Aspirin and the Primary Prevention of Cardiovascular Diseases. An Approach Based on Individualized, Integrated Estimation of Risk

While the use of aspirin in the secondary prevention of cardiovascular (CVD) is well established, aspirin in primary prevention is not systematically recommended because the absolute CV event reduction is similar to the absolute excess in major bleedings. Recently, emerging evidence suggests the possibility that the assumption of aspirin, may also be effective in the prevention of cancer. By adding to the CV prevention benefits the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in the primary prevention in favour of the latter and broaden the indication for treatment with in populations at average risk. While prospective and randomized study are currently investigating the effect of aspirin in prevention of both cancer and CVD, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention could be already based on a balanced evaluation of the benefit/risk ratio

Validation d'un banc d'essais reproduisant les rafales de vent sur véhicule terrestre. Caractérisation de l'écoulement par TR-PIV

Les phénomènes aérodynamiques instationnaires apparaissant autour de véhicules terrestres lors de rafales latérales, demeurent encore mal connus de par les difficultés, tant expérimentales que numériques, à reproduire fidèlement ces situations en laboratoire. L’ISAE a développé un banc d'essai, inspiré des travaux de Ryan et Dominy (Ryan et Dominy [2000]), dans lequel le déferlement de la rafale sur la maquette automobile est reproduit par un jet latéral mobile longitudinalement. L’écoulement généré par ce dispositif est validé PIV résolue en temps dans ce présent document. L’angle de dérapage obtenu lors d’une simulation de rafale présente une évolution temporelle proche du créneau avec un plateau compris voisin de 25°

Etude de l'évolution instationnaire de l'écoulement entourant un véhicule soumis brusquement à un vent latéral

Les techniques de PIV résolue en temps et de PIV stéréoscopique sont appliquées autour de corps automobiles soumis à un coup de vent latéral. Ainsi, l’évolution instationnaire des efforts aérodynamiques peut être interprétée en lien avec la topologie de l’écoulement. On montre en particulier que la réponse instationnaire du véhicule est dominée par le transitoire de la partie arrière. Le développement de la structure tourbillonnaire d’axe longitudinal apparaissant du côté sous le vent du véhicule soumis à un dérapage apparaît jouer un rôle important dans la réponse instationnaire de efforts aérodynamiques

Forces and flow structures evolution on a car body in a sudden crosswind

A vehicle driver is commonly exposed to strong side air flows, for example when passing through a wind gust. The aerodynamic efforts generated in these situations may induce undesired lateral deviations, which can lead to dramatic effects, if the driver is surprised. In order to simulate a sudden yaw angle change on a moving vehicle, a double wind tunnel facility, adapted from the one of Ryan, Dominy, 2000. Wake Surveys Behind a Passenger Car Subjected to a Transient Cross-wind Gust. SAE Technical Paper No. 2000-01-0874 is developed. Two Windsor car body models, differing from their rear geometry, are analysed. The transient evolution of the side force and yaw moment aerodynamic coefficients are interpreted in connection with the unsteady development of the flow, based on TR-PIV and stereoscopic PIV measurements. Our analysis shows that the region which is most sensitive to crosswind is located at the rear part of the leeward flank. However, changes in the rear geometry (from squareback to fastback body) only affect the established lateral coefficients values while transient duration and the force overshoots appear not to be significantly modified. Furthermore, the circulation of the most energetic leeward vortex appears to be correlated with the lateral coefficients transient evolutions

Influenza vaccination for elderly, vulnerable and high-risk subjects: a narrative review and expert opinion

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates

Analyse expérimentale et numérique du comportement de véhicules terrestres en présence d'un vent latéral instationnaire

L aérodynamique latérale des véhicules automobiles suscite de nos jours de plus en plus d intérêt de la part des constructeurs. L automobiliste est en effet soumis quotidiennement à de forts courants d air latéraux, que ce soit lors du dépassement d un autre véhicule, ou alorsen passant dans un couloir de vent du à la topographie du terrain (passage devant un espace entre deux immeubles par exemple). Les efforts aérodynamiques mis en jeu dans ces situations peuvent provoquer des mouvements non désirés du véhicule, pouvant avoir des conséquences dramatiques si le conducteur se laisse surprendre. Des études expérimentales reproduisant les effets d un dérapage dynamique ont mis en évidence des phénomènes transitoires importants mettant à défaut les modèles stationnaires généralement pratiqués par les constructeurs pour qualifier le comportement de leurs véhicules en présence de dérapage. Les mécanismes responsables de ces phénomènes transitoires sont encore mal connus de la communauté scientifique. Ce travail propose d approfondir ce sujet au travers de l étude de l aérodynamique d un véhicule terrestre fixe soumis à un vent longitudinal et à une rafale de vent latéral. Le but principal est d identifier les structures tourbillonnaires au moyen de mesures PIV et de calculs numériques des champs de vitesse autour d une maquette automobile et de les corréler aux efforts aérodynamiques. Un accord entre l ISAT, composante de l Université de Bourgogne, et l Institut Supérieurde l Aéronautique et de l Espace (ISAE) de Toulouse a permis de mener l étude avec les ressources de cet établissement. Le moyen d essai principal, créé par l ISAE, est le banc rafale latérale , constitué d une soufflerie principale et d une soufflerie secondaire, dont la sortie à volet déferlants ( Mexican Wave ) est inspirée de l approche proposée par Ryan et Dominy (2000). L analyse expérimentale a été effectuée à l aide de la PIV résolue en temps et stéréoscopique, et d une balance dard instationnaire à cinq composantes. Un banc numérique identique a été constitué à l aide du logiciel FLUENT , pour des calculs 3D. De plus, un modèle 2D annexe, basé sur la méthode meshless , a été développé pour de futures investigations, en raison de sa robustesse pour des problèmes à fortes discontinuités et sa bonne adaptabilité aux problèmes avec frontières mobiles.Une première phase de ce travail a consisté en la mise au point des bancs expérimental et numérique, avec génération d un champ de dérapage homogène, de 21 dans la zone de mesure. L évolution du dérapage en chaque point respecte bien la forme d un créneau imposé par la rafale. Pour l analyse des efforts, deux géométries de maquette ont été étudiées, à savoir un corps de Windsor à culot droit générant, pour un écoulement longitudinal, des structures de sillage bidimensionnelles, et son homologue à culot incliné de 25, générant des tourbillons cigare . Des pics d efforts ont été observés à l arrivée de la rafale, tout comme la littérature le prédit. Pour ce qui est du coefficient du moment de lacet, les sursauts sont de 29 % et 19 % respectivement pour la maquette à culot droit et celle à culot incliné, par rapport aux valeurs stationnaires. Concernant le coefficient de force de dérive, ils sont de 10 % et 14 %, respectivement. Lors de nos essais, ces efforts se sont établis après 5.5 longueurs de maquette. Afin d expliquer la différence de comportement entre les deux maquettes en termes d efforts, l évolution temporelle des tourbillons nommés, dans ce mémoire, A, B, C et 1 à été discutée. Il en est ressorti une forte corrélation entre la circulation du tourbillon A, le plusénergétique, naissant à l avant du flanc sous le vent de la maquette, et les efforts latéraux, de sorte que ce tourbillon serait le meilleur témoin des phénomènes instationnaires mis en jeu dans l étude de l effet du vent latéral. [...]The automotive manufacturers are nowadays more and more interested in crosswind aerodynamics. Indeed, the driver is subjected every day to strong side air flows, for example when overtaking another vehicle or when passing through a lateral wind wall, generated by terrain topography (as in the case of the passage near the empty space between two buildings).The aerodynamic efforts generated in these situations can lead to undesired lateral deviations,which can be dramatic if the driver is surprised. Different experimental studies, reproducing the effects of a dynamic yaw angle, pointed out the issues of the steady methods, commonly used to qualify the vehicle crosswind behaviour. Little is still known about the physics behind these unsteady phenomena. This is the main topic of this work, by studying the aerodynamics of a fixed vehicle subjected to both a longitudinal flow and a side wind gust. The goal is the identification of the near-vehicle vortex structures, by means of PIV measurements and CFD calculations, and their correlation with the evolution of the efforts. An agreement between the ISAT, a department of the University of Burgundy, and the ISAE of Toulouse, permitted to carry out this research with the resources of the latter laboratory. The work focuses on the use of the rafale latérale (side gust) test bench, made up with a main wind tunnel connected with an auxiliary one by means of a shutter system,whose opening is held by a Mexican Wave law. This approach is inspired by the work of Dominy and Ryan (2000). The experimental analysis was carried out by means of Time-Resolved and stereoscopic PIV, and by a five components unsteady balance as well. Anidentical test bench was numerically reproduced with the 3D CFD software FLUENT .Moreover, an additional 2D CFD model, based on the meshless method, has been developed for future studies. This kind of approximation method has been chosen for its robustness innon-continuous problems and because of its adaptability when moving boundaries are needed.The first phase of this work consisted on wind tunnels set-up, both for the real test bench and for the CFD model. The yaw angle field is homogeneous, 21 in the measurement region. The yaw angle evolution, at given point, respects the step wise behaviour, imposed by the gust passage. As far as the efforts are concerned, two versions of the Windsor body car model were studied, that is a squareback geometry, generating, for longitudinal flows, 2D wakestructures, and a fastback geometry (rear window inclined by 25), producing cone-liketrailing vortices. Force overshoots were seen after the gust arrival, as seen in literature. In particular, the yaw moment coefficient overshoots are 29% and 19% higher than the steady yaw angle tests, for the squareback and the fastback geometries, respectively. If the side forceis concerned, the entities of these overshoots are 10% and 14%, respectively. Our testspointed out that efforts establish after the vehicle has driven 5.5 times its length in thecrosswind. In order to explain the different behaviour of the two geometries, it is discussed about the unsteady evolution of the vortices called, in this report, A, B, C et 1. A strong correlation between the side efforts and the circulation of the most energetic vortex, A,having its origin in the front leeward side of the vehicle. The A vortex is so the best index for the study of the crosswind unsteady phenomena. The coupled analysis between vortex structures and efforts confirmed the presence of a higher side force for the squareback geometry. The inverted effect has been observed for the yaw momentDIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

Paracentrotus lividus roe enhancement by a short-time rearing in offshore cages using two agar-based experimental feed

In this study, we tested the effect of two agar-based biocomposites (differing for the fish meal source), on the Paracentrotus lividus gonad cycle progression and biochemical composition, in an offshore pilot scale trial. The purpose of this study was to identify a feeding regime for P. lividus that would allow adequate gonadal growth without accelerating the gamete maturation, in order to extend the market period. The purpose was pursued through the use of agar as a binding agent in the manufacturing of biocomposites to be used as feed for P. lividus and the realization of special offshore cages. The gonad index, histology, biochemical composition of fatty acids (FA) and free amino acids (FAA) and volatile molecule fingerprint were evaluated. Both the gonad index and the histological analysis showed a slower gametogenesis progression in the gonads of caged sea urchins with respect to the field collected ones, consistent with our previous results obtained testing a similar feed composition in a recirculating system. The amount and the relative proportions of FA and FAA in the gonads of wild and cultured gonads were similar, while the analysis of the volatile substances of the gonads of the sea urchin conducted using the electronic nose, shows that they vary as a result of the different feeding treatments. These results show that P. lividus sea urchins can be housed, under this feeding regime during the recovery phase of the gonads, without acceleration of the maturation of the gametes and thus in conditions to allow the extension of the market period. Moreover, the here tested agar-based biocomposites make it possible to reduce the management costs of the rearing system as they need to be replaced only once a week, and its environmental impact as they guarantee a limited nutrient dispersion in the water

Experimental and Numerical Validation of a Wind Gust Facility

The study of a vehicle moving through a lateral wind gust has always been a difficult task due to the difficulties in granting the right similitude. The facility proposed by Ryan and Dominy has been one of the best options to carry it out. In this approach, a double wind tunnel is used to send a lateral moving gust on a stationary model. Using this idea as a starting point, the ISAE has built a dedicated test bench for lateral wind studies on transient conditions. Experimental work has been carried out by means of time-resolved PIV, aiming at studying the unsteady interpenetration of the two flows coming from each wind tunnel. Meanwhile, a 3D CFD model based on URANS was set up, faithfully reproducing the double wind tunnel. Both the experimental and numerical results are compared, and the evolution of the reproduced wind gust is discussed. Conclusions are finally determined about the validity of this kind of test bench for ground vehicle applications

Clinical phenotype and functional characterization of CASQ2 mutations associated with Catecholaminergic Polymorphic Ventricular Tachycardia

BACKGROUND: Four distinct mutations in the human cardiac calsequestrin gene (CASQ2) have been linked to catecholaminergic polymorphic ventricular tachycardia (CPVT). The mechanisms leading to the clinical phenotype are still poorly understood because only 1 CASQ2 mutation has been characterized in vitro. METHODS AND RESULTS: We identified a homozygous 16-bp deletion at position 339 to 354 leading to a frame shift and a stop codon after 5aa (CASQ2(G112+5X)) in a child with stress-induced ventricular tachycardia and cardiac arrest. The same deletion was also identified in association with a novel point mutation (CASQ2(L167H)) in a highly symptomatic CPVT child who is the first CPVT patient carrier of compound heterozygous CASQ2 mutations. We characterized in vitro the properties of CASQ2 mutants: CASQ2(G112+5X) did not bind Ca2+, whereas CASQ2(L167H) had normal calcium-binding properties. When expressed in rat myocytes, both mutants decreased the sarcoplasmic reticulum Ca2+-storing capacity and reduced the amplitude of I(Ca)-induced Ca2+ transients and of spontaneous Ca2+ sparks in permeabilized myocytes. Exposure of myocytes to isoproterenol caused the development of delayed afterdepolarizations in CASQ2(G112+5X). CONCLUSIONS: CASQ2(L167H) and CASQ2(G112+5X) alter CASQ2 function in cardiac myocytes, which leads to reduction of active sarcoplasmic reticulum Ca2+ release and calcium content. In addition, CASQ2(G112+5X) displays altered calcium-binding properties and leads to delayed afterdepolarizations. We conclude that the 2 CASQ2 mutations identified in CPVT create distinct abnormalities that lead to abnormal intracellular calcium regulation, thus facilitating the development of tachyarrhythmias

Cyclic Peptoids as Mycotoxin Mimics: An Exploration of Their Structural and Biological Properties

Cyclic peptoids have recently emerged as important examples of peptidomimetics for their interesting complexing properties and innate ability to permeate biological barriers. In the present contribution, experimental and theoretical data evidence the intricate conformational and stereochemical properties of five novel hexameric peptoids decorated with N-isopropyl, N-isobutyl, and N-benzyl substituents. Complexation studies by NMR, in the presence of sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaTFPB), theoretical calculations, and single-crystal X-ray analyses indicate that the conformationally stable host/guest metal adducts display architectural ordering comparable to that of the enniatins and beauvericin mycotoxins. Similarly to the natural depsipeptides, the synthetic oligolactam analogues show a correlation between ion transport abilities in artificial liposomes and cytotoxic activity on human cancer cell lines. The reported results demonstrate that the versatile cyclic peptoid scaffold, for its remarkable conformational and complexing properties, can morphologically mimic related natural products and elicit powerful biological activities