Diffusion Coefficients Of D-glucose In Aqueous Carboxymethylcellulose And Carboxypolymethylene Solutions

A micro interferometric method was used to determine pseudo-binary, molecular diffusion coefficients for diffusion of D-glucose in aqueous carboxymethylcellulose (CMC) and aqueous carboxypolymethylene (Carbopol) solutions. An initial solute concentration of about 9 wt. % D-glucose in the aqueous polymer solutions was used. The polymer concentrations for the CMC solutions ranged from 1.2 to 2.2 wt. % and for the Carbopol solutions from 0.18 to 0.28 wt. %. Diffusion coefficients were determined as a function of reduced solute concentration, both with and without the effect of solution volume change during diffusion being considered. © 1969, American Chemical Society. All rights reserved

The immediate effects of passive hip joint mobilization on hip abductor/external rotator muscle strength in patients with anterior knee pain and impaired hip function. A randomized, placebo-controlled crossover trial.

BACKGROUND: Anterior knee pain (AKP) is often associated with persistent hip muscle weakness and facilitatory interventions may be beneficial for managing patients with AKP (pwAKP). Physiotherapists often employ passive oscillatory hip joint mobilizations to increase hip muscle function. However, there is little information about their effectiveness and the mechanisms of action involved. OBJECTIVES: To investigate the immediate effects of passive hip joint mobilization on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function. DESIGN: A double-blinded, randomized, placebo-controlled crossover design. METHOD: Eighteen patients with AKP participated in two sessions of data collection with one week apart. They received passive hip joint mobilization or placebo mobilization in a randomized order. Eccentric hip muscle strength was measured immediately before and after each intervention using a portable hand-held dynamometer. RESULTS: An ANCOVA with the sequence of treatment condition as the independent variable, the within-subject post-treatment differences as the dependent variable and the within-subject pre-treatment differences as the covariate was conducted. Patients showed a significant mean increase in eccentric hip muscle strength of 7.73% (p = 0.001) for the mobilization condition, compared to a mean decrease of 4.22% for the placebo condition. Seventeen out of eighteen participants reported having no pain during any of the strength testing. CONCLUSION: These data suggest that passive hip joint mobilization has an immediate positive effect on eccentric hip abductor/external rotator muscle strength in pwAKP with impaired hip function, even in the absence of current pain

Investigating Hardy–Weinberg equilibrium in case–control or cohort studies or meta-analysis

peer reviewedYu et al. (Breast Cancer Res Treat 117:675-677, 2009) recently stated that testing for deviation from Hardy-Weinberg equilibrium (HWE) is necessary to identify systematic genotyping errors in case-control studies. They criticized a meta-analytic study for the deviation from HWE in the case group of one study. The aim of this article is twofold. First, we derive recommendations on how to test for deviations from HWE in different study designs. Second, we develop a meta-analytic framework for assessing compatibility with HWE or measuring deviation from HWE. The authors sketch the possible reasons behind deviation from HWE and provide guidelines for proper investigation of HWE deviations in different study designs. The authors argue that the standard HWE chi(2) lack of fit test is logically flawed and provide a logically unflawed approach for measuring deviation from HWE using confidence intervals. The proposed method is applicable to meta-analyses of both case-control or cohort association studies. The proposed approach is illustrated using the meta-analysis criticized by Yu et al. Heterogeneity between studies can be assessed. The critique of Yu et al. to the article of Frank et al. (Breast Cancer Res Treat 111:139-144, 2008) can be refuted. Even more, validity of HWE can be proven for the pooled control sample. The authors advocate the use of a confidence interval-based approach to assess HWE. The latter should only be investigated in control populations. In multicenter studies or meta-analysis, deviation from HWE should be analyzed using a meta-analytic approach

Improved Statistics for Genome-Wide Interaction Analysis

Recently, Wu and colleagues [1] proposed two novel statistics for genome-wide interaction analysis using case/control or case-only data. In computer simulations, their proposed case/control statistic outperformed competing approaches, including the fast-epistasis option in PLINK and logistic regression analysis under the correct model; however, reasons for its superior performance were not fully explored. Here we investigate the theoretical properties and performance of Wu et al.'s proposed statistics and explain why, in some circumstances, they outperform competing approaches. Unfortunately, we find minor errors in the formulae for their statistics, resulting in tests that have higher than nominal type 1 error. We also find minor errors in PLINK's fast-epistasis and case-only statistics, although theory and simulations suggest that these errors have only negligible effect on type 1 error. We propose adjusted versions of all four statistics that, both theoretically and in computer simulations, maintain correct type 1 error rates under the null hypothesis. We also investigate statistics based on correlation coefficients that maintain similar control of type 1 error. Although designed to test specifically for interaction, we show that some of these previously-proposed statistics can, in fact, be sensitive to main effects at one or both loci, particularly in the presence of linkage disequilibrium. We propose two new “joint effects” statistics that, provided the disease is rare, are sensitive only to genuine interaction effects. In computer simulations we find, in most situations considered, that highest power is achieved by analysis under the correct genetic model. Such an analysis is unachievable in practice, as we do not know this model. However, generally high power over a wide range of scenarios is exhibited by our joint effects and adjusted Wu statistics. We recommend use of these alternative or adjusted statistics and urge caution when using Wu et al.'s originally-proposed statistics, on account of the inflated error rate that can result

The relationship between patient physiology and cancer-specific survival following curative resection of colorectal cancer

The impact of patient physiology on cancer-specific survival is poorly documented. Patient physiology predicted overall, cancer-specific (Physiology Score>30; HR 8.64 (95% CI 3.00–24.92); P=0.0005) and recurrence-free survival (Physiology Score >30; HR 7.44 (95% CI 1.99–27.73); P=0.003) independent of Dukes stage following potentially curative surgery for colorectal cancer. This independent negative association with survival is a novel observation

Intramuscular Artesunate for Severe Malaria in African Children: A Multicenter Randomized Controlled Trial.

BACKGROUND: Current artesunate (ARS) regimens for severe malaria are complex. Once daily intramuscular (i.m.) injection for 3 d would be simpler and more appropriate for remote health facilities than the current WHO-recommended regimen of five intravenous (i.v.) or i.m. injections over 4 d. We compared both a three-dose i.m. and a three-dose i.v. parenteral ARS regimen with the standard five-dose regimen using a non-inferiority design (with non-inferiority margins of 10%). METHODS AND FINDINGS: This randomized controlled trial included children (0.5-10 y) with severe malaria at seven sites in five African countries to assess whether the efficacy of simplified three-dose regimens is non-inferior to a five-dose regimen. We randomly allocated 1,047 children to receive a total dose of 12 mg/kg ARS as either a control regimen of five i.m. injections of 2.4 mg/kg (at 0, 12, 24, 48, and 72 h) (n = 348) or three injections of 4 mg/kg (at 0, 24, and 48 h) either i.m. (n = 348) or i.v. (n = 351), both of which were the intervention arms. The primary endpoint was the proportion of children with ≥ 99% reduction in parasitemia at 24 h from admission values, measured by microscopists who were blinded to the group allocations. Primary analysis was performed on the per-protocol population, which was 96% of the intention-to-treat population. Secondary analyses included an analysis of host and parasite genotypes as risks for prolongation of parasite clearance kinetics, measured every 6 h, and a Kaplan-Meier analysis to compare parasite clearance kinetics between treatment groups. A post hoc analysis was performed for delayed anemia, defined as hemoglobin ≤ 7 g/dl 7 d or more after admission. The per-protocol population was 1,002 children (five-dose i.m.: n = 331; three-dose i.m.: n = 338; three-dose i.v.: n = 333); 139 participants were lost to follow-up. In the three-dose i.m. arm, 265/338 (78%) children had a ≥ 99% reduction in parasitemia at 24 h compared to 263/331 (79%) receiving the five-dose i.m. regimen, showing non-inferiority of the simplified three-dose regimen to the conventional five-dose regimen (95% CI -7, 5; p = 0.02). In the three-dose i.v. arm, 246/333 (74%) children had ≥ 99% reduction in parasitemia at 24 h; hence, non-inferiority of this regimen to the five-dose control regimen was not shown (95% CI -12, 1; p = 0.24). Delayed parasite clearance was associated with the N86YPfmdr1 genotype. In a post hoc analysis, 192/885 (22%) children developed delayed anemia, an adverse event associated with increased leukocyte counts. There was no observed difference in delayed anemia between treatment arms. A potential limitation of the study is its open-label design, although the primary outcome measures were assessed in a blinded manner. CONCLUSIONS: A simplified three-dose i.m. regimen for severe malaria in African children is non-inferior to the more complex WHO-recommended regimen. Parenteral ARS is associated with a risk of delayed anemia in African children. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR201102000277177

Results of a randomized, double blind, placebo controlled, crossover trial of melatonin for treatment of Nocturia in adults with multiple sclerosis (MeNiMS)

© 2018 The Author(s). Background: Nocturia is a common urinary symptom of multiple sclerosis (MS) which can affect quality of life (QoL) adversely. Melatonin is a hormone known to regulate circadian rhythm and reduce smooth muscle activity such as in the bladder. There is limited evidence supporting use of melatonin to alleviate urinary frequency at night in the treatment of nocturia. The aim of this study was to evaluate the effect of melatonin on the mean number of nocturia episodes per night in patients with MS. Methods: A randomized, double blind, placebo controlled crossover trial was conducted. 34 patients with nocturia secondary to multiple sclerosis underwent a 4-day pre-treatment monitoring phase. The patients were randomized to receive either 2 mg per night (taken at bedtime) of capsulated sustained-release melatonin (Circadin®) or 1 placebo capsule for 6 weeks followed by a crossover to the other regimen for an additional 6 weeks after a 1-month washout period. Results: From the 26 patients who completed the study, there was no significant difference observed in the signs or symptoms of nocturia when taking 2 mg melatonin compared to placebo. The primary outcome measure, mean number of nocturia episodes on bladder diaries, was 1.8/night at baseline, and 1.4/night on melatonin, compared with 1.6 for placebo (Medians 1.70, 1.50, and 1.30 respectively, p = 0.85). There was also no significant difference seen in LUTS, QoL and sleep quality when taking melatonin. No significant safety concerns arose. Conclusions: This small study suggests that a low dose of melatonin taken at bedtime may be ineffective therapy for nocturia in MS. Trial registration: (EudraCT reference) 2012-00418321 registered: 25/01/13. ISRCTN Registry: ISRCTN38687869

Critical literacy as a pedagogical goal in English language teaching

In this chapter, the authors provide an overview of the area of critical literacy as it pertains to second language pedagogy (curriculum and instruction). After considering the historical origins of critical literacy (from antiquity, and including in first language education), they consider how it began to penetrate the field of applied linguistics. They note the geographical and institutional spread of critical literacy practice as documented by published accounts. They then sketch the main features of L2 critical literacy practice. To do this, they acknowledge how practitioners have reported on their practices regarding classroom content and process. The authors also draw attention to the outcomes of these practices as well as challenges that practitioners have encountered in incorporating critical literacy into their second language classrooms

A CFD-DEM solver to model bubbly flow. Part I: Model development and assessment in upward vertical pipes

[EN] In the computational modeling of two-phase flow, many uncertainties are usually faced in simulations and validations with experiments. This has traditionally made it difficult to provide a general method to predict the two-phase flow characteristics for any geometry and condition, even for bubbly flow regimes. Thus, we focus our research on studying in depth the bubbly flow modeling and validation from a critical point of view. The conditions are intentionally limited to scenarios where coalescence and breakup can be neglected, to concentrate on the study of bubble dynamics and its interaction with the main fluid. This study required the development of a solver for bubbly flow with higher resolution level than TFM and a new methodology to obtain the data from the simulation. Part I shows the development of a solver based on the CFD-DEM formulation. The motion of each bubble is computed individually with this solver and aspects as inhomogeneity, nonlinearity of the interfacial forces, bubble-wall interactions and turbulence effects in interfacial forces are taken into account. To develop the solver, several features that are not usually required for traditional CFD-DEM simulations but are relevant for bubbly flow in pipes, have been included. Models for the assignment of void fraction into the grid, seeding of bubbles at the inlet, pressure change influence on the bubble size and turbulence effects on both phases have been assessed and compared with experiments for an upward vertical pipe scenario. Finally, the bubble path for bubbles of different size have been investigated and the interfacial forces analyzed. (C) 2017 Elsevier Ltd. All rights reserved.The authors sincerely thank the ''Plan Nacional de I + D+ i" for funding the project MODEXFLAT ENE2013-48565-C2-1-P and ENE2013-48565-C2-2-P.Peña-Monferrer, C.; Monrós Andreu, G.; Chiva Vicent, S.; Martinez-Cuenca, R.; Muñoz-Cobo, JL. (2018). A CFD-DEM solver to model bubbly flow. Part I: Model development and assessment in upward vertical pipes. Chemical Engineering Science. 176:524-545. https://doi.org/10.1016/j.ces.2017.11.005S52454517

Modulation of the peripheral blood transcriptome by the ingestion of probiotic yoghurt and acidified milk in healthy, young men

The metabolic health benefits of fermented milks have already been investigated using clinical biomarkers but the development of transcriptomic analytics in blood offers an alternative approach that may help to sensitively characterise such effects. We aimed to assess the effects of probiotic yoghurt intake, compared to non-fermented, acidified milk intake, on clinical biomarkers and gene expression in peripheral blood. To this end, a randomised, crossover study was conducted in fourteen healthy, young men to test the two dairy products. For a subset of seven subjects, RNA sequencing was used to measure gene expression in blood collected during postprandial tests and after two weeks daily intake. We found that the postprandial response in insulin was different for probiotic yoghurt as compared to that of acidified milk. Moreover changes in several clinical biomarkers were associated with changes in the expression of genes representing six metabolic genesets. Assessment of the postprandial effects of each dairy product on gene expression by geneset enrichment analysis revealed significant, similar modulation of inflammatory and glycolytic genes after both probiotic yoghurt and acidified milk intake, although distinct kinetic characteristics of the modulation differentiated the dairy products. The aryl hydrocarbon receptor was a major contributor to the down-regulation of the inflammatory genesets and was also positively associated with changes in circulating insulin at 2h after yoghurt intake (p = 0.05). Daily intake of the dairy products showed little effect on the fasting blood transcriptome. Probiotic yoghurt and acidified milk appear to affect similar gene pathways during the postprandial phase but differences in the timing and the extent of this modulation may lead to different physiological consequences. The functional relevance of these differences in gene expression is supported by their associations with circulating biomarkers