Encouraging the scholarship of learning and teaching in an institutional context

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Bcl11b—A Critical Neurodevelopmental Transcription Factor—Roles in Health and Disease

B cell leukemia 11b (Bcl11b) is a zinc finger protein transcription factor with a multiplicity of functions. It works as both a genetic suppressor and activator, acting directly, attaching to promoter regions, as well as indirectly, attaching to promoter-bound transcription factors. Bcl11b is a fundamental transcription factor in fetal development, with important roles for the differentiation and development of various neuronal subtypes in the central nervous system (CNS). It has been used as a specific marker of layer V subcerebral projection neurons as well as striatal interneurons. Bcl11b also has critical developmental functions in the immune, integumentary and cardiac systems, to the extent that Bcl11b knockout mice are incompatible with extra-uterine life. Bcl11b has been implicated in a number of disease states including Huntington’s disease, Alzheimer’s disease, HIV and T-Cell malignancy, amongst others. Bcl11b is a fascinating protein whose critical roles in the CNS and other parts of the body are yet to be fully explicated. This review summarizes the current literature on Bcl11b and its functions in development, health, and disease as well as future directions for research

SOX9 transduction of a human chondrocytic cell line identifies novel genes regulated in primary human chondrocytes and in osteoarthritis

The transcription factor SOX9 is important in maintaining the chondrocyte phenotype. To identify novel genes regulated by SOX9 we investigated changes in gene expression by microarray analysis following retroviral transduction with SOX9 of a human chondrocytic cell line (SW1353). From the results the expression of a group of genes (SRPX, S100A1, APOD, RGC32, CRTL1, MYBPH, CRLF1 and SPINT1) was evaluated further in human articular chondrocytes (HACs). First, the same genes were investigated in primary cultures of HACs following SOX9 transduction, and four were found to be similarly regulated (SRPX, APOD, CRTL1 and S100A1). Second, during dedifferentiation of HACs by passage in monolayer cell culture, during which the expression of SOX9 progressively decreased, four of the genes (S100A1, RGC32, CRTL1 and SPINT1) also decreased in their expression. Third, in samples of osteoarthritic (OA) cartilage, which had decreased SOX9 expression compared with age-matched controls, there was decreased expression of SRPX, APOD, RGC32, CRTL1 and SPINT1. The results showed that a group of genes identified as being upregulated by SOX9 in the initial SW1353 screen were also regulated in expression in healthy and OA cartilage. Other genes initially identified were differently expressed in isolated OA chondrocytes and their expression was unrelated to changes in SOX9. The results thus identified some genes whose expression appeared to be linked to SOX9 expression in isolated chondrocytes and were also altered during cartilage degeneration in osteoarthritis

Three steps to data quality

Background The quality of data in general practice clinical information systems varies enormously. This variability jeopardises the proposed national strategy for an integrated care records service and the capacity of primary care organisations to respond coherently to the demands of clinical governance and the proposed quality-based general practice contract. This is apparent in the difficulty in automating the audit process and in comparing aggregated data from different practices. In an attempt to provide data of adequate quality to support such operational needs, increasing emphasis is being placed on the standardisation of data recording. Objective To develop a conceptual framework to facilitate the recording of standardised data within primary care. Method A multiprofessional group of primary care members from the South Thames Research Network examined leading guidelines for best practice. Using the nominal group technique the group prioritised the information needs of primary care organisations for managing coronary heart disease according to current evidence. Results Information needs identified were prioritized and stratified into a functional framework. Conclusion It has been possible within the context of a primary care research network to produce a framework for standardising data collection. Motivation of front-line clinicians was achieved through the incorporation of their views into the synthesis of the dataset

Cost-Effectiveness of Robot-Assisted Radical Cystectomy vs Open Radical Cystectomy for Patients With Bladder Cancer

IMPORTANCE: The value to payers of robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) when compared with open radical cystectomy (ORC) for patients with bladder cancer is unclear. OBJECTIVES: To compare the cost-effectiveness of iRARC with that of ORC. DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation used individual patient data from a randomized clinical trial at 9 surgical centers in the United Kingdom. Patients with nonmetastatic bladder cancer were recruited from March 20, 2017, to January 29, 2020. The analysis used a health service perspective and a 90-day time horizon, with supplementary analyses exploring patient benefits up to 1 year. Deterministic and probabilistic sensitivity analyses were undertaken. Data were analyzed from January 13, 2022, to March 10, 2023. INTERVENTIONS: Patients were randomized to receive either iRARC (n = 169) or ORC (n = 169). MAIN OUTCOMES AND MEASURES: Costs of surgery were calculated using surgery timings and equipment costs, with other hospital data based on counts of activity. Quality-adjusted life-years were calculated from European Quality of Life 5-Dimension 5-Level instrument responses. Prespecified subgroup analyses were undertaken based on patient characteristics and type of diversion. RESULTS: A total of 305 patients with available outcome data were included in the analysis, with a mean (SD) age of 68.3 (8.1) years, and of whom 241 (79.0%) were men. Robot-assisted radical cystectomy was associated with statistically significant reductions in admissions to intensive therapy (6.35% [95% CI, 0.42%-12.28%]), and readmissions to hospital (14.56% [95% CI, 5.00%-24.11%]), but increases in theater time (31.35 [95% CI, 13.67-49.02] minutes). The additional cost of iRARC per patient was £1124 (95% CI, -£576 to £2824 [US $1622 (95$831 to $4075)]) with an associated gain in quality-adjusted life-years of 0.01124 (95$144 312) per quality-adjusted life-year gained. Robot-assisted radical cystectomy had a much higher probability of being cost-effective for subgroups defined by age, tumor stage, and performance status. CONCLUSIONS AND RELEVANCE: In this economic evaluation of surgery for patients with bladder cancer, iRARC reduced short-term morbidity and some associated costs. While the resulting cost-effectiveness ratio was in excess of thresholds used by many publicly funded health systems, patient subgroups were identified for which iRARC had a high probability of being cost-effective. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03049410

Community nursing needs more silver surfers: a questionnaire survey of primary care nurses' use of information technology

BACKGROUND: In the UK the health service is investing more than ever before in information technology (IT) and primary care nurses will have to work with computers. Information about patients will be almost exclusively held in electronic patient records; and much of the information about best practice is most readily accessible via computer terminals. OBJECTIVE: To examine the influence of age and nursing profession on the level of computer use. METHODS: A questionnaire was developed to examine: access, training received, confidence and use of IT. The survey was carried out in a Sussex Primary Care Trust, in the UK. RESULTS: The questionnaire was sent to 109 nurses with a 64% response rate. Most primary care nurses (89%) use their computer regularly at work: 100% of practice nurses daily, compared with 60% of district nurses and 59% of health visitors (p < 0.01). Access to IT was not significantly different between different age groups; but 91% of practice nurses had their own computer while many district nurses and health visitors had to share (p < 0.01). Nurses over 50 had received more training that their younger colleagues (p < 0.01); yet despite this, they lacked confidence and used computers less (p < 0.001). 96% of practice nurses were confident at in using computerised medical records, compared with 53% of district nurses and 44% of health visitors (p < 0.01.) One-to-one training and workshops were the preferred formats for training, with Internet based learning and printed manuals the least popular (p < 0.001). CONCLUSIONS: Using computers in the surgery has become the norm for primary care nurses. However, nurses over 50, working out in the community, lack the confidence and skill of their younger and practice based colleagues

Initiating undergraduate medical students into communities of research practise: what do supervisors recommend?

Abstract Background Much has been written in the educational literature on the value of communities of practise in enhancing student learning. Here, we take the experience of senior undergraduate medical students involved in short-term research as a member of a team as a paradigm for learning in a community of practise. Based on feedback from experienced supervisors, we offer recommendations for initiating students into the research culture of their team. In so doing, we endeavour to create a bridge between theory and practise through disseminating advice on good supervisory practise, where the supervisor is perceived as an educator responsible for designing the research process to optimize student learning. Methods Using the questionnaire design tool SurveyMonkey and comprehensive lists of contact details of staff who had supervised research projects at the University of Edinburgh during 1995 - 2008, current and previous supervisors were invited to recommend procedures which they had found successful in initiating students into the research culture of a team. Text responses were then coded in the form of derivative recommendations and categorized under general themes and sub-themes. Results Using the chi-square tests of linear trend and association, evidence was found for a positive trend towards more experienced supervisors offering responses (χ2 = 16.833, p 2 = 0.482, p = 0.487, n = 203), respectively. A total of 126 codes were extracted from the text responses of 65 respondents. These codes were simplified to form a complete list of 52 recommendations, which were in turn categorized under seven derivative overarching themes, the most highly represented themes being Connecting the student with others and Cultivating self-efficacy in research competence. Conclusions Through the design of a coding frame for supervisor responses, a wealth of ideas has been captured to make communities of research practise effective mediums for undergraduate student learning. The majority of these recommendations are underpinned by educational theory and have the potential to take the learner beyond the stage of initiation to that of integration within their community of research practise.</p

Multi-domain quantitative recovery following Radical Cystectomy for patients within the iROC (Robot Assisted Radical Cystectomy with intracorporeal urinary diversion versus Open Radical Cystectomy) Randomised Controlled Trial: The first 30 patients

Many patients develop complications after radical cystectomy (RC) [1]. Reductions in morbidity have occurred through centralisation and technical improvements [2], and perhaps through robot-assisted RC (RARC). Whilst RARC is gaining popularity, there are concerns about oncological safety [3] and extracorporeal reconstruction [4], and randomised controlled trials (RCTs) find little difference [5]. We are conducting a prospective RCT comparing open RC and RARC with mandated intracorporeal reconstruction (Robot-assisted Radical Cystectomy with intracorporeal urinary diversion versus Open Radical Cystectomy [iROC] trial) [6]

Characterisation of a Wheat Breeders’ Array suitable for high throughput SNP genotyping of global accessions of hexaploid bread wheat (<i>Triticum aestivium</i>)

Targeted selection and inbreeding have resulted in a lack of genetic diversity in elite hexaploid bread wheat accessions. Reduced diversity can be a limiting factor in the breeding of high yielding varieties and crucially can mean reduced resilience in the face of changing climate and resource pressures. Recent technological advances have enabled the development of molecular markers for use in the assessment and utilization of genetic diversity in hexaploid wheat. Starting with a large collection of 819 571 previously characterized wheat markers, here we describe the identification of 35 143 single nucleotide polymorphism-based markers, which are highly suited to the genotyping of elite hexaploid wheat accessions. To assess their suitability, the markers have been validated using a commercial high-density Affymetrix Axiom® genotyping array (the Wheat Breeders' Array), in a high-throughput 384 microplate configuration, to characterize a diverse global collection of wheat accessions including landraces and elite lines derived from commercial breeding communities. We demonstrate that the Wheat Breeders' Array is also suitable for generating high-density genetic maps of previously uncharacterized populations and for characterizing novel genetic diversity produced by mutagenesis. To facilitate the use of the array by the wheat community, the markers, the associated sequence and the genotype information have been made available through the interactive web site 'CerealsDB'

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy