NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models.

Purpose: The side effects of radiotherapy induced on healthy tissue limit its use. To overcome this issue and fully exploit the potential of radiotherapy to treat cancers, the first-in-class radioenhancer NBTXR3 (functionalized hafnium oxide nanoparticles) has been designed to amplify the effects of radiotherapy. Patients and Methods: Thanks to its physical mode of action, NBTXR3 has the potential to be used to treat any type of solid tumor. Here we demonstrate that NBTXR3 can be used to treat a wide variety of solid cancers. For this, we evaluated different parameters on a large panel of human cancer models, such as nanoparticle endocytosis, in vitro cell death induction, dispersion, and retention of NBTXR3 in the tumor tissue and tumor growth control. Results: Whatever the model considered, we show that NBTXR3 was internalized by cancer cells and persisted within the tumors throughout radiotherapy treatment. NBTXR3 activated by radiotherapy was also more effective in destroying cancer cells and in controlling tumor growth than radiotherapy alone. Beyond the effects of NBTXR3 as single agent, we show that the antitumor efficacy of cisplatin-based chemoradiotherapy treatment was improved when combined with NBTXR3. Conclusion: These data support that NBTXR3 could be universally used to treat solid cancers when radiotherapy is indicated, opening promising new therapeutic perspectives of treatment for the benefit of many patients

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m(2). Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Optimization of a Supply Chain : Christian Dior Couture

Nowadays, all the enterprises in the fashion industry face the problem of variability of supply and demand. Working in fashion implies facing rapid changes, and the success or failure of a company is often determined by the company's ability to adapt and respond quickly to these changes. In addition to having to deal with large quantities of information, the companies must ensure the availability of all their products, in all the stores worldwide, while optimizing inventory levels. This research will focus on Christian Dior Couture and more specifically on the Eyewear. The immediate objective of this research project is to optimize the inventory while maintaining the sales. The information on stock out rates crossed with the sales quantity, the stock and the coverage enables supply chain's managers to make decisions at a store level and at a reference level to reduce the stock at its optimal value without compromising the sales' level. In the future, further studies could be made to try and optimise the reordered quantities in addition to optimizing the current stores' stock

The spectral functions method for acoustic wave diffraction by a stress-free wedge: Theory and validation

International audienceNon Destructive Examination (NDE) of industrial structures requires the modeling of specimen geometry echoes generated by the surfaces (entry, backwall ...) of inspected blocks. For that purpose, the study of plane wave diffraction by a wedge is of great interest. The work presented here is preliminary research to model the case of an elastic wave diffracted by a wedge in the future, for which there exist various modeling approaches but the numerical aspects have only been developed for wedge angles lower thanπ. The spectral functions method has previously been introduced to solve the 2D diffraction problem of an immersed elastic wedge for angles lower thanπ. As a first step, the spectral functions method has been developed here for the diffraction on an acoustic wave by a stress-free wedge, in 2D and for any wedge angle, before studying the elastic wave diffraction from a wedge. In this method, the solution to the diffraction problem is expressed in terms of two unknown functions called the spectral functions. These functions are computed semi-analytically, meaning that they are the sum of two terms. One of them is determined exactly and the other is approached numerically, using a collocation method. Asuccessful numerical validation of the method for all wedge angles is proposed, by comparison with the GTD (Geometrical Theory of Diffraction) solution derived from the exact Sommerfeld integral

O05 - Identification de déviants positifs au sein du projet Opticourses : des achats alimentaires équilibrés malgré un petit budget

National audienceIntroduction et but de l’étudeLes inégalités sociales de santé ont une composante nutritionnelle avérée à laquelle pourrait contribuer le coût plus élevé d’une alimentation équilibrée. Cette association entre coût et qualité de l’alimentation n’a jusqu’ici été étudiée qu’à partir de prix alimentaires standards et non à partir de dépenses réelles. Selon la théorie de la déviance positive, l’étude des achats alimentaires réels devrait permettre d’identifier des foyers de faible statut socio-économique (SES) dont les achats sont de meilleure qualité nutritionnelle. Le but l’étude était d’étudier la relation entre les dépenses alimentaires réelles et la qualité nutritionnelle de l’alimentation au sein d’une population de faible SES, et identifier des « déviants positifs » afin de dégager les caractéristiques de leurs achats alimentaires.Matériel et méthodesDes personnes habitant dans des quartiers défavorisés à Marseille (n = 91) ont été recrutées pour participer à l’intervention d’éducation nutritionnelle Opticourses (opticourses.fr). Elles ont collecté les tickets de caisse des achats alimentaires de leur foyer pendant un mois. Les dépenses alimentaires effectives par jour et par personne (e/j.p.) ainsi que le coût de l’énergie (e/2 000 kcal d’achats) ont ensuite été calculés et corrélés à trois indicateurs de qualité nutritionnelle : le « Mean Adequacy Ratio » (MAR), le « Mean Excess Ratio » (MER) et la densité énergétique (DE). Le MAR et le MER ont été utilisés pour identifier 21 foyers « déviants positifs », c’est-à-dire les foyers dont les achats présentaient une meilleure qualité nutritionnelle (MAR > médiane et MER < médiane).Résultats et Analyse statistiqueUn coût d’énergie plus élevé était associé à un plus fort MAR et à une plus faible DE. Les achats alimentaires des « déviants positifs » avaient une qualité nutritionnelle significativement plus élevée que ceux des autres foyers (+13 % de MAR, −90 % de MER, −22 % de DE), pour un coût similaire (3,34 e/j.p. et 3,17 e/2 000 kcal). On observait dans leurs achats, plus de poisson, plus d’œufs, plus de féculents et plus de fruits et légumes, mais moins d’aliments gras, salés et sucrés, en particulier moins de sucreries, de boissons sucrées et de snacks salés, et enfin moins d’aliments consommés sur le pouce comme des sandwichs ou des pizzas.ConclusionNos résultats confirment que l’association positive entre le coût de l’alimentation et sa qualité nutritionnelle persiste lorsque le coût est mesuré par les dépenses réelles, et non pas estimé sur la base de prix alimentaires standards comme dans toutes les études précédentes. De plus, nos résultats indiquent que, en dépit de la relation globalement positive entre coût et qualité nutritionnelle, certains foyers de faible SES font des achats alimentaires plus sains sans dépenser plus. Les comportements d’achat de ces « déviants positifs » confortent la pertinence de mener des actions qui, comme Opticourses, visent à rendre visibles, disponibles et attractifs les aliments de bon rapport qualité nutritionnelle/prix pour faciliter l’atteinte de l’équilibre nutritionnel avec un petit budget

Two Elastodynamic Incremental Models: The Incremental Theory of Diffraction and a Huygens Method

International audienceThe elastodynamic Geometrical Theory of Diffraction (GTD) has proved to be useful in ultrasonic Non-Destructive Testing (NDT) and utilizes the so-called diffraction coefficients obtained by solving canonical problems, such as diffraction from a half-plane or an infinite wedge. Consequently applying GTD as a ray method leads to several limitations notably when the scatterer contour cannot be locally approximated by a straight infinite line: when the contour has a singularity (for instance at a corner of a rectangular scatterer), the GTD field is therefore spatially non-uniform. In particular, defects encountered in ultrasonic NDT have contours of complex shape and finite length. Incremental models represent an alternative to standard GTD in the view of overcoming its limitations. Two elastodynamic incremental models have been developed to better take into consideration the finite length and shape of the defect contour and provide a more physical representation of the edge diffracted field: the first one is an extension to elastodynamics of the Incremental Theory of Diffraction (ITD) previously developed in electromagnetism while the second one relies on the Huygens principle. These two methods have been tested numerically, showing that they predict a spatially continuous scattered field and their experimental validation is presented in a 3D configuration

Optimiser et valoriser la qualité nutritionnelle de produits transformés: Guide méthodologique et application à des produits méditerranéens

GUIDE PRATIQUE OPTIMEDCe guide, destiné aux industriels et professionnels de l’agroalimentaire, résulte d’un travail collectif entre le CRITT Agroalimentaire PACA, le CTCPA, et l’unité INRA 1260 de recherche en nutrition humaine. Il propose une démarche originale d’optimisation et de valorisation de la qualité nutritionnelle de produits méditerranéens avec la volonté d’inscrire la tradition dans la modernité et la durabilité.La première partie du guide présente la nouvelle pyramide de l’alimentation méditerranéenne entrée au patrimoine culturel de l’Humanité de l’UNESCO en 2010. Cette pyramide promeut la combinaison de produits méditerranéens et leurs fréquences de consommation, pour une bonne couverture des besoinsnutritionnels. Le concept de rétro-innovation, à l’initiative de la démarche OPTIMED, y est également présenté.La deuxième partie détaille la méthode OPTIMED dont l’originalité réside dans l’utilisation de deux outils : la programmation linéaire et le profilage nutritionnel. La programmation linéaire permet d’identifier des formulations optimales d’ingrédients intégrant de multiples contraintes (nutritionnelles, réglementaires, techniques, économiques) tout en respectant la tradition culinaire. Le nouveau système SAINcat,LIM estime et permet de suivre la qualité nutritionnelle globale d’un aliment en prenant mieux en compte des spécificités liées à son appartenance à une catégorie d’aliments (fruits et légumes, légumineuses, céréales, produits laitiers, viandes et oeufs, poissons). La combinaison inédite des deux outils permet de proposer des solutions d’optimisation de la qualité nutritionnelle globale en vue d’une meilleure valorisation des produits.La troisième partie présente l’application de la méthode OPTIMED sur plusieurs produits typiques de l’alimentation méditerranéenne comme la tapenade, la soupe de poissons et la ratatouille

De nouveaux outils pour optimiser les qualités nutritionnelles des produits alimentaires

De nouveaux outils pour optimiser les qualités nutritionnelles des produits alimentaires. 11. Journées Francophones de Nutrition, JFN 201