465 resultados para genetic benefits


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On 22 October 2012, the Australian Federal Government announced the removal of the $1,000 in-house fringe benefits concession when used as part of a salary packaging arrangement. At the time of the announcement, the Federal Government predicted that the removal of the concession would contribute additional tax revenue of $445 million over the following four years as well as an increase of GST payments to the States and Territories. However, anecdotal evidence at the same time indicated that the Australian employer response was to immediately stop providing employees with such in-house fringe benefits via salary sacrificing arrangements. Data presented in this article, collected from a combination of interviews with tax managers of four Australian entities as well as a review of the published archival data, confirms that the abolition of the $1,000 in-house fringe benefits concession was perceived as a negative change, whereby employees were considered the ‘big losers’ despite assertions by the Federal Government to the contrary. Using a conceptual map of tax rule change developed by Oats and Sadler, this article seeks to understand the reasons for this fringe benefits tax change and taxpayer response. In particular, the economic and political factors, and the responses of the relevant taxpayers (employers) are explored. Drawing on behavioural economic concepts, the actions, attitudes and response of employers to the rule change are also examined. The research findings suggest that the decision by Australian employers to cease providing the in-house fringe benefits as part of a salary-packaging arrangement after the legislative amendment was impacted by more than simple rational behaviour.

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Acute anterior uveitis (AAU) involves inflammation of the iris and ciliary body of the eye. It occurs both in isolation and as a complication of ankylosing spondylitis (AS). It is strongly associated with HLA-B*27, but previous studies have suggested that further genetic factors may confer additional risk. We sought to investigate this using the Illumina Exomechip microarray, to compare 1504 cases with AS and AAU, 1805 with AS but no AAU and 21 133 healthy controls. We also used a heterogeneity test to test the differences in effect size between AS with AAU and AS without AAU. In the analysis comparing AS+AAU+ cases versus controls, HLA-B*27 and HLA-A*02:01 were significantly associated with the presence of AAU (P<10−300 and P=6 × 10−8, respectively). Secondary independent association with PSORS1C3 (P=4.7 × 10−5) and TAP2 (P=1.1 × 10−5) were observed in the major histocompatibility complex. There was a new suggestive association with a low-frequency variant at zinc-finger protein 154 in the AS without AAU versus control analysis (zinc-finger protein 154 (ZNF154), P=2.2 × 10−6). Heterogeneity testing showed that rs30187 in ERAP1 has a larger effect on AAU compared with that in AS alone. These findings also suggest that variants in ERAP1 have a differential impact on the risk of AAU when compared with AS, and hence the genetic risk for AAU differs from AS.

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Greater attention is being directed towards incorporating greenery into the built environment as increasing global urbanisation drives the search for sustainable urbanism. This research takes a parametric approach to studying living wall dynamics using three methods to cover a diversity of design parameters and performance criteria. The findings led to a functional typology for living walls based on a range of design, context and performance parameters wider than previously identified. Such parametric studies offer valuable insights into 'transfunctional' living walls for homes, schools and public spaces.

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Background The Pacific Oceania region was one of the last regions of the world to be settled via human migration. Here we outline a settlement of this region that has given rise to a uniquely admixed population. The current Norfolk Island population has arisen from a small number of founders with mixed Caucasian and Polynesian ancestry, descendants of a famous historical event. The ‘Mutiny on the Bounty’ has been told in history books, songs and the big screen, but recently this story can be portrayed through comprehensive molecular genetics. Written history details betrayal and murder leading to the founding of Pitcairn Island by European mutineers and the Polynesian women who left Tahiti with them. Investigation of detailed genealogical records supports historical accounts. Findings Using genetics, we show distinct maternal Polynesian mitochondrial lineages in the present day population, as well as a European centric Y-chromosome phylogeny. These results comprehensively characterise the unique gender-biased admixture of this genetic isolate and further support the historical records relating to Norfolk Island. Conclusions Our results significantly refine previous population genetic studies investigating Polynesian versus Caucasian diversity in the Norfolk Island population and add information that is beneficial to future disease and gene mapping studies.

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The methylenetetrahydrofolate reductase (MTHFR) gene codes for the MTHFR enzyme which plays a key role in the pathway of folate and methionine metabolism. Polymorphisms of genes in this pathway affect its regulation and have been linked to lymphoma. In this study we examined whether we could detect an association between two common non-synonomous MTHFR polymorphisms, 677C>T (rs1801133) and 1298A>C (rs1801131), and susceptibility to non-Hodgkin lymphoma (NHL) in an Australian case-control cohort. We found no significant differences between genotype or allele frequencies for either polymorphisms between lymphoma cases and controls. We also explored whether epigenetic modification of MTHFR, specifically DNA methylation of a CpG island in the MTHFR promoter region, is associated with NHL using blood samples from patients. No difference in methylation levels was detected between the case and control samples suggesting that although hypermethylation of MTHFR has been reported in tumour tissues, particularly in the diffuse large B-cell lymphoma subtype of NHL, methylation of this MTHFR promoter CpG island is not a suitable epigenetic biomarker for NHL diagnosis or prognosis in peripheral blood samples. Further studies into epigenetic variants could focus on genes that are robustly associated with NHL susceptibility.

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Background Located in the Pacific Ocean between Australia and New Zealand, the unique population isolate of Norfolk Island has been shown to exhibit increased prevalence of metabolic disorders (type-2 diabetes, cardiovascular disease) compared to mainland Australia. We investigated this well-established genetic isolate, utilising its unique genomic structure to increase the ability to detect related genetic markers. A pedigree-based genome-wide association study of 16 routinely collected blood-based clinical traits in 382 Norfolk Island individuals was performed. Results A striking association peak was located at chromosome 2q37.1 for both total bilirubin and direct bilirubin, with 29 SNPs reaching statistical significance (P < 1.84 × 10−7). Strong linkage disequilibrium was observed across a 200 kb region spanning the UDP-glucuronosyltransferase family, including UGT1A1, an enzyme known to metabolise bilirubin. Given the epidemiological literature suggesting negative association between CVD-risk and serum bilirubin we further explored potential associations using stepwise multivariate regression, revealing significant association between direct bilirubin concentration and type-2 diabetes risk. In the Norfolk Island cohort increased direct bilirubin was associated with a 28 % reduction in type-2 diabetes risk (OR: 0.72, 95 % CI: 0.57-0.91, P = 0.005). When adjusted for genotypic effects the overall model was validated, with the adjusted model predicting a 30 % reduction in type-2 diabetes risk with increasing direct bilirubin concentrations (OR: 0.70, 95 % CI: 0.53-0.89, P = 0.0001). Conclusions In summary, a pedigree-based GWAS of blood-based clinical traits in the Norfolk Island population has identified variants within the UDPGT family directly associated with serum bilirubin levels, which is in turn implicated with reduced risk of developing type-2 diabetes within this population.

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Polygenic profiling has been proposed for elite endurance performance, using an additive model determining the proportion of optimal alleles in endurance athletes. To investigate this model’s utility for elite triathletes, we genotyped seven polymorphisms previously associated with an endurance polygenic profile (ACE Ins/Del, ACTN3 Arg577Ter, AMPD1 Gln12Ter, CKMM 1170bp/985+185bp, HFE His63Asp, GDF8 Lys153Arg and PPARGC1A Gly482Ser) in a cohort of 196 elite athletes who participated in the 2008 Kona Ironman championship triathlon. Mean performance time (PT) was not significantly different in individual marker analysis. Age, sex, and continent of origin had a significant influence on PT and were adjusted for. Only the AMPD1 endurance-optimal Gln allele was found to be significantly associated with an improvement in PT (model p=5.79 x 10-17, AMPD1 genotype p=0.01). Individual genotypes were combined into a total genotype score (TGS); TGS distribution ranged from 28.6 to 92.9, concordant with prior studies in endurance athletes (mean±SD: 60.75±12.95). TGS distribution was shifted toward higher TGS in the top 10% of athletes, though the mean TGS was not significantly different (p=0.164) and not significantly associated with PT even when adjusted for age, sex, and origin. Receiver operating characteristic curve analysis determined that TGS alone could not significantly predict athlete finishing time with discriminating sensitivity and specificity for three outcomes (less than median PT, less than mean PT, or in the top 10%), though models with the age, sex, continent of origin, and either TGS or AMPD1 genotype could. These results suggest three things: that more sophisticated genetic models may be necessary to accurately predict athlete finishing time in endurance events; that non-genetic factors such as training are hugely influential and should be included in genetic analyses to prevent confounding; and that large collaborations may be necessary to obtain sufficient sample sizes for powerful and complex analyses of endurance performance.

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Improvisation is a central concept in any drama, theatre or performance studies degree. It is a critical skill, which helps performers learn to ‘make it up as they go along’, apply existing skills to new situations and environments, and, of course, adapt find the most effective or creative pathway towards a their aims. As such, the fact that improvisation is rarely listed as a core career competency — even for performing arts graduates, who can struggle to engage with entrepreneurial skill sets they will need to learn to manage their unpredictable portfolio careers when they are couched in business terms — is somewhat strange. This paper examines the benefits of reframing the administrative, management and entrepreneurial skills arts graduates need to navigate a complex, uncertain, constantly changing industrial landscape in terms of improvisation, play, and playful self - performance. It suggests that adding improvisation to our career training arsenal may be worthwhile, not just because it may assist graduates in navigating their way through a portfolio career, but because it may offer a more familiar, user- friendly terminology to assist graduates in understanding the need to develop administrative, management and entrepreneurial as well as artistic skills, and, in a sense, understand the similarities between the two sets of skills.

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BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome-wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six-fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E-08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. Prostate 75:1467–1474, 2015. © 2015 Wiley Periodicals, Inc.

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Despite positive testing in animal studies, more than 80% of novel drug candidates fail to proof their efficacy when tested in humans. This is primarily due to the use of preclinical models that are not able to recapitulate the physiological or pathological processes in humans. Hence, one of the key challenges in the field of translational medicine is to “make the model organism mouse more human.” To get answers to questions that would be prognostic of outcomes in human medicine, the mouse's genome can be altered in order to create a more permissive host that allows the engraftment of human cell systems. It has been shown in the past that these strategies can improve our understanding of tumor immunology. However, the translational benefits of these platforms have still to be proven. In the 21st century, several research groups and consortia around the world take up the challenge to improve our understanding of how to humanize the animal's genetic code, its cells and, based on tissue engineering principles, its extracellular microenvironment, its tissues, or entire organs with the ultimate goal to foster the translation of new therapeutic strategies from bench to bedside. This article provides an overview of the state of the art of humanized models of tumor immunology and highlights future developments in the field such as the application of tissue engineering and regenerative medicine strategies to further enhance humanized murine model systems.

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Genetic and environmental factors affect white matter connectivity in the normal brain, and they also influence diseases in which brain connectivity is altered. Little is known about genetic influences on brain connectivity, despite wide variations in the brain's neural pathways. Here we applied the 'DICCCOL' framework to analyze structural connectivity, in 261 twin pairs (522 participants, mean age: 21.8 y ± 2.7SD). We encoded connectivity patterns by projecting the white matter (WM) bundles of all 'DICCCOLs' as a tracemap (TM). Next we fitted an A/C/E structural equation model to estimate additive genetic (A), common environmental (C), and unique environmental/error (E) components of the observed variations in brain connectivity. We found 44 'heritable DICCCOLs' whose connectivity was genetically influenced (α2>1%); half of them showed significant heritability (α2>20%). Our analysis of genetic influences on WM structural connectivity suggests high heritability for some WM projection patterns, yielding new targets for genome-wide association studies.

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Background Advances in cancer diagnosis and treatment have significantly improved survival rates, through their subsequent health needs are often not adequately addressed by current health services. National Health and Medical Research Council (NHMRC) Partnerships Project awarded a national collaborative project to develop, trial and evaluate clinical benefits and cost effectiveness of an e-health enabled structured health promotion intervention - The Women’s Wellness after Cancer Program (WWACP). The aim of this e-health enabled multimodal intervention is to improve health related quality of life in women previously treated for target cancers. Aim The WWACP is a 12-week web based, interactive, holistic program. Primary outcomes for this project are to promote a positive change in health-related quality of life (HRQoL) and reduction in Body Mass Index (BMI) in the women undertaking WWACP compared to women who receive usual care. Secondary outcomes include managing other side effects of cancer treatment through evidence-based nutrition and exercise practices, dealing with stress, sleep, menopause and sexuality issues. Methods The single-blinded multi-center randomized controlled trial recruited a toatl of 330 women within 24 months of completion of chemotherapy and /or radiotherapy. Women were randomly assigned to either a usual care or intervention group. Women provided with the intervention were provided with an interactive iBook and journal, web interface, and three virtual consultations by experienced cancer nurses. A variety of methods were utilized, to enable positive self- efficacy and lifestyle changes. These include online coaching with a registered nurse trained in the intervention, plus written educational and health promotional information. The program has been delivered through the e-health enabled interfaces, which enables virtual delivery via desktop and mobile computing devices. Importantly this enables accessibility for rural and regional women in Australia who are frequently geographically disadvantaged in terms of health care provision. Results Research focusing on alternative methods of delivering post treatment / or survivorship care in cancer utilizing web based interfaces is limited, but emerging evidence suggests that Internet interventions can increase psychological and physical wellbeing in cancer patients. The WWACP trial aims to establish the effectiveness of delivery of the program in terms of positive patient outcomes and cost effective, flexibility. The trial will be completed in September and results will be presented at the conference. Conclusions Women after acute hematological, breast and gynecological cancer treatments demonstrate good cancer survival rates and face residual health problems which are amenable to behavioral interventions. The conclusion of active treatment is a key 'teachable moment' in which sustainable positive lifestyle change can be achieved if patients receive education and psychological support which targets key treatment related health problems and known chronic disease risk factors.

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Background Interest in the use of healing gardens in healthcare settings to provide therapeutic benefits is increasing, however insight is needed to determine whether patients, patient families and friends, and staff who spend time in these gardens use these in the manner for which they were designed, and experience the benefits suggested by broader research in this field. Objective(s) Visitors to four of the LCCH gardens have left comments in ‘bench diaries’ (visitors books). Analysis of these comments yields valuable insights into the use of the gardens, enabling reflection on the design intent and outcomes and guidance regarding how the gardens might be better utilised, as well as a basis for further investigation into the use and value of the gardens. Method(s) Comments have been coded and analysed using a thematic analysis approach to identify patterns relating to the reasons for which people appear to come to the healing gardens; benefits they appear to receive from spending time there; and features and aspects of the gardens that they appear to appreciate in particular. Only comments related to the gardens have been used in this analysis, with all comments being deidentified. Outcome/Conclusion Comments left in the Adventure Garden and Secret Garden bench diaries were used for the analysis, as Staff Garden and Babies Garden bench diary comments did not relate to the garden. There were no negative comments relating to the gardens, other than one comment requesting additional benches. The vast majority of comments expressed gratitude for the space. The four most frequently observed themes from the comments left in the Secret Garden Bench Diary indicated that they were seeking ‘time out’ from their experiences of being at the hospital, a desire for a ‘dose of nature’ (greenery, beautiful garden, etc), and fresh air, and that the garden space provided a restorative experience to them in some manner. Comments in the Adventure Garden Bench Diary related predominately to the view. Analysis of the comments emphasises the importance of gardens providing multi-sensory experiences that significantly differentiate the space from the hospital ward and provide visitors with a sense of being away, of peacefulness, and of familiarity with the outside world. Positioning gardens with prospect, and solar aspect, appears important in these regards, as does the presence of visible greenery. Adequate seating in locations that provide pleasing views appears particularly important for staff and adult visitors. Whilst comments in the Bench Diaries did not indicate direct awareness of the stress and anxiety-reducing effects that research elsewhere has found from viewing plants and nature, however these effects may underpin many of these experiences that visitors did share.

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In the wake of an almost decade long economic downturn and increasing competition from developing economies, a new agenda in the Australian Government for science, technology, engineering, and mathematics (STEM) education and research has emerged as a national priority. However, to art and design educators, the pervasiveness and apparent exclusivity of STEM can be viewed as another instance of art and design education being relegated to the margins of curriculum (Greene, 1995). In the spirit of interdisciplinarity, there have been some recent calls to expand STEM education to include the arts and design, transforming STEM into STEAM in education (Maeda, 2013). As with STEM, STEAM education emphasises the connections between previously disparate disciplines, meaning that education has been conceptualised in different ways, such as focusing on the creative design thinking process that is fundamental to engineering and art (Bequette & Bequette, 2012). In this article, we discuss divergent creative design thinking process and metacognitive skills, how, and why they may enhance learning in STEM and STEAM.