Untersuchung der Strukturdynamik von offenporigen Schäumen

Ziel der Dissertation war die Schaffung einer Simulationskette, die auf Basis der Charakteristika eines Schaumes eine Vorhersage über die Verteilung der Eigenkreisfrequenzen dieser Schaumsorte ermöglicht. Zur Validierung der Simulationskette dienen an verschiedenen Schaumproben gemessene Eigenkreisfrequenzen für Längs- und Biegeschwingungen. Die Modellierung erfolgte als räumlicher stochastischer Prozess mithilfe der harmonischen Synthese. Notwendige Eingangsgrößen konnten anhand von CT-Scans der Proben bestimmt werden. Zur Bestimmung der Eigenkreisfrequenzen wurden eindimensionale Ansätze wie der Rayleigh-Quotient und die Finite Cell Method (FCM) als dreidimensionaler Ansatz getestet. Es konnte gezeigt werden, dass die FCM in Verbindung mit den modellierten räumlichen Prozessen die gemessenen Verteilungen der Eigenkreisfrequenzen gut abbilden kann. Der eindimensionale Berechnungsansatz eignet sich ebenfalls, jedoch nur für homogene und isotrope Schäume.:Einleitung 1.1 Einordnung 1.2 Charakterisierung von Schäumen 1.3 Motivation 1.4 Aufgaben und Aufbau der Arbeit 2 Wahrscheinlichkeitsrechnung und stochastische Prozesse 2.1 Wahrscheinlichkeitsrechnung und Zufallsvariablen 2.1.1 Wahrscheinlichkeitsrechnung 2.1.2 Zufallsvariablen 2.2 Stochastische Prozesse 2.2.1 Kenngrößen stochastischer Prozesse 2.2.2 Eigenschaften stochastischer Prozesse 2.2.3 Spektralanalyse stationärer stochastischer Prozesse 2.2.4 Schätztheorie 3 Analyse der Schaumproben 3.1 Probekörper 3.2 Auswertung der CT-Daten 3.2.1 Kalibrierung der Grauwerte 3.2.2 Verteilungsfunktion und Mittelwert 3.2.3 Varianz des Schwankungsanteils und mittlerer Füllgrad 3.2.4 Leistungsdichtespektrum und Autokorrelation 3.2.5 Porendurchmesser und Anisotropie 3.2.6 Flächeninhalt und Flächenträgheitsmoment 3.3 Messung des dynamischen Verhaltens 3.3.1 Theoretische Grundlagen zur Auswertung 3.3.2 Vorbereitung der Proben 3.3.3 Längseigenkreisfrequenzen 3.3.4 Biegeeigenkreisfrequenzen 3.3.5 Fazit 4 Simulationsmodelle zur Nachbildung von Schäumen 4.1 Vorüberlegungen zur Modellierung 4.2 Theoretische Grundlagen zur Erzeugung eindimensionaler stochastischer Prozesse 4.2.1 Karhunen-Loeve-Transformation . 4.2.2 Harmonische Synthese 4.2.3 Ergebnisse für Flächeninhaltsprozesse 4.3 Simulation mehrdimensionaler stochastischer Prozesse 4.3.1 Bewertungskriterien für die Qualität der Simulation 4.3.2 Ergebnisse für die virtuellen Schäume 4.3.3 Verbesserter Algorithmus 4.4 Vergleich von virtuellen Schäumen und CT-Daten 4.4.1 Keramikschäume 4.4.2 Metallschäume 4.4.3 Anmerkungen und Fazit 4.5 Erweiterung um den Mittelwert 4.6 Konzept zur Simulation von Prozessen größerer Abmessungen 4.7 Fazit 5 Bestimmung der Eigenkreisfrequenzen 5.1 Materialmodelle für die Betrachtung als eindimensionales Kontinuum 5.2 Eindimensionale Modelle 5.2.1 Modell mit konstantem Querschnitt 5.3 Eindimensionales Modell mit Berücksichtigung der Mikrostruktur 5.4 Dreidimensionales Modell mit der Finite Cell Method 5.4.1 Theoretische Grundlagen 5.4.2 Anpassung und Optimierung der verwendeten Toolbox 5.4.3 Konvergenz und Festlegung der Zellgröße 5.5 Diskussion der Ergebnisse 6 Zusammenfassung und Ausblick Literatur A Daten zu Geometrie und Material der verwendeten Probekörper B Sensoren und Parameter für die MessungThe aim of this thesis was to create a simulation chain which, on the basis of the characteristics of a foam, enables a prediction of the distribution of the eigenfrequencies for this type of foam. Eigenfrequencies measured on different foam samples for longitudinal and flexural vibrations were used to validate the simulation chain. The modeling was done as a spatial stochastic process using harmonic synthesis. Necessary input parameters were determined from CT scans of the specimens. One-dimensional approaches such as the Rayleigh quotient, and the Finite Cell Method (FCM) as a three-dimensional approach were tested in order to determine the eigenfrequencies. It could be shown that the FCM, in conjunction with the modeled spatial processes, is able to reproduce the measured distributions of the eigenfrequencies. The one-dimensional calculation approach is also suitable, but only for homogeneous and isotropic foams.:Einleitung 1.1 Einordnung 1.2 Charakterisierung von Schäumen 1.3 Motivation 1.4 Aufgaben und Aufbau der Arbeit 2 Wahrscheinlichkeitsrechnung und stochastische Prozesse 2.1 Wahrscheinlichkeitsrechnung und Zufallsvariablen 2.1.1 Wahrscheinlichkeitsrechnung 2.1.2 Zufallsvariablen 2.2 Stochastische Prozesse 2.2.1 Kenngrößen stochastischer Prozesse 2.2.2 Eigenschaften stochastischer Prozesse 2.2.3 Spektralanalyse stationärer stochastischer Prozesse 2.2.4 Schätztheorie 3 Analyse der Schaumproben 3.1 Probekörper 3.2 Auswertung der CT-Daten 3.2.1 Kalibrierung der Grauwerte 3.2.2 Verteilungsfunktion und Mittelwert 3.2.3 Varianz des Schwankungsanteils und mittlerer Füllgrad 3.2.4 Leistungsdichtespektrum und Autokorrelation 3.2.5 Porendurchmesser und Anisotropie 3.2.6 Flächeninhalt und Flächenträgheitsmoment 3.3 Messung des dynamischen Verhaltens 3.3.1 Theoretische Grundlagen zur Auswertung 3.3.2 Vorbereitung der Proben 3.3.3 Längseigenkreisfrequenzen 3.3.4 Biegeeigenkreisfrequenzen 3.3.5 Fazit 4 Simulationsmodelle zur Nachbildung von Schäumen 4.1 Vorüberlegungen zur Modellierung 4.2 Theoretische Grundlagen zur Erzeugung eindimensionaler stochastischer Prozesse 4.2.1 Karhunen-Loeve-Transformation . 4.2.2 Harmonische Synthese 4.2.3 Ergebnisse für Flächeninhaltsprozesse 4.3 Simulation mehrdimensionaler stochastischer Prozesse 4.3.1 Bewertungskriterien für die Qualität der Simulation 4.3.2 Ergebnisse für die virtuellen Schäume 4.3.3 Verbesserter Algorithmus 4.4 Vergleich von virtuellen Schäumen und CT-Daten 4.4.1 Keramikschäume 4.4.2 Metallschäume 4.4.3 Anmerkungen und Fazit 4.5 Erweiterung um den Mittelwert 4.6 Konzept zur Simulation von Prozessen größerer Abmessungen 4.7 Fazit 5 Bestimmung der Eigenkreisfrequenzen 5.1 Materialmodelle für die Betrachtung als eindimensionales Kontinuum 5.2 Eindimensionale Modelle 5.2.1 Modell mit konstantem Querschnitt 5.3 Eindimensionales Modell mit Berücksichtigung der Mikrostruktur 5.4 Dreidimensionales Modell mit der Finite Cell Method 5.4.1 Theoretische Grundlagen 5.4.2 Anpassung und Optimierung der verwendeten Toolbox 5.4.3 Konvergenz und Festlegung der Zellgröße 5.5 Diskussion der Ergebnisse 6 Zusammenfassung und Ausblick Literatur A Daten zu Geometrie und Material der verwendeten Probekörper B Sensoren und Parameter für die Messun

PITX2 Modulates Atrial Membrane Potential and the Antiarrhythmic Effects of Sodium-Channel Blockers.

BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs. METHODS: LA PITX2 messenger ribonucleic acid (mRNA) levels were measured in 95 patients undergoing thoracoscopic AF ablation. The effects of flecainide, a sodium (Na(+))-channel blocker, and d,l-sotalol, a potassium channel blocker, were studied in littermate mice with normal and reduced Pitx2c mRNA by electrophysiological study, optical mapping, and patch clamp studies. PITX2-dependent mechanisms of antiarrhythmic drug action were studied in human embryonic kidney (HEK) cells expressing human Na channels and by modeling human action potentials. RESULTS: Flecainide 1 μmol/l was more effective in suppressing atrial arrhythmias in atria with reduced Pitx2c mRNA levels (Pitx2c(+/-)). Resting membrane potential was more depolarized in Pitx2c(+/-) atria, and TWIK-related acid-sensitive K(+) channel 2 (TASK-2) gene and protein expression were decreased. This resulted in enhanced post-repolarization refractoriness and more effective Na-channel inhibition. Defined holding potentials eliminated differences in flecainide's effects between wild-type and Pitx2c(+/-) atrial cardiomyocytes. More positive holding potentials replicated the increased effectiveness of flecainide in blocking human Nav1.5 channels in HEK293 cells. Computer modeling reproduced an enhanced effectiveness of Na-channel block when resting membrane potential was slightly depolarized. CONCLUSIONS: PITX2 mRNA modulates atrial resting membrane potential and thereby alters the effectiveness of Na-channel blockers. PITX2 and ion channels regulating the resting membrane potential may provide novel targets for antiarrhythmic drug development and companion therapeutics in AF

The European Network for Translational Research in Atrial Fibrillation (EUTRAF): objectives and initial results

Atrial fibrillation (AF) is the most common sustained arrhythmia in the general population. As an age-related arrhythmia AF is becoming a huge socio-economic burden for European healthcare systems. Despite significant progress in our understanding of the pathophysiology of AF, therapeutic strategies for AF have not changed substantially and the major challenges in the management of AF are still unmet. This lack of progress may be related to the multifactorial pathogenesis of atrial remodelling and AF that hampers the identification of causative pathophysiological alterations in individual patients. Also, again new mechanisms have been identified and the relative contribution of these mechanisms still has to be established. In November 2010, the European Union launched the large collaborative project EUTRAF (European Network of Translational Research in Atrial Fibrillation) to address these challenges. The main aims of EUTRAF are to study the main mechanisms of initiation and perpetuation of AF, to identify the molecular alterations underlying atrial remodelling, to develop markers allowing to monitor this processes, and suggest strategies to treat AF based on insights in newly defined disease mechanisms. This article reports on the objectives, the structure, and initial results of this networ

Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms:the EAST-AFNET 4 trial

AIMS: Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm control improves clinical outcomes compared to symptom-directed rhythm control. METHODS AND RESULTS: This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA(2)DS(2)-VASc score 3.4, 169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients [e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval [0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19). CONCLUSION: The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20)

Integrating new approaches to atrial fibrillation management: the 6th AFNET/EHRA Consensus Conference.

There are major challenges ahead for clinicians treating patients with atrial fibrillation (AF). The population with AF is expected to expand considerably and yet, apart from anticoagulation, therapies used in AF have not been shown to consistently impact on mortality or reduce adverse cardiovascular events. New approaches to AF management, including the use of novel technologies and structured, integrated care, have the potential to enhance clinical phenotyping or result in better treatment selection and stratified therapy. Here, we report the outcomes of the 6th Consensus Conference of the Atrial Fibrillation Network (AFNET) and the European Heart Rhythm Association (EHRA), held at the European Society of Cardiology Heart House in Sophia Antipolis, France, 17-19 January 2017. Sixty-two global specialists in AF and 13 industry partners met to develop innovative solutions based on new approaches to screening and diagnosis, enhancing integration of AF care, developing clinical pathways for treating complex patients, improving stroke prevention strategies, and better patient selection for heart rate and rhythm control. Ultimately, these approaches can lead to better outcomes for patients with AF

Randomized trials fit for the 21st century. A joint opinion from the European Society of Cardiology, American Heart Association, American College of Cardiology, and the World Heart Federation

© The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. When citing this article, a citation from any of the journals listed is appropriate. For commercial re-use, please contact [email protected] controlled trials are the cornerstone for reliably evaluating therapeutic strategies. However, during the past 25 years, the rules and regulations governing randomized trials and their interpretation have become increasingly burdensome, and the cost and complexity of trials has become prohibitive. The present model is unsustainable, and the development of potentially effective treatments is often stopped prematurely on financial grounds, while existing drug treatments or non-drug interventions (such as screening strategies or management tools) may not be assessed reliably. The current ‘best regulatory practice’ environment, and a lack of consensus on what that requires, too often makes it unduly difficult to undertake efficient randomized trials able to provide reliable evidence about the safety and efficacy of potentially valuable interventions. Inclusion of underrepresented population groups and lack of diversity also remain among the challenges.info:eu-repo/semantics/publishedVersio

2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death the Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC) Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC)

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