Assessing the reliability of ethnicity data recorded in health-related administrative datasets in England.

Objectives During the COVID-19 pandemic, higher mortality among some ethnic minority groups was identified and has become the subject of significant public and government interest, highlighting an urgent requirement to quantify the reliability of ethnicity classification across health administrative data sets, which are utilised in health analysis and pandemic planning. Approach The aim of our work was to assess how ethnicity data recorded in Census and health admin records varied across ethnicities and provide recommendations for how missingness can be accounted for by statisticians. Combining population level data from general practice (GP) records with hospital episode statistics (HES) for patients in England, we created a linked data set with Census 2011 data to reliably assess coverage and missingness between data sources. Most recent and modal ethnicity classifications were derived on a person-level from both HES and GP administrative data for comparison to gold-standard Census 2011 records. Results Agreement rates were calculated to assess the reliability of ethnicity data recorded in health administrative datasets compared to Census data. We found that the agreement rates vary by ethnic group and other demographic characteristics. Furthermore, we highlighted groups of people who exist in one health-admin source, but not Census, and vice versa, illustrating the importance of accounting for the sample bias in health analysis when relying solely on primary or secondary care data sources. Implementation of techniques to account for bias and missingness were tested to propose methodology to improve reliability of ethnicity estimates from both HES and GP data, in order to ensure estimates of health disparities are as accurate as possible. Conclusion We have linked GP records to Census 2011 and HES data to provide population-based ethnicity estimates of coverage, missingness and bias between data sources, in order to improve our understanding of ethnicity data quality. This work aims to inform policies tackling ethnic health inequalities in England

Religious affiliation and the risk of COVID 19 related mortality; a retrospective analysis of variation in pre and post lockdown risk by religious group in England and Wales

AbstractBackgroundCOVID 19 mortality risk is associated with demographic and behavioural factors; furthermore religious gatherings have been linked with the spread of COVID. We sought to understand the variation in the risk of COVID 19 related death across religious groups in the UK both before and after lockdown.MethodsWe conducted a retrospective cohort study of usual residents in England and Wales enumerated at the 2011 Census (n = 48,422,583), for risk of death involving COVID-19 using linked death certificates. Cox regression models were estimated to compare risks between religious groups. Time dependent religion coefficients were added to the model allowing hazard ratios (HRs) pre and post lockdown period to be estimated separately.ResultsCompared to Christians all religious groups had an elevated risk of death involving COVID-19; the largest age adjusted HRs were for Muslim and Jewish males at 2.5 (95% confidence interval 2.3-2.7) and 2.1 (1.9-2.5), respectively. The corresponding HRs for Muslim and Jewish females were 1.9 (1.7-2.1) and 1.5 (1.7-2.1). The difference in risk between groups contracted after lockdown. Those who affiliated with no religion had the lowest risk of COVID 19 related death before and after lockdown.ConclusionThe majority of the variation in COVID 19 mortality risk was explained by controlling for socio demographic and geographic determinants; however, Jews remained at a higher risk of death compared to all other groups. Lockdown measures were associated with reduced differences in COVID 19 mortality rates between religious groups, further research is required to understand the causal mechanisms.</jats:sec

Extracellular Calcium Regulates Postsynaptic Efficacy through Group 1 Metabotropic Glutamate Receptors

Bursts of synaptic transmission are known to induce transient depletion of Ca2+ within the synaptic cleft. Although Ca2+ depletion has been shown to lower presynaptic release probability, effects on the postsynaptic cell have not been reported. In this study, we show that physiologically relevant reductions in extracellular Ca2+ lead to a decrease in synaptic strength between synaptically coupled layer 2/3 cortical pyramidal neurons. Using quantal analysis and mEPSP analysis, we demonstrate that a lowered extracellular Ca2+ produces a reduction in the postsynaptic quantal size in addition to its known effect on release probability. An elevated Mg2+ level can prevent this reduction in postsynaptic efficacy at subphysiological Ca2+ levels. We show that the calcium-dependent effect on postsynaptic quantal size is mediated by group 1 metabotropic glutamate receptors, acting via CaMKII (Ca2+/calmodulin-dependent protein kinase II) and PKC. Therefore, physiologically relevant changes in extracellular Ca2+ can regulate information transfer at cortical synapses via both presynaptic and postsynaptic mechanisms

Quantal Analysis Reveals a Functional Correlation between Presynaptic and Postsynaptic Efficacy in Excitatory Connections from Rat Neocortex

At many central synapses, the presynaptic bouton and postsynaptic density are structurally correlated. However, it is unknown whether this correlation extends to the functional properties of the synapses. To investigate this, we made recordings from synaptically coupled pairs of pyramidal neurons in rat visual cortex. The mean peak amplitude of EPSPs recorded from pairs of L2/3 neurons ranged between 40 μV and 2.9 mV. EPSP rise times were consistent with the majority of the synapses being located on basal dendrites; this was confirmed by full anatomical reconstructions of a subset of connected pairs. Over a third of the connections could be described using a quantal model that assumed simple binomial statistics. Release probability (Pr) and quantal size (Q), as measured at the somatic recording site, showed considerable heterogeneity between connections. However, across the population of connections, values of Pr and Q for individual connections were positively correlated with one another. This correlation also held for inputs to layer 5 pyramidal neurons from both layer 2/3 and neighboring layer 5 pyramidal neurons, suggesting that during development of cortical connections presynaptic and postsynaptic strengths are dependently scaled. For 2/3 to 2/3 connections, mean EPSP amplitude was correlated with both Q and Pr values but uncorrelated with N, the number of functional release sites mediating the connection. The efficacy of a cortical connection is thus set by coordinated presynaptic and postsynaptic strength

Study protocol for the use of time series forecasting and risk analyses to investigate the effect of the COVID-19 pandemic on hospital admissions associated with new-onset disability and frailty in a national, linked electronic health data setting

INTRODUCTION: Older people were at particular risk of morbidity and mortality during COVID-19. Consequently, they experienced formal (externally imposed) and informal (self-imposed) periods of social isolation and quarantine. This is hypothesised to have led to physical deconditioning, new-onset disability and frailty. Disability and frailty are not routinely collated at population level but are associated with increased risk of falls and fractures, which result in hospital admissions. First, we will examine incidence of falls and fractures during COVID-19 (January 2020-March 2022), focusing on differences between incidence over time against expected rates based on historical data, to determine whether there is evidence of new-onset disability and frailty. Second, we will examine whether those with reported SARS-CoV-2 were at higher risk of falls and fractures. METHODS AND ANALYSIS: This study uses the Office for National Statistics (ONS) Public Health Data Asset, a linked population-level dataset combining administrative health records with sociodemographic data of the 2011 Census and National Immunisation Management System COVID-19 vaccination data for England. Administrative hospital records will be extracted based on specific fracture-centric International Classification of Diseases-10 codes in years preceding COVID-19 (2011-2020). Historical episode frequency will be used to predict expected admissions during pandemic years using time series modelling, if COVID-19 had not occurred. Those predicted admission figures will be compared with actual admissions to assess changes in hospital admissions due to public health measures comprising the pandemic response. Hospital admissions in prepandemic years will be stratified by age and geographical characteristics and averaged, then compared with pandemic year admissions to assess more granular changes. Risk modelling will assess risk of experiencing a fall, fracture or frail fall and fracture, if they have reported a positive case of COVID-19. The combination of these techniques will provide insight into changes in hospital admissions from the COVID-19 pandemic. ETHICS AND DISSEMINATION: This study has approval from the National Statistician's Data Ethics Advisory Committee (NSDEC(20)12). Results will be made available to other researchers via academic publication and shared via the ONS website

The Astropy Problem

The Astropy Project (http://astropy.org) is, in its own words, "a community effort to develop a single core package for Astronomy in Python and foster interoperability between Python astronomy packages." For five years this project has been managed, written, and operated as a grassroots, self-organized, almost entirely volunteer effort while the software is used by the majority of the astronomical community. Despite this, the project has always been and remains to this day effectively unfunded. Further, contributors receive little or no formal recognition for creating and supporting what is now critical software. This paper explores the problem in detail, outlines possible solutions to correct this, and presents a few suggestions on how to address the sustainability of general purpose astronomical software

The Methyltransferase WBSCR22/Merm1 Enhances Glucocorticoid Receptor Function and Is Regulated in Lung Inflammation and Cancer

Glucocorticoids (GC) regulate cell fate and immune function. We identified the metastasis-promoting methyltransferase, metastasis-related methyltransferase 1 (WBSCR22/Merm1) as a novel glucocorticoid receptor (GR) regulator relevant to human disease. Merm1 binds the GR co-activator GRIP1 but not GR. Loss of Merm1 impaired both GR transactivation and transrepression by reducing GR recruitment to its binding sites. This was accompanied by loss of GR-dependent H3K4Me3 at a well characterized promoter. Inflammation promotes GC resistance, in part through the actions of TNFα and IFNγ. These cytokines suppressed Merm1 protein expression by driving ubiquitination of two conserved lysine residues. Restoration of Merm1 expression rescued GR transactivation. Cytokine suppression of Merm1 and of GR function was also seen in human lung explants. In addition, striking loss of Merm1 protein was observed in both inflammatory and neoplastic human lung pathologies. In conclusion, Merm1 is a novel regulator of chromatin structure affecting GR recruitment and function, contributing to loss of GC sensitivity in inflammation, with suppressed expression in pulmonary disease

Ingestion of oxygenated water enhances lactate clearance kinetics in trained runners

Abstract Background Drinks with higher dissolved oxygen concentrations have in recent times gained popularity as a potential ergogenic aid, despite a lack of evidence regarding their efficacy. The aim of this study was to assess effects of ingestion of an oxygen supplement (OS) on exercise performance and post-exercise recovery in a group of trained runners. Methods Trained male runners (n = 25, mean ± SD; age 23 ± 6 years, mass 70 ± 9 kg, BMI 21.9 ± 2.7 kg.m−2 VO2max 64 ± 6mL.kg−1.min−1), completed a randomised double blinded, crossover study to assess the effect of ingestion of OS solution on exercise performance and recovery. Trials consisted of a 30min rest period, 5min warm-up, a 5000m treadmill time-trial, and a 30min passive recovery. Participants ingested 6x15mL of either OS or a taste matched placebo during the trials (3 during the rest phase, 1 during exercise and 2 during the recovery). Muscle tissue O2 saturation was measured via near infrared spectroscopy. Blood lactate concentrations were measured prior to, mid-way and directly after the finish of the 5000m time trials and every 3-min during the post-exercise recovery. Results Ingestion of OS did not improve exercise performance. No significant differences were observed for muscle tissue O2 saturation at any time-points. However, lactate clearance was significantly improved during recovery in the OS trials. Both AUC (109 ± 32 vs. 123 ± 38 mmol.min, P < 0.05, d = 0.40) and lactate half-life (λ) (1127 ± 272 vs. 1223 ± 334 s, P < 0.05, d = 0.32) were significantly reduced. Conclusions Despite no evidence of improved exercise performance, ingestion of OS did enhance post-exercise recovery via increased lactate clearance