250 research outputs found

    Hyperferritinemia without iron overload in patients with bilateral cataracts: a case series

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    Hepatologists and internists often encounter patients with unexplained high serum ferritin concentration. After exclusion of hereditary hemochromatosis and hemosiderosis, rare disorders like hereditary hyperferritinemia cataract syndrome should be considered in the differential diagnosis. This autosomal dominant syndrome, that typically presents with juvenile bilateral cataracts, was first described in 1995 and has an increasing number of recognized molecular defects within a regulatory region of the L-ferritin gene (FTL). CASE PRESENTATION: Two patients (32 and 49-year-old Caucasian men) from our ambulatory clinic were suspected as having this syndrome and a genetic analysis was performed. In both patients, sequencing of the FTL 5' region showed previously described mutations within the iron responsive element (FTL c.33 C > A and FTL c.32G > C). CONCLUSION: Hereditary hyperferritinemia cataract syndrome should be considered in all patients with unexplained hyperferritinemia without signs of iron overload, particularly those with juvenile bilateral cataracts. Liver biopsy and phlebotomy should be avoided in this disorder

    Recombinant ADAMTS13 reduces abnormally up-regulated von Willebrand factor in plasma from patients with severe COVID-19

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    Thrombosis affecting the pulmonary and systemic vasculature is common during severe COVID-19 and causes adverse outcomes. Although thrombosis likely results from inflammatory activation of vascular cells, the mediators of thrombosis remain unconfirmed. In a cross-sectional cohort of 36 severe COVID-19 patients, we show that markedly increased plasma von Willebrand factor (VWF) levels were accompanied by a partial reduction in the VWF regulatory protease ADAMTS13. In all patients we find this VWF/ADAMTS13 imbalance to be associated with persistence of ultra-high-molecular-weight (UHMW) VWF multimers that are highly thrombogenic in some disease settings. Incubation of plasma samples from patients with severe COVID-19 with recombinant ADAMTS13 (rADAMTS13) substantially reduced the abnormally high VWF activity, reduced overall multimer size and depleted UHMW VWF multimers in a time and concentration dependent manner. Our data implicate disruption of normal VWF/ADAMTS13 homeostasis in the pathogenesis of severe COVID-19 and indicate that this can be reversed ex vivo by correction of low plasma ADAMTS13 levels. These findings suggest a potential therapeutic role for rADAMTS13 in helping restore haemostatic balance in COVID-19 patients

    Analytic Metaphysics versus Naturalized Metaphysics: The Relevance of Applied Ontology

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    The relevance of analytic metaphysics has come under criticism: Ladyman & Ross, for instance, have suggested do discontinue the field. French & McKenzie have argued in defense of analytic metaphysics that it develops tools that could turn out to be useful for philosophy of physics. In this article, we show first that this heuristic defense of metaphysics can be extended to the scientific field of applied ontology, which uses constructs from analytic metaphysics. Second, we elaborate on a parallel by French & McKenzie between mathematics and metaphysics to show that the whole field of analytic metaphysics, being useful not only for philosophy but also for science, should continue to exist as a largely autonomous field

    Integrated modeling and validation for phase change with natural convection

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    Water-ice systems undergoing melting develop complex spatio-temporal interface dynamics and a non-trivial temperature field. In this contribution, we present computational aspects of a recently conducted validation study that aims at investigating the role of natural convection for cryo-interface dynamics of water-ice. We will present a fixed grid model known as the enthalpy porosity method. It is based on introducing a phase field and employs mixture theory. The resulting PDEs are solved using a finite volume discretization. The second part is devoted to experiments that have been conducted for model validation. The evolving water-ice interface is tracked based on optical images that shows both the water and the ice phase. To segment the phases, we use a binary Mumford Shah method, which yields a piece-wise constant approximation of the imaging data. Its jump set is the reconstruction of the measured phase interface. Our combined simulation and segmentation effort finally enables us to compare the modeled and measured phase interfaces continuously. We conclude with a discussion of our findings

    Soft Image Segmentation: On the Clustering of Irregular, Weighted, Multivariate Marked Networks

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    The contribution exposes and illustrates a general, flexible formalism, together with an associated iterative procedure, aimed at determining soft memberships of marked nodes in a weighted network. Gathering together spatial entities which are both spatially close and similar regarding their features is an issue relevant in image segmentation, spatial clustering, and data analysis in general. Unoriented weighted networks are specified by an ``exchange matrix", determining the probability to select a pair of neighbors. We present a family of membership-dependent free energies, whose local minimization specifies soft clusterings. The free energy additively combines a mutual information, as well as various energy terms, concave or convex in the memberships: within-group inertia, generalized cuts (extending weighted Ncut and modularity), and membership discontinuities (generalizing Dirichlet forms). The framework is closely related to discrete Markov models, random walks, label propagation and spatial autocorrelation (Moran's I), and can express the Mumford-Shah approach. Four small datasets illustrate the theory

    Cohomological Donaldson-Thomas theory of a quiver with potential and quantum enveloping algebras

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    This paper concerns the cohomological aspects of Donaldson-Thomas theory for Jacobi algebras and the associated cohomological Hall algebra, introduced by Kontsevich and Soibelman. We prove the Hodge-theoretic categorification of the integrality conjecture and the wall crossing formula, and furthermore realise the isomorphism in both of these theorems as Poincar\'e-Birkhoff-Witt isomorphisms for the associated cohomological Hall algebra. We do this by defining a perverse filtration on the cohomological Hall algebra, a result of the "hidden properness" of the semisimplification map from the moduli stack of semistable representations of the Jacobi algebra to the coarse moduli space of polystable representations. This enables us to construct a degeneration of the cohomological Hall algebra, for generic stability condition and fixed slope, to a free supercommutative algebra generated by a mixed Hodge structure categorifying the BPS invariants. As a corollary of this construction we furthermore obtain a Lie algebra structure on this mixed Hodge structure - the Lie algebra of BPS invariants - for which the entire cohomological Hall algebra can be seen as the positive part of a Yangian-type quantum group.Comment: v5 final version, 64 pages, to appear in Invent. Math. Many thanks to the anonymous referee for helpful suggestion

    Genotypes at the APOE and SCA2 loci do not predict the course of multiple sclerosis in patients of Portuguese origin

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    Prova tipográfica (In Press)Multiple sclerosis (MS) is a demyelinating disease that affects about one in 500 young Europeans. In order to test the previously proposed influence of the APOE and SCA2 loci on susceptibility to MS, we studied these loci in 243 Portuguese patients and 192 healthy controls and both parents of 92 patients. We did not detect any significant difference when APOE and SCA2 allele frequencies of cases and controls were compared, or when we compared cases with different forms of the disease. Disequilibrium of transmission was tested for both loci in the 92 trios, and we did not observe segregation distortion. To test the influence of the APOE o4 and SCA2 22 CAGs alleles on severity of disease, we compared age at onset and progression rate between groups with and without those alleles. We did not observe an association of the o4 or the 22 CAGs alleles with rate of progression in our total patient population; allele o4 was associated with increased rate of progression of MS in a subset of patients with less than 10 years of the disease. However, globally in the Portuguese population, the APOE and SCA2 genes do not seem to be useful in the clinical context as prognostic markers of this disorder.Fundação para a Ciência e a Tecnologia (FCT) - grant SFRH/BD/9111/2002.Serono Portugal
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