International Migration, Integration and Social Cohesion online publications
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Molecular mechanisms and therapeutic targeting of Fc receptor activation in acute and chronic inflammatory diseases
No full textAntibodies play a crucial role in the host immune response against invading pathogens. By facilitating specific effector functions, they contribute to pathogen clearance and modulation of the immune response. Beyond well-known functions like neutralization, antibodies can trigger a powerful cytokine response mediated by Fc receptor (FcR) activation through a mechanism called antibody-dependent inflammation (ADI). ADI facilitates the rapid secretion of pro-inflammatory cytokines, which, in a pathological situation, plays an important role in effective pathogen clearance. In contrast, if mis-regulated, due to its ability to induce high levels of pro-inflammatory molecules, aberrant ADI can contribute to extensive tissue damage and worsening of disease pathology. In severe COVID-19, aberrantly glycosylated antibodies induce mis-regulated ADI, contributing to a hyperinflammatory phenotype, microvascular thrombosis and pulmonary edema. To successfully counteract aberrant ADI-induced pathology, it is important to understand the underlying molecular mechanisms causing these deteriorating effects. In this thesis, I set out to investigate the molecular mechanisms, as well as potential therapeutic targets, of pathological FcR activation in severe COVID-19 progression. Apart from antibodies, pentraxins can induce the secretion of pro-inflammatory cytokines via FcR activation in a mechanism similar to ADI. CRP-induced pathology has been described in several chronic inflammatory conditions, such as rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Thus, I investigated the molecular mechanism of CRP-induced cytokine induction to explore potential indications for the treatment of chronic inflammatory diseases
Ultra-low-dose chest CT versus chest X-ray for acute pulmonary disease:Clinical and societal implications
Get PDFRadiological imaging plays a pivotal role in clinical decision-making in the work-up of ED patients with non-traumatic pulmonary complaints. Ultra-low-dose chest CT (ULDCT) offers the possibility to obtain detailed imaging at a radiation dose similar to that of conventional chest X-ray (CXR). Optimal implementation of such a novel imaging technique with a higher diagnostic accuracy than the default modality requires evidence on the impact on patient management and efficiency. Therefore, this thesis studied the impact on patient outcome and societal outcome of replacing CXR by ULDCT in patients presenting at the ED with non-traumatic pulmonary complaints. We designed the OPTIMACT trial, a multicenter, pragmatic, non-inferiority randomized controlled trial comparing ULDCT to CXR in consecutive adult patients presenting at the ED with non-traumatic pulmonary complaints. We demonstrated that ULDCT was non-inferior in short-term functional health with minimal differences in hospital admissions, length of stay, mortality, and economic impact compared to CXR. There were more incidental findings, but less additional imaging procedures after 28 days with ULDCT. In patients with an atypical presentation of pneumonia ULDCT performed better than CXR. ULDCT was more accurate in detecting pulmonary infections, but less accurate in detecting pulmonary congestion. Awareness for early radiological features of pulmonary congestion may improve the recognition of pulmonary congestion at ULDCT and CXR.Overall, the results of our trial do not support the unconditional use of ULDCT in the work-up of patients presenting with non-traumatic pulmonary disease at the ED. It is recommended to consider the use of ULDCT instead of CXR in vulnerable patients
Evaluating surgical patient experiences and clinical outcomes
No full textThis thesis explores the significance of patient-centred care in modern surgical practice, focusing on both general and cardiac surgery. Patient-centred care prioritises the patient’s beliefs, values, and experiences, aiming to improve not only traditional clinical outcomes—such as mortality, complications, and technical performance—but also patient-reported outcomes (PROs) like pain, health-related quality of life (HRQoL), and emotional well-being. The introduction highlights that while clinical metrics are well established, PROs remain underutilised, especially in cardiac surgery, despite their importance in capturing the long-term challenges patients face after surgery.The thesis is divided into two main parts. The first part examines chronic post-surgical pain management, particularly the use of neuromodulation techniques such as spinal cord and dorsal root ganglion stimulation. These studies assess both clinical and patient-reported outcomes, demonstrating the value of integrating PROs to evaluate the effectiveness and sustainability of pain management strategies.The second part focuses on cardiac surgery, with special attention to perioperative coagulation management in patients with infective endocarditis (IE) and the use of PROs in patients undergoing thoracic aortic surgery. Surveys and registry analyses reveal significant variation in clinical practice and underscore the need for standardised protocols and better preoperative management. Studies on aortic surgery patients show that survivors face persistent physical, mental, and social challenges, reinforcing the necessity of including PROs in surgical evaluation.Overall, the thesis advocates for a shift towards more personalised, patient-centred surgical care, aligning clinical success with patient-defined goals and long-term quality of life
Sinofuturism as worlding:Imagining futures in sinophone digital art
No full text“Sinofuturism as Worlding: Imagining Futures in Sinophone Digital Art” responds to the prevalence with which politicians, journalists, and opinion makers imagine futures of the Sinophone sphere in either techno-utopian or techno-orientalist terms and as determined by either China or “the West.” It studies Sinophone digital art that has gained prominence and that produces nuanced imaginations of the relation between digital technologies and futures that go beyond reductive geopolitical binaries. The study asks: How does Sinophone digital art imagine technology-infused futures in response to techno-utopian and techno-orientalist imaginations of those futures? To answer this question, it adopts a theoretical framework that consists of three concepts: Sinophone, worlding, and Sinofuturism. These concepts are mobilized to analyze how future-oriented Sinophone digital art brings into being technology-infused futures of Sinophone words. The chapters focus on four themes that are prevalent in imaginations of such futures: connectedness, embodiment, self-care, and artificial intelligence. Case studies include artworks by artists such as LuYang, Lawrence Lek, aaajiao, Miao Ying, Li Yi-Fan, Ye Funa, Betty Apple, and Fei Yining, as well as exhibitions and other materials from art institutes such as Chronus Art Center (Shanghai), M WOODS (Beijing), and Digital Art Center (Taipei). By adopting a method of cultural analysis grounded in art historical and ethnographic methods, a more comprehensive understanding is produced of the multifaceted futures that are being imagined and brought into being across the Sinophone sphere
Google's expansion into security:Platforms, infrastructure, (in)visibility
Get PDFOver the last decade, Big Tech have been extending their socio-political impact by increasingly getting involved in matters of security. As such, Big Tech like Google gain power over what needs to be secured or protected, from whom and how. Concerned with this development, this PhD thesis asks how Google builds on its digital dominance to expand and navigate its position in the security domain. It answers this question from an interdisciplinary perspective that combines critical security studies with platform studies. This approach enables a deep exploration of Google’s security-focused platforms, infrastructure, internet standardization efforts, and expertise in artificial intelligence. The PhD thesis argues that Google builds on its digital dominance to expand and navigate its position in the security domain through its platformization of security, expanding infrastructurally, and by deploying (in)visibility politics. As such, Google’s involvement in security is no longer ambivalent. Google is pro-actively taking steps to shape understandings of security to fit its commercial objectives. Google may align itself with government interests when there is potential for long-term commercial benefit. But Google does not hesitate to treat governments just like any other user of its platform who needs to agree with the terms and conditions if that platform has reached an infrastructural scale and scope. While Google is subject to government regulation in for example the United States and the European Union, Google’s relationship with governments is therefore highly dependent on context
B cells and their signaling pathways:The guiding lights to decipher and target autoimmunity
Get PDFAutoimmunity arises when the immune system misrecognizes self as non-self, leading to chronic inflammation and tissue damage. B cells are central to this process by producing autoantibodies, presenting self-antigens, and secreting pro-inflammatory mediators. This thesis focuses on B cell biology in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), idiopathic inflammatory myopathies (IIM), and rheumatoid arthritis (RA), with the aim of (i) characterizing B cell subsets across immune compartments and inflamed tissues, and (ii) exploring disease-relevant intracellular signaling pathways as therapeutic targets.In AAV, kidney biopsies revealed diverse B and T cell populations, including atypical memory B cells, plasma cells, and pro-inflammatory T helper cells, within a microenvironment shaped by NF-κB and interferon signaling. Furthermore, enhanced canonical and non-canonical NF-κB signatures were identified in peripheral B cells in active AAV, which were effectively inhibited by IKKβ and NIK blockade, resulting in reduced B cell proliferation, differentiation, and autoantibody production. In IIM, characterized by an interferon signature and JAK/STAT activation, B cell profiling uncovered skewed transitional/naïve and memory subsets. Additionally, JAK inhibition preferentially suppressed B cell differentiation and reduced autoantibody production, supporting its therapeutic potential in IIM. In RA, autoreactive ACPA⁺ B cells displayed enhanced proliferation as well as (auto)antibody and cytokine production, which were abrogated by NF-κB inhibition, while JAK inhibition broadly suppressed B cell activity.This thesis demonstrates that targeting NF-κB and JAK/STAT signaling in AAV, IIM and RA modulates autoreactive B cell responses. Targeting these pathways in B cells offers opportunities for more precise therapies, moving beyond broad B cell depletion toward durable, pathway-specific modulation
Timing of light:Circadian and metabolic effects
No full textIn mammals, the circadian timing system consists of a light- sensitive central brain clock located in the hypothalamic suprachiasmatic nucleus (SCN) and various peripheral clocks. Disruption of this circadian system is associated with adverse health problems including adiposity and diabetes mellitus. This thesis aims to study the timing of light, and the circadian and metabolic effects on rats and humans. Chapter 2 investigates the adaptation speed of behavioral and metabolic parameters in a rat model of jet lag and shift work, and the effects of time-restricted food intake as a potential strategy to mitigate the negative effects of such phase-inversions in rats. Chapter 3 investigates possible changes in the liver and muscle insulin signaling pathway, the adaptation speed of the molecular clock in liver, muscle and white adipose tissue (WAT) and the daily body temperature rhythm in the same rat model. Moreover we investigate the effect of high fat diet, either ad libitum or restricted to the dark period, on the adaptation speed after a 12h phase shift of the light/dark cycle in rats. Chapter 4 investigates the blood oxygenation level dependent light responsiveness of the SCN-area in three groups of obese people: 1) normal insulin sensitivity, 2) insulin resistance and 3) type 2 diabetes. Further, we investigate the resting-state functional connectivity from the SCN-area to pre-specified regions of interest in brain as a marker of resting-state SCN-area activity. Chapter 5 investigates the effect of morning bright light exposure on the human WAT transcriptome.<br/
Coding cognition:Representing and communicating information in perceptual and memory systems
No full textThe mammalian brain uses neural networks to perform various impressive cognitive computations. In this thesis, I explore the neural code neural networks use to perform such computations. In chapter 2, we investigate the correlations of spiking activity of entire populations in the freely moving rat between- and within 4 cortical areas: visual cortex, whisker fields of the somatosensory cortex, perirhinal cortex, and the CA1 region of the hippocampus. In chapter 3, we investigate if, besides spikes, the phase-of-firing relative to the theta oscillations of the Local Field Potentials provides a means for the representation of audiovisual information. In chapter 4, we address the contemporary problem of non-sensory related signals in behavioral electrophysiology, and test if a forced delay in a behavioral tasks provides us with a method to isolate sensory related activity from behavior related activity. Lastly, in chapter 5, I summarize the information and discuss the implications for the theoretical model as laid out by Pennartz (2009, 2015)
Let’s talk about sex:Optimising the management of unexplained infertility
Get PDFThis thesis aimed to optimise expectant management (EM) for couples with unexplained infertility, focusing on sexual health. While at least six months of EM is recommended for couples with a favourable prognosis for natural conception, pregnancy rates remain limited, and it often fails to meet their need for action and information, leading to non-adherence and overtreatment.To address these issues, we explored couples’ experiences and identified a need for supportive interactions and advice on managing lifestyle, distress, and sexual challenges via a secure website. Using these insights, literature and expert input, we developed the Pleasure&Pregnancy (P&P) web-based programme, targeting sexual well-being- a critical but overlooked factor in fertility care. A randomised controlled trial evaluated the programme’s effectiveness compared to standard EM. While the P&P programme did not improve pregnancy rates, it enhanced women’s sexual pleasure, orgasm, and satisfaction. Although coital frequency and male sexual functioning decreased in the overall population, engaged users experienced reduced declines in coital frequency and improved male sexual desire. A cross-sectional study revealed that 25% of recently diagnosed couples are at risk of sexual dysfunction, highlighting the importance of prioritising sexual health. Factors like age, anxiety, depression, and relationship distress were associated with poorer sexual functioning. Dyadic analysis confirmed the interdependence of partners’ sexual functioning, emphasising the need for couple-focused fertility research and treatments.This thesis concludes that integrating sexual health support into EM can better address couples’ needs, improve sexual health, and may improve adherence. Further research into the P&P programme’s role in infertility care is recommended
Deserving refugees?:The evolution of a concept in the Dutch Republic (1570-1730s)
Get PDFThe Dutch word for ‘refugee’ (vluchteling) is relatively new according to the Woordenboek der Nederlandsche Taal and traces its origin to the early seventeenth century. It only became common in general language at the end of that century, specifically as a description for Protestants fleeing religious persecution and oppression in France. This linguistic development, however, must be seen in the light of a long-term and broader socio-cultural change in the attitude against foreigners. This study examines this development. It questions when, how and why the concept of ‘the refugee’ evolved into a specific category of migrant. To examine the emergence and evolution of the concept of ‘refugee’ during a period when this term was not part of a formal legal vocabulary, I distinguished between the development of the concept as a type of migrant and the terminology that was actually used. The concept was shaped by the distinction between ‘desirable’ and ‘undesirable’, and between those deemed ‘deserving’ and ‘undeserving’ of aid. The evolution of the ‘deserving refugee’ was driven by administrative needs, religious and geopolitical dynamics, economic interests of local elites, and the advocacy efforts of displaced communities. These factors collectively shaped the understanding of the ‘refugee’