Automated retinal image quality assessment on the UK Biobank dataset for epidemiological studies

Morphological changes in the retinal vascular network are associated with future risk of many systemic and vascular diseases. However, uncertainty over the presence and nature of some of these associations exists. Analysis of data from large population based studies will help to resolve these uncertainties. The QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) retinal image analysis system allows automated processing of large numbers of retinal images. However, an image quality assessment module is needed to achieve full automation. In this paper, we propose such an algorithm, which uses the segmented vessel map to determine the suitability of retinal images for use in the creation of vessel morphometric data suitable for epidemiological studies. This includes an effective 3-dimensional feature set and support vector machine classification. A random subset of 800 retinal images from UK Biobank (a large prospective study of 500,000 middle aged adults; where 68,151 underwent retinal imaging) was used to examine the performance of the image quality algorithm. The algorithm achieved a sensitivity of 95.33% and a specificity of 91.13% for the detection of inadequate images. The strong performance of this image quality algorithm will make rapid automated analysis of vascular morphometry feasible on the entire UK Biobank dataset (and other large retinal datasets), with minimal operator involvement, and at low cost.

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

Is alcohol consumption related to likelihood of reporting chronic widespread pain in people with stable consumption? : Results from UK Biobank

Acknowledgements This research has been conducted using the UK Biobank resource, and was funded by the University of Aberdeen. The authors have no conflicts of interest to declare.

Reference values for handgrip strength in among healthy young adults

Background: Isometric grip strength, evaluated with a handgrip dynamometer, is a marker of current nutritional status and cardiometabolic risk and future morbidity and mortality. We present reference values for handgrip strength in healthy young Colombian adults (aged 18 to 29 years). Methods: The sample comprised 5.647 (2.330 men and 3.317 women) apparently healthy young university students (mean age, 20.6±2.7 years) attending public and private institutions in the cities of Bogota and Cali (Colombia). Handgrip strength was measured two times with a TKK analogue dynamometer in both hands and the highest value used in the analysis. Sex- and age-specific normative values for handgrip strength were calculated using the LMS method and expressed as tabulated percentiles from 3 to 97 and as smoothed centile curves (P3, P10, P25, P50, P75, P90 and P97). Results: Mean values for right and left handgrip strength were 38.1±8.9 and 35.9±8.6 kg for men, and 25.1±8.7 and 23.3±8.2 kg for women, respectively. Handgrip strength increased with age in both sexes and was significantly higher in men in all age categories. The results were generally more homogeneous amongst men than women. Conclusions: Sex- and age-specific handgrip strength normative values among healthy young Colombian adults are defined. This information may be helpful in future studies of secular trends in handgrip strength and to identify clinically relevant cut points for poor nutritional and elevated cardiometabolic risk in a Latin American population. Evidence of decline in handgrip strength before the end of the third decade is of concern and warrants further investigation

Exome-wide analysis of rare coding variation identifies novel associations with COPD and airflow limitation in MOCS3, IFIT3 and SERPINA12

Funding: British Women’s Heart and Health Study is funded by the Department of Health grant no. 90049 and the British Heart Foundation grant no. PG/09/022. British Regional Heart Study is supported by the British Heart Foundation (grant RG/ 13/16/30528). CB (COPDBEAT) received funding from the Medical Research Council UK (grant no. G0601369), CB (COPDBEAT) and AJW (UKCOPD) were supported by the National Institute for Health Research (NIHR Leicester Biomedical Research Unit). MB (COPDBEAT) received funding from the NIHR (grant no. PDF-2013-06-052). Hertfordshire Cohort Study received support from the Medical Research Council, Arthritis Research UK, the International Osteoporosis Foundation and the British Heart Foundation; NIHR Biomedical Research Centre in Nutrition, University of Southampton; NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. Generation Scotland: Scottish Family Health Study is funded by the Chief Scientist Office, Scottish Government Health Directorates, grant number CZD/16/6 and the Scottish Funding Council grant HR03006. EU COPD Gene Scan is funded by the European Union, grant no. QLG1-CT-2001-01012. English Longitudinal Study of Aging is funded by the Institute of Aging, NIH grant No. AG1764406S1. GoDARTs is funded by the Wellcome Trust grants 072960, 084726 and 104970. MDT has been supported by MRC fellowship G0902313. UK Biobank Lung Exome Variant Evaluation study was funded by a Medical Research Council strategic award to MDT, IPH, DPS and LVW (MC_PC_12010)

Feasibility of MR-Based Body Composition Analysis in Large Scale Population Studies

Introduction Quantitative and accurate measurements of fat and muscle in the body are important for prevention and diagnosis of diseases related to obesity and muscle degeneration. Manually segmenting muscle and fat compartments in MR body-images is laborious and time-consuming, hindering implementation in large cohorts. In the present study, the feasibility and success-rate of a Dixon-based MR scan followed by an intensity-normalised, non-rigid, multi-atlas based segmentation was investigated in a cohort of 3,000 subjects. Materials and Methods 3,000 participants in the in-depth phenotyping arm of the UK Biobank imaging study underwent a comprehensive MR examination. All subjects were scanned using a 1.5 T MR-scanner with the dual-echo Dixon Vibe protocol, covering neck to knees. Subjects were scanned with six slabs in supine position, without localizer. Automated body composition analysis was performed using the AMRA Profiler™ system, to segment and quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (ASAT) and thigh muscles. Technical quality assurance was performed and a standard set of acceptance/rejection criteria was established. Descriptive statistics were calculated for all volume measurements and quality assurance metrics. Results Of the 3,000 subjects, 2,995 (99.83%) were analysable for body fat, 2,828 (94.27%) were analysable when body fat and one thigh was included, and 2,775 (92.50%) were fully analysable for body fat and both thigh muscles. Reasons for not being able to analyse datasets were mainly due to missing slabs in the acquisition, or patient positioned so that large parts of the volume was outside of the field-of-view. Discussion and Conclusions In conclusion, this study showed that the rapid UK Biobank MR-protocol was well tolerated by most subjects and sufficiently robust to achieve very high success-rate for body composition analysis. This research has been conducted using the UK Biobank Resource.

EUELC project : a multi-centre, multipurpose study to investigate early stage NSCLC, and to establish a biobank for ongoing collaboration

The European Early Lung Cancer (EUELC) project aims to determine if specific genetic alterations occurring in lung carcinogenesis are detectable in the respiratory epithelium. In order to pursue this objective, nonsmall cell lung cancer (NSCLC) patients with a very high risk of developing progressive lung cancer were recruited from 12 centres in eight European countries: France, Germany, southern Ireland, Italy, the Netherlands, Poland, Spain and the UK. In addition, NSCLC patients were followed up every 6 months for 36 months. A European Bronchial Tissue Bank was set up at the University of Liverpool (Liverpool, UK) to optimise the use of biological specimens. The molecular - pathological investigations were subdivided into specific work packages that were delivered by EUELC Partners. The work packages encompassed mutational analysis, genetic instability, methylation profiling, expression profiling utilising immunohistochemistry and chip-based technologies, as well as in-depth analysis of FHIT and RARβ genes, the telomerase catalytic subunit hTERT and genotyping of susceptibility genes in specific pathways. The EUELC project engendered a tremendous collaborative effort, and it enabled the EUELC Partners to establish protocols for assessing molecular biomarkers in early lung cancer with the view to using such biomarkers for early diagnosis and as intermediate end-points in future chemopreventive programmes. Copyright©ERS Journals Ltd 2009.

Union strategies in representing ‘new workers’ : the case of UK retail union

The purpose of this paper is to explore the changing nature of employee voice through trade union representation in the retail industry. The retail industry is a major employer in the UK and is one of the few private sector service industries with union representation (Griffin et al 2003). The requisite union: the Distributive and Allied Workers (USDAW) union is one of the biggest unions in the country. However, the characteristics of the industry provide unique challenges for employee voice and representation including: high labour turnover; high use of casual, female and student labour; and, variable levels of union recognition (Reynolds et al 2005). Irrespective of these challenges, any extension of representation and organisation by unions in the retail sector is inherently valuable, socially and politically, given that retail workers are often categorised as vulnerable, due to the fact that they are among the lowest paid in the economy, sourced from disadvantages labour markets and increasingly subject to atypical employment arrangements (Broadbridge 2002; Henley 2006; Lynch 2005; Roan 2003).

The legality of tissue transplants for the benefit of family members in the UK and Australia : implications for saviour siblings

The ethics of creating ‘saviour siblings’ for the benefit of another has received much attention, but little consideration has been given to the legal position of those saviours born who may be asked to provide tissue for transplantation to another during childhood. This article examines the ethical issues surrounding minor donation as well as the existing legal framework in the UK and Australia that regulates minors providing tissue for the benefit of another. Against this background the position of minor saviours, who are called upon to donate bone marrow or peripheral blood stem cells, is examined. This analysis suggests that the law does not provide sufficient protection for minor saviours who are called upon to donate to another. It is argued that specific ethical obligations are owed to saviours—that ought to be reflected in the law—in order to protect them from exploitation while they remain minors.

Union strategies in representing ‘new’ workers : the comparative case of UK and Australian retail unions

This paper is a comparative exploratory study of the changing nature of employee voice through trade union representation in the retail industry in the UK and Australia. In both countries, the retail industry is a major employer and is one of the few private sector service industries with significant union membership (Griffin et al 2003). The relevant unions, the Distributive and Allied Workers Union (USDAW) and the Shop, Distributive and Allied Union (SDA), are the fourth largest and largest unions in the UK and Australia respectively. However, despite this seeming numerical strength in membership, the characteristics of the industry provide unique challenges for employee voice and representation. The significance of the study is that any extension of representation and organisation by unions in the retail sector is valuable socially and politically, given that retail workers are often categorised a s vulnerable, due to their low pay, the predominance of disadvantaged labour market groups such a s women and young people, workers’ atypical employment arrangements and, in the case of the UK, variable levels of union recognition which inhibit representation (Broadbridge 2002; Henley 2006; Lynch 2005; Roan & Diamond 2003; Reynolds et al 2005). In addition, specifically comparative projects have value in that they allow some variables relating to the ‘industry’ to be held constant, thus reducing the range of potential explanations of differences in union strategy. They also have value in that the research partners may be more likely to notice and problematise taken-for-granted aspects of practices in another country, thus bringing to the fore key features and potentially leading to theoretical innovation. Finally, such projects may assist in transnational diffusion of union strategy.