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« J’aime le quartier mais on veut s’en sortir tu vois ». Dynamiques d’appropriation et vécu quotidien de la stigmatisation dans un quartier dit prioritaire
No full textInternational audienceThe issue of so-called priority districts crystallizes a certain number of dominant discourses and representations that tend to establish them as a "societal problem". The result is a process of disqualification and stigmatization of the inhabitants of these areas. Based on ethnographic and film work, the aim of this article is to show that this process of stigmatization is not without implications for the way these spaces are experienced and appropriated. It highlights various dynamics of appropriation and relationships to space, and adds complexity to the analysis of the process of stigmatization to which the inhabitants of these urban spaces are subjected.La question des quartiers dits prioritaires cristallise un certain nombre de discours et de représentations dominantes qui tend à les instituer comme « problème de société » (Borrell, 2017, p. 8). Il se met ainsi en place un processus de disqualification et de stigmatisation des habitant·es de ces espaces. En s’appuyant sur un travail ethnographique et filmique, l’enjeu de cet article est de montrer que ce processus de stigmatisation n’est pas sans implications sur la manière de vivre ces espaces et de se les approprier. Ce sont alors diverses dynamiques d’appropriation et de rapports à l’espace qui sont mises en lumière et qui permettent de complexifier l’analyse du processus de stigmatisation dont font l’objet les habitant·es de ces espaces urbains
Safety and efficacy of combined treatment with tumor-infiltrating lymphocytes and oncolytic adenovirus TILT-123 in metastatic melanoma
No full textInternational audienceTumor-infiltrating lymphocytes (TILs) are effective in the treatment of metastatic melanoma (MM), but toxicity limits its application. TILT-123 (igrelimogene litadenorepvec) is an oncolytic adenovirus producing interleukin-2 (IL-2) and tumor necrosis factor (TNF) upon replication. In this phase 1 trial, 17 patients with metastatic checkpoint inhibitor-resistant melanoma are treated with TILT-123 and TILs without preconditioning chemotherapy or postconditioning IL-2. The treatment is safe and feasible. According to computed tomography (CT), the objective response rate is 11.7% (2/17) and disease control is observed in 35% (6/17), including a partial response lasting >8 months and a durable complete response in a mucosal melanoma patient. According to positron emission tomography (PET), disease control is observed in 7/15 (47%) with minor or partial responses in 4/15 (27%). In the initial TILT-123 monotherapy phase of the trial, disease control is observed in 6/17 (35%) and 10/16 (63%) in CT and PET, respectively. The study demonstrates good tolerability and preliminary efficacy
Key Concepts in Clinical Epidemiology: FAIRification of Biomedical Research Data
No full textInternational audienceThe FAIR guiding principles promote Findability, Accessibility, Interoperability, and Reuse of data to enhance data management and stewardship. In biomedicine, particular ethical, legal, and technical barriers complicate research data sharing. To help researchers overcome these challenges, we propose a framework of FAIRification from three dimensions - scientific, technical, and legal/ethical. We advocate for prospective FAIRification of study data, starting with a strong emphasis on planning for data-sharing from the beginning. Reflective questions throughout the process guide researchers to reflect on their situation. Researchers should assess resources and feasibility, secure technical and legal support, consider stakeholder needs, and devise an appropriate data sharing process. Given the sensitivity of biomedical data, confidentiality and security require careful attention. The data sharing strategy should be finalised before the study starts, and documented in relevant study materials. Technical preparation for data sharing follows planning. Data should be well-documented with a data dictionary and metadata to facilitate reuse, and provided in an accessible format. The data can be hosted on a repository to promote sharing and reuse. While a secure repository provides the technical foundation for data protection, effective administration is required to enforce data use agreements and licensing. We also discuss the importance of subsequent management upon data upload. Continued support for researchers and data maintenance are essential for effective reuse. Examples and resources to facilitate FAIRification are included to help researchers navigate challenges and ensure biomedical data is FAIR and reusable
Disulfiram-loaded electrospun fibers with antimicrobial and antitumoral properties for glioblastoma treatment
No full textInternational audienceGlioblastoma (GB) is a malignant brain tumor with low survival rates and a high recurrence ratio due to limited therapeutic arsenal. The repurposed drug disulfiram (DSF), approved for alcoholism treatment, shows promising anticancer and antimicrobial activity, but its poor biopharmaceutical profile hinders its clinical use. This work aimed to develop DSF-loaded silk fibroin (SF) electrospun fibers for controlled release in the postsurgical resection cavity. Incorporating hydroxypropyl-β-cyclodextrin (HPβCD), which formed inclusion complexes with DSF, enhanced drug release rate and antimicrobial activity (>3 logCFUs reduction) against Staphylococcus aureus and Pseudomonas aeruginosa. Addition of CuCl 2 enabled in situ formation of Cu(DDC) 2 complexes, further boosting antimicrobial and in vitro antitumoral effects of the nanofibers (≤ 500 nm) while maintaining adequate mechanical properties. Selective toxicity of DSF and DSF-loaded fibers against glioblastoma cells, while sparing against astrocytes, highlights the potential of the nanofibers for targeted brain cancer therapy. Increased potency of DSF at low concentrations when combined with SF fibers, HPβCD and copper was remarkable. Thus, DSF delivery and bioavailability can be significantly optimized through electrospun nanofibers, which may also allow for more precise dosing. Combination with radiotherapy was also explored to assess the translational potential of DSF as part of a combination therapy regimen for glioblastoma. In vivo studies in a rat model simulating GB surgery confirmed the safety of selected formulations in healthy brain tissue. However, findings suggest that DSFloaded fibers alone may be insufficient for complete tumor eradication, indicating the need for combination with existing therapies to target residual tumor cells effectively
Stigmatization in patients with pigmentation disorders: the ISPOT study
No full textInternational audienceThe ISPOT study, conducted across 48,000 participants in 34 countries, assesses stigmatization in pigmentation disorders using the PUSH-D questionnaire. Findings reveal high stigmatization levels, particularly for vitiligo and melasma, with greater impact among younger individuals and those with fair skin
Qu’est-ce qu’un cancérigène ?Des îlots de connaissances scientifiques dans de profonds océans de controverses :Cas des pesticides inhibiteurs de la succinate déshydrogénase (SDHI)
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Response to comment on “Do we need flexible machine-learning algorithms to assess the effect of long-term exposure to fine particulate matter on mortality?”
No full textIntegrating and Analysing Occupational Health Data Using a Multi-Ontology Approach
No full textInternational audienceA variety of occupational data are collected by health organisations to investigate workplace exposures encountered by workers in their occupational activities and the potential health effects that may arise. These datasets have diverse characteristics and are not inherently designed to interoperate. However, they contain complementary information, which, when analysed collectively, can provide a broader perspective on high-risk occupational scenarios and inform targeted prevention strategies. The objective of this study is to develop a methodology to integrate and analyse heterogeneous French data. For this, ten French occupational databases, provided by six French institutes were used. An Ontology-Based Data Integration approach was employed, involving the mapping of data sources to a domain-specific ontology, namely the Adapted Occupational Exposure Ontology. Four additional ontologies were utilised: the Occupational Exposure Thesaurus, which categorises occupational exposures and hazards; the International Classification of Diseases, which classifies health disorders and diseases; the French Nomenclature of Activities, which identifies activity sectors in France; and the Professions and Socio-professional Categories, which defines occupational classifications. Data integration is primarily achieved through the concept of the “occupational group”, defined as a group of individuals sharing the same sex, occupation, and activity sector. Two case studies derived from the integrated dataset are presented: (1) a quantitative analysis identifying occupational groups at highest risk and most affected by diseases; and (2) a qualitative analysis evaluating the consistency of exposure and disease-related information. The construction sector was selected for these case studies due to its significance in occupational health research and the availability of substantial, relevant data. This methodological approach structures all the data and enables various analysis methods to be designed and implemented, making it possible to envisage targeted responses to current and emerging occupational health problems using specialised tools and queries
Impact of early versus conventional kidney replacement therapy initiation in tumor lysis syndrome: a target trial emulation
No full textInternational audienceBackground In the context of tumor lysis syndrome (TLS), the optimal timing and criteria for initiating kidney replacement therapy (KRT) remain unclear. This study aims to assess the effect of initiating KRT at various phosphatemia thresholds on Major Adverse Kidney Events at day 30 (MAKE30).Methods and results We retrospectively emulated a pragmatic clinical trial comparing the effect of KRT initiation at various phosphatemia thresholds versus a conventional approach during TLS on MAKE30. All consecutive patients admitted to the ICU at Saint-Louis University hospital in Paris and Angers University hospital between January 2007 and June 2020, presenting with laboratory TLS were included. The design criteria of a clinical trial were mimicked by using the cloning, censoring and weighting method. The primary outcome was the MAKE30 composite outcome, considering only KRT requirement between day 7 and day 30 for the dialysis criteria. We evaluated multiple phosphatemia thresholds to guide KRT initiation, ranging from 6.20 mg.dL-1 to 9.30 mg.dL-1. Among the initial population of 220 patients, 192 were included in the emulated trial (median age 60 years old, with non-Hodgkin Lymphoma and Acute Leukemia being the most frequent hematological malignancies). TLS-related AKI occurred in 140 patients, and 75 patients met the criteria for MAKE30. Regardless of the phosphate threshold considered, KRT initiation based on phosphate level was not associated with a significant difference in the MAKE30 rate. KRT requirement during the first 7 days (Odd Ratio [OR] 4.01 [1.65–4.86], p = 0.003) and non-renal SOFA (OR 1.39 per 1 point increment [1.25–1.57], p < 0.001) were identified as factors associated with MAKE30 (multivariable analysis).Conclusion Our results do not support the strategy of KRT initiation based on a sole critical phosphatemia level in TLS patients
Enjeux de recherches sur le lien entre pesticides et santé
No full textNational audienceEnjeux de recherches sur le lien entre pesticides et santé