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

The power of animation:encouraging doctors to access support for psychological wellbeing

The COVID-19 pandemic has exacerbated already high rates of poor psychological wellbeing in doctors. Many doctors perceive a stigma associated with acknowledging psychological wellbeing concerns, resulting in a reluctance to seek support for those concerns. The aim of this study was to develop a theoretically-informed and evidence-based composite narrative animation (CNA) to encourage doctors to access support for psychological wellbeing, and to evaluate the acceptability of the CNA.A composite narrative was developed from an evidence-base of interviews with 27 GP participants across Scotland (May–July 2020). The Behaviour Change Wheel was used to identify behaviour change techniques (BCTs) to be embedded within the CNA. The narrative was turned into a script in collaboration with an animation company. A brief animation ‘Jane the GP’ was developed reflecting specific BCTs.Scottish doctors (n = 83) were asked for their views on acceptability of the CNA concept, and subsequently asked to provide views on the acceptability of the CNA after viewing it. Participants thought the concept of a CNA was novel but may not appeal to all. After viewing the CNA, the widespread view was that it portrayed an authentic experience, could reduce stigma around seeking support for psychological wellbeing, and highlighted formal routes to access such support.CNAs are a novel and acceptable intervention method for encouraging doctors to access support for psychological wellbeing. The use of a theory driven intervention development framework to create the CNA facilitates the link between theory and practice

The power of animation:encouraging doctors to access support for psychological wellbeing

The COVID-19 pandemic has exacerbated already high rates of poor psychological wellbeing in doctors. Many doctors perceive a stigma associated with acknowledging psychological wellbeing concerns, resulting in a reluctance to seek support for those concerns. The aim of this study was to develop a theoretically-informed and evidence-based composite narrative animation (CNA) to encourage doctors to access support for psychological wellbeing, and to evaluate the acceptability of the CNA.A composite narrative was developed from an evidence-base of interviews with 27 GP participants across Scotland (May–July 2020). The Behaviour Change Wheel was used to identify behaviour change techniques (BCTs) to be embedded within the CNA. The narrative was turned into a script in collaboration with an animation company. A brief animation ‘Jane the GP’ was developed reflecting specific BCTs.Scottish doctors (n = 83) were asked for their views on acceptability of the CNA concept, and subsequently asked to provide views on the acceptability of the CNA after viewing it. Participants thought the concept of a CNA was novel but may not appeal to all. After viewing the CNA, the widespread view was that it portrayed an authentic experience, could reduce stigma around seeking support for psychological wellbeing, and highlighted formal routes to access such support.CNAs are a novel and acceptable intervention method for encouraging doctors to access support for psychological wellbeing. The use of a theory driven intervention development framework to create the CNA facilitates the link between theory and practice

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

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

Multicenter Consensus Approach to Evaluation of Neonatal Hypotonia in the Genomic Era: A Review

IMPORTANCE: Infants with hypotonia can present with a variety of potentially severe clinical signs and symptoms and often require invasive testing and multiple procedures. The wide range of clinical presentations and potential etiologies leaves diagnosis and prognosis uncertain, underscoring the need for rapid elucidation of the underlying genetic cause of disease. OBSERVATIONS: The clinical application of exome sequencing or genome sequencing has dramatically improved the timely yield of diagnostic testing for neonatal hypotonia, with diagnostic rates of greater than 50% in academic neonatal intensive care units (NICUs) across Australia, Canada, the UK, and the US, which compose the International Precision Child Health Partnership (IPCHiP). A total of 74% (17 of 23) of patients had a change in clinical care in response to genetic diagnosis, including 2 patients who received targeted therapy. This narrative review discusses the common causes of neonatal hypotonia, the relative benefits and limitations of available testing modalities used in NICUs, and hypotonia management recommendations. CONCLUSIONS AND RELEVANCE: This narrative review summarizes the causes of neonatal hypotonia and the benefits of prompt genetic diagnosis, including improved prognostication and identification of targeted treatments which can improve the short-term and long-term outcomes. Institutional resources can vary among different NICUs; as a result, consideration should be given to rule out a small number of relatively unique conditions for which rapid targeted genetic testing is available. Nevertheless, the consensus recommendation is to use rapid genome or exome sequencing as a first-line testing option for NICU patients with unexplained hypotonia. As part of the IPCHiP, this diagnostic experience will be collected in a central database with the goal of advancing knowledge of neonatal hypotonia and improving evidence-based practice

Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib

Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to generate multiple resistant clones in vitro. These drug-resistant cells demonstrate continued dependence on EGFR and ERBB2 signaling for their viability and have not acquired secondary EGFR mutations. However, they display increased internalization of ligand-activated EGFR, consistent with altered receptor trafficking. Although gefitinib-resistant clones are cross-resistant to related anilinoquinazolines, they demonstrate sensitivity to a class of irreversible inhibitors of EGFR. These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation. Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors. Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib

UK Greenhouse Gas Inventory 1990 to 2021: annual report for submission under the Framework Convention on Climate Change

This is the United Kingdom’s National Inventory Report (NIR) submitted in 2023 to the United Nations Framework Convention on Climate Change (UNFCCC). It contains national greenhouse gas emission estimates for the period 1990-2021, and descriptions of the methods used to produce the estimates. The greenhouse gas inventory (GHGI) is based on the same datasets used by the UK in the National Atmospheric Emissions Inventory (NAEI) for reporting atmospheric emissions under other international agreements. The GHGI is therefore consistent with these other air emissions inventories where they overlap. The greenhouse gas inventory is compiled on behalf of the UK Department for Energy Security and Net Zero (DESNZ) for the Science and Innovation for Climate and Energy (SICE) Directorate, by Ricardo Energy & Environment. We acknowledge the positive support and advice from DESNZ throughout the work, and we are grateful for the help of all those who have contributed to this NIR. A list of the contributors can be found in Chapter 18. The GHGI is compiled according to the Intergovernmental Panel on Climate Change (IPCC) 2006 Guidelines (IPCC, 2006). Each year the inventory is updated to include the latest data available. Improvements to the methodology are backdated as necessary to ensure a consistent time series. Methodological changes are made to take account of new data sources, or new guidance from IPCC, and new research, sponsored by DESNZ or otherwise

An Amish founder variant consolidates disruption of CEP55 as a cause of hydranencephaly and renal dysplasia

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.The centrosomal protein 55 kDa (CEP55 (OMIM 610000)) plays a fundamental role in cell cycle regulation and cytokinesis. However, the precise role of CEP55 in human embryonic growth and development is yet to be fully defined. Here we identified a novel homozygous founder frameshift variant in CEP55, present at low frequency in the Amish community, in two siblings presenting with a lethal foetal disorder. The features of the condition are reminiscent of a Meckel-like syndrome comprising of Potter sequence, hydranencephaly, and cystic dysplastic kidneys. These findings, considered alongside two recent studies of single families reporting loss of function candidate variants in CEP55, confirm disruption of CEP55 function as a cause of this clinical spectrum and enable us to delineate the cardinal clinical features of this disorder, providing important new insights into early human development.Medical Research CouncilNewlife Foundation for disabled childre

Comparing the Epidermal Growth Factor Interaction with Four Different Cell Lines: Intriguing Effects Imply Strong Dependency of Cellular Context

The interaction of the epidermal growth factor (EGF) with its receptor (EGFR) is known to be complex, and the common over-expression of EGF receptor family members in a multitude of tumors makes it important to decipher this interaction and the following signaling pathways. We have investigated the affinity and kinetics of 125I-EGF binding to EGFR in four human tumor cell lines, each using four culturing conditions, in real time by use of LigandTracer®