13 research outputs found

    Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

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    The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

    Advancing Drug Innovation for Neglected Diseases—Criteria for Lead Progression

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    The current drug R&D pipeline for most neglected diseases remains weak, and unlikely to support registration of novel drug classes that meet desired target product profiles in the short term. This calls for sustained investment as well as greater emphasis in the risky upstream drug discovery. Access to technologies, resources, and strong management as well as clear compound progression criteria are factors in the successful implementation of any collaborative drug discovery effort. We discuss how some of these factors have impacted drug discovery for tropical diseases within the past four decades, and highlight new opportunities and challenges through the virtual North–South drug discovery network as well as the rationale for greater participation of institutions in developing countries in product innovation. A set of criteria designed to facilitate compound progression from screening hits to drug candidate selection is presented to guide ongoing efforts

    Integrated dataset of screening hits against multiple neglected disease pathogens.

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    New chemical entities are desperately needed that overcome the limitations of existing drugs for neglected diseases. Screening a diverse library of 10,000 drug-like compounds against 7 neglected disease pathogens resulted in an integrated dataset of 744 hits. We discuss the prioritization of these hits for each pathogen and the strong correlation observed between compounds active against more than two pathogens and mammalian cell toxicity. Our work suggests that the efficiency of early drug discovery for neglected diseases can be enhanced through a collaborative, multi-pathogen approach

    Optical techniques for detecting and identifying biological-warfare agents

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    Rapid and accurate detection and identification of biological agents is an objective of various national security programs. Detection in general is difficult owing to natural clutter and anticipated low concentrations of subject material. Typical detection architectures comprise a nonspecific trigger, a rapid identifier, and a confirming step, often in a laboratory. High-confidence identification must be made prior to taking action, though this must be traded against regrets stemming from delay. Sensing requirements are best established by positing plausible scenarios, two of which are suggested herein. Modern technologies include the use of elastic scatter and ultraviolet laser-induced fluorescence for triggering and standoff detection. Optical and nonoptical techniques are used routinely in analyzing clinical samples used to confirm infection and illness resulting from a biological attack. Today, environmental sensing serves at best as an alert to medical authorities for possible action, which would include sample collection and detailed analysis. This paper surveys the state of the art of sensing at all levels.United States. Dept. of the Air Force (Contract FA8721-05-C-0002)United States. Defense Threat Reduction AgencyUnited States. Dept. of Homeland Securit

    Focal laser ablation as clinical treatment of prostate cancer: Report from a Delphi consensus project

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    Purpose: To define the role of focal laser ablation (FLA) as clinical treatment of prostate cancer (PCa) using the Delphi consensus method. Methods: A panel of international experts in the field of focal therapy (FT) in PCa conducted a collaborative consensus project using the Delphi method. Experts were invited to online questionnaires focusing on patient selection and treatment of PCa with FLA during four subsequent rounds. After each round, outcomes were displayed, and questionnaires were modified based on the comments provided by panelists. Results were finalized and discussed during face-to-face meetings. Results: Thirty-seven experts agreed to participate, and consensus was achieved on 39/43 topics. Clinically significant PCa (csPCa) was defined as any volume Grade Group 2 [Gleason score (GS) 3+4]. Focal therapy was specified as treatment of all csPCa and can be considered primary treatment as an alternative to radical treatment in carefully selected patients. In patients with intermediate-risk PCa (GS 3+4) as well as patients with MRI-visible and biopsy-confirmed local recurrence, FLA is optimal for targeted ablation of a specific magnetic resonance imaging (MRI)-visible focus. However, FLA should not be applied to candidates for active surveillance and close follow-up is required. Suitability for FLA is based on tumor volume, location to vital structures, GS, MRI-visibility, and biopsy confirmation. Conclusion: Focal laser ablation is a promising technique for treatment of clinically localized PCa and should ideally be performed within approved clinical trials. So far, only few studies have reported on FLA and further validation with longer follow-up is mandatory before widespread clinical implementation is justified

    Using evaluation to create 'provisional stabilities': bridging innovation in Higher Education change processes.

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    This article reports the evaluation experience in two SOCRATES (European Union funding mechanism designed to support innovation in teaching and learning) projects focused on change in higher education. The projects were international in scope involving six countries and ten institutions within the last four years. The article reflects on change in institutions specifically, especially those introduced by the use of information and communication technologies, and it suggests the hypothesis that in such a phase of transition, new rules are not yet established and a state of anomie can occur at the level of courses, departments and institutions. The article details what happens in educational institutions in which rules and practices are well established and validated and a new event radically changes or challenges the traditional practices. Instead of the psycho-social notion of ‘resistance to change’, the theory of Durkheim and followers that analyses human responses in times of social change may be of use to interpret situations in which change or the will to change creates conflicting systems of rules and practices. The article will argue for a crucial role for evaluation in negotiating such periods of change
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