My study focused on 1) fragmented seagrass interaction with hydrodynamics and 2) fragmented seagrass interaction with nutrients. My main research questions are: i) How do heterogeneous... Show more My study focused on 1) fragmented seagrass interaction with hydrodynamics and 2) fragmented seagrass interaction with nutrients. My main research questions are: i) How do heterogeneous patches in the seagrass bed interact with the hydrodynamic force? ii) How do the different seagrass properties (density, leaf length) and gap sizes influence flow development inside the gap? iii) How is the advective porewater exchange influenced by the presence of seagrass? and iv) How do the different hydrodynamic factors (diffusion, flow, wave and flow induced by wave) influence porewater exchange from sediment to water column? The results of these studies show that in controlled environments which exclude the effects of factors other than the hydrodynamic conditions, seagrass meadows have the ability to restore and re-homogenize themselves. A wide range of other factors may also play a role in determining whether heterogeneous patches become more or less homogeneous, such as nutrient cycling from sediment into the water column or vice versa, deposition of organic matter, erosion by waves or tidal currents, or animal grazing. This PhD thesis presents findings that elucidate the fundamental processes of seagrass–hydrodynamics interactions, which impact ecological processes such as patch and gap dynamics and advective porewater exchange. Show less
Despite the increasing number of obese patients, evidence-based dosing guidelines are scarce, particularly for obese children and morbidly obese adults (BMI > 40 kg/m2). For both these... Show more Despite the increasing number of obese patients, evidence-based dosing guidelines are scarce, particularly for obese children and morbidly obese adults (BMI > 40 kg/m2). For both these populations, pharmacokinetic studies are needed to provide a basis for evidence-based dosing guidelines. In this thesis, we studied the pharmacokinetics of the CYP3A substrate midazolam, the renally excreted drug metformin and acetaminophen (metabolized by glucuronidation, sulphation and CYP2E1) in obese adolescents and/or morbidly obese adults. We address several currently unanswered questions; Can doses for obese adolescents be predicted on the basis of data obtained in morbidly obese adults? How to analyse pharmacokinetic data in obese adolescents, for whom body weight is influenced by growth, age and obesity? How to achieve safe and effective acetaminophen dosing for morbidly obese patients? The studies described in this thesis contribute to the existing gaps in knowledge regarding the pharmacokinetics and evidence-based dosing of drugs in obese adolescents and morbidly obese adults. Show less
Central to this research is the Urban Future-project, which consists of a large archive of artworks made from 2002 until now. The original question underpinning this project was: what... Show moreCentral to this research is the Urban Future-project, which consists of a large archive of artworks made from 2002 until now. The original question underpinning this project was: what influence do chaos, entropy and fragmentation have on the viability of the rapidly developing urbanizing world? In the course of the research project, the (literature and field) explorations led to the assumption that there is a demonstrable and necessary link between the quality of life in the city and vital social cohesion on the one hand and chaos, entropy and fragmentation on the other. In the artistic part of the research focuses on the question: is it possible to make the supposed connection between quality of urban life and chaos, entropy and fragmentation visible in artwork and, if so, how? In the written dissertation, working methods and strategies are contextualized and analyzed. The visual part derives from an artist's position which uses non-verbal, sensorial strategies to reach new insights. It mainly focuses on the visual and aesthetic possibilities of aspects of fragmentation, chaos and entropy because Scholten considers these aspects, as productive forces, to be the core of the experience of urbanization. Show less
When trying to understand texts, readers engage in various cognitive processes. If all goes well, the engagement in these cognitive processes during reading results in the construction of a... Show moreWhen trying to understand texts, readers engage in various cognitive processes. If all goes well, the engagement in these cognitive processes during reading results in the construction of a coherent mental representation of the text, the essence of successful reading comprehension. To construct such a representation, readers need to monitor the coherence of the text and of their emerging mental representation of what the text is about. The central aim of the empirical studies described is to examine coherence-monitoring processes across development by measuring reader’s ability to detect coherence breaks during reading of narratives. The first part of this dissertation consists of three empirical studies (chapter 2-4). The first study examined whether good and poor comprehenders at age 8-9 and 10-11 detected coherence-breaks during and/or after reading. The second study builds on the first study by examining the protracted development of coherence monitoring in an adolescent population (ages 10-22) using the same task under more challenging circumstances. The third study explored the neural correlates of coherence-break detection in young adults in an fMRI study. The second part of this dissertation consists of two conceptual chapters in which the results are summarized and discussed in a broader theoretical perspective (chapter 5-6). Show less
This is a comprehensive study of Roman literary references to Egypt without preference for one particular period, author or subject, in contrast to most previous scholarship. In doing so, it shows... Show moreThis is a comprehensive study of Roman literary references to Egypt without preference for one particular period, author or subject, in contrast to most previous scholarship. In doing so, it shows that these references vary greatly, are context-dependent, and cannot be rightly understood when interpreted only within the normative and fixated frameworks of negative perceptions of contemporary Egypt or positive perceptions of Egypt’s antiquity. Moreover, this study suggests that approaching Roman literary references from the notion of Roman self-representationis useful for understanding and explaining their multifarious and sometimes contradictory messages. This observation does not imply that every reference to Egypt is therefore ‘Roman’. On the contrary, Egypt was occasionally framed as the Other. Yet the omnipresence of Egypt in Roman literature is of major importance when the Roman identity is at stake. Egypt, then, is neither only the Other, nor only the Self, but always a polyvalent notion in terms of identity-making. Show less
The research described in this thesis focuses on the use of both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to understand cardiac lineage development and disease. To... Show moreThe research described in this thesis focuses on the use of both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) to understand cardiac lineage development and disease. To investigate the possibility of studying inherited cardiac diseases, we compared pluripotent stem cell-derived cardiomyocytes by investigating both a mouse and human model of a complex cardiac overlap syndrome caused by a mutation in the gene SCN5A. We demonstrated that both ESC- and iPSC-derived cardiomyocytes can recapitulate the characteristics of the disease. Furthermore this thesis describes a detailed protocol to differentiate human pluripotent stem cells to cardiomyocytes that was applied in the study comparing hESC- and hiPSC- derived cardiomyocytes at several time points during cardiac differentiation. We targeted fluorescent marker GFP to one allele of NKX2-5 in a human iPSC line that now matched a similar human ESC reporter line previously generated in the laboratory. This offered the opportunity to obtain cardiomyocytes and their precursors at different time points during the differentiation and determine the true degree of similarity between both pluripotent stem cell sources. Additionally the same hESC- and hiPSC-derived cardiomyocytes were compared to a unique set of foetal heart samples. Show less
The aim of the research described in this thesis entitled ‘The use of transcriptomics data in detecting non-genotoxic carcinogens’ was to develop in vitro tests to improve testing strategies for... Show moreThe aim of the research described in this thesis entitled ‘The use of transcriptomics data in detecting non-genotoxic carcinogens’ was to develop in vitro tests to improve testing strategies for cancer hazard assessment of chemicals, to reduce the use of in vivo experiments. The scope of this thesis was twofold. First, an improved in vitro approach to assess genotoxicity was developed, with the intention to reduce the number of misleading positive test results. The emphasis was on characterization of the cell system, primary hepatocytes derived from transgenic mice. Results showed that this cell system will be of added value in genotoxicity testing. In the second part of this thesis, the focus was on the development of a ‘trancriptomics’-based approach to detect modes of action of non-genotoxic carcinogens. It has been demonstrated that the described comparison approach is promising in recognizing gene expression patterns, which can be related to modes of action. In addition, the approach is also suitable to detect toxicity of chemicals in general. In conclusion, through the development of in vitro approaches, as described within this thesis, an important contribution in the improvement of testing strategies for cancer hazard assessment of chemicals has been delivered. Show less
This thesis reviews the available coral studies in the Persian Gulf at a large scale, discusses the environmental challenges for corals in the context of climate change, and expands our... Show more This thesis reviews the available coral studies in the Persian Gulf at a large scale, discusses the environmental challenges for corals in the context of climate change, and expands our knowledge of coral biodiversity and biogeography of the region, highlights the remaining gaps in our knowledge and goes on to provide recommendations for further research. This is of special importance given recent international interest in the region as a harbinger of coral adaptation to climate change as the impacts to the global environment, human society and the economy unfold. Show less
With the rapid development of electronic commerce, logistics management has become more and more important in the procedure of supply chain management. The goal of logistics management is to... Show moreWith the rapid development of electronic commerce, logistics management has become more and more important in the procedure of supply chain management. The goal of logistics management is to satisfy the demands of customers while minimizing the use of resources of the whole process in logistics management from the point of origin to the point of consumption. The logistics management technology has been widely used in the field of engineering and contributes to reducing the total logistics cost. In this thesis, we focus on algorithms based on nature-inspired paradigms to solve dynamic logistics management problems. Results show that the proposed multiple ant system algorithm and the multi-objective cooperative particle swarm algorithm are able to produce good solutions for the vehicle routing problems and inventory routing problems not only in theory but also in practice. Show less
To assess (feasibility) of adherence to treatment guidelines among outpatients with common mental disorders in a routine Dutch clinical outpatient setting for common mental disorders with clinical... Show moreTo assess (feasibility) of adherence to treatment guidelines among outpatients with common mental disorders in a routine Dutch clinical outpatient setting for common mental disorders with clinical treatment data. Also,we studied patient- and therapistfactors influencing guideline-adherence in clinical practice.We established certain characteristics that might hamper tretamnet according to guidelines and more research is needed to assess whether patient in clinical practice do benefit from guidelines. Show less
This dissertation analyzes Esmāʻil Fasih’s war novel, The Winter of 1983 (Zemestān-e 62, 1985) from a narratological standpoint to illuminate how this novel differ from other Iranian wartime novels... Show moreThis dissertation analyzes Esmāʻil Fasih’s war novel, The Winter of 1983 (Zemestān-e 62, 1985) from a narratological standpoint to illuminate how this novel differ from other Iranian wartime novels, since it explores numerous themes and perspectives on the war not explored by the war novels of this period. Whereas many wartime novels describe the active role of the working class in participating in the war, The Winter of 1983 chiefly portrays the upper class’s role, and especially their outlook on the war. In addition, Fasih’s war novel exposes the war the Iranian cities end up in ruins due to the war, an oft-neglected aspect of the war. This dissertation also considers how The Winter of 1983 might be differently categorized, as a novel with a moderate or neutral outlook on the war, the central reason being that the novel features both positive and negative aspects of the war. Show less
This thesis traces and analyses the evolution of domestic space in Maltese vernacular and ‘polite’ houses from the medieval to contemporary times. The houses under study range from humble... Show more This thesis traces and analyses the evolution of domestic space in Maltese vernacular and ‘polite’ houses from the medieval to contemporary times. The houses under study range from humble buildings of modest size, materials and design, like farmhouses or those for the less affluent town-dwellers, to buildings of grand design, like townhouses and palazzi. Owing to the complex nature of the Maltese houses a combination of enquires and a variety of sources was necessary to achieve a holistic picture. This included fieldwork in different parts of the islands, extensive research work in local archives, libraries and museums, an analysis of a sample of literary sources, national censuses and works-of-art, as well as methods of spatial analysis (Space Syntax). Show less
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to destruction of cartilage and bone. The inflammation in the joints is mainly caused by inflammatory cytokines that are... Show moreRheumatoid arthritis (RA) is a chronic inflammatory joint disease leading to destruction of cartilage and bone. The inflammation in the joints is mainly caused by inflammatory cytokines that are over-produced by various types of immune cells. Artritis is an autoimmune disease that is characterized by the presence of autoantibodies. These autoantibodies form immune complexes (IC) which are other important players in joint inflammation because they activate various immune cells by binding to Fc receptors (FcR). Binding and activation of FcRs initiates intracellular signaling that triggers activation and release of various inflammatory mediators. In this thesis we describe a variety of aspects of arthritis research that has been performed to get a better understanding of the underlying molecular and cellular disease mechanisms and to develop novel therapeutic strategies. Show less
The main aim of this thesis is to determine the role of magnetic resonance imaging (MRI) in early rheumatoid arthritis (RA). We set out to improve the MRI protocol and sequences used in arthritis... Show moreThe main aim of this thesis is to determine the role of magnetic resonance imaging (MRI) in early rheumatoid arthritis (RA). We set out to improve the MRI protocol and sequences used in arthritis patients, to detect subclinical inflammation in various patient groups and to describe the clinical implications of MRI. Chapter 1 provides a general introduction to this thesis, in chapter 2 the earliest disease stages of rheumatoid arthritis and the concept of pre-rheumatoid arthritis are further explored. In chapters 3-5 various ways are described to optimize the scanning protocol for arthritis patients. In chapters 6-8 we looked at the presence of inflammation on MRI when no inflammation can be detected at physical examination, i.e. subclinical inflammation. In chapters 9 and 10 we explore some of the clinical implications of the MRI findings. Chapter 11 provides a summary of the thesis and a discussion of the main findings. Show less
In this thesis the effectiveness of concise formats of psycho- and/or pharmacotherapy (concise care) in patients suffering from mild to moderate depressive and anxiety disorders in... Show more In this thesis the effectiveness of concise formats of psycho- and/or pharmacotherapy (concise care) in patients suffering from mild to moderate depressive and anxiety disorders in secondary mental health care is evaluated. A pragmatic randomised controlled equivalence trial was set up and carried out as part of routine clinical practice. Evidence for equivalence of concise care compared with standard care was found. Severity of illness was reduced and general health status and subdomains of quality of life improved in both conditions. Moreover, in concise care, the beneficial effects started earlier and patients were more satisfied with overall treatment than patients in standard care. No significant differences in healthcare costs between both treatments were found. In addition, patients suffering from any anxiety disorder (without comorbid depressive disorder) benefitted less from concise care than from standard care. No other clinical or demographic factors were associated with differential treatment effects. Exploring the agreement between a brief screening questionnaire (the Web Screening Questionnaire (WSQ)), and the gold standard diagnostic interview MINI-Plus, reveals that the WSQ is a good screening tool for depressive and anxiety disorders in clinical practice and it might be a further step in the economization and optimization of mental healthcare. Show less
Metastatic cancer is aggressive and rapidly developing, making it difficult to treat, often leading to mortality. Cancer cells are not isolated, but rather survive and proliferate in complex tumor...Show moreMetastatic cancer is aggressive and rapidly developing, making it difficult to treat, often leading to mortality. Cancer cells are not isolated, but rather survive and proliferate in complex tumor microenvironments. Importantly, tumor cells “educate” immune cells to play a supportive role during cancer progression. Therefore, understanding how cancer cells and immune cells communicate is of pivotal importance to limit tumor progression. In this project, we identified the chemokine receptor CXCR4 and its correspondent ligand, CXCL12, as a key couple that regulate the interaction between tumor cells and immune cells. The research has been performed using the zebrafish xenograft model. This model offers the advantage of looking at tumor-immune cell interaction on a single cell level and in a living whole organism. The transparency of the embryo and the current genetic tools available, in combination with the ease in pharmacological approaches, make this model an excellent tool to determine and impair cancer-microenvironment inter-communication. We showed that inhibiting the CXCL12-CXCR4 axis either on the tumor side or on the immune cell side leads to impaired tumor progression, during the early phases of metastasis formation. We propose that blocking cancer-stroma communication represents a promising therapeutic strategy to fight cancer.Show less
Trauma is a global problem, and carries a high price that is paid by individuals, communities, and nations. Road traffic accidents, industrial injuries, farming accidents and interpersonal... Show moreTrauma is a global problem, and carries a high price that is paid by individuals, communities, and nations. Road traffic accidents, industrial injuries, farming accidents and interpersonal violence account for traumatic injuries with varying prevalences throughout the world. Globally the liver is the most frequent injured intra-abdominal organ following trauma. Selection of patients with liver injuries for nonoperative management, definitive surgical repair or a damage control laparotomy is the topic of ongoing debates. The surgeon, who encounters a severely injured patient with a liver injury, will rapidly need to make several critical decisions. Nonoperative Management of hemodynamically stable patients following blunt and penetrating hepatic trauma is safe in adequately selected patients. Use of damage control techniques is recommended in patients with a major hepatic bleeding or in patients with a minor liver injury with associated vascular injury and before the onset of metabolic failure. As a result of improved survival following severe hepatic parenchymal damage an increase in intrahepatic vascular and biliary complications has become evident. Many of these complications can be prevented by surgical ligation if a laparotomy is warranted, or can be managed by less invasive, percutaneous techniques in the acute (vascular) or secondary (biliary) stage. Show less
Cardiovascular diseases are the leading cause of mortality and morbidity in the current era. Current guidelines base their recommendations for diagnosis and management of cardiovascular diseases on... Show moreCardiovascular diseases are the leading cause of mortality and morbidity in the current era. Current guidelines base their recommendations for diagnosis and management of cardiovascular diseases on several important parameters such as left ventricular (LV) dimension and function, presence of coronary artery disease (CAD) and valve function. Accurate assessment of these parameters is therefore essential for patients with or at risk of cardiovascular diseases and requires the use of invasive and non-invasive testing. Non-invasive testings are in principle preferable, especially for a first-line approach, being safer and generally widely available and easy to perform. The present thesis highlights the use of non-invasive imaging modalities, namely cardiac computed tomography and advanced echocardiography analysis (speckle tracking and calibrated integrated backscatter) to diagnosis and guide the treatment of various cardiovascular diseases. Show less
The rise of ISIS and the recent terrorist attacks in Europe have raised a collective alertness for a potential terrorist attack. The presence of jihadist networks in the Netherlands, and the... Show moreThe rise of ISIS and the recent terrorist attacks in Europe have raised a collective alertness for a potential terrorist attack. The presence of jihadist networks in the Netherlands, and the significant outflow of young people to conflict areas in the Middle East to join the jihad, have greatly enhanced this anxiety. But how are these networks organized and how do they prepare their jihad? How do people get involved in jihadist networks and how important is ideology in that regard? Answering such questions will help to understand how jihadist networks operate, which can be useful knowledge for policy makers and practitioners who aim to counter terrorist threats. Using unique data from police files, interviews, and trial observations, while utilizing different analytical methods, this study provides an in-depth insight into the modus operandi of jihadist networks in the Netherlands. The findings show how jihadist networks have changed over the years and how this development has affected the way jihadists operate. Show less
Aim of this thesis was to evaluate contemporary care and prognosis for patients with acute coronary syndrome and identify pitfalls in its treatment. Complications after coronary stent implantation... Show moreAim of this thesis was to evaluate contemporary care and prognosis for patients with acute coronary syndrome and identify pitfalls in its treatment. Complications after coronary stent implantation were explored and demonstrated that in sirolimus-eluting stents, the benefit of reduced repeat revascularization during one year after primary PCI was not sustained during long-term follow-up. Additionally, an increased risk of very late stent thrombosis was suggested. Late stent malapposition, more commonly observed after this stent type and suspected to be involved in the multifactorial etiology of stent thrombosis, is shown to persist in the greater portion of STEMI patients during long-term follow-up, depending on the degree of vessel wall remodelling and change in plaque burden. Women were identified as a sub-population with poorer prognosis early after STEMI. Identification of high-risk patients, and estimation of infarct size and prognosis, which a single measurement of troponin already may indicate, facilitates individualized treatment and likely results in better outcomes. Although numerous novel treatment modalities emerged in recent years, certain pitfalls become increasingly important. Major bleeding is one of them, responsible for an excess mortality amongst STEMI patients after primary PCI, and should be incorporated in risk stratification models for the choice of treatment strategy. Show less
