Major histocompatibility complex class II (HLA-DRB and -DQB) allele frequencies in Botswana: association with human immunodeficiency virus type 1 infection

Southern Africa is facing an unprecedented public health crisis due to the high prevalence of human immunodeficiency virus type 1 (HIV-1). Vaccine development and testing efforts, mainly based on elicitation of HIV-specific T cells, are under way. To understand the role of human leukocyte antigen (HLA) class II alleles in HIV pathogenesis and to facilitate HLA-based HIV-1 vaccine design, we analyzed the frequencies of HLA class II alleles within the southern African country of Botswana. Common HLA class II alleles were identified within the Botswana population through the molecular genotyping of DRB and DQB1 loci. The DRB1 allele groups DRB1*01, DRB1*02/15, DRB1*03, DRB1*11, and DRB1*13 were encountered at frequencies above 20%. Within the DQB1 locus, DQB1*06 (47.7%) was the most common allele group, followed by DQB1*03 (39.2%) and DQB1*04 (25.8%). We found that DRB1*01 was more common in HIV-negative than in HIV-positive individuals and that those who expressed DRB1*08 had lower median viral loads. We demonstrate that the frequencies of certain HLA class II alleles in this Botswana population differ substantially from those in North American populations, including African-Americans. Common allele groups within Botswana cover large percentages of other African populations and could be targeted in regional vaccine designs.     

A framework for considering the risk‐benefit trade‐off in designing noninferiority trials using composite outcome approaches

When a new treatment regimen is expected to have comparable or slightly worse efficacy to that of the control regimen but has benefits in other domains such as safety and tolerability, a noninferiority (NI) trial may be appropriate but is fraught with difficulty in justifying an acceptable NI margin that is based on both clinical and statistical input. To overcome this, we propose to utilize composite risk‐benefit outcomes that combine elements from domains of importance (eg, efficacy, safety, and tolerability). The composite outcome itself may be analyzed using a superiority framework, or it can be used as a tool at the design stage of a NI trial for selecting an NI margin for efficacy that balances changes in risks and benefits. In the latter case, the choice of NI margin may be based on a novel quantity called the maximum allowable decrease in efficacy (MADE), defined as the marginal difference in efficacy between arms that would yield a null treatment effect for the composite outcome given an assumed distribution for the composite outcome. We observe that MADE: (1) is larger when the safety improvement for the experimental arm is larger, (2) depends on the association between the efficacy and safety outcomes, and (3) depends on the control arm efficacy rate. We use a numerical example for power comparisons between a superiority test for the composite outcome vs a noninferiority test for efficacy using the MADE as the NI margin, and apply the methods to a TB treatment trial.     

Stretchable and Conductive Cellulose/Conductive Polymer Composite Films for On-Skin Strain Sensors

Conductive composite materials have attracted considerable interest of researchers for application in stretchable sensors for wearable health monitoring. In this study, highly stretchable and conductive composite films based on carboxymethyl cellulose (CMC)-poly (3,4-ethylenedioxythiopehe):poly (styrenesulfonate) (PEDOT:PSS) (CMC-PEDOT:PSS) were fabricated. The composite films achieved excellent electrical and mechanical properties by optimizing the lab-synthesized PEDOT:PSS, dimethyl sulfoxide, and glycerol content in the CMC matrix. The optimized composite film exhibited a small increase of only 1.25-fold in relative resistance under 100% strain. The CMC-PEDOT:PSS composite film exhibited outstanding mechanical properties under cyclic tape attachment/detachment, bending, and stretching/releasing tests. The small changes in the relative resistance of the films under mechanical deformation indicated excellent electrical contacts between the conductive PEDOT:PSS in the CMC matrix, and strong bonding strength between CMC and PEDOT:PSS. We fabricated highly stretchable and conformable on-skin sensors based on conductive and stretchable CMC-PEDOT:PSS composite films, which can sensitively monitor subtle bio-signals and human motions such as respiratory humidity, drinking water, speaking, skin touching, skin wrinkling, and finger bending. Because of the outstanding electrical properties of the films, the on-skin sensors can operate with a low power consumption of only a few microwatts. Our approach paves the way for the realization of low-power-consumption stretchable electronics using highly stretchable CMC-PEDOT:PSS composite films.     

Layer-by-layer coating of MIL-100(Fe) on a cotton fabric for purification of water-soluble dyes by the combined effect of adsorption and photocatalytic degradation

Efforts have been made for sustainable development of adsorbents to purify organic contaminants from wastewater. In this study, a MIL-100(Fe) based textile that acts as a reusable adsorbent and photocatalytic agent was developed by synthesizing MIL-100(Fe) onto a cotton fabric by the layer-by-layer (LBL) process using water-based solutions. As the number of LBL cycles increased, the add-on''s of MIL-100(Fe) showed a drastic increase up to 8 cycles, then showed gradual increases with further treatments. The overall adsorption performance was enhanced with the increased MIL-100(Fe) add-on''s, but the specific adsorption efficiency per unit mass of MIL-100(Fe) was reduced as the LBL cycles increased, implying the reduced average adsorption efficiency with a thicker coating. To examine the reusability of the adsorbent, desorption efficiency of RhB was measured. The desorption after the first-time adsorption was not efficient due to the strong binding inside the pores. For the later cycles of adsorption–desorption, desorption occurred more efficiently, probably because RhB molecules were adhered mostly at the outer surface of the MOF layer. Simultaneously, MIL-100(Fe)@cotton demonstrated the photocatalytic degradation performance against RhB in the presence of H₂O₂ by the Fenton reaction. With the combined effect of adsorption and photodegradation, the developed fabric attained 96% removal efficiency for RhB dissolved in water. This study demonstrates an environmentally responsible process of developing a MIL-100(Fe) coated fabric that is readily available for effective removal of organic foulants in water. This fabrication method can be applied as a scalable manufacturing of metal–organic framework-based photocatalytic adsorbent textiles.

A MIL-100(Fe)-based water purifying textile that functions by dual action of adsorption and photocatalytic activity is designed via a layer-by-layer process without using toxic organic solvents.     

Addressing Methodologic Challenges and Minimizing Threats to Validity in Synthesizing Findings from Individual-Level Data Across Longitudinal Randomized Trials

Integrative Data Analysis (IDA) encompasses a collection of methods for data synthesis that pools participant-level data across multiple studies. Compared with single-study analyses, IDA provides larger sample sizes, better representation of participant characteristics, and often increased statistical power. Many of the methods currently available for IDA have focused on examining developmental changes using longitudinal observational studies employing different measures across time and study. However, IDA can also be useful in synthesizing across multiple randomized clinical trials to improve our understanding of the comprehensive effectiveness of interventions, as well as mediators and moderators of those effects. The pooling of data from randomized clinical trials presents a number of methodological challenges, and we discuss ways to examine potential threats to internal and external validity. Using as an illustration a synthesis of 19 randomized clinical trials on the prevention of adolescent depression, we articulate IDA methods that can be used to minimize threats to internal validity, including (1) heterogeneity in the outcome measures across trials, (2) heterogeneity in the follow-up assessments across trials, (3) heterogeneity in the sample characteristics across trials, (4) heterogeneity in the comparison conditions across trials, and (5) heterogeneity in the impact trajectories. We also demonstrate a technique for minimizing threats to external validity in synthesis analysis that may result from non-availability of some trial datasets. The proposed methods rely heavily on latent variable modeling extensions of the latent growth curve model, as well as missing data procedures. The goal is to provide strategies for researchers considering IDA.

     

Effects of proton pump inhibitor use on risk of Clostridium difficile infection: a hospital cohort study

Journal of Gastroenterology - Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed...     

Distribution of internal thoracic artery perforators: A clincal anatomy study

There are various modifications of the transverse rectus abdominis musculocutaneous flap and deep inferior epigastric perforator flap to reduce the morbidity of the donor site or to augment the vascularity of the flap. For microanastomosis of multiple pedicles, multiple recipient vessels or an intervening vein graft should be provided. In addition, alternative perforator‐based flaps used in breast reconstruction have small caliber pedicles. Therefore, small recipient vessels such as internal thoracic artery perforators are more suitable for appropriate microanastomosis. Therefore, it is important to acquaint the distribution and anatomical characteristics of internal thoracic artery perforators. We researched the perforators running in the intercostal spaces under the pectoralis major muscle to provide an overview of the anatomical distribution and characteristics of the perforators in patients who underwent immediate subpectoral implant‐based breast reconstructions. In our study, the major perforators (diameter > 1.5 mm) were easily found 2–7 cm medially between the third and fourth intercostal space and were sparse in the lateral area from the midline of the breast (usually 8–9 cm lateral to the midsternal line) and above the third rib. In each side of the breast, the average number of perforators greater than 1.5 mm was 1.6, and the average number of perforators between 1 mm and 1.5 mm in diameter was 3.2. Our results provide information about perforators in the anterior chest wall related to the breast area. Clin. Anat. 32:471–475, 2019. © 2018 Wiley Periodicals, Inc.     

Comparison of Abdominal Visceral Adipose Tissue Area Measured by Computed Tomography with That Estimated by Bioelectrical Impedance Analysis Method in Korean Subjects

We evaluated the concordance between visceral fat area (VFA) estimated by bioelectrical impedance analysis (BIA) or computed tomography (CT) in Korean subjects with a wide range in age and body mass index (BMI). In 1006 individuals (mean age 55.2 ± 11.8 (19–87) years, mean BMI 26.0 ± 3.5 (17–46) kg/m², 48.9% men), VFA quantified by CT was compared with VFA using multifrequency BIA machines within 15 days. Concordance rates were compared by age or BMI using correlation analysis, Bland-Altman plots, and intraclass correlation coefficient (ICC). Using BIA data, we established a regression formula to reflect CT-VFA. The mean VFAs by CT and BIA were 131.9 ± 57.3 cm² and 110.5 ± 33.9 cm², respectively (r = 0.605, p < 0.001). The mean difference was 21.4 ± 45.6 cm², tending to increase with BMI. In women with BMI <25 kg/m² or age <50 years, the VFAs by BIA were similar to those by CT (ICC = 0.496 in BMI <25 kg/m² and ICC = 0.638 in age <50 years). However, the difference was greater in men with BMI ≥25 kg/m² or age ≥50 years. Applying our formula, the difference between estimations decreased to 0.2 ± 38.2cm². VFA estimated by BIA correlated well with that by CT, but a more accurate formula is needed to match CT data, particularly in older men or subjects with a high BMI.     

Facile synthesis of partially oxidized Mn3O4-functionalized carbon cathodes for rechargeable Li–O2 batteries

High charging overpotential (low energy efficiency) is one of the most important challenges preventing the use of current nonaqueous Li–O₂ batteries. This study demonstrates direct in situ-incorporation of metal oxides on carbon during synthesis and the associated application to nonaqueous Li–O₂ battery catalysts. The partially oxidized Mn₃O₄ (Mn₃O₄/Mn₅O₈)-incorporating carbon cathode shows an average overpotential reduction of ∼8% charge/discharge during 40 cycles in a rechargeable nonaqueous Li–O₂ cell. Here, we suggested the possibility that only a small amount of the oxide species (<5%) could show catalytic effects during charge in a rechargeable Li–O₂ cell.

Only a small amount of manganese oxide species (<5%) in carbon shows catalytic effects during charging in a rechargeable Li–O₂ cell.