Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BackgroundThe WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population.MethodsIn this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895.FindingsWe identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively.InterpretationC-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications.FundingWorld Health Organization

Discutindo a educação ambiental no cotidiano escolar: desenvolvimento de projetos na escola formação inicial e continuada de professores

A presente pesquisa buscou discutir como a Educação Ambiental (EA) vem sendo trabalhada, no Ensino Fundamental e como os docentes desta escola compreendem e vem inserindo a EA no cotidiano escolar., em uma escola estadual do município de Tangará da Serra/MT, Brasil. Para tanto, realizou-se entrevistas com os professores que fazem parte de um projeto interdisciplinar de EA na escola pesquisada. Verificou-se que o projeto da escola não vem conseguindo alcançar os objetivos propostos por: desconhecimento do mesmo, pelos professores; formação deficiente dos professores, não entendimento da EA como processo de ensino-aprendizagem, falta de recursos didáticos, planejamento inadequado das atividades. A partir dessa constatação, procurou-se debater a impossibilidade de tratar do tema fora do trabalho interdisciplinar, bem como, e principalmente, a importância de um estudo mais aprofundado de EA, vinculando teoria e prática, tanto na formação docente, como em projetos escolares, a fim de fugir do tradicional vínculo “EA e ecologia, lixo e horta”.Facultad de Humanidades y Ciencias de la Educació

Last Mile Delivery Cargo Trike & Microhub Marketing Plan

According to the global logistics market report in 2018-2022 the industry will grow at a rate over 7%-year with $357B increase in revenue. A major area of focus during this period is the adoption of the Fifth Party Logistics (5PL) distribution model, meaning a switch from supply chains to supply networks. The 5PL model is often associated with E-Commerce and relies tremendously on integration of new technology such as big data analytics, Blockchain security / contracting, and the Internet of Things (IoT’s). The final trickle down of goods to end users in the 5PL model is also critically dependent on efficient and reliable last mile delivery having a total market value of nearly$40B. Consumers are driving increases in services provided by big names in E-commerce such as Amazon and Walmart. Timely doorstep delivery once considered only for consumer goods is evolving daily to include everything from groceries to medicines. The end user market is now expecting orders to be 100% accurate as well as just in time (JIT). For logistic companies to take full advantage of the 5PL model, an efficient and reliable method for last mile delivery must be secured. An attractive solution to the last mile delivery problem in high population density areas is a high capacity, Eco friendly cargo vehicle, combined with a microhub refill station containing pre-loaded cargo boxes of parcel goods. The vehicle would be highly maneuverable and capable of hauling up to 400 pounds of cargo nearly 30 miles per working shift. The cargo box can be detachable and replaced from a larger trailer system called a microhub containing 4-9 cargo boxes and stationed approximately every 5 miles. The innovative technological solution will be versatile in cost effectively solving last mile delivery in both controlled environments such as college campuses and large venues as well as in less controlled and highly volatile urban environments. If electric or electric assist, additional batteries can be carried to double the daily range or for emergency backup to other vehicles. The success of the product requires relatively nice travel routes similar to the paths used by normal bicycles. Excessively challenging terrain or geography can be expected to reduce battery life. Fit employees of average weight are ideal operators of the system as they will have physical demand and excessive weight would reduce battery life. The system must be capable of delivering to homes, apartments, businesses, and taller buildings that have elevators or lower level delivery stations / lockers. Performance level of the product is equivalent or greater than the car, bike, pedestrian, moped, scooter, van, truck delivery in terms of efficiency and cost. The technology should be quiet, flexible in delivery route options including no car zones, and accommodating to normal parking spots. If designed as a bike vehicle, operation of the vehicle will not require a driver\u27s license, vehicle registration, and have lower maintenance costs than engine powered vehicles. In other words, it will have the capability of a small delivery car/truck but is only limited by bicycle regulations

Characterisation of a highly sensitive troponin I assay and its application to a cardio-healthy population

Background: Abbott Diagnostics have developed a new highly sensitive troponin I (hs-TnI) assay. We have assessed its analytical characteristics and applied the assay to a population of apparently cardio-healthy persons. Methods: We assessed imprecision, bias compared to the previous generation assay, matrix effects, and interferences and applied the assay to an apparently healthy population, deriving the 99th percentile limit of the distribution of values in reference populations for men and women separately. Results: The dynamic range of the assay was ranged from 0.5-50,000 ng/L (pg/mL). The 10 % CV was at a concentration of 3.9 ng/L, and the 20 % CV was at a concentration of 1.8 ng/L. The new and current version of the TnI assay were highly correlated [slope:0.98 (95%CI:0.88-1.07), y-intercept:1.20 (95%CI:-2.35-4.75) r2 = 0.99]. The 99th percentile limit of the distribution of values in a reference population was different for males and females: for males 14.0 ng/L and for females 11.1 ng/L and at these concentrations the assay CV was 5.0 %. TnI was detectable in nearly all patient samples from the healthy reference population (98.6 %). Conclusions: This new hs-TnI assay is able to measure to an order of magnitude lower than the current generation TnI assay from the same manufacturer. With TnI being detectable in nearly all apparently healthy subject samples this suggests that TnI presence does not always indicate cardiomyocyte necrosis

Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine

The tryptophan metabolite kynurenine is an endogenous ligand of the aryl hydrocarbon receptor (AHR). Here, the authors show that AHR targeting in IDO/TDO-expressing tumours counteracts a regulatory T cell/macrophage suppressive axis and synergizes with immune checkpoint blockade to hinder tumour growth