8,082 research outputs found

    Impact case studies submitted to REF2014: the hidden impact of nursing research

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    The UK’s Research Excellence Framework (REF) 2014 rated the research from 154 universities and the impact of research was evaluated in 6975 impact case studies. Nursing was returned within unit of Assessment (UoA) 3 which also included Dentistry, Pharmacy, Allied Health Professions, although nursing research was also submitted within other UoAs. The study aim was to collate and categorise available REF impact case studies involving nursing researchers or on topics of relevance to nursing. Using nurs* as a search term 469 case study entries were retrieved from the REF database and placed into three categories determined by the level of involvement of nurses. Some 80 impact case studies were submitted by nurses across 11 UoAs: the majority being in UoA3 (n=55). A further 50 revealed some relevant impact, though nurses did not have an obvious research role. A total of 248 case studies described actual or potential impact on health or social care but were not associated specifically with nursing. Nursing research has demonstrable impact, however there is a significant body of research with relevance for nursing that has not been associated with the profession in the REF. More attention should be paid to the ‘hidden impact’ of nursing research to ensure the full impact of nursing is recognised

    A new experimental model for assessing drug efficacy against Trypanosoma cruzi infection based on highly sensitive in vivo imaging.

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    The protozoan Trypanosoma cruzi is the causative agent of Chagas disease, one of the world's major neglected infections. Although development of improved antiparasitic drugs is considered a priority, there have been no significant treatment advances in the past 40 years. Factors that have limited progress include an incomplete understanding of pathogenesis, tissue tropism, and disease progression. In addition, in vivo models, which allow parasite burdens to be tracked throughout the chronic stage of infection, have been lacking. To address these issues, we have developed a highly sensitive in vivo imaging system based on bioluminescent T. cruzi, which express a red-shifted luciferase that emits light in the tissue-penetrating orange-red region of the spectrum. The exquisite sensitivity of this noninvasive murine model has been exploited to monitor parasite burden in real time throughout the chronic stage, has allowed the identification of the gastrointestinal tract as the major niche of long-term infection, and has demonstrated that chagasic heart disease can develop in the absence of locally persistent parasites. Here, we review the parameters of the imaging system and describe how this experimental model can be incorporated into drug development programs as a valuable tool for assessing efficacy against both acute and chronic T. cruzi infections

    Biological factors that impinge on Chagas disease drug development.

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    Chagas disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi, and is the most important parasitic infection in Latin America. The current drugs, benznidazole and nifurtimox, are characterized by limited efficacy and toxic side-effects, and treatment failures are frequently observed. The urgent need for new therapeutic approaches is being met by a combined effort from the academic and commercial sectors, together with major input from not-for-profit drug development consortia. With the disappointing outcomes of recent clinical trials against chronic Chagas disease, it has become clear that an incomplete understanding of parasite biology and disease pathogenesis is impacting negatively on the development of more effective drugs. In addition, technical issues, including difficulties in establishing parasitological cure in both human patients and animal models, have greatly complicated the assessment of drug efficacy. Here, we outline the major questions that need to be addressed and discuss technical innovations that can be exploited to accelerate the drug development pipeline

    Host and parasite genetics shape a link between Trypanosoma cruzi infection dynamics and chronic cardiomyopathy.

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    Host and parasite diversity are suspected to be key factors in Chagas disease pathogenesis. Experimental investigation of underlying mechanisms is hampered by a lack of tools to detect scarce, pleiotropic infection foci. We developed sensitive imaging models to track Trypanosoma cruzi infection dynamics and quantify tissue-specific parasite loads, with minimal sampling bias. We used this technology to investigate cardiomyopathy caused by highly divergent parasite strains in BALB/c, C3H/HeN and C57BL/6 mice. The gastrointestinal tract was unexpectedly found to be the primary site of chronic infection in all models. Immunosuppression induced expansion of parasite loads in the gut and was followed by widespread dissemination. These data indicate that differential immune control of T. cruzi occurs between tissues and shows that the large intestine and stomach provide permissive niches for active infection. The end-point frequency of heart-specific infections ranged from 0% in TcVI-CLBR-infected C57BL/6 to 88% in TcI-JR-infected C3H/HeN mice. Nevertheless, infection led to fibrotic cardiac pathology in all models. Heart disease severity was associated with the model-dependent frequency of dissemination outside the gut and inferred cumulative heart-specific parasite loads. We propose a model of cardiac pathogenesis driven by periodic trafficking of parasites into the heart, occurring at a frequency determined by host and parasite genetics

    Assessing the Effectiveness of Curative Benznidazole Treatment in Preventing Chronic Cardiac Pathology in Experimental Models of Chagas Disease.

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    Chagasic heart disease develops in 30% of those infected with the protozoan parasite Trypanosoma cruzi, but can take decades to become symptomatic. Because of this, it has been difficult to assess the extent to which antiparasitic therapy can prevent the development of pathology. We sought to address this question using experimental murine models, exploiting highly sensitive bioluminescent imaging to monitor curative efficacy. Mice were inoculated with bioluminescent parasites and then cured in either the acute or chronic stage of infection with benznidazole. At the experimental endpoint (5 to 6 months postinfection), heart tissue was removed and assessed for inflammation and fibrosis, two widely used markers of cardiac pathology. Infection of BALB/c and C3H/HeN mice with distinct T. cruzi lineages resulted in greatly increased myocardial collagen content at a group level, indicative of fibrotic pathology. When mice were cured by benznidazole in the acute stage, the development of pathology was completely blocked. However, if treatment was delayed until the chronic stage, cardiac fibrosis was observed in the BALB/c model, although the protective effect was maintained in the case of C3H/HeN mice. These experiments therefore demonstrate that curative benznidazole treatment early in murine T. cruzi infections can prevent the development of cardiac fibrosis. They also show that treatment during the chronic stage can block pathology but the effectiveness varies between infection models. If these findings are extendable to humans, it implies that widespread chemotherapeutic intervention targeted at early-stage infections could play a crucial role in reducing Chagas disease morbidity at a population level

    A remark on non-Abelian classical kinetic theory

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    It is known that non-Abelian classical kinetic theory reproduces the Hard Thermal/Dense Loop (HTL/HDL) effective action of QCD, obtained after integrating out the hardest momentum scales from the system, as well as the first higher dimensional operator beyond the HTL/HDL level. We discuss here its applicability at still higher orders, by comparing the exact classical effective action obtained in the static limit, with the 1-loop quantum effective potential. We remark that while correct types of operators arise, the classical colour algebra reproduces correctly the prefactor of the 4-point function trA04tr A_0^4 only for matter in asymptotically high dimensional colour representations.Comment: 6 page

    Culturable Root Endophyte Communities are Shaped by Both Warming and Plant Host Identity in the Rocky Mountains, USA

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    Understanding the biogeographic patterns of root-associated fungi and their sensitivity to temperature may improve predictions of future changes in terrestrial biodiversity and associated ecosystem processes, but data are currently limited. Anticipating change will require combining observational data, which predict how climatic factors limit current species distributions, with direct manipulations of climate, which can isolate responses to specific climate variables. Root endophytes are common symbionts of plants, particularly in arctic and alpine environments, yet their responses to climate warming are not resolved. Here, we directly cultured endophytic fungi from roots collected along altitudinal gradients in replicated mountain watersheds and from a 27 y field warming experiment in the Rocky Mountains, USA, to improve understanding of climate impacts on fungal root endophytes. Fungal taxa that were common at high elevations declined most under climate warming, whereas low elevation dominants responded neutrally or increased with experimental warming. Altitudinal gradients in fungal communities were strongly specific to the plant host species. Specifically, Poa species had 25–60% greater fungal isolate abundance and 25–38% greater fungal diversity at high elevations than at low elevation sites. In contrast, Festuca thurberi had 64% lower fungal diversity on roots at high elevation than at low elevation. Our results help to improve understanding of the potential for climate change to alter plant-fungal interactions in mountain ecosystems

    An overview of cardiovascular risk factor burden in sub-Saharan African countries: a socio-cultural perspective

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    <p>Abstract</p> <p>Background</p> <p>Sub-Saharan African (SSA) countries are currently experiencing one of the most rapid epidemiological transitions characterized by increasing urbanization and changing lifestyle factors. This has resulted in an increase in the incidence of non-communicable diseases, especially cardiovascular disease (CVD). This double burden of communicable and chronic non-communicable diseases has long-term public health impact as it undermines healthcare systems.</p> <p>Purpose</p> <p>The purpose of this paper is to explore the socio-cultural context of CVD risk prevention and treatment in sub-Saharan Africa. We discuss risk factors specific to the SSA context, including poverty, urbanization, developing healthcare systems, traditional healing, lifestyle and socio-cultural factors.</p> <p>Methodology</p> <p>We conducted a search on African Journals On-Line, Medline, PubMed, and PsycINFO databases using combinations of the key country/geographic terms, disease and risk factor specific terms such as "diabetes and Congo" and "hypertension and Nigeria". Research articles on clinical trials were excluded from this overview. Contrarily, articles that reported prevalence and incidence data on CVD risk and/or articles that report on CVD risk-related beliefs and behaviors were included. Both qualitative and quantitative articles were included.</p> <p>Results</p> <p>The epidemic of CVD in SSA is driven by multiple factors working collectively. Lifestyle factors such as diet, exercise and smoking contribute to the increasing rates of CVD in SSA. Some lifestyle factors are considered gendered in that some are salient for women and others for men. For instance, obesity is a predominant risk factor for women compared to men, but smoking still remains mostly a risk factor for men. Additionally, structural and system level issues such as lack of infrastructure for healthcare, urbanization, poverty and lack of government programs also drive this epidemic and hampers proper prevention, surveillance and treatment efforts.</p> <p>Conclusion</p> <p>Using an African-centered cultural framework, the PEN3 model, we explore future directions and efforts to address the epidemic of CVD risk in SSA.</p

    A Simple Derivation of the Hard Thermal Loop Effective Action

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    We use the background field method along with a special gauge condition, to derive the hard thermal loop effective action in a simple manner. The new point in the paper is to relate the effective action explicitly to the S-matrix from the onset.Comment: 11 pages, Latex; lost text after sect. 2 reinserte
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