Clinical evaluation of tuberculosis viability microscopy for assessing treatment response

Background. It is difficult to determine whether early tuberculosis treatment is effective in reducing the infectiousness of patients' sputum, because culture takes weeks and conventional acid-fast sputum microscopy and molecular tests cannot differentiate live from dead tuberculosis. Methods. To assess treatment response, sputum samples (n = 124) from unselected patients (n = 35) with sputum microscopy–positive tuberculosis were tested pretreatment and after 3, 6, and 9 days of empiric first-line therapy. Tuberculosis quantitative viability microscopy with fluorescein diacetate, quantitative culture, and acid-fast auramine microscopy were all performed in triplicate. Results. Tuberculosis quantitative viability microscopy predicted quantitative culture results such that 76% of results agreed within ±1 logarithm (r(S) = 0.85; P < .0001). In 31 patients with non-multidrug-resistant (MDR) tuberculosis, viability and quantitative culture results approximately halved (both 0.27 log reduction, P < .001) daily. For patients with non-MDR tuberculosis and available data, by treatment day 9 there was a >10-fold reduction in viability in 100% (24/24) of cases and quantitative culture in 95% (19/20) of cases. Four other patients subsequently found to have MDR tuberculosis had no significant changes in viability (P = .4) or quantitative culture (P = .6) results during early treatment. The change in viability and quantitative culture results during early treatment differed significantly between patients with non-MDR tuberculosis and those with MDR tuberculosis (both P < .001). Acid-fast microscopy results changed little during early treatment, and this change was similar for non-MDR tuberculosis vs MDR tuberculosis (P = .6). Conclusions. Tuberculosis quantitative viability microscopy is a simple test that within 1 hour predicted quantitative culture results that became available weeks later, rapidly indicating whether patients were responding to tuberculosis therapy

Angiotensin II receptor blockade alleviates calcineurin inhibitor nephrotoxicity by restoring cyclooxygenase 2 expression in kidney cortex

Aim: The use of calcineurin inhibitors such as cyclosporine A (CsA) for immunosuppression after solid organ transplantation is commonly limited by renal side effects. CsA-induced deterioration of glomerular filtration rate and sodium retention may be related to juxtaglomerular dysregulation as a result of suppressed cyclooxygenase 2 (COX-2) and stimulated renin biosynthesis. We tested whether CsA-induced COX-2 suppression is caused by hyperactive renin-angiotensin system (RAS) and whether RAS inhibition may alleviate the related side effects. Methods: Rats received CsA, the RAS inhibitor candesartan, or the COX-2 inhibitor celecoxib acutely (3 days) or chronically (3 weeks). Molecular pathways mediating effects of CsA and RAS on COX-2 were studied in cultured macula densa cells. Results: Pharmacological or siRNA-mediated calcineurin inhibition in cultured cells enhanced COX-2 expression via p38 mitogen-activated protein kinase and NF-kB signalling, whereas angiotensin II abolished these effects. Acute and chronic CsA administration to rats led to RAS activation along with reduced cortical COX-2 expression, creatinine clearance and fractional sodium excretion. Evaluation of major distal salt transporters, NKCC2 and NCC, showed increased levels of their activating phosphorylation upon CsA. Concomitant candesartan treatment blunted these effects acutely and completely normalized the COX-2 expression and renal functional parameters at long term. Celecoxib prevented the candesartan-induced improvements of creatinine clearance and sodium excretion. Conclusion: Suppression of juxtaglomerular COX-2 upon CsA results from RAS activation, which overrides the cell-autonomous, COX-2-stimulatory effects of calcineurin inhibition. Angiotensin II antagonism alleviates CsA nephrotoxicity via the COX-2-dependent normalization of creatinine clearance and sodium excretion

Gravitational lensing in the Kerr-Randers optical geometry

A new geometric method to determine the deflection of light in the equatorial plane of the Kerr solution is presented, whose optical geometry is a surface with a Finsler metric of Randers type. Applying the Gauss-Bonnet theorem to a suitable osculating Riemannian manifold, adapted from a construction by Naz\i m, it is shown explicitly how the two leading terms of the asymptotic deflection angle of gravitational lensing can be found in this way.Comment: 7 pages, 1 figure. Accepted by Gen. Rel. Grav. Version 2: change of notation in sec.

Alternative approaches to achieving community safety and well-being across law enforcement and criminal justice: Western European findings

This paper provides the results from Western Europe of a wider project (Envisaging the Future of Policing and Public Health Globally) for the Global Law Enforcement and Public Health Association (GLEPHA) which aimed to identify policing and public health alternative initiatives to provide community safety and well-being. A desktop review of projects that included evaluation evidence and/or impact of innovative delivery were selected for the study. The criteria allowed the inclusion of international, national, regional, and local initiatives that fit the broader aims of the global “envisaging the future” GLEPHA project. In total, 41 projects were reviewed with varying levels of information on approach and evaluation. Data capture recorded the country, location, funder details, themes (e.g., violence, mental health, drugs), key words, program descriptions, and any links and key findings from evaluation studies. A number of key themes, drivers, and challenges were identified in collaborative work between policing and public health. These included elements of communication and generating a shared language, the need for evaluation to be embedded in the project plan and mobilisation, and the problems with “hot-topic” issues and short-term funding. This paper also outlines two case studies of projects within Western Europe: Violence Reduction Units in the United Kingdom, and the Stockholm prevents Alcohol and Drug Problems (STAD). Key aspects of these projects are presented and the successes and potential challenges discussed. Key recommendations regarding the future of law enforcement and public health–related initiatives are discussed

In search of a working notion of lex sportiva

The emergence of a lex specialis regime and its interaction with the established, governing lex generalis in their overlapping spheres of application is always an intriguing legal relationship to explore. In this article, the focus will be on the development of legal principles and rules that have been/can be collectively described as lex sportiva. However, it is notable that those involved in the consideration, usage and application of this notion have not agreed as to the scope and delimitation of the concept. It is debated whether lex sportiva exists in the first place, its legal sources and its purpose. The risk is for the concept becoming redundant when not vilified as a hidden strategy to exclude non-sports-related law from the ambit of sport. Through an examination of the different propositions to the framework of the term, this article will shed light on the existence, utility and limits of the development of this conceptualisation