479 research outputs found

    Setting in the Modern Short Story

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    The case-only method for gene-environment interaction studies: the independence assumption illustrated with empirical data from the published literature and two population-based control groups, the Carolina Breast Cancer Study and the North Carolina Colon Cancer Study

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    Gene-environment interaction in the etiology of disease is a topic of on-going interest. While there has been increasing use of the case-only study design to investigate gene-environment interaction in cancer, as well as other disease areas, concerns about the underlying assumption that the genetic and environmental exposures are independent in the underlying population (the independence assumption) have not been adequately addressed. The case-only study design requires only cases, no population controls or cohort, to estimate statistical interaction. This design has obvious cost advantages, as well as some methodological and ethical advantages. However, for results to be valid the independence assumption must be met. There has been little investigation into the frequency and magnitude of independence assumption violation for DNA repair genes and smoking, an interaction of particular interest in cancer. Nor have optimal methods for validating the independence assumption received much attention. Empirical data of two types were used to evaluate the independence assumption for selected genetic variants and smoking behavior. A systematic review of the literature identified 55 studies that presented the joint distribution of smoking and SNPs in 3 DNA repair genes (XRCC1 Arg399Gln, Arg194Trp, or Arg280His, XPD Lys751Gln, and Asp312Asn, and XRCC3 Thr241Met). Measures of smoking were ever/never smoking, current/not current smoker, duration of smoking (20 years), intensity (1 pack/day), and pack-years (35 pack-years). The odds ratio for SNP-smoking association in controls (ORz) was used to estimate the gene-environment association in the underlying population. Results showed that ORz was not reliably null for any of the SNP-smoking combinations. Studies with XRCC1 399 / ever-never smoking and XPD 751 / pack-years were too heterogeneous for summary estimates [ranges, ORz (95% confidence interval (CI)): 0.7 (0.4, 1.2) - 1.9 (1.2, 2.8) and 0.8 (0.5, 1.3) - 2.3 (0.8, 6.1), respectively). In addition, estimates for studies considered homogeneous (Cochran's Q p-value <0.10) varied 2- to 5-fold within meta-analysis. No study characteristics were identified that could explain heterogeneity. Data from two population-based control groups, the Carolina Breast Cancer Study and the North Carolina Colon Cancer Study, were used to evaluate the independence assumption for smoking and a panel of eight metabolic and 26 DNA repair genes plausibly related to smoking behavior. ORz was not consistent across smoking measures precluding the use of one smoking measure (e.g. ever-never) as a substitute for evaluating other measures such as duration and dose. In particular, results for smoking status were most often near the null, while measures of smoking amount for the same SNPs were of sufficient magnitude to cause appreciable bias in the case-only estimates (ORz=1.4) approximately half of the time. There were no strong patterns of the magnitude or direction of ORz differing by race, age, gender or biological pathway (xenobiotic metabolism, DNA repair). Taken together, results suggest that ORz should be considered population-specific. Therefore, the independence assumption should be evaluated in the population underlying a case-only study, rather than in a proxy control group(s) or pooled controls. A systematic search for relevant literature and control data, in addition to a comprehensive evaluation of all smoking measures used in the case-only analysis are essential for evaluation of the independence assumption

    Each Brain

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    Each Brain is a 21-minute alternative documentary featuring an interabled and collaborative approach to filmmaking with subjects, Hana Kujawa and Melanie Taddeo-Nxumalo, both experienced profound acquired disability in early adulthood. The film’s central themes are creative collaboration and reframing the experience of disability. Departing from a classic talking head style documentary, Each Brain explores Hana and Melanie’s experience through original abstract visuals, curated stock footage and archival pieces provided by the collaborators themselves. Woven throughout the film is captured audio of an epileptic seizure, soundscapes, recorded letters and poetry as its soundtrack. The result is an immersive film which further explores the lived experience of two women navigating a diagnosis of epilepsy and the perseverance that guides their journeys

    The National Record of Achievement: just another initiative or a useful tool for the future?

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    This thesis sets out to explore why records of achievement (RoA)\ud became part of national education policy in the English education\ud system, whether it is just one more education initiative, like so\ud many others, which only had a relevance and significance at a\ud particular time and within a certain context, or whether it might\ud have a longer-term structural significance within the national\ud education system. The thesis focuses particularly on the significance\ud and role of the first nationally recognised and designed record of\ud achievement - the National Record of Achievement (NRA) - which\ud was introduced in 1991 and has been redesigned as a result of the\ud Dearing Review of 16-19 Qualifications (Dearing 1996).1\ud The thesis argues that there are three major inter-related factors\ud which determine the role that RoA has played or might play within\ud the English education and training system - firstly, and most\ud importantly, the context within which it is developed; secondly, the\ud content or features of the record itself (particularly the change from\ud locally developed and determined records to the National Record of\ud Achievement); and thirdly, the balance in emphasis between the use\ud of the process of recording of achievement and the use of the RoA\ud document itself. These three factors form the basis of a theoretical\ud framework which is developed in Chapter 1 and is then used\ud throughout the thesis to analyse the role of RoA (and specifically the\ud NRA) in the past and in the future.\ud The thesis uses this theoretical framework, as well as a detailed case\ud study, to identify and describe the role that RoA has played in its\ud three major phases of development:\ud Phase 1 (1969-1991) - RoA as a widespread but locally\ud determined education initiative, largely brought in to meet\ud the needs of lower achievers;\ud Phase 2 (1991-1996) - NRA as a national policy instrument for\ud use with all learners to record achievement;\ud Phase 3 (a potential future phase) - NRA as a tool for\ud supporting lifelong learning.\ud The thesis concludes by arguing that it is in the type of role described\ud in Phase 3 that the NRA will become more than just another\ud education policy initiative and will take on a longer-term structural\ud significance within the English education and training system.\ud Dearing, Sir Ron (1996) Review of Qualifications for 16-19 Year Olds, London: DfE
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