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International audience; Background and objectives: Studies focusing on the neurodevelopmental effects of phthalates seldom consider exposure during infancy, a critical period for brain development. Most rely on parent-completed questionnaires to assess child neurodevelopment, which may be subject to reporting error. We studied the associations between prenatal and infancy exposure to phthalates and objective measures of neurodevelopment at the age of two. Methods: We relied on 151 mother-child pairs from the SEPAGES mother-child cohort. Women were asked to collect three spot urine samples per day over seven consecutive days during the second (median: 18.0 gestational weeks) and third (median: 34.2 gestational weeks) trimesters of pregnancy. They then collected one urine sample per day over seven consecutive days from their infants around the age of 12 months. Metabolites of phthalates and non-phthalate plasticizers were measured in within-subject and within-period pools of repeated urine samples. Eye tracking tasks were performed at two years allowing to compute four indicators linked with cognitive development and visual behavior: mean fixation duration, novelty preference, percent time spent looking at the eyes and mean reaction time. Results: Pre-natal exposure to monobenzyl phthalate at the second and third trimesters was associated with shorter fixation durations. In models allowing for interaction with child sex, these associations were only observed among girls. Exposure to di(2-ethylhexyl) phthalate at the third but not the second trimester was associated with increased time spent looking at a novel face and eyes. We observed faster reaction times and decreased time spent looking at the eyes in a face recognition task, with increased post-natal exposure to monoethyl, mono-iso-butyl and mono-n-butyl phthalates. Discussion: Relying on improved exposure assessment, we highlighted associations of pre-and post-natal exposure to phthalates with indicators derived from eye tracking tasks, mainly in girls. Some of these indicators have been affected in individuals with neurodevelopmental disorders.

ImportanceLittle is known about long-term associations of early-life exposure to extreme temperatures with child health and lung function.ObjectivesTo investigate the association of prenatal and postnatal heat or cold exposure with newborn lung function and identify windows of susceptibility.Design, Setting, and ParticipantsThis population-based cohort study (SEPAGES) recruited pregnant women in France between July 8, 2014, and July 24, 2017. Data on temperature exposure, lung function, and covariates were available from 343 mother-child dyads. Data analysis was performed from January 1, 2021, to December 31, 2021.ExposuresMean, SD, minimum, and maximum temperatures at the mother-child’s residence, estimated using a state-of-the-art spatiotemporally resolved model.Main Outcomes and MeasuresOutcome measures were tidal breathing analysis and nitrogen multiple-breath washout test measured at 2 months of age. Adjusted associations between both long-term (35 gestational weeks and first 4 weeks after delivery) and short-term (7 days before lung function test) exposure to ambient temperature and newborn lung function were analyzed using distributed lag nonlinear models.ResultsA total of 343 mother-child pairs were included in the analyses (median [IQR] maternal age at conception, 32 [30.0-35.2] years; 183 [53%] male newborns). A total of 246 mothers and/or fathers (72%) held at least a master’s degree. Among the 160 female newborns (47%), long-term heat exposure (95th vs 50th percentile of mean temperature) was associated with decreased functional residual capacity (−39.7 mL; 95% CI, −68.6 to −10.7 mL for 24 °C vs 12 °C at gestational weeks 20-35 and weeks 0-4 after delivery) and increased respiratory rate (28.0/min; 95% CI, 4.2-51.9/min for 24 °C vs 12 °C at gestational weeks 14-35 and weeks 0-1 after delivery). Long-term cold exposure (5th vs 50th percentile of mean temperature) was associated with lower functional residual capacity (−21.9 mL; 95% CI, −42.4 to −1.3 mL for 1 °C vs 12 °C at gestational weeks 15-29), lower tidal volume (−23.8 mL; 95% CI, −43.1 to −4.4 mL for 1 °C vs 12 °C at gestational weeks 14-35 and weeks 0-4 after delivery), and increased respiratory rate (45.5/min; 95% CI, 10.1-81.0/min for 1 °C vs 12 °C at gestational weeks 6-35 and weeks 0-1 after delivery) in female newborns as well. No consistent association was observed for male newborns or short-term exposure to cold or heat.Conclusions and RelevanceIn this cohort study, long-term heat and cold exposure from the second trimester until 4 weeks after birth was associated with newborn lung volumes, especially among female newborns.

Background Ambient temperature, particularly heat, is increasingly acknowledged as a trigger for preterm delivery but study designs have been limited and results mixed. We aimed to comprehensively evaluate the association between ambient temperature throughout pregnancy and preterm delivery. Methods We estimated daily temperature throughout pregnancy using a cutting-edge spatiotemporal model for 5347 live singleton births from three prospective cohorts in France, 2002–2018. We performed Cox regression (survival analysis) with distributed lags to evaluate time-varying associations with preterm birth simultaneously controlling for exposure during the first 26 weeks and last 30 days of pregnancy. We examined weekly mean, daytime, night-time and variability of temperature, and heatwaves accounting for adaptation to location and season. Results Preterm birth risk was higher following cold (5th vs 50th percentile of mean temperature) 7–9 weeks after conception [relative risk (RR): 1.3, 95% CI: 1.0–1.6 for 2°C vs 11.6°C] and 10–4 days before delivery (RR: 1.6, 95% CI: 1.1–2.1 for 1.2°C vs 12.1°C). Night-time heat (95th vs 50th percentile of minimum temperature; 15.7°C vs 7.4°C) increased risk when exposure occurred within 5 weeks of conception (RR: 2.0, 95% CI: 1.05–3.8) or 20–26 weeks after conception (RR: 2.9, 95% CI: 1.2–6.8). Overall and daytime heat (high mean and maximum temperature) showed consistent effects. We found no clear associations with temperature variability or heatwave indicators, suggesting they may be less relevant for preterm birth. Conclusions In a temperate climate, night-time heat and chronic and acute cold exposures were associated with increased risk of preterm birth. These results suggest night-time heat as a relevant indicator. In the context of rising temperatures and more frequent weather hazards, these results should inform public health policies to reduce the growing burden of preterm births.

International audience; Background: Some synthetic phenols alter pathways involved in fetal development. Despite their high within-subject temporal variability, earlier studies relied on spot urine samples to assess pregnancy exposure. In this study, we examined associations between prenatal phenol exposure and fetal growth. Methods: We measured concentrations of two bisphenols, four parabens, benzophenone-3, and triclosan in 478 pregnant women in two weekly pools of 21 samples each, collected at 18 and 34 gestational weeks. We used adjusted linear regressions to study associations between phenol concentrations and growth outcomes assessed twice during pregnancy and at birth. Results: Benzophenone-3 was positively associated with all ultrasound growth parameters in at least one time point, in males but not females. In females, butylparaben was negatively associated with third-trimester abdominal circumference and weight at birth. We observed isolated associations for triclosan (negative) and for methylparaben and bisphenol S (positive) and late pregnancy fetal growth. Conclusions: Our results suggest associations between prenatal exposure to phenols and fetal growth. Benzophenone-3 was the exposure most consistently (positively) associated across all growth parameters.

For non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values, Graphical abstract Image 1, Highlights • Repeated urine samples were collected and pooled within-subject, within period. • Metabolites of phthalates and DINCH were measured in pooled samples. • Frequencies of detection were overall high. • Pregnancy concentrations of MiBP, MBzP, DEHP and oxo-MINP decreased with time. • Pregnancy concentrations of oh-MiNP and DINCH metabolites increased with time., Relying on a recent cohort (2014–2017) with repeated urine samples collected during pregnancy and infancy, we showed that exposure to phthalates and DINCH is still widespread in the general population.

International audience; Fluid dispersion in small fixed bed reactors under single phase laminar flow conditions is evaluated through accurate predictions of axial Péclet numbers Peax using Direct Numerical Simulations (DNS). The fixed bed packing is obtained through the Discrete Element Method (DEM) code Grains3D. Peax numbers are computed from steady state simulations of the flow. An additional set of equations solving the spatial distribution of the moments of the age distribution is used. This gives access to local information on dead zones or bypasses. Computations are realized with the OpenFOAM® open-source library. Results are close to the experimental data. The DEM-OpenFOAM® workflow benefits from an accurate control of the fluid physical properties and packing geometry, thus leading to a faster production of data than an experimental approach.We first explore the influence of the reactor-to-sphere diameter ratio δ (δ < 4), fluid velocity and molecular diffusivity on the Peax number. The behavior proves much more complex than any previous report, and it can be qualitatively explained by looking at the packing structure. Then, we use the DEM-OpenFOAM® workflow to quantify the uncertainty on the Peax number when repeating the packing of a δ = 4 fixed bed reactor, and we propose that the uncertainty on the Peax number decreases as a function of the reactor length to the power of −0.5.

The aim of this work is to build CFD tools to study heat transfer in packed beds during the thermochemical upgrading process of woody biomass. For that purpose, a numerical workflow capable of investigating heat transfer phenomena inside a packed bed was developed. First, the bed is generated using a Discrete Element Method (DEM) code. Then, a steady-state Direct Numerical Simulation (DNS) solver is used to acquire the flow patterns inside the pores of the bed. Finally, the heat equation is solved for the particles and the fluid in a coupled manner. The results are thoroughly validated against two benchmark cases: flow around a sphere and flow through a packed bed of spheres. The importance of accounting for internal heat resistance for substrates with high Biot number (e.g. wood) is highlighted. Furthermore, the heat transfer phenomena inside a packed bed of torrefied wood chips are investigated. Values of the heat transfer coefficient are also provided ( ≃ 5 W/m 2 /K, for Re i 5, 7.7 for Re = 10). Another interesting finding is the effect of channeling in this type of beds and its impact on the temperature field of the wood chips.

The objective is to improve the learning of a regression model of the hydrocracking process using a reduced number of observations. When a new catalyst is used for the hydrocracking process, a new model must be fitted. Generating new data is expensive and therefore it is advantageous to limit the amount of new data generation. Our idea is to use a second data set of measurements made on a process using an old catalyst. This second data set is large enough to fit performing models for the old catalyst. In this work, we use the knowledge from this old catalyst to learn a model on the new catalyst. This task is a transfer learning task. We show that the results are greatly improved with a Bayesian approach to transfer linear model and kriging model.

International audience; Packed bed reactors with diameters below 1 cm, millipacked beds hereafter, are often used to test catalysts. The prospect of using these reactors for catalytic kinetic measurements is quite attractive, but it requires a better knowledge of the flow characteristics of these reactors. This study focuses on the main hydrodynamic features of millipacked bed reactors in single phase gas flow. The effects of the bed length, gas velocity, reactor/particle diameter ratio (δ) and the use of fine inert powder as porosity filler are investigated via residence time distribution measurements and reactive tests. When using spherical particles, for values of reactor/particle diameter ratios between 1 < δ < 3, the behavior of the Peclet number, Pe, is not monotonous. Lower values of the Pe number for specific values of δ corresponding to large void spaces between the particles and/or between the particles and the walls, have been observed. For values of δ > 3 higher Pe numbers are observed, in particular at high gas velocities, due to the transition to a more uniform packing where the walls are no longer the major constraint. When using cylindrical particles, higher dispersion is observed when the cylinders align on each other along the reactor axis, as compared to when they are randomly arranged in the reactor. A criterion to calculate the maximum conversion that can be achieved neglecting dispersion effects has been proposed, highlighting the situations where it has to be used with caution. The dispersion in these reactors can often be neglected. In case the criterion is not fulfilled, filling the porosity of the beds with powder reduces the dispersion. Using porosity fillers in reactors with internal diameters between 2 and 4 mm showed an improvement of the conversions for n-heptane reforming and methylcyclohexane dehydrogenation, which is attributed to external mass transfer improvement. Fine and spherical powders fill better the porosity and yield lower dispersion and higher mass transfer.

Background: Recent studies have suggested the involvement of several endocrine disruptors, including synthetic phenols and phthalates, in the development of infant behavioural disorders. These stud...

PurposeTo characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length.MethodsThis study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n=254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated.ResultsWomen used prednisone 3 to 292days during pregnancy, with daily doses ranging from

Background Human immunodeficiency virus (HIV)–infected pregnant women increasingly receive antiretroviral therapy (ART) to prevent mother-to-child transmission (PMTCT). Studies suggest HIV-exposed uninfected (HEU) children face higher mortality than HIV-unexposed children, but most evidence relates to the pre-ART era, breastfeeding of limited duration, and considerable maternal mortality. Maternal ART and prolonged breastfeeding while on ART may improve survival, although this has not been reliably quantified. Methods Individual data on 19 219 HEU children from 21 PMTCT trials/cohorts undertaken from 1995 to 2015 in Africa and Asia were pooled to estimate the association between 24-month mortality and maternal/infant factors, using random-effects Cox proportional hazards models. Adjusted attributable fractions of risks computed using the predict function in the R package “frailtypack” were used to estimate the relative contribution of risk factors to overall mortality. Results Cumulative incidence of death was 5.5% (95% confidence interval, 5.1–5.9) by age 24 months. Low birth weight (LBW, Pooled results from 21 studies involving more than 19 000 human immunodeficiency virus–exposed but uninfected children show that an estimated two-thirds of infant deaths are attributable to lack of antiretroviral treatment for mothers, low birth weight, never being breastfed, and mother’s death.

BACKGROUND: Exposure to certain synthetic phenols is of growing concern, in particular among pregnant women, because of their endocrine disrupting nature. Many phenols are still authorized in personal care products (PCP). We aimed to assess if use of PCPs, by pregnant women could influence their urinary concentrations of synthetic phenols. METHODS: We used a panel design with intense urine sample collection. Eight women completed a diary with exact time and use of PCP in three weeks. We measured the concentrations of phenols (four parabens, bisphenol A and S, two dichlorophenols, triclosan, and benzophenone-3) in 178 urine samples, collected during 7 consecutive days at 3 time points during pregnancy. We characterized PCP use as the total number of PCP applications or as a single PCP use (yes / no) in three time windows (0 to 6, 6 to 12 and 12 to 24 before each urine sample collection). We used adjusted linear and Tobit regressions to assess associations between PCP use and phenol urinary concentrations. RESULTS: The total number of PCP applications was positively associated with ethylparaben, propylparaben and butylparaben concentrations. We observed a peak in urinary concentration of ethylparaben, butylparaben and propylparaben at 2.86, 2.55 and 2.67 hours since last PCP use, respectively and twelve different types of PCPs were positively associated with at least one of these parabens. The bisphenol S concentration increased by 12.4% (95%CI: confidence interval: 5.9; 19.3) for each additional PCP application in the 12 to 24 time window and use of specific PCPs such as anti-stretchmarks cream, facial cleanser and shower gel. Associations varied by time window. CONCLUSION: Our study showed that PCP use was associated with a short-term increase in the urinary concentration of ethylparaben, butylparaben and propylparaben, but not methylparaben. This study also reported a positive association between the use of PCPs and the bisphenol S concentration, a finding that warrants further investigation in cohorts with repeated collection of urine samples and detailed information on PCP use.

International audience; Random packed beds of cylindrical, trilobic, and quadrilobic particles in cylindrical and biperiodic containers are numerically studied using Grains3D, a code based on the discrete element method (DEM) that resolves all inelastic collisions and dynamically simulates the loading of packed beds. Particle initial position and orientation are random to mimic industrial or laboratory packing procedures, so that the same simulation repeated again yields a different packed bed structure and thus a different average void fraction. These ”in silico” experiments aim at being able to optimize particle shape in heterogeneous catalysis, in particular with respect to the corresponding bed void fraction that is a critical parameter for pressure drop prediction. These “in silico” experiments are deterministic and accurate but with differences due to the loading procedure. In this paper, we first present our assessment of the uncertainty on average void fraction induced by (i) the initial random position and orientation of inserted particles and (ii) the insertion zone size. Next we investigate the effect of particle shape, namely cylindrical, trilobic, and quadrilobic on the average void fraction as a function of particle length and diameter, and of the container type. Simple correlations are proposed that very well describe the simulations within the aforementioned uncertainty related to the packing procedure. Although the beds made with cylindrical particles are markedly denser, the beds made of the trilobic and quadrilobic particles have a statistically identical void fraction.

Context:Within the community-randomized ANRS 12249 Treatment-as-Prevention trial conducted in rural South Africa, we analysed sexual behaviours stratified by sex over time, comparing immediate antiretroviral therapy irrespective of CD4+ cell count vs. CD4+-guided antiretroviral therapy (start at CD4+ cell count > 350 cells/μl then >500 cells/μl) arms.Methods:As part of the 6-monthly home-based trial rounds, a sexual behaviour individual questionnaire was administered to all residents at least 16 years. We considered seven indicators: sexual intercourse in the past month; at least one regular sexual partner in the past 6 months; at least one casual sexual partner in the past 6 months and more than one sexual partner in the past 6 months; condom use at last sex (CLS) with regular partner, CLS with casual partner, and point prevalence estimate of concurrency. We conducted repeated cross-sectional analyses, stratified by sex. Generalized Estimating Equations models were used, including trial arm, trial time, calendar time and interaction between trial arm and trial time.Results:CLS with regular partner varied between 29–51% and 23–46% for men and women, respectively, with significantly lower odds among women in the control vs. intervention arm by trial end (P

Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a "pathway to pathology". In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay. This was achieved through the measurement of 40 cytokines/chemokines from maternal blood samples collected during the second and third trimesters of pregnancy. Importantly, during the second trimester we identified network enrichment in levels of cytokines including IFN-ɣ, IL-10, TNF-β, TNF-α, and CRP associated with offspring neurodevelopmental delay. However, as elevations in levels of these cytokines have previously been reported in a wide range of neurodevelopmental disorders including autism spectrum disorder and schizophrenia, we suggest that this cytokine profile is likely not disorder specific, but rather may be an indicator of neurodevelopmental delay in general. By contrast, distinct clusters of activated/inhibited cytokines were identified based on maternal alcohol consumption and child neurodevelopmental outcome. Specifically, cytokines including IL-15, IL-10, MDC, and members of the VEGF sub-family were highest in alcohol-consuming mothers of children with neurodevelopmental delay and were identified in both network analyses and examination of individual cytokines, whereas a differential and unique cytokine profile was identified in the case of alcohol-independent child neurodevelopmental delay. We propose that the current findings could provide a critical step towards the development of early biomarkers and possibly interventions for alcohol-related neurodevelopmental delay. Importantly, the current approach could be informative for understanding mechanisms linking maternal immune system dysfunction and adverse child outcomes in a range of other neurodevelopmental disorders.

PURPOSE: Studies of antidepressant safety in pregnancy typically do not address complex patterns of use throughout pregnancy. We performed longitudinal trajectory modeling to describe patterns of antidepressant use in the first 32 weeks of pregnancy, and test whether these trajectories are associated with a reduction in birth weight or gestational age at delivery. METHODS: Our study included 166 pregnant women with deliveries between 2011–2015 who were prescribed an antidepressant between 91 days prior to last menstrual period and 32 weeks of gestation. From electronic medical records, we estimated average daily dose and cumulative dose per week for the first 32 weeks of gestation and for the first 13 weeks postnatal. We clustered women with similar utilization patterns using k-means longitudinal modeling and assessed the associations between trajectory group and birth weight and gestational age at delivery. RESULTS: We identified four cumulative dose trajectory groups and three average daily dose trajectory groups in each period. Relative to the lowest trajectory group, the highest trajectory group during pregnancy was associated with reduced birth weight in multivariable analysis (average daily highest trajectory vs. lowest trajectory β −314.1g, 95% CI −613.7, −15.5) adjusted for depression severity score, maternal age, race, and pregnancy smoking. Trajectory groups were not associated with gestational age at delivery. CONCLUSIONS: The highest trajectory group of antidepressant use in pregnancy was associated with a modest reduction in birth weight but not with gestational age at delivery. Longitudinal trajectories allow for a dynamic visualization and quantification of medication use among pregnant women.

International audience; Fully resolved simulations of the flow through a fixed bed of pellets are performed to better understand the effect of the local microstructure on the energy loss, i.e., pressure drop through the bed. Both mono-disperse and poly-disperse systems as well as spherical and cylindrical pellets (solid particles) are investigated. Using a DEM-DLM/FD simulation method inspired by “Wachs, A. (2009). A DEM-DLM/FD method for direct numerical simulation of particulate flows: sedimentation of polygonal isometric particles in a Newtonian fluid with collisions. Comput. Fluids 38(8), 1608–1628” and implemented here in a Finite Volume context with second order reconstruction of the particle boundary as in “Rahmani, M., Wachs, A. (2014). Free falling and rising of spherical and angular particles. Phys. Fluids 26, 083301”, we evidence that the computed solution converges nicely with mesh refinement and provide guidelines on the grid size to guarantee a satisfactory level of accuracy. Based on these trustworthy simulation results, we investigate the impact of the particle shape as well as the degree of poly-dispersity in the system on the pressure drop over the fixed bed in the viscous regime. Unprecedented simulation results on the flow through a bed of poly-disperse cylinders indicate that the correlation for poly-disperse spheres suggested in “Van der Hoef, M.A., Beetstra, R., Kuipers, J.A.M. (2005). Lattice-Boltzmann simulations of low-Reynolds-number flow past mono- and bidisperse arrays of spheres: results for the permeability and drag force. J. Fluid Mech. 528, 233–254” may still be valid for cylinders of moderate aspect ratio.

Every night, the human brain produces thousands of downstates and spindles during non-REM sleep. Previous studies indicate that spindles originate thalamically and downstates cortically, loosely grouping spindle occurrence. However, the mechanisms whereby the thalamus and cortex interact in generating these sleep phenomena remain poorly understood. Using bipolar depth recordings, we report here a sequence wherein: (1) convergent cortical downstates lead thalamic downstates; (2) thalamic downstates hyperpolarize thalamic cells, thus triggering spindles; and (3) thalamic spindles are focally projected back to cortex, arriving during the down-to-upstate transition when the cortex replays memories. Thalamic intrinsic currents, therefore, may not be continuously available during non-REM sleep, permitting the cortex to control thalamic spindling by inducing downstates. This archetypical cortico-thalamo-cortical sequence could provide the global physiological context for memory consolidation during non-REM sleep., During non-REM sleep, the thalamus produces spindles and the cortex produces downstates, but the interaction between these two areas in these sleep phenomena is not understood. Here, authors describe the dynamic loop between the thalamus and cortex that organizes the production of spindles and downstates in the human brain.

A Taylor–Aris dispersion in laminar capillary flows of magnetic nanofluids submitted to transverse rotating magnetic fields (RMFs) was analyzed with a simple phenomenological mixing approach. The nanofluid residence time distributions (RTDs) measured under RMFs were used to quantify the deviations, with respect to field-free Poiseuille flows, of the axial dispersion induced by the rotating magnetic nanoparticles (MNPs) as a function of MNPs concentration and diameter, and RMF frequency and strength. The attenuation of axial dispersion due to the magnetic field was ascribed to an enhanced transverse diffusion coefficient that thrust tracer radial transport, owing to nanoconvective streams in the nanoparticle neighborhoods, beyond molecular diffusion capability. To estimate the enhanced transverse diffusion coefficient, a semiempirical model was developed in which the nanofluid domain was viewed as an array of identical cells each containing a magnetic nanoparticle at its center. Owing to the nanoparticle r...

article i nfo Article history: Available online xxxx abstract The liquid flow field in a stirred reactor, with catalyst particles contained in a fixed basket, has been inves- tigated by means of CFD RANS (Reynolds-Averaged Navier-Stokes) simulations, using a Realizable k-e model. First results without basket showed a good agreement between simulations and literature, by com- paring impeller power numbers (Np) and liquid velocity pattern. The basket was simulated as a porous medium characterized by its porosity and permeability using the Brinkman-Forchheimer model. When adding the basket, the flow pattern also presents a recirculation but at a lower velocity magnitude. The liquid flows through the central zone of the basket in a radial outward direction. The zones of the catalytic basket above and below this central zone are also crossed radially but in the opposite direction (inward) and at a lower velocity. Using the computed velocities in the basket and the Ranz-Marshall correlation, liquid/solid mass transfer coefficients (ks) were estimated in the different zones of the catalytic basket with reasonable values. We conclude from these calculations that there is a recirculation pattern in the basket and a non-uniformity of velocities inducing differences in mass transfer coefficients in the catalytic basket. Despite the simplicity of the model, results (flow patterns, Np, ks) are in line with previous work (experimental and simulation).

International audience; Catalyst improvement is a key route toward process improvement in terms of yield, energy efficiency and selectivity optimization. The catalyst development strategy includes catalyst testing on a model or real feedstock. This key step has been the focus of many studies during the last decades concerning reactor design, analytical tool development and operating procedures. Most studies aim to determine catalytic grain activity in isothermal conditions so as to be able to understand and predict the kinetics. With catalyst improvement, in the lab-scale reactors available, the mass transfer rate can become the limiting step compared with the reaction rate, especially for fast exothermic reactions. A new reactor geometry is proposed to intensify the mass transfer and to accelerate the fluid superficial velocities: the single pellet string reactor. To characterize this new geometry, a hydrodynamic study was carried out in a horizontal single pellet string reactor with a 4.0 × 4.0 mm2 square section, filled with spherical particles of diameter varying between 2.0 and 4.0 mm. In this hydrodynamic study, visual observations of the flow patterns were performed, as well as pressure drop measurements and residence time distribution analysis in single liquid phase flow and two-phase flows. In every configuration tested, two main regimes were identified: the “isolated bubbles” regime and the “stratified” regime. Peclet number and liquid hold-up were deduced from the residence time distribution analysis. The measured liquid hold-ups are always higher than 0.6, which indicates, in addition to the visual observations and colorimetric tests, that the catalyst is always fully wetted by the liquid film. The axial dispersion measurements showed that the single liquid phase flow cannot be interpreted by a classical axial dispersion model. However, when a gas phase is added, the flow becomes closer to plug flow, with Peclet numbers always higher than 40. It has been shown that the pressure drop is controlled by the liquid/solid friction surface and that the pressure drop is not a limiting parameter in the reactor’s operation (values always lower than 0.1 bar). So, from a hydrodynamic point of view, this new reactor exhibits characteristics suitable for its use in catalytic tests. Finally, this reactor was implemented under reaction conditions to study hydrogenation reactions with a real industrial catalyst. The selective hydrogenation of allene was studied. The string reactor was shown to run isothermal kinetic tests with a very small amount of industrial-sized catalyst particles (less than 2 cc) and to explore kinetics of fast reaction at high space velocities impossible to achieve in standard fixed bed units with appropriate hydrodynamic conditions. For constant residence time, the allene conversion does not vary with pressure and feed flow rate, which confirms that the string reactor allows one to perform catalytic tests with such a fast reaction without external mass transfer resistance.; L’optimisation du catalyseur est une etape cle pour l’optimisation d’un procede catalytique du point de vue des rendements, de l’efficacite energetique et de la selectivite des reactions. La strategie de developpement d’un catalyseur comprend des tests effectues sur des reacteurs pilotes avec des charges reelles ou modeles. Cette etape a fait l’objet de nombreuses etudes ces dernieres decennies portant sur le dimensionnement des reacteurs, l’amelioration des outils d’analyses et les procedures operatoires. La plupart des etudes ont pour but de determiner l’activite catalytique de catalyseur sous forme de grain dans des conditions isothermes de facon a pouvoir determiner les parametres cinetiques de la reaction. Avec l’optimisation des catalyseurs, les flux de transfert de matieres externes aux grains peuvent devenir l’etape limitante, dans les reacteurs de laboratoire standard, par rapport aux flux de reaction. Ce probleme est particulierement critique pour les reactions rapides et tres exothermiques. Une nouvelle geometrie de reacteur est proposee pour intensifier les transferts de matieres autour des grains de catalyseur et accelerer les vitesses superficielles des fluides : le “reacteur filaire”. Pour caracteriser cette nouvelle geometrie de reacteur, une etude hydrodynamique a ete menee avec un reacteur filaire horizontal de section carree de 4,0 × 4,0 mm2 rempli de particules spheriques de diametre compris entre 2 et 4 mm et simulant des grains de catalyseur. Les regimes d’ecoulement ontete etudies a partir d’analyses d’images, des mesures de perte de pression et de distribution de temps de sejour qui ont ete effectuees en ecoulement monophasique liquide et diphasique gaz/liquide. Deux principaux regimes d’ecoulements ont ete observes: un regime de “bulles isolees” et un regime de type “stratifie”. Les retentions liquides sont toujours superieures a 60 %, ce qui indique en complement d’observations visuelles que le catalyseur est toujours correctement irrigue par l’ecoulement liquide. En ecoulement diphasique gaz/liquide, l’ecoulement est de type piston puisque les nombres de Peclet sont toujours superieurs a 40. La perte de pression est principalement controlee par les forces de frottement liquide/solide et les valeurs de perte de pression restent tres faibles en conditions de tests catalytiques (< 0,1 bar). Les caracteristiques hydrodynamiques indiquent donc que ce reacteur est approprie pour des tests catalytiques. Enfin, ce type de reacteur a ete mis en oeuvre en conditions de reactions catalytiques pour effectuer des tests d’un catalyseur commercial pour une reaction d’hydrogenation de l’allene. Le reacteur a permis d’effectuer des tests en conditions isothermes avec une tres faible quantite de catalyseur (inferieure a 2 cc) et d’acceder aux performances catalytiques pour des temps de contact tres courts impossible a atteindre avec des reacteurs a lits fixes conventionnels dans de bonnes conditions hydrodynamiques. Pour un meme temps de sejour, la conversion en allene ne varie pas, ni avec la pression operatoire, ni avec le debit de charge, ce qui confirme que ce type de reacteur permet d’effectuer des tests catalytiques avec des reactions rapides sans limitation aux transferts de matieres externes aux grains.

Heterogeneous catalyst pellets evaluation is performed in smaller and smaller reactors with the main objective of reducing catalyst development costs. Downscaling raises the question: is there a lower limit to the number of pellets that ought to be tested in a reactor so that the results do not depend on which pellets are sampled? Major sources of variability among a catalyst pellet population are dimensions and many parameters that can be grouped as “intrinsic kinetic activity” (porosity, tortuosity, active phase repartition and availability). In this paper, we present a methodology to estimate the incertitude induced by variability on size and kinetics on the evaluation of the apparent kinetic constant in a fixed bed reactor. Analytical expressions are presented to predict this incertitude for sphere and cylinder shaped pellets, with a first order kinetic law in two limiting cases: the absence of mass transfer limitations and presence of severe internal mass transfer limitations. The predicted incertitude scales as the square root of sample population: downsizing increases the incertitude. We propose criteria to evaluate the minimum number of pellets to sample, so that sampling induced variability is lower than an acceptable incertitude, expressed in °C. This acceptable incertitude could be for example a fraction of the experimental temperature incertitude.

International audience; In petroleum refining, γ-alumina is used as a solid support of molybdenum nickel/cobalt promoted catalysts for the hydrotreatment processes, such as hydrodesulfurization. The ever decreasing norms for the sulfur content in gasoline require better and more efficient catalysis, prompting extensive research on the materials and the factors influencing the activity, selectivity and stability of the catalytic processes. In the present study, Magnetic Resonance Imaging Single Point Imaging is tested as a tool to monitor the impregnation of γ-alumina pellets with Ni(NO3)2 aqueous solutions at varying Ni2+ concentration. The method enables a study in the presence of paramagnetic elements in the alumina support, in the conditions of very fast T1 and T2. It is shown that at higher concentrations of metal ions a homogenous distribution in the support is attained faster. A non-linear dependence is observed and a minimum ion concentration of 0.2 M is necessary for achieving short impregnation times of alumina pellets of millimeter size scale.

We investigate the reactive flow through a fixed bed of catalyst particles. Our simulation method belongs to the class of multi-scale approaches and combines nano scale DFT (Density Functional Theory) computations, mean-field kinetics at the micro scale and fully-resolved hydrodynamic simulations at the millimetric scale. At this stage, the simulations at the chemical (nano and micro) scales provide the rate constants needed by the hydrodynamic model in a one-way coupling. In this paper, we focus on the fully-resolved millimetric scale simulation model based on a Distributed Lagrange Multiplier/Fictitious Domain (DLM/FD) method combined with a Finite Volume/Staggered Grid scheme and a high order reconstruction at the fluid/solid interface. In particular, we present various DLM/FD algorithms that supply a divergence free velocity field, a property crucial for the accurate discretization of the additional diffusion-convection equations modeling the chemical reactions. Our method is implemented in our fully MPI platform PeliGRIFF (www.peligriff.com) dedicated to the multi-scale simulation of flows with particles/bubbles/drops. We illustrate the assets of our simulation method on the reactive flow through a pack of 3D cylinders and discuss the forthcoming developments required to extend our approach to a two-way coupling in which the reaction rates are affected by the flow dynamics.Copyright © 2014 by ASME

Erratum : figure 3. Reproduction; International audience; A retrospective study carried out recently in a large sample of men, close to the general population, has reported a significant and strong decline in sperm concentration and morphology in the whole of France between 1989 and 2005. We studied these trends within each region of France. Data were obtained from the Fivnat database. The study sample comprised male partners of sterile women in whom both tubes were absent or blocked. They were located at the assisted reproductive technology center. A Bayesian spatio-temporal model with parametric time trends, adjusted for age, was used to model overall time trends for each region. The results show that sperm concentration decreased in almost all regions of France. Among them, Aquitaine showed the highest decrease and Midi-Pyrénées had the lowest average for the whole period. Regarding total motility, most regions showed a slight increase while Bourgogne showed a steep and significant decrease. While considering sperm morphology, there was a decrease in most of the regions. The decrease in Aquitaine and Midi-Pyrénées was stronger when compared with the overall trend. In conclusion, a decrease in sperm concentration and morphology, already shown at the French metropolitan territory level, was observed in most regions of France. This is consistent with a global change in environmental exposure, according to the endocrine disruptor hypothesis especially. Indeed, ubiquitary exposure to chemicals has been growing in the general population of France since the 1950s, and the results do not appear to support the lifestyle hypothesis. The highest decreases and lowest values are consistently observed in two proximate regions that are both highly agricultural and densely populated.

Are temporal trends and values of semen quality parameters in France identifiable in partners of totally infertile women?Among a sample of 26 609 partners of totally infertile women undergoing an assisted reproductive technology (ART) procedures in the whole of France over a 17-year period, there was a continuous decrease in semen concentration of about 1.9% per year and a significant decrease in the percentage with morphologically normal forms but no global trend for motility.A global decrease in human sperm quality is still debated as geographical differences have been shown, and many criticisms have risen concerning studies with small and biased study populations or inappropriate statistical methodology. However, growing biological, toxicological, experimental and human exposure data support the endocrine disruptors' hypothesis assuming that fetal exposure to endocrine disruptors could impair reproductive outcomes.This was a retrospective and descriptive study using data registered by Fivnat, the professional association in charge of statistics for ART in France during the 1989-2005 study period. Data were provided by 126 main ART centres over the whole metropolitan territory. The source population included 154 712 men, aged 18-70, who were partners of couples undergoing their first ART cycle and for whom semen quality indicators (concentration, total motility and percentage of morphologically normal forms), measured on fresh ejaculated semen, were available.The study population was 26 609 partners of women who had both tubes either absent or blocked. The temporal trends for each indicator of semen quality were modelled using a generalized additive model that allowed for nonlinear relationships between variables and were adjusted for season and age. In-depth sensitivity analyses included the reiteration of the analysis on data from a second spermiogram available for each man and on another subsample of men diagnosed as fertile. Variables such as centre, technique (standard in vitro fertilization or intra-cytoplasmic sperm injection) and an interaction factor between technique and time were also included in the model.There was a significant and continuous decrease in sperm concentration of 32.2% [26.3-36.3] during the study period. Projections indicate that concentration for a 35-year-old man went from an average of 73.6 million/ml [69.0-78.4] in 1989 to 49.9 million/ml [43.5-54.7] in 2005. A significant, but not quantifiable, decrease in the percentage of sperm with morphologically normal forms along the 17-year period was also observed. There was no global trend but a slight, significant increase in total motility between 1994 and 1998 was observed. The results were robust after sensitivity analysis.Socioeconomic status could not be controlled for. Despite universal access to medical services in France, couples undergoing ART are expected to have a higher educational level on average compared with those of the general population. Therefore, the real values in the general population could be slightly lower than those presented and the decrease possibly stronger, as the population study is less likely to smoke or be overweight, two factors known to impair semen quality.As the men were selected without a priori knowledge regarding their semen quality characteristics, the results are expected to be close to the values in the general French population. The very large sample size and the robustness of the results confer great statistical power and credibility to the results. To our knowledge, it is the first study concluding a severe and general decrease in sperm concentration and morphology at the scale of a whole country over a substantial period. This constitutes a serious public health warning. The link with the environment particularly needs to be determined.

Background Immunodominance and sequence diversity are major hurdles in the development of effective HIV vaccines. We tested the hypothesis that a vaccine candidate composed of strictly Conserved Elements (CE) of the HIV proteome excluding the variable regions would help overcome problems of viral sequence diversity and potential negative effects of immunodominance. Seven CE were identified in p24. Vaccination of macaques with p55DNA failed to elicit cellular or humoral immune responses to the CE, while epitopes outside of the CE were immunogenic.

Results The mean pairwise AA diversity among the 66 SIVMAC251 Env sequences was 0.38%, and they differed from the vaccine strain SIV SME543 (Env) by 21.94%. The repeated low-dose challenge resulted in infections with an average of 1.7 founder variants with no evidence that the vaccine restricted the number of variants (p = 0.813). We explored whether the vaccine induced a sieve effect, i.e. whether breakthrough viruses differed between the vaccine and control groups. There was no difference for full-length Env sequences. Focusing on Env segments preferentially recognized by vaccinated monkeys in antibody arrays, we identified a sieve effect in the Env-V2 segment AA163-193: sequences from vaccinated animals were more divergent from the vaccine SIVSME543 or from the challenge stock SIVMAC251 than sequences in control animals (p ≤ 0.002).

International audience; In this work, we are interested in a better understanding of the local packing structure of fixed bed reactors made of cylindrical pellets packed in cylindrical tubes. Packing of cylindrical particles is simulated using Grains3D DEM code and results are analyzed in terms of void fraction using 3D analysis tools. With tube diameter as a secondary parameter, we investigate the porous structure depending on the pellet length distribution: average porosity, radial porosity, orientation of the pellets and variability of those indicators when repeating the numerical experiments.

Background: In the current context of increasing unsafe sex, HIV incidence may have evolved, depending on HIV prevalence in sexual networks and, among HIV-infected persons who practice unsafe sex, on their infectivity and partners' HIV serostatus. We examined calendar trends in sexual behaviours at risk of HIV-1 transmission (SBR) among 967 adults followed since primary HIV infection (ANRS PRIMO cohort) and relationship with current treatments and viral load. Methods: Patients completed since 2000 self-administered questionnaires on sexual practices every 6 months. SBR with HIV-negative/unknown partners were analyzed among 155 heterosexual women, 142 heterosexual men and 670 MSM by using logistic generalized estimating equation models (6656 visits). Results: During 2000-2009, the frequency of SBR did not increase significantly among women with steady partners; risk factors were a low education level and alcohol/ smoking use. Among heterosexual men with steady partners, the frequency of SBR doubled since 2006; during this period, the only associated factor was combined antiretroviral treatment for at least 6 months or viral load less than 400copies/ml. Among MSM, SBR increased gradually over time; SBR with steady partners was associated with a low education level and alcohol use. SBR was more frequent among MSM with casual partners; no association with viral load was found. Conclusion: In France, recent trends and risk factors in unprotected sex with HIV-negative/unknown partners differ according to sex/sexual preference. The recent increase in SBR among heterosexual men with low viral load may be related to increasing awareness of the 'treatment-as-prevention' concept. The lack of association between SBR and viral load among MSM supports use of treatment-as-prevention as part of diversified prevention strategies.

International audience; The purpose of this study is to investigate the influence of torrefaction on wood grinding energy. Wood chips were torrefied at different temperatures and durations. The energy required to obtain fine powder was measured. Particle size analyses were carried out on each powder sample. It is showed that torrefaction decreases both grinding energy and particle size distribution. A criterion to compare grindability of natural and torrefied wood is proposed. It takes into account both grinding energy and particle size distribution. It accounts the energy required for grinding particles to sizes inferior to 200 μm, for given grinding conditions. Torrefaction is characterised by the anhydrous weight loss (AWL) of wood. For AWL inferior to around 8%, grinding energy decreases fast. Over 8%, grinding energy decreases at a slow rate. Particle size distribution decreases linearly as the AWL increases. Both for spruce and beech, the grinding criterion is decreased of 93% when the AWL is around 28%.

International audience; Beech and spruce chips were torrefied in a batch rotating pilot kiln. For each torrefaction the temperature curve of the moving chips bed was recorded. The anhydrous weight loss (AWL) of each torrefaction was measured. Effect of torrefaction temperature and duration on the AWL was studied. In order to optimise short time torrefaction, models that can estimate the AWL from the chips temperature curve are required. Three phenomenological models were successfully applied. They all gave good correlations between experimental and calculated AWL. These three models can be employed to optimise industrial torrefaction. However, the more complex they are, the more difficult it is to understand their physical meaning. It is thus preferable to use simple model for the industrial control of torrefaction.

Open Access Oral presentation OA06-06 LB. Evidence of vaccine-induced changes in breakthrough HIV-1 strains from the Step trial M Rolland1, S Tovanabutra2, PB Gilbert3, E Sanders-Buell2, L Heath1, AC deCamp3, CC Magaret3, M Bose2, A Bradfield2, A O'Sullivan2, J Crossler2, W Deng1, H Zhao1, K Wong1, DN Raugi1, J Hural3, S Dubey3, N Frahm3, NL Michael4, J Shiver5, L Corey3, F Li3, SG Self3, J Kim4, S Buchbinder6, DR Casimiro5, MN Robertson5, MJ McElrath3, FE McCutchan4 and JI Mullins*1

K-complexes (KCs) are thought to play a key role in sleep homeostasis and memory consolidation; however, their generation and propagation remain unclear. The commonly held view from scalp EEG findings is that KCs are primarily generated in medial frontal cortex and propagate parietally, whereas an electrocorticography (ECOG) study suggested dorsolateral prefrontal generators and an absence of KCs in many areas. In order to resolve these differing views, we used unambiguously focal bipolar depth electrode recordings in patients with intractable epilepsy to investigate spatiotemporal relationships of human KCs. KCs were marked manually on each channel, and local generation was confirmed with decreased gamma power. In most cases (76%), KCs occurred in a single location, and rarely (1%) in all locations. However, if automatically detected KC-like phenomena were included, only 15% occurred in a single location, and 27% occurred in all recorded locations. Locally generated KCs were found in all sampled areas, including cingulate, ventral temporal, and occipital cortices. Surprisingly, KCs were smallest and occurred least frequently in anterior prefrontal channels. When KCs occur on two channels, their peak order is consistent in only 13% of cases, usually from prefrontal to lateral temporal. Overall, the anterior–posterior separation of electrode pairs explained only 2% of the variance in their latencies. KCs in stages 2 and 3 had similar characteristics. These results open a novel view where KCs overall are universal cortical phenomena, but each KC may variably involve small or large cortical regions and spread in variable directions, allowing flexible and heterogeneous contributions to sleep homeostasis and memory consolidation.