113 research outputs found

    National Koala Disease Risk Analysis Report Appendices V1.2

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    These appendices comprise the methods and literature reviews that underpin the National Koala Disease Risk Analysis Report (KDRA). That document identifies the knowledge base, information gaps, risk assessments and critical control points for koala disease hazards. The national focus of the KDRA provides a clear, evidence-based assessment of koala disease which will be of value in evaluating disease risk at all regional levels and for koalas in all management situations (captive, rehabilitation and free-ranging). The KDRA is a key guiding document for actions to achieve a vision of ‚Äúsustainable, resilient and healthy populations of koalas, living in positive welfare within healthy ecosystems across their range‚ÄĚ

    National Koala Disease Risk Analysis Report V 1.2

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    The Koala Disease Risk Analysis (KDRA) identifies the knowledge base, information gaps, risk assessments and critical control points for koala disease hazards. The national focus of the KDRA provides a clear, evidence-based assessment of koala disease which will be of value in evaluating disease risk at all regional levels and for koalas in all management situations (captive, rehabilitation and free-ranging). The KDRA is a key guiding document for actions to achieve a vision of “sustainable, resilient and healthy populations of koalas, living in positive welfare within healthy ecosystems across their range

    Size and shape dependent photoluminescence and excited state decay rates of diamondoids

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    Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG gef√∂rderten) Allianz- bzw. Nationallizenz frei zug√§nglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.We present photoluminescence spectra and excited state decay rates of a series of diamondoids, which represent molecular structural analogues to hydrogen-passivated bulk diamond. Specific isomers of the five smallest diamondoids (adamantane‚Äďpentamantane) have been brought into the gas phase and irradiated with synchrotron radiation. All investigated compounds show intrinsic photoluminescence in the ultraviolet spectral region. The emission spectra exhibit pronounced vibrational fine structure which is analyzed using quantum chemical calculations. We show that the geometrical relaxation of the first excited state of adamantane, exhibiting Rydberg character, leads to the loss of Td symmetry. The luminescence of adamantane is attributed to a transition from the delocalized first excited state into different vibrational modes of the electronic ground state. Similar geometrical changes of the excited state structure have also been identified in the other investigated diamondoids. The excited state decay rates show a clear dependence on the size of the diamondoid, but are independent of the particle geometry, further indicating a loss of particle symmetry upon electronic excitation.DFG, FOR 1282, Controlling the electronic structure of semiconductor nanoparticles by doping and hybrid formatio

    Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions

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    TIE2-expressing monocytes/macrophages (TEM) are a highly proangiogenic subset of myeloid cells in tumors. Here, we show that circulating human TEMs are already preprogrammed in the circulation to be more angiogenic and express higher levels of such proangiogenic genes as matrix metalloproteinase-9 (MMP-9), VEGFA, COX-2, and WNT5A than TIE2(-) monocytes. Additionally, angiopoietin-2 (ANG-2) markedly enhanced the proangiogenic activity of TEMs and increased their expression of two proangiogenic enzymes: thymidine phosphorylase (TP) and cathepsin B (CTSB). Three "alternatively activated" (or M2-like) macrophage markers were also upregulated by ANG-2 in TEMs: interleukin-10, mannose receptor (MRC1), and CCL17. To investigate the effects of ANG-2 on the phenotype and function of TEMs in tumors, we used a double-transgenic (DT) mouse model in which ANG-2 was specifically overexpressed by endothelial cells. Syngeneic tumors grown in these ANG-2 DT mice were more vascularized and contained greater numbers of TEMs than those in wild-type (WT) mice. In both tumor types, expression of MMP-9 and MRC1 was mainly restricted to tumor TEMs rather than TIE2(-) macrophages. Furthermore, tumor TEMs expressed higher levels of MRC1, TP, and CTSB in ANG-2 DT tumors than WT tumors. Taken together, our data show that although circulating TEMs are innately proangiogenic, exposure to tumor-derived ANG-2 stimulates these cells to exhibit a broader, tumor-promoting phenotype. As such, the ANG-2-TEM axis may represent a new target for antiangiogenic cancer therapies

    First experience with a new negative pressure incision management system on surgical incisions after cardiac surgery in high risk patients

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    <p>Abstract</p> <p>Background</p> <p>Sternal wound infection remains a serious potential complication after cardiac surgery. A recent development for preventing wound complications after surgery is the adjunctive treatment of closed incisions with negative pressure wound therapy. Suggested mechanisms of preventive action are improving the local blood flow, removing fluids and components in these fluids, helping keep the incision edges together, protecting the wound from external contamination and promoting incision healing. This work reports on our initial evaluation and clinical experience with the Prevena‚ĄĘIncision Management System, a recently introduced new negative pressure wound therapy system specifically developed for treating closed surgical incisions and helping prevent potential complications. We evaluated the new treatment on sternal surgical incisions in patients with multiple co-morbidities and consequently a high risk for wound complications.</p> <p>Methods</p> <p>The Prevena‚ĄĘincision management system was used in 10 patients with a mean Fowler risk score of 15.1 [Range 8-30]. The negative pressure dressing was applied immediately after surgery and left in place for 5 days with a continuous application of -125 mmHg negative pressure. Wounds and surrounding skin were inspected immediately after removal of the Prevena‚ĄĘ incision management system and at day 30 after surgery.</p> <p>Results</p> <p>Wounds and surrounding skin showed complete wound healing with the absence of skin lesions due to the negative pressure after removal of the Prevena‚ĄĘ dressing. No device-related complications were observed. No wound complications occurred in this high risk group of patients until at least 30 days after surgery.</p> <p>Conclusions</p> <p>The Prevena‚ĄĘsystem appears to be safe, easy to use and may help achieve uncomplicated wound healing in patients at risk of developing wound complications after cardiothoracic surgery.</p

    Taking a hard line with biotemplating: cobalt-doped magnetite magnetic nanoparticle arrays.

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    Rapid advancements made in technology, and the drive towards miniaturisation, means that we require reliable, sustainable and cost effective methods of manufacturing a wide range of nanomaterials. In this bioinspired study, we take advantage of millions of years of evolution, and adapt a biomineralisation protein for surface patterning of biotemplated magnetic nanoparticles (MNPs). We employ soft-lithographic micro-contact printing to pattern a recombinant version of the biomineralisation protein Mms6 (derived from the magnetotactic bacterium Magnetospirillum magneticum AMB-1). The Mms6 attaches to gold surfaces via a cysteine residue introduced into the N-terminal region. The surface bound protein biotemplates highly uniform MNPs of magnetite onto patterned surfaces during an aqueous mineralisation reaction (with a mean diameter of 90 ¬Ī 15 nm). The simple addition of 6% cobalt to the mineralisation reaction maintains the uniformity in grain size (with a mean diameter of 84 ¬Ī 14 nm), and results in the production of MNPs with a much higher coercivity (increased from ‚Čą156 Oe to ‚Čą377 Oe). Biotemplating magnetic nanoparticles on patterned surfaces could form a novel, environmentally friendly route for the production of bit-patterned media, potentially the next generation of ultra-high density magnetic data storage devices. This is a simple method to fine-tune the magnetic hardness of the surface biotemplated MNPs, and could easily be adapted to biotemplate a wide range of different nanomaterials on surfaces to create a range of biologically templated devices

    Concurrent Oral 1 - Rheumatoid Arthritis: Treatment [OP4-OP9]: OP4. Inhibition of Radiographic Progression and Improvements in Physical Function at 2 Years, with Increasing Clinical Efficacy Over Time, in Rheumatoid Arthritis (Ra) Patients Treated with Tocilizumab (Tcz): The Lithe Study

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    Background: Patients with moderate to severe RA who remained on methotrexate (MTX) despite inadequate response were treated with TCZ in a double-blind, randomized, controlled phase 3 trial. Results of a 2-year planned analysis from this study are presented. Methods: Patients were randomized to treatment with TCZ 4‚ÄČmg/kg‚ÄČ+‚ÄČMTX (TCZ4), TCZ 8‚ÄČmg/kg‚ÄČ+‚ÄČMTX (TCZ8) or placebo‚ÄČ+‚ÄČMTX (CON) every 4 weeks. If patients failed to respond (‚ÄČ60% of patients and the DAS28 remission (DAS28 <‚ÄČ2.6) rate was 48% at week 52 and continued to increase to week 104. By week 52, patients treated with TCZ8 had clinically significant improvements in SJC that were maintained through week 104. Rates per 100 PY for adverse events (AEs) were higher in TCZ8 and TCZ4 (263.6, 275.4) vs CON patients (251.4) while rates for serious AEs were comparable (11.4, 12.1, 10.9, respectively). Rates per 100 PY of AEs leading to withdrawal (7.4, 32.5, 4.8) and treatment modification (8.4, 30.7, 20.4) were higher in TCZ8 and TCZ4 vs CON patients, respectively and death rates were comparable (0.6, 0.2, 0.4). Conclusions: Treatment with TCZ‚ÄČ+‚ÄČMTX inhibits radiographic progression over 2 years and improves physical function as shown by DAS28 remission, LDAS and low SJC, with a manageable safety profile. Disclosure statement: E.A., F. Hoffmann-La Roche - Employee. P.A., F. Hoffmann-La Roche - Employee. R.B.-V., F. Hoffmann-La Roche - Honoraria. R.F., Genentech - Research Funding, Honoraria. J.K., F. Hoffmann-La Roche - Research funding, Honorari

    Developing priority variables ("ecosystem Essential Ocean Variables" ‚ÄĒ eEOVs) for observing dynamics and change in Southern Ocean ecosystems

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    Reliable statements about variability and change in marine ecosystems and their underlying causes are needed to report on their status and to guide management. Here we use the Framework on Ocean Observing (FOO) to begin developing ecosystem Essential Ocean Variables (eEOVs) for the Southern Ocean Observing System (SOOS). An eEOV is a defined biological or ecological quantity, which is derived from field observations, and which contributes significantly to assessments of Southern Ocean ecosystems. Here, assessments are concerned with estimating status and trends in ecosystem properties, attribution of trends to causes, and predicting future trajectories. eEOVs should be feasible to collect at appropriate spatial and temporal scales and are useful to the extent that they contribute to direct estimation of trends and/or attribution, and/or development of ecological (statistical or simulation) models to support assessments. In this paper we outline the rationale, including establishing a set of criteria, for selecting eEOVs for the SOOS and develop a list of candidate eEOVs for further evaluation. Other than habitat variables, nine types of eEOVs for Southern Ocean taxa are identified within three classes: state (magnitude, genetic/species, size spectrum), predator‚Äďprey (diet, foraging range), and autecology (phenology, reproductive rate, individual growth rate, detritus). Most candidates for the suite of Southern Ocean taxa relate to state or diet. Candidate autecological eEOVs have not been developed other than for marine mammals and birds. We consider some of the spatial and temporal issues that will influence the adoption and use of eEOVs in an observing system in the Southern Ocean, noting that existing operations and platforms potentially provide coverage of the four main sectors of the region ‚ÄĒ the East and West Pacific, Atlantic and Indian. Lastly, we discuss the importance of simulation modelling in helping with the design of the observing system in the long term. Regional boundary: south of 30¬įS

    Generalised Anxiety Disorder ‚Äď A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression

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    Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS

    Using observational data to emulate a randomized trial of dynamic treatment switching strategies

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    BACKGROUND: When a clinical treatment fails or shows suboptimal results, the question of when to switch to another treatment arises. Treatment switching strategies are often dynamic because the time of switching depends on the evolution of an individual's time-varying covariates. Dynamic strategies can be directly compared in randomized trials. For example, HIV-infected individuals receiving antiretroviral therapy could be randomized to switching therapy within 90 days of HIV-1 RNA crossing above a threshold of either 400 copies/ml (tight-control strategy) or 1000 copies/ml (loose-control strategy).METHODS: We review an approach to emulate a randomized trial of dynamic switching strategies using observational data from the Antiretroviral Therapy Cohort Collaboration, the Centers for AIDS Research Network of Integrated Clinical Systems and the HIV-CAUSAL Collaboration. We estimated the comparative effect of tight-control vs. loose-control strategies on death and AIDS or death via inverse-probability weighting.RESULTS: Of 43 803 individuals who initiated an eligible antiretroviral therapy regimen in 2002 or later, 2001 met the baseline inclusion criteria for the mortality analysis and 1641 for the AIDS or death analysis. There were 21 deaths and 33 AIDS or death events in the tight-control group, and 28 deaths and 41 AIDS or death events in the loose-control group. Compared with tight control, the adjusted hazard ratios (95% confidence interval) for loose control were 1.10 (0.73, 1.66) for death, and 1.04 (0.86, 1.27) for AIDS or death.CONCLUSIONS: Although our effective sample sizes were small and our estimates imprecise, the described methodological approach can serve as an example for future analyses
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