Developing a typology of the roles public contributors undertake to establish legitimacy: A longitudinal case study of patient and public involvement in a health network

Objective To identify how public contributors established their legitimacy in the functioning of a patient and public involvement programme at a health network. Design A longitudinal case study with three embedded units (projects) involving public contributors. Interviews (n=24), observations (n=27) and documentary data collection occurred over 16 months. Setting The West of England Academic Health Science Network (WEAHSN), 1 of 15 regional AHSNs in England. Participants Interviews were conducted with public contributors (n=5) and professionals (n=19) who were staff from the WEAHSN, its member organisations and its partners. Results Public contributors established their legitimacy by using nine distinct roles: (1) lived experience, as a patient or carer; (2) occupational knowledge, offering job-related expertise; (3) occupational skills, offering aptitude developed through employment; (4) patient advocate, promoting the interests of patients; (5) keeper of the public purse, encouraging wise spending; (6) intuitive public, piloting materials suitable for the general public; (7) fresh-eyed reviewer, critiquing materials; (8) critical friend, critiquing progress and proposing new initiatives and (9) boundary spanner, urging professionals to work across organisations. Individual public contributors occupied many, but not all, of the roles. Conclusions Lived experience is only one of nine distinct public contributor roles. The WEAHSN provided a benign context for the study because in a health network public contributors are one of many parties seeking to establish legitimacy through finding valuable roles. The nine roles can be organised into a typology according to whether the basis for legitimacy lies in: the public contributor's knowledge, skills and experience; citizenship through the aspiration to achieve a broad public good; or being an outsider. The typology shows how public contributors can be involved in work where lived experience appears to lack relevance: strategic decision making; research unconnected to particular conditions; or acute service delivery

Quantum Mechanical Aspects of Cell Microtubules: Science Fiction or Realistic Possibility?

Recent experimental research with marine algae points towards quantum entanglement at ambient temperature, with correlations between essential biological units separated by distances as long as 20 Angstr\"oms. The associated decoherence times, due to environmental influences, are found to be of order 400 fs. This prompted some authors to connect such findings with the possibility of some kind of quantum computation taking place in these biological entities: within the decoherence time scales, the cell "quantum calculates" the optimal "path" along which energy and signal would be transported more efficiently. Prompted by these experimental results, in this talk I remind the audience of a related topic proposed several years ago in connection with the possible r\^ole of quantum mechanics and/or field theory on dissipation-free energy transfer in microtubules (MT), which constitute fundamental cell substructures. Quantum entanglement between tubulin dimers was argued to be possible, provided there exists sufficient isolation from other environmental cell effects. The model was based on certain ferroelectric aspects of MT. In the talk I review the model and the associated experimental tests so far and discuss future directions, especially in view of the algae photo-experiments.Comment: 31 pages latex, 11 pdf figures, uses special macros, Invited Plenary Talk at DICE2010, Castello Pasquini, Castiglioncello (Italy), September 13-18 201

Barriers, facilitators, and survival strategies for GPs seeking treatment for distress:a qualitative study

BACKGROUND: GPs are under increasing pressure due to a lack of resources, a diminishing workforce, and rising patient demand. As a result, they may feel stressed, burnt out, anxious, or depressed. AIM: To establish what might help or hinder GPs experiencing mental distress as they consider seeking help for their symptoms, and to explore potential survival strategies. DESIGN AND SETTING: The authors recruited 47 GP participants via e-mails to doctors attending a specialist service, adverts to local medical committees (LMCs) nationally and in GP publications, social media, and snowballing. Participants self-identified as either currently living with mental distress, returning to work following treatment, off sick or retired early as a result of mental distress, or without experience of mental distress. Interviews were conducted face to face or over the telephone. METHOD: Transcripts were uploaded to NVivo 11 and analysed using thematic analysis. RESULTS: Barriers and facilitators were related to work, stigma, and symptoms. Specifically, GPs discussed feeling a need to attend work, the stigma surrounding mental ill health, and issues around time, confidentiality, and privacy. Participants also reported difficulties accessing good-quality treatment. GPs also talked about cutting down or varying work content, or asserting boundaries to protect themselves. CONCLUSION: Systemic changes, such as further information about specialist services designed to help GPs, are needed to support individual GPs and protect the profession from further damage

A lightweight magnetically shielded room with active shielding

Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40–60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a ‘window coil’ active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG

Abstracts from the NIHR INVOLVE Conference 2017

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Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

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