361 research outputs found

    Evaluating the cost-effectiveness of biologic treatments for psoriatic arthritis: : can we make better use of patient data registries?

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    The primary aim of this study is to explore the extent to which registry data may fulfill the evidence requirements of cost-effectiveness analysis (CEA) studies evaluating biologic therapies for the treatment of psoriatic arthritis (PsA), where trial data are lacking or insufficient. In addition, the paper aims to identify how future data collection in PsA registries might be better tailored to inform CEA research. A review of the literature was performed to identify existing registries containing PsA patients. Where possible, information was extracted on the design and characteristics of the registries. The registries were then appraised according to a set of criteria that was formulated based on the methods currently used to model PsA in the CEA literature. A review of the literature identified 21 potentially relevant registries from around the world containing patients with PsA. There was substantial variation regarding the extent to which the registries, as a whole, were useful for the purposes of CEA studies. There were also notable disparities found in terms of the accessibility of the registries to researchers. The critical review conducted in this study showed that all of the registries identified are potentially useful, at least in some degree, for the purposes of informing CEA studies in PsA. However, no individual registry on its own was found to meet all of the evidence requirements when considering how the disease has been modeled previously

    Historical perspectives on pastoralism and land tenure transformation in Ngamiland, Botswana: What are the policy and institutional lessons?

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    Pastoral societies in dryland Africa continue to face changes to their pastoral systems. These systems are influenced by a range of historical factors but little use is made of this information to design policies that suit pastoralists’ landscapes. This article provides a synthesis of historical perspectives on pastoral land use and tenure transformations in Ngamiland, south of the Okavango Delta, Botswana. Little documentation of herders’ historical perspectives exists and less is known about how past experiences can be applied to sustainable pastoralism policies. In this article, current land use pressing issues are examined and analysed within the context of past experiences. We use a series of oral histories with key informants, focus group discussions, expert interviews and rangelands field observations. Ngamiland historical perspectives depict a pastoral landscape that has been shaped by a variety of factors; livestock diseases, Human-wildlife-conflicts, droughts, land tenure transformations associated with rangeland policies and the pastoral identity of the Ovaherero/Ovambanderu ethnic groups. Pastoralists have followed unique trajectories, specific to their rangeland conditions and socio-cultural context. Resilience to climate shocks and diseases has been weakened by inequitable patterns of control over rangeland resources. We recommend institutional diversity such that from experiences of the past, lessons can be drawn of the sort of processes and institutions required for pastoralism policies including targeted pastoralists’ adaptations. Using pastoralists to provide information, especially in the area of indigenous knowledge, strategies can be developed to link conservation of wildlife and rangelands with pastoral production by developing ecologically-sensitive low-volume tourism that pastoral communities can tap in to diversify their livelihoods

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Barriers to the uptake and use of feedback in the context of summative assessment

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    Despite calls for feedback to be incorporated in all assessments, a dichotomy exists between formative and summative assessments. When feedback is provided in a summative context, it is not always used effectively by learners. In this study we explored the reasons for this. We conducted individual interviews with 17 students who had recently received web based feedback following a summative assessment. Constant comparative analysis was conducted for recurring themes. The summative assessment culture, with a focus on avoiding failure, was a dominant and negative influence on the use of feedback. Strong emotions were prevalent throughout the period of assessment and feedback, which reinforced the focus on the need to pass, rather than excel. These affective factors were heightened by interactions with others. The influence of prior learning experiences affected expectations about achievement and the need to use feedback. The summative assessment and subsequent feedback appeared disconnected from future clinical workplace learning. Socio-cultural influences and barriers to feedback need to be understood before attempting to provide feedback after all assessments. A move away from the summative assessment culture may be needed in order to maximise the learning potential of assessments

    Toxoplasma gondii Lysine Acetyltransferase GCN5-A Functions in the Cellular Response to Alkaline Stress and Expression of Cyst Genes

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    Parasitic protozoa such as the apicomplexan Toxoplasma gondii progress through their life cycle in response to stimuli in the environment or host organism. Very little is known about how proliferating tachyzoites reprogram their expressed genome in response to stresses that prompt development into latent bradyzoite cysts. We have previously linked histone acetylation with the expression of stage-specific genes, but the factors involved remain to be determined. We sought to determine if GCN5, which operates as a transcriptional co-activator by virtue of its histone acetyltransferase (HAT) activity, contributed to stress-induced changes in gene expression in Toxoplasma. In contrast to other lower eukaryotes, Toxoplasma has duplicated its GCN5 lysine acetyltransferase (KAT). Disruption of the gene encoding for TgGCN5-A in type I RH strain did not produce a severe phenotype under normal culture conditions, but here we show that the TgGCN5-A null mutant is deficient in responding to alkaline pH, a common stress used to induce bradyzoite differentiation in vitro. We performed a genome-wide analysis of the Toxoplasma transcriptional response to alkaline pH stress, finding that parasites deleted for TgGCN5-A fail to up-regulate 74% of the stress response genes that are induced 2-fold or more in wild-type. Using chromatin immunoprecipitation, we verify an enrichment of TgGCN5-A at the upstream regions of genes activated by alkaline pH exposure. The TgGCN5-A knockout is also incapable of up-regulating key marker genes expressed during development of the latent cyst form, and is impaired in its ability to recover from alkaline stress. Complementation of the TgGCN5-A knockout restores the expression of these stress-induced genes and reverses the stress recovery defect. These results establish TgGCN5-A as a major contributor to the alkaline stress response in RH strain Toxoplasma

    Role of Secreted Conjunctival Mucosal Cytokine and Chemokine Proteins in Different Stages of Trachomatous Disease

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    Trachoma, a disease of antiquity dating back to the 16th century B.C.E., predominates among developing countries, where it remains the primary cause of preventable blindness worldwide. In trachoma, recurrent Chlamydia trachomatis bacterial infections during childhood are thought to result in inflammation and subsequent conjunctival scarring that can progress to trichiasis (TT; chronic trachoma; inversion of ≥1 eyelash that touches the globe of the eye). The trachomatous follicular grade (TF; active disease) is a self-limiting disease, suggesting the coexistence of protective inflammatory proteins. The trachomatous inflammatory grade (TI; active disease) is more likely to progress to trachomatous scarring (TS; chronic trachoma). To date, there are only a handful of studies that have examined the immune response in trachoma, and these were primarily based on gene expression. Characterizing quantified conjunctival mucosal immune differences for secreted proteins among individuals with no, active, and chronic trachoma may identify protein biomarkers associated with protection versus disease, which would greatly aid our understanding of the immunopathogenesis of trachoma. In this study, we characterized 25 cytokine and chemokine proteins for all trachoma grades. We identified eight cytokines and chemokines as risk factors for chronic trachoma and four as protective. Together, these findings further characterize the immunopathologic responses involved during trachoma, which will likely aid in the design of a vaccine and immunomodulating therapeutics for trachoma

    Athlete brand construction: A perspective based on fans’ perceptions

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    Abstract The purpose of this study was to develop a framework for understanding the antecedents and components of athlete brand. Based on a set of 21 interviews conducted in three different countries, a detailed framework is proposed including five antecedents and two components of athlete brand. The antecedents are media (social media, mass media, video games and major sport events), oral communications (word of mouth, and rumors and narratives), impression management, social agents (parents, family members, friends and community), and teams and sport (sport interest, team interest and team geographical location). In turn, the components of athlete brand are related with on-field attributes (behavior, team, achievements, style of play and skills) and off-field attributes (physical attraction, lifestyle, personal appeal, ethnicity and entertainment). Complementarily, these components of athlete brand are proposed to have an impact on fans' loyalty towards the athlete. Implications of these findings for building and managing athlete brand are discussed, and directions for future studies are provided
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