49 research outputs found
The maker-breaker domination game and the minimum degree question
No full textThe Maker Breaker Domination game is a two-player positional game played on a finite simple graph. The two players, Dominator and Staller, alternately take turns in claiming one previously unclaimed vertex until all the vertices are claimed. Dominator wins if, at the end of the game, his vertices form a dominating set. Otherwise, Staller wins. Given a positive integer d, define β(d) to be the minimal integer such that there exists a graph of minimum degree d on β(d) vertices, on which Staller wins going second. The Erdős-Selfridge theorem implies β(d) ≥ 2^(d+1) , and a construction due to Valentin Gledel gives β(d) ≤ 2^(d+1) + 2d. We prove that the upper bound coming from Gledel’s construction is tight for d ≤ 3. For general d, we furthermore show β(d) ≥ 2^(d+1) + 2.Author Paul Hametner, BScMasterarbeit Johannes Kepler Universität Linz 202
Role and clinical utility of pramipexole extended release in the treatment of early Parkinson's disease
No full textEva-Maria Hametner, Klaus Seppi, Werner PoeweDepartment of Neurology, Innsbruck Medical University, Innsbruck, AustriaAbstract: The aim of this article is to provide a short review of the most relevant pharmacological and clinical data on pramipexole extended release (ER) as well as to address the clinical utility and potential advantages of a once-daily formulation especially in the treatment of early Parkinson's disease (PD). Pramipexole is widely established as a symptomatic treatment in early as well as advanced PD. The development of an ER formulation, with stable pramipexole plasma concentration over 24 hours, now offers a bioequivalent once-daily alternative. Double-blind randomized controlled trials in early and advanced PD, have established noninferiority of pramipexole ER compared with immediate release as well as superiority of both formulations over placebo. The overnight switch from the standard to the once-daily formulation was shown to be successful in >80% of patients without requiring any dose adjustments. Potential benefits of the prolonged-release design, which have not yet been formally demonstrated in the pivotal trial program, include improved compliance and a potential for better symptomatic control, particularly in patients with early disease that can be managed with monotherapy.Keywords: pramipexole, Parkinson's disease, extended release, compliance, contro
Covid-19 effects on arterial stiffness and vascular ageing: Cartesian study rationale and protocol
No full textIn December 2019, an outbreak of pneumonia caused by a novel Coronavirus (COVID-19) spread rapidly worldwide. Although the clinical manifestations of COVID-19 are dominated by respiratory symptoms, the cardiovascular system is extensively affected at multiple levels. Due to the unprecedented consequences of the COVID-19 pandemic, the ARTERY society decided to launch the Covid-19 effects on ARTErial StIffness and vascular AgeiNg (CARTESIAN) study — the first international multicentre study into the effects of COVID-19 on non-invasive biomarkers of vascular ageing. The main study objective is to evaluate the presence of Early Vascular Ageing (EVA) 6 and 12 months after COVID-19 infection. Secondary objectives are to study the effect of COVID-19 disease severity on EVA, to investigate the role of psychosocial factors in COVID-19 induced EVA, and to investigate the potential modifying effect of comorbidities and chronic treatments. In the CARTESIAN study, a broad array of cardiovascular measurements, including carotid-femoral pulse wave velocity, central blood pressure, carotid ultrasound, brachial flow-mediated dilatation, will be performed. To date, 43 centres from 21 countries have agreed to participate, with an expected study population of >2500 individuals. To our knowledge, CARTESIAN will be the first study to provide insight into the relationship between COVID-19, its severity, and early vascular ageing in a large cohort, potentially enabling future care and diagnostics to be more focused on the most vulnerable
EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
No full textPURPOSE
The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.
PARTICIPANTS
All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).
FINDINGS TO DATE
Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.
FUTURE PLANS
This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements
Anwendung der Reservoir-Theorie zur Schätzung von Blutflussparametern
No full textKardiovaskuläre Erkrankungen sind die häufigste Todesursache weltweit. Modellbildung und Simulation des Herz-Kreislaufsystems dient der Verbesserung von diagnostischen Prozessen. Das Ziel sind frühe Interventionen um die Wahrscheinlichkeit, eine kardiovaskuläre Erkrankung zu bekommen, zu reduzieren. \\Die Diplomarbeit zeigt, wie vaskuläre und Blutflussparameter mittels des 3-elementi-gen Windkesselmodells und des Reservoirmodells geschätzt werden können. Das Ziel ist, Blutflussparameter, vor allem das Schlagvolumen, mit Hilfe der Blutdruckkurve zu schätzen. Resultate der theoretischen Untersuchung werden auf Patientendaten aus der Space4all Studie, durchgeführt vom DLR (Deutsches Zentrum für Luft- und Raumfahrt) und dem AIT (Austrian Institute of Technology) und finanziert von der ESA (European Space Agency) und NASA (National Aeronautics and Space Administration), angewandt. Die Space4all-Studie untersucht 24 TeilnehmerInnen während eines 60-tägigen Bettruhe-Aufenthalts, bei dem der Körper 6\% mit dem Kopf nach unten gelagert ist, um Schwerelosigkeit im All zu simulieren. \\Für die Untersuchungen wird das 3-elementige Windkesselmodell, ein nulldimensionales Modell, welches das Dämpfen des periodisch vom Herzen ausgeworfenen Blutvolumens beschreibt, verwendet. Es wird durch eine lineare gewöhnliche Differentialgleichung aufgestellt. Das Windkesselmodell wird verknüpft mit dem Reservoirmodell, welches über ein eindimensionales Netzwerkmodell hergeleitet wird. Das Reservoirmodell trennt die Druckkurve in den Exzessdruck und den Reservoirdruck. Die Autorin implementiert das 3-elementige Windkesselmodell und eine künstliche Flusskurve in Matlab. Damit werden 2187 Druckkurven erzeugt, indem die Windkes-sel-Parameter und spezielle Punkte der Flusskurve variiert werden. Diese werden an den Reservoiralgorithmus als Input übergeben, der die Aufspaltung in Reservoir- und Exzessdruck durchführt. Die Effekte der verschiedenen Inputparameter auf die Reservoir-Outputparameter werden untersucht, indem jeder Inputparameter individuell variiert wird. Weiters führt die Autorin eine Sensitivitätsanalyse bestehend aus einer Kategorie- und einer Clusteranalyse durch. Anschließend wendet sie die Resultate auf die Patientendaten der Space4all-Studie an. \\Durch die Untersuchung der künstlichen Druckkurven zeigt die Diplomarbeit, dass der Reservoirdruck hauptsächlich von den Windkesselparametern abhängt, mit Ausnahme des Aortenwiderstands. Der Exzessdruck hingegen wird hauptsächlich durch die Flussparameter, sowie den Aortenwiderstand beeinflusst. Die Sensititvitätsanalyse zeigt, ob und in welchen Konstellationen sich die Effekte der Inputparameter ausgegleichen. Ausgleichende Effekte werden zwischen dem Flussmaximum, der Dehnbarkeit der Arterien, dem Aortenwiderstand und der Auswurfdauer gefunden. Die Autorin schätzt die Flusskurve und das daraus resultierende Schlagvolumen (SV) mit Hilfe des kombinierten Modells und validiert die Simulationsergebnisse anschließend mit dem aus den Doppler Ultraschallbildern berechneten SV. Zwischen dem modellierten und gemessenen SV wurde eine Korrelation von 0.51 gefunden. Es wurden keine deutlichen Änderungen im arteriellen Widerstand während des Experiments gefunden. Das Flussmaximum jedoch nahm ab, im Durchschnitt um 60 93 ml/s und damit auch das SV der meisten TeilnehmerInnen. Schlussendlich wurde gezeigt, dass man mit dem Reservoir-Windkesselmodell den Skalierungsfaktor zwischen dem Fluss und dem Exzessdruck gut schätzen kann. Ausreißer erhöhen jedoch die Standardabweichung beim Schlagvolumen. Die Simulationsergebnisse zeigen, dass Änderungen in zwei oder mehreren Inputparametern gegensätzliche und somit ausgleichende Effekte auf die Druckkurve haben können. Mit Hilfe von Nebenbedingungen bei der Optimierung können diese Effekte besser erklärt und getrennt werden. Das Miteinbeziehen der Herzrate als variablen Parameter könnte eine Verbesserung der theoretischen Untersuchungen bringen und die Änderungen der Herzfunktion während des Experminents besser erklären.Cardiovascular diseases are the number one cause of death worldwide. Modelling and simulation of the cardiovascular system aims to improve diagnostic processes and enables early intervention to prevent and decrease the probability of cardiovascular diseases.\\The thesis shows how to estimate vascular and blood flow parameters using a combination of the 3-element Windkessel model and the reservoir model. The aim is to obtain blood flow parameter estimates, in particular stroke volume, by using blood pressure measurements only. Results from the theoretical investigations are used on patient data from the \textit{Space4all} study, performed by DLR (Deutsches Zentrum für Luft- und Raumfahrt) and AIT (Austrian Institute of Technology) and funded by ESA (European Space Agency) and NASA (National Aeronautics and Space Administration). The Space4all study examined 24 participants throughout 60 days of 6\% head down tilt bed rest to simulate microgravity in space. \\The investigations make use of the 3-element Windkessel model, which is a lumped parameter model that describes the smoothing of pulsatile blood flow through a linear ordinary differential equation. It is coupled with the reservoir model, that is derived through a one-dimensional network model and separates the pressure curve into excess pressure and reservoir pressure.The author implements the 3-element Windkessel model and an artificial flow curve in Matlab and creates 2187 pressure curves by varying the Windkessel parameters and characteristic points of the flow curve. These curves are given as input to the reservoir algorithm, which returns reservoir and excess pressure. The effects on the reservoir output parameters are investigated when varying each input parameter individually. Furthermore, the author performs a sensitivity analysis consisting of a category and a cluster analysis. She then applies the results to real patient data from the Space4all study.\\Through investigations of the artificial pressure curves the thesis shows that the reservoir pressure is mostly affected by the Windkessel parameters with the exception of the aortic resistance parameter. The excess pressure on the other hand is mostly affected by the flow parameters and the aortic resistance. With the sensitivity analysis, cancelling effects between the flow maximum, the compliance, the aortic resistance and the ejection duration are found and further investigated. The author estimates the patient's flow curve and stroke volume (SV) through the combined model and validates the simulation results through the SV calculated from Doppler ultrasound measurements. Between modelled and measured SV, a correlation of 0.51 was found. The resistances did not change significantly over the course of the experiment, however the maximum flow velocity decreased on average by 60 93 ml/s, and thus the SV decreased for most participants.\\In conclusion the Windkessel-reservoir model estimates the scaling between the flow and excess pressure curve on average well, however outliers increase the total standard deviation for the stroke volume. The simulation results show that changes in two or more parameters can have adverse effects on the pressure curve and thus cancel one another. Constrained optimization explains and helps to separate these effects. An improvement for the theoretical investigation would be the incorporation of the heart rate as a varying parameter which could further explain the changes in the heart function during the experiment
Recanalization Therapies for Large Vessel Occlusion Due to Cervical Artery Dissection: A Cohort Study of the EVA-TRISP Collaboration.
No full textBACKGROUND AND PURPOSE
This study aimed to investigate the effect of endovascular treatment (EVT, with or without intravenous thrombolysis [IVT]) versus IVT alone on outcomes in patients with acute ischemic stroke (AIS) and intracranial large vessel occlusion (LVO) attributable to cervical artery dissection (CeAD).
METHODS
This multinational cohort study was conducted based on prospectively collected data from the EVA-TRISP (EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients) collaboration. Consecutive patients (2015-2019) with AIS-LVO attributable to CeAD treated with EVT and/or IVT were included. Primary outcome measures were (1) favorable 3-month outcome (modified Rankin Scale score 0-2) and (2) complete recanalization (thrombolysis in cerebral infarction scale 2b/3). Odds ratios with 95% confidence intervals (OR [95% CI]) from logistic regression models were calculated (unadjusted, adjusted). Secondary analyses were performed in the patients with LVO in the anterior circulation (LVOant) including propensity score matching.
RESULTS
Among 290 patients, 222 (76.6%) had EVT and 68 (23.4%) IVT alone. EVT-treated patients had more severe strokes (National Institutes of Health Stroke Scale score, median [interquartile range]: 14 [10-19] vs. 4 [2-7], P<0.001). The frequency of favorable 3-month outcome did not differ significantly between both groups (EVT: 64.0% vs. IVT: 86.8%; ORadjusted 0.56 [0.24-1.32]). EVT was associated with higher rates of recanalization (80.5% vs. 40.7%; ORadjusted 8.85 [4.28-18.29]) compared to IVT. All secondary analyses showed higher recanalization rates in the EVT-group, which however never translated into better functional outcome rates compared to the IVT-group.
CONCLUSION
We observed no signal of superiority of EVT over IVT regarding functional outcome in CeAD-patients with AIS and LVO despite higher rates of complete recanalization with EVT. Whether pathophysiological CeAD-characteristics or their younger age might explain this observation deserves further research
Prädiktives Energiemanagement für Brennstoffzellen-Lkw
No full textIn fuel cell electric trucks, the energy management strategy controls the operation of the fuel cell and battery systems. Besides the considerable impact on fuel consumption and driving range, properly designing this control function is essential to ensure that the powertrain components meet the lifetime requirements of long-haul transportation. Even though the literature on energy management strategies for fuel cell electric vehicles is vast, there is a fundamental research gap in studies focused on long-haul trucks, nowadays considered the most promising fuel cell application in the automotive sector. During his doctoral studies, the author has conducted state-of-the-art investigations and addressed this gap in several publications, significantly contributing to the research on energy management strategies for fuel cell electric trucks. The present doctoral thesis describes his research on the topic and summarizes the most relevant findings. In particular, it proposes innovative energy management strategies to reduce the fuel consumption and component degradation of fuel cell electric trucks and foster their market penetration. The main focus of this thesis is predictive energy management, a topic that will play a critical role in the development of intelligent fuel cell electric trucks. Indeed, the thesis demonstrates that implementing predictive strategies is the only effective way to achieve optimal vehicle performance in high-demanding driving cycles (for example, due to the heavy truckloads on mountain routes). In particular, considering long-term elevation forecasts is essential to anticipate driving conditions that are challenging from an energy management standpoint and achieve optimal performance. One of the main contributions of this thesis is the development of a dual-stage control structure for predictive energy management strategies that enables achieving optimal performance even in challenging route topographies. The dual-stage structure has two advantageous characteristics. First, it can consider the elevation profile of the entire route in the energy management optimization with low computational complexity. Second, it allows the implementation of dynamic programming to find globally optimal solutions, overcoming the well-known barriers of non-causality and high computational complexity. Moreover, the proposed predictive energy management strategy has high flexibility regarding the optimization targets. Initially, it is implemented to optimize only the fuel consumption while controlling the battery state of charge. Then, an innovative formulation is presented for the simultaneous and multi-objective optimization of fuel consumption, fuel cell degradation, and battery degradation. The benefits of this predictive and health-conscious energy management strategy are assessed in real-world driving scenarios, also considering different battery sizes and degradation states. Eventually, the simulation results demonstrate the absolute superiority of the proposed strategy against standard approaches. The thesis also proposes innovative solutions to establish synergies between the energy management strategy and other control functions from a holistic standpoint. Novel concepts are presented to significantly reduce degradation by exploiting the interaction with battery thermal management and the intelligent activation of multi-module fuel cell systems. Moreover, the co-optimization of vehicle speed and energy management using dynamic programming is proposed for optimal eco-driving, substantially reducing fuel consumption and enabling longer driving ranges to cope with the limited hydrogen refueling infrastructure. Eventually, the innovative strategies proposed in this thesis can significantly contribute to the development and market penetration of fuel cell electric trucks thanks to lower fuel consumption and component degradation. Indeed, by adopting these strategies, truck manufacturers can achieve better performance and lower ownership costs, closing the gap with conventional diesel trucks for long-haul transportation.In Brennstoffzellen-Elektro-Lkws regelt die Energiemanagementstrategie den Betrieb der Brennstoffzellen- und Batteriesysteme. Neben den beträchtlichen Auswirkungen auf den Kraftstoffverbrauch und die Reichweite ist die richtige Auslegung dieser Steuerungsfunktion von entscheidender Bedeutung, um sicherzustellen, dass die Komponenten des Antriebsstrangs die Anforderungen an die Lebensdauer im Fernverkehr erfüllen. Obwohl die Literatur über Energiemanagementstrategien für Brennstoffzellen-Elektrofahrzeuge sehr umfangreich ist, gibt es eine grundlegende Forschungslücke bei Studien zum Thema Langstrecken-Lkw, welcher heutzutage als die vielversprechendste Brennstoffzellenanwendung im Automobilsektor gilt.Während seines Promotionsstudiums hat der Autor Untersuchungen nach dem neuesten Stand der Technik durchgeführt und die Forschungslücke in mehreren Veröffentlichungen aufgegriffen, wodurch er einen wesentlichen Beitrag zur Erforschung von Energiemanagementstrategien für Brennstoffzellen-Elektro-Lkw geleistet hat. Die vorliegende Dissertation beschreibt seine Forschungen zu diesem Thema und fasst die wichtigsten Erkenntnisse zusammen. Insbesondere werden innovative Energiemanagementstrategien vorgeschlagen, um den Kraftstoffverbrauch und die Bauteildegradation von Brennstoffzellen-Elektrofahrzeugen zu reduzieren und deren Marktdurchdringung zu fördern. Das Hauptaugenmerk dieser Arbeit liegt auf dem prädiktiven Energiemanagement, einem Thema, das bei der Entwicklung von intelligenten Brennstoffzellen-Elektrofahrzeugen eine entscheidende Rolle spielen wird. In dieser Arbeit wird veranschaulicht, dass die Implementierung von prädiktiven Strategien der einzige effektive Weg ist, um eine optimale Fahrzeugleistung in anspruchsvollen Fahrzyklen, wie etwa aufgrund einer vollen Lkw-Ladung auf Bergstrecken, zu erreichen. Insbesondere die Berücksichtigung langfristiger Höhenprognosen ist von entscheidender Bedeutung, um Fahrbedingungen zu antizipieren, die aus Sicht des Energiemanagements schwierig sind, und um eine optimale Leistung zu erzielen.Einer der Hauptbeiträge dieser Arbeit ist die Entwicklung einer zweistufigen Regelstruktur für prädiktive Energiemanagementstrategien, die es ermöglicht, auch bei anspruchsvollen Streckentopographien eine optimale Leistung zu erzielen. Die zweistufige Struktur hat zwei vorteilhafte Eigenschaften. Erstens kann sie das Höhenprofil der gesamten Strecke bei der Optimierung des Energiemanagements mit geringem Rechenaufwand berücksichtigen. Zweitens ermöglicht sie die Implementierung der dynamischen Programmierung, um global optimale Lösungen zu finden, und überwindet damit die bekannten Hindernisse der Nicht-Kausalität und der hohen Rechenkomplexität. Darüber hinaus bietet die vorgeschlagene prädiktive Energiemanagementstrategie eine hohe Flexibilität in Bezug auf die Optimierungsziele. Zunächst wird sie so implementiert, dass nur der Kraftstoffverbrauch optimiert wird, während der Ladezustand der Batterie geregelt wird. Anschließend wird eine innovative Formulierung für die gleichzeitige und mehrzielorientierte Optimierung des Kraftstoffverbrauchs, der Degradation der Brennstoffzelle und der Degradation der Batterie vorgestellt. Die Vorteile dieser vorausschauenden und Energiemanagementstrategie werden in realen Fahrszenarien bewertet, wobei auch unterschiedliche Batteriegrößen und Degradationszustände berücksichtigt werden. Schließlich zeigen die Simulationsergebnisse die absolute Überlegenheit der vorgeschlagenen Strategie gegenüber Standardansätzen. In dieser Arbeit werden auch innovative Lösungen vorgeschlagen, um Synergien zwischen der Energiemanagementstrategie und anderen Regelfunktionen aus einem ganzheitlichen Blickwinkel heraus zu schaffen. Es werden neuartige Konzepte vorgestellt, um durch Ausnutzung des Zusammenspiels vom Thermomanagement der Batterie und der intelligenten Ansteuerung von Mehrmodul-Brennstoffzellensystemen die Degradation deutlich zu reduzieren. Darüber hinaus wird die Ko-Optimierung von Fahrzeuggeschwindigkeit und Energiemanagement mittels dynamischer Programmierung für ein optimales ökologisches Fahrkonzept vorgeschlagen.Dies ermöglicht eine erhebliche Reduzierung des Kraftstoffverbrauchs sowie eine Erhöhung der Reichweite, wodurch das Problem der begrenzten Infrastruktur für die Wasserstoffbetankung bewältigt wird.Letztendlich können die in dieser Arbeit vorgeschlagenen innovativen Strategien dank des geringeren Kraftstoffverbrauchs und der geringeren Abnutzung der Komponenten erheblich zur Entwicklung und Marktdurchdringung von Elektro-Lkw mit Brennstoffzellen beitragen. Durch die Anwendung dieser Strategien können Lkw-Hersteller niedrigere Betriebskosten erzielen und so die Lücke zu herkömmlichen Diesel-Lkw im Fernverkehr schließen
Isoxazolinyl Spironuceosides by Nitrile Oxide Cycloadditions to 7-Methylenepyrrolo[1,2-c]pyrimidin-1(5H)-one
No full text
Additive prognostic value of vascular aging and coronary artery calcium for all-cause mortality in the Heinz Nixdorf Recall Study
No full textBackground
Vascular aging, defined by aortic pulse wave velocity (aoPWV), as well as coronary artery calcium (CaC), are emerging risk predictors.
Purpose
To investigate the prognostic role of functional (vascular aging) and structural (CaC) arterial parameters in individuals without established cardiovascular disease.
Methods
We utilized our recently established population-based reference values for healthy (HVA), normal (NVA) and early (EVA) vascular aging in the poipulation-based Heinz Nixdorf Recall (HNR) study. HVA was the lowest, and EVA the highest age- and sex-specific decile of estimated aoPWV, derived from radial waveforms with a validated regression formula. CaC was measured with electron beam computed tomography (Agatston-score). The additive prognostic value of both parameters for all-cause mortality was tested, using Kaplan Meier curves and Cox Regression models. The latter included age, sex, diastolic blood pressure, cholesterol, and diabetes as covariates
