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Persönlichkeit im Kontext von Autismus und Alexithymie
Get PDFPersönlichkeitsstörungen spielen im Umfeld von Autismus-Spektrum-Störungen (ASS) des Öfteren eine Rolle, sei es als Komorbiditäten oder aufgrund einer Überlappung von Symptomen als mögliche Differentialdiagnosen. Das Konzept der Alexithymie wiederum bezeichnet Schwierigkeiten im Erkennen und Benennen der eigenen Emotionen und ist in der Allgemeinbevölkerung mit einer Rate von ungefähr 10% vertreten. Unter Autist*innen ist die Häufigkeit deutlich höher, wobei die Literaturangaben stark schwanken. Die vorliegende Dissertation befasst sich mit den Zusammenhängen zwischen autistischen und alexithymen Zügen sowie schizoiden, Borderline-, narzisstischen, vermeidenden und zwanghaften Persönlichkeitsmustern in drei Gruppen: bei Personen mit einer diagnostizierten ASS, Personen ohne ASS, jedoch mit einer anderweitigen sozialen Interaktionsstörung, sowie in einer neurotypischen Kontrollgruppe. Die interessierenden Zusammenhänge wurden mithilfe von multiplen linearen Regressionsanalysen untersucht. Autistische Züge zeigten sich als signifikanter Prädiktor für schizoide Persönlichkeitsmuster in der ASS-Gruppe sowie für zwanghafte Persönlichkeitsmuster in allen drei Gruppen. Alexithyme Züge stellten einen signifikanten Prädiktor für schizoide sowie für Borderline-Persönlichkeitsmuster in der Kontrollgruppe dar.Personality disorders often play a role in the context of autism spectrum disorders (ASD), either as a comorbidity or due to an overlap of symptoms as possible differential diagnoses. The concept of alexithymia again refers to difficulties in identifying and de-scribing one's own emotions and is represented in the general population at a rate of about 10%. Among autistic individuals, the prevalence is notably higher, although the literature varies widely. This thesis deals with the relations between autistic and alexi-thymic traits as well as schizoid, borderline, narcissistic, avoidant, and obsessive-com-pulsive personality patterns in three groups: individuals diagnosed with ASD, individuals without ASD but some other social interaction disorder, and a neurotypical control group. The associations of interest were examined using multiple linear regression analyses. Autistic traits significantly predicted schizoid personality patterns in the ASD group and obsessive-compulsive personality patterns in all three groups. Alexithymic traits repre-sented a significant predictor of schizoid and borderline personality patterns in the control group
The art of balance: canonical and non-canonical mechanisms of developmental neurogenesis
Get PDFThe seat of our higher cognitive functions—the brain—originates from a simple sheet of cells known as neural stem cells (NSCs). They give rise to neurons and other essential cell types that constitute the brain during development. The process of generating neurons, or neurogenesis, has captivated scientists for decades, if not centuries. Yet, we are still scratching the surface of understanding how NSCs balance their plasticity with their commitment to differentiate into neurons.
One focal point of research lies in the role of transcription factors (TFs). These potent regulators of gene expression are pivotal in determining cell fate and have been extensively studied in the context of NSCs. While numerous TFs critical to neurogenesis have been identified, the search continues for a universal regulator—a pan-factor—that regulates neural stem cell fate and neurogenesis. Furthermore, beyond transcriptional control, emerging evidence suggests the importance of non-canonical mechanisms that remain largely unexplored but may hold the key to uncovering novel regulatory pathways in neurogenesis.
In this thesis, I will explore both canonical and non-canonical mechanisms that govern the balance between self-maintenance and differentiation of NSCs during developmental neurogenesis. Understanding these mechanisms is not only essential for decoding the complexities of brain development but also carries significant implications for developing therapies for neurodevelopmental disorders and brain injuries
Identifizierung molekularbiologischer und klinischer Risikoindikatoren bei Patienten mit Lungenfibrose
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Improved sampling techniques for the simulation of biocatalytic reaction mechanisms
Get PDFIn recent years, the dramatic improvement of computer hardware, as well as remarkable algorithmic advances, enabled accurate computer simulations of ever-growing molecular systems.
Nowadays, with the help of composite quantum-mechanical/molecular-mechanical (QM/MM) methods, it is possible to model 'electronic' processes, like chemical reaction mechanisms that involve covalent bond rearrangements, in extended biological macromolecules with thousands of atoms.
Such systems are frequently characterized by remarkable structural flexibility and potential energy surfaces full of local minima.
Therefore, to enable the calculation of accurate ensemble properties, representative sampling of their configurational landscape is required, usually employing molecular dynamics (MD) simulations.
However, it is crucial that the trajectories obtained are sufficiently long to resolve rare events, i.e., phenomena that occur on macromolecular timescales and are beyond the reach of conventional all-atom molecular dynamics (MD) simulations.
Hence, importance sampling techniques are applied to accelerate transitions between metastable states.
In addition to accelerating sampling, such methods must provide accurate estimates of reaction free energy differences and kinetic rates of chemical transitions, such that the most likely reaction mechanisms can be found.
In this dissertation, several improvements of importance sampling techniques are presented.
The focus lies on highly efficient algorithms, which are suitable for use together with an accurate QM/MM treatment of the electronic structure based on density functional theory (DFT), which still limits MD simulations to timescales of only a few hundred picoseconds due to their computational demand.
The result is a versatile toolbox of sampling algorithms, which is made publicly available in the open-source adaptive-sampling Python package, that is highly useful for modeling intricate biocatalytic reaction mechanisms in explicit protein environments.
This is demonstrated by its application to the simulation of challenging enzymatic systems that catalyze intricate biochemical transitions, such as ribonucleic acid (RNA) modification, adenosine triphosphate (ATP) hydrolysis, or long-range biological protonation dynamics
Interacting white dwarfs in binaries and triples
Get PDFWhite dwarfs are the most common endpoints of stellar evolution and play a crucial role in various astrophysical phenomena, such as thermonuclear explosions, compact binary mergers, and gravitational wave sources. While the evolution of white dwarfs in binary systems has been extensively studied, many open questions remain, particularly regarding the interactions that lead to thermonuclear events such as Type Ia supernovae. Moreover, the role of hierarchical triples in shaping white dwarf formation and interactions is less well understood. In this thesis, I investigate how both binary and triple-star dynamics shape the white dwarf population and influence their interactions.
First, I conduct a population synthesis study of hierarchical triples using the Multiple Stellar Evolution MSE code, focusing on the impact of stellar evolution, binary interactions, and dynamical effects on white dwarf formation. This study simultaneously considers both the single and double degenerate channels and accounts for triples across the entire parameter space, including those with tight inner binaries. Additionally, I investigate the effects of typically overlooked or uncertain physics, such as fly-bys and common envelope prescription parameters. By comparing the outcomes of triple and binary evolution channels, I assess the significance of triples in producing Type Ia supernovae.
Next, I use the MESA stellar evolution code to model He star + white dwarf systems in detail. These simulations represent the most up-to-date study of single degenerate progenitors, exploring an extensive grid of hot subdwarf + white dwarf configurations and their possible evolutionary outcomes, including double white dwarf formation, helium novae, and thermonuclear explosions. Additionally, I calculate the runaway velocities of surviving donor stars in systems where an explosion occurs.
Finally, I examine the contribution of white dwarfs from the triple channel to the Galactic population of double white dwarfs detectable by the Laser Interferometer Space Antenna (LISA). By combining MSE with a Milky Way-like galaxy model from cosmological simulations TNG50, I construct a synthetic Galactic white dwarf population and compare the contribution from triple systems to that of isolated binaries. While previous studies have primarily focused on binary formation and evolution in isolation, this work presents the first detailed investigation into the role of triple stellar evolution in shaping the LISA double white dwarf population. I predict both the total number of double white dwarfs from the triple channel contributing to LISA's astrophysical noise and the number of individually resolvable double white dwarfs.
This thesis emphasizes the critical role of binary and hierarchical triple systems in the formation and evolution of white dwarfs, as well as their influence on shaping the observable population of compact objects. The findings have significant implications for gravitational wave astronomy, interacting white dwarf binaries, progenitors of Type Ia supernovae, and our broader understanding of binary and multiple-star evolution
Stumme Ischämien bei Patienten im Zustand nach einem embolischen Schlaganfall unbekannter Ursache - Prävalenz und prädiktive Faktoren
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Embolische Schlaganfälle unbekannter Ursache (embolic stroke of undetermined source, ESUS) stellen einen beträchtlichen Anteil aller ischämischen Schlaganfälle dar, wobei das Risiko eines Schlaganfallrezidivs relevant hoch ist.
Neben klinisch manifesten Ischämien ereignen sich typischerweise auch klinisch
stumme Ischämien, deren Prävalenz und Bedeutung in der ESUS-Population noch unzureichend erforscht ist. Diese Arbeit zielt darauf ab, die Prävalenz stummer Ischämien nach ESUS zu bestimmen und potenzielle prädiktive Faktoren für ihr Auftreten zu identifizieren, um die Sekundärprophylaxe von ESUS zu verbessern.
Material und Methoden:
In dieser Teilstudie wurden 91 Teilnehmer der Catch-up-ESUS-Studie (n=567) zwischen 2018 und 2021 eingeschlossen, die einen ESUS erlitten und im Rahmen der klinischen Routine eine Magnetresonanztomographie (MRT) des Gehirns im Verlauf durchgeführt hatten. Während des stationären Aufenthalts des Index-ESUS wurden demografische, klinische und bildgebende Parameter erhoben. Zusätzlich wurden während der Followup-Untersuchungen Daten wie die modifizierte Rankin-Skala (mRS), kardiovaskuläre Risikofaktoren, medikamentöse Sekundärprophylaxe, sowie das Vorhandensein von Vorhofflimmern (VHF) oder eines persistierenden Foramen ovale (PFO) erfasst. Die Hauptvariablen, die während des Follow-ups mittels MRT untersucht wurden, waren das Auftreten einer stummen Hirnischämie und/oder eines klinischen Schlaganfallrezidivs.
Ergebnisse:
In der vorliegenden Studienpopulation traten bei 16 der 91 eingeschlossenen Patienten (17,6 %) während des durchschnittlichen Follow-up-Zeitraums von 809 ± 352 Tagen neue Hirnischämien auf. Stumme Ischämien traten bei 9 Patienten (9,9 %) auf, während 7 klinische Reinfarkte bei 11 Patienten (12,1 %) diagnostiziert wurden. Die Analyse potenzieller prädiktiver Faktoren erfolgte anhand von drei Vergleichsgruppen: Patienten ohne Schlaganfall-Rezidiv im Vergleich zu denen mit stummen, klinischen und sowohl stummen als auch klinischen Reinfarkten; Patienten mit stummen Ischämien im Vergleich zu denen mit klinischen Reinfarkten; Patienten ohne Schlaganfall-Rezidiv im Vergleich zu denen mit jeglicher Art von Schlaganfall-Rezidiv. Weder das Geschlecht noch kardiovaskuläre Risikofaktoren, VHF oder PFO erwiesen sich als prädiktiv für stumme Ischämien. Ebenso hatte die Wahl der medikamentösen Sekundärprophylaxe keinen Einfluss auf die Manifestation von stummen Ischämien und es konnte keine Assoziation zwischen der Lokalisation des Index- und des Reinfarkts festgestellt werden. Allerdings zeigten Patienten mit stummen Ischämien eine höhere funktionelle Beeinträchtigung im Vergleich zu Patienten ohne Rezidiv. Insbesondere zum Zeitpunkt des Follow-up wiesen Patienten mit Reinfarkt einen signifikant höheren mRS-Wert auf (1,0 - 2,3 ± 1,5 - 2,1 vs. 0,3 ± 0,9, p = 0,001). Bereits bei der Aufnahme neigten Patienten mit stummen Ischämien ebenfalls zu höheren mRS-Werten im Vergleich zu denen ohne Reinfarkt (2,8 ± 1,9 vs. 1,9 ± 1,3, p = 0,57).
Schlussfolgerung:
Die Haupterkenntnis dieser Arbeit ist das häufige Auftreten sowohl klinisch stummer
als auch manifest auftretender Re-Infarkte in der ESUS-Population. Jedoch konnten
keine eindeutigen prädiktiven Faktoren für das Auftreten von stummen Ischämien
nach einem ESUS identifiziert werden. Insbesondere Patienten mit einer schweren
funktionellen Beeinträchtigung scheinen häufiger betroffen zu sein. Diese Patientengruppe könnte dahingehend von einer engmaschigeren klinischen Überwachung
oder einer routinemäßigen MRT-Verlaufsbildgebung profitieren. Es bedarf weiterer
prospektiver Studien zu diesem Thema, um sekundäre Präventionsstrategien zu entwickeln, welche die Prognose von ESUS-Patienten verbessern könnten
Predictors and dynamics of household Mtb transmission in high tuberculosis incidence settings
Get PDFIntroduction: Tuberculosis (TB) remains a critical global health challenge, disproportionately affecting high-burden regions in Southern Africa. Household contacts of people with TB (PWTB) face elevated risks of Mycobacterium tuberculosis (Mtb) infection, yet gaps persist in understanding predictors of transmission and the role of multimorbidity (e.g., HIV, malnutrition, non-communicable diseases). This PhD research investigated predictors and transmission dynamics of household Mtb in high TB incidence settings.
Methods: The research was nested within the multinational ERASE-TB cohort study in which household contacts (≥10 years) of adult microbiologically confirmed (medium-high) PWTB were recruited from Zimbabwe, Mozambique and Tanzania. Three interrelated studies were conducted. The first characterised multimorbidity and socioeconomic disparities in TB-affected households. The second developed and evaluated predictive models for Mtb infection (IGRA positivity) among household contacts using multivariable regression with cross-validation and decision curve analysis. The third employed mixed-effects logistic regression to assess influence of HIV/ART status of PWTB on household transmission dynamics.
Results: Findings from the first study reveal a substantial burden of chronic conditions and socioeconomic disparities that amplify TB risk. Multimorbidity affected 61% of adults, with high prevalence of HIV (15%), malnutrition (18%), and diabetes (9.4%). Predictive models demonstrated limited utility (AUROC: 0.59–0.60), reflecting challenges in using individual- and household-level factors for Mtb infection risk stratification in settings with high community transmission. The third study demonstrated that HIV-positive PWTB not on ART exhibited 55% lower odds of household Mtb transmission (aOR: 0.45, 95% CI: 0.29–0.69) compared to HIV-negative PWTB and those on ART, even after controlling for bacterial burden and symptom duration.
Conclusion: Household Mtb transmission in high-burden settings is shaped by intersecting biological, socioeconomic, and structural factors. Findings emphasize the importance of integrated health screening as a means to improve household health and potentially reduce risk of progression to TB among household members. While predictive models showed limited clinical utility, this underscores the dominance of community transmission. The reduction in transmission among untreated HIV-positive PWTB challenges conventional assumptions, suggesting unmeasured behavioural or healthcare access mediators. Policies must prioritize integrated health screening among TB-affected households, context-adapted Mtb diagnostics, and innovative TB/HIV program integration. Future research should explore feasibility of integrated health screening, develop effective and affordable diagnostic tools and explore mechanisms underlying HIV/ART-related transmission dynamics to optimize prevention strategies
Software developers in the age of AI
Get PDFThe introduction and widespread adoption of Artificial Intelligence and data-driven applications, i.e. software systems that rely on large sets of data to define their functionality, have created a paradigmatic shift in many areas of our lives, not just for end users but particularly for professional software developers.
In this dissertation, we take a human-computer-interaction perspective on how technologies like Machine Learning have affected software developers, their work practices, tools, methods, etc. To this end, we consider two perspectives:
First, just as data-driven applications have enabled new types of applications and solutions to challenges in many areas, they have also given software developers new tools and approaches for writing and creating software. For example, natural language processing has yielded systems for quickly generating working code from informal descriptions.
Besides new tools, applying Machine Learning techniques to the wide landscape of existing development tools also promises to improve the work of developers, e.g. with personalized and adaptive tools. Thus, the first half of this dissertation will be dedicated to investigating how data-driven applications can be applied to enhance the software development experience.
However, for developers, the widespread adoption of data-driven applications has a second consequence: the kind of software they write changes to incorporate these data-driven functionalities. Since there are paradigmatic differences in how data-driven systems operate, compared to more traditional software systems, this naturally also affects how they are developed and what their underlying code looks like. Therefore, the second part of this dissertation is first concerned with these differences from a human-centered perspective, particularly how developer behavior differs when working on the development of data-driven and traditional software systems, focusing on code reading. Since this demonstrated that data-driven development has its unique challenges, we then consider how tool support can help developers in these changing circumstances. To this end, we explore the literature on tooling. This revealed both evolving and new tools for this new reality but also highlighted areas where development tools can still be improved and tailored to the requirements of data-driven development. Thus, we finally explore new tool implementations to address the challenges of data-driven development as well as the needs and wishes of developers that we elicited throughout this work.
Insights from these two parts demonstrate how the changes in the underlying technology also drive changes in the human perspective.
As the technology continues to evolve at a growing pace, it will become equally important to continuously assess this relationship to address any potential mismatch, ensure the continued quality of software in the face of ever-increasing complexity, and ensure developers can continue to effectively leverage these technologies to shape our lives with technology. This work therefore can only contribute only a momentary assessment of the state of software development and a foundation for future research into how data-driven applications continue to affect software developers
