Comparative Long-Term Effect of Three Anti-P2Y12 Drugs after Percutaneous Angioplasty: An Observational Study Based on Electronic Drug Adherence Monitoring

Aims: Dual platelet inhibition using anti-P2Y12 drugs and aspirin is the standard of care in patients after percutaneous coronary interventions (PCI). Prasugrel and ticagrelor have been shown to be more potent than clopidogrel with less high on-treatment platelet reactivity. Whether differences in long-term adherence to these drugs can partly explain different antiplatelet efficacy has not been studied so far. The objective was to compare the long-term P2Y12 receptor inhibition and drug adherence to different anti-P2Y12 drugs, and to assess the impact of adherence on the pharmacodynamic effect.Methods: Monocentric, prospective, observational study. Stable outpatients treated with clopidogrel 75 mg once daily, prasugrel 10 mg once daily or ticagrelor 90 mg twice daily after PCI with stent implantation were included. Drug adherence was recorded during 6 months using electronic monitoring. Platelet responsiveness was assessed with the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) at inclusion, 3 and 6 months.Results: 120 patients had VASP-PRI and adherence data available. At 6-months, mean VASP-PRI (±SD) was 17.7 ± 11.0% with ticagrelor, 29.2 ± 15.5% with prasugrel and 47.2 ± 17.6% with clopidogrel (ANOVA, P < 0.0001).Median [IQR] taking adherence was 96 [82–100]% with ticagrelor, 100 [97–101]% with prasugrel and 100 [99–101]% with clopidogrel (p = 0.0001). Median [IQR] correct dosing was 88 [73–95]% with ticagrelor, 97 [92.5–98]% with prasugrel and 98 [96–99]% with clopidogrel (p = 0.0001).Anti-P2Y12 drug (p ≤ 0.001) and diabetes (p = 0.014) emerged as predictors of poor antiplatelet response after adjusting for age, BMI, sex, and CYP2C19∗2 carriers status.Conclusion: Drug adherence to anti-P2Y12 drugs assessed with electronic monitoring was very high. However, anti-P2Y12 drugs showed significant differences in antiplatelet activity, with newer anti-P2Y12 drugs ticagrelor and prasugrel exerting a stronger P2Y12 receptor inhibition.These data suggest that pharmacokinetic-pharmacodynamic differences between oral anti-P2Y12 drugs are more important than adherence in determining antiplatelet efficacy when adherence to prescription is high.The study was registered (Current Controlled Trials ISRCTN85949729)

The political dynamics of portfolio design in European democracies

Austrian Research Association (ÖFG) and the Austrian Science Fund (FWF) under grant P25490

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies.publishedVersio

Cold atoms in space: community workshop summary and proposed road-map

We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with the European Space Agency (ESA) and national space and research funding agencies

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Intoxication oculaire au formaldéhyde

International audienceLe formaldéhyde est une molécule incolore, gazeuse à température ambiante et soluble dans l'eau. Il est produit par une réaction entre l'ozone et différents alcènes. Son utilisation très générale comme conservateur et antibactérien en fait un polluant majeur. Les cellules de l'oeil et des tissus respiratoires sont en première ligne face à cette molécule. Des études concluantes ont déjà été réalisées sur l'atteinte du système respiratoire, c'est pourquoi nous cherchons à évaluer la toxicité du formaldéhyde pour les cellules de l'oeil, notamment son implication dans le syndrome de l'oeil sec. Pour évaluer cette toxicité, le système Vitrocell® a été utilisé. L'étude comporte 5 groupes, un groupe de cellules témoins cultivées à l'incubateur et immergées dans un liquide, le second groupe s'est vu retirer le liquide surnageant. Au troisième groupe a été ajouté un flux d'air sans formaldéhyde et les deux derniers groupes ont eu un flux d'air contenant du formaldéhyde à des concentrations de 100 μg/m 3 et 1200 μg/m 3. Nous avons étudié la production d'adénosine triphosphate (ATP) et de lactate déshydrogénase (LDH) de ces cellules afin d'évaluer leur viabilité dans les différentes conditions, ainsi que la production de différents facteurs de l'inflammation tels que l'interleukine 6 (IL-6), le facteur inhibant la migration des macrophages (MIF), la chimiokine de motif C-X-C et ligand 8 (CXCL8) et la chimiokine ligand 2 (CCL2). La stimulation de production de leur ARN est aussi étudiée. Au regard des résultats de ces expériences, le formaldéhyde n'a pas d'effet majeur sur la viabilité cellulaire, ni sur la production de cytokines inflammatoires qui semble surtout être influencée par le retrait du surnageant et l'ajout d'un flux d'air. Cependant, concentré à 1200 μg/mᶟ, le formaldéhyde semble influencer la quantité des ARN des différentes cytokines étudiées. Il pourrait donc avoir une influence génique

Brown Rot Strikes Prunus Fruit: An Ancient Fight Almost Always Lost

Brown rot (BR) caused by Monilinia spp., has been an economic problem for the stone fruit market due to dramatic losses, mainly during the postharvest period. There is much literature about basic aspects of Monilinia spp. infection, which indicates that environment significantly influences its occurrence in the orchard. However, progress is needed to sustainably limit this disease: the pathogen is able to develop resistance to pesticides, and most of BR resistance research programs in plant models perish. Solving this problem becomes important due to the need to decrease chemical treatments and reduce residues on fruit. Thus, research has recently increased, exploring a wide range of disease control strategies (e.g., genetic, chemical, physical). Summarizing this information is difficult, as studies evaluate different Monilinia and Prunus model species, with diverse strategies and protocols. Thus, the purpose of this review is to present the diversity and distribution of agents causing BR, focusing on the biochemical mechanisms of Monilinia spp. infection both of the fungi and of the fruit, and report on the resistance sources in Prunus germplasm. This review comprehensively compiles the information currently available to better understand mechanisms related to BR resistance."FruitBreedomics" European Project (Seventh Frame Program) FP7-265582 CONICYT, Chile (Post-Doctoral Fellowship) 74130043 CONICYT, Chile (Academy Insertion Grant) 79140020 CAPES foundation Brazilian Ministry of Educatio

Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016

International audienc