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Genomic landscape of diffuse glioma revealed by whole genome sequencing
No full textDiffuse gliomas are the commonest malignant primary brain tumour in adults. Herein, we present analysis of the genomic landscape of adult glioma, by whole genome sequencing of 403 tumours (256 glioblastoma, 89 astrocytoma, 58 oligodendroglioma; 338 primary, 65 recurrence). We identify an extended catalogue of recurrent coding and non-coding genetic mutations that represents a source for future studies and provides a high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and extrachromosomal DNA. Finally, we relate these to clinical outcome. As well as identifying drug targets for treatment of glioma our findings offer the prospect of improving treatment allocation with established targeted therapies.publishe
Der Klimawandel – ein Spielverderber? : Klimapositive und ressourcenschonende Anpassungen in Spielen mit Mobilitätsbezug
No full textDiese Dissertation untersucht die Integration von Umweltthemen sowie Nachhaltigkeitsnarrative in verschiedenen Spielarten im Rahmen des Eco-Criticism und Eco Modding. Ein besonderes Augenmerk liegt auf der Definition und Modifikation von Ressourcenknappheit innerhalb von Spielen mit Bezug zu Mobilität, um die Verbindung zwischen Umweltbewusstsein, climate emotions und Gaming-Praktiken zu vertiefen und neue Erkenntnisse zu generieren. Dabei wird untersucht, inwiefern der Klimawandel in Spielen als Spielverderber empfunden wird oder auch als Anreiz für innovative Spielmechaniken dienen kann, selbst in Spielen, die diesen nicht als Hauptthema haben.
Das Untersuchungsprogramm umfasst eine autoethnographische Analyse, Gedankenexperimente im Rahmen von Workshops und Lehrveranstaltungen sowie Expert*innen-Interviews. Diese vielschichtige Methodik ermöglicht eine gründliche Untersuchung des historischen, soziokulturellen und ökologischen Kontextes. Basierend auf dem Konzept der Affordanzen, das die Interaktionsmöglichkeiten zwischen Individuen und ihrer Umwelt fokussiert, wird ein theoretisches Gerüst geschaffen, das die Untersuchung von Ökomodifikationen in Spielen mit Mobilitätsbezug und deren Umgang mit Ressourcenknappheit unterstützt.
Im Zentrum der Untersuchung steht eine Analyse der Handlungsanweisungen im Rahmen von Affordanzen, die durch die Modifikation von Spielen mit Mobilitätsbezug geschaffen werden, um den Herausforderungen der Ressourcenknappheit zu begegnen. Diese Untersuchung trägt nicht nur zu einem vertieften Verständnis von Umweltthemen im Kontext des Gamings bei, sondern bietet auch Impulse für die Förderung eines nachhaltigen Bewusstseins und Handelns. Die Erkenntnisse dieser Dissertation tragen somit nicht nur zur Weiterentwicklung der Ludologie bei, sondern auch zur Sensibilisierung für Umweltfragen in der Gaming-Community.
Abschließend stellt diese Arbeit einen wichtigen Beitrag zur Erforschung des Zusammenspiels von Umweltthemen und digitalen Medien dar und unterstreicht die Bedeutung eines umweltbewussten Ansatzes im Gaming. Durch die Verknüpfung von theoretischen Konzepten mit praxisnahen Analysen liefert diese Dissertation eine umfassende Grundlage für zukünftige Studien und kann als Impuls für die Entwicklung umweltbewusster Spiele und Gaming-Plattformen dienen.publishe
Abstract rule learning promotes cognitive flexibility in complex environments across species
No full textRapid learning in complex and changing environments is a hallmark of intelligent behavior. Humans achieve this in part through abstract concepts applicable to multiple, related situations. It is unclear, however, whether the computational mechanisms underlying rapid learning are unique to humans or also exist in other species. We combined behavioral, computational and electrophysiological analyses of a multidimensional rule-learning paradigm in male rats and in humans. We report that both species infer task rules by sequentially testing different hypotheses, rather than learning the correct action for all possible cue combinations. Neural substrates of hypothetical rules were detected in prefrontal network activity of both species. This species-conserved mechanism reduces task dimensionality and explains key experimental observations: sudden behavioral transitions and facilitated learning after prior experience. Our findings help to narrow the explanatory gap between human macroscopic and rodent microcircuit levels and provide a foundation for the translational investigation of impaired cognitive flexibility.publishe
How Can Selective Processing of Vaccination Information Be Diminished?
No full textBackground: Selective processing of attitude-consistent information is a substantial obstacle in convincing vaccine-skeptical people of the benefits of vaccinations. Aims: This study tests (i) which types of information are particularly prone to such selective information processing, and (ii) whether a deliberative (vs. implemental) mindset focusing on potential benefits and harms may diminish its effects. Method: 612 Mturk participants were randomized into an implemental or deliberative mindset and received a flu vaccine-skeptical narrative, a flu vaccination facts box transparently summarizing risks and benefits, and a message by the Center for Disease Prevention and Control (CDC) in favor of the flu vaccine either referring to COVID-19 or not. We tested how these variations affected the acceptance of and the willingness to share each message. Furthermore, we evaluated their impact on flu vaccination attitudes and intentions. Results: The mindset manipulation failed to diminish generally prevalent selective information processing. While vaccine-skeptics did not accept and like the CDC message referring to COVID-19 (particularly in a deliberative mindset), they generally accepted the vaccination facts box more readily compared to both CDC messages. Limitations: Future studies should particularly focus on vaccine-skeptics and experimentally test the effects of facts boxes also on vaccination attitudes and intentions. Conclusion: While mindsets were ineffective, more general and transparent information may be more likely to reach an anti-vaccine audience.publishe
The hole dug deeper : Flash floods, income disparities, and labor informality in Brazil
No full textThis paper studies the differential effect of flash floods on income across deciles and the role informality plays in this relationship. While previous research has established that natural hazards will have distinct economic impacts depending on an individual's position on the income distribution, they have largely failed to explore the precise mechanisms driving the variegated impact. In this paper, I explore multiple potential avenues through which climate disasters can have a pronounced impact on the lower versus middle and upper income groups in developing countries. I leverage survey microdata from Brazil in the period 2012–2022 to explore how informal employment (which accounts for a large proportion of workers in low and middle-income countries) and employment in vulnerable sectors leaves low-income individuals more vulnerable than those at higher levels of the income distribution to the economic impacts of climate disasters. This higher degree of vulnerability leads to larger income losses at the lower end of the income distribution up to a year after a flash flood, implying short-term increases in income inequality in affected regions. I find that this differential impact operates primarily through the predominance of informal employment among poorer workers. My work highlights the necessity of policies to reduce informal employment and mitigate the impacts on vulnerable sectors as natural hazards become more common and more destructive.publishe
Addressing the burden of violence on global mental health : contributions of Narrative Exposure Therapy across different health systems
No full textO transtorno de estresse pós-traumático (TEPT) configura-se como um importante desafio para a saúde mental global, especialmente em contextos marcados por violência cumulativa, migração forçada e desigualdades estruturais. A Terapia de Exposição Narrativa (NET, acrônimo em inglês) é uma intervenção breve e focada no trauma, que promove a reconstrução da memória autobiográfica por meio da narrativa cronológica dos eventos de vida. Ao possibilitar a integração de experiências traumáticas fragmentadas em uma narrativa coerente, a NET facilita o processamento emocional e restaura a continuidade das histórias de vida interrompidas. Esta série de casos regionais examina a integração da NET nos sistemas de saúde mental do Brasil, República Democrática do Congo, Alemanha, Suíça, Japão, México, Reino Unido e Escandinávia. Com base em experiências diversas de implementação, o estudo identifica tanto condições favoráveis quanto desafios persistentes. Os resultados mostram que a NET é uma intervenção viável e adaptável a diferentes contextos socioculturais e níveis de recursos, especialmente quando apoiada por supervisão contínua, estratégias de deslocamento de tarefas e colaboração intersetorial. A incorporação da NET nas estruturas de serviços existentes ampliou o acesso a cuidados com enfoque no trauma baseados em evidências para populações frequentemente excluídas do tratamento especializado. Esses achados ressaltam o papel crítico de políticas públicas informadas pelo trauma na resposta às consequências da violência para a saúde mental em escala global.publishe
Risk diversification and vote decisions in mixed-member electoral systems
No full textThis paper builds on the literature about mixed-member electoral systems, exploring how ballot design interacts with voter behavior. We present a theoretical model for vote decision-making in mixed-member systems that takes into account the interaction between both tiers. The model is grounded in a spatial model for vote decision-making under risk and inspired by the logic of portfolio diversification under risk. Accordingly, voters are modeled as risk-averse decision-makers who may prefer diversified vote packages (i.e. split-ticket) when party and candidate uncertainties are highly correlated. The risk diversification strategy abates when voters cast their votes sequentially. This finding provides a potential explanation for the impact of vote sequence in mixed-member systems, an under-investigated topic in the literature. It thus links the established literature on mixed-member systems with scholarship on ballot design and its effects. Additionally, the paper’s analysis explores the implications of combining the proposed model with the well-established wasted vote model.publishe
Using the Thermal Power of Light to Affect Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
No full textMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and poorly understood multisystem disease with an unclear cause and pathophysiology. Diagnosis remains difficult due to the absence of specific biomarkers, so the condition must be identified based solely on clinical symptoms, which vary greatly between individuals in both type and severity. Alongside the primary symptom of debilitating fatigue, patients commonly experience cognitive impairments such as memory and concentration problems, muscle and joint pain, non-restorative sleep, dizziness, and a phenomenon known as post-exertional malaise (PEM), where even minor physical or mental exertion leads to a significant worsening of symptoms. These symptoms often result in severe disability, with some patients confined to bed and unable to participate in normal daily life.
For decades, ME/CFS has been largely neglected by the medical and scientific communities, leading to a lack of knowledge and the absence of causal treatments. Current therapeutic approaches focus only on symptom management, typically involving medications or behavioral therapies designed to help patients adapt to their limitations and possibly regain some level of activity.
This thesis explores the potential of hyperthermia—an artificially induced elevation of body temperature—as a novel treatment option for ME/CFS. Hyperthermia has long been used in cancer therapy and has also demonstrated positive effects in treating severe depression and arterial hypertension, although the underlying cellular and molecular mechanisms remain poorly understood.
The study is divided into three parts. The first part compares key cellular processes—autophagy and mitochondrial function—in peripheral blood mononuclear cells (PBMCs) from healthy individuals and ME/CFS patients. The results show elevated autophagy and increased mitochondrial activity in ME/CFS patients compared to healthy controls. The second part consists of an ex vivo hyperthermia experiment in which PBMCs and fibroblasts from both healthy donors and ME/CFS patients were exposed to one hour of heat at 39°C. This treatment increased autophagy and slightly reduced mitochondrial function. Additionally, gene expression related to these processes was analyzed.
The third part is an in vivo study in which nine ME/CFS patients underwent a one-hour whole-body hyperthermia session using water-filtered infrared-A radiation, raising their core body temperature to 39°C. Unlike the ex vivo results, the in vivo treatment reduced the previously elevated autophagy levels in ME/CFS patients back to normal and enhanced mitochondrial function. Since the in vivo results more accurately reflect the effects on the whole organism, they are considered more relevant for evaluating the therapeutic potential of hyperthermia.
The observed differences between ex vivo and in vivo responses provide a foundation for developing a new hypothesis regarding the pathophysiology of ME/CFS, which is discussed in the thesis. Overall, the results suggest that hyperthermia may be a promising treatment strategy for ME/CFS, capable of normalizing dysregulated cellular processes and improving energy metabolism.publishe
Mentoring und Coaching in der Lehrerinnen- und Lehrerbildung
No full textMentoring und Coaching sind vieldiskutierte Formate der schulpraktischen Professionalisierung. Dieser Beitrag skizziert den jeweiligen Begriff und Gegenstand, stellt gängige Konzeptionen vor, referiert den Forschungsstand und diskutiert die Bedingungen erfolgreicher Professionalisierung durch Mentoring und Coaching.publishe
Community diversity shapes persisting soil legacy effects of individual plant species on subsequent plant performance
No full textPositive plant diversity–productivity relationships have partly been attributed to decreasing abundances of belowground specialist plant antagonists with increasing plant diversity, resulting in less negative plant–soil feedbacks (PSFs) on establishing conspecific plant individuals. Yet, generalist plant antagonists also contribute to negative PSFs among conspecific and heterospecific plants. Possibly, contributions of generalist plant antagonists to PSF outcomes may become more important in high-diversity communities due to diversity-driven specialist plant–antagonist dilution, but this has remained untested. We set up a three-phase pot experiment to examine how plant diversity affects the differences between conspecific and heterospecific PSFs. In the first (‘pre-conditioning') phase, we conditioned soils with communities of one, two, four or eight species. By mixing soils within each diversity level, we created soil mixtures with legacies of all eight species, which only differed in the diversity level at which the plants conditioned the soils. We then established monocultures of all eight species in each mixture (‘conditioning phase') and finally examined feedback responses of all individual species (‘feedback phase'). We tested the hypothesis that compared to heterospecific PSFs, conspecific PSFs are most negative in soil mixtures with a legacy of the lowest plant diversity, but become less negative in soil mixtures with legacies of increasing plant diversity. Diversity legacy and pre-conditioning-phase conspecific biomass positively or negatively affected plant performance in the feedback phase, depending on species identity. Plants experienced more negative conspecific than heterospecific feedback, but this effect did not depend on soil legacies established in the pre-conditioning phase. Our study shows that diverse plant communities leave persistent soil legacies that differ from combined legacies of lower-diversity communities, indicating that plant–soil interactions of individual plants are affected by the community context. However, our study does not provide evidence that community diversity predictably affects differences between conspecific and heterospecific PSF interactions.publishe