A Politico-Communal Reading of the Rose

Lettura del Fiore in rapporto alle fonti retoriche e politiche di ambiente comunal

Direct numerical simulation of turbulent premixed flames using intrinsic low-dimensional manifolds

International audienceIn order to carry out numerical simulations taking into account detailed chemistry effects with a realistic computing cost, we describe in this work a new method to generate intrinsic low-dimensional manifold (ILDM) databases. This method is based on a continuation procedure to determine the manifold. We use in practice manifolds with two chemical dimensions in this work. Validations are performed for a homogeneous reaction system and one-dimensional laminar premixed CO/H2 /air flames. Computing times are reduced by a factor of 20 compared to the detailed chemistry case. We also check two different projection methods used to project the diffusion term on the manifold. We observe that a simple perpendicular projection is appropriate for our configuration. The final part of this paper describes the implementation of the ILDM method in the direct numerical simulation code parcomb. A comparison with corresponding detailed chemistry results is shown, proving that this reduction technique is appropriate for the investigation of turbulent combustion problems. The CPU time is reduced by a factor of 2.6 when using the ILDM method

Microservices-Based Architecture to Support the Adaptive RECORDS-Trial

Information systems used by platform trials should handle changes that are not predefined. Unfortunately, the technical architecture of most existing clinical data management systems (CDMS) do not support changes to be incorporated into an ongoing trial. Adaptive clinical trials need advanced architectural solutions setup to enable biomarker stratification and enrichment strategy necessary for the adaptive clinical trial operation. This short paper presents the microservices-based architecture solution that is used to run and support the adaptive RECORDS-Trial

Numerical and experimental study of NO emission in laminar partially premixed flames

International audienceA partially premixed methane/air flame in a two-dimensional configuration was studied in this work. The configuration was close to those used in real domestic boilers. The flame structure and flow pattern were calculated by implementing a complex chemistry and detailed transport formulation in an industrial computational fluid dynamics code (ESTET). A postprocessing method was used to predict NO emission. Computations were performed for two configurations. The two cases had the same primary and secondary mass flow rates and equivalence ratios. The only difference between them was the introduction of an insert inside the primary injector. Both results were compared with measurements. In both cases, calculations were in good agreement with the flame shapes observed experimentally. The classical burner showed a Bunsen-type flame, while the one with an insert had a totally different shape (butterfly-type flame). NO emission levels were also well predicted in both configurations. The butterfly flame induced a reduction in NO emission. The reduction seemed to be due to the increased mixing between the burned gases and the secondary air jet, which homogenized the temperature distribution and reduced the maximum temperature. These calculations combined with the postprocessing technique for NO prediction needed only few hours of CPU time on a classical workstation. This demonstrates the possibility for burner and boiler manufacturers to use numerical simulations to predict relatively complex configurations in terms of flame structure and pollutant emissions

Using numerical simulations to predict partially-premixed laminar flames in a domestic burner

International audienceNew numerical tools have been developed these last years in order to achieve a better understanding of the mechanisms acting in pollutant formation in complex combustion devices. Among these, the Flame Prolongation of ILDM (FPI) method seems to be of great interest for the simulation of the turbulent flame computations, in particular those using PDF models. Before performing computations in PDF codes using FPI, we have checked in the present work the method in a very stiff case, partially-premixed laminar combustion. At the same time, we have also performed numerical simulations using detailed chemistry and Fourier Transform InfraRed (FTIR) measurements on an idealized 2D boiler. The results show a good agreement for the temperature and H2O concentration profiles using these three different techniques. The results suggest that using the FPI method in PDF codes could considerably improve the accuracy of the existing results

The NEDD8-activating enzyme inhibitor MLN4924 sensitizes a TNFR1+ subgroup of multiple myeloma cells for TNF-induced cell death

The NEDD8-activating enzyme (NAE) inhibitor MLN4924 inhibits cullin-RING ubiquitin ligase complexes including the SKP1-cullin-F-box E3 ligase beta TrCP. MLN4924 therefore inhibits also the beta TrCP-dependent activation of the classical and the alternative NF kappa B pathway. In this work, we found that a subgroup of multiple myeloma cell lines (e.g., RPMI-8226, MM.1S, KMS-12BM) and about half of the primary myeloma samples tested are sensitized to TNF-induced cell death by MLN4924. This correlated with MLN4924-mediated inhibition of TNF-induced activation of the classical NF kappa B pathway and reduced the efficacy of TNF-induced TNFR1 signaling complex formation. Interestingly, binding studies revealed a straightforward correlation between cell surface TNFR1 expression in multiple myeloma cell lines and their sensitivity for MLN4924/TNF-induced cell death. The cell surface expression levels of TNFR1 in the investigated MM cell lines largely correlated with TNFR1 mRNA expression. This suggests that the variable levels of cell surface expression of TNFR1 in myeloma cell lines are decisive for TNF/MLN4924 sensitivity. Indeed, introduction of TNFR1 into TNFR1-negative TNF/MLN4924-resistant KMS-11BM cells, was sufficient to sensitize this cell line for TNF/MLN4924-induced cell death. Thus, MLN4924 might be especially effective in myeloma patients with TNFR1(+) myeloma cells and a TNFhigh tumor microenvironment

How to Improve Cancer Patients ENrollment in Clinical Trials From rEal-Life Databases Using the Observational Medical Outcomes Partnership Oncology Extension: Results of the PENELOPE Initiative in Urologic Cancers

International audiencePURPOSE To compare the computability of Observational Medical Outcomes Partnership (OMOP)–based queries related to prescreening of patients using two versions of the OMOP common data model (CDM; v5.3 and v5.4) and to assess the performance of the Greater Paris University Hospital (APHP) prescreening tool.MATERIALS AND METHODS We identified the prescreening information items being relevant for prescreening of patients with cancer. We randomly selected 15 academic and industry-sponsored urology phase I-IV clinical trials (CTs) launched at APHP between 2016 and 2021. The computability of the related prescreening criteria (PC) was defined by their translation rate in OMOP-compliant queries and by their execution rate on the APHP clinical data warehouse (CDW) containing data of 205,977 patients with cancer. The overall performance of the prescreening tool was assessed by the rate of true- and false-positive cases of three randomly selected CTs.RESULTS We defined a list of 15 minimal information items being relevant for patients' prescreening. We identified 83 PC of the 534 eligibility criteria from the 15 CTs. We translated 33 and 62 PC in queries on the basis of OMOP CDM v5.3 and v5.4, respectively (translation rates of 40% and 75%, respectively). Of the 33 PC translated in the v5.3 of the OMOP CDM, 19 could be executed on the APHP CDW (execution rate of 58%). Of 83 PC, the computability rate on the APHP CDW reached 23%. On the basis of three CTs, we identified 17, 32, and 63 patients as being potentially eligible for inclusion in those CTs, resulting in positive predictive values of 53%, 41%, and 21%, respectively. CONCLUSION We showed that PC could be formalized according to the OMOP CDM and that the oncology extension increased their translation rate through better representation of cancer natural history

AP-HP Health Data Space (AHDS) to the Test of the Covid-19 Pandemic

Sharing observational and interventional health data within a common data space enables university hospitals to leverage such data for biomedical discovery and moving towards a learning health system. Objective: To describe the AP-HP Health Data Space (AHDS) and the IT services supporting piloting, research, innovation and patient care. Methods: Built on three pillars – governance and ethics, technology and valorization – the AHDS and its major component, the Clinical Data Warehouse (CDW) have been developed since 2015. Results: The AP-HP CDW has been made available at scale to AP-HP both healthcare professionals and public or private partners in January 2017. Supported by an institutional secured and high-performance cloud and an ecosystem of tools, mostly open source, the AHDS integrates a large amount of massive healthcare data collected during care and research activities. As of December 2021, the AHDS operates the electronic data capture for almost +840 clinical trials sponsored by AP-HP, the CDW is enabling the processing of health data from more than 11 million patients and generated +200 secondary data marts from IRB authorized research projects. During the Covid-19 pandemic, AHDS has had to evolve quickly to support administrative professionals and caregivers heavily involved in the reorganization of both patient care and biomedical research. Conclusion: The AP-HP Data Space is a key facilitator for data-driven evidence generation and making the health system more efficient and personalized