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The impact of COVID-19 on children and clinical paediatric care in Munich: an observational study during the first wave of the 2020 pandemic
Get PDFWhile significant research has been conducted to examine the impact COVID-19 had on adults during the early phases of the ongoing pandemic, the extent to which children were affected remains largely unexplored. This thesis presents data on how the clinical care of the children’s hospital of the Ludwig-Maximilians-University (LMU) in Munich was affected during the first wave of the pandemic (March to May 2020) and provides a qualitative description of how COVID-19 manifested in children. Additionally, preliminary clinical parameters as potential predictors for the development of severe COVD-19 in children are presented. To do so, data from the paediatric hospital were collected, and a cohort of 12 hospitalised children with COVID-19 was recruited and observed.
During the first wave of the SARS-CoV-2 pandemic in 2020, the total number of children presented at the paediatric care in Munich (LMU) decreased by approximately 40% in comparison to the same time period in 2019 (P=.017), and the number of children admitted due to common infectious diseases (such as respiratory or gastrointestinal infections other than COVID-19) decreased by 74% (P=.013). In context of nationally overrun and exhausted health care systems, these findings indicate that children were less impacted by the first wave of the pandemic in comparison to older age groups. Of the children that were admitted to Munich’s paediatric hospitals due to a SARS-CoV-2 infection during the first wave, the majority (58%) presented with mild symptoms such as fever, cough and rhinitis. Two children within the cohort developed life-threatening severe hyperinflammatory syndromes such as PIMS and sHLH with ARDS, while three children remained asymptomatic during their entire period of infection.
On the basis of 12 hospitalised patients, the following factors can be described to be potentially associated with having a higher risk of developing a severe course of COVID-19 in children: young age (mean=2 years), pre-existing conditions including congenital heart diseases (PFO, ASD II and AVSD) or Down Syndrome. Additionally, the following clinical parameters were observed in children with a severe course of disease: highly elevated levels of IL-6, IL-2, CRP and Procalcitonin, occurrence of emesis, longer duration of fever, development of hyperinflammatory syndromes (sHLH, PIMS), prolonged duration of hospitalisation and treatment with IVIG and corticosteroids.
The small cohort size (n=12) associated to the low hospitalisation rates of children in the first wave, was insufficient to identify statistically significant predictors for developing a severe course of COVID-19 and only provide the description of the observations we made in this period of time. This remains subject of ongoing research within the hospital following an immunological and genetic approach
The traces in use design concept
Get PDFToday's environments increasingly comprise a network of smart and interactive devices that change our perception and relationship with our surroundings. This enables us to access massive information and functionality at our fingertips but may also induce overload and stress and reduce our mental well-being. Additionally, it triggers changes in spatial usage and onsite behaviors, challenging cities to preserve their places' authenticity and social and cultural identity.
These environmental changes push human-computer interaction (HCI) to research the design space of human-environment interaction and develop new design approaches and concepts that support designing for shared multi-user contexts. This also requires designing interactions in relation to the target environment's social, cultural, and spatial conditions to preserve their identity. Experiencing interaction under consideration of these relations fosters sense- and meaning-making, which strengthens users' feelings of belonging, understanding, and social connectedness. However, HCI research lacks design concepts and approaches to contextualizing interfaces so that they can promote this effect.
The thesis approaches the gap with the goal of developing a design concept to contextualize interfaces for meaningful human-environment interaction. For this, I present a three-step process, including identifying design approaches and requirements for shared environments, the theoretical development of the design concept Traces in Use, and the concept's empirical evaluation in physical, augmented, and virtual reality human-environment interactions.
My work shows that the Traces in Use concept can implicitly increase interfaces' social and cultural meaning and, thus, supports their contextualization. The Traces in Use concept developed in this thesis is a strong design concept for creating meaningful human-environment interactions, which supports place-making and social connectedness in three different realities. Additionally, the concept responds to the need for preserving places' authenticity and identity by reusing natural and recognizable features of physical reality environments, aka traces, that embody temporal courses and socio-cultural behaviors.
My work also reveals outstanding research questions and opportunities relevant to human-computer and human-environment interactions. This includes evaluating the concept further in different cultural contexts and with user groups or exploring their potential for meaningful mixed-reality contextualization. The thesis approaches a subject of the HCI Grand Challenges by providing a concept to create meaningful human-environment interactions and revealing various additional challenges for future research.Heutige Umgebungen bestehen zunehmend aus einem Netzwerk intelligenter und interaktiver Geräte, die unsere Wahrnehmung und Beziehung zu unserer Umgebung verändern. Dies ermöglicht uns den Zugriff auf massive Informationen und Funktionen auf Knopfdruck, kann aber auch zu Überlastung und Stress führen und unser geistiges Wohlbefinden beeinträchtigen. Darüber hinaus löst es Veränderungen in der Raumnutzung und im Verhalten vor Ort aus, welches zu Verlusten der authentischen Ortscharaktere und deren soziale und kulturelle Identität führen kann.
Diese Veränderungen führen dazu, dass der Forschungsbereich Mensch-Computer-Interaktion (HCI) den Gestaltungsraum der Mensch-Umwelt-Interaktion erforscht, um neue Designansätze und -konzepte zu entwickeln, die gemeinsame Multi-User-Kontexte unterstützen. Dies erfordert auch die Gestaltung von Interaktionen, die die sozialen, kulturellen und räumlichen Bedingungen der Zielumgebung berücksichtigen, um deren Identität zu bewahren. Interaktionserfahrungen, die diese Beziehungen berücksichtigen, förden die Sinn- und Bedeutungsbildung, womit das Zugehörigkeitsgefühl, das Verständnis und die soziale Verbundenheit der Benutzer:innen gestärkt wird. Der HCI-Forschung fehlen jedoch Designkonzepte und Ansätze zur Kontextualisierung von Interfaces, um diese Wirkung zu fördern.
Die Arbeit zielt darauf ab, ein Designkonzept zu entwickeln, um Interfaces für eine sinn- und bedeutungsvolle Mensch-Umwelt-Interaktion zu kontextualisieren. Dazu stelle ich einen dreistufigen Prozess vor. Dieser umfasst die Identifizierung von Designansätzen und -anforderungen für gemeinsam genutzte Umgebungen, die theoretische Entwicklung des Designkonzepts Traces in Use und die empirische Konzeptevaluierung in virtuellen, augmentierten und physischen Mensch-Umwelt-Interaktionen.
Meine Arbeit zeigt, dass das Traces in Use-Konzept implizit die soziale und kulturelle Bedeutung von Interfaces erhöhen kann und somit deren Kontextualisierung unterstützt. Das in dieser Arbeit entwickelte Traces in Use-Konzept ist ein starkes Designkonzept zur Erstellung sinnvoller Mensch-Umwelt-Interaktionen, welches die Raumverbundenheit und -gestaltung und soziale Verbundenheit in virtueller, augmentierter und physischer Realität unterstützt. Darüber hinaus reagiert das Konzept auf die Notwendigkeit, die Authentizität und Identität von Orten zu bewahren, indem natürliche und erkennbare Merkmale physischer Realitätsumgebungen, wiederverwendet werden, auch bekannt als Spuren, die zeitliche Verläufe und soziokulturelle Verhaltensweisen verkörpern.
Meine Arbeit zeigt zudem weiterführende Forschungsfragen und Möglichkeiten auf, die für Mensch-Computer- und Mensch-Umwelt-Interaktionen relevant sind. Dazu gehört die weitere Evaluierung des Konzepts in verschiedenen kulturellen Kontexten und Benutzergruppen oder die Erkundung ihres Potenzials für eine sinnvolle realitätsübergreifende Kontextualisierung. Die Arbeit nähert sich einem Thema der "Seven Grand Challenges", indem sie ein Designkonzept zur Erstellung sinn- und bedeutungsvoller Mensch-Umwelt-Interaktionen bereitstellt und verschiedene zusätzliche Herausforderungen für zukünftige Forschung aufzeigt
Entwicklung und Evaluierung gynäkologischer low-fidelity Modelle der Hündin zur Integration in die veterinärmedizinische Lehre
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Computational methods and reproducible analysis in regulatory genomics
Get PDFWhile the modern field of genomics is exploding with new experimental techniques that push the limits of what is possible, computational methods designed to process and extract useful information from these data try to keep up in order to reliably improve our understanding of gene regulation. In this thesis, we developed reproducible computational pipelines and algorithms to study gene regulation at different levels or stages. We begin by reviewing core ideas required for understanding cells and their regulatory mechanisms and the main experimental sequencing-based assays used to characterize biological systems at the molecular level. We then introduce the two separate projects that comprise this thesis.
In our first project, we dissect the contribution of three competing pathways involved in heterochromatic silencing, namely, Pol II occupancy (PO), transcription efficiency (TE), and RNA stability (RS), by comparing heterochromatic and euchromatic regions in Schizosaccharomyces pombe (S.pombe). We characterize each of these regulatory pathways as ratios between expression levels of corresponding high-throughput sequencing assays, PO ( mu ChIP-seq/ wt ChIP-seq), TE (RIP-seq/ChIP-seq) and RS (pA-RNA/RIP-seq), and quantify the relative effects that mutants lacking core components associated with each pathway (i.e., chromatin modifiers, RNAi, and RNA degradation) have on heterochromatic silencing.
In our second project, we study how dynamic biological processes, such as development, are regulated and can be characterized at the molecular level by complex (non-linear) single-cell RNA sequencing (scRNA-seq) trajectories, focusing on how such processes can be compared using our novel tool Trajan. We introduce TrajanR, our accompanying R package, that facilitates the standardization and pre-processing of Trajan input data, trajectory inference, and alignment computation under different parameter schemes and provides various visualization options, enabling the analysis of scRNA-seq trajectories in complex settings. We demonstrate the accuracy of Trajan’s alignments through extensive experimentation on simulated data. We also showcase how our TrajanR package facilitates the study of scRNA-seq data based on the analysis of two independent real-world datasets.
Finally, we conclude with a discussion of both projects presented in this thesis and an outlook for the future
Media literacy education against fake news
Get PDFIn recent years, fake news has emerged as a significant obstacle of modern times. By fueling distrust in established media organizations and public institutions, it hinders efforts to tackle the pressing challenges of our time, such as global pandemics and climate change. In response, educational science, along with other disciplines such as communication science and psychology, developed measures to combat the widespread influence of misinformation. These strategies aim to counter biases, promote media and information literacy, and provide cognitive preventative measures to mitigate the impact of encountering false or misleading information online. However, research on one key strategy frequently employed by fake news disseminators, namely framing, remains scarce. This thesis seeks to address this gap by conducting an analysis of the strategic framing of typical fake news content (Study 1) and implementing an educational intervention to promote media literacy by improving discernment of both truthful and fake news (Study 2). Furthermore, these findings are incorporated into the broader framework of the persuasion knowledge model to provide an additional and complementary perspective on the challenge of fake news
Proteomic heterogeneity of glial cells of the central nervous system
Get PDFMammalian brain and retina, both part of the central nervous system (CNS), contain a multitude of distinct glial cell populations. On a rough scale they can be categorized for example as oligodendrocytes, microglia and astroglia. While oligodendroglia are mostly absent from the eye, astrocytes line the inner surface of the retina and microglia reside between its nuclear layers. Most importantly, the retina has its own kind of specialized glial cells: Müller glia. These long cells are evenly distributed, span the whole thickness of the retina and fulfil similar homeostatic functions as astrocytes in the brain. As the CNS is divided in functional and anatomical subunits that additionally differ by species, the respective glia are also thought to vary in their duties. In this work I addressed the question which cellular functions are shared between, and which are specific for astroglial cells from different brain regions and retina. Additionally, Müller cell heterogeneity was under special scrutiny focusing on cells from the macular and peripheral human retina.
As glial cells constitute only a subpopulation of all CNS cells, it was necessary to enrich our cells of interest to make the following analysis as precise as possible. We achieved this by magnetic bead associated cell sorting. These cell fractions were then subjected to tandem mass spectrometry and served as the basis of the subsequent work. To extract the information hidden in such complex datasets, I used various bioinformatics tools to break them down into smaller protein lists that allowed conclusions on their role in glial biology. Furthermore, I selected individual proteins for in-depth validation and functional examination.
I identified transcription factors of the nuclear factor 1 family to be expressed across glial cells of all contemplated regions and species, which corroborated their reported role in gliogenesis of brain and retina. Several of the pathways with interregional differential expression, including candidate proteins SLMAP and ZEB1, converged onto Hippo pathway signaling and alternative splicing. Furthermore, Müller cells of the human macula displayed an increased expression of proteins of the extracellular matrix, cell adhesion and exosomal pathways hinting towards a shift in the extracellular milieu. In this context, I showed how EPPK1 might play a role in establishing the intricate Müller cell morphology, their biomechanical properties and the secretion of extracellular vesicles.
Finally, the proteomic datasets generated as part of my thesis have expanded our understanding of the biology of glia in different regions of the CNS and the retina specifically. The present findings will help to better understand the regional adaptions of astrocytes and Müller cells allowing the development of better tools or treatments targeting the desired subpopulations and translate insights between them
Langzeitergebnisse der intravitrealen Therapie der neovaskulären altersbedingten Makuladegeneration
Get PDFSingle and combined use of fall-risk-increasing drugs and fracture risk
Get PDFBackground. While many drug groups are associated with falls in older people, less is known about absolute increases in risk and how these risks vary across different groups of drugs or individuals.
Method and Design. We conducted a population based nested case control study among people aged ≥65 years in the Scottish regions of Tayside and Fife. Cases were individuals hospitalised with a fracture between 2010 and 2020, to whom we matched up to 10 controls. We examined relative and ab-solute risks of drug groups known as “Fall-Risk-Increasing Drugs” (FRIDs), alone and in combination, and among younger and older (≥75 years) adults. Adjusting for previous hospitalisations, drug use and laboratory data, we used conditional logistic regression to quantify associations between drug exposures and outcomes. We conducted four sensitivity analyses to test the robustness of our findings.
Results. The cohort comprised 246 535 people aged ≥65 years, of whom 18,456 suffered an incident fracture. Fracture risks were significantly in-creased for most FRIDs examined. Absolute risks were much larger among older vs younger people and both relative and absolute risks increased with the number of FRIDs combined. Overall, the highest absolute increase in risk were found in people aged ≥75 years for selective serotonin reuptake inhibitors (number needed to harm 53), tricyclic antidepressants (NNH 81), antipsychotics (NNH 75) and use of three or more FRIDs (NNH ≤66).
Conclusion. Patients aged ≥75 years prescribed antidepressants or anti-psychotics or taking three or more drugs that increase risk of falls may bene-fit most from deprescribing interventions