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Altered neurovascular coupling as measured by optical imaging: a biomarker for Alzheimer’s disease
(2017)
Hintergrund
Die Anwendung und das Verständnis von Statistik sind sehr wichtig für die biomedizinische Forschung und für die klinische Praxis. Dies gilt insbesondere auch zur Abschätzung der Möglichkeiten unterschiedlichster Diagnostik- und Therapieoptionen beim Glaukom. Die scheinbare Komplexität der Statistik, die zum Teil dem „gesunden Menschenverstand“ zu widersprechen scheint, zusammen mit der nur vorsichtigen Akzeptanz der Statistik bei vielen Medizinern können zu bewussten und unbewussten Manipulationen bei der Datendarstellung und -interpretation führen.
Ziel der Arbeit
Ziel ist die verständliche Darstellung einiger typischer Fehler in der medizinisch-statistischen Datenbehandlung.
Material und Methoden
Anhand hypothetischer Beispiele aus der Glaukomdiagnostik erfolgen die Darstellung der Wirkung eines hypotensiven Medikamentes sowie die Beurteilung der Ergebnisse eines diagnostischen Tests. Es werden die typischsten statistischen Einsatzbereiche und Irrtumsquellen ausführlich und verständlich analysiert
Ergebnisse
Mechanismen von Datenmanipulation und falscher Dateninterpretation werden aufgeklärt. Typische Irrtumsquellen bei der statistischen Auswertung und Datendarstellung werden dabei erläutert.
Schlussfolgerungen
Die erläuterten praktischen Beispiele zeigen die Notwendigkeit, die Grundlagen der Statistik zu verstehen und korrekt anwenden zu können. Fehlendes Grundlagenwissen und Halbwissen der medizinischen Statistik können zu folgenschweren Missverständnissen und falschen Entscheidungen in der medizinischen Forschung, aber auch in der klinischen Praxis führen.
Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gefäßveränderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gefäße beeinflussen im prä-, post- und kapillaren Bereich den Blutfluss und strömungsbedingte Stoffwechselverhältnisse passiv und aktiv über den Gefäßdurchmesser. Retinale Gefäße gleichen von Aufbau und Funktion den zerebralen Gefäßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gefäßweiten berechneten Biomarkern soll eine Aussage über die Prognose von systemischen vaskulär bedingten Erkrankungen getroffen werden. Die statische retinale Gefäßanalyse befasst sich mit der Untersuchung des Zustandes der prä- und postkapillaren Gefäßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gefäßanalyse wird der Längsschnitt eines retinalen Gefäßes nicht invasiv funktionell und strukturell über einen Zeitraum vor, während und nach einer spezifischen vaskulären Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ansätzen. Mittels retinaler Gefäßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gynäkologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgeführt. Mit der statischen retinalen Gefäßanalyse steht eine kostengünstige, reproduzierbare, nicht invasive Screeningtechnik zur Verfügung, um eine prognostische Aussage über die Gefäßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gefäßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gefäße zeitkontinuierlich untersucht. Die Evaluation vaskulärer Erkrankungen sowie zerebro- bzw. kardiovaskulärer Morbidität und Mortalität mittels mehrerer methodologischer Modalitäten retinaler Gefäßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftsträchtige diagnostische Perspektive. Die interdisziplinäre klinische Anwendung dieser vaskulären Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten.
Can vascular function be assessed by the interpretation of retinal vascular diameter changes?
(2011)
Purpose: It was demonstrated previously that retinal pulse wave velocity (rPWV) as a measure of retinal arterial stiffness is increased in aged anamnestically healthy volunteers compared with young healthy subjects. Using novel methodology of rPWV assessment this finding was confirmed and investigated whether it might relate to the increased blood pressure usually accompanying the aging process, rather than to the aging itself.
Methods: A total of 12 young 25.5-year-old (24.0–28.8) [median(1st quartile–3rd quartile)] and 12 senior 68.5-year-old (63.8–71.8) anamnestically healthy volunteers; and 12 senior 63.0-year-old (60.8–65.0) validated healthy volunteers and 12 young 33.0-year-old (29.5–35.0) hypertensive patients were examined. Time-dependent alterations of vessel diameter were assessed by the Dynamic Vessel Analyzer in a retinal artery of each subject. The data were filtered and processed using mathematical signal analysis and rPWVs were calculated.
Results: rPWV amounted to 1200 (990-1470) RU (relative units)/s in the hypertensive group and to 1040 (700-2230) RU/s in anamnestically healthy seniors. These differed significantly from rPWVs in young healthy group (410 [280–500] RU/s) and in validated healthy seniors (400 [320–510] RU/s). rPWV associated with age and mean arterial pressure (MAP) in the pooled cohort excluded validated healthy seniors. In a regression model these associations remain when alternately adjusted for MAP and age. When including validated healthy seniors in the pooled cohort only association with MAP remains.
Conclusions: Both aging (with not excluded cardiovascular risk factors) and mild hypertension are associated with elevated rPWV. rPWV increases to a similar extent both in young mildly hypertensive subjects and in aged anamnestically healthy persons. Healthy aging is not associated with increased rPWV.
Purpose: Image analysis by the retinal vessel analyzer (RVA) observes retinal vessels in their dynamic state online noninvasively along a chosen vessel segment. It has been found that high-frequency diameter changes in the retinal artery blood column along the vessel increase significantly in anamnestically healthy volunteers with increasing age and in patients with glaucoma during vascular dilation. This study was undertaken to investigate whether longitudinal sections of the retinal artery blood column are altered in systemic hypertension.
Methods: Retinal arteries of 15 untreated patients with essential arterial hypertension (age, 50.9 ± 11.9 years) and of 15 age-matched anamnestically healthy volunteers were examined by RVA. After baseline assessment, a monochromatic luminance flicker (530–600 nm; 12.5 Hz; 20 s) was applied to evoke retinal vasodilation. Differences in amplitude and frequency of spatial artery blood column diameter change along segments (longitudinal arterial profiles) of 1 mm in length were measured and analyzed using Fourier transformation.
Results: In the control group, average reduced power spectra (ARPS) of longitudinal arterial profiles did not differ when arteries changed from constriction to dilation. In the systemic hypertension group, ARPS during constriction, baseline, and restoration were identical and differed from ARPS during dilation (P < 0.05). Longitudinal arterial profiles in both groups showed significant dissimilitude at baseline and restoration (P < 0.05).
Conclusions: The retinal artery blood column demonstrates microstructural alterations in systemic hypertension and is less irregular along the vessel axis during vessel dilation. These microstructural changes may be an indication of alterations in vessel wall rigidity, vascular endothelial function, and smooth muscle cells in this disease, leading to impaired perfusion and regulation.
Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.
The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept.
Applications of Graph Transformations with Industrial Relevance Lecture Notes in Computer Science, 2004, Volume 3062/2004, 434-439, DOI: http://dx.doi.org/10.1007/978-3-540-25959-6_33 This paper gives a brief overview of the tools we have developed to support conceptual design in civil engineering. Based on the UPGRADE framework, two applications, one for the knowledge engineer and another for architects allow to store domain specific knowledge and to use this knowledge during conceptual design. Consistency analyses check the design against the defined knowledge and inform the architect if rules are violated.
In: Advances in intelligent computing in engineering : proceedings of the 9.International EG-ICE Workshop ; Darmstadt, (01 - 03 August) 2002 / Martina Schnellenbach-Held ... (eds.) . - Düsseldorf: VDI-Verl., 2002 .- Fortschritt-Berichte VDI, Reihe 4, Bauingenieurwesen ; 180 ; S. 1-35 The paper describes a novel way to support conceptual design in civil engineering. The designer uses semantical tools guaranteeing certain internal structures of the design result but also the fulfillment of various constraints. Two different approaches and corresponding tools are discussed: (a) Visually specified tools with automatic code generation to determine a design structure as well as fixing various constraints a design has to obey. These tools are also valuable for design knowledge specialist. (b) Extensions of existing CAD tools to provide semantical knowledge to be used by an architect. It is sketched how these different tools can be combined in the future. The main part of the paper discusses the concepts and realization of two prototypes following the two above approaches. The paper especially discusses that specific graphs and the specification of their structure are useful for both tool realization projects.
In: Advanced Engineering Informatics. Vol 21, Issue 1, 2007, Pages 67-83 http://dx.doi.org/10.1016/j.aei.2006.10.001 eds. J.C. Kunz, I.F.C. Smith and T. Tomiyama, Elsevier, Seite 1-22 Current CAD tools are not able to support the conceptual design phase, and none of them provides a consistency analysis for sketches produced by architects. This phase is fundamental and crucial for the whole design and construction process of a building. To give architects a better support, we developed a CAD tool for conceptual design and a knowledge specification tool. The knowledge is specific to one class of buildings and it can be reused. Based on a dynamic and domain-specific knowledge ontology, different types of design rules formalize this knowledge in a graph-based form. An expressive visual language provides a user-friendly, human readable representation. Finally, a consistency analysis tool enables conceptual designs to be checked against this formal conceptual knowledge. In this article, we concentrate on the knowledge specification part. For that, we introduce the concepts and usage of a novel visual language and describe its semantics. To demonstrate the usability of our approach, two graph-based visual tools for knowledge specification and conceptual design are explained.
WS GTaD-2003 - The 1st Workshop on Graph Transformations and Design ed Grabska, E., Seite 6-7, Jagiellonian University Krakow. 2 pages
Applications of Graph Transformations with Industrial Relevance Lecture Notes in Computer Science, 2004, Volume 3062/2004, 90-105, DOI: 10.1007/978-3-540-25959-6_7 In this paper we discuss how tools for conceptual design in civil engineering can be developed using graph transformation specifications. These tools consist of three parts: (a) for elaborating specific conceptual knowledge (knowledge engineer), (b) for working out conceptual design results (architect), and (c) automatic consistency analyses which guarantee that design results are consistent with the underlying specific conceptual knowledge. For the realization of such tools we use a machinery based on graph transformations. In a traditional PROGRES tool specification the conceptual knowledge for a class of buildings is hard-wired within the specification. This is not appropriate for the experimentation platform approach we present in this paper, as objects and relations for conceptual knowledge are due to many changes, implied by evaluation of their use and corresponding improvements. Therefore, we introduce a parametric specification method with the following characteristics: (1) The underlying specific knowledge for a class of buildings is not fixed. Instead, it is built up as a data base by using the knowledge tools. (2) The specification for the architect tools also does not incorporate specific conceptual knowledge. (3) An incremental checker guarantees whether a design result is consistent with the current state of the underlying conceptual knowledge (data base).
ITCE-2003 - 4th Joint Symposium on Information Technology in Civil Engineering ed Flood, I., Seite 1-12, ASCE (CD-ROM), Nashville, USA In this paper we discussed graph based tools to support architects during the conceptual design phase. Conceptual Design is defined before constructive design; the used concepts are more abstract. We develop two graph based approaches, a topdown using the graph rewriting system PROGRES and a more industrially oriented approach, where we extend the CAD system ArchiCAD. In both approaches, knowledge can be defined by a knowledge engineer, in the top-down approach in the domain model graph, in the bottom-up approach in the in an XML file. The defined knowledge is used to incrementally check the sketch and to inform the architect about violations of the defined knowledge. Our goal is to discover design error as soon as possible and to support the architect to design buildings with consideration of conceptual knowledge.
In: Forum Bauinformatik 2005 : junge Wissenschaftler forschen / [Lehrstuhl Bauinformatik, Brandenburgische Technische Universität Cottbus. Frank Schley ... (Hrsg.)]. - Cottbus : Techn. Universität 2005. S. 1-10 ISBN 3-934934-11-0
Mittels eines operationalen Ansatzes zur Semantikdefinition wird am Bei-spiel des konzeptuellen Gebäudeentwurfs ein Regelsystem formalisiert. Dazu werdenzwei Teile, zum einen das Regelwissen, zum anderen ein konzeptueller Entwurfsplan zunächst informell eingeführt und dann formal beschrieben. Darauf aufbauend wird die Grundlage für eine Konsistenzprüfung des konzeptuellen Entwurfs gegen das Regel-wissen formal angeben
In: Proceedings of the 39th Annual Hawaii International Conference on System Sciences, 2006. HICSS '06 http://dx.doi.org/10.1109/HICSS.2006.200 The conceptual design phase at the beginning of the building construction process is not adequately supported by any CAD-tool. Conceptual design support needs regarding two aspects: first, the architect must be able to develop conceptual sketches that provide abstraction from constructive details. Second, conceptually relevant knowledge should be available to check these conceptual sketches. The paper deals with knowledge to formalize for conceptual design. To enable domain experts formalizing knowledge, a graph-based specification is presented that allows the development of a domain ontology and design rules specific for one class of buildings at runtime. The provided tool support illustrates the introduced concepts and demonstrates the consistency analysis between knowledge and conceptual design.
In: Proc. of the 11th Intl. Conf. on Computing in Civil and Building Engineering (ICCCBE-XI) ed. Hugues Rivard, Montreal, Canada, Seite 1-12, ACSE (CD-ROM), 2006 Currently, the conceptual design phase is not adequately supported by any CAD tool. Neither the support while elaborating conceptual sketches, nor the automatic proof of correctness with respect to effective restrictions is currently provided by any commercial tool. To enable domain experts to store the common as well as their personal domain knowledge, we develop a visual language for knowledge formalization. In this paper, a major extension to the already existing concepts is introduced. The possibility to define rule dependencies extends the expressiveness of the knowledge definition language and contributes to the usability of our approach.
In: Computer Aided Architectural Design Futures 2005 2005, Part 4, 207-216, DOI: http://dx.doi.org/10.1007/1-4020-3698-1_19 The conceptual design at the beginning of the building construction process is essential for the success of a building project. Even if some CAD tools allow elaborating conceptual sketches, they rather focus on the shape of the building elements and not on their functionality. We introduce semantic roomobjects and roomlinks, by way of example to the CAD tool ArchiCAD. These extensions provide a basis for specifying the organisation and functionality of a building and free architects being forced to directly produce detailed constructive sketches. Furthermore, we introduce consistency analyses of the conceptual sketch, based on an ontology containing conceptual relevant knowledge, specific to one class of buildings.