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Investigation of calcitonin-gene related peptide levels in tear fluid during nitroglycerin induced migraine attacks
Get PDFNeurological soft signs in adolescents are associated with brain structure and postural control
Get PDFNeurological soft signs (NSS) are minor deviations from the norm in sensory and motor performance. NSS exist in the general population but are more frequently found in cohorts with neurodevelopmental disorders. NSS are considered a diffuse and unspecific marker of altered neurodevelopment but receive increasing attention since the presence of NSS in children has been found to be predictive of psychiatric disorders in late adolescence. To date, only little is known about potential neurodevelopmental alterations that may underlay the presence of NSS. The prevalence of NSS has been shown to decrease during adolescence as part of continued neural development and brain re-wiring processes. Therefore, adolescence has been proposed as an important phase for the manifestation or outgrowing of NSS. The underlying mechanisms that may underly this process, however, are largely unknown. As NSS are subtle signs and commonly identified by subjective observer-based neurological examinations, quantitative tools may help to objectively investigate functional and structural correlates associated with NSS.
For the work included in this dissertation, healthy adolescent athletes from three European countries were investigated. All participants underwent a neurological examination, resulting in a categorization of participants into groups with and without NSS (NSS+/NSS-). A total NSS score was calculated to provide a continuous measure spanning the whole spectrum of NSS. Two quantitative tools were used to investigate functional and structural correlates of NSS in healthy adolescents: Study I) Instrumented force plate measures to investigate postural control (Bonke et al., 2023), and Study II) Structural magnetic resonance imaging to investigate brain morphology and white matter microstructure (Bonke et al., 2022).
Study I aimed to investigate the incremental value of instrumented force plate measures in addition to observer-based neurological examinations. Such associations have not been assessed before but are important for capturing subtle alterations in postural control. This will help to acquire a more comprehensive assessment of motor development. We found no statistically significant differences in postural control between NSS+ and NSS- group. However, participants performing non-optimal in the diadochokinesis sub-test measuring pronation/supination of forearms showed significantly reduced postural control in the medial-lateral (ML) direction. Moreover, the total NSS score correlated significantly with postural control performance in the ML direction. Findings from this study reveal that adolescents with NSS, and in particular adolescents that perform non-optimal in pronation/supination movements of the forearms also perform worse in ML postural control assessed by force plate assessments. As pronation/supination movements of forearms and ML postural control continue to mature until adolescence, it can be assumed that these functions are related and may indicate altered motor development.
Study II aimed to identify and characterize NSS-related brain structure alterations using structural magnetic resonance imaging. NSS-related brain structure alterations have not yet been investigated in healthy adolescents. However, this investigation is of high relevance to better understand potential alterations in adolescent brain-rewiring processes related to NSS. Using T1-weighted imaging, we found significantly higher gyrification in the left superior frontal and parietal lobe in the group of adolescents with NSS, likely reflecting alterations in synaptic pruning. We did not find differences in cortical volume or thickness. Using diffusion tensor imaging, we found lower tissue fractional anisotropy (FAt) and higher tissue radial diffusivity (RDt) in widespread white matter clusters in the group of adolescents with NSS, likely indicating alterations in myelination. Findings from this study reveal that NSS in healthy adolescents are associated with brain structure alterations that can be objectively quantified using magnetic resonance imaging. As of now, the relevance of NSS-related brain structure alterations in otherwise healthy adolescents is not fully understood. Future studies should assess whether these alterations may explain the described association between NSS and psychiatric disorders.
In summary, the work presented in this doctoral dissertation uses two different quantitative measures to objectively investigate functional and structural differences between adolescents with and without NSS. Insights derived from this work show the beneficial use of instrumented tools to complement neurological examinations for a better understanding of functional and structural correlates of NSS. This work will help to generate a more complete picture of NSS-related developmental alterations and potentially related psychiatric vulnerabilities. Future research should make use of larger and more representative datasets to replicate, as well as extend our findings. Specific attention should be drawn on the investigation of factors that contribute to the development of NSS, longitudinal studies that allow to capture NSS-related alterations in developmental trajectories, as well as on investigating the underlying neural mechanisms of NSS
Dust dynamics and distribution in protoplanetary disks
Get PDFFeinkörniger Staub ist der grundlegende Baustein von terrestrischen Planeten wie der Erde, die um junge Sterne entstehen. Gleichzeitig beeinflusst der Staub astronomische Beobachtungen, da er den Hauptbeitrag zur Opazität in den Gasscheiben leistet, die entstehende Sterne umgeben (sog. protoplanetare Scheiben). Daher sind genaue Modelle der Verteilung und Bewegung von Staub in protoplanetaren Scheiben von entscheidender Bedeutung für das Verständnis der Anfangsbedingungen der Planetenentstehung und für die Interpretation astronomischer Beobachtungen von jungen Planeten- und Sternensystemen. Dieses Thema ist besonders relevant, da neueste astronomischen Beobachtungen protoplanetarer Scheiben neue Maßstäbe in Bezug auf Auflösung und Empfindlichkeit setzen und dadurch unser derzeitiges Verständnis und unsere Modelle infrage stellen.
In dieser Arbeit präsentiere ich ein neuartiges und in sich konsistentes Modell der turbulenten Durchmischung von Staub. Das Modell bestätigt detaillierte Vorhersagen, wobei Nachteile früherer Modelle hinsichtlich der Drehimpulserhaltung, der uneindeutigen Definition der durchmischten Größe und Auswirkungen der Bahndynamik wegfallen. Somit verbessern wir die Beschreibung der Bewegung von Staub in turbulenten protoplanetaren Scheiben maßgeblich.
Anschließend zeige ich auf, wie turbulente Durchmischung von Staub und andere Transportphänomene im frühen Sonnensystem, den Mangel an beständigen Kohlenstoffverbindungen, im inneren Bereich des heutigen Sonnensystems erklären kann.
Im Folgenden konzentriert sich die Arbeit auf die dreidimensionale Verteilung des Staubs in protoplanetaren Scheiben in Gegenwart eines Riesenplaneten. Mithilfe von hydrodynamischen Zwei-Fluid-Simulationen (Gas + Staub) finden wir, dass ein Planet die Staubverteilung in protoplanetaren Scheiben stark beeinflusst. Wir beschreiben beobachtbare Merkmale in synthetischen Radiowellenbeobachtungen, die es erlauben, auf die Anwesenheit eines unentdeckten Riesenplaneten in einer protoplanetaren Scheibe zu schließen.
Schließlich untersuchen wir die Verwirbelung von Staub durch einen Riesenplaneten, zusätzlich zur Durchmischung durch turbulentes Gas. Wir konzentrieren uns dabei auf deren kombinierte Wirkung auf die dreidimensionale Verteilung des Staubs und untersuchen Merkmale, die mit Radiowellenbeobachtungen einer protoplanetarer Scheibe beobachtbar sind und Rückschlüsse auf die Anwesenheit eines noch unentdeckten Planeten erlauben.
Diese Arbeit bietet neue Einblicke in die Dynamik von Staub in turbulenten protoplanetaren Scheiben und liefert eine Erklärung für den Mangel an beständigen Kohlenstoffverbindungen im inneren Sonnensystem. Außerdem beschreiben wir mögliche beobachtbare Merkmale von noch unentdeckten Riesenplaneten in Radiowellenbeobachtungen von protoplanetaren Scheiben.Fine-grained dust is the fundamental building block of terrestrial planets, like Earth, that form around young stars. At the same time, the dust distribution in the gaseous disks around forming stars, so-called protoplanetary disks, influences astronomical observations, because dust is the main contributor to the opacity in protoplanetary disks. Therefore, accurate models of the distribution and dynamics of dust are critical to understanding the initial stages of planet formation and interpreting astronomical observations of forming planetary and stellar systems. This is particularly relevant because recent astronomical observations of protoplanetary disks have reached new heights in terms of resolution and sensitivity, challenging our current understanding and models.
In this thesis, I introduce a novel and self-consistent turbulent dust transport model based on a density-weighted mean-field theory that also captures non-local transport effects. The model improves upon the limitations of earlier models related to the conservation of angular momentum, the ambiguous nature of the transported quantity, and the transport effects of orbital dynamics. We therefore provide an improved description of dust dynamics in turbulent protoplanetary disks.
Subsequently, I present how turbulent dust dynamics and transport in the early Solar System can explain the lack of refractory carbon in the inner Solar System today.
The thesis then focuses on the three-dimensional dust distribution in protoplanetary disks in the presence of an embedded giant planet. With the help of radiative two-fluid (gas+dust) hydrodynamic simulations, we find that a planet significantly influences the dust distribution in protoplanetary disks. We identify observational signatures in synthetic radio continuum observations that hint at the potential presence of a yet undetected giant planet in a protoplanetary disk.
Finally, we investigate dust stirring by a giant planet in addition to dust mixing caused by turbulent gas. We focus on the combined effects on the three-dimensional dust morphology and study observable effects of turbulent and planetary dust stirring in radio continuum observations of protoplanetary disks with an embedded planet.
Our work provides novel insights into turbulent dust dynamics in protoplanetary disks and offers an explanation for the lack of refractory carbon in the inner Solar System. We also describe observational signatures of giant planets in protoplanetary disks that help with the interpretation of continuum observations. These results help guide astronomers toward the detection of forming and yet unobserved planets in protoplanetary disks
Retrospektive Untersuchung einer neuen multidisziplinären Versorgungsstruktur für Patienten mit einer Erkrankung aus dem schizophrenen Formenkreis, basierend auf vorhandenen Routinedaten
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Translationale Evaluation innovativer Radioliganden für die Positronen-Emissions-Tomographie des Glioblastoms
Get PDFAssessing a population’s need for healthcare
Get PDFThe need for healthcare corresponds to the level of treatable morbidity in a population and is a vital component in healthcare planning to estimate the required number of physicians. As such, the need for healthcare is a complex construct that is ought to be approximated through a robust theoretical concept, considering central indicators. However, a systematic assessment of current methodologies to estimate needs-based supply of physicians using central requirements is missing. In Germany, physician planning follows a supply-based approach using physician-to-population ratios, which are adapted with a demographic factor. In recent years, it was found that multimorbidity (the occurrence of multiple conditions in one individual) is correlated with healthcare utilisation and it has seen a steady increase in prevalence. Thus, multimorbidity as a central driver of need was declared a major challenge for health systems – including Germany – as health systems are centred on single-disease treatment approaches and fragmented in the provision of healthcare. Yet information on the distribution of multimorbid individuals is ambiguous.
This thesis aims to enhance knowledge in both areas: (1) needs-based planning of physicians and (2) necessity to integrate regional multimorbidity in office-based physician planning.
First, a methodological review was conducted to assess current approaches that estimate needs-based supply of physicians through a set of quality criteria while determining the role of multimorbidity. The review highlighted differences in the conceptual frameworks, data bases, modelling approaches and integration of future trends. It was also found that approaches estimating needs-based supply of physicians against quality criteria revealed several weaknesses and methodological gaps, with none of the studies meeting all quality criteria. Importantly, no incorporation of multimorbidity measures in needs-based physician planning was found.
Second, a cross-sectional study was conducted to analyse regional variations of multimorbidity levels in four physician disciplines in Germany: General practitioners (GPs), neurologists, ophthalmologists, and orthopaedic specialists. Bernoulli cluster analysis was applied to detect high-rate and low-rate clusters of multimorbid patients per discipline, with the results tested for robustness through spatial autocorrelation mapping. Additionally, high-rate clusters were compared with the available supply of physicians. The study identified significant variations in the regional distribution of multimorbidity levels. High-rate clusters with varying size and location were predominantly found in central and eastern Germany for all physician groups. The comparison of high-rate clusters with supply demonstrated that almost all high-rate clusters of specialised physicians were met by average supply that exceeded the targeted coverage, but high-rate clusters of GPs were met with average supply below targeted coverage in 5 out of 11 clusters.
To conclude, the methodological weaknesses identified in the systematic review can now be tackled by policymakers and scholars alike to improve future needs-based planning of physicians. Moreover, the variations in regional distribution of multimorbidity clusters highlight the importance of integrating multimorbidity measures when estimating the need for office-based physicians. These findings can be used as an additional resource to reform German physician planning as it will help to direct the planning focus on areas of increased need for healthcare services and care coordination. Given the situation in general practice, improvements in GP care should be targeted most urgently
Prognose und Ergebnisse der operativen Therapie von Patienten mit Knochenmetastasen eines Mammakarzinoms
Get PDFEs wurden 115 Patienten (132 Operationen) mit Knochenmetastasen nach Mammakarzinom ausgewertet, die im Zeitraum 1980 bis 2005 an der Orthopädischen Klinik und Poliklinik der Ludwig-Maximilians-Universität München operativ versorgt wurden.
Patienten ohne pathologische Frakturen und ohne viszerale Metastasen sowie Patienten, bei denen ein R0-Status erreicht werden konnte, hatten eine höhere Überlebenswahrscheinlichkeit. Patienten mit nur einer solitären Knochenmetastase überlebten signifikant länger. Hatten die Patienten jemals eine tumorfreie Zeit, wirkte sich dies ebenfalls positiv auf das Gesamtüberle-ben aus.
Weder das Alter der Patienten in dieser untersuchten Gruppe noch die Zeit zwischen der Diagnose des Primärtumors und der operativen Versorgung der Knochenmetastasen hatten einen signifikanten Einfluss auf die Überlebenszeiten