International Migration, Integration and Social Cohesion online publications
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Peripheral blood compounds in schizophrenia and major depressive disorder
Get PDFSchizophrenia and major depressive disorder (MDD) have traditionally been considered distinct disorders, yet they share overlapping symptoms, including mood disturbances, apathy, and cognitive impairment. Increasing evidence points to shared biological mechanisms, particularly involving immune function, neuroplasticity, and energy metabolism. This thesis investigates alterations in peripheral blood markers across these domains, focusing on drug-naïve first-episode patients, the effects of psychotropic treatment, the efficacy of anti-inflammatory augmentation, and the potential utility of blood-based biomarkers for predicting outcomes and guiding treatment.Three meta-analyses were conducted. The first showed that drug-naïve first-episode patients with schizophrenia or MDD exhibit alterations in neuroplasticity- and immune-related markers, with additional disturbances in glucose metabolism specific to schizophrenia. The second demonstrated that treatment tends to normalize neuroplasticity and immune alterations while worsening glucose regulation in schizophrenia. The third, a comprehensive analysis of 51 compounds in antipsychotic-naïve schizophrenia patients, confirmed widespread abnormalities at illness onset in neuroplasticity, immune function, and energy metabolism. Longitudinal analyses revealed improvements in neuroplasticity and immune markers following treatment, but further deterioration in energy metabolism.Serum analyses from two large cohorts revealed shared metabolic alterations — elevated leptin and insulin levels — in both schizophrenia and MDD, particularly during active episodes. A population-based study linked higher body mass index and altered lipid profiles to psychotic-like experiences, suggesting that metabolic dysfunction may represent a broader vulnerability factor.A meta-analysis of anti-inflammatory augmentation therapies showed beneficial effects, particularly in early illness and for negative symptoms. Finally, a machine learning study identified baseline markers of inflammation and endothelial function as predictors of negative symptom severity in schizophrenia six years later.These findings support a biologically informed, cross-diagnostic approach to psychiatry and highlight the potential of blood-based biomarkers to guide personalized, mechanism-based care
Exploring the long-term course of psychosis:Understanding longitudinal changes and interrelationships between recovery domains in different phases of psychotic disorders
Get PDFPsychotic disorders are disruptive on multiple aspects of life. In this doctoral thesis I evaluated longitudinal changes in patients with psychotic disorders on the following recovery domains: social functioning, symptoms, personal recovery or quality of life and cognition. In part 1 I investigated longitudinal changes in the four recovery domains separately through meta-analyses that included studies evaluating longitudinal changes in patients with psychotic disorders over a follow-up period of at least 1 year. The influence of the patients’ duration of illness and other personal, clinical and social patient characteristics on these longitudinal changes were also evaluated. In part 2 I investigated to what extent changes in one recovery domain was associated with changes in another recovery domain through both a meta-analysis and through a longitudinal cohort study. Overall, results indicated that people with psychotic disorders improve substantially over time in symptoms and social functioning, especially for patients with early psychosis, but cognition and personal recovery showed modest or no improvement over time. Improvement in social functioning, symptoms and cognition were associated with one another, indicating that longitudinal changes in these recovery domains might reinforce each other. Changes in personal recovery were hardly associated with changes in other recovery domains. This suggests that improvements in social functioning and symptoms did not translate into a more positive subjective experience of overcoming mental illness. This thesis taught us that improvement in time in patients with psychotic disorders is possible, but special attention is needed for long-term improvement in cognition and personal recovery
Quantitative MRI in pancreatic and liver diseases:From technical optimization to clinical application
Get PDFQuantitative MRI techniques provide non-invasive biomarkers of tissue properties, with potential to inform personalized treatment strategies. This thesis investigates the optimization, validation, and clinical application of multiple quantitative MRI methods in pancreatic and liver diseases.In pancreatic ductal adenocarcinoma (PDAC), MR elastography (MRE) was optimized and shown to reliably quantify pancreatic stiffness and viscosity, revealing increased values in tumors compared to non-tumorous tissue. Furthermore, dynamic contrast-enhanced MRI (DCE-MRI) acquisition and reconstruction were systematically optimized for abdominal applications. Phantom and in vivo scans demonstrate that tailored protocols enable accurate pharmacokinetic parameter estimation while maintaining image quality. Histopathological validation of quantitative MRI techniques in PDAC revealed that microvascular density correlated with intravoxel-incoherent motion diffusion-weighted (IVIM-DWI) and T2* metrics, while collagen density correlated with T2*, supporting their value as tissue biomarkers.Clinical utility of these techniques in PDAC patients is shown in a multicenter phase I/II clinical trial evaluated combined chemotherapy and LDE225 in metastatic PDAC patients. Quantitative MRI demonstrated treatment-induced increases in diffusion and perfusion parameters, with IVIM-DWI showing prognostic potential for overall survival. Beyond pancreatic cancer, quantitative MRI was applied to metabolic dysfunction-associated steatotic liver disease (MASLD). In a cohort of 91 patients, quantitative MRI parameters, particularly when combined with laboratory markers, differentiated disease activity, fibrosis, and severity stages with strong correlation to histopathology.The findings of this thesis underscore the value of quantitative MRI for characterizing tissue microenvironments in pancreatic and liver diseases. While technical and translational challenges remain, optimized protocols and histopathological validation advance the clinical integration of these techniques
Follow the trace:Evaluating physical and digital forensic findings given activity level propositions using Bayesian networks
No full textForensic scientists face questions ranging from “What is the source ofthis trace?” to more complex issues like “Who did what, when, where,and how?” These latter questions, known as “activity level questions,”become particularly challenging when they involve multiple types oftraces, such as DNA traces and fibers. Evaluating the combined strengthof evidence in these cases provides great value to the court but requiresmanaging numerous probabilities arising from various uncertainties. Suchcomplex casework requires structured probabilistic reasoning, and Bayesiannetworks prove to be valuable tools for this purpose.By using fictive case examples throughout this work, we advocate thebenefits of the LR framework and Bayesian networks for evaluating forensicfindings given activity level propositions across various disciplines—including digital forensic science.The result? A collection of “building blocks” representing generalprobabilistic forensic problems and two template Bayesian networksapplicable to both mono- and interdisciplinary casework that map pathwaysfrom alleged activities to traces found on items of interest (i.e., “Follow thetrace”). Additionally, two use cases in digital forensic science are presented:one involving iPhone Health app data and another addressing Trojan horsedefense cases.This work aims to serve as a valuable reference for forensic scientists intheir casework and research while also providing useful insights for otherprofessionals in the forensic and legal fields
Threatened preterm birth and beyond:Clinical management and child follow-up
No full textDespite advances in obstetric care, the optimal management of threatened preterm birth remains to be determined. This thesis contributes to improving the management of threatened preterm birth by evaluating the role of tocolytics and investigating the optimal timing of birth in late preterm prelabour rupture of membranes, considering both short- and long-term child outcomes. Furthermore, this thesis discusses different approaches to long-term follow-up research of children prenatally exposed to obstetric interventions, an area that still receives limited focus. Future studies must further refine the risk assessment of threatened preterm birth, and the evaluation of long-term child outcomes should be standardised in preterm birth studies. Ultimately, by aligning treatment strategies with individual risk profiles, we can improve outcomes not only at birth, but throughout childhood and beyond
Breaking the chain of deception:A multi-stakeholder perspective on deceptive advertising and the potential of blockchain as a solution
No full textDeceptive advertising is a growing problem in the contemporary digital environment, exacerbated by increasing digitalisation and over-reliance of media companies on advertising revenue. These developments have created a complex and non-transparent online advertising ecosystem, enabling deceptive practices to operate undetected. Deceptive advertising undermines consumer well-being, imposes financial and reputational costs on industry stakeholders, and erodes societal trust by amplifying disinformation. While regulators have introduced measures to empower consumers, news media also play a pivotal role in shaping public perceptions of deceptive advertising and influencing how other stakeholders prioritise and address the issue. The widespread impact of deceptive advertising across the entire online advertising ecosystem highlights the need for a multi-stakeholder approach that includes consumers, the online advertising industry, and the news media.This dissertation explores perceptions of deceptive advertising from this multi-stakeholder perspective and investigates whether, and how, blockchain technology can serve as a potential solution. It examines how the news media frame deceptive advertising, how consumers’ beliefs and experiences shape their protection motivations, how industry experts perceive the issue and blockchain’s potential, and whether blockchain-based ad authenticity disclosures influence consumer perceptions of ad and brand credibility.Findings reveal that although all stakeholders acknowledge deceptive advertising as an issue, advertising industry experts differ in their assessment of its severity, and many consumers underestimate their susceptibility. While theoretically blockchain can reduce the impact of deceptive advertising by enhancing transparency and credibility, practical implementation faces substantial challenges. Effective application requires favourable regulation, consumer education, and adoption across the entire online advertising ecosystem
Pancreatic cancer treatment:A multidisciplinary study towards an evidence-based and patient-centered approach
Get PDFThis doctoral thesis provides a comprehensive exploration of pancreatic cancer, integrating population-based data, clinical trial data, and patient-reported outcomes to better understand disease patterns, evaluate treatment strategies, and examine the well-being of patients throughout the course of the disease.Chapter 2 analyzes how real-world survival scenarios for pancreatic cancer have evolved over a 16-year period. Chapter 3 investigates the influence of sex and gender on treatment allocation and survival among patients with early-stage (stage I–III) disease in the Netherlands. Chapter 4 presents findings from the international randomized NAPAN trial, which compared second-line treatment strategies for patients with metastatic pancreatic cancer progressing after gemcitabine-based therapy. Chapter 5 describes the study protocol of the PREOPANC-5 trial, designed to improve outcomes for patients with borderline resectable pancreatic cancer. Chapters 6 and 7 focus on patient-reported outcomes. Chapter 6 examines changes in health-related quality of life (HRQoL) over time across different treatment pathways. Chapter 7 assesses the prevalence and development of anxiety and depression and identifies patient and treatment characteristics associated with more severe psychological symptoms.Overall, this thesis demonstrates the evolving landscape of pancreatic cancer, where survival improvements should progress in parallel with attention to quality of life and psychological wellbeing. It reaffirms the clinical value of established regimens, explores novel strategies, and underscores the need to address treatment disparities and ensure equitable access. As survival gains remain modest, integrating the patient perspective into both research and clinical practice should be considered a key priority for future innovation
Teaching towards historical expertise:Developing students’ ability to reason causally in history
Get PDFExplaining historical events is an important goal in history education, but not much is known about pedagogical approaches to support this reasoning. In this dissertation, we therefore developed and investigated a learning-environment intended to foster students’ ability for causal historical reasoning. Based on the model of domain learning and the framework of historical reasoning, we defined causal historical reasoning as a construct consisting of (knowledge of) second-order concepts, causal strategies and epistemological beliefs.In the first study, we designed a lesson-unit on the First World War and conducted a quasi-experimental study with 11th-grade preuniversity students. In a second study, we replicated the experiment in a randomized controlled design. We concluded that explicit teaching constituted an indispensable principle in developing causal historical reasoning. Students in the experimental (explicit) condition showed greater improvement on the knowledge of causal strategies and second-order concepts. Furthermore, these students reported learning-gains related to epistemological aspects of causal explanations. At post-test in the experimental condition, a strong correlation was found between epistemological beliefs and students’ interest. Applying knowledge of causal historical reasoning in a document-based writing-task remained difficult for students. A qualitative study showed that students were able to integrate aspects of causal historical reasoning in their texts, but that they struggled with the argumentative nature of the task. Throughout the studies, epistemological beliefs surfaced as an important dimension of students’ historical reasoning, but assessing these beliefs was complex. Therefore, in the final study, we developed a new questionnaire aimed at evaluating naïve and nuanced epistemological beliefs.<br/
Mechanistic insights into energy transfer in highly doped upconversion nanoparticles
Get PDFHighly doped upconversion nanoparticles (UCNPs) feature complex energy transfer dynamics that enable strong luminescence but also introduce significant challenges such as cross-relaxation and concentration quenching. This thesis presents a comprehensive investigation into the underlying mechanisms of energy transfer in highly doped UCNPs and explores strategies to enhance their upconversion luminescence (UCL). Cryogenic temperature conditions are employed to effectively suppress non-radiative losses in Er³⁺-rich systems, leading to pronounced luminescence enhancement. Additionally, modulation of cross-relaxation channels enables finely tuned temperature-dependent emission, allowing these materials to function as highly sensitive luminescent thermometers. To further improve excitation efficiency and mitigate photothermal effects, Er-rich systems are integrated with Nd³⁺ sensitization, enabling effective 808 nm excitation and enhanced UCL output compared to conventional 980 nm systems. Beyond mechanistic studies, the practical versatility of highly doped UCNPs is demonstrated in two light-driven systems: near-infrared-triggered photoclick reactions and optically powered rotary molecular motors. Together, these results provide deep mechanistic insights into lanthanide-doped nanomaterials and establish a versatile platform for next-generation UCNPs with enhanced performance in photochemistry, biomedical imaging, optical sensing, and nanoscale photonic applications
Microbial alchemy in ulcerative colitis:Crafting the recipe for fecal microbiota transplantation
Get PDFThis thesis explores the therapeutic potential of fecal microbiota transplantation (FMT) in ulcerative colitis (UC), an inflammatory bowel disease with rising incidence. It is structured into three parts.Part 1 addresses the scientific rationale and methodology behind FMT. It demonstrates that higher bacterial alpha-diversity in both donors and recipients is associated with improved clinical response. It also shows that anoxic processing of donor feces preserves obligate anaerobes better than standard anaerobic methods, potentially enhancing treatment efficacy. Part 2 focuses on the practical application of FMT in UC. It presents the protocol of the TURN2 trial, a randomized controlled study integrating donor selection based on microbiota profiles and anaerobic stool processing. It also provides insights into the challenges and costs of donor screening at Amsterdam UMC, underscoring the need to develop donor-independent microbiota-based therapies.Part 3 investigates microbial interactions beyond bacteria. It shows that the protozoa Blastocystis spp. and Dientamoeba fragilis are more prevalent in healthy individuals than UC patients, and their presence correlates with higher bacterial diversity and lower yeast overgrowth. These findings question the routine exclusion of these organisms in donor screening and highlight the need to better understand their ecological role in the gut.Together, the studies in this thesis aim to advance FMT towards a more effective, evidence-based, and ecologically informed treatment strategy for UC