Lost in translation: how can education about dementia be effectively integrated into medical school contexts? A realist synthesis

\ua9 Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. OBJECTIVES: The prevalence of dementia in both community and hospital settings requires a clinical workforce that is skilled in diagnosis and management of the condition to competently care for patients. Though evidence of successful educational interventions about dementia exists, effective translation into medical school curricula is the exception rather than the norm. DESIGN: We adopted a realist synthesis approach following Realist And MEta-narrative Evidence Syntheses: Evolving Standards (RAMESES) guidelines to answer the following questions: (1) what are the barriers to integrating effective interventions about dementia into medical school curricula and (2) where they are successfully delivered, what are the contextual factors that allow for this enactment? DATA SOURCES: We searched PubMed, Embase, CINAHL and PsycINFO using the MesH terms Schools, Medical; Students, Medical; Education, Medical AND Neurocognitive disorders or the closest possible set of terms within each database. ELIGIBILITY CRITERIA: Undergraduate or graduate entry medical school programme, teaching and learning focussing on dementia, evaluating student outcomes (satisfaction, knowledge, skills, attitudes or behaviours), interventions described clearly enough to classify teaching method, any research design (quantitative and qualitative), English language. DATA EXTRACTION AND SYNTHESIS: We used a shared spreadsheet to enter key information about eligible studies and the reasons for excluding studies that did not fit eligibility criteria. We extracted descriptive data about the nature of educational interventions and narrative information as to barriers and facilitators to implementing those interventions. RESULTS: Our initial literature search identified 16 relevant papers for review. Systematic extraction of data informed the development of an initial programme theory (IPT) structured around four contextual barriers: \u27culture\u27, \u27concern for patient welfare\u27, \u27student attitudes\u27 and \u27logistics\u27 with associated facilitatory mechanisms embed medical education about dementia. CONCLUSIONS: We outline the process of generating our IPT, including overlap with Cultural Historical Activity Theory. We outline our intention to refine our programme theory through ongoing review of the evidence base and collaboration with stakeholders, with the aim of finalising a model for successful integration of dementia education

CamDec: Advancing axis P1435-LE video camera security using honeypot-based deception

The explosion of online video streaming in recent years resulted in advanced services both in terms of efficiency and convenience. However, Internet-connected video cameras are prone to exploitation, leading to information security issues and data privacy concerns. The proliferation of video-capable Internet of Things devices and cloud-managed surveillance systems further extend these security issues and concerns. In this paper, a novel approach is proposed for video camera deception via honeypots, offering increased security measures compared to what is available on conventional Internet-enabled video cameras

Teaching functional patterns through robotic applications

We present our approach to teaching functional programming to First Year Computer Science stu- dents at Middlesex University through projects in robotics. A holistic approach is taken to the cur- riculum, emphasising the connections between different subject areas. A key part of the students’ learning is through practical projects that draw upon and integrate the taught material. To support these, we developed the Middlesex Robotic plaTfOrm (MIRTO), an open-source platform built using Raspberry Pi, Arduino, HUB-ee wheels and running Racket (a LISP dialect). In this paper we present the motivations for our choices and explain how a number of concepts of functional programming may be employed when programming robotic applications. We present some students’ work with robotics projects: we consider the use of robotics projects to have been a success, both for their value in reinforcing students’ understanding of programming concepts and for their value in motivating the students

De novo mutations in EIF2B1 affecting eIF2 signaling cause neonatal/early onset diabetes and transient hepatic dysfunction

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this recordData and resource availability. EIF2B1 mutation details have been deposited in the Decipher database (https://decipher.sanger.ac.uk/). All other data sets generated and/or analysed for this study are available from the corresponding author upon reasonable request.Permanent neonatal diabetes is caused by reduced β-cell number or impaired β-cell function. Understanding the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 permanent neonatal diabetes patients and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified 2 further patients with de novo EIF2B1 variants. In addition to diabetes, 4/5 patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation which occurs under stress conditions and triggers expression of stress-response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.European Foundation for the Study of DiabetesDiabetes UKDiabetes Research and Wellness FoundationWellcome TrustNational Institute for Health Research (NIHR)Royal Societ

A systematic review of combined surgery and brachytherapy approaches for children and young people with relapsed and refractory rhabdomyosarcoma (Local-REFoRMS)

Approximately one third of children with rhabdomyosarcoma relapse or have refractory disease. Treatment approaches include a combination of systemic therapies and local therapies, directed at tumour site(s). This review was conducted to evaluate the effectiveness and safety of the combination of surgery and brachytherapy as local therapy for treating children and young people with relapsed/refractory rhabdomyosarcoma. This review identified studies based on a previous systematic review looking at the treatments for children and young people under 18 years old with relapsed/refractory rhabdomyosarcoma. Studies conducted after 2000 were included. Survival outcomes, relapse rates, adverse events and functional outcomes were extracted. From 16,965 records identified in the baseline systematic review, 205 included the words 'AMORE' or 'brachytherapy', and were screened for eligibility in this substudy. Thirteen studies met the inclusion criteria for Local-REFoRMS, including over 55 relapsed and refractory rhabdomyosarcoma patients. Most studies were retrospective cohort studies conducted within Europe. Most patients had embryonal disease within the head and neck or bladder/prostate regions, and received local therapy for first relapse. Approximately one quarter of patients relapsed following surgery and brachytherapy, with local relapses occurring more than metastatic relapse. Adverse events and functional outcomes were infrequently reported, but related to the site of surgery and brachytherapy. Study quality was limited by inconsistent reporting and potential selection bias. Outcomes following surgery and brachytherapy for a selected group of relapsed and refractory rhabdomyosarcoma show reasonable benefits, but reporting was often unclear and based on small sample sizes

Supporting doctors’ well-being and resilience during COVID-19 : a framework for rapid and rigorous intervention development

Authors thank the Chief Scientist Office, Scotland for supporting the research.This paper aims to outline the development of a theoretically informed and evidence-based intervention strategy to underpin interventions to support the well-being of doctors during COVID-19 and beyond; delineate new ways of working were employed to ensure a rapid and rigorous process of intervention development and present the resulting novel framework for intervention development. The research comprised four workstreams: literature review (WS1), qualitative study (WS2), intervention development and implementation (WS3) and evaluation (WS4). Due to time constraints, we employed a parallel design for WS1–3 with the findings of WS1–2 informing WS3 on a continual basis. WS3 was underpinned by the Behaviour Change Wheel. We recruited expert panels to assist with intervention development. We reflected on decisions taken to facilitate the rapid yet rigorous process of intervention development. The empirical output was a theoretically informed and evidence-based intervention strategy to underpin interventions to support doctors' well-being during COVID-19 and beyond. The methodological output was a novel framework that facilitates rapid and rigorous development of interventions. The intervention strategy provides a foundation for development and evaluation of tailored interventions to support doctors' well-being. The novel framework provides guidance for the development of interventions where the situation demands a rapid yet rigorous development process.Publisher PDFPeer reviewe

Diagnosis of lethal or prenatal-onset autosomal recessive disorders by parental exome sequencing.

OBJECTIVE: Rare genetic disorders resulting in prenatal or neonatal death are genetically heterogeneous, but testing is often limited by the availability of fetal DNA, leaving couples without a potential prenatal test for future pregnancies. We describe our novel strategy of exome sequencing parental DNA samples to diagnose recessive monogenic disorders in an audit of the first 50 couples referred. METHOD: Exome sequencing was carried out in a consecutive series of 50 couples who had 1 or more pregnancies affected with a lethal or prenatal-onset disorder. In all cases, there was insufficient DNA for exome sequencing of the affected fetus. Heterozygous rare variants (MAF < 0.001) in the same gene in both parents were selected for analysis. Likely, disease-causing variants were tested in fetal DNA to confirm co-segregation. RESULTS: Parental exome analysis identified heterozygous pathogenic (or likely pathogenic) variants in 24 different genes in 26/50 couples (52%). Where 2 or more fetuses were affected, a genetic diagnosis was obtained in 18/29 cases (62%). In most cases, the clinical features were typical of the disorder, but in others, they result from a hypomorphic variant or represent the most severe form of a variable phenotypic spectrum. CONCLUSION: We conclude that exome sequencing of parental samples is a powerful strategy with high clinical utility for the genetic diagnosis of lethal or prenatal-onset recessive disorders. © 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd

SavvyCNV: Genome-wide CNV calling from off-target reads

This is the uncorrected proof. The final version is available on open access from Public Library of Science via the DOI in this recordData Availability: The SavvyCNV tool and the code used to run the benchmarking comparisons are freely available on github. The tool is available at https://github.com/rdemolgen/SavvySuite. The code used to run the benchmarking comparisons is available at: https://github.com/exeter-matthew-wakeling/SavvyCNV_benchmarking. Our study uses the ICR96 data set for benchmarking, which is publicly available and can be accessed through the European-Genome phenome Archive (EGA) under the accession number EGAS00001002428. The dataset of 2591 samples referred to the molecular genetics department at the Royal Devon and Exeter Hospital for genetic testing cannot be shared due to patient confidentiality issues, as the genotype data could be used to identify individuals and so cannot be made openly available. Requests for access to the anonymised data by researchers will be considered following an application to the Genetic Beta Cell Research Bank (https://www.diabetesgenes.org/current-research/genetic-beta-cell-research-bank/) with proposals reviewed by the Genetic Data Access Committee.Identifying copy number variants (CNVs) can provide diagnoses to patients and provide important biological insights into human health and disease. Current exome and targeted sequencing approaches cannot detect clinically and biologically-relevant CNVs outside their target area. We present SavvyCNV, a tool which uses off-target read data from exome and targeted sequencing data to call germline CNVs genome-wide. Up to 70% of sequencing reads from exome and targeted sequencing fall outside the targeted regions. We have developed a new tool, SavvyCNV, to exploit this 'free data' to call CNVs across the genome. We benchmarked SavvyCNV against five state-of-the-art CNV callers using truth sets generated from genome sequencing data and Multiplex Ligation-dependent Probe Amplification assays. SavvyCNV called CNVs with high precision and recall, outperforming the five other tools at calling CNVs genome-wide, using off-target or on-target reads from targeted panel and exome sequencing. We then applied SavvyCNV to clinical samples sequenced using a targeted panel and were able to call previously undetected clinically-relevant CNVs, highlighting the utility of this tool within the diagnostic setting. SavvyCNV outperforms existing tools for calling CNVs from off-target reads. It can call CNVs genome-wide from targeted panel and exome data, increasing the utility and diagnostic yield of these tests. SavvyCNV is freely available at https://github.com/rdemolgen/SavvySuite.Medical Research Council (MRC)Research EnglandDiabetes U

De novo mutations in EIF2B1 affecting eIF2 signaling cause neonatal/early onset diabetes and transient hepatic dysfunction

Permanent neonatal diabetes is caused by reduced β-cell number or impaired β-cell function. Understanding the genetic basis of this disorder highlights fundamental β-cell mechanisms. We performed trio genome sequencing for 44 permanent neonatal diabetes patients and their unaffected parents to identify causative de novo variants. Replication studies were performed in 188 patients diagnosed with diabetes before 2 years of age without a genetic diagnosis. EIF2B1 (encoding the eIF2B complex α subunit) was the only gene with novel de novo variants (all missense) in at least three patients. Replication studies identified 2 further patients with de novo EIF2B1 variants. In addition to diabetes, 4/5 patients had hepatitis-like episodes in childhood. The EIF2B1 de novo mutations were found to map to the same protein surface. We propose that these variants render the eIF2B complex insensitive to eIF2 phosphorylation which occurs under stress conditions and triggers expression of stress-response genes. Failure of eIF2B to sense eIF2 phosphorylation likely leads to unregulated unfolded protein response and cell death. Our results establish de novo EIF2B1 mutations as a novel cause of permanent diabetes and liver dysfunction. These findings confirm the importance of cell stress regulation for β-cells and highlight EIF2B1’s fundamental role within this pathway.Includes NIHR and Wellcome Trust. Wellcome Trust 200848/Z/16/

Negotiating queer and religious identities in higher education: queering ‘progression’ in the ‘university experience’

This article addresses the negotiation of ‘queer religious’ student identities in UK higher education. The ‘university experience’ has generally been characterised as a period of intense transformation and self-exploration, with complex and overlapping personal and social influences significantly shaping educational spaces, subjects and subjectivities. Engaging with ideas about progressive tolerance and becoming, often contrasted against ‘backwards’ religious homophobia as a sentiment/space/subject ‘outside’ education, this article follows the experiences and expectations of queer Christian students. In asking whether notions of ‘queering higher education’ (Rumens 2014 Rumens, N. 2014. “Queer Business: Towards Queering the Purpose of the Business School.” In The Entrepreneurial University: Public Engagements, Intersecting Impacts, edited by Y. Taylor, 82–104. Basingstoke: Palgrave Macmillan.) ‘fit’ with queer-identifying religious youth, the article explores how educational experiences are narrated and made sense of as ‘progressive’. Educational transitions allow (some) sexual-religious subjects to negotiate identities more freely, albeit with ongoing constraints. Yet perceptions of what, where and who is deemed ‘progressive’ and ‘backwards’ with regard to sexuality and religion need to be met with caution, where the ‘university experience’ can shape and shake sexual-religious identity