Myocarditis, disseminated infection, and early viral persistence following experimental coxsackievirus B infection of cynomolgus monkeys.

Coxsackievirus B (CVB) infection is a common cause of acute viral myocarditis. The clinical presentation of myocarditis caused by this enterovirus is highly variable, ranging from mildly symptoms to complete hemodynamic collapse. These variations in initial symptoms and in the immediate and long term outcomes of this disease have impeded development of effective treatment strategies. Nine cynomolgus monkeys were inoculated with myocarditic strains of CVB. Virological studies performed up to 28 days post-inoculation demonstrated the development of neutralizing antibody in all animals, and the presence of CVB in plasma. High dose intravenous inoculation (n = 2) resulted in severe disseminated disease, while low dose intravenous (n = 6) or oral infection (1 animal) resulted in clinically unapparent infection. Transient, minor, echocardiographic abnormalities were noted in several animals, but no animals displayed signs of significant acute cardiac failure. Although viremia rapidly resolved, signs of myocardial inflammation and injury were observed in all animals at the time of necropsy, and CVB was detected in postmortem myocardial specimens up to 28 days PI. This non-human primate system replicates many features of illness in acute coxsackievirus myocarditis and demonstrates that myocardial involvement may be common in enteroviral infection; it may provide a model system for testing of treatment strategies for enteroviral infections and acute coxsackievirus myocarditis

Micromechanics Contribution to Coupled Transport and Mechanical Properties of Fractured Geomaterials

International audienceThis article is devoted to the modelling of interdependent mechanical and hydraulic behaviours of geomaterials in presence of a single through-wall fracture by means of micromechanics arguments. Experimental results of fractured concrete samples show non-linear evolutions for both mechanical and hydraulic behaviours with respect to confinement intensity. These non-linear responses are interpreted by the progressive closure of crack-like pores defining the pore volume of the fracture interfacial domain. Disregarding tortuosity effects, we adopt a 2D representation for these cracks. The key role of the fracture initial porosity is also emphasized. It allows to discuss the shape of the distribution of the local apertures distribution function classically used, intercepted here in terms of the distribution of initial crack–aspect ratio within the fracture domain. Application on fractured concrete samples shows the capability of the theoretical model to accurately reproduce the experimental results

Etanchéité de l'interface argilite-bentonite re-saturée et soumise à une pression de gaz, dans le contexte du stockage profond de déchets radioactifs

En France, le système de stockage profond de déchets radioactifs envisagé est constitué d une barrière naturelle (roche hôte argileuse, argilite) et de barrières artificielles, comprenant des bouchons d argile gonflante (bentonite)-sable pour son scellement. L'objectif de cette thèse est d étudier l efficacité du gonflement et du scellement des bouchons placés dans l argilite, sous l effet, à la fois, d une pression d eau et d une pression de gaz (tel que formé dans le tunnel). Pour évaluer la capacité de scellement du bouchon bentonite/sable partiellement saturé en eau, on a évalué sa perméabilité au gaz Kgaz sous pression de confinement variable (jusqu à 12MPa). L'étanchéité au gaz (Kgaz =9MPa si la saturation est d au moins 86-91%. Par ailleurs, nous avons évalué le gonflement et l'étanchéité du bouchon de bentonite-sable imbibé d eau dans un tube d argilite ou de Plexiglas-aluminium lisse ou rugueux. La présence de gaz diminue la pression effective de gonflement (et la pression de percée de gaz) à partir d une pression Pgaz= 4 MPa. Après saturation complète en eau, l écoulement continu de gaz au travers du bouchon seul se fait à Pgaz=7-8MPa s il dispose d une interface lisse avec un autre matériau (tube métallique), alors que celui au travers de l ensemble bouchon/argilite a lieu à Pgaz=7-7,5MPa. Le passage à travers le bouchon gonflé au contact d une interface rugueuse se fait à une pression de gaz bien supérieure à la pression de gonflement du bouchon. Les essais de percée de gaz montrent que l'interface et l'argilite sont deux voies possibles de migration de gaz lorsque l ensemble bouchon/roche hôte est complètement saturéIn France, the deep underground nuclear waste repository consists of a natural barrier (in an argillaceous rock named argillite), associated to artificial barriers, including plugs of swelling clay (bentonite)-sand for tunnel sealing purposes. The main objective of this thesis is to assess the sealing efficiency of the bentonite-sand plug in contact with argillite, in presence of both water and gas pressures. To assess the sealing ability of partially water-saturated bentonite/sand plugs, their gas permeability is measured under varying confining pressure (up to 12MPa). It is observed that tightness to gas is achieved under confinement greater than 9MPafor saturation levels of at least 86-91%. We than assess the sealing efficiency of the bentonite-sand plug placed in a tube of argillite or of Plexiglas-aluminium (with a smooth or a rough interface). The presence of pressurized gas affects the effective swelling pressure at values Pgas from 4MPa. Continuous gas breakthrough of fully water-saturated bentonite-sand plugs is obtained for gas pressures on the order of full swelling pressure (7-8MPa), whenever the plug is applied along a smooth interface. Whenever a rough interface is used in contact with the bentonite-sand plug, a gas pressure significantly greater than its swelling pressure is needed for gas to pass continuously. Gas breakthrough tests show that the interface between plug/argillite or the argillite itself are two preferential pathways for gas migration, when the assembly is fully saturatedVILLENEUVE D'ASCQ-ECLI (590092307) / SudocSudocFranceF

Pkd1 Regulates Lymphatic Vascular Morphogenesis during Development.

Lymphatic vessels arise during development through sprouting of precursor cells from veins, which is regulated by known signaling and transcriptional mechanisms. The ongoing elaboration of vessels to form a network is less well understood. This involves cell polarization, coordinated migration, adhesion, mixing, regression, and shape rearrangements. We identified a zebrafish mutant, lymphatic and cardiac defects 1 (lyc1), with reduced lymphatic vessel development. A mutation in polycystic kidney disease 1a was responsible for the phenotype. PKD1 is the most frequently mutated gene in autosomal dominant polycystic kidney disease (ADPKD). Initial lymphatic precursor sprouting is normal in lyc1 mutants, but ongoing migration fails. Loss of Pkd1 in mice has no effect on precursor sprouting but leads to failed morphogenesis of the subcutaneous lymphatic network. Individual lymphatic endothelial cells display defective polarity, elongation, and adherens junctions. This work identifies a highly selective and unexpected role for Pkd1 in lymphatic vessel morphogenesis during development

New International Guidelines and Consensus on the Use of Lung Ultrasound

Following the innovations and new discoveries of the last 10 years in the field of lung ultrasound (LUS), a multidisciplinary panel of international LUS experts from six countries and from different fields (clinical and technical) reviewed and updated the original international consensus for point-of-care LUS, dated 2012. As a result, a total of 20 statements have been produced. Each statement is complemented by guidelines and future developments proposals. The statements are furthermore classified based on their nature as technical (5), clinical (11), educational (3), and safety (1) statements

Use of Hydrothermal Carbonization and Cold Atmospheric Plasma for Surface Modification of Brewer’s Spent Grain and Activated Carbon

This paper presents results that show the effect of hydrothermal carbonization and subsequent cold plasma jet treatment with helium and argon on the structure and sorption properties of a material—spent brewery grain. Treatment of activated carbon, with a cold atmospheric plasma jet, was used comparatively. The effect of activation on the pore structure of the materials was carried out by the volumetric method at low pressure (N2, 77 K). The specific surface area as well as the total pore volume, average pore size, and pore size distribution were determined using different theoretical models. A high improvement in the sorption capacity parameter was obtained for hydrochars after cold atmospheric plasma jet treatment with an increase of 7.5 times (using He) and 11.6 times (using Ar) compared with hydrochars before cold atmospheric plasma jet treatment. The increase in specific surface area was five-fold (He) and fifteen-fold (Ar). For activated carbon, such a large change was not obtained after plasma activation. Regardless of the gas used, the increase in structural parameter values was 1.1–1.3

Structural Basis of PP2A Inhibition by Small t Antigen

The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity by displacing regulatory B subunits from the A subunit. We have determined the crystal structure of full-length ST in complex with PP2A A subunit at 3.1 Å resolution. ST consists of an N-terminal J domain and a C-terminal unique domain that contains two zinc-binding motifs. Both the J domain and second zinc-binding motif interact with the intra-HEAT-repeat loops of HEAT repeats 3–7 of the A subunit, which overlaps with the binding site of the PP2A B56 subunit. Intriguingly, the first zinc-binding motif is in a position that may allow it to directly interact with and inhibit the phosphatase activity of the PP2A catalytic C subunit. These observations provide a structural basis for understanding the oncogenic functions of ST

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised