148 research outputs found

    Le rôle de l'ingénieur agronome dans la situation politique de l'agriculture vénézuélienne : 1936-1948

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    L'article montre les origines d'une nouvelle profession, celle des ingénieurs agronomes au Vénézuéla entre la mort de J.V. GOMEZ et la dictature de 1948. Marquée par la modernisation, l'agronomie sera l'un des acteurs de la transformation rapide du pays. Elle bénéficiera de conditions satisfaisantes mais ne s'interrogera pas sur le sens des transformations en cours ni sur le caractère tropical de son agriculture. Discipline avant tout au service de l'Etat, l'agronomie sera aussi un moyen privilégié pour l'accès à un statut social reconnu, un moyen d'ascension sociale qui se fera au détriment des aspects techniques. La réforme agraire enfin polarisera l'attention sur les aspects plus politiques, brûlants, il est vrai, dans cette période mouvementée de l'histoire du pays. (Résumé d'auteur

    The polo-like kinase 1 (PLK1) inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia

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    CD56 is expressed in 15–20% of acute myeloid leukaemias (AML) and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8), generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56+ monoblastic AML (M5a). The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1) has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST) expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively). Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML

    PO-315 The mutational and transcriptome landscape of infant B-cell acute lymphoblastic leukaemia: the INTERFANT treatment protocol experience

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    Introduction Infant B-cell precursor acute lymphoblastic leukaemia (iBCP-ALL) has dismal prognosis, especially with MLLgene rearrangements (MLLr) which are hallmark clonal leukemogenic drivers. Molecular pathogenesis of MLLr-iBCP-ALL remain somehow enigmatic and in vivo recreation of MLLriBCP-ALL is challenging. Material and methods We performed whole-genome, exome, targetted and RNA-sequencing on an Interfant study discovery cohort of 50 iBCP-ALLs (27MLL-AF4+, including relapses, 5MLL-AF9+and 10non-MLL). An independent validation cohort of 82iBCP-ALLs (43MLL-AF4+, 11MLL-AF9+, and 28non-MLL) was used for targeted DNA-sequencing/qRT-PCR. Results and discussions iBCP-ALL shows an extremely low frequency of somatic mutations, irrespective of the presence/subtype of MLLr, with the predominant leukemic clone carrying a mean of 2.5 non-silent mutations. Recurrent mutations were exclusively found in KRAS and NRAS, which were more frequent in the MLL-AF4+than in MLL-AF9+/non-MLL iBCPALL due to common NRAS mutations found in MLL-AF4 +infants (32% vs 6%; p Conclusion iBCP-ALL shows a silent mutational landscape regardless the MLL status. The expression of AF4-MLL associates to a better prognosis and specific upregulation of HOXA cluster genes. A pre-BCR early progenitor/stem cell may represent the cell-of-origin for both the t(4;11) and RAS mutations

    First-Order Contaminant Removal in the Hyporheic Zone of Streams: Physical Insights from a Simple Analytical Model

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    A simple analytical model is presented for the removal of stream-borne contaminants by hyporheic exchange across duned or rippled streambeds. The model assumes a steady-state balance between contaminant supply from the stream and first-order reaction in the sediment. Hyporheic exchange occurs by bed form pumping, in which water and contaminants flow into bed forms in high-pressure regions (downwelling zones) and out of bed forms in low-pressure regions (upwelling zones). Model-predicted contaminant concentrations are higher in downwelling zones than upwelling zones, reflecting the strong coupling that exists between transport and reaction in these systems. When flow-averaged, the concentration difference across upwelling and downwelling zones drives a net contaminant flux into the sediment bed proportional to the average downwelling velocity. The downwelling velocity is functionally equivalent to a mass transfer coefficient, and can be estimated from stream state variables including stream velocity, bed form geometry, and the hydraulic conductivity and porosity of the sediment. Increasing the mass transfer coefficient increases the fraction of streamwater cycling through the hyporheic zone (per unit length of stream) but also decreases the time contaminants undergo first-order reaction in the sediment. As a consequence, small changes in stream state variables can significantly alter the performance of hyporheic zone treatment systems

    Postoperative outcomes in oesophagectomy with trainee involvement

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    BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

    An Adaptive Monitoring Scheme for Automatic Control of Anaesthesia in dynamic surgical environments based on Bispectral Index and Blood Pressure.

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    During surgical procedures, bispectral index (BIS) is a well-known measure used to determine the patient's depth of anesthesia (DOA). However, BIS readings can be subject to interference from many factors during surgery, and other parameters such as blood pressure (BP) and heart rate (HR) can provide more stable indicators. However, anesthesiologist still consider BIS as a primary measure to determine if the patient is correctly anaesthetized while relaying on the other physiological parameters to monitor and ensure the patient's status is maintained. The automatic control of administering anesthesia using intelligent control systems has been the subject of recent research in order to alleviate the burden on the anesthetist to manually adjust drug dosage in response physiological changes for sustaining DOA. A system proposed for the automatic control of anesthesia based on type-2 Self Organizing Fuzzy Logic Controllers (T2-SOFLCs) has been shown to be effective in the control of DOA under simulated scenarios while contending with uncertainties due to signal noise and dynamic changes in pharmacodynamics (PD) and pharmacokinetic (PK) effects of the drug on the body. This study considers both BIS and BP as part of an adaptive automatic control scheme, which can adjust to the monitoring of either parameter in response to changes in the availability and reliability of BIS signals during surgery. The simulation of different control schemes using BIS data obtained during real surgical procedures to emulate noise and interference factors have been conducted. The use of either or both combined parameters for controlling the delivery Propofol to maintain safe target set points for DOA are evaluated. The results show that combing BIS and BP based on the proposed adaptive control scheme can ensure the target set points and the correct amount of drug in the body is maintained even with the intermittent loss of BIS signal that could otherwise disrupt an automated control system

    Aligning evidence generation and use across health, development, and environment

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    © 2019 The Authors Although health, development, and environment challenges are interconnected, evidence remains fractured across sectors due to methodological and conceptual differences in research and practice. Aligned methods are needed to support Sustainable Development Goal advances and similar agendas. The Bridge Collaborative, an emergent research-practice collaboration, presents principles and recommendations that help harmonize methods for evidence generation and use. Recommendations were generated in the context of designing and evaluating evidence of impact for interventions related to five global challenges (stabilizing the global climate, making food production sustainable, decreasing air pollution and respiratory disease, improving sanitation and water security, and solving hunger and malnutrition) and serve as a starting point for further iteration and testing in a broader set of contexts and disciplines. We adopted six principles and emphasize three methodological recommendations: (1) creation of compatible results chains, (2) consideration of all relevant types of evidence, and (3) evaluation of strength of evidence using a unified rubric. We provide detailed suggestions for how these recommendations can be applied in practice, streamlining efforts to apply multi-objective approaches and/or synthesize evidence in multidisciplinary or transdisciplinary teams. These recommendations advance the necessary process of reconciling existing evidence standards in health, development, and environment, and initiate a common basis for integrated evidence generation and use in research, practice, and policy design
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