Modelling risk at low exposure railway level crossings : supporting an argument for low-cost level crossing warning devices with lower levels of safety integrity

This paper describes a risk model for estimating the likelihood of collisions at low-exposure railway level crossings, demonstrating the effect that differences in safety integrity can have on the likelihood of a collision. The model facilitates the comparison of safety benefits between level crossings with passive controls (stop or give-way signs) and level crossings that have been hypothetically upgraded with conventional or low-cost warning devices. The scenario presented illustrates how treatment of a cross-section of level crossings with low cost devices can provide a greater safety benefit compared to treatment with conventional warning devices for the same budget.

A meta-analysis of pigmentary characteristics, sun sensitivity, freckling and melanocytic nevi and risk of basal cell carcinoma of the skin

Objective: To calculate pooled risk estimates of the association between pigmentary characteristics and basal cell carcinoma (BCC) of the skin. Methods: We searched three electronic databases and reviewed the reference lists of the retrieved articles until July 2012 to identify eligible epidemiologic studies. Eligible studies were those published in between 1965 and July 2012 that permitted quantitative assessment of the association between histologically-confirmed BCC and any of the following characteristics: hair colour, eye colour, skin colour, skin phototype, tanning and burning ability, and presence of freckling or melanocytic nevi. We included 29 studies from 2236 initially identified. We calculated summary odds ratios (ORs) using weighted averages of the log OR, using random effects models. Results: We found strongest associations with red hair (OR 2.02; 95% CI: 1.68, 2.44), fair skin colour (OR 2.11; 95% CI: 1.56, 2.86), and having skin that burns and never tans (OR 2.03; 95% CI: 1.73, 2.38). All other factors had weaker but positive associations with BCC, with the exception of freckling of the face in adulthood which showed no association. Conclusions: Although most studies report risk estimates that are in the same direction, there is significant heterogeneity in the size of the estimates. The associations were quite modest and remarkably similar, with ORs between about 1.5 and 2.5 for the highest risk level for each factor. Given the public health impact of BCC, this meta-analysis will make a valuable contribution to our understanding of BCC.

Fraud risk and the visibility of carbon

In recent years, carbon has been increasingly rendered ‘visible’ both discursively and through political processes that have imbued it with economic value. Greenhouse gas (GHG) emissions have been constructed as social and environmental costs and their reduction or avoidance as social and economic gain. The ‘marketisation’ of carbon, which has been facilitated through various compliance schemes such as the European Union Emissions Trading Scheme (EU ETS), the Kyoto Protocol, the proposed Australian Emissions Reduction Scheme and through the voluntary carbon credit market, have attempted to bring carbon into the ‘foreground’ as an economic liability and/or opportunity. Accompanying the increasing economic visibility of carbon are reports of frauds and scams – the ‘gaming of carbon markets’(Chan 2010). As Lohmann (2010: 21) points out, ‘what are conventionally classed as scams or frauds are an inevitable feature of carbon offset markets, not something that could be eliminated by regulation targeting the specific businesses or state agencies involved’. This paper critiques the disparate discourses of fraud risk in carbon markets and examines cases of fraud within emerging landscapes of green criminology.

An envirogenomic signature is associated with risk of IBD-related surgery in a population-based Crohn’s Disease cohort

BACKGROUND AND AIMS: Crohn's disease (CD) is an inflammatory bowel disease (IBD) caused by a combination of genetic, clinical, and environmental factors. Identification of CD patients at high risk of requiring surgery may assist clinicians to decide on a top-down or step-up treatment approach. METHODS: We conducted a retrospective case-control analysis of a population-based cohort of 503 CD patients. A regression-based data reduction approach was used to systematically analyse 63 genomic, clinical and environmental factors for association with IBD-related surgery as the primary outcome variable. RESULTS: A multi-factor model was identified that yielded the highest predictive accuracy for need for surgery. The factors included in the model were the NOD2 genotype (OR = 1.607, P = 2.3 × 10(-5)), having ever had perianal disease (OR = 2.847, P = 4 × 10(-6)), being post-diagnosis smokers (OR = 6.312, P = 7.4 × 10(-3)), being an ex-smoker at diagnosis (OR = 2.405, P = 1.1 × 10(-3)) and age (OR = 1.012, P = 4.4 × 10(-3)). Diagnostic testing for this multi-factor model produced an area under the curve of 0.681 (P = 1 × 10(-4)) and an odds ratio of 3.169, (95 % CI P = 1 × 10(-4)) which was higher than any factor considered independently. CONCLUSIONS: The results of this study require validation in other populations but represent a step forward in the development of more accurate prognostic tests for clinicians to prescribe the most optimal treatment approach for complicated CD patients.

Epistatic effects of potassium channel variation on cardiac repolarization and atrial fibrillation risk

Objectives The aim of this study was to evaluate the role of cardiac K+ channel gene variants in families with atrial fibrillation (AF). Background The K+ channels play a major role in atrial repolarization but single mutations in cardiac K+ channel genes are infrequently present in AF families. The collective effect of background K+ channel variants of varying prevalence and effect size on the atrial substrate for AF is largely unexplored. Methods Genes encoding the major cardiac K+ channels were resequenced in 80 AF probands. Nonsynonymous coding sequence variants identified in AF probands were evaluated in 240 control subjects. Novel variants were characterized using patch-clamp techniques and in silico modeling was performed using the Courtemanche atrial cell model. Results Nineteen nonsynonymous variants in 9 genes were found, including 11 rare variants. Rare variants were more frequent in AF probands (18.8% vs. 4.2%, p < 0.001), and the mean number of variants was greater (0.21 vs. 0.04, p < 0.001). The majority of K+ channel variants individually had modest functional effects. Modeling simulations to evaluate combinations of K+ channel variants of varying population frequency indicated that simultaneous small perturbations of multiple current densities had nonlinear interactions and could result in substantial (>30 ms) shortening or lengthening of action potential duration as well as increased dispersion of repolarization. Conclusions Families with AF show an excess of rare functional K+ channel gene variants of varying phenotypic effect size that may contribute to an atrial arrhythmogenic substrate. Atrial cell modeling is a useful tool to assess epistatic interactions between multiple variants.

Modeling the cumulative genetic risk for multiple sclerosis from genome-wide association data

Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.

Single nucleotide polymorphism in hsa-mir-196a-2 and breast cancer risk : a case control study

microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic groups.

Variants in the human potassium channel gene (KCNN3) are associated with migraine in a high risk genetic isolate

The calcium-activated potassium ion channel gene (KCNN3) is located in the vicinity of the familial hemiplegic migraine type 2 locus on chromosome 1q21.3. This gene is expressed in the central nervous system and plays a role in neural excitability. Previous association studies have provided some, although not conclusive, evidence for involvement of this gene in migraine susceptibility. To elucidate KCNN3 involvement in migraine, we performed gene-wide SNP genotyping in a high-risk genetic isolate from Norfolk Island, a population descended from a small number of eighteenth century Isle of Man ‘Bounty Mutineer’ and Tahitian founders. Phenotype information was available for 377 individuals who are related through the single, well-defined Norfolk pedigree (96 were affected: 64 MA, 32 MO). A total of 85 SNPs spanning the KCNN3 gene were genotyped in a sub-sample of 285 related individuals (76 affected), all core members of the extensive Norfolk Island ‘Bounty Mutineer’ genealogy. All genotyping was performed using the Illumina BeadArray platform. The analysis was performed using the statistical program SOLAR v4.0.6 assuming an additive model of allelic effect adjusted for the effects of age and sex. Haplotype analysis was undertaken using the program HAPLOVIEW v4.0. A total of four intronic SNPs in the KCNN3 gene displayed significant association (P < 0.05) with migraine. Two SNPs, rs73532286 and rs6426929, separated by approximately 0.1 kb, displayed complete LD (r 2 = 1.00, D′ = 1.00, D′ 95% CI = 0.96–1.00). In all cases, the minor allele led to a decrease in migraine risk (beta coefficient = 0.286–0.315), suggesting that common gene variants confer an increased risk of migraine in the Norfolk pedigree. This effect may be explained by founder effect in this genetic isolate. This study provides evidence for association of variants in the KCNN3 ion channel gene with migraine susceptibility in the Norfolk genetic isolate with the rarer allelic variants conferring a possible protective role. This the first comprehensive analysis of this potential candidate gene in migraine and also the first study that has utilised the unique Norfolk Island large pedigree isolate to implicate a specific migraine gene. Studies of additional variants in KCNN3 in the Norfolk pedigree are now required (e.g. polyglutamine variants) and further analyses in other population data sets are required to clarify the association of the KCNN3 gene and migraine risk in the general outbred population.

Examining the stability of transport behaviours for high-risk early adolescents

Transport related injury is a leading cause of death and disability for adolescents and represents a substantial burden on public health and the community as a whole. Adolescents appear to have a growing risk of harm due to the co-existence of increasing alcohol use and engagement in risky transport behaviours. Understanding more about the development and stability of these behaviours by young adolescents over time could be beneficial in targeting transport injury prevention interventions for high-risk adolescents. In Australia alcohol use begins to increase significantly through the early and middle adolescent years even though the majority of these young people are still in school. Aim This paper reports on changes over a six month period in alcohol use, anger management experiences and transport risk taking behaviours including riding a bicycle without a helmet and under-age driving for high-risk adolescents and non high-risk early adolescents. Year 9 students (N=1,005) from 20 schools in Queensland, Australia completed a baseline survey in the first half of 2012 and at a six month follow up. Respondents at both times were asked about their engagement in risk taking behaviours measured by Mak’s adolescent delinquency scale, which included five transport related items. They were also asked to rate their alcohol use for the preceding three month period. The stability of these risk taking indicators was measured by comparing baseline results with the six month follow up. Results High-risk adolescents were more likely to report change in their alcohol use and transport behaviours when compared with non high-risk adolescents over a six month period. There were no significant changes in control of anger for either group. Demographic characteristics were not shown to have any significant effect on the stability of risk indicators for high-risk adolescents and non high-risk adolescents. Differences were found in the stability of risk taking indicators for high-risk adolescents and non high-risk adolescents. The findings of this paper have implications in targeting transport risk behaviour change interventions to meet the needs of high-risk adolescents.

Outdoor worker sun protection project : a comprehensive applied research project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviour practices 2010 – 2013

The QUT Outdoor Worker Sun Protection (OWSP) project undertook a comprehensive applied health promotion project to demonstrate the effectiveness of sun protection measures which influence high risk outdoor workers in Queensland to adopt sun safe behaviours. The three year project (2010-2013) was driven by two key concepts: 1) The hierarchy of control, which is used to address risks in the workplace, advocates for six control measures that need to be considered in order of priority (refer to Section 3.4.2); and 2) the Ottawa Charter which recommends five action means to achieve health promotion (refer to Section 2.1). The project framework was underpinned by a participatory action research approach that valued peoples’ input, took advantage of existing skills and resources, and stimulated innovation (refer to Section 4.2). Fourteen workplaces (small and large) with a majority outdoor workforce were recruited across regional Queensland (Darling Downs, Northwest, Mackay and Cairns) from four industries types: 1) building and construction, 2) rural and farming, 3) local government, and 4) public sector. A workplace champion was identified at each workplace and was supported (through resource provision, regular contact and site visits) over a 14 to 18 month intervention period to make sun safety a priority in their workplace. Employees and employers were independently assessed for pre- and postintervention sun protection behaviours. As part of the intervention, an individualised sun safety action plan was developed in conjunction with each workplace to guide changes across six key strategy areas including: 1) Policy (e.g., adopt sun safety practices during all company events); 2) Structural and environmental (e.g., shade on worksites; eliminate or minimise reflective surfaces); 3) Personal protective equipment (PPE) (e.g., trial different types of sunscreens, or wide-brimmed hats); 4) Education and awareness (e.g., include sun safety in inductions and toolbox talks; send reminder emails or text messages to workers);5) Role modelling (e.g., by managers, supervisors, workplace champions and mentors); and 6) Skin examinations (e.g., allow time off work for skin checks). The participatory action process revealed that there was no “one size fits all” approach to sun safety in the workplace; a comprehensive, tailored approach was fundamental. This included providing workplaces with information, resources, skills, know how, incentives and practical help. For example, workplaces engaged in farming complete differing seasonal tasks across the year and needed to prepare for optimal sun safety of their workers during less labour intensive times. In some construction workplaces, long pants were considered a trip hazard and could not be used as part of a PPE strategy. Culture change was difficult to achieve and workplace champions needed guidance on the steps to facilitate this (e.g., influencing leaders through peer support, mentoring and role modelling). With the assistance of the project team the majority of workplaces were able to successfully implement the sun safety strategies contained within their action plans, up skilling them in the evidence for sun safety, how to overcome barriers, how to negotiate with all relevant parties and assess success. The most important enablers to the implementation of a successful action plan were a pro-active workplace champion, strong employee engagement, supportive management, the use of highly visual educational resources, and external support (provided by the project team through regular contact either directly through phone calls or indirectly through emails and e-newsletters). Identified barriers included a lack of time, the multiple roles of workplace champions, (especially among smaller workplaces), competing issues leading to a lack of priority for sun safety, the culture of outdoor workers, and costs or budgeting constraints. The level of sun safety awareness, knowledge, and sun protective behaviours reported by the workers increased between pre-and post-intervention. Of the nine sun protective behaviours that were assessed, the largest changes reported included a 26% increase in workers who “usually or always” wore a broad-brimmed hat, a 20% increase in the use of natural shade, a 19% increase in workers wearing long-sleeved collared shirts, and a 16% increase in workers wearing long trousers.

What are the offence and offender risk factors for Indigenous repeat drink drivers in Queensland Australia?

Background Road crashes contribute to high injury rates in Indigenous population in Aust, NZ, Canada and USA Alcohol one of the leading risk factors for road crashes: 31.5% Indigenous drivers in remote areas over 0.05mg/100ml, compared to 7.4 percent of non-Indigenous counterparts 17.5% Indigenous drivers in regional areas over 0.05mg/100ml compared to 3.8 percent of non-Indigenous counterparts Indigenous peoples are overrepresented in alcohol-related fatality rates, with this group 40% more likely to be killed

Fresh frozen cadavers as a tool to educate student paramedics in procedural skills

Objectives – To describe the development of an educational workshop to develop procedural skills in undergraduate Paramedic students using fresh frozen cadavers and to report the student’s assessment of the program. Methods – A six-hour anatomy based workshop was developed using fresh frozen cadavers to teach a range of airway and invasive procedural skills to second year undergraduate paramedic students. Embedded QUAN (qual) methodology will be utilised to evaluate the student’s satisfaction, perception and quality of teaching as compared to other existing clinical teaching techniques such as high fidelity simulation. Students will be asked to complete an anonymous validated survey (10 questions formulated on a 5 point Likert scale) and provide a qualitative feedback pre and post the six-hour workshop. Results – This is a prospective study planned for September 2013. Low-risk human research ethics are being sought. Teaching evaluation results from the inaugural 2012 workshop (undergraduate and postgraduate Paramedic students) and interim results for 2013 will be presented. Conclusions – Clinical teaching using fresh frozen cadavers thus far has predominately been used in the education of medical and surgical trainees. A number of studies have found them to be effective and in some cases superior to traditional high fidelity simulation teaching strategies. Fresh frozen cadavers are said to provide perfect anatomy, normal tissue consistency and a realistic operative training experience (Lloyd, Maxwell-Armstrong et al. 2011). The authors believe that this study will show that the use of fresh frozen cadavers offers a safe and effective mode to teach procedural skills to student paramedics that will help bridge the skills gap and increase confidence prior to students undertaking such interventions on living patients. A modified training program may be formulated for general practitioners undertaking Emergency Medicine Advanced Rural Skills.

Principal component and linkage analysis of cardiovascular risk traits in the Norfolk isolate

OBJECTIVE(S): An individual's risk of developing cardiovascular disease (CVD) is influenced by genetic factors. This study focussed on mapping genetic loci for CVD-risk traits in a unique population isolate derived from Norfolk Island. METHODS: This investigation focussed on 377 individuals descended from the population founders. Principal component analysis was used to extract orthogonal components from 11 cardiovascular risk traits. Multipoint variance component methods were used to assess genome-wide linkage using SOLAR to the derived factors. A total of 285 of the 377 related individuals were informative for linkage analysis. RESULTS: A total of 4 principal components accounting for 83% of the total variance were derived. Principal component 1 was loaded with body size indicators; principal component 2 with body size, cholesterol and triglyceride levels; principal component 3 with the blood pressures; and principal component 4 with LDL-cholesterol and total cholesterol levels. Suggestive evidence of linkage for principal component 2 (h(2) = 0.35) was observed on chromosome 5q35 (LOD = 1.85; p = 0.0008). While peak regions on chromosome 10p11.2 (LOD = 1.27; p = 0.005) and 12q13 (LOD = 1.63; p = 0.003) were observed to segregate with principal components 1 (h(2) = 0.33) and 4 (h(2) = 0.42), respectively. CONCLUSION(S): This study investigated a number of CVD risk traits in a unique isolated population. Findings support the clustering of CVD risk traits and provide interesting evidence of a region on chromosome 5q35 segregating with weight, waist circumference, HDL-c and total triglyceride levels.

Linkage mapping of CVD risk traits in the isolated Norfolk Island population

To understand the underlying genetic architecture of cardiovascular disease (CVD) risk traits, we undertook a genome-wide linkage scan to identify CVD quantitative trait loci (QTLs) in 377 individuals from the Norfolk Island population. The central aim of this research focused on the utilization of a genetically and geographically isolated population of individuals from Norfolk Island for the purposes of variance component linkage analysis to identify QTLs involved in CVD risk traits. Substantial evidence supports the involvement of traits such as systolic and diastolic blood pressures, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, body mass index and triglycerides as important risk factors for CVD pathogenesis. In addition to the environmental inXuences of poor diet, reduced physical activity, increasing age, cigarette smoking and alcohol consumption, many studies have illustrated a strong involvement of genetic components in the CVD phenotype through family and twin studies. We undertook a genome scan using 400 markers spaced approximately 10 cM in 600 individuals from Norfolk Island. Genotype data was analyzed using the variance components methods of SOLAR. Our results gave a peak LOD score of 2.01 localizing to chromosome 1p36 for systolic blood pressure and replicated previously implicated loci for other CVD relevant QTLs.

Genetic polymorphisms in DPF3 associated with risk of breast cancer and lymph node metastases

Background Several studies have identified rare genetic variations responsible for many cases of familial breast cancer but their contribution to total breast cancer incidence is relatively small. More common genetic variations with low penetrance have been postulated to account for a higher proportion of the population risk of breast cancer. Methods and Results In an effort to identify genes that influence non-familial breast cancer risk, we tested over 25,000 single nucleotide polymorphisms (SNPs) located within approximately 14,000 genes in a large-scale case-control study in 254 German women with breast cancer and 268 age-matched women without malignant disease. We identified a marker on chromosome 14q24.3-q31.1 that was marginally associated with breast cancer status (OR = 1.5, P = 0.07). Genotypes for this SNP were also significantly associated with indicators of breast cancer severity, including presence of lymph node metastases ( P = 0.006) and earlier age of onset ( P = 0.01). The association with breast cancer status was replicated in two independent samples (OR = 1.35, P = 0.05). High-density association fine mapping showed that the association spanned about 80 kb of the zinc-finger gene DPF3 (also known as CERD4 ). One SNP in intron 1 was found to be more strongly associated with breast cancer status in all three sample collections (OR = 1.6, P = 0.003) as well as with increased lymph node metastases ( P = 0.01) and tumor size ( P = 0.01). Conclusion Polymorphisms in the 5' region of DPF3 were associated with increased risk of breast cancer development, lymph node metastases, age of onset, and tumor size in women of European ancestry. This large-scale association study suggests that genetic variation in DPF3 contributes to breast cancer susceptibility and severity.