Geographical variation in certification rates of blindness and sight impairment in England, 2008-2009

To examine and interpret the variation in the incidence of blindness and sight impairment in England by PCT, as reported by the Certificate of Vision Impairment (CVI). Design: Analysis of national certification data. Setting: All Primary Care Trusts, England. Participants: 23 773 CVI certifications issued from 2008 to 2009. Main Outcome measures: Crude and Age standardised rates of CVI data for blindness and sight loss by PCT. Methods: The crude and age standardised CVI rates per 100 000 were calculated with Spearman's rank correlation used to assess whether there was any evidence of association between CVI rates with Index of Multiple Deprivation (IMD) and the Programme Spend for Vision. Results: There was high-level variation, almost 11-fold (coefficient of variation 38%) in standardised CVI blindness and sight impairment annual certification rates across PCTs. The mean rate was 43.7 and the SD 16.7. We found little evidence of an association between the rate of blindness and sight impairment with either the IMD or Programme Spend on Vision. Conclusions: The wide geographical variation we found raises questions about the quality of the data and whether there is genuine unmet need for prevention of sight loss. It is a concern for public health practitioners who will be interpreting these data locally and nationally as the CVI data will form the basis of the public health indicator ‘preventable sight loss’. Poor-quality data and inadequate interpretation will only create confusion if not addressed adequately from the outset. There is an urgent need to address the shortcomings of the current data collection system and to educate all public health practitioners

Faculty Email Exchanges

Email exchanges between University of Denver and Northwestern University on studies of John Evans and the Sand Creek Massacre

University of Denver John Evans Study Report

Universities are dedicated to the discovery and dissemination of knowledge. They are conservators of humanity\u27s past. They cherish their own pasts, honoring forbears with statues and portraits and in the names of buildings. To study or teach at a [university] is to be a member of a community that exists across time, a participant in a procession that began centuries ago and that will continue long after we are gone. If an institution professing these principles cannot squarely face its own history, it is hard to imagine how any other institution, let alone our nation, might do so. -Report of the Brown University Steering Committee on Slavery and Justice, page 6, 2006. The University of Denver was founded in 1864 by John Evans. John Evans had been appointed by President Abraham Lincoln in 1862 to be the second territorial governor of Colorado. He served in that capacity until 1865. This committee is inquiring into the nature of John Evans’ involvement in the political and economic processes that led to the appropriation of Indian Lands in Colorado and, more specifically, to the 1864 killing of Cheyenne and Arapahoe villagers at Sand Creek. It consists of faculty and staff from DU and other institutions. Given the impending 150-year anniversaries of the Sand Creek Massacre and DU’s founding, it is appropriate to evaluate John Evans’ place in the university’s history and the ways in which we recognize his contributions. The committee is working in tandem with a similarly constituted committee at Northwestern University, which John Evans co-founded in 1853. The NU and DU committees will coordinate research and share information. The DU committee will generate a report of our findings and a set of recommendations for actions that the university should take as a result of our report

Motor Competence between Children with and without Additional Learning Needs: A Cross-Sectional Population-Level Study

The aim of this study was to examine associations in motor competence between children with additional learning needs (ALN) and typically developing children. This cross-sectional study involved a nationally representative cohort of 4555 children (48.98% boys; 11.35 ± 0.65 years) from sixty-five schools across Wales (UK). Demographic data were collected from schools, and children were assessed using the Dragon Challenge assessment of motor competence, which consists of nine tasks completed in a timed circuit. A multi-nominal multi-level model with random intercept was fitted to explore the proficiency between children with ALN and those without. In all nine motor competence tasks, typically developing children demonstrated higher levels of proficiency than their peers with ALN, with these associations evident after accounting for age, sex, ethnicity, and socioeconomic status. This study highlights motor competence inequalities at a population level and emphasises the need for policymakers, practitioners, and researchers to prioritise motor competence development, particularly for children with ALN

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability

A cross-sectional study on the deprivation and sex differences in health-related fitness measures in school children

This study aimed to investigate deprivation and sex differences in selected health-relatedfitness measures in 9-12-year-old children. Data were captured on 3,407 children (49.3% boys; aged 10.5 ± 0.6 years). Cardiorespiratory fitness(20 m multistage shuttle run test; 20 m MSRT), muscular strength (handgrip strength) and body mass index (BMI) were measured. Welsh Index of Multiple Deprivation (WIMD) scores were used to make quintile groups. A two-way Analysis of Variance examined differences in BMI z-score by sex and WIMD quintiles. Two-wayAnalysis of Covariances investigated the effect of sex and WIMD quintiles on grip strength and shuttles achieved in 20 m MSRT, adjusting for BMI z-score and maturation, repectively. Independent of sex, children in the middle quintile had a significantly higher mean BMI z-score (p = 0.029) than their least deprived counterparts. There was a significant increase in grip strength (p = 0.005) and20 m MSRT (boys p < 0.001; girls p = 0.028) between most and least deprived quintiles. Significant differences in 20 m MSRT score were more apparent with decreases in deprivation in boys.Overall, inequalities exist in health-related fitness by sex and deprivation. These results can be used to inform focused services to improve current and future health

Evans Committee Statement on Pioneer

Letter from University of Denver faculty and alumni on the university\u27s use of the \u27Pioneer\u27 moniker

Identification of autoantigens and their potential post-translational modification in EGPA and severe eosinophilic asthma

BackgroundThe chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase (MPO) in ANCA-positive EGPA (eosinophilic granulomatosis with polyangiitis). Previous research has shown that oxidative post-translational modification (oxPTM) of proteins is an important mechanism by which autoantibody responses may escape immune tolerance. Autoantibodies to oxPTM autoantigens in SEA have not previously been studied.MethodsPatients with EGPA and SEA were recruited as well as healthy control participants. Autoantigen agnostic approach: Participant serum was incubated with slides of unstimulated and PMA-stimulated neutrophils and eosinophils, and autoantibodies to granulocytes were identified by immunofluorescence with anti-human IgG FITC antibody. Target autoantigen approach: Candidate proteins were identified from previous literature and FANTOM5 gene set analysis for eosinophil expressed proteins. Serum IgG autoantibodies to these proteins, in native and oxPTM form, were detected by indirect ELISA.ResultsImmunofluorescence studies showed that serum from patients with known ANCA stained for IgG against neutrophils as expected. In addition, serum from 9 of 17 tested SEA patients stained for IgG to PMA-stimulated neutrophils undergoing NETosis. Immunofluorescent staining of eosinophil slides was evident with serum from all participants (healthy and with eosinophilic disease) with diffuse cytoplasmic staining except for one SEA individual in whom subtle nuclear staining was evident. FANTOM5 gene set analysis identified TREM1 (triggering receptor expressed on myeloid cells 1) and IL-1 receptor 2 (IL1R2) as eosinophil-specific targets to test for autoantibody responses in addition to MPO, eosinophil peroxidase (EPX), and Collagen-V identified from previous literature. Indirect ELISAs found high concentrations of serum autoantibodies to Collagen-V, MPO, and TREM1 in a higher proportion of SEA patients than healthy controls. High concentrations of serum autoantibodies to EPX were evident in serum from both healthy and SEA participants. The proportion of patients with positive autoantibody ELISAs was not increased when examining oxPTM compared to native proteins.DiscussionAlthough none of the target proteins studied showed high sensitivity for SEA, the high proportion of patients positive for at least one serum autoantibody shows the potential of more research on autoantibody serology to improve diagnostic testing for severe asthma.Clinical trial registrationClinicalTrials.gov, identifier, NCT04671446

The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus.

BACKGROUND: The molecular heterogeneity of autoimmune and inflammatory diseases has been one of the main obstacles to the development of safe and specific therapeutic options. Here, we evaluated the diagnostic and clinical value of a robust, inexpensive, immunoassay detecting the circulating soluble form of the monocyte-specific surface receptor sialic acid binding Ig-like lectin 1 (sSIGLEC-1). METHODS: We developed an immunoassay to measure sSIGLEC-1 in small volumes of plasma/serum from systemic lupus erythematosus (SLE) patients (n = 75) and healthy donors (n = 504). Samples from systemic sclerosis patients (n = 99) were studied as an autoimmune control. We investigated the correlation between sSIGLEC-1 and both monocyte surface SIGLEC-1 and type I interferon-regulated gene (IRG) expression. Associations of sSIGLEC-1 with clinical features were evaluated in an independent cohort of SLE patients (n = 656). RESULTS: Plasma concentrations of sSIGLEC-1 strongly correlated with expression of SIGLEC-1 on the surface of blood monocytes and with IRG expression in SLE patients. We found ancestry-related differences in sSIGLEC-1 concentrations in SLE patients, with patients of non-European ancestry showing higher levels compared to patients of European ancestry. Higher sSIGLEC-1 concentrations were associated with lower serum complement component 3 and increased frequency of renal complications in European patients, but not with the SLE Disease Activity Index clinical score. CONCLUSIONS: Our sSIGLEC-1 immunoassay provides a specific and easily assayed marker for monocyte-macrophage activation, and interferonopathy in SLE and other diseases. Further studies can extend its clinical associations and its potential use to stratify patients and as a secondary endpoint in clinical trials

Genomics of Drug Sensitivity in Cancer (GDSC): a Resource for Therapeutic Biomarker Discovery in Cancer Cells

Alterations in cancer genomes strongly influence clinical responses to treatment and in many instances are potent biomarkers for response to drugs. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) is the largest public resource for information on drug sensitivity in cancer cells and molecular markers of drug response. Data are freely available without restriction. GDSC currently contains drug sensitivity data for almost 75 000 experiments, describing response to 138 anticancer drugs across almost 700 cancer cell lines. To identify molecular markers of drug response, cell line drug sensitivity data are integrated with large genomic datasets obtained from the Catalogue of Somatic Mutations in Cancer database, including information on somatic mutations in cancer genes, gene amplification and deletion, tissue type and transcriptional data. Analysis of GDSC data is through a web portal focused on identifying molecular biomarkers of drug sensitivity based on queries of specific anticancer drugs or cancer genes. Graphical representations of the data are used throughout with links to related resources and all datasets are fully downloadable. GDSC provides a unique resource incorporating large drug sensitivity and genomic datasets to facilitate the discovery of new therapeutic biomarkers for cancer therapies