Conception d'une alarme et gestion des risques dans la chimie : vers une approche développementale

Les "emballements de réaction" constituent une source majeure d'accidents dans les processus chimiques. On présente ici quelques enseignements issus de l'implantation, dans un site de production de la chimie fine, d'un système de détection des emballements de réaction. On présente quelques arguments qui suggèrent de comprendre le dispositif mis en place pour mener cette implantation comme un processus conjoint de développement des situations de travail et des acteurs qui participent au processus de conception. On tire, en conclusion, quelques enseignements sur la gestion des risques dans la chimie fine

Fracture initiation in multi-phase materials: a systematic three-dimensional approach using a FFT-based solver

This paper studies a two-phase material with a microstructure composed of a hard brittle reinforcement phase embedded in a soft ductile matrix. It addresses the full three-dimensional nature of the microstructure and macroscopic deformation. A large ensemble of periodic microstructures is used, whereby the individual grains of the two phases are modeled using equi-sized cubes. A particular solution strategy relying on the Fast Fourier Transform is adopted, which has a high computational efficiency both in terms of speed and memory footprint, thus enabling a statistically meaningful analysis. This solution method naturally accompanies the regular microstructural model, as the Fast Fourier Transform relies on a regular grid. Using the many considered microstructures as an ensemble, the average arrangement of phases around fracture initiation sites is objectively identified by the correlation between microstructure and fracture initiation -- in three dimensions. The results show that fracture initiates where regions of the hard phase are interrupted by bands of the soft phase that are aligned with the direction of maximum shear. In such regions, the hard phase is arranged such that the area of the phase boundary perpendicular to the principal strain direction is maximum, leading to high hydrostatic tensile stresses, while not interrupting the shear bands that form in the soft phase. The local incompatibility that is present around the shear bands is responsible for a high plastic strain. By comparing the response to a two-dimensional microstructure it is observed that the response is qualitatively similar (both macroscopically and microscopically). One important difference is that the local strain partitioning between the two phases is over-predicted by the two-dimensional microstructure, leading to an overestimation of damage

Adopción del sistema de seguimiento de actividades porcinas en la Provincia de Córdoba

Tesis (Magister en Ciencias Agropecuarias.)--UNC- Facultad de Ciencias Agropecuarias, 2014.En la Argentina las pequeñas y medianas empresas porcinas concentran alrededor del 50% de las cerdas madres en producción. Estas empresas son vulnerables frente a los vaivenes de la economía del país debido que tienen limitaciones en la gestión empresarial. Con el propósito de aportar al mejoramiento de la gestión en estas empresas se desarrolló un sistema informático denominado Sistema de Seguimiento de Actividades Porcinas (SAP). El objetivo principal de este trabajo fue determinar la valoración y las características de utilización del SAP desde la visión de los diferentes usuarios en la provincia de Córdoba. La información se obtuvo entrevistando a los usuarios del SAP en la provincia de Córdoba en los meses de junio, julio y agosto de 2012. El estudio revela que sólo el 12% de los usuarios tiene como única actividad en sus establecimientos la producción porcina, mientras que el resto (88%) comparte esta producción con otras actividades agropecuarias. Los profesionales que asesoran un criadero de cerdos participan activamente en el SAP. La capacitación en la utilización del SAP fue decisiva para su aprovechamiento por parte de los usuarios. La población analizada en el estudio se corresponde con los pequeños y medianos productores porcinos, que coincide con el tipo de usuarios objetivo del programa. Se pudo corroborar la hipótesis planteada sobre la implementación del SAP como herramienta de gestión de los establecimientos porcinos y la continuidad en su uso están influidas por: la valoración que el productor tiene con respecto a la utilización de los registros, el grado de tecnología aplicado al sistema productivo y el tipo de asesoramiento profesional que se realiza en el establecimiento. El mayor conocimiento de los usuarios de sus sistemas productivos porcinos dentro del establecimiento está relacionado con la implementación del programa SAP. El asesor técnico tiene un rol fundamental en el uso de registros y análisis de resultados, contribuyendo eficazmente en la percepción positiva e implementación del SAP en los pequeños y medianos productores porcinos.In Argentina, small and medium-size swine companies assemble about 50% of sows in production. These companies are vulnerable to fluctuations in the economy of the country due to the fact that they have limitations in their business management capacities. In order to contribute to the improvement of such companies ́ management, a software system called “Swine Activities Monitoring System” (S.A.M.S) was developed. The main objective of this work was to determine S.A.M.S ́s value as well as its characteristics of use as seen from the perspective of different users in Córdoba province. The information gathered was obtained by interviewing S.A.M.S users in Córdoba province within the months of June, July and August 2012.The study reveals that only 12% of its users work on pig production exclusively in their farms; whereas, the rest (88%) work on pig production and other agricultural activities simultaneously. Professional pig farm advisors take active part in the S.A.M.S. Training in the use of S.A.M.S was decisive for its users own profit. The population analyzed in the present study corresponds to small and medium-size swine companies, which coincides with the target users of the software. The hypothesis suggested could be proved- both the implementation and steady use of S.A.M.S as a pig farm management tool are influenced by the producer ́s valuing of the use of records, the level of technology applied to the production system and the type of professional advice given to the establishment. The more the S.A.M.S software is used by companies, the better informed users are about their swine farming systems. Technical advisors play a fundamental role in the use of records and in result analysis, by effectively contributing with small and medium-size swine companies ́ positive perception and adoption of this management tool

Design of an alarm and risk management in chemistry. Some lessons learned from interdisciplinary research

International audienceIn this communication, we would like to contribute some elements from inderdisciplinary research whose purpose was to develop an aid system designed to prevent "chemical runaways" taking place along with their consequences at human level (death), environmental level (SEVESO type companies) and industrial level (destruction of installations). This project follows an inquiry we made into a chemical runaway in a nuclear plant in 1994. The accident was fatal for one operator. In this case, two hours before the explosion, the operators realised that something was wrong. The five operators tried to get out of the unit a few seconds before the explosion. This type of result (which was largely confirmed by other analyses) shows that process operators often think that the time they have before an explosion is more than it really is. Our aim was the design of a system that would warn operators of the arrival of a chemical runaway and would predict the time remaining until an imminent explosion

Platform optimization and cost analysis in a floating offshore wind farm

Floating offshore wind represents a new frontier of renewable energies. The absence of a fixed structure allows exploiting wind potential in deep seas, like the Atlantic Ocean and Mediterranean Sea, characterized by high availability and wind potential. However, a floating offshore wind system, which includes an offshore turbine, floating platform, moorings, anchors, and electrical system, requires very high capital investments: One of the most relevant cost items is the floating substructure. This work focuses on the choice of a floating platform that minimizes the global weight, in order to reduce the material cost, but ensuring buoyancy and static stability. Subsequently, the optimized platform is used to define a wind farm located near the island of Pantelleria, Italy in order to meet the island’s electricity needs. A sensitivity analysis to estimate the Levelized Cost Of Energy is presented, analyzing the parameters that influence it most, like Capacity Factor, Weighted Average Capital Cost (WACC) and number of wind turbines

Dynamic Modeling of an Offshore Floating Wind Turbine for Application in the Mediterranean Sea

Wind power is emerging as one of the most sustainable and low-cost options for energy production. Far-offshore floating wind turbines are attractive in view of exploiting high wind availability sites while minimizing environmental and landscape impact. In the last few years, some offshore floating wind farms were deployed in Northern Europe for technology validation, with very promising results. At present time, however, no offshore wind farm installations have been developed in the Mediterranean Sea. The aim of this work is to comprehensively model an offshore floating wind turbine and examine the behavior resulting from a wide spectrum of sea and wind states typical of the Mediterranean Sea. The flexible and accessible in-house model developed for this purpose is compared with the reference model FAST v8.16 for verifying its reliability. Then, a simulation campaign is carried out to estimate the wind turbine LCOE (Levelized Cost of Energy). Based on this, the best substructure is chosen and the convenience of the investment is evaluated

Evaluating Islatravir Administered Via Microneedle Array Patch for Long-Acting HIV Pre-exposure Prophylaxis Using Physiologically Based Pharmacokinetic Modelling

Background and objectivesTechnologies for long-acting administration of antiretrovirals (ARVs) for the prevention and treatment of HIV are at the forefront of research initiatives aiming to tackle issues surrounding drug adherence with the current standard of once-daily oral administration. Islatravir (ISL) is an emerging ARV that shows promising characteristics for long-acting prevention and treatment both orally as well as through alternative routes of administration. Microneedle array patches (MAPs) are a pain-free and discreet transdermal delivery technology that offer extended-release administration of nanoparticulate drugs. This study aimed to utilise physiologically based pharmacokinetic (PBPK) modelling to predict the pharmacokinetics resulting from ISL administered via MAP and to identify key MAP characteristics required to sustain effective concentrations over extended dosing intervals.MethodsA PBPK model describing the conversion of ISL to ISL-triphosphate (ISL-TP) and its whole-body disposition was developed and verified against observed clinical data for orally administered ISL in healthy adults. An intradermal PBPK model was integrated with the ISL PBPK model to predict the dose and nanoparticle release rate required for MAP administration strategies capable of achieving a minimum ISL-TP target concentration of 0.05 pmol/106 PBMCs over extended dosing intervals. MAP design was limited to a maximum therapeutic area of 20 cm2 with a dose loading of 4.09 mg/cm2 and a minimum duration of 3 months. Due to the lack of available clinical data, a range of nanoparticle release rates and MAP bioavailability scenarios were simulated to provide an overview of potential clinical outcomes.ResultsThe ISL PBPK model was successfully verified, with predicted vs observed ratios falling within 0.5-2-fold. ISL MAP doses ranging from 15 to 80 mg were predicted to sustain ISL-TP concentrations above the minimum target concentration at 3, 6 and 12 months after administration. Nanoparticle release rate and MAP bioavailability were found to have a major impact on whether dosing strategies achieved the criteria. Minimum doses of 15 mg and 60 mg with a nanoparticle release rate of 0.0005 h-1 and bioavailability ranging from 25 to 100% were predicted to achieve effective ISL-TP concentrations up to 3 and 6 months, respectively. Doses of 15 mg and 30 mg with a nanoparticle release rate of 0.0005 h-1 were also able to attain the target concentration up to 6 months after MAP administration, albeit with a minimum bioavailability of 75% and 50%, respectively. Furthermore, when simulating a bioavailability of 100%, an 80 mg ISL MAP was predicted to sustain ISL-TP concentrations above the minimum target concentration up to 12 months after administration.ConclusionsThe ISL PBPK model successfully predicted ISL and ISL-TP pharmacokinetics across a range of orally administered regimens. The integrated intradermal PBPK model outlined optimal MAP dose and nanoparticle release rates for effective ISL-TP concentrations up to 12 months, providing justification for further investigation of ISL as a candidate for MAP administration

RYR1 gene variability and effect on meat pH in Argentinean hybrids swines = Variabilidad del gen RYR1 y efecto en el pH de la carne en cerdos híbridos argentinos

The RYR1 gene is the principal cause of the porcine stress syndrome (PSS) and the presence of pale, soft and exudative meat (PSE) in swine. In Argentina there are no reports about the variability of RYR1 gene in hybrid swine and its effect on the quality of carcass. By PCR-HRM we analyzed 403 hybrids swines from Argentina and 65.0% were homozygous NN, 30.8% heterozygous Nn and 4,2% homozygous nn. Additionally, a significant effect (p <0.0001) of the RYR1 gene was detected on the pH of carcass at 45 minutes after slaughter. Normal genotypes NN showed the highest pH values at 45 minutes after slaughter (6.27), heterozygous Nn showed intermediate pH values (5.94) and homozygous susceptible nn showed the lowest pH values (5.64). Argentina present high incidence of Nn and nn genotypes for the RYR1 gene in relation to Brazil, the principal pig producer of Latin America. Additionally the RYR1 gene affects the pH of the meat, one of the principal parameters in the determination of the PSE meat.El gen RYR1 es la principal causa del síndrome de estrés porcino (PSS) y la presencia de carne pálida, blanda y exudativa (PSE) en los cerdos. En Argentina no existen informes sobre la variabilidad de dicho gen en cerdos híbridos y su efecto sobre la calidad de la canal. Por PCR-HRM se analizaron 403 cerdos híbridos de Argentina y el 65,0% eran homocigotos NN, 30.8% heterocigotos Nn y el 4,2% homocigotos nn. Además, se detectó un efecto significativo (p <0,0001) del gen RYR1 en el pH de la canal a los 45 minutos post faena. Los genotipos NN mostraron los mayores valores de pH a los 45 minutos después del sacrificio (6.27), los heterocigotos Nn mostraron valores intermedios de pH (5,94) y los homocigotos nn presentaron los valores más bajos de pH (5,64). Argentina presenta alta incidencia de los genotipos Nn y nn del gen RYR1 en relación a Brasil, el principal productor de cerdos de América Latina. Además, el gen RYR1 afecta al pH de la carne, uno de los principales parámetros para la determinación de carnes PSE.EEA Marcos JuárezFil: Marini, Sebastián José. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Vanzetti, Leonardo Sebastian. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez. Grupo Biotecnología y Recursos Genéticos; ArgentinaFil: Borelli, Valeria Soledad. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Las Breñas; ArgentinaFil: Villarreal, Augusto Orlando. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Santiago del Estero; ArgentinaFil: Denegri, David. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Cottura, Germán Andrés. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Panichelli, Darío. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Silva, Patricia. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Departamento de Producción Animal. Cátedra de Nutrición Animal; ArgentinaFil: Campagna, D. Universidad Nacional de Rosario. Facultad de Ciencias Agrarias. Departamento de Producción Animal. Cátedra de Producción Animal; ArgentinaFil: Brunori, Jorge Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Brunori, Jorge Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Franco, Raul Enrique. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; Argentin

Predicting Drug-Drug Interactions between Rifampicin and Ritonavir-Boosted Atazanavir Using PBPK Modelling

ObjectivesThe aim of this study was to simulate the drug-drug interaction (DDI) between ritonavir-boosted atazanavir (ATV/r) and rifampicin (RIF) using physiologically based pharmacokinetic (PBPK) modelling, and to predict suitable dose adjustments for ATV/r for the treatment of people living with HIV (PLWH) co-infected with tuberculosis.MethodsA whole-body DDI PBPK model was designed using Simbiology 9.6.0 (MATLAB R2019a) and verified against reported clinical data for all drugs administered alone and concomitantly. The model contained the induction mechanisms of RIF and ritonavir (RTV), the inhibition effect of RTV for the enzymes involved in the DDI, and the induction and inhibition mechanisms of RIF and RTV on the uptake and efflux hepatic transporters. The model was considered verified if the observed versus predicted pharmacokinetic values were within twofold. Alternative ATV/r dosing regimens were simulated to achieve the trough concentration (Ctrough) clinical cut-off of 150 ng/mL.ResultsThe PBPK model was successfully verified according to the criteria. Simulation of different dose adjustments predicted that a change in regimen to twice-daily ATV/r (300/100 or 300/200 mg) may alleviate the induction effect of RIF on ATV Ctrough, with > 95% of individuals predicted to achieve Ctrough above the clinical cut-off.ConclusionsThe developed PBPK model characterized the induction-mediated DDI between RIF and ATV/r, accurately predicting the reduction of ATV plasma concentrations in line with observed clinical data. A change in the ATV/r dosing regimen from once-daily to twice-daily was predicted to mitigate the effect of the DDI on the Ctrough of ATV, maintaining plasma concentration levels above the therapeutic threshold for most patients