What determines spatiotemporal variations in cold-weather-related mortality in England?

Ph. D ThesisMortality rates in England are higher during the winter period (December-March) compared to other seasons. Most excess winter deaths are caused by respiratory and circulatory conditions, which are exacerbated by cold temperatures. Excess winter mortality rates vary between areas and years. This research investigated spatial and spatiotemporal variations in excess mortality across small areas of England in relation to winter season, cold weather and other explanatory factors. A systematic review was undertaken, which identified factors associated with modified risk of specific types of winter- and cold-related adverse health and social outcome, and assessed the effectiveness of interventions on reducing these adverse impacts. Evidence-based pathway models were developed of associations between winter season or cold exposure and circulatory and respiratory health outcomes, in relation to explanatory factors. Secondary data were identified to represent variables from the pathway models in analyses. Poisson regression models were implemented using a Bayesian approach to evaluate spatial and spatiotemporal variations in observed-to-expected mortality ratios from circulatory and respiratory conditions in relation to covariates, across English Local Authorities and between: winter seasons, periods of cold and warmer weather and months of the year. Climatic factors were associated with spatiotemporal variations in mortality ratios between winter periods, but were less important determinants of excess mortality across the year. This supports the use of weather forecasting services to alert health and social care providers to predicted adverse weather conditions, in order to support individuals with circulatory and respiratory conditions during the winter period. The effects of social factors were similar for circulatory and respiratory conditions and were predominantly non-seasonal. Thus, interventions could be developed to reduce spatial variations in excess mortality from both condition groups on a year-round basis. Further research using morbidity outcome data could provide information to reduce spatial variations in excess medical consultation rates across England.ESRC, Newcastle University’s Applied Epidemiology researc

Understanding and modelling of surface and groundwater interactions

The connections between surface water and groundwater systems remain poorly understood in many catchments throughout the world and yet they are fundamental to effectively managing water resources. Managing water resources in an integrated manner is not straightforward, particularly if both resources are being utilised, and especially in those regions that suffer problems of data scarcity. This study explores some of the principle issues associated with understanding and practically modelling surface and groundwater interactions. In South Africa, there remains much controversy over the most appropriate type of integrated model to be used and the way forward in terms of the development of the discipline; part of the disagreement stems from the fact that we cannot validate models adequately. This is largely due to traditional forms of model testing having limited power as it is difficult to differentiate between the uncertainties within different model structures, different sets of alternative parameter values and in the input data used to run the model. While model structural uncertainties are important to consider, the uncertainty from input data error together with parameter estimation error are often more significant to the overall residual error, and essential to consider if we want to achieve reliable predictions for water resource decisions. While new philosophies and theories on modelling and results validation have been developed (Beven, 2002; Gupta et al., 2008), in many cases models are not only still being validated and compared using sparse and uncertain datasets, but also expected to produce reliable predictions based on the flawed data. The approach in this study is focused on fundamental understanding of hydrological systems rather than calibration based modelling and promotes the use of all the available 'hard' and 'soft' data together with thoughtful conceptual examination of the processes occurring in an environment to ensure as far as possible that a model is generating sensible results by simulating the correct processes. The first part of the thesis focuses on characterising the 'typical' interaction environments found in South Africa. It was found that many traditional perceptual models are not necessarily applicable to South African conditions, largely due to the relative importance of unsaturated zone processes and the complexity of the dominantly fractured rock environments. The interaction environments were categorised into four main 'types' of environment. These include karst, primary, fractured rock (secondary), and alluvial environments. Processes critical to Integrated Water Resource Management (IWRM) were defined within each interaction type as a guideline to setting a model up to realistically represent the dominant processes in the respective settings. The second part of the thesis addressed the application and evaluation of the modified Pitman model (Hughes, 2004), which allows for surface and groundwater interaction behaviour at the catchment scale to be simulated. The issue is whether, given the different sources of uncertainty in the modelling process, we can differentiate one conceptual flow path from another in trying to refine the understanding and consequently have more faith in model predictions. Seven example catchments were selected from around South Africa to assess whether reliable integrated assessments can be carried out given the existing data. Specific catchment perceptual models were used to identify the critical processes occurring in each setting and the Pitman model was assessed on whether it could represent them (structural uncertainty). The available knowledge of specific environments or catchments was then examined in an attempt to resolve the parameter uncertainty present within each catchment and ensure the subsequent model setup was correctly representing the process understanding as far as possible. The confidence in the quantitative results inevitably varied with the amount and quality of the data available. While the model was deemed to be robust based on the behavioural results obtained in the majority of the case studies, in many cases a quantitative validation of the outputs was just not possible based on the available data. In these cases, the model was judged on its ability to represent the conceptualisation of the processes occurring in the catchments. While the lack of appropriate data means there will always be considerable uncertainty surrounding model validation, it can be argued that improved process understanding in an environment can be used to validate model outcomes to a degree, by assessing whether a model is getting the right results for the right reasons. Many water resource decisions are still made without adequate account being taken of the uncertainties inherent in assessing the response of hydrological systems. Certainly, with all the possible sources of uncertainty in a data scarce country such as South Africa, pure calibration based modelling is unlikely to produce reliable information for water resource managers as it can produce the right results for the wrong reasons. Thus it becomes essential to incorporate conceptual thinking into the modelling process, so that at the very least we are able to conclude that a model generates estimates that are consistent with, and reflect, our understanding (however limited) of the catchment processes. It is fairly clear that achieving the optimum model of a hydrological system may be fraught with difficulty, if not impossible. This makes it very difficult from a practitioner's point of view to decide which model and uncertainty estimation method to use. According to Beven (2009), this may be a transitional problem and in the future it may become clearer as we learn more about how to estimate the uncertainties associated with hydrological systems. Until then, a better understanding of the fundamental and most critical hydrogeological processes should be used to critically test and improve model predictions as far as possible. A major focus of the study was to identify whether the modified Pitman model could provide a practical tool for water resource managers by reliably determining the available water resource. The incorporation of surface and groundwater interaction routines seems to have resulted in a more robust and realistic model of basin hydrology. The overall conclusion is that the model, although simplified, is capable of representing the catchment scale processes that occur under most South African conditions

The mindful path to compassion in an adult mental health group

A naturalistic study was undertaken within an NHS setting to explore the effectiveness and satisfaction with a Mindfulness-Based Cognitive Therapy and Mindful Self-Compassion group programme in an adult mental health population. Outcome measures and qualitative feedback suggested beneficial effects and high levels of satisfaction

Comparing predictive abilities of longitudinal child growth models

© 2018 John Wiley & Sons, Ltd. The Bill and Melinda Gates Foundation's Healthy Birth, Growth and Development knowledge integration project aims to improve the overall health and well-being of children across the world. The project aims to integrate information from multiple child growth studies to allow health professionals and policy makers to make informed decisions about interventions in lower and middle income countries. To achieve this goal, we must first understand the conditions that impact on the growth and development of children, and this requires sensible models for characterising different growth patterns. The contribution of this paper is to provide a quantitative comparison of the predictive abilities of various statistical growth modelling techniques based on a novel leave-one-out validation approach. The majority of existing studies have used raw growth data for modelling, but we show that fitting models to standardised data provide more accurate estimation and prediction. Our work is illustrated with an example from a study into child development in a middle income country in South America

Mapping early environment using communication deviance: a longitudinal study of maternal sensitivity toward 6-month-old children

Communication deviance (CD) reflects features of the content or manner of a person's speech that may confuse the listener and inhibit the establishment of a shared focus of attention. The construct was developed in the context of the study of familial risks for psychosis based on hypotheses regarding its effects during childhood. It is not known whether parental CD is associated with nonverbal parental behaviors that may be important in early development. This study explored the association between CD in a cohort of mothers (n = 287) at 32 weeks gestation and maternal sensitivity with infants at 29 weeks in a standard play procedure. Maternal CD predicted lower overall maternal sensitivity (B = -.385; p < .001), and the effect was somewhat greater for sensitivity to infant distress (B = -.514; p < .001) than for sensitivity to nondistress (B = -.311; p < .01). After controlling for maternal age, IQ and depression, and for socioeconomic deprivation, the associations with overall sensitivity and sensitivity to distress remained significant. The findings provide new pointers to intergenerational transmission of vulnerability involving processes implicated in both verbal and nonverbal parental behaviors

Powered mobility interventions for very young children with mobility limitations to aid participation and positive development:the EMPoWER evidence synthesis

Background One-fifth of all disabled children have mobility limitations. Early provision of powered mobility for very young children (aged < 5 years) is hypothesised to trigger positive developmental changes. However, the optimum age at which to introduce powered mobility is unknown. Objective The aim of this project was to synthesise existing evidence regarding the effectiveness and cost-effectiveness of powered mobility for very young children, compared with the more common practice of powered mobility provision from the age of 5 years. Review methods The study was planned as a mixed-methods evidence synthesis and economic modelling study. First, evidence relating to the effectiveness, cost-effectiveness, acceptability, feasibility and anticipated outcomes of paediatric powered mobility interventions was reviewed. A convergent mixed-methods evidence synthesis was undertaken using framework synthesis, and a separate qualitative evidence synthesis was undertaken using thematic synthesis. The two syntheses were subsequently compared and contrasted to develop a logic model for evaluating the outcomes of powered mobility interventions for children. Because there were insufficient published data, it was not possible to develop a robust economic model. Instead, a budget impact analysis was conducted to estimate the cost of increased powered mobility provision for very young children, using cost data from publicly available sources. Data sources A range of bibliographic databases [Cumulative Index to Nursing and Allied Health Literature (CINHAL), MEDLINE, EMBASE™ (Elsevier, Amsterdam, the Netherlands), Physiotherapy Evidence Database (PEDro), Occupational Therapy Systematic Evaluation of Evidence (OTseeker), Applied Social Sciences Index and Abstracts (ASSIA), PsycINFO, Science Citation Index (SCI; Clarivate Analytics, Philadelphia, PA, USA), Social Sciences Citation Index™ (SSCI; Clarivate Analytics), Conference Proceedings Citation Index – Science (CPCI-S; Clarivate Analytics), Conference Proceedings Citation Index – Social Science & Humanities (CPCI-SSH; Clarivate Analytics), Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database (NHS EED), Health Technology Assessment (HTA) Database and OpenGrey] was systematically searched and the included studies were quality appraised. Searches were carried out in June 2018 and updated in October 2019. The date ranges searched covered from 1946 to September 2019. Results In total, 89 studies were included in the review. Only two randomised controlled trials were identified. The overall quality of the evidence was low. No conclusive evidence was found about the effectiveness or cost-effectiveness of powered mobility in children aged either < 5 or ≥ 5 years. However, strong support was found that powered mobility interventions have a positive impact on children’s movement and mobility, and moderate support was found for the impact on children’s participation, play and social interactions and on the safety outcome of accidents and pain. ‘Fit’ between the child, the equipment and the environment was found to be important, as were the outcomes related to a child’s independence, freedom and self-expression. The evidence supported two distinct conceptualisations of the primary powered mobility outcome, movement and mobility: the former is ‘movement for movement’s sake’ and the latter destination-focused mobility. Powered mobility should be focused on ‘movement for movement’s sake’ in the first instance. From the budget impact analysis, it was estimated that, annually, the NHS spends £1.89M on the provision of powered mobility for very young children, which is < 2% of total wheelchair service expenditure. Limitations The original research question could not be answered because there was a lack of appropriately powered published research. Conclusions Early powered mobility is likely to have multiple benefits for very young children, despite the lack of robust evidence to demonstrate this. Age is not the key factor; instead, the focus should be on providing developmentally appropriate interventions and focusing on ‘movement for movement’s sake’. Future work Future research should focus on developing, implementing, evaluating and comparing different approaches to early powered mobility. Study registration This study is registered as PROSPERO CRD42018096449. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology programme and will be published in full in Health Technology Assessment; Vol. 24, No. 50. See the NIHR Journals Library website for further project information

Visit-to-Visit Variability of Blood Pressure and Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis

Visit-to-visit variability of blood pressure (BP) has been associated with cardiovascular disease (CVD) and mortality in some but not all studies. We conducted a systematic review and meta-analysis to examine the association between visit-to-visit variability of BP and CVD and all-cause mortality. Medical databases were searched through June 4, 2014, for studies meeting the following eligibility criteria: adult participants; BP measurements at ≥3 visits; follow-up for CVD, coronary heart disease, stroke, or mortality outcomes; events confirmed via database, death certificate, or event ascertainment committee; and adjustment for confounders. Data were extracted by 2 reviewers and pooled using a random-effects model. Overall, 8870 abstracts were identified of which 37 studies, representing 41 separate cohorts, met inclusion criteria. Across studies, visit-to-visit variability of systolic BP and diastolic BP showed significant associations with outcomes in 181 of 312 (58.0%) and 61 of 188 (32.4%) analyses, respectively. Few studies provided sufficient data for pooling risk estimates. For each 5 mm Hg higher SD of systolic BP, the pooled hazard ratio for stroke across 7 cohorts was 1.17 (95% confidence interval [CI], 1.07–1.28), for coronary heart disease across 4 cohorts was 1.27 (95% CI, 1.07–1.51), for CVD across 5 cohorts was 1.12 (95% CI, 0.98–1.28), for CVD mortality across 5 cohorts was 1.22 (95% CI, 1.09–1.35), and for all-cause mortality across 4 cohorts was 1.20 (95% CI, 1.05–1.36). In summary, modest associations between visit-to-visit variability of BP and CVD and all-cause mortality are present in published studies. However, these findings are limited by the small amount of data available for meta-analysis

Associations between insulin and glucose concentrations and anthropometric measures of fat mass in Australian adolescents

<p>Abstract</p> <p>Background</p> <p>One of the most serious, yet common co-morbidities of obesity is insulin resistance, which if untreated may progress to type 2 diabetes. This paper describes the insulin and glucose concentration distributions, the prevalence of elevated insulin, the associations between insulin and body mass index (BMI), waist circumference, waist-to-height ratio (WHtR) and fat mass index in a representative sample of Australian adolescents.</p> <p>Methods</p> <p>Cross-sectional population-based study of adolescent boys and girls (N = 496, mean age 15.3 years) attending schools in metropolitan Sydney, Australia. Fasting venous blood collected and analysed for insulin and glucose concentrations. Height, weight, waist circumference measured, BMI and waist-to-height ratio calculated. Pubertal status self-reported.</p> <p>Results</p> <p>Glucose concentrations were normally distributed and were not associated with adiposity. Insulin concentrations were distributed logarithmically, were higher among girls than boys overall and within the same ranges of BMI and waist circumference, but were lower among girls than boys within the same ranges of fat mass adjusted for height. The prevalence of elevated insulin concentration (defined as > 100 pmol/L) was 15.9% and 17.1% among boys and girls, respectively. Correlations between insulin concentration and BMI, waist circumference, WHtR and fat mass adjusted for height were 0.53, 0.49, 0.51 and 0.55, among boys, respectively, and 0.35, 0.40, 0.42 and 0.34, among girls, respectively.</p> <p>Conclusions</p> <p>Elevated insulin is highly correlated with adiposity in adolescents. BMI and WHtR are simple measures that can be used to identify young people who should be screened for insulin resistance and other co-morbidities.</p

Whole genome sequencing for the diagnosis of neurological repeat expansion disorders in the UK: a retrospective diagnostic accuracy and prospective clinical validation study

BACKGROUND: Repeat expansion disorders affect about 1 in 3000 individuals and are clinically heterogeneous diseases caused by expansions of short tandem DNA repeats. Genetic testing is often locus-specific, resulting in underdiagnosis of people who have atypical clinical presentations, especially in paediatric patients without a previous positive family history. Whole genome sequencing is increasingly used as a first-line test for other rare genetic disorders, and we aimed to assess its performance in the diagnosis of patients with neurological repeat expansion disorders. METHODS: We retrospectively assessed the diagnostic accuracy of whole genome sequencing to detect the most common repeat expansion loci associated with neurological outcomes (AR, ATN1, ATXN1, ATXN2, ATXN3, ATXN7, C9orf72, CACNA1A, DMPK, FMR1, FXN, HTT, and TBP) using samples obtained within the National Health Service in England from patients who were suspected of having neurological disorders; previous PCR test results were used as the reference standard. The clinical accuracy of whole genome sequencing to detect repeat expansions was prospectively examined in previously genetically tested and undiagnosed patients recruited in 2013-17 to the 100 000 Genomes Project in the UK, who were suspected of having a genetic neurological disorder (familial or early-onset forms of ataxia, neuropathy, spastic paraplegia, dementia, motor neuron disease, parkinsonian movement disorders, intellectual disability, or neuromuscular disorders). If a repeat expansion call was made using whole genome sequencing, PCR was used to confirm the result. FINDINGS: The diagnostic accuracy of whole genome sequencing to detect repeat expansions was evaluated against 793 PCR tests previously performed within the NHS from 404 patients. Whole genome sequencing correctly classified 215 of 221 expanded alleles and 1316 of 1321 non-expanded alleles, showing 97·3% sensitivity (95% CI 94·2-99·0) and 99·6% specificity (99·1-99·9) across the 13 disease-associated loci when compared with PCR test results. In samples from 11 631 patients in the 100 000 Genomes Project, whole genome sequencing identified 81 repeat expansions, which were also tested by PCR: 68 were confirmed as repeat expansions in the full pathogenic range, 11 were non-pathogenic intermediate expansions or premutations, and two were non-expanded repeats (16% false discovery rate). INTERPRETATION: In our study, whole genome sequencing for the detection of repeat expansions showed high sensitivity and specificity, and it led to identification of neurological repeat expansion disorders in previously undiagnosed patients. These findings support implementation of whole genome sequencing in clinical laboratories for diagnosis of patients who have a neurological presentation consistent with a repeat expansion disorder. FUNDING: Medical Research Council, Department of Health and Social Care, National Health Service England, National Institute for Health Research, and Illumina

The influence of music genre on explosive power, repetitions to failure and mood responses during resistance exercise

Objectives: To investigate the influence of different music genres on the psychological, psychophysical and psychophysiological responses during power-based and strength-based resistance exercises. Design: Repeated-measures counterbalanced design. Method: Sixteen resistance-trained participants completed an explosive power test in the squat and bench exercises at 30% 1RM across no music, electronic dance music, metal and self-selected conditions. Peak and mean values were recorded for power and velocity. A progressive loading protocol assessed the impact of condition on repetitions to failure at 60, 70 and 80% 1RM in the squat and bench exercises. For all tests, recording of heart rate and rating of perceived exertion were completed after every set, blood lactate after protocol completion, and mood states before and after. Results: Using magnitude-based inferences, music either had no effect or a small detrimental effect on power and velocity, depending on the exercise. Repetitions to failure increased by a small to moderate amount for all music conditions compared to no music at low but not high intensities. Self-selected music provided additional small benefits in repetitions than other music conditions. Rating of perceived exertion was similar between self-selected, metal and no music conditions, whereas electronic dance music revealed higher responses. Vigour increased after all music conditions but remained unchanged in no music. Conclusions: Explosive power exercises either remain unchanged or are disadvantaged when completed to music. Various music genres could improve repetition to failure training at low to moderate intensities, although individuals might expect greatest improvements using self-selected music, without concomitant increases in perceived effort