9,102 research outputs found

    A Third-order and a Fourth-order Iteration Process for Nonlinear Equations

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    Convergence proof and procedure for third-order and fourth-order iteration process for nonlinear equations - Newton-Raphson second-order iteratio

    Pathogenicity of anti-ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura.

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    BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally < 10%) has not been formally investigated. METHODS: We analysed 92 acquired TTP episodes at presentation, through treatment and remission/relapse using epitope mapping and functional analyses to understand the pathogenic mechanisms of anti-ADAMTS13 IgG. RESULTS: 89/92 of TTP episodes had IgG recognising the ADAMTS13 N-terminal domains. The central spacer domain was the only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in autoantibody specificity were detected in 9/16 patients at relapse, suggesting a continued development of the disease. Functional analyses on IgG from 43 patients revealed inhibitory IgG were limited to anti-spacer domain antibodies. However, 15/43 patients had autoantibodies with no detectable inhibitory action and as many as 32/43 patients had autoantibodies with inhibitory function that was insufficient to account for the severe deficiency state, suggesting that in many patients there is an alternative pathogenic mechanism. We therefore analysed plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We demonstrated markedly reduced ADAMTS13 antigen levels in all presentation samples, median 6% normal (range 0-47%), with 84/91 patients having < 25% ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation was associated with increased mortality (odds ratio 5.7). CONCLUSIONS: Anti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP

    Decision Tree Analysis as a Supplementary Tool to Enhance Histomorphological Differentiation when Distinguishing Human from Non-human Cranial Bone in both Burnt and Unburnt States: A feasibility study

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    This feasibility study was undertaken to describe and record the histological characteristics of burnt and unburnt cranial bone fragments from human and non-human bones. Reference series of fully mineralised, transverse sections of cranial bone, from all variables and specimen states were prepared by manual cutting and semi-automated grinding and polishing methods. A photomicrograph catalogue reflecting differences in burnt and unburnt bone from human and non-humans was recorded and qualitative analysis was performed using an established classification system based on primary bone characteristics. The histomorphology associated with human and non-human samples was, for the main part, preserved following burning at high temperature. Clearly, fibro-lamellar complex tissue subtypes, such as plexiform or laminar primary bone, were only present in non-human bones. A decision tree analysis based on histological features provided a definitive identification key for distinguishing human from non-human bone, with an accuracy of 100%. The decision tree for samples where burning was unknown was 96% accurate, and multi-step classification to taxon was possible with 100% accuracy. The results of this feasibility study, strongly suggest that histology remains a viable alternative technique if fragments of cranial bone require forensic examination in both burnt and unburnt states. The decision tree analysis may provide an additional, but vital tool to enhance data interpretation. Further studies are needed to assess variation in histomorphology taking into account other cranial bones, ontogeny, species and burning conditions

    Priority sectors in city regions? Some issues from a study of the Cardiff Capital Region

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    The City Region is becoming the spatial focus for economic development policy across many parts of the European continent. But these functional regions have taken on a new impetus in the UK with the introduction of ‘city deals’ aimed at improving network and coordination of actors in local authorities. One of the goals of city regions is to improve industrial policy particularly lacking since the abolition of many of the Regional Development Agencies across the UK. However, city regions in developing policy appear to be following in an unquestioning manner the industrial priorities of earlier institutions, and nowhere is this more obvious than in the case of the identification of priority industry development sectors. Too often the selection of industries and clusters for special support has been undertaken in an unquestioning manner. In this paper we focus on the case of the Cardiff Capital Region. We review approaches to identify priority sectors in this case and the problems associated with this policy approach

    Noncommutative resolutions of ADE fibered Calabi-Yau threefolds

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    In this paper we construct noncommutative resolutions of a certain class of Calabi-Yau threefolds studied by F. Cachazo, S. Katz and C. Vafa. The threefolds under consideration are fibered over a complex plane with the fibers being deformed Kleinian singularities. The construction is in terms of a noncommutative algebra introduced by V. Ginzburg, which we call the "N=1 ADE quiver algebra"

    Study of Giant Pairing Vibrations with neutron-rich nuclei

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    We investigate the possible signature of the presence of giant pairing states at excitation energy of about 10 MeV via two-particle transfer reactions induced by neutron-rich weakly-bound projectiles. Performing particle-particle RPA calculations on 208^{208}Pb and BCS+RPA calculations on 116^{116}Sn, we obtain the pairing strength distribution for two particles addition and removal modes. Estimates of two-particle transfer cross sections can be obtained in the framework of the 'macroscopic model'. The weak-binding nature of the projectile kinematically favours transitions to high-lying states. In the case of (~^6He, \~^4He) reaction we predict a population of the Giant Pairing Vibration with cross sections of the order of a millibarn, dominating over the mismatched transition to the ground state.Comment: Talk presented in occasion of the VII School-Semina r on Heavy Ion Physics hosted by the Flerov Laboratory (FLNR/JINR) Dubna, Russia from May 27 to June 2, 200

    PMS8 THE BUDGET IMPACT OF LOWER GPA ADHERENCE IN PATIENTS WITH CHRONIC NON-STEROIDAL AND COX-2 INHIBITOR USE

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