769 research outputs found

    motifDiverge: a model for assessing the statistical significance of gene regulatory motif divergence between two DNA sequences

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    Next-generation sequencing technology enables the identification of thousands of gene regulatory sequences in many cell types and organisms. We consider the problem of testing if two such sequences differ in their number of binding site motifs for a given transcription factor (TF) protein. Binding site motifs impart regulatory function by providing TFs the opportunity to bind to genomic elements and thereby affect the expression of nearby genes. Evolutionary changes to such functional DNA are hypothesized to be major contributors to phenotypic diversity within and between species; but despite the importance of TF motifs for gene expression, no method exists to test for motif loss or gain. Assuming that motif counts are Binomially distributed, and allowing for dependencies between motif instances in evolutionarily related sequences, we derive the probability mass function of the difference in motif counts between two nucleotide sequences. We provide a method to numerically estimate this distribution from genomic data and show through simulations that our estimator is accurate. Finally, we introduce the R package {\tt motifDiverge} that implements our methodology and illustrate its application to gene regulatory enhancers identified by a mouse developmental time course experiment. While this study was motivated by analysis of regulatory motifs, our results can be applied to any problem involving two correlated Bernoulli trials

    Evaluating and developing GP appraisal processes

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    EXECUTIVE SUMMARY: Introduction: This report details findings from a study undertaken by the School of Primary Care, Severn Deanery and the School of Health and Social Care, Faculty of Health and Life Sciences, University of the West of England, Bristol (UWE) between November 2008 and November 2009 to evaluate and develop GP appraisal processes in an area in the South West of England.A process of licensing for all doctors practising medicine in the UK is currently being implemented by the General Medical Council (GMC). All licensed doctors will need to demonstrate at regular intervals that their practice meets the generic standards set by the GMC, as described in Good Medical Practice (GMC 2006). Licensing will involve a process of revalidation for individual practitioners. It is planned to incorporate revalidation into the current appraisal processes for all medical professionals (GMC 2008).Although a statutory requirement, GP appraisal has until recently had primarily a formative, developmental purpose (DH 2002). Despite being obligatory, the uptake of GP appraisal has been problematic and inconsistent (Martin et al 2003). To date, only a limited amount of research or evaluation about GP appraisal has been published. However, there is recognised tension between the concept of appraisal as both a supportive developmental process and as a measure for judging fitness to practise.STUDY AIMA: This study set out to evaluate existing evidence submitted by GPs for the purposes of appraisal, and to explore how a model for appraisal could be developed that meets the needs of revalidation but also acts as a developmental process for individual GPs.METHODS: Both qualitative and quantitative methods were used for this study, in order to provide both breadth and depth to the evaluation. Quantitative data sources comprised all the appraisal evidence checklists used by appraisers in one Primary Care Trust (PCT) over the financial year April 2008 to May 2009 (n=123). The evidence checklist provides a basic template for recording the types of evidence a GP appraisee submits for appraisal purposes, and whether the evidence submitted relates to an individual’s personal practice, or to organisational practice within the GP practice as a whole. Data were analysed using descriptive statistics. Comparative analysis of types of evidence was conducted for appraiser, appraisee age and appraisee status.Qualitative data were collected through 5 focus groups held with 23 attendees at a GP appraisal stakeholder event hosted by the Deanery, and through interviews with all the appraisal leads for PCTs within the Deanery’s geographical area (n=7). Data were analysed thematically.The study was approved by a University research ethics sub-committee.MAIN FINDINGS AND POINTS FOR CONSIDERATION: Findings from this study raise particular points for consideration in relation to the appraiser role; the nature of evidence required for appraisal; the situation of sessional doctors; appraisee age; sharing expertise and experience; and the role of the Deanery in appraisal.Appraiser role: Most focus group and interview participants were adamant that appraisal should retain a strong developmental element. Clear definition of the role and appropriate national training were seen as essential factors contributing to the success of the process.Evidence required for appraisal: A notable feature of the focus group data was the confusion expressed by many participants about the nature and amount of evidence required for appraisal. Given the perception that appraisal for revalidation is extremely time-consuming for individual GPs, it was felt that having a clear brief about the evidence required is essential. The revised RCGP guidelines published after these data were collected (RCGP 2009, 2010) may go some way to ameliorating this problem, particularly with respect to the description of what constitutes audit for appraisal purposes.Sessional doctors: Many focus group participants and at least one appraisal lead were concerned that sessional doctors would have problems collecting the required evidence for appraisal. However, the data from this study also suggest that these problems can be addressed. The checklist data revealed very few substantive differences between principal and sessional doctors with regard to evidence submitted for appraisal. In particular, there was no statistically significant difference between the proportions of principal and sessional doctors who provided supporting information concerning their personal practice in relation to significant events, data or audit collection, multi-source feedback and complaints; this was notable, as these four areas have been identified as potentially problematic for sessional doctors (RCGP 2009, 2010). A number of the study participants were able to provide anecdotal evidence concerning innovative practice among sessional doctors with respect to the collection of evidence for appraisal, both at personal and collective levels. All these data, taken together, suggest that sessional doctors’ problems in this regard may be overstated, as long as appropriate support is provided by employing practices and PCTs.Appraisee age: The stereotype of the older GP, near retirement and not computer-literate, and not wishing to engage with appraisal, was present in the data. However, this was counterbalanced by examples of exceptions, and concern expressed about some younger, part-time GPs, whose personal circumstances do not support their involvement in appraisal. No differences were found in the checklist data between younger and older GPs with regard to the evidence they provided for appraisal. This applied to all GPs, and also only to locum GPs. It appears that difficulties encountered arise due to individuals’ particular circumstances or personalities, rather than because they belong to a defined category of appraisee.Sharing expertise and experience: A very strong feature of the qualitative data was the extent to which participants enthused about the benefits they experience when presented with opportunities for sharing expertise and experience. A number of suggestions concerning format were made, including both face to face and on-line media.The role of the Deanery in appraisal: There was no consistency with regard to participants’ opinions about the degree to which the Deanery should be involved in the co-ordination of the appraisal process. However, all the participants, both from the focus groups and the appraisal leads, were clear that the Deanery has a valuable role to play in training and preparation for appraisal for both appraisers and appraisees. They welcomed the idea that the Deanery could provide fora for sharing expertise and experience, as well as providing structured, dedicated preparation for appraisees. The Deanery was also thought to be well placed to help address any lack of consistency among appraisers through appropriate training.RECOMMENDATIONS:1. Change the organisational culture of practices and trusts to encourage access for sessional and locum doctors to Clinical Governance, Significant Event, Audit and Data Collection, through meetings and improved communication. This could be accelerated by including locum access as a quality criterion to be reviewed at practice inspections by PCTs or by the Care Quality Commission.2. Encourage, establish and facilitate fora and self directed groups for isolated locums and sessional GPs.3. Provide examples of innovative ways of collecting evidence for this group.4. Establish new tools designed specifically for this group, such as patient and colleague feedback

    Failure of an Educational Intervention to Improve Consultation and Implications for Healthcare Consultation.

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    INTRODUCTION: Consultation of another physician for his or her specialized expertise regarding a patient's care is a common occurrence in most physicians' daily practice, especially in the emergency department (ED). Therefore, the ability to communicate effectively with another physician during a patient consultation is an essential skill. However, there has been limited research on a standardized method for a physician to physician consultation with little guidance on teaching consultations to physicians in training. The objective of our study was to measure the effect of a structured consultation intervention on both content standardization and quality of medical student consultations. METHODS: Senior medical students were assessed on a required emergency medicine rotation with a physician phone consultation during a standardized, simulated chest pain case. The intervention groups received a standard consult checklist as part of their orientation to the rotation, followed by a video recording of a good consult call and a bad consult call with commentary from an emergency physician. The intervention was given to students every other month, alternating with a control group who received no additional education. Recordings were reviewed by three second-year internal medicine residents pursuing a fellowship in cardiology. Each recording was evaluated by two of the three reviewers and scored using a standardized checklist. RESULTS: Providing a standardized consultation intervention did not improve students' ability to communicate with consultants. In addition, there was variability between evaluators in regards to how they received the same information and how they perceived the quality of the same recorded consultation calls. Evaluator inter-rater reliability (IRR) was poor on the questions of 1) would you have any other questions of the student calling the consult and 2) did the student calling the consult provide an accurate account of information and case detail. The IRR was also poor on objective data such as whether the student stated their name. CONCLUSIONS: A brief intervention may not be enough to change complex behavior such as a physician to physician consultant communication. Importantly, despite consultants listening to the same audio recordings, the information was processed differently. Future investigations should focus on both those delivering as well as those receiving a consultation

    Development of a standardized communication intervention bundle for use at a medical training hospital intensive care unit

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    How to cite this article: Pollard K, Wessman BT. Development of a Standardized Communication Intervention Bundle for Use at a Medical Training Hospital Intensive Care Unit. Indian J Crit Care Med 2019;23(5):234-235

    An evaluation of the foundation degree in healthcare science

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    This project evaluated the innovative Foundation Degree in Healthcare Science course launched by the Faculty of Health & Applied Sciences, UWE, in partnership with Cogent: Skills for Science, Modernising Scientific Careers and Healthcare science employers. A qualitative mixed-methods approach was used to gather perceptions of students and staff. Key messages:1. Timely information about the structure, timings and cost of the programme is important to allow students and workplace mentors to manage the competing demands of study time and workload. 2 Smoothly functioning IT and appropriate use of technology enhanced learning (TEL) are vital for the blended learning approach to be successful. 3 Students have felt that their feedback has been listened to and acted on by academic staff. 4 Service colleagues value the programme as it helps to develop knowledge and confidence in staff who are already team member

    SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2.

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    SIRT1 and SIRT3 are NAD+-dependent protein deacetylases that are evolutionarily conserved across mammals. These proteins are located in the cytoplasm/nucleus and mitochondria, respectively. Previous reports demonstrated that human SIRT1 deacetylates Acetyl-CoA Synthase 1 (AceCS1) in the cytoplasm, whereas SIRT3 deacetylates the homologous Acetyl-CoA Synthase 2 (AceCS2) in the mitochondria. We recently showed that 3-hydroxy-3-methylglutaryl CoA synthase 2 (HMGCS2) is deacetylated by SIRT3 in mitochondria, and we demonstrate here that SIRT1 deacetylates the homologous 3-hydroxy-3-methylglutaryl CoA synthase 1 (HMGCS1) in the cytoplasm. This novel pattern of substrate homology between cytoplasmic SIRT1 and mitochondrial SIRT3 suggests that considering evolutionary relationships between the sirtuins and their substrates may help to identify and understand the functions and interactions of this gene family. In this perspective, we take a first step by characterizing the evolutionary history of the sirtuins and these substrate families

    Evaluating student learning in an interprofessional curriculum: the relevance of pre-qualifying inter-professional education for future professional practice

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    The focus of this study was qualified health and social care professionals’ views about their experience of pre-qualifying interprofessional education (IPE). Adult nurses, midwives, physiotherapists, and social workers were interviewed
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