159 research outputs found

    PEArL: a systems approach to demonstrating authenticity in information systems design

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    The process of information systems (IS) design has been dominated by the demands inherent in providing a technical solution to a perceived problem or need. Engineering IS design methods applied in order to satisfy the problem situation tend to have a preoccupation with verifying specifications as being mathematically correct. Diffculties arise when the ideas underpinning verification are extended in an attempt to ‘prove’ the validity of a proposed design for an IS. A pure engineering approach does not facilitate a response to the subjective elements within social situations, which experience has shown to be essential in demonstrating the pertinence of new designs to those concerned. We suggest that, by applying interpretivist systems ideas, it is possible to support concerned individuals in reflecting upon crucial aspects of the inquiry, enabling those individuals to judge the relevance or ‘authenticity’ of the learning, according to their own values and beliefs. The elements of participants, engagement, authority, relationships and learning are suggested as being crucial. These make up the mnemonic PEArL, which is offered as an aide-mémoire for those concerned with IS design

    Structural characterisation of neutrophil glycans by ultra sensitive mass spectrometric glycomics methodology

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    Neutrophils are the most abundant white blood cells in humans and play a vital role in several aspects of the immune response. Numerous reports have implicated neutrophil glycosylation as an important factor in mediating these interactions. We report here the application of high sensitivity glycomics methodologies, including matrix assisted laser desorption ionisation (MALDI-TOF) and MALDI-TOF/TOF analyses, to the structural analysis of N- and O-linked carbohydrates released from two samples of neutrophils, prepared by two separate and geographically remote laboratories. The data produced demonstrates that the cells display a diverse range of sialylated and fucosylated complex glycans, with a high level of similarity between the two preparations

    Defining an International Standard Set of Outcome Measures for Patients With Hip or Knee Osteoarthritis: Consensus of the International Consortium for Health Outcomes Measurement Hip and Knee Osteoarthritis Working Group

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    Objective: To define a minimum Standard Set of outcome measures and case-mix factors for monitoring, comparing, and improving health care for patients with clinically diagnosed hip or knee osteoarthritis (OA), with a focus on defining the outcomes that matter most to patients. Methods: An international working group of patients, arthroplasty register experts, orthopedic surgeons, primary care physicians, rheumatologists, and physiotherapists representing 10 countries was assembled to review existing literature and practices for assessing outcomes of pharmacologic and nonpharmacologic OA therapies, including surgery. A series of 8 teleconferences, incorporating a modified Delphi process, were held to reach consensus. Results: The working group reached consensus on a concise set of outcome measures to evaluate patients’ joint pain, physical functioning, health-related quality of life, work status, mortality, reoperations, readmissions, and overall satisfaction with treatment result. To support analysis of these outcome measures, pertinent baseline characteristics and risk factor metrics were defined. Annual outcome measurement is recommended for all patients. Conclusion: We have defined a Standard Set of outcome measures for monitoring the care of people with clinically diagnosed hip or knee OA that is appropriate for use across all treatment and care settings. We believe this Standard Set provides meaningful, comparable, and easy to interpret measures ready to implement in clinics and/or registries globally. We view this set as an initial step that, when combined with cost data, will facilitate value-based health care improvements in the treatment of hip and knee OA

    Reclaiming the humanity in personality Disorder.

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    This paper provides a commentary upon the nursing care of individuals diagnosed with personality disorder and associated education courses. The discussion focuses upon recent policy trends in the UK as a point of departure. This policy discourse is critical of mainstream mental health services in previously operating to exclude such individuals. One of the consequences has been a recent growth in interest in relevant training courses, many of which devote significant attention to staff attitudes regarding this client group. Various previous researchers and commentators have remarked upon the implications for practice of a perceived negative attitude among care staff. We reflect upon our own anecdotal experience of developing and delivering new university-based courses for practitioners working in the field of personality disorder to offer a particular critique of the UK context, in which this policy, training, and practice is framed. Social constructionist theories are drawn on to offer insights into public and practitioner discourse and the possible effects on therapeutic relationships. The available discourse constructs individuals with a diagnosis of personality disorder as essentially different from other people. We argue that staff training and practice development initiatives are likely to be more successful if such discourse is challenged, and attempts are made in therapeutic encounters to recognize shared characteristics and positive attributes as much as perceived difference and negative attributes. We refer to this as a re-engagement with common humanity. Despite the singular national context, the discursive themes explored are not necessarily restricted to the UK

    Caenorhabditis elegans N-glycan Core β-galactoside Confers Sensitivity towards Nematotoxic Fungal Galectin CGL2

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    The physiological role of fungal galectins has remained elusive. Here, we show that feeding of a mushroom galectin, Coprinopsis cinerea CGL2, to Caenorhabditis elegans inhibited development and reproduction and ultimately resulted in killing of this nematode. The lack of toxicity of a carbohydrate-binding defective CGL2 variant and the resistance of a C. elegans mutant defective in GDP-fucose biosynthesis suggested that CGL2-mediated nematotoxicity depends on the interaction between the galectin and a fucose-containing glycoconjugate. A screen for CGL2-resistant worm mutants identified this glycoconjugate as a Galβ1,4Fucα1,6 modification of C. elegans N-glycan cores. Analysis of N-glycan structures in wild type and CGL2-resistant nematodes confirmed this finding and allowed the identification of a novel putative glycosyltransferase required for the biosynthesis of this glycoepitope. The X-ray crystal structure of a complex between CGL2 and the Galβ1,4Fucα1,6GlcNAc trisaccharide at 1.5 Å resolution revealed the biophysical basis for this interaction. Our results suggest that fungal galectins play a role in the defense of fungi against predators by binding to specific glycoconjugates of these organisms

    Cell-active Small Molecule Inhibitors of the DNA-damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG) : Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides

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    DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly­(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone <b>8a</b>, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives <b>33d</b> and <b>35d</b> were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure–activity relationships of these novel inhibitors

    Updated T2K measurements of muon neutrino and antineutrino disappearance using 1.5 x 10(21) protons on target

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    We report measurements by the T2K experiment of the parameters θ23\theta_{23} and Δm322\Delta m^{2}_{32} governing the disappearance of muon neutrinos and antineutrinos in the three flavor neutrino oscillation model. Utilizing the ability of the experiment to run with either a mainly neutrino or a mainly antineutrino beam, the parameters are measured separately for neutrinos and antineutrinos. Using 7.482×10207.482 \times 10^{20} POT in neutrino running mode and 7.471×10207.471 \times 10^{20} POT in antineutrino mode, T2K obtained, sin2(θ23)=0.510.07+0.08\sin^{2}(\theta_{23})=0.51^{+0.08}_{-0.07} and Δm322=2.530.13+0.15×103\Delta m^{2}_{32} = 2.53^{+0.15}_{-0.13} \times 10^{-3}eV2^{2}/c4^{4} for neutrinos, and sin2(θ23)=0.420.07+0.25\sin^{2}({\overline{\theta}}_{23})=0.42^{+0.25}_{-0.07} and Δm232=2.550.27+0.33×103{\Delta\overline{m}^2}_{32} = 2.55^{+0.33}_{-0.27} \times 10^{-3}eV2^{2}/c4^{4} for antineutrinos (assuming normal mass ordering). No significant differences between the values of the parameters describing the disappearance of muon neutrinos and antineutrinos were observed.Comment: 8 pages, 2 figure

    Measurement of ¯νμ and νμ charged current inclusive cross sections and their ratio with the T2K off-axis near detector

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    We report a measurement of cross section σ(νμ+nucleus→μ−+X) and the first measurements of the cross section σ(¯νμ+nucleus→μ++X) and their ratio R(σ(¯ν)σ(ν)) at (anti) neutrino energies below 1.5 GeV. We determine the single momentum bin cross section measurements, averaged over the T2K ¯ν/ν-flux, for the detector target material (mainly carbon, oxygen, hydrogen and copper) with phase space restricted laboratory frame kinematics of θμ500  MeV/c. The results are σ(¯ν)=(0.900±0.029(stat)±0.088(syst))×10−39 and σ(ν)=(2.41±0.022(stat)±0.231(syst))×10−39 in units of cm2/nucleon and R(σ(¯ν)σ(ν))=0.373±0.012(stat)±0.015(syst)

    The epitaxy of gold

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    Race, psychopathy and subjectivity

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