525 resultados para Digby plays.
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This study examined the level, the prevalence of and the factors associated with depression among male casual laborers in Hanoi. Social mapping was done to recruit and interview 450 men aged over 18 years, mostly unskilled and unregistered laborers from 135 street venues across 13 districts of the city using a structured questionnaire. Most were from rural and mountainous provinces and did manual works such as motorbike taxi drivers, porters, construction workers, small traders and others in the current city. The prevalence of self-reported depressive symptoms (25 %) was high. Structural equation modeling showed that marriage, family separation and living with peers or partners were three significant distal risk factors, while illicit drug use and low social connectedness were proximal predictors of depression. Of all factors, social connectedness appeared to be the most important because it plays a mediating role. Drug use was an independent risk factor. This study provides a model to understand the mental health of male casual laborers and to develop culturally appropriate intervention programs for these men
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International Design Competition for Qatar Psychiatric Hospital. The scheme for the Al Wakra Respite and Recovery Centre delivers on an all-in attitude toward evidence-based design. It sets new benchmarks in so many ways: the way it allows excellent separation between patient cohorts without unnecessary or visible restrictions; the way it allows sharing of most of the clinical kit and spaces; the way services reticulation and facilities management takes place without compromising security and safety; the ways It abandons the institutional axioms that are still so ubiquitous elsewhere, so it can appear as the friendly, welcoming and wholesome; the way it allows incredible flexibility to allow changes or flexion on the fly; the way it has such ‘good bones’ for more structural changes as the future unfolds. But most importantly, the scheme will be exemplary in the way the building itself plays a role in promoting the recovery and mental well-being of its residents. Like no other, the Centre will rise to the challenges of supporting and inspiring an exemplary mental health service and promote the well-being of the patients. The 160 bed scheme allows for 43,000m2 of landscape, packed with wholesome things to do and experience. The Aspire zone even has stables and a falconry, both to celebrate the love that Qatari people have for horses and birds.
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Driver distraction through mobile phone use in the car is a growing road safety concern. This paper presents findings of a survey (N = 528), which seeks to better understand the predictors of mobile phone use while driving in young (18-25) adult drivers. The survey investigated factors and motivations such as young adults' boredom proneness and their social connectedness, as well as their general mobile phone use and phone use in the car. We found, e.g., that boredom proneness plays a larger role (compared to social connectedness) in determining how much a young male uses their phone in the car (compared to young females). Despite the study’s limitations, this initial understanding allows us to better design and develop innovative HCI interventions that prevent young adults, particularly males, from phone use while driving in a way that appeals to their needs.
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Metformin is the most commonly used pharmacological therapy for type 2 diabetes. We report a genome-wide association study for glycemic response to metformin in 1,024 Scottish individuals with type 2 diabetes with replication in two cohorts including 1,783 Scottish individuals and 1,113 individuals from the UK Prospective Diabetes Study. In a combined meta-analysis, we identified a SNP, rs11212617, associated with treatment success (n = 3,920, P = 2.9 P×-9, odds ratio = 1.35, 95% CI 1.22-1.49) at a locus containing ATM, the ataxia telangiectasia mutated gene. In a rat hepatoma cell line, inhibition of ATM with KU-55933 attenuated the phosphorylation and activation of AMP-activated protein kinase in response to metformin. We conclude that ATM, a gene known to be involved in DNA repair and cell cycle control, plays a role in the effect of metformin upstream of AMP-activated protein kinase, and variation in this gene alters glycemic response to metformin. © 2011 Nature America, Inc. All rights reserved.
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To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.
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Background: The vast majority of BRCA1 missense sequence variants remain uncharacterised for their possible effect on protein expression and function, and therefore are unclassified in terms of their pathogenicity. BRCA1 plays diverse cellular roles and it is unlikely that any single functional assay will accurately reflect the total cellular implications of missense mutations in this gene. Objective: To elucidate the effect of two BRCA1 variants, 5236G>C (G1706A) and 5242C>A (A1708E) on BRCA1 function, and to survey the relative usefulness of several assays to direct the characterisation of other unclassified variants in BRCA genes. Methods and Results: Data from a range of bioinformatic, genetic, and histopathological analyses, and in vitro functional assays indicated that the 1708E variant was associated with the disruption of different cellular functions of BRCA1. In transient transfection experiments in T47D and 293T cells, the 1708E product was mislocalised to the cytoplasm and induced centrosome amplification in 293T cells. The 1708E variant also failed to transactivate transcription of reporter constructs in mammalian transcriptional transactivation assays. In contrast, the 1706A variant displayed a phenotype comparable to wildtype BRCA1 in these assays. Consistent with functional data, tumours from 1708E carriers showed typical BRCA1 pathology, while tumour material from 1706A carriers displayed few histopathological features associated with BRCA1 related tumours. Conclusions: A comprehensive range of genetic, bioinformatic, and functional analyses have been combined for the characterisation of BRCA1 unclassified sequence variants. Consistent with the functional analyses, the combined odds of causality calculated for the 1706A variant after multifactorial likelihood analysis (1:142) indicates a definitive classification of this variant as "benign". In contrast, functional assays of the 1708E variant indicate that it is pathogenic, possibly through subcellular mislocalisation. However, the combined odds of 262:1 in favour of causality of this variant does not meet the minimal ratio of 1000:1 for classification as pathogenic, and A1708E remains formally designated as unclassified. Our findings highlight the importance of comprehensive genetic information, together with detailed functional analysis for the definitive categorisation of unclassified sequence variants. This combination of analyses may have direct application to the characterisation of other unclassified variants in BRCA1 and BRCA2.
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With increasing motorisation, road safety has become a major concern within Oman. Internationally, traffic policing plays a major role in improving road safety. Within Oman, the Royal Oman Police's (ROP) Directorate General of Traffic is responsible for policing traffic laws. Many common enforcement approaches originate from culturally different jurisdictions. The ROP is a relatively young policing force and may have different operational practices. Prior to applying practices from other jurisdictions it is important to understand the beliefs and expectations within the Directorate General of Traffic. Further, there is a need for individuals to understand their role and what is expected of them. Therefore, it is important to explore the agreement between levels of the ROP to determine how strategies and expectations transfer within the organisation. Interviews were conducted with 19 police officers from various levels of the ROP. A number of themes and findings emerged. Individuals at the upper level of the traffic police had a clear knowledge of the role of the ROP, believed that traffic police know what is expected of them, are well trained in their role and can have a very positive influence on road safety. These beliefs were less certain lower within the organisations with traffic officers having little knowledge of the role of the ROP or what was expected of them, felt undertrained, and believed their peers have little positive impact on road safety. There is a need to address barriers within the ROP in order to positively impact road safety.
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The membrane-bound ceruloplasmin homolog hephaestin plays a critical role in intestinal iron absorption. The aims of this study were to clone the rat hephaestin gene and to examine its expression in the gastrointestinal tract in relation to other genes encoding iron transport proteins. The rat hephaestin gene was isolated from intestinal mRNA and was found to encode a protein 96% identical to mouse hephaestin. Analysis by ribonuclease protection assay and Western blotting showed that hephaestin was expressed at high levels throughout the small intestine and colon. Immunofluorescence localized the hephaestin protein to the mature villus enterocytes with little or no expression in the crypts. Variations in iron status had a small but nonsignificant effect on hephaestin expression in the duodenum. The high sequence conservation between rat and mouse hephaestin is consistent with this protein playing a central role in intestinal iron absorption, although its precise function remains to be determined.
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This research investigates Bhutan Civil Service Human Resource Management strategies, policies and practices, and their contribution to achieving the national goal of Gross National Happiness. The study finds that the HRM of the Bhutanese civil service is meeting its strategic objective of contributing to GNH. The civil service in Bhutan plays an important role in socio-economic development, influences private sector practices, strengthens good governance and provides continuity to the government. Participants in the study were government ministers and senior, highly experienced civil servants. A model of civil service HRM in Bhutan is developed.
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Runx2-Cbfal, a Runt transcription factor, plays important roles during skeletal development. It is required for differentiation and function of osteoblasts. In its absence, chondrocyte hypertrophy is severely impaired and there is no vascularization of cartilage templates during skeletal development. These tissue-specific functions of Runx2 are likely to be dependent on its interaction with other proteins. We have therefore searched for proteins that may modulate the activity of Runx2. The yeast two-hybrid system was used to identify a groucho homologue, Grg5, as a Runx2-interacting protein. Grg5 enhances Runx2 activity in a cell culture-based assay and by analyses of postnatal growth in mice we demonstrate that Grg5 and Runx2 interact genetically. We also show that Runx2 haploinsufficiency in the absence of Grg5 results in a more severe delay in ossification of cranial sutures and fontanels than occurs with Runx2 haploinsufficiency on a wild-type background. Finally, we find shortening of the proliferative and hypertrophic zones, and expansion of the resting zone in the growth plates of Runx2(+/-)Grg5(-/-) mice that are associated with reduced Ihh expression and Indian hedgehog (Ihh) signaling. We therefore conclude that Grg5 enhances Runx2 activity in vivo.
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Epigenetics plays a crucial role in schizophrenia susceptibility. In a previous study, we identified over 4500 differentially methylated sites in prefrontal cortex (PFC) samples from schizophrenia patients. We believe this was the first genome-wide methylation study performed on human brain tissue using the Illumina Infinium HumanMethylation450 Bead Chip. To understand the biological significance of these results, we sought to identify a smaller number of differentially methylated regions (DMRs) of more functional relevance compared with individual differentially methylated sites. Since our schizophrenia whole genome methylation study was performed, another study analysing two separate data sets of post-mortem tissue in the PFC from schizophrenia patients has been published. We analysed all three data sets using the bumphunter function found in the Bioconductor package minfi to identify regions that are consistently differentially methylated across distinct cohorts. We identified seven regions that are consistently differentially methylated in schizophrenia, despite considerable heterogeneity in the methylation profiles of patients with schizophrenia. The regions were near CERS3, DPPA5, PRDM9, DDX43, REC8, LY6G5C and a region on chromosome 10. Of particular interest is PRDM9 which encodes a histone methyltransferase that is essential for meiotic recombination and is known to tag genes for epigenetic transcriptional activation. These seven DMRs are likely to be key epigenetic factors in the aetiology of schizophrenia and normal brain neurodevelopment.
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Perceiving students, science students especially, as mere consumers of facts and information belies the importance of a need to engage them with the principles underlying those facts and is counter-intuitive to the facilitation of knowledge and understanding. Traditional didactic lecture approaches need a re-think if student classroom engagement and active learning are to be valued over fact memorisation and fact recall. In our undergraduate biomedical science programs across Years 1, 2 and 3 in the Faculty of Health at QUT, we have developed an authentic learning model with an embedded suite of pedagogical strategies that foster classroom engagement and allow for active learning in the sub-discipline area of medical bacteriology. The suite of pedagogical tools we have developed have been designed to enable their translation, with appropriate fine-tuning, to most biomedical and allied health discipline teaching and learning contexts. Indeed, aspects of the pedagogy have been successfully translated to the nursing microbiology study stream at QUT. The aims underpinning the pedagogy are for our students to: (1) Connect scientific theory with scientific practice in a more direct and authentic way, (2) Construct factual knowledge and facilitate a deeper understanding, and (3) Develop and refine their higher order flexible thinking and problem solving skills, both semi-independently and independently. The mindset and role of the teaching staff is critical to this approach since for the strategy to be successful tertiary teachers need to abandon traditional instructional modalities based on one-way information delivery. Face-to-face classroom interactions between students and lecturer enable realisation of pedagogical aims (1), (2) and (3). The strategy we have adopted encourages teachers to view themselves more as expert guides in what is very much a student-focused process of scientific exploration and learning. Specific pedagogical strategies embedded in the authentic learning model we have developed include: (i) interactive lecture-tutorial hybrids or lectorials featuring teacher role-plays as well as class-level question-and-answer sessions, (ii) inclusion of “dry” laboratory activities during lectorials to prepare students for the wet laboratory to follow, (iii) real-world problem-solving exercises conducted during both lectorials and wet laboratory sessions, and (iv) designing class activities and formative assessments that probe a student’s higher order flexible thinking skills. Flexible thinking in this context encompasses analytical, critical, deductive, scientific and professional thinking modes. The strategic approach outlined above is designed to provide multiple opportunities for students to apply principles flexibly according to a given situation or context, to adapt methods of inquiry strategically, to go beyond mechanical application of formulaic approaches, and to as much as possible self-appraise their own thinking and problem solving. The pedagogical tools have been developed within both workplace (real world) and theoretical frameworks. The philosophical core of the pedagogy is a coherent pathway of teaching and learning which we, and many of our students, believe is more conducive to student engagement and active learning in the classroom. Qualitative and quantitative data derived from online and hardcopy evaluations, solicited and unsolicited student and graduate feedback, anecdotal evidence as well as peer review indicate that: (i) our students are engaging with the pedagogy, (ii) a constructivist, authentic-learning approach promotes active learning, and (iii) students are better prepared for workplace transition.
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Background Ensuring efficient and effective delivery of health care to an aging population has been a major driver for a review of the health workforce in Australia. As part of this review a new National Registration and Accreditation Scheme (NRAS) has evolved with one goal being to improve workforce flexibility. With increased flexibility there have been discussions about the role specialist scopes of practice plays. This study explored the role of gender and other work related characteristics in relation to contemporary scope of podiatry practice and specialisation in Australia. Methods A cross sectional survey was administered through an on-line survey tool on behalf of the Australasian Podiatry Council. Descriptive data was collected over a three-week period. Queensland University of Technology Human Research Ethics approval was sought and confirmed exemption from review, exemption number 1400000791. Results Of the podiatrists participating in this survey (n=218), they were predominately female (66%), early career (34%, 0-9 years) and work in private practices (78%) in multi-podiatrists centres (41%). Relationship between clinical activities performed and “self-perception” of performing a “specialist role” was significant for practitioners who undertook treatment of specific patient groups. The largest area of interest was biomechanics (n=65), followed closely by diabetes (n=61), a third area identified was paediatrics (n=26). Self-perception of specialist status was compared with gender, years of experience, location, primary work environment and clinical practice. When practitioners are asked to categorise themselves to be either “generalist” or “specialist/ generalist with a special interest” podiatrist, male gender was identified as being the only factor which would predict perception of status; 64% males identified as specialist, as opposed to 49% of female survey respondents (Chi square, df = 1, P = 0.044). Self-perception of specialist status was not explained by years of experience, location, working in rural versus urban environment, state worked in, or part-time/full-time work status. Conclusions In conclusion; gender, work environment plus area of interest form a complex relationship, which appear to influence both perception and reality of service provision. Incorporation of specialisation activity (surgical podiatry along with endorsement for use of scheduled medicines) will have lasting impact on the scope of the podiatry profession in Australia. To meet community expectation and maintain high standards, the addition of new subspecialties may be indicated.
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Breast cancer incidence and mortality rates are increasing despite our current knowledge on the disease. Ninety-five percent of breast cancer cases correspond to sporadic forms of the disease and are believed to involve an interaction between environmental and genetic determinants. The microRNA 17–92 cluster host gene (MIR17HG) has been shown to regulate expression of genes involved in breast cancer development and progression. Study of single-nucleotide polymorphisms (SNPs) located in this cluster gene could help provide a further understanding of its role in breast cancer. Therefore, this study investigated six SNPs in the MIR17HG using two independent Australian Caucasian case–control populations (GRC-BC and GU-CCQ BB populations) to determine association to breast cancer susceptibility. Genotyping was undertaken using chip-based matrix assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry (MS). We found significant association between rs4824505 and breast cancer at the allelic level in both study cohorts (GRC-BC p = 0.01 and GU-CCQ BB p = 0.03). Furthermore, haplotypic analysis of results from our combined population determined a significant association between rs4824505/rs7336610 and breast cancer susceptibility (p = 5 × 10−4). Our study is the first to show that the A allele of rs4824505 and the AC haplotype of rs4824505/rs7336610 are associated with risk of breast cancer development. However, definitive validation of this finding requires larger cohorts or populations in different ethnical backgrounds. Finally, functional studies of these SNPs could provide a deeper understanding of the role that MIR17HG plays in the pathophysiology of breast cancer.
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Introduction Xanthine oxidase (XO) is distributed in mammals largely in the liver and small intestine, but also is highly active in milk where it generates hydrogen peroxide (H2O2). Adult human saliva is low in hypoxanthine and xanthine, the substrates of XO, and high in the lactoperoxidase substrate thiocyanate, but saliva of neonates has not been examined. Results Median concentrations of hypoxanthine and xanthine in neonatal saliva (27 and 19 μM respectively) were ten-fold higher than in adult saliva (2.1 and 1.7 μM). Fresh breastmilk contained 27.3±12.2 μM H2O2 but mixing baby saliva with breastmilk additionally generated >40 μM H2O2, sufficient to inhibit growth of the opportunistic pathogens Staphylococcus aureus and Salmonella spp. Oral peroxidase activity in neonatal saliva was variable but low (median 7 U/L, range 2–449) compared to adults (620 U/L, 48–1348), while peroxidase substrate thiocyanate in neonatal saliva was surprisingly high. Baby but not adult saliva also contained nucleosides and nucleobases that encouraged growth of the commensal bacteria Lactobacillus, but inhibited opportunistic pathogens; these nucleosides/bases may also promote growth of immature gut cells. Transition from neonatal to adult saliva pattern occurred during the weaning period. A survey of saliva from domesticated mammals revealed wide variation in nucleoside/base patterns. Discussion and Conclusion During breast-feeding, baby saliva reacts with breastmilk to produce reactive oxygen species, while simultaneously providing growth-promoting nucleotide precursors. Milk thus plays more than a simply nutritional role in mammals, interacting with infant saliva to produce a potent combination of stimulatory and inhibitory metabolites that regulate early oral–and hence gut–microbiota. Consequently, milk-saliva mixing appears to represent unique biochemical synergism which boosts early innate immunity.