Altérations de la repolarisation ventriculaire induites par l’exercice dans la sténose congénitale modérée de la valve aortique

Introduction: La surcharge de pression ventriculaire augmente à l’exercice chez les patients avec une sténose de valve aortique (SVA). Lorsqu’il n’y a aucun symptôme apparent, il est cependant difficile d’indiquer l’intervention chirurgicale en utilisant seulement les indices de surcharge de pression ventriculaire. D’autres paramètres, tels que la dispersion de la repolarisation ventriculaire (d-QT), qui augmentent avec le gradient de pression transvalvulaire (GPT), n’ont pas été étudiés dans la SVA. L’objectif de l’étude était de déterminer le modèle de réponse du segment QT et de la d-QT à l’épreuve d’effort chez des enfants avec une SVA congénitale modérée afin d’évaluer l’impact de la surcharge de pression ventriculaire selon une perspective électrophysiologique. Matériel et méthodes: 15 patients SVA modérés ont été comparés à 15 sujets contrôles appariés pour l’âge (14.8±2.5 ans vs. 14.2±1.5 ans) et pour le sexe (66,7% de sujets mâles). Tous les sujets ont fait une épreuve d’effort avec enregistrement électrocardiographique à 12 dérivations. Le segment QT a été mesuré à partir du début du complexe QRS jusqu’à l’apex de l’onde T (QTa) au repos, à l’effort maximal ainsi qu’après 1 et 3 minutes de récupération. La longueur du segment QT a été corrigée selon l’équation de Fridericia et la d-QT a été calculée. Résultats: La longueur du segment QT corrigée (QTc) était similaire au repos entre les groupes d’étude, mais était significativement élevée chez les SVA en comparaison avec le groupe contrôle à l’effort maximal (p=0.004) ainsi qu’après 1 (p<0.001) et 3 (p<0.001) minutes de récupération. Une interaction significative a été identifiée entre les groupes pour la d-QT (p=0.034) et les tests post hoc ont révélé une différence significative seulement au repos (p=0.001). Conclusions: Les anomalies de repolarisation ventriculaire peuvent être révélées par l’évaluation de la repolarisation électrique lors de l’épreuve d’effort chez les SVA modérées asymptomatiques. L’utilisation de la réponse du QT à l’effort pourrait être bénéfique pour l’optimisation de la stratification du risque chez ces patients.Introduction: Pressure overload increases in patients with moderate aortic valvular stenosis (AVS) during acute exercise. In the absence of symptoms, it remains difficult however, to discriminate patients for surgery based only on pressure overload. Other parameters, such as the dispersion of ventricular repolarisation (d-QT), which reportedly increases with the transvalvular pressure gradient, have not been fully studied in AVS. The aim of the study was to determine the pattern of QT and d-QT response to exercise testing in children with moderate AVS to evaluate the impact of pressure overload from an electrophysiological perspective. Materials and methods: 15 moderate AVS patients were compared to 15 controls paired for age (14.8±2.5 vs. 14.2±1.5 years old) and gender (66.7% male). All subjects underwent exercise stress testing with 12-lead ECG recording. QT was measured from the onset of QRS to the apex (QTa) at rest, peak exercise, 1 and 3 minutes of recovery. QT was corrected using the Fridericia equation and d-QT was calculated. Results: Resting QTc was similar among the study groups, but increased significantly in AVS in comparison to the control group at maximal effort (p=0.004) and after 1 (p<0.001) and 3 (p<0.001) minutes of recovery. A significant interaction was identified between groups for d-QT (p=0.034) and post-hoc tests revealed a significant difference only at rest (p=0.001). Conclusions: Ventricular repolarisation abnormalities can be unmasked and highlighted by the assessment of electrical repolarisation during exercise challenge in asymptomatic moderate AVS. Using QT response to exercise could be beneficial for better optimisation of risk stratification in these patients

Pseudogap phase of cuprate superconductors confined by Fermi surface topology

The properties of cuprate high-temperature superconductors are largely shaped by competing phases whose nature is often a mystery. Chiefly among them is the pseudogap phase, which sets in at a doping $p^*$ that is material-dependent. What determines $p^*$ is currently an open question. Here we show that the pseudogap cannot open on an electron-like Fermi surface, and can only exist below the doping $p_{FS}$ at which the large Fermi surface goes from hole-like to electron-like, so that $p^*$ $\leq$ $p_{FS}$. We derive this result from high-magnetic-field transport measurements in La$_{1.6-x}$Nd$_{0.4}$Sr$_x$CuO$_4$ under pressure, which reveal a large and unexpected shift of $p^*$ with pressure, driven by a corresponding shift in $p_{FS}$. This necessary condition for pseudogap formation, imposed by details of the Fermi surface, is a strong constraint for theories of the pseudogap phase. Our finding that $p^*$ can be tuned with a modest pressure opens a new route for experimental studies of the pseudogap.Comment: 15 pages, 5 figures, 7 supplemental figure

Human mesenchymal stromal cell-secreted lactate induces M2-macrophage differentiation by metabolic reprogramming

Human mesenchymal stromal cells (MSC) have been shown to dampen immune response and promote tissue repair, but the underlying mechanisms are still under investigation. Herein, we demonstrate that umbilical cord-derived MSC (UC-MSC) alter the phenotype and function of monocyte-derived dendritic cells (DC) through lactate-mediated metabolic reprogramming. UC-MSC can secrete large quantities of lactate and, when present during monocyte-to-DC differentiation, induce instead the acquisition of M2-macrophage features in terms of morphology, surface markers, migratory properties and antigen presentation capacity. Microarray expression profiling indicates that UC-MSC modify the expression of metabolic-related genes and induce a M2-macrophage expression signature. Importantly, monocyte-derived DC obtained in presence of UC-MSC, polarize naïve allogeneic CD4+ T-cells into Th2 cells. Treatment of UC-MSC with an inhibitor of lactate dehydrogenase strongly decreases lactate concentration in culture supernatant and abrogates the effect on monocyte-to- DC differentiation. Metabolic analysis further revealed that UC-MSC decrease oxidative phosphorylation in differentiating monocytes while strongly increasing the spare respiratory capacity proportional to the amount of secreted lactate. Because both MSC and monocytes are recruited in vivo at the site of tissue damage and inflammation, we propose the local increase of lactate concentration induced by UC-MSC and the consequent enrichment in M2-macrophage generation as a mechanism to achieve immunomodulation

Taxation and Economic Efficiency: Results from a Canadian CGE Model

This paper introduces a dynamic general equilibrium tax model of the Canadian economy. The model incorporates each of the major taxes in Canada and features adjustment dynamics, intertemporal optimization, imperfect substitution between domestic and foreign goods and assets, and industry disaggregation. In addition to describing the model, this study uses it to compare the effects of different tax measures on the Canadian economy with a focus on measures that directly target investment and saving. Cette étude présente un modèle d’équilibre général dynamique de taxation de l’économie canadienne. Le modèle, qui incorpore les principales taxes canadienne, se caractérise, entre autres, par l’optimisation intertemporelle des agents, la substitution imparfaite entre biens et actifs de provenances domestique et étrangère, ainsi que par la désagrégation sectorielle de l’économie. Outre la description du modèle, l’étude compare les effets de différents instruments de taxation sur l’économie canadienne avec une emphase sur les instruments ciblant directement l’investissement et l’épargne.

Experience Rating Employment Insurance Contributions

Unless demonstrated to the contrary, the invisible hand of the price system is the most efficient means to allocate resources and maximize economic performance. This suggests experience rating of an insurance scheme for unemployment. Simulation results from a 95-sector general equilibrium model, developed especially for studying this issue, show that a move to experience rating has the potential to substantially reduce unemployment, and increase output, wage income and employment, both in aggregate terms and in most sectors of the economy.

Sensitivity of T c to pressure and magnetic field in the cuprate superconductor YBa2Cu3 Oy:Evidence of charge-order suppression by pressure

Cuprate superconductors have a universal tendency to form charge density-wave (CDW) order which competes with superconductivity and is strongest at a doping $p \simeq 0.12$. Here we show that in the archetypal cuprate YBa$_{2}$Cu$_{3}$O$_{y}$ (YBCO) pressure suppresses charge order, but does not affect the pseudogap phase. This is based on transport measurements under pressure, which reveal that the onset of the pseudogap at $T^*$ is independent of pressure, while the negative Hall effect, a clear signature of CDW order in YBCO, is suppressed by pressure. We also find that pressure and magnetic field shift the superconducting transition temperature $T_{\rm c}$ of YBCO in the same way as a function of doping - but in opposite directions - and most effectively at $p \simeq 0.12$. This shows that the competition between superconductivity and CDW order can be tuned in two ways, either by suppressing superconductivity with field or suppressing CDW order by pressure. Based on existing high-pressure data and our own work, we observe that when CDW order is fully suppressed at high pressure, the so-called "1/8 anomaly" in the superconducting dome vanishes, revealing a smooth $T_{\rm c}$ dome which now peaks at $p \simeq 0.13$. We propose that this $T_{\rm c}$ dome is shaped by the competing effects of the pseudogap phase below its critical point $p^{\star} \sim 0.19$ and spin order at low doping.Comment: New Hall data added. 11 pages, 9 figures and 2 table