International Migration, Integration and Social Cohesion online publications
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EU coordinating competences:Hardening norms in European socio-economic governance
Full text linkThis 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
Invasive ventilation and closed-loop ventilation in critically ill patients
Full text linkThe aim of this thesis was to investigate the association of ventilation strategies, including closed-loop ventilation, with clinical outcomes in critically ill patients.In the first part of this thesis, we focused on patients with COVID–ARDS.Using the PRoVAcT–COVID database, we explored whether different PEEP/FiO₂ strategies were associated with better outcomes. In a large multicenter cohort, a high PEEP/low FiO₂ strategy was associated with improved ICU survival. Further analysis showed that this effect was moderated by respiratory subphenotypes— only patients with the low mechanical power phenotype appeared to benefit. We then studied the timing of spontaneous ventilation initiation and found that an early transition to spontaneous breathing was not associated with improved outcomes. Additionally, we investigated the incidence of air leaks and found it to be relatively high but comparable to rates in pre–COVID ARDS. The second part of this thesis focused on closed–loop ventilation.A systematic review of 51 randomized controlled trials highlighted that closed–loop ventilation may optimize ventilator settings and reduce workload. In a prospective cross–over study in ABI patients, we demonstrated that automated ventilation significantly increased the proportion of breaths within optimal protective zones and reduced the proportion in critical zones, outperforming conventional ventilation. These findings support the effectiveness of closed–loop ventilation in improving the delivery of lung- and brain-protective ventilation.<br/
A transnational social contract:How a plurality of actors shape the rights of Indian low-wage labor emigrants along the India-Gulf Cooperation Council migration corridor
Full text linkMany low-wage employed migrant workers worldwide face precarious jobs, unsafe conditions, and poor living situations. The India-Gulf Cooperation Countries (GCC) corridor exemplifies this: India sends the most migrants globally, and approximately half of all Indian migrants stay in the GCC region, where most work in so-called unskilled job categories. Migrant-origin states such as India potentially deploy a variety of policy tools to protect and enforce their citizens’ labor and human rights abroad. However, despite the norm of supporting and providing rights to their nationals abroad, this is not an obligation states have. This dissertation shows that the rights Indian emigrants receive are informed by notions of deservingness and membership negotiated and shaped by a plurality of local, subnational, national, trans- and international state and non-state actors.Drawing on document analysis, observations, and interviews with actors involved in the transnational policy process of emigration and emigrant policymaking in the GCC region and India, the dissertation finds that the Indian state differentiates its policies along labels of high and low-skilled migration and that differentiated access to social protection and other citizenry rights also results from varying subnational incorporation of emigrants and practices of CSOs in the origin and destination context which support emigrants in procuring rights
History and physics entangled:Disciplinary intersections in the long nineteenth century
Full text linkThis dissertation uncovers historical relations between two knowledge disciplines that are usually defined in contrasting terms: history and physics. My main claim is that the histories of these disciplines have crucially depended on one another: they are “entangled.” To support this claim, I describe the sharing of three knowledge-making tools by historians and physicists in nineteenth-century German-speaking contexts: the concept of “fact,” the epistemic virtue of “exactitude,” and the method of source criticism. I argue that, by sharing these tools of knowledge making – which I subsume under the notion of “cognitive goods” — German historians and physicists defined the boundaries of their disciplines, while also maintaining a common, empirically oriented culture of knowledge making. I also pay attention to the divergences that emerged as part of these disciplinary intersections. In particular, I show that historians and physicists assigned different roles and interpretations to the concepts, virtues, and methods that they shared. This illustrates a fundamental aspect of how disciplinary communities interact: when they share tools of knowledge making, these tools inevitably transform. Finally, this dissertation aims to contribute to a better understanding of the historical relation between the natural sciences and the humanities. Previous historiography has dealt with these areas of knowledge mostly in separate terms. However, as this entangled history illustrates, disciplines that we today consider as belonging to the humanities or the natural sciences, turn out to have an intimately connected history. Hence, their histories should be studied not separately, but in relation to one another
Making the show go on:A study of sound engineers in French and Dutch fields of music production
Full text linkWhile the collective nature of artistic creation has been long accounted for in works such as Howard Becker’s Art Worlds, very few insights and empirical accounts of the role of technical crews exist to this date. Using a combination of qualitative and quantitative methods, this thesis provides an understanding of the specific contribution of sound technicians in music production, framed as technical intermediaries, and uses this case to include technicians in a revised theoretical framing of the collective production of symbolic goods.Insights from Randall Collins’ interaction ritual chains and Jeffrey Alexander’s cultural performances are used to frame music performances as rituals intending to provide emotional outcomes and social bonding to their participants. The role of technical intermediaries in music performances is to create the material conditions necessary to achieve the emotional outcomes which are their purpose. They bring artistic contents, in their physical forms, to audiences, while preserving the systems of meaning conceived by artists and cultural intermediaries.This thesis describes various implications of bringing technicians in the analysis of the collective mechanisms of cultural production. It questions the notion of generalized symmetry central to actor-network theory and science and technology studies. It proposes an alternative interpretation of Baumol’s law and the “cost disease” of performing arts. It argues that music genres might not be an analytic category best fitted to analyse social practices surrounding music. Finally, it brings insights on sound technicians’ careers and division of work in music production
Between shared and conflicting interests:The political economy of the markets for public debt in the Dutch Republic, 1600-1795
Full text linkExploring proteolytic strategies to improve huntingtin clearance in cell models for Huntington's disease
Full text linkHuntington’s disease (HD) is a neurodegenerative disorder, caused by an expanded polyglutamine (polyQ) tract close to the N-terminus of the mutant huntingtin protein (mHTT). The primary goal of this thesis was to explore proteolytic strategies to improve mHTT clearance, as a therapeutic strategy to delay the onset of the disease. To study how proteasome complexes are altered in HD we used murine models of HD. In addition, cellular models for HD were used to modify (proteasomal) degradation to determine the effect on mHTT turnover. This thesis contributes to a better understanding of how changes in the proteostasis machinery affect the degradation of polyQ fragments and ultimately mHTT levels. While we found that PA28αβ and IDE upregulation improves the degradation of polyQ fragments, the opposite effect (decreased turnover) was observed on polyQ containing mHTT fragments. This suggests that not the polyQ stretch itself, but rather the (misfolded) protein context hinders the degradation of mHTT. Moreover, as observed with PA28αβ and IDE, an increase in mHTT aggregation was detected, despite no direct effect on the turnover of soluble mHTT levels was seen. This indicates that protein aggregation is not only driven by the total levels of an aggregation-prone protein, but is also (directly or indirectly) influenced by other factors, such as chaperone function. Finally, the regulation of the different pathways is tightly connected, and a defect in one system, leads to the upregulation of a compensatory pathway. Which was observed after RPN10 silencing
Impact of diversity on cardiovascular health:Insights from the HELIUS study
Full text linkThis thesis explores cardiovascular ageing and its determinants, focusing on differences by sex and ethnicity. We used data from the HELIUS cohort study, a large, multi-ethnic, population-based study in Amsterdam. Part I introduces a conceptual framework for cardiovascular ageing, defined as the progressive deterioration of the cardiac and vascular systems. Key biomarkers, such as pulse wave velocity (PWV), carotid intima-media thickness (IMT), and NT-proBNP, were identified, with an emphasis on the need for ethnic-specific cut-off values. We also examined ethnic differences in carotid plaque presence and IMT, revealing significant disparities. Additionally, longitudinal data showed increasing ethnic differences BMI levels over time, particularly among younger individuals. Part II focuses on hypertension as a key determinant of cardiovascular ageing. Longitudinal analyses revealed widening disparities in systolic blood pressure levels among Ghanaian, Moroccan, and Turkish groups compared to the Dutch. We also explored sex differences in hypertension phenotypes. Compared to men, women had a higher risk of developing sustained hypertension, particularly those with isolated diastolic hypertension, highlighting the need for closer blood pressure monitoring in young women. Part III examines the impact of cardiovascular risk factors on cerebrovascular health. MRI data showed that higher BMI and diabetes were associated with lower brain volumes, while hypertension and a history of cardiovascular disease correlated with white matter hyperintensities. Associations between cardiovascular risk factors and cerebral blood flow were weaker. Finally, carotid plaque components, such as lipid cores, calcifications, and intraplaque hemorrhage, were associated with distinct cardiovascular risk factors
Paving the way for nucleic acid-based HIV-1 envelope vaccines
Full text linkHuman immunodeficiency virus type 1 (HIV-1) remains a major global health challenge, with no effective prophylactic vaccine despite decades of dedicated research. The viral envelope glycoprotein (Env) trimer is the sole target of neutralizing antibodies and a central focus for vaccine development. However, its remarkable sequence diversity, inherent instability, and dense glycan shield, among other factors, hinder the induction of broadly neutralizing antibodies (bNAbs). This thesis explores novel strategies to stabilize Env trimers, enhance their antigenic properties, and improve their suitability for RNA- and other nucleic acid-based vaccine platforms.We first investigated natural mechanisms of Env stabilization by introducing destabilizing mutations and identifying compensatory changes that emerged during viral evolution. Building on these and other prior insights, we engineered hyperstable trimers and found that increased stability led to stronger and more consistent neutralizing antibody responses. By selectively masking immunodominant epitopes with glycans, we redirected immune responses toward subdominant epitopes with greater potential to induce bNAbs.We also developed the Triple Tandem Trimer (TTT) platform, which encodes all three protomers of an HIV-1 Env or influenza hemagglutinin (HA) trimer within a single gene, ensuring exclusive trimer expression. TTT immunogens formed native-like trimers, induced diminished non-neutralizing responses, and enabled the design of chimeric trimers that could simplify sequential vaccine regimens by integrating different immunization stages into a single immunogen.Finally, we engineered RNA-delivered, membrane-bound, germline-targeting Env immunogens that potently activated rare bNAb precursors in knock-in mouse models and outperformed soluble counterparts in triggering these targeted responses.Collectively, these approaches advance the design of stable, immunofocused Env immunogens optimized for nucleic acid-based vaccine delivery, and offer promising tools and strategies for the development of an effective HIV-1 vaccine
Cancer-associated thrombosis:Mechanisms, prediction, and treatment
No full textThis thesis explores the mechanisms, prediction, and treatment of cancer-associated thrombosis (CAT). In Part I, we investigated biological mechanisms contributing to venous thromboembolism (VTE) in patients with cancer. In a review, we described germline and somatic mutations associated with increased VTE risk. A transcriptomic analysis in pancreatic cancer suggested a potential role of interleukin-33 in VTE development, whereas a protein profiling approach did not identify candidate protein predictors.In Part II, we focused on risk prediction. A new CAT risk score was validated in a large Danish cohort, classifying more patients with VTE as high risk compared with the guideline-recommended Khorana score, while maintaining similar discriminatory performance. An individual patient data meta-analysis of >2,200 patients with cancer identified predictors of recurrent VTE during anticoagulation (age, breast cancer, metastatic disease, direct oral anticoagulant use, and index deep-vein thrombosis). However, predictive accuracy was modest, underscoring the limitations of models relying only on baseline predictors at the start of anticoagulation.In Part III, we evaluated treatment of recurrent VTE despite anticoagulation. A post-hoc analysis of the Hokusai VTE Cancer trial revealed heterogeneous management strategies and high rates of recurrence, bleeding, and mortality. In a prospective observational study, a low-molecular-weight heparin dose escalation strategy did not clearly reduce second recurrences.Overall, this thesis underscores the complexity of cancer-associated thrombosis, the limitations of current prediction tools, and the poor outcomes of recurrent VTE, highlighting the need for improved biomarkers and treatment strategies.<br/