2,156 research outputs found

    Association of a Genetic Risk Score With Body Mass Index

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    Empirically assessing the plausibility of unconfoundedness in observational studies

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    The possibility of unmeasured confounding is one of the main limitations for causal inference from observational studies. There are different methods for partially empirically assessing the plausibility of unconfoundedness. However, most currently available methods require (at least partial) assumptions about the confounding structure, which may be difficult to know in practice. In this paper we describe a simple strategy for empirically assessing the plausibility of conditional unconfoundedness (i.e., whether the candidate set of covariates suffices for confounding adjustment) which does not require any assumptions about the confounding structure, requiring instead assumptions related to temporal ordering between covariates, exposure and outcome (which can be guaranteed by design), measurement error and selection into the study. The proposed method essentially relies on testing the association between a subset of covariates (those associated with the exposure given all other covariates) and the outcome conditional on the remaining covariates and the exposure. We describe the assumptions underlying the method, provide proofs, use simulations to corroborate the theory and illustrate the method with an applied example assessing the causal effect of length-for-age measured in childhood and intelligence quotient measured in adulthood using data from the 1982 Pelotas (Brazil) birth cohort. We also discuss the implications of measurement error and some important limitations

    Empirically assessing the plausibility of unconfoundedness in observational studies

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    The possibility of unmeasured confounding is one of the main limitations for causal inference from observational studies. There are different methods for partially empirically assessing the plausibility of unconfoundedness. However, most currently available methods require (at least partial) assumptions about the confounding structure, which may be difficult to know in practice. In this paper we describe a simple strategy for empirically assessing the plausibility of conditional unconfoundedness (i.e., whether the candidate set of covariates suffices for confounding adjustment) which does not require any assumptions about the confounding structure, requiring instead assumptions related to temporal ordering between covariates, exposure and outcome (which can be guaranteed by design), measurement error and selection into the study. The proposed method essentially relies on testing the association between a subset of covariates (those associated with the exposure given all other covariates) and the outcome conditional on the remaining covariates and the exposure. We describe the assumptions underlying the method, provide proofs, use simulations to corroborate the theory and illustrate the method with an applied example assessing the causal effect of length-for-age measured in childhood and intelligence quotient measured in adulthood using data from the 1982 Pelotas (Brazil) birth cohort. We also discuss the implications of measurement error and some important limitations

    Transformational change in healthcare: an examination of four case studies

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    Objectives Healthcare leaders around the world are calling for radical, transformational change of our health and care systems. This will be a difficult and complex task. In this article, we examine case studies in which transformational change has been achieved, and seek to learn from these experiences. Methods We used the case study method to investigate examples of transformational change in healthcare. The case studies were identified from preliminary doctoral research into the transition towards future sustainable health and social care systems. Evidence was collected from multiple sources, key features of each case study were displayed in a matrix and thematic analysis was conducted. The results are presented in narrative form. Results Four case studies were selected: two from the US, one from Australia and one from the UK. The notable features are discussed for each case study. There were many common factors: a well communicated vision, innovative redesign, extensive consultation and engagement with staff and patients, performance management, automated information management and high-quality leadership. Conclusions Although there were some notable differences between the case studies, overall the characteristics of success were similar and collectively provide a blueprint for transformational change in healthcare. What is known about the topic? Healthcare leaders around the world are calling for radical redesign of our systems in order to meet the challenges of modern society. What does this paper add? There are some remarkable examples of transformational change in healthcare. The key factors in success are similar across the case studies. What are the implications for practitioners? Collectively, these key factors can guide future attempts at transformational change in healthcare. </jats:p

    MR-pheWAS with stratification and interaction:Searching for the causal effects of smoking heaviness identified an effect on facial aging

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    Mendelian randomization (MR) is an established approach to evaluate the effect of an exposure on an outcome. The gene-by-environment (GxE) study design can be used to determine whether the genetic instrument affects the outcome through pathways other than via the exposure of interest (horizontal pleiotropy). MR phenome-wide association studies (MR-pheWAS) search for the effects of an exposure, and can be conducted in UK Biobank using the PHESANT package. In this proof-of-principle study, we introduce the novel GxE MR-pheWAS approach, that combines MR-pheWAS with the use of GxE interactions. This method aims to identify the presence of effects of an exposure while simultaneously investigating horizontal pleiotropy. We systematically test for the presence of causal effects of smoking heaviness-stratifying on smoking status (ever versus never)-as an exemplar. If a genetic variant is associated with smoking heaviness (but not smoking initiation), and this variant affects an outcome (at least partially) via tobacco intake, we would expect the effect of the variant on the outcome to differ in ever versus never smokers. We used PHESANT to test for the presence of effects of smoking heaviness, instrumented by genetic variant rs16969968, among never and ever smokers respectively, in UK Biobank. We ranked results by the strength of interaction between ever and never smokers. We replicated previously established effects of smoking heaviness, including detrimental effects on lung function. Novel results included a detrimental effect of heavier smoking on facial aging. We have demonstrated how GxE MR-pheWAS can be used to identify potential effects of an exposure, while simultaneously assessing whether results may be biased by horizontal pleiotropy

    Teaching for life? midlife narratives from female classroom teachers who considered leaving the profession

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    Career decision-making research has focused primarily on occupation change as a discrete event and emphasised occupational mobility. Not all of those who consider changing occupation do so though, and this study explored the narrative accounts of nine female teachers who had considered leaving the profession, but remained teaching at midlife. Narrative plotlines illustrated how this decision-making process evolved across the career span and revealed individual experiences ranging from reconciliation to on-going disaffection with teaching. Thematic analysis identified factors associated with occupational embeddedness in understanding why these women stayed and the potential for embedding issues to constrain women's occupational mobility. Implications for career counselling include exploring occupational decision-making across the career span, recognising the impact of embedding forces on women's teaching careers and supporting those who feel unable to leave this demanding occupation

    Refugees’ narratives of career barriers and professional identity

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    Purpose: This paper examines how refugees from a professional career domain restore a coherent narrative when confronting barriers to recognition of their former career status. It focuses in particular on the identity work in which they engage in order to reconcile tensions between their current status as refugees and their professional identity. Design/method/approach: Fifteen refugees to the UK who were professionally qualified in medicine or teaching in their country of origin took part in interviews or focus groups exploring career barriers, plans and future aspirations. Initial inductive thematic analysis identified recognition of professional identities as a primary concern. Further analytic iterations between theory and empirical material sharpened the focus on identifying the tensions in their professional identity work. Findings: Participants struggled both to restore their former professional identity and to develop alternative identities. Professional identity work limited, but also sustained them in the face of barriers they encountered as refugees. Practical implications: More support for refugee career development would facilitate adaptation to local job markets, thereby addressing gaps in Education and Health services in the UK. Originality value: Highlights the tensions in refugee professional identity work and particularly the challenges and rewards of professional identification in the face of employment barriers
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