204 research outputs found

    ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle

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    The Allergic Rhinitis and its Impact on Asthma (ARIA) initiative commenced during a World Health Organization workshop in 1999. The initial goals were (1) to propose a new allergic rhinitis classification, (2) to promote the concept of multi-morbidity in asthma a

    ALK-positive histiocytosis: a new clinicopathologic spectrum highlighting neurologic involvement and responses to ALK inhibition

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    ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in three infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALKrearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (seven and twelve from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated-ERK, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, while CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, ten with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis, and provides guidance for the clinical management of this emerging histiocytic entity.Molecular tumour pathology - and tumour genetic

    INELASTIC PROPERTIES OF ICE Ih AT LOW TEMPERATURES AND HIGH PRESSURES

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    Le but de notre programme de recherche est d'étudier le comportement rhéologique de glaces soumises aux mêmes conditions que celles existant à l'intérieur de satellites des planètes extérieures afin de connaître leurs lois de déformation. Pour cela, nous avons effectué 100 essais de compression à vitesse de déformation constante pour des pressions allant jusqu'à 500 MPa et pour des températures aussi basses que 77 K. Pour P > 30 MPa, la glace Ih se fracture par instabilité de cisaillement produisant des fautes dans la direction du maximum de contrainte de cisaillement et la contrainte de fissuration est indépendante de la pression. Ce comportement inhabituel peut-être associé à des transformations de phases localisées dans les zones de cisaillement. La résistance en régime stationnaire suit des lois rhéologiques thermiquement activées décrites par des lois de puissance, avec différents paramètres d'écoulement dépendant des gammes de températures étudiées. Les lois d'écoulement seront discutées en relation avec les divers mécanismes de déformation déduits des microstructures observées optiquement et en comparaison avec d'autres travaux.The aim of our research programme is to explore the rheological behavior of H2O ices under conditions appropriate to the interiors of the icy satellites of the outer planets in order to give insight into their deformation. To this end, we have performed over 100 constant-strain-rate compression tests at pressures to 500 MPa and temperatures as low as 77 K. At P > 30 MPa, ice Ih fails by a shear instability producing faults in the maximum shear stress orientation and failure strength typically is independent of pressure. This unusual faulting behavior is thought to be connected with phase transformations localized in the shear zones. The steady-state strength follows rheological laws of the thermally-activated power-law type, with different flow law parameters depending on the range of test temperatures. The flow laws will be discussed with reference to the operating deformation mechanisms as deduced from optical-scale microstructures and comparison with other work
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