1,939 research outputs found

    What Secrets You Hide

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    Spaces and places : negotiating learning in the context of new technology

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    The need for a deeper understanding of students' experiences of e-learning, particularly amongst widening access students, forms the motivation for this work. The three key themes of higher education policy, tech nology- enhanced learning, and student personal space were used to develop a framework for analysing the match (or mismatch) between the potential learner's circumstances and how these circumstances impact on the ability of the learner to create their own unique learning environment.\ud To enable a more intimate insight into student classroom and out-ofclassroom learning experiences, interviews using the 'Biographic- Narrative- Interpretative Method (BNIM)' were undertaken (Wengraf, 2001). These narratives enable personal and individual accounts of behaviour, and place the work within the phenomenological tradition.\ud The findings reveal how students draw upon their life experiences outside of the university to 'colonise' their learning spaces, and to construct their view of 'self' as student. Further, their creation of this space impacts on those around them; control over one space seems to permit flexibility elsewhere. Students from deprived backgrounds face more complex challenges in trying to combine and prioritise the competing demands of education, work and family life.\ud The implications from this study are that, in the context of a new managerialist agenda, government and university policy should incorporate a vision of the learning spaces offered to students, and take account of diverse student voices. Inside and outside of the formal classroom, tutors need to change their perceptions as to what is valued as meaningful knowledge construction. Furthermore, differing student experiences need to be acknowledged when designing appropriate and meaningful learning environments - including online environments. \u

    Context Is key: Delineating the unique functions of IFNĪ± and IFNĪ² in disease

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    Type I interferons (IFNs) are critical effector cytokines of the immune system and were originally known for their important role in protecting against viral infections; however, they have more recently been shown to play protective or detrimental roles in many disease states. Type I IFNs consist of IFNĪ±, IFNĪ², IFNĻµ, IFNĪŗ, IFNĻ‰, and a few others, and they all signal through a shared receptor to exert a wide range of biological activities, including antiviral, antiproliferative, proapoptotic, and immunomodulatory effects. Though the individual type I IFN subtypes possess overlapping functions, there is growing appreciation that they also have unique properties. In this review, we summarize some of the mechanisms underlying differential expression of and signaling by type I IFNs, and we discuss examples of differential functions of IFNĪ± and IFNĪ² in models of infectious disease, cancer, and autoimmunity

    Childhood Healthcare Experience, Healthcare Attitudes, and Optimism as Predictors of Adolescentsā€™ Healthcare Behavior

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    Late adolescence and early adulthood is a time when people establish many of their life-style behaviors. Thus, in order to promote optimal health, it is important to identify factors predictive of young adultsā€™ healthcare behavior. This study evaluated the relationship between measures of childhood healthcare experience, healthcare attitudes, and optimism with young adultsā€™ healthcare behavior in a sample of college students (n = 100). Results suggested that prior healthcare experience, attitudes about healthcare, and optimism are associated with current healthcare behavior. In addition, the relation between childhood healthcare experience and current healthcare behavior was moderated by optimism, such that those who reported both more negative childhood healthcare experiences and low levels of optimism reported the least adaptive healthcare behaviors and those who reported the most positive childhood healthcare experience and the highest levels of optimism reported the most adaptive healthcare behavior

    Dermal and muscle fibroblasts and skeletal myofibers survive chikungunya virus infection and harbor persistent RNA

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    Chikungunya virus (CHIKV) is an arthritogenic alphavirus that acutely causes fever as well as severe joint and muscle pain. Chronic musculoskeletal pain persists in a substantial fraction of patients for months to years after the initial infection, yet we still have a poor understanding of what promotes chronic disease. While replicating virus has not been detected in joint-associated tissues of patients with persistent arthritis nor in various animal models at convalescent time points, viral RNA is detected months after acute infection. To identify the cells that might contribute to pathogenesis during this chronic phase, we developed a recombinant CHIKV that expresses Cre recombinase (CHIKV-3'-Cre). CHIKV-3'-Cre replicated in myoblasts and fibroblasts, and it induced arthritis during the acute phase in mice. Importantly, it also induced chronic disease, including persistent viral RNA and chronic myositis and synovitis similar to wild-type virus. CHIKV-3'-Cre infection of tdTomato reporter mice resulted in a population of tdTomato+ cells that persisted for at least 112 days. Immunofluorescence and flow cytometric profiling revealed that these tdTomato+ cells predominantly were myofibers and dermal and muscle fibroblasts. Treatment with an antibody against Mxra8, a recently defined host receptor for CHIKV, reduced the number of tdTomato+ cells in the chronic phase and diminished the levels of chronic viral RNA, implicating these tdTomato+ cells as the reservoir of chronic viral RNA. Finally, isolation and flow cytometry-based sorting of the tdTomato+ fibroblasts from the skin and ankle and analysis for viral RNA revealed that the tdTomato+ cells harbor most of the persistent CHIKV RNA at chronic time points. Therefore, this CHIKV-3'-Cre and tdTomato reporter mouse system identifies the cells that survive CHIKV infection in vivo and are enriched for persistent CHIKV RNA. This model represents a useful tool for studying CHIKV pathogenesis in the acute and chronic stages of disease

    Distinct roles of interferon alpha and beta in controlling chikungunya virus replication and modulating neutrophil-mediated inflammation

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    Type I interferons (IFNs) are key mediators of the innate immune response. Although members of this family of cytokines signal through a single shared receptor, biochemical and functional variation exists in response to different IFN subtypes. While previous work has demonstrated that type I IFNs are essential to control infection by chikungunya virus (CHIKV), a globally emerging alphavirus, the contributions of individual IFN subtypes remain undefined. To address this question, we evaluated CHIKV pathogenesis in mice lacking IFN-Ī² (IFN-Ī² knockout [IFN-Ī²-KO] mice or mice treated with an IFN-Ī²-blocking antibody) or IFN-Ī± (IFN regulatory factor 7 knockout [IRF7-KO] mice or mice treated with a pan-IFN-Ī±-blocking antibody). Mice lacking either IFN-Ī± or IFN-Ī² developed severe clinical disease following infection with CHIKV, with a marked increase in foot swelling compared to wild-type mice. Virological analysis revealed that mice lacking IFN-Ī± sustained elevated infection in the infected ankle and in distant tissues. In contrast, IFN-Ī²-KO mice displayed minimal differences in viral burdens within the ankle or at distal sites and instead had an altered cellular immune response. Mice lacking IFN-Ī² had increased neutrophil infiltration into musculoskeletal tissues, and depletion of neutrophils in IFN-Ī²-KO but not IRF7-KO mice mitigated musculoskeletal disease caused by CHIKV. Our findings suggest disparate roles for the IFN subtypes during CHIKV infection, with IFN-Ī± limiting early viral replication and dissemination and IFN-Ī² modulating neutrophil-mediated inflammation

    Reduction of Catheter Associated Urinary Tract Infections (CAUTI) in a Critical Care Setting

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    Urinary tract infections (UTIs) are the most common type of healthcare associated infections. Seventy five percent are related to indwelling urinary catheters. These infections come with increased morbidity and mortality risk. A team of intensive care providers at a large academic tertiary medical center initiated a quality improvement project to reduce the number of CAUTIs. Baseline data established the total number of catheter days and CAUTIs by month. A subsequent root cause analysis was completed and several counter measures were developed to include a KPI implementation to track that all intensive care providers are educated in CAUTI and creation of a special care quality team. As a result of the countermeasure implementations, the number of CAUTIs has decreased. Next steps includes development and rollout of best practice indwelling urinary catheter maintenance

    Association of NCF2, IKZF1, IRF8, IFIH1, and TYK2 with Systemic Lupus Erythematosus

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    Systemic lupus erythematosus (SLE) is a complex trait characterised by the production of a range of auto-antibodies and a diverse set of clinical phenotypes. Currently, āˆ¼8% of the genetic contribution to SLE in Europeans is known, following publication of several moderate-sized genome-wide (GW) association studies, which identified loci with a strong effect (OR>1.3). In order to identify additional genes contributing to SLE susceptibility, we conducted a replication study in a UK dataset (870 cases, 5,551 controls) of 23 variants that showed moderate-risk for lupus in previous studies. Association analysis in the UK dataset and subsequent meta-analysis with the published data identified five SLE susceptibility genes reaching genome-wide levels of significance (Pcomb<5Ɨ10āˆ’8): NCF2 (Pcombā€Š=ā€Š2.87Ɨ10āˆ’11), IKZF1 (Pcombā€Š=ā€Š2.33Ɨ10āˆ’9), IRF8 (Pcombā€Š=ā€Š1.24Ɨ10āˆ’8), IFIH1 (Pcombā€Š=ā€Š1.63Ɨ10āˆ’8), and TYK2 (Pcombā€Š=ā€Š3.88Ɨ10āˆ’8). Each of the five new loci identified here can be mapped into interferon signalling pathways, which are known to play a key role in the pathogenesis of SLE. These results increase the number of established susceptibility genes for lupus to āˆ¼30 and validate the importance of using large datasets to confirm associations of loci which moderately increase the risk for disease

    Living Under Coronavirus and Injecting Drugs in Bristol (LUCID-B): a qualitative study of experiences of COVID-19 among people who inject drugs

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    BACKGROUND: : People who inject drugs (PWID) are a high-risk group for COVID-19 transmission and serious health consequences. Restrictions imposed in the UK in response to the pandemic led to rapid health and housing service alterations. We aimed to examine PWID experiences of: 1) challenges relating to the COVID-19 public health measures; 2) changes to opioid substitution therapy (OST) and harm reduction services; and 3) perceived effects of COVID-19 on drug use patterns and risk behaviour. METHODS: : Telephone semi-structured interviews were conducted with 28 PWID in Bristol, Southwest of England. Analysis followed a reflexive thematic analysis. RESULTS: : Concern about COVID-19 and adherence to public health guidance varied. Efforts made by services to continue providing support during the pandemic were appreciated and some changes were preferred, such as less frequent OST collection, relaxation of supervised consumption and needle and syringe programmes (NSP) home delivery. However, remote forms of contact were highlighted as less beneficial and more difficult to engage with than in-person contact. Public health guidance advising people to ā€˜stay homeā€™ led to increased isolation, boredom, and time to ruminate which impacted negatively on mental health. Lockdown restrictions directly impacted on sources of income and routine. Changes in drug use were explained as a consequence of isolation and fewer interactions with peers, problems accessing drugs, reduced drug purity and reduced financial resources. CONCLUSION: : This study captures the significant impacts and challenges of the COVID-19 pandemic on the lives of PWID. While rapid adaptations to service delivery to help mitigate the risks of COVID-19 were appreciated and some changes such as relaxation of supervised daily OST consumption were viewed positively, barriers to access need further attention. Going forwards there may be opportunities to harness the positive aspects of some changes to services
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