Mapping eQTLs in the Norfolk Island genetic isolate identifies candidate genes for CVD risk traits

Cardiovascular disease (CVD) affects millions of people worldwide and is influenced by numerous factors, including lifestyle and genetics. Expression quantitative trait loci (eQTLs) influence gene expression and are good candidates for CVD risk. Founder-effect pedigrees can provide additional power to map genes associated with disease risk. Therefore, we identified eQTLs in the genetic isolate of Norfolk Island (NI) and tested for associations between these and CVD risk factors. We measured genome-wide transcript levels of blood lymphocytes in 330 individuals and used pedigree-based heritability analysis to identify heritable transcripts. eQTLs were identified by genome-wide association testing of these transcripts. Testing for association between CVD risk factors (i.e., blood lipids, blood pressure, and body fat indices) and eQTLs revealed 1,712 heritable transcripts (p < 0.05) with heritability values ranging from 0.18 to 0.84. From these, we identified 200 cis-acting and 70 trans-acting eQTLs (p < 1.84 × 10(-7)) An eQTL-centric analysis of CVD risk traits revealed multiple associations, including 12 previously associated with CVD-related traits. Trait versus eQTL regression modeling identified four CVD risk candidates (NAAA, PAPSS1, NME1, and PRDX1), all of which have known biological roles in disease. In addition, we implicated several genes previously associated with CVD risk traits, including MTHFR and FN3KRP. We have successfully identified a panel of eQTLs in the NI pedigree and used this to implicate several genes in CVD risk. Future studies are required for further assessing the functional importance of these eQTLs and whether the findings here also relate to outbred populations.

Root caries patterns and risk factors of middle-aged and elderly people in China

The objectives of this study were to describe root caries patterns of Chinese adults and to analyze the effect of selected demographic and socioeconomic factors on these patterns. A total sample of 1080 residents aged 35-44-years-old and 1080 residents aged 65-74-years-old from three urban and three rural survey sites in Hubei Province participated in both an oral health interview and a clinical oral health examination. Root surface caries prevalence rates were 13.1% in the middle-aged group and 43.9% in the elderly group. The mean number of teeth affected by caries in the middle-aged group was reported at 0.21 and 1.0 in the elderly group. Mean Root Caries Index (RCI) scores of the middle-aged were reported at 6.29 and elderly subjects were reported at 11.95. Elderly people living in rural areas reported a higher RCI score (13.24) than those living in urban areas (10.70). A significantly higher frequency of root surface caries was observed in elderly participants (P < 0.001, OR = 3.80) and ethnic minorities (P < 0.001, OR = 1.93). In addition, smokers, nontea drinkers, and those with an annual household income of 10,000 yuan or less tended to have higher caries prevalence. RCI figures for the different tooth types ranged from 1% to 16%, indicating a wide variation in attack rates. In conclusion, our study suggests that root surface caries occurrence is high among the Chinese adult population, especially older adults. With an increasing number of retained teeth in both middle-aged and elderly people, root caries is a growing disease in the People's Republic of China which deserves more attention in future research.

Molecular profiling of human mammary gland links breast cancer risk to a p27(+) cell population with progenitor characteristics

Early full-term pregnancy is one of the most effective natural protections against breast cancer. To investigate this effect, we have characterized the global gene expression and epigenetic profiles of multiple cell types from normal breast tissue of nulliparous and parous women and carriers of BRCA1 or BRCA2 mutations. We found significant differences in CD44+ progenitor cells, where the levels of many stem cell-related genes and pathways, including the cell-cycle regulator p27, are lower in parous women without BRCA1/BRCA2 mutations. We also noted a significant reduction in the frequency of CD44+p27+ cells in parous women and showed, using explant cultures, that parity-related signaling pathways play a role in regulating the number of p27+ cells and their proliferation. Our results suggest that pathways controlling p27+ mammary epithelial cells and the numbers of these cells relate to breast cancer risk and can be explored for cancer risk assessment and prevention.

Aligning off-balance sheet risk, on-balance sheet risk and audit fees: a PLS path modelling analysis

This study focuses on using the partial least squares (PLS) path modelling technique in archival auditing research by replicating the data and research questions from prior bank audit fee studies. PLS path modelling allows for inter-correlations among audit fee determinants by establishing latent constructs and multiple relationship paths in one simultaneous PLS path model. Endogeneity concerns about auditor choice can also be addressed with PLS path modelling. With a sample of US bank holding companies for the period 2003-2009, we examine the associations among on-balance sheet financial risks, off-balance sheet risks and audit fees, and also address the pervasive client size effect, and the effect of the self-selection of auditors. The results endorse the dominating effect of size on audit fees, both directly and indirectly via its impacts on other audit fee determinants. By simultaneously considering the self-selection of auditors, we still find audit fee premiums on Big N auditors, which is the second important factor on audit fee determination. On-balance-sheet financial risk measures in terms of capital adequacy, loan composition, earnings and asset quality performance have positive impacts on audit fees. After allowing for the positive influence of on-balance sheet financial risks and entity size on off-balance sheet risk, the off-balance sheet risk measure, SECRISK, is still positively associated with bank audit fees, both before and after the onset of the financial crisis. The consistent results from this study compared with prior literature provide supporting evidence and enhance confidence on the application of this new research technique in archival accounting studies.

Aligning off-balance sheet risk, on-balance sheet risk and audit fees: a PLS path modelling analysis

This study focuses on using the partial least squares (PLS) path modelling methodology in archival auditing research by replicating the data and research questions from prior bank audit fee studies. PLS path modelling allows for inter-correlations among audit fee determinants by establishing latent constructs and multiple relationship paths in one simultaneous PLS path model. Endogeneity concerns about auditor choice can also be addressed with PLS path modelling. With a sample of US bank holding companies for the period 2003-2009, we examine the associations among on-balance sheet financial risks, off-balance sheet risks and audit fees, and also address the pervasive client size effect, and the effect of the self-selection of auditors. The results endorse the dominating effect of size on audit fees, both directly and indirectly via its impacts on other audit fee determinants. By simultaneously considering the self-selection of auditors, we still find audit fee premiums on Big N auditors, which is the second important factor on audit fee determination. On-balance-sheet financial risk measures in terms of capital adequacy, loan composition, earnings and asset quality performance have positive impacts on audit fees. After allowing for the positive influence of on-balance sheet financial risks and entity size on off-balance sheet risk, the off-balance sheet risk measure, SECRISK, is still positively associated with bank audit fees, both before and after the onset of the financial crisis. The consistent results from this study compared with prior literature provide supporting evidence and enhance confidence on the application of this new research technique in archival accounting studies.

Herpes simplex 2 risk among women in a polygynous setting in rural West Africa

OBJECTIVES: To determine risk factors for herpes simplex 2 (HSV2) infection in women in a polygynous rural Gambian population. METHODS: Data from women who participated in a cross-sectional survey of reproductive health were matched to their own and, for women who had been or were married (ever-married), their spouses' data collected in a cross-sectional survey of fertility interests, including information on marital histories. RESULTS: Data were available on 150 never-married and 525 ever-married women. HSV2 prevalence was 16% amongst never-married women and 36% amongst ever-married women. For ever-married women, their own personal characteristics (age, ethnicity and genital cutting status) and events from their husbands' marriage history were important determinants of HSV2 infection. Women whose husbands married for the first time over age 35 were at greater risk than women whose husbands married by age 24 [odds ratio (OR) 2.72, 95% confidence interval (CI) 1.20-6.10]. Women whose husband reported interest in a new marriage were more likely to be HSV2 positive (OR 1.91, 95% CI 1.18-3.09). Women whose husbands were currently monogamous but had had previous marriages (OR 2.76, 95% CI 1.30-5.88) and women in currently polygynous marriages (OR 2.88, 95% CI 1.66-5.01) were three times as likely to be HSV2 positive as women who were their husband's only wife ever. CONCLUSION: Much transmission of HSV2 in this setting occurs within marriage where opportunity for personal protection is limited. High levels of transmission within marriage may undermine the impact of sexual behaviour change programmes aiming to reduce HSV2 and HIV incidence and complicate their evaluation.

A comparison of factors influencing perceived risk by French and Australian cyclists and drivers

Differences in the levels of risk perceived by cyclists and car drivers may contribute to the dangers in their interactions. Levels of perceived risk have been shown to vary according to personal and environmental factors and between countries. Cycling rates in France are higher than in Australia, particularly among women. This study investigated whether cultural differences between France and Australia are reflected in perceived risks for experienced adult cyclists and drivers in the two countries. In online surveys, regular cyclists (France 336, Australia 444) and drivers (France 92, Australia 151) were asked to rate the level of risk in six situations: failure to yield; going through a red light; not signalling when turning; swerving; tail-gating; and not checking traffic. The effects of type of interacting vehicle and participant type on perceived risk were similar in France and Australia. However, the influence of responsibility for the risky behaviour differed according to participant type, type of situation and nationality. When the bicycle rider committed the road rule violation, Australian cyclists and drivers gave higher risk ratings than French cyclists and drivers. In both countries, cyclists rated themselves significantly higher than drivers on the perceived control and overconfidence subscales of the perceived skill measure. The French cyclists rated themselves higher than Australian cyclists on these scales, which could be responsible for overall lower perceived risk levels when interacting with a bike. Australian cyclists rated themselves significantly lower than drivers on the incompetence subscale but French cyclists rated themselves higher than drivers. In both countries incompetence scores were positively related to levels of perceived risk. Weekly time was associated with perceived risk in Australia but not in France. Frequency of traffic violations was not associated with perceived risk in either country. In conclusion, levels of perceived risk differed between drivers and cyclists in both countries and were influenced by type of interacting vehicle, experience and perceived skill. However, some differences between the results from the two countries merit further investigation to shed light on potential improvements in safety and cycling participation.

Eccentric hamstring strength and hamstring injury risk in Australian footballers

Purpose Is eccentric hamstring strength and between limb imbalance in eccentric strength, measured during the Nordic hamstring exercise, a risk factor for hamstring strain injury (HSI)? Methods Elite Australian footballers (n=210) from five different teams participated. Eccentric hamstring strength during the Nordic was taken at the commencement and conclusion of preseason training and in season. Injury history and demographic data were also collected. Reports on prospectively occurring HSIs were completed by team medical staff. Relative risk (RR) was determined for univariate data and logistic regression was employed for multivariate data. Results Twenty-eight HSIs were recorded. Eccentric hamstring strength below 256N at the start of preseason and 279N at the end of preseason increased risk of future HSI 2.7 (relative risk, 2.7; 95% confidence interval, 1.3 to 5.5; p = 0.006) and 4.3 fold (relative risk, 4.3; 95% confidence interval, 1.7 to 11.0; p = 0.002) respectively. Between limb imbalance in strength of greater than 10% did not increase the risk of future HSI. Univariate analysis did not reveal a significantly greater relative risk for future HSI in athletes who had sustained a lower limb injury of any kind within the last 12 months. Logistic regression revealed interactions between both athlete age and history of HSI with eccentric hamstring strength, whereby the likelihood of future HSI in older athletes or athletes with a history of HSI was reduced if an athlete had high levels of eccentric strength. Conclusion Low levels of eccentric hamstring strength increased the risk of future HSI. Interaction effects suggest that the additional risk of future HSI associated with advancing age or previous injury was mitigated by higher levels of eccentric hamstring strength.

An integrated modeling and risk analysis tool for mine water interactions

Poor mine water management can lead to corporate, environmental and social risks. These risks become more pronounced as mining operations move into areas of water scarcity and/or increase climatic variability while also managing increased demand, lower ore grades and increased strip ratios. Therefore, it is vital that mine sites better understand these risks in order to implement management practices to address them. Systems models provide an effective approach to understand complex networks, particularly across multiple scales. Previous work has represented mine water interactions using systems model on a mine site scale. Here, we expand on that work by present an integrated tool that uses a systems modeling approach to represent mine water interactions on a site and regional scale and then analyses the risks associated with events stemming from those interactions. A case study is presented to represent three indicative corporate, environmental and social risks associated with a mine site that exists in a water scarce region. The tool is generic and flexible, and can be used in many scenarios to provide significant potential utility to the mining industry.

Assessment of Geogenic Contaminants in Water Co-Produced with Coal Seam Gas Extraction in Queensland, Australia : Implications for Human Health Risk

Organic compounds in Australian coal seam gas produced water (CSG water) are poorly understood despite their environmental contamination potential. In this study, the presence of some organic substances is identified from government-held CSG water-quality data from the Bowen and Surat Basins, Queensland. These records revealed the presence of polycyclic aromatic hydrocarbons (PAHs) in 27% of samples of CSG water from the Walloon Coal Measures at concentrations <1 µg/L, and it is likely these compounds leached from in situ coals. PAHs identified from wells include naphthalene, phenanthrene, chrysene and dibenz[a,h]anthracene. In addition, the likelihood of coal-derived organic compounds leaching to groundwater is assessed by undertaking toxicity leaching experiments using coal rank and water chemistry as variables. These tests suggest higher molecular weight PAHs (including benzo[a]pyrene) leach from higher rank coals, whereas lower molecular weight PAHs leach at greater concentrations from lower rank coal. Some of the identified organic compounds have carcinogenic or health risk potential, but they are unlikely to be acutely toxic at the observed concentrations which are almost negligible (largely due to the hydrophobicity of such compounds). Hence, this study will be useful to practitioners assessing CSG water related environmental and health risk.

AR and gamification concepts to reduce driver boredom and risk taking behaviours

Young males are over-represented in road crashes. Part of the problem is their proneness to boredom, a hardwired personality factor that can lead to risky driving. This paper presents a theoretical understanding of boredom in the driving context and demonstrates convincing arguments to investigate the role of boredom further. Specifically, this paper calls for the design of innovative technologies and applications that make safe driving more pleasurable and stimulating for young males, e.g., by applying gamification techniques. We propose two design concepts through the following questions: A. Can the simulation of risky driving reduce actual risky driving? B. Can the replacement of risky driving stimuli with alternative stimuli reduce risky driving? We argue that considering these questions in the future design of automotive user-interfaces and personal ubiquitous computing devices could effectively reduce risky driving behaviours among young males.

The impact of litigation risk on the strategic timing of management earnings forecasts

This paper examines whether managers strategically time their earnings forecasts (MEFs) as litigation risk increases. We find as litigation risk increases, the propensity to release a delayed forecast until after the market is closed (AMC) or a Friday decreases but not proportionally more for bad news than for good news. Host costly this behaviour is to investors is questionable as share price returns do not reveal any under-reaction to strategically timed bad news MEF released AMC. We also find evidence consistent with managers timing their MEFs during a natural no-trading period to better disseminate information.

Continuing to drive while sleepy : the influence of sleepiness countermeasures, motivation for driving sleepy, and risk perception

Driver sleepiness is a major contributor to road crashes. The current study sought to examine the association between perceptions of effectiveness of six sleepiness countermeasures and their relationship with self-reports of continuing to drive while sleepy among 309 drivers after controlling for the influence of age, sex, motivation for driving sleepy, and risk perception of sleepy driving. The results demonstrate that the variables of age, sex, motivation, and risk perception were significantly associated with self-reports of continuing to drive while sleepy and only one countermeasure was associated with self-reports of continuing to drive while sleepy. Further, it was found that age differences in self-reports of continuing to drive while sleepy was mediated by participants’ motivation and risk perception. These findings highlight modifiable factors that could be focused on with interventions that seek to modify drivers’ attitudes and behaviours of driving while sleepy.

Community engagement for disaster resilience : flood risk management in Jakarta, Indonesia

Understanding dynamics of interactions between community groups and government agencies is crucial to improve community resilience for flood risk reduction through effective community engagement strategies. Overall, a variety of approaches are available, however they are limited in their application. Based on research of a case study in Kampung Melayu Village in Jakarta, further complexity in engaging community emerges in planning policy which requires the relocation of households living in floodplains. This complexity arises in decision-making processes due to barriers to communication. This obstacle highlights the need for a simplified approach for an effective flood risk management which will be further explored in this paper. Qualitative analyses will be undertaken following semi-structured interviews conducted with key actors within government agencies, non-governmental organisations (NGOs), and representatives of communities. The analyses involve investigation of barriers and constraints on community engagement in flood risk management, particularly relevant to collaboration mechanism, perception of risk, and technical literacy to flood risk. These analyses result in potential redirection of community consultation strategies to lead to a more effective collaboration among stakeholders in the decision-making processes. As a result, greater effectiveness in plan implementation of flood risk management potentially improves disaster resilience in the future.