808 research outputs found

    Emergency healthcare of the future

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    Emergency healthcare is a high profile component of modern healthcare systems, which over the past three decades has fundamentally transformed in many countries. However, despite this rapid development, and associated investments in service standards, there is a high level of concern with the performance of emergency health services relating principally to system wide congestion. The factors driving this problem are complex but relate largely to the combined impact of growing demand, expanded scope of care and blocked access to inpatient beds. These factors are unlikely to disappear in the medium term despite the National Emergency Access Target. The aim of this article is to stimulate a conversation about the future design and functioning of emergency healthcare systems; examining what we understand about the problem and proposing a rationale that may underpin future strategic approaches. This is also an invitation to join the conversation

    Digital Rights in Asia: Rethinking Regional and International Agenda

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    In this chapter we explore the appropriate conception and agenda for digital rights and associated governance in Asia. We do so from the perspective of an Australian location in the Asian region, and informed by interdisciplinary research on digital rights. Our starting point is a dissatisfaction with the framing, assumptions, and norms of digital rights globally. At the risk of simplification, we will argue that the dominant ways of framing digital rights and governance continue to be modelled on a limited repertoire of Western experiences and concepts of digital technology, rights, and freedom. digital rights are often left off the agenda in the discussion of digital transformations, especially the highly visible, mainstream, official, and authorized discussions. Such theoretical, empirical, comparative, and cross-sectoral work is urgently needed, not least because questions of digital rights and governance are moving beyond earlier, if still pressing issues of freedom of expression to a wider range of privacy, data justice, labour rights, communication rights, governance, and democratization issues, posed by the new platforms (such as sharing and caring economy). Not only are such new Asian and inter-Asia theorisations and practices of rights and governance important in this region (especially for countries such as Australia), but they stand to help us rethink and confront the impasses and political and conceptual problems with dominant global digital rights thinking. In turn, this project of reimagining and mainstreaming digital rights conceptions, practices, and norms makes a powerful contribution to advancing key issues and challenges arising in contemporary Asia. The expansion of digital transactions across Asia requires more comprehensive and considered rights frameworks to guarantee social justice, citizenship and political participation, as well the economic benefits of the many initiatives underway. Otherwise the danger is that digital transformations can hinder rather than advance social progress.University of Sydney Sydney Research Excellence Initiativ

    Impact of sub-inhibitory antibiotics on fibronectin-mediated host cell adhesion and invasion by Staphylococcus aureus

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    <p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>is a well-armed pathogen prevalent in severe infections such as endocarditis and osteomyelitis. Fibronectin-binding proteins A and B, encoded by <it>fnb</it>A/B, are major pathogenesis determinants in these infections through their involvement in <it>S. aureus </it>adhesion to and invasion of host cells. Sub-minimum inhibitory concentrations (sub-MICs) of antibiotics, frequently occurring <it>in vivo </it>because of impaired drug diffusion at the infection site, can alter <it>S. aureus </it>phenotype. We therefore investigated their impact on <it>S. aureus </it>fibronectin-mediated adhesiveness and invasiveness.</p> <p>Methods</p> <p>After <it>in vitro </it>challenge of <it>S. aureus </it>8325-4 and clinical isolates with sub-MICs of major anti-staphylococcal agents, we explored <it>fnb</it>A/B transcription levels, bacterial adhesiveness to immobilised human fibronectin and human osteoblasts in culture, and bacterial invasion of human osteoblasts.</p> <p>Results</p> <p>Oxacillin, moxifloxacin and linezolid led to the development of a hyper-adhesive phenotype in the fibronectin adhesion assay that was consistent with an increase in <it>fnb</it>A/B transcription. Conversely, rifampin treatment decreased fibronectin binding in all strains tested without affecting <it>fnb</it>A/B transcription. Gentamicin and vancomycin had no impact on fibronectin binding or <it>fnb</it>A/B transcription levels. Only oxacillin-treated <it>S. aureus </it>displayed a significantly increased adhesion to cultured osteoblasts, but its invasiveness did not differ from that of untreated controls.</p> <p>Conclusion</p> <p>Our findings demonstrate that several antibiotics at sub-MICs modulate fibronectin binding in <it>S. aureus </it>in a drug-specific fashion. However, hyper- and hypo- adhesive phenotypes observed in controlled <it>in vitro </it>conditions were not fully confirmed in whole cell infection assays. The relevance of adhesion modulation during <it>in vivo </it>infections is thus still uncertain and requires further investigations.</p

    Development of chemical proteomics for the folateome and analysis of the kinetoplastid folateome

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    The folate pathway has been extensively studied in a number of organisms, with its essentiality exploited by a number of drugs. However, there has been little success in developing drugs that target folate metabolism in the kinetoplastids. Despite compounds being identified which show significant inhibition of the parasite enzymes, this activity does not translate well into cellular and animal models of disease. Understanding to which enzymes antifolates bind under physiological conditions and how this corresponds to the phenotypic response could provide insight on how to target the folate pathway in these organisms. To facilitate this, we have adopted a chemical proteomics approach to study binding of compounds to enzymes of folate metabolism. Clinical and literature antifolate compounds were immobilized onto resins to allow for “pull down” of the proteins in the “folateome”. Using competition studies, proteins, which bind the beads specifically and nonspecifically, were identified in parasite lysate (Trypanosoma brucei and Leishmania major) for each antifolate compound. Proteins were identified through tryptic digest, tandem mass tag (TMT) labeling of peptides followed by LC-MS/MS. This approach was further exploited by creating a combined folate resin (folate beads). The resin could pull down up to 9 proteins from the folateome. This information could be exploited in gaining a better understanding of folate metabolism in kinetoplastids and other organisms

    How to measure work functions from aqueous solutions

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    The recent application of concepts from condensed-matter physics to photoelectron spectroscopy (PES) of volatile, liquid-phase systems has enabled the measurement of electronic energetics of liquids on an absolute scale. Particularly, vertical ionization energies, VIEs, of liquid water and aqueous solutions, both in the bulk and at associated interfaces, can now be routinely determined. These IEs are referenced to the local vacuum level, which is the appropriate quantity for condensed matter with associated surfaces, including liquids. Here, we connect this newly accessible energy level to another important surface property, namely, the solution work function, eΦliq\Phi_{liq}. We lay out the prerequisites for and unique challenges of determining eΦ\Phi of aqueous solutions and liquids in general. We demonstrate - for a model aqueous solution with a tetra-n-butylammonium iodide (TBAI) surfactant solute - that concentration-dependent work functions, associated with the surface dipoles generated by the segregated interfacial layer of TBA+^+ and I^-ions, can be accurately measured under controlled conditions. We detail the nature of surface potentials, uniquely tied to the nature of the flowing-liquid sample, which must be eliminated or quantified to enable such measurements. This allows us to refer measured spectra of aqueous solutions to the Fermi level and quantitatively assign surfactant concentration-dependent spectral shifts to competing work function and electronic-structure effects, the latter determining, e.g., (electro)chemical reactivity. We describe the extension of liquid-jet PES to quantitatively access concentration-dependent surface descriptors that have so far been restricted to solid-phase measurements. These studies thus mark the beginning of a new era in the characterization of the interfacial electronic structure of aqueous solutions and liquids more generally.Comment: Main manuscript: 26 pages, 7 figures. Supporting information: 5 pages, 5 figure

    Towards Regional Safety Assessment of Bridge Infrastructure

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    In the aftermath of disasters, it is increasingly recognized that while their occurrence is often inevitable, proactive risk management through adequate prioritization and preventative measures ought to be of utmost importance. Regions with large infrastructure networks (e.g. roadway bridges) exposed to different types of hazards and structural ageing/deteriorating over time are particularly vulnerable. Such vulnerability can become even more relevant in developing countries, which can face higher challenges in coping with extreme events. This paper describes a study on the bridge infrastructure network in the Former Yugoslav Republic of Macedonia (FYROM), Israel and Italy as part of the project INFRA-NAT (www.infra-nat.eu). An extended database of each countrys bridge population is developed through a data collection form and allows for a detailed exposure model of the bridge network to be compiled. By considering the general characteristics of the bridge population, a representative sample of bridges is chosen to develop fragility functions for bridges exposed to seismic hazard. The connectivity of the network is modelled and the entire bridge network vulnerability is considered in a more comprehensive and global manner for seismic hazard and infrastructure ageing. The scope of this work is to provide practical web-based tools and databases for each country with which more informed decisions can be made related to the most vulnerable parts of the country and where resources should be invested for increased resilience.This research has been carried out under the INFRANAT project (www.infra-nat.eu) co-funded by European Commission ECHO – Humanitarian Aid and Civil Protection. Project reference: 783298 – INFRA-NAT – UCPM-2017-PP-AG

    The Adipose Renin-Angiotensin System Modulates Systemic Markers of Insulin Sensitivity and Activates the Intrarenal Renin-Angiotensin System

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    Background. The adipose tissue renin-angiotensin system (RAS) contributes to regulation of fat mass and may also impact systemic functions such as blood pressure and metabolism. Methods and results. A panel of mouse models including mice lacking angiotensinogen, Agt (Agt-KO), mice expressing Agt solely in adipose tissue (aP2-Agt/Agt-KO), and mice overexpressing Agt in adipose tissue (aP2-Agt) was studied. Total body weight, epididymal fat pad weight, and circulating levels of leptin, insulin, and resistin were significantly decreased in Agt-KO mice, while plasma adiponectin levels were increased. aP2-Agt mice exhibited increased adiposity and plasma leptin and insulin levels compared to wild type (WT) controls. Angiotensinogen and type I Ang II receptor protein levels were also elevated in kidney of aP2-Agt mice. Conclusion. These findings demonstrate that alterations in adipose RAS activity significantly impact both local and systemic physiology in a way that may contribute to the detrimental health effects of obesity
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