The medical doctor (degree) apprenticeship.

In this article we explore the United Kingdom context of apprenticeships and the history of development of the use of the term apprentice in medicine. We describe the development of the Medical Doctor Degree Apprenticeship (MDDA) in England and how Anglia Ruskin University (ARU) has approached the development of the MDDA. We explore the rationale for developing the MDDA in Essex, the structure of the apprenticeship at ARU (which comprises 20% of employed time in NHS work and 80% in education undertaking the medical degree), the challenges and issues we encountered and mitigations we put in place. We describe the importance of stakeholder engagement (especially with direct entry medical students, medical professionals, and members of the university staff). The role of the employer is critical to the development and delivery of MDDA. The important role of regulators in developing and monitoring MDDA is the complexity of funding arrangements. Finally, we offer reflections on the development journey thus far.

Obstetric management for pregnant women with Klippel-Trenaunay syndrome: A UK case report and review of the literature.

Klippel-Trenaunay Syndrome (KTS) is a rare congenital vascular disorder characterized by extensive capillary and venous malformations that pose unique challenges during pregnancy. This case report discusses the successful management of a 34-year-old pregnant woman with KTS who had two caesarean sections, resulting in the birth of two healthy babies. Despite the lack of evidence-based guidelines for obstetrical management in KTS, a multidisciplinary team collaborated to devise a high-risk thrombosis management plan, involving the use of compression stocking and low molecular weight heparin prophylaxis. The patient's elevated risk of thrombosis, exacerbated during pregnancy, informed the decision of caesarean sections, aligning with finding that in most KTS pregnancies, this method of delivery based on obstetric indications and arteriovenous malformations is chosen. This case highlights the importance of systematic and patient-centered care, advocating for comprehensive obstetric management guidelines to address the unique challenges posed by KTS during pregnancy. Further research is warranted to enhance our understanding and refine guidelines for individuals with vascular abnormalities linked to KTS.

Neurodiversity in the healthcare profession.

The term neurodiversity was coined in the 1990s to describe a diversity in thinking, learning, and processing the world around us, and is associated with strengths as well as challenges. Rates of diagnosis of neurodivergent conditions are rising rapidly amongst patients and healthcare professionals, largely due to a recent surge in awareness and understanding of neurodiverse conditions and more inclusive diagnostic criteria. Societal adaptation, however, has lagged, and likely explains some of the psychosocial comorbidities of neurodiversity, as individuals are forced to adapt their personality and how they display their emotions to fit societal norms. There remains a lack of awareness and understanding of neurodiversity amongst the healthcare professions. There is also very limited published literature on the challenges and strengths of this group in the clinical environment. Here, we use a case study, focusing on attention deficit hyperactivity disorder to explore the relationship between neurodiversity and work from the perspective of a neurodiverse health care professional. We challenge the notion that neurodiversity itself is a disability, but more likely a result of lack of societal awareness and adaption. We suggest accommodations and training in the clinical environment to raise awareness and support neurodiverse healthcare professionals in order that they flourish rather than struggle in the workplace.

Protocol of a mixed method research design to study medical respite programs for persons experiencing homelessness.

Medical Respite Programs (MRPs) characterize a care model that has been developed to address the health care and social needs of persons experiencing homelessness by providing post-acute hospital care in a safe environment. Although this model has been shown to reduce hospitalizations, improve health outcomes and increase access to health services, prior studies of MRP programs and outcomes have been limited to individual sites and may not generalize to the population of individuals receiving MRP care. This study protocol describes a mixed method design to collect organizational, provider, and patient-level data from a sample of MRPs.

A mixed methods study to understand perinatal mental healthcare referral decisions among midwives and health visitors in the UK.

Background: In the UK approximately half of women requiring perinatal mental health (PNMH) care do not receive treatment despite having routine contact with midwives (MWs) and health visitors (HVs). Limited research has been undertaken regarding MWs'/HVs' decision-making around referring women for secondary PNMH care. In particular, the impact that the level of local secondary PNMH services may have on MWs'/HVs' referral decisions is unexplored. Aim: To understand MWs'/HVs' decision-making in relation to referring women with identified PNMH problems, to identify barriers and facilitators to effective and timely referrals including any impact of the local secondary PNMH service provision. Methods: Participants were recruited from four National Health Service (NHS) Trusts in England, located across two geographical areas, that provided different types of PNMH services. One area had PNMH services that met National Institute for Health and Care Excellence (NICE) guidelines; the other area had no secondary PNMH services. A sequential mixed methods design was used: In-depth semi-structured interviews with practising MWs/HVs (n = 24) to explore their approach to PNMH referral decision-making, analysed using thematic analysis; Questionnaire offered to all practising MWs/HVs in the two geographical areas to measure factors that may impact on PNMH referral decision-making allowing for statistical comparisons to be made between the professional groups/geographical areas. Findings: Three themes were identified from the interviews that impacted on MWs'/HVs' PNMH referral decision-making: identifying need; education, skills and experience; and referral pathways.Questionnaire response rate 13.1% (n = 99). The most reported facilitators to referral decision-making were a trusted relationship between MWs/HVs and women and routine enquiry about women's mental health; the most reported barriers were stigma associated with mental ill-health and women's perceived fear of child removal. Conclusion: Fundamental to MWs'/HVs' decision-making was their perceived relationship between themselves and women. Although PNMH service provision is important for women to ensure they receive appropriate PNMH care, service provision appeared less important to MWs'/HVs' referral decision-making than how maternity/health visiting services were delivered. Further important factors to MWs/HVs were to the ability to provide continuity of carer with women allowing MWs/HVs to identify women who would benefit from referral for secondary PNMH care.

Running a paediatric ambulatory sleep service in a pandemic and beyond.

OBJECTIVES: In response COVID-19, re-establishing safe elective services was prioritised in the UK. We assess the impact on face-to-face hospital attendance, cost and efficiency of implementing a virtual sleep clinic (intervention 1) to screen for children requiring level 3 ambulatory sleep studies using newly implemented ENT-UK guidelines for obstructive sleep apnoea (OSA) investigation (intervention 2). OBJECTIVES: (1) compare the proportion of children attending sleep clinic undertaking a sleep study before and after implementation of these interventions; (2) compare clinic cancellations and first-time success rates of sleep studies before and after intervention. DESIGN: Retrospective analysis. SETTING: District general hospital paediatric sleep clinic. PARTICIPANTS: Children aged 3 months to 16 years referred to sleep clinic by ENT for investigation of OSA over 3 months immediately following interventions (1 June 2020 - 1 September 2020) to the same period in the previous year (1 June 2019 - 1 September 2019). MAIN OUTCOME MEASURES: Number of children attending sleep clinic, date of birth/age of children attending sleep clinic, number of children undergoing sleep study, diagnostic outcomes, number of appointment cancellations, number of first-time sleep study failures. RESULTS: Post intervention, there was a significant reduction in the proportion of children undertaking ambulatory sleep studies, and nonsignificant reductions in appointment cancellations and in first-time sleep study failures. CONCLUSIONS: The introduction of the virtual sleep clinic meant that only those children requiring a sleep study attended a face-to-face appointment, which led to reduced face-to-face attendance. There were also unintended cost-effectiveness and efficiency benefits, with potential longer-term learning implications for the wider sleep community and other diagnostic services.

The impact of the COVID-19 pandemic on the lifestyle and behaviours, mental health and education of students studying healthcare-related courses at a British university.

BACKGROUND: The COVID-19 pandemic has affected most industries, including health education. In this study, we surveyed students studying healthcare-related courses at our university on how their lifestyles and behaviours, mental health and education had been affected by the pandemic. METHODS: Mixed methods cross-sectional study. RESULTS: Two hundred thirty-three students responded to the questionnaire. Lifestyle and behaviours: 51.5% of the participants changed their diet (n=120); 45.5% (n=106) exercised less; 66.5% (n=155) experienced a change in sleep; 51.1% (n=119) reported a change in appetite. Mental health: 84.2% (n=196) reported worrying too much about different things; 61.9% (n=144) could not stop or control worrying; 71.2% experienced trouble relaxing on several days or more (n=166). At least sometimes, 72.1% (n=168) felt unable to cope with things they had to do; 8.5% (n=20) never, or almost never, felt confident about handling personal problems. Education: 65.7% (n=153) struggled to complete learning outcomes with online delivery; 82% (n=191) worried about practical skills being affected; 60.5% (n=141) worried about the impact of COVID-19 on their future career. Almost half (48.9%, n=114) believed that online teaching should be part of the standard curriculum. CONCLUSION: In general, there was a negative impact on behaviours, lifestyle and mental health and virtual education was perceived as necessary in making up for the loss of face to face experiences. Students' mental health and educational needs have been affected by the current pandemic and healthcare educational facilities must respond to these needs to ensure students continue to receive the support they need.

Reinventing Undergraduate Clinical Placements with a Switch to Delivery by Clinical Teaching Fellows.

PURPOSE: Undergraduate clinical placements have the potential for significant improvement. Previous research has shown the growing value of clinical teaching fellows (CTFs) within medical education. Changing traditional placements to a model whereby CTFs have defined roles and lead the majority of teaching can positively reinvent undergraduate clinical teaching. We wanted to see how a structured teaching programme delivered by CTFs could affect student experience and personal development within a large associate teaching hospital. We consider how such a model could be implemented and explore the opportunities for CTFs to develop in personal and professional capacities. METHODS: A mixed methods study was organised to assess student experience of a CTF-led placement. A novel structured teaching programme was delivered by 14 CTFs, who provided or were involved with the majority of teaching for all medical students. Thematic analysis was conducted on focus groups with 48 final year medical students from Queen Mary University of London following completion of their clinical placements. The same students were asked to complete an anonymous survey from which results were analysed using modified 5-point Likert scales. RESULTS: Eight themes were identified from the focus groups. Students appreciated the increased individualisation, relevance and variety of teaching and the ability to record progress. Other perceived effects were higher teacher to student ratios, more learning opportunities and increased familiarity and reliability with CTFs. Of the students surveyed, 96% felt their overall placement experience was very good in comparison to previous placements elsewhere. Survey results supported focus group themes and demonstrated perceived growth in students' personal development. CONCLUSION: Placement models where CTFs lead most teaching can improve medical undergraduate experience and training. A move towards CTF-delivered teaching can be of financial benefit to hospital trusts whilst allowing time for junior doctors to explore different clinical specialities and hone their teaching skills.

A Distributed Whole Genome Sequencing Benchmark Study.

Population sequencing often requires collaboration across a distributed network of sequencing centers for the timely processing of thousands of samples. In such massive efforts, it is important that participating scientists can be confident that the accuracy of the sequence data produced is not affected by which center generates the data. A study was conducted across three established sequencing centers, located in Montreal, Toronto, and Vancouver, constituting Canada's Genomics Enterprise (www.cgen.ca). Whole genome sequencing was performed at each center, on three genomic DNA replicates from three well-characterized cell lines. Secondary analysis pipelines employed by each site were applied to sequence data from each of the sites, resulting in three datasets for each of four variables (cell line, replicate, sequencing center, and analysis pipeline), for a total of 81 datasets. These datasets were each assessed according to multiple quality metrics including concordance with benchmark variant truth sets to assess consistent quality across all three conditions for each variable. Three-way concordance analysis of variants across conditions for each variable was performed. Our results showed that the variant concordance between datasets differing only by sequencing center was similar to the concordance for datasets differing only by replicate, using the same analysis pipeline. We also showed that the statistically significant differences between datasets result from the analysis pipeline used, which can be unified and updated as new approaches become available. We conclude that genome sequencing projects can rely on the quality and reproducibility of aggregate data generated across a network of distributed sites.

Acheron/Larp6 Is a Survival Protein That Protects Skeletal Muscle From Programmed Cell Death During Development.

The term programmed cell death (PCD) was coined in 1965 to describe the loss of the intersegmental muscles (ISMs) of moths at the end of metamorphosis. While it was subsequently demonstrated that this hormonally controlled death requires de novo gene expression, the signal transduction pathway that couples hormone action to cell death is largely unknown. Using the ISMs from the tobacco hawkmoth Manduca sexta, we have found that Acheron/LARP6 mRNA is induced ∼1,000-fold on the day the muscles become committed to die. Acheron functions as a survival protein that protects cells until cell death is initiated at eclosion (emergence), at which point it becomes phosphorylated and degraded in response to the peptide Eclosion Hormone (EH). Acheron binds to a novel BH3-only protein that we have named BBH1 (BAD/BNIP3 homology 1). BBH1 accumulates on the day the ISMs become committed to die and is presumably liberated when Acheron is degraded. This is correlated with the release and rapid degradation of cytochrome c and the subsequent demise of the cell. RNAi experiments in the fruit fly Drosophila confirmed that loss of Acheron results in precocious ecdysial muscle death while targeting BBH1 prevents death altogether. Acheron is highly expressed in neurons and muscles in humans and drives metastatic processes in some cancers, suggesting that it may represent a novel survival protein that protects terminally differentiated cells and some cancers from death.

Factors affecting the embedding of integrated primary-secondary care into a health district.

With the aging population, the tide of chronic disease is rising with attendant increases in health service need. Integrated care and patient-centred approaches, which established partnerships between a regional Hospital and health service (HHS), the local primary health network and local general practitioners (GPs), were identified as exemplars of an approach needed to support growing community health needs. This paper summarises the findings from a process evaluation of four GP-specialist care integration programs with the aim of identifying recommendations for embedding integrated GP-specialist care into routine practice within the HHS. The process evaluation of the integration programs drew on input from a multidisciplinary expert advisory group and data collected through face-to-face semi-structured interviews with key stakeholders, as well as surveys of participating GPs and patients. Overarching findings were identified and grouped under six themes: interdisciplinary teamwork; communication and information exchange; the use of shared care guidelines or pathways; training and education; access and accessibility; and funding. Within each theme, key challenges and enablers emerged. The findings of this study highlight benefits and challenges associated with the establishment of integrated care between primary and secondary care providers, leading to the development of key recommendations for routine integration.

Improvement in overactive bladder symptoms in patients using functional electrical stimulation of the common peroneal nerve for walking.

OBJECTIVE: Functional electrical stimulation is used to improve walking speed and reduces falls in people with upper motor neurone foot-drop. Following anecdotal observations of changes in bladder symptoms, an observational study was performed to explore this association further. DESIGN: A total of 47 consecutive patients attending for setup with functional electrical stimulation during a six-month period were asked to complete a questionnaire assessing bladder symptoms (ICIQ-OAB (International Consultation on Incontinence Questionnaire Overactive Bladder)) at baseline and three months during routine appointments. SUBJECTS: In all, 35 (75%) had multiple sclerosis and the other 12 subjects had a total of 9 diagnoses including 3 with stroke. Other conditions included cerebral palsy, motor neurone disease, hereditary spastic paraparesis, meningioma and spinocerebellar ataxias. RESULTS: Improvement in overactive bladder symptoms was not significant in the whole cohort, however, was significant in patients with multiple sclerosis ( n = 35; mean change in ICIQ-OAB score 1.0, P = 0.043). Specifically, significant improvements were seen in urgency and urge incontinence in multiple sclerosis patients. There was a significant negative correlation of moderate strength within the multiple sclerosis cohort between baseline walking speed and subsequent change in ICIQ-OAB score (correlation coefficient of r = -0.40, P = 0.046). Thus, greater changes in bladder symptoms were seen with lower baseline walking speeds. CONCLUSION: The results of this exploratory study suggest that functional electrical stimulation use does improve overactive bladder symptoms in people with multiple sclerosis. Further exploration is needed to study this association and explore whether the mechanism is similar to that of percutaneous tibial nerve stimulation, a recognized treatment for the overactive bladder.

A dated molecular phylogeny of mite harvestmen (Arachnida: Opiliones: Cyphophthalmi) elucidates ancient diversification dynamics in the Australian Wet Tropics.

Austropurcellia, a genus of dispersal-limited arachnids endemic to isolated patches of coastal rainforest in Queensland, Australia, has a remarkable biogeographic history. The genus is a member of the family Pettalidae, which has a classical temperate Gondwanan distribution; previous work has suggested that Austropurcellia is an ancient lineage, with an origin that predates Gondwanan rifting. Subsequently, this lineage has persisted through major climatic fluctuations, such as major aridification during the Miocene and contraction and fragmentation of forest habitats during the Last Glacial Maximum (LGM). In order to understand Austropurcellia's evolutionary and biogeographic history, we generated DNA sequences from both mitochondrial and nuclear loci and combined this information with previously published datasets for the globally-distributed suborder Cyphophthalmi (i.e., all mite harvestmen). We generated phylogenetic trees using maximum likelihood and Bayesian approaches to date divergences using a relaxed molecular clock. According to our estimates, the family Pettalidae diversified in the late Jurassic, in accordance with Gondwanan vicariance. Within Pettalidae, Austropurcellia split from its sister group in the early Cretaceous and began to diversify some 15 Ma later. Therefore, its presence in Australia predates continental rifting-making it one of very few hypothesized examples of Gondwanan vicariance that have withstood rigorous testing. We found a steady rate of diversification within the genus, with no evidence for a shift in rate associated with Miocene aridification. Ages of splits between species predate the Pleistocene, consistent with a "museum" model in which forest refugia acted to preserve existing lineages rather than drive speciation within the group.

Fank1 and Jazf1 promote multiciliated cell differentiation in the mouse airway epithelium.

The airways are lined by secretory and multiciliated cells which function together to remove particles and debris from the respiratory tract. The transcriptome of multiciliated cells has been extensively studied, but the function of many of the genes identified is unknown. We have established an assay to test the ability of over-expressed transcripts to promote multiciliated cell differentiation in mouse embryonic tracheal explants. Overexpression data indicated that Fibronectin type 3 and ankyrin repeat domains 1 (Fank1) and JAZF zinc finger 1 (Jazf1) promoted multiciliated cell differentiation alone, and cooperatively with the canonical multiciliated cell transcription factor Foxj1. Moreover, knock-down of Fank1 or Jazf1 in adult mouse airway epithelial cultures demonstrated that these factors are both required for ciliated cell differentiation in vitro This analysis identifies Fank1 and Jazf1 as novel regulators of multiciliated cell differentiation. Moreover, we show that they are likely to function downstream of IL6 signalling and upstream of Foxj1 activity in the process of ciliated cell differentiation. In addition, our in vitro explant assay provides a convenient method for preliminary investigation of over-expression phenotypes in the developing mouse airways.This article has an associated First Person interview with the first author of the paper.

A revised dated phylogeny of scorpions: Phylogenomic support for ancient divergence of the temperate Gondwanan family Bothriuridae.

The scorpion family Bothriuridae occupies a subset of landmasses formerly constituting East and West temperate Gondwana, but its relationship to other scorpion families is in question. Whereas morphological data have strongly supported a sister group relationship of Bothriuridae and the superfamily Scorpionoidea, a recent phylogenomic analysis recovered a basal placement of bothriurids within Iurida, albeit sampling only a single exemplar. Here we reexamined the phylogenetic placement of the family Bothriuridae, sampling six bothriurid exemplars representing both East and West Gondwana, using transcriptomic data. Our results demonstrate that the sister group relationship of Bothriuridae to the clade ("Chactoidea" + Scorpionoidea) is supported by the inclusion of additional bothriurid taxa, and that this placement is insensitive to matrix completeness or partitioning by evolutionary rate. We also estimated divergence times within the order Scorpiones using multiple fossil calibrations, to infer whether the family Bothriuridae is sufficiently old to be characterized as a true Gondwanan lineage. We show that scorpions underwent ancient diversification between the Devonian and early Carboniferous. The age interval of the bothriurids sampled (a derived group that excludes exemplars from South Africa) spans the timing of breakup of temperate Gondwana.

Human embryonic lung epithelial tips are multipotent progenitors that can be expanded in vitro as long-term self-renewing organoids.

The embryonic mouse lung is a widely used substitute for human lung development. For example, attempts to differentiate human pluripotent stem cells to lung epithelium rely on passing through progenitor states that have only been described in mouse. The tip epithelium of the branching mouse lung is a multipotent progenitor pool that self-renews and produces differentiating descendants. We hypothesized that the human distal tip epithelium is an analogous progenitor population and tested this by examining morphology, gene expression and in vitro self-renewal and differentiation capacity of human tips. These experiments confirm that human and mouse tips are analogous and identify signalling pathways that are sufficient for long-term self-renewal of human tips as differentiation-competent organoids. Moreover, we identify mouse-human differences, including markers that define progenitor states and signalling requirements for long-term self-renewal. Our organoid system provides a genetically-tractable tool that will allow these human-specific features of lung development to be investigated.

Breast Cancer Risk and Progressive Histology in Serial Benign Biopsies.

Background: More than 1 million women per year in the United States with benign breast biopsies are known to be at elevated risk for breast cancer (BC), with risk stratified on histologic categories of epithelial proliferation. Here we assessed women who had serial benign biopsies over time and how changes in the histologic classification affected BC risk. Methods: In the Mayo Clinic Benign Breast Disease Cohort of 13 466 women, 1414 women had multiple metachronous benign biopsies (10.5%). Both initial and subsequent biopsies were assessed histologically. BC risk for clinical and prognostic factors was assessed using subdistribution models to account for competing risks, and logistic regression/Wilcoxon/chi-square tests to assess covariates. All statistical tests were two-sided. Results: Breast cancer risk for women with serial biopsies, stratified by histologic category in the later biopsies, was similar to women with a single biopsy. We found that changes in histological category between initial and subsequent biopsy statistically significantly impacted BC risk. Women with nonproliferative initial findings and subsequent proliferative findings had an increased risk (hazard ratio [HR] = 1.77, 95% confidence interval [CI] = 1.06 to 2.94, P = .03) compared with no change. Among women with proliferative disease without atypia at initial biopsy, risk decreased if later biopsy regressed to nonproliferative (HR = 0.49, 95% CI = 0.25 to 0.98) and increased if later biopsy showed progression to atypical hyperplasia (HR = 1.49, 95% CI = 0.73 to 3.05) compared with no change ( P = .04). Conclusions: We found that breast cancer risk increases in women with progressive epithelial proliferation over time and decreases in women whose biopsies show less proliferation. This finding has important implications for effective clinical management of the 100 000 women per year who have multiple benign breast biopsies.

SOX2 Drives Bronchial Dysplasia in a Novel Organotypic Model of Early Human Squamous Lung Cancer.

RATIONALE: Improving the early detection and chemoprevention of lung cancer are key to improving outcomes. The pathobiology of early squamous lung cancer is poorly understood. We have shown that amplification of sex-determining region Y-box 2 (SOX2) is an early and consistent event in the pathogenesis of this disease, but its functional oncogenic potential remains uncertain. We tested the impact of deregulated SOX2 expression in a novel organotypic system that recreates the molecular and microenvironmental context in which squamous carcinogenesis occurs. OBJECTIVES: (1) To develop an in vitro model of bronchial dysplasia that recapitulates key molecular and phenotypic characteristics of the human disease; (2) to test the hypothesis that SOX2 deregulation is a key early event in the pathogenesis of bronchial dysplasia; and (3) to use the model for studies on pathogenesis and chemoprevention. METHODS: We engineered the inducible activation of oncogenes in immortalized bronchial epithelial cells. We used three-dimensional tissue culture to build an organotypic model of bronchial dysplasia. MEASUREMENTS AND MAIN RESULTS: We recapitulated human bronchial dysplasia in vitro. SOX2 deregulation drives dysplasia, and loss of tumor promoter 53 is a cooperating genetic event that potentiates the dysplastic phenotype. Deregulated SOX2 alters critical genes implicated in hallmarks of cancer progression. Targeted inhibition of AKT prevents the initiation of the dysplastic phenotype. CONCLUSIONS: In the appropriate genetic and microenvironmental context, acute deregulation of SOX2 drives bronchial dysplasia. This confirms its oncogenic potential in human cells and affords novel insights into the impact of SOX2 deregulation. This model can be used to test therapeutic agents aimed at chemoprevention.