Transport inspectorates are looking for novel methods to identify dangerous behavior, ultimately to reduce risks associated to the movements of people and goods. We explore a data-driven approach... Show moreTransport inspectorates are looking for novel methods to identify dangerous behavior, ultimately to reduce risks associated to the movements of people and goods. We explore a data-driven approach to arrive at smart inspections of vehicles. Inspections are smart when they are performed (1) accurate, (2) automated, (3) fair, and (4) in an interpretable manner. We leverage tools from the network science and machine learning domain to encode the behavioral aspect of vehicle’s behavior. Tools used in this thesis include community detection, link prediction, and assortativity. We explore their applicability and provide technical methods. In the final chapter, we also discuss the matter of fairness in machine learning. Show less
The focus of this thesis is on the technical methods which help promote the movement towards Trustworthy AI, specifically within the Inspectorate of the Netherlands.The goal is develop and assess... Show moreThe focus of this thesis is on the technical methods which help promote the movement towards Trustworthy AI, specifically within the Inspectorate of the Netherlands.The goal is develop and assess the technical methods which are required to shift the actions of the Inspectorate to a data-driven paradigm, concretely under a supervised classification framework of machine learning.The aspect of reliability is addressed as a data quality concern, viz. missingness and noise.The aspect of fairness is addressed as a counter to bias in the selection process of inspections.The conclusion is that, whilst no complete solution has yet been suggested, it is possible to address the concerns related to data quality and data bias, culminating in well-performing classification models which are reliable and fair. Show less
Pulmonary embolism is a serious and potentially life-threatening disease in the acute phase, and may also have a major impact on a patient’s daily life in the long run. The overall aim of this... Show morePulmonary embolism is a serious and potentially life-threatening disease in the acute phase, and may also have a major impact on a patient’s daily life in the long run. The overall aim of this thesis was evaluating important aspects of the post-pulmonary embolism syndrome with an emphasis on early diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) and the associated consequence for patients’ prognosis. Show less
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss and declined cognitive functioning. Brain changes in AD involve grey matter atrophy and changes in brain... Show moreAlzheimer’s disease (AD) is a neurodegenerative disease characterized by memory loss and declined cognitive functioning. Brain changes in AD involve grey matter atrophy and changes in brain function. These different brain characteristics can respectively be visualized with structural and functional MRI scans. These MRI modalities have been used for AD classification, but studies typically only include a limited number of features. In this thesis we derived multiple types of features from each MRI modality, and combined those to discriminate AD patients and elderly controls. First, we showed that AD classification accuracy increases when combining multiple types of measures from a single MRI modality. This was shown for structural MRI scans in chapter 2, and for resting state fMRI scans in chapter 3. In chapter 4 we evaluated whether MRI based AD classification models can discriminate AD in a diverse clinical population as well. This worked to some extent, and it worked best using structural MRI scans. In chapter 5 we used baseline multimodal MRI scans from the same diverse clinical population to predict two-year follow-up cognitive decline. Decline was predicted above chance level for the MMSE, but not for six other neuropsychological tests. Show less
This dissertation examines how in eighteenth-century Europe, naturalists sought to study, grasp and capture the world of fish. Working on the intersection of the history of science and book history... Show moreThis dissertation examines how in eighteenth-century Europe, naturalists sought to study, grasp and capture the world of fish. Working on the intersection of the history of science and book history, this research aims to shed light on how naturalists came to present themselves as authorities in an emerging field. It does so by focussing on a set of ‘fish books’, i.e., natural historical works that describe and depict fish. The first is Francis Willughby and John Ray’s "Historia piscium" (Oxford, 1686); the second Peter Artedi’s "Ichthyologia sive opera omnia de piscibus" (Leiden, 1738), and the third Marcus Élieser Bloch’s twelve volume series "Allgemeine Naturgeschichte der Fische" (Berlin, 1782–1795). These works are analysed alongside correspondences, manuscripts and natural historical collections. Together, these sources show that the development of the study of fish in this period can be best be understood as a process of continuous demarcation. This dissertation argues that the study of fish was subject to recurrent debates on subject, method and practitioner, and that such discussions were of both epistemological and social nature. In presenting their fish books, naturalists leveraged such discussions as to secure a place for themselves in the capricious environment of early modern natural history. Show less
Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disease characterised by the progressive degeneration of the frontal and temporal lobes, which results in behavioural (behavioural... Show moreFrontotemporal dementia (FTD) is a heterogeneous neurodegenerative disease characterised by the progressive degeneration of the frontal and temporal lobes, which results in behavioural (behavioural variant FTD) and language (primary progressive aphasia) disorders. No effective therapies currently exist to cure FTD or slow disease progression. However, efforts are being made to develop disease modifying treatments, which aim to reverse or inhibit pathological processes leading up to neuronal cell death. Therefore, the ability to diagnose FTD before brain atrophy (i.e., irreversible brain damage) is crucial. Approximately 10–30% of all FTD patients have a familial form, often caused by mutations in the genes MAPT, GRN or a repeat expansion in the gene C9orf72. These families offer the unique opportunity to study mutation carriers in the presymptomatic stage, where early pathological changes may already occur, but subjects are cognitively healthy. In this dissertation, we used multimodal MRI and machine learning to investigate whether MRI biomarkers for FTD have diagnostic value on the single-subject level to detect FTD-related differences in the presymptomatic disease stage. Furthermore, we aimed to advance the combination of resting-state functional MRI data between scanners. Lastly, we studied potential biomarkers for the differentiation between early stages of FTD and Alzheimer’s disease. Show less
Carotid atherosclerosis, a disease in which plaque builds up inside the vessel wall, is a major cause of ischemic stroke. Traditionally, atherosclerosis risk stratification is heavily based on... Show moreCarotid atherosclerosis, a disease in which plaque builds up inside the vessel wall, is a major cause of ischemic stroke. Traditionally, atherosclerosis risk stratification is heavily based on the percentage of stenosis. However, a growing body of evidence suggests that luminal stenosis may not be the only cause of symptoms but the plaque composition may be more likely to impact the disease outcome. High-resolution vessel wall magnetic resonance imaging (VWMRI) is one of the most promising modalities for visualizing and evaluating carotid atherosclerotic plaque. The quantitative assessment of carotid atherosclerotic disease requires vessel wall segmentation and plaque classification, which is generally performed by manual delineations. However, manual contour tracing is labor-intensive, time-consuming and subject to inter-observer and inter-scan variability, which makes manual image analysis impractical for studies where large volume of data needs to be processed. Therefore, the main goal of this thesis is to: 1) develop approaches to automatically, robustly and reproducibly segment the carotid vessel wall and classify the atherosclerotic plaque from multi-spectral VWMRI; 2) validate the developed methods with reference standard; 3) extract the imaging biomarkers that can assist carotid artery disease evaluation. Show less
De belangrijkste resultaten van dit proefschrift: de ASAS classificatie criteria voor axSpA blijken robuust en zijn goed toepasbaar in een setting waarbij de waarschijnlijkheid op axSpA lager is... Show moreDe belangrijkste resultaten van dit proefschrift: de ASAS classificatie criteria voor axSpA blijken robuust en zijn goed toepasbaar in een setting waarbij de waarschijnlijkheid op axSpA lager is dan waarin de criteria ontwikkeld zijn. Daarnaast is er op basis van bevindingen in dit proefschrift een belangrijke aanpassing doorgevoerd in een hulpmiddel dat reumatologen begeleidt in het diagnostische proces van (vroege) axSpA. Tevens is het MRI protocol van het SPACE cohort aangepast nadat de toegevoegde waarde van het toedienen van een contrastvloeistof bij het maken van MRI’s nihil bleek te zijn, met als resultaat dat er sinds april 2012 geen MRI’s meer worden gemaakt met de toediening van gadolinium. Dit proefschrift biedt ook adequate handvatten voor verder onderzoek naar de optimale definitie van een positieve MRI. Bovendien worden discrepanties aangaande de beoordeling door verschillende soorten lezers van afwijkingen in de rug (op röntgenfoto’s en MRI’s) aan het licht gebracht waardoor de vraag naar voren komt of training in het onderscheiden van axSpA afwijkingen en afwijkingen die niet gerelateerd zijn aan axSpA van potentiële belang is op de betrouwbaarheid van het beoordelen van afwijkingen in de rug. De onderzoeken in dit proefschrift leveren een bijdrage aan betere herkenning en behandeling van axSpA. Show less
The Mbam languages of Cameroon have a unique position in Bantu linguistics. Being in between “narrow” Bantu and “wide” Bantu, they sometimes pattern with the one and sometimes with the other, and... Show moreThe Mbam languages of Cameroon have a unique position in Bantu linguistics. Being in between “narrow” Bantu and “wide” Bantu, they sometimes pattern with the one and sometimes with the other, and as such are a rich motherlode for comparative and historical research. The Mbam languages have another point of interest as well. They have been previously analysed as standard 7 vowel languages (/i,e,ɛ,a,ɔ,o,u/) with Advanced Tongue Root (ATR) harmony. While vowel harmony in African languages has received a lot of attention and study, and the vowel-harmony systems of not a few of the Mbam languages have been studied, most of the previous studies have been on individual languages. This study seeks to analyse and compare the vowel systems of ten Mbam languages as a group: both their vowel inventories and their vowel-harmony systems. Various issues in vowel harmony, such as neutral vowels, directionality in and domains of vowel harmony are discussed. This study also proposes a phonological explanation for the functioning of the complex vowel-harmony systems found in the Mbam languages. Finally this study considers the internal classification of the Mbam languages and their position in the wider linguistic context of the Bantu and Bantoid languages. Show less
Hoverflies of the subfamily Microdontinae (Diptera: Syrphidae) have a reputation for causing confusion. Their diversity in shape and size is astonishing: from large, furry-haired species and... Show moreHoverflies of the subfamily Microdontinae (Diptera: Syrphidae) have a reputation for causing confusion. Their diversity in shape and size is astonishing: from large, furry-haired species and convincing wasp-mimics to tiny, unsightly creatures, easily mistaken for something uninteresting. The larvae resemble slugs so much that biologists have described them as molluscs on several occasions. Worldwide, hundreds of species of Microdontinae have been described, but so far there has been no comprehensive attempt to unravel this hotchpotch of names. This thesis examines the phylogenetic relationships of Microdontinae, based on morphological and molecular characters, in order to construct a new classification of the subfamily. A total number of 51 (sub)genera (11 new) are recognized, in which 472 valid species (49 new) are classified, resulting in many new combinations. The newly proposed classification facilitates species level taxonomy. In addition, it should provide a framework for further research on biogeography, (cryptic) speciation and evolution of host specialization. This thesis takes a first shot at some of these subjects by exploring the taxonomy of Neotropical Microdontinae that mimic stingless bees, reviewing and evaluating the associations of these flies with ants, and speculating on their historical biogeography. Show less
The concept of distance is a fundamental notion that forms a basis for the orientation in space. It is related to the scientific measurement process: quantitative measurements result in numerical... Show moreThe concept of distance is a fundamental notion that forms a basis for the orientation in space. It is related to the scientific measurement process: quantitative measurements result in numerical values, and these can be immediately translated into distances. Vice versa, a set of mutual distances defines an abstract Euclidean space. Each system is thereby represented as a point, whose Euclidean distances approximate the original distances as close as possible. If the original distance measures interesting properties, these can be found back as interesting patterns in this space. This idea is applied to complex systems: The act of breathing, the structure and activity of the brain, and dynamical systems and time series in general. In all these situations, optimal transportation distances are used; these measure how much work is needed to transform one probability distribution into another. The reconstructed Euclidean space then permits to apply multivariate statistical methods. In particular, canonical discriminant analysis makes it possible to distinguish between distinct classes of systems, e.g., between healthy and diseased lungs. This offers new diagnostic perspectives in the assessment of lung and brain diseases, and also offers a new approach to numerical bifurcation analysis and to quantify synchronization in dynamical systems. Show less
The term primary cutaneous B-cell lymphomas refers to a heterogeneous group of B-cell non-Hodgkin lymphomas, that present in the skin without evidence of extracutaneous disease at the time of... Show moreThe term primary cutaneous B-cell lymphomas refers to a heterogeneous group of B-cell non-Hodgkin lymphomas, that present in the skin without evidence of extracutaneous disease at the time of diagnosis. In recent years, there has been considerable debate regarding the classification and terminology of the group of primary cutaneous B-cell lymphomas and different classification schemes were used. In the new WHO-EORTC consensus classification for cutaneous lymphomas published in 2005, three major groups of primary cutaneous B-cell lymphoma are distinguished: primary cutaneous marginal zone B-cell lymphoma and primary cutaneous follicle center lymphoma with a good prognosis, and primary cutaneous diffuse large B-cell lymphoma, leg type with an intermediate prognosis. Studies presented in this thesis focus on three aspects of these primary cutaneous B-cell lymphomas: (1) the clinical usefulness of the WHO-EORTC classification in daily practice, (2) the validity of prognostic parameters reported in previous studies and identified in patient groups classified according to previously used classification schemes and (3) optimal management for the different types of primary cutaneous B-cell lymphomas as defined in the WHO-EORTC classification. Show less
Primair cutane B-cel lymfomen (CBCL) vormen een heterogene groep van non-Hodgkin lymfomen die zich primair in de huid manifesteren zonder aanwezigheid van extracutane lokalisaties. Volgens de in... Show morePrimair cutane B-cel lymfomen (CBCL) vormen een heterogene groep van non-Hodgkin lymfomen die zich primair in de huid manifesteren zonder aanwezigheid van extracutane lokalisaties. Volgens de in Nederland toegepaste EORTC-classificatie kunnen 3 typen CBCL onderscheiden worden: het primair cutaan immunocytoom of marginale zone B-cel lymfoom, het primair cutaan follikelcentrumcel lymfoom en het primair cutaan grootcellig B-cel lymfoom van het been. De studies in dit proefschrift hebben door middel van clinicopathologisch onderzoek en verschillende moleculair biologische technieken (waaronder genexpressie analyse, array-CGH en FISH-analyse) geresulteerd in de identificatie van een aantal nieuwe diagnostische en prognostische markers en daarnaast specifieke genetische kenmerken van de verschillende typen CBCL aangetoond. Deze resultaten hebben in de eerste plaats geleid tot een betere definitie van de verschillende typen CBCL. Daarnaast hebben de resultaten van deze studies een belangrijke rol gespeeld in de totstandkoming van een nieuwe consensus classificatie voor cutane lymfomen in 2005. In deze WHO-EORTC classificatie worden de volgende 3 belangrijkste typen CBCL onderscheiden: het primair cutaan marginale zone B-cel lymfoom, het primair cutaan follikelcentrum lymfoom en het primair cutaan grootcellig B-cel lymfoom, been type. Show less
The feasibility of earprint individualization depends upon the amount of variation in prints of different ears, but also upon that in prints of a single ear. In order to determine the limits to... Show moreThe feasibility of earprint individualization depends upon the amount of variation in prints of different ears, but also upon that in prints of a single ear. In order to determine the limits to intra-individual variation, we need to explore its potential causes. As the amount of force that is applied by the ear to the listening surface influences the appearance of the earprint, we investigated factors potentially affecting this force, such as the level and frequency of a target sound, and the level of ambient noise. We also investigated whether presence or absence of a target sound was of influence. Additionally, we explored if the duration of listening, and whether the ear had been recently cleaned or not, affected the appearance of an earprint. To evaluate the extent to which features may vary with passing time, we further attempted to determine the rate of growth of the external ear during adult life. As a next step, we then compared realistic intra-individual variation in earprints with a very small degree of inter-individual variation, i.e., that in prints of identical twins. To do so, we explored a method to fully automatically analyze prints. To our knowledge, this was the first time that any method capable of fully automated earprint comparisons has been described. Show less
Primary cutaneous lymphoma form a seperate group of non-Hodgkin lymphoma. Apart from the usual nodal presentation of a lymphoma, less frequently a lymphoma develops in an extranodal site. The skin... Show morePrimary cutaneous lymphoma form a seperate group of non-Hodgkin lymphoma. Apart from the usual nodal presentation of a lymphoma, less frequently a lymphoma develops in an extranodal site. The skin is, after the gastrointestinal tract, the most frequent site of extranodal lymphoma. If the skin is the primary site of involvement, i.e. no extracutaneous sites are involved at diagnosis, these lymphomas are called primary cutaneous lymphoma. In this thesis different types of primary cutaneous lymphoma are evaluated and discussed. In chapter 2 a large group of primary cutaneous CD30+ lympoproliferations is described and compared with a group of systemic CD30+ ALCL with skin localisations. Lymphomatoid papulosis and primary cutaneous CD30+ CTCL are closely related conditions and should be considered as a spectrum, with a comparable, excellent, prognosis. Multiagent chemotherapy (MAC) could not induce long lasting remissions, in fact all patients treated with MAC developed one or more (cutaneous) relapses. Therefor MAC is only indicated in case of extracuteneous localisations. In chapter 3 a group of CD30-negative T-cell lymphomas presenting in the skin that could not be diagnosed as MF, SS or SPTL are evaluated. In this group there were few survivors, apart from a rare group of patients with primary cutaneous lymphoma with small-medium sized CD4+/CD8-neoplastic T-cells (less than 30% large cells). In particular, patients with localized disease had an excellent prognosis. In chapter 4 haematological malignancies presenting in the skin and expressing CD56 were collected, both from the Dutch cutaneous lymphoma group and literature. In general these types of malignancies had a poor prognosis, except for patients with primary cutaneous CD30+ LPD, that showed a similar good prognosis as CD56-negative cases. Most cases belonged to the group of nasal-type NK/T-cell lymphoma and the group of CD4+, CD56+ hematodermic neoplasm (formerly also designated as blastic NK-cell lymphoma. In addition, CD56 was expressed in some SPTL, rare primary cutaneous CD30-negative large T-cell lymphomas, skin localisations of acute myeloid leukemia and CD30+ CTCL. In most of these groups CD56 expression did not affect prognosis. However, in SPTL CD56 expression proved a marker for gamma/delta T-cell origin and these cases showed a poorer prognosis as compared to SPTL with an alpha/beta phenotype (that were usually CD56-negative). In the new WHO-EORTC classification the category of SPTL only includes cases with an alpha/beta-positive phenotype, whereas cases with a gamma/delta positive phenotype are included in the provisional category of cutaneous gamma/delta-positive T-cell lymphoma. In chapter 5 a rare case of lymphomatoid papulosis with CD56-expression was presented and the frequency of co-expression of CD56 in primary cutaneous CD30+ LPD was analyzed. CD56 expression was found in approximately 10% of CD30+ LPD (both LyP and primary CD30+ CTCL). However, these CD56+ cases were not found to have a different prognosis from CD56 negative cases. In chapter 6 a European multicenter study on primary cutaneous large B-cell lymphomas is presented. Patients with primary cutaneous large B-cell lymphoma of the leg showed a poorer prognosis as patients with primary cutaneous follicle center cell lymphoma (PCFCCL). Moreover, round cell morphology was identified as a poor prognostic parameter. Although this was closely related to presentation on the leg(s), also in the group of PCFCCL the presence of a predominance of cells with round nuclei (centroblasts and immunoblasts) was associated with a poorer prognosis. The results of this study contributed to a new category in the WHO-EORTC classification, designated primary cutaneous large B-cell lymphoma (PCLBCL), leg-type, indicating that both patients with the classical presentation on the leg(s) as patients showing the same morphology and immunophenotype (bcl-2+, Mum-1/ IRF4+) on other sites are included in this group. Presentation with multifocal lesions proved to be a poor prognostic parameter for PCLBCL-leg-type, but not for PCFCCL. In chapter 7 treatment results in multifocal primary CBCL were analyzed. The main question in this study was if PCFCCL presenting with multifocal skin lesions should be treated with MAC. The study showed that MAC is only indicated in PCLBCL, leg-type and not in (multifocal) PCFCCL. Radiotherapy on multiple sites appeared equally effective as MAC in these patients. In chapter 8 the frequency of CNS-involvement in CBCL patients of the Dutch cutaneous lymphoma group. was evaluated. The frequency was low. Only 4/140 patients with a primary CBCL developed CNS involvement in the course of their disease. Interestingly 3 of these 4 patients were PCFCCL, a lymphoma usually with an excellent prognosis. Only 4 disease related deaths were reported in this group of which 3 with CNS involvement. The reason for this relatively high prevalence of CNS involvement in PCFCCL is unclear. The studies presented in this thesis have provided important information, which has contributed to the recent development of the WHO-EORTC classification. Moreover, they have contributed to updated guidelines for the treatment of the different types of primary cutaneous lymphomas, as presented in TABLE 2 in chapter 9. Show less
