54 research outputs found

    Putting It into Practice: Using Feminist Fractured Foundationalism in Researching Children in the Concentration Camps of the South African War

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    Feminist fractured foundationalism has been developed over a series of collaborative writings as a combined epistemology and methodology, although it has mainly been discussed in epistemological terms. It was operationalised as a methodology in a joint research project in South Africa concerned with investigating two important ways that the experiences of children in the South African War 1899-1902, in particular in the concentration camps established during its commando and 'scorched earth' phase, were represented contemporaneously: in the official records, and in photography. The details of the research and writing process involved are provided around discussion of the nine strategies that compose feminist fractured foundationalism and its strengths and limitations in methodological terms are reviewed.Feminist Fractured Foundationalism, Feminist Methodology, Feminist Epistemology, Feminist Sociology, South African War 1899-1902, Concentration Camps, Children, Retrievable Documents, Photographs

    The ESRC's 2010 Framework for Research Ethics: Fit for Research Purpose?

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    The ESRC\'s (2010) Framework for Research Ethics extends the remit of its 2005 research ethics framework in three significant ways: the system is to be fully mandatory and it will no longer possible to make the case that no out of the ordinary ethical issues arise; the Research Ethics Committees (RECs) set up under the ESRC\'s 2005 document have extended remit, including reviewing all research proposals accepted by the ESRC and other funding bodies; and funding will depend on the REC review, with its purview extending through a project\'s life. The 2010 document is reviewed in detail and the conclusion is drawn that it is not fit for purpose. Six wider issues raised by the FRE document are discussed: the consultation process by the ESRC was insufficient and the informed consent of the social science community was not obtained; the ethics creep involved will involve unnecessary bureaucratisation; the RECs will operate without expert discipline-specific knowledge using unethical generalist criteria; the overall effects long-term will be deleterious to the research base; the FRE document unacceptably ignores the professional associations and their research ethics guidelines; and the ESRC\'s system of the expert peer review of funding applications will be undermined.Framework for Research Ethics, ESRC, Research Ethics, Audit Creep

    The genetics of virus particle shape in equine influenza A virus

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    Background Many human strains of influenza A virus produce highly pleomorphic virus particles that at the extremes can be approximated as either spheres of around 100 nm diameter or filaments of similar cross-section but elongated to lengths of many microns. The role filamentous virions play in the virus life cycle remains enigmatic. Objectives/Methods Here, we set out to define the morphology and genetics of virus particle shape in equine influenza A virus, using reverse genetics and microscopy of infected cells. Results and Conclusions The majority of H3N8 strains tested were found to produce filamentous virions, as did the prototype H7N7 A/eq/Prague/56 strain. The exception was the prototype H3N8 isolate, A/eq/Miami/63. Reassortment of equine influenza virus M genes from filamentous and non-filamentous strains into the non-filamentous human virus A/PR/8/34 confirmed that segment 7 is a major determinant of particle shape. Sequence analysis identified three M1 amino acid polymorphisms plausibly associated with determining virion morphology, and the introduction of these changes into viruses confirmed the importance of two: S85N and N231D. However, while either change alone affected filament production, the greatest effect was seen when the polymorphisms were introduced in conjunction. Thus, influenza A viruses from equine hosts also produce filamentous virions, and the major genetic determinants are set by the M1 protein. However, the precise sequence determinants are different to those previously identified in human or porcine viruses

    Budding of filamentous and non-filamentous influenza A virus occurs via a VPS4 and VPS28-independent pathway

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    The mechanism of membrane scission during influenza A virus budding has been the subject of controversy. We confirm that influenza M1 binds VPS28, a subunit of the ESCRT-1 complex. However, confocal microscopy of infected cells showed no marked colocalisation between M1 and VPS28 or VPS4 ESCRT proteins, or relocalisation of the cellular proteins. Trafficking of HA and M1 appeared normal when endosomal sorting was impaired by expression of inactive VPS4. Overexpression of either isoform of VPS28 or wildtype or dominant negative VPS4 proteins did not alter production of filamentous virions. SiRNA depletion of endogenous VPS28 had no significant effect on influenza virus replication. Furthermore, cells expressing wildtype or dominant-negative VPS4 replicated filamentous and non-filamentous strains of influenza to similar titres, indicating that influenza release is VPS4-independent. Overall, we see no role for the ESCRT pathway in influenza virus budding and the significance of the M1-VPS28 interaction remains to be determined. (C) 2009 Elsevier Inc. All rights reserved

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

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    Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

    Workshop on Raising Data using the RDBES and TAF (WKRDBESRaiseTAF; outputs from 2022 meeting)

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    41 páginasThe Workshop on Raising Data using the RDBES and TAF (WKRDBES-Raise&TAF) met online (26–30 of September 2022) to evaluate the use of the Regional Database and Estimation System (RDBES) format to reproduce the 2022 InterCatch input and output, identifying a Transparent Assessment Framework (TAF) structure to organize the intermediate steps and to propose standardized output formats. The main outcomes of WKRDBES-Raise&TAF were: · RDBES provides sufficient support for current national estimation protocols. However, some minor issues were reported that hampered an exact reproduction of the estimates. Therefore, adaptations of the data model should not be excluded completely. · All the input to stock assessment that InterCatch currently provides, could be reproduced. The participants started from the current stock extracts that can be downloaded from InterCatch. · A workflow was proposed with a national TAF repository for each country, a stock estimation repository and a stock assessment repository. The intermediate output of those repositories will be stored in an ‘intermediate output database’ and depending on the user role, you will get access to the relevant stages in this workflow. · The following requirements for the standard output formats were defined: they cannot be more restrictive than the InterCatch input and output format; they should present measures of uncertainty and sample sizes (for national estimates) and should have a configurable domain definition (for national estimates). Despite those successful outcomes, the current plan for transition to an operational system was concluded to be too optimistic. WKRDBES-Raise&TAF therefore recommends to the Working Group on Governance of the Regional Database and Estimation System (WGRDBESGOV) to revise the roadmap and allow RDBES to be in a test phase also for 2023. WKRDBES-Raise&TAF felt the need to test the proposed workflow on a small scale and therefore recommends to the WGRDBESGOV to arrange a workshop where two stocks (pok.27.3a46 (Saithe (Pollachius virens) in Subareas 4, 6 and Division 3.a (North Sea, Rockall and West of Scotland, Skagerrak and Kattegat) and wit.27.3a47d (Witch (Glyptocephalus cynoglossus) in Subarea 4 and Divisions 3.a and 7.d (North Sea, Skagerrak and Kattegat, eastern English Channel)) will be set up to go through the whole flow.Peer reviewe
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