Aspirine wordt door miljoenen mensen wereldwijd gebruikt ter preventie van hart- en vaatziekten. De meeste mensen nemen aspirine 's ochtends in, maar het optimale inname tijdstip is niet bekend. In... Show moreAspirine wordt door miljoenen mensen wereldwijd gebruikt ter preventie van hart- en vaatziekten. De meeste mensen nemen aspirine 's ochtends in, maar het optimale inname tijdstip is niet bekend. In dit proefschrift is onderzocht voordelig is om aspirine 's avonds in te nemen in plaats van 's ochtends. Kort samengevat was het idee hierachter als volgt. Bloeddruk is een belangrijke risicofactor voor hart- en vaatziekten; eerder onderzoek suggereerde dat de bloeddruk kan worden verlaagd door aspirine 's avonds in te nemen in plaats van 's ochtends. Dit was echter nog nooit onderzocht bij pati_nten die al aspirine gebruiken. Bij 290 pati_nten die aspirine gebruikten werd onderzocht of avond aspirine de bloeddruk verlaagt. Dit bleek niet het geval. Verder is bekend dat hart- en vaatziekten vaker 's ochtends voorkomen. Een van de oorzaken is een verhoogde activiteit van bloedplaatjes tijdens de ochtenduren, waardoor het risico op een bloedstolsel (met een hart- of herseninfarct tot gevolg) hoger is tijdens de ochtenduren. Onderzocht werd of de bloedplaatjes activiteit tijdens de ochtenduren beter geremd kan worden door aspirine 's avonds in te nemen in plaats van 's ochtends. Dit bleek inderdaad zo te zijn. Dit is mogelijk voordelig voor alle pati_nten die aspirine gebruiken Show less
In this thesis, we perform fundamental spectroscopic studies of organic fluorescent chromophores (dyes) for temperatures from 1-10 Kelvins. We use confocal and wide-field fluorescence microscopy... Show moreIn this thesis, we perform fundamental spectroscopic studies of organic fluorescent chromophores (dyes) for temperatures from 1-10 Kelvins. We use confocal and wide-field fluorescence microscopy techniques. We analyzed the spectroscopic properties of well-known dyes, such as perylene, terrylene and dibenzoterrylene embedded in different solids. By doing this systematically, we correlate the presence of methyl groups in the host-crystal (Chapter 2) with the strong spectral diffusion of the resonant line, which lead to spectral broadening and frequency instabilities of the guest DBT. In contrast, the absence or substitution of methyl groups by chloride showed any of these effects. We found that the fluorescent properties of perylene in ortho-dichlorobenzene and terrylene in para-dichlorobenzene solids were those expected for the single quantum system. No reports of lifetime-limited excitation lines for perylene were ever reported till now. Even further, we report the coupling of an acoustic wave created by a macroscopic object to the optical response of a single molecule. The shot-noise limited sensitivity from the response of the single molecule to the displacement of the fork's prongs was found to be in the sub-nanometer regime. Perylene in o-DCB will be used to perform the single molecule all-optical transistor proposed in the introduction. Show less
To commemorate the Dutch Revolt people from both the Northern and Southern Netherlands commissioned, kept, and collected a large variety of objects. From paintings to clay pipes, from hearth plates... Show moreTo commemorate the Dutch Revolt people from both the Northern and Southern Netherlands commissioned, kept, and collected a large variety of objects. From paintings to clay pipes, from hearth plates to gable stones, from clothing to cannonballs; all these objects were used to either remember of forget the war in the late sixteenth and seventeenth century. Especially on an urban level many of these material memories survive. They are part of an urban memory landscape, a set of shared memories which survived on several levels of the urban community and involved multiple stakeholders such as the magistrate, the church, corporations, and individual citizens. Within the urban community these stakeholders used diverse objects to promulgate a certain message about the Revolt. Subsequently this could become part of a city's urban identity and civic representation. Whether in the Dutch Republic or in the Habsburg Netherlands cities were well aware of their options either to include, exclude or reinterpret stories about the past. Material memories of the Dutch Revolt were therefore continuously and carefully (re)selected and used to reflect on what the urban community had gone through during eighty years of war Show less
Approximately 2.5% of the electorate in the Netherlands is member of a political party. This modestly sized group plays an important role in representative democracies: members are part of the... Show moreApproximately 2.5% of the electorate in the Netherlands is member of a political party. This modestly sized group plays an important role in representative democracies: members are part of the electorate and of their party and function as intermediaries between voters and elected officials. There is, however, debate as to the role of party members. The impression exists that members of the same party are internally divided over important political issues, that it is largely impossible to distinguish between members of different parties substantively, and that members differ in terms of views and backgrounds, and thereby drive a wedge between voters and elected officials. Based on the Leyden Party Member Survey, this study investigates how internally cohesive, externally different and representative in terms of membership Dutch parties are. This study's findings suggest, at least for the Netherlands, that the view that party members are obstacles is factually incorrect. In general, party members are internally quite cohesive and adopt a shared, substantive position that differentiates from the position of members of other parties. Although their demographic profile deviates, members' substantive views are congruent with those of the voters and MPs of their party. Show less
Euthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding... Show moreEuthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding physician-patient relationship. Secondly a thorough knowlegde of the requirements of due care is necessary, for patients as well as for physicians. Physicians and patients should both be educated upon the possibilites provided in the law. Show less
To prevent a large software system from collapsing under its own complexity, its code needs to be well-structured. Ideally we want all code related to a certain feature to be grouped together _... Show moreTo prevent a large software system from collapsing under its own complexity, its code needs to be well-structured. Ideally we want all code related to a certain feature to be grouped together __called feature modularization__ and code belonging to different features not to mix __ called separation of concerns. But many concerns are known as 'cross-cutting concerns'. By their very nature their implementation needs to be spread around the code base. The software engineering discipline that has the most to gain from those properties is Software Product Line Engineering. It is concerned with the development and maintenance of multiple software systems at the same time, each possessing a different (but often overlapping) set of features. This gives rise to an additional need: The code for a given feature must not only be separated and modular; it also needs to be composable and able to deal gracefully with the presence or absence of other features. This thesis presents Abstract Delta Modeling, a formal framework developed to achieve these goals in software. The thesis is a product of the European HATS project. It formalizes the techniques of delta modeling, the main approach to variability used by HATS Show less
This thesis is an exploration of the subject of historical record linkage. The general goal of historical record linkage is to discover relations between historical entities in a database, for any... Show moreThis thesis is an exploration of the subject of historical record linkage. The general goal of historical record linkage is to discover relations between historical entities in a database, for any specific definition of relation, entity and database. Although this task originates from historical research, multiple disciplines are involved. Increasing volumes of data necessitate the use of automated or semi-automated linkage procedures, which is in the domain of computer science. Linkage methodologies depend heavily on the nature of the data itself, often requiring analysis based on onomastics (i.e., the study of person names) or general linguistics. To understand the dynamics of natural language one could be tempted to look at the source of language, i.e., humans, either on the individual cognitive level or as group behaviour. This further increases the multidisciplinarity of the subject by including cognitive psychology. Every discipline addresses a subset of problem aspects, all of which can contribute either to practical solutions for linkage problems or to further insights into the subject matter. Show less
The work presented in this thesis is an investigation of the immune responses induced by chronic schistosomiasis in Gabonese schoolchildren. By investigating concurrently various aspects of the... Show moreThe work presented in this thesis is an investigation of the immune responses induced by chronic schistosomiasis in Gabonese schoolchildren. By investigating concurrently various aspects of the immune response, including innate, adaptive and regulatory responses, we are able to gain a more in-depth understanding of the dynamic changes brought about by infection. Through a number of cross-sectional and longitudinal studies we show that S. haematobium infection induces increased frequencies of regulatory B (Breg) and T (Treg) cell subsets which are associated with increased levels of IL-10 and adaptive immune hypo-responsiveness. Anti-schistosome treatment results in the reduction of regulatory subsets, an increase in effector T cells and alleviation of suppressed antigen immune responses. By showing that Treg cells are linked to effector responses and that schistosomes can induce Breg cells, the scene is set for future studies to determine antigen specificity of these cells as well as ways to control their activity. As regulatory responses have been shown to be not only important in chronic infectious disease, but also in chronic inflammatory diseases the knowledge gained here may be of substantial value to the health of those living in both low- to middle-income countries as well as high-income countries. Show less
Over the last 20 years large efforts have been made in developing and optimising modelling techniques for DoE usage in engine calibration. A prerequisite for optimally applying DoE test designs... Show moreOver the last 20 years large efforts have been made in developing and optimising modelling techniques for DoE usage in engine calibration. A prerequisite for optimally applying DoE test designs is the detailed knowledge of the engine’s operating boundaries enclosing the ‘design space’. Known boundaries can be implemented in the DoE test plan such that no test points are planned in a region where the engine cannot or should not be operated. Four mathematical approaches have been analysed and compared on the problem statement ‘Which design space description method is most suitable for combustion engine calibration test applications?’: - Convex hull method (CH) - Prediction error variance (PEV) - Support vector machine (SVM) - Support vector machine with a leave-one-out optimisation (SVM-LOO) It can be concluded that the two SVM-based methods are the most suitable methods to describe a boundary. The quality of the assessment will be the primary selection criterion and therefore the SVM-LOO shows the most potential. Since the initial application of a design space description method will be offline, a longer boundary training time and new test point allocation time, e.g., required for the SVM and SVM-LOO methods, are acceptable for the current calibration problems. Show less
Recent studies indicate that there is a global rise in the prevalence of asthma and other allergic disorders. Several epidemiological studies conducted in countries endemic for parasitic worms ... Show moreRecent studies indicate that there is a global rise in the prevalence of asthma and other allergic disorders. Several epidemiological studies conducted in countries endemic for parasitic worms (helminths) have reported an inverse association between the presence of helminth infections and allergic disease. The main objectives of the study described in this thesis were to: i. To determine urban-rural differences in allergy outcomes in Ghana, West Africa ii. To examine the association between helminth infections and allergies iii. To characterize IgE responses associated with helminth infections and allergies The thesis describes cross-sectional studies among schoolchildren aged 5-16 years living in urban and rural areas of Southern Ghana. Study findings showed marked urban-rural differences in the prevalence of allergy outcomes with current infection with the waterborne helminth schistosoma being inversely associated with mite skin prick test allergic sensitization. In the study population, elevated levels of allergen specific IgE were observed that did not translate into skin reactivity or reported symptoms. Differences in gene expression profiles were also observed between urban and rural children. Overall, study findings indicate that factors associated with urbanization such as reduced exposure to parasitic worms are associated with the increased prevalence of allergy outcomes in Ghanaian children Show less
Demographic changes will result in a tidal wave of hip fractures in the growing group of frail octo- and nonagenarian citizens. These osteoporotic fractures are a major burden to the patients__... Show moreDemographic changes will result in a tidal wave of hip fractures in the growing group of frail octo- and nonagenarian citizens. These osteoporotic fractures are a major burden to the patients__ quality of life. Despite all preventive measures, predominantly focusing on osteoporosis medication, the total number of second, contralateral hip fractures has not declined over the past decades. Complications and institutionalization after surgery of these second hip fractures are increased and can be held responsible for a decrease in quality of life for these patients and high healthcare costs. In this thesis Elastomer femoroplasty (EF) is introduced as a new modality in the prevention of hip fracture surgey We found that in, in-vitro, cadaver, biomechanical experiments, EF prevents dislocation after fracture and after fracture-loading compared to untreated control femurs. These preventively treated hip fractures can be cyclically loaded with forces that well exceed the loads during normal gait. Elastomer Femoroplasty is a feasible and a readily available, minimal invasive technique to prevent second hip fracture surgery. It can be applied during ipsilateral hip fracture surgery and does not need a separate operation or anesthesia. Furermore, due to the nature of this surgical intervention, patient compliance after EF is 100%. Show less
Three Christian films have become popular in the Commune of Cobly of today's Republic of Benin, notably the American "Jesus Film" (1979), the American-Ivorian film "La Solution" (1994) and the... Show moreThree Christian films have become popular in the Commune of Cobly of today's Republic of Benin, notably the American "Jesus Film" (1979), the American-Ivorian film "La Solution" (1994) and the Beninese video film "Yatin: Lieu de souffrance" (2002). The discussion centres on how people receive and understand these films together with the digital video technology that facilitate their recent success. Christian films are so important in this part of Benin that the question needs to be raised whether Christianity is shifting from a religion of the book towards a religion of film. The theoretical starting point is semiotics, a theory that has been foundational not only for film, media and media reception studies, but more recently also for the study of materiality. This thesis' main theoretical contribution is a critique of semiotics, arguing that this theory, which has been foundational to Western science, is in fact too limiting. Semiotics, even in its Peircean orientation, cannot sufficiently explain how people in the Commune of Cobly understand shrines, film and media more generally, both through their material manifestations and interactively in terms of communication. Instead, a process called "presencing", which goes beyond semiotics, can explain better people's understanding of shrines and media. Show less
Allogeneic stem cell transplantation is a potentially curative treatment for many hematological malignancies. The beneficial Graft-versus-Leukemia (GvL) effect is thereby mediated by donor-derived... Show moreAllogeneic stem cell transplantation is a potentially curative treatment for many hematological malignancies. The beneficial Graft-versus-Leukemia (GvL) effect is thereby mediated by donor-derived T-cells recognizing the malignant cells of the patient as foreign. However, the same T-cells might also target healthy non-hematopoietic cells of the patient such as skin, liver and gut causing a detrimental and sometimes lethal side effect, referred to as Graft-versus-Host disease (GvHD). In HLA-matched stem cell transplantation donor-derived T-cells recognize polymorphic peptides presented in self-HLA, so called minor histocompatibility antigens (MiHA). One strategy to induce GvL effect without GvHD is to exploit CD4+ T-cells, as HLA class II molecules are normally predominantly expressed on the hematopoietic system. However, under inflammatory conditions HLA class II might be up-regulated on non-hematopoietic tissues. Furthermore, until recently the identification of HLA class II restricted MiHAs was hampered by technical limitations. In this thesis we identified four new HLA class II restricted MiHA and characterized their intracellular processing and presentation in HLA class II. Furthermore we analyzed the possibility to separate GvL effect and GvHD based on differential intracellular processing of different antigen Show less
In this thesis I aimed to explore further finesses in the cellular dynamics of the two corticosteroid receptors, the MR and the GR, in both their membrane-associated and their nuclear... Show moreIn this thesis I aimed to explore further finesses in the cellular dynamics of the two corticosteroid receptors, the MR and the GR, in both their membrane-associated and their nuclear subpopulations. Amongst others I quantified the dynamics of the receptors at the membrane (only MR) and at the chromatin Show less
Since heterogeneity in depressed patients makes treatment decisions difficult and treatment often unsuccessful, we seek to identify certain subtypes of depression. 30 to 40% of depressed patients... Show moreSince heterogeneity in depressed patients makes treatment decisions difficult and treatment often unsuccessful, we seek to identify certain subtypes of depression. 30 to 40% of depressed patients have anger regulation problems; from irritability to anger attacks. What is the significance of anger in depression? Does it signify a subtype of depression? In the NESDA cohort, we compared a large sample of currently depressed patients with irritability to currently depressed patients without irritability. Irritable depressed patients had more symptoms of depression, more often had comorbid anxiety and had more often attempted suicide than non-irritable depressed patients. In a student sample, we investigated the role of the MAOA genotype and found that women with the high expression variant are possibly more vulnerable to anger or aggression during depression. Using acute tryptophan depletion we temporarily lowered serotonin in remitted depressed patients with and without anger regulation problems during their depression. We found no cognitive differences between the two groups, but the experiment did show us that depressed patients with anger regulation problems may be more serotonergically vulnerable. Further research is needed to elucidate best suited treatment strategies for anger regulation problems in depression Show less
The results of the studies included in this thesis suggest that the incidence of ABI in children and youth is considerable. Moreover, it was found that relatively many have long-term health... Show moreThe results of the studies included in this thesis suggest that the incidence of ABI in children and youth is considerable. Moreover, it was found that relatively many have long-term health problems, including limitations in psychosocial functioning, participation and QoL and that the impact on their families is substantial. These findings underscore the need for an increasing awareness for the impact of paediatric ABI. One study explored the effects of usage of serious gaming found that physical activity, the speed of information processing, attention, response inhibition, and parent-perceived Quality of life (QoL) were improved directly after the intervention. Participation is the most relevant outcome of recovery and main goal of rehabilitation. However, a better general understanding and improvements of assessment and treatment are required to decrease the impact of paediatric ABI on participation of youth and their families. Recommendations based on this thesis are: a) implement the ICF-model to improve comprehension of participation (problems) after paediatric ABI; b) measure and monitor participation after paediatric TBI and NTBI and c) develop and evaluate trajectories optimising participation. Show less
Since the first reports of human induced pluripotent stem cells (hiPSC), the field of pluripotent stem cell (PSC) research has grown in leap and bounds, particularly in the area of (cardiac)... Show moreSince the first reports of human induced pluripotent stem cells (hiPSC), the field of pluripotent stem cell (PSC) research has grown in leap and bounds, particularly in the area of (cardiac) disease modeling. This is in part because it is fairly easy to produce cardiomyocytes from hPSC and also there are now more assays available which can determine phenotypic behavior. This thesis describes and discusses improvements to reprogramming technology as well as its use in cardiac development and disease modeling Show less
This thesis is about migraine. Three elements are discussed. First element is preventive treatment, second element is attack treatment and the third part focuses on medication overuse headache. The... Show moreThis thesis is about migraine. Three elements are discussed. First element is preventive treatment, second element is attack treatment and the third part focuses on medication overuse headache. The preventive treatment of migraine is a valuable intervention in primary care. If preventive treatment is applied, usually only one attempt with one type of medication is performed. A number of considerations hinder GPs to address preventive treatment of migraine. Also several patient-related aspects cause that the GP differ from national guidelines. The decision to start preventive treatment is based on a complex of considerations from the patient. For example, experienced suffering from migraine and interaction with family, colleagues and general practitioner. Interest in preventive therapy increases with increased concerns about migraine symptoms. In attack treatment of migraine, most patients had a clear preference for one of both treatments. Preference correlated only moderately with the commonly used "two-hour pain-free score." Multi-attack, crossover, 'patient preference' studies are well able to detect clinically relevant differences between existing treatments. Overuse of triptans, resulting in chronic headaches is common and causes unnecessary costs. The common thread through this thesis is what patients want in migraine and which interventions they prefer: patients' preference in migraine. Show less
Over the last years major advances have been made in the field of C. difficile research. Despite the continuous progress of research in C. difficile epidemiology and molecular biology. This thesis... Show moreOver the last years major advances have been made in the field of C. difficile research. Despite the continuous progress of research in C. difficile epidemiology and molecular biology. This thesis shows that the development of molecular based techniques in detecetion and typing of C. difficile could be very valuable in combatting CDI. This also applies for the genetics and molecular biology of C. difficile in understanding the virulence of C. difficile. However, the continuing development of new techniques, both typing and genetics manipulation tools, has also led to the recognition of potential weaknesses of the currently frequent used techniques. Therefore, it is of utmost importance to keep up with the technical progress in the field of C. difficile research to enable further elucidation of the mechanisms that determine the virulence of C. difficile. Show less
Thrombosis is considered to be a multifactorial disease in which both genetic and acquired risk factors are involved to cause disease. Over the past years epidemiological studies have revealed a... Show moreThrombosis is considered to be a multifactorial disease in which both genetic and acquired risk factors are involved to cause disease. Over the past years epidemiological studies have revealed a number of acquired risk factors that increase the risk of venous thrombosis. Some acquired risk factors of venous thrombosis are associated with a hypercoagulable state, which may be to a certain extent dependent on the dysregulation of gene expression in the liver, as the liver is the major organ that produces coagulation factors. Coagulation gene transcription can be modulated at different levels through hepatic transcription factors, co-regulatory or intermediate proteins, however, the exact contribution of these modulators to coagulation gene transcription is largely unknown. We aimed to study the mechanisms by which hepatic coagulation gene transcription is regulated, in order to increase our understanding of how thrombotic risks conditions coincide with hypercoagulable state. RNA interference (via synthetic small interfering RNA; siRNA) was used as a tool to study genes involved in coagulation and coagulation control in mice. Studies described in this dissertation may contribute to a better understanding of which genes are involved in coagulation (control) and how thrombotic risk factors result in a hypercoagulable state Show less
