Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness. Deep inspirations affect airway narrowing and may therefore play a role in airway hyperresponsiveness in... Show moreAsthma is characterized by chronic airway inflammation and airway hyperresponsiveness. Deep inspirations affect airway narrowing and may therefore play a role in airway hyperresponsiveness in asthma. The studies described in this thesis were all directed at further elucidating the (patho)physiological mechanism underlying deep inspiration-induced bronchodilation or to restoring this protective mechanism in asthma. We showed that deep inspiration-induced bronchodilation is reduced in asthma and that this reduction is related to increased numbers of CD4+ lymphocytes in the bronchial submucosa and to increased numbers of mast cells in airway smooth muscle bundles in bronchial biopsies. In addition, impaired deep inspiration-induced bronchodilation is related to lower expression of several smooth muscle proteins (calponin, desmin, and MLCK) in bronchial biopsies, whereas lung function and airway hyperresponsiveness wa s related to higher expression of alpha-SM-actin, desmin and elastin. Further, pulmonary congestion had no influence on airway responses to deep inspiration as measured in patients with mitral valve disease. A course of high-dose corticosteroid treatment increased bronchodilation following deep inspiration in patients with asthma, whereas treatment with tiotropium for 21 days had no effect on airway responses to deep inspiration. Positive-pressure inflation of the lungs reduced airway narrowing, even in patients who showed no airway dilation following an active deep inspiration. Show less
Improving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of... Show moreImproving survival rates in children and adolescents with malignant bone tumours, paved the way to the application of new surgical extremity-salvage techniques. For the surgical treatment of malignant bone tumours of the lower extremity, there are a number of resection options (amputation, limb sparing, and rotationplasty) available. Each option has its own indication and after the surgery different advantages and disadvantages. The debate is whether limb-salvage or ablative surgery is advantageous for the individual patient. Purpose of the studies presented in this thesis are evaluate and compare QoL, functional ability and physical activity levels among children and young adults in the first years after bone cancer surgery of the leg. A cross sectional and a prospective study were conducted in the Dutch university bone cancer centres. The results of the cross-sectional study show that outcomes are equivalent for those undergoing limb salvage or ablative surgery. The results of the prospective study showed that; survivors improve in the two years following resection of the bone tumour and the resulting limb-sparing or ablative surgery at all domains evaluated, with the exception of the mental QoL domains. These improvements were most pronounced over the first year after surgery. Show less
The purpose of the research presented in this thesis was to gain insight into social-psychological mechanisms that underlie negative attitudes towards the Roma, i.e. Romaphobia, among adolescents.... Show moreThe purpose of the research presented in this thesis was to gain insight into social-psychological mechanisms that underlie negative attitudes towards the Roma, i.e. Romaphobia, among adolescents. Drawing from the threat theory (Stephan & Stephan, 1996, 2000), we found evidence that the perception of economic and symbolic threat mediates relationships between national in-group attitudes and acculturation preferences, on the one hand, and Romaphobia on the other. Perceived threat to the continued transmission of and support for one’s heritage culture and economic welfare was the basis for nationalistic adolescents’ Romaphobia. Moreover, adolescents who endorsed ethnocentric acculturation strategies, characterized by a relative degree of rejection of Roma’s culture (assimilation), contact with Roma (segregation), or both (marginalization), perceived more threat and Romaphobia. In contrast, youth who favored Roma integration perceived lower levels of threat and more favorable attitudes toward the Roma. This model of relationships appeared to be structurally similar between the Netherlands and Serbia, two countries that clearly differ with respect to minority proportion and status. Explanations are discussed as well as implications for theory and prejudice reduction in diverse intercultural settings. Show less
The aim of this thesis is to gain insight into the associations between experiences of parental love withdrawal, oxytocin, and asymmetric frontal brain activity (reflecting basic motivational... Show moreThe aim of this thesis is to gain insight into the associations between experiences of parental love withdrawal, oxytocin, and asymmetric frontal brain activity (reflecting basic motivational tendencies) on the one hand, and (neural) processing of and responses to socio-emotional stimuli on the other. The first chapters focus on the neural processing of emotional stimuli, investigating whether experiences of love withdrawal (Chapters 2 and 3) and oxytocin administration (Chapter 3) are related to event-related potential (ERP) responses to emotional facial expressions accompanying feedback, within a double-blind, placebo-controlled, within-subjects design. Chapter 4 focuses on behavioral responses to emotionally relevant information: donating money to charity after viewing a video of a child in need. The central question in this chapter is whether asymmetric frontal brain activity, as a measure of approach-withdrawal motivation, predicts charitable donations, and, in addition, the possibility that asymmetric frontal brain activity mediates or moderates effects of oxytocin and parental love withdrawal on donating behavior is explored. Show less
This dissertation addresses the semantics of pluractional verbs in Hausa. The notion of pluractionality is discussed and delimited with respect to related phenomena such as aspect. A detailed... Show moreThis dissertation addresses the semantics of pluractional verbs in Hausa. The notion of pluractionality is discussed and delimited with respect to related phenomena such as aspect. A detailed description of pluractionality in Hausa is provided, presenting new data based on the author’s fieldwork. This description lays the empirical groundwork for a theoretical analysis of pluractionality. The interpretation of pluractional verbs in Hausa is viewed as the result of three semi-independent meaning components: event plurality, the non-equivalence condition constraining the process of event individuation, and additional conditions on use following from the fact that Hausa pluractionals are ‘special’ plurals. These three components do not all have the same status, both with respect to each other and across speakers. This accounts for some of the specific properties of Hausa pluractionals, as well as for much of the extensive variation in the use and interpretation of pluractionals among speakers of Hausa. This thesis is of interest to both descriptive and theoretical linguists working on Hausa, pluractionality, or plurality in general. Show less
This dissertation investigates whether and how gradability is manifested in the nominal domain, as well as the implications this could have for theories of the representation of gradability. It is... Show moreThis dissertation investigates whether and how gradability is manifested in the nominal domain, as well as the implications this could have for theories of the representation of gradability. It is shown that the various gradability diagnostics proposed in the literature not only yield different results, but that they do not actually work as could be expected. In case after case, other factors turn out to underlie the noted effects: epistemicity and evidentiality (cf. the epistemic verb seem and real-type adjectives), the expression of a value judgment (e.g. N of an N constructions), the delineation of salient sub-kinds identifiable by natural consequences (cf. internal such) and abstract size modification (e.g. when a size adjective like big modifies a noun denoting an instance of a property or a set of individuals defined in terms of such an abstract object). Our investigation leads to the unexpected conclusion that,there are no grammatical contexts in the nominal domain that are exclusively reserved for a particular class of nouns that could properly be called gradable. As a result, there is no motivation for postulating a degree structure in the syntactic representation of nouns. In addition, there are no expressions performing the type of semantic operations familiar from degree modification in the adjectival domain that would indicate the existence of a grammatically accessible gradable structure in the semantics of nouns at the lexical level. The tale of this dissertation is therefore a cautionary one: arguments to reduce gradability in the nominal and in the adjectival domain to the same phenomenon are misguided. This study shows the importance of a cross-categorial perspective for a better understanding of gradability. It is of interest to a general syntactic and semantic readership. Show less
Moeliono heeft gekeken naar de ruimtelijke ordening, op papier en in de praktijk. Hij vraagt zich af of de Indonesische wetgeving burgers voldoende beschermt tegen onrechtmatig optreden van de... Show moreMoeliono heeft gekeken naar de ruimtelijke ordening, op papier en in de praktijk. Hij vraagt zich af of de Indonesische wetgeving burgers voldoende beschermt tegen onrechtmatig optreden van de overheid. Dat blijkt helaas niet het geval. De lokale overheid is eenzijdig gericht op economische groei en voert een weinig consistent beleid op het gebied van ruimtelijke ordening. Bovendien blijkt de wetgeving niet eenduidig te zijn, wanneer burgers verdreven dreigen te worden en voor hun rechten willen opkomen. Vergunningen In praktijk vormen vergunningen het belangrijkste beleidsinstrument voor het grondgebruik. Bovenop de bestuursstructuur, gedecentraliseerd na de val van Soeharto, is nu een top-down planningsmechanisme gelegd. Verwarring alom. Ambtenaren bepalen tot in detail wat wel en wat niet mag, zonder daarbij veel aandacht te schenken aan de lokale bevolking. Zelfs als de vergunningverlening duidelijk in strijd is met de regels, is het moeilijk te achterhalen bij welke instantie je verhaal kunt halen. Moeliono’s case studies van West-Java en Bandung leveren zo een somber beeld op van de ruimtelijke ordening. Die zou alleen kunnen verbeteren door de wetgeving grondig te herzien en de bestuurspraktijk te veranderen. Show less
We study stochastic models of non-equilibrium which are exactly solvable with the technique of duality and self-duality. The models include a new class of particle systems which are bosonic, i.e.,... Show moreWe study stochastic models of non-equilibrium which are exactly solvable with the technique of duality and self-duality. The models include a new class of particle systems which are bosonic, i.e., models where there is an attractive interaction between the particles and as a consequence condensation phenomena can occur. Our models belong to the class of interacting particle systems, or systems of interacting diffusions. Via the technique of duality, we connect models of interacting diffusions (e.g. Brownian Momentum Process) to simpler interacting particle systems (e.g. Symmetric Inclusion Process), both in equilibrium and non-equilibrium settings. Part of the thesis is devoted to develop a general formalism for duality. Show less
Today, about 1 billion people are estimated to live in ‘slums’ worldwide. This number will only grow and urban poverty worsen unless radical measures are taken. While it is generally acknowledged... Show moreToday, about 1 billion people are estimated to live in ‘slums’ worldwide. This number will only grow and urban poverty worsen unless radical measures are taken. While it is generally acknowledged in the international development debate that breaking the circle of poverty requires multiple strategies, there is renewed attention for approaches that centre on the issue of tenure security. This means landholders are protected against involuntary removal from the land on which they reside, unless through due process of law and payment of proper compensation. The prevailing approach to the provision of tenure security is land registration. And while the land registration approach currently dominates policy, there has been little research into the effects of registration, particularly in urban areas. What research has been conducted, contests the benefits of this approach. As a result, we witness increasing interest in alternative approaches which generally combine protective administrative or legal measures against eviction with the provision of basic services and credit facilities. The author describes and analyses the extent to which formal, semiformal, and informal tenure arrangements that can be found in kampongs (typical low-income settlements) in Indonesia provide tenure security to the country’s urban poor, particularly since 1998, when Indonesia embarked on an ambitious political and legal reform programme. The author reviews the current legal framework that applies to urban land tenure in Indonesia. In addition, based on rich material that was acquired through empirical research in the city of Bandung, there are a number of case studies presented in which the urban poor’s tenure security was put to the test. Finally, drawing on statistical data, the author analyses the urban poor’s perceptions regarding their tenure security and whether and, if so, how this influences their housing investment behaviour. Following this analysis, the author evaluates the socio-economic benefits of current approaches to attaining tenure security. And with these findings, there are policy suggestions and contributions to theory formation presented to further the current international development debate on tenure security. Show less
Isolated hepatic perfusion (IHP) involves complete vascular isolation of the liver to allow local treatment of the liver. During this procedure the blood circulation of the liver is temporarily... Show moreIsolated hepatic perfusion (IHP) involves complete vascular isolation of the liver to allow local treatment of the liver. During this procedure the blood circulation of the liver is temporarily isolated from the systemic circulation. Although IHP made a promising start in the early 90s, currently it is faced by many challenges. In view of recent developments in systemic treatment, the absence of significant improvement of the technique and the lack of new applicable agents, IHP should not be considered a standard treatment option for colorectal cancer patients with isolated liver metastases. Possibly, a role still exists for IHP in the treatment of liver metastases from non-colorectal cancer origin. Whether under these circumstances, IHP can still attract the interest of both clinical and surgical oncologists necessary for further improvements, remains the question. Show less
Schizophrenia is a devastating mental disorder characterized by a hyperactive dopamine system and deregulated stress system. Human studies have suggested that the schizophrenia symptoms precipitate... Show moreSchizophrenia is a devastating mental disorder characterized by a hyperactive dopamine system and deregulated stress system. Human studies have suggested that the schizophrenia symptoms precipitate if a hyperactive dopaminergic genotype interacts with adverse life experiences that activate the stress system. To examine this gene-by-environment interaction, we exposed rats genetically-selected for enhanced apomorphine susceptibility to two stress-provoking life events, poor maternal care early-in-life, and isolation rearing later-in-life. This promoted the development of schizophrenia endophenotypes. Our experiments involved two complementary steps: First, we focused on the immediate endocrine adaptations to maternal separation in common rats. It is known that a single episode of prolonged maternal separation slowly increases corticosterone levels in the neonate rat. We discovered that if the pups had been previously exposed to maternal separation, this rise in corticosterone was abolished, suggesting that the pups had learned to predict the return of the dam. While readily adapting to repeated maternal absence, the pups, surprisingly, stayed alert and displayed a rapid response to an acute stressor. We then investigated whether pup__s stress responsiveness was influenced by the context of maternal separation. It appeared that the experience of being kept in isolation in a novel environment during repeated maternal separation, rather than the maternal absence per se, caused priming of the amygdala fear pathway, with lasting consequences for the responsiveness of the neuroendocrine and behavioral stress system. These endocrine and behavioral alterations, caused by early-life stress experience, consisted of schizophrenia-like phenotypes. Second, we sought to investigate the interplay of such early-life stress experience with schizophrenia genetic predisposition and/or later-life social stress experience. Thus, we were able to test the three-hit (cumulative stress) and the developmental mismatch hypotheses. The former states that exposure to earlylife adversity and later-life psychosocial stressors, superimposed on genetic susceptibility, result in a severe schizophrenia-like phenotype. The latter proposes that experiences early-in-life program the developing brain in preparation for the future. In the case of genetically-predisposed apomorphine susceptible rats (schizophrenia-susceptible), we provide strong evidence for the three-hit hypothesis. In the case of the nongenetically selected Wistar rats, the mismatch hypothesis is supported since the outcome of early-life stress often negatively interacted with the pre-puberty social context. In agreement with the three-hit hypothesis of schizophrenia, we conclude from the current experiments that early-life stress experience in interaction with highly reactive dopaminergic alleles, leads to amygdala priming that, together with additional stressors, precipitate schizophrenia. Show less
In Baas in eigen Boek wordt de ontwikkeling geschetst die zich in de Gereformeerde Kerken in Nederland (GKN) tussen ongeveer 1880 en 1980 voltrok wat betreft hun visie op de darwinistische... Show moreIn Baas in eigen Boek wordt de ontwikkeling geschetst die zich in de Gereformeerde Kerken in Nederland (GKN) tussen ongeveer 1880 en 1980 voltrok wat betreft hun visie op de darwinistische evolutietheorie en in het bijzonder de daaruit voortvloeiende wereldbeschouwing. De evolutietheorie bleek decennialang onverenigbaar met 'eenvoudighistorische' en vrijwel letterlijke lezing van het scheppingsverhaal in het eerste Bijbelboek Genesis die in de GKN gangbaar was. Kerkelijke gezagsdragers, theologen en natuur-onderzoekers voerden hier verhitte debatten over, zo laat Kruyswijk zien. De ontzuiling van de jaren zestig van de twintigste eeuw droeg ertoe bij dat gereformeerde natuuronderzoekers deze lezing van Genesis niet langer konden volhouden. Mede door hun toedoen namen de GKN in 1981 officieel een narratieve interpretatie van de Bijbelse geschiedschrijving aan. Principiële bezwaren tegen de evolutie-theorie waren daarmee weggenomen. Veel gereformeerden bleven niettemin aan het 'eenvoudig-historische' gezag van de Bijbel vasthouden. Show less
The text mainly deals with the Eurasian evolutionary history of mammoths. It focuses on the time bracket 1.0-0.6 Ma, within which Mammuthus meridionalis (the southern mammoth) finally became... Show moreThe text mainly deals with the Eurasian evolutionary history of mammoths. It focuses on the time bracket 1.0-0.6 Ma, within which Mammuthus meridionalis (the southern mammoth) finally became extinct in Europe. Its descendant,the initially eastern Asian steppe mammoth (M. trogontherii) was a comparatively late immigrant in Europe (c. 1.2-1.0 Ma)and then for a time was the only mammoth species there. European sites that yielded relevant material are rivised. The probability of hybridisation between the said species, suggested by the occurrence of so-called mosaic molars, is discussed. In addition, a number of subspecific taxa traditionally referred to M. meridionalis is now ascribed to M. trogontherii, which reduces the role played by M. meridionalis at the end of the Early Pleistocene. Show less
Major advances have been made in the treatment of rheumatoid arthritis, a potentially chronic disabling disease which poses a large burden on both patients and society. By early start of disease... Show moreMajor advances have been made in the treatment of rheumatoid arthritis, a potentially chronic disabling disease which poses a large burden on both patients and society. By early start of disease-modifying antirheumatic drugs, including methotrexate as a prominent drug, the use of combination therapies including prednisone or biologicals, and tight control of disease activity, many patients are able to reach a state of clinical remission and some can even taper and stop antirheumatic therapy. Challenges lie in correctly identifying the earliest manifestations of the disease, starting the right treatment sufficiently early, tailored to the individual patient, and setting the optimal treatment goal at which to steer therapy adjustments. This thesis has made a start towards tackling several of these challenges and discusses further necessary steps that may lead to a fundamental change in the outlook of patients with rheumatoid arthritis. Show less
The peripheral Mongolic languages of the Qinghai-Gansu area in China comprise Eastern Yugur (Shira Yugur) and the Shirongol languages. The latter can be subdivided in a Monguor branch, consisting... Show moreThe peripheral Mongolic languages of the Qinghai-Gansu area in China comprise Eastern Yugur (Shira Yugur) and the Shirongol languages. The latter can be subdivided in a Monguor branch, consisting of Mongghul and Mangghuer, and a Baoanic branch, consisting of Baoan, Kangjia, and Dongxiang (Santa). The internal taxonomy of the Qinghai-Gansu languages will be discussed in a separate section. The Qinghai-Gansu languages are increasingly well-described. They have also been the subject of studies in language contact, mostly in the context of the Amdo or Qinghai-Gansu Sprachbund. This study will approach the phonology of Qinghai-Gansu Mongolic from a comparative historical viewpoint. It provides an overview of the phonological developments of the Qinghai-Gansu languages, comparing them to the reconstructed ancestral language. At the same time it will investigate the archaic features that can be found in these languages, in order to improve the reconstructions of individual Mongolic lexemes. The book ends with a comparative supplement of about 1350 reconstructed Common Mongolic items, accompanied by the modern forms they are based on and, where necessary, arguments for the chosen reconstruction. Show less
Technological innovation has helped the zebrafish embryo gain ground as a disease model and an assay system for drug screening. Here, we review the use of zebrafish embryos and early larvae in... Show moreTechnological innovation has helped the zebrafish embryo gain ground as a disease model and an assay system for drug screening. Here, we review the use of zebrafish embryos and early larvae in applied biomedical research, using selected cases. We look at the use of zebrafish embryos as disease models, taking fetal alcohol syndrome and tuberculosis as examples. We discuss advances in imaging, in culture techniques (including microfluidics), and in drug delivery (including new techniques for the robotic injection of compounds into the egg). The use of zebrafish embryos in early stages of drug safety-screening is discussed. So too are the new behavioral assays that are being adapted from rodent research for use in zebrafish embryos, and which may become relevant in validating the effects of neuroactive compounds such as anxiolytics and antidepressants. Readouts, such as morphological screening and cardiac function, are examined. There are several drawbacks in the zebrafish model. One is its very rapid development, which means that screening with zebrafish is analogous to __screening on a run-away train.__ Therefore, we argue that zebrafish embryos need to be precisely staged when used in acute assays, so as to ensure a consistent window of developmental exposure. We believe that zebrafish embryo screens can be used in the pre-regulatory phases of drug development, although more validation studies are needed to overcome industry scepticism. Finally, the zebrafish poses no challenge to the position of rodent models: it is complementary to them, especially in early stages of drug research. Show less
Rethinking Ostia presents an archaeological and spatial approach to Roman urbanism, focused on Rome’s port city. The study proceeds along the route of a ‘spatial investigation’, offering a fresh... Show moreRethinking Ostia presents an archaeological and spatial approach to Roman urbanism, focused on Rome’s port city. The study proceeds along the route of a ‘spatial investigation’, offering a fresh look and detailed insights into the past society and the built environment of this port town. Following a scaled approach, the work examines different aspects of Ostia’s urban landscape, applying Space Syntax’s methods for spatial analysis to the urban neighbourhood of one city block – Insula IV ii, selected buildings (Ostia’s guild seats), and the entire street system. All through the study a ‘Space First’ policy has been followed, combining archaeological research with today’s insights into urban planning. The heart of this scalar approach is the complete re-working of the archaeological evidence and its interpretative potential for the city block, Insula IV ii. This neighbourhood enjoys an excellent location and boasts a striking variety of buildings including the well-known Terme del Faro, the Caseggiato dell’Ercole, and the Caupona del Pavone, but till now has not been studied in its entirety and within its own social and spatial context. Through a careful reconstruction of the Insula’s development over the first three centuries AD, the work fills a lacuna – but more importantly it reveals the way everyday life was structured in the city, and how this evolved over time in response to internal and external influences on the lives of its inhabitants. Rethinking Ostia draws upon archaeological data and extensive spatial analyses, both carefully documented and illustrated. The findings highlight the active role of space in structuring social activity in the ancient city. Show less
This thesis describes the PROMODE-study, which investigated in a pragmatic way whether a pro-active approach in primary care by screening for depressive symptoms, followed by an intervention offer... Show moreThis thesis describes the PROMODE-study, which investigated in a pragmatic way whether a pro-active approach in primary care by screening for depressive symptoms, followed by an intervention offer to persons of 75 years and over who screened positive, is (cost)effective to detect and relieve suffering from depressive symptoms at old age. We compared two screening methods regarding yield and costs. Furthermore, we found that scores of the 15-item Geriatric Depression Scale were higher when this screening questionnaire was self-administered than when interviewer-administered. In our intervention study, a cluster-randomised controlled trial, we found that the stepped-care intervention program was not (cost)effective compared with usual care in general practice, possibly due to a low uptake of the offered course being the main part of the intervention. In a qualitative study we explored the limiting and motivating factors for accepting course participation. This revealed that most persons were not (yet) prepared to accept the unsolicited intervention offer, although perceived needs to relieve depressive symptoms seemed to largely match the elements of the course. It is discussed that a more selective approach, aimed at high risk-groups and focussing on need for and readiness to accept help, might increase efficiency of a combined screening-intervention program. Show less
Pituitary insufficiency in the presence of a pituitary macroadenoma or after pituitary irradiation is frequently reported. In addition, pituitary insufficiency is increasingly reported after... Show morePituitary insufficiency in the presence of a pituitary macroadenoma or after pituitary irradiation is frequently reported. In addition, pituitary insufficiency is increasingly reported after traumatic head injuries. The correct evaluation and interpretation, however, of the pituitary axes, and consequently, the potential therapeutical consequences are a matter of controversies. The studies reported in this thesis aim to provide better insight into the complexity of different endocrine tests used for the evaluation of possible pituitary insufficiency and in the treatment of patients with pituitary insufficiency. Show less
The small proline-rich (SPRR) proteins are generally known for their involvement in the formation and adaptation of the skin__s barrier. During the cornification process, they are cross-linked... Show moreThe small proline-rich (SPRR) proteins are generally known for their involvement in the formation and adaptation of the skin__s barrier. During the cornification process, they are cross-linked within the cornified cell envelope (CE) and as such they are responsible for the physical and permeability barrier function of our skin. In this thesis, the novel antioxidant properties of the SPRR proteins are described. As part of the CE, these proteins provide a natural antioxidant shield to our skin and act as our first line of defence against reactive oxygen species (ROS). Also during wound healing, SPRR proteins can directly reduce toxic ROS levels. This activity is directly related to their ability to promote cell migration and is essential in order to allow wound closure. A literature-based meta-analysis revealed their up-regulation in various forms of tissue injury, ranging from heart infarction and commensal-induced gut responses to nerve regeneration and burn injury. Apparently, SPRR proteins have a far more widespread role in wound healing and tissue remodelling than their established function in skin cornification. Likely, SPRR proteins provide all tissues with an efficient, finely tuneable antioxidant barrier, specifically adapted to the tissue involved and the damage inflicted. Show less
