Genetic impacts on DNA methylation help elucidate regulatory genomic processes.

BACKGROUND: Pinpointing genetic impacts on DNA methylation can improve our understanding of pathways that underlie gene regulation and disease risk. RESULTS: We report heritability and methylation quantitative trait locus (meQTL) analysis at 724,499 CpGs profiled with the Illumina Infinium MethylationEPIC array in 2358 blood samples from three UK cohorts. Methylation levels at 34.2% of CpGs are affected by SNPs, and 98% of effects are cis-acting or within 1 Mbp of the tested CpG. Our results are consistent with meQTL analyses based on the former Illumina Infinium HumanMethylation450 array. Both SNPs and CpGs with meQTLs are overrepresented in enhancers, which have improved coverage on this platform compared to previous approaches. Co-localisation analyses across genetic effects on DNA methylation and 56 human traits identify 1520 co-localisations across 1325 unique CpGs and 34 phenotypes, including in disease-relevant genes, such as USP1 and DOCK7 (total cholesterol levels), and ICOSLG (inflammatory bowel disease). Enrichment analysis of meQTLs and integration with expression QTLs give insights into mechanisms underlying cis-meQTLs (e.g. through disruption of transcription factor binding sites for CTCF and SMC3) and trans-meQTLs (e.g. through regulating the expression of ACD and SENP7 which can modulate DNA methylation at distal sites). CONCLUSIONS: Our findings improve the characterisation of the mechanisms underlying DNA methylation variability and are informative for prioritisation of GWAS variants for functional follow-ups. The MeQTL EPIC Database and viewer are available online at https://epicmeqtl.kcl.ac.uk .

Adult retrospective report of child abuse and prospective indicators of childhood harm: a population birth cohort study.

BACKGROUND: We aim to determine whether adult retrospective report of child abuse is associated with greater risk of prospectively assessed harmful environments in childhood. We assessed possible recall basis by adult depression status. METHODS: At 45 years, participants of the 1958 British birth cohort (N = 9308) reported a range of abuse types (by 16 years). Prospective data, ages 7-16 years, were obtained for impoverished upbringing, hazardous conditions, anti-social behaviours and 16 years poor parent-child relationships. We estimated associations between retrospective report of child abuse and prospectively measured harm using (i) odds ratios (ORs, 95% confidence intervals) and (ii) positive predictive values (PPVs). PPVs were calculated stratified by adult depression status. RESULTS: Prevalence of retrospectively reported abuse ranged from 10.7% (psychological) to 1.60% (sexual) and 14.8% reported ≥ 1 type; prospectively recorded harm ranged from 10% (hazardous conditions/poor parent-child relationships) to 20% (anti-social behaviours). Adults retrospectively reporting abuse were more likely to have had harmful childhood environments: 52.4% had ≥ 1 indicator of harm (vs. 35.6% among others); ORsex-adjusted for poor relationships with parents was 2.98 (2.50, 3.54). For retrospectively reported (vs. none) abuse, there was a trend of increasing relative risk ratio with number of harms, from 1.75 (1.50, 2.03) for 1 to 4.68 (3.39, 6.45) for 3/4 childhood harms. The PPV of ≥ 1 prospectively recorded harm did not differ between depressed (0.58 (0.52, 0.64)) and non-depressed (0.58 (0.55, 0.61)) groups. CONCLUSIONS: In a population cohort, adult retrospective report of child abuse was associated with several harms, prospectively measured from childhood to adolescence, providing support for the validity of retrospective report-based research. Findings suggest retrospectively reported child abuse is not biased by depression in adulthood.

Child maltreatment, early life socioeconomic disadvantage and all-cause mortality in mid-adulthood: findings from a prospective British birth cohort.

OBJECTIVES: Early-life adversities (ELAs) such as child maltreatment (neglect and abuse) and socioeconomic disadvantage have been associated with adult mortality. However, evidence is sparse for specific types of ELA. We aimed to establish whether specific ELAs (ie, different types of child maltreatment and socioeconomic disadvantage) were associated independently with all-cause mortality in mid-adulthood and to examine potential intermediary pathways. DESIGN: Prospective cohort study. SETTING: 1958 British birth cohort: a longitudinal, population-based sample of individuals born in Great Britain during a single week in March 1958. PARTICIPANTS: 9310 males and females with data on child maltreatment and mortality (44/45-58 years). OUTCOME MEASURES: Mortality follow-up from 2002/2003 to 2016 when participants were aged 44/45-58 years. Death was ascertained via the NHS Central Register (N=296) or cohort maintenance activities (N=16). RESULTS: Prevalence of ELAs ranged from 1.6% (sexual abuse) to 11% (psychological abuse). Several, but not all, ELAs were associated with increased risk of premature death, independent of covariates and other adversities; adjusted HRs were 2.64 (95% CI 1.52 to 4.59) for sexual abuse, 1.93 (95% CI 1.45 to 2.58) for socioeconomic disadvantage, 1.73 (95% CI 1.11 to 2.71) for physical abuse and 1.43 (95% CI 1.03 to 1.98) for neglect. After adjustment for covariates and other adversities, no associations with mortality were observed for psychological and witnessing abuse. Regarding potential intermediaries (including adult socioeconomic factors, behaviours, adiposity, mental health and cardiometabolic markers), most associations attenuated after accounting for adult health behaviours (particularly smoking). In addition, early-life socioeconomic disadvantage and neglect associations attenuated after accounting for adult socioeconomic factors. The association for sexual abuse and premature mortality was largely unaffected by potential intermediaries. CONCLUSIONS: Associations with premature mortality varied by type of ELA: associations for sexual and physical abuse, neglect and socioeconomic disadvantage were independent of each other. Different types of ELAs could influence premature mortality via different pathways; this requires further research.

A Bidirectional Mendelian Randomization Study to evaluate the causal role of reduced blood vitamin D levels with type 2 diabetes risk in South Asians and Europeans.

CONTEXT: Multiple observational studies have reported an inverse relationship between 25-hydroxyvitamin D concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results of short- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been inconsistent. OBJECTIVES AND METHODS: To evaluate the causal role of reduced blood 25(OH)D in T2D, here we have performed a bidirectional Mendelian randomization study using 59,890 individuals (5,862 T2D cases and 54,028 controls) from European and Asian Indian ancestries. We used six known SNPs, including three T2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluate the causality and direction of the association between T2D and circulating 25(OH)D concentration. RESULTS: Results of the combined meta-analysis of eight participating studies showed that a composite score of three T2D SNPs would significantly increase T2D risk by an odds ratio (OR) of 1.24, p = 1.82 × 10-32; Z score 11.86, which, however, had no significant association with 25(OH)D status (Beta -0.02nmol/L ± SE 0.01nmol/L; p = 0.83; Z score -0.21). Likewise, the genetically instrumented composite score of 25(OH)D lowering alleles significantly decreased 25(OH)D concentrations (-2.1nmol/L ± SE 0.1nmol/L, p = 7.92 × 10-78; Z score -18.68) but was not associated with increased risk for T2D (OR 1.00, p = 0.12; Z score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as an individual genetic instrument, a per allele reduction of 25(OH)D concentration (-4.2nmol/L ± SE 0.3nmol/L) was predicted to increase T2D risk by 5%, p = 0.004; Z score 2.84. This effect, however, was not seen in other 25(OH)D SNPs (GC rs2282679, CYP2R1 rs12794714) when used as an individual instrument. CONCLUSION: Our new data on this bidirectional Mendelian randomization study suggests that genetically instrumented T2D risk does not cause changes in 25(OH)D levels. However, genetically regulated 25(OH)D deficiency due to vitamin D synthesis gene (DHCR7) may influence the risk of T2D.

A cross-country qualitative study on contraceptive method mix: contraceptive decisionmaking among youth.

BACKGROUND: Youth ages 15 to 24, who comprise a large portion of sub-Saharan Africa, face a higher burden of unmet contraceptive need than adults. Despite increased international and national commitments to improving young people's access to contraception, significant barriers impede their access to a full range of methods. To further explore these barriers among youth in Kenya, Nigeria, and Uganda, we conducted a qualitative study to capture the challenges that affect contraceptive method decisionmaking and complicate youth access to the full method mix. METHODS: To understand factors that impact young people's contraceptive decisionmaking process across all three countries, we conducted a total of 35 focus group discussions with 171 youth ages 15 to 24 and 130 in-depth interviews with key stakeholders working in youth family planning. Questionnaires aligned with the High Impact Practices in Family Planning's elements of adolescent-friendly contraceptive services. Data were coded with MAXQDA and analyzed using a framework for contraceptive decisionmaking to identify relevant patterns and themes. RESULTS: In all three countries, youth reported that condoms are the most commonly sought contraceptive method because they are easiest to access and because youth have limited knowledge of other methods. Youth from diverse settings shared uncertainty and concern about the safety and side effects of many methods other than condoms, complicating their ability to take full advantage of other available methods. While most youth in Kenya, Nigeria, and Uganda reported at least moderate confidence in obtaining the information needed to help choose a method, and only a few youth reported that they are completely unable to access contraceptives, other barriers still present a major deterrent for youth, including cost, inconvenient facility hours and long wait times, and stigma from family, community members, and providers. CONCLUSIONS: Young people's ability to fully exercise their method choice remains limited despite availability of services, leading them to take the path of least resistance. Program implementers and policymakers should consider the diverse and often interconnected barriers that youth face in attempting to enjoy the benefits of a full spectrum of contraceptive methods and design multi-level interventions to mitigate such barriers.

Despite increased international and national commitments to improving young people's access to contraception, youth ages 15 to 24 face significant barriers to accessing a full range of contraceptive methods. This study conducted in-depth interviews with key stakeholders and focus group discussions with youth in Kenya, Nigeria, and Uganda to understand what factors impact youth's decision to use or not use certain contraceptive methods. In all three countries, youth reported that condoms are the most commonly sought contraceptive method because they are easiest to access and because youth have limited knowledge of other methods. Youth from diverse settings shared uncertainty and concern about the safety and side effects of many methods other than condoms. While most youth in Kenya, Nigeria, and Uganda reported at least moderate confidence in obtaining the information needed to help choose a method, other barriers like cost, inconvenient facility hours and long wait times, and stigma from family, community members, and providers still present a major deterrent for youth who want information on contraceptive methods. Program implementers and policymakers should consider the diverse and often interconnected barriers that youth face in attempting to enjoy the benefits of a full spectrum of contraceptive methods and design multi-level interventions to mitigate such barriers.

Evasins: Tick Salivary Proteins that Inhibit Mammalian Chemokines.

Ticks are hematophagous arachnids that parasitize mammals and other hosts, feeding on their blood. Ticks secrete numerous salivary factors that enhance host blood flow or suppress the host inflammatory response. The recruitment of leukocytes, a hallmark of inflammation, is regulated by chemokines, which activate chemokine receptors on the leukocytes. Ticks target this process by secreting glycoproteins called Evasins, which bind to chemokines and prevent leukocyte recruitment. This review describes the recent discovery of numerous Evasins produced by ticks, their classification into two structural and functional classes, and the efficacy of Evasins in animal models of inflammatory diseases. The review also proposes a standard nomenclature system for Evasins and discusses the potential of repurposing or engineering Evasins as therapeutic anti-inflammatory agents.

Exploring the links between unhealthy eating behaviour and heavy alcohol use in the social, emotional and cultural lives of young adults (aged 18-25): A qualitative research study.

Alcohol use peaks in early adulthood and can contribute both directly and indirectly to unhealthy weight gain. This is the first qualitative study to explore the links between unhealthy eating behaviour and heavy alcohol use in the social, emotional and cultural lives of young adults. We conducted 45 in-depth interviews with 18-25-year-olds in North-East England to inform development of a dual-focused intervention to reduce health risk due to excess weight gain and alcohol use. Data were analysed thematically, following the principles of constant comparison, resulting in three intersecting themes: (1) how food and alcohol consumption currently link together for this population group; (2) influences upon linked eating and drinking behaviours and (3) young adults' feelings and concerns about linked eating and drinking behaviours. Socio-cultural, physical and emotional links between food and alcohol consumption were an unquestioned norm among young adults. Eating patterns linked to alcohol use were not tied only to hunger, but also to sociability, traditions and identity. Young adults conceptualised and calculated risks to weight, appearance and social status, rather than to long-term health. This study is the first to evidence the deeply interconnected nature of food and alcohol consumption for many young adults. Findings have important implications for intervention development, UK public health policy and practice, and point to a need for similar research in other countries.

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9.

BACKGROUND: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. RESULTS: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer's disease - outcomes for which large-scale trial data were unavailable. CONCLUSIONS: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate.

David vs. Goliath: The Structure, Function, and Clinical Prospects of Antibody Fragments.

Since the licensing of the first monoclonal antibody therapy in 1986, monoclonal antibodies have become the largest class of biopharmaceuticals with over 80 antibodies currently approved for a variety of disease indications. The development of smaller, antigen binding antibody fragments, derived from conventional antibodies or produced recombinantly, has been growing at a fast pace. Antibody fragments can be used on their own or linked to other molecules to generate numerous possibilities for bispecific, multi-specific, multimeric, or multifunctional molecules, and to achieve a variety of biological effects. They offer several advantages over full-length monoclonal antibodies, particularly a lower cost of goods, and because of their small size they can penetrate tissues, access challenging epitopes, and have potentially reduced immunogenicity. In this review, we will discuss the structure, production, and mechanism of action of EMA/FDA-approved fragments and of those in clinical and pre-clinical development. We will also discuss current topics of interest surrounding the potential use of antibody fragments for intracellular targeting and blood-brain barrier (BBB) penetration.

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.

The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

Midlife reversibility of early-established biobehavioral risk factors: A research agenda.

Epidemiological evidence links exposure to early life adversities-such as childhood maltreatment-with impaired health and well-being in adulthood. Since these effects are usually unrecognized or untreated in childhood, preventive and remediating interventions in adults are needed. Our focus on adulthood prompted three major questions. First, does our increased understanding of mechanisms accounting for the long-term effects of early life adversities help delineate underlying dimensions that underscore key similarities and differences among these adversities? Second, can adults accurately report on adversities they experienced in childhood? Third, can we identify malleable risk processes in adulthood that might be targets for preventive intervention? Supported by the National Institute on Aging, the U.K. Economic and Social and the Biotechnology and Biological Sciences Research Councils, a network of researchers in human and animal development addressed these questions through meetings and literature review. A small number of dimensions may adequately distinguish among a range of co-occurring childhood adversities. Widely used adult ascertainments of childhood adversity are poorly related to prospective ascertainment. Strategies for preventive interventions should be aimed both at adults who were actually exposed to adversity as well as those who recall adversity, but the targeted risk processes may be different. Now is an opportune time to support research on adult interventions based on unfolding research on critical periods of sensitivity to adversity in fetal and child development, on improved understanding of risk mechanisms that may persist across the life span, and on new insights on enhancing neuroplasticity in adults. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Active Learning on Center Stage: Theater as a Tool for Medical Education.

Introduction: Knowledge and skill development related to communication must incorporate both affective and behavioral components, which are often difficult to deliver in a learning activity. Using theater techniques and principles can provide medical educators with tools to teach communication concepts. Methods: This 75-minute faculty development workshop presents a variety of techniques from theater and adapts them for use in medical education. Using examples related to diversity and inclusion, this session addresses general educational and theater principles, role-play, sociodrama, applied improvisation, and practical aspects of involving theater partners. The session materials include a PowerPoint presentation with facilitator notes, interactive activities to demonstrate each modality, and an evaluation. The sessions can be extended to longer formats as needed. Results: Forty-five participants at Learn Serve Lead 2016: The AAMC Annual Meeting attended the 75-minute session. We emailed 32 participants 5 months after the conference, and eight responded. Participants reported that their confidence level in using theater techniques as a tool for medical education increased from low-to-medium confidence presession to high confidence postsession. All survey respondents who were actively teaching said they had made changes to their teaching based on the workshop. All commented that they appreciated the active learning in the session. Many indicated they would appreciate video or other follow-up resources. Discussion: Principles and techniques from theater are effective tools to convey difficult-to-teach concepts related to communication. This workshop presents tools to implement activities in teaching these difficult concepts.

Childhood maltreatment and biomarkers for cardiometabolic disease in mid-adulthood in a prospective British birth cohort: associations and potential explanations.

OBJECTIVES: Research on associations between childhood maltreatment and adult cardiometabolic disease risk is sparse. We aimed to investigate associations between different forms of child maltreatment and mid-adult cardiometabolic markers and whether potential intermediaries could account for the associations observed. SETTING: 1958 British birth cohort. PARTICIPANTS: Approximately 9000 cohort members with data on cardiometabolic markers. OUTCOMES: Adult (45y) cardiometabolic markers (blood pressure, lipids and glycated haemoglobin [HbA1c]). RESULTS: Seventeen per cent of participants were identified as neglected; 6.1%, 1.6% and 10.0% were identified as experiencing physical, sexual and psychological abuse, respectively. Childhood neglect and physical abuse were associated with high body mass index (BMI) and large waist circumference when adjusting for early-life covariates. For neglect, the adjusted odds ratio (AOR) was 1.16 (95% CI: 1.02 to 1.32) and 1.15 (1.02 to 1.30) for general and central obesity, respectively, and for physical abuse, the respective AOR was 1.36 (1.13 to 1.64) and 1.38 (1.16 to 1.65). Neglect was also associated with raised triglycerides by 3.9 (0.3 to 7.5)% and HbA1c by 1.2 (0.4 to 2.0)%, and among females, lower high-density lipoprotein cholesterol (HDL-c) by 0.05 (0.01 to 0.08)mmol/L after adjustment. For physical abuse, the AOR was 1.25 (1.00 to 1.56) for high low-density lipoprotein cholesterol, HbA1c was raised by 2.5 (0.7 to 4.3)% (in males) and HDL-c was lower by 0.06 (0.01 to 0.12)mmol/L (in females). Associations for sexual abuse were similar to those for physical abuse but 95% CIs were wide. For psychological abuse, the AOR for elevated triglycerides was 1.21 (1.02 to 1.44) and HDL-c was lower by 0.04 (0.01 to 0.07)mmol/L. Maltreatments were not associated with raised blood pressure. In analyses of potential intermediary factors, several associations attenuated after adjustment for adult lifestyles (mainly smoking and alcohol consumption rather than physical activity) and child-to-adult BMI. CONCLUSIONS: Childhood maltreatments, particularly neglect and physical abuse, were associated with greater adiposity and poorer lipid and HbA1c profiles decades later in adulthood. Associations were modest but independent of early-life factors linked to these outcomes. Findings implicate adult lifestyles as an important intermediary between child maltreatment and outcomes.

Non-Pharmacological Interventions to Reduce Unhealthy Eating and Risky Drinking in Young Adults Aged 18⁻25 Years: A Systematic Review and Meta-Analysis.

Alcohol use peaks in early adulthood and can contribute both directly and indirectly to unhealthy weight gain. This review aimed to systematically evaluate the effectiveness of preventative targeted interventions focused on reducing unhealthy eating behavior and linked alcohol use in 18⁻25-year-olds. Twelve electronic databases were searched from inception to June 2018 for trials or experimental studies, of any duration or follow-up. Eight studies (seven with student populations) met the inclusion criteria. Pooled estimates demonstrated inconclusive evidence that receiving an intervention resulted in changes to self-reported fruit and vegetable consumption (mean change/daily servings: 0.33; 95% CI -0.22 to 0.87) and alcohol consumption (mean reduction of 0.6 units/week; CI -1.35 to 0.19). There was also little difference in the number of binge drinking episodes per week between intervention and control groups (-0.01 sessions; CI -0.07 to 0.04). This review identified only a small number of relevant studies. Importantly, included studies did not assess whether (and how) unhealthy eating behaviors and alcohol use link together. Further exploratory work is needed to inform the development of appropriate interventions, with outcome measures that have the capacity to link food and alcohol consumption, in order to establish behavior change in this population group.

Assessing the function of pneumococcal neuraminidases NanA, NanB and NanC in in vitro and in vivo lung infection models using monoclonal antibodies.

Streptococcus pneumoniae isolates express up to three neuraminidases (sialidases), NanA, NanB and NanC, all of which cleave the terminal sialic acid of glycan-structures that decorate host cell surfaces. Most research has focused on the role of NanA with limited investigations evaluating the roles of all three neuraminidases in host-pathogen interactions. We generated two highly potent monoclonal antibodies (mAbs), one that blocks the enzymatic activity of NanA and one cross-neutralizing NanB and NanC. Total neuraminidase activity of clinical S. pneumoniae isolates could be inhibited by this mAb combination in enzymatic assays. To detect desialylation of cell surfaces by pneumococcal neuraminidases, primary human tracheal/bronchial mucocilial epithelial tissues were infected with S. pneumoniae and stained with peanut lectin. Simultaneous targeting of the neuraminidases was required to prevent desialylation, suggesting that inhibition of NanA alone is not sufficient to preserve terminal lung glycans. Importantly, we also found that all three neuraminidases increased the interaction of S. pneumoniae with human airway epithelial cells. Lectin-staining of lung tissues of mice pre-treated with mAbs before intranasal challenge with S. pneumoniae confirmed that both anti-NanA and anti-NanBC mAbs were required to effectively block desialylation of the respiratory epithelium in vivo. Despite this, no effect on survival, reduction in pulmonary bacterial load, or significant changes in cytokine responses were observed. This suggests that neuraminidases have no pivotal role in this murine pneumonia model that is induced by high bacterial challenge inocula and does not progress from colonization as it happens in the human host.

Examining Associations between Body Mass Index in 18⁻25 Year-Olds and Energy Intake from Alcohol: Findings from the Health Survey for England and the Scottish Health Survey.

Evidence on the relationship between alcohol consumption and body mass index (BMI) is mixed, particularly for young adults. This study explored the relationship between energy obtained from alcoholic beverages and BMI using data for 18⁻25 year-olds (n = 7691) from pooled cross-sections of the 2008⁻2014 Health Survey for England and the Scottish Health Survey. Energy obtained from alcoholic beverages (excluding mixers) on the heaviest drinking day in the past week was expressed as percentage of total recommended dietary allowance (RDA) of energy (% RDA Energy). Linear regressions were estimated of BMI on alcohol intake categories controlling for intake frequency, physical activity, longstanding illness and other covariates, with separate analyses for men and women, and by beverage type. Significant associations with BMI were observed with the 'Very High' category of alcohol intake (>75% RDA Energy) for men (p < 0.001, 1.74, 95% confidence interval (CI) 0.98, 2.49) and with the "High" (>50% to 75% RDA Energy) (p < 0.001, 1.67, 95% CI 0.26, 2.58) and above category for women, when compared with the Low (>0⁻25% RDA Energy) category. Young adults drinking the highest levels of alcohol on a single occasion were more likely to be obese than those with the lowest intake. Interventions to address internationally rising youth obesity rates should also consider reducing alcohol consumption by increasing alcohol prices, and reducing availability and marketing exposure.

Obesity and depressive symptoms in mid-life: a population-based cohort study.

BACKGROUND: Obesity and depression are both highly prevalent public health disorders and evidence on their relationship is inconsistent. This study examined whether depressive symptoms are associated with current obesity, and further, whether obesity in turn is associated with an increased odds of depressive symptoms five years later after accounting for potential lifestyle confounders and depressive symptoms at baseline. METHODS: Data were obtained from the 1958 British birth cohort (N = 9217 for cross-sectional and 7340 for prospective analysis). Clinical Interview Schedule-Revised and Mental Health Inventory-5 were used for screening depressive symptoms at ages 45 and 50 years, respectively. General and central obesity were defined using measurements of body mass index (BMI) and waist circumference (WC) at 45 years, respectively. RESULTS: There was a cross-sectional association between depressive symptoms and obesity: participants with ≥2 depressive symptoms had 31% (95%CI 11% to 55%) higher odds of general and 26% higher odds of central obesity (95%CI 8% to 47%). In prospective analyses, both general and central obesity were associated with higher odds of depressive symptoms five years later among women but not in men (Pinteraction < 0.01). After adjustment for depressive symptoms at baseline, sociodemographic and lifestyle factors, women with general obesity had 38% (95% CI 7% to 77%) and women with central obesity 34% (95%CI 9% to 65%) higher odds of depression compared to others. CONCLUSIONS: Depressive symptoms are associated with concurrent obesity and related lifestyle factors among women and men in mid-life. Our study suggests that obesity in turn affects long-term risk of depressive symptoms in women but not in men, independently of concurrent associations, providing an important target group for the implementation of preventative strategies.

Advancing Professional Development Through a Community of Practice: the New England Network for Faculty Affairs.

INTRODUCTION: In an era of competing priorities, funding is increasingly restricted for offices of faculty affairs and development. Opportunities for professional staff to grow and network through attendance at national meetings and to share best practices are limited. We sought to describe a community of practice established to enhance the professional development of faculty affairs professionals and to document its impact. METHODS: We outlined the process of formation of the New England Network for Faculty Affairs (NENFA), reviewed the pedagogical approaches to professional development, and surveyed members to evaluate the impact of NENFA on their activities, professional network and their institutions. RESULTS: After a successful 2011 initial meeting, NENFA created an organizing committee and conducted a needs assessment among potential members. NENFA's charter, mission, goals, and structure were based on survey results. NENFA's regional community of practice grew to 31 institutions and held 10 meetings over 5 years. Meetings have examined a faculty development topic in depth using multiple learning formats to engage participants from academic medical centers and allied professions. Results from a 2015 member survey confirmed the value of NENFA. Multiple members documented changes in practice as a result of participating. DISCUSSION: NENFA has been sustained by volunteer leadership, collaboration, and the value that the group has brought to its members. We propose that a "community of practice" offers an effective model for collaborative learning among individuals at different institutions within a competitive health care environment. We recommend that the approach be replicated in other regions.

Child maltreatment as a predictor of adult physical functioning in a prospective British birth cohort.

OBJECTIVE: Child maltreatment (abuse and neglect) has established associations with mental health; however, little is known about its relationship with physical functioning. Physical functioning (ie, the ability to perform the physical tasks of daily living) in adulthood is an important outcome to consider, as it is strongly associated with an individual's ability to work, and future disability and dependency. We aimed to establish whether maltreatment was associated with physical functioning, independent of other early-life factors. SETTING: 1958 British birth cohort. PARTICIPANTS: 8150 males and females with data on abuse and who participated at age 50 years. OUTCOME MEASURES: The primary outcome was poor physical functioning at 50 years (<65 on the Short-Form 36 survey physical functioning subscale). Secondary outcomes included mental health and self-reported health at 50 years. RESULTS: 23% of participants reported at least one type of maltreatment; 12% were identified with poor physical functioning. Neglect (ORadj 1.55, 95% CI 1.24 to 1.93), psychological abuse (ORadj 1.49, 1.17-1.88) and sexual abuse (ORadj 2.56, 1.66-3.96) were associated with poor physical functioning independent of other maltreatments and covariates, including childhood social class, birth weight and childhood illness. Odds of poor physical functioning increased with multiple types of maltreatment (ptrend <0.001); ORadj ranged from 1.49 (1.23-1.82) for a single type to 2.09 (1.53-2.87) for those reporting > 3 types of maltreatment, compared with those with none. Associations of similar magnitude were observed for mental and self-reported health outcomes. CONCLUSIONS: Child neglect, psychological and sexual abuse were associated with poor physical functioning at 50 years, with accumulating risk for those with multiple types of maltreatment. Associations were independent of numerous early-life factors and were comparable in magnitude to those observed for mental health and self-rated health. Prevention or alleviation of the ill effects of maltreatment could be an effective policy intervention to promote healthy ageing.

Non-pharmacological interventions designed to reduce health risks due to unhealthy eating behaviour and linked risky or excessive drinking in adults aged 18-25 years: a systematic review protocol.

BACKGROUND: Excess body weight and heavy alcohol consumption are two of the greatest contributors to global disease. Alcohol use peaks in early adulthood. Alcohol consumption can also exacerbate weight gain. A high body mass index and heavy drinking are independently associated with liver disease but, in combination, they produce an intensified risk of damage, with individuals from lower socio-economic status groups disproportionately affected. METHODS: We will conduct searches in MEDLINE, Embase, PubMed, PsycINFO, ERIC, ASSIA, Web of Knowledge (WoK), Scopus, CINAHL via EBSCO, LILACS, CENTRAL and ProQuest Dissertations and Theses for studies that assess targeted preventative interventions of any length of time or duration of follow-up that are focused on reducing unhealthy eating behaviour and linked risky alcohol use in 18-25-year-olds. Primary outcomes will be reported changes in: (1) dietary, nutritional or energy intake and (2) alcohol consumption. We will include all randomised controlled trials (RCTs) including cluster RCTs; randomised trials; non-randomised controlled trials; interrupted time series; quasi-experimental; cohort involving concurrent or historical controls and controlled before and after studies. Database searches will be supplemented with searches of Google Scholar, hand searches of key journals and backward and forward citation searches of reference lists of identified papers. Search records will be independently screened by two researchers, with full-text copies of potentially relevant papers retrieved for in-depth review against the inclusion criteria. Methodological quality of RCTs will be evaluated using the Cochrane risk of bias tool. Other study designs will be evaluated using the Cochrane Public Health Review Group's recommended Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Studies will be pooled by meta-analysis and/or narrative synthesis as appropriate for the nature of the data retrieved. DISCUSSION: It is anticipated that exploration of intervention effectiveness and characteristics (including theory base, behaviour change technique; modality, delivery agent(s) and training of intervention deliverers, including their professional status; and frequency/duration of exposure) will aid subsequent co-design and piloting of a future intervention to help reduce health risk and social inequalities due to excess weight gain and alcohol consumption. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016040128 .