500 research outputs found

    2002 Philip C. Jessup International Moot Court Competition

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    The Republic of Turingia and the Republic of Babbage have brought their case before this Court by notification of the Special Agreement as provided for by Article 40(1) of the Statute of the International Court of Justice

    Debridement for periprosthetic joint infections: future therapies

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    Darwin, the devil, and the management of transmissible cancers

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    Modern conservation science frequently relies on genetic tools to manage imperiled populations threatened by processes such as habitat fragmentation and infectious diseases. Translocation of individuals to restore genetic diversity (genetic rescue) is increasingly used to manage vulnerable populations, but it can swamp local adaptations and lead to outbreeding depression. Thus, genetic management is context dependent and needs evaluation across multiple generations . Genomic studies can help evaluate the extent to which populations are locally adapted to assess the costs and benefits of translocations. Predicting the long‐term fitness effects of genetic interventions and their evolutionary consequences is a vital step in managing dwindling populations threatened by emerging infectious diseases

    Regulation of cardiac ryanodine receptor function by the cyclic-GMP dependent protein kinase G

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    Background: The cGMP-dependent protein kinase G (PKG) phosphorylates the cardiac ryanodine receptor (RyR2) in vitro. We aimed to determine whether modulation of endogenous PKG alters RyR2-mediated spontaneous Ca2+ release and whether this effect is linked to a change in RyR2 phosphorylation. Methods: & Results: Human embryonic kidney (HEK293) cells with inducible RyR2 expression were treated with the cGMP analogue 8-Br-cGMP (100 μM) to activate endogenous PKG. In cells transfected with luminal Ca2+ sensor, D1ER, PKG activation significantly reduced the threshold for RyR2-mediated spontaneous Ca2+ release (93.9 ± 0.4% of store size with vehicle vs. 91.7 ± 0.8% with 8-Br-cGMP, P = 0.04). Mutation of the proposed PKG phosphorylation sites, S2808 and S2030, either individually or as a combination, prevented the decrease in Ca2+ release threshold induced by endogenous PKG activation. Interestingly, despite a functional dependence on expression of RyR2 phosphorylation sites, 8-Br-cGMP activation of PKG did not promote a detectable change in S2808 phosphorylation (P = 0.9). Paradoxically, pharmacological inhibition of PKG with KT 5823 (1 μM) also reduced the threshold for spontaneous Ca2+ release through RyR2 without affecting S2808 phosphorylation. Silencing RNA knockdown of endogenous PKG expression also had no quantifiable effect on RyR2 S2808 phosphorylation (P = 0.9). However, unlike PKG inhibition with KT 5823, PKG knockdown did not alter spontaneous Ca2+ release propensity or luminal Ca2+ handling. Conclusion: In an intact cell model, activation of endogenous PKG reduces the threshold for RyR2-mediated spontaneous Ca2+ release in a manner dependent on the RyR2 phosphorylation sites S2808 and S2030. This study clarifies the regulation of RyR2 Ca2+ release by endogenous PKG and functionally implicates the role of RyR2 phosphorylation.Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. University of Otago; Nueva ZelandaFil: Aitken Buck, Hamish M.. University of Otago; Nueva ZelandaFil: Chakraborty, Akash D.. University of Otago; Nueva ZelandaFil: Worthington, Luke P. I.. University of Otago; Nueva ZelandaFil: Cully, Tanya R.. University of Otago; Nueva ZelandaFil: Lamberts, Regis R.. University of Otago; Nueva ZelandaFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Jones, Peter P.. University of Otago; Nueva Zeland

    Benefits outweigh the risks: a consensus statement on the risks of physical activity for people living with long-term conditions

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    Introduction The benefits of physical activity for people living with long-term conditions (LTCs) are well established. However, the risks of physical activity are less well documented. The fear of exacerbating symptoms and causing adverse events is a persuasive barrier to physical activity in this population. This work aimed to agree clear statements for use by healthcare professionals about medical risks of physical activity for people living with LTCs through expert consensus. These statements addressed the following questions: (1) Is increasing physical activity safe for people living with one or more LTC? (2) Are the symptoms and clinical syndromes associated with common LTCs aggravated in the short or long term by increasing physical activity levels? (3) What specific risks should healthcare professionals consider when advising symptomatic people with one or more LTCs to increase their physical activity levels? Methods Statements were developed in a multistage process, guided by the Appraisal of Guidelines for Research and Evaluation tool. A patient and clinician involvement process, a rapid literature review and a steering group workshop informed the development of draft symptom and syndrome-based statements. We then tested and refined the draft statements and supporting evidence using a three-stage modified online Delphi study, incorporating a multidisciplinary expert panel with a broad range of clinical specialties. Results Twenty-eight experts completed the Delphi process. All statements achieved consensus with a final agreement between 88.5%–96.5%. Five ‘impact statements’ conclude that (1) for people living with LTCs, the benefits of physical activity far outweigh the risks, (2) despite the risks being very low, perceived risk is high, (3) person-centred conversations are essential for addressing perceived risk, (4) everybody has their own starting point and (5) people should stop and seek medical attention if they experience a dramatic increase in symptoms. In addition, eight symptom/syndrome-based statements discuss specific risks for musculoskeletal pain, fatigue, shortness of breath, cardiac chest pain, palpitations, dysglycaemia, cognitive impairment and falls and frailty. Conclusion Clear, consistent messaging on risk across healthcare will improve people living with LTCs confidence to be physically active. Addressing the fear of adverse events on an individual level will help healthcare professionals affect meaningful behavioural change in day-to-day practice. Evidence does not support routine preparticipation medical clearance for people with stable LTCs if they build up gradually from their current level. The need for medical guidance, as opposed to clearance, should be determined by individuals with specific concerns about active symptoms. As part of a system-wide approach, consistent messaging from healthcare professionals around risk will also help reduce cross-sector barriers to engagement for this population.Output Status: Forthcoming/Available Onlin

    Broadening environmental governance ontologies to enhance ecosystem-based management in Aotearoa New Zealand

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    Ecosystem-based management (EBM) is a holistic approach to managing marine environments that can potentially reconcile cross-sectoral conflicts, scale mismatches, and fulfil sustainability objectives. In Aotearoa New Zealand (Aotearoa NZ), the operationalisation of EBM has been uneven; however, a set of principles to guide EBM in Aotearoa NZ provides a useful foundation to enable and enhance its uptake and to support governance approaches that attend to the rights, values, interests, and knowledges of Māori, the Indigenous peoples of Aotearoa. In acknowledging the need to give attention to the governance of marine environments, we apply insights from the ‘relational turn’ in social sciences and sustainability science to explore the ontological and epistemological broadening of ‘governance’ to identify opportunities for alternative forms of governance that accommodate Indigenous ways of knowing. We propose four pou (or enabling conditions) that generate alternatives to governance models underpinned by a ‘modernist’ (dualistic, technocratic) ontology: (i) enacting interactive administrative arrangements; (ii) diversifying knowledge production; (iii) prioritising equity, justice, and social difference; and (iv) recognising interconnections and interconnectedness. Our analysis of seven governance examples exposes evidence of radical and progressive transformations occurring within Aotearoa NZ regarding conceptions of the environment and the role of people in it that could support the wider uptake of EBM. Rather than advocating a ‘perfect model’ of governance for EBM, we find potential in EBM as a strategic approach to managing marine environments because of the synergies with Indigenous and relational ontologies, which lie in the emphasis on interconnectedness, inclusivity, diversity, and relationality
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