88 research outputs found

    Water weathering in rocks discontinuities

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    The behavior of rock discontinuities at different spatial scales remains a major challenge for scientists who want to understand the rock alteration, both in the triggering of rock-fall and in the evolution of the cliffs. Our research aim to take into account the geomorphological features related to the slopes and rock discontinuities subject to weathering conditions. Several studies show the physical effect of water in the alteration of rock through cracks and micro cracks. In Cultural Heritage point of view, a rock discontinuity could be described or analyzed as the interface between stone and joint in buildings. The mechanical and physical discontinuity behavior and its time evolution have a strong influence on the onset of instability of the blocks and on their strength. The effects of climate change (increase of rainfall, temperature fluctuation...), may significantly increase the inception of phenomena such rock falls, stone degradation and damages on monuments. The aim of this study is to characterize the chemical influence of water flowing inside the discontinuity and also through the porous stone matrix. This paper focus on experiments performed in order to analyze the effects of physical and chemical alteration on the mechanical behavior of porous limestone. Limestone is a both commonly stone used in construction of cultural heritage buildings and found on French territory. These experiments could have some interesting results in restoration or conservation of building. We'll present the results of the first two experiments performed in quasi-static and dynamic of the flowing process. The observation and the monitoring of the alteration process are performed in order to determine the physical and chemical reactions involved in this phenomenon. This one we'll be linked to the mechanical aspect of the massif and or the building

    Multi-scale analysis of water alteration on the rockslope stability framework

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    International audienceWater is an important weathering factor on rock discontinuities and in rock mass mechanical behavior. The increase of rainfall in frequency or in intensity highlights some problems on the rock slope stability analysis. The aim of this paper is the multi scale analysis of the chemical impact of water on rock (surface roughness and matrix). In this study we show how water induces degradation and thus may decreases the stability of the discontinuous rock mass. Water is known to have significant erosion and dissolution effects on rock surface or rock matrix. The chemical features of water such as temperature, pH or salinity make it a 'good' candidate to rock degradation. This study has two main components. The first one is the study of water-solid chemical mechanisms and the other is the analysis of the mechanical response of the discontinuity modified by the water alteration. The stability of the rock mass is naturally a function of the type and the space distribution of discontinuities. The study aims also to evaluate the effect of water flow on the rock slope stability and it is performed at two space scales: laboratory (micro scale and macro scale) and in situ scales. The last one is still under investigation and will be presented

    Genetic determination of the effect of post-translational modification on the innate immune response to the 19 kDa lipoprotein of Mycobacterium tuberculosis

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    <p>Abstract</p> <p>Background</p> <p>The 19 kDa lipoprotein of <it>Mycobacterium tuberculosis </it>(MTB) is an important target of the innate immune response. To investigate the effect of post-translation modification of this protein on innate recognition in the context of the whole bacillus, we derived a recombinant <it>M. tuberculosis </it>H37Rv that lacked the 19 kDa gene (Δ19) and complemented this strain by reintroduction of the 19 kDa gene into the chromosome as a single copy to produce Δ19::19. We also reintroduced the 19 kDa gene in two modified forms that lacked motifs for acylation (Δ19::19NA) and <it>O</it>-glycosylation (Δ19::19NOG).</p> <p>Results</p> <p>Both acylation and <it>O</it>-glycosylation were necessary for the protein to remain within the cell. IL-1 Beta secretion from human monocytes was significantly reduced by deletion of the 19 kDa gene (p < 0.02). Complementation by the wild type, but not the mutagenised gene reversed this phenotype. The effect of deletion and complementation on IL-12p40 and TNF secretion was less marked with no statistically significant differences between strains. Although deletion of the 19 kDa reduced apoptosis, an effect that could also only be reversed by complementation with the wild type gene, the results were variable between donors and did not achieve statistical significance.</p> <p>Conclusion</p> <p>These results confirm in the context of the whole bacillus an important role for post-translational modification of the 19 kDa on both the cellular location and immune response to this protein.</p

    Evidence review of what works for health systems strengthening, where and when?

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    Comprehensive reviews of health system strengthening (HSS) interventions are rare, partly because of lack of clarity on definitions of the term but also the potentially huge scale of the evidence. We reflect on the process of undertaking such an evidence review recently, drawing out suggestions on definitions of HSS and approaches to assessment, as well as summarising some key conclusions from the current evidence base. The key elements of a clear definition include, in our view, consideration of scope (with effects cutting across building blocks in practice, even if not in intervention design, and also tackling more than one disease), scale (having national reach and cutting across levels of the system), sustainability (effects being sustained over time and addressing systemic blockages), and effects (impacting on health outcomes, equity, financial risk protection, and responsiveness). We also argue that agreeing a framework for design and evaluation of HSS is urgent. Most HSS interventions have theories of change relating to specific system blocks, but more work is needed on capturing their spillover effects and their contribution to meeting overarching health system process goals. We make some initial suggestions about such goals, to reflect the features that characterise a “strong health system.” We highlight that current findings on “what works” are just indicative, given the limitations and biases in what has been studied and how, and argue that there is need to rethink evaluation methods for HSS beyond finite interventions and narrow outcomes. Clearer concepts, frameworks, and methods can support more coherent HSS investment

    Effect of an Education Programme for South Asians with Asthma and Their Clinicians: A Cluster Randomised Controlled Trial (OEDIPUS).

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    BACKGROUND: People with asthma from ethnic minority groups experience significant morbidity. Culturally-specific interventions to reduce asthma morbidity are rare. We tested the hypothesis that a culturally-specific education programme, adapted from promising theory-based interventions developed in the USA, would reduce unscheduled care for South Asians with asthma in the UK. METHODS: A cluster randomised controlled trial, set in two east London boroughs. 105 of 107 eligible general practices were randomised to usual care or the education programme. Participants were south Asians with asthma aged 3 years and older with recent unscheduled care. The programme had two components: the Physician Asthma Care Education (PACE) programme and the Chronic Disease Self Management Programme (CDSMP), targeted at clinicians and patients with asthma respectively. Both were culturally adapted for south Asians with asthma. Specialist nurses, and primary care teams from intervention practices were trained using the PACE programme. South Asian participants attended an outpatient appointment; those registered with intervention practices received self-management training from PACE-trained specialist nurses, a follow-up appointment with PACE-trained primary care practices, and an invitation to attend the CDSMP. Patients from control practices received usual care. Primary outcome was unscheduled care. FINDINGS: 375 south Asians with asthma from 84 general practices took part, 183 registered with intervention practices and 192 with control practices. Primary outcome data were available for 358/375 (95.5%) of participants. The intervention had no effect on time to first unscheduled attendance for asthma (Adjusted Hazard Ratio AHR = 1.19 95% CI 0.92 to 1.53). Time to first review in primary care was reduced (AHR = 2.22, (1.67 to 2.95). Asthma-related quality of life and self-efficacy were improved at 3 months (adjusted mean difference -2.56, (-3.89 to -1.24); 0.44, (0.05 to 0.82) respectively. CONCLUSIONS: A multi-component education programme adapted for south Asians with asthma did not reduce unscheduled care but did improve follow-up in primary care, self-efficacy and quality of life. More effective interventions are needed for south Asians with asthma

    Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

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    There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

    Innate activation of human primary epithelial cells broadens the host response to Mycobacterium tuberculosis in the airways

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    Early events in the human airways determining whether exposure to Mycobacterium tuberculosis (Mtb) results in acquisition of infection are poorly understood. Epithelial cells are the dominant cell type in the lungs, but little is known about their role in tuberculosis. We hypothesised that human primary airway epithelial cells are part of the first line of defense against Mtb-infection and contribute to the protective host response in the human respiratory tract. We modelled these early airway-interactions with human primary bronchial epithelial cells (PBECs) and alveolar macrophages. By combining in vitro infection and transwell co-culture models with a global transcriptomic approach, we identified PBECs to be inert to direct Mtb-infection, yet to be potent responders within an Mtb-activated immune network, mediated by IL1β and type I interferon (IFN). Activation of PBECs by Mtb-infected alveolar macrophages and monocytes increased expression of known and novel antimycobacterial peptides, defensins and S100-family members and epithelial-myeloid interactions further shaped the immunological environment during Mtb-infection by promoting neutrophil influx. This is the first in depth analysis of the primary epithelial response to infection and offers new insights into their emerging role in tuberculosis through complementing and amplifying responses to Mtb

    Effects of eight neuropsychiatric copy number variants on human brain structure

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    Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions
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