International Migration, Integration and Social Cohesion online publications
Not a member yet
484620 research outputs found
Sort by
Immune infiltration and activation in breast tumors
Get PDFIn this thesis, we explore the antitumor response of immune cells against breast tumors and investigate how these findings can be clinically applied to improve patient treatment. Tumor cells are continuously in contact with other cells in their environment and can exhibit characteristics that the immune system perceives as foreign. This enables immune cells to infiltrate the microenvironment, recognize the tumor cells, initiate an immune response, and facilitate the clearance of the tumor cells. However, tumor cells can also manipulate their surrounding microenvironment in a way that inhibits the activity of immune cells, thereby preventing an immune response. With the advent of immune checkpoint inhibition therapy, it has become possible to activate immune cells that are suppressed by the tumor, thereby enabling the clearance of the tumor.Adding immune checkpoint inhibitors to chemotherapy has markedly increased response rates for patients with primary triple-negative breast cancer. To better tailor treatment options to individual patients and more accurately predict disease progression, it is necessary to gain more knowledge about the complex properties of the tumor microenvironment.This thesis first compares methods for investigating and profiling the tumor microenvironment in patients with early-stage breast cancer. We examine the comparability of different techniques and employ methods in clinical cohort studies that go beyond merely quantifying tumor infiltrating lymphocytes. Next, we examine various determinants of the tumor microenvironment and explore how these characteristics can be used to improve immunotherapy for patients with triple-negative breast cancer (BELLINI trial, Nederlof et al. and TONIC trial Voorwerk et al.) and whether elements of the microenvironment can be used to predict clinical response
Human spermatogonial stem cells:Growing hope for infertile male childhood cancer survivors
No full textThis dissertation focuses on male survivors of childhood cancer, who can become infertile due to the gonadotoxic effects of cancer treatments. Whereas adolescent and adult men can cryopreserve sperm prior to treatment as a method of fertility preservation, this option is not available to pre-pubertal patients due to the absence of spermatogenesis in the pre-pubertal testis. However, these patients are offered the option to collect and cryopreserve a testicular biopsy, harboring the spermatogonial stem cells (SSCs), which are present from birth onwards. In case of infertility in later life, the biopsy can be used to retrieve testicular cells including these SSCs, culture them to increase their numbers and autotransplant them into the healthy testis to restore spermatogenesis in the adult cancer survivor. However, this treatment is not clinically available yet, although good results have been obtained in animal models. The research described in this work aimed to review knowledge gaps in the field; optimize the culture of SSCs to reduce the previously observed hindering overgrowth of somatic testicular cells; investigate ways to facilitate clinical implementation of the culture by using xenofree, scaled-up methods; and uncover perspectives of cancer survivors on the potential future use of this technique. We found that growth of somatic cells could be limited by a combination of adaptations to the culture temperature, culture surface and medium components including growth factors. Additionally, patient perspectives revealed the necessity of a focus on reproductive autonomy during the course of their treatment, fertility consultations and future therapy
The creation of obligations under international law by diplomatic assurances issued in the context of expulsion
No full textThis study examines whether diplomatic assurances issued from one state to another in the situation of the expulsion of individuals can create obligations under international law. The study is conducted against the background of non-refoulement, the legal duty of states to refrain from expelling individuals to states where they may face a risk of torture, persecution or other serious mistreatment. This obligation prohibits expulsion when the predictable risk to the person surpasses a certain threshold. As part of the risk appraisal, a receiving state may provide “diplomatic assurances” to alleviate the concerns of the expelling state. If these assurances sufficiently mitigate the risk, then nonrefoulement is not implicated. Yet it remains unclear whether such assurances create any obligations under international law. It is often said that diplomatic assurances are merely political pledges, but this casual, overbroad assertion fails to appreciate the subtle differences among assurances as well as the nuances in international practice. This study finds that assurances in fact can create obligations under international law, in certain conditions. In turn, where assurances create obligations, states giving those assurances should incur state responsibility if they mistreat the person contrary to the assurances, opening the door to the traditional means of enforcement. More broadly, if the conditions under which assurances create obligations were explicated and acknowledged in international practice, expelling states may predict with greater confidence that an individual will not be mistreated, and non-refoulement would not be implicated.</p
Vaccination in patients with a hematologic condition:Challenging the dogmas in vaccination of the immunocompromised
No full textPatients 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
Animating metamaterials with non-reciprocity
Get PDFComplex material responses can be achieved by engineering the interactions between a material’s internal components and the geometry that organizes them. Yet even the most sophisticated designed materials remain limited compared to the adaptive, far-from-equilibrium behavior observed in living systems. This thesis explores how materials can be endowed with dynamical and autonomous behavior by embedding non-reciprocal interactions—forces that violate action-reaction symmetry—directly into their structure.This thesis explores the interplay between non-reciprocity and nonlinearity in active elastic metamaterials, which leads to emergent behaviors such as unidirectional soliton propagation, self-spontaneous locomotion, and cyclical shape changes. These effects arise not from external programming or centralized control, but from structured internal asymmetries and feedback. First, we uncover new classes of driven-dissipative solitons, including both topological and breathing solitons. Then, we focus on limit cycle dynamics in odd elastic metamaterials that generate robotic functionalities such as locomotion. We demonstrate how their vibrational spectra exhibit active phonon gaps which depend on the material's geometry. Finally, we uncover wave coarsening, a synchronization mechanism for waves mediated by the momentum-conserving nature of non-reciprocal and non-pairwise interactions.Taken together, this thesis offers a framework for designing active solids—materials that respond actively to deformations, mimicking certain aspects of biological autonomy such as locomotion and shape changing. This points toward a new generation of active matter that blurs the line between material and machine, capable of movement, adaptation, and decision-making
Let misophonia be heard:Advancing recognition, diagnostics and treatment of misophonia in youth
No full textMisophonia 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
Young citizens and their parents, peers, and teachers in a changing world:Social contexts of citizenship competences in adolesence
Get PDFCitizenship knowledge, attitudes, and skills enable adolescents to understand and participate in a pluriform and democratic society. Adolescents today grow up in a complex and uncertain world, facing serious challenges. In different social settings, adolescents share opinions, exchange ideas, practice principles of democracy, and experience what it means to be part of a community. This dissertation aimed to enhance understanding of the associations between adolescents’ citizenship competences and contextual factors. The central research question was: “To what extent are adolescents’ experiences with their parents, peers, and teachers, as well as their concerns about the world’s future, associated with their citizenship competences?”. A quantitative, large-scale, and representative dataset among adolescents in the Netherlands (13-14 years old) was used. The data included a civic knowledge test, a questionnaire on civic attitudes, engagement and skills, and a questionnaire about European issues. By including additional questions about parents and peers, a unique dataset was created that provided deeper insight into adolescents’ citizenship competences in relation to various important social contexts. Three main conclusions are drawn: 1) Adolescents’ citizenship competences are associated with their (interrelated) experiences with their parents, peers, and teachers; 2) Even in times of societal and educational changes, adolescents’ experiences within schools remain important for their citizenship competences; and 3) Civic engagement in adolescence manifests in various ways and is intertwined with individual perspectives on macrosocial issues. Taken together, this dissertation underscores the importance of acknowledging adolescents’ social contexts and their own macrosocial concerns to understand and support their citizenship competences
Foreign investment screening in the European Union:The state of exception in investment law
No full textThis thesis argues that the institutionalisation of security as a dominant paradigm under the FDI Screening Regulation constitutes a state of exception in EU investment law. Against the backdrop of successive crises, investment regulation has shifted from a paradigm of liberalisation to one defined by security. Drawing on the theories of Carl Schmitt, Giorgio Agamben, and Achille Mbembe, the thesis identifies three defining features of this state of exception: the tension between the security exception and the rule of law, the friend-enemy paradigm, and the conflation of security and economic interests.The European framework for investment screening is characterised by an open-ended scope of application, indeterminate screening criteria, broad discretion, a lack of transparency, and limited judicial review. These characteristics blur the boundary between law and politics and subtly erode the rule of law. Investment screening law, policy, and decision practice are furthermore shaped by a friend-enemy paradigm that frames foreign investors as trusted allies or security threats. The thesis demonstrates that investment screening pursues a wide range of security, economic and geopolitical interests. To resolve the state of exception in EU investment law, the framework should be reformed through the specification of clear, objective, and non-discriminatory screening criteria
Risk factors and implications of anaesthesia induced hypotension
No full textThis thesis studied haemodynamic perturbation in the perioperative and intensive care settings. The aims of the chapters were to: · Evaluate the implications of the use of different thresholds of hypotension in perioperative haemodynamic research. (Chapter 2) · Provide an overview of the echocardiographic changes in cardiac function due to general anaesthesia and intermittent positive pressure ventilation. (Chapter 3) · Determine the modifiable risk factors in anaesthesia induction for post-induction hypotension. (Chapter 4) · Explore whether time of day of anaesthesia induction affects the incidence of haemodynamic instability. (Chapter 5) · Compile the literature on biological sex as a risk factor of post-induction and intra-operative hypotension. (Chapter 6) · Investigate the performance of a hypotension-prediction algorithm in spontaneously breathing patients without ventilatory support in the post-operative and intensive care settings. (Chapter 7) · Chapter 9 discusses the implications of the aforementioned research and the avenues for future research that remain.</p
Brick is warmer than concrete:Aesthetic anxiety and the making of architecture in Eastern European cities
Get PDFAs numerous projects of beautifying cities make it clear, the appearance of built environments is gaining more and more relevance. How cities look concerns not only architects and inhabitants, but state officials, investors, and international organizations, all interested in making urban space as aesthetically pleasing as possible. While effects of urban beautifications have been well documented—they increase property values, crystallize a city’s ‘brand,’ and drive the displacement of marginalized populations— why ‘beauty’ is so powerful and efficient in asserting particular political projects remains underexplored. Bridging insights from cultural sociology, geography, and science and technology studies, this dissertation explains how material aesthetics of architecture come to be invested with cultural power. The study is built around two case studies, Wrocław in Poland and Klaipėda in Lithuania, and it reveals how ‘beauty’ and ‘ugliness’ of architecture were understood in both cities in the period from 1945 until today, and how these understandings are practiced nowadays when architectural professionals resolve dilemmas concerning designing, reconstructing, and maintaining buildings of various historical periods. Drawing upon archival materials, go-alongs, and more than one hundred interviews with architects, planners, state officials, and activists in both cities, the dissertation offers a comprehensive analysis of how notions of ‘beautiful’ and ‘ugly’ architecture can turn into critical terrains where meanings of the past, history, the nation, and the state acquire strong emotional resonances for individuals and are experienced as personally relevant to them