Mental health in UK Biobank: development, implementation and results from an online questionnaire completed by 157 366 participants

Background UK Biobank is a well-characterised cohort of over 500 000 participants that offers unique opportunities to investigate multiple diseases and risk factors. Aims An online mental health questionnaire completed by UK Biobank participants was expected to expand the potential for research into mental disorders. Method An expert working group designed the questionnaire, using established measures where possible, and consulting with a patient group regarding acceptability. Case definitions were defined using operational criteria for lifetime depression, mania, anxiety disorder, psychotic-like experiences and self-harm, as well as current post-traumatic stress and alcohol use disorders. Results 157 366 completed online questionnaires were available by August 2017. Comparison of self-reported diagnosed mental disorder with a contemporary study shows a similar prevalence, despite respondents being of higher average socioeconomic status than the general population across a range of indicators. Thirty-five per cent (55 750) of participants had at least one defined syndrome, of which lifetime depression was the most common at 24% (37 434). There was extensive comorbidity among the syndromes. Mental disorders were associated with high neuroticism score, adverse life events and long-term illness; addiction and bipolar affective disorder in particular were associated with measures of deprivation. Conclusions The questionnaire represents a very large mental health survey in itself, and the results presented here show high face validity, although caution is needed owing to selection bias. Built into UK Biobank, these data intersect with other health data to offer unparalleled potential for crosscutting biomedical research involving mental health

Mapping genomic and transcriptomic alterations spatially in epithelial cells adjacent to human breast carcinoma.

Almost all genomic studies of breast cancer have focused on well-established tumours because it is technically challenging to study the earliest mutational events occurring in human breast epithelial cells. To address this we created a unique dataset of epithelial samples ductoscopically obtained from ducts leading to breast carcinomas and matched samples from ducts on the opposite side of the nipple. Here, we demonstrate that perturbations in mRNA abundance, with increasing proximity to tumour, cannot be explained by copy number aberrations. Rather, we find a possibility of field cancerization surrounding the primary tumour by constructing a classifier that evaluates where epithelial samples were obtained relative to a tumour (cross-validated micro-averaged AUC = 0.74). We implement a spectral co-clustering algorithm to define biclusters. Relating to over-represented bicluster pathways, we further validate two genes with tissue microarrays and in vitro experiments. We highlight evidence suggesting that bicluster perturbation occurs early in tumour development

Climate-driven tipping-points could lead to sudden, high-intensity parasite outbreaks

Parasitic nematodes represent one of the most pervasive and significant challenges to grazing livestock, and their intensity and distribution are strongly influenced by climate. Parasite levels and species composition have already shifted under climate change, with nematode parasite intensity frequently low in newly colonized areas, but sudden large-scale outbreaks are becoming increasingly common. These outbreaks compromise both food security and animal welfare, yet there is a paucity of predictions on how climate change will influence livestock parasites. This study aims to assess how climate change can affect parasite risk. Using a process-based approach, we determine how changes in temperature-sensitive elements of outbreaks influence parasite dynamics, to explore the potential for climate change to influence livestock helminth infections. We show that changes in temperate-sensitive parameters can result in nonlinear responses in outbreak dynamics, leading to distinct 'tipping-points' in nematode parasite burdens. Through applying two mechanistic models, of varying complexity, our approach demonstrates that these nonlinear responses are robust to the inclusion of a number of realistic processes that are present in livestock systems. Our study demonstrates that small changes in climatic conditions around critical thresholds may result in dramatic changes in parasite burdens

Thoracic Periaortic and Visceral Adipose Tissue and Their Cross-sectional Associations with Measures of Vascular Function

Objective: Perivascular fat may have a local adverse effect on the vasculature. We evaluated whether thoracic periaortic adipose tissue (TAT), a type of perivascular fat, and visceral adipose tissue (VAT) are associated with vascular function. Design and Methods TAT and VAT were quantified in Framingham Heart Study participants using multidetector computed tomography; vascular function was assessed using brachial artery vasodilator function, peripheral arterial tone and arterial tonometry (n= 2735, 48% women, mean age 50 years, mean BMI 27.7 kg/m2). Using multiple linear regression, we examined relations between TAT, VAT, and vascular measures while adjusting for cardiovascular risk factors. Results: Mean TAT and VAT volumes were 13.2 and 1763 cm3. TAT and VAT were associated with multiple vascular function measures after multivariable adjustment. After BMI adjustment, TAT and VAT remained negatively associated with peripheral arterial tone and inverse carotid femoral pulse wave velocity (p0.06). Conclusion: Thoracic periaortic and visceral fat are associated with microvascular function and large artery stiffness after BMI adjustment. These findings support the growing recognition of associations between ectopic fat and vascular function

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio

Amyloid ? influences the relationship between cortical thickness and vascular load.

INTRODUCTION: Cortical thickness has been proposed as a biomarker of Alzheimer's disease (AD)- related neurodegeneration, but the nature of its relationship with amyloid beta (A?) deposition and white matter hyperintensity volume (WMHV) in cognitively normal adults is unclear. METHODS: We investigated the influences of A? status (negative/positive) and WMHV on cortical thickness in 408 cognitively normal adults aged 69.2 to 71.9 years who underwent 18F-Florbetapir positron emission tomography (PET) and structural magnetic resonance imaging (MRI). Two previously defined Alzheimer's disease (AD) cortical signature regions and the major cortical lobes were selected as regions of interest (ROIs) for cortical thickness. RESULTS: Higher WMHV, but not A? status, predicted lower cortical thickness across all participants, in all ROIs. Conversely, when A?-positive participants were considered alone, higher WMHV predicted higher cortical thickness in a temporal AD-signature region. DISCUSSION: WMHV may differentially influence cortical thickness depending on the presence or absence of A?, potentially reflecting different pathological mechanisms

Surgical and medical second trimester abortion in South Africa: A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>A high percentage of abortions performed in South Africa are in the second trimester. However, little research focuses on women's experiences seeking second trimester abortion or the efficacy and safety of these services.</p> <p>The objectives are to document clinical and acceptability outcomes of second trimester medical and surgical abortion as performed at public hospitals in the Western Cape Province.</p> <p>Methods</p> <p>We performed a cross-sectional study of women undergoing abortion at 12.1-20.9 weeks at five hospitals in Western Cape Province, South Africa in 2008. Two hundred and twenty women underwent D&E with misoprostol cervical priming, and 84 underwent induction with misoprostol alone. Information was obtained about the procedure and immediate complications, and women were interviewed after recovery.</p> <p>Results</p> <p>Median gestational age at abortion was earlier for D&E clients compared to induction (16.0 weeks vs. 18.1 weeks, p < 0.001). D&E clients reported shorter intervals between first clinic visit and abortion (median 17 vs. 30 days, p < 0.001). D&E was more effective than induction (99.5% vs. 50.0% of cases completed on-site without unplanned surgical procedure, p < 0.001). Although immediate complications were similar (43.8% D&E vs. 52.4% induction), all three major complications occurred with induction. Early fetal expulsion occurred in 43.3% of D&E cases. While D&E clients reported higher pain levels and emotional discomfort, most women were satisfied with their experience.</p> <p>Conclusions</p> <p>As currently performed in South Africa, second trimester abortions by D&E were more effective than induction procedures, required shorter hospital stay, had fewer major immediate complications and were associated with shorter delays accessing care. Both services can be improved by implementing evidence-based protocols.</p

Predicting Impacts of Climate Change on Fasciola hepatica Risk

Fasciola hepatica (liver fluke) is a physically and economically devastating parasitic trematode whose rise in recent years has been attributed to climate change. Climate has an impact on the free-living stages of the parasite and its intermediate host Lymnaea truncatula, with the interactions between rainfall and temperature having the greatest influence on transmission efficacy. There have been a number of short term climate driven forecasts developed to predict the following season's infection risk, with the Ollerenshaw index being the most widely used. Through the synthesis of a modified Ollerenshaw index with the UKCP09 fine scale climate projection data we have developed long term seasonal risk forecasts up to 2070 at a 25 km square resolution. Additionally UKCIP gridded datasets at 5 km square resolution from 1970-2006 were used to highlight the climate-driven increase to date. The maps show unprecedented levels of future fasciolosis risk in parts of the UK, with risk of serious epidemics in Wales by 2050. The seasonal risk maps demonstrate the possible change in the timing of disease outbreaks due to increased risk from overwintering larvae. Despite an overall long term increase in all regions of the UK, spatio-temporal variation in risk levels is expected. Infection risk will reduce in some areas and fluctuate greatly in others with a predicted decrease in summer infection for parts of the UK due to restricted water availability. This forecast is the first approximation of the potential impacts of climate change on fasciolosis risk in the UK. It can be used as a basis for indicating where active disease surveillance should be targeted and where the development of improved mitigation or adaptation measures is likely to bring the greatest benefits