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Detecting epistatic drivers of human phenotypes is a considerable challenge. Traditional approaches use regression to sequentially test multiplicative interaction terms involving pairs of genetic variants. For higher-order interactions and genome-wide large-scale data, this strategy is computationally intractable. Moreover, multiplicative terms used in regression modeling may not capture the form of biological interactions. Building on the Predictability, Computability, Stability (PCS) framework, we introduce the epiTree pipeline to extract higher-order interactions from genomic data using tree-based models. The epiTree pipeline first selects a set of variants derived from tissue-specific estimates of gene expression. Next, it uses iterative random forests (iRF) to search training data for candidate Boolean interactions (pairwise and higher-order). We derive significance tests for interactions, based on a stabilized likelihood ratio test, by simulating Boolean tree-structured null (no epistasis) and alternative (epistasis) distributions on hold-out test data. Finally, our pipeline computes PCS epistasis p-values that probabilisticly quantify improvement in prediction accuracy via bootstrap sampling on the test set. We validate the epiTree pipeline in two case studies using data from the UK Biobank: predicting red hair and multiple sclerosis (MS). In the case of predicting red hair, epiTree recovers known epistatic interactions surrounding MC1R and novel interactions, representing non-linearities not captured by logistic regression models. In the case of predicting MS, a more complex phenotype than red hair, epiTree rankings prioritize novel interactions surrounding HLA-DRB1, a variant previously associated with MS in several populations. Taken together, these results highlight the potential for epiTree rankings to help reduce the design space for follow up experiments. [ABSTRACT FROM AUTHOR]

Hikers and hillwalkers typically use the gradient in the direction of travel (walking slope) as the main variable in established methods for predicting walking time (via the walking speed) along a route. Research into fell-running has suggested further variables which may improve speed algorithms in this context; the gradient of the terrain (hill slope) and the level of terrain obstruction. Recent improvements in data availability, as well as widespread use of GPS tracking now make it possible to explore these variables in a walking speed model at a sufficient scale to test statistical significance. We tested various established models used to predict walking speed against public GPS data from almost 88,000 km of UK walking / hiking tracks. Tracks were filtered to remove breaks and non-walking sections. A new generalised linear model (GLM) was then used to predict walking speeds. Key differences between the GLM and established rules were that the GLM considered the gradient of the terrain (hill slope) irrespective of walking slope, as well as the terrain type and level of terrain obstruction in off-road travel. All of these factors were shown to be highly significant, and this is supported by a lower root-mean-square-error compared to existing functions. We also observed an increase in RMSE between the GLM and established methods as hill slope increases, further supporting the importance of this variable. [ABSTRACT FROM AUTHOR]

The coefficient of determination (R 2) is a well-established measure to indicate the predictive ability of polygenic scores (PGSs). However, the sampling variance of R 2 is rarely considered so that 95% confidence intervals (CI) are not usually reported. Moreover, when comparisons are made between PGSs based on different discovery samples, the sampling covariance of R 2 is required to test the difference between them. Here, we show how to estimate the variance and covariance of R 2 values to assess the 95% CI and p value of the R 2 difference. We apply this approach to real data calculating PGSs in 28,880 European participants derived from UK Biobank (UKBB) and Biobank Japan (BBJ) GWAS summary statistics for cholesterol and BMI. We quantify the significantly higher predictive ability of UKBB PGSs compared to BBJ PGSs (p value 7.6e−31 for cholesterol and 1.4e−50 for BMI). A joint model of UKBB and BBJ PGSs significantly improves the predictive ability, compared to a model of UKBB PGS only (p value 3.5e−05 for cholesterol and 1.3e−28 for BMI). We also show that the predictive ability of regulatory SNPs is significantly enriched over non-regulatory SNPs for cholesterol (p value 8.9e−26 for UKBB and 3.8e−17 for BBJ). We suggest that the proposed approach (available in R package r2redux) should be used to test the statistical significance of difference between pairs of PGSs, which may help to draw a correct conclusion about the comparative predictive ability of PGSs. R 2 is a well-established measure for the reliability of polygenic score models although its significance test is rarely considered in this context. We release an R package r2redux that allows formal statistical comparison of two polygenic score models, providing the 95% confidence interval and significance of R 2 difference. [ABSTRACT FROM AUTHOR]

In this article, we present Biologically Annotated Neural Networks (BANNs), a nonlinear probabilistic framework for association mapping in genome-wide association (GWA) studies. BANNs are feedforward models with partially connected architectures that are based on biological annotations. This setup yields a fully interpretable neural network where the input layer encodes SNP-level effects, and the hidden layer models the aggregated effects among SNP-sets. We treat the weights and connections of the network as random variables with prior distributions that reflect how genetic effects manifest at different genomic scales. The BANNs software uses variational inference to provide posterior summaries which allow researchers to simultaneously perform (i) mapping with SNPs and (ii) enrichment analyses with SNP-sets on complex traits. Through simulations, we show that our method improves upon state-of-the-art association mapping and enrichment approaches across a wide range of genetic architectures. We then further illustrate the benefits of BANNs by analyzing real GWA data assayed in approximately 2,000 heterogenous stock of mice from the Wellcome Trust Centre for Human Genetics and approximately 7,000 individuals from the Framingham Heart Study. Lastly, using a random subset of individuals of European ancestry from the UK Biobank, we show that BANNs is able to replicate known associations in high and low-density lipoprotein cholesterol content. Author summary: A common goal in genome-wide association (GWA) studies is to characterize the relationship between genotypic and phenotypic variation. Linear models are widely used tools in GWA analyses, in part, because they provide significance measures which detail how individual single nucleotide polymorphisms (SNPs) are statistically associated with a trait or disease of interest. However, traditional linear regression largely ignores non-additive genetic variation, and the univariate SNP-level mapping approach has been shown to be underpowered and challenging to interpret for certain trait architectures. While nonlinear methods such as neural networks are well known to account for complex data structures, these same algorithms have also been criticized as "black box" since they do not naturally carry out statistical hypothesis testing like classic linear models. This limitation has prevented nonlinear regression approaches from being used for association mapping tasks in GWA applications. Here, we present Biologically Annotated Neural Networks (BANNs): a flexible class of feedforward models with partially connected architectures that are based on biological annotations. The BANN framework uses approximate Bayesian inference to provide interpretable probabilistic summaries which can be used for simultaneous (i) mapping with SNPs and (ii) enrichment analyses with SNP-sets (e.g., genes or signaling pathways). We illustrate the benefits of our method over state-of-the-art approaches using extensive simulations. We also demonstrate the ability of BANNs to recover novel and previously discovered genomic associations using quantitative traits from the Wellcome Trust Centre for Human Genetics, the Framingham Heart Study, and the UK Biobank. [ABSTRACT FROM AUTHOR]

England’s national Improving Access to Psychological Therapies (IAPT) programme advocates stepped care as its organizational delivery of psychological therapies to common mental health problems. There is limited evidence regarding the efficacy of stepped care as a service delivery model, heterogeneity of definition and differences in model implementation in both research and routine practice, hence outcome comparison in terms of effectiveness of model is difficult. Despite sound evidence of the efficacy of low intensity interventions there appears to be a perpetuation of the notion that severity and complexity should only be treated by a high intensity intervention through the continuation of a stratified care model. Yet no psychotherapy treatment is found to be more superior to another, and not enough is known about what works for whom to aid the matching of treatment decision. In the absence of understanding precise treatment factors optimal for recovery, it may be useful to better understand the impact of a service delivery model, and whether different models achieve different outcomes. This study aims to contribute to the discussion regarding the stepped care definition and delivery, and explores the impact on clinical outcomes where different types of stepped care have been implemented within the same service. An observational cohort study analysed retrospective data (n = 16,723) over a 4 year period, in a single IAPT service, where delivery changed from one type of stepped care model to another. We compared the outcomes of treatment completers with a stratified care model and a progression care model. We also explored the assumption that patients who score severe on psychological measures, and therefore are potentially complex, would achieve better outcomes in a stratified model. Outcomes in each model type were compared, alongside baseline factor variables. A significant association was observed between a recovery outcome and model type, with patients 1.5 times more likely to recover in the progression delivery model. The potential implications are that with a progression stepped care model of service delivery, more patients can be treated with a lower intensity intervention, even with initial severe presentations, ensuring that only those that need high intensity CBT or equivalent are stepped up. This could provide services with an effective clinical model that is efficient and potentially more cost effective. [ABSTRACT FROM AUTHOR]

Background: Arts for health interventions are an accepted option for medical management of mental wellbeing in health care. Updated findings are presented from a prospective longitudinal follow-up (observational) design study of an arts on referral programme in UK general practice, over a 7-year period (2009-2016). Methods: Primary care process and mental wellbeing outcomes were investigated, including progress through the intervention, changes in mental wellbeing, and factors associated with those outcomes. A total of n = 1297 patients were referred to an eight or 10-week intervention over a period from 2009 to 2016. Patient sociodemographic information was recorded at baseline, and patient progress (e.g. attendance) assessed throughout the intervention. Results: Of all referrals, 51.7% completed their course of prescribed art (the intervention). Of those that attended, 74.7% engaged with the intervention as rated by the artists leading the courses. A significant increase in wellbeing was observed from pre- to postintervention (t = -19.29, df = 523, P < 0.001, two-tailed) for those that completed and/or engaged. A sub sample (N= 103) of these referrals self-reported multi-morbidities. These multiple health care service users were majority completers (79.6%), and were rated as having engaged (81.0%). This group also had a significant increase in wellbeing, although this was smaller than for the group as a whole (t = -7.38, df=68, P < 0.001). Conclusion: Findings confirm that art interventions can be effective in the promotion of well-being for those that complete, including those referred with multi-morbidity, with significant changes in wellbeing evident across the intervention periods. [ABSTRACT FROM AUTHOR]

Vegetables are commonly rejected by children, making it is important to consider factors that are associated with children's fussiness with vegetables. The current study aimed to investigate whether fussiness with vegetables is associated with a number of factors including caregiver and child vegetable consumption; caregivers' general feeding practices; and caregivers' vegetable-specific feeding practices. Caregivers ( N = 297) of preschool children completed questionnaire measures of their child's fussiness with vegetables, as well as several caregiver and child factors hypothesised to be associated with children's fussiness with vegetables. Findings indicate that children who are fussier with vegetables consume a smaller quantity of vegetables and that almost all have caregivers who eat a smaller quantity of vegetables. Children's fussiness with vegetables was not significantly related to any general feeding practices used by caregivers. However, children's fussiness with vegetables was significantly associated with the use of several vegetable specific feeding practices. Caregivers of fussier children used more encouragement/pressure to eat with vegetables ( r = 0.14, p = .01), hid vegetables within other foods more often ( r = 0.30, p = <.01), used more food rewards for vegetable consumption ( r = 0.19, p <.01), more other rewards for vegetable consumption ( r = 0.21, p < .01), and compromised more when feeding vegetables ( r = 0.14, p = .01). These findings suggest that rather than caregivers' general feeding practices being related to children's fussiness with vegetables, the specific feeding practices used when vegetables are rejected are more significant. It may therefore be helpful to develop advice for caregivers about which feeding practices to avoid when faced with a child who is fussy about eating vegetables. [ABSTRACT FROM AUTHOR]

Context: Spinal axial rotation is required for many functional and sporting activities. Eighty percent of axial rotation occurs in the thoracic spine. Existing measures of thoracic spine rotation commonly involve laboratory equipment, use a seated position, and include lumbar motion. A simple performance-based outcome measure would allow clinicians to evaluate isolated thoracic spine rotation. Currently, no valid measure exists. Objective: To explore the criterion and concurrent validity of a digital inclinometer (DI) and iPhone Clinometer app (iPhone) for measuring thoracic spine rotation using the heel-sit position. Design: Controlled laboratory study. Setting: University laboratory. Patients or Other Participants: A total of 23 asymptomatic healthy participants (14 men, 9 women; age = 25.82 ± 4.28 years, height = 170.26 ± 8.01 cm, mass = 67.50 ± 9.46 kg, body mass index = 23.26 ± 2.79) were recruited from a student population. Main Outcome Measure(s): We took DI and iPhone measurements of thoracic spine rotation in the heel-sit position concurrently with dual-motion analysis (laboratory measure) and ultrasound imaging of the underlying bony tissue motion (reference standard). To determine the criterion and concurrent validity, we used the Pearson product moment correlation coefficient (r, 2 tailed) and Bland-Altman plots. Results: The DI (r = 0.88, P < .001) and iPhone (r = 0.88, P < .001) demonstrated strong criterion validity. Both also had strong concurrent validity (r = 0.98, P < .001). Bland-Altman plots illustrated mean differences of 5.82° (95% confidence interval [CI] = 20.37°, -8.73°) and 4.94° (95% CI = 19.23°, -9.35°) between the DI and iPhone, respectively, and the reference standard and 0.87° (95% CI = 6.79°, -5.05°) between the DI and iPhone. Conclusions: The DI and iPhone provided valid measures of thoracic spine rotation in the heel-sit position. Both can be used in clinical practice to assess thoracic spine rotation, which may be valuable when evaluating thoracic dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To quantify the impact of neuroradiologist presence on head and neck cancer (HNC) radiotherapy peer review (PR) changes. Methods: Prospective data were collected from HNC radiotherapy PR meetings; major, minor, and organ at risk (OAR) changes recorded. Differences in changes made with a neuroradiologist present were determined. χ2 tests of statistical significance were performed. Multivariate logistic regression identified potential predictors of changes. Results: Prospective PR was performed in 125/160 (78%) patients undergoing radical (chemo)radiotherapy for HNC between October 2018 and September 2019. Full PR documentation was available for 120/160 meetings (75%), with a neuroradiologist present in 53/120 (44%). Overall, 51/120 (42.5%) had changes made to target volumes or OARs. When a neuroradiologist was present, 29/53 (55%) of plans had changes made, compared to 22/67 (33%) in their absence. On multivariate analysis, neuroradiologist presence significantly influenced any changes made during the PR meetings (OR 2.59; 95% CI 1.05–6.43; p = 0.039). Conclusion: Neuroradiologist presence at PR meetings significantly influences changes made to HNC contouring, likely improving consistency and enhancing quality assurance. Advances in knowledge: This is the first published UK series demonstrating that a collaborative approach between radiology and oncology in PR meetings is significant in leading to contour changes for HNC. [ABSTRACT FROM AUTHOR]

Background: Passive overconsumption is the increase in energy intake driven by the high-fat energy-dense food environment. This can be explained in part because dietary fat has a weaker effect on satiation (i.e. process that terminates feeding). Habitually active individuals show improved satiety (i.e. process involved in post-meal suppression of hunger) but any improvement in satiation is unknown. Here we examined whether habitual physical activity mitigates passive overconsumption through enhanced satiation in response to a high-fat meal. Methods: Twenty-one non-obese individuals with high levels of physical activity (HiPA) and 19 individuals with low levels of physical activity (LoPA) matched for body mass index (mean = 22.8 kg/m²) were recruited. Passive overconsumption was assessed by comparing ad libitum energy intake from covertly manipulated high-fat (HFAT; 50% fat) or high-carbohydrate (HCHO; 70% carbohydrate) meals in a randomized crossover design. Habitual physical activity was assessed using SenseWear accelerometers (SWA). Body composition, resting metabolic rate, eating behaviour traits, fasting appetite-related peptides and hedonic food reward were also measured. Results: In the whole sample, passive overconsumption was observed with greater energy intake at HFAT compared to HCHO (p < 0.01), without any differences between activity groups (p > 0.05). SWA confirmed that HiPA were more active than LoPA (p < 0.01). HiPA had lower body fat and greater fat-free mass than LoPA (p < 0.05 for both) but did not differ in resting metabolic rate, eating behaviour traits, appetite-related peptides or food reward (p > 0.05 for all). Conclusions: Non-obese individuals with high or low physical activity levels but matched for BMI showed similar susceptibility to passive overconsumption when consuming an ad libitum high-fat compared to a high-carbohydrate meal. This occurred despite increased total daily energy expenditure and improved body composition in HiPA. Greater differences in body composition and/or physical activity levels may be required to impact on satiation. [ABSTRACT FROM AUTHOR]

Screening cytosine-phosphate-guanine dinucleotide (CpG) DNA methylation sites in association with some covariate(s) is desired due to high dimensionality. We incorporate surrogate variable analyses (SVAs) into (ordinary or robust) linear regressions and utilize training and testing samples for nested validation to screen CpG sites. SVA is to account for variations in the methylation not explained by the specified covariate(s) and adjust for confounding effects. To make it easier to users, this screening method is built into a user-friendly R package, ttScreening, with efficient algorithms implemented. Various simulations were implemented to examine the robustness and sensitivity of the method compared to the classical approaches controlling for multiple testing: the false discovery rates-based (FDR-based) and the Bonferroni-based methods. The proposed approach in general performs better and has the potential to control both types I and II errors. We applied ttScreening to 383,998 CpG sites in association with maternal smoking, one of the leading factors for cancer risk. [ABSTRACT FROM AUTHOR]

Background: Personal and family data forms, completed by women referred to breast cancer genetics clinics, are valuable tools for verification and extension of family history, crucial steps in accurate risk evaluation. A significant minority of women do not complete and return these forms, despite reminders, even when completion is a pre‐requisite for a clinic appointment. Objective: To facilitate access of women at increased familial risk of breast cancer to screening and counselling services by investigating reasons for non‐return of the forms. Participants and Design: Based on a single regional ‘breast cancer family’ service in the UK, Analysis of quantitative data comparing women who did not return forms (n = 55) with those who had done so (n = 59), together with qualitative evaluation of potential barriers to form‐completion through semi‐structured telephone interviews with a random subset of ‘non‐returners’ (n = 23). Results: Non‐returners have higher proportions of the very young (below the age at which surveillance could be offered) and of women from lower social deprivation categories. Interviews revealed that the majority of non‐returners are anxious, rather than unconcerned about their breast cancer risk and circumstances and attitudes contributed to non‐compliance. Twenty‐one participants confirmed that they would welcome an appointment at a ‘breast cancer family’ clinic, but nine did not attend for the appointment. They were significantly younger than those who attend, but were not at lower familial risk. Discussion and Conclusions: Many women who fail to complete and return a family history form would benefit from risk assessment and genetic counselling. Several steps are suggested that might help them access the relevant services. [ABSTRACT FROM AUTHOR]

Quantitative analyses of the macronutrient content of eight popular commercial 'ready-to-feed' baby meals for 6-9-month old infants in the UK market have been undertaken in order to ascertain their nutritional suitability in relation to the total daily dietary intake as well as nutritional profiling of the products. The chemical analyses conducted included Kjeldhal for protein, acid hydrolysis and extraction for fat, phenol sulphuric acid for carbohydrate and Association of Official Analytical Chemists 985.29 for fibre. The only difference found between different varieties (meat- and vegetable-based) was with respect to the protein content ( P = 0.04) per 100 g of food. The experimentally determined concentrations of macronutrients (g/100 kcal) were compared with the declared values provided by the manufacturers on the product labels and, despite some variations, the values obtained comply with regulatory requirements ( Commission Directive 2006/125/ EC). The total daily intake of fat (27.0 g per day) - based on the menu composed from commercial complementary food - is suggested to exceed the daily recommended values for fat (31%), if the intake of snacks and desserts are incorporated. These findings imply that the formulation of recipes, based on a standard commercial menu, is an important consideration in relation to the nutritional quality of the diet of infants. [ABSTRACT FROM AUTHOR]

Political scientists often theorize that an explanatory variable should have 'no effect' and support this claim by demonstrating that its coefficient's estimate is not statistically significant. This empirical argument is quite weak, but I introduce applied researchers to simple, powerful tools that can strengthen their arguments for this hypothesis. With several supporting examples, I illustrate that researchers can use 90% confidence intervals to argue against meaningful effects and provide persuasive evidence for their hypothesis. [ABSTRACT FROM AUTHOR]

There has been a worldwide epidemic of obesity in recent decades. In animal studies, there is convincing evidence that light exposure causes weight gain, even when calorie intake and physical activity are held constant. Disruption of sleep and circadian rhythms by exposure to light at night (LAN) might be one mechanism contributing to the rise in obesity, but it has not been well-investigated in humans. Using multinomial logistic regression, we examined the association between exposure to LAN and obesity in questionnaire data from over 100,000 women in the Breakthrough Generations Study, a cohort study of women aged 16 years or older who were living in the United Kingdom and recruited during 2003–2012. The odds of obesity, measured using body mass index, waist:hip ratio, waist:height ratio, and waist circumference, increased with increasing levels of LAN exposure (P < 0.001), even after adjustment for potential confounders such as sleep duration, alcohol intake, physical activity, and current smoking. We found a significant association between LAN exposure and obesity which was not explained by potential confounders we could measure. While the possibility of residual confounding cannot be excluded, the pattern is intriguing, accords with the results of animal experiments, and warrants further investigation. [ABSTRACT FROM PUBLISHER]

Background: Goal-directed fluid therapy (GDFT) has been shown to reduce complications and hospital length of stay following major surgery. However, there has been no assessment regarding its use in clinical practice. Methods: An electronic survey was administered to randomly selected anaesthetists from the United Kingdom (UK, n = 2000) and the United States of America (USA, n = 2000), and 500 anaesthetists from Australia/New Zealand (AUS/NZ). Preferences, clinical use and attitudes towards GDFT were investigated. Results were collated to examine regional differences. Results: The response rates from the UK (n = 708) and AUS/NZ (n = 180) were 35%, and 36% respectively. The response rate from the USA was very low (n = 178; 9%). GDFT use was significantly more common in the UK than in AUS/NZ (p < 0.01). The Oesophageal Doppler Monitor was the most preferred instrument in the UK (n = 362; h76%) with no clear preferences in other regions. GDFT was most commonly utilised in major abdominal surgery and for patients with significant comorbidities. The commonest reasons stated for not using GDFT were either lack of availability of monitoring tools (AUS/NZ: 57 (70%); UK: 94 (64%)) or a lack of experience with instruments (AUS/NZ: 43 (53%); UK: 51 (35%)). A subset of respondents (AUS/NZ: 22(27%); UK: 45 (30%)) felt GDFT provided no perceived benefit. Enthusiasm towards the use of GDFT in the absence of existing barriers was high. Conclusion: Several hypotheses were generated regarding important differences in the use of GDFT between anaesthetists from the UK and AUS/NZ. There is significant interest in utilising GDFT in clinical practice and existing barriers should be addressed. [ABSTRACT FROM AUTHOR]

There has been a recent increase in interest among evolutionary researchers in the hypothesis that humans evolved as cooperative breeders, using extended family support to help decrease offspring mortality and increase the number of children that can be successfully reared. In this study, data drawn from the 1970 longitudinal British cohort study were analysed to determine whether extended family support encourages fertility in contemporary Britain. The results showed that at age 30, reported frequency that participants saw their own parents (but not in-laws) and the closeness of the bond between the participant and their own parents were associated with an increased likelihood of having a child between ages 30 and 34. Financial help and reported grandparental childcare were not significantly positively associated with births from age 30 to 34. Men's income was positively associated with likelihood of birth, whereas women's income increased likelihood of birth only for working women with at least one child. While it was predicted that grandparental financial and childcare help would increase the likelihood of reproduction by lowering the cost to the parent of having a child, it appears that the mere physical presence of supportive parents rather than their financial or childcare help encouraged reproduction in the 1970 British birth cohort sample. [ABSTRACT FROM AUTHOR]

The use of religious/spiritual resources may increase when dealing with the stress of a cancer diagnosis. However, there has been very little research conducted into changes in religious/spiritual beliefs and practices as a result of a cancer diagnosis outside the USA. The aim of this study was to examine the impact of a breast cancer diagnosis on patients' religious/spiritual beliefs and practices in the UK where religious practice is different. The study used two methods. One compared the religious/spiritual beliefs and practices of 202 patients newly diagnosed with breast cancer with those of a control group of healthy women ( n = 110). The other examined patients' perceived change in religious/spiritual beliefs and practices at the time of surgery with those in the year prior to surgery. The aspects of religiousness/spirituality assessed were: levels of religiosity/spirituality, strength of faith, belief in God as well as private and public practices. Patient's perceived their belief in God, strength of faith and private religious/spiritual practices to have significantly increased shortly after surgery compared with the year prior to surgery. However, there were no significant differences in religious/spiritual beliefs and practices between patients and healthy participants. Change scores demonstrated both a reduction and an increase in religious/spiritual beliefs and practices. Although belief in God, strength of faith and private religious/spiritual practices were perceived by patients to be significantly higher after their cancer diagnosis, no significant differences in religious/spiritual beliefs and practices were found between the cancer group at the time of surgery and the control group. Different methodologies appear to produce different results and may explain contradictions in past US studies. Limitations of this study are discussed and suggestions for future research are made. [ABSTRACT FROM AUTHOR]

Background: Endometrial cancer is the most common gynaecological cancer in the western world, the incidence increasing in the United Kingdom by over 40% since 1993. Two types of endometrial cancer exist - oestrogen-dependent type 1 with good prognosis and non-oestrogen-dependent type 2 with poor prognosis. The histopathological distribution of the increase in endometrial cancer is unknown. This study investigates the observed incidence trends of the two types, the age, stage, and socioeconomic distribution of this increase and survival outcome.Methods: Data were analysed from 6867 women with endometrial cancer registered between 1994 and 2006, at a UK population-based cancer registry.Results: Increased endometrial cancer incidence is confined to type 1 cancers with a significant increase in age standardised incidence rate (ASR) from 12.0 per 100,000 (confidence interval (CI) 10.7-13.2) in 1994 to 16.3 per 100,000 (CI 14.9-17.7), P<0.001 in 2006, while ASR of type 2 cancer changed from 2.5 per 100,000 (CI 2.0-3.1) in 1994 to 2.2 per 100,000 (CI 1.7-2.7) in 2006, which was not statistically significant P>0.05. Increase in type 1 cancer is most marked in age groups 60-69 years (P<0.001) and 70-79 years (P<0.001) and distributed equally among socioeconomic quintiles. While outcome for type 1 cancer has improved, 1-year survival in type 2 cancer is unchanged from 73.1% in 1994 to 74.3%, P=0.089 and 5-year survival decreased from 55.1% to 40.9%, P=0.001.Conclusion: Increased incidence in endometrial cancer is confined to type 1 cancers, seen most in the 60-79 age groups and across all socioeconomic quintiles. Survival in type 2 cancer has decreased significantly. Urgent research is needed to investigate prevention strategies in type 1 and improve therapy in type 2 cancers. [ABSTRACT FROM AUTHOR]

Context: Cooling the neck region can improve the ability to exercise in a hot environment. It might improve performance by dampening the perceived level of thermal strain, allowing individuals to override inhibitory signals. Objective: To investigate whether the enhanced ability to exercise in a hot environment observed when cooling the neck region occurs because of dampening the perceived level of thermal strain experienced and the subsequent overriding of inhibitory signals. Design: Crossover study. Setting: Walk-in environmental chamber. Patients or Other Participants: Eight endurance-trained, nonacclimated men (age = 26 ± 2 years, height = 1.79 ± 0.04 m, mass = 77.0 ± 6.2 kg, maximal oxygen uptake [VO2max] = 56.2 ± 9.2 mL·kg-1·min-1) participated. Intervention(s): Participants completed 4 running tests at approximately 70% VO2max to volitional exhaustion: 2 familiarization trials followed by 2 experimental trials (cooling collar [CC] and no collar [NC]). Trials were separated by 7 days. Familiarization and NC trials were performed without a collar and used to assess the test variability. Main Outcome Measure(s): Time to volitional exhaustion, heart rate, rectal temperature, neck skin temperature, rating of perceived exertion, thermal sensation, and feeling scale (pleasure/displeasure) were measured. Results: Time to volitional exhaustion was increased by 13.5% ± 3.8% (CC = 43.15 ± 12.82 minutes, NC = 38.20 ± 11.70 minutes; t7 = 9.923, P < .001) with the CC, which reduced mean neck skin temperature throughout the test (P < .001). Participants terminated exercise at identical levels of perceived exertion, thermal sensation, and feeling scale, but the CC enabled participants to tolerate higher rectal temperatures (CC = 39.61 °C ± 0.45°C, NC = 39.18°C ± 0.7°C; t7 = -3.217, P = .02) and heart rates (CC = 181 ± 6 beats/min, NC = 178 ± 9 beats/min; t7 = -2.664, P = .03) at the point of termination. Conclusions: Cooling the neck increased the time taken to reach volitional exhaustion by dampening the perceived levels of thermal strain. [ABSTRACT FROM AUTHOR]

Abstract: Numerous economic studies have shown a strong positive correlation between health and years of schooling. The question at the centre of this research is whether the correlation between health and education represents a causal relation. This paper uses changes in compulsory schooling laws in the United Kingdom to test this hypothesis. Multiple measures of overall health are used. The results provide evidence of a causal relation running from more schooling to better health which is much larger than standard regression estimates suggest. [Copyright &y& Elsevier]

Measurements of mercury in ambient air are assuming greater importance, because of increasing health concerns and European legislation. In order to have confidence in measured values and to assess compliance with target values, measurements must be made with validated methodologies which have traceable uncertainty statements associated with them. This paper presents a practical uncertainty budget for the measurement of vapour-phase mercury in ambient air, sampling onto a gold-coated silica adsorption tube and measuring with atomic fluorescence spectrometry. Moreover, this budget may be generalised for other related measurement methods for mercury vapour and other ambient air pollutants. All significant sources of uncertainty are discussed and estimated. Expanded relative uncertainties at the 95% confidence interval of approximately 17% are estimated for exemplar measurements made by the National Physical Laboratory (NPL) as part of the UK Heavy Metals Monitoring Network. [Copyright &y& Elsevier]

Background: A commonly reported problem with the conduct of multicentre randomised controlled trials (RCTs) is that recruitment is often slower or more difficult than expected, with many trials failing to reach their planned sample size within the timescale and funding originally envisaged. The aim of this study was to explore factors that may have been associated with good and poor recruitment in a cohort of multicentre trials funded by two public bodies: the UK Medical Research Council (MRC) and the Health Technology Assessment (HTA) Programme. Methods: The cohort of trials was identified from the administrative databases held by the two funding bodies. 114 trials that recruited participants between 1994 and 2002 met the inclusion criteria. The full scientific applications and subsequent trial reports submitted by the trial teams to the funders provided the principal data sources. Associations between trial characteristics and recruitment success were tested using the Chi-squared test, or Fisher's exact test where appropriate. Results: Less than a third (31%) of the trials achieved their original recruitment target and half (53%) were awarded an extension. The proportion achieving targets did not appear to improve over time. The overall start to recruitment was delayed in 47 (41%) trials and early recruitment problems were identified in 77 (63%) trials. The inter-relationship between trial features and recruitment success was complex. A variety of strategies were employed to try to increase recruitment, but their success could not be assessed. Conclusion: Recruitment problems are complex and challenging. Many of the trials in the cohort experienced recruitment difficulties. Trials often required extended recruitment periods (sometimes supported by additional funds). While this is of continuing concern, success in addressing the trial question may be more important than recruitment alone. [ABSTRACT FROM AUTHOR]

The article presents a study examining pregnancy outcomes in cystic fibrosis patients for more than 10-year period from an adult cystic fibrosis centre in Great Britain. The study used respiratory and obstetric records of pregnancies during 2003-2013. Results showed that a decline in lung function at delivery was noted which was a sign for further decline in function during the subsequent postpartum period.

Both the definition of economic activity and the definition of periodicity seem to determine whether there are long tides in economic affairs. Spectral analysis of growth rates finds no long waves in the U.S., U.K., and Sweden, but this is consistent with the appearance of long classical (upcross) swings in the deviations from trend of several raw data series. These upcross oscillations may not be independent components of economic evolution but merely distorted reflections of trend growth processes. [ABSTRACT FROM AUTHOR]