Diffusion imaging markers of cerebral small vessel disease

Diffusion magnetic resonance imaging (MRI) is widely used as a research tool to assess (subtle) alterations of the cerebral white matter. Measures derived from diffusion MRI appear to be valuable markers for cerebral small vessel disease (SVD). However, SVD is frequently co-occurring with Alzheimer’s disease (AD), and disturbed white matter integrity and altered diffusion measures are considered key findings in both conditions. Yet, the contribution of SVD and AD to diffusion alterations is unclear, which hampers the interpretation of research studies in patients with mixed disease, e.g. memory clinic patients. Study 1 of this thesis aimed to clarify the effect of SVD and AD on diffusion measures by including multiple (memory clinic) samples covering the entire spectrum of SVD, mixed disease, and AD. We calculated diffusion measures from diffusion tensor imaging (DTI) and free water imaging. Within each sample of the disease spectrum, we applied simple regression analyses and multivariable random forest analyses between AD biomarkers (amyloid-beta, tau), conventional MRI markers of SVD, and global diffusion measures. Furthermore, we investigated regional associations between tau on positron emission tomography (PET) and diffusion measures in voxel-wise analyses. Our main findings are that conventional MRI markers of SVD were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analyses across all memory clinic samples. Regional analyses between tau PET and diffusion measures were not significant. We conclude that SVD rather than AD determines diffusion alterations in memory clinic patients. Our findings validate diffusion measures as markers for SVD. Study 2 applied diffusion MRI markers to study gait impairment in SVD. Gait impairment is a commonly reported clinical deficit in SVD patients, but the underlying mechanisms are still debated. The proposed mechanisms include SVD-related white matter alterations resulting in impaired supraspinal locomotor control, cognitive deficits (e.g. planning and execution of movements), and factors independent of SVD, such as age-related instability (e.g. joint wear, sarcopenia) and comorbidities (e.g. neurodegenerative pathology). A reason for the lack of knowledge on gait impairment in SVD is that studies in elderly, sporadic SVD patients are typically confounded by effects of normal-aging and age-related comorbidities. Therefore, Study 2 of this thesis aimed to study the effect of pure SVD on gait performance in a relatively young sample of genetically defined SVD patients without age-related confounding. We performed comprehensive gait assessment using an electronic walkway to obtain multiple spatio-temporal gait parameters standardized based on data from healthy controls. Importantly, we tested the association between diffusion MRI markers of SVD-related white matter alterations and gait performance, since (strategic) white matter alterations are discussed as a major cause of gait decline in the elderly. Furthermore, we assessed the relation between cognitive deficits and gait performance. Our main finding is that, despite severe white matter alterations in pure SVD patients, gait performance was relatively preserved. Cognitive deficits in our study participants were not related to gait impairment. Thus, our results query isolated white matter alterations, in the absence of comorbidities, as a main factor of gait impairment in SVD and suggest that their combination with age-related comorbidities and/or normal-aging may play a crucial role in gait decline. In conclusion, diffusion measures are valid MRI markers of SVD-related white matter alterations. They have significant value both in future research on altered white matter and potentially also in the diagnostic work-up of memory clinic patients, to differentiate between vascular and neurodegenerative disease. Researchers may select target populations for clinical trials based on diffusion measures, e.g. to identify patients with a low SVD burden as targets for prevention and early intervention in SVD. Clinicians and researchers should always consider SVD as the origin of diffusion alterations in patients with mixed pathology. The field of application of diffusion measures is wide and may provide new insights into effects of subtle white matter alterations on clinical deficits, as shown in Study 2 on gait impairment in pure SVD. Future studies should investigate measures from advanced diffusion models and diffusion-based brain network analysis, to further elucidate the mechanisms of clinical deficits in SVD patients

Diffusion imaging markers of cerebral small vessel disease

Diffusion magnetic resonance imaging (MRI) is widely used as a research tool to assess (subtle) alterations of the cerebral white matter. Measures derived from diffusion MRI appear to be valuable markers for cerebral small vessel disease (SVD). However, SVD is frequently co-occurring with Alzheimer’s disease (AD), and disturbed white matter integrity and altered diffusion measures are considered key findings in both conditions. Yet, the contribution of SVD and AD to diffusion alterations is unclear, which hampers the interpretation of research studies in patients with mixed disease, e.g. memory clinic patients. Study 1 of this thesis aimed to clarify the effect of SVD and AD on diffusion measures by including multiple (memory clinic) samples covering the entire spectrum of SVD, mixed disease, and AD. We calculated diffusion measures from diffusion tensor imaging (DTI) and free water imaging. Within each sample of the disease spectrum, we applied simple regression analyses and multivariable random forest analyses between AD biomarkers (amyloid-beta, tau), conventional MRI markers of SVD, and global diffusion measures. Furthermore, we investigated regional associations between tau on positron emission tomography (PET) and diffusion measures in voxel-wise analyses. Our main findings are that conventional MRI markers of SVD were strongly associated with diffusion measures and showed a higher contribution than AD biomarkers in multivariable analyses across all memory clinic samples. Regional analyses between tau PET and diffusion measures were not significant. We conclude that SVD rather than AD determines diffusion alterations in memory clinic patients. Our findings validate diffusion measures as markers for SVD. Study 2 applied diffusion MRI markers to study gait impairment in SVD. Gait impairment is a commonly reported clinical deficit in SVD patients, but the underlying mechanisms are still debated. The proposed mechanisms include SVD-related white matter alterations resulting in impaired supraspinal locomotor control, cognitive deficits (e.g. planning and execution of movements), and factors independent of SVD, such as age-related instability (e.g. joint wear, sarcopenia) and comorbidities (e.g. neurodegenerative pathology). A reason for the lack of knowledge on gait impairment in SVD is that studies in elderly, sporadic SVD patients are typically confounded by effects of normal-aging and age-related comorbidities. Therefore, Study 2 of this thesis aimed to study the effect of pure SVD on gait performance in a relatively young sample of genetically defined SVD patients without age-related confounding. We performed comprehensive gait assessment using an electronic walkway to obtain multiple spatio-temporal gait parameters standardized based on data from healthy controls. Importantly, we tested the association between diffusion MRI markers of SVD-related white matter alterations and gait performance, since (strategic) white matter alterations are discussed as a major cause of gait decline in the elderly. Furthermore, we assessed the relation between cognitive deficits and gait performance. Our main finding is that, despite severe white matter alterations in pure SVD patients, gait performance was relatively preserved. Cognitive deficits in our study participants were not related to gait impairment. Thus, our results query isolated white matter alterations, in the absence of comorbidities, as a main factor of gait impairment in SVD and suggest that their combination with age-related comorbidities and/or normal-aging may play a crucial role in gait decline. In conclusion, diffusion measures are valid MRI markers of SVD-related white matter alterations. They have significant value both in future research on altered white matter and potentially also in the diagnostic work-up of memory clinic patients, to differentiate between vascular and neurodegenerative disease. Researchers may select target populations for clinical trials based on diffusion measures, e.g. to identify patients with a low SVD burden as targets for prevention and early intervention in SVD. Clinicians and researchers should always consider SVD as the origin of diffusion alterations in patients with mixed pathology. The field of application of diffusion measures is wide and may provide new insights into effects of subtle white matter alterations on clinical deficits, as shown in Study 2 on gait impairment in pure SVD. Future studies should investigate measures from advanced diffusion models and diffusion-based brain network analysis, to further elucidate the mechanisms of clinical deficits in SVD patients

Die Erfassung der Höhenänderung von Ostalpengletschern in den Zeiträumen 1950-1959-1969

In a continuation of Richard Finsterwalder's work of 1950 eight selected glaciers in the Eastern Alps have been photogrammetrically surveyed and mapped on a scale of 1:10.000 in the years 1959 and 1969 in order to establish a record of glacier variation. From a comparison of isohypses of the 1950, 1959 and 1969 surveys the height changes of the glacier surfaces have been determined for approximately two decades. This yielded an average raise of 0,1 m per year, while an average sinking of glacier surfaces of 0,6 m per year had been found for the period 1920-1950

GRIN2A: Kandidatengen bei idiopathischen (genetischen) Epilepsien im Kindesalter

Ziel dieser Arbeit war die Identifikation und Analyse neuer Kandidatengene für häufige, idiopathische (genetische) Epilepsien. Es wurden unterschiedliche Methoden zur Generierung neuer Kandidatengene eingesetzt. GRIN2A wurde auf Grund der physiologischen und biologischen Eigenschaften als primäres Kandidatengen bei idiopathischen Epilepsien für weitere Analysen ausgewählt

Brücken bauen: Die Exlibris von Ernst G. Preuß

Eine erfolgreiche und zielführende Provenienzforschung bemisst sich u.a. an der eindeutigen Identifikation von Eigner*innenzeichen wie Widmungen, Unterschriften und Exlibris, sowie der Restitution der untersuchten Objekte. Am Beispiel der Identifikationsgeschichte der Exlibris des in Deutschland als Jude verfolgten und ins Exil getriebenen Sozialpolitikers Ernst G. Preuß (1891–1966) wird nachgezeichnet, wie hilfreich ein offener Umgang mit erhobenen Forschungsdaten und wie entscheidend die Inanspruchnahme nichtbibliothekarischer Fachkompetenzen sein kann, um eine solche Provenienzforschung umsetzen zu können.Successful and purposeful provenance research is measured, among other things, by the clear identification of owner’s marks such as dedications, signatures and bookplates, as well as the restitution of the objects examined. Using the example of the identification process of the bookplates of the social policy expert Ernst G. Preuß (1891–1966), who was persecuted as Jewish in Nazi Germany and forced into exile, it is shown how helpful it can be to deal openly with the research data collected and how essential it is to draw on the expertise of non-librarians in order to implement a provenance research of this kind

A 360-degree view of actor engagement in service co-creation

In recent years, discussion surrounding the construct of customer engagement in service research has gained significant attention from academics and practitioners alike. The discussion of engagement, an important topic for service research, has focused on the customer, neglecting the roles of other actors, such as employees, who can play a large part in the value co-creation process. This paper is a call-to-action for academics to include a 360-degree view of engagement into the service research discourse. The employment of a service ecosystems perspective is suggested to include engagement from an actor-to-actor perspective. The objective is to focus on all actors who intend to participate, already actively participate in, or actors who are disengaged from the value co-creation process in such systems

Paris-Berlin-Paris. The retracement of one route of Nazi-looted books from France and the way to bring them back

Ce colloque s’est tenu les jeudi et vendredi 23 et 24 mars 2017, à la Bibliothèque universitaire des langues et civilisations et à la Bibliothèque nationale de France, Il a été organisé par le Centre Gabriel Naudé de l\u27Ecole nationale supérieure des sciences de l\u27information et des bibliothèques (ENSSIB), l\u27Institut d\u27histoire du temps présent (IHTP, UMR CNRS Paris 8) et l\u27Université Paris Diderot (EA Identités, cultures, territoires), avec le soutien de la Bibliothèque nationale de France, de la Bibliothèque universitaire des langues et civilisations (BULAC), de la Fondation pour la Mémoire de la Shoah, de la Claims Foundation, de la Fondation Maison des Sciences de l\u27Homme et du Deutscher Akademischer Austauschdienst. Au cours de ce colloque, une douzaine de livres, datant du XVIIe siècle et retrouvés dans ses collections par la Bibliothèque centrale et régionale de Berlin (Zentral -und Landesbibliothek) ont été restitués à trois ministères français (ministère des Affaires étrangères, ministère de l\u27Intérieur, ministère de la Justice) auxquels ils avaient été spoliées en juin 1940. Un registre manuscrit d\u27état civil des années 1751-1771, spolié à la commune de Verpel (Ardennes) lui sera également restitué. Associé à ce colloque en ligne, les Presses de l’Enssib proposent Où sont les bibliothèques françaises spoliées par les nazis ? ouvrage coordonné par Martine Poulain qui a rassemblé les contributions, enrichies, concernant particulièrement l’histoire d’environ 14 000 livres spoliés et déposés dans une quarantaine de bibliothèques françaises entre 1950 et 1953, et leurs caractéristiques. https://presses.enssib.fr/catalogue/ou-sont-les-bibliotheques-francaises-spoliees-par-les-nazi

Intentionality and transformative services: Wellbeing co-creation and spill-over effects

In recent years, the service discipline has seen the emergence of a number of novel conceptual approaches, one in particular, called Transformative Service Research (TSR) focuses on wellbeing improvement and relieving suffering through service. However, service related wellbeing efforts can have both intended but also unintended consequences when aiming at co-creating value with individuals, communities or society at large. Nevertheless, academic debate lacks clarity regarding the effects of the directedness of service exchange and the outcome of transformative service in regard to, but also beyond, the focal actors involved. Directedness of service co-creation is closely related to the construct of intentionality. This conceptual paper aims to untangle this pivotal construct to comprehend actors’ intended co-creative wellbeing efforts to alleviate suffering of other actors, and it pays attention to potential unintended side effects. The paper synthesizes literature from philosophy and psychology relating to the construct of intentionality and applies it to wellbeing co-creation and co-destruction. Illustrative scenarios are used to support the lines of argument. The paper demonstrates how applying the literature on intentionality to transformative service contexts can assist in bringing greater transparency to the discussion of the directedness of service related wellbeing efforts and potential spill-over effects. When designing transformative services to improve wellbeing, service providers are urged to develop an awareness regarding their services and potential side effects. Likewise, policymakers responsible for devising, revising and (re-)implementing healthcare and social policies should consider such potential spill-over effects when formulating public policy guidelines. Equally, service scholars should integrate the construct of intentionality in any discussion of service-to-service exchange. This paper is amongst the first to draw on the concept of intentionality and introduces it to service research in the context of wellbeing co-creation

Equilibrating Resources and Challenges during Crises: A Framework for Service Ecosystem Wellbeing

Purpose: This article explores the impact of crises, such as the coronavirus pandemic, on service industries, service customers, and the service research community. It contextualizes pandemics in the realm of disasters and crises, and how they influence actors' well-being across the different levels of the service ecosystem. The paper introduces a resources–challenges equilibrium (RCE) framework across system levels to facilitate service ecosystem well-being and outlines a research agenda for service scholars. Design/methodology/approach: Literature on disasters, crises, service and well-being is synthesized to embed the COVID-19 pandemic in these bodies of work. The material is then distilled to introduce the novel RCE framework for service ecosystems, and points of departure for researchers are developed. Findings: A service ecosystems view of well-being co-creation entails a dynamic interplay of actors' challenges faced and resource pools available at the different system levels. Research limitations/implications: Service scholars are called to action to conduct timely and relevant research on pandemics and other crises, that affect service industry, service customers, and society at large. This conceptual paper focuses on service industries and service research and therefore excludes other industries and research domains. Practical implications: Managers of service businesses as well as heads of governmental agencies and policy makers require an understanding of the interdependence of the different system levels and the challenges faced versus the resources available to each individual actor as well as to communities and organizations. Social implications: Disasters can change the social as well as the service-related fabric of society and industry. New behaviors have to be learned and new processes put in place for society to maintain well-being and for service industry's survival. Originality/value: This paper fuses the coronavirus pandemic with service and well-being research, introduces a resources-challenges equilibrium framework for service ecosystem well-being and outlines a research agenda