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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]

Purpose: Simulation training is an ever-growing means of healthcare education and often involves simulated participants (SPs), commonly known as actors. Simulation-based education (SBE) can sometimes endanger SPs, and as such we have created a safety checklist for them to follow. This study describes how we developed the checklist through a quality improvement project, and then evaluated feedback responses to assess whether SPs felt our checklist was safe. Methods: The checklist was provided to SPs working in an acute trust simulation service when delivering multidisciplinary SBE over 4 months. Using multiple plan--do--study--act cycles, the checklist was refined by reflecting on SP feedback to ensure that the standards of the safe simulation were met. We collected 21 responses from September to December 2021 after SPs completed an SBE event. Results: The responses showed that 100% of SPs felt safe during SBE when using our checklist. The average "confidence in safety" rating before using the checklist was 6.8/10, which increased significantly to 9.2/10 after using the checklist (P<0.0005). The checklist was refined throughout the 4 months and implemented in adult and pediatric SBE as a standard operating procedure. Conclusion: We recommend using our safety checklist as a standard operating procedure to improve the confidence and safety of SPs during safe and effective simulations. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to inquire about pre-requisites and benefits of collaboration in the UK and India, testing for significance of country context. Design/methodology/approach: The survey data set includes 118 UK-based and 175 India-based small and medium enterprises (SMEs). This paper applies a grounded theory research design, given that to date, no sufficient SME sector-specific, quantitative frameworks have been published. Findings: India-based SMEs are more inclined towards frequent collaboration. Soft variables such as perceived trustworthiness or past commitment, appear to be significant when explaining whether or not SMEs in India enter into a collaboration. Operations-driven motives play the most significant role for them, whereas for UK-based SMEs, product design-related collaboration motives are of more importance. Research limitations/implications: The developed cross-country and country-specific collaboration variables will facilitate SME studies under a consistent and complete framework. Practical implications: Business associations and SME owners in the UK can use the research to gain an Indian perspective and vice versa. This study concludes a stylised framework for SME owners and managers to classify collaboration patterns in a country. Originality/value: While previous research established concepts and practices of SME collaboration, this is the first paper that quantitatively addresses the attitudes and experiences that SME owners hold when initialising inter-firm collaboration. [ABSTRACT FROM AUTHOR]

Research reveals that organisations in general are keen to provide their staff with the support needed to boost their competency in BIM and subsequently leverage the effectiveness of its implementation. However, employers need a decision-making tool to make better informed investments in specific work-based education and training that addresses the immediate upskilling needs of their employees. Therefore, the aim of this research project is to investigate the significance of Work-Based Education and Training (WBET) needs through the development of an Organisational Upskilling Model (OUM). A comprehensive literature review retrieved 25 hypotheses that were tested for significance from a questionnaire survey completed by 73 AEC professionals working for a large-scale UK engineering consultancy. Based on the current expert sample, the study revealed a holistic inter-organisational agreement that technology training is in high demand. Whereas, the organisational body of knowledge needs only to be better publicised, as employees were unaware of its immediate availability. OUM proved that the most influential variables to BIM Uptake were Attitude (R2 = 0.569 & Q2 = 0.395), User Competency (R2 = 0.523 & Q2 = 0.369), and Organisational Support (R2 = 0.400 & Q2 = 0.233). Informed by their in-house culture, OUM enabled the sponsoring engineering consultant to predict immediate WBET upskilling needs and plan for the required capital investment. However, 'OUM' may be applied by any BIM-adopting organisation seeking WBET informed decision-making assistance for better upskilling, continuous improvement, organisational learning, and ultimately business growth. [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]

This paper describes an empirical study of UK rights issues, involving various tests of semi-strong form market efficiency with respect to the announcement of rights issues. In addition, the Price Pressure Hypothesis, which asserts that equity issues, by increasing the supply of shares, temporarily depress the share price, is tested against the competing Substitution Hypothesis. Since this involves estimating the demand curve for a company's shares, our results provide evidence not only on market efficiency but also on market liquidity, and whether companies can raise new equity at existing market prices. The study is also of methodological interest in that it uses a number of alternative models for testing market efficiency, thus allowing us to test the sensitivity of our conclusions to the particular methodology employed. This is also one of the first studies to use the new London Share Price Database (LSPD), which is the first comprehensive source of UK share returns data to become available for research purposes. [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]

Background Cryptosporidium is a major cause of gastroenteritis (cryptosporidiosis). Case and outbreak report rates vary geographically, which may in part reflect public health practice. Methods To examine the public health management of cryptosporidiosis, an online questionnaire was administered to the 28 Health Protection Teams (HPTs) in England and Wales in 2014. Practices for investigation and management of cases and outbreaks were compared. Results Practice varied among the 24 (86%) respondents in terms of who undertook actions (HPT or Local Authority) to investigate and manage cryptosporidiosis. HPTs without exceedance monitoring detected fewer outbreaks (1/5, 20%) than those with it (13/19, 68%) (P = 0.12), and those that always administered a risk-factor questionnaire detected more outbreaks (12/19, 63%) than those who did this only sometimes (2/5, 40%) (P = 0.62). Significantly more HPTs with a system to detect common exposures reported at least one outbreak (14/19, 74%) compared to HPTs with no system (0/5) (P = 0.01). Conclusions Applying exceedance monitoring, using a standardized questionnaire taking into account the incubation period for Cryptosporidium, and having a structured system to detect common exposures increased outbreak detection. Information about all cases should be shared between local public health authorities, and current guidance used for the prevention of spread. [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]

Background: Although dietary flavonoid intake has been associated with less weight gain, there are limited data on its impact on fat mass, and to our knowledge, the contribution of genetic factors to this relation has not previously been assessed. Objective: We examined the associations between flavonoid intakes and fat mass. Design: In a study of 2734 healthy, female twins aged 18-83 y from the TwinsUK registry, intakes of total flavonoids and 7 subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, polymers, and proanthocyanidins) were calculated with the use of food-frequency questionnaires. Measures of dual-energy X-ray absorptiometry-derived fat mass included the limb-to-trunk fat mass ratio (FMR), fat mass index, and central fat mass index. Results: In cross-sectional multivariable analyses, higher intake of anthocyanins, flavonols, and proanthocyanidins were associated with a lower FMR with mean ± SE differences between extreme quintiles of 20.036 0.02 (P-trend = 0.02),20.03 ± 0.02 (P-trend = 0.03), and 20.05 ± 0.02 (P-trend < 0.01), respectively. These associations were not markedly changed after further adjustment for fiber and total fruit and vegetable intakes. In monozygotic, intakediscordant twin pairs, twins with higher intakes of flavan-3-ols (n = 154, P = 0.03), flavonols (n = 173, P = 0.03), and proanthocyanidins (n = 172, P < 0.01) had a significantly lower FMR than that of their co-twins with within-pair differences of 3-4%. Furthermore, in confirmatory food-based analyses, twins with higher intakes of flavonolrich foods (onions, tea, and pears; P = 0.01) and proanthocyanidin-rich foods (apples and cocoa drinks; P = 0.04) and, in younger participants (aged <50 y) only, of anthocyanin-rich foods (berries, pears, grapes, and wine; P = 0.01) had a 3-9% lower FMR than that of their co-twins. Conclusions: These data suggest that higher habitual intake of a number of flavonoids, including anthocyanins, flavan-3-ols, flavonols, and proanthocyanidins, are associated with lower fat mass independent of shared genetic and common environmental factors. Intervention trials are needed to further examine the effect of flavonoid-rich foods on body composition. [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]

Background: Obesity is increasing in parallel with greater all-day food availability. The latter may promote meal irregularity, dysregulation of the energy balance, and poor metabolic health. Objective: We investigated the effect of meal irregularity on the thermic effect of food (TEF), lipid concentrations, carbohydrate metabolism, subjective appetite, and gut hormones in healthy women. Design: Eleven normal-weight women (18-40 y of age) were recruited in a randomized crossover trial with two 14-d isoenergetic diet periods (identical foods provided and free living) that were separated by a 14-d habitual diet washout period. In period 1, participants followed a regular meal pattern (6 meals/d) or an irregular meal pattern (3-9 meals/d), and in period 2, the alternative meal pattern was followed. Before and after each period, when participants were fasting and for 3 h after intake of a test drink, measurements were taken of energy expenditure, circulating glucose, lipids (fasting only), insulin, glucagon-like peptide 1 (GLP-1), peptide YY (PYY), and ghrelin. An ad libitum test meal was offered. Subjective appetite ratings were assessed while fasting, after the test drink, after the ad libitum meal, and during the intervention. Continuous interstitial glucose monitoring was undertaken for 3 consecutive days during each intervention, and the ambulatory activity pattern was recorded (ambulatory energy expenditure estimation). Results: Regularity was associated with a greater TEF (P, 0.05) and a lower incremental area under the curve (iAUC) for glucose after intake of the test drink (over 3 h) and, for some identical meals, during the 2 interventions (over 90 min) (day 7: after breakfast; day 9: after lunch and dinner). There was no difference between treatments for the test-drink gut hormone response. A time effect was noted for fasting GLP-1, fasting PYY, PYY responses, and hunger-rating responses to the test drink (P < 0.05). Lower hunger and higher fullness ratings were seen premeal and post-meal during the regular period while subjects were free living. Conclusion: Meal regularity appears to be associated with greater TEF and lower glucose responses, which may favor weight management and metabolic health. This trial was registered at clinical-trials.gov as NCT02052076. [ABSTRACT FROM AUTHOR]

Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil-containing lipid emulsions. Objective: The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content. Design: We conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial. Results: We randomly assigned 168 infants born at,31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for non-adipose mass [adjusted mean difference: 1.0 g (95% CI: -108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations >7 mmol/L or >10 mmol/L, respectively (75% compared with 49%, P < 0.01; 49% compared with 18%, P < 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: 20.8 cm (95% CI: 21.5, -0.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes. Conclusion: Imm-RDI of parenteral amino acids does not benefit body composition or growth to term and may be harmful. This trial was registered at www.isrctn.com as ISRCTN29665319 and at eudract.ema.europa.eu as EudraCT 2009-016731-34. [ABSTRACT FROM AUTHOR]

Background: The mechanism and clinical significance of low circulating 25-hydroxyvitamin D [25(OH)D] in obese people are unknown. Low total 25(OH)D may be due to low vitamin D-binding proteins (DBPs) or faster metabolic clearance. However, obese people have a higher bone mineral density (BMD), which suggests that low 25(OH)D may not be associated with adverse consequences for bone. Objective: We sought to determine whether 1) vitamin D metabolism and 2) its association with bone health differ by body weight. Design: We conducted a cross-sectional observational study of 223 normal-weight, overweight, and obese men and women aged 25-75 y in South Yorkshire, United Kingdom, in the fall and spring. A subgroup of 106 subjects was also assessed in the winter. We used novel techniques, including an immunoassay for free 25(OH)D, a stable isotope for the 25(OH)D3 half-life, and high-resolution quantitative tomography, to make a detailed assessment of vitamin D physiology and bone health. Results: Serum total 25(OH)D was lower in obese and overweight subjects than in normal-weight subjects in the fall and spring (geometric means: 45.0 and 40.8 compared with 58.6 nmol/L, respectively; P < 0.001) but not in the winter. Serum 25(OH)D was inversely correlated with body mass index (BMI) in the fall and spring and in the winter. Free 25(OH)D and 1,25-dihydroxyvitamin D [1,25(OH)2D] were lower in obese subjects. DBP, the DBP genotype, and the 25(OH)D3 half-life did not differ between BMI groups. Bone turnover was lower, and bone density was higher, in obese people. Conclusions: Total and free 25(OH)D and 1,25(OH)2D are lower at higher BMI, which cannot be explained by lower DBP or the shorter half-life of 25(OH)D3. We speculate that low 25(OH)D in obesity is due to a greater pool of distribution. Lower 25(OH)D may not reflect at-risk skeletal health in obese people, and BMI should be considered when interpreting serum 25(OH)D as a marker of vitamin D status. [ABSTRACT FROM AUTHOR]

Background: Poorly absorbed fermentable carbohydrates can provoke irritable bowel syndrome (IBS) symptoms by escaping absorption in the small bowel and being rapidly fermented in the colon in some susceptible subjects. IBS patients often are anxious and stressed, and stress accelerates small bowel transit, which may exacerbate malabsorption. Objective: In this study we investigated the effect of an intravenous injection of corticotropin-releasing factor (CRF) on fructose malabsorption and the resulting volume of water in the small bowel. Design: We performed a randomized, placebo-controlled crossover study of CRF compared with saline injection in 11 male and 10 female healthy subjects, examining the effect on the malabsorption of a 40-g fructose test meal and its transit through the gut, which was assessed by serial MRI and breath hydrogen measurement. Orocecal transit was assessed with the use of the lactose [13C]ureide breath test and the adrenal response to CRF was assessed by serial salivary cortisol measurements. Results: CRF injection caused a significant increase in salivary cortisol, which lasted for 135 min. Small bowel water content (SBWC) rose from baseline, peaking at 45 min after fructose ingestion, whereas breath hydrogen peaked later, at 75 min. The area under the curve for SBWC from –15 min to 135 min was significantly lower after CRF compared with saline [mean difference: 5911 mL · min (95% CI: 18.4, 11,803 mL · min), P = 0.049]. Considering all subjects, the percentage change in ascending colon volume rose significantly after CRF. This increase was significant for male (P = 0.026), but not female, volunteers. Conclusions: CRF constricts the small bowel and increases fructose malabsorption, as shown by increased ascending colon volumes. This mechanism may help to explain the increased sensitivity of some stressed individuals to fructose malabsorption. This trial was registered at clinicaltrials.gov as NCT01763281. [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: The causal nature of associations between breakfast and health remain unclear in obese individuals. Objective: We sought to conduct a randomized controlled trial to examine causal links between breakfast habits and components of energy balance in free-living obese humans. Design: The Bath Breakfast Project is a randomized controlled trial with repeated measures at baseline and follow-up among a cohort in South West England aged 21-60 y with dual-energy X-ray absorpti-ometry-derived fat mass indexes of ≥13 kg/m² for women (n = 15) and ≥9 kg/m² for men (n = 8). Components of energy balance (resting metabolic rate, physical activity thermogenesis, diet-induced thermo-genesis, and energy intake) were measured under free-living conditions with random allocation to daily breakfast (≥700 kcal before 1100) or extended fasting (0 kcal until 1200) for 6 wk, with baseline and follow-up measures of health markers (e.g., hematology/adipose biopsies). Results: Breakfast resulted in greater physical activity thermogenesis during the morning than when fasting during that period (difference: 188 kcal/d; 95% CI: 40, 335) but without any consistent effect on 24-h physical activity thermogenesis (difference: 272 kcal/d; 95% CI: -254, 798). Energy intake was not significantly greater with breakfast than fasting (difference: 338 kcal/d; 95% CI: 2313, 988). Body mass increased across both groups over time but with no treatment effects on body composition or any change in resting metabolic rate (stable within 8 kcal/d). Metabolic/cardiovascular health also did not respond to treatments, except for a reduced insulinemic response to an oral-glucose-tolerance test over time with daily breakfast relative to an increase with daily fasting (P = 0.05). Conclusions: In obese adults, daily breakfast leads to greater physical activity during the morning, whereas morning fasting results in partial dietary compensation (i.e., greater energy intake) later in the day. There were no differences between groups in weight change and most health outcomes, but insulin sensitivity increased with breakfast relative to fasting. This trial was registered at www.isrctn.org as ISRCTN31521726. [ABSTRACT FROM AUTHOR]

Background: The beneficial cardiovascular effects of vegetables may be underpinned by their high inorganic nitrate content. Objective: We sought to examine the effects of a 6-wk once-daily intake of dietary nitrate (nitrate-rich beetroot juice) compared with placebo intake (nitrate-depleted beetroot juice) on vascular and platelet function in untreated hypercholesterolemics. Design: A total of 69 subjects were recruited in this randomized, double-blind, placebo-controlled parallel study. The primary endpoint was the change in vascular function determined with the use of ultrasound flow-mediated dilatation (FMD). Results: Baseline characteristics were similar between the groups, with primary outcome data available for 67 patients. Dietary nitrate resulted in an absolute increase in the FMD response of 1.1% (an ~24% improvement from baseline) with a worsening of 0.3% in the placebo group (P < 0.001). A small improvement in the aortic pulse wave velocity (i.e., a decrease of 0.22 m/s; 95% CI: -0.4, -0.3 m/s) was evident in the nitrate group, showing a trend (P = 0.06) to improvement in comparison with the placebo group. Dietary nitrate also caused a small but significant reduction (7.6%) in platelet-monocyte aggregates compared with an increase of 10.1% in the placebo group (P = 0.004), with statistically significant reductions in stimulated (ex vivo) P-selectin expression compared with the placebo group (P < 0.05) but no significant changes in unstimulated expression. No adverse effects of dietary nitrate were detected. The composition of the salivary microbiome was altered after the nitrate treatment but not after the placebo treatment (P < 0.01). The proportions of 78 bacterial taxa were different after the nitrate treatment; of those taxa present, 2 taxa were responsible for >1% of this change, with the proportions of Rothia mucilaginosa trending to increase and Neisseria flavescens (P < 0.01) increased after nitrate treatment relative to after placebo treatment. Conclusions: Sustained dietary nitrate ingestion improves vascular function in hypercholesterolemic patients. These changes are associated with alterations in the oral microbiome and, in particular, nitrate-reducing genera. Our findings provide additional support for the assessment of the potential of dietary nitrate as a preventative strategy against atherogenesis in larger cohorts. This trial was registered at clinicaltrials.gov as NCT01493752. [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]

Background: Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. Objective: We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). Design: This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. Results: There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 µmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 µmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. Conclusions: The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159. [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: 123I-FP-CIT (DaTSCAN) SPECT studies of the nigrostriatal pathway are a valuable tool in the diagnosis of movement disorders. However some scans are reported as equivocal with potential adverse consequences. We investigated whether the use of quantification of tracer uptake within the striatum can be used to reduce the number of equivocal reports. MATERIAL AND METHODS: BRASS software (Hermes, Sweden) was used to quantify striatal tracer uptake in DaTSCAN stud- ies of patients referred to our institution. Scans were quantified and numerical limits were determined to distinguish between normal and abnormal scans. Scans were then re-reported both with, and without, the use of quantification. Number of equivocal reports and accuracy of reporting between the two types of reporting were compared. RESULTS: Scan reporting using quantification led to a significant reduction in the number of equivocal reports with no significant change in reporting accuracy. CONCLUSION: Automated quantification of DaTSCAN studies with BRASS and the use of numerical limits can decrease the number of equivocal reports without affecting report accuracy. [ABSTRACT FROM AUTHOR]

Background: The manipulation of the composition of foods consumed as between-meal snacks may aid daily energy restriction. Objectives: We compared the effects of the consumption of 2 energy-matched snack bars on appetite, energy intake (EI), and metabolic and endocrine responses. In addition, we investigated whether the acute effects of the consumption of snacks were maintained under free-living conditions and whether the habitual daily consumption of the snack over 14 d influenced these effects. Design: Ten lean men [mean ± SD age: 30.7 ± 9.7 y; body mass index (in kg/m²): 23.2 ± 2.8] consumed a whey protein and polydextrose (PPX) snack bar or an isoenergetic control snack bar as a midmorning, between-meal snack for 14 consecutive days in a double-blind, randomized, crossover design. The two 14-d intervention phases were separated by a 14-d washout period. On the first (day 1) and last (day 15) days of each intervention phase, appetite, food intake, and blood metabolite and endocrine responses were assessed under laboratory conditions. Free-living EI was recorded on days 4, 8, and 12 of interventions. Results: Total daily EI was significantly lower when the PPX snack was consumed during experimental days (10,149 ± 831 compared with 11,931 ± 896 kJ; P < 0.01), and daily EI remained lower when the PPX snack was consumed during the free-living part of the intervention (7904 ± 610 compared with 9041 ± 928 kJ; P < 0.05). The PPX snack was associated with lower glucose and ghrelin and higher glucagon-like peptide 1 and peptide tyrosine-tyrosine responses. Conclusion: The manipulation of the composition of foods consumed as snacks is an effective way to limit subsequent EI. This trial was registered at clinicaltrials.gov as NCT01927926. [ABSTRACT FROM AUTHOR]

Background: The long-term impact of early malnutrition on human capital outcomes remains unclear, and existing evidence has come largely from observational studies. Objective: We compared the impact of a nutritional supplement given during pregnancy or lactation in rural Gambia on educational performance and cognitive ability in offspring at their maturity. Design: This study was a follow-up of a randomized trial of prenatal high protein and energy supplementation conducted between 1989 and 1994. Subjects were 16-22 y of age at follow-up, and information was collected on schooling achievement and cognitive ability by using the Raven's progressive matrices test, Mill Hill vocabulary test, and forward and backward digit-span tests. Results: A total of 1459 individuals were traced and interviewed and represented 71% of the original cohort and 81% of the surviving cohort. There was no difference in cognitive ability or educational attainment between treatment groups by using any of the methods of assessment. Conclusion: We have shown little evidence to support a long-term effect of prenatal protein-energy supplementation compared with supplementation during lactation on cognitive development in rural Gambians. This trial was registered at http://www.controlled-trials.com as ISRCTN72582014 [ABSTRACT FROM AUTHOR]

Background: Twin and family studies that estimated the heritability of daily physical activity have been limited by poor measurement quality and a small sample size. Objective: We examined the heritability of daily physical activity and sedentary behavior assessed objectively by using combined heart rate and movement sensing in a large twin study. Design: Physical activity traits were assessed in daily life for a mean (±SD) 6.7 ± 1.1 d in 1654 twins from 420 monozygotic and 352 dizygotic same-sex twin pairs aged 56.3 ± 10.4 y with body mass index (in kg/m²) of 26.1 ± 4.8. We estimated the average daily movement, physical activity energy expenditure, and time spent in moderate-to-vigorous intensity physical activity and sedentary behavior from heart rate and acceleration data. We used structural equation modeling to examine the contribution of additive genetic, shared environmental, and unique environmental factors to between-individual variation in traits. Results: Additive genetic factors (ie, heritability) explained 47% of the variance in physical activity energy expenditure (95% CI: 23%, 53%) and time spent in moderate-to-vigorous intensity physical activity (95% CI: 29%, 54%), 35% of the variance in acceleration of the trunk (95% CI: 0%, 44%), and 31% of the variance in the time spent in sedentary behavior (95% CI: 9%, 51%). The remaining variance was predominantly explained by unique environmental factors and random error, whereas shared environmental factors played only a marginal role for all traits with a range of 0-15%. Conclusions: The between-individual variation in daily physical activity and sedentary behavior is mainly a result of environmental influences. Nevertheless, genetic factors explain up to one-half of the variance, suggesting that innate biological processes may be driving some of our daily physical activity. [ABSTRACT FROM AUTHOR]

The diversity of the associations of dietary glycaemic index (GI) and glycaemic load (GL) with dietary intake and body fatness observed in epidemiological studies may be partly due to the differences in underlying dietary intake patterns. We examined the cross-sectional associations of dietary GI and GL with food and nutrient intakes and indices of body fatness in 818 children aged 4–10 years and 818 adolescents aged 11–18 years in Britain, based on the data from the National Diet and Nutrition Survey. Dietary intake was assessed using a 7 d weighed dietary record. Overweight was defined as BMI ≥ 85th percentile of the age- and sex-specific British growth reference data. Central obesity was defined as waist:height ratio (WHtR) ≥ 0·5 (adolescents only). Breads, breakfast cereals and potatoes were the positive predictive food groups for dietary GI, while dairy products, fruit juice, other cereals and fruit were the negative predictors. Dietary GL was closely correlated with carbohydrate intake. Dietary GI showed no associations with overweight or central obesity. Conversely, dietary GL showed an independent association with a higher risk of overweight in children and a higher risk of central obesity (but not overweight) in adolescents. However, dietary GI and GL were not associated with BMI z-score in children and adolescents or WHtR in adolescents. In conclusion, the present study showed that dietary GL was independently associated with overweight in children and with central obesity in adolescents. Nevertheless, given no associations when body fatness measures were treated as continuous variables, the results must be interpreted cautiously. [ABSTRACT FROM PUBLISHER]

Objectives: Objectives: To investigate patients’ views about their lowest tolerable blood glucose level and explore symptoms they may develop below that level. Design: A semi-structured patient interview. Setting: Outpatient clinic for older people (≥75 years) with diabetes. Participants: Patients attending an outpatient clinic over a six months period who are monitoring their blood glucose at home and able to participate in interview. Results: Sixty one patients gave answers to the interview questions. Mean (SD) age was 82.3 (3.9) years and 33 (54%) were females. All patients indicated that they were usually aware when hypoglycaemia occurs but the symptoms reported were mostly non specific. The threshold for hypoglycaemia was 5 mmol/L in 13 (21%) patients, 6 mmol/L in 14 (23%) patients, 7 mmol/L in 13 (21%) patients, 8 mmol/L in 17 (28%) patients and 9 mmol/L in 4 (7%) patients. There was no significant difference between patients who were symptomatic at a higher blood glucose level (>6mmo/L) and those who developed symptoms at a lower level (≤6mmol/L). Conclusion: Older people with diabetes who seem to be aware of hypoglycaemia report mostly non specific symptoms. The threshold of experiencing hypoglycaemic symptoms appears to be higher than the usually defined <4mmol/L. [ABSTRACT FROM AUTHOR]

Dry plantar skin is associated with considerable morbidity, and patient compliance with emollient treatment regimens is notoriously poor. Two 25% urea foot creams are listed on the UK Drug Tariff, but only one is recommended solely as a once-daily treatment.This article assesses the efficacy, tolerability and patient preference of two 25% urea foot creams to determine the implications for patient compliance and treatment outcomes. [ABSTRACT FROM AUTHOR]

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]

The n-3 PUFA are a unique class of fatty acids that cannot be manufactured by the body, and must be acquired via dietary sources. In the UK, as well as in other Western nations, these ‘essential’ fatty acids are consumed in quantities that fall below government guidelines. The present study explored the effects of 12 weeks' dietary supplementation with 1 g/d of two types of fish oil (FO; DHA-rich and EPA-rich) in 159 healthy young adults aged 18–35 years. An assessment of performance on a battery of computerised cognitive tasks and mood measures took place before and following the 12-week treatment regimen. Venous blood samples were also supplied by participants at both time points which were later analysed for serum fatty acid concentrations. Despite good adherence to the study protocol – as reflected in increased concentrations of n-3 serum fatty acids – compared with placebo, the observed effects of both active treatments were minimal. The only finding of note revealed that supplementation with EPA-rich FO may reduce subjective mental fatigue at times of high cognitive demand, although further investigation is required. These findings, taken together with other recent reports of null effects, suggest that dietary supplementation with n-3 PUFA in healthy, normally developing and impairment-free populations is unlikely to result in cognitive enhancement. [ABSTRACT FROM PUBLISHER]

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]

Background. Early discontinuation of adjuvant endocrine therapy may affect the outcome of treatment in breast cancer patients. The aim of this study was to assess age-specific persistence and age-specific survival outcome based on persistence status. Methods. Patients enrolled in the Tamoxifen Exemestane Adjuvant Multinational trial were included. Nonpersistence was defined as discontinuing the assigned endocrine treatment within 1 year of follow-up because of adverse events, intercurrent illness, patient refusal, or other reasons. Endpoints were the breast cancer-specific and overall survival times. Analyses were stratified by age at diagnosis (<65 years, 65-74 years, ≥75 years). Results. Overall, 3,142 postmenopausal breast cancer patients were included: 1,682 were aged <65 years, 951 were aged 65-74 years, and 509 were aged ≥75 years. Older age was associated with a higher proportion of nonpersistence within 1 year of follow-up. In patients aged<65 years, nonpersistent patients had lower breast cancer- specific and overall survival probabilities. In patients aged 65-74 years and patients aged ≥75 years, the survival times of persistent and nonpersistent patients were similar. Conclusion. Nonpersistence within 1 year of follow-up was associated with lower breast cancer-specific and overall survival probabilities in patients aged <65 years, but it was not associated with survival outcomes in patients aged 65-74 years or in patients aged>75 years. These results suggest that extrapolation of outcomes from a young to an elderly breast cancer population may be insufficient and urge age-specific breast cancer studies. [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]