64 research outputs found
Ăvaluation multicritĂšre de systĂšmes de culture zĂ©ro-pesticides en grande culture et polyculture-Ă©levage (RĂ©seau RĂ©s0Pest)
Dans le cadre du plan Ecophyto, un rĂ©seau dâexpĂ©rimentations systĂšme a Ă©tĂ© mis en place en FrancemĂ©tropolitaine, avec pour objectif de concevoir et dâĂ©valuer des systĂšmes de culture sans pesticides.Les systĂšmes ont Ă©tĂ© mis en place dans des situations variĂ©es (diffĂ©rents climats, types de sol, filiĂšres)et concernent les grandes cultures et la polyculture Ă©levage. Une Ă©valuation multicritĂšre (Criter 5.4,MASC 2.0) a Ă©tĂ© conduite sur la pĂ©riode 2013-2017. On nâobserve pas de dĂ©gradation de la capacitĂ©productive Ă long-terme, ni de la qualitĂ© sanitaire des rĂ©coltes et la contribution au dĂ©veloppementdurable des huit systĂšmes testĂ©s est considĂ©rĂ©e «faible Ă moyenne» pour la polyculture Ă©levage et«moyenne Ă Ă©levĂ©e» à «élevĂ©e» pour la grande culture. La durabilitĂ© environnementale est « Ă©levĂ©e » à «trĂšs Ă©levĂ©e» pour tous les systĂšmes et câest la durabilitĂ© sociale qui est la moins favorable en raisondâune «trĂšs faible» contribution Ă lâemploi. La rentabilitĂ© montre de fortes diffĂ©rences entre systĂšmes,allant de « trĂšs faible » à « trĂšs Ă©levĂ©e » mais aucune valorisation Ă©conomique particuliĂšre des rĂ©coltesproduites sans pesticides nâa Ă©tĂ© appliquĂ©e. Les rĂ©sultats prĂ©sentĂ©s dĂ©bouchent sur de nouvellesperspectives pour une rĂ©duction significative de lâutilisation des pesticides en France
Comparing the evaluation and development of the quality of Justice in Finland, France, Hungary, Italy and The Netherlands
The comparative report is based on the five national reports drafted as part of the research project âHandle with care: Assessing and designing methods for evaluation and development of the quality of justiceâ: namely, the Finnish, French, Hungarian, Italian, and Dutch National Reports. One of the projectâs aims is to identify national practices that could be implemented in other countries in order to improve the quality of the services provided by courts. For that reason, we had to understand what kind of practices exist and what kind of innovative practices were emerging. Five countries were chosen to represent an interesting sample. This report uses the findings of the national reports to identify trends in national approaches and experiences in evaluating and promoting justice quality. It does not seek to assess or evaluate each national system comprehensively; the data collected at national level in each of the five countries are compared to identify common trends and diverging paths, outliers, and weaknesses as well as to verify whether the systems in place are comprehensive, reliable, coherent, and effective venues to evaluate and improve the quality of justice
Dactinomycin induces complete remission associated with nucleolar stress response in relapsed/refractory NPM1-mutated AML
Acute myeloid leukemia (AML) with mutated NPM1 accounts for one-third of newly diagnosed AML. Despite recent advances, treatment of relapsed/refractory NPM1-mutated AML remains challenging, with the majority of patients eventually dying due to disease progression. Moreover, the prognosis is particularly poor in elderly and unfit patients, mainly because they cannot receive intensive treatment. Therefore, alternative treatment strategies are needed. Dactinomycin is a low-cost chemotherapeutic agent, which has been anecdotally reported to induce remission in NPM1-mutated patients, although its mechanism of action remains unclear. Here, we describe the results of a single-center phase 2 pilot study investigating the safety and efficacy of single-agent dactinomycin in relapsed/refractory NPM1-mutated adult AML patients, demonstrating that this drug can induce complete responses and is relatively well tolerated. We also provide evidence that the activity of dactinomycin associates with nucleolar stress both in vitro and in vivo in patients. Finally, we show that low-dose dactinomycin generates more efficient stress response in cells expressing NPM1 mutant compared to wild-type cells, suggesting that NPM1-mutated AML may be more sensitive to nucleolar stress. In conclusion, we establish that dactinomycin is a potential therapeutic alternative in relapsed/refractory NPM1-mutated AML that deserves further investigation in larger clinical studies
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Continuation vs Discontinuation of Renin-Angiotensin System Inhibitors Before Major Noncardiac Surgery
ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (nâ=â1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (nâ=â1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; Pâ=â.85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449
α1H mRNA in single skeletal muscle fibres accounts for T-type calcium current transient expression during fetal development in mice
Calcium channels are essential for excitation-contraction coupling and muscle development. At the end of fetal life, two types of Ca2+ currents can be recorded in muscle cells. Whereas L-type Ca2+ channels have been extensively studied, T-type channels have been poorly characterized in skeletal muscle. We describe here the functional and molecular properties of T-type calcium channels in developing mouse skeletal muscle. The T-type current density increased transiently during prenatal myogenesis with a maximum at embryonic day E16 followed by a drastic decrease until birth. This current showed similar electrophysiological and pharmacological properties at all examined stages. It displayed a wide window current centred at about â35 and â55 mV in 10 and 2 mm external Ca2+, respectively. Activation and inactivation kinetics were fast (3 and 16 ms, respectively). The current was inhibited by nickel and amiloride with an IC50 of 5.4 and 156 ÎŒm, respectively, values similar to those described for cloned T-type α1H channels. Whole muscle tissue RT-PCR analysis revealed mRNAs corresponding to α1H and α1G subunits in the fetus but not in the adult. However, single-fibre RT-PCR demonstrated that only α1H mRNA was present in prenatal fibres, suggesting that the α1G transcript present in muscle tissue must be expressed by non-skeletal muscle cells. Altogether, these results demonstrate that the α1H subunit generates functional T-type calcium channels in developing skeletal muscle fibres and suggest that these channels are involved in the early stages of muscle differentiation
Gérer les adventices sans herbicides: Exemple des systÚmes de culture (SdC) testés dans le réseau expérimental « zéro pesticides » Rés0Pest
systĂšmes de culture innovants minimisant le recours aux pesticides, en combinant des leviers agronomiques et en valorisant les rĂ©gulations biologiques, en grande culture et polyculture-Ă©levage. Il a vu le jour en 2012 et regroupe 8 dispositifs expĂ©rimentaux (INRA et lycĂ©e agricole dâAuzeville) dans lesquels sont testĂ©s des systĂšmes de culture ayant en commun de ne pas recourir aux pesticides. Ses objectifs sont de : - concevoir et expĂ©rimenter des systĂšmes de culture sans pesticide dans diffĂ©rentes situations de production ; dâen Ă©valuer les performances agronomiques, Ă©conomiques, environnementales et sociales ; - analyser lâeffet de ces systĂšmes sur lâĂ©volution des communautĂ©s, notamment les bioagresseurs, et les rĂ©gulations biologiques. Outre lâinterdiction du recours aux pesticides, les systĂšmes testĂ©s doivent chercher Ă maximiser une production respectueuse des exigences des filiĂšres locales (les cultures de vente reprĂ©sentatives de la rĂ©gion doivent ĂȘtre maintenues et les critĂšres de qualitĂ© des productions sont recherchĂ©s) et Ă maintenir le revenu de lâagriculteur. Les successions de cultures sont donc diffĂ©rentes selon les sites. Les systĂšmes de culture sont construits selon les principes de la protection intĂ©grĂ©e en combinant des techniques alternatives, Ă©prouvĂ©es ou suggĂ©rĂ©es par la bibliographie et les connaissances actuelles sur les bioagresseurs, en vue de rĂ©duire les risques de dĂ©veloppement des bioagresseurs et de favoriser la mise en place de rĂ©gulations biologiques. Bien quâils aient Ă©tĂ© conçus indĂ©pendamment les uns des autres, les systĂšmes de culture RĂ©s0Pest utilisent des techniques communes pour la lutte contre les adventices, certaines Ă©tant raisonnĂ©es au niveau de la rotation (allongement de la rotation, diversification des cultures et des pĂ©riodes de semis, alternance labour/non-labour, implantation de CIPAN, âŠ), dâautres au niveau de lâitinĂ©raire technique de chaque culture (faux-semis, dĂ©sherbage mĂ©canique, date et densitĂ© de semisâŠ). MalgrĂ© son positionnement « zĂ©ro pesticide » trĂšs en rupture avec lâagriculture conventionnelle, RĂ©s0Pest se distingue de lâAgriculture Biologique par lâalimentation azotĂ©e des cultures. En effet, la fertilisation minĂ©rale chimique est utilisĂ©e pour viser un rendement plus Ă©levĂ©, ce qui n'est pas sans consĂ©quence sur le dĂ©veloppement des adventives et des autres bioagresseurs. RĂ©s0Pest permet donc dâobtenir des rĂ©fĂ©rences originales intĂ©ressantes tant pour lâagriculture dite conventionnelle que pour lâAgriculture Biologique. Un tronc commun de mesures et dâobservations a Ă©tĂ© mis en place sur le rĂ©seau dans le but de conduire un diagnostic agronomique et en particulier de suivre lâĂ©volution de la flore adventice. Les trois premiĂšres campagnes expĂ©rimentales ont dĂ©jĂ permis de tirer des premiers enseignements sur la faisabilitĂ© et la maitrise de certaines combinaisons de techniques. Les expĂ©rimentations seront maintenues Ă minima pour les 3 prochaines campagnes culturales de maniĂšre Ă rendre possible lâĂ©tude des effets cumulatifs sur le long terme, en particulier sur la flore adventice
Variation in Lipid Species Profiles among Leukemic Cells Significantly Impacts Their Sensitivity to the Drug Targeting of Lipid Metabolism and the Prognosis of AML Patients
International audienceSeveral studies have linked bad prognoses of acute myeloid leukemia (AML) to the ability of leukemic cells to reprogram their metabolism and, in particular, their lipid metabolism. In this context, we performed âin-depthâ characterization of fatty acids (FAs) and lipid species in leukemic cell lines and in plasma from AML patients. We firstly showed that leukemic cell lines harbored significant differences in their lipid profiles at steady state, and that under nutrient stress, they developed common mechanisms of protection that led to variation in the same lipid species; this highlights that the remodeling of lipid species is a major and shared mechanism of adaptation to stress in leukemic cells. We also showed that sensitivity to etomoxir, which blocks fatty acid oxidation (FAO), was dependent on the initial lipid profile of cell lines, suggesting that only a particular âlipidic phenotypeâ is sensitive to the drug targeting of FAO. We then showed that the lipid profiles of plasma samples from AML patients were significantly correlated with the prognosis of patients. In particular, we highlighted the impact of phosphocholine and phosphatidyl-choline metabolism on patientsâ survival. In conclusion, our data show that balance between lipid species is a phenotypic marker of the diversity of leukemic cells that significantly influences their proliferation and resistance to stress, and thereby, the prognosis of AML patients
Gérer les adventices sans herbicides: Exemple des systÚmes de culture (SdC) testés dans le réseau expérimental « zéro pesticides » Rés0Pest
National audiencesystĂšmes de culture innovants minimisant le recours aux pesticides, en combinant des leviers agronomiques et en valorisant les rĂ©gulations biologiques, en grande culture et polyculture-Ă©levage. Il a vu le jour en 2012 et regroupe 8 dispositifs expĂ©rimentaux (INRA et lycĂ©e agricole dâAuzeville) dans lesquels sont testĂ©s des systĂšmes de culture ayant en commun de ne pas recourir aux pesticides. Ses objectifs sont de : - concevoir et expĂ©rimenter des systĂšmes de culture sans pesticide dans diffĂ©rentes situations de production ; dâen Ă©valuer les performances agronomiques, Ă©conomiques, environnementales et sociales ; - analyser lâeffet de ces systĂšmes sur lâĂ©volution des communautĂ©s, notamment les bioagresseurs, et les rĂ©gulations biologiques. Outre lâinterdiction du recours aux pesticides, les systĂšmes testĂ©s doivent chercher Ă maximiser une production respectueuse des exigences des filiĂšres locales (les cultures de vente reprĂ©sentatives de la rĂ©gion doivent ĂȘtre maintenues et les critĂšres de qualitĂ© des productions sont recherchĂ©s) et Ă maintenir le revenu de lâagriculteur. Les successions de cultures sont donc diffĂ©rentes selon les sites. Les systĂšmes de culture sont construits selon les principes de la protection intĂ©grĂ©e en combinant des techniques alternatives, Ă©prouvĂ©es ou suggĂ©rĂ©es par la bibliographie et les connaissances actuelles sur les bioagresseurs, en vue de rĂ©duire les risques de dĂ©veloppement des bioagresseurs et de favoriser la mise en place de rĂ©gulations biologiques. Bien quâils aient Ă©tĂ© conçus indĂ©pendamment les uns des autres, les systĂšmes de culture RĂ©s0Pest utilisent des techniques communes pour la lutte contre les adventices, certaines Ă©tant raisonnĂ©es au niveau de la rotation (allongement de la rotation, diversification des cultures et des pĂ©riodes de semis, alternance labour/non-labour, implantation de CIPAN, âŠ), dâautres au niveau de lâitinĂ©raire technique de chaque culture (faux-semis, dĂ©sherbage mĂ©canique, date et densitĂ© de semisâŠ). MalgrĂ© son positionnement « zĂ©ro pesticide » trĂšs en rupture avec lâagriculture conventionnelle, RĂ©s0Pest se distingue de lâAgriculture Biologique par lâalimentation azotĂ©e des cultures. En effet, la fertilisation minĂ©rale chimique est utilisĂ©e pour viser un rendement plus Ă©levĂ©, ce qui n'est pas sans consĂ©quence sur le dĂ©veloppement des adventives et des autres bioagresseurs. RĂ©s0Pest permet donc dâobtenir des rĂ©fĂ©rences originales intĂ©ressantes tant pour lâagriculture dite conventionnelle que pour lâAgriculture Biologique. Un tronc commun de mesures et dâobservations a Ă©tĂ© mis en place sur le rĂ©seau dans le but de conduire un diagnostic agronomique et en particulier de suivre lâĂ©volution de la flore adventice. Les trois premiĂšres campagnes expĂ©rimentales ont dĂ©jĂ permis de tirer des premiers enseignements sur la faisabilitĂ© et la maitrise de certaines combinaisons de techniques. Les expĂ©rimentations seront maintenues Ă minima pour les 3 prochaines campagnes culturales de maniĂšre Ă rendre possible lâĂ©tude des effets cumulatifs sur le long terme, en particulier sur la flore adventice
Ăvaluation multicritĂšre de systĂšmes de culture zĂ©ro-pesticides en grande culture et polyculture-Ă©levage (RĂ©seau RĂ©s0Pest)
Dans le cadre du plan Ecophyto, un rĂ©seau dâexpĂ©rimentations systĂšme a Ă©tĂ© mis en place en France
mĂ©tropolitaine, avec pour objectif de concevoir et dâĂ©valuer des systĂšmes de culture sans pesticides.
Les systÚmes ont été mis en place dans des situations variées (différents climats, types de sol, filiÚres)
et concernent les grandes cultures et la polyculture Ă©levage. Une Ă©valuation multicritĂšre (Criter 5.4,
MASC 2.0) a Ă©tĂ© conduite sur la pĂ©riode 2013-2017. On nâobserve pas de dĂ©gradation de la capacitĂ©
productive à long-terme, ni de la qualité sanitaire des récoltes et la contribution au développement
durable des huit systÚmes testés est considérée «faible à moyenne» pour la polyculture élevage et
«moyenne Ă Ă©levĂ©e» à «élevĂ©e» pour la grande culture. La durabilitĂ© environnementale est « Ă©levĂ©e » Ă
«trĂšs Ă©levĂ©e» pour tous les systĂšmes et câest la durabilitĂ© sociale qui est la moins favorable en raison
dâune «trĂšs faible» contribution Ă lâemploi. La rentabilitĂ© montre de fortes diffĂ©rences entre systĂšmes,
allant de « trÚs faible » à « trÚs élevée » mais aucune valorisation économique particuliÚre des récoltes
produites sans pesticides nâa Ă©tĂ© appliquĂ©e. Les rĂ©sultats prĂ©sentĂ©s dĂ©bouchent sur de nouvelles
perspectives pour une rĂ©duction significative de lâutilisation des pesticides en France.In the framework of Ecophyto, a network of eight system experiments was set up in order to design and assess pesticide-free cropping systems in the main French agricultural areas. The tested cropping systems cover a wide range of production situations (different climates, soils and agricultural sectors) for arable crop and multicrop-livestock farming. A multi-criteria analysis (Criter 5.4 and MASC 2.0) was conducted to assess the overall sustainability of the eight tested cropping systems over the 2013-2017 period. We observe neither degradation of the long-term productive capacity nor degradation of the sanitary quality of the harvests The overall sustainability of the eight cropping systems was assessed as âlow to mediumâ for the multicrop-livestock systems, and âmedium to highâ to âhighâ for the arable cropping systems. The environmental sustainability is "high" to "very-high" for all systems and the less favourable sustainability is the social one because of a "very low" contribution to employment. The profitability shows strong differences between systems, going from âvery low" to "very high" but no particular economic valuation of the harvests produced without pesticides was applied. The presented results draw new perspectives towards a major reduction of pesticide use in France
FLT3-ITD impedes retinoic acid, but not arsenic, responses in murine acute promyelocytic leukemias.
Acute promyelocytic leukemia (APL) is often associated with activating FLT3 signaling mutations. These are highly related to hyperleukocytosis, a major adverse risk factor with chemotherapy-based regimens. APL is a model for oncogene-targeted therapies: all-trans retinoic acid (ATRA) and arsenic both target and degrade its ProMyelocytic Leukemia/Retinoic Acid Receptor α (PML/RARA) driver. The combined ATRA/arsenic regimen now cures virtually all patients with standard-risk APL. Although FLT3-internal tandem duplication (ITD) was an adverse risk factor for historical ATRA/chemotherapy regimens, the molecular bases for this effect remain unknown. Using mouse APL models, we unexpectedly demonstrate that FLT3-ITD severely blunts ATRA response. Remarkably, although the transcriptional output of initial ATRA response is unaffected, ATRA-induced PML/RARA degradation is blunted, as is PML nuclear body reformation and activation of P53 signaling. Critically, the combination of ATRA and arsenic fully rescues therapeutic response in FLT3-ITD APLs, restoring PML/RARA degradation, PML nuclear body reformation, P53 activation, and APL eradication. Moreover, arsenic targeting of normal PML also contributes to APL response in vivo. These unexpected results explain the less favorable outcome of FLT3-ITD APLs with ATRA-based regimens, and stress the key role of PML nuclear bodies in APL eradication by the ATRA/arsenic combination
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