Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript

Abstract Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P = 3.9 × 10−22). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P = 1.9 × 10−34). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk.

When non-significance may be significant : lessons learned from a study of the development, implementation and evaluation of a fleet risk assessment tool

This paper reports on the development and implementation of a self-report risk assessment tool that was developed in an attempt to increase the efficacy of crash prediction within Australian fleet settings. This study forms a part of a broader program of research into work related road safety and identification of driving risk. The first phase of the study involved a series of focus groups being conducted with 217 professional drivers which revealed that the following factors were proposed to influence driving performance: Fatigue, Knowledge of risk, Mood, Impatience and frustration, Speed limits, Experience, Other road users, Passengers, Health, and Culture. The second phase of the study involved piloting the newly developed 38 item Driving Risk Assessment Scale - Work Version (DRAS-WV) with 546 professional drivers. Factor analytic techniques identified a 9 factor solution that was comprised of speeding, aggression, time pressure, distraction, casualness, awareness, maintenance, fatigue and minor damage. Speeding and aggressive driving manoeuvres were identified to be the most frequent aberrant driving behaviours engaged in by the sample. However, a series of logistic regression analyses undertaken to determine the DRAS-WV scale’s ability to predict self-reported crashes revealed limited predictive efficacy e.g., 10% of crashes. This paper outlines proposed reasons for this limited predictive ability of the DRAS-WV as well as provides suggestions regarding the future of research that aims to develop methods to identify “at risk” drivers.

The health and cost implications of high body mass index in Australian Defence Force personnel.

BACKGROUND: Frequent illness and injury among workers with high body mass index (BMI) can raise the costs of employee healthcare and reduce workforce maintenance and productivity. These issues are particularly important in vocational settings such as the military, which require good physical health, regular attendance and teamwork to operate efficiently. The purpose of this study was to compare the incidence of injury and illness, absenteeism, productivity, healthcare usage and administrative outcomes among Australian Defence Force personnel with varying BMI. METHODS: Personnel were grouped into cohorts according to the following ranges for (BMI): normal (18.5-24.9 kg/m²; n = 197), overweight (25-29.9 kg/m²; n = 154) and obese (≥30 kg/m²) with restricted body fat (≤28 % for females, ≤24 % for males) (n = 148) and with no restriction on body fat (n = 180). Medical records for each individual were audited retrospectively to record the incidence of injury and illness, absenteeism, productivity, healthcare usage (i.e., consultation with medical specialists, hospital stays, medical investigations, prescriptions) and administrative outcomes (e.g., discharge from service) over one year. These data were then grouped and compared between the cohorts. RESULTS: The prevalence of injury and illness, cost of medical specialist consultations and cost of medical scans were all higher (p <0.05) in both obese cohorts compared with the normal cohort. The estimated productivity losses from restricted work days were also higher (p <0.05) in the obese cohort with no restriction on body fat compared with the normal cohort. Within the obese cohort, the prevalence of injury and illness, healthcare usage and productivity were not significantly greater in the obese cohort with no restriction on body fat compared with the cohort with restricted body fat. The number of restricted work days, the rate of re-classification of Medical Employment Classification and the rate of discharge from service were similar between all four cohorts. CONCLUSIONS: High BMI in the military increases healthcare usage, but does not disrupt workforce maintenance. The greater prevalence of injury and illness, greater healthcare usage and lower productivity in obese Australian Defence Force personnel is not related to higher levels of body fat.

A left realist approach to antifeminist fathers’ rights groups

Despite earlier critiques of left realists’ failure to adequately address feminist concerns, recent left realist theorizing and empirical research have made valuable contributions to the understanding of woman abuse and other forms of gendered violence. Left realism has further potential to contribute to the criminological understanding of woman abuse and its contributing socioeconomic and cultural contexts. This article describes left realists’ early efforts to include gender in analyses of crime. It then summarizes feminist critiques of left realism and reviews the work that has responded to them. Drawing upon two prominent strands of feminist left realist theorizing about violence and gender, the paper proposes a preliminary left realist theory of antifeminist fathers’ rights group activism. It then outlines a provisional research agenda on antifeminist fathers’ rights groups, and proposes short and long term policies and practices to enhance the safety of abused mothers and their children following divorce or separation.

Foot pain and functional limitation in healthy adults with hallux valgus : a cross-sectional study

Background Hallux valgus (HV) is a very common deformity of the first metatarsophalangeal joint that often requires surgical correction. However, the association between structural HV deformity and related foot pain and disability is unclear. Furthermore, no previous studies have investigated concerns about appearance and difficulty with footwear in a population with HV not seeking surgical correction. The aim of this cross-sectional study was to investigate foot pain, functional limitation, concern about appearance and difficulty with footwear in otherwise healthy adults with HV compared to controls. Methods Thirty volunteers with HV (radiographic HV angle >15 degrees) and 30 matched controls were recruited for this study (50 women, 10 men; mean age 44.4 years, range 20 to 76 years). Differences between groups were examined for self-reported foot pain and disability, satisfaction with appearance, footwear difficulty, and pressure-pain threshold at the first metatarsophalangeal joint. Functional measures included balance tests, walking performance, and hallux muscle strength (abduction and plantarflexion). Mean differences (MD) and 95% confidence intervals (CI) were calculated. Results All self-report measures showed that HV was associated with higher levels of foot pain and disability and significant concerns about appearance and footwear (p < 0.001). Lower pressure-pain threshold was measured at the medial first metatarsophalangeal joint in participants with HV (MD = -133.3 kPa, CI: -251.5 to -15.1). Participants with HV also showed reduced hallux plantarflexion strength (MD = -37.1 N, CI: -55.4 to -18.8) and abduction strength (MD = -9.8 N, CI: -15.6 to -4.0), and increased mediolateral sway when standing with both feet with eyes closed (MD = 0.34 cm, CI: 0.04 to 0.63). Conclusions These findings show that HV negatively impacts on self-reported foot pain and function, and concerns about foot appearance and footwear in otherwise healthy adults. There was also evidence of impaired hallux muscle strength and increased postural sway in HV subjects compared to controls, although general physical functioning and participation in physical activity were not adversely affected.

Inhaled particle counts on bicycle commute routes of low and high proximity to motorised traffic

Frequent exposure to ultrafine particles (UFP) is associated with detrimental effects on cardiopulmonary function and health. UFP dose and therefore the associated health risk are a factor of exposure frequency, duration, and magnitude of (therefore also proximity to) a UFP emission source. Bicycle commuters using on-road routes during peak traffic times are sharing a microenvironment with high levels of motorised traffic, a major UFP emission source. Inhaled particle counts were measured along popular pre-identified bicycle commute route alterations of low (LOW) and high (HIGH) motorised traffic to the same inner-city destination at peak commute traffic times. During commute, real-time particle number concentration (PNC; mostly in the UFP range) and particle diameter (PD), heart and respiratory rate, geographical location, and meteorological variables were measured. To determine inhaled particle counts, ventilation rate was calculated from heart-rate-ventilation associations, produced from periodic exercise testing. Total mean PNC of LOW (compared to HIGH) was reduced (1.56 x e4 ± 0.38 x e4 versus 3.06 x e4 ± 0.53 x e4 ppcc; p = 0.012). Total estimated ventilation rate did not vary significantly between LOW and HIGH (43 ± 5 versus 46 ± 9 L•min; p = 0.136); however, due to total mean PNC, accumulated inhaled particle counts were 48% lower in LOW, compared to HIGH (7.6 x e8 ± 1.5 x e8 versus 14.6 x e8 ± 1.8 x e8; p = 0.003). For bicycle commuting at peak morning commute times, inhaled particle counts and therefore cardiopulmonary health risk may be substantially reduced by decreasing exposure to motorised traffic, which should be considered by both bicycle commuters and urban planners.

A limb lost every 3 hours: can Australia reduce amputations in people with diabetes?

Recommendations to improve national diabetes-related foot disease (DRFD) care • National data collection on incidence and outcomes of DRFD. • Improved access to care, through the Medicare Benefits Schedule, for people with diabetes who have a current or past foot complication. • Standardised national model for interdisciplinary DRFD care. • National accreditation of interdisciplinary foot clinics and staff. • Subsidies for evidence-based treatments for DRFD, including medical-grade footwear and pressure off-loading devices. • Holistic diabetes care initiatives to “close the gap” on inequities in health outcomes for Aboriginal and Torres Strait Islander peoples.

Australian Diabetes Foot Network : management of diabetes-related foot ulceration — a clinical update

Summary Appropriate assessment and management of diabetes-related foot ulcers (DRFUs) is essential to reduce amputation risk. Management requires debridement, wound dressing, pressure off-loading, good glycaemic control and potentially antibiotic therapy and vascular intervention. As a minimum, all DRFUs should be managed by a doctor and a podiatrist and/or wound care nurse. Health professionals unable to provide appropriate care for people with DRFUs should promptly refer individuals to professionals with the requisite knowledge and skills. Indicators for immediate referral to an emergency department or multidisciplinary foot care team (MFCT) include gangrene, limb-threatening ischaemia, deep ulcers (bone, joint or tendon in the wound base), ascending cellulitis, systemic symptoms of infection and abscesses. Referral to an MFCT should occur if there is lack of wound progress after 4 weeks of appropriate treatment.

What are the key conditions associated with lower limb amputations in a major Australian teaching hospital?

Background Lower extremity amputation results in significant global morbidity and mortality. Australia appears to have a paucity of studies investigating lower extremity amputation. The primary aim of this retrospective study was to investigate key conditions associated with lower extremity amputations in an Australian population. Secondary objectives were to determine the influence of age and sex on lower extremity amputations, and the reliability of hospital coded amputations. Methods: Lower extremity amputation cases performed at the Princess Alexandra Hospital (Brisbane, Australia) between July 2006 and June 2007 were identified through the relevant hospital discharge dataset (n = 197). All eligible clinical records were interrogated for age, sex, key condition associated with amputation, amputation site, first ever amputation status and the accuracy of the original hospital coding. Exclusion criteria included records unavailable for audit and cases where the key condition was unable to be determined. Chi-squared, t-tests, ANOVA and post hoc tests were used to determine differences between groups. Kappa statistics were used to measure reliability between coded and audited amputations. A minimum significance level of p < 0.05 was used throughout. Results: One hundred and eighty-six cases were eligible and audited. Overall 69% were male, 56% were first amputations, 54% were major amputations, and mean age was 62 ± 16 years. Key conditions associated included type 2 diabetes (53%), peripheral arterial disease (non-diabetes) (18%), trauma (8%), type 1 diabetes (7%) and malignant tumours (5%). Differences in ages at amputation were associated with trauma 36 ± 10 years, type 1 diabetes 52 ± 12 years and type 2 diabetes 67 ± 10 years (p < 0.01). Reliability of original hospital coding was high with Kappa values over 0.8 for all variables. Conclusions: This study, the first in over 20 years to report on all levels of lower extremity amputations in Australia, found that people undergoing amputation are more likely to be older, male and have diabetes. It is recommended that large prospective studies are implemented and national lower extremity amputation rates are established to address the large preventable burden of lower extremity amputation in Australia.

Lost and found : improving ascertainment of refugee-background Australians in population datasets

Humanitarian entrants remain invisible in existing populations datasets, and this has significant implications for health care and health policy. We suggest adding 'year of arrival' to population datasets; enabling the combination of 'country of birth' and 'year of arrival' to be used as a proxy for refugee status.

Insights into the role and function of L2, the minor capsid protein of papillomaviruses

Human papillomaviruses (HPV) are responsible for the most common human sexually transmitted viral infections, and high-risk types are responsible for causing cervical and other cancers. The minor capsid protein L2 of HPV plays important roles in virus entry into cells, localisation of viral components to the nucleus, in DNA binding, capsid formation and stability. It also elicits antibodies that are more cross-reactive between HPV types than does the major capsid protein L1, making it an attractive potential target for new-generation, more broadly protective subunit vaccines against HPV infections. However, its low abundance in natural capsids-12-72 molecules per 360 copies of L1-limits its immunogenicity. This review will explore the biological roles of the protein, and prospects for its use in new vaccines. © 2009 Springer-Verlag.

Who succeeds at university? factors predicting academic performance in first year Australian university students

With the increasing diversity of students attending university, there is a growing interest in the factors predicting academic performance. This study is a prospective investigation of the academic, psychosocial, cognitive, and demographic predictors of academic performance of first year Australian university students. Questionnaires were distributed to 197 first year students 4 to 8 weeks prior to the end of semester exams and overall grade point averages were collected at semester completion. Previous academic performance was identified as the most significant predictor of university performance. Integration into university, self efficacy, and employment responsibilities were also predictive of university grades. Identifying the factors that influence academic performance can improve the targeting of interventions and support services for students at risk of academic problems.

Brokering innovation to better leverage R&D investment

What is the contribution of innovation brokers in leveraging research and development (R&D) investment to enhance industry-wide capabilities? The case of the Australian Cooperative Research Centre for Construction Innovation (CRC CI) is considered in the context of motivating supply chain firms to improve their organizational capabilities in order to acquire, assimilate, transfer and exploit R&D outcomes to their advantage, and to create broader industry and national benefits. A previous audit and analysis has shown an increase in business R&D investment since 2001. The role of the CRC CI in contributing to growth in the absorptive capacity of the Australian construction industry as a whole is illustrated through two programmes: digital modelling building information modelling (BIM) and construction site safety. Numerous positive outcomes in productivity, quality, improved safety and competitiveness were achieved between 2001 and 2009.

(Re)visioning the centre : education reform and the “ideal” citizen of the future

Discourses of public education reform, like that exemplified within the Queensland Government’s future vision document, Queensland State Education-2010 (QSE-2010), position schooling as a panacea to pervasive social instability and a means to achieve a new consensus. However, in unravelling the many conflicting statements that conjoin to form education policy and inform related literature (Ball, 1993), it becomes clear that education reform discourse is polyvalent (Foucault, 1977). Alongside visionary statements that speak of public education as a vehicle for social justice are the (re)visionary or those reflecting neoliberal individualism and a conservative politics. In this paper, it is argued that the latter coagulate to form strategic discursive practices which work to (re)secure dominant relations of power. Further, discussion of the characteristics needed by the “ideal” future citizen of Queensland reflect efforts to ‘tame change through the making of the child’ (Popkewitz, 2004, p.201). The casualties of this (re)vision and the refusal to investigate the pathologies of “traditional” schooling are the children who, for whatever reason, do not conform to the norm of the desired school child as an “ideal” citizen-in-the-making and who become relegated to alternative educational settings.