Plos One
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The emergence of Mycobacterium tuberculosis strains resistant to current first-line antibiotic regimens constitutes a major global health threat. New treatments against multidrug-resistant tuberculosis (MDR-TB) are thus eagerly needed in particular in countries with a high MDR-TB prevalence. In this context, macozinone (PBTZ169), a promising drug candidate with an unique mode of action and highly potent in vitro tuberculocidal properties against MDR Mycobacterium strains, has now reached the clinical phase and has been notably tested in healthy male volunteers in Switzerland. ⋯ The overall methodology was fully validated according to current recommendations (FDA, EMEA) for bioanalytical methods, which include selectivity, carryover, qualitative and quantitative matrix effect, extraction recovery, process efficiency, trueness, precision, accuracy profiles, method and instrument detection limits, integrity to dilution, anticoagulant comparison and short- and long-term stabilities. Stability studies on the reduced metabolite H2-PBTZ169 have shown no significant impact on the actual PBTZ169 concentrations determined with the proposed assay. This simplified, rapid, sensitive and robust methodology has been applied to the bioanalysis of human plasma samples collected within the frame of a phase I clinical study in healthy volunteers receiving PBTZ169.
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Comparative Study
A comparative study on machine learning based algorithms for prediction of motorcycle crash severity.
Motorcycle crash severity is under-researched in Ghana. Thus, the probable risk factors and association between these factors and motorcycle crash severity outcomes is not known. Traditional statistical models have intrinsic assumptions and pre-defined correlations that, if flouted, can generate inaccurate results. ⋯ Also, the relative importance analysis of the attribute was conducted to determine the impact of these attributes on injury severity outcomes. The results of the study reveal that the predictions of machine learning algorithms are superior to the MNLM in accuracy and effectiveness, and the RF-based algorithms show the overall best agreement with the experimental data out of the three machine learning algorithms, for its global optimization and extrapolation ability. Location type, time of the crash, settlement type, collision partner, collision type, road separation, road surface type, the day of the week, and road shoulder condition were found as the critical determinants of motorcycle crash injury severity.
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Data on initiation and utilization of direct-acting antiviral therapies for hepatitis C virus infection in the United States are limited. This study evaluated treatment initiation, time to treatment, and real-world effectiveness of direct-acting antiviral therapy in individuals with hepatitis C virus infection treated during the first 2 years of availability of all-oral direct-acting antiviral therapies. ⋯ In the early years of the direct-acting antiviral era, <10% of people diagnosed with chronic hepatitis C virus infection received direct-acting antiviral treatment; median time to treatment initiation was 300 days. Future analyses should evaluate time to treatment initiation among those with less advanced fibrosis.
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Black men who have sex with men, who account for less than 1% of the U.S. population, account for approximately 25% of new HIV infections annually. Condomless anal sex contributes to HIV infection among black men who have sex with men. The capacity to recover quickly from difficulties (resilience) may be protective against condomless anal sex, but has been understudied among black men who have sex with men. Psychosocial factors related to resilience, i.e., condom use self-efficacy and internalized homophobia, may also affect condomless anal sex. We assessed the association between resilience, condom use self-efficacy, internalized homophobia and condomless anal sex among black men who have sex with men. ⋯ Within this sample of black men who have sex with men, condomless anal sex was prevalent. Greater resilience was not protective against condomless anal sex. Interventions that support condom use are warranted for black men who have sex with men.
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Positive fluid balance is a prognostic factor for mortality in patients with sepsis; however, the association between cumulated fluid balance (CFB) and sepsis-induced multi-organ dysfunction syndrome (MODS) has yet to be elucidated. In this study, we sought to determine whether CFB is correlated with MODS and mortality in cases of septic shock. ⋯ 72-hr CFB appears to be correlated with the likelihood of developing MODS and mortality in patients with septic shock. Thus, it appears that 72-hr CFB could perhaps be used as an indicator for MODS and a predictor for mortality in those patients.