64 research outputs found

    Surgery for scapula process fractures: Good outcome in 26 patients

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    Background Generally, scapula process fractures (coracoid and acromion) have been treated nonoperatively with favorable outcome, with the exception of widely displaced fractures. Very little has been published, however, regarding the operative management of such fractures and the literature that is available involves very few patients. Our hypothesis was that operative treatment of displaced acromion and coracoid fractures is a safe and effective treatment that yields favorable surgical results

    Genotypic Diversity Is Associated with Clinical Outcome and Phenotype in Cryptococcal Meningitis across Southern Africa.

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    Cryptococcal meningitis is a major cause of mortality throughout the developing world, yet little is known about the genetic markers underlying Cryptococcal virulence and patient outcome. We studied a cohort of 230 Cryptococcus neoformans (Cn) isolates from HIV-positive South African clinical trial patients with detailed clinical follow-up using multi-locus sequence typing and in vitro phenotypic virulence assays, correlating these data with clinical and fungal markers of disease in the patient. South African Cn displayed high levels of genetic diversity and locus variability compared to globally distributed types, and we identified 50 sequence types grouped within the main molecular types VNI, VNII and VNB, with 72% of isolates typed into one of seven 'high frequency' sequence types. Spatial analysis of patients' cryptococcal genotype was not shown to be clustered geographically, which might argue against recent local acquisition and in favour of reactivation of latent infection. Through comparison of MLST genotyping data with clinical parameters, we found a relationship between genetic lineage and clinical outcome, with patients infected with the VNB lineage having significantly worse survival (n=8, HR 3.35, CI 1.51-7.20, p=0.003), and this was maintained even after adjustment for known prognostic indicators and treatment regimen. Comparison of fungal genotype with in vitro phenotype (phagocytosis, laccase activity and CSF survival) performed on a subset of 89 isolates revealed evidence of lineage-associated virulence phenotype, with the VNII lineage displaying increased laccase activity (p=0.001) and ex vivo CSF survival (p=0.0001). These findings show that Cryptococcus neoformans is a phenotypically heterogeneous pathogen, and that lineage plays an important role in cryptococcal virulence during human infection. Furthermore, a detailed understanding of the genetic diversity in Southern Africa will support further investigation into how genetic diversity is structured across African environments, allowing assessment of the risks different ecotypes pose to infection

    A Live-Attenuated HSV-2 ICP0− Virus Elicits 10 to 100 Times Greater Protection against Genital Herpes than a Glycoprotein D Subunit Vaccine

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    Glycoprotein D (gD-2) is the entry receptor of herpes simplex virus 2 (HSV-2), and is the immunogen in the pharmaceutical industry's lead HSV-2 vaccine candidate. Efforts to prevent genital herpes using gD-2 subunit vaccines have been ongoing for 20 years at a cost in excess of $100 million. To date, gD-2 vaccines have yielded equivocal protection in clinical trials. Therefore, using a small animal model, we sought to determine if a live-attenuated HSV-2 ICP0− virus would elicit better protection against genital herpes than a gD-2 subunit vaccine. Mice immunized with gD-2 and a potent adjuvant (alum+monophosphoryl lipid A) produced high titers of gD-2 antibody. While gD-2-immunized mice possessed significant resistance to HSV-2, only 3 of 45 gD-2-immunized mice survived an overwhelming challenge of the vagina or eyes with wild-type HSV-2 (MS strain). In contrast, 114 of 115 mice immunized with a live HSV-2 ICP0− virus, 0ΔNLS, survived the same HSV-2 MS challenges. Likewise, 0ΔNLS-immunized mice shed an average 125-fold less HSV-2 MS challenge virus per vagina relative to gD-2-immunized mice. In vivo imaging demonstrated that a luciferase-expressing HSV-2 challenge virus failed to establish a detectable infection in 0ΔNLS-immunized mice, whereas the same virus readily infected naïve and gD-2-immunized mice. Collectively, these results suggest that a HSV-2 vaccine might be more likely to prevent genital herpes if it contained a live-attenuated HSV-2 virus rather than a single HSV-2 protein

    2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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    Neurostimulation, doping, and the spirit of sport

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    There is increasing interest in using neuro-stimulation devices to achieve an ergogenic effect in elite athletes. Although the World Anti-Doping Authority (WADA) does not currently prohibit neuro-stimulation techniques, a number of researchers have called on WADA to consider its position on this issue. Focusing on trans-cranial direct current stimulation (tDCS) as a case study of an imminent so-called ‘neuro-doping’ intervention, we argue that the emerging evidence suggests that tDCS may meet WADA’s own criteria (pertaining to safety, performance-enhancing effect, and incompatibility with the ‘spirit of sport’) for a method’s inclusion on its list of prohibited substances and methods. We begin by surveying WADA’s general approach to doping, and highlight important limitations to the current evidence base regarding the performance-enhancing effect of pharmacological doping substances. We then review the current evidence base for the safety and efficacy of tDCS, and argue that despite significant shortcomings, it may be sufficient for WADA to consider prohibiting tDCS, in light of the comparable flaws in the evidence base for pharmacological doping substances. In the second half of the paper, we argue that the question of whether WADA ought to ban tDCS turns significantly on the question of whether it is compatible with the ‘spirit of sport’ criterion. We critique some of the previously published positions on this, and advocate our own sport-specific and application-specific approach. Despite these arguments, we finally conclude by suggesting that tDCS ought to be monitored rather than prohibited due to compelling non-ideal considerations

    General Didactics and Instructional Design: eyes like twins A transatlantic dialogue about similarities and differences, about the past and the future of two sciences of learning and teaching

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    State of the Climate in 2016

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