2,011 research outputs found

    Vices of distrust

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    One of the first things that comes to mind when we think of the special issue’s theme, “Trust in a Social and Digital World” is the epidemic of ‘fake news’ and a cluster of trust- relevant vices we commonly associate with those who share it, click on it, and believe it. Fake news consumers are, among other things, gullible and naïve. (How many times have you seen someone share the increasingly dated and non-binding Facebook privacy message hoax, or a meme that includes a dramatic picture and a powerful looking statistic, but no references to that statistic?) Many are also dogmatic: intellectually and/or emotionally tied to a view point, and as a result, too quick to uncritically trust whatever aligns with it. Gullibility, naivety, and dogmatism are all examples of vices that lead to us trust when we shouldn’t. The effects of these kinds of vices can be dangerous. (So dangerous, in fact, that in August 2019, the United States F.B.I. for the first time listed ‘conspiracy theories’ as among the top domestic terror threats.) Our aim here, however, is to explore the other side of the coin: those character vices that lead us to refrain from trusting when we should trust. For ease of reference, call these vices of distrust. Vices of distrust are dangerous in their own right, and in ways that often harm others along with oneself. The three vices of distrust we want explore—with a particular focus on their manifestations online—are: closemindedness, emulousness, and arrogance. Each contributes to vicious distrust in its own distinctive way

    Combination of hydrogel nanoparticles and proteomics to reveal secreted proteins associated with decidualization of human uterine stromal cells

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    <p>Abstract</p> <p>Background</p> <p>Identification of secreted proteins of low abundance is often limited by abundant and high molecular weight (MW) proteins. We have optimised a procedure to overcome this limitation.</p> <p>Results</p> <p>Low MW proteins in the conditioned media of cultured cells were first captured using dual-size exclusion/affinity hydrogel nanoparticles and their identities were then revealed by proteomics.</p> <p>Conclusions</p> <p>This technique enables the analysis of secreted proteins of cultured cells low MW and low abundance.</p

    Rational ligand design for metal ion recognition. Synthesis of a N-benzylated N2S3-donor macrocycle for enhanced silver(I) discrimination

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    Four previously documented ligand design strategies for achieving Ag(I) discrimination have been applied to the design of a new N-benzylated N2S3-donor macrocycle; the latter shows high selectivity for Ag(I) over Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Pb(II) in log K and bulk membrane transport studies

    Interaction of Co(II), Ni(II) and Cu(II) with dibenzo-substituted macrocyclic ligands incorporating both symmetrically and unsymmetrically arranged N, O and S donors

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    The synthesis and characterisation of four 17-membered, dibenzo-substituted macrocyclic ligands incorporating unsymmetrical arrangements of their N3S2, N3O2 and N3OS (two ligands) donor atoms are described; these rings complete the matrix of related macrocyclic systems incorporating both symmetric and unsymmetric donor sets reported previously. The X-ray structures of three of the new macrocycles are reported. In two of the Cu(II) structures only three of the possible five donor atoms present in the corresponding macrocyclic ligand bind to the Cu(II) site, whereas all five donors are coordinated in each of the remaining complexes. The interaction of Co(II), Ni(II) and Cu(II) with the unsymmetric macrocycle series has been investigated by potentiometric (pH) titration in 95% methanol; X-ray structures of two nickel and three copper complexes of these ligands, each exhibiting 1 : 1 (M :L) ratios, have been obtained. The results are discussed in the context of previous results for these metals with the analogous 17-membered ring systems incorporating symmetrical arrangements of their donor atoms, with emphasis being given to both the influence of the donor atom set, as well as the donor atom sequence, on the nature of the resulting complexes

    Evidence and methods required to evaluate the impact for patients who use social prescribing : a rapid systematic review and qualitative interviews

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    Background Social prescribing encourages health-care and other professionals to refer patients to a link worker, who will develop a personalised plan to improve the patient’s health and well-being. We explore the feasibility of evaluating the service. Objective The objective was to answer the following research questions. (1) What are the most important evaluation questions that an impact study could investigate? (2) What data are already available at a local or national level and what else would be needed? (3) Are there sites delivering at a large enough scale and in a position to take part in an impact study? (4) How could the known challenges to evaluation (e.g. information governance and identifying a control group) be addressed? Data sources Data sources included MEDLINE ALL (via Ovid), searched from inception to 14 February 2019, and the first 100 hits of a Google (Google Inc., Mountain View, CA, USA) search. Review methods Rapid systematic review – electronic searches up to February 2019. Studies included any study design or outcomes. Screening was conducted by one reviewer; eligibility assessment and data extraction were undertaken by two reviewers. Data were synthesised narratively. Qualitative interviews – data from 25 participants in different regions of England were analysed using a pragmatic framework approach across 12 areas including prior data collection, delivery sites, scale and processes of current service delivery, and known challenges to evaluation. Views of key stakeholders (i.e. patients and academics) were captured. Results Rapid systematic review – 27 out of 124 studies were included. We identified outcomes and highlighted research challenges. Important evaluation questions included identification of the most appropriate (1) outcomes and (2) methods for dealing with heterogeneity. Qualitative interviews – social prescribing programmes are holistic in nature, covering domains such as social isolation and finance. Service provision is heterogeneous. The follow-on services that patients access are often underfunded or short term. Available data – there was significant heterogeneity in data availability, format and follow-up. Data were collected using a range of tools in ad hoc databases across sites. Non-attendance data were frequently not captured. Service users are more deprived and vulnerable than the overall practice population. Feasibility and potential limitations of an evaluation – current data collection is limited in determining the effectiveness of the link worker social prescribing model; therefore, uniform data collection across sites is needed. Standardised outcomes and process measures are required. Cost–utility analysis could provide comparative values for assessment alongside other NHS interventions. Limitations This was a rapid systematic review that did not include a systematic quality assessment of studies. COVID-19 had an impact on the shape of the service. We were not able to examine the potential causal mechanisms in any detail. Conclusions We describe possible future research approaches to determine effectiveness and cost-effectiveness evaluations; all are limited in their application. (1) Evaluation using currently available, routinely collected health-care, costing and outcomes data. (2) Evaluative mixed-methods research to capture the complexity of social prescribing through understanding heterogeneous service delivery across comparative settings. Cost-effectiveness evaluation using routinely available costing and outcomes data to supplement qualitative data. (3) Interventional evaluative research, such as a cluster randomised controlled trial focused on the link worker model. Cost-effectiveness data collected as part of the trial. Future work Mature data are currently not available. There needs to be an agreement across schemes on the key outcomes that need to be measured, harmonisation of data collection, and follow-up referrals (how and when). Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 29. See the NIHR Journals Library website for further project information

    Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers

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    Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-gamma, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid-related orphan receptor gamma t (ROR gamma t), whereas ROR gamma t(lo) MAIT cells predominantly express T-bet and produce IFN-gamma. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from V alpha 19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease
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