Influence of offset weak zones on the development of rift basins: Activation and abandonment during continental extension and breakup: Offset weak zones and rift basins

International audienceWe use numerical modelling to investigate reactivation of inherited Offset Weak Zones (OWZ) in continental crust and Mantle Weak Zones (MWZ) to form offset rift basins during continental rifting and breakup. Offset rift basins are basins that are set off/offset from the main rift/locus of breakup. Weak zones embedded in a stiff layer are preferentially and rapidly reactivated, whereas the same zones are either ignored or slowly reactivated when embedded in pliable layers. Here `Stiff' implies a nonlinear flow law with a high stress exponent (n ~ 10,000), a plastic material, and `Pliable' means a low stress exponent (n ~2 - 5) as in ductile, power-law creep of rocks. Whether offset rift basins form during rifting of a composite lithosphere, (i.e. comprising stiff and pliable layers) depends on the competition between necking instabilities that develop at the weak zones in the stiff layers, and the coupling between the stiff and pliable layers. Stiff/cratonic lithosphere results in early localization of the deformation at the MWZ, rapid necking and breakup without developing offset rift basins. In contrast, warm pliable lithosphere develops significant offset basins and has protracted rifting because the MWZ is now embedded in a pliable layer. We also investigate the influence of OWZ dip, sedimentation, and the sensitivity of reactivation to the distance from OWZ to the MWZ, and to the size of the MWZ. A tectonic rifting styles diagram is used to show that the model results agree with natural examples

Sequential biogenesis of host cell membrane rearrangements induced by hepatitis C virus infection.: HCV-induced membrane rearrangements

International audienceLike most positive-strand RNA viruses, hepatitis C virus (HCV) forms a membrane-associated replication complex consisting of replicating RNA, viral and host proteins anchored to altered cell membranes. We used a combination of qualitative and quantitative electron microscopy (EM), immuno-EM, and the 3D reconstruction of serial EM sections to analyze the host cell membrane alterations induced by HCV. Three different types of membrane alteration were observed: vesicles in clusters (ViCs), contiguous vesicles (CVs), and double-membrane vesicles (DMVs). The main ultrastructural change observed early in infection was the formation of a network of CVs surrounding the lipid droplets. Later stages in the infectious cycle were characterized by a large increase in the number of DMVs, which may be derived from the CVs. These DMVs are thought to constitute the membranous structures harboring the viral replication complexes in which viral replication is firmly and permanently established and to protect the virus against double-stranded RNA-triggered host antiviral responses

Encapsulation of epsilon-Viniferin into Multi-Lamellar Liposomes: Development of a Rapid, Easy and Cost-Efficient Separation Method to Determine the Encapsulation Efficiency

Onion-type multi-lamellar liposomes (MLLs), composed of a mixture of phosphatidylcholine and Tween 80, were analyzed for their ability to encapsulate epsilon-Viniferin (epsilon Vin), a resveratrol dimer. Their encapsulation efficiency (EE) was measured by UV-VIS spectroscopy using three different separation methods-ultracentrifugation, size exclusion chromatography, and a more original and advantageous one, based on adsorption filtration. The adsorption filtration method consists indeed of using syringe filters to retain the molecule of interest, and not the liposomes as usually performed. The process is rapid (less than 10 min), easy to handle, and inexpensive in terms of sample amount (around 2 mg of liposomes) and equipment (one syringe filter is required). Whatever the separation method, a similar EE value was determined, validating the proposed method. A total of 80% +/- 4% of epsilon Vin was found to be encapsulated leading to a 6.1% payload, roughly twice those reported for resveratrol-loaded liposomes. Finally, the release kinetics of epsilon Vin from MLLs was followed for a 77 day period, demonstrating a slow release of the polyphenol

Beneficial Effects of ε-Viniferin on Obesity and Related Health Alterations

Viniferin is a phenolic compound belonging to the group of stilbenoids. In particular, ε-viniferin is a dimer of resveratrol, found in many plant genders, among which grapes (Vitis vinifera) are a primary source. Due to the fact that ε-viniferin is mainly present in the woody parts of plants, their use as a source of this bioactive compound is a very interesting issue in a circular economy. Both, in vitro studies carried out in pre-adipocytes and mature adipocytes and in vivo studies addressed in mice show that ε-viniferin is able to reduce fat accumulation. Moreover, it prevents the development of some obesity co-morbidities, such as type 2 diabetes, dyslipidemias, hypertension and fatty liver. ε-viniferin can be absorbed orally, but it shows a very low bioavailability. In this scenario, further research on animal models is needed to confirm the effects reported in a great number of studies; to determine which metabolites are involved, including the main one responsible for the biological effects observed and the mechanisms that justify these effects. In a further phase, human studies should be addressed in order to use ε-viniferin as a new tool for obesity management, as a nutraceutical or to be included in functional foods.This research was funded by CIBEROBN under Grant CB12/03/30007 and the Government of the Basque Country (IT1482-22)

In Vivo Genotoxicity Evaluation of a Stilbene Extract Prior to Its Use as a Natural Additive: A Combination of the Micronucleus Test and the Comet Assay

Genotoxic data of substances that could be used as food additives are required by the European Food Safety Authority. In this sense, the use of an extract from grapevine shoots containing a stilbene richness of 99% (ST-99), due to its antioxidant and antibacterial activities, has been proposed as an alternative to sulfur dioxide in wine. The aim of this work was to study, for the first time, the in vivo genotoxic effects produced in rats orally exposed to 90, 180, or 360 mg ST-99/kg body weight at 0, 24, and 45 h. The combination of micronucleus assay in bone marrow (OECD 474) and standard (OECD 489) and enzyme-modified comet assay was used to determine the genotoxicity on cells isolated from stomach, liver, and blood of exposed animals. The ST-99 revealed no in vivo genotoxicity. These results were corroborated by analytical studies that confirm the presence of stilbenes and their metabolites in plasma and tissues. Moreover, to complete these findings, a histopathological study was performed under light microscopy in liver and stomach showing only slight modifications in both organs at the highest concentration used. The present work confirms that this extract is not genotoxic presenting a good profile for its potential application as a preservative in the wine industry.España Ministerio de Economía, Industria y Competitividad and INIA RTA2015-00005-C02-0

Gray matter hypertrophy and thickening with obstructive sleep apnea in middle-aged and older adults

Rationale: Obstructive sleep apnea causes intermittent hypoxemia, hemodynamic fluctuations, and sleep fragmentation, all of which could damage cerebral gray matter that can be indirectly assessed with neuroimaging. Objectives: To investigate whether markers of obstructive sleep apnea severity are associated with gray matter changes among middle-aged and older individuals. Methods: Seventy-one subjects (ages: 55 to 76; apnea–hypopnea index: 0.2 to 96.6 events/h) were evaluated with magnetic resonance imaging. Two techniques were used: 1) voxel-based morphometry, which measures gray matter volume and concentration; 2) FreeSurfer automated segmentation, which estimates the volume of predefined cortical/subcortical regions and cortical thickness. Regression analyses were performed between gray matter characteristics and markers of obstructive sleep apnea severity (hypoxemia, respiratory disturbances, sleep fragmentation). Measurements and Main Results: Subjects had few symptoms, i.e. sleepiness, depression, anxiety and cognitive deficits. While no association was found with voxel-based morphometry, FreeSurfer revealed increased gray matter with obstructive sleep apnea. Higher levels of hypoxemia correlated with increased volume and thickness of the left lateral prefrontal cortex as well as increased thickness of the right frontal pole, the right lateral parietal lobules, and the left posterior cingulate cortex. Respiratory disturbances positively correlated with right amygdala volume while more severe sleep fragmentation was associated with increased thickness of the inferior frontal gyrus. Conclusions: Gray matter hypertrophy and thickening were associated with hypoxemia, respiratory disturbances, and sleep fragmentation. These structural changes in a group of middle-aged and older individuals may represent adaptive/reactive brain mechanisms attributed to a presymptomatic stage of obstructive sleep apnea

QR Prediction for Statistical Data Integration

n this paper, we investigate how a big non-probability database can be used to improve estimates from a small probability sample through data integration techniques. In the situation where the study variable is observed in both data sources, Kim and Tam (2021) proposed two design-consistent estimators that can be justified through dual frame survey theory. First, we provide conditions ensuring that these estimators are more eÿcient than the Horvitz-Thompson estimator when the probability sample is selected using either Poisson sampling or simple random sampling without replacement. Then, we study the class of QR predictors, proposed by Särndal and Wright (1984) to handle the case where the non-probability database contains auxiliary variables but no study variable. We provide conditions ensuring that the QR predictor is asymptotically design-unbiased. Assuming the probability sampling design is not informative, the QR predictor is also model-unbiased regardless of the validity of those conditions. We compare the design properties of di˙erent predictors, in the class of QR predictors, through a simulation study. They include a model-based predictor, a model-assisted estimator and a cosmetic estimator. In our simulation setups, the cosmetic estimator performed slightly better than the model-assisted estimator. As expected, the model-based predictor did not perform well when the underlying model was misspecified

Many-to-One indirect sampling with application to the French postal traffic estimation

In social and economic surveys, it can be difficult to directly reach units of the target population, and indirect sampling is often advocated to solve this issue. In indirect sampling, the sample is drawn from a frame population that is linked to the target population, and estimation of tar-get population parameters is typically achieved through the Generalized Weight Share Method (GWSM). This method provides a weight, for every unit of the target population, that depends on the one hand, on the sam-pling weights in the frame population and, on the other hand, on the link weights between the frame population and the target population. In the present study, we focus on the situation in which the units from the frame population are linked to one and only one unit from the target population (Many-to-One case). This situation is encountered at the French postal service where addresses are sampled instead of postman rounds. We aim at understanding of the impact of the link weights on the efficiency of the GWSM estimators. We derive variance expressions and optimality results for a large class of sampling designs. Moreover, we note that the Many-to-One case can lead to too many links to observe. We alleviate the problem by introducing an intermediate population and double indirect sampling. The question of the loss of precision in this situation is discussed in detail through theoretical results and simulations. These findings help to ex-plain the loss of precision of double GWSM estimators observed recently at the French postal service

Right ventricular function declines after cardiac surgery in adult patients with congenital heart disease

Right ventricular function (RVF) is often selectively declined after coronary artery bypass graft surgery. In adult patients with congenital heart disease (CHD) the incidence and persistence of declined RVF after cardiac surgery is unknown. The current study aimed to describe RVF after cardiac surgery in these patients. Adult CHD patients operated between January 2008 and December 2009 in the Academic Medical Centre in Amsterdam were studied. Clinical characteristics, laboratory tests, surgical data and intensive care unit outcome were obtained from medical records. RVF was measured by trans-thoracic echocardiography (TTE) and expressed by tricuspid annular plane systolic excursion (TAPSE), tissue Doppler imaging (RV S’) and myocardial performance index (MPI) pre-operatively and direct, at intermediate and late follow up. Of a total of 185 operated, 86 patients (mean age 39 ± 13 years, 54% male) had echo data available. There was a significant fall in RVF after cardiac surgery. TAPSE and RV S’ were significantly higher and MPI was significantly lower pre-operatively compared to direct post-operative values (TAPSE 22 ± 5 versus 13 ± 3 mm (P < 0.01), RV S’ 11 ± 4 versus 8 ± 2 cm/s (P < 0.01) and MPI 0.36 ± 0.14 vs 0.62 ± 0.25; P < 0.01). There were no significant differences in left ventricular function pre-operatively compared to post-operative values. Right-sided surgery was performed in 33, left-sided surgery in 37 and both sided surgery in 16 patients. Decline in RVF was equal for those groups. Patients with severe decline in RVF, were patients who underwent tricuspid valve surgery. Decline in RVF was associated with post-operative myocardial creatine kinase level and maximal troponin T level. There was no association between decline in RVF and clinical outcome on the intensive care unit. 18 months post-operatively, most RVF parameters had recovered to pre-operative values, but TAPSE which remained still lower (P < 0.01). CHD patients have a decline in RVF directly after cardiac surgery, regardless the side of surgery. Although a gradual improvement was observed, complete recovery was not seen 18 months post-operatively

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation