The EU Center of Excellence for Exascale in Solid Earth (ChEESE): Implementation, results, and roadmap for the second phase

publishedVersio

Componente della Redazione di Lavoro e Diritto, rivista di Classe A

[Background]: Mastocytosis are rare diseases characterized by an accumulation of clonal mast cells (MCs) in one or multiple organs or tissues. Patients with systemic mastocytosis (SM), whose MCs frequently arbor the activating D816V KIT mutation, may have indolent to aggressive diseases, and they may experience MC mediator related symptoms. Indolent SM with recurrent anaphylaxis or vascular collapse in the absence of skin lesions, ISMs(-), is a specific subtype indolent SM (ISM), and this clonal MC activation disorder represents a significant fraction of all MC activation syndromes. The V560G KIT mutation is extremely rare in patients with SM and its biological and prognostic impact remains unknown. [Case presentation]: A 15-year old boy was referred to our hospital because of repeated episodes of flushing, hypotension and syncope since the age of 3-years, preceded by skin lesions compatible with mastocytosis on histopathology that had disappeared in the late-early childhood. Diagnosis of ISM, more precisely the ISMs(-) variant, was confirmed based on the clinical manifestations together with increased baseline serum tryptase levels and the presence of morphologically atypical, mature appearing (CD117+high, FcεRI+) phenotypically aberrant (CD2+, CD25+) MCs, expressing activation-associated markers (CD63, CD69), in the bone marrow. Molecular genetic studies revealed the presence of the KIT V560G mutation in bone marrow MCs, but not in other bone marrow cells, whereas the screening for mutations in codon 816 of KIT was negative. The patient was treated with oral disodium cromoglycate and the disease had a favorable outcome after an eleven-year follow-up period, during which progressively lower serum tryptase levels together with the fully disappearance of all clinical manifestations was observed. [Conclusions]: To the best of our knowledge this first report of a patient with ISM, whose bone marrow MCs carry the KIT V560G activating mutation, manifesting as recurrent spontaneous episodes of flushing and vascular collapse in the absence of skin lesions at the time of diagnosis, in whom disodium cromoglycate had led to long term clinical remission.Peer Reviewe

Probabilistic Tsunami Hazard Analysis: Multiple Sources and Global Applications

International audienceApplying probabilistic methods to infrequent but devastating natural events is intrinsicallychallenging. For tsunami analyses, a suite of geophysical assessments should be in principle evaluatedbecause of the different causes generating tsunamis (earthquakes, landslides, volcanic activity,meteorological events, and asteroid impacts) with varying mean recurrence rates. Probabilistic TsunamiHazard Analyses (PTHAs) are conducted in different areas of the world at global, regional, and local scaleswith the aim of understanding tsunami hazard to inform tsunami risk reduction activities. PTHAs enhanceknowledge of the potential tsunamigenic threat by estimating the probability of exceeding specificlevels of tsunami intensity metrics (e.g., run-up or maximum inundation heights) within a certain period oftime (exposure time) at given locations (target sites); these estimates can be summarized in hazard mapsor hazard curves. This discussion presents a broad overview of PTHA, including (i) sources and mechanismsof tsunami generation, emphasizing the variety and complexity of the tsunami sources and their generationmechanisms, (ii) developments in modeling the propagation and impact of tsunami waves, and (iii)statistical procedures for tsunami hazard estimates that include the associated epistemic and aleatoricuncertainties. Key elements in understanding the potential tsunami hazard are discussed, in light of therapid development of PTHA methods during the last decade and the globally distributed applications,including the importance of considering multiple sources, their relative intensities, probabilities ofoccurrence, and uncertainties in an integrated and consistent probabilistic framework