Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis

Variation in body iron is associated with or causes diseases, including anaemia and iron overload. Here, we analyse genetic association data on biochemical markers of iron status from 11 European-population studies, with replication in eight additional cohorts (total up to 48,972 subjects). We find 11 genome-wide-significant (P<5 × 10−8) loci, some including known iron-related genes (​HFE, ​SLC40A1, ​TF, ​TFR2, ​TFRC, ​TMPRSS6) and others novel (​ABO, ​ARNTL, ​FADS2, ​NAT2, ​TEX14). SNPs at ​ARNTL, ​TF, and ​TFR2 affect iron markers in ​HFE C282Y homozygotes at risk for hemochromatosis. There is substantial overlap between our iron loci and loci affecting erythrocyte and lipid phenotypes. These results will facilitate investigation of the roles of iron in disease.

Prevalence of diet related risk factors for chronic disease in male prisoners in a high secure prison

BACKGROUND/OBJECTIVES Research on prisoners is limited and demonstrates a group with disproportionate numbers from disadvantaged backgrounds, known to have a high burden of disease, much of which is diet related. The aim of this study was to gauge the presence of markers of chronic disease, as a basis for food and nutrition policy in prisons. METHODS/SUBJECTS A cross-sectional study design was used with a convenience sample of prisoners in a male 945 bed high secure facility. Face to face interviews with physical measures of height, weight, body fat, waist circumference and blood pressure were collected along with fasting bloods. Data was confirmed with facility records, observations and staff interviews. Full ethics approval was obtained. Results were compared with studies of Australian prisoners and the general population. RESULTS The mean age was 35.5 years (n=120). Prevalence rates were: obesity 14%, diabetes 5%, hypertension 26.7% and smoking 55.8%. Self-report of daily physical activity was 84%, with 51% participating ≥two times daily. Standard food provision was consistent with dietary recommendations, except sodium was high. Where fasting bloods were obtained (n=78) dyslipidaemia was 56.4% with the Metabolic Syndrome present in 26%. CONCLUSIONS Prevalence of diabetes and heart disease risk appear similar to the general population, however obesity was lower and smoking higher. The data provides evidence that markers of chronic disease are present, with this the first study to describe the Metabolic Syndrome in prisoners. Food and nutrition policy in this setting is complex and should address the duty of care issues that exist.

Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis

Background We examined pituitary volume before the onset of psychosis in subjects who were at ultra-high risk (UHR) for developing psychosis. Methods Pituitary volume was measured on 1.5-mm, coronal, 1.5-T magnetic resonance images in 94 UHR subjects recruited from admissions to the Personal Assessment and Crisis Evaluation Clinic in Melbourne, Australia and in 49 healthy control subjects. The UHR subjects were scanned at baseline and were followed clinically for a minimum of 1 year to detect transition to psychosis. Results Within the UHR group, a larger baseline pituitary volume was a significant predictor of future transition to psychosis. The UHR subjects who later went on to develop psychosis (UHR-P, n = 31) had a significantly larger (+12%; p = .001) baseline pituitary volume compared with UHR subjects who did not go on to develop psychosis (UHR-NP, n = 63). The survival analysis conducted by Cox regression showed that the risk of developing psychosis during the follow-up increased by 20% for every 10% increase in baseline pituitary volume (p = .002). Baseline pituitary volume of the UHR-NP subjects was smaller not only compared with UHR-P (as described above) but also compared with control subjects (−6%; p = .032). Conclusions The phase before the onset of psychosis is associated with a larger pituitary volume, suggesting activation of the HPA axis.

Weight-related risk perception among healthy and overweight pregnant women: A cross-sectional study

Objective The objective of this study was to evaluate weight-related risk perception in early pregnancy and to compare this perception between women commencing pregnancy healthy weight and overweight. Study design Pregnant women (n=664) aged 29±5 (mean±s.d.) years were recruited from a metropolitan teaching hospital in Australia. A self-administered questionnaire was completed at around 16 weeks of gestation. Height measured at baseline and self-reported pre-pregnancy weight were used to calculate body mass index. Cross-sectional analysis was conducted. Differences between groups were assessed using chi-squared tests for categorical variables and t-tests or Mann–Whitney U tests for continuous variables depending on distribution. Result Excess gestational weight gain (GWG) during pregnancy was more important in leading to health problems for women or their child compared with pre-pregnancy weight. Personal risk perception for complications was low for all women, although overweight women had slightly higher scores than healthy-weight women (2.4±1.0 vs 2.9±1.0; P<0.001). All women perceived their risk for complications to be below that of an average pregnant woman. Conclusion Women should be informed of the risk associated with their pre-pregnancy weight (in the case of maternal overweight) and excess GWG. If efforts to raise risk awareness are to result in preventative action, this information needs to be accompanied by advice and appropriate support on how to reduce risk.

The influence of financial risk tolerance and risk perception on individual investment decision-making in a financial advice context

The aim of this thesis is to examine how risk tolerance and risk perception, two important but often misunderstood constructs, jointly influence client investment decisions in a financial advice context. By distinguishing the roles of these two risk constructs in client decision-making, in this thesis a new direction in studying financial/investment risks is provided while practice and regulation in the financial services industry is potentially informed. Based on the literature relating to risks and individual decision-making, a theoretical framework is developed and relevant hypotheses are tested in two studies with financial adviser clients in Australia. Results reveal that financial risk tolerance influences asset allocation both directly and indirectly through risk perception. The intervening role of risk perception suggests that risk tolerance affects how clients perceive the riskiness of an investment product which influences client decision-making.

Prevalence and risk factors of refractive errors among schoolchildren in Shiraz, Iran

Purpose: To determine the prevalence and risk factors of refractive errors among schoolchildren in Shiraz, Iran. Methods: In a cross-sectional study, using random cluster sampling, 3065 Shiraz schoolchildren were selected in this study. The participants totaled 2683; 1872 elementary and middle school and 811 high school students. For the primary and middle schoolchildren, cycloplegic refraction and for the high school students, non-cycloplegic autorefraction was measured. Myopia, defined as spherical equivalent (SE) refraction -0.50 diopter (D) or worse, hyperopia as SE +2.00D and +0.50D or more for cycloplegic and noncycloplegic refractions respectively, and astigmatism as cylinder -0.75D or worse. Results: The prevalence of refractive errors in elementary and middle school students was: myopia 4.35 % (95% confidence interval (CI), 2.89 -5.81), hyperopia 5.04 % (95%CI, 3.49 -6.58) and astigmatism 11.79 % (95%CI, 10.21 -13.38). For high school students, these rates were 22.4 % (95%CI, 18.44 -26.36), 10.52 % (95%CI, 6.75 -14.29) and 20.99% (95%CI, 16.55 -25.44), respectively.The prevalence of myopia increased with age in primary and middle school students (OR=1.15, 95% CI, 0.98 to1.33, p=0.073). Conclusions: The result of this study indicated a relatively low prevalence of refractive errors among schoolchildren in Shiraz according to the protocol by "Refractive Error Study in Children" (RESC) in other investigations.

Environmental health risk assessment of dioxin in foods and the sustainability of public health interventions at severe dioxin hot spots in Vietnam

This study assessed environmental health risk from dioxin in foods and sustainability of risk reduction programs at two heavily contaminated former military sites in Vietnam. The study involved 1000 household surveys, analysis of food samples and in-depth discussions with residents and officials. The findings indicate that more than 40 years after the war, local residents still experience high exposure to dioxin if they consume local high risk foods. Public health intervention programs were rated moderately to well sustained. Internal migration, and lack of clear, official guidance and sensitivity regarding dioxin issues were the main challenges for sustainability of prevention programs.

Queer Youth Research/ers: A reflexive account of risk and intimacy in an ethical (mine)field

In contemporary Western societies, the years between childhood and young adulthood are commonly understood to be (trans)formative in the reflexive project of sexual self-making (Russell et al. 2012). As sexual subjects in the making, youthful bodies, desires and sexual activities are often perceived as both volatile and vulnerable, thus subjected to instruction and discipline, protection and surveillance. Accordingly, young people’s sexual proximities are closely monitored by social institutions and ‘(hetero)normalising regimes’ (Warner 1999) for any signs that may compromise the end goal of development—a ‘normal’ reproductive heterosexual monogamous adult.

The influence of family history of hypertension on disease prevalence and associated metabolic risk factors among Sri Lankan adults

Background Hypertension is a major contributor to the global non-communicable disease burden. Family history is an important non-modifiable risk factor for hypertension. The present study aims to describe the influence of family history (FH) on hypertension prevalence and associated metabolic risk factors in a large cohort of South Asian adults, from a nationally representative sample from Sri Lanka. Methods A cross-sectional survey among 5,000 Sri Lankan adults, evaluating FH at the levels of parents, grandparents, siblings and children. A binary logistic regression analysis was performed in all patients with ‘presence of hypertension’ as dichotomous dependent variable and using family history in parents, grandparents, siblings and children as binary independent variables. The adjusted odds ratio controlling for confounders (age, gender, body mass index, diabetes, hyperlipidemia and physical activity) are presented below. Results In all adults the prevalence of hypertension was significantly higher in patients with a FH (29.3 %, n = 572/1951) than those without (24.4 %, n = 616/2530) (p < 0.001). Presence of a FH significantly increased the risk of hypertension (OR:1.29; 95 % CI:1.13-1.47), obesity (OR:1.36; 95 % CI: 1.27–1.45), central obesity (OR:1.30; 95 % CI 1.22–1.40) and metabolic syndrome (OR:1.19; 95 % CI: 1.08–1.30). In all adults presence of family history in parents (OR:1.28; 95 % CI: 1.12–1.48), grandparents (OR:1.34; 95 % CI: 1.20–1.50) and siblings (OR:1.27; 95 % CI: 1.21–1.33) all were associated with significantly increased risk of developing hypertension. Conclusions Our results show that the prevalence of hypertension was significantly higher in those with a FH of hypertension. FH of hypertension was also associated with the prevalence of obesity, central obesity and metabolic syndrome. Individuals with a FH of hypertension form an easily identifiable group who may benefit from targeted interventions.

Risk factors for hospital re-presentation among older adults following fragility fractures: Protocol for a systematic review

Background After being discharged from hospital following the acute management of a fragility fracture, older adults may re-present to hospital emergency departments in the post-discharge period. Early re-presentation to hospital, which includes hospital readmissions, and emergency department presentations without admission, may be considered undesirable for individuals, hospital institutions and society. The identification of modifiable risk factors for hospital re-representation following initial fracture management may prove useful for informing policy or practice initiatives that seek to minimise the need for older adults to re-present to hospital early after they have been discharged from their initial inpatient care. The purpose of this systematic review is to identify correlates of hospital re-presentation in older patients who have been discharged from hospital following clinical management of fragility fractures. Methods/Design The review will follow the PRISMA-P reporting guidelines for systematic reviews. Four electronic databases (Pubmed, CINAHL, Embase, and Scopus) will be searched. A suite of search terms will identify peer-reviewed articles that have examined the correlates of hospital re-presentation in older adults (mean age of 65 years or older) who have been discharged from hospital following treatment for fragility fractures. The Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies will be used to assess the quality of the studies. The strength of evidence will be assessed through best evidence synthesis. Clinical and methodological heterogeneity across studies are likely to impede meta-analyses. Discussion The best evidence synthesis will outline correlates of hospital re-presentations in this clinical group. This synthesis will take into account potential risks of bias for each study, while permitting inclusion of findings from a range of quantitative study designs. It is anticipated that findings from the review will be useful in identifying potentially modifiable risk factors that have relevance in policy, practice and research priorities to improve the management of patients with fragility fractures. Systematic Review Registration PROSPERO CRD42015019379

Our future is at risk: Disclose the Trans-Pacific Partnership now

Christmas has come early this year for big corporations. Wikileaks has revealed that the Trans-Pacific Partnership contains a swag of corporate gifts and baubles. The leaked intellectual property chapter of the TPP looks like it has been dictated by the United States Chamber of Commerce. Among other things, the agreement seeks to provide for longer and stronger copyright protection for transnational corporations. - See more at: https://newmatilda.com/2013/11/15/our-future-risk-disclose-tpp-now#sthash.axbmON9X.dpuf

Evaluating and predicting overall process risk using event logs

Companies standardise and automate their business processes in order to improve process eff ciency and minimise operational risks. However, it is di fficult to eliminate all process risks during the process design stage due to the fact that processes often run in complex and changeable environments and rely on human resources. Timely identification of process risks is crucial in order to insure the achievement of process goals. Business processes are often supported by information systems that record information about their executions in event logs. In this article we present an approach and a supporting tool for the evaluation of the overall process risk and for the prediction of process outcomes based on the analysis of information recorded in event logs. It can help managers evaluate the overall risk exposure of their business processes, track the evolution of overall process risk, identify changes and predict process outcomes based on the current value of overall process risk. The approach was implemented and validated using synthetic event logs and through a case study with a real event log.

Common Alzheimer's disease risk variant within the CLU gene affects white matter microstructure in young adults

There is a strong genetic risk for late-onset Alzheimer's disease (AD), but so far few gene variants have been identified that reliably contribute to that risk. A newly confirmed genetic risk allele C of the clusterin (CLU) gene variant rs11136000 is carried by ~88% of Caucasians. The C allele confers a 1.16 greater odds of developing late-onset AD than the T allele. AD patients have reductions in regional white matter integrity. We evaluated whether the CLU risk variant was similarly associated with lower white matter integrity in healthy young humans. Evidence of early brain differences would offer a target for intervention decades before symptom onset. We scanned 398 healthy young adults (mean age, 23.6 ± 2.2 years) with diffusion tensor imaging, a variation of magnetic resonance imaging sensitive to white matter integrity in the living brain. We assessed genetic associations using mixed-model regression at each point in the brain to map the profile of these associations with white matter integrity. Each C allele copy of the CLUvariant was associated with lower fractional anisotropy-a widely accepted measure of white matter integrity-in multiple brain regions, including several known to degenerate in AD. These regions included the splenium of the corpus callosum, the fornix, cingulum, and superior and inferior longitudinal fasciculi in both brain hemispheres. Young healthy carriers of the CLU gene risk variant showed a distinct profile of lower white matter integrity that may increase vulnerability to developing AD later in life.

Alzheimer's disease risk gene, GAB2, is associated with regional brain volume differences in 755 young healthy twins

The development of late-onset Alzheimer's disease (LOAD) is under strong genetic control and there is great interest in the genetic variants that confer increased risk. The Alzheimer's disease risk gene, growth factor receptor bound protein 2-associated protein (GAB2), has been shown to provide a 1.27- 1.51 increased odds of developing LOAD for rs7101429 major allele carriers, in case-control analysis. GAB2 is expressed across the brain throughout life, and its role in LOAD pathology is well understood. Recent studies have begun to examine the effect of genetic variation in the GAB2 gene on differences in the brain. However, the effect of GAB2 on the young adult brain has yet to be considered. Here we found a significant association between the GAB2 gene and morphological brain differences in 755 young adult twins (469 females) (M = 23.1, SD = 3.1 years), using a gene-based test with principal components regression (PCReg). Detectable differences in brain morphology are therefore associated with variation in the GAB2 gene, even in young adults, long before the typical age of onset of Alzheimer's disease.