An approach for stability analysis of systems with varying sampling rate

In dieser Arbeit wird ein Verfahren zur Stabilitätsprüfung hybrider Systeme beschrieben. Das entwickelte Verfahren lässt es zu, einen garantiert stabilen Bereich für die Variation der Abtastzeit anzugeben. Da veränderliche Abtastzeiten äquivalent zu variierenden Laufzeiten sind, wie sie beispielsweise durch Bussysteme verursacht werden, kann das Verfahren auch auf dezentrale hybride Regelungen angewendet werden, bei denen Sensoren und Aktoren über Bussysteme mit der Regelung gekoppelt sind. Die zur Herleitung des Verfahrens eingesetzten Methoden basieren auf dem Begriff der robusten Stabilität, die es ermöglicht, Stabilität für Systeme zu garantieren, die Unsicherheiten unterliegen. Daher wird die veränderliche Abtastzeit in einem ersten Schritt durch einen nichtlinearen Eingriff modelliert und anschließend in eine äquivalente Unsicherheit umgerechnet. Die Darstellung des mit Unsicherheiten behafteten Systems erfolgt als lineare Fraktionaltransformation. Anhand dieses Modells wird anschließend die Stabilität in Bezug auf eine Variation der Abtastzeit untersucht. Als Ergebnis des Verfahrens erhält man einen Bereich für die Abtastzeit, in dem Stabilität für das Gesamtsystem garantiert werden kann. Dabei ist es unerheblich, mit welcher Dynamik die Abtastzeit verändert wird. Anschließend werden die theoretischen Ergebnisse anhand eines realen Systems verifiziert. Dazu wurde im Rahmen eines Industrieprojektes ein Versuchsstand mit vier auf Winkelgleichlauf zu regelnden Gleichstromantrieben aufgebaut, eine Regelung entworfen und diese in eine speicherprogrammierbare Steuerung implementiert. Die Kommunikation der Regelung mit den Stellgliedern und der Messwerterfassung erfolgte über ein Bussystem. Nach der Modellierung des Gesamtsystems wird mit Hilfe des entwickelten Verfahrens der garantiert stabile Bereich für die Variationsbreite der Abtastzeit am Versuchsstand berechnet und die so bestimmten Stabilitätsgrenzen durch Messungen am Prüfstand verifiziert.In this thesis, a method is presented which allows the specification of stability margins for hybrid control systems composed of a sampled data feedback controller with varying sampling time and a continous linear system. The developed method provides lower und upper bounds for the sampling time and thus defining a range within guaranteed stability is ensured. The effect of varying sampling time and varying time delays of bus systems are equivalent. Therefore, the presented method can also be used for stability tests of decentralized controlled hybrid systems where the sensors and the actuators are linked to the controller by various bus systems. The derivation of the method is based on concepts of robust stability, which allows stability tests for systems with uncertainties. In a first step the varying sampling time is modeled by a non-linear operation. Afterwards, the non-linearity is converted into an uncertainty. Now the system can be represented as a linear fractional transformation. Based on this model the stability of the time varying system can be analyzed with respect to variations of sampling time. As a result this method specifies a range for the sampling time within which stability of the varying system can be guaranteed, regardless of the dynamics of the variation. Afterwards, the theoretical results are verified by measurements on a real system. A test bed was set up within the frame of an industrial project. The controllers were implemented in a programmable logic controller to ensure position synchronisation of four DC motors. All communications between the controller, actuators and sensors are established by bus systems. After modeling the overall system, the presented method is used to determine the stability margins of the test bed concerning the sampling time. Finally, the calculated bounds are verified by measurements

CD33 auf humanen Mikroglia und seine Rolle bei der Entstehung von Morbus Alzheimer

Mikroglia repräsentieren das Immunsystem im ZNS und nehmen somit eine zentrale Rolle auch bei neurodegenerativen Erkrankungen ein. In der vorliegenden Arbeit wurde die Expression des CD33-Rezeptor auf humanen Mikroglia untersucht, um die mögliche Rolle der Mikroglia in der Pathogenese des Morbus Alzheimer genauer aufzuklären. Zusammenfassend konnte in der vorliegenden Arbeit der Nachweis einer Transkription des cd33-Gens mittels PCR und einer CD33-Rezeptor-Expression auf iPSdM-Mikroglialinien mittels Immunozytochemie und Durchflusszytometrie erbracht werden. Durch Sialidase-Behandlung ließ sich das Detektionsniveau von CD33 in der Durchflusszytometrie deutlich erhöhen, da maskierende Sialinsäuren welche auf der Zelloberfläche cis- und trans-Bindungen mit CD33 eingehen um ein konstitutives inhibitorisches Signal aufrecht zu erhalten, durch Sialidasen abgespalten werden. In menschlichem Gehirngewebe konnten die in den iPSdM gewonnenen Daten bezüglich Transkription und Expression verifiziert werden. Bei der immuno-histochemischen Analyse menschlicher Gehirnschnitte von Kontroll- und Alzheimer-Patienten zeigte sich eine gesteigerte Expressionsrate von CD33 auf den Mikroglia der Alzheimer-Patienten, welche auf eine höhere Expressionsrate von Protein pro Zelle verursacht wurde. Die Anzahl der Mikroglia in den untersuchten Gehirnschnitten zeigte eine gering erhöhte Zellzahl bei den Alzheimer-Patienten. Diese Daten sind gut mit kürzlich publizierten Arbeiten vereinbar, welche sich demselben Thema widmeten

Interactive cohort exploration for spinocerebellar ataxias using synthetic cohort data for visualization

Motivation: Visualization of data is a crucial step to understanding and deriving hypotheses from clinical data. However, for clinicians, visualization often comes with great effort due to the lack of technical knowledge about data handling and visualization. The application offers an easy-to-use solution with an intuitive design that enables various kinds of plotting functions. The aim was to provide an intuitive solution with a low entrance barrier for clinical users. Little to no onboarding is required before creating plots, while the complexity of questions can grow up to specific corner cases. To allow for an easy start and testing with SCAview, we incorporated a synthetic cohort dataset based on real data of rare neurological movement disorders: the most common autosomal-dominantly inherited spinocerebellar ataxias (SCAs) type 1, 2, 3, and 6 (SCA1, 2, 3 and 6). Methods: We created a Django-based backend application that serves the data to a React-based frontend that uses Plotly for plotting. A synthetic cohort was created to deploy a version of SCAview without violating any data protection guidelines. Here, we added normal distributed noise to the data and therefore prevent re-identification while keeping distributions and general correlations. Results: This work presents SCAview, an user-friendly, interactive web-based service that enables data visualization in a clickable interface allowing intuitive graphical handling that aims to enable data visualization in a clickable interface. The service is deployed and can be tested with a synthetic cohort created based on a large, longitudinal dataset from observational studies in the most common SCAs

The Diagnostic Value of Cerebrospinal Fluid Lactate for Detection of Sepsis in Community-Acquired Bacterial Meningitis

Community-acquired bacterial meningitis conveys significant morbidity and mortality due to intracranial and systemic complications, and sepsis is a major contributor to the latter. While cerebrospinal fluid (CSF) analysis is essential in the diagnosis of bacterial meningitis, its predictive utility for detection of sepsis is unknown. We investigated the diagnostic performance of CSF parameters for sepsis defined by the Sepsis-3 criteria in a retrospective cohort of patients with community-acquired bacterial meningitis. Among 103 patients, 69.5% developed sepsis. CSF lactate was associated with sepsis with an odds ratio of 1.11 (p = 0.022), while CSF cell counts, glucose and protein levels were not (all p > 0.4). Employing the optimal cutoff of 8.2 mmol/L, elevated CSF lactate resulted in a sensitivity of 81.5% and specificity of 61.5% for sepsis. In exploratory analyses, CSF lactate was also associated with in-hospital mortality with an odds ratio of 1.21 (p = 0.011). Elevated CSF lactate might contribute to early diagnosis of sepsis as well as prognostication in patients with community-acquired bacterial meningitis

Patient-reported, health economic and psychosocial outcomes in patients with Friedreich ataxia (PROFA): protocol of an observational study using momentary data assessments via mobile health app

Introduction Friedreich ataxia (FA) is the most common hereditary ataxia in Europe, characterised by progressively worsening movement and speech impairments with a typical onset before the age of 25 years. The symptoms affect the patients’ health-related quality of life (HRQoL) and psychosocial health. FA leads to an increasing need for care, associated with an economic burden. Little is known about the impact of FA on daily lives and HRQoL. To fill that gap, we will assess patient-reported, psychosocial and economic outcomes using momentary data assessment via a mobile health application (app).Methods and analysis The PROFA Study is a prospective observational study. Patients with FA (n=200) will be recruited at six European study centres (Germany, France and Austria). We will interview patients at baseline in the study centre and subsequently assess the patients’ health at home via mobile health app. Patients will self-report ataxia severity, HRQoL, speech and hearing disabilities, coping strategies and well-being, health services usage, adverse health events and productivity losses due to informal care on a daily to monthly basis on the app for 6 months. Our study aims to (1) validate measurements of HRQoL and psychosocial health, (2) assess the usability of the mobile health app, and (3) use descriptive and multivariate statistics to analyse patient-reported and economic outcomes and the interaction effects between these outcomes. Insights into the app’s usability could be used for future studies using momentary data assessments to measure outcomes of patients with FA.Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of the University Medicine of Greifswald, (BB096/22a, 26 October 2022) and from all local ethics committees of the participating study sites. Findings of the study will be published in peer-reviewed journals, presented at relevant international/national congresses and disseminated to German and French Patient Advocacy Organizations.Trial registration number ClinicalTrials.gov Registry (NCT05943002); Pre-results

Autosomal Recessive Cerebellar Ataxias in Europe: Frequency, Onset, and Severity in 677 Patients

Progress in next-generation sequencing has led to an explosion of novel genes and phenotypes of autosomal recessive cerebellar ataxias (ARCAs) in the last decade, with >170 recessive conditions manifesting with ataxia identified.1 With large-scale natural history and mechanistic treatment trials on the horizon for many ARCAs, up-to-date knowledge is required not only on relative frequencies but also on real-world age and disease severity distributions as key information for trial design planning and recruitment. In this multicenter study, we provide data on the relative frequency of ARCAs in Europe, delineate the spectrum of age at disease onset, and present real-world data on disease severity distributions of patients with ARCA that help to inform future trial planning