Objectives To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the... Show moreObjectives To investigate the prevalence of axial spondyloarthritis (axSpA) in patients with chronic back pain (CBP) of less than 2 years (2y) duration referred to the rheumatologist, the development of diagnosis over time, and patient characteristics of those developing definite (d-)axSpA over 2y. Methods We analysed the 2y data from SPondyloArthritis Caught Early, a European cohort of patients (<45 years) with CBP (>= 3 months, <= 2y) of unknown origin. The diagnostic workup comprised evaluation of clinical SpA features, acute phase reactants, HLA-B27, radiographs and MRI (sacroiliac joints and spine), with repeated assessments. At each visit (baseline, 3 months, 1y and 2y), rheumatologists reported a diagnosis of axSpA or non-axSpA with level of confidence (LoC; 0-not confident at all to 10-very confident). Main outcome: axSpA diagnosis with LoC >= 7 (d-axSpA) at 2y. Results In 552 patients with CBP, d-axSpA was diagnosed in 175 (32%) at baseline and 165 (30%) at 2y. Baseline diagnosis remained rather stable: at 2y, baseline d-axSpA was revised in 5% of patients, while 8% 'gained' d-axSpA. Diagnostic uncertainty persisted in 30%. HLA-B27+ and baseline sacroiliitis imaging discriminated best 2y-d-axSpA versus 2y-d-non-axSpA patients. Good response to non-steroidal anti-inflammatory drugs and MRI-sacroiliitis most frequently developed over follow-up in patients with a new d-axSpA diagnosis. Of the patients who developed MRI-sacroiliitis, 7/8 were HLA-B27+ and 5/8 male. Conclusion A diagnosis of d-axSpA can be reliably made in nearly one-third of patients with CBP referred to the rheumatologist, but diagnostic uncertainty may persist in 5%-30% after 2y. Repeated assessments yield is modest, but repeating MRI may be worthwhile in male HLA-B27+ patients. Show less
Background: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies... Show moreBackground: Recent advances in data-driven computational approaches have been helpful in devising tools to objectively diagnose psychiatric disorders. However, current machine learning studies limited to small homogeneous samples, different methodologies, and different imaging collection protocols, limit the ability to directly compare and generalize their results. Here we aimed to classify individuals with PTSD versus controls and assess the generalizability using a large heterogeneous brain datasets from the ENIGMA-PGC PTSD Working group. Methods: We analyzed brain MRI data from 3,477 structural-MRI; 2,495 resting state-fMRI; and 1,952 diffusion-MRI. First, we identified the brain features that best distinguish individuals with PTSD from controls using traditional machine learning methods. Second, we assessed the utility of the denoising variational autoencoder (DVAE) and evaluated its classification performance. Third, we assessed the generalizability and reproducibility of both models using leave-one-site-out cross-validation procedure for each modality. Results: We found lower performance in classifying PTSD vs. controls with data from over 20 sites (60 % test AUC for s-MRI, 59 % for rs-fMRI and 56 % for D-MRI), as compared to other studies run on single-site data. The performance increased when classifying PTSD from HC without trauma history in each modality (75 % AUC). The classification performance remained intact when applying the DVAE framework, which reduced the number of features. Finally, we found that the DVAE framework achieved better generalization to unseen datasets compared with the traditional machine learning frameworks, albeit performance was slightly above chance. Conclusion: These results have the potential to provide a baseline classification performance for PTSD when using large scale neuroimaging datasets. Our findings show that the control group used can heavily affect classification performance. The DVAE framework provided better generalizability for the multi-site data. This may be more significant in clinical practice since the neuroimaging-based diagnostic DVAE classification models are much less site-specific, rendering them more generalizable. Show less
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
Arend, B.W.H. van der; Verhagen, I.E.; Leeuwen, M. van; Arend, M.Q.T.P. van der; Casteren, D.S. van; Terwindt, G.M. 2023
BackgroundThere is a need for standardization of the definition of a migraine day for clinical and research purposes. MethodsWe prospectively compared different definitions of a migraine day with E... Show moreBackgroundThere is a need for standardization of the definition of a migraine day for clinical and research purposes. MethodsWe prospectively compared different definitions of a migraine day with E-diary data of n = 1494 patients with migraine. We used a baseline definition based on migraine characteristics with a duration of >= 4 hours OR triptan intake (independently from its effect) OR (visual) aura lasting 5-60 minutes. ResultsOf all migraine days defined by triptan intake only, 66.2% had a duration <4 hours. Adjusting the headache duration criterion to >= 30 minutes led to a decrease in days defined by triptan intake only and resulted in a 5.4% increase in total migraine days (equals 0.45 migraine day increase in monthly migraine days). These additional migraine days had a median duration of 2.5 hours. ConclusionWe propose to define a migraine day as follows: 1) (a) headache duration >= 30 minutes; (b) matching >= 2 of four characteristics: unilateral, pulsating, moderate to severe pain, aggravation by or causing avoidance of routine physical activity; and (c) during headache >= 1 of the following: nausea and/or vomiting, photophobia and phonophobia or 2) (visual) aura duration 5-60 minutes or 3) a day with headache for which acute migraine-specific medication is used irrespective of its effect. 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
Based on recent achievements in phylogenetic studies of the Brassicaceae, a novel infrafamilial classification is proposed that includes major improvements at the subfamilial and supertribal levels... Show moreBased on recent achievements in phylogenetic studies of the Brassicaceae, a novel infrafamilial classification is proposed that includes major improvements at the subfamilial and supertribal levels. Herein, the family is subdivided into two subfamilies, Aethionemoideae (subfam. nov.) and Brassicoideae. The Brassicoideae, with 57 of the 58 tribes of Brassicaceae, are further partitioned into five supertribes, including the previously recognized Brassicodae and the newly established Arabodae, Camelinodae, Heliophilodae, and Hesperodae. Additional tribus-level contributions include descriptions of the newly recognized Arabidopsideae, Asperuginoideae, Hemilophieae, Schrenkielleae, and resurrection of the Chamireae and Subularieae. Further detailed comments on 17 tribes in need of clarifications are provided. Show less
Monitoring the illegal trade of wool fibres of wild vicun~a (Vicugna vicugna) and guanaco (Lama guanicoe) is highly desirable. The high market value of fleece from these camelid species poses a... Show moreMonitoring the illegal trade of wool fibres of wild vicun~a (Vicugna vicugna) and guanaco (Lama guanicoe) is highly desirable. The high market value of fleece from these camelid species poses a threat to their wild populations. A previous study showed that direct analysis in real time time-of-flight mass spectrometry (DART-TOFMS) effectively identifies wool fibres to species. Producing high-resolution data in a short period of time makes DART-TOFMS a reliable identification tool, even though data analysis can still be improved. The present study proposes a novel data analysing pipeline based on Convolutional Neural Networks (CNN), applicable to any kind of DART-TOF MS data. We tested our proposed method on keratin fibres of four camelid species (Vicugna vicugna: n 1⁄4 19; Vicugna pacos: n 1⁄4 20; Lama guanicoe: n 1⁄4 20, and Lama glama: n 1⁄4 20). Analyses showed that selecting 512 ions with the highest relative intensity provides the best resolution and yields 100% accuracy for species identification. Show less
This paper introduces the Bradley-Terry regression trunk model, a novel probabilistic approach for the analysis of preference data expressed through paired comparison rankings. In some cases, it... Show moreThis paper introduces the Bradley-Terry regression trunk model, a novel probabilistic approach for the analysis of preference data expressed through paired comparison rankings. In some cases, it may be reasonable to assume that the preferences expressed by individuals depend on their characteristics. Within the framework of tree-based partitioning, we specify a tree-based model estimating the joint effects of subject-specific covariates over and above their main effects. We, therefore, combine a tree-based model and the log-linear Bradley-Terry model using the outcome of the comparisons as response variable. The proposed model provides a solution to discover interaction effects when no a-priori hypotheses are available. It produces a small tree, called trunk, that represents a fair compromise between a simple interpretation of the interaction effects and an easy to read partition of judges based on their characteristics and the preferences they have expressed. We present an application on a real dataset following two different approaches, and a simulation study to test the model's performance. Simulations showed that the quality of the model performance increases when the number of rankings and objects increases. In addition, the performance is considerably amplified when the judges' characteristics have a high impact on their choices. 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
This International evidence-based nomenclature and classification consensus on the congenital bicuspid aortic valve and its aortopathy recognizes 3 types of bicuspid aortic valve: 1. Fused type,... Show moreThis International evidence-based nomenclature and classification consensus on the congenital bicuspid aortic valve and its aortopathy recognizes 3 types of bicuspid aortic valve: 1. Fused type, with 3 phenotypes: right-left cusp fusion, right-non cusp fusion and left-non cusp fusion; 2. 2-sinus type with 2 phenotypes: Latero-lateral and antero-posterior; and 3. Partial-fusion or forme fruste. This consensus recognizes 3 bicuspid-aortopathy types: 1. Ascending phenotype; root phenotype; and 3. extended phenotypes. Show less
This International evidence-based nomenclature and classification consensus on the congenital bicuspid aortic valve and its aortopathy recognizes 3 types of bicuspid aortic valve: 1. Fused type,... Show moreThis International evidence-based nomenclature and classification consensus on the congenital bicuspid aortic valve and its aortopathy recognizes 3 types of bicuspid aortic valve: 1. Fused type, with 3 phenotypes: right-left cusp fusion, right-non cusp fusion and left-non cusp fusion; 2. 2-sinus type with 2 phenotypes: Latero-lateral and antero-posterior; and 3. Partial-fusion or forme fruste. This consensus recognizes 3 bicuspid-aortopathy types: 1. Ascending phenotype; root phenotype; and 3. extended phenotypes. Show less
This International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion,... Show moreThis International Consensus Classification and Nomenclature for the congenital bicuspid aortic valve condition recognizes 3 types of bicuspid valves: 1. The fused type (right-left cusp fusion, right-non-coronary cusp fusion and left-non-coronary cusp fusion phenotypes); 2. The 2-sinus type (latero-lateral and antero-posterior phenotypes); and 3. The partial-fusion (forme fruste) type. The presence of raphe and the symmetry of the fused type phenotypes are critical aspects to describe. The International Consensus also recognizes 3 types of bicuspid valve-associated aortopathy: 1. The ascending phenotype; 2. The root phenotype; and 3. Extended phenotypes. Show less
Rutgers, J.J.; Banki, T.; Kamp, A. van der; Waterlander, T.J.; Scheijde-Vermeulen, M.A.; Heuvel-Eibrink, M.M. van den; ... ; Krijger, R.R. de 2021
Background Histopathological classification of Wilms tumors determines treatment regimen. Machine learning has been shown to contribute to histopathological classification in various malignancies... Show moreBackground Histopathological classification of Wilms tumors determines treatment regimen. Machine learning has been shown to contribute to histopathological classification in various malignancies but requires large numbers of manually annotated images and thus specific pathological knowledge. This study aimed to assess whether trained, inexperienced observers could contribute to reliable annotation of Wilms tumor components for classification performed by machine learning. Methods Four inexperienced observers (medical students) were trained in histopathology of normal kidneys and Wilms tumors by an experienced observer (pediatric pathologist). Twenty randomly selected scanned Wilms tumor-slides (from n = 1472 slides) were annotated, and annotations were independently classified by both the inexperienced observers and two experienced pediatric pathologists. Agreement between the six observers and for each tissue element was measured using kappa statistics (kappa). Results Pairwise interobserver agreement between all inexperienced and experienced observers was high (range: 0.845-0.950). The interobserver variability for the different histological elements, including all vital tumor components and therapy-related effects, showed high values for all kappa-coefficients (> 0.827). Conclusions Inexperienced observers can be trained to recognize specific histopathological tumor and tissue elements with high interobserver agreement with experienced observers. Nevertheless, supervision by experienced pathologists remains necessary. Results of this study can be used to facilitate more rapid progress for supervised machine learning-based algorithm development in pediatric pathology and beyond. Show less
Renewed calls for decolonizing anthropology in the 21st century raise the question of what work earlier waves of decolonization since the 1960s have left undone. Some of this work should focus on... Show moreRenewed calls for decolonizing anthropology in the 21st century raise the question of what work earlier waves of decolonization since the 1960s have left undone. Some of this work should focus on the classification of human differences, which figured prominently in all phases of the discipline’s history: as a methodology in its racist phases, as an object of study during its late colonial phase of professionalization, as self-critical reflexivity in the 1980s and 1990s, and as a renewed critique in the 21st century. Can a universal methodology of studying classifications of human kinds arise from the discipline’s past of colonial stereotyping? I argue affirmatively, through an approach that recognizes time as the epistemic condition that connects past and present positions to present and future methodologies. Firstly, my analysis distinguishes the parochial embedding in colonial culture of Durkheim and Mauss’ ideas about classification from their more universal intentions. This is then developed into a threefold reflexive and timeful methodology of studying classification’s nominal-descriptive, constructive, and interventionist dimensions—a process of adding temporality to the study of classification. Subsequently, Antenor Firmin’s 19th-century critique of racial classifications, and W. E. B. Du Bois’s theory of double consciousness help to show how this threefold methodology addresses the insufficiently theorized process of being classified and discriminated against through racial categories wielded by the powers that be. These arguments radicalize the essay’s timeful perspective by concluding that we need to avoid modernist uses of time as classification and adopt the aforementioned threefold methodology in order to put time in classifications of human kinds. This reverses modern positivism’s subordination to methodological rules of the epistemic conditions posed by contingent history and shows instead that the universal goals of methodology should be understood as a future ideal. 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
Purpose To describe the clinical characteristics and outcome of polypoidal choroidal vasculopathy (PCV), also known as aneurysmal type 1 (sub-retinal pigment epithelium (RPE)) neovascularization,... Show morePurpose To describe the clinical characteristics and outcome of polypoidal choroidal vasculopathy (PCV), also known as aneurysmal type 1 (sub-retinal pigment epithelium (RPE)) neovascularization, in Caucasian patients. Methods Single-centre study in 66 Caucasian patients with a diagnosis of PCV based on optical coherence tomography scan and indocyanine green angiography. Clinical characteristics and multimodal imaging were collected and assessed by an experienced retina specialist. Results This study involved 74 eyes of 66 patients with PCV, with a mean age at onset of 73 years and a female preponderance of 66%. The mean number of polypoidal lesions per eye was 1 (range: 1-5 lesions), out of which 75% was located in the macula and 19% in the peripapillary region. Of the 74 eyes, 37 eyes (50%) had PCV associated with a drusenoidal neovascular age-related macular degeneration (AMD) phenotype (PCV-AMD) and 18 eyes (24%) had PCV associated with non-polypoidal type 1 choroidal neovascularization/branching vascular network (PCV-BVN) without signs of drusenoidal AMD, while 19 eyes (26%) had idiopathic, isolated PCV (iPCV). The mean subfoveal choroidal thickness measured in 22 patients was 245 mu m (range: 71-420 mu m). In 51% of patients, the initially performed therapy showed good anatomical recovery (resolution of intra- and subretinal fluid). Conclusions A spectrum of PCV (aneurysmal type 1/sub-RPE neovascularization) can be seen in Caucasian patients. PCV associated with a drusenoidal neovascular AMD phenotype in Caucasians is phenotypically and presumably pathophysiologically more associated with neovascular AMD (PCV-AMD: type A PCV). However, this may not be the case for patients with PCV with non-polypoidal type 1 choroidal neovascularization or BVN and no signs of drusenoidal AMD (PCV-BVN: type B PCV), and for patients with idiopathic PCV without associated drusen or BVN (iPCV; type C PCV). Most patients have a thin choroid, even when drusen are absent. For the entire patient group, a moderate anatomical recovery was observed after treatment. Show less
