Performance of the 2007 WHO Algorithm to diagnose Smear-negative Pulmonary Tuberculosis in a HIV prevalent setting

The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya

The Global Trachoma Mapping Project: Methodology of a 34-Country Population-Based Study.

PURPOSE: To complete the baseline trachoma map worldwide by conducting population-based surveys in an estimated 1238 suspected endemic districts of 34 countries. METHODS: A series of national and sub-national projects owned, managed and staffed by ministries of health, conduct house-to-house cluster random sample surveys in evaluation units, which generally correspond to "health district" size: populations of 100,000-250,000 people. In each evaluation unit, we invite all residents aged 1 year and older from h households in each of c clusters to be examined for clinical signs of trachoma, where h is the number of households that can be seen by 1 team in 1 day, and the product h × c is calculated to facilitate recruitment of 1019 children aged 1-9 years. In addition to individual-level demographic and clinical data, household-level water, sanitation and hygiene data are entered into the purpose-built LINKS application on Android smartphones, transmitted to the Cloud, and cleaned, analyzed and ministry-of-health-approved via a secure web-based portal. The main outcome measures are the evaluation unit-level prevalence of follicular trachoma in children aged 1-9 years, prevalence of trachomatous trichiasis in adults aged 15 + years, percentage of households using safe methods for disposal of human feces, and percentage of households with proximate access to water for personal hygiene purposes. RESULTS: In the first year of fieldwork, 347 field teams commenced work in 21 projects in 7 countries. CONCLUSION: With an approach that is innovative in design and scale, we aim to complete baseline mapping of trachoma throughout the world in 2015

Use of twitter data for waste minimisation in beef supply chain

Approximately one third of the food produced is discarded or lost, which accounts for 1.3 billion tons per annum. The waste is being generated throughout the supply chain viz. farmers, wholesalers/processors, logistics, retailers and consumers. The majority of waste occurs at the interface of retailers and consumers. Many global retailers are making efforts to extract intelligence from customer’s complaints left at retail store to backtrack their supply chain to mitigate the waste. However, majority of the customers don’t leave the complaints in the store because of various reasons like inconvenience, lack of time, distance, ignorance etc. In current digital world, consumers are active on social media and express their sentiments, thoughts, and opinions about a particular product freely. For example, on an average, 45,000 tweets are tweeted daily related to beef products to express their likes and dislikes. These tweets are large in volume, scattered and unstructured in nature. In this study, twitter data is utilised to develop waste minimization strategies by backtracking the supply chain. The execution process of proposed framework is demonstrated for beef supply chain. The proposed model is generic enough and can be applied to other domains as well

Valence can control the nonexponential viscoelastic relaxation of multivalent reversible gels

Gels made of telechelic polymers connected by reversible crosslinkers are a versatile design platform for biocompatible viscoelastic materials. Their linear response to a step strain displays a fast, near-exponential relaxation when using low valence crosslinkers, while larger supramolecular crosslinkers bring about much slower dynamics involving a wide distribution of time scales whose physical origin is still debated. Here, we propose a model where the relaxation of polymer gels in the dilute regime originates from elementary events in which the bonds connecting two neighboring crosslinkers all disconnect. Larger crosslinkers allow for a greater average number of bonds connecting them, but also generate more heterogeneity. We characterize the resulting distribution of relaxation time scales analytically, and accurately reproduce stress relaxation measurements on metal-coordinated hydrogels with a variety of crosslinker sizes including ions, metal-organic cages, and nanoparticles. Our approach is simple enough to be extended to any crosslinker size and could thus be harnessed for the rational design of complex viscoelastic materials.Comment: 6 pages 5 figures 1 table for the main text and 9 pages 7 figures for the supplemen

Subtherapeutic Meropenem Antibiotic Exposure in Children With Septic Shock Assessed by Noncompartmental Pharmacokinetic Analysis in a Prospective Dataset.

OBJECTIVES: To define meropenem plasma concentrations and pharmacodynamic exposure metrics in children with septic shock during the first 3 days of PICU hospitalization. DESIGN: Pharmacokinetic sampling was undertaken in 19 subjects receiving standard meropenem dosing (20 mg/kg/dose, 8 hr) recruited from March 2019 to March 2022. Sampling occurred once each day following meropenem given 24 hours apart, during the first 3 PICU days. Data analysis was completed in 2023 and noncompartmental analysis was performed to assess pharmacodynamic exposure targets for sepsis. Clearance and volume of distribution at 20 mg/kg/dose were used to simulate mean exposures at 40 and 60 mg/kg/dose. SETTING: PICU in a tertiary care center. SUBJECTS: Patients 4 weeks old or older with hypotension requiring fluid resuscitation and vasopressor therapy, receiving meropenem as empiric therapy for sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Augmented renal clearance (ARC) was documented in eight of 19 subjects, previously associated with subtherapeutic plasma concentrations, while three of 19 had acute kidney injury and decreased renal clearance. When assessed by pharmacodynamic exposure targets for sepsis (plasma meropenem concentrations above the minimum inhibitory concentration [MIC] of Pseudomonas aeruginosa for 70% or 100% of the dosing interval), ten of 19 and nine of 19 children, respectively, had subtherapeutic plasma meropenem exposures during PICU day 1, even for pathogens with an MIC considered susceptible by U.S. Food and Drug Administration criteria. Therapeutic meropenem pharmacodynamic exposures were associated with a positive 24-hour fluid balance on PICU day 1 and a negative 24-hour fluid balance by day 3, although profound variability was noted in fluid administered and renal output. CONCLUSIONS: Given the variability in meropenem systemic exposure in pediatric septic shock, therapeutic drug monitoring, or monitoring for ARC, is suggested during the first days of hospitalization to allow daily assessments of dosing needs to achieve pharmacodynamic exposure targets for sepsis

Polyoxazoline-Based Bottlebrush and Brush-Arm Star Polymers via ROMP: Syntheses and Applications as Organic Radical Contrast Agents

Copyright © 2019 American Chemical Society. The synthesis of functional poly(2-alkyl-2-oxazoline) (PAOx) copolymers with complex nanoarchitectures using a graft-through ring-opening metathesis polymerization (ROMP) approach is described. First, well-defined norbornene-terminated poly(2-ethyl-2-oxazoline) (PEtOx) macromonomers (MM) were prepared by cationic ring-opening polymerization. ROMP of these MMs produced bottlebrush copolymers with PEtOx side chains. In addition, PEtOx-based branched MMs bearing a terminal alkyne group were prepared and conjugated to an azide-containing bis-spirocyclohexyl nitroxide via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). ROMP of this branched MM, followed by in situ cross-linking, provided PEtOx-based brush-arm star polymers (BASPs) with nitroxide radicals localized at the core-shell interface. These PEtOx-based nitroxide-containing BASPs displayed relaxivity values on par with state-of-the-art polyethylene glycol (PEG)-based nitroxide materials, making them promising as organic radical contrast agents for metal-free magnetic resonance imaging (MRI)

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

Efficacy of the Janus kinase 1/2 inhibitor ruxolitinib in the treatment of vasculopathy associated with TMEM173-activating mutations in 3 children

International audienc

Toward a multiscale modeling framework for understanding serotonergic function

Despite its importance in regulating emotion and mental wellbeing, the complex structure and function of the serotonergic system present formidable challenges toward understanding its mechanisms. In this paper, we review studies investigating the interactions between serotonergic and related brain systems and their behavior at multiple scales, with a focus on biologically-based computational modeling. We first discuss serotonergic intracellular signaling and neuronal excitability, followed by neuronal circuit and systems levels. At each level of organization, we will discuss the experimental work accompanied by related computational modeling work. We then suggest that a multiscale modeling approach that integrates the various levels of neurobiological organization could potentially transform the way we understand the complex functions associated with serotonin