Defining the optimal dose of rifapentine for pulmonary tuberculosis: Exposure-response relations from two phase II clinical trials.

Rifapentine is a highly active antituberculosis antibiotic with treatment-shortening potential; however, exposure-response relations and the dose needed for maximal bactericidal activity have not been established. We used pharmacokinetic/pharmacodynamic data from 657 adults with pulmonary tuberculosis participating in treatment trials to compare rifapentine (n = 405) with rifampin (n = 252) as part of intensive-phase therapy. Population pharmacokinetic/pharmacodynamic analyses were performed with nonlinear mixed-effects modeling. Time to stable culture conversion of sputum to negative was determined in cultures obtained over 4 months of therapy. Rifapentine exposures were lower in participants who were coinfected with human immunodeficiency virus, black, male, or fasting when taking drug. Rifapentine exposure, large lung cavity size, and geographic region were independently associated with time to culture conversion in liquid media. Maximal treatment efficacy is likely achieved with rifapentine at 1,200 mg daily. Patients with large lung cavities appear less responsive to treatment, even at high rifapentine doses

Investigating Executive Working Memory and Phonological Short-Term Memory in Relation to Fluency and Self-Repair Behavior in L2 Speech

This paper reports the findings of a study investigating the relationship of executive working memory (WM) and phonological short-term memory (PSTM) to fluency and self-repair behavior during an unrehearsed oral task performed by second language (L2) speakers of English at two levels of proficiency, elementary and lower intermediate. Correlational analyses revealed a negative relationship between executive WM and number of pauses in the lower intermediate L2 speakers. However, no reliable association was found in our sample between executive WM or PSTM and self-repair behavior in terms of either frequency or type of self-repair. Taken together, our findings suggest that while executive WM may enhance performance at the conceptualization and formulation stages of the speech production process, self-repair behavior in L2 speakers may depend on factors other than working memory

Exploring the time and frequency domain connectedness of oil prices and metal prices

© 2019 Elsevier Ltd This paper explores the time and frequency domain connectedness between oil prices and metal prices for the period of 1980M1-2017M5. We employ DECO-GARCH model for equi-correlation among commodity under consideration, Diebold and Yilmaz (2014), for time domain, and Barunik and Krehlik (2017), for frequency domain (i.e., frequencies considered are: 1–4 months, 4–8 months, 8–15 months and more than 15 months) connectedness measures. The dynamic connectedness is examined by applying a rolling window method in time and frequency domain. Besides, network plots are also made based on the pair-wise net connectedness between the variables. The results for time domain analysis show that the overall connectedness of the system has been just 3.39%. The empirical results of frequency domain connectedness show that total connectedness varies at different frequencies. The maximum contribution is observed at short-term frequency, (1–4 months; 1.65%) and the lowest contribution at medium-term frequency (8–15 months; 0.45%.). The contribution from the highest frequency, which corresponds to more than 15 months’ period, is just 0.56%. The network analysis shows that Zinc is net receiver

Inhibition, flexibility, working memory and planning in autism spectrum disorders with and without comorbid ADHD-symptoms

<p>Abstract</p> <p>Background</p> <p>Recent studies have not paid a great deal of attention to comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms in autistic children even though it is well known that almost half of children with autism spectrum disorder (ASD) suffer from hyperactivity, inattention and impulsivity. The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD.</p> <p>Methods</p> <p>Children aged 6 to 18 years old with ADHD (n = 20) or ASD (High-Functioning autism or Asperger syndrome) with (n = 20) and without (n = 20) comorbid ADHD and a typically developing group (n = 20) were compared on a battery of EF tasks comprising inhibition, flexibility, working memory and planning tasks. A MANOVA, effect sizes as well as correlations between ADHD-symptomatology and EF performance were calculated. Age- and IQ-corrected z scores were used.</p> <p>Results</p> <p>There was a significant effect for the factor group (F = 1.55; dF = 42; p = .02). Post-hoc analysis revealed significant differences between the ADHD and the TD group on the inhibition task for false alarms (p = .01) and between the ADHD group, the ASD+ group (p = .03), the ASD- group (p = .02) and the TD group (p = .01) for omissions. Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities. The ASD+ group showed compared to the ASD- group more problems in inhibitory performance but not in the working memory task.</p> <p>Conclusion</p> <p>Our findings replicate previous results reporting impairment of ADHD children in inhibition and working memory tasks and of ASD children in planning and flexibility abilities. The ASD + group showed similarities to the ADHD group with regard to inhibitory but not to working memory deficits. Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children.</p

Benefit of enactment over oral repetition of verbal instruction does not require additional working memory during encoding

For this research, we used a dual-task approach to investigate the involvement of working memory in following written instructions. In two experiments, participants read instructions to perform a series of actions on objects and then recalled the instructions either by spoken repetition or performance of the action sequence. Participants engaged in concurrent articulatory suppression, backward-counting, and spatial-tapping tasks during the presentation of the instructions, in order to disrupt the phonological-loop, central-executive, and visuospatial-sketchpad components of working memory, respectively. Recall accuracy was substantially disrupted by all three concurrent tasks, indicating that encoding and retaining verbal instructions depends on multiple components of working memory. The accuracy of recalling the instructions was greater when the actions were performed than when the instructions were repeated, and this advantage was unaffected by the concurrent tasks, suggesting that the benefit of enactment over oral repetition does not cost additional working memory resource

Being Barefoot. Prevalence at Home, in School and during Sport: A Cross-Sectional Survey of 714 New Zealand Secondary School Boys

Background: It may be assumed that a combination of culture, climate and economic resource are the major reasons that non-industrialised countries have a higher prevalence of barefoot activity. New Zealand is an industrialised country with comparable resources to that of many European countries; however, it seems to remain socially acceptable to carry out barefoot activities. A chance observation of students competing barefoot on a tartan track, prompted us to determine the prevalence of barefoot activity in an all-boys secondary school in Auckland New Zealand. Method: An 11-question survey was administered at an Auckland boys secondary school, of high socioeconomic status, to determine the footwear habits of students (n=714) during: a) daily life b) school life (c) physical education class and (d) sport. To classify students as habitually barefoot or shod, students were asked to select whether they were barefoot most of the time (2-points), half of the time (1-point) or none of the time (0-points) in three settings: around the house, during sport and during school. A score of ≥3 was required to be considered habitually barefoot. Participants were also asked to specify, when running at their most recent athletics event (100m – 3,000m) on a track, whether they ran barefoot, in shoes, in spikes or another type of footwear. Finally, participants were asked to indicate if leg pain had interrupted running during the previous 12-months. Analysis was conducted using IBM SPSS. Results: 45% (95% CI: 41.5% - 49.5%) of the participants in our sample were classified as habitually barefoot. More than half of the sample reported being barefoot most of the time at home (n=404, 56.6%) and during PE class (n=420, 58.8%). Over 50% of the sample reported being barefoot half of the time or more during sport (n=380, 53.2%). A smaller amount went to the supermarket (n=140, 19.6%) or took the bus (n=59, 8.3%) whilst barefoot around half of the time or more. The percentage of barefoot competitors declined with increasing distance: 100m (46.5%), 200m (41.8%), 400m (38%), 800m (31%), 1500m (31%) and 3,000m (20%). The prevalence of leg pain interfering with running was 23.5%. There was no difference in the prevalence of leg pain between those classified as habitually barefoot and shod (Χ2(1, N=603) = 0.005, p = 0.946). Conclusion: The results of this survey demonstrate that over 50% of students at an all-boys secondary school in Auckland, of high socioeconomic status, are barefoot at home, during physical education and sport half of the time or more. These results may point towards a cultural difference between New Zealand and other modern industrialised countries

A Weak Neutralizing Antibody Response to Hepatitis C Virus Envelope Glycoprotein Enhances Virus Infection

We have completed a phase 1 safety and immunogenicity trial with hepatitis C virus (HCV) envelope glycoproteins, E1 and E2, with MF59 adjuvant as a candidate vaccine. Neutralizing activity to HCV genotype 1a was detected in approximately 25% of the vaccinee sera. In this study, we evaluated vaccinee sera from poor responders as a potential source of antibody dependent enhancement (ADE) of HCV infection. Sera with poor neutralizing activity enhanced cell culture grown HCV genotype 1a or 2a, and surrogate VSV/HCV pseudotype infection titer, in a dilution dependent manner. Surrogate pseudotypes generated from individual HCV glycoproteins suggested that antibody to the E2 glycoprotein; but not the E1 glycoprotein, was the principle target for enhancing infection. Antibody specific to FcRII expressed on the hepatic cell surface or to the Fc portion of Ig blocked enhancement of HCV infection by vaccinee sera. Together, the results from in vitro studies suggested that enhancement of viral infectivity may occur in the absence of a strong antibody response to HCV envelope glycoproteins

Socioeconomic Predictors of Cognition in Ugandan Children: Implications for Community Interventions

Background: Several interventions to improve cognition in at risk children have been suggested. Identification of key variables predicting cognition is necessary to guide these interventions. This study was conducted to identify these variables in Ugandan children and guide such interventions. Methods: A cohort of 89 healthy children (45 females) aged 5 to 12 years old were followed over 24 months and had cognitive tests measuring visual spatial processing, memory, attention and spatial learning administered at baseline, 6 months and 24 months. Nutritional status, child’s educational level, maternal education, socioeconomic status and quality of the home environment were also measured at baseline. A multivariate, longitudinal model was then used to identify predictors of cognition over the 24 months. Results: A higher child’s education level was associated with better memory (p = 0.03), attention (p = 0.005) and spatial learning scores over the 24 months (p = 0.05); higher nutrition scores predicted better visual spatial processing (p = 0.002) and spatial learning scores (p = 0.008); and a higher home environment score predicted a better memory score (p = 0.03). Conclusion: Cognition in Ugandan children is predicted by child’s education, nutritional status and the home environment

A defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome

Multinucleate cellular syncytial formation is a hallmark of skeletal muscle differentiation. Myomaker, encoded by Mymk (Tmem8c), is a well-conserved plasma membrane protein required for myoblast fusion to form multinucleated myotubes in mouse, chick, and zebrafish. Here, we report that autosomal recessive mutations in MYMK (OMIM 615345) cause Carey-Fineman-Ziter syndrome in humans (CFZS; OMIM 254940) by reducing but not eliminating MYMK function. We characterize MYMK-CFZS as a congenital myopathy with marked facial weakness and additional clinical and pathologic features that distinguish it from other congenital neuromuscular syndromes. We show that a heterologous cell fusion assay in vitro and allelic complementation experiments in mymk knockdown and mymk insT/insT zebrafish in vivo can differentiate between MYMK wild type, hypomorphic and null alleles. Collectively, these data establish that MYMK activity is necessary for normal muscle development and maintenance in humans, and expand the spectrum of congenital myopathies to include cell-cell fusion deficits