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Ever since the 1970s, politicised debates have raged over the teaching of history, dubbed the 'history wars'. These debates continue to impact primary and secondary teachers' choices of history curriculum foci to this day. This research aimed to discover history teachers' understanding of how to develop diversity within their history curricula and to discuss the possible pitfalls of their decision making. We set out to answer the following questions: (1) How do history teachers and subject leads understand the concept of diversification within the history curriculum? (2) How are schools approaching the diversification of their history curriculum? We carried out this project collaboratively with 10 history teachers and subject leads from four primary and three secondary schools in Kent, South-East England. As a result, we have developed a model of 'school diversification' and make several recommendations to support the development and teaching of increasingly diverse history lessons, within the confines of the current National Curriculum. This project adds to the literature by privileging the voice of teachers within classrooms and including collaboration between teachers of all phases within history education in English schools to support the development of diversity within their practice.

The need for improved wet adhesives has driven research on mussel-inspired materials incorporating dihydroxyphenylalanine (DOPA) and related analogs of the parent catechol, but their susceptibility to oxidation limits practical application of these functionalities. Here, we investigate the molecular-level adhesion of the catechol analogs dihydroxybenzamide (DHB) and hydroxypyridinone (HOPO) as a function of pH. We find that the molecular structure of the catechol analogs influences their susceptibility to oxidation in alkaline conditions, with HOPO emerging as a particularly promising candidate for pH-tolerant adhesives for diverse environmental conditions.

Abstract Understanding the genetic basis of routinely-acquired blood tests can provide insights into several aspects of human physiology. We report a genome-wide association study of 42 quantitative blood test traits defined using Electronic Healthcare Records (EHRs) of ~50,000 British Bangladeshi and British Pakistani adults. We demonstrate a causal variant within the PIEZO1 locus which was associated with alterations in red cell traits and glycated haemoglobin. Conditional analysis and within-ancestry fine mapping confirmed that this signal is driven by a missense variant - chr16-88716656-G-TT - which is common in South Asian ancestries (MAF 3.9%) but ultra-rare in other ancestries. Carriers of the T allele had lower mean HbA1c values, lower HbA1c values for a given level of random or fasting glucose, and delayed diagnosis of Type 2 Diabetes Mellitus. Our results shed light on the genetic basis of clinically-relevant traits in an under-represented population, and emphasise the importance of ancestral diversity in genetic studies.

Abstract MYCN amplification predicts poor prognosis in childhood neuroblastoma. To identify MYCN oncogenic signal dependencies we performed N-ethyl-N-nitrosourea (ENU) mutagenesis on the germline of neuroblastoma-prone TH-MYCN transgenic mice to generate founders which had lost tumorigenesis. Sequencing of the mutant mouse genomes identified the Ring Finger Protein 121 (RNF121 WT ) gene mutated to RNFM158R associated with heritable loss of tumorigenicity. While the RNF121WT protein localised predominantly to the cis-Golgi Complex, the RNF121 M158R mutation in Helix 4 of its transmembrane domain caused reduced RNF121 protein stability and absent Golgi localisation. RNF121WT expression markedly increased during TH-MYCN tumorigenesis, whereas hemizygous RNF121 WT gene deletion reduced TH-MYCN tumorigenicity. The RNF121WT-enhanced growth of MYCN-amplified neuroblastoma cells depended on RNF121WT transmembrane Helix 5. RNF121WT directly bound MYCN protein and enhanced its stability. High RNF121 mRNA expression associated with poor prognosis in human neuroblastoma tissues and another MYC-driven malignancy, laryngeal cancer. RNF121 is thus an essential oncogenic cofactor for MYCN and a target for drug development.

Abstract Neuroepithelial tumors with fusion of PLAGL1 or amplification of PLAGL1/PLAGL2 have recently been described often with ependymoma-like or embryonal histology respectively. To further evaluate emerging entities with PLAG-family genetic alterations, the histologic, molecular, clinical, and imaging features are described for 8 clinical cases encountered at St. Jude (EWSR1-PLAGL1 fusion n = 6; PLAGL1 amplification n = 1; PLAGL2 amplification n = 1). A histologic feature observed on initial resection in a subset (4/6) of supratentorial neuroepithelial tumors with EWSR1-PLAGL1 rearrangement was the presence of concurrent ependymal and ganglionic differentiation. This ranged from prominent clusters of ganglion cells within ependymoma/subependymoma-like areas, to interspersed ganglion cells of low to moderate frequency among otherwise ependymal-like histology, or focal areas with a ganglion cell component. When present, the combination of ependymal-like and ganglionic features within a supratentorial neuroepithelial tumor may raise consideration for an EWSR1-PLAGL1 fusion, and prompt initiation of appropriate molecular testing such as RNA sequencing and methylation profiling. One of the EWSR1-PLAGL1 fusion cases showed subclonal INI1 loss in a region containing small clusters of rhabdoid/embryonal cells, and developed a prominent ganglion cell component on recurrence. As such, EWSR1-PLAGL1 neuroepithelial tumors are a tumor type in which acquired inactivation of SMARCB1 and development of AT/RT features may occur and lead to clinical progression. In contrast, the PLAGL2 and PLAGL1 amplified cases showed either embryonal histology or contained an embryonal component with a significant degree of desmin staining, which could also serve to raise consideration for a PLAG entity when present. Continued compilation of associated clinical data and histopathologic findings will be critical for understanding emerging entities with PLAG-family genetic alterations.

Abstract Oxidative weathering of organic carbon in sedimentary rocks is a major source of CO2 to the atmosphere over geological timescales, but the size of this emission pathway in Earth's past has not been directly quantified due to a lack of available proxy approaches. We have measured the rhenium isotope composition of organic‐rich rocks sampled from unweathered drill cores and weathered outcrops in south Texas, whose stratigraphic successions can be tightly correlated. Oxidative weathering of more than 90% of the organic carbon and ∼85% of the rhenium is accompanied by a shift to lower rhenium isotope compositions in the weathered outcrops. The calculated isotope composition of rhenium weathered from the initial bedrock for individual samples varies systematically by ∼0.7‰ with different fractions of rhenium loss. This variation can be empirically modeled with isotope fractionation factors of α = 1.0002–1.0008. Our results indicate that the isotope composition of rhenium delivered to the oceans can be altered by weathering intensity of rock organic matter and that the rhenium isotope composition of seawater is sensitive to past oxidative weathering and associated CO2 emissions.

This case presents a 35-year-old male with spinal predominant neurofibromatosis-1 who developed an incomplete spinal cord injury (C3 Asia C) which did not improve despite urgent decompressive surgery for multiple cervical neurofibromas. This report outlines a novel indication for intrathecal baclofen. The patient suffered from lower limb weakness with severe spasticity and required assistance of at least two for all activities. The aim of rehabilitation was to improve overall tone while focusing on independence, mobility and quality of life. After a successful trial of intrathecal baclofen, he underwent implantation of an intrathecal baclofen pump. The dose was gradually increased while he received a progressive programme of stretching and functional rehabilitation therapy. After 6 weeks, his MAS had improved to 1–2/4 and he had progressed to independent transfers, independence for most activities of daily living and was able to discharge to his family home with minimal support.

Abstract Anthropogenic disturbances and the subsequent loss of biodiversity are altering species abundances and communities. Since species vary in their pathogen competence, spatio-temporal changes in host assemblages may lead to changes in disease dynamics. We explore how longitudinal changes in bat species assemblages affect the disease dynamics of coronaviruses (CoVs) in more than 2300 cave-dwelling bats captured over two years from five caves in Ghana. This reveals uneven CoV infection patterns between closely related species, with the alpha-CoV 229E-like and SARS-related beta-CoV 2b emerging as multi-host pathogens. Prevalence and infection likelihood for both phylogenetically distinct CoVs is influenced by the abundance of competent species and naïve subadults. Broadly, bat species vary in CoV competence, and highly competent species are more common in less diverse communities, leading to increased CoV prevalence in less diverse bat assemblages. In line with the One Health framework, our work supports the notion that biodiversity conservation may be the most proactive measure to prevent the spread of pathogens with zoonotic potential.

The Royal College of Physicians (RCP) Chief Registrar Programme (CRP) emerged from the RCP Future Hospital Commission Report (2013) and aimed to address development of clinical leadership and quality improvement to maintain high standards of patient safety and experience. The 2016 pilot created a new senior leadership role recruiting doctors in training committed to quality improvement and leadership development to champion delivering change in trusts, supported by a year-long bespoke development programme designed and delivered by the RCP. Following validation of the pilot's impact, the CRP has evolved to become a ‘flagship’ programme for the RCP with increasing penetrance across the UK to maximise impact for chief registrars to lead and deliver quality improvement in trusts. The longer-term goal is that enthusiastic early leaders will deliver sustainable and impactful change regionally and in the wider NHS. This article seeks to explore the CRP development themes and reflects on the learning from the programme and the experiences of chief registrars. The CRP has evolved during a time of significant healthcare challenge with the programme delivering a future generation of medical leaders to navigate these challenges, deliver improvement and innovation across the health sector. We show how chief registrars and alumni can continue to drive forward widespread impact on individuals, organisations and the wider NHS, providing a strategic solution to meet current and future challenges in the NHS.

BackgroundObesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic.Methods and findingsWith the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before (δ-prepandemic) and during (δ-pandemic) the pandemic and identified individuals with rapid weight gain (>0.5 kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period (δ-change = δ-pandemic-δ-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain (δ-change ≥1.84 kg/m2/year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p < 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p < 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p < 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p < 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p < 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of weight gain between the prepandemic and pandemic periods. However, changes in healthcare activity during the pandemic may have introduced new bias to the data.ConclusionsWe found female sex, younger age, deprivation, white British ethnicity, and mental health conditions were associated with rapid pandemic weight gain and extreme acceleration in rate of weight gain between the prepandemic and pandemic periods. Our findings highlight the need to incorporate sociodemographic, physical, and mental health characteristics when formulating research, policies, and interventions targeting BMI in the period of post pandemic service restoration and in future pandemic planning.

Background Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic. Methods and findings With the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before ([delta]-prepandemic) and during ([delta]-pandemic) the pandemic and identified individuals with rapid weight gain (>0.5 kg/m.sup.2 /year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period ([delta]-change = [delta]-pandemic-[delta]-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain ([delta]-change [greater than or equal to]1.84 kg/m.sup.2 /year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m.sup.2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m.sup.2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p < 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p < 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p < 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p < 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p < 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of weight gain between the prepandemic and pandemic periods. However, changes in healthcare activity during the pandemic may have introduced new bias to the data. Conclusions We found female sex, younger age, deprivation, white British ethnicity, and mental health conditions were associated with rapid pandemic weight gain and extreme acceleration in rate of weight gain between the prepandemic and pandemic periods. Our findings highlight the need to incorporate sociodemographic, physical, and mental health characteristics when formulating research, policies, and interventions targeting BMI in the period of post pandemic service restoration and in future pandemic planning., Author(s): Miriam Samuel 1,*, Robin Y. Park 2, Sophie V. Eastwood 3, Fabiola Eto 1, Caroline E. Morton 1,2, Daniel Stow 1, Sebastian Bacon 2, Amir Mehrkar 2, Jessica Morley [...]