An integration of bioclimatic, soil, and topographic indicators for viticulture suitability using multi-criteria evaluation: a case study in the Western slopes of Jabal Al Arab-Syria

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Digital tools in allergy and respiratory care

Patient care in the allergy and respiratory fields is advancing rapidly, offering the possibility of the inclusion of a variety of digital tools that aim to improve outcomes of care. Impaired access to several health care facilities during the COVID-19 pandemic has considerably increased the appetite and need for the inclusion of e-health tools amongst end-users. Consequently, a multitude of different e-health tools have been launched worldwide with various registration and access options, and with a wide range of offered benefits. From the perspective of both patients and healthcare providers (HCPs), as well as from a legal and device-related perspective, several features are important for the acceptance, effectiveness,and long-term use of e-health tools. Patients and physicians have different needs and expectations of how digital tools might be of help in the care pathway. There is a need for standardization by defining quality assurance criteria.Therefore, the Upper Airway Diseases Committee of the World Allergy Organization (WAO) has taken the initiative to define and propose criteria for quality, appeal, and applicability of e-health tools in the allergy and respiratory care fields from a patient, clinician, and academic perspective with the ultimate aim to improve patient health and outcomes of care

Zilucoplan in immune-mediated necrotising myopathy: a phase 2, randomised, double-blind, placebo-controlled, multicentre trial

BACKGROUND: Immune-mediated necrotising myopathy is an autoimmune myopathy characterised by proximal muscle weakness, high creatine kinase concentrations, and autoantibodies recognising 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) or the signal recognition particle (SRP). No approved therapies exist for people with immune-mediated necrotising myopathy. Previous studies have suggested that complement activation might be pathogenic in immune-mediated necrotising myopathy; therefore, zilucoplan, a complement C5 (C5) inhibitor, could be a potential therapy. We aimed to evaluate the efficacy, safety, and tolerability of zilucoplan in adult participants with anti-HMGCR or anti-SRP autoantibody-positive immune-mediated necrotising myopathy. METHODS: IMNM-01 was a phase 2, multicentre, randomised, double-blind, placebo-controlled study done at 15 hospital sites across the USA, the UK, France, and the Netherlands. Participants aged 18–74 years were eligible for inclusion if they had a clinically confirmed diagnosis of immune-mediated necrotising myopathy, positive serology for anti-HMGCR or anti-SRP autoantibodies, clinical evidence of weakness, serum total creatine kinase concentration of more than 1000 U/L at screening, and no change in glucocorticoids or other immunosuppressive therapies for 30 days before baseline or expected during the first 8 weeks of the study. Participants were randomly assigned (1:1) to receive daily subcutaneous zilucoplan (0·3 mg/kg) or placebo for 8 weeks by use of a computerised randomisation algorithm; with optional enrolment in the study open-label extension. Randomisation was stratified by autoantibody status. Participants and study staff were masked to treatment group assignment. Primary efficacy endpoint (in the intent-to-treat population, defined as all participants who were randomly assigned to a treatment group) was percent change from baseline to week 8 in creatine kinase concentrations. Safety analyses were performed on the safety population (participants who received at least one dose of study drug during the main study, irrespective of whether they continued to the extension period—study participants were analysed on the basis of the treatment received). This study is registered with ClinicalTrials.gov, NCT04025632. FINDINGS: Between Nov 7, 2019, and Jan 7, 2021, we randomly assigned 27 participants (13 female and 14 male) to receive zilucoplan (n=12) or placebo (n=15). All 27 participants completed the 8-week main study. At week 8 there were no significant differences between treatment groups in median percent change of creatine kinase concentrations versus baseline (–15·1% [IQR –31·1 to 3·2] in the zilucoplan group vs –16·3% [–43·8 to 5·9] in the placebo group; p=0·46) and no clinically relevant improvement over time within the treatment group despite target engagement based on mode of action. There were no unexpected adverse safety or tolerability findings. Treatment-emergent adverse events were reported in nine (75%) of 12 participants in the zilucoplan group, and in 13 (87%) of 15 participants in the placebo group, and serious treatment-emergent adverse events were reported in zero participants in the zilucoplan group and three (20%) participants in the placebo group. The most frequent treatment-emergent adverse events were headache (four [33%] participants in the zilucoplan group and four [27%] participants in the placebo group) and nausea (three [25%] participants in the zilucoplan group and three [20%] participants in the placebo group). INTERPRETATION: C5 inhibition does not appear to be an efficacious treatment modality for people with immune-mediated necrotising myopathy. Rather than being the primary driver for disease activity, complement activation might be secondary to muscle injury. FUNDING: Ra Pharmaceuticals (now part of UCB Pharma)

Alterations in vasomotor control of coronary resistance vessels in remodelled myocardium of swine with a recent myocardial infarction

The mechanism underlying the progressive deterioration of left ventricular (LV) dysfunction after myocardial infarction (MI) towards overt heart failure remains incompletely understood, but may involve impairments in coronary blood flow regulation within remodelled myocardium leading to intermittent myocardial ischemia. Blood flow to the remodelled myocardium is hampered as the coronary vasculature does not grow commensurate with the increase in LV mass and because extravascular compression of the coronary vasculature is increased. In addition to these factors, an increase in coronary vasomotor tone, secondary to neurohumoral activation and endothelial dysfunction, could also contribute to the impaired myocardial oxygen supply. Consequently, we explored, in a series of studies, the alterations in regulation of coronary resistance vessel tone in remodelled myocardium of swine with a 2 to 3-week-old MI. These studies indicate that myocardial oxygen balance is perturbed in remodelled myocardium, thereby forcing the myocardium to increase its oxygen extraction. These perturbations do not appear to be the result of blunted β-adrenergic or endothelial NO-mediated coronary vasodilator influences, and are opposed by an increased vasodilator influence through opening of KATP channels. Unexpectedly, we observed that despite increased circulating levels of noradrenaline, angiotensin II and endothelin-1, α-adrenergic tone remained negligible, while the coronary vasoconstrictor influences of endogenous endothelin and angiotensin II were virtually abolished. We conclude that, early after MI, perturbations in myocardial oxygen balance are observed in remodelled myocardium. However, adaptive alterations in coronary resistance vessel control, consisting of increased vasodilator influences in conjunction with blunted vasoconstrictor influences, act to minimize the impairments of myocardial oxygen balance

Mise au point de la mesure de sections efficaces de réactions (n,XN) par spectroscopie g prompte sur des cibles très radioactives

La loi Bataille fait obligation au CNRS de développer des recherches sur le retraitement des déchets nucléaires. C est dans ce cadre que notre équipe GRACE (Groupe de Recherche sur l Aval du Cycle Electronucléaire) de l IPHC a entrepris des mesures nécessaires à la mise au point des réacteurs hybrides. Le champ de recherche s est élargi puisqu il inclut maintenant des études visant à développer le cycle de Thorium. GRACE s est plus précisément attaché à mesurer des sections efficaces de réactions (n,xng) mal connues jusqu à présent ou pour lesquelles aucune mesure n existe. Les mesures ont été effectuées auprès du faisceau blanc de Gelina (IRMM Geel, Euratom). La technique de temps de vol a été appliquée. La spectroscopie g en ligne, utilisée pour étudier les réactions (n,xng), requiert avant tout de mesurer l énergie des rayons g avec une bonne résolution. A cause de l existence d un flash g créé en même temps que le faisceau, il faut aussi un temps mort très faible, de façon à pouvoir détecter les neutrons de haute énergie. GRACE a réussi à concilier ces deux impératifs en mettant au point une nouvelle méthode basée sur la digitalisation et le traitement numérique du signal. Des mesures de section efficaces (n,xng) sur le 206,207,208Pb ont été réalisées ainsi avec succès à Geel, à l aide des détecteurs coaxiaux de gros volume et à une distance de vol de 200 m. Le travail présenté dans ce mémoire a consisté à adapter la méthode pour rendre possible la spectroscopie g en ligne sur des cibles radioactives. Pour cela, la nouvelle mesure s est déroulée sur une piste de vol de 30 m, et des détecteurs germanium planaires ont été utilisés. Dans un premier temps, et afin de s assurer du bon fonctionnement du nouveau dispositif expérimental, des mesures de sections efficaces (n,n g) sur une cible de plomb naturel ont été effectuées et les résultats sont comparés à ceux de la mesure à 200 m et aux calculs du code TALYS. Ensuite, les sections efficaces inélastiques partielles sur le 182,186W ont été mesurées entre le seuil de la réaction et 8 MeV. Enfin, une cible de 235U enrichie à 93,2 % a été bombardée et trois transitions dues à la réaction 235U(n,2ng)234U ont été analysées avec succès dont celle de l état 8+ vers l état 6+ jamais mesurée avant. Ce travail est une étape essentielle pour utiliser cette nouvelle méthode afin de mesurer des réactions (n,2ng) sur l 233U.The Bataille law obliged the CNRS to develop researches on the reprocessing of the nuclear waste. It is in this frame that our group GRACE (Groupe de Recherche sur l Aval du Cycle Electronucléaire) of the IPHC began researches that contribute to the development of the hybrid reactors. However, the field of research widened because it now includes studies to develop the Thorium cycle. GRACE has undertaken measurements of (n,xng) reactions cross sections badly known or for which no measurement exists yet. The experiments were performed at the white neutron beam generated by GELINA facility in Geel, Belgium. The time of flight technique was applied. The g spectroscopy used for these measurements requires the detection of g rays with a good energy resolution. Because of the existence of a g flash created at the same time as the neutron beam, a short dead time is also required, to be able to detect the high energy neutrons. GRACE managed to conciliate these two imperatives by finalizing a new method based on the digital treatment of the signal. Using large HPGe coaxial detectors, (n,xng) cross sections measurements on the 206,207,208Pb nuclei were successfully realized at a 200 m flight path. The work presented in this thesis consists in adapting the method to highly radioactive targets. For that reason, the new measurement took place on a 30 m flight path and planar germanium detectors were used. In order to check the correct functioning of the new experimental method, (n,n g) cross section measurements on a natural lead target were done and the results found were compared with the experiments at 200 m and with the theoretical calculations of the TALYS code. After that, the partial inelastic scattering cross sections on the 182,186W were performed from the threshold up to 8 Mev. Finally, a 93,2% enriched 235U target was bombarded and three transitions due to the 235U(n,2ng)234U reaction were successfully analysed including the one from the 8+ to the 6+ state, never measured before. This work is an essential step for using this new method in order to measure the (n,2ng) reaction cross sections on the highly radioactive 233U isotope.STRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF