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Research note: Compound-specific isotopic analysis in 34S-labelled chicken tissues using high resolution gas chromatography/mass spectrometry
No full textInternational audienceMany food supplements include sulphur (S)-containing additives such as methionine or synthetic compounds like 2-hydroxy-S-methyl-thiobutyric acid (HMTBA). However, monitoring the metabolic use efficiency of S-containing additive is challenging, and requires specific methods, based on isotopic labelling. The most direct route is the utilisation of 34S-enriched material and subsequent measurement of 34S-abundance in tissues. While this can be carried out routinely using elemental analysis coupled with isotope ratio mass spectrometry (IRMS) for bulk S from raw tissue material, there is currently no IRMS-based method adapted to compound-specific isotopic analysis for sulphur. Here, we present a method based on gas chromatography coupled to high resolution mass spectrometry (GC-MS) to measure 34S-abundance in both free and protein-bound S containing amino acids. This method elaborates on metabolomics based on GC-MS analysis of trimethylsilylated extracts. Specific ion fragments comprising a sulphur atom could be identified and their isotopic pattern was used to compute % 34S. The high resolution was useful to avoid the confounding effect of natural carbon (13C2) or (18O) isotopologues but required a correction for silicium (Si) isotope because the mass excess of 30Si (+ 1.9968 a.m.u.) was close to that of 34S (+ 1.9957 a.m.u.) and therefore the 30Si and 34S isotopologues could not be separated. This technique was applied to broilers fed with 34S-labelled methionine and showed that 34S could be easily traced in different organs. 34S-methionine redistributed mostly to homocysteine with little 34S-enrichment in cysteine and taurine, due to the isotopic dilution by food cysteine supply. The results show that our method can be implemented to follow the metabolic incorporation of S-containing additives such as methionine in broilers
Comprehensive approach of executive functions in children with neurofibromatosis type 1.
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Intermediate-Dose Cytarabine as Postinduction AML Therapy
No full textInternational audienceBackground: We conducted a randomized controlled trial to compare intermediate doses (IDAC) with high doses of cytarabine (HDAC) as postinduction therapy in patients 18 to 60 years of age with newly diagnosed acute myeloid leukemia (AML). The main objectives were to evaluate noninferiority in overall survival (OS) after IDAC and safety.Methods: Patients 18 to 60 years of age with newly diagnosed AML, except those with core-binding factor, acute promyelocytic, Philadelphia chromosome-positive, or post-myeloproliferative neoplasm AML, were eligible. After the induction course, we randomly assigned patients to either IDAC (1500 mg/m2/12 hours) or HDAC (3000 mg/m2/12 hours). Patients with intermediate- and adverse-risk AML were eligible for allogeneic hematopoietic stem cell transplantation (HSCT) in first remission. The primary end point was OS in a predefined per-protocol analysis population. The primary analyses were performed in 1132 randomly assigned patients, with a noninferiority outcome adjusted on the European Leukemia Net (ELN) 2022 risk group, the use of induction anthracycline, the response to induction, and HSCT as a function of time following treatment.Results: At 5 years, OS was estimated at 59.3% (95% confidence interval [CI], 55.0 to 63.3) in the IDAC group versus 57.5% (95% CI, 53.3 to 61.5) in the HDAC group (adjusted hazard ratio, 0.96; 95% CI, 0.80 to 1.15; noninferiority test, P=0.0042). A preplanned analysis was unable to detect any interaction between IDAC or HDAC treatment effect and patient subgroups, including those defined by the ELN 2022 risk group or response to induction prior to random assignment. In addition, the severity of chemotherapy-induced myelosuppression and the incidence of related adverse events were lower after IDAC.Conclusions: Our trial shows noninferior outcomes in patients 18 to 60 years of age with newly diagnosed AML treated with low- versus high-dose cytarabine; this occurred with similar or lower toxicities.(Funded by the Regional Clinical Research Office, Angers and others; EudraCT number, 2014-000699-24; ClinicalTrials.gov number, NCT02416388)
Development and Validation of a Liquid Chromatography High‐Resolution Mass Spectrometry Method for Blood Desmopressin Quantification and Its Application in Hemophilia A Patients
No full textInternational audienceDesmopressin (DDAVP), which indirectly increases Coagulation Factor VIII concentrations in the blood, is a common treatment for bleeding disorders such as von Willebrand disease or hemophilia A. However, DDAVP exhibits significant variability in response due to interindividual differences in pharmacokinetics. Consequently, exploring its pharmacokinetics is of primary importance to better understand the relationship between DDAVP administration and therapeutic outcomes. To that end, the measurement of DDAVP concentration is essential. This article describes the development and validation of a liquid chromatography method coupled with high‐resolution mass spectrometry detection for quantifying DDAVP in human plasma. After sample pretreatment involving protein precipitation followed by solid‐phase extraction, quantification was based on the four most intense isotopes, utilizing targeted single ion monitoring, with a method range of 20–2000 pg.mL−1. For the four QC levels, accuracy and precision for both inter‐ and intra‐assay measurements were below 11.6% and 13.8%, respectively, meeting FDA recommendations. After validation, this method was applied to a cohort of 10 patients with a deficiency in Coagulation Factor VIII, who received 0.3 μg.kg−1 of desmopressin acetate. The mean volume of distribution at steady state was 18.8 L (CV% 26.7), the mean clearance was 7.8 L.h−1 (CV% 25.1), and the mean half‐life was 1.8 h (CV% 14.7). Offering valuable insights into the pharmacokinetics of DDAVP, this method will be useful for further studies and holds promise for optimizing treatment regimens in this patient population
Du développement aux transitions soutenables dans les territoires : vers un renouvellement de la notion de ressource territoriale
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: Portrait of an Amateur by Himself and Others
No full textInternational audienceBased on his publications and a number of archives, this article analyzes the way É. Rivière defines and presents himself as a researcher. This self-representation is contrasted with the viewpoints of his contemporaries to highlight a series of contrasts and tensions. É. Rivière embodies a polygraph who is increasingly at odds with the imperatives of specialization within prehistory, so much so that the credibility of his work is undermined. Well-connected to the major Parisian institutions, he is poorly integrated into the local networks of amateurs working in the field. This positioning and lack of legitimacy contributed to the many polemics that punctuated the prehistorian's career.the prehistorian’s career.Cet article analyse, à partir de ses publications et de quelques archives, la manière dont É. Rivière se définit et se met en scène en tant que chercheur. Cette autoreprésentation est confrontée aux points de vue de ses contemporains afin de mettre en lumière une série de contrastes et de tensions. É. Rivière incarne une figure de polygraphe en décalage croissant avec les impératifs de spécialisation qui s'imposent au sein de la préhistoire, si bien que la crédibilité de ses travaux en est fragilisée. Bien connecté aux grandes institutions parisiennes, il est mal inséré dans les réseaux locaux d'amateurs qui oeuvrent sur le terrain. Ce positionnement et ce déficit de légitimité favorisent les nombreuses polémiques qui ponctuent la carrière du préhistorien
Prévention des effets du mésusage des écrans chez les enfants de moins de 18ans par les médecins généralistes : création et évaluation du site internet www.appli-ecrans.fr
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Tiers-lieux de l'ESS et évaluation : enjeux méthodologiques avec la méthode Q
No full textInternational audienceCette communication examine l'utilisation de la méthode Q pour comprendre la dynamique de fréquentation des tiers-lieux (TL), en particulier ceux relevant de l'économie sociale et solidaire (ESS) qui endossent un rôle de transformation sociale. Elle le développement et la nature hybride des TL, ainsi que les défis liés à leur financement et à leur légitimité. L'étude se concentre sur l'atelier de cuisine d'un TL spécifique, La Cocotte Solidaire, pour explorer les motivations et les points de vue variés des participants, démontrant comment la méthode Q peut révéler des profils d'usagers distincts et la dynamique d'interaction au sein de ces espaces. Dans le cadre d'une recherche-action, la méthode Q offre une approche systématique et transparente pertinente pour saisir la subjectivité, ses résultats sont en revanche très contextualisés et difficiles à généraliser
Exploring the link between personality dimensions and non-motor fluctuations in Parkinson's disease
No full textInternational audienceBackground: Parkinson's disease (PD) patients on dopaminergic drugs may experience non-motor fluctuations (NMFs) which are often heterogeneous and respond variably to treatments.Objective: We evaluated if personality was associated to NMFs and could modulate the NMFs responsiveness to dopaminergic medication and deep brain stimulation of the sub-thalamic nucleus (STN-DBS).Methods: From the PREDISTIM cohort, personality dimensions of 235 PD patients were assessed by the Temperament and Character Inventory (TCI) before STN-DBS (V0). NMFs were evaluated using the NMFs Severity Scale at V0 and one year after STN-DBS (V1). Linear regression models were performed between TCI dimensions and NMFs at V0; and logistic regression models were done between TCI dimensions and 1) groups of dopa-sensitive patients (responders to ON medication at V0) versus non-dopa-sensitive ones, and 2) responders versus non-responders to STN-DBS at V1. Odds ratios (OR) were also calculated.Results: Significant associations were found between two TCI personality dimensions (“Harm Avoidance” and “Self-Directedness”) and severity of NMFs in OFF medication at V0: PD patients with higher Harm Avoidance and lower Self-Directedness scores having more NMFs. TCI personality dimensions were not associated with the dopa-sensitivity while Novelty Seeking was significantly associated with the STN-DBS-responder group for the psychiatric (OR = 1.09 [1.02–1.17]) and for the dysautonomic NMFs (OR = 1.11 [1.04–1.18]).Conclusions: Certain personality dimensions (Harm Avoidance and Self-Directedness) are associated with NMFs severity at baseline, and PD patients with high Novelty Seeking seem to be better candidates for NMFs improvement after STN-DBS.Plain Language SummaryNon-motor fluctuations are highly invalidating for patients with Parkinson's disease and their response to treatments is variable. This new research examined personality dimensions impact on non-motor fluctuations and their responsiveness to dopaminergic medication and to deep brain stimulation. Two hundred and thirty-five patients with Parkinson's disease participated in the study and filled out several questionnaires to score their personality dimensions and their non-motor fluctuations severity before and after one year of deep brain stimulation. Comparisons were done between different groups of patients according to their response to dopaminergic treatments and to deep brain stimulation. As results, patients with personality traits of high “Harm Avoidance” (more anxious individuals) and low “Self-Directedness” (less goal-oriented individuals) had globally more non-motor fluctuations, and the personality dimension of “Novelty Seeking” (impulsive individuals) was related to a better non-motor fluctuations responsiveness to deep brain stimulation. Hence, non-motor fluctuations are associated with some specific personality dimensions on top of early onset of Parkinson's disease, long disease-duration, high doses of levodopa and female gender. Moreover, Parkinson's disease patients with impulsive-like personality seem to be better candidates for non-motor fluctuations improvement after deep brain stimulation
Time is Ticking: French healthcare teams and their managers navigating time challenges with their collective competency
No full textInternational audienceThis study explores the time management challenges faced by French healthcare teams and their managers. It examines how these teams use their collective competencies to overcome these challenges. The research question, ‘How does the care team use its collective competency to address time management challenges?’ addresses a crucial matter: the pressing issue of deteriorating working conditions in healthcare, characterised by increased work intensity, overload, and time pressure. Understanding this relationship leads to increased job satisfaction, decreased absenteeism, and improved efficiency in healthcare. This study explores the theoretical foundations of temporality management and collective competency. It defines these key terms and examines how time management for healthcare professionals can be implemented in a concrete way. The methodology includes a qualitative approach, using observations and interviews with healthcare managers and their teams. It presents two case studies conducted at a university medical centre in western France: one in a neurovascular unit and the other in the operating room. The findings highlight the complexity of managing work schedules and the role of collective competency in addressing these challenges. A thematic analysis has been conducted using Nvvio to extract quotes that identify key attributes of collective competency and discuss how these attributes help the response to temporality management challenges. From a theoretical perspective the research contributes to the understanding of temporality management in healthcare and the role of collective competency in addressing these challenges. It suggests that effective time management in healthcare requires a collective approach that leverages the collective competency of care teams. From amanagerial perspective, it shows the challenges faced by healthcare managers in managing their teams’ time