height were used there was no evidence of associations with SEP. In HICs, more studies reported associations between disadvantaged SEP and higher FM among girls comparative to boys. CONCLUSIONS: Inequalities in FM are evident in HICs and, in the opposite direction, in MICs and follow similar trends to inequalities for BMI. Inequalities in height are likely important in understanding inequalities in FFM

Life course socioeconomic position and body composition in adulthood: a systematic review and narrative synthesis

INTRODUCTION: Multiple systematic reviews have investigated the relation between socioeconomic position (SEP) and body mass index (BMI) throughout the life course. However, BMI does not capture quantity and distribution of fat and muscle, which are better indicators of obesity than BMI, and have been independently linked to adverse health outcomes. Less is known about the relation between SEP and body composition, and the literature has not been reviewed. We therefore systematically reviewed the literature on the association between life course SEP and body composition in adulthood. METHODS: A protocol was registered on PROSPERO (CRD42019119937), and the review followed PRISMA guidelines. An electronic search of three databases (MEDLINE, Embase Classic + Embase and SPORTDiscus) was conducted. Original studies in the English language were included that examine the association between any recognised measure of SEP at any age and body composition (fat mass, fat-free mass, ratio and distribution) in adulthood, measured using a direct technique, i.e., not an anthropometric measure. A narrative synthesis was conducted. RESULTS: A total of 47 papers were included in the final review, none were from low-income countries (LICs). Greater advantage in childhood and adulthood was associated with lower fat levels in high-income countries (HICs). Associations in the opposite direction were found exclusively in middle-income countries (MICs). No studies in MICs reported associations for childhood SEP. For measures of lean mass, the majority of papers reported no association, or greater advantage in adulthood associated with higher lean mass, with little variation between HICs and MICs. Associations in HICs are more often observed in women than men. CONCLUSION: The results indicate that fat measures follow similar patterns to those seen for BMI, and that women in HICs are more likely to experience inequalities in both fat and lean measures. Further research in LICs and MICs is needed

Novel compound mutations in the mitochondrial translation elongation factor (TSFM) gene cause severe cardiomyopathy with myocardial fibro-adipose replacement

Primary mitochondrial dysfunction is an under-appreciated cause of cardiomyopathy, especially when cardiac symptoms are the unique or prevalent manifestation of disease. Here, we report an unusual presentation of mitochondrial cardiomyopathy, with dilated phenotype and pathologic evidence of biventricular fibro-adipose replacement, in a 33-year old woman who underwent cardiac transplant. Whole exome sequencing revealed two novel compound heterozygous variants in the TSFM gene, coding for the mitochondrial translation elongation factor EF-Ts. This protein participates in the elongation step of mitochondrial translation by binding and stabilizing the translation elongation factor Tu (EF-Tu). Bioinformatics analysis predicted a destabilization of the EF-Ts variants complex with EF-Tu, in agreement with the dramatic steady-state level reduction of both proteins in the clinically affected myocardium, which demonstrated a combined respiratory chain enzyme deficiency. In patient fibroblasts, the decrease of EF-Ts was paralleled by up-regulation of EF-Tu and induction of genes involved in mitochondrial biogenesis, along with increased expression of respiratory chain subunits and normal oxygen consumption rate. Our report extends the current picture of morphologic phenotypes associated with mitochondrial cardiomyopathies and confirms the heart as a main target of TSFM dysfunction. The compensatory response detected in patient fibroblasts might explain the tissue-specific expression of TSFM-associated disease

Simultaneous Extraction of the Fermi constant and PMNS matrix elements in the presence of a fourth generation

Several recent studies performed on constraints of a fourth generation of quarks and leptons suffer from the ad-hoc assumption that 3 x 3 unitarity holds for the first three generations in the neutrino sector. Only under this assumption one is able to determine the Fermi constant G_F from the muon lifetime measurement with the claimed precision of G_F = 1.16637 (1) x 10^-5 GeV^-2. We study how well G_F can be extracted within the framework of four generations from leptonic and radiative mu and tau decays, as well as from K_l3 decays and leptonic decays of charged pions, and we discuss the role of lepton universality tests in this context. We emphasize that constraints on a fourth generation from quark and lepton flavour observables and from electroweak precision observables can only be obtained in a consistent way if these three sectors are considered simultaneously. In the combined fit to leptonic and radiative mu and tau decays, K_l3 decays and leptonic decays of charged pions we find a p-value of 2.6% for the fourth generation matrix element |U_{e 4}|=0 of the neutrino mixing matrix.Comment: 19 pages, 3 figures with 16 subfigures, references and text added refering to earlier related work, figures and text in discussion section added, results and conclusions unchange

Angle-dependence of quantum oscillations in YBa2Cu3O6.59 shows free spin behaviour of quasiparticles

Measurements of quantum oscillations in the cuprate superconductors afford a new opportunity to assess the extent to which the electronic properties of these materials yield to a description rooted in Fermi liquid theory. However, such an analysis is hampered by the small number of oscillatory periods observed. Here we employ a genetic algorithm to globally model the field, angular, and temperature dependence of the quantum oscillations observed in the resistivity of YBa2Cu3O6.59. This approach successfully fits an entire data set to a Fermi surface comprised of two small, quasi-2-dimensional cylinders. A key feature of the data is the first identification of the effect of Zeeman splitting, which separates spin-up and spin-down contributions, indicating that the quasiparticles in the cuprates behave as nearly free spins, constraining the source of the Fermi surface reconstruction to something other than a conventional spin density wave with moments parallel to the CuO2 planes.Comment: 8 pages, 4 figure

Measuring the effect of enhanced cleaning in a UK hospital : a prospective cross-over study

Increasing hospital-acquired infections have generated much attention over the last decade. There is evidence that hygienic cleaning has a role in the control of hospital-acquired infections. This study aimed to evaluate the potential impact of one additional cleaner by using microbiological standards based on aerobic colony counts and the presence of Staphylococcus aureus including meticillin-resistant S. aureus. We introduced an additional cleaner into two matched wards from Monday to Friday, with each ward receiving enhanced cleaning for six months in a cross-over design. Ten hand-touch sites on both wards were screened weekly using standardised methods and patients were monitored for meticillin-resistant S. aureus infection throughout the year-long study. Patient and environmental meticillin-resistant S. aureus isolates were characterised using molecular methods in order to investigate temporal and clonal relationships. Enhanced cleaning was associated with a 32.5% reduction in levels of microbial contamination at handtouch sites when wards received enhanced cleaning (P < 0.0001: 95% CI 20.2%, 42.9%). Near-patient sites (lockers, overbed tables and beds) were more frequently contaminated with meticillin-resistant S. aureus/S. aureus than sites further from the patient (P = 0.065). Genotyping identified indistinguishable strains from both handtouch sites and patients. There was a 26.6% reduction in new meticillin-resistant S. aureus infections on the wards receiving extra cleaning, despite higher meticillin-resistant S. aureus patient-days and bed occupancy rates during enhanced cleaning periods (P = 0.032: 95% CI 7.7%, 92.3%). Adjusting for meticillin-resistant S. aureus patient-days and based upon nine new meticillin-resistant S. aureus infections seen during routine cleaning, we expected 13 new infections during enhanced cleaning periods rather than the four that actually occurred. Clusters of new meticillin-resistant S. aureus infections were identified 2 to 4 weeks after the cleaner left both wards. Enhanced cleaning saved the hospital £30,000 to £70,000.Introducing one extra cleaner produced a measurable effect on the clinical environment, with apparent benefit to patients regarding meticillin-resistant S. aureus infection. Molecular epidemiological methods supported the possibility that patients acquired meticillin-resistant S. aureus from environmental sources. These findings suggest that additional research is warranted to further clarify the environmental, clinical and economic impact of enhanced hygienic cleaning as a component in the control of hospital-acquired infection

Cross-sectional associations between air pollution and chronic bronchitis: an ESCAPE meta-analysis across five cohorts

BACKGROUND: This study aimed to assess associations of outdoor air pollution on prevalence of chronic bronchitis symptoms in adults in five cohort studies (Asthma-E3N, ECRHS, NSHD, SALIA, SAPALDIA) participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE) project. METHODS: Annual average particulate matter (PM10, PM2.5, PMabsorbance, PMcoarse), NO2, nitrogen oxides (NOx) and road traffic measures modelled from ESCAPE measurement campaigns 2008-2011 were assigned to home address at most recent assessments (1998-2011). Symptoms examined were chronic bronchitis (cough and phlegm for &ge;3 months of the year for &ge;2 years), chronic cough (with/without phlegm) and chronic phlegm (with/without cough). Cohort-specific cross-sectional multivariable logistic regression analyses were conducted using common confounder sets (age, sex, smoking, interview season, education), followed by meta-analysis. RESULTS: 15 279 and 10 537 participants respectively were included in the main NO2 and PM analyses at assessments in 1998-2011. Overall, there were no statistically significant associations with any air pollutant or traffic exposure. Sensitivity analyses including in asthmatics only, females only or using back-extrapolated NO2 and PM10 for assessments in 1985-2002 (ECRHS, NSHD, SALIA, SAPALDIA) did not alter conclusions. In never-smokers, all associations were positive, but reached statistical significance only for chronic phlegm with PMcoarse OR 1.31 (1.05 to 1.64) per 5 &micro;g/m(3) increase and PM10 with similar effect size. Sensitivity analyses of older cohorts showed increased risk of chronic cough with PM2.5abs (black carbon) exposures. CONCLUSIONS: Results do not show consistent associations between chronic bronchitis symptoms and current traffic-related air pollution in adult European populations