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Additional file 1: Table S1. Organ Specific Baseline Characteristics and Ventilation Parameters. Table S2. Primary Endpoint, COVID 19 patients only. Table S3. Primary Endpoint (PaO2/FiO2 ratio Day 5), adjusted by Ventilatory ratio and therapy. Table S4. Primary Endpoint in age strata. Figure S1. A) PaO2/FiO2 (min) during follow up with Iloprost vs placebo, B) PaO2/FiO2 (max) during follow up with Iloprost vs placebo. C) PaO2/FiO2 before and during therapy with Iloprost vs placebo total cohort, D) Covid-19 Positive, E) Covid-19 negative. Figure S2. Ventilatory ratio (VR) in the Placebo and treatment arm. Figure S3. A) Ninety-day mortality rates in COVID-19-negative and COVID-19-positive patients and B) 90-day mortality rates in COVID-19-negative patients in the Iloprost-treated group compared with control (NaCl)-treated patients. Figure S4. Subgroup analysis.

Additional file 3. Supplemental Table 2: Comparison of Barthel index at follow up in COVID-19 vs. Non-COVID-19 groups (ANOVA type test, after multiple imputation n = 144).

Additional file 1: Fig. S1. Receiver operating characteristic-ROC–for a high disability (Barthel Index between 0–60) after 180 days and SOFA score at day 5. (n = 98).

Additional file 2. Supplemental Table 1: Risk factors for high disability* at day 180 (multivariable analysis by binary logistic regression after multiple imputation n=144).

Additional file 4. Supplemental Table 3: Mixed effects model results showing the relationship between SOFA score and Barthel index at day 180.

The White Paper presented here is a consensus document produced by a group of 24 experts from non-governmental organisations, academia, and regulatory science, working in the field of pesticides, risk assessment, law, and human and environmental health. It identifies a range of shortfalls in the safety assessment of pesticides in Europe that result in the unrestricted use of potentially dangerous substances in agricultural fields and open spaces. The White Paper is intended to provide expert input into the ongoing evaluation of the EU legislation on pesticides, proposes 18 concrete solutions on how to improve the risk assessment and risk management of pesticides in Europe, in line with the requirements of EU law. It supports the implementation of a higher level of protection from pesticides in Europe, as the EU law demands. Ultimately, it aims to promote the development and implementation of sustainable, non-chemical pest management practices in our food production system., The White Paper was developed by members of the coalition Citizens for Science in Pesticide Regulation, in an initiative of Pesticide Action Network Europe. The development process was initiated by the authors during a workshop held in Brussels in April 2018. Based on this work, a manifesto was produced which calls for "rigorous science, safe food and healthy environment" through reform of the pesticide risk assessment process. As of 18 January 2019 the manifesto had gathered more than 130 civil society and institutional supporters. More information about Citizens for Science in Pesticide Regulation and its activities can be found here: https://citizens4pesticidereform.eu/

International audience; We present the design of a widely tunable monolithic source on GaAs/AlGaAs. It consists of a quantum-well distributed feedback (DFB) laser vertically coupled with a waveguide engineered for nonlinear frequency conversion. No regrowth or alignment is necessary, and all the structure stems from a single epitaxy step. Light is emitted by the 0.98 μm DFB laser and transmitted to the underlying waveguide by an adiabatic taper, where it can undergo parametric down-conversion, providing signal and idler beams around 2 μm. Transfer rates and tolerances for transfer and conversion efficiency are calculated to be compatible with the tolerances of current fabrication processes. We estimate that an OPO threshold can be reached in the underlying waveguide for a laser emitted power of 20–100 mW, if high-reflectivity distributed Bragg reflectors (DBRs) are used.

The work presented in this thesis deals with the design, fabrication and characterization of sources intended to function as both laser diodes and optical parametric oscillators. These lasers are designed to emit on a higher order mode to allow parametric frequency conversion with fundamental modes of the guide at half frequency. The laser diode and OPO share the same optical cavity; to ensure phase matching and correct nominal structure deviations induced during epitaxial processing, the ridge width is used as a control parameter of the effective indices. The proposed diodes are therefore narrow (3-5 μm) and etched deeply. Consequently, it is potentially interesting to use quantum dots to limit non-radiative recombination on the sidewalls. In the context of this work, we have designed diodes based on this principle for the two GaAs/AlGaAs and InGaAsP/InP systems, which respectively allow to potentially obtain an OPO emission in the vicinity of 2 μm or 3 μm. In the case of InGaAsP/InP, we previously studied the refractive index of InGaAsP alloys in a wavelength range not covered by literature to this day. This data was acquired via effective m-line index measurements of InGaAsP guiding layers epitaxially grown on and lattice-matched to an InP substrate. For optimized laser-OPO structures, simulations show that the OPO threshold should be obtained for an intracavity pump power of a few hundred mW, which is realistic to achieve for state-of-the-art laser diodes. We have studied the electro-optical properties of GaAs/AlGaAs quantum well laser diodes made on the basis of our designs; the observation of the laser effect on the TE2 mode validates the original vertical design of our laser diodes. For the manufacture of narrow-ridge lasers-OPOs, we have developed new manufacturing processes on the Plateforme Technologique Amont (Upstream Technology Platform, CEA - Grenoble), including deep etching (> 10 μm) by ICP-RIE. Finally, we have proposed an alternative diode-OPO concept, comprising distinct laser and OPO cavities coupled by an adiabatic taper, Le travail présenté dans cette thèse porte sur la conception, la fabrication et la caractérisation de sources prévues pour fonctionner à la fois comme diode laser et comme oscillateur paramétrique optique. Ces lasers sont conçus pour émettre sur un mode d’ordre supérieur afin de permettre une conversion de fréquence paramétrique avec les modes fondamentaux du guide à la fréquence moitié. La diode laser et l’OPO partagent la même cavité optique ; pour assurer l’accord de phase et corriger les écarts à la structure nominale induits lors de l’élaboration par épitaxie, la largeur de ruban est utilisée comme paramètre de contrôle des indices efficaces. Les diodes proposées sont donc étroites (3-5 µm) et gravées profondément. En conséquence, il est potentiellement intéressant d’utiliser des boîtes quantiques pour limiter les recombinaisons non radiatives sur les flancs. Dans le cadre de ce travail, nous avons conçu des diodes basées sur ce principe pour les deux systèmes GaAs/AlGaAs et InGaAsP/InP, qui permettent respectivement d’obtenir potentiellement une émission OPO au voisinage de 2 µm ou de 3 µm. Dans le cas de l’InGaAsP/InP, nous avons étudié au préalable l’indice de réfraction des alliages InGaAsP dans une plage de longueur d’onde jusque-là non couverte par la littérature. Ces données ont été acquises via des mesures d’indice efficace (m-lines) de couches guidantes d’InGaAsP épitaxiées en accord de maille sur un substrat d’InP. Pour des structures laser-OPO optimisées, les simulations montrent que le seuil OPO devrait être obtenu pour une puissance de pompe intracavité de quelques centaines de mW, qu’il est réaliste d’atteindre pour des diodes laser à l’état de l’art. Nous avons étudié les propriétés électro-optiques de diodes lasers à puits quantiques GaAs/AlGaAs réalisées sur la base de nos dessins; l’observation de l’effet laser sur le mode TE2 valide le dessin vertical original de nos diodes lasers. En vue de la fabrication de laser-OPO à ruban étroit, nous avons développé des procédés de fabrication nouveaux sur la Plateforme Technologique Amont (CEA – Grenoble), notamment la gravure profonde (>10 µm) par ICP-RIE. Enfin, nous avons proposé un concept alternatif de diode-OPO, comprenant des cavités laser et OPO distinctes couplées par un taper adiabatique

We present the design of a widely tunable monolithic source on GaAs/AlGaAs. It consists of a quantum-well distributed feedback (DFB) laser vertically coupled with a waveguide engineered for nonlinear frequency conversion. No regrowth or alignment is necessary, and all the structure stems from a single epitaxy step. Light is emitted by the 0.98 μm DFB laser and transmitted to the underlying waveguide by an adiabatic taper, where it can undergo parametric down-conversion, providing signal and idler beams around 2 μm. Transfer rates and tolerances for transfer and conversion efficiency are calculated to be compatible with the tolerances of current fabrication processes. We estimate that an OPO threshold can be reached in the underlying waveguide for a laser emitted power of 20–100 mW, if high-reflectivity distributed Bragg reflectors (DBRs) are used.

If the use of mechanical restraint evolved through the centuries, the questionings which it causes remain whole. In addition, for a long time a gap in the law persisted feeding its legitimacy. Very recently a law was promulgated relating to it specifically: the law of January 26th, 2016. It is in this context that we are particularly interested in this practice. The studies on the subject prove to be quasi exclusively centered on its indication, its effectiveness or even to which profile of patients measurement is applied. This is why not wishing to study its legitimacy but rather the way in which it was done, we completed this work. It is about a retrospective study of type CAS-witness, unicentric, realized in the psychiatric center of orientation and reception at the hospital Saint-Anne in Paris, on the whole of the patients having been contained included from July 1st,2016 to December 31st, 2016. We studied the sociodemographic characteristics (age and sex), environmental characteristics (conditions of arrival, existence of recent triggering factors, multitude, sex, age and statues of the professionals) and clinical characteristics (reasons for consultation, toxic taking, antecedents and assumptions diagnostic) as well as the duration of mechanical restraint of these patients. It results from it factors appearing significant (conditions of arrival, schedule and days of application being able to reflect the manpower of the professionals, existence of elements deteriorating the communication, presence of delirious ideas). In addition, the lack of significativity of some results could be explained by the size of our sample.; Si l’utilisation de la contention a évolué à travers les siècles, les questionnements qu’elle suscite restent entiers. Par ailleurs pendant longtemps a persisté un vide juridique alimentant sa légitimité. Très récemment a été promulguée une loi la concernant spécifiquement : la loi du 26 janvier 2016. C’est dans ce contexte que nous nous sommes particulièrement intéressés à cette pratique. Les études sur le sujet s’avère être quasi exclusivement centrées sur son indication, son efficacité ou bien encore à quel profil de patients la mesure est appliquée. C’est pourquoi ne souhaitant pas étudier sa légitimité mais plutôt la manière dont elle était mise œuvre, nous avons réalisé ce travail. Il s’agit d’une étude rétrospective de type cas-témoin, unicentrique réalisée au centre psychiatrique d’orientation et d’’accueil à l’hôpital Sainte-Anne sur l’ensemble des patients ayant été contenus du 1er juillet 2016 au 31 décembre inclus. Nous avons étudié les caractéristiques sociodémographiques (âge et sexe), environnementales (conditions d’arrivée, existence de facteurs déclenchant récents, affluence, sexe, âge et statuts des professionnels) et cliniques ( motifs de consultation, prise de toxiques, antécédents et hypothèses diagnostiques) ainsi que la durée de contention des patients. Il en résulte des facteurs apparaissant significatifs (conditions d’arrivée, horaire et jours de contention pouvant refléter l’effectif des professionnels, existence d’éléments altérant la communication, la présence d’idées délirantes). Par ailleurs le manque de significativité de certains résultats pourrait s’expliquer par un manque de puissance du à la taille de notre échantillon.

Identification of genes with evolutionary conserved and enriched expression in pancreatic exocrine cells. Venn diagram showing the number of exocrine-enriched genes found only in zebrafish, mouse or human, and those displaying conserved endocrine-enrichment in two species or in the three species (shown in intersections). Due to gene duplications in some species and often in zebrafish, the number of corresponding murine (M) or human (H) orthologous genes is given in brackets in each intersection. The full list of conserved exocrine-enriched genes is given in Additional file 7: Table S5. (PDF 4 kb)