Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

Green Plants in the Red: A Baseline Global Assessment for the IUCN Sampled Red List Index for Plants

Plants provide fundamental support systems for life on Earth and are the basis for all terrestrial ecosystems; a decline in plant diversity will be detrimental to all other groups of organisms including humans. Decline in plant diversity has been hard to quantify, due to the huge numbers of known and yet to be discovered species and the lack of an adequate baseline assessment of extinction risk against which to track changes. The biodiversity of many remote parts of the world remains poorly known, and the rate of new assessments of extinction risk for individual plant species approximates the rate at which new plant species are described. Thus the question ‘How threatened are plants?’ is still very difficult to answer accurately. While completing assessments for each species of plant remains a distant prospect, by assessing a randomly selected sample of species the Sampled Red List Index for Plants gives, for the first time, an accurate view of how threatened plants are across the world. It represents the first key phase of ongoing efforts to monitor the status of the world’s plants. More than 20% of plant species assessed are threatened with extinction, and the habitat with the most threatened species is overwhelmingly tropical rain forest, where the greatest threat to plants is anthropogenic habitat conversion, for arable and livestock agriculture, and harvesting of natural resources. Gymnosperms (e.g. conifers and cycads) are the most threatened group, while a third of plant species included in this study have yet to receive an assessment or are so poorly known that we cannot yet ascertain whether they are threatened or not. This study provides a baseline assessment from which trends in the status of plant biodiversity can be measured and periodically reassessed

Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?

Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value=2.57x10-4) and rs9960767 (p-value=6.23x10-4). Replication in an independent sample of 16-year-olds (N=3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed

Socioeconomic position across the lifecourse & allostatic load: data from the West of Scotland Twenty-07 cohort study

Background: We examined how socioeconomic position (SEP) across the lifecourse (three critical periods, social mobility and accumulated over time) is associated with allostatic load (a measure of cumulative physiological burden). Methods. Data are from the West of Scotland Twenty-07 Study, with respondents aged 35 (n = 740), 55 (n = 817) and 75 (n = 483). SEP measures representing childhood, the transition to adulthood and adulthood SEP were used. Allostatic load was produced by summing nine binary biomarker scores (1 = in the highest-risk quartile). Linear regressions were used for each of the lifecourse models; with model fits compared using partial F-tests. Results: For those aged 35 and 55, higher SEP was associated with lower allostatic load (no association in the 75-year-olds). The accumulation model (more time spent with higher SEP) had the best model fit in those aged 35 (b = -0.50, 95%CI = -0.68, -0.32, P = 0.002) and 55 (b = -0.31, 95%CI = -0.49, -0.12, P < 0.001). However, the relative contributions of each life-stage differed, with adulthood SEP less strongly associated with allostatic load. Conclusions: Long-term, accumulated higher SEP has been shown to be associated with lower allostatic load (less physiological burden). However, the transition to adulthood may represent a particularly sensitive period for SEP to impact on allostatic load. © 2014 Robertson et al.; licensee BioMed Central Ltd

Impacts of selected Ecological Focus Area options in European farmed landscapes on climate regulation and pollination services: a systematic map protocol

Background: This systematic map protocol responds to an urgent policy need to evaluate key environmental benefits of new compulsory greening measures in the European Union’s Common Agricultural Policy (CAP), with the aim of building a policy better linked to environmental performance. The systematic map will focus on Ecological Focus Areas (EFAs), in which larger arable farmers must dedicate 5% of their arable land to ecologically beneficial habitats, landscape features and land uses. The European Commission’s Joint Research Centre has used a software tool called the ‘EFA calculator’ to inform the European Commission about environmental benefits of EFA implementation. However, there are gaps in the EFA calculator’s coverage of ecosystem services, especially ‘global climate regulation’, and an opportunity to use systematic mapping methods to enhance its capture of evidence, in advance of forthcoming CAP reforms. We describe a method for assembling a database of relevant, peer-reviewed research conducted in all agricultural landscapes in Europe and neighbouring countries with similar biogeography, addressing the primary question: what are the impacts of selected EFA features in agricultural land on two policy-relevant ecosystem service outcomes—global climate regulation and pollination? The method is streamlined to allow results in good time for the current, time-limited opportunity to influence reforms of the CAP greening measures at European and Member State level. Methods: We will search four bibliographic databases in English, using a predefined and tested search string that focuses on a subset of EFA options and ecosystem service outcomes. The options and outcomes are selected as those with particular policy relevance and traction. Only articles in English will be included. We will screen search results at title, abstract and full text levels, recording the number of studies deemed non-relevant (with reasons at full text). A systematic map database that displays the meta-data (i.e. descriptive summary information about settings and methods) of relevant studies will be produced following full text assessment. The systematic map database will be published as a MS-Excel database. The nature and extent of the evidence base will be discussed, and the applicability of methods to convert the available evidence into EFA calculator scores will be assessed

Work-family life courses and BMI trajectories in three British birth cohorts.

BACKGROUND/OBJECTIVES: Combining work and family responsibilities has previously been associated with improved health in mid-life, yet little is known about how these associations change over time (both biographical and historical) and whether this extends to body mass index (BMI) trajectories for British men and women. The purpose of this study was to investigate relationships between work-family life courses and BMI trajectories across adulthood (16-42 years) for men and women in three British birth cohorts. SUBJECTS/METHODS: Multiply imputed data from three nationally representative British birth cohorts were used-the MRC National Survey of Health and Development (NSHD; 1946 birth cohort, n=3012), the National Child Development Study (NCDS; 1958 birth cohort, n=9614) and the British Cohort Study (BCS; 1970 birth cohort, n=8140). A typology of work-family life course types was developed using multi-channel sequence analysis, linking annual information on work, partnerships and parenthood from 16 to 42 years. Work-family life courses were related to BMI trajectories using multi-level growth models. Analyses adjusted for indicators of prior health, birthweight, child BMI, educational attainment and socioeconomic position across the life course, and were stratified by gender and cohort. RESULTS: Work-family life courses characterised by earlier transitions to parenthood and weaker long-term links to employment were associated with greater increases in BMI across adulthood. Some of these differences, particularly for work-family groups, which are becoming increasingly non-normative, became more pronounced across cohorts (for example, increases in BMI between 16 and 42 years in long-term homemaking women: NSHD: 4.35 kg m-2, 95% confidence interval (CI): 3.44, 5.26; NCDS: 5.53 kg m-2, 95% CI: 5.18, 5.88; BCS: 6.69 kg m-2, 95% CI: 6.36, 7.02). CONCLUSIONS: Becoming a parent earlier and weaker long-term ties to employment are associated with greater increases in BMI across adulthood in British men and women.Rebecca Lacey, Anne McMunn, Amanda Sacker and Meena Kumari received funding from the European Research Council (grant number: ERC-2011-StG_20101124, PI: Anne McMunn). Steven Bell also received funding from the European Research Council (grant number: ERCStG-2012-309337_Alcohol-Lifecourse, PI: Annie Britton) and UK Medical Research Council/Alcohol Research UK (MR/M006638/1). Amanda Sacker, Anne McMunn and Meena Kumari additionally received support from the Economic and Social Research Council’s International Centre for Life Course Studies in Society and Health (grant number: ES/J019119/1). DK is supported by the UK Medical Research Council (MC_UU_12019/1). The MRC National Survey of Health and Development is funded by the UK Medical Research Council. Peggy McDonough and Diana Worts were supported by the Canadian Institutes of Health Research grant MOP 119526 and the Social Sciences and Humanities Research Council grant 43512-1267

Specific and individuated death reflection fosters identity integration

Identity integration is the process wherein a person assimilates multiple or conflicting identities (e.g., beliefs, values, needs) into a coherent, unified self-concept. Three experiments examined whether contemplating mortality in a specific and individuated manner (i.e., via the death reflection manipulation) facilitated outcomes indicative of identity integration. Participants in the death reflection condition (vs. control conditions) considered positive and negative life experiences as equally important in shaping their current identity (Experiment 1), regarded self-serving values and other-serving values as equally important life principles (Experiment 2), and were equally motivated to pursue growth-oriented and security-oriented needs (Experiment 3). Death reflection motivates individuals to integrate conflicting aspects of their identity into a coherent self-concept. Given that identity integration is associated with higher well-being, the findings have implications for understanding the psychological benefits of existential contemplation

Unlocking the in vivo therapeutic potential of radiation-activated photodynamic therapy for locally advanced rectal cancer with lymph node involvement

Background: Rectal cancer is a leading cause of cancer-related mortality worldwide. The recurrence of locally advanced rectal cancer (LARC), particularly in cases involving lymph node-positive tumours, remains a critical challenge in rectal cancer management. In this study, a therapeutic strategy, radiation-activated photodynamic therapy (RA-PDT), for the treatment of LARC with lymph node-positive tumours was developed and evaluated. Methods: RA-PDT was achieved by using a lipid-polymer hybrid nanoplatform loaded with verteporfin (VP) and functionalised with folic acid (FA) as a targeting molecule. Upon receiving a single 4 Gy fraction of radiation, VP was effectively activated, generating sufficient reactive oxygen species (ROS) to induce cancer cell death–however surrounding tissue was less affected and was spared. The efficacy of this strategy was assessed through in vitro cytotoxicity studies in HCT116 cells, as well as in orthotopic and subcutaneous mouse models. In vivo lymph node tumour progression was also evaluated. Findings: RA-PDT effectively generated ROS following 4 Gy irradiation and exhibited significant cytotoxicity in HCT116 cells. In vivo, this strategy largely inhibited primary tumour growth in both orthotopic and subcutaneous mouse models while also suppressing lymph node tumour progression. Surrounding tissues were minimally affected, highlighting the precision and safety of this approach. Interpretation: RA-PDT demonstrates potential as a safe therapeutic strategy for LARC, paving the way for its clinical translation. Funding: This study was supported by the Australian National Health and Medical Research Council (GNT1181889), fellowship award (2019/CDF1013) from Cancer Institute NSW, Australia, the Australian Research Council Centre of Excellence for Nanoscale Biophotonics (CE140100003), UNSW SHARP funding, project grant from National Foundation for Medical Research and Innovation, Australia, International Research Training Program Scholarship (IRTP) from Australian Government, PhD Research Scholar Award from Sydney Vital Translational Cancer Research, and Translational Cancer Research Network PhD Scholarship Top-up award

Genome-wide association for major depression through age at onset stratification

BACKGROUND: Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. METHODS: Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease. RESULTS: We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11–1.21, p = 5.2 × 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. CONCLUSIONS: We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder

Diversity of Staphylococcus aureus Isolates in European Wildlife

Staphylococcus aureus is a well-known colonizer and cause of infection among animals and it has been described from numerous domestic and wild animal species. The aim of the present study was to investigate the molecular epidemiology of S. aureus in a convenience sample of European wildlife and to review what previously has been observed in the subject field. 124 S. aureus isolates were collected from wildlife in Germany, Austria and Sweden; they were characterized by DNA microarray hybridization and, for isolates with novel hybridization patterns, by multilocus sequence typing (MLST). The isolates were assigned to 29 clonal complexes and singleton sequence types (CC1, CC5, CC6, CC7, CC8, CC9, CC12, CC15, CC22, CC25, CC30, CC49, CC59, CC88, CC97, CC130, CC133, CC398, ST425, CC599, CC692, CC707, ST890, CC1956, ST2425, CC2671, ST2691, CC2767 and ST2963), some of which (ST2425, ST2691, ST2963) were not described previously. Resistance rates in wildlife strains were rather low and mecA-MRSA isolates were rare (n = 6). mecC-MRSA (n = 8) were identified from a fox, a fallow deer, hares and hedgehogs. The common cattle- associated lineages CC479 and CC705 were not detected in wildlife in the present study while, in contrast, a third common cattle lineage, CC97, was found to be common among cervids. No Staphylococcus argenteus or Staphylococcus schweitzeri-like isolates were found. Systematic studies are required to monitor the possible transmission of human- and livestock- associated S. aureus/MRSA to wildlife and vice versa as well as the possible transmission, by unprotected contact to animals. The prevalence of S. aureus/MRSA in wildlife as well as its population structures in different wildlife host species warrants further investigation