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

Heavy-Fermions in LiV2O4: Kondo-Compensation vs. Spin-Liquid Behavior?

7Li NMR measurements were performed in the metallic spinel LiV2O4. The temperature dependencies of the line width, the Knight shift and the spin-lattice relaxation rate were investigated in the temperature range 30 mK < T < 280 K. For temperatures T < 1 K we observe a spin-lattice relaxation rate which slows down exponentially. The NMR results can be explained by a spin-liquid behavior and the opening of a spin gap of the order 0.6 K

An evaluation of cross-efficiency methods: With an application to warehouse performance

Cross-efficiency measurement is an extension of Data Envelopment Analysis that allows for tie-breaking ranking of the Decision Making Units (DMUs) using all the peer evaluations. In this article we examine the theory of cross-efficiency measurement by comparing a selection of methods popular in the literature. These methods are applied to performance measurement of European warehouses. We develop a cross-efficiency method based on a rank-order DEA model to accommodate the ordinal nature of some key variables characterizing warehouse performance. This is one of the first comparisons of methods on a real-life dataset and the first time that a model allowing for qualitative variables is included in such a comparison. Our results show that the choice of model matters, as one obtains statistically different rankings from each one of them. This holds in particular for the multiplicative and game-theoretic methods whose results diverge from the classic method. From a managerial perspective, focused on the applicability of the methods, we evaluate them through a multidimensional metric which considers their capability to rank DMUs, their ease of implementation, and their robustness to sensitivity analyses. We conclude that standard weight-restriction methods, as initiated by Sexton et al. [48], perform as well as recently introduced, more sophisticated alternativesSpanish Ministry of Science and Innovation (Ministerio de Ciencia e Innovación), the State Research Agency (Agencia Estatal de Investigación) and the European Regional Development Fund (Fondo Europeo de Desarrollo Regional) under grants EIN2020-11226

Consensus recommendations for transcranial color-coded duplex sonography for the assessment of intracranial arteries in clinical trials on acute stroke

BACKGROUND AND PURPOSE: Transcranial color-coded duplex sonography has become a standard diagnostic technique to assess the intracranial arterial status in acute stroke. It is increasingly used for the evaluation of prognosis and the success of revascularization in multicenter trials. The aim of this international consensus procedure was to develop recommendations on the methodology and documentation to be used for assessment of intracranial occlusion and for monitoring of recanalization. METHODS: Thirty-five experts participated in the consensus process. The presented recommendations were approved during a meeting of the consensus group in October 2008 in Giessen, Germany. The project was an initiative of the German Competence Network Stroke and performed under the auspices of the Neurosonology Research Group of the World Federation of Neurology. RESULTS: Recommendations are given on how examinations should be performed in the time-limited situation of acute stroke, including criteria to assess the quality of the acoustic bone window, the use of echo contrast agents, and the evaluation of intracranial vessel status. The important issues of the examiners' training and experience, the documentation, and analysis of study results are addressed. One central aspect was the development of standardized criteria for diagnosis of arterial occlusion. A transcranial color-coded duplex sonography recanalization score based on objective hemodynamic criteria is introduced (consensus on grading intracranial flow obstruction [COGIF] score). CONCLUSIONS: This work presents consensus statements in an attempt to standardize the application of transcranial color-coded duplex sonography in the setting of acute stroke research, aiming to improve the reliability and reproducibility of the results of future stroke studies

Development of a High-Throughput Screening Assay Based on the 3-Dimensional Pannus Model for Rheumatoid Arthritis

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.The 3-dimensional (3-D) pannus model for rheumatoid arthritis (RA) is based on the interactive co-culture of cartilage and synovial fibroblasts (SFs). Besides the investigation of the pathogenesis of RA, it can be used to analyze the active profiles of antirheumatic pharmaceuticals and other bioactive substances under in vitro conditions. For a potential application in the industrial drug-screening process as a transitional step between 2-dimensional (2-D) cell-based assays and in vivo animal studies, the pannus model was developed into an in vitro high-throughput screening (HTS) assay. Using the CyBi™-Disk workstation for parallel liquid handling, the main cell culture steps of cell seeding and cultivation were automated. Chondrocytes were isolated from articular cartilage and seeded directly into 96-well microplates in high-density pellets to ensure formation of cartilage-specific extracellular matrix (ECM). Cell seeding was performed automatically and manually to compare both processes regarding accuracy, reproducibility, consistency, and handling time. For automated cultivation of the chondrocyte pellet cultures, a sequential program was developed using the CyBio Control software to minimize shear forces and handling time. After 14 days of cultivation, the pannus model was completed by coating the cartilage pellets with a layer of human SFs. The effects due to automation in comparison to manual handling were analyzed by optical analysis of the pellets, histological and immunohistochemical staining, and real-time PCR. Automation of this in vitro model was successfully achieved and resulted in an improved quality of the generated pannus cultures by enhancing the formation of cartilage-specific ECM. In addition, automated cell seeding and media exchange increased the efficiency due to a reduction of labor intensity and handling time. (Journal of Biomolecular Screening 2007:956-965)BMBF, 0313604A, Verbundprojekt: Evaluierung eines interagierenden 3D Testsystems als Krankheitsmodell der rheumatoiden Arthritis (in vitro Pannus Modell) zur effektiven Prüfung von Wirkstoffen, Teilprojekt 1BMBF, 0313604B, Verbundprojekt: Entwicklung eines interagierenden 3D Testsystems als Krankheitsmodell der rheumatoiden Arthritis (in vitro Pannus Modell) zur effektiven Prüfung von Wirkstoffen, Teilprojekt

Dynamical effects induced by long range activation in a nonequilibrium reaction-diffusion system

We both show experimentally and numerically that the time scales separation introduced by long range activation can induce oscillations and excitability in nonequilibrium reaction-diffusion systems that would otherwise only exhibit bistability. Namely, we show that the Chlorite-Tetrathionate reaction, where autocatalytic species diffuses faster than the substrates, the spatial bistability domain in the nonequilibrium phase diagram is extended with oscillatory and excitability domains. A simple model and a more realistic model qualitatively account for the observed behavior. The latter model provides quantitative agreement with the experiments.Comment: 19 pages + 9 figure

Overcoming water diffusion limitations in hydrogels via microtubular graphene networks for soft actuators

Hydrogel-based soft actuators can operate in sensitive environments, bridging the gap of rigid machines interacting with soft matter. However, while stimuli-responsive hydrogels can undergo extreme reversible volume changes of up to ~90%, water transport in hydrogel actuators is in general limited by their poroelastic behavior. For poly(N-isopropylacrylamide) (PNIPAM) the actuation performance is even further compromised by the formation of a dense skin layer. Here we show, that incorporating a bioinspired microtube graphene network into a PNIPAM matrix with a total porosity of only 5.4 % dramatically enhances actuation dynamics by up to ~400 % and actuation stress by ~4000 % without sacrificing the mechanical stability, overcoming the water transport limitations. The graphene network provides both untethered light-controlled and electrically-powered actuation. We anticipate that the concept provides a versatile platform for enhancing the functionality of soft matter by combining responsive and two-dimensional materials, paving the way towards designing soft intelligent matter.Comment: Shared First-authorship: Margarethe Hauck and Lena Marie Saur

Stability of a metallic state in the two-orbital Hubbard model

Electron correlations in the two-orbital Hubbard model at half-filling are investigated by combining dynamical mean field theory with the exact diagonalization method. We systematically study how the interplay of the intra- and inter-band Coulomb interactions, together with the Hund coupling, affects the metal-insulator transition. It is found that if the intra- and inter-band Coulomb interactions are nearly equal, the Fermi-liquid state is stabilized due to orbital fluctuations up to fairly large interactions, while the system is immediately driven to the Mott insulating phase away from this condition. The effects of the isotropic and anisotropic Hund coupling are also addressed.Comment: 7 pages, 9 figure