Molecular imaging plays a vital role in current medical diagnostics. There is a constant need for new and improved molecular imaging agents in terms of resolution, specificity, stability, safety... Show moreMolecular imaging plays a vital role in current medical diagnostics. There is a constant need for new and improved molecular imaging agents in terms of resolution, specificity, stability, safety and cost. The research described in this thesis deals with the development of activatable luminescence lifetime imaging agents as well as with the use of supramolecular chemistry to introduce cell surface modifications to living cells. Show less
This book defends political obligation, stating that people are morally obligated to obey the law of their state, if the law is at least reasonably just. The defense is based on the tradition of... Show moreThis book defends political obligation, stating that people are morally obligated to obey the law of their state, if the law is at least reasonably just. The defense is based on the tradition of the Kantian political philosophy and legal philosophy, and it is a defense mainly against political anarchists. They believe that the only possible justification for political obligation should be voluntarist, proving people’s deliberate undertakings to incur the obligation. Since no attempt in the voluntarist approach is justifiable, political obligation does not exist from the a posterior point of view. As a consequence, political legitimacy, which is claimed to be the other side of the same concept of political obligation, fails to obtain its justification, and no state is legitimate. The exploration in this book contends that a voluntarist basis is neither necessary nor sufficient for people to be obligated to obey the law. And this contention earns the space for justifying political obligation on an involuntarist ground, meaning that people can be imposed on a moral obligation to obey the law without any voluntary actions incurring this obligation. This involuntarist ground is what I name the “moral necessity thesis”. Show less
In this dissertation we developed statistical tools for analyzing multivariate binary data. In many disciplines multivariate binary data, in which there are multiple binary dependent variables and... Show moreIn this dissertation we developed statistical tools for analyzing multivariate binary data. In many disciplines multivariate binary data, in which there are multiple binary dependent variables and one or more independent variables, are often collected. In this dissertation we further developed the IPC model for analyzing multivariate binary data. The IPC model is a probabilistic multidimensional unfolding model and closely related to the Ideal Point Discriminant Analysis (IPDA). In Chapter 4, we proposed a Multivariate Logistic Distance (MLD) model for analyzing multivariate binary data. The MLD model unifies two domains of statistical methods, i.e., Multidimensional Scaling (MDS) and Generalized Linear Model (GLM). The MLD model can be used to simultaneously assess the dimensional structure of the data and to study the effect of the predictor variables on the response variables. For the NESDA data, for example, a researcher can use the MLD model to determine the dimensional structure of the mental disorders, and to investigate effect of the personality traits and the background variables on prevalence of the mental disorders. Show less
BAV morphology and especially the presence and extent of a raphe is of clinical importance, as a complete raphe predisposes to more valvular dysfunction and aortopathy. Regarding variations in... Show moreBAV morphology and especially the presence and extent of a raphe is of clinical importance, as a complete raphe predisposes to more valvular dysfunction and aortopathy. Regarding variations in coronary anatomy, it turns out that patients with left-right BAVs without raphe and patients with BAV and CoA more often have a left dominant coronary artery system. Patients with left-right BAVs without raphe also seem more at risk of developing significant coronary artery disease. In addition, separate ostia of the LAD and LCX are more common in these patients. Patients with Turner syndrome and BAV do not show significant differences in coronary dominance as compared to patients with Turner syndrome with TAV and to patients with isolated BAV. However, patients with TS and BAV show more separate ostia of the LAD and LCX as compared to patients with isolated BAV. In BAV with associated complex congenital heart disease, a high take-off of the coronary arteries, occurred more frequently than reported in structurally normal hearts and in hearts with isolated BAV. Finally, there should be awareness of possible bilateral semilunar valvular disease, which is associated with strictly bicuspid BAVs and in many cases related to chromosomal abnormalities. Show less
The principal aims of this book are to provide a comprehensive reconstruction of the urban systems of the Iberian Peninsula during the High Empire and to explain why these systems looked the... Show moreThe principal aims of this book are to provide a comprehensive reconstruction of the urban systems of the Iberian Peninsula during the High Empire and to explain why these systems looked the way they did. While some chapters focus on settlements that were cities or towns from a juridical point of view, the implications of using a purely functional definition of towns are also explored. Key themes include continuities and discontinuities between pre-Roman and Roman settlement patterns, the geographical distribution of cities belonging to various size brackets, economic relationships between self-governing cities and their territories, and the role of cities as nodes in road systems and maritime networks. In addition, it is argued that a considerable number of self-governing communities in Roman Spain and Portugal were polycentric rather based on a single urban centre. Show less
Kidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of... Show moreKidney transplantation is the preferred treatment of patients with end stage renal disease, as it provides longer patient survival and better quality of life compared to dialysis. Prediction of DGF, response to steroid resistant rejection and long-term graft outcome remain difficult when using merely clinical parameters. Numerous studies have reported on the predictive value of molecular markers for AR and worse graft outcome. However, the heterogeneity of AR and the variation among transplant centers leads to controversial results and preclude a more general clinical application. In the first part of this thesis, we aimed to investigate the molecular markers of steroid resistance and long-term graft survival on the basis of acute rejection biopsies. In the second part, we focused on genetic variants associated with acute rejection in kidney transplantation. In the final part we described the possible immune regulatory effect of S100 calcium binding proteins. Show less
This thesis explores the influence of prescriptivism on language use in American English. It does so by studying the relationship between language advice literature, patterns of language use,... Show moreThis thesis explores the influence of prescriptivism on language use in American English. It does so by studying the relationship between language advice literature, patterns of language use, and speakers’ attitudes. The thesis shows that the genre of usage guides, routinely associated with prescriptivism, is undergoing change to reflect processes of change in progress in American English. Furthermore, prescriptivism and language use are shown to mutually influence each other. Show less
Is de geboden cardiologische zorg `sufficiently safe' ? Dit proefschrift richtte zich op de vraag hoe je kwaliteit van zorg kan meten om te kijken of de geboden zorg voor de behandeling van acuut... Show moreIs de geboden cardiologische zorg `sufficiently safe' ? Dit proefschrift richtte zich op de vraag hoe je kwaliteit van zorg kan meten om te kijken of de geboden zorg voor de behandeling van acuut coronair syndroom sufficiently safe is en deed dit middels twee methoden: lokaal dossieronderzoek ten aanzien van patiëntveiligheid (Deel 1) en nationaal declaratie data-registratie voor kwaliteit-van-zorg onderzoek (Deel 2). Waar declaratiedata in detail moet inleveren, levert dossieronderzoek in op de efficiëntie. De twee verschillende methodes vullen elkaar aan en dienen een verschillend doel: veiligheid en kwaliteit van zorg. De geboden zorg lijkt veilig, maar toch ervaart 13% zorggerelateerde schade bij de behandeling van een acuut coronair syndroom. Welk onderzoek is hiervoor nodig? Dossieronderzoek is zeer arbeidsintensief, zelfs een onderzoek binnen het heldere MISSION!-protocol leidt nog tot heterogene antwoorden op causale relaties van zorggerelateerde schade. Real-time monitoring van afwijkende processen met reeds geregistreerde data biedt meer inzicht in zorggerelateerde schade. De geboden zorg lijkt volgens de richtlijnen te gaan, maar toch krijgt slechts 49% zijn preventieve medicatie. Ook hier is ruimte voor verbetering. Toekomstige analyses met declaratiedata, gecombineerd met klinische data en andere databronnen, kan meer inzicht geven om zo de kwaliteit van zorg continu te blijven verbeteren. Show less
Quality and safety improvement is a relatively novel discipline in healthcare practice and research that solidified in the early 21st century. Since then, various systems have been installed to... Show moreQuality and safety improvement is a relatively novel discipline in healthcare practice and research that solidified in the early 21st century. Since then, various systems have been installed to collect information on various types of adverse outcomes, such as adverse events, incidents and patient complaints. Data from these systems can be used to evaluate care delivered to individual cases as well as to study aggregated data for patterns, trends and other insights. More research is warranted to assess whether these systems actually meet the objective of continuous, systemwide learning and improvement. It was expected that existing practices could benefit from individual optimization as well as better integration, because most of this intelligence is currently stored and used in isolation. The research in this PhD thesis focused on how we can learn most effectively from various types of adverse outcomes in healthcare, in order to continuously improve the care delivered to patients. Specific research questions included how we can learn from: i) case discussions at morbidity and mortality conferences ; ii) integrating available information sources (e.g., incidents, patient experiences); iii) the context of everyday practice that produces both adverse and desired outcomes. Show less
HPV has evolved mechanisms to resist immune attack. I showed that HPV impaired necroptosis induced by IFNγ and TNFα by down-regulation of RIPK3 expression. Methyltransferase inhibitor DZNeP... Show moreHPV has evolved mechanisms to resist immune attack. I showed that HPV impaired necroptosis induced by IFNγ and TNFα by down-regulation of RIPK3 expression. Methyltransferase inhibitor DZNeP restored the expression of RIPK3 in HPV+ keratinocytes, and increased the necroptosis in HPV+ keratinocytes. Simultaneously, hrHPV effectively inhibited IFNγ/TNFα-mediated arrest of cell growth by down-regulating IFITM1. Then I studied HPV associated oropharyngeal squamous cell cancer (OPSCC). The OPSCC infiltrating HPV specific CD4+ Tcells produce cytokines such as IFNγ and TNFα. I found that HPV16-positive tumor cells lacked expression of RIPK3, which were not sensitive to the necroptosis induced by IFNγ /TNFα. I also showed that a combination of IFNγ and TNFα with cisplatin synergized in killing tumor cells. Last but not least I showed that combination of the clinically applied EGFR inhibitor Cetuximab and IFNγ/TNFα increased gene expression of multiple cytokines, including CXCL9, CXCL10 and CCL5, which may attract more lymphocytes to the tumor site. By using the inhibitors of the targets downstream of EGFR, I found that JNK and MEK1 played major role in mediating the suppression of CCL5, CXCL9 and CXCL10 expression. Show less
Should GNSS cause damage to its users or any third parties, who shall be responsible or liable, and how? Is it fair enough to force a GNSS provider to bear the burden of compensation given GNSS... Show moreShould GNSS cause damage to its users or any third parties, who shall be responsible or liable, and how? Is it fair enough to force a GNSS provider to bear the burden of compensation given GNSS open signals are provided free of charge to an undetermined scope? Could a GNSS provider release its civil liability by the doctrine of Sovereign Immunity if that provider is a public authority? This research is designed to explore whether current international laws are adequate to deal with those questions. If so, how those international laws apply? If not, where is the legal gap, and how should we move forward? This research is composed of four parts. Part I transfers the focus gradually from GNSS technical matters to legal issues, and then to civil liability in particular. Part II concerns a conceptual analysis of GNSS civil liability, serving as a basis for any further study. Part III checks the applicability and the adequacy of current international air and space laws to the case where GNSS cause damage. Part IV tries to find a roadmap to move forward for the issue of GNSS civil liability in a feasible way. Show less
Het oostelijk deel van West-Friesland was in de midden- en late bronstijd (ca. 1600-800 v. Chr.) een dichtbevolkt gebied met vele boerendorpjes. Door de goede conserveringsomstandigheden is de... Show moreHet oostelijk deel van West-Friesland was in de midden- en late bronstijd (ca. 1600-800 v. Chr.) een dichtbevolkt gebied met vele boerendorpjes. Door de goede conserveringsomstandigheden is de regio een schatkamer van de overblijfselen uit die tijd. In deze studie zijn oude opgravingsgegevens uitgewerkt en vertaald naar nieuwe inzichten in de inrichting en ontwikkeling van dit indrukwekkende prehistorische cultuurlandschap. Een van de opvallende resultaten van dit onderzoek is dat de nederzettingsterreinen vaak vele generaties bewoond zijn, maar tegelijkertijd een dynamisch karakter hebben. Continuïteit was er op locaties waar een huisplaats is ingericht: nieuwe boerderijen werden vaak generaties lang op dezelfde plaats als de voorgangers gebouwd. Maar we zien ook dat huisplaatsen die generaties lang bewoond zijn geweest, op een zeker moment werden opgegeven en een andere functie krijgen. Door de lange bewoningsduur van terreinen en goede conservering en herkenbaarheid van grondsporen, zijn de Westfriese vindplaatsen bij uitstek geschikt om deze dynamiek in beeld te brengen. Veel beter dan elders in Nederland is het mogelijk inzicht te krijgen in de keuzes die men in de bronstijd heeft gemaakt bij de inrichting van het landschap. Dat maakt deze studie een ijkpunt voor bronstijdonderzoek in Nederland, maar ook in Noordwest-Europa. Show less
The research contained in this dissertation explores the origins of fire making in prehistory, focusing primarily on the fire use practices and fire production capacities of Neandertals. The... Show moreThe research contained in this dissertation explores the origins of fire making in prehistory, focusing primarily on the fire use practices and fire production capacities of Neandertals. The dissertation is comprised of four peer-reviewed articles published in the journals Quaternary International, PLoS ONE, Journal of Archaeological Science and Scientific Reports, respectively, which are flanked by an introductory and synthesis chapter. The early chapters confront the debate surrounding the prevalence of fire use by Neandertals and discuss avenues by which we, as archaeologists, can better understand how fire use manifests in the Palaeolithic archaeological record. The latter chapters seek to provide a means for identifying artefactual evidence for fire making by Neandertals, ultimately presenting a series of French Middle Palaeolithic tools that exhibit use traces suggesting they were employed as fire starters, making these the earliest evidence for the regular production of fire by humans currently known. Show less
Whenever someone makes a statement, they take stance on what they are talking about. Their utterance presents the propositional content of their message and at the same time shares their position... Show moreWhenever someone makes a statement, they take stance on what they are talking about. Their utterance presents the propositional content of their message and at the same time shares their position regarding the subject of talk. They convey their support or opposition, affiliation or disaffiliation, their like or dislike of the topic of talk. Subsequent, related, contributions similarly do not only react to the content of the earlier message, but to the associated stance taken by the other participant as well. Every interaction thus requires careful management of both the content discussed and the interpersonal relations between those involved. This dissertation investigates how people manage their informal interactions by means of phatic communicative structures. It explores to what extent the choices made by speakers are cross-linguistically stable or language specific, as differences in conversational style could affect intercultural communication and understanding. Three types of linguistic behavior are addressed: offering support and agreement, reproducing meaning (and form), and collaboratively constructing a single message. The preferences across and within these three types are contrasted for Dutch and Indonesian speakers. Show less
The effect of donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation is difficult to determine and currently unknown. The thesis describes different statistical methods the... Show moreThe effect of donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation is difficult to determine and currently unknown. The thesis describes different statistical methods the determine the effect of DLI after T-cell depleted allogeneic stem cell transplantation for ALL, AML, MDS, relapse AML and multiple myeloma. The effect on bone marrow disease appears strong as compared to extramudullary disease. Show less
De precieze aard van de rechtsverhouding tussen leerling, ouders en school in het primair en voortgezet bekostigd onderwijs is geen uitgemaakte zaak. De wet zwijgt hierover en de rechtspraak biedt... Show moreDe precieze aard van de rechtsverhouding tussen leerling, ouders en school in het primair en voortgezet bekostigd onderwijs is geen uitgemaakte zaak. De wet zwijgt hierover en de rechtspraak biedt geen uitsluitsel. De literatuur ziet verschillende mogelijkheden, van civielrechtelijke, bestuursrechtelijke of gemengde aard, met referte aan onder meer het onderscheid tussen openbaar en bijzonder onderwijs en publiekrechtelijke normering van het onderwijs. Dit proefschrift bekijkt de rechtsverhouding tussen leerling, ouders en school vanuit contractenrechtelijk perspectief. Het neemt als uitgangspunt dat de rechtsverhouding gekwalificeerd kan worden als overeenkomst: een onderwijsovereenkomst. Wat brengt toepassing van het contractenrecht in de onderwijsverhouding mee? Wat heeft het contractenrecht de onderwijsverhouding te bieden? Fundamentele leerstukken van het contractenrecht op het gebied van de totstandkoming, de inhoud en de remedies worden toegepast in de context van het onderwijs, telkens met inachtneming van publiekrechtelijke normen. Show less
This dissertation provides new insights into language variation and change in late eighteenth- and early nineteenth-century Dutch. More specifically, it investigates whether and to what extent... Show moreThis dissertation provides new insights into language variation and change in late eighteenth- and early nineteenth-century Dutch. More specifically, it investigates whether and to what extent official language policy measures exerted influence on actual language practice.During the nation-building period around 1800, the Northern Netherlands witnessed the introduction of a national language policy, which aimed at the spread of a homogeneous written standard variety of Dutch, symbolising 'the' nation. In concrete terms, these top-down endeavours resulted in the first official codification of the Dutch orthography (Siegenbeek 1804) and grammar (Weiland 1805). Despite marking a decisive turning point in the standardisation history of Dutch, the effectiveness of the so-called schrijftaalregeling 'written language regulation' has never been investigated empirically.Taking a historical-sociolinguistic approach, this dissertation aims to fill this research gap by examining the impact of language policy on patterns of variation and change. How successful was the schrijftaalregeling in disseminating the officialised norms across the population at large, as envisaged by the government? Making use of the newly compiled Going Dutch Corpus, a diachronic multi-genre corpus comprising more than 420,000 words of authentic usage data (private letters, diaries and travelogues, newspapers), a wide range of orthographic and morphosyntactic features is analysed. Show less
The research is dedicated to Gilbert Blin’s work in staging operas of the seventeenth and eighteenth centuries. Nourished by a decade of productions for the Boston Early Music Festival, the first... Show moreThe research is dedicated to Gilbert Blin’s work in staging operas of the seventeenth and eighteenth centuries. Nourished by a decade of productions for the Boston Early Music Festival, the first objective of his dissertation is to enable a better understanding of both his creative and interpretive processes in the operatic field. The main research question he attempts to answer in his dissertation can be phrased as follows: how can a post-modern stage director use historical research for creative purposes? The title of this dissertation, The Reflections of Memory, is the appellation Gilbert Blin has been giving to his current approach as an artist and constitutes a conceptual answer to this question Show less
The availability of indicators based on social media has opened the possibility to track the online interactions between social media users and scholarly entities. Indicators derived from these... Show moreThe availability of indicators based on social media has opened the possibility to track the online interactions between social media users and scholarly entities. Indicators derived from these online interactions reflect aspects such as how often, by whom, and when are scholarly publications mentioned and discussed on social media platforms. These new indicators, popularly known as altmetrics and more technically referred as social media metrics are usually proposed as potential alternatives to citation-based indicators to inform research evaluation. The research presented in this book provides the state of the art in the possibilities of social media metrics for informing research evaluation. The main ambition is to increase the knowledge and understanding of the limitations, challenges, and actual possibilities of social media metrics for research evaluation. This thesis describes the presence and distribution of different social media metrics across scientific publications and their relationship with traditional impact indicators. It further describes the main characteristics of publications mentioned in Mendeley as one of the main social media metrics platforms. Moreover, critical challenges regarding data quality issues of social media data are thoroughly described and discussed. Finally, some possibilities and applications of social media metrics for informing research evaluation are presented. Show less
The aim of this dissertation is to explore what adaptations are needed to improve the fit of a parenting intervention for use in multi-ethnic disadvantaged neighborhoods. A bottom-up approach is... Show moreThe aim of this dissertation is to explore what adaptations are needed to improve the fit of a parenting intervention for use in multi-ethnic disadvantaged neighborhoods. A bottom-up approach is used to assess parents’ perspectives regarding their parenting experiences, and to identify their needs and stressors. Data is collected among parents with an ethnic minority and low socioeconomic status background. Each chapter is a part of a stepwise approach that led to the selection of an intervention, and its adaptation for and evaluation in a multi-ethnic disadvantaged neighbourhood. It was found that a focus on coping strategies to handle stress and unhelpful emotions is not a standard theme in parenting interventions, while this would be beneficial for ethnic minority and low SES parents. The intervention module ‘Coping with stress and unhelpful emotions’ was developed to be incorporated into an existing parenting intervention to assist parents in handling their emotions and decreasing the impact of stress, and simultaneously regulating their parenting behavior. An evaluation study showed the relevance of this in-built module for parents living in multi-ethnic disadvantaged neighborhoods and also yielded recommendations to further improve the module. Show less
