Time courses and quantitative analysis of atrial fibrillation episode number and duration after circular plus linear left atrial lesions: trigger elimination or substrate modification: early or delayed cure?

OBJECTIVES We sought to analyze the time course of atrial fibrillation (AF) episodes before and after circular plus linear left atrial ablation and the percentage of patients with complete freedom from AF after ablation by using serial seven-day electrocardiograms (ECGs). BACKGROUND The curative treatment of AF targets the pathophysiological corner stones of AF (i.e., the initiating triggers and/or the perpetuation of AF). The pathophysiological complexity of both may not result in an "all-or-nothing" response but may modify number and duration of AF episodes. METHODS In patients with highly symptomatic AF, circular plus linear ablation lesions were placed around the left and right pulmonary veins, between the two circles, and from the left circle to the mitral annulus using the electroanatomic mapping system. Repetitive continuous 7-day ECGs administered before and after catheter ablation were used for rhythm follow-up. RESULTS In 100 patients with paroxysmal (n = 80) and persistent (n = 20) AF, relative duration of time spent in AF significantly decreased over time (35 +/- 37% before ablation, 26 +/- 41% directly after ablation, and 10 +/- 22% after 12 months). Freedom from AF stepwise increased in patients with paroxysmal AF and after 12 months measured at 88% or 74% depending on whether 24-h ECG or 7-day ECG was used. Complete pulmonary vein isolation was demonstrated in <20% of the circular lesions. CONCLUSIONS The results obtained in patients with AF treated with circular plus linear left atrial lesions strongly indicate that substrate modification is the main underlying pathophysiologic mechanism and that it results in a delayed cure instead of an immediate cure.

In vitro drug causality assessment in Stevens-Johnson syndrome - alternatives for lymphocyte transformation test

BACKGROUND Patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are often exposed simultaneously to a few potentially culprit drugs. However, both the standard lymphocyte transformation tests (LTT) with proliferation as the assay end-point as well as skin tests, if done, are often negative. OBJECTIVE As provocation tests are considered too dangerous, there is an urgent need to identify the relevant drug in SJS/TEN and to improve sensitivity of tests able to identify the causative drug. METHODS Fifteen patients with SJS/TEN with the ALDEN score ≥ 6 and 18 drug-exposed controls were included. Peripheral blood mononuclear cells (PBMC) were isolated and cultured under defined conditions with drugs. LTT was compared to the following end-points: cytokine levels in cell culture supernatant, number of granzyme B secreting cells by ELISpot and intracellular staining for granulysin and IFNγ in CD3(+) CD4(+), CD3(+) CD8(+) and NKp46(+) cells. To further enhance sensitivity, the effect of IL-7/IL-15 pre-incubation of PBMC was evaluated. RESULTS Lymphocyte transformation tests was positive in only 4/15 patients (sensitivity 27%, CI: 8-55%). Similarly, with granzyme B-ELISpot culprit drugs were positive in 5/15 patients (sensitivity 33%, CI: 12-62%). The expression of granulysin was significantly induced in NKp46(+) and CD3(+) CD4(+) cells (sensitivity 40%, CI: 16-68% and 53%, CI: 27-79% respectively). Cytokine production could be demonstrated in 38%, CI: 14-68% and 43%, CI: 18-71% of patients for IL-2 and IL-5, respectively, and in 55%, CI: 23-83% for IFNγ. Pre-incubation with IL-7/IL-15 enhanced drug-specific response only in a few patients. Specificities of tested assays were in the range of 95 (CI: 80-99%)-100% (CI: 90-100%). CONCLUSIONS AND CLINICAL RELEVANCE Granulysin expression in CD3(+) CD4(+) , Granzyme B-ELISpot and IFNγ production considered together provided a sensitivity of 80% (CI: 52-96%) and specificity of 95% (80-99%). Thus, this study demonstrated that combining different assays may be a feasible approach to identify the causative drug of SJS/TEN reactions; however, confirmation on another group of patients is necessary.

Comparing the performance of hyperbolic and circular rod quadrupole mass spectrometers with applied higher order auxiliary excitation

This work applies higher order auxiliary excitation techniques to two types of quadrupole mass spectrometers (QMSs): commercial systems and spaceborne instruments. The operational settings of a circular rod geometry commercial system and an engineering test-bed for a hyperbolic rod geometry spaceborne instrument were matched, with the relative performance of each sensor characterized with and without applied excitation using isotopic measurements of Kr+. Each instrument was operated at the limit of the test electronics to determine the effect of auxiliary excitation on extending instrument capabilities. For the circular rod sensor, with applied excitation, a doubling of the mass resolution at 1% of peak transmission resulted from the elimination of the low-mass side peak tail typical of such rod geometries. The mass peak stability and ion rejection efficiency were also increased by factors of 2 and 10, respectively, with voltage scan lines passing through the center of stability islands formed from auxiliary excitation. Auxiliary excitation also resulted in factors of 6 and 2 in peak stability and ion rejection efficiency, respectively, for the hyperbolic rod sensor. These results not only have significant implications for the use of circular rod quadrupoles with applied excitation as a suitable replacement for traditional hyperbolic rod sensors, but also for extending the capabilities of existing hyperbolic rod QMSs for the next generation of spaceborne instruments and low-mass commercial systems.

Das enthüllte Preußenthum oder Deutschlands Zukunft unter Preußischer Oberherrschaft, unter welcher Gestalt sie auch eintrete : Mit besonderer Rücksicht auf die Preußische Circular-Note vom 23. Januar 1849

Boberach: Die preußische Zirkularnote für einen Engeren Bund ist ein Meisterstück der Diplomatie, aber Preußen und seinem König ist nicht zu trauen, sie würden nur ein preußisches Kaisertum mit preußischer Bürokratie aufrichten. Das preußische Großmachtstreben würde sofort die kleineren Einzelstaaten bedrohen. - Wentzke: Die Note an und für sich ist ein diplomatisches Meisterstück, indem sie die Notwendigkeit des österreichischen Kaiserstaates für Deutschland und die Ehrlichkeit der preußischen Politik hervorhebt. Leider aber hat die Vergangenheit Preußens, seine Großmachtsgelüste, zu tiefen Anlaß zum Mißtrauen gegeben. Dazu hat die Heuchelei der Reaktion unter Friedrich Wilhelm IV. den Höhepunkt erreicht. Wird Preußens König deutscher Kaiser, so wird er zunächst die kleineren Staaten vernichten und durch seine Bureaukratie das preußische Kaisertum aufrichten

What do brain network interactions tell about cognitive processes? How to seek causality?

Optimal adjustment of brain networks allows the biased processing of information in response to the demand of environments and is therefore prerequisite for adaptive behaviour. It is widely shown that a biased state of networks is associated with a particular cognitive process. However, those associations were identified by backward categorization of trials and cannot provide a causal association with cognitive processes. This problem still remains a big obstacle to advance the state of our field in particular human cognitive neuroscience. In my talk, I will present two approaches to address the causal relationships between brain network interactions and behaviour. Firstly, we combined connectivity analysis of fMRI data and a machine leaning method to predict inter-individual differences of behaviour and responsiveness to environmental demands. The connectivity-based classification approach outperforms local activation-based classification analysis, suggesting that interactions in brain networks carry information of instantaneous cognitive processes. Secondly, we have recently established a brand new method combining transcranial alternating current stimulation (tACS), transcranial magnetic stimulation (TMS), and EEG. We use the method to measure signal transmission between brain areas while introducing extrinsic oscillatory brain activity and to study causal association between oscillatory activity and behaviour. We show that phase-matched oscillatory activity creates the phase-dependent modulation of signal transmission between brain areas, while phase-shifted oscillatory activity blunts the phase-dependent modulation. The results suggest that phase coherence between brain areas plays a cardinal role in signal transmission in the brain networks. In sum, I argue that causal approaches will provide more concreate backbones to cognitive neuroscience.

Circular Nº 1

Primera circular de las XXI Jornadas de Cátedra y Carreras de Educación Especial de las Universidades Nacionales (RUEDES) y XV Jornadas Nacionales de la Red de Estudiantes de Cátedras y Carreras de Educación Especial (RECCEE). Se desarrollarán el 6,7 y 8 de septiembre de 2012 en la Facultad de Humanidades y Ciencias Sociales de la Universidad Nacional de la Patagonia San Juan Bosco (Comodoro Rivadavia, Chubut, Argentina). El tema de estas Jornadas es "las relaciones entre la educación común y especial. Dilemas de una construcción socio-educativa".

Córdoba en pedazos : habitar/circular en contextos sociosegregados

La ciudad de Córdoba se ha ido constituyendo como ciudad turística/ciudad espectáculo, a través de un “embellecimiento estratégico" que la vuelve extraña a sus propios habitantes, especialmente a los de clases subalternas. Las presentes reflexiones abordan las experiencias de habitar/desplazarse por la ciudad de estos sujetos durante la última década. Partimos de una breve referencia a la forma sociohabitacional ciudad barrio como respuesta de vivienda social generada por el Gobierno Provincial que impactó fuertemente en la experiencia de los “beneficiarios" como en el perfil de la ciudad. Desde una perspectiva metodológica en clave benjaminiana orientada a “pensar en/a partir de imágenes", presentamos algunas escenas expresivas de los modos de habitar, percibir y sentirse en la ciudad, algunas imágenes que condensan ciertos estados de sentir que manifiestan los pobladores -mediante la palabra pero también mediante la forma de apropiación de la vivienda y del barrio observada-. Ponemos en juego estas imágenes con otras, producto de una encuesta realizada en las ciudades barrio. Buscamos así reconstruir algunos de los fragmentos de la urbe cordobesa tal como es vivida, pedazos que abarcan el mero espacio de la casa, y trayectos fuertemente segregados por clase.