52 research outputs found

    Indigenous governance bibliography

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    AIATSIS has compiled this bibliography on Indigenous governance as part of its Indigenous Governance Building: Mapping current and future research and practical resource needs project. It is to be read in conjunction with an AIATSIS bibliography on free, prior and informed consent, engagement and consultation, and other bibliographies relating to various aspects of Indigenous governance which have been included in the following pages and are also available via the project webpage linked above. The term ‘governance’ is wide reaching and it has not been possible to cover all Indigenous governance related topics comprehensively. Within the context of this project governance is broadly defined as a cultural construct where the principles and standards of what constitutes ‘good’, ‘good enough’, ‘strong’, ‘legitimate’, ‘ineffective’, ‘corrupt’ or ‘bad’ governance are informed by culturally-based values, traditions and ideologies; and vary significantly between different societies. There is no end-point goal of ‘perfect’ governance that will eventually be achieved in the future. Rather, governance is adaptive according to context and circumstances. This means it may swing between effectiveness and dysfunction. It is to be found as much in people’s daily self-determined practices, processes and relationships, as it is in visible structures and formal institutions

    Managing clinical uncertainty: an ethnographic study of the impact of critical care outreach on end‐of‐life transitions in ward‐based critically ill patients with a life‐limiting illness

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    © 2018 Crown copyright. Journal of Clinical Nursing © 2018 John Wiley & Sons LtdRapid response teams, such as critical care outreach teams, have prominent roles in managing end-of-life transitions in critical illness, often questioning appropriateness of treatment escalation. Clinical uncertainty presents clinicians with dilemmas in how and when to escalate or de-escalate treatment. Aims and objectives: To explore how critical care outreach team decision-making processes affect the management of transition points for critically ill, ward-based patients with a life-limiting illness. Methods: An ethnographic study across two hospitals observed transition points and decisions to de-escalate treatment, through the lens of critical care outreach. In-depth interviews were carried out to elucidate rationales for practices witnessed in observations. Detailed field notes were taken and placed in a descriptive account. Ethnographic data were analysed, categorised and organised into themes using thematic analysis. Findings: Data were collected over 74 weeks, encompassing 32 observation periods with 20 staff, totalling more than 150 hr. Ten formal staff interviews and 20 informal staff interviews were undertaken. Three main themes emerged: early decision-making and the role of critical care outreach; communicating end-of-life transitions; end-of-life care and the input of critical care outreach. Findings suggest there is a negotiation to achieve smooth transitions for individual patients, between critical care outreach, and parent or ward medical teams. This process of negotiation is subject to many factors that either hinder or facilitate timely transitions. Conclusions: Critical care outreach teams have an important role in shared decision-making. Associated emotional costs relate to conflict with parent medical teams, and working as lone practitioners. The cultural contexts in which teams work have a significant effect on their interactions and agency. Relevance to practice: There needs to be a cultural shift towards early and open discussion of treatment goals and limitations of medical treatment, particularly when facing serious illness. With training and competencies, outreach nurses are well placed to facilitate these discussions.Peer reviewe

    The Novel Application of Geometric Morphometrics with Principal Component Analysis to Existing G Protein-Coupled Receptor (GPCR) Structures

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    The G protein-coupled receptor (GPCR) superfamily is a large group of membrane proteins which, because of their vast involvement in cell signalling pathways, are implicated in a plethora of disease states and are therefore considered to be key drug targets. Despite advances in techniques to study these receptors, current prophylaxis is often limited due to the challenging nature of their dynamic, complex structures. Greater knowledge and understanding of their intricate structural rearrangements will therefore undoubtedly aid structure-based drug design against GPCRs. Disciplines such as anthropology and palaeontology often use geometric morphometrics to measure variation between shapes and we have therefore applied this technique to analyse GPCR structures in a three-dimensional manner, using principal component analysis. Our aim was to create a novel system able to discriminate between GPCR structures and discover variation between them, correlated with a variety of receptor characteristics. This was conducted by assessing shape changes at the extra- and intracellular faces of the transmembrane helix bundle, analysing the XYZ coordinates of the amino acids at those positions. We have demonstrated that GPCR structures can be classified based on characteristics such as activation state, bound ligands and fusion proteins, with the most significant results focussed at the intracellular face. Conversely, our analyses provide evidence that thermostabilising mutations do not cause significant differences when compared to non-mutated GPCRs. We believe that this is the first time geometric morphometrics has been applied to membrane proteins on this scale, and believe it can be used as a future tool in sense-checking newly resolved structures and planning experimental design

    Master of Pharmacy students’ knowledge and awareness of antibiotic use, resistance and stewardship

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    Background. Antibiotic resistance has become a global public health concern. In this study we investigated the knowledge and awareness of antibiotic use, resistance and stewardship, held by the pharmacy students currently studying at the University of Brighton.Study design. This was a cross-sectional, online survey, and email invitations to participate were sent to all students attending our Master of Pharmacy (MPharm) course (n = 583). Students’ knowledge was assessed with 29 items; responses for these were totaled before comparison among students.Comparison of scores between groups of students was performed using the Kruskal-Wallis or the MannWhitney test, as appropriate.Results. The response rate was 32%. The overall median knowledge score was 7.9. There was a statistically significant difference in knowledge scores between years of study (p = 0.02), particularly between year of study 1 (7.6) and 4 (8.3). A statistically significant difference was found between the knowledge scores of male (8.4) and female (7.9) students (p = 0.03). Most students believed a strong knowledge of antibiotics, and microbiology and infection control is important for their pharmacy careers and more than 90% agreed that antibiotic resistance will be a greater clinical problem in thefuture.Conclusions. Although the MPharm students studied achieved good overall knowledge scores, a significant proportion showed a lack of understanding with regards to some important aspects of antibiotic resistance mechanisms, factors promoting the emergence and spread of antibioticresistance, and antibiotic stewardship policies

    Conditional Conservatism and Labor Investment Efficiency

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    Prior literature documents that asymmetric timely recognition of losses versus gains (also known as conditional conservatism) can induce management to make more efficient investment decisions by mitigating information asymmetry between management and investors and providing early signals about the profitability of projects undertaken. In this paper, we investigate the impact of conservatism on an important investment decision that has been overlooked, namely investment in labor. We find that conservatism is negatively associated with labor investment inefficiency; more specifically, conservatism reduces inefficiency investment practices on the labor market, including over-hiring, under-firing, under-hiring, and over-firing. Our results hold after controlling for managerial ability, corporate governance and other investments

    A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection

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    The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734–736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo

    Impairment of circulating endothelial progenitors in Down syndrome

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    <p>Abstract</p> <p>Background</p> <p>Pathological angiogenesis represents a critical issue in the progression of many diseases. Down syndrome is postulated to be a systemic anti-angiogenesis disease model, possibly due to increased expression of anti-angiogenic regulators on chromosome 21. The aim of our study was to elucidate some features of circulating endothelial progenitor cells in the context of this syndrome.</p> <p>Methods</p> <p>Circulating endothelial progenitors of Down syndrome affected individuals were isolated, <it>in vitro </it>cultured and analyzed by confocal and transmission electron microscopy. ELISA was performed to measure SDF-1α plasma levels in Down syndrome and euploid individuals. Moreover, qRT-PCR was used to quantify expression levels of <it>CXCL12 </it>gene and of its receptor in progenitor cells. The functional impairment of Down progenitors was evaluated through their susceptibility to hydroperoxide-induced oxidative stress with BODIPY assay and the major vulnerability to the infection with human pathogens. The differential expression of crucial genes in Down progenitor cells was evaluated by microarray analysis.</p> <p>Results</p> <p>We detected a marked decrease of progenitors' number in young Down individuals compared to euploid, cell size increase and some major detrimental morphological changes. Moreover, Down syndrome patients also exhibited decreased SDF-1α plasma levels and their progenitors had a reduced expression of SDF-1α encoding gene and of its membrane receptor. We further demonstrated that their progenitor cells are more susceptible to hydroperoxide-induced oxidative stress and infection with Bartonella henselae. Further, we observed that most of the differentially expressed genes belong to angiogenesis, immune response and inflammation pathways, and that infected progenitors with trisomy 21 have a more pronounced perturbation of immune response genes than infected euploid cells.</p> <p>Conclusions</p> <p>Our data provide evidences for a reduced number and altered morphology of endothelial progenitor cells in Down syndrome, also showing the higher susceptibility to oxidative stress and to pathogen infection compared to euploid cells, thereby confirming the angiogenesis and immune response deficit observed in Down syndrome individuals.</p

    Multi-messenger observations of a binary neutron star merger

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    On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

    Ocular indicators of Alzheimer’s: exploring disease in the retina

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