237 research outputs found

    New oral anticoagulants and their reversal agents

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    Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients\u27 quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

    A Unified Analysis of Balancing Domain Decomposition by Constraints for Discontinuous Galerkin Discretizations

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    The BDDC algorithm is extended to a large class of discontinuous Galerkin (DG) discretizations of second order elliptic problems. An estimate of C(1 + log(H/h))2 is obtained for the condition number of the preconditioned system where C is a constant independent of h or H or large jumps in the coefficient of the problem. Numerical simulations are presented which confirm the theoretical results. A key component for the development and analysis of the BDDC algorithm is a novel perspective presenting the DG discretization as the sum of element-wise “local” bilinear forms. The element-wise perspective allows for a simple unified analysis of a variety of DG methods and leads naturally to the appropriate choice for the subdomain-wise local bilinear forms. Additionally, this new perspective enables a connection to be drawn between the DG discretization and a related continuous finite element discretization to simplify the analysis of the BDDC algorithm.Boeing CompanyMassachusetts Institute of Technology (Zakhartchenko Fellowship

    Problematika određivanja količine istaloženih azotnih jedinjenja na slatinska staništa nacionalne ekološke mreže

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    The exceedance in the critical load of nitrogen compounds is used by the European Environment Agency as an indicator of the biodiversity loss risk. This paper provides a general overview of continental saline habitats vulnerability (Slatine - in Serbian) located in central Banat within the National Ecological Network, caused by the deposition of nitrogen compounds. These compounds originate from manure of selected category of animals raised in settlements located in the vicinity of protected areas. The data on short-range deposition of nitrogen compounds within two zones were used for determining the areas of impact: the zone of probable impact (0-500 m) and the zone of potential impact (500-2000 m). According to the calculation results, the most vulnerable locations which, for the most part, belong to 'Rusanda' protected area, are the pastures directly surrounding village Kumane, pastures bordering Rusanda salty lake, including the lake itself.Prekoračenja kritičnih opterećenja azotnim jedinjenjima se koriste kao indikatori rizika gubitka biodiverziteta od strane Evropske agencije za životnu sredinu. U radu je dat okvirni prikaz ugroženosti slatinskih staništa nacionalne ekološke mreže koja je uzrokovana taloženjem azotnih jedinjenja iz stajnjaka izabranih životinja, poreklom iz naselja koja se nalaze u okruženju zaštićenih područja srednjeg dela Banata. Za određivanje oblasti uticaja korišćeni su podaci o kratkom dometu taloženja azotnih jedinjenja, unutar dva pojasa: pojas verovatnog uticaja (od granice zaštićenog područja do 500 m) i pojas mogućeg uticaja (500-2000 m). Na osnovu rezultata proračuna, kao posebno ugroženi lokaliteti izdvajaju se pašnjačke površine u neposrednom okruženju naselja Kumane koje najvećim delom pripadaju zaštićenom području 'Rusanda', pašnjaci uz Rusandu, kao i samo jezero

    New oral anticoagulants and their reversal agents

    Get PDF
    Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients\u27 quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

    Early growth response gene-2 (Egr-2) regulates the development of B and T cells

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    The study was supported by Arthritis Research UK. Copyright @ 2011 Li et al.BACKGROUND: Understanding of how transcription factors are involved in lymphocyte development still remains a challenge. It has been shown that Egr-2 deficiency results in impaired NKT cell development and defective positive selection of T cells. Here we investigated the development of T, B and NKT cells in Egr-2 transgenic mice and the roles in the regulation of distinct stages of B and T cell development. METHODS AND FINDINGS: The expression of Egr1, 2 and 3 were analysed at different stages of T and B cell development by RT-PCT and results showed that the expression was strictly regulated at different stages. Forced expression of Egr-2 in CD2+ lymphocytes resulted in a severe reduction of CD4+CD8+ (DP) cells in thymus and pro-B cells in bone marrow, which was associated with reduced expression of Notch1 in ISP thymocytes and Pax5 in pro-B cells, suggesting that retraction of Egr-2 at the ISP and pro-B cell stages is important for the activation of lineage differentiation programs. In contrast to reduction of DP and pro-B cells, Egr-2 enhanced the maturation of DP cells into single positive (SP) T and NKT cells in thymus, and immature B cells into mature B cells in bone marrow. CONCLUSIONS: Our results demonstrate that Egr-2 expressed in restricted stages of lymphocyte development plays a dynamic, but similar role for the development of T, NKT and B cells.This article is provided by the Brunel Open Access publishing fund
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