The use of embolic signal detection in multicenter trials to evaluate antiplatelet efficacy: signal analysis and quality control mechanisms in the CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial

<p><b>Background and Purpose:</b> The CARESS (Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic carotid Stenosis) trial proved the effectiveness of the combination of clopidogrel and aspirin compared with aspirin alone in reducing presence and number of microembolic signals (MES) in patients with recently symptomatic carotid stenosis. The present study aimed at installing primary and secondary quality control measures in CARESS because MES evaluation relies on subjective judgment by human experts.</p> <p><b>Methods:</b> As primary quality control, centers participating in CARESS evaluated a reference digital audio tape (DAT) before the study containing both MES and artifacts. Interobserver agreement of classifying signals as MES was expressed as proportions of specific agreement of positive ratings (ps±values). For all DATs included in CARESS (n=300), online number of MES and off-line number of MES read by the central reader were compared using correlation coefficients. As secondary control, a sample of 16 of 300 DATs was cross-validated by another independent reader (post-trial validator).</p> <p><b>Results:</b> For the reference tape, the cumulative ps±value was 0.894 based on 12 of 14 observers. Two observers with very different results improved after a training procedure. Agreement between post-trial validator and central reader was ps+=0.805, indicating very good agreement. Correlation between online evaluation and off-line evaluation of DATs was very good overall (cumulative ρ=0.84; P<0.001).</p> <p><b>Conclusion:</b> Multicenter studies using MES as outcome parameter are feasible. However, primary and secondary quality control procedures are important.</p&gt

A dynamic logic for every season

This paper introduces a method to build dynamic logics with a graded semantics. The construction is parametrized by a structure to support both the spaces of truth and of the domain of computations. Possible instantiations of the method range from classical assertional) dynamic logic to less common graded logics suitable to deal with programs whose transitional semantics exhibits fuzzy or weighted behaviour.This leads to the systematic derivation of program logics tailored to specific program classes

Extreme objects with arbitrary large mass, or density, and arbitrary size

We consider a generalization of the interior Schwarzschild solution that we match to the exterior one to build global C^1 models that can have arbitrary large mass, or density, with arbitrary size. This is possible because of a new insight into the problem of localizing the center of symmetry of the models and the use of principal transformations to understand the structure of space.Comment: 20 pages, 6 figures. Fixed one reference. Added a new equatio

Avalanches in self-organized critical neural networks: A minimal model for the neural SOC universality class

The brain keeps its overall dynamics in a corridor of intermediate activity and it has been a long standing question what possible mechanism could achieve this task. Mechanisms from the field of statistical physics have long been suggesting that this homeostasis of brain activity could occur even without a central regulator, via self-organization on the level of neurons and their interactions, alone. Such physical mechanisms from the class of self-organized criticality exhibit characteristic dynamical signatures, similar to seismic activity related to earthquakes. Measurements of cortex rest activity showed first signs of dynamical signatures potentially pointing to self-organized critical dynamics in the brain. Indeed, recent more accurate measurements allowed for a detailed comparison with scaling theory of non-equilibrium critical phenomena, proving the existence of criticality in cortex dynamics. We here compare this new evaluation of cortex activity data to the predictions of the earliest physics spin model of self-organized critical neural networks. We find that the model matches with the recent experimental data and its interpretation in terms of dynamical signatures for criticality in the brain. The combination of signatures for criticality, power law distributions of avalanche sizes and durations, as well as a specific scaling relationship between anomalous exponents, defines a universality class characteristic of the particular critical phenomenon observed in the neural experiments. The spin model is a candidate for a minimal model of a self-organized critical adaptive network for the universality class of neural criticality. As a prototype model, it provides the background for models that include more biological details, yet share the same universality class characteristic of the homeostasis of activity in the brain.Comment: 17 pages, 5 figure

Relativistic Celestial Mechanics with PPN Parameters

Starting from the global parametrized post-Newtonian (PPN) reference system with two PPN parameters $\gamma$ and $\beta$ we consider a space-bounded subsystem of matter and construct a local reference system for that subsystem in which the influence of external masses reduces to tidal effects. Both the metric tensor of the local PPN reference system in the first post-Newtonian approximation as well as the coordinate transformations between the global PPN reference system and the local one are constructed in explicit form. The terms proportional to $\eta=4\beta-\gamma-3$ reflecting a violation of the equivalence principle are discussed in detail. We suggest an empirical definition of multipole moments which are intended to play the same role in PPN celestial mechanics as the Blanchet-Damour moments in General Relativity. Starting with the metric tensor in the local PPN reference system we derive translational equations of motion of a test particle in that system. The translational and rotational equations of motion for center of mass and spin of each of $N$ extended massive bodies possessing arbitrary multipole structure are derived. As an application of the general equations of motion a monopole-spin dipole model is considered and the known PPN equations of motion of mass monopoles with spins are rederived.Comment: 71 page

Post-Newtonian approximation for isolated systems calculated by matched asymptotic expansions

Two long-standing problems with the post-Newtonian approximation for isolated slowly-moving systems in general relativity are: (i) the appearance at high post-Newtonian orders of divergent Poisson integrals, casting a doubt on the soundness of the post-Newtonian series; (ii) the domain of validity of the approximation which is limited to the near-zone of the source, and prevents one, a priori, from incorporating the condition of no-incoming radiation, to be imposed at past null infinity. In this article, we resolve the problem (i) by iterating the post-Newtonian hierarchy of equations by means of a new (Poisson-type) integral operator that is free of divergencies, and the problem (ii) by matching the post-Newtonian near-zone field to the exterior field of the source, known from previous work as a multipolar-post-Minkowskian expansion satisfying the relevant boundary conditions at infinity. As a result, we obtain an algorithm for iterating the post-Newtonian series up to any order, and we determine the terms, present in the post-Newtonian field, that are associated with the gravitational-radiation reaction onto an isolated slowly-moving matter system.Comment: 61 pages, to appear in Phys. Rev.

Magnetic and intruder rotational bands in (113)In

©2005 American Physical SocietyExcited states in ¹¹³In were populated via the reactions ¹⁰⁰Mo(¹⁸O,p4n)¹¹³In and ¹¹⁰Pd(7Li,4n)¹¹³In. The two known ΔJ = 2 intruder bands, based on the πg7/2 ⊗ d5/2 and πh11/2 orbitals, have been extended by 8¯h to spins (49/2+)¯h and (55/2−)¯h, respectively. The previous finding of three sequences of ΔJ = 1 γ -ray transitions has been confirmed. A self-consistent cranked shell-model calculation gives a good description of the contrasting alignment patterns of the two ΔJ = 2 intruder bands. The intruder bands, the known sequences ofM1 transitions, and spherical levels together represent a coexistence of three different excitation modes in this nucleus.S. Naguleswaran, R. S. Chakrawarthy, U. Garg, K. L. Lamkin, G. Smith, J. C. Walpe, A. Galindo-Uribarri, V. P. Janzen, D. C. Radford, R. Kaczarowski, D. B. Fossan, D. R. Lafosse, P. Vaska, Ch. Droste, T. Morek, S. Pilotte, J. DeGraaf, T. Drake, and R. Wys

THE UTILISATION OF VALUE BASED MANAGEMENT IN THE STRATEGIC MANAGEMENT OF GERMAN’S AUTOMOTIVE INDUSTRY

The purpose of this research paper is to analyse the value-based management commitment of automotive enterprises and to examine the factors that explain the control parameters in automotive industry. There have been a few empirical studies published in the German’s automotive sector but most of the existing studies failed to provide evidence of utilisation of value-based management in the strategic management in the automotive sector. The German automotive industry’s development is closely related to global economic developments. Previous research work has considered control parameters of enterprises but there is little evidence on the factors that explain which control parameters are used in automotive industry. A survey based on annual reports from the year 2008 to 2011 is used. In total, 20 annual reports of automotive companies were analysed. The results show that automotive companies, especially Original Equipment Manufacturers (OEMs) and listed suppliers, have committed to value-oriented management and have implemented value-oriented approaches. However, not all of the suppliers are communicating this in their reports. The results also show that Economic Value Added (EVA) is the leading key indicator in the automotive industry

Impact of voluntary exercise and housing conditions on hippocampal glucocorticoid receptor, miR-124 and anxiety

Background: Lack of physical activity and increased levels of stress contribute to the development of multiple physical and mental disorders. An increasing number of studies relate voluntary exercise with greater resilience to psychological stress, a process that is highly regulated by the hypothalamic-pituitary-adrenal (HPA) axis. However, the molecular mechanisms underlying the beneficial effects of exercise on stress resilience are still poorly understood. Here we have studied the impact of long term exercise and housing conditions on: a) hippocampal expression of glucocorticoid receptor (Nr3c1), b) epigenetic regulation of Nr3c1 (DNA methylation at the Nr3c1-1F promoter and miR-124 expression), c) anxiety (elevated plus maze, EPM), and d) adrenal gland weight and adrenocorticotropic hormone receptor (Mc2r) expression. Results: Exercise increased Nr3c1 and Nr3c1-1F expression and decreased miR-124 levels in the hippocampus in single-housed mice, suggesting enhanced resilience to stress. The opposite was found for pair-housed animals. Bisulfite sequencing showed virtually no DNA methylation in the Nr3c1-1F promoter region. Single-housing increased the time spent on stretch attend postures. Exercise decreased the time spent at the open arms of the EPM, however, the mobility of the exercise groups was significantly lower. Exercise had opposite effects on the adrenal gland weight of single and pair-housed mice, while it had no effect on adrenal Mc2r expression. Conclusions: These results suggest that exercise exerts a positive impact on stress resilience in single-housed mice that could be mediated by decreasing miR-124 and increasing Nr3c1 expression in the hippocampus. However, pair-housing reverses these effects possibly due to stress from dominance disputes between pairs