Expert assessments of strategies to enhance global nuclear security

Historically, the U.S. has sought to use commercial trade in nuclear technologies to influence international nuclear security standards and promote nonproliferation. Concern has grown that, with a stagnating domestic nuclear industry and declining export industry, the U.S. will lose a significant tool of foreign policy and leverage in maintaining strong international standards. While the issue has been discussed extensively in the policy community and used as a powerful rhetorical tool to motivate tangentially related policies such as subsidizing existing U.S. nuclear plants, no one has systematically assessed the issue, structured the problem and proposed and evaluated potential solutions. Here we briefly analyze the current international state of play, and then outline a set of specific strategies the U.S. might adopt on its own, or promote internationally, to retain its influence. Building on the literature, nuclear security and nuclear power experts assisted us in framing the issues and then, in a participatory workshop, helped us to assess and refine possible strategies. While not all experts agreed that U.S. influence has already declined, most indicated that it likely would decline in the future if present domestic and international trends continue. Although none of the proposed strategies that we advanced or that the experts suggested are likely to be effective in the short term, several warrant ongoing refinements and, if they can be implemented, might have beneficial impacts in coming decades

Antibiotic microbial assay using kinetic-reading microplate system

The aim of this study was to determine the optimal experimental conditions to develop a methodology for microbiological assay of apramycin employing microplate and kinetic reading mode, and to validate the developed method, through evaluation of parameters of selectivity, linearity, linear range, limits of detection and quantification, accuracy and precision. The turbidimetric assay principle is simple: the test solution is added to a suspension of test microorganism in culture media, the mixture is incubated under appropriate conditions and the microbial growth is measured by photometric reading. Microplate with kinetic reading mode employed in antibiotic assay is of considerable interest since it allows reduction of material and analysis time and enables a large number of samples to be analyzed simultaneously, with automated reading and calculating. Established conditions considered the standard-curve of apramycin at concentrations from 5.0 to 35.0 &#956;g mL-1, and tryptic soy broth inoculated with 5% Escherichia coli (ATCC 8739) suspension. Satisfactory results were obtained with 2 hours of incubation. The developed method showed appropriate selectivity, linearity in the range from 5.0 to 35.0 &#956;g mL-1, limits of detection and quantification of 0.1 and 0.4 &#956;g mL-1, respectively, as well as satisfactory accuracy (recuperation = 98.5%) and precision (RSD = 6.0%). Microplate assay combined the characteristics of microbiological (evaluation of antibiotic activity against sensitive test microorganism) and physico-chemical (operationally straightforward and faster results) assays.<br>O objetivo deste trabalho é determinar as condições experimentais ideais para o desenvolvimento de metodologia para a dosagem microbiológica de apramicina empregando microplacas e modo de leitura cinético e validar o método desenvolvido, através da avaliação dos parâmetros de especificidade e seletividade, linearidade, faixa ou intervalo linear, limite de detecção e quantificação, exatidão e precisão. O ensaio turbidimétrico é simples: a solução-teste é adicionada à suspensão de microrganismo-teste em meio de cultura, a mistura é incubada em condições apropriadas e o crescimento microbiano é medido por meio de leitura fotométrica. O emprego de método de microplacas com leitura cínética para a dosagem de antibióticos é de interesse considerável, uma vez que possibilita reduzir quantidade de material e tempo de análise necessários e permite o ensaio de grande número de amostras simultaneamente, com leitura e cálculo automatizados. As condições estabelecidas abrangem curva-padrão de apramicina com concentrações entre 5 e 35 &#956;g/mL, e emprego de meio de cultura caldo de triptona-soja inoculado com Escherichia coli (ATCC 8739) na proporção de 5%. Foram obtidos resultados satisfatórios após 2 horas de incubação. O método desenvolvido apresentou especificidade e seletividade adequadas, linearidade na faixa de 5 a 35 &#956;g/mL, limite de detecção e quantificação de 0,1 e 0,4 &#956;g/mL, respectivamente, exatidão (recuperação = 98,5%) e precisão (DPR = 6,0%) satisfatórias. O ensaio em microplaca agrega características dos ensaios microbiológicos (avaliação da atividade do antibiótico frente a microrganismo-teste sensível) e físico-químicos (facilidade operacional e maior rapidez na obtenção dos resultados)

Finding genetically-supported drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome

Parkinson’s disease is a neurodegenerative movement disorder that currently has no disease-modifying treatment, partly owing to inefficiencies in drug target identification and validation. We use Mendelian randomization to investigate over 3,000 genes that encode druggable proteins and predict their efficacy as drug targets for Parkinson’s disease. We use expression and protein quantitative trait loci to mimic exposure to medications, and we examine the causal effect on Parkinson’s disease risk (in two large cohorts), age at onset and progression. We propose 23 drug-targeting mechanisms for Parkinson’s disease, including four possible drug repurposing opportunities and two drugs which may increase Parkinson’s disease risk. Of these, we put forward six drug targets with the strongest Mendelian randomization evidence. There is remarkably little overlap between our drug targets to reduce Parkinson’s disease risk versus progression, suggesting different molecular mechanisms. Drugs with genetic support are considerably more likely to succeed in clinical trials, and we provide compelling genetic evidence and an analysis pipeline to prioritise Parkinson’s disease drug development