Power in periods: a Foucauldian-feminist exploration of menstruation in an all-girls’ secondary school in South Africa

Absenteeism from school among girls due to a lack of menstrual health management (MHM) products has increasingly attracted attention from researchers and activists in recent years. Having highlighted the challenges caused by a lack of MHM products, the focus has been on the available facilities at schools to ensure MHM. Many schools in South Africa lack water, sanitation and hygiene (WASH) to ensure hygiene standards for the removal of bodily excre-ment, which further causes distress to girls needing MHM while at school. To investigate fur-ther the MHM challenges girls face, apart from access to products and WASH, this qualita-tive study purposively selected an all-girls’ school with access to good sanitation facilities. This research uses Foucauldian Discourse Analysis and Feminist Theory to explore the forms of discipline and control that girls experience at school to contain their bodily functioning and fluids, and the forms of resistance and support that girls encounter with MHM at school. I will argue that the ambivalent meanings girls acquire about menstruation at home and in soci-ety persist at school despite their own views that menstruation is normal. While MHM prod-ucts and WASH facilities need to be freely available, the problematic social response to men-struation is what needs to be addressed in order to emancipate women from the social patriar-chal power that informs their understanding that menstruation is shameful. MHM cannot only encompass products and facilities but needs to encompass a change in societal views of sex-ual and reproductive health.Thesis (MA) -- Faculty of Humanities, Psychology, 202

Toward interoperable bioscience data

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Genetics 44 (2012): 121-126, doi:10.1038/ng.1054.To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision.The authors also acknowledge the following funding sources in particular: UK Biotechnology and Biological Sciences Research Council (BBSRC) BB/I000771/1 to S.-A.S. and A.T.; UK BBSRC BB/I025840/1 to S.-A.S.; UK BBSRC BB/I000917/1 to D.F.; EU CarcinoGENOMICS (PL037712) to J.K.; US National Institutes of Health (NIH) 1RC2CA148222-01 to W.H. and the HSCI; US MIRADA LTERS DEB-0717390 and Alfred P. Sloan Foundation (ICoMM) to L.A.-Z.; Swiss Federal Government through the Federal Office of Education and Science (FOES) to L.B. and I.X.; EU Innovative Medicines Initiative (IMI) Open PHACTS 115191 to C.T.E.; US Department of Energy (DOE) DE-AC02- 06CH11357 and Arthur P. Sloan Foundation (2011- 6-05) to J.G.; UK BBSRC SysMO-DB2 BB/I004637/1 and BBG0102181 to C.G.; UK BBSRC BB/I000933/1 to C.S. and J.L.G.; UK MRC UD99999906 to J.L.G.; US NIH R21 MH087336 (National Institute of Mental Health) and R00 GM079953 (National Institute of General Medical Science) to A.L.; NIH U54 HG006097 to J.C. and C.E.S.; Australian government through the National Collaborative Research Infrastructure Strategy (NCRIS); BIRN U24-RR025736 and BioScholar RO1-GM083871 to G.B. and the 2009 Super Science initiative to C.A.S

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Single index of multimorbidity did not predict multiple outcomes

Background and ObjectivesMeasurement of multimorbidity and comorbidity is important in epidemiologic and health services research. The aim of this research was to derive a generic multimorbidity index based on patient self-report, incorporating severity, for predicting a range of outcomes.MethodsThe dataset was obtained from a trial including 1,541 Veterans and war widows aged 70 years and over. The survey included sociodemographics, hospital admissions, SF-36, and information on deaths was obtained. The methods of Charlson were used to derive Multimorbidity Indices.ResultsAll indices predicted quality of life, with decreasing quality of life for each increase in multimorbidity category. Multimorbidity scores incorporating severity significantly contributed to the prediction of mortality, hospital admission, and follow-up quality of life, regardless of adjustment for baseline quality of life.ConclusionsOur results indicate that a single index cannot predict a variety of relevant outcomes. Consequently, research undertaken to assess the impact of intervention or illness on health outcomes should use an index that is valid for predicting the specific outcome of interest

Disinvestment and value-based purchasing strategies for pharmaceuticals : an international review

Pharmaceutical expenditure has increased rapidly across many OECD countries over the past three decades. This growth is an increasing concern for Governments and other third party payers seeking to provide equitable and comprehensive healthcare within sustainable budgets. In order to create headroom for increasing utilisation, and to fund new high cost therapies there is an active push to ‘disinvest’ from low-value drugs. The aim of this article is to review how reimbursement policy decision makers have sought to partially or completely disinvest from drugs in a range of OECD countries (UK, France, Canada, Australia and New Zealand) where they are publicly funded or subsidised. We employed a systematic literature search strategy and the incorporation of grey literature known to the authorship team. We canvass key policy instruments from each country to outline: key approaches to the identification of candidate drugs for disinvestment assessment (passive approaches versus more active approaches); Methods of disinvestment and value-based purchasing: de-listing, restricting treatment, price or reimbursement rate reductions, encouraging generic prescribing; Lessons learnt from the various approaches; The potential role of coverage with evidence development, and; The need for careful stakeholder management. Dedicated sections are provided with detailed coverage of policy approaches (with drug examples) from each country. Historically countries have relied on ‘passive disinvestment’, however due to (i) the availability of new cost-effectiveness evidence or (ii) ‘leakage’ in drug utilisation or (iii) market failure in terms of price competition, there is an increasing focus towards ‘active disinvestment’. Isolating low-value drugs that would create headroom for innovative new products to enter the market is also motivating disinvestment efforts by multiple parties, including industry. Historically disinvestment has mainly taken the form of price reductions, especially when market failures are perceived to exist, and restricting treatment to sub-populations, particularly when a drug is no longer considered value for money. There is considerable experimentation internationally in mechanisms for disinvestment and the opportunity for countries to learn from each other. Ongoing evaluation of disinvestment strategies is essential, and ought to be reported in the peer-reviewed literature