Fine-mapping identifies multiple prostate cancer risk loci on 5p15 some associating with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease.

Modification of advanced programmatic risk analysis and management model for the whole project life cycle’s risks

The advanced programmatic risk analysis and management model (APRAM) is one of the recently developed methods that can be used for risk analysis and management purposes considering schedule, cost, and quality risks simultaneously. However, this model considers those failure risks that occur only over the design and construction phases of a project’s life cycle. While it can be sufficient for some projects for which the required cost during the operating life is much less than the budget required over the construction period, it should be modified in relation to infrastructure projects because the associated costs during the operating life cycle are significant. In this paper, a modified APRAM is proposed, which can consider potential risks that might occur over the entire life cycle of the project, including technical and managerial failure risks. Therefore, the modified model can be used as an efficient decision-support tool for construction managers in the housing industry in which various alternatives might be technically available. The modified method is demonstrated by using a real building project, and this demonstration shows that it can be employed efficiently by construction managers. The Delphi method was applied in order to figure out the failure events and their associated probabilities. The results show that although the initial cost of a cold-formed steel structural system is higher than a conventional construction system, the former’s failure cost is much lower than the latter’s

Does fundamental indexation lead to better risk-adjusted returns? New evidence from Australian Securities Exchange

We investigate the claims of superiority of fundamental indexation strategy over capitalisation-weighted indexation by using data for Australian Securities Exchange (ASX) listed stocks. Whilst our results are in line with the outperformance observed in other geographical markets, we find that the excess returns from fundamental indexation in Australian market are much higher. On a rolling 5-year basis, the fundamental index always outperforms the capitalisation-weighted index. Our results suggest that superior performance of fundamental indexation could not be entirely attributed to value, size, or momentum effects. The outperformance persists even after adjusting for slightly higher transaction costs related to turnover.

The financial life well-lived: psychological benefits of financial planning

As the financial planning industry undergoes a series of reforms aimed at increased professionalism and improved quality of advice, financial planner training in Australia and elsewhere has begun to acknowledge the importance of interdisciplinary knowledge bases in informing both curriculum design and professoinal practice (e.g. FPA2009). This paper underscores the importance of the process of financial planning by providing a conceptual analysis of the six step financial planning process using key mechanisms derived from theory and research in cognate disciplines such as psychology and well-being. The paper identifies how these mechanisms may operate to impact client well-being in the financial planning context. The conceptual mapping of th emechanisms to process elements of financial planning is a unique contribution to the financial planning literature and offers a further framework in the armamentarium of researchers interested in pursuing questions around the value of financial planning. The conceptual framework derived from the analysis also adds to the growing body of literature aimed at developing an integrated model of financial planning.

Managing the health effects of temperature in response to climate change : challenges ahead

BACKGROUND: Although many studies have shown that high temperatures are associated with an increased risk of mortality and morbidity, there has been little research on managing the process of planned adaptation to alleviate the health effects of heat events and climate change. In particular, economic evaluation of public health adaptation strategies has been largely absent from both the scientific literature and public policy discussion. OBJECTIVES: his paper aims to discuss how public health organizations should implement adaptation strategies, and how to improve the evidence base for policies to protect health from heat events and climate change. DISCUSSION: Public health adaptation strategies to cope with heat events and climate change fall into two categories: reducing the heat exposure and managing the health risks. Strategies require a range of actions, including timely public health and medical advice, improvements to housing and urban planning, early warning systems, and the assurance that health care and social systems are ready to act. Some of these actions are costly, and the implementation should be based on the cost-effectiveness analysis given scarce financial resources. Therefore, research is required not only on the temperature-related health costs, but also on the costs and benefits of adaptation options. The scientific community must ensure that the health co-benefits of climate change policies are recognized, understood and quantified. CONCLUSIONS: The integration of climate change adaptation into current public health practice is needed to ensure they increase future resilience. The economic evaluation of temperature-related health costs and public health adaptation strategies are particularly important for policy decisions.

Risk factors for moderate and severe microbial keratitis in daily wear contact lens users

Objective: To establish risk factors for moderate and severe microbial keratitis among daily contact lens (CL) wearers in Australia. Design: A prospective, 12-month, population-based, case-control study. Participants: New cases of moderate and severe microbial keratitis in daily wear CL users presenting in Australia over a 12-month period were identified through surveillance of all ophthalmic practitioners. Case detection was augmented by record audits at major ophthalmic centers. Controls were users of daily wear CLs in the community identified using a national telephone survey. Testing: Cases and controls were interviewed by telephone to determine subject demographics and CL wear history. Multiple binary logistic regression was used to determine independent risk factors and univariate population attributable risk percentage (PAR%) was estimated for each risk factor.; Main Outcome Measures: Independent risk factors, relative risk (with 95% confidence intervals [CIs]), and PAR%. Results: There were 90 eligible moderate and severe cases related to daily wear of CLs reported during the study period. We identified 1090 community controls using daily wear CLs. Independent risk factors for moderate and severe keratitis while adjusting for age, gender, and lens material type included poor storage case hygiene 6.4× (95% CI, 1.9-21.8; PAR, 49%), infrequent storage case replacement 5.4× (95% CI, 1.5-18.9; PAR, 27%), solution type 7.2× (95% CI, 2.3-22.5; PAR, 35%), occasional overnight lens use (<1 night per week) 6.5× (95% CI, 1.3-31.7; PAR, 23%), high socioeconomic status 4.1× (95% CI, 1.2-14.4; PAR, 31%), and smoking 3.7× (95% CI, 1.1-12.8; PAR, 31%). Conclusions: Moderate and severe microbial keratitis associated with daily use of CLs was independently associated with factors likely to cause contamination of CL storage cases (frequency of storage case replacement, hygiene, and solution type). Other factors included occasional overnight use of CLs, smoking, and socioeconomic class. Disease load may be considerably reduced by attention to modifiable risk factors related to CL storage case practice.

A comparison of perceived crash risk among cyclists and drivers in Brisbane

The Queensland Government has implemented strategies promoting a shift from individual car use to active transport, a transition which requires drivers to adapt to sharing the road with increased numbers of people cycling through transport network. For this to occur safely, changes in both road infrastructure and road user expectations and behaviors will be needed. Creating separate cycle infrastructure does not remove the need for cyclists to commence, cross or finish travel on shared roads. Currently intersections are one of the predominant shared road spaces where crashes result in cyclists being injured or killed. This research investigates how Brisbane cyclists and drivers perceive risk when interacting with other road users at intersections. The current study replicates a French study conducted by co-authors Chaurand and Delhomme in 2011 and extends it to assess gender effects which have been reported in other Australian cycling research. An online survey was administered to experienced cyclists and drivers. Participants rated the level of risk they felt when imagining a number of different road situations. Based on the earlier French study it is expected that perceived crash risk will be influenced both by the participant’s mode of travel and the type of interacting vehicle and perceived risk will be greater when the interaction is with a car than a bicycle. It is predicted that risk perception will decrease as the level of experience increases and that male participants will have a higher perception of skill and lower perception of risk than females. The findings of this Queensland study will provide a valuable insight into perceived risk and the traffic behaviours of drivers and cyclists when interacting with other road users and results will be available for presentation at the Congress.

Genetic association of the KLK4 locus with risk of prostate cancer

The Kallikrein-related peptidase, KLK4, has been shown to be significantly overexpressed in prostate tumours in numerous studies and is suggested to be a potential biomarker for prostate cancer. KLK4 may also play a role in prostate cancer progression through its involvement in epithelial-mesenchymal transition, a more aggressive phenotype, and metastases to bone. It is well known that genetic variation has the potential to affect gene expression and/or various protein characteristics and hence we sought to investigate the possible role of single nucleotide polymorphisms (SNPs) in the KLK4 gene in prostate cancer. Assessment of 61 SNPs in the KLK4 locus (±10 kb) in approximately 1300 prostate cancer cases and 1300 male controls for associations with prostate cancer risk and/or prostate tumour aggressiveness (Gleason score <7 versus ≥7) revealed 7 SNPs to be associated with a decreased risk of prostate cancer at the Ptrend<0.05 significance level. Three of these SNPs, rs268923, rs56112930 and the HapMap tagSNP rs7248321, are located several kb upstream of KLK4; rs1654551 encodes a non-synonymous serine to alanine substitution at position 22 of the long isoform of the KLK4 protein, and the remaining 3 risk-associated SNPs, rs1701927, rs1090649 and rs806019, are located downstream of KLK4 and are in high linkage disequilibrium with each other (r2≥0.98). Our findings provide suggestive evidence of a role for genetic variation in the KLK4 locus in prostate cancer predisposition.

Inflammation, hepatic enzymes and resistance training in individuals with metabolic risk factors

AIMS: Increases in inflammatory markers, hepatic enzymes and physical inactivity are associated with the development of the metabolic syndrome (MetS). We examined whether inflammatory markers and hepatic enzymes are correlated with traditional risk factors for MetS and studied the effects of resistance training (RT) on these emerging risk factors in individuals with a high number of metabolic risk factors (HiMF, 2.9 +/- 0.8) and those with a low number of metabolic risk factors (LoMF, 0.5 +/- 0.5). METHODS: Twenty-eight men and 27 women aged 50.8 +/- 6.5 years (mean +/- sd) participated in the study. Participants were randomized to four groups, HiMF training (HiMFT), HiMF control (HiMFC), LoMF training (LoMFT) and LoMF control (LoMFC). Before and after 10 weeks of RT [3 days/week, seven exercises, three sets with intensity gradually increased from 40-50% of one repetition maximum (1RM) to 75-85% of 1RM], blood samples were obtained for the measurement of pro-inflammatory cytokines, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT). RESULTS: At baseline, HiMF had higher interleukin-6 (33.9%), CRP (57.1%), GGT (45.2%) and ALT (40.6%) levels, compared with LoMF (all P < 0.05). CRP, GGT and ALT correlated with the number of risk factors (r = 0.48, 0.51 and 0.57, respectively, all P < 0.01) and with other anthropometric and clinical measures (r range from 0.26 to 0.60, P < 0.05). RT did not significantly alter inflammatory markers or hepatic enzymes (all P > 0.05). CONCLUSIONS: HiMF was associated with increased inflammatory markers and hepatic enzyme concentrations. RT did not reduce inflammatory markers and hepatic enzymes in individuals with HiMF.

When financial incentives do more good than harm : a checklist

Financial incentives can sometimes improve the quality of clinical practice, but they may also be an expensive distraction. Paul Glasziou and colleagues have devised a checklist to help prevent their premature or inappropriate implementation

Real-time risk monitoring in business processes : a sensor-based approach

This article proposes an approach for real-time monitoring of risks in executable business process models. The approach considers risks in all phases of the business process management lifecycle, from process design, where risks are defined on top of process models, through to process diagnosis, where risks are detected during process execution. The approach has been realized via a distributed, sensor-based architecture. At design-time, sensors are defined to specify risk conditions which when fulfilled, are a likely indicator of negative process states (faults) to eventuate. Both historical and current process execution data can be used to compose such conditions. At run-time, each sensor independently notifies a sensor manager when a risk is detected. In turn, the sensor manager interacts with the monitoring component of a business process management system to prompt the results to process administrators who may take remedial actions. The proposed architecture has been implemented on top of the YAWL system, and evaluated through performance measurements and usability tests with students. The results show that risk conditions can be computed efficiently and that the approach is perceived as useful by the participants in the tests.

Can a community pharmacy sleep assessment tool aid the identification of patients at risk of sleep disorders in the community : a pilot study

Background: When experiencing sleep problems for the first time, consumers may often approach community pharmacists for advice as they are easily accessible health care professionals in the community. In Australian community pharmacies there are no specific tools available for use by pharmacists to assist with the assessment and handling of consumers with sleep enquiries. Objective: To assess the feasibility of improving the detection of sleep disorders within the community through the pilot of a newly developed Community Pharmacy Sleep Assessment Tool (COP-SAT). Method: The COP-SAT was designed to incorporate elements from a number of existing, standardized, and validated clinical screening measures. The COP-SAT was trialed in four Australian community pharmacies over a 4-week period. Key findings: A total of 241 community pharmacy consumers were assessed using the COP-SAT. A total of 74 (30.7%) were assessed as being at risk of insomnia, 26 (10.7%) were at risk of daytime sleepiness, 19 (7.9%) were at risk of obstructive sleep apnea, and 121 (50.2%) were regular snorers. A total of 116 (48.1%) participants indicated that they consume caffeine before bedtime, of which 55 (47%) had associated symptoms of sleep onset insomnia. Moreover, 85 (35%) consumed alcohol before bedtime, of which 50 (58%) experienced fragmented sleep, 50 (58%) were regular snorers, and nine (10.6%) had apnea symptoms. The COP-SAT was feasible in the community pharmacy setting. The prevalence of sleep disorders in the sampled population was high, but generally consistent with previous studies on the general population. Conclusion: A large proportion of participants reported sleep disorder symptoms, and a link was found between the consumption of alcohol and caffeine substances at bedtime and associated symptoms. While larger studies are needed to assess the clinical properties of the tool, the results of this feasibility study have demonstrated that the COP-SAT may be a practical tool for the identification of patients at risk of developing sleep disorders in the community.

Pilot evaluation of an adolescent risk and injury prevention programme incorporating curriculum and school connectedness components

School connectedness is an important protective factor for adolescent risk-taking behaviour. This study examined a pilot version of the Skills for Preventing Injury in Youth (SPIY) programme, combining teacher professional development for increasing school connectedness (connectedness component) with a risk and injury prevention curriculum for early adolescents (curriculum component). A process evaluation was conducted on the connectedness component, involving assessments of programme reach, participant receptiveness and initial use, and a preliminary impact evaluation was conducted on the combined connectedness and curriculum programme. The connectedness component was well received by teacher participants, who saw benefits for both themselves and their students. Classroom observation also showed that teachers who received professional development made use of the programme strategies. Grade 8 students who participated in the SPIY programme were less likely to report violent behaviour at six-month follow-up than were control students, and trends also suggested reduced transport injuries. The results of this research support the use of the combined SPIY connectedness and curriculum components in a large-scale effectiveness trial to assess the impact of the programme on students’ connectedness, risk-taking and associated injuries.