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Mcl1 in control of life and death of dopamine neurons
No full textIn this thesis we investigated survival and cell death of dopaminergic neurons in the framework of Parkinson’s disease (PD). PD is one of the most prevalent neurodegenerative disorders characterized by loss of dopamine neurons of the substantia nigra pars compacta (SNpc). Attenuating this loss of dopamine neurons would be extremely beneficial for PD patients. Therefore, it is key to understand how dopaminergic neurons develop and why they degenerate both during development and adulthood, as they might share a common machinery. As the intrinsic mitochondrial-dependent pathway of apoptosis has been implied to underlie cell death in PD, we initially focused on the orchestrators of this pathway: the Bcl2 protein family. We aimed to identify the weak link in this family both during development and adulthood, identify its regulation and potentially strengthening this protein to enhance the survival rate of dopaminergic neurons
Optimizing strategies in pancreatic and hepato-biliary surgery
No full textThis thesis aims to improve perioperative strategies in HPB surgery. Part I focuses on finding the optimal analgesic strategy and investigates the impact of continuous wound infiltration (CWI) versus epidural analgesia. Part II includes studies on one of the most threatening complications of pancreatic surgery: postoperative pancreatic fistula (POPF). Part III consists of studies on worldwide perioperative practices in liver surgery, fluid therapy, new-onset diabetes after pancreatoduodenectomy (PD), and outcome prediction in HPB surgery
Children and adolescents growing up with perinatal HIV:Long-term outcomes and comorbities
No full textPerinatally acquired HIV (PHIV) progresses more rapidly than adult-acquired HIV and affects children during critical periods of immune and neurodevelopment. Although combination antiretroviral therapy (cART) has transformed PHIV into a manageable chronic condition, youth with PHIV remain at increased risk for neurocognitive, immune, metabolic, and cardiovascular complications. This thesis investigates long-term health outcomes, underlying mechanisms, and progression of comorbidities in PHIV youth on cART, using data from the NOVICE study and multi-omics approaches.The results show that while plasma neurofilament light chain does not indicate active neuroaxonal injury, cognitive impairments persist over time. Multi-omics analyses reveal sustained immune activation, inflammation, and metabolic dysregulation (“inflammageing”), which likely contribute to neurocognitive deficits. Moreover, gut microbiome composition appears similar to matched controls, suggesting minimal microbiome alterations under effective cART. Lipidomic profiles and cardiometabolic markers, including lipoprotein(a), are largely comparable to uninfected peers, though specific cART regimens may influence lipid metabolism.Overall, PHIV youth exhibit a complex interplay of persistent immune-metabolic disturbances and cognitive impairment, increasing long-term vulnerability to comorbidities. These findings underscore the need for longitudinal studies to further evaluate long-term outcomes, specifically cognitive and metabolic assessments, in PHIV youth to improve long-term health and to provide further insight into the underlying pathofysiology
A history of the First World War's Caucasus campaign, 1914-1918
No full textA History of the First World War’s Caucasus Campaign, 1914-1918 investigates a relatively little-known episode of the First World War. The entry into the campaign of the Ottoman, Russian, British, and German empires has had a major impact on the march of events in the Middle Eastern theatre of the war as it eventually led to the exit from war of a major Entente Power and the defeat of a major Central Power. The engagement of these empires in warfare shaped the late-campaign armistice, affected the post-campaign peace treaties, and profoundly influenced the configuration of forces and definition of borders in the broader area of the campaign. This thesis examines the interplay between warfare and its impact on military and political strategy of the campaign participants. By determining the military strategic considerations that lay behind their decisions to employ troops, this research defines military strategic goals that were perused and the motives that underlay the choices of various decision-makers. At the macro level, this study seeks to integrate the Caucasus campaign into the mainstream of the First World War history as part and parcel of the war that was waged and experienced in the Ottoman Empire, Russia, Britain, and Germany. In more specific terms, this research seeks to highlight the role the campaign had played in these belligerent states’ war strategy as part of the global confrontation between the Entente Powers and the Central Powers. With this stated aim, this work takes a new and innovative approach to the history of this forgotten military campaign, arguing that the campaign was strategically important for both coalitions that fought the war.</p
Roberto Bolaño and the labyrinthine mode:Navigating neoliberal modernity
No full textThis project analyses how the textual strategies deployed by the Chilean author Roberto Bolaño contribute to a critical (re)framing of neoliberal modernity. To do this, it proposes an understanding of Bolaño’s fiction through ‘the labyrinthine mode’: a literary poetics that replicates the effects of trying to navigate a labyrinth. Not only is the labyrinth metaphor consistently used to describe Bolaño’s fiction, it also has a rich cultural heritage within Latin American literature more generally. For instance, in the work of Bolaño’s predecessors – immortalised under the banner of the Latin American boom – the labyrinth was synonymous with national solitude and the struggle to achieve modernity, particularly as a result of the legacies of colonialism. Bolaño’s labyrinthine mode represents a challenge to this escape-driven narrative. Writing in the wake of the dictatorial instalment of neoliberalism in his native Chile and beyond, Bolaño posits the labyrinth as an inescapable structure that also operates within the space-time of the globalised present. In doing this, he prepares the ground for an immanent critique of neoliberal modernity – a critique that foregrounds the networks of violence that underpin late capitalism whilst simultaneously establishing narrative and affective lines of flight through which hope may emerge
Derailing the belt and road:Film, social media screen culture, and globalization from China
No full textThis dissertation examines the cultural dimensions of China’s most significant geopolitical project—the Belt and Road Initiative (BRI). Rather than offering a comprehensive account of a meticulously planned BRI, the focus lies on how the initiative is continually derailed, particularly through its negotiation and contestation within the cinematic sector.To trace these derailments, the dissertation begins by positioning the BRI within China’s broader globalization strategy from a cultural perspective. By exploring why the initiative is named after the ancient Silk Road, it reveals how the BRI embodies China’s new globalization imagination. Building on this premise, the dissertation investigates why such an alternative vision is so strongly desired. It argues that the failure of Hollywood in China proves that nationalism and cultural confidence play a critical role. The key transformation, it suggests, lies in a shift of cultural confidence—from how China is seen by others to who is authorized to represent China globally.In this context, although China’s imagined globalization may appear coherent in official discourse, the dissertation shows how it becomes fragmented in practice. For instance, at events such as the Silk Road International Film Festival, state narratives encounter competing actors pursuing their own agendas. The dissertation concludes that such derailment is not only common but inevitable. In today’s globalized world, China’s state power is not absolute; it must frequently negotiate and compromise—even with less powerful actors. It is precisely these moments of negotiation, contestation, and creative resistance that form the heart of this study
The Poetics of Vulnerability:Early Modern Women's Poetry, 1560-1665
No full textThis thesis takes vulnerability as its starting point to examine early modern women’s lyric poetry written in English between 1560 and 1665. Adopting a capacious approach to vulnerability that attends to both the exposure to possible harm—both physical and emotional—as well as more dynamic relational affects, this research examines lyric poems by Anne Lock (c. 1534-before 1602), Isabella Whitney (fl. 1567-1573), Aemilia Lanyer (bap. 1569-1645), Hester Pulter (1605-1678), and Katherine Philips (1632-1664). At a time when the sheer breadth of women’s literary agency is being uncovered, why should we concern ourselves with a return to questions of vulnerability in early modern women’s poetry? The answer, this thesis argues, lies in recognising the multivalent function of vulnerability—including its overlapping philosophical, ethical, religious, political, and aesthetic dimensions—in early modernity. With particular attention given to the granular workings of poetic form as well as the affordances of lyric poetry in early modern English literary culture, the five case studies in this thesis collectively demonstrate that vulnerability offers a mode of storytelling, a language of faith, and a framework for thinking about virtuous self-governance and the ethical dimensions of care
Biomarkers and diagnostic tests for coagulopathies in the critically ill and injured
No full textCoagulopathy is a severe complication of both critical illness and injury, contributing to morbidity and mortality. As such, there is a clear clinical need for improved hemostasis management. However, to date, methods of (early) detection of coagulopathy are limited. Coagulopathy in the critically ill has many phenotypes, ranging from a hyper- to a hypocoagulable state that can give rise to multiple hemostatic complications including thrombosis and bleeding, which can also occur simultaneously. Early clinical suspicion of thrombosis is important to guide timing of imaging tools. Evidently, the assessment of risk of thrombosis and bleeding is important for decisions about timing and dose of anticoagulant therapy. Additionally, a better understanding of the risk of bleeding can help decisions about specific procoagulant interventions. In the critically injured, coagulopathy also frequently occurs, with an inability to clot during bleeding, which may transition to a hypercoagulable state after bleeding has been contained. Rotational thromboelastometry (ROTEM) is used as a point-of-care test to guide bleeding, but knowledge about the coagulation disturbances that underlie the test results is limited. In this thesis, the potential of biomarkers and of ROTEM to estimate risks of hemostatic complications from coagulopathies in the critically ill and injured is explored
Animal hunts in late antiquity:Continuities and changes between the 4th and 6th century AD in the east of the Roman empire
No full textAnimal hunts (lat. venationes) were a popular form of mass entertainment in the Roman empire, from their origins in the republican period until Late Antiquity. Venationes continued to be presented even after gladiator fights, with which animal hunts were traditionally combined, disappeared from public life. They endured despite facing harsh and persistent opposition by Christian critics from the 2nd century AD onwards. The present thesis seeks to understand the reasons for the persistence and popularity of venationes in the late antique East from the beginning of the 4th century AD onward and for their eventual end in the mid-6th century AD. In previous scholarship, animal hunts have mostly been discussed in general works on Roman spectacles, in which they have often been sidelined next to gladiator fights and chariot racing. Additionally, evidence stemming from later periods and from outside Rome has received little attention. By centring animal hunts, this dissertation fills a lacuna in current research on Roman spectacles and highlights the unique circumstances and developments of venationes in Late Antiquity. The dissertation looks at a variety of sources to bring together local practices, inter-provincial networks, and imperial policies for a comprehensive understanding of the cultural and social significance of animal hunts for late antique society. By studying animal hunts as a historical instance of human-animal interaction, the dissertation acknowledges that animals are central to what venationes looked like, what venues were needed to accommodate them, what was necessary to organise them, and how the spectators and critics saw them
Deep brain stimulation and cognition in managing motor fluctuations in Parkinson's disease
No full textParkinson’s disease (PD) is one of the fastest growing neurodegenerative disorders worldwide. Motor symptoms are initially managed with levodopa and adjunctive oral therapy, namely catechol-O-methyltransferase inhibitors (COMT-Is), dopamine receptor agonists (DRAs), or monoamine oxidase B inhibitors (MAOB-Is). Part I of this thesis presents a systematic review with network meta-analysis of randomized controlled trials comparing the efficacy and safety of COMT-Is, DRAs and MAOB-Is as adjunctive oral therapy to levodopa in PD patients experiencing motor fluctuations. All adjunctive drug classes improved motor symptoms, activities of daily living, and quality of life, but DRAs, particularly pramipexole immediate release, were associated with the largest improvements. In Part II cognitive outcomes following subthalamic nucleus deep brain stimulation (STN DBS) in PD patients were examined. Overall, STN DBS appears to be a cognitively safe intervention, with cognitive outcomes comparable to continuous intrajejunal levodopa infusion and only a transient moderate decline in verbal fluency compared to best medical treatment (BMT). Furthermore, STN DBS induces a clinically meaningful motor improvement in PD patients with cognitive impairment, but the improvement may be smaller than in patients who are not cognitively affected. Lastly, smaller volume of the nucleus basalis of Meynert was associated with Parkinson’s disease dementia (PDD) at baseline, but not with cognitive decline six months after STN DBS. Part III aimed to facilitate future research in cognitively impaired PD patients by introducing the DBS-MODE trial, a randomized controlled study comparing DBS with BMT in PDD, and by providing practical recommendations for obtaining informed consent in PD patients with cognitive impairment.</p