136 research outputs found

    Critical perspectives on ‘consumer involvement’ in health research: epistemological dissonance and the know-do gap

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    Researchers in the area of health and social care (both in Australia and internationally) are encouraged to involve consumers throughout the research process, often on ethical, political and methodological grounds, or simply as ‘good practice’. This paper presents findings from a qualitative study in the UK of researchers’ experiences and views of consumer involvement in health research. Two main themes are presented in the paper. Firstly, we explore the ‘know-do gap’ which relates to the tensions between researchers’ perceptions of the potential benefits of, and their actual practices in relation to, consumer involvement. Secondly, we focus on one of the reasons for this ‘know-do gap’, namely epistemological dissonance. Findings are linked to issues around consumerism in research, lay/professional knowledges, the (re)production of professional and consumer identities and the maintenance of boundaries between consumers and researchers

    Protein tyrosine phosphatase PTPN22 regulates LFA-1 dependent Th1 responses

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    A missense C1858T single nucleotide polymorphism within PTPN22 is a strong genetic risk factor for the development of multiple autoimmune diseases. PTPN22 encodes a protein tyrosine phosphatase that negatively regulates immuno-receptor proximal Src and Syk family kinases. Notably, PTPN22 negatively regulates kinases downstream of T-cell receptor (TCR) and LFA-1, thereby setting thresholds for T-cell activation. Alterations to the quality of TCR and LFA-1 engagement at the immune synapse and the regulation of downstream signals can have profound effects on the type of effector T-cell response induced. Here we describe how IFNγ+ Th1 responses are potentiated in Ptpn22−/− T-cells and in T-cells from mice expressing Ptpn22R619W (the mouse orthologue of the human genetic variant) as they age, or following repeated immune challenge, and explore the mechanisms contributing to the expansion of Th1 cells. Specifically, we uncover two LFA-1-ICAM dependent mechanisms; one T-cell intrinsic, and one T-cell extrinsic. Firstly, we found that in vitro anti-CD3/LFA-1 induced Th1 responses were enhanced in Ptpn22−/− T-cells compared to WT, whereas anti-CD3/anti-CD28 induced IFNy responses were similar. These data were associated with an enhanced ability of Ptpn22−/− T-cells to engage ICAM-1 at the immune synapse when incubated on planar lipid bilayers, and to form conjugates with dendritic cells. Secondly, we observed a T-cell extrinsic mechanism whereby repeated stimulation of WT OT-II T-cells with LPS and OVA323-339 pulsed Ptpn22−/− bone marrow derived dendritic cells (BMDCs) was sufficient to enhance Th1 cell development compared to WT BMDCs. Furthermore, this response could be reversed by LFA-1 blockade. Our data point to two related but distinct mechanisms by which PTPN22 regulates LFA-1 dependent signals to enhance Th1 development, highlighting how perturbations to PTPN22 function over time to regulate the balance of the immune response

    CONTRA: copy number analysis for targeted resequencing

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    Motivation: In light of the increasing adoption of targeted resequencing (TR) as a cost-effective strategy to identify disease-causing variants, a robust method for copy number variation (CNV) analysis is needed to maximize the value of this promising technology

    Formation of a conceptual framework during the development of a patient-reported outcome measure for early gastrointestinal recovery: Phase I of the PRO-diGi study

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    Aim: Patients admitted to hospital for abdominal surgery often experience gastrointestinal dysfunction. Many studies have reported outcomes following gastrointestinal dysfunction, yet there is no unified definition of recovery or a validated patient-reported outcome measure (PROM). The first stage of PROM development requires formation of a conceptual framework to identify key themes to patients. The aim of this study was to utilize semistructured interviews to identify core themes and concepts relevant to patients to facilitate development of a conceptual framework. Method: Adult patients admitted to hospital for major gastrointestinal, urological or gynaecological surgery, in an emergency or elective setting, were eligible to participate. Patients treated nonoperatively for small bowel obstruction were also eligible. Interviews were conducted by telephone, audio-recorded, transcribed, coded and analysed using NVivo software by two researchers and reviewed by lay members of the steering group. Interviews continued until data saturation was reached. Ethical approval was gained prior to interviews (21/WA/0231). Results: Twenty nine interviews were completed (17 men, median age 64 years) across three specialties (20 gastrointestinal, six gynaecological, three urological). Two overarching themes of ‘general recovery’ and ‘gastrointestinal symptoms’ were identified. General recovery included three themes: ‘life impact’, ‘mental impact’, including anxiety, and ‘physical impact’, including fatigue. Gastrointestinal symptoms included three themes: ‘abdominal symptoms’ such as pain, ‘diet and appetite’ and ‘expulsory function’, such as stool frequency. A total of 18 gastrointestinal symptoms were identified during patient recovery—many of which lasted several weeks following discharge. Conclusion: This study reports a range of gastrointestinal and nongastrointestinal symptoms experienced by patients during early gastrointestinal recovery. Identified symptoms have been synthesized into a conceptual framework to enable development of a definitive PROM for early gastrointestinal recovery

    Biodiverse perennial meadows have aesthetic value and increase residents’ perceptions of site quality in urban green-space

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    We used photo-elicitation studies and a controlled perennial meadow creation experiment at ten urban green-spaces in southern England (five experimental sites and five control sites) to assess green-space visitors’ responses to urban meadows. Multiple meadows, which varied in their structural diversity (height) and plant species richness, were created at each experimental site. Photo elicitation demonstrated that meadows were generally preferred to herbaceous borders and formal bedding planting. Moreover, our experimental meadows had higher preference scores than a treatment that replicated mown amenity grassland, and meadow creation improved site quality and appreciation across a wide range of people. Meadows that contained more plant species and some structural diversity (i.e. were tall or of medium height) were most preferred. The magnitude of these preferences was lower amongst people that used the sites the most, probably due to a strong attachment to the site, i.e. sense of place. People with greater eco-centricity (i.e. those who used the countryside more frequently, had greater ability to identify plant species and exhibited more support for conservation) responded more positively to meadow vegetation. Crucially a wide range of respondents was willing to tolerate the appearance of meadows outside the flowering season, especially when provided with information on their biodiversity and aesthetic benefits and potential cost savings (from reduced cutting frequencies). Re-designing urban green-spaces and parks through the creation of species rich meadows can provide a win–win strategy for biodiversity and people, and potentially improve connections between the two

    Painting the Nation:Examining the Intersection Between Politics and the Visual Arts Market in Emerging Economies

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    Politics and art have throughout history, intersected in diverse and complex ways. Ideologies and political systems have used the arts to create a certain image and, depending on the form of government this has varied from clear-cut state propaganda, to patronage, to more indirect arms-length funding procedures. Therefore, artists working within the macro-level socio-political context cannot help but be influenced, inspired and sometimes restricted by these policies and political influences. This article examines the contemporary art markets of two emerging, Socialist economies to investigate the relationship between state pol-itics and the contemporary visual arts market. We argue that the respective governments and art worlds are trying to construct a brand narrative for their nations, but that these discourses are often at cross-purposes. In doing so, we illustrate that it is impos-sible to separate a consideration of the artwork from the macro-level context in which it is produced, distributed, and consumed

    The Iso2k Database: A global compilation of paleo-δ18O and δ2H records to aid understanding of Common Era climate

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    Reconstructions of global hydroclimate during the Common Era (CE; the past ~ 2000 years) are important for providing context for current and future global environmental change. Stable isotope ratios in water are quantitative indicators of hydroclimate on regional to global scales, and these signals are encoded in a wide range of natural geologic archives. Here we present the Iso2k database, a global compilation of previously published datasets from a variety of natural archives that record the stable oxygen (δ18O) or hydrogen (δ2H) isotopic composition of environmental waters, which reflect hydroclimate changes over the CE. The Iso2k database contains 756 isotope records from the terrestrial and marine realms, including: glacier and ground ice (205); speleothems (68); corals, sclerosponges, and mollusks (145); wood (81); lake sediments and other terrestrial sediments (e.g., loess) (158); and marine sediments (99). Individual datasets have temporal resolutions ranging from sub-annual to centennial, and include chronological data where available. A fundamental feature of the database is its comprehensive metadata, which will assist both experts and non-experts in the interpretation of each record and in data synthesis. Key metadata fields have standardized vocabularies to facilitate comparisons across diverse archives and with climate model simulated fields. This is the first global-scale collection of water isotope proxy records from multiple types of geological and biological archives. It is suitable for evaluating hydroclimate processes through time and space using large-scale synthesis, model-data intercomparison and (paleo)data assimilation. The Iso2k database is available for download at: https://doi.org/10.6084/m9.figshare.11553162 (McKay and Konecky, 2020)

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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