Université de Versailles Saint-Quentin
Recent publications
Background Severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2)-induced acute respiratory distress syndrome (ARDS) causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS–CoV-2-induced ARDS. Methods This multicentre, double-blind, randomized, placebo-controlled trial (STROMA–CoV-2) recruited adults (≥ 18 years) with SARS–CoV-2-induced early (< 96 h) mild-to-severe ARDS in 10 French centres. Patients were randomly assigned to receive three intravenous infusions of 10 ⁶ UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen (PaO 2 /FiO 2 )-ratio change between baseline (day (D) 0) and D7. Results Among the 107 patients screened for eligibility from April 6, 2020, to October 29, 2020, 45 were enrolled, randomized and analyzed. PaO 2 /FiO 2 changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups (medians [IQR] 54.3 [− 15.5 to 93.3] vs 25.3 [− 33.3 to 104.6], respectively; ANCOVA estimated treatment effect 7.4, 95% CI − 44.7 to 59.7; P = 0.77). Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment. Conclusions D0-to-D7 PaO 2 /FiO 2 changes for intravenous UC-MSCs-versus placebo-treated adults with SARS–CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with any serious adverse events during treatment or thereafter (until D28). Larger trials enrolling patients earlier during the course of their ARDS are needed to further assess UC-MSCs efficacy in this context. Trial registration : NCT04333368. Registered 01 April 2020, https://clinicaltrials.gov/ct2/history/NCT04333368 .
Purpose Informal caregivers may be at high risk for psychotic experiences (PE) due to caregiving related stress, sleep issues, or other potential mechanisms, but this has not been previously investigated in the general adult population. Thus, we examined the association between caregiving and PE, and its mediators, in a large sample of adults from 48 low- and middle-income countries (LMICs). Methods Cross-sectional, community-based data from the World Health Organization (WHO) World Health Survey were analyzed. Informal caregivers referred to those who provided help to a relative or friend (adult or child) in the past year, because this person has a long-term physical or mental illness or disability, or is getting old and weak. PE were assessed using the WHO Composite International Diagnostic Interview psychosis screen. Multivariable logistic regression and mediation analyses were conducted. Results Data on 224,842 individuals were analyzed. The mean (SD) age was 38.3 (16.0) years (range 18–120 years) and 50.7% were females. After adjustment for age, sex, and country, in the overall sample, caregiving was associated with 1.67 (95%CI = 1.56–1.79) times higher odds for PE. Sleep/energy explained the largest proportion of the association between caregiving and PE (13.9%), followed by pain/discomfort (11.5%), perceived stress (7.6%), depression (6.2%), and cognition (3.5%). Conclusion Caregivers in LMICs are at higher risk of PE. Future studies are warranted to gain a further understanding of the underlying mechanisms, and to assess whether addressing the identified mediators can lead to lower risk for PE among caregivers.
A sensitive and rapid liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of tryptophan (Trp) and ten metabolites of kynurenine pathway, including kynurenine (Kyn), 3-hydroxy-kynurenine (3-HK), kynurenic acid (KA), xanthurenic acid (XA), 3-Hydroxy-anthranilic acid (3-HANA), quinolinic acid (QA), nicotinic acid mononucleotide (NaMN), picolinic acid (Pic), nicotinamide (NAM) and nicotinic acid (NA) in both plasma and urine. This LC-MS/MS method was used to predict the occurrence of acute kidney injury (AKI) in a cohort of patients with cardiac surgery under cardiopulmonary bypass (CPB). Urinary concentrations of Pic, as well as Pic to Trp and Pic to 3-HANA ratios were highly predictive of an AKI episode the week after CPB, indicating that Pic could be a predictive biomarker of AKI. Thus, monitoring the kynurenine pathway activity with this LC–MS/MS method is a clinically relevant tool to identify new biomarkers of kidney injury.
Vehicular Visible Light Communication (VLC) has recently attracted much interest from researchers and scientists. This technology enables the connectivity between the vehicles and the infrastructures along the road utilizing the Lighting-Emitting-Diodes based vehicle HeadLights (HLs) and TailLights (TLs) as wireless transmitters. This paper investigates the performance of a Vehicle-to-Vehicle VLC system using a Multiple-Input Multiple-Output (MIMO) scheme. Specifically, we establish the MIMO transmission system by using the two HLs of the source vehicle as wireless transmitters and multiple receivers (RXs) installed at the rear of the destination vehicle as wireless receivers. We consider different numbers of RXs, which result in various MIMO configurations, i.e., 2×2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2\times 2$$\end{document}, 2×3\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2\times 3$$\end{document}, and 2×4\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2\times 4$$\end{document}. We conduct a channel modeling study based on the non-sequential ray-tracing capabilities of the OpticStudio software to obtain the optical channel gain, considering the possibility of both horizontal and vertical displacement between vehicles. We then explore the contribution of each RX in the total received power. In addition, we investigate the effect of weather conditions, modulation orders, and artificial light sources on the bit error rate (BER) performance of the considered MIMO configurations. The obtained results demonstrate that deploying the MIMO with higher orders can significantly enhance the system performance, particularly when there is a lateral shift between the two cars. It has been drawn from our results that the required SNR to achieve a BER of 10-4\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{-4}$$\end{document} reduces by 6 dB when 2×4\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2\times 4$$\end{document} MIMO configuration is deployed compared to the 2×2\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$2\times 2$$\end{document} MIMO configuration.
Background Muscle-invasive bladder cancer (MIBC) and upper urinary tract urothelial carcinoma (UTUC) are molecularly heterogeneous. Despite chemotherapies, immunotherapies, or anti-fibroblast growth factor receptor (FGFR) treatments, these tumors are still of a poor outcome. Our objective was to develop a bank of patient-derived xenografts (PDXs) recapitulating the molecular heterogeneity of MIBC and UTUC, to facilitate the preclinical identification of therapies. Methods Fresh tumors were obtained from patients and subcutaneously engrafted into immune-compromised mice. Patient tumors and matched PDXs were compared regarding histopathology, transcriptomic (microarrays), and genomic profiles [targeted Next-Generation Sequencing (NGS)]. Several PDXs were treated with chemotherapy (cisplatin/gemcitabine) or targeted therapies [FGFR and epidermal growth factor (EGFR) inhibitors]. Results A total of 31 PDXs were established from 1 non-MIBC, 25 MIBC, and 5 upper urinary tract tumors, including 28 urothelial (UC) and 3 squamous cell carcinomas (SCCs). Integrated genomic and transcriptomic profiling identified the PDXs of three different consensus molecular subtypes [basal/squamous (Ba/Sq), luminal papillary, and luminal unstable] and included FGFR3 -mutated PDXs. High histological and genomic concordance was found between matched patient tumor/PDX. Discordance in molecular subtypes, such as a Ba/Sq patient tumor giving rise to a luminal papillary PDX, was observed (n=5) at molecular and histological levels. Ten models were treated with cisplatin-based chemotherapy, and we did not observe any association between subtypes and the response. Of the three Ba/Sq models treated with anti-EGFR therapy, two models were sensitive, and one model, of the sarcomatoid variant, was resistant. The treatment of three FGFR3-mutant PDXs with combined FGFR/EGFR inhibitors was more efficient than anti-FGFR3 treatment alone. Conclusions We developed preclinical PDX models that recapitulate the molecular heterogeneity of MIBCs and UTUC, including actionable mutations, which will represent an essential tool in therapy development. The pharmacological characterization of the PDXs suggested that the upper urinary tract and MIBCs, not only UC but also SCC, with similar molecular characteristics could benefit from the same treatments including anti-FGFR for FGFR3-mutated tumors and anti-EGFR for basal ones and showed a benefit for combined FGFR/EGFR inhibition in FGFR3-mutant PDXs, compared to FGFR inhibition alone.
Transcranial direct current stimulation (tDCS) is growingly applied to the cerebellum to modulate the activity of cerebellar circuitry, affecting both motor and cognitive performances in a polarity-specific manner. The remote effects of tDCS are mediated in particular via the dentato-thalamo-cortical pathway. We showed recently that tDCS of the cerebellum exerts dynamic effects on resting state networks. We tested the neural hypothesis that tDCS reconfigurates brain networks involved in motor execution (ME) and motor mental imagery (MMI). We combined tDCS applied over the right cerebellum and fMRI to investigate tDCS-induced reconfiguration of ME- and MMI-related networks using a randomized, sham-controlled design in 21 right-handed healthy volunteers. Subjects were instructed to draw circles at comfortable speed and to imagine drawing circles with their right hand. fMRI data were recorded after real anodal stimulation (1.5 mA, 20 min) or sham tDCS. Real tDCS compared with SHAM specifically reconfigurated the functional links between the main intrinsic connected networks, especially the central executive network, in relation with lobule VII, and the salience network. The right cerebellum mainly influenced prefrontal and anterior cingulate areas in both tasks, and improved the overt motor performance. During MMI, the cerebellum also modulated the default-mode network and associative visual areas. These results demonstrate that tDCS of the cerebellum represents a novel tool to modulate cognitive brain networks controlling motor execution and mental imagery, tuning the activity of remote cortical regions. This approach opens novel doors for the non-invasive neuromodulation of disorders involving cerebello-thalamo-cortical paths.
Objective: To compare different antibiotic prophylaxis administered after preterm premature rupture of membranes to determine if any were associated with differences in obstetric and/or neonatal outcomes and/or neurodevelopmental outcomes at two years of corrected age. Design: Prospective, nationwide, population-based EPIPAGE-2 cohort study of preterm infants. Setting: France, 2011 SAMPLE: We included 492 women with a singleton pregnancy and a diagnosis of preterm premature rupture of membranes at 24-31 weeks. Exclusion criteria were contraindication to expectant management or indication for antibiotic therapy other than preterm premature rupture of membranes. Antibiotic prophylaxis was categorized as amoxicillin (n=345), macrolide (n=30), third-generation cephalosporin (n=45) or any combinations covering Streptococcus agalactiae and >90% of Escherichia coli (n=72), initiated within 24 hours after preterm premature rupture of membranes. Methods: Population-averaged robust Poisson models. Main outcome measures: Survival at discharge without severe neonatal morbidity, 2-year neurodevelopment. Results: With amoxicillin, macrolide, third-generation cephalosporin and combinations, 78.5%, 83.9%, 93.6% and 86.0% of neonates were discharged alive without severe morbidity. The administration of third-generation cephalosporin or any E. coli-targeting combinations was associated with improved survival without severe morbidity (adjusted Risk Ratio 1.25 [95% confidence interval 1.08-1.45]; and 1.10 [1.01-1.20], respectively) compared with amoxicillin. We evidenced no increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen. Conclusion: In preterm premature rupture of membranes at 24-31 weeks, antibiotic prophylaxis based on third-generation cephalosporin may be associated with improved survival without severe neonatal morbidity when compared with amoxicillin, with no evidence of increase in neonatal sepsis related to third-generation cephalosporin-resistant pathogen.
Purpose This study aimed to determine the long-term effectiveness of augmentation ileocystoplasty (AI) associated with supra-trigonal cystectomy on clinical and urodynamic variables, and the safety of the intervention in individuals with spinal cord injury (SCI). Materials and methods Single-center, retrospective study of all patients with SCI who underwent AI with supra-trigonal cystectomy from January 1994, with a follow-up of more than 8 years. The primary outcome was the sustained long-term effectiveness of AI with supra-trigonal cystectomy on clinical and urodynamic variables. The secondary outcome was the long-term safety of this procedure. Results We included 77 patients: 57% were female, mean (SD) age was 52.0 (13.0) years, 77% had paraplegia, and median time since onset was 25.0 [19; 30] years. Long-term success rate (evaluated 13 [10; 15] years post AI) was 93.5% for urodynamic parameters and 76.6% for urinary incontinence. Results of the short- and long-term post-AI assessments did not differ for any urodynamic or clinical variables. Bladder lithiasis occurred in 20.5% of cases and ≥ 1 febrile urinary tract infection occurred in 55.8%, mostly within the first 2 years of follow-up. No cases of bladder cancer were diagnosed. Conclusion AI associated with supra-trigonal cystectomy in patients with SCI is safe and effective in both the short term and long term. Regular urodynamic assessment is not necessary in clinically stable patients with low bladder risk; however, close monitoring is important because of the risk of urological complications.
This review summarizes our current understanding of the outer heliosphere and local interstellar medium (LISM) inferred from observations and modeling of interplanetary Lyman-α\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\alpha $\end{document} emission. The emission is produced by solar Lyman-α\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\alpha $\end{document} photons (121.567 nm) backscattered by interstellar H atoms inflowing to the heliosphere from the LISM. Studies of Lyman-α\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\alpha $\end{document} radiation determined the parameters of interstellar hydrogen within a few astronomical units from the Sun. The interstellar hydrogen atoms appeared to be decelerated, heated, and shifted compared to the helium atoms. The detected deceleration and heating proved the existence of secondary hydrogen atoms created near the heliopause. This finding supports the discovery of a Hydrogen Wall beyond the heliosphere consisting of heated hydrogen observed in HST/GHRS Lyman-α\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\alpha $\end{document} absorption spectra toward nearby stars. The shift of the interstellar hydrogen bulk velocity was the first observational evidence of the global heliosphere asymmetry confirmed later by Voyager in situ measurements. SOHO/SWAN all-sky maps of the backscattered Lyman-α\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\alpha $\end{document} intensity identified variations of the solar wind mass flux with heliolatitude and time. In particular, two maxima at mid-latitudes were discovered during solar activity maximum, which Ulysses missed due to its specific trajectory. Finally, Voyager/UVS and New Horizons/Alice UV spectrographs discovered extraheliospheric Lyman-α\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\alpha $\end{document} emission. We review these scientific breakthroughs, outline open science questions, and discuss potential future heliospheric Lyman-α\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$\alpha $\end{document} experiments.
Background Riociguat and balloon pulmonary angioplasty (BPA) are treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, randomised controlled trials comparing these treatments are lacking. We aimed to evaluate the efficacy and safety of BPA versus riociguat in patients with inoperable CTEPH. Methods In this phase 3, multicentre, open-label, parallel-group, randomised controlled trial done in 23 French centres of expertise for pulmonary hypertension, we enrolled treatment-naive patients aged 18–80 years with newly diagnosed, inoperable CTEPH and pulmonary vascular resistance of more than 320 dyn·s/cm⁵. Patients were randomly assigned (1:1) to BPA or riociguat via a web-based randomisation system, with block randomisation (block sizes of two or four patients) without stratification. The primary endpoint was change in pulmonary vascular resistance at week 26, expressed as percentage of baseline pulmonary vascular resistance in the intention-to-treat population. Safety analyses were done in all patients who received at least one dose of riociguat or had at least one BPA session. Patients who completed the RACE trial continued into an ancillary 26-week follow-up during which symptomatic patients with pulmonary vascular resistance of more than 320 dyn·s/cm⁵ benefited from add-on riociguat after BPA or add-on BPA after riociguat. This trial is registered at ClinicalTrials.gov, NCT02634203, and is completed. Findings Between Jan 19, 2016, and Jan 18, 2019, 105 patients were randomly assigned to riociguat (n=53) or BPA (n=52). At week 26, the geometric mean pulmonary vascular resistance decreased to 39·9% (95% CI 36·2–44·0) of baseline pulmonary vascular resistance in the BPA group and 66·7% (60·5–73·5) of baseline pulmonary vascular resistance in the riociguat group (ratio of geometric means 0·60, 95% CI 0·52–0·69; p<0·0001). Treatment-related serious adverse events occurred in 22 (42%) of 52 patients in the BPA group and five (9%) of 53 patients in the riociguat group. The most frequent treatment-related serious adverse events were lung injury (18 [35%] of 52 patients) in the BPA group and severe hypotension with syncope (two [4%] of 53 patients) in the riociguat group. There were no treatment-related deaths. At week 52, a similar reduction in pulmonary vascular resistance was observed in patients treated with first-line riociguat or first-line BPA (ratio of geometric means 0·91, 95% CI 0·79–1·04). The incidence of BPA-related serious adverse events was lower in patients who were pretreated with riociguat (five [14%] of 36 patients vs 22 [42%] of 52 patients). Interpretation At week 26, pulmonary vascular resistance reduction was more pronounced with BPA than with riociguat, but treatment-related serious adverse events were more common with BPA. The finding of fewer BPA-related serious adverse events among patients who were pretreated with riociguat in the follow-up study compared with those who received BPA as first-line treatment points to the potential benefits of a multimodality approach to treatment in patients with inoperable CTEPH. Further studies are needed to explore the effects of sequential treatment combining one or two medications and BPA in patients with inoperable CTEPH. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health and Bayer HealthCare. Translation For the French translation of the abstract see Supplementary Materials section.
Trifluorometylselenolation via C‐H activation is barely described in literature. In particular, no such vinylic functionalization has been yet described. Herein, a palladium‐catalyzed trifluoromethylselenolation of vinylic C‐H bonds is described. The 5‐methoxy‐8‐aminoquinoline has been used as auxiliary directing group to perform this reaction. The reaction gives excellent yields with α‐substituted compounds whatever the substituents and a micro wave activation can be used to accelerate the reaction. With β‐substituted substrates lower yields, but still satisfactory, are obtained. This methodology was also successfully extended to other fluoroalkylselenyl groups.
The implementation of high-throughput diagnostic sequencing has led to the generation of large amounts of mutational data, making their interpretation more complex and responsible for long delays. It has been important to prioritize certain analyses, particularly those of “actionable” genes in diagnostic situations, involving specific treatment and/or management. In our project, we carried out an objective assessment of the clinical actionability of genes involved in myopathies, for which only few data obtained methodologically exist to date. Using the ClinGen Actionability criteria, we scored the clinical actionability of all 199 genes implicated in myopathies published by FILNEMUS for the “National French consensus on gene Lists for the diagnosis of myopathies using next generation sequencing”. We objectified that 63 myopathy genes were actionable with the currently available data. Among the 36 myopathy genes with the highest actionability scores, only 8 had been scored to date by ClinGen. The data obtained through these methodological tools are an important resource for strategic choices in diagnostic approaches and the management of genetic myopathies. The clinical actionability of genes has to be considered as an evolving concept, in relation to progresses in disease knowledge and therapeutic approaches.
Background: Neurogenic detrusor overactivity (NDO) is a severe pathological condition characterized by involuntary detrusor contractions leading to urine leakage. This condition is frequent after spinal cord injury (SCI). Gene therapy for NDO requires the development of vectors that express therapeutic transgenes driven by sensory neuron-specific promoters. The aim of this study was to develop and assess tools for the characterization of sensory neuron-specific promoters in dorsal root ganglia (DRG) neurons after transduction with herpes simplex virus type 1 (HSV-1)-based amplicon defective vectors. Methods: The HSV-1 vector genome encoded two independent transcription cassettes: one expressed firefly luciferase (FLuc) driven by different promoters' candidates (rTRPV1, rASIC3, rCGRP, or hCGRP), and the other expressed a reporter gene driven by an invariable promoter. The strength and selectivity of promoters was assessed in organotypic cultures of explanted adult DRG, or sympathetic and parasympathetic ganglia from control and SCI rats. Results: The rCGRP promoter induced selective expression in the DRG of normal rats. The rTRPV-1 promoter, which did not display selective activity in control rats, induced selective expression in DRG explanted from SCI rats. Conclusions: This study provides a methodology to assess sensory neuron-specific promoters, opening new perspectives for future gene therapy for NDO.
Energy systems are often socio-technical complex systems that are facing new challenges regarding technological and environmental changes. Because of their complex nature, they cannot be approached solely through analytical modeling, hence the inefficiency of most classical modeling approaches. In this article, a Hybrid Approach based on both systemic and analytical modeling is presented and applied to a case study. From this novel approach, a model—the Multi-Institution Building Energy System—is presented. It allowed us to highlight and detail the need for greater governance of energy systems. The socio-technical solutions identified to answer the issues of governance (Accuracy, Reliability and Fairness) were DevOps methodology and the use of Distributed Microservices Architecture. Based on this framework, the design of a Decision Support System assuring and exploiting state-of-the-art scalable tools for data management and machine learning factories is described in this article. Moreover, we wish to set up the conceptual basis necessary for the design of a generic theoretical framework of optimization applicable to complex socio-technical systems in the context of the management of a shared resource.
Background Early-onset neonatal sepsis (EOS) is a rare condition but an important cause of severe morbidity and mortality in neonates. Methods This is a prospective observational study in neonates born at ≥34 weeks of gestation (WG). The primary endpoint was EOS, defined by isolation of pathogenic species from blood culture and/or cerebrospinal fluid culture within 72 hours after birth. Data on EOS were collected exhaustively from all maternity wards in Paris area (April 2019–March 2021). Results 108 EOS were recorded (annual incidence, 0.32 per 1000 live births; 95% CI 0.26 to 0.38). In term infants, the most frequent pathogens were group B Streptococcus (GBS) (n=47) and Escherichia coli (n=20); in late preterm infants, the most frequent pathogens were E. coli (n=15) and GBS (n=7). Fifteen meningitis cases were diagnosed. Five E. coli strains (14%) were resistant to both amoxicillin and gentamicin, which is an empiric treatment for EOS. Of the 54 infants with GBS infections, 35 were born from mothers with negative GBS prepartum screening test and 8 from mothers with no screening. Two deaths were reported, both in term infants ( Proteus mirabilis and E. coli ). Conclusion In neonates ≥34 WG born in the Paris area, GBS was twice as frequent as E. coli in term infants. EOS was six times more frequent in late preterm than in term infants and was due to E. coli in 60% of cases. Prevention of GBS EOS and empiric antibiotic treatment of EOS could be improved.
The clamping mechanism plays an important role in obtaining high-quality products of the injection molding process. The clamping mechanism of the five-point double-toggle has been widely used for the high-speed plastics injection molding machine. The purpose of this paper is to optimize the five-point double-toggle clamping mechanism through multi-body dynamics analysis. This work also provides guidelines and a clear understanding for designing the clamping system in an injection molding machine with various clamping forces. The theoretical calculation has been handled first and then the computational model has been verified in this study. In addition, the effects of clamping forces on the main dimensions, including movable-fixed plate thickness, tie-bar diameter, and average link cross-section have been investigated theoretically and numerically. The results show that the optimal design allows reaching a high force amplified ratio and that the obtained mechanism has good kinematic performance and works steadily with lower energy consumption and lower cost than the preliminary design. Moreover, the relationships between the parameters such as the critical angles of the double-toggle clamping mechanism, the ratio of force amplification, and the stroke of movable mold have been found in this work. The optimized parameters will yield useful knowledge to design and manufacture the clamping mechanism of the microinjection molding machine in practice.
Construction is one of the sectors most at risk in terms of health and safety. The social security system attributes more than 14\% of the accidents recorded in 2018 to the construction sector. In addition to safety risks, construction workers are exposed to occupational diseases. Musculoskeletal disorders (MSD) are at the top list of the most frequent occupational diseases. In order to address these issues, construction companies have implemented health and safety policy to protect their employees. This policy provides, among other things, for an improvement in the organizational aspect of work, the adaptation of work to people and training. Training is carried out according to a classic methodology: theoretical and practical training. The training represents constraints of cost, duration and organization. The content must be adapted to specific profiles, be repeatable and allow the trainers to assess the level of the trainees. For training on the right gestures and posture to avoid the risk of MSDs, the impact of virtual reality (VR) training is less relevant due to the lack of haptic feedback. In this article, we propose to evaluate with the construction workers a new training methodology based on visual immersion and a robotic platform for haptic interaction with motion tracking. This methodology is evaluated for a particular task: the formwork panel adjustment, a highly risky operation on a highly sensitive tool.We believe that this approach would allow to better engage the construction workers during training on the formwork, to ensure their safety and awareness of MSD risks. The objective through this method is to enable the construction workers to understand the risks linked to their job, to train them to avoid risks, and to enable the trainer to benefit from a tool for monitoring and supporting the construction workers. In order to validate the methodology, experiments were conducted and questionnaires were submitted to two profiles of people: novices and professionals. This experimentation shows an acceptance of the solution by the construction workers.
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1,818 members
Lauric Henneton
  • Département des Etudes Anglophones
Valérie Daux
  • Laboratoire des Sciences du Climat et de l'Environnement (LSCE)
Mateo Cordier
  • Observatoire des Sciences de l'Univers de l´UVSQ (OVSQ)
Vincent Le Moigne
  • UFR des Sciences de la Santé Simone Veil
Gérard Férey
  • UFR des Sciences
Versailles, France