1,682 research outputs found

    Personal epistemologies and disciplinarity in the workplace: implications for international students in higher education

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    Workplace experiences for international students undertaking higher education programs are important aspects of their university experience. This is because many of the programs in which they are enrolled are directed towards particular occupations. Nevertheless, these workplace experiences can be both engaging and daunting for all, but perhaps no more so than for international students, who may be unfamiliar with Australian workplace mores and practices, and therefore less able to understand and negotiate with them than their domestic counterparts. Not only do international students have to become familiar with the requirements of their selected profession but also need to understand and negotiate unfamiliar cultural environments. These students often have to engage in complex and demanding learning processes when engaging in work placements, perhaps more so than their domestic peers. Because of these discipline-based and workplace environmental challenges, it is necessary for these students and their mentors or supervisors to try and effectively mediate their participation and learning in the work placements. If all of those involved in work placements are aware of these factors, then the experiences and outcomes should potentially be more beneficial for all parties (i.e., students, supervisors, university staff, and workplaces). These issues are explored in this chapter through the notions of disciplinarity, which attends to the epistemological nuances of particular study or knowledge areas and how students develop skills as disciplinary professionals. With a focus on international students, the elaborations of these issues are explored through consideration of interculturalisation and how both the experiences and experiencing of international students impacts upon the success of their work placements. Using these concepts as explanatory bases stands to permit the illumination and elaboration of the complexity of factors and processes occurring as these students learn about, and participate in, their selected professional discipline and the cultural environment of its practice

    Patient-centric trials for therapeutic development in precision oncology

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    An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

    Bisexual women's understandings of social marginalisation: 'The heterosexuals don't understand US but nor do the lesbians'

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    Drawing on interviews with 20 self-identified bisexual women, this paper contributes to the limited psychological literature on bisexual women by exploring their experiences of social marginalisation. These (mainly white and middle class) British bisexual women reported that they did not feel at home in either lesbian or lesbian, gay, bisexual and transgender communities, nor in the wider (heteronormative) society. They identified a number of understandings - bisexuality as a temporary phase on the path to a fully realised lesbian or heterosexual identity and bisexuals as immature, confused, greedy, untrustworthy, highly sexual and incapable of monogamy - which they reported as arising from lesbian, gay, bisexual and transgender communities and the wider society. The women refuted these accounts which they stated did not reflect their experiences of bisexual identity and which positioned bisexuality as invisible and invalid. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav

    Binomial Mitotic Segregation of MYCN-Carrying Double Minutes in Neuroblastoma Illustrates the Role of Randomness in Oncogene Amplification

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    BACKGROUND: Amplification of the oncogene MYCN in double minutes (DMs) is a common finding in neuroblastoma (NB). Because DMs lack centromeric sequences it has been unclear how NB cells retain and amplify extrachromosomal MYCN copies during tumour development. PRINCIPAL FINDINGS: We show that MYCN-carrying DMs in NB cells translocate from the nuclear interior to the periphery of the condensing chromatin at transition from interphase to prophase and are preferentially located adjacent to the telomere repeat sequences of the chromosomes throughout cell division. However, DM segregation was not affected by disruption of the telosome nucleoprotein complex and DMs readily migrated from human to murine chromatin in human/mouse cell hybrids, indicating that they do not bind to specific positional elements in human chromosomes. Scoring DM copy-numbers in ana/telophase cells revealed that DM segregation could be closely approximated by a binomial random distribution. Colony-forming assay demonstrated a strong growth-advantage for NB cells with high DM (MYCN) copy-numbers, compared to NB cells with lower copy-numbers. In fact, the overall distribution of DMs in growing NB cell populations could be readily reproduced by a mathematical model assuming binomial segregation at cell division combined with a proliferative advantage for cells with high DM copy-numbers. CONCLUSION: Binomial segregation at cell division explains the high degree of MYCN copy-number variability in NB. Our findings also provide a proof-of-principle for oncogene amplification through creation of genetic diversity by random events followed by Darwinian selection

    Global, local and focused geographic clustering for case-control data with residential histories

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    BACKGROUND: This paper introduces a new approach for evaluating clustering in case-control data that accounts for residential histories. Although many statistics have been proposed for assessing local, focused and global clustering in health outcomes, few, if any, exist for evaluating clusters when individuals are mobile. METHODS: Local, global and focused tests for residential histories are developed based on sets of matrices of nearest neighbor relationships that reflect the changing topology of cases and controls. Exposure traces are defined that account for the latency between exposure and disease manifestation, and that use exposure windows whose duration may vary. Several of the methods so derived are applied to evaluate clustering of residential histories in a case-control study of bladder cancer in south eastern Michigan. These data are still being collected and the analysis is conducted for demonstration purposes only. RESULTS: Statistically significant clustering of residential histories of cases was found but is likely due to delayed reporting of cases by one of the hospitals participating in the study. CONCLUSION: Data with residential histories are preferable when causative exposures and disease latencies occur on a long enough time span that human mobility matters. To analyze such data, methods are needed that take residential histories into account

    Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet

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    Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer's disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD

    Ancient DNA Resolves Identity and Phylogeny of New Zealand's Extinct and Living Quail (Coturnix sp.)

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    BACKGROUND: The New Zealand quail, Coturnix novaezealandiae, was widespread throughout New Zealand until its rapid extinction in the 1870's. To date, confusion continues to exist concerning the identity of C. novaezealandiae and its phylogenetic relationship to Coturnix species in neighbouring Australia, two of which, C. ypsilophora and C. pectoralis, were introduced into New Zealand as game birds. The Australian brown quail, C. ypsilophora, was the only species thought to establish with current populations distributed mainly in the northern part of the North Island of New Zealand. Owing to the similarities between C. ypsilophora, C. pectoralis, and C. novaezealandiae, uncertainty has arisen over whether the New Zealand quail is indeed extinct, with suggestions that remnant populations of C. novaezealandiae may have survived on offshore islands. METHODOLOGY/PRINCIPAL FINDINGS: Using fresh and historical samples of Coturnix sp. from New Zealand and Australia, DNA analysis of selected mitochondrial regions was carried out to determine phylogenetic relationships and species status. Results show that Coturnix sp. specimens from the New Zealand mainland and offshore island Tiritiri Matangi are not the New Zealand quail but are genetically identical to C. ypsilophora from Australia and can be classified as the same species. Furthermore, cytochrome b and COI barcoding analysis of the New Zealand quail and Australia's C. pectoralis, often confused in museum collections, show that they are indeed separate species that diverged approximately 5 million years ago (mya). Gross morphological analysis of these birds suggests a parallel loss of sustained flight with very little change in other phenotypic characters such as plumage or skeletal structure. CONCLUSION/SIGNIFICANCE: Ancient DNA has proved invaluable for the detailed analysis and identification of extinct and morphologically cryptic taxa such as that of quail and can provide insights into the timing of evolutionary changes that influence morphology

    Effects of intrauterine food restriction and long-term dietary supplementation with L-arginine on age-related changes in renal function and structure of rats

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    We have previously demonstrated that restricting intrauterine food by 50% in 3-mo-old rats produced lower nephron numbers and early-onset hypertension, the latter being normalized by L-arginine administration. in 18-mo-old rats, such restriction increased glomerulosclerosis. in this study, we expanded our investigation, evaluating functional, morphologic, and immunohistochemical parameters in intrauterine-food-restricted 18-mo-old rats, either receiving L-arginine (RA18) or not (R18). Age-matched, non-food-restricted controls were assigned to similar groups with L-arginine (CA18) and without (C18). After weaning, L-arginine was given daily for 17 mo. No functional or morphologic changes were observed in C IS rats. the R18 rats developed early-onset hypertension, which persisted throughout the observation period, as well its significant proteinuria from 12 mo on. in RA18 rats, L-arginine decreased both blood pressure levels and proteinuria, and glomerular diameter was si,significantly smaller than in R18 rats (115.63 +/- 2.2 versus 134.8 +/- 1.0 mu m, p < 0.05). However, in RA18 rats, glomerular filtration rate remained depressed. Although L-arginine prevented glomerulosclerosis (R18 = 14%, RA18 = 4%; p < 0.05), glomerular expression of fibronectin and desmin was still greater in RA18 rats than in controls. Our data show that, although L-arginine prevented hypertension and proteinuria, glomerular injury still occurred, suggesting that intrauterine food restriction may be one of the leading causes of impaired renal function in adult life.Universidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilUniv São Paulo, Ribeirao Preto Sch Med, Dept Physiol & Biophys, Brookline, MA 02146 USAUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Physiol, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, EPM, Dept Morphol,Embrol Div, BR-04023900 São Paulo, BrazilWeb of Scienc
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