The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

Molecular characterisation of environmental enterococci derived from water samples and assessment of associated public health hazards

Enterococci are versatile Gram-positive bacteria that can survive under extreme conditions. Most enterococci are non-virulent and found in the gastrointestinal tract of humans and animals. Other strains are opportunistic pathogens that contribute to a large number of nosocomial infections globally. Epidemiological studies demonstrated a direct relationship between the density of enterococci in surface waters and the risk of swimmer-associated gastroenteritis. The distribution of infectious enterococcal strains from the hospital environment or other sources to environmental water bodies through sewage discharge or other means, could increase the prevalence of these strains in the human population. Environmental water quality studies may benefit from focusing on a subset of Enterococcus spp. that are consistently associated with sources of faecal pollution such as domestic sewage, rather than testing for the entire genus. E. faecalis and E. faecium are potentially good focal species for such studies, as they have been consistently identified as the dominant Enterococcus spp. in human faeces and sewage. On the other hand enterococcal infections are predominantly caused by E. faecalis and E. faecium. The characterisation of E. faecalis and E. faecium is important in studying their population structures, particularly in environmental samples. In developing and implementing rapid, robust molecular genotyping techniques, it is possible to more accurately establish the relationship between human and environmental enterococci. Of particular importance, is to determine the distribution of high risk enterococcal clonal complexes, such as E. faecium clonal complex 17 and E. faecalis clonal complexes 2 and 9 in recreational waters. These clonal complexes are recognized as particularly pathogenic enterococcal genotypes that cause severe disease in humans globally. The Pimpama-Coomera watershed is located in South East Queensland, Australia and was investigated in this study mainly because it is used intensively for agriculture and recreational purposes and has a strong anthropogenic impact. The primary aim of this study was to develop novel, universally applicable, robust, rapid and cost effective genotyping methods which are likely to yield more definitive results for the routine monitoring of E. faecalis and E. faecium, particularly in environmental water sources. To fullfill this aim, new genotyping methods were developed based on the interrogation of highly informative single nucleotide polymorphisms (SNPs) located in housekeeping genes of both E. faecalis and E. faecium. SNP genotyping was successfully applied in field investigations of the Coomera watershed, South-East Queensland, Australia. E. faecalis and E. faecium isolates were grouped into 29 and 23 SNP profiles respectively. This study showed the high longitudinal diversity of E. faecalis and E. faecium over a period of two years, and both human-related and human-specific SNP profiles were identified. Furthermore, 4.25% of E. faecium strains isolated from water was found to correspond to the important clonal complex-17 (CC17). Strains that belong to CC17 cause the majority of hospital outbreaks and clinical infections globally. Of the six sampling sites of the Coomera River, Paradise Point had the highest number of human-related and human-specific E. faecalis and E. faecium SNP profiles. The secondary aim of this study was to determine the antibiotic-resistance profiles and virulence traits associated with environmental E. faecalis and E. faecium isolates compared to human pathogenic E. faecalis and E. faecium isolates. This was performed to predict the potential health risks associated with coming into contact with these strains in the Coomera watershed. In general, clinical isolates were found to be more resistant to all the antibiotics tested compared to water isolates and they harbored more virulence traits. Multi-drug resistance was more prevalent in clinical isolates (71.18% of E. faecalis and 70.3 % of E. faecium) compared to water isolates (only 5.66 % E. faecium). However, tetracycline, gentamicin, ciprofloxacin and ampicillin resistance was observed in water isolates. The virulence gene esp was the most prevalent virulence determinant observed in clinical isolates (67.79% of E. faecalis and 70.37 % of E. faecium), and this gene has been described as a human-specific marker used for microbial source tracking (MST). The presence of esp in water isolates (16.36% of E. faecalis and 19.14% of E. faecium) could be indicative of human faecal contamination in these waterways. Finally, in order to compare overall gene expression between environmental and clinical strains of E. faecalis, a comparative gene hybridization study was performed. The results of this investigation clearly demonstrated the up-regulation of genes associated with pathogenicity in E. faecalis isolated from water. The expression study was performed at physiological temperatures relative to ambient temperatures. The up-regulation of virulence genes demonstrates that environmental strains of E. faecalis can pose an increased health risk which can lead to serious disease, particularly if these strains belong to the virulent CC17 group. The genotyping techniques developed in this study not only provide a rapid, robust and highly discriminatory tool to characterize E. faecalis and E. faecium, but also enables the efficient identification of virulent enterococci that are distributed in environmental water sources.

Effects of enhanced somatosensory information on postural stability in older people and people with Parkinson’s disease

The somatosensory system plays an important role in balance control and age-related changes to this system have been implicated in falls. Parkinson’s disease (PD) is a chronic and progressive disease of the brain, characterized by postural instability and gait disturbance. Previous research has shown that deficiencies in somatosensory feedback may contribute to the poorer postural control demonstrated by PD individuals. However, few studies have comprehensively explored differences in somatosensory function and postural control between PD participants and healthy older individuals. The soles of the feet contain many cutaneous mechanoreceptors that provide important somatosensory information sources for postural control. Different types of insole devices have been developed to enhance this somatosensory information and improve postural stability, but these devices are often too complex and expensive to integrate into daily life. Textured insoles provide a more passive intervention that may be an inexpensive and accessible means to enhance the somatosensory input from the plantar surface of the feet. However, to date, there has been little work conducted to test the efficacy of enhanced somatosensory input induced by textured insoles in both healthy and PD populations during standing and walking. Therefore, the aims of this thesis were to determine: 1) whether textured insole surfaces can improve postural stability by enhancing somatosensory information in younger and older adults, 2) the differences between healthy older participants and PD participants for measures of physiological function and postural stability during standing and walking, 3) how changes in somatosensory information affect postural stability in both groups during standing and walking; and 4), whether textured insoles can improve postural stability in both groups during standing and walking. To address these aims, Study 1 recruited seven older individuals and ten healthy young controls to investigate the effects of two textured insole surfaces on postural stability while performing standing balance tests on a force plate. Participants were tested under three insole surface conditions: 1) barefoot; 2) standing on a hard textured insole surface; and 3), standing on a soft textured insole surface. Measurements derived from the centre of pressure displacement included the range of anterior-posterior and medial-lateral displacement, path length and the 90% confidence elliptical area (C90 area). Results of study 1 revealed a significant Group*Surface*Insole interaction for the four measures. Both textured insole surfaces reduced postural sway for the older group, especially in the eyes closed condition on the foam surface. However, participants reported that the soft textured insole surface was more comfortable and, hence, the soft textured insoles were adopted for Studies 2 and 3. For Study 2, 20 healthy older adults (controls) and 20 participants with Parkinson’s disease were recruited. Participants were evaluated using a series of physiological assessments that included touch sensitivity, vibratory perception, and pain and temperature threshold detection. Furthermore, nerve function and somatosensory evoked potentials tests were utilized to provide detailed information regarding peripheral nerve function for these participants. Standing balance and walking were assessed on different surfaces using a force plate and the 3D Vicon motion analysis system, respectively. Data derived from the force plate included the range of anterior-posterior and medial-lateral sway, while measures of stride length, stride period, cadence, double support time, stance phase, velocity and stride timing variability were reported for the walking assessment. The results of this study demonstrated that the PD group had decrements in somatosensory function compared to the healthy older control group. For electrodiagnosis, PD participants had poorer nerve function than controls, as evidenced by slower nerve conduction velocities and longer latencies in sural nerve and prolonged latency in the P37 somatosensory evoked potential. Furthermore, the PD group displayed more postural sway in both the anterior-posterior and medial-lateral directions relative to controls and these differences were increased when standing on a foam surface. With respect to the gait assessment, the PD group took shorter strides and had a reduced stride period compared with the control group. Furthermore, the PD group spent more time in the stance phase and had increased cadence and stride timing variability than the controls. Compared with walking on the firm surface, the two groups demonstrated different gait adaptations while walking on the uneven surface. Controls increased their stride length and stride period and decreased their cadence, which resulted in a consistent walking velocity on both surfaces. Conversely, while the PD patients also increased their stride period and decreased their cadence and stance period on the uneven surface, they did not increase their stride length and, hence walked slower on the uneven surface. In the PD group, there was a strong positive association between decreased somatosensory function and decreased clinical balance, as assessed by the Tinetti test. Poorer somatosensory function was also strongly positively correlated with the temporospatial gait parameters, especially shorter stride length. Study 3 evaluated the effects of manipulating the somatosensory information from the plantar surface of the feet using textured insoles in the same populations assessed in Study 2. For this study, participants performed the standing and walking balance tests under three footwear conditions: 1) barefoot; 2) with smooth insoles; and 3), with textured insoles. Standing balance and walking were evaluated using a force plate and a Vicon motion analysis system and the data were analysed in the same way outlined for Study 2. The findings showed that the smooth and textured insoles caused different effects on postural control during both the standing and walking trials. Both insoles decreased medial-lateral sway to the same level on the firm surface. The greatest benefits were observed in the PD group while wearing the textured insole. When standing under a more challenging condition on the foam surface with eyes closed, only the textured insole decreased medial-lateral sway in the PD group. With respect to the gait trials, both insoles increased walking velocity, stride length and stride time and decreased cadence, but these changes were more pronounced for the textured insoles. The effects of the textured insoles were evident under challenging conditions in the PD group and increased walking velocity and stride length, while decreasing cadence. Textured insoles were also effective in reducing the time spent in the double support and stance phases of the gait cycle and did not increase stride timing variability, as was the case for the smooth insoles for the PD group. The results of this study suggest that textured insoles, such as those evaluated in this research, may provide a low-cost means of improving postural stability in high-risk groups, such as people with PD, which may act as an important intervention to prevent falls.

Quantity of documentation of maltreatment risk factors in injury-related paediatric hospitalisations

Background While child maltreatment is recognised as a global problem, solid epidemiological data on the prevalence of child maltreatment and risk factors associated with child maltreatment is lacking in Australia and internationally. There have been recent calls for action to improve the evidence-base capturing and describing child abuse, particularly those data captured within the health sector. This paper describes the quantity of documentation of maltreatment risk factors in injury-related paediatric hospitalisations in Queensland, Australia. Methods This study involved a retrospective medical record review, text extraction and coding methodology to assess the quantity of documentation of risk factors and the subsequent utility of data in hospital records for describing child maltreatment and data linkage to Child Protection Service (CPS). Results There were 433 children in the maltreatment group and 462 in the unintentional injury group for whom medical records could be reviewed. Almost 93% of the any maltreatment code sample, but only 11% of the unintentional injury sample had documentation identified indicating the presence of any of 20 risk factors. In the maltreatment group the most commonly documented risk factor was history of abuse (41%). In those with an unintentional injury, the most commonly documented risk factor was alcohol abuse of the child or family (3%). More than 93% of the maltreatment sample also linked to a child protection record. Of concern are the 16% of those children who linked to child protection who did not have documented risk factors in the medical record. Conclusion Given the importance of the medical record as a source of information about children presenting to hospital for treatment and as a potential source of evidence for legal action the lack of documentation is of concern. The details surrounding the injury admission and consideration of any maltreatment related risk factors, both identifying their presence and ruling them out are required for each and every case. This highlights the need for additional training for clinicians to understand the importance of their documentation in child injury cases.

Charitable grants and donations from maching gaming sources : Does it all work out in the wash up?

Material for this paper comes partly from a report commissioned by the Department of Family Services, Aboriginal and Islander Affairs. The report is the result of a multi-strategy research project designed to assess the impact of gaming machines on the fundraising capacity of charitable and community organisations in Queensland. The first Queensland gaming machine was commissioned on 11 February 1992. By 30 November 1994 there were: · 636 clubs operating 13,162 gaming machines · 436 hotels/taverns operating 3,468 gaming machines.1 It was anticipated that the introduction of gaming machines would impact on charities and community organisations. The adverse impacts would be through competition with charity gaming and disposable income that might otherwise be directed towards donations. Some also expressed concern that charities would be relied on to finance social services for problem gamblers. This paper seeks to describe the donations and grants derived by charities from Gaming Machine revenues. Such revenues primarily come from either government distributions from its gaming machine taxes and levies or gaming machine club donations. A final comment is made on the opinions of charitable fundraising professionals about the impact of gaming machine levies on club donations.

Risk management and injury prevention : competencies, behaviours, and attitudes to safety in the construction industry

Work in the Australian construction industry is fraught with risk and the potential for serious harm. The industry is consistently placed within the three most hazardous industries to work along with other industries such as mining and transport (National Occupational Health and Safety Commission, 2003). In the 2001 to 2002 period, construction work killed 39 people and injured 13,250 more. Hence, more effort is required to reduce the injury rate and maximise the value of the rehabilitation/back-to-work process.

DRD2 C957T and TaqIA genotyping reveals gender effects and unique low-risk and high-risk genotypes in alcohol dependence

AIMS: As recent conflicting reports describe a genetic association between both the C- and the T-alleles of the dopamine D2 receptor (DRD2) C957T polymorphism (rs6277) in alcohol-dependent subjects, our aim was to examine this polymorphism and TaqIA (rs1800497) in Australian alcohol-dependent subjects. METHODS: The C957T polymorphism was genotyped in 228 patients with alcohol dependence (72 females and 156 males) and 228 healthy controls. RESULTS: The C-allele and C/C genotype of C957T was associated with alcohol dependence, whereas the TaqIA polymorphism was not. When analysed separately for C957T, males showed an even stronger association with the C-allele and females showed no association. The C957T and TaqIA haplotyping revealed a strong association with alcohol dependence and a double-genotype analysis (combining C957T and TaqIA genotypes) revealed that the relative risk of different genotypes varied by up to 27-fold with the TT/A1A2 having an 8.5-fold lower risk of alcohol dependence than other genotypes. CONCLUSION: Decreased DRD2 binding associated with the C-allele of the DRD2 C957T polymorphism is likely to be important in the underlying pathophysiology of at least some forms of alcohol dependence, and this effect appears to be limited to males only.

Educational stress among Chinese adolescents : measurement, risk factors and associations with mental health

Academic pressure among adolescents is a major risk factor for poor mental health and suicide and other harmful behaviours. While this is a worldwide phenomenon, it appears to be especially pronounced in China and other East Asian countries. Despite a growing body of research into adolescent mental health in recent years, the multiple constructs within the ‘educational stress’ phenomenon have not been clearly articulated in Chinese contexts. Further, the individual, family, school and peer influencing factors for educational stress and its associations with adolescent mental health are not well understood. An in-depth investigation may provide important information for the ongoing educational reform in Mainland China with a special focus on students’ mental health and wellbeing. The primary goal of this study was to examine the relative contribution of educational stress to poor mental health, in comparison to other well-known individual, family, school and peer factors. Another important task was to identify significant risk factors for educational stress. In addition, due to the lack of a culturally suitable instrument for educational stress in this population, a new tool – the Educational Stress Scale for Adolescents (ESSA) was initially developed in this study and tested for reliability and validity. A self-administered questionnaire was used to collect information from convenient samples of secondary school students in Shandong, China. The pilot survey was conducted with 347 students (grades 8 and 11) to test the psychometric properties of the ESSA and other scales or questions in the questionnaire. Based on factor analysis and reliability and validity testing, the 16-item scale (the ESSA) with five factors showed adequate to good internal consistency, 2-week test-retest reliability, and satisfactory concurrent and predictive validity. Its factor structure was further demonstrated in the main survey with a confirmatory factor analysis illustrating a good fit of the proposed model based on a confirmatory factor analysis. The reliabilities of other scales and questions were also adequate to be used in this study. The main survey was subsequently conducted with a sample of 1627 secondary school (grades 7-12) students to examine the influencing factors of educational stress and its associations with mental health outcomes, including depression, happiness and suicidal behaviours. A wide range of individual, family, school and peer factors were found to have a significant association with the total ESSA and subscale scores. Most of the strong factors for academic stress were school or study-related, including rural school location, low school connectedness, perceived poor academic grades and frequent emotional conflicts with teachers and peers. Unexpectedly, family and parental factors, such as parental bonding, family connectedness and conflicts with parents were found to have little or no association with educational stress. Educational stress was the most predictive variable for depression, but was not strongly associated with happiness. It had a strong association with suicide ideation but not with suicide attempts. Among five subscales of the ESSA, ‘Study despondency’ score had the strongest associations with these mental health measures. Surprising, two subscales, ‘Self-expectation’ and ‘Worry about grades’ showed a protective effect on suicidal behaviours. An additional analysis revealed that although academic pressure was the most commonly reported reason for suicidal thinking, the occurrence of problems in peer relationships such as peer teasing and bullying, and romantic problems had a much stronger relationship with actual attempts. This study provides some insights into the nature and health implications of educational stress among Chinese adolescents. Findings in this study suggest that interventions on educational stress should focus on school environment and academic factors. Intervention programs focused on educational stress may have a high impact on the prevalence of common mental disorders such as depression. Efforts to increase perceived happiness however should cover a wider range of individual, family and school factors. The importance of healthy peer relationships should be adequately emphasised in suicide prevention. In addition, the newly developed scale (the ESSA) demonstrates sound psychometric properties and is expected to be used in future research into academic-related stress among secondary school adolescents.

Seasonal variation in cardiovascular disease risk factors in a subarctic population : the Tromso Study 1979-2008

Background Seasonal changes in cardiovascular disease (CVD) risk factors may be due to exposure to seasonal environmental variables like temperature and acute infections or seasonal behavioural patterns in physical activity and diet. Investigating the seasonal pattern of risk factors should help determine the causes of the seasonal pattern in CVD. Few studies have investigated the seasonal variation in risk factors using repeated measurements from the same individual, which is important as individual and population seasonal patterns may differ. Methods The authors investigated the seasonal pattern in systolic and diastolic blood pressure, heart rate, body weight, total cholesterol, triglycerides, high-density lipoprotein cholesterol, C reactive protein and fibrinogen. Measurements came from 38 037 participants in the population-based cohort, the Tromsø Study, examined up to eight times from 1979 to 2008. Individual and population seasonal patterns were estimated using a cosinor in a mixed model. Results All risk factors had a highly statistically significant seasonal pattern with a peak time in winter, except for triglycerides (peak in autumn), C reactive protein and fibrinogen (peak in spring). The sizes of the seasonal variations were clinically modest. Conclusions Although the authors found highly statistically significant individual seasonal patterns for all risk factors, the sizes of the changes were modest, probably because this subarctic population is well adapted to a harsh climate. Better protection against seasonal risk factors like cold weather could help reduce the winter excess in CVD observed in milder climates.

Evaluation of coronary angiographic projections to balance the clinical yield with the radiation risk

Objective: Radiation safety principles dictate that imaging procedures should minimise the radiation risks involved, without compromising diagnostic performance. This study aims to define a core set of views that maximises clinical information yield for minimum radiation risk. Angiographers would supplement these views as clinically indicated. Methods: An algorithm was developed to combine published data detailing the quality of information derived for the major coronary artery segments through the use of a common set of views in angiography with data relating to the dose–area product and scatter radiation associated with these views. Results: The optimum view set for the left coronary system comprised four views: left anterior oblique (LAO) with cranial (Cr) tilt, shallow right anterior oblique (AP-RAO) with caudal (Ca) tilt, RAO with Ca tilt and AP-RAO with Cr tilt. For the right coronary system three views were identified: LAO with Cr tilt, RAO and AP-RAO with Cr tilt. An alternative left coronary view set including a left lateral achieved minimally superior efficiency (,5%), but with an ,8% higher radiation dose to the patient and 40% higher cardiologist dose. Conclusion: This algorithm identifies a core set of angiographic views that optimises the information yield and minimises radiation risk. This basic data set would be supplemented by additional clinically determined views selected by the angiographer for each case. The decision to use additional views for diagnostic angiography and interventions would be assisted by referencing a table of relative radiation doses for the views being considered.

Risk taking by motorcyclists : rider training and stages of change

Motorcyclists in Australia have been found to be 30 times more likely to be killed per kilometre travelled than car occupants and 40 times more likely to be seriously injured. One approach to preventing motorcycle-related injury is through training and education. While there is traditionally a major focus on developing riding skills during training for motorcyclists, there is also a need for training to promote safe riding to reduce subsequent risk taking. The Transtheoretical Model, commonly known as the ‘Stages of Change’ model, provides a rationale to support incremental behaviour change for risky riding that may be facilitated through motorcycle rider training and education. A sample of 438 learner motorcyclists attended a rider training program in Queensland, Australia, with the stages of change to adopt a safe riding mindset and safe riding practices being measured upon commencement of the course (Time 1) and then again upon completion (Time 2). A small subset of the original sample (n=45) responded at follow up 24 months post training (Time 3). Consistent with the aims of training, results showed a significant shift from the contemplation stage to the subsequent stages of change for participants between Time 1 and Time 2. Progression to the later stages in the model was found for the subset of participants that responded at the Time 3 follow up. Issues of questionnaire design and the utility of the Transtheoretical Model for motorcycle rider training are discussed.

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.