Statistical method on nonrandom clustering with application to somatic mutations in cancer

<p>Abstract</p> <p>Background</p> <p>Human cancer is caused by the accumulation of tumor-specific mutations in oncogenes and tumor suppressors that confer a selective growth advantage to cells. As a consequence of genomic instability and high levels of proliferation, many passenger mutations that do not contribute to the cancer phenotype arise alongside mutations that drive oncogenesis. While several approaches have been developed to separate driver mutations from passengers, few approaches can specifically identify activating driver mutations in oncogenes, which are more amenable for pharmacological intervention.</p> <p>Results</p> <p>We propose a new statistical method for detecting activating mutations in cancer by identifying nonrandom clusters of amino acid mutations in protein sequences. A probability model is derived using order statistics assuming that the location of amino acid mutations on a protein follows a uniform distribution. Our statistical measure is the differences between pair-wise order statistics, which is equivalent to the size of an amino acid mutation cluster, and the probabilities are derived from exact and approximate distributions of the statistical measure. Using data in the Catalog of Somatic Mutations in Cancer (COSMIC) database, we have demonstrated that our method detects well-known clusters of activating mutations in KRAS, BRAF, PI3K, and <it>β</it>-catenin. The method can also identify new cancer targets as well as gain-of-function mutations in tumor suppressors.</p> <p>Conclusions</p> <p>Our proposed method is useful to discover activating driver mutations in cancer by identifying nonrandom clusters of somatic amino acid mutations in protein sequences.</p

Advanced Nurse Practitioners’ (Emergency) perceptions of their role, positionality and professional identity: a narrative inquiry

Aims To explore Advanced Nurse Practitioners' (Emergency) perceptions of their role, positionality and professional identity. Background Advanced nursing practice was formally established in the Republic of Ireland in 2001 with 336 Advanced Nurse Practitioners currently registered increasing to a critical mass of 750 by 2021. Advanced practitioners (Emergency) provide full emergency care for a specific cohort of clients with unscheduled, undifferentiated and undiagnosed conditions. Design Qualitative narrative inquiry using Bourdieu's concepts of habitus, field and capital as the theoretical framework was undertaken. Methods Data were collected in ten in‐depth interviews and thematic analysis applied. Results Five key themes emerged: participants' career pathways, personal and professional transitions, role dimensions and core concepts, position in the organisation and emergent professional identity. Role‐transitioning and a change in habitus, field and capital revealed the uniqueness of their nursing role. Minimising waiting times, timely patient care and patient satisfaction were key performance indicators. A heightened awareness regarding higher‐level decision‐making, autonomy and accountability are integral to advanced practice. Conclusion This study presents unique insights into the advanced nurse practitioner role covering recruitment, organisational culture changes required and support to ease transition emerged. Impact Better understanding the motivation to undertake the role, the transition experience and use of advanced practice skills‐sets will inform the targets for the future recruitment and retention of Advanced Nurse Practitioners are met nationally and internationally. Dissatisfaction with previous management roles and wanting to be clinically‐close to patients were motivations to follow an advanced practice clinical career trajectory. Positionality and emergent professional identity are key enablers ensuring advanced practitioners' roles demonstrate the attributes of advanced practice. Educators could use the findings to develop recruitment, retention and progression strategies. Disseminating the role and scopes of practice could positively influence collaborative models of service delivery and policy development

A cycle of brain gain, waste and drain - a qualitative study of non-EU migrant doctors in Ireland.

BACKGROUND: Ireland is heavily reliant on non-EU migrant health workers to staff its health system. Shortages of locally trained health workers and policies which facilitate health worker migration have contributed to this trend. This paper provides insight into the experiences of non-EU migrant doctors in the Irish health workforce. METHOD: In-depth interviews were conducted with 37 non-EU migrant doctors in Ireland in 2011/2012. RESULTS: Respondents believed they had been recruited to fill junior hospital doctor 'service' posts. These posts are unpopular with locally trained doctors due to the limited career progression they provide. Respondents felt that their hopes for career progression and postgraduate training in Ireland had gone unrealised and that they were becoming de-skilled. As a result, most respondents were actively considering onward migration from Ireland. DISCUSSION & CONCLUSIONS: Failure to align the expectations of non-EU migrant doctors with the requirements of the health system has resulted in considerable frustration and a cycle of brain gain, waste and drain. The underlying reasons for high mobility into and out of the Irish medical workforce must be addressed if this cycle is to be broken. The heavy reliance on non-EU migrant doctors to staff the medical workforce has distracted from the underlying workforce challenges facing the Irish medical workforce

Safety design for the 6AM6 alkaline dry battery

Translated from Japanese (Natl. Tech. Rep. Oct 1986 v. 32(5) p. 69-73)SIGLEAvailable from British Library Document Supply Centre- DSC:9022.381(HSE-Trans--12504)T / BLDSC - British Library Document Supply CentreGBUnited Kingdo