Including all voices in international data-sharing governance

Background Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will bring a number of benefits and enable advances in healthcare and medicine by allowing the maximum returns from the investment in research, as well as reducing waste and promoting transparency. As this approach gains momentum, these data-sharing practices have implications for many kinds of research as they become standard practice across the world. Main text The governance frameworks that have been developed to support biomedical research are not well equipped to deal with the complexities of international data sharing. This system is nationally based and is dependent upon expert committees for oversight and compliance, which has often led to piece-meal decisionmaking. This system tends to perpetuate inequalities by obscuring the contributions and the important role of different data providers along the data stream, whether they be low- or middle-income country researchers, patients, research participants, groups, or communities. As research and data-sharing activities are largely publicly funded, there is a strong moral argument for including the people who provide the data in decision-making and to develop governance systems for their continued participation. Conclusions We recommend that governance of science becomes more transparent, representative, and responsive to the voices of many constituencies by conducting public consultations about data-sharing addressing issues of access and use; including all data providers in decision-making about the use and sharing of data along the whole of the data stream; and using digital technologies to encourage accessibility, transparency, and accountability. We anticipate that this approach could enhance the legitimacy of the research process, generate insights that may otherwise be overlooked or ignored, and help to bring valuable perspectives into the decision-making around international data sharing.</p

Salmonella enterica serovar Typhi lipopolysaccharide O-antigen modification impact on serum resistance and antibody recognition

Salmonella enterica serovar Typhi is a human-restricted Gram-negative bacterial pathogen responsible for causing an estimated 27 million cases of typhoid fever annually, leading to 217,000 deaths, and current vaccines do not offer full protection. The O-antigen side chain of the lipopolysaccharide is an immunodominant antigen, can define host-pathogen interactions, and is under consideration as a vaccine target for some Gram-negative species. The composition of the O-antigen can be modified by the activity of glycosyltransferase (gtr) operons acquired by horizontal gene transfer. Here we investigate the role of two gtr operons that we identified in the S. Typhi genome. Strains were engineered to express specific gtr operons. Full chemical analysis of the O-antigens of these strains identified gtr-dependent glucosylation and acetylation. The glucosylated form of the O-antigen mediated enhanced survival in human serum and decreased complement binding. A single nucleotide deviation from an epigenetic phase variation signature sequence rendered the expression of this glucosylating gtr operon uniform in the population. In contrast, the expression of the acetylating gtrC gene is controlled by epigenetic phase variation. Acetylation did not affect serum survival, but phase variation can be an immune evasion mechanism, and thus, this modification may contribute to persistence in a host. In murine immunization studies, both O-antigen modifications were generally immunodominant. Our results emphasize that natural O-antigen modifications should be taken into consideration when assessing responses to vaccines, especially O-antigen-based vaccines, and that the Salmonella gtr repertoire may confound the protective efficacy of broad-ranging Salmonella lipopolysaccharide conjugate vaccines

New times, new politics: history and memory during the final years of the CPGB

This article examines the relationship between collective memory, historical interpretation and political identity. It focuses on the dissolution of the Communist Party of Great Britain (CPGB) as constructed through collective narrative memory, and on Marxist interpretations of history. The divisions within the party and the wider Marxist community, stretching from 1956 until 1991, were often framed around questions of historical interpretation. The events of 1989–1991 created an historical and mnemonic crisis for CPGB members who struggled to reconcile their past identities with their present situation. Unlike the outward-facing revisionism of other political parties, this was an intensely personal affair. The solution for many was to emphasise the need to find new ways to progress socialist aims, without relying on a discredited grand narrative. In contrast, other Communist parties, such as the Communist Party of Britain, which had been established (or ‘re-established’) in 1988, fared rather better. By adhering to the international party line of renewal and continued struggle, the party was able to hold its narrative together, condemning the excesses of totalitarian regimes, while reaffirming the need for international class struggle

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19

\ua9 2023 The Author(s)Background: Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. Methods: Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. Findings: Forty patients (32M:8F, age: 22–98), 345 ROIs and &gt;900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. Interpretation: The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. Funding: UK Research and Innovation/ Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust

Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study

Background: The presence of measles virus (MV) RNA in bowel tissue from children with autism spectrum disorders (ASD) and gastrointestinal (GI) disturbances was reported in 1998. Subsequent investigations found no associations between MV exposure and ASD but did not test for the presence of MV RNA in bowel or focus on children with ASD and GI disturbances. Failure to replicate the original study design may contribute to continued public concern with respect to the safety of the measles, mumps, and rubella (MMR) vaccine. Methodology/Principal Findings: The objective of this case-control study was to determine whether children with GI disturbances and autism are more likely than children with GI disturbances alone to have MV RNA and/or inflammation in bowel tissues and if autism and/or GI episode onset relate temporally to receipt of MMR. The sample was an age-matched group of US children undergoing clinically-indicated ileocolonoscopy. Ileal and cecal tissues from 25 children with autism and GI disturbances and 13 children with GI disturbances alone (controls) were evaluated by real-time reverse transcription (RT)-PCR for presence of MV RNA in three laboratories blinded to diagnosis, including one wherein the original findings suggesting a link between MV and ASD were reported. The temporal order of onset of GI episodes and autism relative to timing of MMR administration was examined. We found no differences between case and control groups in the presence of MV RNA in ileum and cecum. Results were consistent across the three laboratory sites. GI symptom and autism onset were unrelated to MMR timing. Eighty-eight percent of ASD cases had behavioral regression. Conclusions/Significance: This study provides strong evidence against association of autism with persistent MV RNA in the GI tract or MMR exposure. Autism with GI disturbances is associated with elevated rates of regression in language or other skills and may represent an endophenotype distinct from other ASD

Asteroseismology

Asteroseismology is the determination of the interior structures of stars by using their oscillations as seismic waves. Simple explanations of the astrophysical background and some basic theoretical considerations needed in this rapidly evolving field are followed by introductions to the most important concepts and methods on the basis of example. Previous and potential applications of asteroseismology are reviewed and future trends are attempted to be foreseen.Comment: 38 pages, 13 figures, to appear in: "Planets, Stars and Stellar Systems", eds. T. D. Oswalt et al., Springer Verla

Paroxetine reduces crying in young women watching emotional movies

Rationale: Crying is a unique human emotional reaction that has not received much attention from researchers. Little is known about its underlying neurobiological mechanisms, although there is some indirect evidence suggesting the involvement of central serotonin. Objectives: We examined the acute effects of the administration of 20 mg paroxetine on the crying of young, healthy females in response to emotional movies. Methods: We applied a double-blind, crossover randomised design with 25 healthy young females as study participants. On separate days, they received either paroxetine or placebo and were exposed to one of two emotional movies: 'Once Were Warriors' and 'Brian's Song'. Crying was assessed by self-report. In addition, the reactions to emotional International Affective Picture System (IAPS) pictures and mood were measured. Results: Paroxetine had a significant inhibitory effect on crying. During both films, the paroxetine group cried significantly less than the placebo group. In contrast, no effects on mood and only minor effects on the reaction to the IAPS pictures were observed. Conclusions: A single dose of paroxetine inhibits emotional crying significantly. It is not sure what the underlying mechanism is. However, since there was no effect on mood and only minor effects on the response to emotional pictures, we postulate that paroxetine mainly acts on the physiological processes involved in the crying response