New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Meta-analysis of telomere length in 19 713 subjects reveals high heritability, stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10−61) than father–offspring correlation (r=0.33; P-value=7.01 × 10−5), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10−5). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10−30) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10−23) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10−10). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10−9 to P = 1.8 × 10−40) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10−3 to P = 1.2 × 10−13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Plasma-enhanced synthesis of bioactive polymeric coatings from monoterpene alcohols: A combined experimental and theoretical study

This paper describes the synthesis and characterization of a novel organic polymer coating for the prevention of the growth of Pseudomonas aeruginosa on the solid surface of three-dimensional objects. Substrata were encapsulated with polyterpenol thin films prepared from terpinen-4-ol using radio frequency plasma enhanced chemical vapor deposition. Terpinen-4-ol is a constituent of tea tree oil with known antibacterial properties. The influence of deposition power on the chemical structure, surface composition, and ultimately the antibacterial inhibitory activity of the resulting polyterpenol thin films was studied using X-ray photoelectron spectroscopy (XPS), water contact angle measurement, atomic force microscopy (AFM), and 3-D interactive visualization and statistical approximation of the topographic profiles. The experimental results were consistent with those predicted by molecular simulations. The extent of bacterial attachment and extracellular polymeric substances (EPS) production was analyzed using scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). Polyterpenol films deposited at lower power were particularly effective against P. aeruginosa due to the preservation of original terpinen-4-ol molecules in the film structure. The proposed antimicrobial and antifouling coating can be potentially integrated into medical and other clinically relevant devices to prevent bacterial growth and to minimize bacteria-associated adverse host responses.

Cost and outcomes of assessing patients with chest pain in an Australian emergency department

Objectives: We sought to characterise the demographics, length of admission, final diagnoses, long-term outcome and costs associated with the population who presented to an Australian emergency department (ED) with symptoms of possible acute coronary syndrome (ACS). Design, setting and participants: Prospectively collected data on ED patients presenting with suspected ACS between November 2008 and February 2011 was used, including data on presentation and at 30 days after presentation. Information on patient disposition, length of stay and costs incurred was extracted from hospital administration records. Main outcome measures: Primary outcomes were mean and median cost and length of hospital stay. Secondary outcomes were diagnosis of ACS, other cardiovascular conditions or non-cardiovascular conditions within 30 days of presentation. Results: An ACS was diagnosed in 103 (11.1%) of the 926 patients recruited. 193 patients (20.8%) were diagnosed with other cardiovascular-related conditions and 622 patients (67.2%) had non-cardiac-related chest pain. ACS events occurred in 0 and 11 (1.9%) of the low-risk and intermediate-risk groups, respectively. Ninety-two (28.0%) of the 329 high-risk patients had an ACS event. Patients with a proven ACS, high-grade atrioventricular block, pulmonary embolism and other respiratory conditions had the longest length of stay. The mean cost was highest in the ACS group ($13 509; 95% CI, $11 794–$15 223) followed by other cardiovascular conditions ($7283; 95% CI, $6152–$8415) and non-cardiovascular conditions ($3331; 95% CI, $2976–$3685). Conclusions: Most ED patients with symptoms of possible ACS do not have a cardiac cause for their presentation. The current guideline-based process of assessment is lengthy, costly and consumes significant resources. Investigation of strategies to shorten this process or reduce the need for objective cardiac testing in patients at intermediate risk according to the National Heart Foundation and Cardiac Society of Australia and New Zealand guideline is required.

A lifespan perspective on emotion regulation, stress, and well-being in the workplace

Researchers in the field of occupational stress and well-being are increasingly interested in the role of emotion regulation in the work context. Emotion regulation has also been widely investigated in the area of lifespan developmental psychology, with findings indicating that the ability to modify one's emotions represents a domain in which age-related growth is possible. In this chapter, we integrate the literatures on aging, emotion regulation, and occupational stress and well-being. To this end, we review key theories and empirical findings in each of these areas, summarize existing research on age, emotion regulation, and stress and well-being at work, and develop a conceptual model on how aging affects emotion regulation and the stress process in work settings to guide future research. According to the model, age will affect: (1) what kinds of affective work events are encountered and how often; (2) the appraisal of and initial emotional response to affective work events (emotion generation), and; (3) the management of emotions and coping with affective work events (emotion regulation). The model has implications for researchers and practitioners who want to understand and facilitate successful emotion regulation and stress reduction in the workplace among different age groups.

Psychological consequences of false-positive screening mammograms in the UK

- Objectives To identify the psychological effects of false-positive screening mammograms in the UK. - Methods Systematic review of all controlled studies and qualitative studies of women with a false-positive screening mammogram. The control group participants had normal mammograms. All psychological outcomes including returning for routine screening were permitted. All studies had a narrative synthesis. - Results The searches returned seven includable studies (7/4423). Heterogeneity was such that meta-analysis was not possible. Studies using disease-specific measures found that, compared to normal results, there could be enduring psychological distress that lasted up to 3 years; the level of distress was related to the degree of invasiveness of the assessment. At 3 years the relative risks were, further mammography, 1.28 (95% CI 0.82 to 2.00), fine needle aspiration 1.80 (95% CI 1.17 to 2.77), biopsy 2.07 (95% CI 1.22 to 3.52) and early recall 1.82 (95% CI 1.22 to 2.72). Studies that used generic measures of anxiety and depression found no such impact up to 3 months after screening. Evidence suggests that women with false-positive mammograms have an increased likelihood of failing to reattend for routine screening, relative risk 0.97 (95% CI 0.96 to 0.98) compared with women with normal mammograms. - Conclusions Having a false-positive screening mammogram can cause breast cancer-specific distress for up to 3 years. The degree of distress is related to the invasiveness of the assessment. Women with false-positive mammograms are less likely to return for routine assessment than those with normal ones.

Educators’ perspectives about how older hospital patients can engage in a falls prevention education programme: A qualitative process evaluation

- Objectives Falls are the most frequent adverse event reported in hospitals. Patient and staff education delivered by trained educators significantly reduced falls and injurious falls in an older rehabilitation population. The purpose of the study was to explore the educators’ perspectives of delivering the education and to conceptualise how the programme worked to prevent falls among older patients who received the education. - Design A qualitative exploratory study. - Methods Data were gathered from three sources: conducting a focus group and an interview (n=10 educators), written educator notes and reflective researcher field notes based on interactions with the educators during the primary study. The educators delivered the programme on eight rehabilitation wards for periods of between 10 and 40 weeks. They provided older patients with individualised education to engage in falls prevention and provided staff with education to support patient actions. Data were thematically analysed and presented using a conceptual framework. - Results Falls prevention education led to mutual understanding between staff and patients which assisted patients to engage in falls prevention behaviours. Mutual understanding was derived from the following observations: the educators perceived that they could facilitate an effective three-way interaction between staff actions, patient actions and the ward environment which led to behaviour change on the wards. This included engaging with staff and patients, and assisting them to reconcile differing perspectives about falls prevention behaviours. - Conclusions Individualised falls prevention education effectively provides patients who receive it with the capability and motivation to develop and undertake behavioural strategies that reduce their falls, if supported by staff and the ward environment.

Age, Occupational Strain, and Well-Being: A Person-Environment Fit Perspective

We develop a conceptual model, based on person-environment fit theory, which explains how employee age affects occupational strain and well-being. We begin by explaining how age directly affects different dimensions of objective and subjective P-E fit. Next, we illustrate how age can moderate the relationship between objective P-E fit and subjective P-E fit. Third, we discuss how age can moderate the relationships between P-E fit, on one hand, and occupational strain and well-being on the other. Fourth, we explain how age can impact occupational strain and well-being directly independent of P-E fit. The chapter concludes with implications for future research and practice.

Bayesian synthetic likelihood

Having the ability to work with complex models can be highly beneficial, but the computational cost of doing so is often large. Complex models often have intractable likelihoods, so methods that directly use the likelihood function are infeasible. In these situations, the benefits of working with likelihood-free methods become apparent. Likelihood-free methods, such as parametric Bayesian indirect likelihood that uses the likelihood of an alternative parametric auxiliary model, have been explored throughout the literature as a good alternative when the model of interest is complex. One of these methods is called the synthetic likelihood (SL), which assumes a multivariate normal approximation to the likelihood of a summary statistic of interest. This paper explores the accuracy and computational efficiency of the Bayesian version of the synthetic likelihood (BSL) approach in comparison to a competitor known as approximate Bayesian computation (ABC) and its sensitivity to its tuning parameters and assumptions. We relate BSL to pseudo-marginal methods and propose to use an alternative SL that uses an unbiased estimator of the exact working normal likelihood when the summary statistic has a multivariate normal distribution. Several applications of varying complexity are considered to illustrate the findings of this paper.

Residential tariff structure and battery energy storage impact in queensland LV network

Distributed renewable energy has become a significant contender in the supply of power in the distribution network in Queensland and throughout the world. As the cost of battery storage falls, distribution utilities turn their attention to the impacts of battery storage and other storage technologies on the low voltage (LV) network. With access to detailed residential energy usage data, Energex's available residential tariffs are investigated for their effectiveness in providing customers with financial incentives to move to Time-of Use based tariffs and to reward use of battery storage.