First observations and performance of the RPW instrument onboard the Solar Orbiter mission

The Radio and Plasma Waves (RPW) instrument on the ESA Solar Orbiter mission is designed to measure in situ magnetic and electric fields and waves from the continuum up to several hundred kHz. The RPW also observes solar and heliospheric radio emissions up to 16 MHz. It was switched on and its antennae were successfully deployed two days after the launch of Solar Orbiter on February 10, 2020. Since then, the instrument has acquired enough data to make it possible to assess its performance and the electromagnetic disturbances it experiences. In this article, we assess its scientific performance and present the first RPW observations. In particular, we focus on a statistical analysis of the first observations of interplanetary dust by the instrument’s Thermal Noise Receiver. We also review the electro-magnetic disturbances that RPW suffers, especially those which potential users of the instrument data should be aware of before starting their research work

Advanced Methods for Dose and Regimen Finding During Drug Development: Summary of the EMA/EFPIA Workshop on Dose Finding (London 4-5 December 2014)

Inadequate dose selection for confirmatory trials is currently still one of the most challenging issues in drug development, as illustrated by high rates of late-stage attritions in clinical development and postmarketing commitments required by regulatory institutions. In an effort to shift the current paradigm in dose and regimen selection and highlight the availability and usefulness of well-established and regulatory-acceptable methods, the European Medicines Agency (EMA) in collaboration with the European Federation of Pharmaceutical Industries Association (EFPIA) hosted a multistakeholder workshop on dose finding (London 4-5 December 2014). Some methodologies that could constitute a toolkit for drug developers and regulators were presented. These methods are described in the present report: they include five advanced methods for data analysis (empirical regression models, pharmacometrics models, quantitative systems pharmacology models, MCP-Mod, and model averaging) and three methods for study design optimization (Fisher information matrix (FIM)-based methods, clinical trial simulations, and adaptive studies). Pairwise comparisons were also discussed during the workshop; however, mostly for historical reasons. This paper discusses the added value and limitations of these methods as well as challenges for their implementation. Some applications in different therapeutic areas are also summarized, in line with the discussions at the workshop. There was agreement at the workshop on the fact that selection of dose for phase III is an estimation problem and should not be addressed via hypothesis testing. Dose selection for phase III trials should be informed by well-designed dose-finding studies; however, the specific choice of method(s) will depend on several aspects and it is not possible to recommend a generalized decision tree. There are many valuable methods available, the methods are not mutually exclusive, and they should be used in conjunction to ensure a scientifically rigorous understanding of the dosing rationale

COVID-19 vaccine-readiness for anti-CD20-depleting therapy in autoimmune diseases

Although most autoimmune diseases are considered to be CD4 T cell- or antibody-mediated, many respond to CD20-depleting antibodies that have limited influence on CD4 and plasma cells. This includes rituximab, oblinutuzumab and ofatumumab that are used in cancer, rheumatoid arthritis and off-label in a large number of other autoimmunities and ocrelizumab in multiple sclerosis. Recently, the COVID-19 pandemic created concerns about immunosuppression in autoimmunity, leading to cessation or a delay in immunotherapy treatments. However, based on the known and emerging biology of autoimmunity and COVID-19, it was hypothesised that while B cell depletion should not necessarily expose people to severe SARS-CoV-2-related issues, it may inhibit protective immunity following infection and vaccination. As such, drug-induced B cell subset inhibition, that controls at least some autoimmunities, would not influence innate and CD8 T cell responses, which are central to SARS-CoV-2 elimination, nor the hypercoagulation and innate inflammation causing severe morbidity. This is supported clinically, as the majority of SARS-CoV-2-infected, CD20-depleted people with autoimmunity have recovered. However, protective neutralizing antibody and vaccination responses are predicted to be blunted until naive B cells repopulate, based on B cell repopulation kinetics and vaccination responses, from published rituximab and unpublished ocrelizumab (NCT00676715, NCT02545868) trial data, shown here. This suggests that it may be possible to undertake dose interruption to maintain inflammatory disease control, while allowing effective vaccination against SARS-CoV-29, if and when an effective vaccine is available

The human early-life exposome (HELIX): project rationale and design

Background: Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure–health effect relationships. The “exposome” concept encompasses the totality of exposures from conception onward, complementing the genome. Objectives: The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the “early-life exposome.” Here we describe the general design of the project. Methods: In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother–child pairs, and biomarkers will be measured in a subset of 1,200 mother–child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure–response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. Conclusions: HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome

Erratum: The solar orbiter radio and plasma waves (RPW) instrument (Astronomy and Astrophysics (2020) 642 (A12) DOI: 10.1051/0004-6361/201936214)

The erratum concerns Fig. 9 entitled "Antenna radio-electrical properties" for which some of the parameters are not correct. The new figure with new parameters is provided in Fig. 1 of this corrigendum. Fig. 1. Corrected Antenna radio-electrical properties. (Figure Presented)

Nouvelle gouvernance, nouveaux conflits ? : chapitre V

[Departement_IRSTEA]Territoires [TR1_IRSTEA]DTAMNational audienceL'inscription à titre de "paysage culturel" d'un territoire implique d'une part la création d'un nouveau territoire de protection et d'action, d'autre part la mise en place de nouvelles modalités de gestion du site conformes aux exigences de la politique du patrimoine mondial. C'est à l'analyse des formes et des modalités de la mise en oeuvre de ce nouveau quotidien des territoires du Patrimoine mondial que l'on s'arrête dans ce chapitre

Nouvelle gouvernance, nouveaux conflits ? : chapitre V

[Departement_IRSTEA]Territoires [TR1_IRSTEA]DTAMNational audienceL'inscription à titre de "paysage culturel" d'un territoire implique d'une part la création d'un nouveau territoire de protection et d'action, d'autre part la mise en place de nouvelles modalités de gestion du site conformes aux exigences de la politique du patrimoine mondial. C'est à l'analyse des formes et des modalités de la mise en oeuvre de ce nouveau quotidien des territoires du Patrimoine mondial que l'on s'arrête dans ce chapitre

Cartographie par SIG de la production de sédiments des bassins versants torrentiels : exemple du Gourron (Pyrénées Centrales)

Prediction of sediment yield from torrential basins is an important objective for research upon torrential floods ingeenering. In this case study, a conceptual model is tested ; it is based on both slopes and channels abilities to provide materials and upon a torrent coefficient (representing transport capacity). Using a GIS makes parameters estimation easier. The tributaries basins of the Gourron are ordered. This order is compared, as measurements are lacking, to a field estimation. This rough validation is good. / La prédiction de la production de sédiments des bassins versants torrentiels est un objectif important de la recherche en ingénierie des risques de crues torrentielles. Dans cette étude de cas , on teste un modèle conceptuel basé sur les potentialités respectives des versants et des lits à fournir des matériaux et sur un indice de torrentialité (traduisant les possibilités de transport). L'utilisation d'un SIG facilite l'acquisition des paramètres nécessaires. Un classement en valeur relative des sous-bassins affluents du Gourron est élaboré. Il est confronté, à défaut de mesures, à une expertise sur le terrain. Cette validation sommaire est satisfaisante