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EU coordinating competences:Hardening norms in European socio-economic governance
Get PDFThis dissertation aims to contribute to the theoretical discussion in EU legal scholarship on the relationship between law and other approaches to governance which coexist and interact with law in the EU legal order. More specifically, it analyzes the exercise of EU coordinating competences as one key instance of governance which differs from law in important ways. What is meant by EU coordinating competences is economic, employment and social policy coordination in the EU as laid down in Article 5 TFEU. The argument advanced in this dissertation is that we can observe a hardening of policy coordination over time in all three policy areas. In other words, the norms adopted through policy coordination processes can no longer be characterized as non-binding (or voluntary) even if they are formally laid down in non-binding legal instruments. More importantly, law has played a crucial role in the hardening of economic, employment and social policy coordination in the EU since the onset of the euro crisis. This finding supports the broader argument advanced in this dissertation that law and other approaches to governance in the EU are characterized by a relationship of mutual transformation
Mind the gap!:Inequalities in democratic support among adolescents
No full textInequalities in democratic support are undesirable. When certain groups are less engaged in democracy, their interests will be underrepresented, leading to suboptimal democratic outcomes for these groups. However, large inequalities in democratic support are found, especially based on educational attainment. In order for governments to design and time policy interventions that are aimed at mitigating these inequalities more effectively, it is important to have a better understanding of their origins and the way they develop. This dissertation therefore studies the origins of inequalities in democratic support among young people. The results show that Dutch adolescents generally support democracy, reject non-democratic alternatives, endorse core democratic values and intend to participate in the political process. It is quite worrisome, however, that the educational gap in democratic support that is observed among adults is already present from a young age, and proves to be quite stable and persistent. The findings in this dissertation show that these inequalities originate at least to some extent in the period before secondary education, and are not easily remedied by (on-site) citizenship education
Pathways of entrepreneurial urban governance:Spatial dynamics and community politics in Istanbul's regeneration
Get PDFWhat happens when urban governance adopts state-driven entrepreneurialism? Istanbul—a city metamorphosed into a canvas with its towering megaprojects—tells a profound tale of power, policy failures, and post-populist adaptations. Through the lens of Istanbul's transformation, the dissertation focuses on socio-spatial dynamics and community politics of entrepreneurial urban governance. While this governance model promises economic growth and innovation, this study reveals a fundamental tension: even as it generates new forms of social capital and community engagement, it simultaneously intensifies socio-spatial inequalities and marginalizes resistance and contestation, especially through state-led interventions. Highlighting Istanbul’s large-scale regeneration as a case to understand the broader phenomena of non-Western entrepreneurial governance, this dissertation contributes more diverse perspectives to urban governance scholarship. The outcomes demonstrate how state-driven entrepreneurial strategies are not fixed in one mode but fluctuate depending on scenarios shaped by resistance, negotiations, or multi-level interactions among urban actors. These governance mechanisms move back and forth between contrasting approaches—from top-down planning to self-organization and to post-populist politics.This dissertation argues that authoritarian entrepreneurial governance paradoxically creates conditions for local innovation and resistance. Local actors leverage state-designed tools and frameworks to challenge the system itself, either by re-politicizing depoliticized governance frameworks or by shaping community politics through market-driven imperatives. Urban residents display varieties of ‘entrepreneurial citizenship’, institutionalizing self-organization or adopting post-populist responses that imitate entrepreneurial practices of the state and property developers. This demonstrates how entrepreneurial governance, even in authoritarian contexts, can emerge as a platform for negotiated urban governance
Multidisciplinary developments in rectal cancer care and lateral nodal disease
Get PDFGedurende de laatste decennia zijn de behandelopties voor rectumcarcinoom aanzienlijk verbeterd dankzij betere herkenning, selectieve radiotherapie en nieuwe chirurgische technieken. In dit proefschrift zijn de multidisciplinaire ontwikkelingen in kaart gebracht en hiaten geïdentificeerd waar mogelijkheden liggen voor verdere verbeteringen.Het eerste deel van dit proefschrift behandelt de incidentie, herkenning en klinische kenmerken van zowel primair als recidiverend rectumcarcinoom. Het blijkt dat de incidentie van mismatch-repair deficiënte (dMMR) tumoren laag is (2.8%), maar dat deze tumoren, in tegenstelling tot coloncarcinoom, goed reageren op neoadjuvante (chemo)radiatie. Daarnaast wordt beschreven dat aanwezigheid van extramurale veneuze invasie op MRI-scan een belangrijke prognostische factor is voor een slechtere overleving. Verder heeft een afname van het gebruik van neoadjuvante (chemo)radiatie bijgedragen aan een grotere kans op curatieve behandeling van lokaal recidiverend rectumcarcinoom.Deel twee onderzoekt de chirurgische behandelingen van het rectumcarcinoom. Lokale excisie bleek bij actieve opvolging een hoger risico op lokaal recidief te hebben, maar een lager stoma-risico. Bovendien zijn lokale recidieven na lokale excisie bijna altijd goed te behandelen. Verder blijkt dat de keuze voor chirurgische technieken, zoals TME met anastomose of lage Hartmann’s procedure, varieert tussen ziekenhuizen. Het derde deel richt zich op de behandeling van laterale lymfeklieren. Deze klieren zijn geassocieerd met een hoger risico op lokaal recidief, maar niet op afstandsmetastasen. Dit deel benadrukt ook het belang van nauwkeurige herkenning, risicoclassificatie en gestandaardiseerde bestraling voor betere behandelresultaten. Daarnaast wordt ook het protocol van de LaNoReC-trial beschreven, deze studie onderzoekt de effectiviteit van een multidisciplinaire aanpak bij patiënten met laterale lymfeklieren
A focus on craniomaxillofacial giant cell neoplasms
Get PDFThis thesis investigates giant cell neoplasms occurring within the craniomaxillofacial skeleton, a group of rare bone lesions characterised by the presence of multinucleated osteoclast-like giant cells. The clinical presentation, location, biological behaviour, and treatment outcomes of these lesions vary widely, presenting significant challenges and complexities in clinical practice. The research presented in this thesis aims to explore the pathogenesis of these lesions, enhance the diagnostic capabilities and classification by evaluating both clinical and non-clinical features along with various disease patterns, and improve treatment outcomes by analysing data on the efficacy and toxicity of various (non-surgical) interventions. The findings demonstrate that the integration of clinical, radiological and new molecular data allows for better diagnostic accuracy and differentiation between the various types of craniomaxillofacial giant cell lesions. However, the complex biology of these lesions remains only partially understood, which particularly complicates the prediction of their diverse biological behaviours. The results of pharmacological therapies show promise in minimising the morbidity associated with surgery and reducing the risk of recurrence, especially in aggressive cases. Nonetheless, ongoing research is essential to optimise current treatment approaches and to identify novel, non-surgical strategies that target the underlying biological mechanisms driving these lesions
Genders as genres:Understanding dynamic categories
Get PDFWhat does it mean to be of a particular gender? I answer this question with an account of genders as dynamic categories, exploring the analogy between what genders are (e.g., men or women) and what genres are (e.g., Novels, Ballads, or Hip-Hop). For instance, due to its relation to other and earlier pieces, we recognize, e.g., a particular song as Hip-Hop. However, the piece will also develop that genre further. Likewise, e.g., the category of men emerges, persists and transforms through a specific sort of response of individuals to earlier supposed men, which emerges in social interactions.Drawing on critical and (trans-)feminist theory, phenomenologist, enactivist, and systems theoretical approaches, I show that gender categories themselves develop in a dynamic between three elements: (1) at any given time, there is an enactment class of individuals ambiguously belonging to the category in question; (2) these individuals are, in an embodied and intersubjective way, enacted as practical reinterpretations of earlier members of that category; (3) this unfolds in a matrix of hermeneutic and material relations, which loop with both the class and the enaction.Thereby, that an individual is gendered, emerges between two levels of enaction, that of bodily people and that of the dynamic between them. As what an individual is gendered in enaction, however, is constituted by relations within and beyond that situation. This responsive realization gives rise to feedbacking histories of acts, people, relations, and enactment classes, thus explaining how gender can be both solid and open to change
Optimizing and personalizing Barrett’s neoplasia management:Facilitating future transition
Get PDFIn recent years, the incidence of esophageal cancer, particularly adenocarcinoma, has risen significantly in Western countries. Barrett’s Esophagus (BE) is a recognized precursor to this malignancy. Patients with BE are regularly monitored through endoscopy to detect abnormal cells or cancer at an early, treatable stage. A combined therapeutic approach comprising of endoscopic resection of abnormalities and ablation of Barrett’s mucosa has been demonstrated to be both effective and safe for patients with low-grade dysplasia, high-grade dysplasia, or early esophageal cancer. Part 1 of this dissertation introduces endoscopic eradication therapy (EET), addresses common procedural errors in managing Barrett’s-related neoplasia and provides practical recommendations for endoscopists to mitigate these errors.Part 2 examines the expansion of endoscopic treatment criteria for esophageal cancer. It evaluates the outcomes of endoscopic submucosal dissections (ESD) in the Netherlands and evaluates the risk of residual neoplasia in patients with non-radical (R1) resections, i.e. presence of tumor cells in the deep resection margin following endoscopic therapy. ESD has proven safe and effective for the removal of (deep) invasive submucosal tumors. Furthermore, the studies indicated that only half of the patients with R1 resections were diagnosed with residual tumor tissue, suggesting that current recommendations for additional surgery after R1 resection may lead to overtreatment of some patients. Furthermore, the importance of expert centers for managing patients with ultra-long Barrett segments, given their higher risk of neoplastic progression, is also discussed.Part 3 focuses on personalized care following successful endoscopic treatment for Barrett’s-related neoplasia. The natural progression course of untreated dysplasia to a symptomatic cancer stage was evaluated. Additionally, the risk of mortality from non-esophageal cancer causes was evaluated in the population of patients after successful EET, which was nearly 40 times greater than mortality from esophageal cancer recurrence. The Charlson Comorbidity Index proved useful in predicting this mortality risk. These studies may offer valuable insights for future treatment strategies
Patients’ rights protection and artificial intelligence in the European Union
No full textEuropean patients are increasingly confronted with the algorithmisation of healthcare. This transformation of healthcare presents both significant opportunities and substantial risks. Before fully embracing this revolution, it is important to pause and think about the actual implications of introducing artificial intelligence (AI) in healthcare, reflecting on whose needs are being addressed, and whose rights might be overlooked in the process. The topic of this dissertation is the safeguarding of the rights of patients in the European Union (EU) in light of the increasing use of AI technologies in healthcare, within the context of expanding EU integration through the Digital Single Market. The central aim is to assess whether the current EU legal frameworks adequately protect patients' rights against the algorithmisation of healthcare. Additionally, it proposes alternative legal approaches to ensure more robust protections for patients in this rapidly evolving sector
Designing multifunctional enzymatic devices for biosensing and chemical conversion
Get PDFThis thesis investigates the design of multifunctional enzymatic devices for biosensing and chemical conversion, focusing on enhancing biosensor performance and stability through enzyme and materials engineering. Biosensors are indispensable in modern diagnostics, enabling the rapid and accurate detection of biomarkers crucial for early disease diagnosis. However, their practical application is constrained by limitations in sensitivity, selectivity, and stability. This research addresses these challenges by combining engineered enzymes and materials with diverse electrochemical, optical, and photothermal properties to enhance biosensor functionality. Electrochemical biosensors, while highly sensitive, face challenges related to biomolecule stability during their complex construction. Chapter 2 introduces a thermostable engineered urate oxidase (UOx), which significantly enhances stability and detection range. This engineered enzyme enables the development of robust biosensors suitable for diverse diagnostic conditions. Chapter 3 extends this application to optical biosensors, introducing a redox-reversible probe with engineered UOx, NADPH oxidase (YcnD), or monoamine oxidase (MAO-D5) for increased thermal stability and recyclability. This sustainable design reduces waste while maintaining high sensitivity. In Chapter 4, photothermal biosensors utilizing engineered UOx or aspartate oxidase (AspOx) are developed for uric acid or aspartic acid detection, respectively. These devices, powered by sunlight and featuring recyclable photothermal agents, offer cost-effective and non-invasive solutions for chronic disease management. Beyond biosensing, Chapter 5 demonstrates the versatility of bio-electrochemistry for chemical conversion by presenting a bioelectrocatalytic system for the asymmetric alkene reduction catalyzed by flavin-dependent ene-reductases. This approach addresses flavin cofactor recycling challenges and simplifies industrial processes
Exploring the therapeutic potential of immune checkpoint modulation in preclinical models of inflammatory diseases
Get PDFAtherosclerosis, a lipid-driven inflammatory disease of large arteries, is a leading cause of cardiovascular disease. While lipid-lowering therapies are effective, some patients retain a residual inflammatory risk, highlighting the need for alternative anti-inflammatory treatments. This thesis investigates the therapeutic potential of immune checkpoint modulation in preclinical models of inflammatory diseases.The first part examines the role of immune checkpoints in T cell-mediated inflammation. It begins by exploring E3 ubiquitin ligases as intracellular immune checkpoints, focusing on the E3 ubiquitin ligase CBL-B. We demonstrate that CBL-B deletion reduces atherosclerosis in mice while promoting T cell activation and T cell plaque infiltration. Next, we identify a novel binding partner for the immune checkpoint CD40L, RACK1, and reveal its role in Th1 cell stabilization. A systematic review and meta-analysis follow, showing that cancer-targeted immune checkpoint inhibitors can accelerate atherosclerosis. Finally, we explore the hypothesis that statins may enhance the efficacy of these immune checkpoint inhibitors.The second part evaluates CD40-TRAF6-targeted therapy, which has shown promise in atherosclerotic mice. Extending this research, we investigate its effects in atherosclerotic pigs, providing an initial analysis, and in secondary haemophagocytic lymphohistiocytosis (sHLH), an acute hyperinflammatory condition. A literature review highlights the roke of immune checkpoints in sHLH, and a pilot study implicates CD40 in the inflammatory response.Overall, this thesis advances understanding of immune checkpoints and highlights their potential as therapeutic targets in inflammatory diseases