The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Flexural Behavior of Carbon Textile-Reinforced Geopolymer Composite Thin Plate

Textile-reinforced Portland cement-based concrete has been researched and developed over the last few decades. It was widely used in a different range of applications, such as repair and/or strengthening of structural elements, thin walls, lightweight structures, façade elements, and others. Due to its varied application, this study aims to develop the carbon textile-reinforced geopolymer composite. Specimens of rectangular form with the dimensions of 400 × 100 × 15 mm3, reinforced with carbon textile, were produced. Four-point bending test was used to evaluate the effect of carbon textile on the mechanical strength of reinforced geopolymer composite based on the three factors: the different mortar compositions corresponding to the addition of the chopped basalt fiber (BF), the number of carbon textile layers, and the different thicknesses of the mortar cover layer. Besides that, a small part of the pull-out test was also considered to assess the adhesion strength at the interface between carbon textile and geopolymer mortar. The experimental results from the four-point bending test showed that the mechanical strength of composite specimens increased when the content of the chopped basalt fiber increased. With the increasing number of the textile layers, the specimens improved the flexural strength significantly. However, the flexural toughness of the specimens reinforced with three textile layers did not improve, as compared to those reinforced with two textile layers. The experimental results for the specimens related to the mortar cover thicknesses indicated that specimens with the mortar cover thickness of 2 mm provide the best strength. The experimental results from the pull-out tests showed that all the specimens have the same failure mode by slipping of the fiber yarn from the matrix

Le niveau moyen de la mer en Istrie à l’époque romaine

International audienc

Fas receptor is required for estrogen deficiency-induced bone loss in mice

Bone mass is determined by bone cell differentiation, activity, and death, which mainly occur through apoptosis. Apoptosis can be triggered by death receptor Fas (CD95), expressed on osteoblasts and osteoclasts and may be regulated by estrogen. We have previously shown that signaling through Fas inhibits osteoblast differentiation. In this study we analyzed Fas as a possible mediator of bone loss induced by estrogen withdrawal. At 4 weeks after ovariectomy (OVX), Fas gene expression was greater in osteoblasts and lower in osteoclasts in ovariectomized C57BL/6J (wild type (wt)) mice compared with sham-operated animals. OVX was unable to induce bone loss in mice with a gene knockout for Fas (Fas -/- mice). The number of osteoclasts increased in wt mice after OVX, whereas it remained unchanged in Fas -/- mice. OVX induced greater stimulation of osteoblastogenesis in Fas -/- than in wt mice, with higher expression of osteoblast-specific genes. Direct effects on bone cell differentiation and apoptosis in vivo were confirmed in vitro, in which addition of estradiol decreased Fas expression and partially abrogated the apoptotic and differentiation-inhibitory effect of Fas in osteoblast lineage cells, while having no effect on Fas-induced apoptosis in osteoclast lineage cells. In conclusion, the Fas receptor has an important role in the pathogenesis of postmenopausal osteoporosis by mediating apoptosis and inhibiting differentiation of osteoblast lineage cells. Modulation of Fas effects on bone cells may be used as a therapeutic target in the treatment of osteoresorptive disorders

Méthodes de relevés de vestiges submergés

International audienc

Mechanical properties of geopolymer foam at high temperature

In this work, geopolymer foam composites containing waste basalt fibre (10, 30, and 50%wt) were exposed to elevated temperatures of 200, 400, 600, 800 and 1000∘C. With an increase in high temperature, the geopolymer foams material exhibits a decrease in compressive strength and bending strength. When heated above 600∘C, geopolymer foams materials exhibit a significant reduction in mechanical properties. It shows clearly with the naked eye that surface cracks in case of samples containing 10% of basalt filler. However, when increasing fillers with basalt fibres up to 30% and 50%, the cracking of the sample surface is no longer visible to the naked eye. Especially when the temperature increases, the mechanical properties also increase without decreasing in the sample of 50% by weighing to the binder. The results show that reinforcing the geopolymer foams with basalt ground fibre improves the mechanical properties at high temperatures

Oxidation of Са2+-Binding Domain of NADPH Oxidase 5 (NOX5): Toward Understanding the Mechanism of Inactivation of NOX5 by ROS.

NOX5 protein, one of the most active generators of reactive oxygen species (ROS), plays an important role in many processes, including regulation of cell growth, death and differentiation. Because of its central role in ROS generation, it needs to be tightly regulated to guarantee cellular homeostasis. Contrary to other members of NADPH-oxidases family, NOX5 has its own regulatory calcium-binding domain and thus could be activated directly by calcium ions. While several mechanisms of activation have been described, very little is known about the mechanisms that could prevent the overproduction of ROS by NOX5. In the present study using calorimetric methods and circular dichroism we found that oxidation of cysteine and methionine residues of NOX5 decreases binding of Ca2+ ions and perturbs both secondary and tertiary structure of protein. Our data strongly suggest that oxidation of calcium-binding domain of NOX5 could be implicated in its inactivation, serving as a possible defense mechanism against oxidative stress

Sequence of the fragment 1–169 of Human NOX5 (isoform β) with four aligned EF-hand calcium-binding motives.

<p>Canonical EF-hand motives are shown in red, and non-canonical (with deletion at position Y) in brown. Amino acids which are involved in calcium binding (in positions 1, 3, 5, 7, 9 and 12 of motives) are underlined and are denoted by X, Y, Z, -Y, -X and -Z. Met1, Met 77, Cys107 and Met155 residues subjected to oxidation are shown in green.</p