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The Global Alliance for Genomics and Health (GA4GH) is developing a suite of coordinated standards for genomics for healthcare. The Phenopacket is a new GA4GH standard for sharing disease and phenotype information that characterizes an individual person or biosample, linking that individual to detailed phenotypic descriptions, genetic information, diagnoses, and treatments. We present a detailed example that illustrates how to use the schema to represent the clinical course of a patient with retinoblastoma, including demographic information, the clinical diagnosis, phenotypic features and clinical measurements, an examination of the extirpated tumor, therapies, and the results of genomic analysis. The Phenopacket Schema, together with other GA4GH data and technical standards, will enable data exchange and provide a foundation for the computational analysis of disease and phenotype information to improve our ability to diagnose and conduct research on all types of disorders, including cancer and rare diseases., The Alan Turing Institute

The purpose of this study was to examine the relationships and connections within the family and the local Christian church community influencing spiritual wellbeing of young people engaged with Christian spirituality. Questions have arisen recently about the role of spiritual wellbeing in strengthening resilience of youth. To explore this association, this research focused on the relationships and connectedness of people who attend one religious organisation as one means of enhancing their spiritual wellbeing. Two separate but complementary theories underpinned this research: the bioecological theory of human development (Bronfenbrenner 2001a) and the international family strengths model (DeFrain & Asay 2007a). In line with the purposes of an instrumental case study, different sources of data (quantitative and qualitative) were collected on the phenomenon of interest‚ÄövÑvÆspiritual wellbeing. Utilising a survey method, a theoretical purposive sample of sixty five people participated in this study. Through an abductive analysis process, the research identified a model of five spiritual strengths that enhance peace and life satisfaction and strengthen youth resilience within the lives of the young people in this study. Spiritual wellbeing and resilience were shown to be interrelated and ecologically bound. This case study presents one possible explanation for the often observed yet poorly understood relationship between spiritual wellbeing and positive youth outcomes, such as resilience. The author recommends measurement of resilience and strategies that aim to strengthen youth resilience should include spiritual wellbeing however, further research is required that considers how best to incorporate spiritual wellbeing into both resilience measures and health promoting strategies. It is also recommended that replica studies with people who belong to other spirituality types, and who may implement differing spiritual practices, are needed to test the proposed model of spiritual strengths and the identified relationship to resilience.

Additional file 1: Fig. S1. Cumulative incidence of first long-term follow-up visit to the orthopaedic department in years since primary surgery. Table S1. Adjusted regression models for revision and mortality.

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Additional file 1. RO DBT: Interview topic guide

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.

Traditional models of future alcohol use in adolescents have used variable-centered approaches, predicting alcohol use from a set of variables across entire samples or populations. Following the proposition that predictive factors may vary in adolescents as a function of family history, we used a two-pronged approach by first defining clusters of familial risk, followed by prediction analyses within each cluster. Thus, for the first time in adolescents, we tested whether adolescents with a family history of drug abuse exhibit a set of predictors different from adolescents without a family history. We apply this approach to a genetic risk score and individual differences in personality, cognition, behavior (risk-taking and discounting) substance use behavior at age 14, life events, and functional brain imaging, to predict scores on the alcohol use disorders identification test (AUDIT) at age 14 and 16 in a sample of adolescents (N = 1659 at baseline, N = 1327 at follow-up) from the IMAGEN cohort, a longitudinal community-based cohort of adolescents. In the absence of familial risk (n = 616), individual differences in baseline drinking, personality measures (extraversion, negative thinking), discounting behaviors, life events, and ventral striatal activation during reward anticipation were significantly associated with future AUDIT scores, while the overall model explained 22% of the variance in future AUDIT. In the presence of familial risk (n = 711), drinking behavior at age 14, personality measures (extraversion, impulsivity), behavioral risk-taking, and life events were significantly associated with future AUDIT scores, explaining 20.1% of the overall variance. Results suggest that individual differences in personality, cognition, life events, brain function, and drinking behavior contribute differentially to the prediction of future alcohol misuse. This approach may inform more individualized preventive interventions.

Additional file 1.

Supplemental material, TPS900596 Supplemental Material for An ethnic-group comparison of caregiver beliefs about early psychotic illness in a UK sample: Implications for evidence-based caregiver interventions by Lindsay M Smith, Juliana Onwumere, Tom KJ Craig and Elizabeth Kuipers: on behalf of the eGFR-C Study Group in Transcultural Psychiatry

Suppose we are given a video of a rotating object and suppose we want to determine the rate of rotation solely from the video itself and its known frame rate. In this thesis, we present a new mathematical operator called the Geometric Sum Transform (GST) that can help one determine the angular frequency of the object in question. The GST is a generalization of the discrete Fourier transform (DFT) and as such, the two transforms have much in common. However, whereas the DFT is applied to a sequence of scalars, the GST can be applied to a sequence of vectors. Most importantly, we show that the GST, like the DFT, can (1) be used to estimate frequency and (2) can be computed surprisingly quickly. Indeed, we provide a Fast Geometric Sum Transform (FGST) algorithm that computes the GST in O(N logN) matrix-vector multiplications, where N is the number of images in the video sequence. This is a vast improvement over the O(N2) such multiplications required for a direct computation of the GST. The remainder of this thesis is devoted to proving other properties of the GST and giving proof-of-concept numerical examples.

BACKGROUND: Chronic heart failure, a common cause of morbidity and mortality, is frequently associated with sleep-disordered breathing, which may be detrimental through a variety of haemodynamic, autonomic and vascular mechanisms. Whilst associated with increased morbidity and mortality, sleep-disordered breathing is often unrecognised and yet presents a potential therapeutic target in patients with chronic heart failure. OBJECTIVES: The aims of the thesis were, in patients with stable symptomatic chronic heart failure treated with optimal contemporary heart failure therapy: first, to determine prospectively the prevalence of sleep-disordered breathing; second, to compare the clinical characteristics of those patients with sleep-disordered breathing to those without sleep-disordered breathing; third, to assess the accuracy and clinical utility of a limited sleep study system, compared with polysomnography, for diagnosing sleep-disordered breathing; and finally, fourth, to establish whether treatment of obstructive sleep apnoea with nocturnal continuous positive airway pressure improves subjective and objective measures ofheart failure severity. METHODS: Patients with stable symptomatic chronic heart failure were screened for sleep-disordered breathing by home sleep study. Daytime sleepiness was assessed by Epworth Sleepiness Scale and heart failure severity by symptom class, left ventricular ejection fraction and serum N-terminal pro-brain natriuretic peptide concentrations. In a subset ofpatients, synchronous in-laboratory limited sleep studies and polysomonography, and home limited sleep studies, were performed prospectively. Patients with obstructive sleep apnoea and stable symptomatic chronic heart failure were randomised to nocturnal auto-titrating continuous positive airway pressure or sham for six weeks each in crossover design. Study co-primary endpoints were changes in peak VO2 and six minute walk distance and secondary endpoints changes in left ventricular ejection fraction, VE/VCO2 slope, neurohormonal markers and quality of life RESULTS: In the era of modern therapy, sleep-disordered breathing is common in patients with stable symptomatic chronic heart failure, predominantly obstructive in aetiology, without clear relationship to heart failure severity and is difficult to diagnose because ofmajor overlap in symptomatology. Limited sleep studies compare well diagnostically to polysomnography when tested under identical patient and environmental conditions but less so when tested in the home setting. Auto-titrating continuous positive airway pressure improves daytime sleepiness in patients with obstructive sleep apnoea and chronic heart failure but not other subjective or objective measures of heart failure severity. CONCLUSIONS: Sleep-disordered breathing is difficult to detect clinically in patients with chronic heart failure, and as such, the diagnosis is reliant on accurate sleep studies. However, the clinical utility of limited sleep studies in detection and diagnosis of sleep-disordered breathing is restricted by a number of technical and situational factors which are exacerbated in patients with chronic heart failure. The potential therapeutic benefits of continuous positive airway pressure in patients with obstructive sleep apnoea and chronic heart failure are achieved by alleviation of obstructive sleep apnoea rather than by improvement in cardiac function; however, efficacy of continuous positive airway pressure therapy may in part be limited by poor patient tolerability and compliance.