Антикоагулянтная терапия при фибрилляции предсердий в реальной практике: проблемы и перспективы

In the review of the current literature urgent issues of treatment of patients with atrial fibrillation are analyzed, namely prevention of thrombosis and the use of anticoagulants therapy. The article describes the current possibilities of prevention thromboembolic complications in patients with atrial fibrillation at high risk. The fact of insufficient use of preventive antithrombotic therapy in patients with atrial fibrillation with high thrombotic risk is demonstrated, which is associated both with incomplete adherence of doctors to the implementation of clinical recommendations, and with low adherence of patients to receiving prescribed anticoagulants. The review of the literature discusses the difficulties of the use of oral anticoagulants, in particular direct action and their high financial burden, and anticoagulants indirect action and instability of their pharmacological effect. The article demonstrates the difficulties of warfarin therapy, such as insufficient adherence to treatment, genetic characteristics of the patient, alimentary and drug interactions. When discussing the issue of insufficient adherence, it is shown that the data on adherence to drug therapy are not homogeneous and do not fully take into account the influence of patient-dependent characteristics. The prospects of developing an individualized algorithm for choosing an anticoagulant for long-term administration for patients with atrial fibrillation from the position of a patient-oriented approach are separately discussed.В обзоре современной литературы анализируются актуальные проблемы лечения больных фибрилляцией предсердий, а именно тромбопрофилактика и применение антикоагулянтной терапии. В статье описываются современные возможности профилактики тромбоэмболических осложнений у больных фибрилляцией предсердий высокого риска. Демонстрируется факт недостаточного использования профилактической антитромботической терапии у пациентов при фибрилляции предсердий с высоким тромботическим риском, что связано как с неполным выполнением клинических рекомендаций врачом, так и с низкой приверженностью пациентов к приему назначенных антикоагулянтов. В обзоре литературы обсуждаются трудности применения оральных антикоагулянтов, в частности препаратов прямого действия и их высокое финансовое бремя, а также антикоагулянтов непрямого действия и нестабильность их фармакологического эффекта. В статье демонстрируются трудности терапии варфарином, такие как недостаточная приверженность лечению, генетические особенности пациента, алиментарные и лекарственные взаимодействия. Показано, что данные по приверженности к лекарственной терапии не отличаются однородностью и не в полной мере учитывают влияние пациентзависимых характеристик. Отдельно обсуждается разработка индивидуализированного алгоритма по выбору антикоагулянта для длительного применения у больных фибрилляцией предсердий с позиции пациентоориентированного подхода

Isovector soft dipole mode in 6Be

By using the 1H(6Li,6Be)n charge-exchange reaction, continuum states in 6Be were populated up to E_t=16 MeV, E_t being the 6Be energy above its three-body decay threshold. In kinematically complete measurements performed by detecting alpha+p+p coincidences, an E_t spectrum of high statistics was obtained, containing approximately ~5x10^6 events. The spectrum provides detailed correlation information about the well-known 0^+ ground state of 6Be at E_t=1.37 MeV and its 2^+ state at E_t=3.05 MeV. Moreover, a broad structure extending from 4 to 16 MeV was observed. It contains negative parity states populated by Delta L=1 angular momentum transfer without other significant contributions. This structure can be interpreted as a novel phenomenon, i.e. the isovector soft dipole mode associated with the 6Li ground state. The population of this mode in the charge-exchange reaction is a dominant phenomenon for this reaction, being responsible for about 60% of the cross section obtained in the measured energy range.Comment: 8 pages, 7 figure

Theory and computation of covariant Lyapunov vectors

Lyapunov exponents are well-known characteristic numbers that describe growth rates of perturbations applied to a trajectory of a dynamical system in different state space directions. Covariant (or characteristic) Lyapunov vectors indicate these directions. Though the concept of these vectors has been known for a long time, they became practically computable only recently due to algorithms suggested by Ginelli et al. [Phys. Rev. Lett. 99, 2007, 130601] and by Wolfe and Samelson [Tellus 59A, 2007, 355]. In view of the great interest in covariant Lyapunov vectors and their wide range of potential applications, in this article we summarize the available information related to Lyapunov vectors and provide a detailed explanation of both the theoretical basics and numerical algorithms. We introduce the notion of adjoint covariant Lyapunov vectors. The angles between these vectors and the original covariant vectors are norm-independent and can be considered as characteristic numbers. Moreover, we present and study in detail an improved approach for computing covariant Lyapunov vectors. Also we describe, how one can test for hyperbolicity of chaotic dynamics without explicitly computing covariant vectors.Comment: 21 pages, 5 figure

Особенности пробоподготовки лизатов для повышения эффективности выделения белковых партнеров целевых белков, кодируемых генами 18-ой хромосомы человека

The aim of this work was to test modifications of the standard protocol for the sample preparation of cell/tissue lysate before performing the affinity isolation of lysate protein partners for the target protein (bait protein) which is covalently immobilized on an inert sorbent (e.g. BrCN-, SH-Sepharose 4B) or a carrier (e.g. paramagnetic nanoparticles). The series of our previous works on applying the approach to direct molecular fishing procedure with combination of affinity chromatography and LC-MS/MS analysis using a number of proteins, encoded by the genes of human chromosome 18, have shown that there are at least two problems affecting the specificity and the effectiveness of this procedure. These include: (i) redundancy of the background proteins in the eluates from an affinity sorbent (carrier) due to isolation of multiprotein complexes “labeled” with a direct protein partner which binds with a bait protein immobilized on the sorbent; (ii) low enrichment of the eluates with appropriate protein partners due to the fact that some direct protein partners in the lysate exist in stable “wild type” complexes with the bait protein itself. This means that latter group of protein partners will not be sufficiently isolated from lysate. Therefore, in order to increase the specificity and efficiency of affinity isolation of protein partners for the bait protein, we modified the standard protocol of lysate preparation and the preliminary step on dissociation of lysate protein complexes was added. Several model experiments for the choice of regeneration solution, assessment of their efficiency in the dissociation of lysate protein complexes as well as the stability and binding capacity of proteins were performed under the control of surface plasmon resonance (SPR) biosensor Biacore 3000 using HepG2 cell lysate. It was shown that acid treatment and incubation of the cell lysate for one min on ice (final lysate dilution 20 times) and subsequent neutralization (pH shift from 2.0 to 7.4) resulted in maximal dissociation of the lysate protein complexes without significant negative effects on the protein-protein interactions tested.Целью работы было экспериментальное тестирование модификации стандартного протокола пробоподготовки клеточного/ тканевого лизата перед выполнением процедуры аффинного выделения из него белков-партнеров для целевого белка (белка-наживки), иммобилизованного на инертном сорбенте или парамагнитных наночастицах. Цикл наших предыдущих работ, посвященных прямому молекулярному фишингу с сопряжением хроматографических и масс-спектрометрических методов и технологии парамагнитных наночастиц c использованием ряда белков 18-ой хромосомы человека и также других белков показал, что существуют, по крайне мере, две проблемы, влияющие на специфичность и эффективность данной процедуры: (i) избыточность фоновых белков в элюатах с аффинного сорбента, обусловленная выделением мультибелковых комплексов, меченых прямым партнером, который связывается с целевым белком на сорбенте; (ii) низкая обогащенность элюатов белками-партнерами целевой группы обусловленная тем, что та или иная часть прямых белков-партнеров в лизате находится в составе стабильных комплексов «дикого типа» с самим белком-наживкой и не будет в достаточной степени выделена из лизата. Поэтому для повышения специфичности и эффективности аффинного выделения белков-партнеров целевого белка нами предложена модификация стандартной пробоподготовки, заключающаяся в предварительной диссоциации белковых комплексов лизата. Модельные эксперименты по выбору регенерационного раствора, оценке стабильности и связывающей способности белков при его воздействии, а также оценка эффективности диссоциации комплексов в лизате были выполнены под контролем оптического биосенсора Biacore 3000 («GE Healthcare», США) с использованием лизата клеточной культуры гепатокарциномы человека (HepG2) и рекомбинантных препаратов белков, кодируемых генами 18-ой хромосомы человека, Показано, что кислотная обработка разбавленного в 20 раз лизата с кратковременной экспозицией в течение 1 мин на льду и с последующей нейтрализацией (с рН 2.0 до рН 7.4) приводила к максимальной диссоциации белковых комплексов лизата, не оказывая существенного негативного влияния на тестируемые белок- белковые взаимодействия

Distribution of sedimentary rock types through time in a back-arc basin: A case study from the Jurassic of the Greater Caucasus (Northern Neotethys)

Abstract The evolution of sedimentary basins can be explored by analyzing the changes in their lithologies and lithofacies (i.e. predominant lithologies). The Greater Caucasus Basin, which was located at the northern margin of the Neotethys Ocean, represents a complete Sinemurian-Tithonian succession. A quantitative analysis of compiled datasets suggests that principal lithologies and lithofacies are represented by siliciclastics, shale and carbonates. The relative abundance of siliciclastics and shale decreased throughout the Jurassic, whereas that of carbonates increased. Evaporites are known from the Upper Jurassic, while volcaniclastics and volcanics, as well as coals, are known only in the Lower to Middle Jurassic. Siliceous rocks are extremely rare. Lithology and lithofacies proportions change accordingly. The Sinemurian-Bathonian sedimentary complex is siliciclastic-and-shale-dominated, whereas the Callovian-Tithonian sedimentary complex is carbonate-dominated. A major change in the character of sedimentation occurred during the Aalenian-Callovian time interval. Regional transgressions and regressions were more important controls of changes in the sedimentary rock proportions than average basin depth. Landward shoreline shifts were especially favorable for carbonate accumulation, whereas siliciclastics and shale were deposited preferentially in regressive settings. An extended area of the marine basin, its lower average depth, and a sharp bathymetric gradient favored a higher diversity of sedimentation. An orogeny at the Triassic-Jurassic transition was responsible for a large proportion of siliciclastics and extensive conglomerate deposition. An arcarc collision in the Middle Jurassic also enhanced the siliciclastic deposition. Both phases of tectonic activity were linked with an increase in volcanics and volcaniclastics. Volcanism itself might have been an important control on sedimentation. A transition to carbonate-dominated sedimentation occurred in the Late Jurassic, reflecting a tectonically calm period

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters