Overview of the current use of levosimendan in France: a prospective observational cohort study

Abstract Background Following the results of randomized controlled trials on levosimendan, French health authorities requested an update of the current use and side-effects of this medication on a national scale. Method The France-LEVO registry was a prospective observational cohort study reflecting the indications, dosing regimens, and side-effects of levosimendan, as well as patient outcomes over a year. Results The patients included ( n = 602) represented 29.6% of the national yearly use of levosimendan in France. They were treated for cardiogenic shock ( n = 250, 41.5%), decompensated heart failure ( n = 127, 21.1%), cardiac surgery-related low cardiac output prophylaxis and/or treatment ( n = 86, 14.3%), and weaning from veno-arterial extracorporeal membrane oxygenation ( n = 82, 13.6%). They received 0.18 ± 0.07 µg/kg/min levosimendan over 26 ± 8 h. An initial bolus was administered in 45 patients (7.5%), 103 (17.1%) received repeated infusions, and 461 (76.6%) received inotropes and or vasoactive agents concomitantly. Hypotension was reported in 218 patients (36.2%), atrial fibrillation in 85 (14.1%), and serious adverse events in 17 (2.8%). 136 patients (22.6%) died in hospital, and 26 (4.3%) during the 90-day follow-up. Conclusions We observed that levosimendan was used in accordance with recent recommendations by French physicians. Hypotension and atrial fibrillation remained the most frequent side-effects, while serious adverse event potentially attributable to levosimendan were infrequent. The results suggest that this medication was safe and potentially associated with some benefit in the population studied

Impact du vieillissement et de la fertilité minérale sur l'allocation du carbone entre croissance, respiration, stockage et reproduction chez le chêne et le hêtre : Approche expérimentale et modélisation

In order to increase our understanding of carbon allocation in broadleaved species, our research consisted of studying the effects of ageing and soil mineral fertility on the carbon allocation between growth, storage and reproduction for oaks and beech. Ageing was studied over a forest succession using a chronosequences approach. Two liming experiments were investigated in order to study the variation of carbon allocation with soil mineral fertility in contrasting situations. The productivity decline in beech was followed by substantial changes in carbon allocation, with a continuous decrease of carbon allocation to growth, to the benefit of reproduction and storage functions. Conversely, carbon allocation in oak remained stable during its entire development. The dendrochronological analysis of inter-annual variations of radial growth shown also that beech and oaks presented contrasted climate-response of growth. There was clear evidence of a long-term increase with time in radial growth in both species. We also observed a long-term increase of inter-annual variations of growth with time for beech but not for oaks. The declining beech presented a sharp decreasing allocation to growth to the benefit of the carbon storage compounds. Moreover, liming induced an temporary increase of radial growth. However, the increase of carbohydrates in limed beeches was still significant 15 after treatment compare to the controls. These results suggested that the stock of carbohydrates is a key parameter of the physiological integrity for adult beeches. These results concerning the intrinsic (ageing) and external (liming, climate) factors of carbon allocation in oaks and beech enabled to confirm two contrasted models of carbon functioning.Dans le but de progresser dans la compréhension des déterminismes de l'allocation du carbone chez les feuillus, ce travail de recherche a consisté à étudier les effets de l'espèce (chênes, hêtre), du vieillissement, du climat et de la fertilité minérale sur la répartition du carbone assimilé par la photosynthèse entre croissance, stockage de composés de réserves carbonées et reproduction. Les effets du vieillissement ont été étudiés à l'échelle de la révolution forestière au travers de deux chronoséquences. Deux dispositifs d'amendement ont permis d'analyser les effets de la fertilité minérale du sol sur l'allocation du carbone dans l'arbre. Au cours du vieillissement du hêtre, l'allocation de carbone à la croissance, majoritaire pendant la phase juvénile, diminue progressivement au profit du stockage de composés de réserves et de la reproduction. En revanche, cette allocation demeure constante au cours du développement du chêne sessile. L'étude dendroclimatique des variations interannuelles de la croissance radiale montre également que les deux espèces répondent de façon contrastée aux variations climatiques. L'augmentation de la productivité à long terme a été mise en évidence pour les deux espèces. Au contraire du chêne, cette augmentation du niveau de croissance s'accompagne d'une forte variabilité interannuelle de la croissance radiale chez le hêtre. En condition de dépérissement chez le hêtre, l'allocation du carbone à la croissance chute drastiquement au profit de l'allocation aux réserves, permettant aux arbres dépérissants de maintenir des concentrations en composés de réserves glucidiques identiques à celles des arbres sains. Par ailleurs, l'amélioration du niveau de fertilité minérale de la station (par amendement) engendre une augmentation transitoire de la croissance radiale. Des concentrations en composés de réserves carbonées plus élevées chez les hêtres amendés ont été observées 15 ans après le traitement. Ces deux résultats suggèrent l'importance du niveau de réserves dans le maintien de l'intégrité physiologique des arbres adultes. Les résultats de cette étude des facteurs intrinsèques (âge,) et externes (fertilité minérale, climat) de variation de l'allocation du carbone chez le chêne et le hêtre, enrichie des enseignements de la littérature, ont permis de confirmer deux modèles de fonctionnement carboné contrastés

Impact du vieillissement et de la fertilité minérale sur l'allocation du carbone entre croissance, respiration, stockage et reproduction chez le chêne et le hêtre (Approche expérimentale et modélisation)

Dans le but de progresser dans la compréhension des déterminismes de l'allocation du carbone chez les feuillus, ce travail de recherche a consisté à étudier les effets de l'espèce (chênes, hêtre), du vieillissement, du climat et de la fertilité minérale sur la répartition du carbone assimilé par la photosynthèse entre croissance, stockage de composés de réserves carbonées et reproduction. Les effets du vieillissement ont été étudiés à l'échelle de la révolution forestière au travers de deux chronoséquences. Deux dispositifs d'amendement ont permis d'analyser les effets de la fertilité minérale du sol sur l'allocation du carbone dans l'arbre. Au cours du vieillissement du hêtre, l'allocation de carbone à la croissance, majoritaire pendant la phase juvénile, diminue progressivement au profit du stockage de composés de reserves et de la reproduction. En revanche, cette allocation demeure constante au cours du développement du chêne sessile. L'étude dendroclimatique des variations interannuelles de la croissance radiale montre également que les deux espèces répondent de façon contrastée aux variations climatiques. L'augmentation de la productivité à long terme a été mise en évidence pour les deux espèces. Au contraire du chêne, cette augmentation du niveau de croissance s'accompagne d'une forte variabilité interannuelle de la croissance radiale chez le hêtre. En condition de dépérissement chez le hêtre, l'allocation du carbone à la croissance chute drastiquement au profit de l'allocation aux réserves, permettant aux arbres dépérissants de maintenir des concentrations en composés de réserves glucidiques identiques à celles des arbres sains. Par ailleurs, l'amélioration du niveau de fertilité minérale de la station (par amendement) engendre une augmentation transitoire de la croissance radiale. Des concentrations en composés de réserves carbonées plus élevées chez les hêtres amendés ont été observées 15 ans après le traitement. Ces deux résultats suggèrent l'importance du niveau de réserves dans le maintien de l'intégrité physiologique des arbres adultes. Les résultats de cette étude des facteurs intrinsèques (âge,) et externes (fertilité minérale, climat) de variation de l'allocation du carbone chez le chêne et le hêtre, enrichie des enseignements de la littérature, ont permis de confirmer deux modèles de fonctionnement carboné contrastés.In order to increase our understanding of carbon allocation in broadleaved species, our research consisted of studying the effects of ageing and soil mineral fertility on the carbon allocation between growth, storage and reproduction for oaks and beech. Ageing was studied over a forest succession using a chronosequences approach. Two liming experiments were investigated in order to study the variation of carbon allocation with soil mineral fertility in contrasting situations. The productivity decline in beech was followed by substantial changes in carbon allocation, with a continuous decrease of carbon allocation to growth, to the benefit of reproduction and storage functions. Conversely, carbon allocation in oak remained stable during its entire development. The dendrochronological analysis of inter-annual variations of radial growth shown also that beech and oaks presented contrasted climate-response of growth. There was clear evidence of a long-term increase with time in radial growth in both species. We also observed a long-term increase of inter-annual variations of growth with time for beech but not for oaks. The declining beech presented a sharp decreasing allocation to growth to the benefit of the carbon storage compounds. Moreover, liming induced an temporary increase of radial growth. However, the increase of carbohydrates in limed beeches was still significant 15 after treatment compare to the controls. These results suggested that the stock of carbohydrates is a key parameter of the physiological integrity for adult beeches. These results concerning the intrinsic (ageing) and external (liming, climate) factors of carbon allocation in oaks and beech enabled to confirm two contrasted models of carbon functioning.NANCY1-Bib. numérique (543959902) / SudocSudocFranceF

Etude de l'allocation de carbone chez le jeune chêne et le hêtre en fonction l'âge et de la fertilité : approche expérimentale et modélisation

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Age-related variation in carbon allocation at tree and stand scales in beech (Fagus sylvatica L.) and sessile oak (Quercus petraea (Matt.) Liebl.) using a chronosequence approach

International audienceTwo types of physiological mechanisms can contribute to growth decline with age: (i) the mechanisms leading to the reduction of carbon assimilation (input) and (ii) those leading to modification of the resource economy. Surprisingly, the processes relating to carbon allocation have been little investigated as compared to research on the processes governing carbon assimilation. The objective of this paper was thus to test the hypothesis that growth decrease related to age is accompanied by changes in carbon allocation to the benefit of storage and reproductive functions in two contrasting broad-leaved species: beech (Fagus sylvatica L.) and sessile oak (Quercus petraea (Matt.) Liebl.). Age-related changes in carbon allocation were studied using a chronosequence approach. Chronosequences, each consisting of several even-aged stands ranging from 14 to 175 years old for beech and from 30 to 134 years old for sessile oak, were divided into five or six age classes. In this study, carbon allocations to growth, storage and reproduction were defined as the relative amount of carbon invested in biomass increment, carbohydrate increment and seed production, respectively. Tree-ring width and allometric relationships were used to assess biomass increment at the tree and stand scales. Below-ground biomass was assessed using a specific allometric relationship between root: shoot ratio and age, established from the literature review. Seasonal variations of carbohydrate concentrations were used to assess carbon allocation to storage. Reproduction effort was quantified for beech stands by collecting seed and cupule production. Age-related flagging of biomass productivity was assessed at the tree and stand scales, and carbohydrate quantities in trees increased with age for both species. Seed and cupule production increased with stand age in beech from 56 gC m−2 year−1 at 30 years old to 129 gCm−2 year−1 at 138 years old. In beech, carbon allocation to storage and reproductive functions increased with age to the detriment of carbon allocation to growth functions. In contrast, the carbon balance between growth and storage remained constant between age classes in sessile oak. The contrasting age-related changes in carbon allocation between beech and sessile oak are discussed with reference to the differences in growing environment, phenology and hydraulic properties of ring-porous and diffuse-porous species

Etude de l'allocation de carbone chez le jeune chêne et le hêtre en fonction l'âge et de la fertilité : approche expérimentale et modélisation

National audienc

Induction for Termination

Rapport interne.We propose a new approach to prove termination of innermost rewriting, based on induction, abstraction and narrowing. The induction ordering is not explicitly given a priori, but its existence is checked along the proof, by testing satisfiability of ordering constraints. A rule-based description of the technique is given, as well as a few examples to illustrate the method

New Insights into the Pathogenesis of Giant Cell Arteritis: Mechanisms Involved in Maintaining Vascular Inflammation

The giant cell arteritis (GCA) pathophysiology is complex and multifactorial, involving a predisposing genetic background, the role of immune aging and the activation of vascular dendritic cells by an unknown trigger. Once activated, dendritic cells recruit CD4 T cells and induce their activation, proliferation and polarization into Th1 and Th17, which produce interferon-gamma (IFN-γ) and interleukin-17 (IL-17), respectively. IFN-γ triggers the production of chemokines by vascular smooth muscle cells, which leads to the recruitment of additional CD4 and CD8 T cells and also monocytes that differentiate into macrophages. Recent data have shown that IL-17, IFN-γ and GM-CSF induce the differentiation of macrophage subpopulations, which play a role in the destruction of the arterial wall, in neoangiogenesis or intimal hyperplasia. Under the influence of different mediators, mainly endothelin-1 and PDGF, vascular smooth muscle cells migrate to the intima, proliferate and change their phenotype to become myofibroblasts that further proliferate and produce extracellular matrix proteins, increasing the vascular stenosis. In addition, several defects in the immune regulatory mechanisms probably contribute to chronic vascular inflammation in GCA: a defect in the PD-1/PD-L1 pathway, a quantitative and qualitative Treg deficiency, the implication of resident cells, the role of GM-CSF and IL-6, the implication of the NOTCH pathway and the role of mucosal-associated invariant T cells and tissue-resident memory T cells

Vingt ans d'informatique en histoire médiévale

Fossier Lucie, Carpentier Elisabeth, Genet Jean-Philippe, Millet Hélène, Parisse Michel. Vingt ans d'informatique en histoire médiévale. In: Actes des congrès de la Société des historiens médiévistes de l'enseignement supérieur public, 20ᵉ congrès, Paris, 1989. L'histoire médiévale en France. Bilan et perspectives. pp. 501-525

Functional responses of white spruce to snowshoe hare herbivory at the treeline.

Herbivores can modify the rate of shrub and treeline advance. Both direct and indirect effects of herbivory may simultaneously interact to affect the growth rates of plants at this ecotone. We investigated the effect of snowshoe hare herbivory on the height of white spruce at two treeline locations in Alaska, USA. White spruce is expanding its distribution both upwards in elevation and northward in latitude because of climate warming, and snowshoe hares are already present in areas likely to be colonized by spruce. We hypothesized that herbivory would result in browsed individuals having reduced height, suggesting herbivory is a direct, negative effect on spruce treeline advance. We found an interactive effect between browsing history and spruce age. When young (under 30 years old), individuals that were browsed tended to be taller than unbrowsed individuals. However, older seedlings (over 30 years old) that had been browsed were shorter than unbrowsed individuals of the same age. Hares suppress faster growing individuals that are initially taller by preferentially browsing them as they emerge above the winter snowpack. This reduced height, in combination with increased mortality associated with browsing, is predicted to slow the advance of both latitudinal and altitudinal treeline expansions and alter the structure of treeline forests