As a human commensal, Staphylococcus aureus colonizes more than half of the population. Colonized persons are often asymptomatic and can be colonized in the anterior nares, throat, groin, and other... Show moreAs a human commensal, Staphylococcus aureus colonizes more than half of the population. Colonized persons are often asymptomatic and can be colonized in the anterior nares, throat, groin, and other body sites. In only a minority, S. aureus causes disease - ranging from common and relatively benign infections such as folliculitis to severe invasive infections such as endocarditis, spondylodiscitis, and bacteremia. S. aureus is the leading cause of mortality by bloodstream infections worldwide. A major additional complicating factor is the capacity of S. aureus to develop antimicrobial resistance. Colonization with methicillin-resistant S. aureus (MRSA) increases infection risk even more than its susceptible counterpart. MRSA is currently the leading cause of mortality attributable to antimicrobial resistance in the world. Despite the high prevalence and global burden of S. aureus, many questions remain unanswered with respect to the management and risk factors of both colonization and invasive infection. Research is continuously ongoing in order to unravel the complexities of this extraordinary pathogen and the diseases it causes in humans. This thesis aims to address the optimization of MRSA decolonization and some of the frequently encountered challenges in S. aureus bacteremia management. Show less
Dutch civil law sets out several sanctions in the form of loss of rights due to inactive or inconsistent behaviour of the creditor. This book focuses on two specific manifestations of this... Show moreDutch civil law sets out several sanctions in the form of loss of rights due to inactive or inconsistent behaviour of the creditor. This book focuses on two specific manifestations of this mechanism: a specific application of the doctrine of estoppel in Dutch law of obligations and the statutory expiration periods set out by article 6:89 and 7:23 under 1 of the Dutch Civil Code. These articles stipulate that the creditor loses all of its claims if he does not complain about any defects in the performance of the debtor as soon as possible after discovery of any such defect. Show less
Surgery is a key treatment option for prostate cancer patients which is rapidly evolving with the rise of minimally invasive robotic techniques and image-guided surgery. In these approach, Enhanced... Show moreSurgery is a key treatment option for prostate cancer patients which is rapidly evolving with the rise of minimally invasive robotic techniques and image-guided surgery. In these approach, Enhanced dexterity and decision-making, help improve the surgeon-robot-patient interaction. By improving this level of interaction, surgery can achieve a level of precision that leads to improved patient outcomes. As such, improved environmental awareness during surgery can aid more precise targeting of cancerous tissues and better protection of healthy tissues. This means that technological innovations, such as target-specific radiopharmaceuticals and advanced surgical sensory modalities, are necessary to enhance surgical perception. The influence of such perception-enhancing technologies on surgeons' actions can best be objectively assessed by analyzing the movements of surgical instruments, performed during these procedures. Digitized instrument kinematics provide a wealth of data representative of the interaction dexterity and decision-making that, until now, has been largely neglected in the field of image-guided surgery. This work represents a significant first step toward incorporating interactive perception assessments into image-guided surgery. The aim is to evaluate the influence of newly developed technologies and guide the design of future advancements. Show less
5000 years ago, a migration shaped Europe’s future. Migrating communities spread across Europe within two centuries, leaving lasting changes in connectivity, language, and genetics. Yet these... Show more5000 years ago, a migration shaped Europe’s future. Migrating communities spread across Europe within two centuries, leaving lasting changes in connectivity, language, and genetics. Yet these migrating communities did not enter an empty continent. Across Europe, they encountered indigenous communities with millennia-old roots. What interactions between migrating and indigenous communities drove the changes seen in the archaeological record? This dissertation sheds new light on this question with an innovative approach to ceramics. Ceramics bear traces of production techniques which potters learned and applied to create them. The approach outlined here can quantitatively assess the amount of shared knowledge between potters from these traces by combining the chaîne opératoire method with network analysis and probability theory. This approach is applied to ceramics from migrating Corded Ware communities and indigenous Funnel Beaker West communities in the Netherlands to detect whether potters in these communities interacted and shared knowledge. The outcomes offer a unique perspective on this period and prehistoric migrations in general. Migrating and indigenous communities are shown to co-exist for several centuries at the start of the third millennium BCE with evidence for migrant potters learning repeatedly from indigenous potters and incorporating this knowledge into the production of Corded Ware vessels. Show less
This thesis investigates the application of deep learning techniques in image analysis across various domains, focusing on four main themes: feature extraction, classification, segmentation, and... Show moreThis thesis investigates the application of deep learning techniques in image analysis across various domains, focusing on four main themes: feature extraction, classification, segmentation, and integration, demonstrating the transformative potential of these technologies. The research begins by addressing feature extraction and classification challenges in agricultural biotechnology. It introduces efficient deep Convolutional Neural Networks (CNNs) that significantly automate and enhance corn seed classification accuracy, surpassing traditional methods. The second theme uses advanced CNNs to classify the ripeness stages of mulberries, enhancing sorting accuracy and improving post-harvest processing, which potentially increases economic value and eliminates the need for specialist assessments. The third theme applies CNNs for segmenting microscope images, particularly focusing on zebrafish larvae in high-throughput settings, demonstrating their ability to accurately differentiate larvae, which supports high-throughput screening and facilitates biological research advancements. The final theme integrates deep learning with Natural Language Processing (NLP) to refine image captioning techniques, creating more precise, context-aware descriptions beneficial to various fields like biomedical imaging and digital media. Employing state-of-the-art deep learning models, the thesis tackles distinct, challenging problems, setting new benchmarks and paving the way for future research. This work underscores the efficacy of deep learning in enhancing image analysis and processing, revolutionizing multiple industries and fostering significant societal and technological advancements. Show less
****Posthumous PhD ceremony held on September 18, 2024 ; originally designated on September 6, 2023.****Security Force Assistance (SFA), enhancing the capability and capacity of foreign... Show more****Posthumous PhD ceremony held on September 18, 2024 ; originally designated on September 6, 2023.****Security Force Assistance (SFA), enhancing the capability and capacity of foreign securityforces, is increasingly considered a valuable tool in of Western States’ international policy.To be sure, equipping, training and mentoring local troops is not a novel phenomenon.Yet, accompanying and mentoring the recipient forces in combat arguably remains oneof the most challenging aspects of SFA. During the war in Afghanistan, allied OperationalMentoring and Liaison Teams (OMLTs) operated shoulder to shoulder with AfghanNational Army units in austere conditions. Although enhancing Afghan security forceswas regarded a central tenet in the allied campaign, the OMLTs were initially grantedlimited attention by the various troop contributing nations. This research examines theBritish, Dutch and Belgian OMLTs and their efforts to adapt to their challenging tasks.Furthermore, it sheds light on the relationship between Western troops and Afghanforces with occasional diverging professional views. As a theoretical lens this study utilises Military Innovation theory to analyse the adaptation processes within each case study. Finally, the research breaks new empirical ground by examining a vast range of sources. The three case studies are based on archivalrecords, official evaluations, regimental histories, surveys and over 220 semistructuredinterviews Show less
BACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS\nIntranasal administration of respiratory vaccines offers many advantages such as eliciting both systemic and mucosal immunity at the point of viral entry.... Show moreBACKGROUND\nMETHODS\nRESULTS\nCONCLUSIONS\nIntranasal administration of respiratory vaccines offers many advantages such as eliciting both systemic and mucosal immunity at the point of viral entry. Immunogenicity of intranasal vaccination can be improved through the use of adjuvants. Bacteria-like particles derived fromLactococcus lactishave the potential to serve as a vaccine adjuvant.This clinical study investigated the safety, reactogenicity and immunogenicity of intranasal seasonal influenza vaccine adjuvanted with gram-positive matrix particles (FluGEM®).\nThis was a first-in-human, randomized, double-blind, controlled, dose-escalation study performed at the Centre for Human Drug Research (CHDR), the Netherlands. Participants aged 18-49 were randomized in a 3:1 ratio to receive FluGem® in ascending doses (two-dose regimens) together with a standard trivalent inactivated influenza vaccine or unadjuvanted TIV only. Primary outcomes were safety and tolerability. Secondary outcomes were serum hemagglutination inhibition (HI) antibody titers and mucosal IgA. The most immunogenic dose was used in an additionalelderly cohort (>65 years).\nNinty participants were included. Intranasal FluGem®was safe and well tolerated. The majority of adverse events were mild (97.4 %) with (un)solicited adverse events comparable across all dose levels and control groups. All groups showed geometric mean increases ≥ 2.5-fold. Seroconversion (≥40 % participants) was achieved at both day 21 (single-dose) and 42 (two-dose) for the 1.25 mg dose and on day 42 (two-dose only) for the 2.5 mg dose. Highest geometric mean IgA increases were observed in the 1.25 mg group on day 21. Immunogenicity was less pronounced in elderly.\nIntranasal vaccination of FluGEM®was safe and tolerable in healthy adult volunteers aged 18-49 years and 65 and older. Highest immunogenicity was observed for 1.25 mg and 2.5 mg doses (compared to 5 mg) suggesting a potential non-linear dose-response relationship.More research is needed to further investigate the capabilities of bacteria-like peptides as adjuvants. Show less
This thesis advances the scope of DWI in MRI, with a particular focus on water/fat separated msh-EPI based on chemical shift encoding. It outlines ways to simplify the data acquisition, boiling it... Show moreThis thesis advances the scope of DWI in MRI, with a particular focus on water/fat separated msh-EPI based on chemical shift encoding. It outlines ways to simplify the data acquisition, boiling it down to the essential, producing diffusion weighted images with chemical shift encoding on top in a very efficient manner. It presents different algorithms for effective water/fat separation and improved image reconstruction. These methods address challenges such as spatial shifts of fat signals and motion-induced shot-to-shot phase variations to improve the image quality and accuracy of DWI, and shows the application in different anatomical regions, such as leg, brain, head-neck and prostate. The research combines advanced modeling techniques, such as SENSE-based approaches and structured low-rank concepts, to achieve superior image quality and make significant contributions to the application of DWI in potential clinical diagnostics. Show less
Research indicates that interactions with law enforcement, determinative of access to justice is far from positive for racial minorities and women and is often characterized by suspicion,... Show moreResearch indicates that interactions with law enforcement, determinative of access to justice is far from positive for racial minorities and women and is often characterized by suspicion, unfriendliness and dismissal of complaints. This conduct is not easily captured by prohibitive regulation although it can amount to discrimination proscribed by equality laws. Training, monitoring and codes of conduct have had limited effect. This book, therefore, explores another approach to legally compliant behaviour, a lens which focuses on the internalization of norms underlying laws and regulations, through persuasive technology. Drawing from the nudge theory, as well as Lessig's articulation of the influence of norms and architecture on behaviour, this book takes an interdisciplinary approach, rooted in a broader view of the law's impact on human cognition and decision making and technology's impact on behaviour. The inter-disciplinary lens combines an understanding of the cognitive and organizational factors driving discrimination with behaviour change theories such as the social identity theory, and technological artefacts like conversational agents that can influence behaviour, to proffer an alternative solution. This work constitutes the first steps towards addressing discriminatory behaviour by leveraging the ubiquity and versatility of technology to regulate behaviour in accordance with the law and its intentions. Show less
The dissertation explores the intricate relationship between family dynamics, legal practices, and the status of women in Ba County during nineteenth century (1803-1873). It delves into how family... Show moreThe dissertation explores the intricate relationship between family dynamics, legal practices, and the status of women in Ba County during nineteenth century (1803-1873). It delves into how family members leveraged the Great Qing Code and Confucian values, particularly the cult of female chastity and made use of the identity of women to gain advantage in court. The research examined 617 cases from the Ba County Archive in order to shed light on the interplay of law, state ideology, and patriarchal systems. The legal records offer a “representational reality”, influenced by state ideology, rather than an accurate depiction of women’s lives. Legal cases highlighted the instrumental use of women, their lack of agency, and disputes over their ownership, but the passive status of women was just a representational reality. Family relationships and litigation strategies were the key to understanding the narratives on women in the Ba County Archive, and the passive status of women was a result of such depiction. Show less
This thesis describes innovative interventions that aim to improve clinical workplace learning in a clerkship internal medicine. Clinical workplace learning is challenging in many aspects. It takes... Show moreThis thesis describes innovative interventions that aim to improve clinical workplace learning in a clerkship internal medicine. Clinical workplace learning is challenging in many aspects. It takes place through participation in actual patient care and is dependent on collaboration with other healthcare professionals. The workplace may consist of physical, online and virtual learning environments, The interventions in this thesis targeted these three elements by the development and analysis of 1). interprofessional learning activities in a Clinical Teaching Unit (CTU), 2) a Small Private Online Course (SPOC) using theoretical and practical educational principles to stimulate motivation and collaborative learning, and 3). remote learning in a virtual environment using head-mounted cameras at bedside. The findings imply that implementation of a CTU not only facilitates the integration of patient care and education but also the integration of different professions working together. The SPOC is a useful and accessible addition to the clinical learning environment, however online collaboration remains challenging. Virtual learning with cameras on site could offer sustainable opportunities for interprofessional, crossinstitutional or even international learning with real patient encounters. Show less
Software development is a complex process. It is important that software products become stable and maintainable assets. We examine and extend a software development framework that has been... Show moreSoftware development is a complex process. It is important that software products become stable and maintainable assets. We examine and extend a software development framework that has been designed to support development in a flexible manner, namely Scrum. We apply machine learning methods in the hope to better understand what happens during the development process and provide predictions of Scrum sprint progress and product backlog sizes, among other indications of success. To obtain our data set, we design and construct a data acquisition pipeline using agent-based networking and query templates for generalized feature extraction. We provide overviews and in-depth reports for decision support and highlights of other aspects of the development ecosystem through information visualizations. Show less
Protoplanetary disks are the gas and dust environments where planetary systems form around young stars. Using observations from the Atacama Large Millimeter/submillimeter Array (ALMA) this thesis... Show moreProtoplanetary disks are the gas and dust environments where planetary systems form around young stars. Using observations from the Atacama Large Millimeter/submillimeter Array (ALMA) this thesis analyses the gaseous molecular reservoir, using multiple tracers to resolve the 3D structure of protoplanetary disks. Using observational and theoretical methods the focus is to study the vertical disk structure, which is expected to contain crucial information on the material distribution, thermal and radiative disk structure. This work presents new techniques to use the vertical dimension as a probe of the planet-forming conditions, obtaining measurements of material turbulence, total disk mass and molecular depletion. Overall, the results from this thesis have laid the foundations for many future studies focusing on resolving the initial planet-forming conditions throughout the 3D protoplanetary disk structure. Show less
Pseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this... Show morePseudomonas Aeruginosa is a Gram-negative bacterium which can form biofilms, increasing its resistance against antibiotics and the host immune system. Polysaccharides are an integral part of this biofilm, one of these polysaccharides is called Psl. PslG is a glycosidase, able to cleave this polysaccharide, Psl, into smaller fragments. This decreases the antibiotic resistance of P. Aeruginosa. Interestingly PslG is produced by P. Aeruginosa itself, where it is found on the synthesis gene of Psl. The exact effects of PslG remain partly unknown. Moreover, only hypotheses have been made as to why P. Aeruginosa expresses such an enzyme. Here we have developed a set of activity-based probes based on Psl to discover the mode of action of PslG. Subsequently, a set of inhibitors have been designed based on the Psl motive and the mechanism of action of PslG. PslG was then co-crystallized with the inhibitors in order to study their binding interactions. Show less
This thesis explores the role of lipid mediators (LM) in osteoarthritis (OA), examining their profiles in patients and how therapeutic interventions influence these profiles. The first part reviews... Show moreThis thesis explores the role of lipid mediators (LM) in osteoarthritis (OA), examining their profiles in patients and how therapeutic interventions influence these profiles. The first part reviews the therapeutic potential of LM, particularly in non-weight-bearing joints, validated through the Hand OA Prednisolone Efficacy (HOPE) study. The second part focuses on LM regulation during the inflammatory response, identifying their role in innate and adaptive immunity, particularly in monocyte-derived macrophages. The third part investigates the mechanisms by which pro-inflammatory and pro-resolving LMs function, using 17-HDHA and oleic acid as models to study their effects on cellular behavior and inflammation resolution. Show less
Healthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of... Show moreHealthy aging is one of the prime goals in today's society and atherosclerosis is among the greatest causes of morbidity in elderly. Cardiovascular disease patients receiving treatment are often of advanced aged and have an aged immune system, which limits translating experimental findings to the patient. It is therefore essential to take aging into consideration when investigating immune cells and their responses in atherosclerosis studies. This thesis describes research exploring the impact of aging on the immunological landscape in atherosclerotic cardiovascular disease using single-cell profiling. Through the use of a highly translational aging mouse model of atherosclerosis, we characterized inflammation in the plaques of young versus old mice. We discovered new cell types (T and B cells) not present in young mice with atherosclerosis. These cells secrete a variety of inflammatory factors that may contribute to the disease process and exacerbate arteriosclerosis. While the aged B cell is more prevalent in female mice, the aged T cell is more abundant in male mice. We then also found these aged cells in the blood and plaques of cardiovascular disease patients. These aged cell types could be interesting targets for future treatments against progression of atherosclerotic cardiovascular disease. Show less
