194 research outputs found

    The unseen and unacceptable face of digital libraries

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    The social and organizational aspects of digital libraries are often overlooked but this paper reviews how they can affect users' awareness and acceptance of digital libraries. An analysis of research conducted within two contrasting domains (Clinical and Academic) is presented which highlights issues of user interactions, work practices and the organizational social structures. The combined study comprises an analysis of 98 in-depth interviews and focus groups with lecturers, librarians and hospital clinicians. The importance of current and past roles of the library, and how users interacted with it, are revealed. Web-based digital libraries, while alleviating most library resource and interaction problems, require a change in librarians' and DL designers' roles and interaction patterns if they are to be implemented acceptably and effectively. Without this role change, users will at best be unaware of these digital resources and at worst feel threatened by them. The findings of this paper highlight the importance on DL design and implementation of the social context and supporting user communication (i.e. collaboration and consultation) in their information search and usage activities

    The 28 November 2020 Landslide, Tsunami, and Outburst Flood – A Hazard Cascade Associated With Rapid Deglaciation at Elliot Creek, British Columbia, Canada

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    We describe and model the evolution of a recent landslide, tsunami, outburst flood, and sediment plume in the southern Coast Mountains, British Columbia, Canada. On November 28, 2020, about 18 million m3 of rock descended 1,000 m from a steep valley wall and traveled across the toe of a glacier before entering a 0.6 km2 glacier lake and producing >100-m high run-up. Water overtopped the lake outlet and scoured a 10-km long channel before depositing debris on a 2-km2 fan below the lake outlet. Floodwater, organic debris, and fine sediment entered a fjord where it produced a 60+km long sediment plume and altered turbidity, water temperature, and water chemistry for weeks. The outburst flood destroyed forest and salmon spawning habitat. Physically based models of the landslide, tsunami, and flood provide real-time simulations of the event and can improve understanding of similar hazard cascades and the risk they pose

    Fibronectin III 13-14 Domains Induce Joint Damage via Toll-Like Receptor 4 Activation and Synergize with Interleukin-1 and Tumour Necrosis Factor

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    Cartilage loss is a feature of chronic arthritis. It results from degradation of the extracellular matrix which is composed predominantly of aggrecan and type II collagen. Extracellular matrix degradation is mediated by aggrecanases and matrix metalloproteinases (MMPs). Recently, a number of endogenous matrix molecules, including fibronectin (FN), have been implicated in mediating cartilage degradation. We were interested in studying the C-terminal heparin-binding region of FN since it mediates aggrecan and type II collagen breakdown in cartilage, but the specific FN domains responsible for proteolytic enzyme activity and their receptors in cartilage are unknown. In this study, the ability of recombinant FN domains to induce cartilage breakdown was tested. We found that the FN III 13-14 domains in the C-terminal heparin-binding region of FN are potent inducers of aggrecanase activity in articular cartilage. In murine studies, the FN III 13-14-induced aggrecanase activity was inhibited in Toll-like receptor 4 (TLR4) knockout mice but not wild-type mice. FN III 13-14 domains also synergized with the known catabolic cytokines interleukin-1α and tumour necrosis factor and induced secretion of MMP-1, MMP-3, gp38 and serum amyloid-like protein A in chondrocytes. Our studies provide a mechanistic link between the innate immune receptor TLR4 and sterile arthritis induced by the FN III 13-14 domains of the endogenous matrix molecule FN

    Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress.

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    Endothelial microparticles (EMPs) are endothelium-derived submicron vesicles that are released in response to diverse stimuli and are elevated in cardiovascular disease, which is correlated with risk factors. This study investigates the effect of EMPs on endothelial cell function and dysfunction in a model of free fatty acid (FFA) palmitate-induced oxidative stress. EMPs were generated from TNF-α-stimulated HUVECs and quantified by using flow cytometry. HUVECs were treated with and without palmitate in the presence or absence of EMPs. EMPs were found to carry functional eNOS and to protect against oxidative stress by positively regulating eNOS/Akt signaling, which restored NO production, increased superoxide dismutase and catalase, and suppressed NADPH oxidase and reactive oxygen species (ROS) production, with the involvement of NF-erythroid 2-related factor 2 and heme oxygenase-1. Conversely, under normal conditions, EMPs reduced NO release and increased ROS and redox-sensitive marker expression. In addition, functional assays using EMP-treated mouse aortic rings that were performed under homeostatic conditions demonstrated a decline in endothelium-dependent vasodilatation, but restored the functional response under lipid-induced oxidative stress. These data indicate that EMPs harbor functional eNOS and potentially play a role in the feedback loop of damage and repair during homeostasis, but are also effective in protecting against FFA-induced oxidative stress; thus, EMP function is reflected by the microenvironment.-Mahmoud, A. M., Wilkinson, F. L., McCarthy, E. M., Moreno-Martinez, D., Langford-Smith, A., Romero, M., Duarte, J., Alexander, M. Y. Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress

    Theatre and time ecology: deceleration in Stifters Dinge

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    This article explores the production of ‘time ecology’ in two works of postdramatic theatre: Heiner Goebbels’ Stifters Dinge (2007) and Philippe Quesne’s L’Effet de Serge (2007). By focusing on the practice of deceleration, it argues that theatre’s ecological potential resides not so much in its ability to represent the world, but rather in its capacity for producing new types of temporal experience that purposefully seek to break with modernity’s regime of historicity and the accelerated rhythms that it has given rise to. Importantly, my concern with deceleration is not an argument for slowness per se; on the contrary, I am interested in highlighting the presence of multiple and interpenetrating timescales and rhythms. As well as exposing the full extent of theatre’s temporal potential, such a concern with postdramatic ‘chronographies’ offers an implicit critique of dramatic theatre’s extant practices of eco-dramaturgy that, all too often, attempt to construct a linear narrative which is invested in conventional sequential models of temporality (beginning, middle, end)

    Decision tools in health care: focus on the problem, not the solution

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    BACKGROUND: Systematic reviews or randomised-controlled trials usually help to establish the effectiveness of drugs and other health technologies, but are rarely sufficient by themselves to ensure actual clinical use of the technology. The process from innovation to routine clinical use is complex. Numerous computerised decision support systems (DSS) have been developed, but many fail to be taken up into actual use. Some developers construct technologically advanced systems with little relevance to the real world. Others did not determine whether a clinical need exists. With NHS investing £5 billion in computer systems, also occurring in other countries, there is an urgent need to shift from a technology-driven approach to one that identifies and employs the most cost-effective method to manage knowledge, regardless of the technology. The generic term, 'decision tool' (DT), is therefore suggested to demonstrate that these aids, which seem different technically, are conceptually the same from a clinical viewpoint. DISCUSSION: Many computerised DSSs failed for various reasons, for example, they were not based on best available knowledge; there was insufficient emphasis on their need for high quality clinical data; their development was technology-led; or evaluation methods were misapplied. We argue that DSSs and other computer-based, paper-based and even mechanical decision aids are members of a wider family of decision tools. A DT is an active knowledge resource that uses patient data to generate case specific advice, which supports decision making about individual patients by health professionals, the patients themselves or others concerned about them. The identification of DTs as a consistent and important category of health technology should encourage the sharing of lessons between DT developers and users and reduce the frequency of decision tool projects focusing only on technology. The focus of evaluation should become more clinical, with the impact of computer-based DTs being evaluated against other computer, paper- or mechanical tools, to identify the most cost effective tool for each clinical problem. SUMMARY: We suggested the generic term 'decision tool' to demonstrate that decision-making aids, such as computerised DSSs, paper algorithms, and reminders are conceptually the same, so the methods to evaluate them should be the same

    Identifying chondroprotective diet-derived bioactives and investigating their synergism

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    Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role

    What is the future of targeted therapy in rheumatology: biologics or small molecules?

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    Background: Until late in the 20th century, the therapy of rheumatic diseases relied on the use of drugs that had been developed through empirical approaches without detailed understanding of the molecular mechanisms involved. That approach changed with the introduction of biologic therapeutics at the end of the 20th century and by the recent development of small-molecule inhibitors of intracellular signal transduction pathways. Here we compare and discuss the advantages and disadvantages of those two groups of targeted anti-inflammatory therapeutics.Discussion: TNF-blocking biologic agents were introduced into the therapy of rheumatoid arthritis and other autoimmune and inflammatory diseases in the late 1990s. Further biologic agents targeting cytokine networks or specific lymphocyte subsets have since been added to the armamentarium of anti-rheumatic therapy. During the last few years, another wave of novel discoveries led to the development of a new class of small molecule anti-inflammatory compounds targeting intracellular signal transduction molecules, such as tyrosine kinases. In all those cases, the specific targets of the drugs are well defined and significant knowledge about their role in the disease pathomechanism is available, qualifying them for being targeted therapeutics for inflammatory rheumatic diseases. While both groups of targeted therapeutics offer significant clinical benefit, they clearly differ in several aspects, such as the localization of their targets, their route of administration and target specificity, as well as technical details such as manufacturing procedures and cost basis. In this debate paper, we compare the advantages and disadvantages of the two different approaches, aiming to shed light on the possible future of targeted therapies.Summary: Biologic therapeutics and small-molecule inhibitors both have significant advantages and disadvantages in the therapy of rheumatic diseases. The future of targeted therapies is one of the most exciting questions of current rheumatology research and therapy. © 2014 Mócsai et al.; licensee BioMed Central Ltd

    Evaluation of storm impact on sandy beaches of the Gulf of Valencia using Landsat imagery series

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    Supplementary data associated with this article can be found in the online version, at http://dx.doi.org/10.1016/j.geomorph.2014.02.020. These data include Google maps of the most important areas described in this article.The impact of storms on sandy beaches and the subsequent recovery process is described from an analysis of the shoreline positions obtained from Landsat 5 TM and Landsat 7 ETM + imagery. Shoreline extraction is based on an algorithm previously proposed by the authors that enables a positioning accuracy of 5 m root mean square error (RMSE). The impact of six storms registered over a period of seven months (between November 2001 and May 2002) and the beach recovery processes until December 2002 across a 100 km segment of the Gulf of Valencia on the Spanish Mediterranean coast were analysed by comparing 12 shoreline positions. The multiple shoreline positions obtained from Landsat images provide very useful information for describing the impact of storms and the recovery process across large segments of microtidal coast. This enables the identification of differences not only in the magnitude of change produced by a particular event but also in the cumulative effect associated with several storm events, and in the study of how the beach recovery process takes place. The results show a high level of spatial variability. Beaches with steep slopes experienced fewer changes than shallow slopes. The existence of well developed foredunes in some areas minimised the reduction in the beach width after the storms. Coastal orientation was another important factor in explaining storm impact and the recovery process. This factor affects not only the way the waves interact with the beaches but also the sediment longshore transport: beach regeneration is slower when the transport of sediments is limited by artificial infrastructures (groins, jetties, ports) or natural sediment traps (headlands). The main limitations of using the proposed methodology to obtain the shoreline position from Landsat images are related to: (i) the precision in the shoreline detection; (ii) the nature of the indicator obtained, that is, the water/land interface; and (iii) the registration instant defined by the image acquisition time. However, the high frequency of the data acquisition and the possibility to cover large coastal areas bring a new perspective that enriches other methods and tools used by coastal scientists.The authors appreciate the financial support provided by the Spanish Ministerio de Ciencia e Innovacion in the framework of the Projects CGL2009-14220-C02-01 and CGL2010-19591. We also thank the Direccion General de Costas in Valencia for making available the data for the tests and analysis. Finally, we would like to thank the useful suggestions provided by the anonymous referees and the assigned editor, which enabled us to improve the quality of this paper.Pardo Pascual, JE.; Almonacid Caballer, J.; Ruiz Fernández, LÁ.; Palomar-Vázquez, J.; Rodrigo-Alemany, R. (2014). Evaluation of storm impact on sandy beaches of the Gulf of Valencia using Landsat imagery series. Geomorphology. 214:388-401. doi:10.1016/j.geomorph.2014.02.020S38840121
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