39 research outputs found

    Communities of practice: acknowledging vulnerability to improve resilience in healthcare teams.

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    The majority of healthcare professionals regularly witness fragility, suffering, pain and death in their professional lives. Such experiences may increase the risk of burnout and compassion fatigue, especially if they are without self-awareness and a healthy work environment. Acquiring a deeper understanding of vulnerability inherent to their professional work will be of crucial importance to face these risks. From a relational ethics perspective, the role of the team is critical in the development of professional values which can help to cope with the inherent vulnerability of healthcare professionals. The focus of this paper is the role of Communities of Practice as a source of resilience, since they can create a reflective space for recognising and sharing their experiences of vulnerability that arises as part of their work. This shared knowledge can be a source of strength while simultaneously increasing the confidence and resilience of the healthcare team

    Experimental application to a water delivery canal of a distributed MPC with stability constraints

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    In this work, a novel distributed MPC algorithm, denoted D-SIORHC, is applied to upstream local control of a pilot water delivery canal. The D-SIORHC algorithm is based on MPC control agents that incorporate stability constraints and communicate only with their adjacent neighbors in order to achieve a coordinated action. Experimental results that show the effect of the parameters configuring the local controllers are presented

    Human Genome-Wide RNAi Screen Identifies an Essential Role for Inositol Pyrophosphates in Type-I Interferon Response

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    The pattern recognition receptor RIG-I is critical for Type-I interferon production. However, the global regulation of RIG-I signaling is only partially understood. Using a human genome-wide RNAi-screen, we identified 226 novel regulatory proteins of RIG-I mediated interferon-β production. Furthermore, the screen identified a metabolic pathway that synthesizes the inositol pyrophosphate 1-IP7 as a previously unrecognized positive regulator of interferon production. Detailed genetic and biochemical experiments demonstrated that the kinase activities of IPPK, PPIP5K1 and PPIP5K2 (which convert IP5 to1-IP7) were critical for both interferon induction, and the control of cellular infection by Sendai and influenza A viruses. Conversely, ectopically expressed inositol pyrophosphate-hydrolases DIPPs attenuated interferon transcription. Mechanistic experiments in intact cells revealed that the expression of IPPK, PPIP5K1 and PPIP5K2 was needed for the phosphorylation and activation of IRF3, a transcription factor for interferon. The addition of purified individual inositol pyrophosphates to a cell free reconstituted RIG-I signaling assay further identified 1-IP7 as an essential component required for IRF3 activation. The inositol pyrophosphate may act by β-phosphoryl transfer, since its action was not recapitulated by a synthetic phosphonoacetate analogue of 1-IP7. This study thus identified several novel regulators of RIG-I, and a new role for inositol pyrophosphates in augmenting innate immune responses to viral infection that may have therapeutic applications

    Hepatitis C virus envelope glycoprotein E2: isolation and characterisation of a functional core domain

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    © 2010 Dr. Kathleen McCaffreyHepatitis C virus (HCV) is a major indicator of liver disease and over 200 million chronic infections are estimated worldwide. No vaccine is available and current treatments report limited efficacy. A strong neutralizing antibody response is a key determinant in clearance of acute HCV infection although often appears delayed as broadly neutralizing antibodies do not appear until after chronic infection is established. Recent studies suggest that HCV evades neutralization through the accumulation of immune escape variants within a highly variable, immunodominant sequence of the viral envelope glycoprotein E2. The E1 and E2 envelope glycoproteins are transmembrane proteins that are embedded in the viral membrane and mediate virus attachment and entry into liver cells. The E2 glycoprotein has been shown to interact with the cellular receptors scavenger receptor class B type 1 (SRB1) and CD81 during virus entry and is a major target for neutralizing antibodies. There is currently no high-resolution structure of the HCV E2 glycoprotein to further understand its mechanism of viral entry or immune evasion. However, a soluble E2 ectodomain fragment has been identified that can be efficiently secreted from cells and displays CD81 receptor-binding function. The E2 ectodomain has three discrete variable regions interspersed between conserved CD81-binding motifs: the immunodominant hypervariable region 1 (HVR1), hypervariable region 2 (HVR2) and the intergenotypic variable region (igVR). In this study, simultaneous substitution of these variable regions (VRs) with short, flexible linker motifs within diverse E2 ectodomain sequences was described with the retention of both native folding and CD81 binding function. This indicated that the E2 VRs are excluded from the functional core domain of the glycoprotein. The conserved E2 core domain, lacking all three VRs, was further shown to elicit higher titers of broadly neutralizing antibodies than the unmodified E2 ectodomain suggesting that the VRs occlude conserved neutralization-sensitive epitopes within the underlying core domain. The E2 VRs were demonstrated to modulate CD81 binding in a manner consistent with solvent-exposed structures and illustrated a potential mechanism by which the VRs could mediate immune evasion during acute infection. Therefore, the conserved E2 core domain was proposed to represent a novel and improved antigen for redirecting the immune response towards conserved, neutralization-sensitive epitopes within the E2 glycoprotein. Further biochemical and functional characterization of the E2 core domain is also presented towards optimization of this antigen as viable candidate for future vaccine trials

    Conventional Wisdoms of Woody Biomass Utilization

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    60 p.Despite efforts to increase biomass utilization, uncertainty exists regarding the characteristics necessary to stimulate biomass utilization, effectiveness of agency and local efforts, and the role of partnerships in building the types of capacity necessary to expedite biomass removal. The purpose of this study is to identify and assess utilization challenges in different parts of the United States. The information collected through case studies is used to address persistent conventional wisdoms to biomass utilization that may help land managers better accomplish project objectives through informed planning and implementation. It may also be used to illuminate particular barriers to biomass utilization that can be addressed through policy development at the local, state, or national level.In addition to the Joint Fire Science Program who funded this project, we thank the Ford Foundation, University of Oregon, and USDA Forest Service Northern Research Station for their generous contributions

    Characterizing Lessons Learned from Federal Biomass Removal Projects

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    The idea of offsetting the costs of wildfire hazardous fuels reduction treatments by selling the biomass removed is appealing. There are however challenges to biomass utilization that impedes progress. For instance, the lack of biomass processing capacity may impede progress in some regions, while in other regions an inconsistent supply of biomass available for wood products markets limits private investment. Despite efforts to increase biomass utilization, uncertainty exists of regarding the characteristics necessary to stimulate biomass utilization, effectiveness of agency and local efforts, and the role of partnerships in building the types of capacity necessary to expedite biomass removal. The purpose of this study is to identify and assess utilization challenges in different parts of the United States. The information collected through case studies is used to address persistent conventional wisdoms to biomass utilization that may help land managers better accomplish project objectives through informed planning and implementation. It may also be used to illuminate particular barriers to biomass utilization that can be addressed through policy development at the local, state, or national level. The specific project objectives were to: · Examine the local social and physical context in which biomass utilization strategies have developed in regions of the country with varied resources and wildfire risks; · Identify the types of utilization activities accomplished in each case, focusing on agency, industry, and community factors contributing to project accomplishment; · Characterize key challenges to biomass utilization experienced in each case and the strategies employed to overcome them and achieve local objectives; · Assess the roles of collaborative partnerships in facilitating hazardous fuel reduction planning, implementation, and capacity building for biomass utilization; and · Capture and share lessons about the approaches used to implement biomass remova

    Endosomal PrP Trafficking

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    First Report of Orchid Fleck Virus in Lilyturf (Liriope spicata) in Australia

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    Liriope spicata (Asparagaceae) is an evergreen ornamental plant commonly referred to as lilyturf, creeping liriope, monkey grass, or creeping lilyturf, and is widely grown as groundcover and for erosion control (Fantz 2008). In April 2015, lilyturf plants with bright yellow flecks on the leaves were observed in landscape plantings across the St. Lucia campus of the University of Queensland, Brisbane, Australia. These symptoms were reminiscent of those observed on leaves of orchid species infected by Orchid fleck virus (OFV) (Kubo et al. 2009). Symptomatic leaf samples were collected and analyzed in a JEM-1400 transmission electron microscope (JEOL Ltd., Tokyo, Japan). Leaf dips were prepared by breaking up symptomatic tissue in 1% ammonium molybdate, pH 7.0 negative stain and extracts were placed on nitrocellulose-coated copper grids. Digital micrographs were captured with an Orius digital camera (Gatan Inc., Pleasanton, CA). Typical nonenveloped, rhabdovirus-like, bacilliform particles measuring ∼45 × 95 nm were observed, similar to those of OFV from infected orchids (Kondo et al. 2006). Total RNA was extracted from symptomatic tissue using an RNeasy Plant Mini Kit (Qiagen) and subjected to RT-PCR using the Superscript III One Step RT-PCR System with Platinum Taq DNA Polymerase (Thermo Fisher) and OFV nucleoprotein (N) gene primers polydT/SP6 (5′-GATTTAGGTGACACTATAGTTTTTTTTTTTTTTTTT(A/G/C)-3′) and mN2 (5′-TGCAGGAATATAGCCGACATGTT-3′) (Blanchfield et al. 2001). Agarose gel electrophoresis showed a single amplicon of ∼800 bp, comparable to the OFV positive control. DNA from both the lilyturf (DAF Plant Virus Collection Accession No. 5216) and a cymbidium OFV control (Accession No. 703) amplicons were gel-purified and cloned into pGEM-T Easy vector (Promega, Madison, WI) and sequenced using dideoxynucleotide sequencing at the Australian Genome Research Facility (Brisbane, Australia). A GenBank BLASTx search of the lilyturf virus N gene sequence of 658 nt showed 100% match to the N protein sequence of an Australian OFV isolate (Genbank Accession No. AAK09392 and e-value 1e-143). The partial N gene nucleotide sequence of the lilyturf OFV isolate #5216 was 99% identical to the cymbidium OFV isolate. Both sequences have been deposited in GenBank with Accession Nos. KT947974 and KT947975, respectively. Based on the observed symptoms, particle morphology, N gene amplicon using OFV primers, and high sequence identity with other OFV sequences, we conclude that the lilyturf plants were infected with OFV. This is the first report of OFV infecting L. spicata. This alternative host may play a possible role in OFV spread to orchids or other ornamental species that are colonized by its Brevipalpus sp. mite vector
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