923 research outputs found

    A conserved filamentous assembly underlies the structure of the meiotic chromosome axis.

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    The meiotic chromosome axis plays key roles in meiotic chromosome organization and recombination, yet the underlying protein components of this structure are highly diverged. Here, we show that 'axis core proteins' from budding yeast (Red1), mammals (SYCP2/SYCP3), and plants (ASY3/ASY4) are evolutionarily related and play equivalent roles in chromosome axis assembly. We first identify 'closure motifs' in each complex that recruit meiotic HORMADs, the master regulators of meiotic recombination. We next find that axis core proteins form homotetrameric (Red1) or heterotetrameric (SYCP2:SYCP3 and ASY3:ASY4) coiled-coil assemblies that further oligomerize into micron-length filaments. Thus, the meiotic chromosome axis core in fungi, mammals, and plants shares a common molecular architecture, and likely also plays conserved roles in meiotic chromosome axis assembly and recombination control

    Empirical Challenges in Organizational Aesthetics Research: Towards a Sensual Methodology

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    Despite growing scholarly interest in aesthetic dimensions of organizational life, there is a lack of literature expressly engaging with the methodological mechanics of 'doing aesthetics research'. This article addresses that gap. It begins with an overview of the conceptual idiosyncrasies of 'aesthetics' as a facet of human existence and maps out the challenges these pose for empirical research methodology. A review of methodological approaches adopted to date in empirical studies of organizational aesthetics is then presented. The remainder of the article draws on the author's experiences and suggests methods and techniques to address both conceptual and practical challenges encountered during the execution of an organizational aesthetics research project. The article calls for a firmer focus on the aesthetic experiences of organizational members in addition to those of researchers and concludes with some suggestions as to the future of such 'sensual methodologies' </jats:p

    Breathing Easy: Lung Health and Associated Conditions in the Day Care Setting

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    Introduction: Air pollutants are associated with many health risks. Children in the day care environment are uniquely suscept-ible to lung damage, infection, systemic illness & pollutant triggered hypersensitivity reactions. The latest public report by the CDC reports Vermont’s (VT) asthma rate is the high-est in the country at 11.1%. This project compared VT’s day care regulations regarding specific environmental factors linked with health risks to regulations in six surrounding New England states. We sought to assess whether VT’s regulations adequately protect children in day carehttps://scholarworks.uvm.edu/comphp_gallery/1064/thumbnail.jp

    Community Hospitals in Selected High Income Countries: A Scoping Review of Approaches and Models.

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    BACKGROUND: There is no single definition of a community hospital in the UK, despite its long history. We sought to understand the nature and scope of service provision in community hospitals, within the UK and other high-income countries. METHODS: We undertook a scoping review of literature on community hospitals published from 2005 to 2014. Data were extracted on features of the hospital model and the services provided, with results presented as a narrative synthesis. RESULTS: 75 studies were included from ten countries. Community hospitals provide a wide range of services, with wide diversity of provision appearing to reflect local needs. Community hospitals are staffed by a mixture of general practitioners (GPs), nurses, allied health professionals and healthcare assistants. We found many examples of collaborative working arrangements between community hospitals and other health care organisations, including colocation of services, shared workforce with primary care and close collaboration with acute specialists. CONCLUSIONS: Community hospitals are able to provide a diverse range of services, responding to geographical and health system contexts. Their collaborative nature may be particularly important in the design of future models of care delivery, where emphasis is placed on integration of care with a key focus on patient-centred care.This project was funded by the National Institute for Health Research Health Services and Delivery Research programme (project number 12/177/14)

    Wet Paint: Visual Culture in a Changing Britain – A Round Table Debate

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    Political decisions and debates regarding the interregional and interna- tional partnerships that constitute Great Britain, including those over Scottish Independence, EVEL (English Votes for English Laws) and proposed legislation on an ‘in/out’ referendum on British membership of the European Union, have contributed to, and intensified, the examination of Britain’s institutions, as well as its national emblems and arche- types. In light of such a dynamic situation, Visual Culture in Britain has asked representatives of British universities, the museum sector and research centres to respond to the idea of a changing Britain through the prism of British art and visual culture, using cogent examples wherever possible, and to outline their observations, understandings and positions within this rapidly developing context

    Green IS Research: A Modernity Perspective

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    Over the past two decades, the information systems community has become engaged in improving the environmental effects of information systems and technologies, which has given rise to the green IS field. Despite increasing interest, some have suggested that progress toward meaningful solutions for sustainability has been too slow. Responding to these concerns, we examine the development of green IS research using the modernity perspective to understand green IS’s evolution and to present alternative perspectives to motivate future research. From a sample of over 80 green IS papers published over a 15-year period, we identify four main patterns of modernity that are manifest in green IS research. These patterns include the importance of the individual in solving environmental problems; science as the main source of solutions; and the emergence of an artificial science approach, reliance on technology, and growth as businesses’ ultimate goals. Further, our analysis reveals that green IS research has started to demonstrate elements of a hyper-modernity perspective that emphasizes reflexivity. We argue that future green IS research should continue on this path and propose a conceptual framework inspired by hyper-modernity and centered on reflexivity that could serve as a guide for future research

    Salinomycin and Other Ionophores as a New Class of Antimalarial Drugs with Transmission-Blocking Activity

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    The drug target profile proposed by the Medicines for Malaria Venture for a malaria elimination/eradication policy focuses on molecules active on both asexual and sexual stages of Plasmodium, thus with both curative and transmission-blocking activities. The aim of the present work was to investigate whether the class of monovalent ionophores, which includes drugs used in veterinary medicine and that were recently proposed as human anticancer agents, meets these requirements. The activity of salinomycin, monensin, and nigericin on Plasmodium falciparum asexual and sexual erythrocytic stages and on the development of the Plasmodium berghei and P. falciparum mosquito stages is reported here. Gametocytogenesis of the P. falciparum strain 3D7 was induced in vitro, and gametocytes at stage II and III or stage IV and V of development were treated for different lengths of time with the ionophores and their viability measured with the parasite lactate dehydrogenase (pLDH) assay. The monovalent ionophores efficiently killed both asexual parasites and gametocytes with a nanomolar 50% inhibitory concentration (IC50). Salinomycin showed a fast speed of kill compared to that of standard drugs, and the potency was higher on stage IV and V than on stage II and III gametocytes. The ionophores inhibited ookinete development and subsequent oocyst formation in the mosquito midgut, confirming their transmission-blocking activity. Potential toxicity due to hemolysis was excluded, since only infected and not normal erythrocytes were damaged by ionophores. Our data strongly support the downstream exploration of monovalent ionophores for repositioning as new antimalarial and transmission-blocking leads

    POTs: Protective Optimization Technologies

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    Algorithmic fairness aims to address the economic, moral, social, and political impact that digital systems have on populations through solutions that can be applied by service providers. Fairness frameworks do so, in part, by mapping these problems to a narrow definition and assuming the service providers can be trusted to deploy countermeasures. Not surprisingly, these decisions limit fairness frameworks' ability to capture a variety of harms caused by systems. We characterize fairness limitations using concepts from requirements engineering and from social sciences. We show that the focus on algorithms' inputs and outputs misses harms that arise from systems interacting with the world; that the focus on bias and discrimination omits broader harms on populations and their environments; and that relying on service providers excludes scenarios where they are not cooperative or intentionally adversarial. We propose Protective Optimization Technologies (POTs). POTs provide means for affected parties to address the negative impacts of systems in the environment, expanding avenues for political contestation. POTs intervene from outside the system, do not require service providers to cooperate, and can serve to correct, shift, or expose harms that systems impose on populations and their environments. We illustrate the potential and limitations of POTs in two case studies: countering road congestion caused by traffic-beating applications, and recalibrating credit scoring for loan applicants.Comment: Appears in Conference on Fairness, Accountability, and Transparency (FAT* 2020). Bogdan Kulynych and Rebekah Overdorf contributed equally to this work. Version v1/v2 by Seda G\"urses, Rebekah Overdorf, and Ero Balsa was presented at HotPETS 2018 and at PiMLAI 201

    Acupuncture for chronic pain and depression in primary care:a programme of research

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    Abstract Background There has been an increase in the utilisation of acupuncture in recent years, yet the evidence base is insufficiently well established to be certain about its clinical effectiveness and cost-effectiveness. Addressing the questions related to the evidence base will reduce uncertainty and help policy- and decision-makers with regard to whether or not wider access is appropriate and provides value for money. Aim Our aim was to establish the most reliable evidence on the clinical effectiveness and cost-effectiveness of acupuncture for chronic pain by drawing on relevant evidence, including recent high-quality trials, and to develop fresh evidence on acupuncture for depression. To extend the evidence base we synthesised the results of published trials using robust systematic review methodology and conducted a randomised controlled trial (RCT) of acupuncture for depression. Methods and results We synthesised the evidence from high-quality trials of acupuncture for chronic pain, consisting of musculoskeletal pain related to the neck and low back, osteoarthritis of the knee, and headache and migraine, involving nearly 18,000 patients. In an individual patient data (IPD) pairwise meta-analysis, acupuncture was significantly better than both sham acupuncture (p < 0.001) and usual care (p < 0.001) for all conditions. Using network meta-analyses, we compared acupuncture with other physical therapies for osteoarthritis of the knee. In both an analysis of all available evidence and an analysis of a subset of better-quality trials, using aggregate-level data, we found acupuncture to be one of the more effective therapies. We developed new Bayesian methods for analysing multiple individual patient-level data sets to evaluate heterogeneous continuous outcomes. An accompanying cost-effectiveness analysis found transcutaneous electrical nerve stimulation (TENS) to be cost-effective for osteoarthritis at a threshold of £20,000 per quality-adjusted life-year when all trials were synthesised. When the analysis was restricted to trials of higher quality with adequate allocation concealment, acupuncture was cost-effective. In a RCT of acupuncture or counselling compared with usual care for depression, in which half the patients were also experiencing comorbid pain, we found acupuncture and counselling to be clinically effective and acupuncture to be cost-effective. For patients in whom acupuncture is inappropriate or unavailable, counselling is cost-effective. Conclusion We have provided the most robust evidence from high-quality trials on acupuncture for chronic pain. The synthesis of high-quality IPD found that acupuncture was more effective than both usual care and sham acupuncture. Acupuncture is one of the more clinically effective physical therapies for osteoarthritis and is also cost-effective if only high-quality trials are analysed. When all trials are analysed, TENS is cost-effective. Promising clinical and economic evidence on acupuncture for depression needs to be extended to other contexts and settings. For the conditions we have investigated, the drawing together of evidence on acupuncture from this programme of research has substantially reduced levels of uncertainty. We have identified directions for further research. Our research also provides a valuable basis for considering the potential role of acupuncture as a referral option in health care and enabling providers and policy-makers to make decisions based on robust sources of evidence
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