International Migration, Integration and Social Cohesion online publications
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Vaccination in patients with a hematologic condition:Challenging the dogmas in vaccination of the immunocompromised
Full text linkPatients with hematologic conditions are often immunocompromised due to the disease or the therapy they receive. This makes them prone to severe infections and infection-related mortality. Some infections can be prevented through vaccination. However, a key question remains: how effective are these vaccines in this immunocompromised population? In this thesis, I will explore vaccine immunogenicity in patients with hematologic conditions and seek to understand how their immunodeficiencies influence vaccine-induced immune responses. In part I of this thesis, humoral immune responses obtained after pneumococcal polysaccharide and conjugated vaccination are discussed in patients after allogeneic hematopoietic stem cell transplantation and patients with chronic lymphocytic leukemia. In part II, this thesis focused on the humoral and cellular immune response after SARS-CoV-2 mRNA vaccination in seventeen cohorts of patients with different hematologic conditions and treatments. We demonstrated that vaccination of these immunocompromised individuals is more effective than initially expected, inducing potent cellular and humoral immunity in the majority of patients, provided that multi-dose vaccination schedules are followed. This was observed both for mRNA vaccines and for conjugated vaccines. In case of high disease prevalence, for example in flu season or during a pandemic, inactivated vaccines should not be postponed in these patients, irrespective of treatment status, because it is more important to develop as much protection as possible, instead of achieving a protection rate comparable to that of healthy individuals. Future research should focus on both humoral and cellular immune responses after vaccination and always investigate the effect of booster vaccination(s) in this population
Hybrid luminescent systems based on rare-earth-doped upconversion nanoparticles:Mechanisms and wide range temperature sensing
No full textLanthanide-doped upconversion nanoparticles (UCNPs) are promising candidates for advanced optical applications, yet their efficiency remains a critical challenge. This thesis presents a systematic study to enhance the luminescence and functionality of UCNPs through energy transfer engineering, host lattice design, and nanocomposite strategies.The energy transfer mechanism in the Yb3+-Ho3+ system by tailoring core-shell-shell nanostructures is explored and optimized, which enable efficient cooperative sensitization upconversion (CSU), especially at cryogenic temperatures. Building on this, a photonic nanostructure incorporating polymethyl methacrylate (PMMA) opal photonic crystals is designed to further enhance the emission of this system via photonic bandgap modulation, resulting a 4,300-fold upconversion luminescence enhancement at 80 K and enabling high-sensitivity cryogenic thermometry.Next, a highly sensitive temperature probe based on a heavily doped Er³⁺ system is developed, where cross-relaxation effects provide reliable and ultra-sensitive luminescence thermometry. To further boost the upconversion performance, alkaline-earth-based cubic host matrices (M1-xErF2+x, M = Ca, Sr, Ba) are introduced to modify the host-dopant interactions. Among them, SrErF5@SrYF5 nanoparticles exhibit over 8-fold enhanced emission and pronounced thermal responsiveness.Finally, a novel composite is constructed by integrating cubic-phase BaYbF5:Tm3+ UCNPs with CsPbBr3 perovskite quantum dots. The excellent lattice match facilitates energy transfer and produces dual-mode optical output, demonstrating potential in multifunctional nanophotonics.Together, this work advances the design of high-performance UCNP platforms and broadens their applications in low-temperature sensing, optical devices, and hybrid nanophotonic systems.</p
Developing digital health interventions for falls prevention:An innovative user-centered design approach
Full text linkDigital health interventions are promising for improving the efficiency and quality of care delivery, but their broader adoption remains limited due to design approaches that often do not adequately address user needs. This dissertation aimed to enhance the iterative cycle of User-Centered Design (UCD) and applied this improved cycle for the development of two digital falls prevention interventions for use by health care professionals (HCPs), namely an online multifactorial falls risk assessment tool (i.e., Fall Analysis 2.0) and a medication-related clinical decision support system (i.e., ADFICE_IT CDSS). Chapters 2 and 3 detail the construction of theory-driven personas and journey maps to foster user-focused thinking and guide design and implementation requirements for the Fall Analysis 2.0. Chapter 4 demonstrates how interdisciplinary collaboration supported the development of the ADFICE_IT CDSS. Chapter 5 introduces a novel approach to usability problem prioritization, emphasizing severity based on the problem’s potential negative impact on the secondary (patient) rather than primary (HCP) user experience. In chapter 6, the effectiveness, user experience, and implementation of the Fall Analysis 2.0 is examined in Dutch primary care, revealing that the UCD developed tool positively influenced HCPs falls risk management behavior by facilitating fully completed multifactorial falls risk assessments in older adults at high risk of falling. Together, the findings set new standards for the development and testing of UCD-driven digital health interventions for HCPs, both within and beyond the context of falls prevention. The final chapter discusses the implications of these findings for research and (clinical) practice
Let misophonia be heard:Advancing recognition, diagnostics and treatment of misophonia in youth
Full text linkMisophonia is a recently identified disorder of decreased tolerance to specific sounds or associated stimuli (so-called “triggers”). Triggers primarily include human-made sounds such as eating or breathing. Confrontation with triggers elicits intense emotional, behavioral and physiological responses that are difficult to control. Misophonia typically develops during childhood and has considerable consequences for the daily lives of children and families. Often, children can no longer eat, sleep or travel by car together with their family, and they experience problems at school and with friends. There is a great need for adequate diagnostics and evidence-based treatment. The main aim of this thesis is to improve care for children, adolescents and families suffering from misophonia. We present the first controlled study worldwide investigating misophonia in 95 children and adolescents (aged 8-18). We: 1) assessed clinical characteristics, psychiatric comorbidity and quality of life; 2) designed and validated two child-specific questionnaires for screening and severity assessment of misophonia in children and adolescents; 3) performed a randomized controlled trial (RCT) investigating combined cognitive behavioral and psychomotor group therapy (CBT+PMT); 4) performed a cost-of-illness study investigating the financial burden of misophonia on families and society. This thesis underlines the importance of classifying misophonia as a discrete disorder. By providing two validated questionnaires and the first evidence-based treatment, this thesis paves the way for improved recognition, diagnostics and treatment of misophonia in youth
The art of restitution:Pursuing justice through restitution committees for Nazi-looted art
Full text linkLooted art has long been associated with war, but the Nazi regime elevated cultural plunder to an unprecedented scale, making it a central instrument in the persecution of Jews and other targeted groups. Early post-war restitution proved limited, and since the late 1990s new mechanisms were established in response to international calls for long-overdue justice.This thesis examines the evolving approaches to Nazi-looted art restitution in Austria, the United Kingdom, and the Netherlands, focusing on the committees created to adjudicate such claims. It argues that a paradigm shift has occurred: from a strictly legal to a morally driven, victim-centred framework. These committees prioritize recognition of suffering and procedural justice, yet face the challenge of balancing legal certainty with morally just outcomes.From an institutional perspective, the study shows that all three committees deliberately departed from traditional legal frameworks, favouring flexible procedures and accessibility. While initially praised, this informality exposed weaknesses such as lack of transparency, juridification, and dependence on the executive. Substantively, their approaches diverge: Austria remains rooted in legal doctrine, the UK embraces moral reasoning, and the Netherlands has developed a discretionary framework that increasingly acknowledges historical injustices and victim agency.Engaging with scholarly debates, this thesis advocates a hybrid model that embeds moral reasoning within a legal framework. Sustainable legitimacy requires legal safeguards to ensure transparency, independence, and procedural clarity, while leaving space for moral considerations. Only such a hybrid paradigm can reconcile legal structure with recognition of historical injustice, strengthening victims’ agency and ensuring context-sensitive restitution
Next-generation bNAbs:Antibody engineering strategies for HIV-1 cure
Full text linkDespite ART effectively suppressing HIV-1 replication, viral reservoirs persist and prevent a cure. Broadly neutralizing antibodies (bNAbs) can neutralize virions and mediate clearance of infected cells, but their efficacy is limited by low Env density, high viral diversity, immune cell exhaustion, and short antibody half-life. To address these challenges, this thesis focused on antibody engineering strategies to enhance bNAb potency, effector function, and capacity to eliminate HIV-1–infected cells. Engineering approaches included developing multivalent constructs to increase Env binding, glycoengineering to boost FcγRIIIa affinity and NK cell activation, and Fc modifications to enhance complement-dependent cytotoxicity. Subclass switching, hinge elongation, and introduction of activating mutations further optimized antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). In addition, bispecific antibodies were designed to simultaneously target HIV-1 Env and NK cell receptors, achieving improved immune cell recruitment and killing of infected cells. Overall, this thesis demonstrates that antibody engineering can overcome key limitations of current bNAb therapies. By improving effector function, immune engagement, and mechanisms of infected cell clearance, engineered antibodies show strong potential to reduce the viral reservoir. These findings support the advancement of next-generation antibody therapies as a promising step toward durable ART-free control or a functional cure for HIV-1
Navigating progestrone-driven gene regulatory networks in the mammary gland
No full textThe genome contains all the information required for organismal development and homeostasis, but gene expression must be tightly regulated in time and space. Enhancers (non-coding DNA elements) play a central role in this regulation by binding transcription factors and facilitating 3D chromatin interactions with target genes. This thesis explores how the steroid hormone progesterone, via its receptor (PR), controls gene expression through enhancer activity, with a focus on the mammary gland.First, we developed new molecular tools to visualize PR signaling at the single-cell level and optimized conditions for robust detection. Next, we used these tools to perform a detailed analysis of the enhancer landscape of Wnt4, a key PR target gene in mammary tissue. We identified a shared 3D enhancer hub that consists of both PR as well as GRHL2 bound enhancers that regulates Wnt4 in both mouse and human mammary tissues via a two-step model. Furthermore, we identified Wnt4 enhancers in the mous kidney and lung and compared them to the enhancers identified in the mammary gland. We found that these enhancers were not conserved between tissues, sugessting tissue-specific regulation of Wnt4.</p
Pathogenic mechanisms and therapeutic target discovery in chronic immune-mediated inflammatory diseases:Insights into the role of the lymphatic system and drug repurposing strategies
No full textThe aim of this thesis was to unravel pathogenetic mechanisms and identify novel therapeutic strategies in immune-mediated inflammatory diseases (IMIDs), with a focus on the lymphatic system in inflammatory bowel disease (IBD) and on transcriptomics-driven drug repurposing across IMIDs.In the first part of this thesis, we investigated the role of lymphoid structures in IBD pathogenesis, treatment response, and immunogenicity to biologics. We showed that mesenteric lymph nodes and lymphatic vessels actively shape immune priming, antigen presentation, and lymphocyte trafficking. Using cytometry-based profiling, we found that anti-drug antibody formation against anti-TNF therapies was associated with elevated B-cell and dendritic cell frequencies within lymph nodes. Furthermore, we demonstrated that sphingosine-1-phosphate receptor (S1PR) modulators, such as etrasimod, profoundly alter T-cell migration, highlighting lymphocyte trafficking as a tractable therapeutic axis in IBD.In the second part, we applied transcriptome-guided drug repurposing pipelines to identify novel therapeutic candidates. In systemic lupus erythematosus, we uncovered compounds, which could potentially restore monocyte-derived pathologic gene signatures, including heat shock protein-90 and inflammasome inhibitors. In individuals at risk for rheumatoid arthritis, we identified agents targeting the PI3K kinase and matrix metalloproteinase-9 pathways that could reverse preclinical synovial signatures, thus offering preventive potential. In Crohn’s disease–associated intestinal fibrosis, we discovered that dual blockade of PI3K and histone deacetylases synergistically attenuated fibroblast activation, proposing a new anti-fibrotic strategy.We conclude that the lymphatic system function is a central determinant of IBD pathogenesis and treatment outcomes, while omics-based drug repurposing provides promising, cost-efficient avenues for precision therapy across IMIDs. These insights pave the way for mechanism-driven interventions to improve outcomes in autoimmunity
Direct oral anticoagulants for atrial fibrillation:On comparing apples and oranges
Full text linkAtrial fibrillation is the most common sustained cardiac arrhythmia. It increases the risk of thromboembolism, which oral anticoagulants reduce effectively. For decades, vitamin K antagonists were the only class of oral anticoagulants available, but their narrow therapeutic window and need for close monitoring limited their use. Direct oral anticoagulants (DOACs) offered safer, more convenient alternatives, backed by robust phase III trials. This thesis examines key concerns that arose after their approval and widespread use in clinical practice.Part I reviews nonadherence and treatment patterns. Tracing the history of anticoagulant trials, we see how DOACs became the preferred agents. Large cohort studies reveal a clinician preference for factor Xa inhibitors, show that switching and serious nonadherence are relatively uncommon, and identify candidate predictors for both outcomes.Part II focuses on higher-risk patients and off-label dosing. We found sex differences in how clinicians assess frailty using clinical judgment alone. Patients with atrial fibrillation and atherosclerotic disease in routine practice show better cardiovascular health and fewer events than those in original trials — likely due to patient selection, improved care, or tailored treatment. We critique flawed off-label dosing studies and recommend integrating clinical judgment into DOAC dosing decisions for higher-risk individuals. Finally, we show that higher event rates seen with apixaban in daily practice mainly reflect patients’ underlying risk, not off-label dosing.Part III is on drug-level monitoring. We updated DOAC on-therapy ranges to aid interpretation of measured levels, and we found that a single apixaban measurement may help personalize dose selection.<br/
Endoscopic duodenal ablation for the treatment of type 2 diabetes:New insights and techniques
Full text linkMetabolic disorders such as type 2 diabetes (T2D) are rising worldwide. Largely due to poor diet and lack of exercise. Growing evidence highlights the duodenum, as a key regulator of glucose metabolism. Patients undergoing gastric bypass surgery often show rapid improvement in blood glucose within days, long before significant weight loss occurs. This suggests that bypassing the duodenum itself plays a major role in metabolic benefits. Based on this insight, new therapies have been developed that affect the duodenal mucosa. Since it is easily accessible via upper gastrointestinal endoscopy. One such approach is duodenal mucosal resurfacing (DMR), an endoscopic ablation technique that removes and regenerates the duodenal mucosa. Clinical studies have shown significant improvements in glucose control, with many patients able to discontinue insulin while maintaining stable blood glucose levels. Another technique is recellularization via electroporation therapy (ReCET), that uses electroporation (pulsed electric fields) to induce similar mucosal renewal in the duodenum. Both techniques have demonstrated durable effects without complications. Beyond glucose regulation, duodenal ablation also improves related metabolic conditions, including fatty liver disease, visceral fat accumulation, and cardiovascular risk factors. Additional research is ongoing to better understand the underlying hormonal and cellular mechanisms.In conclusion, duodenal ablation represents a safe and promising option for the treatment of T2D. Future studies aim to refine these techniques and identify which patient groups will benefit most