Assessment of retinal structure and visual function in association with diabetic peripheral neuropathy

Diabetes is an increasingly prevalent disease worldwide. Providing early management of the complications can prevent morbidity and mortality in this population. Peripheral neuropathy, a significant complication of diabetes, is the major cause of foot ulceration and amputation in diabetes. Delay in attending to complication of the disease contributes to significant medical expenses for diabetic patients and the community. Early structural changes to the neural components of the retina have been demonstrated to occur prior to the clinically visible retinal vasculature complication of diabetic retinopathy. Additionally visual functionloss has been shown to exist before the ophthalmoscopic manifestations of vasculature damage. The purpose of this thesis was to evaluate the relationship between diabetic peripheral neuropathy and both retinal structure and visual function. The key question was whether diabetic peripheral neuropathy is the potential underlying factor responsible for retinal anatomical change and visual functional loss in people with diabetes. This study was conducted on a cohort with type 2 diabetes. Retinal nerve fibre layer thickness was assessed by means of Optical Coherence Tomography (OCT). Visual function was assessed using two different methods; Standard Automated Perimetry (SAP) and flicker perimetry were performed within the central 30 degrees of fixation. The level of diabetic peripheral neuropathy (DPN) was assessed using two techniques - Quantitative Sensory Testing and Neuropathy Disability Score (NDS). These techniques are known to be capable of detecting DPN at very early stages. NDS has also been shown as a gold standard for detecting 'risk of foot ulceration'. Findings reported in this thesis showed that RNFL thickness, particularly in the inferior quadrant, has a significant association with severity of DPN when the condition has been assessed using NDS. More specifically it was observed that inferior RNFL thickness has the ability to differentiate individuals who are at higher risk of foot ulceration from those who are at lower risk, indicating that RNFL thickness can predict late-staged DPN. Investigating the association between RNFL and QST did not show any meaningful interaction, which indicates that RNFL thickness for this cohort was not as predictive of neuropathy status as NDS. In both of these studies, control participants did not have different results from the type 2 cohort who did not DPN suggesting that RNFL thickness is not a marker for diagnosing DPN at early stages. The latter finding also indicated that diabetes per se, is unlikely to affect the RNFL thickness. Visual function as measured by SAP and flicker perimetry was found to be associated with severity of peripheral neuropathy as measured by NDS. These findings were also capable of differentiating individuals at higher risk of foot ulceration; however, visual function also proved not to be a maker for early diagnosis of DPN. It was found that neither SAP, nor flicker sensitivity have meaningful associations with DPN when neuropathy status was measured using QST. Importantly diabetic retinopathy did not explain any of the findings in these experiments. The work described here is valuable as no other research to date has investigated the association between diabetic peripheral neuropathy and either retinal structure or visual function.

The association between leisure motivation and recovery: A pilot study

Background and aims: Recovery from mental illness may be facilitated by participation in activities that provide meaning and purpose in the lives of consumers. Leisure participation can be a major source of enjoyment as well as mental and physical well-being. Methods and results: This study examined the association between consumers’ motivation to engage in leisure and their self-reported perception of recovery in a sample of 44 Clubhouse members. The Leisure Motivation Scale and the Recovery Assessment Scale were used to measure the association between leisure motivation and recovery. The results indicated a statistically significant association between leisure motivation and recovery. Conclusion: These findings have implications for service delivery within mental health settings, as occupational therapists may be able to design leisure-based programs more effectively if they can understand the needs and motives for participation. More emphasis should be placed on supporting consumers to re-integrate and be socially included within the community through leisure-based initiatives.

Neuropsychological development in children with early and continuously treated phenylketonuria : association with biochemical markers

PKU is a genetically inherited inborn error of metabolism caused by a deficiency of the enzyme phenylalanine hydroxylase. The failure of this enzyme causes incomplete metabolism of protein ingested in the diet, specifically the conversion of one amino acid, phenylalanine, to tyrosine, which is a precursor to the neurotransmitter dopamine. Rising levels of phenylalanine is toxic to the developing brain, disrupting the formation of white matter tracts. The impact of tyrosine deficiency is not as well understood, but is hypothesized to lead to a low dopamine environment for the developing brain. Detection in the newborn period and continuous treatment (a low protein phe-restricted diet supplemented with phenylalanine-free protein formulas) has resulted in children with early and continuously treated PKU now developing normal I.Q. However, deficits in executive function (EF) are common, leading to a rate of Attention Deficit Hyperactivity Disorder (ADHD) up to five times the norm. EF worsens with exposure to higher phenylalanine levels, however recent research has demonstrated that a high phenylalanine to tyrosine ratio (phenylalanine:tyrosine ratio), which is hypothesised to lead to poorer dopamine function, has a more negative impact on EF than phenylalanine levels alone. Research and treatment of PKU is currently phenylalanine-focused, with little investigation of the impact of tyrosine on neuropsychological development. There is no current consensus as to the veracity of tyrosine monitoring or treatment in this population. Further, the research agenda in this population has demonstrated a primary focus on EF impairment alone, even though there may be additional neuropsychological skills compromised (e.g., mood, visuospatial deficits). The aim of this PhD research was to identify residual neuropsychological deficits in a cohort of children with early and continuously treated phenylketonuria, at two time points in development (early childhood and early adolescence), separated by eight years. In addition, this research sought to determine which biochemical markers were associated with neuropsychological impairments. A clinical practice survey was also undertaken to ascertain the current level of monitoring/treatment of tyrosine in this population. Thirteen children with early and continuously treated PKU were tested at mean age 5.9 years and again at mean age 13.95 years on several neuropsychological measures. Four children with hyperphenylalaninemia (a milder version of PKU) were also tested at both time points and provide a comparison group in analyses. Associations between neuropsychological function and biochemical markers were analysed. A between groups analysis in adolescence was also conducted (children with PKU compared to their siblings) on parent report measures of EF and mood. Minor EF impairments were evident in the PKU group by age 6 years and these persisted into adolescence. Life-long exposure to high phenylalanine:tyrosine ratio and/or low tyrosine independent of phenylalanine were significantly associated with EF impairments at both time points. Over half the children with PKU showed severe impairment on a visuospatial task, and this was associated only with concurrent levels of tyrosine in adolescence. Children with PKU also showed a statistically significant decline in a language comprehension task from 6 years to adolescence (going from normal to subnormal), this deficit was associated with lifetime levels of phenylalanine. In comparison, the four children with hyperphenylalaninemia demonstrated normal function at both time points, across all measures. No statistically significant differences were detected between children with PKU and their siblings on the parent report of EF and mood. However, depressive symptoms were significantly correlated with: EF; long term high phe:tyr exposure; and low tyrosine levels independent of phenylalanine. The practice survey of metabolic clinics from 12 countries indicated a high level of variability in terms of monitoring/treatment of tyrosine in this population. Whilst over 80% of clinics surveyed routinely monitored tyrosine levels in their child patients, 25% reported treatment strategies to increase tyrosine (and thereby lower the phenylalanine:tyrosine ratio) under a variety of patient presentation conditions. Overall, these studies have shown that EF impairments associated with PKU provide support for the dopamine-deficiency model. A language comprehension task showed a different trajectory, serving a timely reminder that non-EF functions also remain vulnerable in this population; and that normal function in childhood does not guarantee normal function by adolescence. Mood impairments were associated with EF impairments as well as long term measures of phenylalanine:tyrosine and/or tyrosine. The implications of this research for enhanced clinical guidelines are discussed given varied current practice.

A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer

The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region. Methods: We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer. Results: The duplication allele had a frequency of 0.34 in the normal controls. There was a nonsignificant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours. Conclusion: The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.

Association between feeding style and weight gain in infants aged 2–7 months

Introduction: Feeding on demand supports an infant’s innate capacity to respond to hunger and satiety cues and may promote later self-regulation of intake. Our aim was to examine whether feeding style (on demand vs to schedule) is associated with weight gain in early life. Methods: Participants were first-time mothers of healthy term infants enrolled NOURISH, an RCT evaluating an intervention to promote positive early feeding practices. Baseline assessment occurred when infants were aged 2-7 months. Infants able to be categorised clearly as feeding on demand or to schedule (mothers self report) were included in the logistic regression analysis. The model was adjusted for gender, breastfeeding and maternal age, education, BMI. Weight gain was defined as a positive difference in baseline minus birthweight z-scores (WHO standards) which indicated tracking above weight percentile. Results: Data from 356 infants with a mean age of 4.4 (SD 1.0) months were available. Of these, 197 (55%) were fed on demand, 42 (12%) were fed on schedule. There was no statistical association between feeding style and weight gain [OR=0.72 (95%CI 0.35-1.46), P=0.36]. Formula fed infants were three times more likely to be fed on schedule and formula feeding was independently associated with increased weight gain [OR=2.02 (95%CI 1.11-3.66), P=0.021]. Conclusion: In this preliminary analysis the association between feeding style and weight gain did not reach statistical significance, however , the effect size may be clinically relevant and future analysis will include the full study sample (N=698).

The association between maternal infant feeding practices and child weight at 11-17 months in first-time Australian mothers

Introduction: Emerging evidence reveals that early feeding practices are associated with child food intake, eating behaviour and weight status. This cross-sectional analysis examined the association between maternal infant feeding practices/beliefs and child weight in Australian infants aged 11-17 months. Methods: Participants were 293 first-time mothers of healthy term infants (144 boys, mean age 14±1 months) enrolled in the NOURISH RCT. Mothers self-reported infant feeding practices and beliefs using the Infant Feeding Questionnaire (Baughcum, 2001). Anthropometric data were also measured at baseline (infants aged 4 months). Multiple regression analysis was used, adjusting for infant age, gender, birth weight, infant feeding mode (breast vs. formula), maternal perceptions of infant weight status, pre-pregnancy weight, weight concern, age and education. Results: The average child weight-for-age z-score (WAZ) was 0.62±0.83 (range:-1.56 to 2.94) and the mean change in WAZ (WAZ change) from 4 to 14 months was 0.62±0.69 (range:-1.50 to 2.76). Feeding practices/beliefs partly explained child WAZ (R2=0.28) and WAZ change (R2=0.13) in the adjusted models. While child weight status at 14 months was inversely associated with responsive feeding (e.g. baby feeds whenever she wants, feeding to stop baby being unsettled) (β=-0.104, p=0.06) and maternal concern about the child becoming underweight (β=-0.224, p<0.001), it was positively associated with mother’s concern about child overweight (β=0.197, p<0.05). Birth weight, infant’s age, maternal weight concern and perceiving her child as overweight were significant covariates. WAZ change was only significantly associated with responsive feeding (β=-0.147, p<0.05). Conclusion: Responsive feeding may be an important strategy to promote healthy child weight.

Pollutant concentrations within households in Lao PDR and association with housing characteristics and occupants' activities

The paper presents the results of a study conducted to investigate indoor air quality within residential dwellings in Lao PDR. Results from PM 10, CO, and NO2 measurements inside 167 dwellings in Lao PDR over a five month period (December 2005-April 2006) are discussed as a function of household characteristics and occupant activities. Extremely high PM10 and NO2 concentrations (12 h mean PM10 concentrations 1275 ± 98 μg m-3 and 1183 ± 99 μg m-3 in Vientiane and Bolikhamxay provinces, respectively; 12 h mean NO2 concentrations 1210 ± 94 μg m-3 and 561 ± 45 μg m-3 in Vientiane and Bolikhamxay, respectively) were measured within the dwellings. Correlations, ANOVA analysis (univariate and multivariate), and linear regression results suggest a substantial contribution from cookingandsmoking.The PM10 concentrations were significantly higher in houses without a chimney compared to houses in which cooking occurred on a stove with a chimney. However, no significant differences in pollutantconcentrations were observed as a function of cooking location. Furthermore, PM10 and NO2 concentrations were higher in houses in which smoking occurred, suggestive of a relationship between increased indoor concentrations and smoking (0.05 < p < 0.10). Resuspension of dust from soil floors was another significant source of PM10 inside the house (634 μg m-3, p < 0.05).

The association between objectively measured neighborhood features and walking in middle-aged adults

Purpose: To explore the role of the neighborhood environment in supporting walking Design: Cross sectional study of 10,286 residents of 200 neighborhoods. Participants were selected using a stratified two-stage cluster design. Data were collected by mail survey (68.5% response rate). Setting: The Brisbane City Local Government Area, Australia, 2007. Subjects: Brisbane residents aged 40 to 65 years. Measures Environmental: street connectivity, residential density, hilliness, tree coverage, bikeways, and street lights within a one kilometer circular buffer from each resident’s home; and network distance to nearest river or coast, public transport, shop, and park. Walking: minutes in the previous week categorized as < 30 minutes, ≥ 30 < 90 minutes, ≥ 90 < 150 minutes, ≥ 150 < 300 minutes, and ≥ 300 minutes. Analysis: The association between each neighborhood characteristic and walking was examined using multilevel multinomial logistic regression and the model parameters were estimated using Markov chain Monte Carlo simulation. Results: After adjustment for individual factors, the likelihood of walking for more than 300 minutes (relative to <30 minutes) was highest in areas with the most connectivity (OR=1.93, 99% CI 1.32-2.80), the greatest residential density (OR=1.47, 99% CI 1.02-2.12), the least tree coverage (OR=1.69, 99% CI 1.13-2.51), the most bikeways (OR=1.60, 99% CI 1.16-2.21), and the most street lights (OR=1.50, 99% CI 1.07-2.11). The likelihood of walking for more than 300 minutes was also higher among those who lived closest to a river or the coast (OR=2.06, 99% CI 1.41-3.02). Conclusion: The likelihood of meeting (and exceeding) physical activity recommendations on the basis of walking was higher in neighborhoods with greater street connectivity and residential density, more street lights and bikeways, closer proximity to waterways, and less tree coverage. Interventions targeting these neighborhood characteristics may lead to improved environmental quality as well as lower rates of overweight and obesity and associated chromic disease.

Interacting constraints of defensive pressure and ball displacement trajectories shape locomotor pointing behaviours in association football

Performance of locomotor pointing tasks (goal-directed locomotion) in sport is typically constrained by dynamic factors, such as positioning of opponents and objects for interception. In the team sport of association football, performers have to coordinate their gait with ball displacement when dribbling and when trying to prevent opponent interception when running to kick a ball. This thesis comprises two studies analysing the movement patterns during locomotor pointing of eight experienced youth football players under static and dynamic constraints by manipulating levels of ball displacement (ball stationary or moving) and defensive pressure (defenders absent, or positioned near or far during performance). ANOVA with repeated measures was used to analyse effects of these task constraints on gait parameters during the run-up and cross performance sub-phase. Experiment 1 revealed outcomes consistent with previous research on locomotor pointing. When under defensive pressure, participants performed the run-up more quickly, concurrently modifying footfall placements relative to the ball location over trials. In experiment 2 players coordinated their gait relative to a moving ball significantly differently when under defensive pressure. Despite no specific task instructions being provided beforehand, context dependent constraints interacted to influence footfall placements over trials and running velocity of participants in different conditions. Data suggest that coaches need to manipulate task constraints carefully to facilitate emergent movement behaviours during practice in team games like football.

Conference report: Lights, Camera, Action : Spotlight on Tourism in the New Millennium. 31st Annual Travel and Tourism Research Association Conference.

The 31st TTRA conference was held in California’s San Fernando Valley, home of Hollywood and Burbank’s movie and television studios. The twin themes of Hollywood and the new Millennium promised and delivered “something old, yet something new”. The meeting offered a historical summary, not only of the year in review but also of many features of travel research since the first literature in the field appeared in the 1970s. Also, the millennium theme set the scene for some stimulating and forward thinking discussions. The Hollywood location offered an opportunity to ponder on the value of the movie-induced tourism for Los Angeles, at a time when Hollywood Boulevard was in the midst of a much needed redevelopment programme. Hollywood Chamber of Commerce speaker Oscar Arslanian acknowledged that the face of the famous district had become tired, and that its ability to continue to attract visitors in the future lay in redeveloping its past heritage. In line with the Hollywood theme a feature of the conference was a series of six special sessions with “Stars of Travel Research”. These sessions featured: Clare Gunn, Stanley Plog, Charles Gouldner, John Hunt, Brent Ritchie, Geoffrey Crouch, Peter Williams, Douglas Frechtling, Turgut Var, Robert Christie-Mill, and John Crotts. Delegates were indeed privileged to hear from many of the pioneers of tourism research. Clare Gunn, Charles Goeldner, Turgut Var and Stanley Plog, for example, traced the history of different aspects of the tourism literature, and in line with the millennium theme, offered some thought provoking discussion on the future challenges facing tourism. These included; the commodotisation of airlines and destinations, airport and traffic congestion, environment sustainability responsibility and the looming burst of the baby-boomer bubble. Included in the conference proceedings are four papers presented by five of the “Stars”. Brent Ritchie and Geoffrey Crouch discuss the critical success factors for destinations, Clare Gunn shares his concerns about tourism being a smokestack industry, Doug Frechtling provides forecasts of outbound travel from 20 countries, and Charles Gouldner, who has attended all 31 TTRA conferences, reflects on the changes that have taken place in tourism research over 35 years...

What explains the association between socioeconomic status and depression among Vietnamese adults?

Background Depression is a major public health problem worldwide and is currently ranked second to heart disease for years lost due to disability. For many decades, international research has found that depressive symptoms occur more frequently among low socioeconomic (SES) individuals than their more-advantaged peers. However, the reasons as to why those of low socioeconomic groups suffer more depressive symptoms are not well understood. Studies investigating the prevalence of depression and its association with SES emanate largely from developed countries, with little research among developing countries. In particular, there is a serious dearth of research on depression and no investigation of its association with SES in Vietnam. The aims of the research presented in this Thesis are to: estimate the prevalence of depressive symptoms among Vietnamese adults, examine the nature and extent of the association between SES and depression and to elucidate causal pathways linking SES to depressive symptoms Methods The research was conducted between September 2008 and November 2009 in Hue city in central Vietnam and used a combination of qualitative (in-depth interviews) and quantitative (survey) data collection methods. The qualitative study contributed to the development of the theoretical model and to the refinement of culturally-appropriate data collection instruments for the quantitative study. The main survey comprised a cross-sectional population–based survey with randomised cluster sampling. A sample of 1976 respondents aged between 25-55 years from ten randomly-selected residential zones (quarters) of Hue city completed the questionnaire (response rate 95.5%). Measures SES was classified using three indicators: education, occupation and income. The Center for Epidemiologic Studies-Depression (CES-D) scale was used to measure depressive symptoms (range0-51, mean=11.0, SD=8.5). Three cut-off points for the CES-D scores were applied: ‘at risk for clinical depression’ (16 or above), ‘depressive symptoms’ (above 21) and ‘depression’ (above 25). Six psychosocial indicators: life time trauma, chronic stress, recent life events, social support, self esteem, and mastery were hypothesized to mediate the association between SES and depressive symptoms. Analyses The prevalence of depressive symptoms were analysed using bivariate analyses. The multivariable analytic phase comprised of ordinary least squares regression, in accordance with Baron and Kenny’s three-step framework for mediation modeling. All analyses were adjusted for a range of confounders, including age, marital status, smoking, drinking and chronic diseases and the mediation models were stratified by gender. Results Among these Vietnamese adults, 24.3% were at or above the cut-off for being ‘at risk for clinical depression’, 11.9% were classified as having depressive symptoms and 6.8% were categorised as having depression. SES was inversely related to depressive symptoms: the least educated those with low occupational status or with the lowest incomes reported more depressive symptoms. Socioeconomicallydisadvantaged individuals were more likely to report experiencing stress (life time trauma, chronic stress or recent life events), perceived less social support and reported fewer personal resources (self esteem and mastery) than their moreadvantaged counterparts. These psychosocial resources were all significantly associated with depressive symptoms independent of SES. Each psychosocial factor showed a significant mediating effect on the association between SES and depressive symptoms. This was found for all measures of SES, and for males and females. In particular, personal resources (mastery, self esteem) and chronic stress accounted for a substantial proportion of the variation in depressive symptoms between socioeconomic groups. Social support and recent life events contributed modestly to socioeconomic differences in depressive symptoms, whereas lifetime trauma contributed the least to these inequalities. Conclusion This is the first known study in Vietnam or any developing country to systematically examine the extent to which psychosocial factors mediate the relationship between SES and depression. The study contributes new evidence regarding the burden of depression in Vietnam. The findings have practical relevance for advocacy, for mental health promotion and health-care services, and point to the need for programs that focus on building a sense of personal mastery and self esteem. More broadly, the work presented in this Thesis contributes to the international scientific literature on the social determinants of depression.

A note on the ‘Linsanity’ of measuring the relative efficiency of National Basketball Association (NBA) guards

This note examines the productive efficiency of 62 starting guards during the 2011/12 National Basketball Association (NBA) season. This period coincides with the phenomenal and largely unanticipated performance of New York Knicks’ starting point guard Jeremy Lin and the attendant public and media hype known as Linsanity. We employ a data envelopment analysis (DEA) approach that includes allowance for an undesirable output, here turnovers per game, with the desirable outputs of points, rebounds, assists, steals, and blocks per game and an input of minutes per game. The results indicate that depending upon the specification, between 29 and 42 percent of NBA guards are fully efficient, including Jeremy Lin, with a mean inefficiency of 3.7 and 19.2 percent. However, while Jeremy Lin is technically efficient, he seldom serves as a benchmark for inefficient players, at least when compared with established players such as Chris Paul and Dwayne Wade. This suggests the uniqueness of Jeremy Lin’s productive solution and may explain why his unique style of play, encompassing individual brilliance, unselfish play, and team leadership, is of such broad public appeal.

Association of immunoproteasomes with the endoplasmic reticulum

Proteasomes are complex multisubunit proteases which play a critical role in intracellular proteolysis. Immunoproteasomes, which contain three c-interferon-inducible subunits, are a subset of proteasomes which have a specialized function in antigen processing for presentation by the MHC class I pathway. Two of the c-interferon inducible subunits, LMP2 and LMP7, are encoded within the MHC class II region adjacent to the two TAP (transporter associated with antigen presentation) genes. We have investigated the localization of immunoproteasomes using monoclonal antibodies to LMP2 and LMP7. Immunoproteasomes were strongly enriched around the endoplasmic reticulum as judged by double-immuno¯uorescence experiments with anticalreticulin antibodies, but were also present in the nucleus and throughout the cytosol. In contrast, proteasome subunit C2, which is present in all proteasomes, was found to be evenly distributed throughout the cytoplasm and in the nucleus, as was the delta subunit, which is replaced by LMP2 in immunoproteasomes. c-Interferon increased the level of immunoproteasomes, but had no effect on their distribution. Our results provide the ®rst direct evidence that immunoproteasomes are strongly enriched at the endoplasmic reticulum, where they may be located close to the TAP transporter to provide efficient transport of peptides into the lumen of the endoplasmic recticulum for association with MHC class I molecules.

Children physical activity correlates and parent physical activity do not have a strong association with physical activity amongst adolescents

Background: Physical activity is a key modifiable behavior impacting a number of important health outcomes. The path to developing chronic diseases commonly commences with lifestyle patterns developed during childhood and adolescence. This study examined whether parent physical activity and other factors correlated with physical activity amongst children are associated with self-reported physical activity in adolescents. Methods: A total of 115 adolescents (aged 12-14) and their parents completed questionnaire assessments. Self-reported physical activity was measured amongst adolescents and their parents using the International Physical Activity Questionnaire for Adolescents (IPAQ-A), and the International Physical Activity Questionnaire (IPAQ) respectively. Adolescents also completed the Children’s Physical Activity Correlates (CPAC), which measured factors that have previously demonstrated association with physical activity amongst children. To examine whether parent physical activity or items from the CPAC were associated with self-reported adolescent physical activity, backward step-wise regression was undertaken. One item was removed at each step in descending order of significance (until two tailed item alpha=0.05 was achieved). Results: A total of 93 (80.9%) adolescents and their parents had complete data sets and were included in the analysis. Independent variables were removed in the order: perceptions of parental role modeling; importance of exercise; perceptions of parental encouragement; peer acceptance; fun of physical exertion; perceived competence; parent physical activity; self-esteem; liking of exercise; and parental influence. The only variable remaining in the model was ‘liking of games and sport’ (p=0.003, adjusted r-squared=0.085). Discussion: These findings indicate that factors associated with self-reported physical activity in adolescents are not necessarily the same as younger children (aged 8-11). While ‘liking of games and sport’ was included in the final model, the r-squared value did not indicate a strong association. Interestingly, parent self-reported physical activity was not included in the final model. It is likely that adolescent physical activity may be influenced by a variety of direct and indirect forms of socialization. These findings do support the view that intrinsically motivated themes such as the liking of games and sport take precedence over outside influences, like those presented by parents, in determining youth physical activity behaviors. These findings do not suggest that parents have no influence on adolescent physical activity patterns, but rather, the influence is likely to be more complex than physical activity behavior modeling perceived by the adolescent. Further research in this field is warranted in order to better understand potential contributors to successful physical activity promotion interventions amongst young adolescents.

Association between prostinogen (KLK15) genetic variants and prostate cancer risk and aggressiveness in Australia and a meta-analysis of GWAS data

Background: Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives: We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources: Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results: Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p, 0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77-0.93; p = 2.7610 24). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions: Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes.