The central inquiry of this thesis revolves around how ontology can adequately accommodate the existence of necessary physical relations. Initially, the thesis demonstrates the imperative... Show moreThe central inquiry of this thesis revolves around how ontology can adequately accommodate the existence of necessary physical relations. Initially, the thesis demonstrates the imperative acknowledgment of necessary physical relations by showcasing the failure of Neo-Humean theories. Subsequently, it embarks on an investigation of the foundational explanation of physical necessity. This investigation scrutinizes two distinct accounts of necessary physical relations: dispositionalism and ontological structural realism (OSR), typically perceived as contrasting approaches to elucidating physical necessity. The thesis contends that the individuation regress inherent in dispositionalism compels its alignment with OSR. It then identifies a deficiency within the current OSR framework concerning the elucidation of the relationship between mathematical and physical necessity, attributing this shortfall to OSR's lack of ontological discussion regarding the nature of relations and structures. In response, this thesis endeavors to construct an ontological framework based on the relation of coexistence. This framework is demonstrated to encompass isomorphic counterparts of all mathematical structures within any mathematical reductionist program, as well as the isomorphic counterparts of all physical structures derived from these mathematical foundations. Such a framework facilitates the differentiation between mathematical and physical structures, thereby elucidating the distinction between mathematical and physical necessity. Show less
This dissertation examines the educational positions of children of immigrants in the Netherlands from 1980 to 2020. In particular, the influence of migration background and socioeconomic factors... Show moreThis dissertation examines the educational positions of children of immigrants in the Netherlands from 1980 to 2020. In particular, the influence of migration background and socioeconomic factors on educational positions is studied. Findings reveal substantial progress in education for migrant children overall, especially among the second generation, younger cohorts, and girls with a migrant background, indicating promising upward mobility within the education system for many of these children. The family environment impacts educational outcomes, with socioeconomic background playing a crucial role. Higher parental incomes correlate with higher education levels for children in both the short and long term. Additionally, the living environment affects outcomes such as school dropout rates, especially among boys from migrant backgrounds in larger cities. They are more prone to leaving education prematurely than their female or non-migrant peers. Despite institutional barriers and discrimination within the education system, these children demonstrate an upward trend in education, highlighting the need for further research incorporating discrimination as a factor. Show less
This thesis focuses on the clinical outcomes after Descemet membrane endothelial keratoplasty (DMEK). Chapter 2 describes the suitability of septic donor corneas for transplantation and the... Show moreThis thesis focuses on the clinical outcomes after Descemet membrane endothelial keratoplasty (DMEK). Chapter 2 describes the suitability of septic donor corneas for transplantation and the clinical outcomes after DMEK using septic versus non-septic donor corneas. Chapter 3 aims to analyze the incidence of cataract extraction in eyes that previously underwent DMEK surgery and the effect of the phacoemulsification procedure on the endothelial cell density (ECD) after DMEK. Chapter 4 of the thesis concentrates on the 6-month ECD after DMEK, as it is one of the benchmark parameters for graft performance. In this chapter, the relation between the ECD 6 months after DMEK and its predictive value for 5-year graft survival in FECD eyes are discussed. Chapter 5 evaluates the 10-year graft survival and clinical outcome results of the first 100 eyes that received DMEK. Chapter 6 presents a larger case series of DMEK eyes where the 10-year clinical outcomes and graft survival after DMEK are analyzed based on the surgical indication of the eye and the preoperative severityof FECD. Show less
Mucosal melanomas (MM) are malignant tumours arising from melanocytes located at the mucosal lining of the head and neck region or the respiratory, gastrointestinal, anorectal, or genital tract.... Show moreMucosal melanomas (MM) are malignant tumours arising from melanocytes located at the mucosal lining of the head and neck region or the respiratory, gastrointestinal, anorectal, or genital tract. Due to the low incidence the disease is still poorly understood and management is mostly based on guidelines of cutaneous melanoma (CM). Survival of patients with MM is poor and regardless of stage is worse than that of CM. This is explained by the advanced stage at diagnosis and high recurrence rates of MM. Moreover, whilst immunotherapeutic agents have revolutionized the therapeutic landscape in CM, in MM, the efficacy is low and survival has not improved since the introduction of these therapies.The MM located at the vulva (VMM) account for 60% of the female genital tract MM and together with the head and neck region are the most common locations of MM. In line with the MM located at all other locations, prognosis is poor. Whilst the majority of the patients is diagnosed with local disease, the aggressive course of disease is demonstrated by the high recurrence rates with short time to recurrence with a median overall survival of 33 months. To improve outcomes in MM, there is a critical need for clinical trials specifically designed for this disease and international collaboration. Show less
This thesis starts with a literature review on the observation of aggression, then describes the development and implementation of an Observation Checklist in 2 Dutch Juvenile Justice Institutions ... Show moreThis thesis starts with a literature review on the observation of aggression, then describes the development and implementation of an Observation Checklist in 2 Dutch Juvenile Justice Institutions (JJI) and concludes with two papers researching the added value of data harvested with this tool, both for risk assessment and cultural sensitive assessment. Show less
The growing number of older patients presenting to Emergency Departments (EDs) requires better risk stratification to guide treatment and dispositiondecisions. Therefore, it is essential to... Show moreThe growing number of older patients presenting to Emergency Departments (EDs) requires better risk stratification to guide treatment and dispositiondecisions. Therefore, it is essential to understand the effect of age on the associations between physiological variables and outcomes. More importantly, most risk tools are not age or sex adjusted and are not based on a statistical approach. An age and sex adjusted risk tool could improve risk stratification in the ED.This thesis is divided into three parts and has four aims, regarding ageadjusted interpretation of physiological variables for risk stratification in ED patients, developing a new age- and sex-adjusted risk tool for the hospital, and describing potential bias if risk tools are used for comparing the quality of care among departments. Show less
There is an increasing number of adults who suffer from cardiovascular diseases (CVD). These patients would benefit from a healthy lifestyle, as this improves the prognosis of CVD. However, even... Show moreThere is an increasing number of adults who suffer from cardiovascular diseases (CVD). These patients would benefit from a healthy lifestyle, as this improves the prognosis of CVD. However, even though improving one’s health and lifestyle is the focus of cardiac rehabilitation, CVD patients need support to also maintain a healthy lifestyle after their rehabilitation has ended. Even though the support of a healthcare professional seems to be an important factor in successful lifestyle change, there are barriers that hinder professionals from providing lifestyle support, such as a lack of time or expertise. Since the involvement of healthcare professionals is also not always possible or desirable, it is important to further investigate possibilities to provide patients with a self-help eHealth intervention. In such self-help eHealth interventions, feedback is automatically provided, making the interference of a healthcare professional no longer needed. However, self-help eHealth interventions can suffer from a low uptake and a low level of adherence. This PhD dissertation therefore focuses on (1) mapping out the needs and wishes of both healthcare professionals and CVD patients with regard to (human-supported and self-help) eHealth lifestyle interventions, and (2) investigating if and how self-help eHealth lifestyle interventions could be optimised. Show less
Molecular materials have been a subject of interest in fundamental research and applications for decades, and have been studied as bulk crystals, (thin) films and as individual molecules, due to... Show moreMolecular materials have been a subject of interest in fundamental research and applications for decades, and have been studied as bulk crystals, (thin) films and as individual molecules, due to the large variety in their properties. This dissertation explores pentacene crystals near the two-dimensional limit, i.e. in films of one to a few monolayers, primarily using an experimental technique called Low Energy Electron Microscopy (LEEM). We utilize the interaction of low-energy electrons with the molecular layers to learn about the properties of the layers, and also employ low-energy electrons as an external stimulus to create controlled changes in the properties of the sample. We study the real-time dynamics of growth of pentacene layers on various substrates. We study beam irradiation damage to molecular layers due to exposure to low-energy electrons, with implications for technological processes such as electron-beam lithography. We study photoemission and secondary electron emission from the molecular layers and highlight the critical role of unoccupied electronic band structure above the vacuum level in these processes. Finally, we present the design of, as well as the first scientific measurements in, a cryogenic sample chamber for LEEM that enables novel experiments addressing questions in surface science and condensed matter physics. Show less
Cognitive processes play an important role in human mate choice. However, far less is known about this topic in non-human animals. In this thesis, I take a comparative approach to sexually... Show moreCognitive processes play an important role in human mate choice. However, far less is known about this topic in non-human animals. In this thesis, I take a comparative approach to sexually selective cognition by studying humans (Homo sapiens) and Bornean orang-utans (Pongo pygmaeus). I start by reviewing the literature on sexually selective cognition. Hereafter, I show that visual, but not auditory or olfactory attractiveness, plays a major role in initial human mate choice. Furthermore, I show that attractiveness has a profound influence on visual attention in humans, and that attentional biases towards attractive conspecifics may be associated with mate choice. I explore the same topic in Bornean orang-utans by presenting them with stimuli of fully developed males or males experiencing arrested development. The results of these studies suggest that orang-utans preferentially attend to fully developed males, but only in the eye-tracking task and not in touchscreen tasks. The last chapter explores vocalisations, and suggests that orang-utan mate preferences might reflect in female vocal behaviour. Altogether, the results of this thesis suggest that humans and orang-utans show cognitive biases towards mate-relevant traits. However, better understanding of the link between such biases and actual mate choice remains of pivotal importance. Show less
Adverse drug reactions on sexual functioning (sADRs) may seriously decrease a person's quality of life. This topic is barely discussed in healthcare practice, partly because of little knowledge... Show moreAdverse drug reactions on sexual functioning (sADRs) may seriously decrease a person's quality of life. This topic is barely discussed in healthcare practice, partly because of little knowledge about the association between drugs and sexual function. Research in this thesis supplements this knowledge with quantitative methods, identifying drugs associated with sADRs and taking the first steps in characterizing the population with these drugs in use. In the second part of the thesis, qualitative methods were used to describe the current practice and the potential role of healthcare providers regarding sADRs in primary care, especially in the community pharmacy. With the acquired knowledge, materials have been developed for primary healthcare providers to discuss and agree on local policy about sADRs in their own region. Initial experiences with these materials showed greater awareness of the subject among the healthcare providers concerned. Show less
This thesis contributes to the evidence-base of the influence of patient factors, surgical approach and implant design on outcomes after total hip replacement (THA).A systematic review (SR) shows... Show moreThis thesis contributes to the evidence-base of the influence of patient factors, surgical approach and implant design on outcomes after total hip replacement (THA).A systematic review (SR) shows that there is strong evidence for BMI, age, comorbidity, preoperative functioning and mental health as predictors of physical functioning. A predictive model based on data from this thesis emphasizes preoperative functioning, mental health and pain as predictors.To treat hip fractures, the posterolateral (PLA) and direct lateral surgical approach (DLA) are the most commonly used. The PLA may cause more dislocations, but seems to result in less walking problems and abductor insufficiency than the DLA. All investigated surgical approaches for primary THA resulted in a significant improvement in patient reported outcome measures (PROMs). The anterior and posterolateral approaches provided greater improvement in physical function and pain, but clinical differences were small.A multicenter randomized trial comparing two hip stems is described. No significant difference has been demonstrated between the Collum Femoris Preserving (CFP) and Zweymüller stem in physical function at 5 years or implant survival at 12 years, although CFP may be inferior in cup revisions. A SR suggests lower dislocation rates and revisions for dual mobility cups in THA, but high quality evidence is lacking. Therefore, we designed an RCT comparing dual mobility cups with unipolar cups in older patients.In addition to providing insights into the influence of patient, surgical and implant characteristics on outcome after (total) hip arthroplasty, this thesis provides suggestions for the design of future clinical trials. Show less
The Base Erosion and Profit Shifting (BEPS) Project was initiated by the Organization for Economic Co-operation and Development and G20 in 2013 to address tax avoidance schemes used by... Show moreThe Base Erosion and Profit Shifting (BEPS) Project was initiated by the Organization for Economic Co-operation and Development and G20 in 2013 to address tax avoidance schemes used by multinational enterprises (MNEs). Drawing on interviews with a range of tax policy stakeholders, this book analyses the BEPS Project’s impact on developing countries’ approaches to combatting international tax avoidance, developing novel typologies to categorize policies and conducting case studies in Colombia, India, Nigeria, and Senegal. Contrary to public communication surrounding it, the BEPS Project does not endorse any kind of approach against tax avoidance, but puts an emphasis on finely delineating responses rather than blunt measures to tackle the problem. However, blunter approaches have been used more often by developing countries due to limited administrative resources. Examining countries’ responses, this research uncovers that the BEPS Project has influenced approaches to transfer pricing, albeit with delays and varied enforcement. The study also reveals discrepancies in addressing treaty shopping, showcasing measures beyond BEPS recommendations that countries adopt when revenue losses are high. The findings further show that the interplay between different governmental departments is pivotal in shaping policy responses to tax avoidance. Show less
The aim of this thesis is to develop noise robust electrical properties tomography (EPT) reconstruction methods that are free from tissue transition artifacts to support clinical applications for... Show moreThe aim of this thesis is to develop noise robust electrical properties tomography (EPT) reconstruction methods that are free from tissue transition artifacts to support clinical applications for complex tissue structures such as the brain. In particular the contrast-source inversion approach is pursued. This focus of this thesis is on the reconstruction of the electrical properties from the transmit field of radiofrequency coils most frequently available in magnetic resonance imaging. Show less
Parental socialization refers to the process through which parents transmit values and beliefs to their children. During this process, children learn to understand the world and shape their social... Show moreParental socialization refers to the process through which parents transmit values and beliefs to their children. During this process, children learn to understand the world and shape their social functioning. The impact of parental socialization can vary across different cultures. My research focuses on family interactions within Chinese cultures, emphasizing the importance of cultural nuances when examining the role of parental behaviors in children's social development. The study utilized samples of Chinese children and their parents, employing various research methods, including observations, interviews, and questionnaires. The findings indicated that Chinese mothers' psychological control had a relatively minor negative effect on children's emotion regulation and social anxiety. Additionally, the research revealed racism and colorism among Chinese children, which were associated with mothers' color-evasive socialization behaviors. Chinese mothers did not avoid talking about racial appearance and cultural background, which contrasts with studies in White Western populations where most White mothers showed color evasion. Chinese mothers’ acknowledgement of shared culture predicted children’s positive attitudes towards their own racial ingroup with a darker skin tone. My research underscores the unique features of Chinese culture that play a pivotal role in shaping the nature and consequences of parental socialization on children's social functioning. It highlights that Western theories related to parenting and color-evasive socialization may need adaptation when applied to non-Western cultural contexts. Show less
This research concerns the role of metabolic sensor AMPK, which is activated during low energy levels, and known to suppress the activation of some immune cells. I studied how AMPK regulates the... Show moreThis research concerns the role of metabolic sensor AMPK, which is activated during low energy levels, and known to suppress the activation of some immune cells. I studied how AMPK regulates the function of dendritic cells (DCs), immune cells that are key regulators of the adaptive immune response. Key findings include that drug-induced AMPK activation in DCs results in metabolic rewiring that leads to immunosuppressive DCs. Furthermore, we show that the AMPK signaling axis in DCs is important for protection against obesity-induced inflammation, while AMPK in DCs inhibits the anti-tumor immune response and thereby promoting tumor growth. Therefore, AMPK activation in DCs may be a promising strategy for the generation of therapeutic tolerogenic DCs, while AMPK inhibition may be beneficial for DC-based cancer therapies. Together, these findings contribute to a better understanding of AMPK as regulator of immunity and tolerance in dendritic cells. Show less
The thesis assess the robustness of 4D flow MRI for analyzing aortic hemodynamics and valvular flow, as well as exploring the clinical potential of this technique in patients with aortic and... Show moreThe thesis assess the robustness of 4D flow MRI for analyzing aortic hemodynamics and valvular flow, as well as exploring the clinical potential of this technique in patients with aortic and valvular disease. The first part of the thesis evaluates the reproducibility of segmenting the aortic lumen and calculating various hemodynamic parameters, demonstrating that these processes can be performed accurately and consistently. The second part examines the natural course of aortic hemodynamics during aging, concluding that hemodynamic parameters remain relatively stable. Furthermore, different hemodynamic phenotypes are identified in patients with aortic root and ascending aortic dilatation, possibly explaining the presence of dilatation. Show less
Cancer immunotherapy has experienced remarkable advances in the last decades. Striking clinical responses have been achieved for several solid cancers, particularly cancer types with a high... Show moreCancer immunotherapy has experienced remarkable advances in the last decades. Striking clinical responses have been achieved for several solid cancers, particularly cancer types with a high mutation burden, which placed tumour-mutated antigens (neoantigens) centre stage as targets of tumour immunity and cancer immunotherapy. Neoantigens can be presented in complex with HLA molecules on the tumour cell surface, where T cells with the correct specificity can recognize the neoantigen as ‘non-self’ which will trigger killing of the tumour cell by the T cell. In theory, cancers with a low/moderate mutation burden that present neoantigens in complex with HLA class molecules could still be eligible for T cell-mediated immunotherapy. This thesis, describes the finding that neoantigen-specific T cells are present in mismatch-repair proficient (MMR-p) colorectal cancer patients, a low mutation burden cancer type. Moreover, CD39 and CD103 were found as cell surface markers that pinpoint the T cell population that contains the neoantigen-specific T cells. In addition, subsequent metastasis of a melanoma patient cohort were studied and revealed that also at advanced, late-stage disease, neoantigen-directed T cell therapy is, in theory, still applicable. Taken together, the studies reveal potential for the development of neoantigen-directed cancer immunotherapy for a broader patient population. Show less
The endothelium is a crucial component of the vascular system, and its proper function is vital for microcirculatory function and by extension cardiovascular health. Hence, endothelial dysfunction... Show moreThe endothelium is a crucial component of the vascular system, and its proper function is vital for microcirculatory function and by extension cardiovascular health. Hence, endothelial dysfunction is involved in a majority of cardiovascular disease and poses a high societal burden. Endothelial nitric oxide bioavailability is essential for a healthy microcirculation. The first half of this thesis investigates the reliability of imaging techniques that non-invasively assess the microcirculation and nitric oxide bioavailability, including laser speckle contrast imaging, Doppler flowmetry, dark field microscopy, skin fluorescence imaging and near infrared spectroscopy. In addition, the vascular effects of a mixed meal and a far-infrared light emitting patch, as measured with the imaging methods, are assessed. Finally, differences in microcirculatory function in people with mitochondrial disorders and healthy volunteers are explored. In the second half of the thesis, first-in-human and proof-of-mechanism studies with a soluble guanylyl cyclase stimulator and a phosphodiesterase inhibitor are described, drugs thought to enact some of their effects through modulation of vascular function downstream of nitric oxide. The thesis concludes with a critical appraisal of the investigated imaging modalities and their potential for inclusion in future clinical trials with drugs aiming to affect the microcirculation. Show less
In the current global context, there is a pressing need to address sustainable energy supplies to safeguard our Planet and its ecosystems. The choices made by human society have a significant... Show moreIn the current global context, there is a pressing need to address sustainable energy supplies to safeguard our Planet and its ecosystems. The choices made by human society have a significant impact on genetic evolution and climate. To ensure a better future for all, it is crucial to exercise foresight, foster collaboration across various sectors, and reach agreements based on fair and ethical principles. Science plays a pivotal role in advancing energy conversion, offering the potential for significant scientific breakthroughs that contribute to the protection and respect of our World. Specifically, the development of solar-to-fuel devices holds promise for achieving this transition to green energy. This Ph.D. dissertation centers on the development and functionalization of 2D membranes and materials, which constitute integral components of these conversion devices. The optimization of functionalized 2D materials necessitates a comprehensive computational design approach. This involves the adoption of a multiscale computational framework for the thorough design of these materials and the precise prediction and understanding of molecular processes, encompassing molecular self-assembly, ion transport, and catalytic surface reactions. Show less
