MECHANICAL BEHAVIOUR AND RUPTURE IN CLAYEY ROCKS STUDIED BY X-RAY MICRO-TOMOGRAPHY AND 3D-DIGITAL IMAGE CORRELATION

International audienceThe mechanical behaviour and the rupture of clayey rocks have been experimentally studied by performing in situ triaxial tests on a synchrotron beamline i.e. performing X-ray micro tomography scans under mechanical loading. The 3D images obtained at different steps of the test were then analysed by 3D-Digital Image Correlation method in order to measure incremental strain fields. The results allow to clearly detect the onset of shear strain localization and to characterize its development in a 3D complex pattern

Les objets actuels de la recherche en éducation

Cet article a pour thème « les objets actuels de la recherche en éducation ». Fruit de la collaboration de plusieurs spécialistes du domaine, il donne à voir l'étendue de l'espace qu'occupent les chercheurs en éducation, l'exigence posée par les méthodes à l'endroit de leur objet et l'ampleur des défis qui les attendent. Recherche pédagogique, recherche sur les pratiques, recherche en didactique, recherche sur les fondements et recherche disciplinaire, entre autres champs de recherche en éducation, coexistent et trouvent leur légitimité. Ces recherches contribuent autant à définir l'objet des sciences de l'éducation qu'à enrichir la réflexion sur les pratiques.This article which develops the theme of current topics of research in education is the result of a collaborative project among several experts in this area, and presents a description of the vast field in which educational researchers work, the methodological requirements related to the various research areas, and the important challenges which researchers confront. Research in the disciplines, in didactics, in pedagogy, in foundations and in practices, among other fields of research in education, co-exist and find a legitimate place in this arena. This article contributes both to defining the object of educational research and to enriching the debate and thinking about research practices.Este articulo tiene por tema "los sujetos actuales de la investigacion en education". Fruto de la colaboracion de varios especialistas del sector, el trabajo présenta un amplio panorama del espacio que ocupan los investigadores en education, las exigencias que imponen los métodos especificos al objeto de estudio y la amplitud de los desafios que los acechan. Investigacion disciplinaria, investigacion didatica, investigacion pedagogica, investigaciôn sobre los fundamentos e investigacion sobre la prâcticas, entre otros campos de investigacion, coexisten y se ligitiman mutuamente. Estas investigaciones contribuyen tan to para définir el objeto de las ciencias de la educacion como para enriquecer la reflexion sobre su prâctica.Dieser Artikel beschâftigt sich mit den "gegenwârtigen Gegenstânden der Bildungsforschung" und stellt von Spezialisten in diesem Bereich gemeinsam erarbeitete Ergebnisse vor. Dièse vermitteln einen Eindruck von den weitgefâcherten Forschungsaufgaben auf dem Bildungssektor, von den methodologischen Erfordernissen im Hinblick auf die Gegenstânde sowie von den Herausforderungen, die die Forscher erwarten. Disziplingebundene Forschung, didaktische Forschung, pâdagogische Forschung, Grundlagenund Praxisforschung, um nur einige Bereiche zu nennen, koexistieren und erweisen ihre Legitimitât. Dièse Forschungen tragen dazu bei, den Gegenstand der Erziehungswissenschaft nàher zu bestimmen sowie die Reflexion iiber die Erziehungspraxis zu bereichern

Caractérisation expérimentale de la déformation et de la rupture localisée dans une argilite

Nous présentons une étude expérimentale de caractérisation de la rupture par localisation de la déformation dans une roche argileuse. Des essais triaxiaux ont été effectués sur une ligne de lumière de l'ESRF pour obtenir des reconstructions microtomographiques en volume à différents stades de l'essai. Une mesure du champ de la déformation a été faite en associant aux images obtenues une méthode de corrélation d'images en volume. Ces résultats permettent d'identifier très clairement le seuil d'initiation de la localisation, et le mode de déformation dans les bandes

In vitro prediction of stop-codon suppression by intravenous gentamicin in patients with cystic fibrosis: a pilot study

BACKGROUND: Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which acts as a chloride channel activated by cyclic AMP (cAMP). The most frequent mutation found in 70% of CF patients is F508del, while premature stop mutations are found in about 10% of patients. In vitro aminoglycoside antibiotics (e.g. gentamicin) suppress nonsense mutations located in CFTR permitting translation to continue to the natural termination codon. Pharmacologic suppression of stop mutations within the CFTR may be of benefit to a significant number of patients. Our pilot study was conducted to determine whether intravenous gentamicin suppresses stop codons in CF patients and whether it has clinical benefits. METHODS: A dual gene reporter system was used to determine the gentamicin-induced readthrough level of the most frequent stop mutations within the CFTR in the French population. We investigated readthrough efficiency in response to 10 mg/kg once-daily intravenous gentamicin perfusions in patients with and without stop mutations. Respiratory function, sweat chloride concentration, nasal potential difference (NPD) and CFTR expression in nasal epithelial cells were measured at baseline and after 15 days of treatment. RESULTS: After in vitro gentamicin incubation, the readthrough efficiency for the Y122X mutation was at least five times higher than that for G542X, R1162X, and W1282X. In six of the nine patients with the Y122X mutation, CFTR immunodetection showed protein at the membrane of the nasal epithelial cells and the CFTR-dependent Cl(- )secretion in NPD measurements increased significantly. Respiratory status also improved in these patients, irrespective of the gentamicin sensitivity of the bacteria present in the sputum. Mean sweat chloride concentration decreased significantly and normalised in two patients. Clinical status, NPD and sweat Cl(- )values did not change in the Y122X patients with no protein expression, in patients with the other stop mutations investigated in vitro and those without stop mutations. CONCLUSION: Suppression of stop mutations in the CFTR gene with parenteral gentamicin can be predicted in vitro and is associated with clinical benefit and significant modification of the CFTR-mediated Cl(- )transport in nasal and sweat gland epithelium

Deletion of the myeloid endothelin-B receptor confers long-term protection from angiotensin II-mediated renal, retinal & vascular injury

International audienceThe endothelin system may be an important player in hypertensive end-organ injury as endothelin-1 increases blood pressure and is pro-inflammatory. The immune system is emerging as an important regulator of blood pressure and we have shown that the early hypertensive response to angiotensin-II infusion was amplified in mice deficient of myeloid endothelin-B (ETB) receptors (LysM-CreEdnrblox/lox). Hypothesizing that these mice would display enhanced organ injury, we gave angiotensin-II to LysM-CreEdnrblox/lox and littermate controls (Ednrblox/lox) for six weeks. Unexpectedly, LysM-CreEdnrblox/lox mice were significantly protected from organ injury, with less proteinuria, glomerulosclerosis and inflammation of the kidney compared to controls. In the eye, LysM-CreEdnrblox/lox mice had fewer retinal hemorrhages, less microglial activation and less vessel rarefaction. Cardiac remodeling and dysfunction were similar in both groups at week six but LysM-CreEdnrblox/lox mice had better endothelial function. Although blood pressure was initially higher in LysM-CreEdnrblox/lox mice, this was not sustained. A natriuretic switch at about two weeks, due to enhanced ETB signaling in the kidney, induced a hypertensive reversal. By week six, blood pressure was lower in LysM-CreEdnrblox/lox mice than in controls. At six weeks, macrophages from LysM-CreEdnrblox/lox mice were more anti-inflammatory and had greater phagocytic ability compared to the macrophages of Ednrblox/lox mice. Thus, myeloid cell ETB receptor signaling drives this injury both through amplifying hypertension and by inflammatory polarization of macrophages

Technological developments as an answer to bridge management challenges

IABSE Symposium 2019, Towards a Resilient Built Environment - Risk and Asset Management, GUIMARAES, PORTUGAL, 27-/03/2019 - 29/03/2019Bridge management is a challenge as owners have to deal with limited financial resources to maintain the functionalities and safety of ageing structures. Demands on transportation networks change, due to regulatory developments, society's evolution and shifts with high expectations on the operational performance of roadway bridges with reduced congestion, delay, and accidents. To minimize intrusion in the transport flow, inspection and monitoring methods should be non?destructive, minimally invasive. They should be capable of yielding rapid and accurate inspection results allowing an adequate response from the asset manager. Research aims at including autonomously operating equipment (e.g. robotics), non?intrusive (remote or proximity) observation techniques, or other methods that ensure quality and performance control of the roadway bridges in time, more safely, more quickly and/or to a higher degree of accuracy and precision.The innovation subgroup in COST action TU1406 investigates novel condition monitoring and sensing technologies for the assessment of structural serviceability and safety. Advanced, integrated, cost-effective and reliable instrumentation solutions, techniques and concepts are looked at with the aim to provide data, that will be used to compute innovative performance indicators. In this context, this paper briefly reminds some significant challenges associated with bridge management and presents three examples of innovation in bridge monitoring and NDT investigation techniques

Frailty assessment for COVID-19 follow-up: a prospective cohort study.

BACKGROUND The Clinical Frailty Scale (CFS) is increasingly used for clinical decision making in acute care but little is known about frailty after COVID-19. OBJECTIVES To investigate frailty and the CFS for post-COVID-19 follow-up. METHODS This prospective multicentre cohort study included COVID-19 survivors aged ≥50 years presenting for a follow-up visit ≥3 months after the acute illness. Nine centres retrospectively collected pre-COVID-19 CFS and prospectively CFS at follow-up. Three centres completed the Frailty Index (FI), the short physical performance battery (SPPB), 30 s sit-to-stand test and handgrip strength measurements. Mixed effect logistic regression models accounting for repeated measurements and potential confounders were used to investigate factors associated with post-COVID-19 CFS. Criterion and construct validity were determined by correlating the CFS to other concurrently assessed frailty measurements and measures of respiratory impairment, respectively. RESULTS Of the 288 participants 65% were men, mean (SD) age was 65.1 (9) years. Median (IQR) CFS at follow-up was 3 (2-3), 21% were vulnerable or frail (CFS ≥4). The CFS was responsive to change, correlated with the FI (r=0.69, p<0.001), the SPPB score (r=-0.48, p<0.001) (criterion validity) and with the St George's Respiratory Questionnaire score (r=0.59, p<0.001), forced vital capacity %-predicted (r=-0.25, p<0.001), 6 min walk distance (r=-0.39, p<0.001) and modified Medical Research Council (mMRC) (r=0.59, p<0.001). Dyspnoea was significantly associated with a higher odds for vulnerability/frailty (per one mMRC adjusted OR 2.01 (95% CI 1.13 to 3.58), p=0.02). CONCLUSIONS The CFS significantly increases with COVID-19, and dyspnoea is an important risk factor for post-COVID-19 frailty and should be addressed thoroughly

Mycobacterium abscessus and Children with Cystic Fibrosis

We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5–22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including 10 with >3 positive samples (versus 3 patients for M. avium complex). The M. abscessus isolates from 14 patients were typed by pulsed-field gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out a common environmental reservoir or person-to-person transmission. Water samples collected in the cystic fibrosis center were negative for M. abscessus. This major mycobacterial pathogen in children and teenagers with cystic fibrosis does not appear to be acquired nosocomially

The endothelin B receptor plays a crucial role in the adhesion of neutrophils to the endothelium in sickle cell disease

Although the primary origin of sickle cell disease is a hemoglobin disorder, many types of cells contribute considerably to the pathophysiology of the disease. The adhesion of neutrophils to activated endothelium is critical in the pathophysiology of sickle cell disease and targeting neutrophils and their interactions with endothelium represents an important opportunity for the development of new therapeutics. We focused on endothelin-1, a mediator involved in neutrophil activation and recruitment in tissues, and investigated the involvement of the endothelin receptors in the interaction of neutrophils with endothelial cells. We used fluorescence intravital microscopy analyses of the microcirculation in sickle mice and quantitative microfluidic fluorescence microscopy of human blood. Both experiments on the mouse model and patients indicate that blocking endothelin receptors, particularly ETB receptor, strongly influences neutrophil recruitment under inflammatory conditions in sickle cell disease. We show that human neutrophils have functional ETB receptors with calcium signaling capability, leading to increased adhesion to the endothelium through effects on both endothelial cells and neutrophils. Intact ETB function was found to be required for tumor necrosis factor α-dependent upregulation of CD11b on neutrophils. Furthermore, we confirmed that human neutrophils synthesize endothelin-1, which may be involved in autocrine and paracrine pathophysiological actions. Thus, the endothelin-ETB axis should be considered as a cytokine-like potent pro-inflammatory pathway in sickle cell disease. Blockade of endothelin receptors, including ETB, may provide major benefits for preventing or treating vaso-occlusive crises in sickle cell patients