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Ordering Aspect and the temporal interpretation of Karitiana subordinate clauses
No full textInternational audienceThis paper addresses the issue of the temporal interpretation of subordinate clauses in Karitiana, a Tupi language spoken in Northwest Brazil (Storto 1999). We compare the temporal interpretation of subordinate clauses in Karitiana with that of other languages where subordinate clauses are (at least on the surface) tenseless. We establish three patterns of temporal construals, drawing the implications for possible analyses. We conclude that Karitiana shows a freedom of temporal interpretation that must be imputed to a covert semantically underspecified higher aspectual head (Ordering Aspect (ASPord)) in Rullman & Matthewson’s (2018) typology
Chronic cadmium exposure promotes TRPM7-dependent acquisition of a myofibroblast-like phenotype in pancreatic stellate cells
No full textInternational audienceCadmium (Cd) is a metallic pollutant which has been classified as a possible pancreatic carcinogen. Cd uses similar ion channels than divalent cations to accumulate into the cells. These include the Transient Receptor Potential Cation Channel Subfamily M Member 7 (TRPM7) which has been also shown as a biomarker of pancreatic cancer. Pancreatic carcinogenesis is associated with the establishment of a fibrous stroma induced by pancreatic stellate cell (PSC) activation. Although several stress factors have been identified as activators of PSCs, the impact of pollutants, particularly Cd, is still unknown. Here, we chronically exposed human PSCs to Cd and we observed that Cd-exposed cells acquired a myofibroblast-like phenotype. Moreover, TRPM7 expression and activity were upregulated following Cd exposure. Both TRPM7 inhibition by silencing or NS8593 treatment prevented the Cd-induced PSC cell migration indicating that TRPM7 regulated PSC activation. We used a model of indirect co-culture to study the impact of PSC on MIA PaCa-2 cancer cell migration. Interestingly, we showed that Cd-exposed PSCs stimulated MIA PaCa-2 cancer cell migration to a greater extent than non-exposed PSCs. TRPM7 inhibition in PSCs abolished the migration of cancer cells. Finally, in a mouse model with the KRASG12D mutation inducing spontaneous pancreatic intraepithelial neoplasia, Cd exposure aggravates collagen deposition in fibrotic areas showing high α-SMA and TRPM7 expressions. In summary, our study showed that Cd exposure upregulates TRPM7 leading to PSC activation and aggravation of precancerous pancreatic fibrosis in viv
Management of nontuberculous mycobacterial Pulmonary disease refractory to guideline-based therapy: A systematic review.
No full textInternational audienceIntroduction: Managing patients with nontuberculous mycobacterial pulmonary disease (NTM-PD) unresponsive to guideline-based therapy remains challenging due to limited treatment options and complex disease progression. This study systematically reviewed existing literature on management strategies and emerging therapeutic approaches for refractory NTM-PD.Methods: We systematically reviewed studies on NTM-PD treatment failure published from inception until 31 January 2024, examining associated factors, intensification strategies, and supportive measures. Twenty-five studies met the inclusion criteria, mostly retrospective and observational, focusing on pulmonary disease by Mycobacterium avium complex and Mycobacterium abscessus species. Findings were synthesised qualitatively because of substancial heterogeneity in study design and outcomes.Results: Before treatment intensification or de-escalation, the impact of antibiotics on health-related quality of life and microbiological factors, including acquired resistance and pathogen shifts, should be assessed. Severe baseline radiological findings and multiple prior regimen modifications were associated with lower treatment success. Evidence for supportive interventions-such as nutritional counselling, respiratory rehabilitation, and psychosocial support-remains limited. Intermittent intravenous antibiotics may aid symptom control. Depending on NTM species, additional antibiotics have been explored to intensify treatment, though evidence is largely observational. Surgical resection may be considered for localised disease, but recurrence risk remains substantial, particularly with preoperative positive cultures. Novel therapeutic approaches remain under investigation as potential alternatives.Discussion: This systematic review underscores the complexity of managing refractory NTM-PD, highlighting the role of treatment intensification, symptom control, supportive measures, and knowledge gaps. While no standardised approach exists, individualised strategies incorporating clinical, microbiological, and radiological factors remain essential for optimising patient outcomes
Careful ventilation in acute respiratory distress syndrome: the protocol of the CAVIARDS international multicentre randomised basket trial
No full textInternational audienceIntroduction Acute respiratory distress syndrome (ARDS) is a major public health problem, accounting for 23% of intubated patients and associated with high mortality rates. Although lifesaving, invasive mechanical ventilation can worsen lung injury when ventilator settings are poorly adjusted to lung physiology. We hypothesise that individualising ventilator settings via (1) the bedside assessment of lung recruitability using a one-breath derecruitment manoeuvre and measurement of airway opening pressure to set positive end-expiratory pressure (PEEP), (2) controlling the distending pressure and (3) controlling respiratory drive improves ARDS outcomes. Methods and analysis The CAreful Ventilation In ARDS trial is an investigator-led multicentre (33 centres in eight countries), open-label, randomised controlled basket trial comparing two ventilation strategies in two subpopulations of moderate-to-severe ARDS: induced or not by COVID-19. A total of 740 patients will be randomised (370 in each substudy) in a 1:1 ratio to individualised ventilator settings or to using traditional PEEP to inspired fraction of oxygen tables for PEEP setting. Indications for proning and weaning strategies are similar in both arms. The primary outcome is all-cause mortality at day 60. Secondary outcomes include duration of mechanical ventilation, duration of intensive care unit (ICU) and hospital stay, organ dysfunction, barotrauma and mortality in ICU, at day 28 and in hospital. Ethics and dissemination Ethics approval has been obtained for all participating centres: Unity Health Toronto Research Ethics Board (for three centres: St Michael’s Hospital, Toronto General Hospital and Toronto Western Hospital); Comité de Ética de Investigación con Medicamentos del Hospital Universitari Vall d’Hebron; Comité de protection des personnes Ile de France III; Comité d'Ética de la Investigatción con Medicamentos de la Fundació de Gestió Sanitària del Hospital de la Santa Creu i Sant Pau; Comitato Etico—Fondazione Policlinico Gemelli; Comitato Etico di Area Vasta Emilia Centro; NYU Langone Health Institutional Review Board; Comité Ético Científico de Ciencias de la Salud; Il Comitato Etico Area 1 dell’Azienda Ospedaliero-Universitaria ‘Ospedali Riuniti’ di Foggia; HIGA ‘Eva Perón’ Comité de Bioética; Comité de Revisión Institucional del Hospital Británico Comité de Ética en Investigación; Complejo Médico Churruca-Visca Comité de Ética Biomédica; Comité de Ética SATI Comité de Ética en Investigación; Comité de Ética en Investigación del CEMIC; Comité de Ética SATI Comité de Ética en Investigación; Medical Research Ethics Committees United. Findings will be disseminated in peer review journals and conference presentations. Trial registration number NCT03963622
Un malaise du nouveau-né prématuré pas si banal : Cas clinique didactique
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Psychometric validation of the French version Comprehensive Assessment of Prospective Memory and age-related differences
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Translation and Validation of the Pain Resilience Scale in a French Population Suffering From Chronic Pain
No full textInternational audienceABSTRACT Objective The present study aimed to translate and validate the French version of the Pain Resilience Scale (PRS) that was initially created and validated within English‐speaking populations. Methods A total of 137 participants experiencing chronic pain completed the French version of the PRS and other questionnaires commonly used to evaluate resilience or vulnerability towards pain. Of these, 71 participants successfully retook the PRS measure within 15 days of their initial participation. A principal component analysis was employed to evaluate the internal structure of the questionnaire. Following classical test theory, internal consistency, convergent validity, and test‐retest reliability were checked for the chosen model. Lastly, an item response theory analysis (IRT) was conducted for the 2 PRS dimensions. Factor analyses identified a two‐factor solution consistent to the original English version of the PRS. Results The findings demonstrated that the scale's internal consistency and test‐retest reliability meet the requirements for classical psychometric qualities. The overall PRS score and its subscales showed good convergent validity with measures assessing resilience or vulnerability processes to pain. IRT results highlighted difficulties with some items on each of the 2 dimensions that complement the results of the previous classical analyses. Conclusions The French version of the PRS scale is a reliable tool for measuring pain‐specific resilience toward persistent pain
Life-threatening thrombotic events revealing systemic lupus erythematosus in a patient with chronic myelomonocytic leukaemia
No full textInternational audienceAssociations between systemic autoimmune and inflammatory diseases and myelodysplastic syndromes have been reported for at least 25 years, suggesting a potential pathogenic link. We present the case of a 62-year-old woman with chronic myelomonocytic leukaemia, initially diagnosed in August 2022 based on persistent monocytosis, thrombocytopenia, polyclonal hypergammaglobulinemia, NRAS and SCMA1 mutations, and cytogenetic abnormalities (46 chromosomes with a long arm deletion of chromosome 16). In August 2024, she was hospitalized for worsening general condition and dyspnoea, revealing hyperleukocytosis (206 g/l), progressive monocytosis, medullary infiltration, and bilateral pericardial/pleural effusions. A positron emission tomography scan demonstrated bone marrow hypermetabolism and splenomegaly. Treatment with azacitidine and venetoclax was initiated, but weeks later, she developed ST elevation myocardial infarction, ischemic stroke, and deep vein thrombosis, requiring intensive care. Immunological testing showed high-titre antinuclear antibodies (1/1280), anti-Ro52, anti-Sm/RNP, and anti-U1 RNP and complement consumption, leading to a diagnosis of systemic lupus erythematosus (American College of Rheumatology/ European League Against Rheumatism 2019 criteria). Hydroxychloroquine was started, followed by hydroxycarbamide, azacitidine, and ruxolitinib due to persistent hyperleukocytosis (peaking at 100 g/l), resulting in clinical and biological improvement. The patient underwent allogeneic stem cell transplantation in mid-March 2025. This case highlights the complex interplay between hematologic malignancies and autoimmune diseases, emphasizing the need for multidisciplinary management
P0663 Comparative Effectiveness of Advanced Therapies between Ulcerative Proctitis and More Extensive Forms of Ulcerative Colitis: Results from a Multicenter Real-World Study
No full textInternational audienceBackground Most pivotal trials for advanced therapies in ulcerative colitis (UC) exclude patients with isolated rectal disease. This study compares treatment effectiveness between E1 (rectal) and E2/E3 (left-sided or extensive) UC. Methods This analysis pooled individual-level data from several multicentre, retrospective, real-world comparative studies. All consecutive patients with active disease (partial Mayo score (PMS) > 2) who initiated an advanced therapy after failure of at least one biologic were included. The primary outcome was steroid-free symptomatic remission, defined as a PMS ≤ 2 at week 14 (W14). The comparison for the primary outcome was adjusted for potential confounders, including concomitant medications. The secondary outcome was discontinuation-free survival. A subgroup analysis of the primary outcome was performed within each therapeutic class. Results A total of 608 patients were included: 73 were E1 and 535 E2/E3. Among them, 48% were female, the median age was 39 years [interquartile range: 27–54], and the median disease duration was 6 years [3–10]. Overall, 38% of patients were initiating a second-line advanced therapy, 35% a third-line, 17% a fourth-line, and 4% a fifth-line treatment. The initiated drug was vedolizumab in 28% of cases, ustekinumab in 24%, and a JAK inhibitor (tofacitinib, filgotinib, or upadacitinib) in 48%. A concomitant treatment was prescribed in 256 patients (42%): 76 (13%) with 5-aminosalicylates, 55 (9%) an immunomodulator and 166 (27%) corticosteroids. E1 disease was not significantly associated with a different rate of symptomatic remission at week 14 in univariate analysis (OR = 1.50 [95% CI: 0.94–2.89], p = 0.09). In the multivariate analysis adjusted for age, disease duration, baseline PMS, elevated baseline CRP, concomitant therapy, and number of prior treatment lines, disease extent was not associated with remission (OR = 1.75 [0.87–3.70], p = 0.13). Conversely, an elevated PMS was independently associated with lower rates of remission (OR = 0.84 [0.75–0.95], p = 0.004). Survival analysis showed no difference between the two groups in time to treatment discontinuation for failure (HR = 0.78 [0.56–1.10], p = 0.20), Figure. Subgroup analyses by therapeutic class found no difference in efficacy according to disease extent, whether for vedolizumab (OR = 0.91 [0.30–2.84]), ustekinumab (OR = 1.81 [0.32–14.32]), or JAK inhibitors (OR = 2.63 [0.94–10.0]) (all non-significant). Conclusion In this large multicenter real-world cohort, advanced therapies demonstrated similar efficacy in patients with isolated rectal UC compared with those with more extensive disease, underscoring the need to adequately treat this disease location. Conflict of interest: Dr. Hupé, Marianne: Abbvie, Takeda, Celltrion Healthcare, Pfizer, Johnson & Johnson, Lilly, Amgen Uzzan, Mathieu: Grant: ECCO-IOIBD, Fondation pour la Recherche Medicale (FRM), SNFGE Personal Fees: Abbvie, Takeda, Celltrion, Janssen, Amgen, Alfasigma, Pfizer Altwegg, Romain: Advisory boards from Abbvie, Takeda, Johnson and Johnson, Lilly, Alphasigma, Celltrion, Pfizer, Amgen, Biogen, Sandoz, Ferring Bouguen, Guillaume: Grant: Abbvie, Ferisinus Personal Fees: Abbvie, Takeda, Fresinus, Amgen, Biogène, Arena, Ferring, Gilead, Janssen, MSD, Pfizer, Sandoz, Takeda, Tillots, Vifor pharma Nachury, Maria: Abbvie, Alfa Sigma, Biosynex, Celltrion, Galapagos, Janssen, Lilly, MSD, Pfizer, Takeda Domas, Quentin: No conflict of interest Fumery, Mathurin: Grant: Pfizer Personal Fees: Abbvie, Janssen, Takeda, MSD, Biogen, Amgen, Sandoz, Fresenius, Gilead, Celgene, Galapagos, Mylan, Tillots, Ferring, Pfizer, Hospira, CTMA, Boehringer, Lilly, Arena Non-financial Support: Abbvie, Janssen, Takeda, MSD, Galapagos, Ferring, Pfizer Tretón, Xavier: Personal Fees: Lectures and advisory board : Abbvie, Celltrion, MSD, Johnson & Johnson, Takeda, Amgen, Alphasigma, Lilly, Pfizer Other: participations: Thabor Therapeutics Amiot, Aurelien: Personal Fees: Abbvie, Fresenius-Kabi, Adacyte, Tillotts pharma, Janssen, Pfizer, Biogen, AMgen, Sandoz, Takeda, Galapagos, Eli Lilly Vuitton, Lucine: Abbvie, Amgen, Viatris, Celltrion, Janssen, Takeda, Lilly, Pfizer, Dr Falk Pharma, MSD, Ferring, Galapagos Caillo, Ludovic: Abbvie, Amgen, Celltrion, Ferring, Fresenius, Lilly, Jonhson & Jonhson, MSD, Pfizer, Takeda, Sandoz Gilletta de Saint Joseph, Cyrielle: Speaker/ consultant fees from Abbvie, AlfaSigma, Amgen, Celltrion, Ferring, Fresenius, Janssen, Lilly, Pfizer, Takeda and Tillots Pereira, Bruno: No conflict of interest Buisson, Anthony: Grant: Abbvie, Celltrion, Pfizer and Takeda Personal Fees: Abbvie, Amgen, Arena, Biogen, Celltrion, Ferring, Janssen, MSD, Pfizer, Roche, Sanofi-Aventis, Takeda, Tillotts, Vifor Pharma
: Une analyse des Adieux d’un sex-symbol
No full textInternational audienceLa chanson "Les Adieux d’un sex-symbol" se trouve au cœur de nombreux fils narratifs dans Starmania. Je propose ici de l’analyser en partant de la performance particulièrement marquante de Diane Dufresne, sa première interprète – qui a aussi contribué à la genèse de l’œuvre, puisque c’est à travers sa voix que Michel Berger a entendu pour la première fois des textes écrits par Luc Plamondon, ce qui lui a donné l’envie de travailler avec lui. Après quelques éléments d’analyse formelle textuelle et musicale, j’analyserai une performance scénique et vocale de Diane Dufresne sur scène