Ebola virus (EBOV) is highly pathogenic, with a predisposition to cause outbreaks in human populations accompanied by significant mortality. Owing to the lack of approved therapies, screening programmes of potentially efficacious drugs have been undertaken. One of these studies has demonstrated the possible utility of chloroquine against EBOV using pseudotyped assays. In mouse models of EBOV disease there are conflicting reports of the therapeutic effects of chloroquine. There are currently no reports of its efficacy using the larger and more stringent guinea pig model of infection. In this study we have shown that replication of live EBOV is impaired by chloroquine in vitro. However, no protective effects were observed in vivo when EBOV-infected guinea pigs were treated with chloroquine. These results advocate that chloroquine should not be considered as a treatment strategy for EBOV.
This paper explores the relevance of the Elaborated Social Identity Model of Crowd Behaviour and Procedural Justice Theory to an understanding of both the presence and absence of collective conflict during football (soccer) crowd events. It provides an analysis of data gathered during longitudinal ethnographic study of fans of Cardiff City Football Club-a group of supporters with a notorious history of involvement in 'hooliganism' within the English domestic Football Leagues. The analysis suggests that the perceived legitimacy among fans of the way they were policed affected the internal dynamics, patterns of collective action and overall levels of 'compliance' among the fan group. On this basis, we contend that these processes mediated both a long-term decline but also the sporadic reemergence of collective conflict during crowd events involving the fans. The paper concludes by exploring the implications of our analysis for informing policy, practice and theory, particularly with respect to the importance of policing with consent as a route to conflict reduction in domestic football.
Crimean-Congo Hemorrhagic Fever (CCHF) is a severe tick-borne disease, endemic in many countries in Africa, the Middle East, Eastern Europe and Asia. Between 15–70% of reported cases are fatal with no approved vaccine available. In the present study, the attenuated poxvirus vector, Modified Vaccinia virus Ankara, was used to develop a recombinant candidate vaccine expressing the CCHF virus nucleoprotein. Cellular and humoral immunogenicity was confirmed in 2 mouse strains, including type I interferon receptor knockout mice, which are susceptible to CCHF disease. Despite the immune responses generated post-immunisation, the vaccine failed to protect animals from lethal disease in a challenge model.
A key debate in late 1990s Britain is the "normalization" of illicit drug use among young people. This qualitative research study explores recreational drug use (mainly cannabis and cocaine) among an adult friendship network in an inner London neighborhood. It finds that the use of these drugs is accepted as a normal and routine aspect of daily life. In addition to patterns of drug consumption and drug dealing, some aspects of risk perception are also described. Adults are neglected in current UK drug policy debates. "Normal" adult recreational drug use poses the need for a new public health policy agenda for the new century.
Ferrets are widely used to study human influenza virus infection. Their airway physiology and cell receptor distribution makes them ideal for the analysis of pathogenesis and virus transmission, and for testing the efficacy of anti-influenza interventions and vaccines. The 2009 pandemic influenza virus (H1N1pdm09) induces mild to moderate respiratory disease in infected ferrets, following inoculation with 106 plaque-forming units (pfu) of virus. We have demonstrated that reducing the challenge dose to 102 pfu delays the onset of clinical signs by 1 day, and results in a modest reduction in clinical signs, and a less rapid nasal cavity innate immune response. There was also a delay in virus production in the upper respiratory tract, this was up to 9-fold greater and virus shedding was prolonged. Progression of infection to the lower respiratory tract was not noticeably delayed by the reduction in virus challenge. A dose of 104 pfu gave an infection that was intermediate between those of the 106 pfu and 102 pfu doses. To address the hypothesis that using a more authentic low challenge dose would facilitate a more sensitive model for antiviral efficacy, we used the well-known neuraminidase inhibitor, oseltamivir. Oseltamivir-treated and untreated ferrets were challenged with high (106 pfu) and low (102 pfu) doses of influenza H1N1pdm09 virus. The low dose treated ferrets showed significant delays in innate immune response and virus shedding, delayed onset of pathological changes in the nasal cavity, and reduced pathological changes and viral RNA load in the lung, relative to untreated ferrets. Importantly, these observations were not seen in treated animals when the high dose challenge was used. In summary, low dose challenge gives a disease that more closely parallels the disease parameters of human influenza infection, and provides an improved pre-clinical model for the assessment of influenza therapeutics, and potentially, influenza vaccines.
Drawing on four `tales from the field', provided one each by the authors, this article examines the ethical and moral dilemmas ethnographers can face during their research. In particular, we address two key questions. First, what does being ethical actually involve? Second, is there a moral duty owed by researchers and, if so, to whom is this duty owed? The article reviews current debates over ethics in ethnographic research, specifically the responsibilities of the researcher to his/her research subjects, before turning to the four `tales from the field'. These tales form the basis for a discussion of a researcher's ethical responsibilities when confronted with wrongdoing, in different forms, in the course of their fieldwork.
A key feature of Mycobacterium tuberculosis is its ability to become dormant in the host. Little is known of the mechanisms by which these bacilli are able to persist in this state. Therefore, the focus of this study was to emulate environmental conditions encountered by M. tuberculosis in the granuloma, and determine the effect of such conditions on the physiology and infectivity of the organism. Non-replicating persistent (NRP) M. tuberculosis was established by the gradual depletion of nutrients in an oxygen-replete and controlled environment. In contrast to rapidly dividing bacilli, NRP bacteria exhibited a distinct phenotype by accumulating an extracellular matrix rich in free mycolate and lipoglycans, with increased arabinosylation. Microarray studies demonstrated a substantial down-regulation of genes involved in energy metabolism in NRP bacteria. Despite this reduction in metabolic activity, cells were still able to infect guinea pigs, but with a delay in the development of disease when compared to exponential phase bacilli. Using these approaches to investigate the interplay between the changing environment of the host and altered physiology of NRP bacteria, this study sheds new light on the conditions that are pertinent to M. tuberculosis dormancy and how this organism could be establishing latent disease.
This paper provides a detailed case study of a small, but extremely busy, 'middle market' drug distribution network in the North of England. It derives from a larger
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