Mucosal delivery of tuberculosis vaccines: a review of current approaches and challenges.

Introduction: Tuberculosis (TB) remains a major health threat and it is now clear that the current vaccine, BCG, is unable to arrest the global TB epidemic. A new vaccine is needed to either replace or boost BCG so that a better level of protection could be achieved. The route of entry of Mycobacterium tuberculosis, the causative organism, is via inhalation making TB primarily a respiratory disease. There is therefore good reason to hypothesize that a mucosally delivered vaccine against TB could be more effective than one delivered via the systemic route.Areas covered: This review summarizes the progress that has been made in the area of TB mucosal vaccines in the last few years. It highlights some of the strengths and shortcomings of the published evidence and aims to discuss immunological and practical considerations in the development of mucosal vaccines.Expert opinion: There is a growing body of evidence that the mucosal approach to vaccination against TB is feasible and should be pursued. However, further key studies are necessary to both improve our understanding of the protective immune mechanisms operating in the mucosa and the technical aspects of aerosolized delivery, before such a vaccine could become a feasible, deployable strategy

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the "treat all" strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER=£9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries. © 2014 The Authors

Priorizando la Agricultura Sostenible Adaptada al Clima (ASAC) en Guatemala

La seguridad alimentaria en Guatemala cada vez se ve más afectada por eventos climáticos extremos como sequías prolongadas, precipitaciones intensas e irregulares, heladas entre otros. En este contexto, el Ministerio de Agricultura, Ganadería y Alimentación de Guatemala (MAGA) ha contemplado en sus políticas y estrategias de trabajo el vínculo entre la agricultura y el cambio climático, buscando fomentar la resiliencia de los productores frente a los desafíos climáticos. Estas acciones han coincidido con debates mundiales sobre el concepto de Agricultura Sostenible Adaptada al Clima (ASAC), que hace énfasis en el incremento sostenible de la productividad, mientras que se aumenta la capacidad adaptativa de los agricultores y se disminuyen las emisiones de gases de efecto invernadero (GEI) del sector. Con el fin de apoyar el proceso de priorización de inversiones en ASAC en el país, el programa de investigación del CGIAR en Cambio Climático, Agricultura y Seguridad Alimentaria (CCAFS, por sus siglas en inglés), el Centro Internacional de Agricultura Tropical (CIAT) y MAGA han establecido una alianza estratégica que permite potencializar las capacidades institucionales y el desarrollo de programas y proyectos sistémicos en temas ASAC. El presente documento hace referencia al estado actual y el pilotaje del proceso de priorización de inversiones en ASAC iniciado por CCAFS y CIAT en Guatemala

The EEG spectral properties of meditation and mind wandering differ between experienced meditators and novices

Data and code availability statement: Raw EEG data and MATLAB code will be publicly available in the Open Science Framework webpage (see https://osf.io/3uszv/?view_only=d41ddd2200e642cf9992a016cb739b90).Supplementary materials are available online at: https://www.sciencedirect.com/science/article/pii/S1053811921009423?via%3Dihub#sec0018 .Copyright © 2021 The Authors. Previous literature suggests that individuals with meditation training become less distracted during meditation practice. In this study, we assess whether putative differences in the subjective experience of meditation between meditators and non-meditators are reflected in EEG spectral modulations. For this purpose, we recorded electroencephalography (EEG) during rest and two breath focus meditations (with and without experience sampling) in a group of 29 adult participants with more than 3 years of meditation experience and a control group of 29 participants without any meditation experience. Experience sampling in one of the meditation conditions allowed us to disentangle periods of breath focus from mind wandering (i.e. moments of distraction driven by task-irrelevant thoughts) during meditation practice. Overall, meditators reported a greater level of focus and reduced mind wandering during meditation practice than controls. In line with these reports, EEG spectral modulations associated with meditation and mind wandering also differed significantly between meditators and controls. While meditators (but not controls) showed a significant decrease in individual alpha frequency / amplitude and a steeper 1/f slope during meditation relative to rest, controls (but not meditators) showed a relative increase in individual alpha amplitude during mind wandering relative to breath focus periods. Together, our results show that the subjective experience of meditation and mind wandering differs between meditators and novices and that this is reflected in oscillatory and non-oscillatory properties of EEG.Branco Weiss fellowship of the Society in Science–ETH Zurich; Grants from the Flanders Fund for Scientific Research (FWO G079017N and G046321N); European Varela Awards (Mind & Life Europe)

Synthetic Lethality of Chk1 Inhibition Combined with p53 and/or p21 Loss During a DNA Damage Response in Normal and Tumor Cells

Cell cycle checkpoints ensure genome integrity and are frequently compromised in human cancers. A therapeutic strategy being explored takes advantage of checkpoint defects in p53-deficient tumors in order to sensitize them to DNA-damaging agents by eliminating Chk1-mediated checkpoint responses. Using mouse models, we demonstrated that p21 is a key determinant of how cells respond to the combination of DNA damage and Chk1 inhibition (combination therapy) in normal cells as well as in tumors. Loss of p21 sensitized normal cells to the combination therapy much more than did p53 loss and the enhanced lethality was partially blocked by CDK inhibition. In addition, basal pools of p21 (p53 independent) provided p53 null cells with protection from the combination therapy. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition. As p21 levels are low in a significant fraction of colorectal tumors, they are predicted to be particularly sensitive to the combination therapy. Results reported in this study support this prediction

Asthma Prevalence, Knowledge, and Perceptions among Secondary School Pupils in Rural and Urban Costal Districts in Tanzania.

Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils' perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma. A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of "diagnosed" asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A >= 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma. The mean age of participants was 16.8 (+/-1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers. The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils' perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis B in the UK: systematic review and economic evaluation

The copyright line for this article was changed on 18 November 2016 after original online publication. Abbreviations: CEAF cost-effectiveness frontier. CHB chronic hepatitis B. CI confidence intervals. FN false negative. FP false positive. HBV hepatitis B virus. HCC hepatocellular carcinoma. ICER incremental cost-effectiveness ratio. NITs noninvasive tests. QUADAS Quality Assessment of Diagnostic Accuracy Studies. QUALYs quality-adjusted-life-years. TN true negative. TP true positive.Copyright © 2015 The Authors. We compared the cost-effectiveness of various noninvasive tests (NITs) in patients with chronic hepatitis B and elevated transaminases and/or viral load who would normally undergo liver biopsy to inform treatment decisions. We searched various databases until April 2012. We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes quality-adjusted-life-years (QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four decision-making strategies: testing with NITs and treating patients with fibrosis stage ≥F2, testing with liver biopsy and treating patients with ≥F2, treat none (watchful waiting) and treat all irrespective of fibrosis. Treating all patients without prior fibrosis assessment had an incremental cost-effectiveness ratio (ICER) of £28 137 per additional QALY gained for HBeAg-negative patients. For HBeAg-positive patients, using Fibroscan was the most cost-effective option with an ICER of £23 345. The base case results remained robust in the majority of sensitivity analyses, but were sensitive to changes in the ≥F2 prevalence and the benefit of treatment in patients with F0–F1. For HBeAg-negative patients, strategies excluding NITs were the most cost-effective: treating all patients regardless of fibrosis level if the high cost-effectiveness threshold of £30 000 is accepted; watchful waiting if not. For HBeAg-positive patients, using Fibroscan to identify and treat those with ≥F2 was the most cost-effective option.The analysis for Hepatitis B was part of a larger project funded by The National Institute for Health Research Health Technology Assessment (HTA project 09/114/02) and will be published in full in the Health Technology Assessment journal series. Visit the HTA programme website for more details www.hta.ac.uk/link to project page

Education can improve the negative perception of a threatened long-lived scavenging bird, the Andean condor

Human-wildlife conflicts currently represent one of the main conservation problems for wildlife species around the world. Vultures have serious conservation concerns, many of which are related to people's adverse perception about them due to the belief that they prey on livestock. Our aim was to assess local perception and the factors influencing people's perception of the largest scavenging bird in South America, the Andean condor. For this, we interviewed 112 people from Valle Fértil, San Juan province, a rural area of central west Argentina. Overall, people in the area mostly have an elementary education, and their most important activity is livestock rearing. The results showed that, in general, most people perceive the Andean condor as an injurious species and, in fact, some people recognize that they still kill condors. We identified two major factors that affect this perception, the education level of villagers and their relationship with livestock ranching. Our study suggests that conservation of condors and other similar scavengers depends on education programs designed to change the negative perception people have about them. Such programs should be particularly focused on ranchers since they are the ones who have the worst perception of these scavengers. We suggest that highlighting the central ecological role of scavengers and recovering their cultural value would be fundamental to reverse their persecution and their negative perception by people.Fil: Cailly Arnulphi, Verónica Beatríz. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Lambertucci, Sergio Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; ArgentinaFil: Borghi, Carlos Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; Argentin

Towards sustainable processing of columbite group minerals: elucidating the relation between dielectric properties and physico-chemical transformations in the mineral phase

Current methodologies for the extraction of tantalum and niobium pose a serious threat to human beings and the environment due to the use of hydrofluoric acid (HF). Niobium and tantalum metal powders and pentoxides are widely used for energy efficient devices and components. However, the current processing methods for niobium and tantalum metals and oxides are energy inefficient. This dichotomy between materials use for energy applications and their inefficient processing is the main motivation for exploring a new methodology for the extraction of these two oxides, investigating the microwave absorption properties of the reaction products formed during the alkali roasting of niobium-tantalum bearing minerals with sodium bicarbonate. The experimental findings from dielectric measurement at elevated temperatures demonstrate an exponential increase in the values of the dielectric properties as a result of the formation of NaNbO3-NaTaO3solid solutions at temperatures above 700 °C. The investigation of the evolution of the dielectric properties during the roasting reaction is a key feature in underpinning the mechanism for designing a new microwave assisted high-temperature process for the selective separation of niobium and tantalum oxides from the remainder mineral crystalline lattice