Testing for sexually transmitted infections in general practice: cross-sectional study

Background: Primary care is an important provider of sexual health care in England. We sought to explore the extent of testing for chlamydia and HIV in general practice and its relation to associated measures of sexual health in two contrasting geographical settings.Methods: We analysed chlamydia and HIV testing data from 64 general practices and one genitourinary medicine (GUM) clinic in Brent (from mid-2003 to mid-2006) and 143 general practices and two GUM clinics in Avon (2004). We examined associations between practice testing status, practice characteristics and hypothesised markers of population need (area level teenage conception rates and Index of Multiple Deprivation, IMD scores).Results: No HIV or chlamydia testing was done in 19% (12/64) of general practices in Brent, compared to 2.1% (3/143) in Avon. In Brent, the mean age of general practitioners (GPs) in Brent practices that tested for chlamydia or HIV was lower than in those that had not conducted testing. Practices where no HIV testing was done had slightly higher local teenage conception rates (median 23.5 vs. 17.4/1000 women aged 15-44, p = 0.07) and served more deprived areas (median IMD score 27.1 vs. 21.8, p = 0.05). Mean yearly chlamydia and HIV testing rates, in practices that did test were 33.2 and 0.6 (per 1000 patients aged 15-44 years) in Brent, and 34.1 and 10.3 in Avon, respectively. In Brent practices only 20% of chlamydia tests were conducted in patients aged under 25 years, compared with 39% in Avon.Conclusions: There are substantial geographical differences in the intensity of chlamydia and HIV testing in general practice. Interventions to facilitate sexually transmitted infection and HIV testing in general practice are needed to improve access to effective sexual health care. The use of routinely-collected laboratory, practice-level and demographic data for monitoring sexual health service provision and informing service planning should be more widely evaluated

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals

Consumo e gênero: uma revisão da produção historiográfica recente sobre a América Latina no século XX

A partir de una revisión de la producción historiográfica reciente que estudia el siglo XX, este artículo muestra la relevancia del género para la construcción de una historia del consumo en América Latina. Con este objetivo, se enfoca el análisis en tres líneas de investigación que, desde una aproximación interseccional, aportan nuevas miradas y preguntas: la primera destaca la dimensión política del consumo, centrándose en la relación entre género y clase; la segunda aborda consumo y trabajo doméstico, señalando el vínculo entre género y nación; y la tercera analiza cultura material y corporalidades, destacando la articulación entre género y edad.Starting from a recent historiographical production’s revision studying the 20th Century, this article depicts the relevance of gender for the history of consumption-building in Latin America. Bearing that in mind, the analysis is geared to three researching lines, contributing with new perspectives and questions, as from an inter sectorial approach: the first one highlights the political dimension of consumption based upon the interaction between gender and class; the second addresses consumption and domestic work, displaying a link between gender and nation, and the third one analyses material culture and corporality emphasizing upon the articulation between gender and age.A partir de uma revisão da produção historiográfica recente que estuda o século XX, este artigo mostra a relevância do gênero para a construção de uma história do consumo na América Latina. Com esse objetivo, a análise está focada em três linhas de pesquisa que, sob uma aproximação interseccional, contribuem com novos olhares e perguntas: a primeira destaca a dimensão política do consumo e foca-se na relação gênero e classe; a segunda aborda consumo e trabalho doméstico, e sinaliza o vínculo entre gênero e nação; a terceira analisa cultura material e corporalidade, e destaca a articulação entre gênero e idade.Fil: Pérez, Inés. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Sociologia; Argentina. Universidad Nacional de Mar del Plata. Facultad de Humanidades. Departamento de Historia. Centro de Estudios Históricos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentin

Identifying cancer-associated leukocyte profiles using high-resolution flow cytometry screening and machine learning

BackgroundMachine learning (ML) is a valuable tool with the potential to aid clinical decision making. Adoption of ML to this end requires data that reliably correlates with the clinical outcome of interest; the advantage of ML is that it can model these correlations from complex multiparameter data sets that can be difficult to interpret conventionally. While currently available clinical data can be used in ML for this purpose, there exists the potential to discover new “biomarkers” that will enhance the effectiveness of ML in clinical decision making. Since the interaction of the immune system and cancer is a hallmark of tumor establishment and progression, one potential area for cancer biomarker discovery is through the investigation of cancer-related immune cell signatures. Hence, we hypothesize that blood immune cell signatures can act as a biomarker for cancer progression.MethodsTo probe this, we have developed and tested a multiparameter cell-surface marker screening pipeline, using flow cytometry to obtain high-resolution systemic leukocyte population profiles that correlate with detection and characterization of several cancers in murine syngeneic tumor models.ResultsWe discovered a signature of several blood leukocyte subsets, the most notable of which were monocyte subsets, that could be used to train CATboost ML models to predict the presence and type of cancer present in the animals.ConclusionsOur findings highlight the potential utility of a screening approach to identify robust leukocyte biomarkers for cancer detection and characterization. This pipeline can easily be adapted to screen for cancer specific leukocyte markers from the blood of cancer patient

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Origins and Outcomes of Electoral Institutions in African Hybrid Regimes: A Comparative Perspective

In the early 1990s most African countries carried out extensive reforms of their electoral regimes. Adopting a historical institutionalist approach, this paper critically examines the role of institutional path dependence in accounting for the setup of six African electoral regimes. For this purpose, we distinguish between different types of path dependence. The paper further analyzes the extent to which the development of electoral institutions contributed to the regime-type outcome (democratic/hybrid/autocratic). The main emphasis herein is on so-called hybrid regimes; in other words, regimes existing in the grey zone between democracy and autocracy. The paper finds that, while institutional path dependence has a limited but important impact on the setup of the electoral regimes, it is ultimately the process of decision-making during critical junctures that accounts for the regime type outcome. Hybrid regimes lack long-term institutional ownership