This thesis described the further development of the controlled human hookworm model and several applications of this model. First, the hookworm egg excretion is modelled over time using Bayesian... Show moreThis thesis described the further development of the controlled human hookworm model and several applications of this model. First, the hookworm egg excretion is modelled over time using Bayesian statistics, resulting in the description of a plateau phase in egg output. Repeated infections a re then investigated as a means to improve the accuracy and statistical power of this output as an outcome measure. The hereby established model is then applied in an immunization study, which shows that it is possible to develop a protective response against short-term larval infection. The skin phase and IgG1 seem to play a role in the development of this protection. Furthermore, gut microbiome changes during controlled hookworm infection are described. Also, volunteers’ motivations and decision making process are investigated, resulting in the characterization of controlled human infection participants as ‘deliberate decision-makers’ and not ‘money-oriented risk-takers’. Following up on the findings in the study described, the importance of a multidisciplinary approach for the improvement of controlled human infection trials is argued in the discussion, with several recommendations made for further collaborative efforts in order to maximise social and scientific output of these studies. Show less
Earlier detection of pancreatic cancer is necessary to improve its poor prognosis. Currently, screening of the general population is not feasible due to the relatively low lifetime risk. However,... Show moreEarlier detection of pancreatic cancer is necessary to improve its poor prognosis. Currently, screening of the general population is not feasible due to the relatively low lifetime risk. However, up to one in ten cases occur in individuals with a strong family history of germline mutation carriers, known as high-risk individuals (HRIs). For these HRIs, pancreatic cancer surveillance in expert centers is recommended. The first part of this thesis focuses on evaluating the effectiveness of pancreatic cancer surveillance in carriers of a germline CD2KNA/p16 mutation who have a very high lifetime risk of developing pancreatic cancer. The second part focuses on various aspects to improve pancreatic cancer surveillance programs, including the study of biomarkers, risk stratification, and assessment of psychosocial aspects. Finally, attention is given to the identification of individuals at increased risk from the general population. Show less
Colorectal cancer (CRC) screening programs have been established worldwide to prevent the development of CRC and to detect it early. CRC screening can be targeted at average- or high-risk... Show moreColorectal cancer (CRC) screening programs have been established worldwide to prevent the development of CRC and to detect it early. CRC screening can be targeted at average- or high-risk individuals. For average-risk individuals, the Dutch fecal immunochemical testing (FIT)-based CRC screening program was introduced in 2014, inviting all individuals aged 55-75 biennially. In Part I of this thesis, outcomes of the CRC screening program in the Netherlands are analyzed (i.e., CRC incidence, mortality, stage distribution, treatment). To optimize the balance between benefits and harms of CRC screening, risk stratification based on fecal hemoglobin concentrations after negative FIT could be the way forward. Part II describes the study protocol of a randomized controlled trail on personalized CRC screening and evaluates the information needs of the target population for personalized CRC screening strategies. For high-risk individuals, intensified CRC screening and surveillance may be needed, given these individuals have higher risk of developing CRC during their lifetime. Testicular cancer survivors treated with platinum-based chemotherapy can be considered high-risk individuals, as they have an increased risk of developing second primary gastrointestinal malignancies. Part III of this thesis explores the carcinogenesis of CRC and the yield of colonoscopy in these individuals. Show less
Creutzig, F.; Simoes, S. G.; Leipold, S.; Berrill, P.; Azevedo, I.; Edelenbosch, O.; ... ; Wilson, C. 2024
As fossil fuels are phased out in favour of renewable energy, electric cars and other low-carbon technologies, the future clean energy system is likely to require less overall mining than the... Show moreAs fossil fuels are phased out in favour of renewable energy, electric cars and other low-carbon technologies, the future clean energy system is likely to require less overall mining than the current fossil-fuelled system. However, material extraction and waste flows, new infrastructure development, land-use change, and the provision of new types of goods and services associated with decarbonization will produce social and environmental pressures at localized to regional scales. Demand-side solutions can achieve the important outcome of reducing both the scale of the climate challenge and material resource requirements. Interdisciplinary systems modelling and analysis are needed to identify opportunities and trade-offs for demand-led mitigation strategies that explicitly consider planetary boundaries associated with Earth’s material resources. Show less
Oratie uitgesproken door Prof. Dr. Suzan Verberne bij de aanvaarding van het ambt van hoogleraar Natural Language Processing aan de Universiteit Leiden op maandag 3 juni 2024_______________________... Show moreOratie uitgesproken door Prof. Dr. Suzan Verberne bij de aanvaarding van het ambt van hoogleraar Natural Language Processing aan de Universiteit Leiden op maandag 3 juni 2024____________________________________________________________Text also in English : Is the search engine of the future a chatbot? Show less
Background: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To... Show moreBackground: Measures against COVID-19 in nursing homes affected not only clients but also staff. However, staff perspectives on the importance of these measures remain underexplored. Objective: To investigate measures related to staff during the COVID-19 pandemic, staff perspectives of important measures and the involvement of staff in deciding on these measures. Design: A qualitative study. Setting(s): We analysed minutes of nursing home outbreak teams in the Netherlands and conducted group meetings with Dutch nursing home staff in different positions, prioritizing measures and discussing staff' involvement in deciding on the measures. Participants were recruited purposefully. Participants: The minutes of 41 nursing home organizations were collected during March-November, 2020. Four group meetings were organized in the same period, each with 5 to 7 participants, resulting in 23 participants. Methods: The meeting minutes were analysed using qualitative content analysis, whereas reflexive thematic analysis was used for the group meeting data. The group meetings were conducted online and structured by the Nominal Group Technique to discuss the importance of measures for staff. Results: Measures implemented for staff focused on prevention of COVID-19 transmission, (suspension of) educational activities, testing, additional tasks and staffing capacity, promoting wellbeing, and other means of support. The implemented measures overlapped with the measures considered important by staff. In addition, staff considered measures on decision-making support and communication to be important. Staff prioritized the measures in the group meetings because they affected their well-being, workforce scheduling, decision-making, or infection prevention. Furthermore, the group meetings revealed that decision-making shifted from mainly implementing national measures to more context-adjusted decision-making in the staff's or clients' situations. Conclusions: We showed that although nursing home staff were not always involved in decisionmaking during the first COVID-19 wave, there was overlap between the measures implemented by the organizations and measures considered important by staff. We suggest that organizations Show less
Nanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken... Show moreNanoplastics can cause severe malformations in chicken embryos. To improve our understanding of the toxicity of nanoplastics to embryos, we have studied their biodistribution in living chicken embryos. We injected the embryos in the vitelline vein at stages 18–19. We injected polystyrene nanoparticles (PS-NPs) tagged with europium- or fluorescence. Their biodistribution was tracked using inductively-coupled plasma mass spectrometry on tissue lysates, paraffin histology, and vibratome sections analysed by machine learning algorithms. PS-NPs were found at high levels in the heart, liver and kidneys. Furthermore, PS-NPs crossed the endocardium of the heart at sites of epithelial-mesenchymal transformation; they also crossed the liver endothelium. Finally, we detected PS-NPs in the allantoic fluid, consistent with their being excreted by the kidneys. Our study shows the power of the chicken embryo model for analysing the biodistribution of nanoplastics in embryos. Such experiments are difficult or impossible in mammalian embryos. These findings are a major advance in our understanding of the biodistribution and tissue-specific accumulation of PS-NPs in developing animals. Show less
Predicting the development of rheumatoid arthritis (RA) in an early stage through magnetic resonance imaging (MRI) can initiate timely treatment and improve long-term patient outcomes. Although... Show morePredicting the development of rheumatoid arthritis (RA) in an early stage through magnetic resonance imaging (MRI) can initiate timely treatment and improve long-term patient outcomes. Although manual prediction is time-consuming and requires expert knowledge, automatic RA prediction has not been fully investigated. While standard models fail to achieve acceptable performance, we present a consistency-based deep learning framework to classify and predict RA automatically and precisely, including an output-standardized model, customized self-supervised pretraining and a loss function that is based on label consistency between original and augmented inputs. For training and evaluation, we used a database, containing 5945 MRI scans of carpal, metacarpophalangeal (MCP), and metatarsophalangeal (MTP) joints, from 2151 subjects obtained over a period of ten years. Four (three classification- and one prediction-) tasks were defined to distinguish two patient groups (with recent-onset arthritis and clinically suspect arthralgia) from healthy controls and RA from other arthritis patients within the recent-onset arthritis group, and predict RA development in a period of two years within the clinically suspect arthralgia group. The proposed method was evaluated with the area under the receiver operating curve (AUROC) on a separate test set, achieving mean AUROCs of 83.6%, 83.3%, and 69.7% in the three classification tasks, and 67.8% in the prediction task. This proves the existence of early signs of RA in MRI and the potential of a consistency-based deep learning model to detect these early signs and predict RA Show less
Rede uitgesproken door Prof. dr. Anton Jan van Zonneveld ter gelegenheid van zijn afscheid als hoogleraarNierziekten, in het bijzonder de experimentele vasculaire geneeskunde aan de Universiteit... Show moreRede uitgesproken door Prof. dr. Anton Jan van Zonneveld ter gelegenheid van zijn afscheid als hoogleraarNierziekten, in het bijzonder de experimentele vasculaire geneeskunde aan de Universiteit Leiden op vrijdag 31 mei 2024 Show less
Background: The risk of urinary tract infections (UTIs) is increased by unnecessary placement and prolonged use of urinary catheters. Aim: To assess whether inappropriate use of catheters and... Show moreBackground: The risk of urinary tract infections (UTIs) is increased by unnecessary placement and prolonged use of urinary catheters. Aim: To assess whether inappropriate use of catheters and catheter-associated UTI were reduced through patient participation. Methods: In this multicentre, interrupted time-series and before-and-after study, we implemented a patient-centred app which provides catheter advice for patients, together with clinical lessons, feedback via e-mails and support rounds for staff members. Data on catheter use and infections were collected during a six-month baseline and a six-month intervention period on 13 wards in four hospitals in the Netherlands. Dutch Trial Register: NL7178. Findings: Between June 25th, 2018 and August 1st, 2019, 6556 patients were included in 24 point-prevalence surveys, 3285 (50%) at baseline and 3271 (50%) during the intervention. During the intervention 249 app users and a median of seven new app users per week were registered (interquartile range: 5.5e13.0). At baseline, inappropriate catheter use was registered for 175 (21.9%) out of 798 catheters, compared to 55 (7.0%) out of 786 during the intervention. Time-series analysis showed a non-significant decrease of inappropriate use of 5.8% (95% confidence interval: e3.76 to 15.45; P ¼ 0.219), with an odds ratio of 0.27 (0.19e0.37; P < 0.001). Catheter-associated UTI decreased by 3.0% (1.3e4.6; P ¼ 0.001), with odds ratio 0.541 (0.408e0.716; P < 0.001). Show less
BackgroundWhen research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus among interested stakeholders. In these processes, the... Show moreBackgroundWhen research evidence is limited, inconsistent, or absent, healthcare decisions and policies need to be based on consensus among interested stakeholders. In these processes, the knowledge, experience, and expertise of health professionals, researchers, policymakers, and the public are systematically collected and synthesised to reach agreed clinical recommendations and/or priorities. However, despite the influence of consensus exercises, the methods used to achieve agreement are often poorly reported. The ACCORD (ACcurate COnsensus Reporting Document) guideline was developed to help report any consensus methods used in biomedical research, regardless of the health field, techniques used, or application. This explanatory document facilitates the use of the ACCORD checklist.Methods and findingsThis paper was built collaboratively based on classic and contemporary literature on consensus methods and publications reporting their use. For each ACCORD checklist item, this explanation and elaboration document unpacks the pieces of information that should be reported and provides a rationale on why it is essential to describe them in detail. Furthermore, this document offers a glossary of terms used in consensus exercises to clarify the meaning of common terms used across consensus methods, to promote uniformity, and to support understanding for consumers who read consensus statements, position statements, or clinical practice guidelines (CPGs). The items are followed by examples of reporting items from the ACCORD guideline, in text, tables, and figures.ConclusionsThe ACCORD materials—including the reporting guideline and this explanation and elaboration document—can be used by anyone reporting a consensus exercise used in the context of health research. As a reporting guideline, ACCORD helps researchers to be transparent about the materials, resources (both human and financial), and procedures used in their investigations so readers can judge the trustworthiness and applicability of their results/recommendations. Show less
This contribution describes societies and institutes in the Netherlands that played key roles in scholarly research on the Ancient Near East and Egypt. Public interest followed academic... Show moreThis contribution describes societies and institutes in the Netherlands that played key roles in scholarly research on the Ancient Near East and Egypt. Public interest followed academic developments at a distance. Leading figures, almost all academics, are briefly discussed.After a promising start in the 19th century, development in Dutch Egyptology was mostly limited to religious studies. Assyriology was largely a side-interest for theologians. While other European countries founded national scholarly societies and financed grand expeditions, attention in the Netherland was mainly directed to the Dutch East-Indies, with Oriental studies mostly a function of colonial administration, in combination with Semitic languages (connected to Bible studies).During the first quarter of the 20th century, Oriental studies in the Netherlands were marked by proliferation and specialisation – albeit with a continued emphasis on language studies, and usually from a biblical perspective. The general public was not yet involved. The second quarter of the 20th century saw further diversification of the field, a failed marriage between Ancient Near Eastern and Classical studies, and a broadening audience.After World War II, the range of history, language studies, and archaeology fully developed in the Netherlands. Internationalisation, rising population and student numbers, and economic growth were instrumental. The fourth quarter of the 20th century was characterised by the definitive division between Middle and Far Eastern versus Ancient Near Eastern studies. State-funded research was the norm; the popular audience increased.In the first quarter of the 21st century (not comprehensively addressed in this contribution) state-funded research declined while modest private initiatives (societies of museum and excavation “friends”) can be observed. Show less
Dental calculus. This small, hard, inconspicuous substance that forms on the teeth of humans and animals contains a surprising amount of information about our lives. During its formation and growth... Show moreDental calculus. This small, hard, inconspicuous substance that forms on the teeth of humans and animals contains a surprising amount of information about our lives. During its formation and growth as a living biofilm, it accumulates a wide variety particles, especially bacteria and food debris.What makes this so interesting to archaeologists is that, when plaque hardens and forms dental calculus, these particles become trapped and well-protected against removal and degradation during hundreds to thousands of years, preserving a picture of past activities.The major problem—one of the major problems, for there are several—one of the many major problems is that this picture was never a complete picture of a lifetime of activities, and that picture fades over time. We know that these problems exist and that they limit our interpretations of past activities. What we need to do is approach these problems at a fundamental level. In my dissertation I introduce a protocol for growing artificial dental calculus. Working with a very controlled model allows me to explore the influence of a wide range of factors that may affect the uptake of particles into dental calculus, and better explain why and how our picture is incomplete. Show less
Tuberculosis (TB) is associated with 1.5 million deaths annually. There is a need exists to optimize both current as well as novel antibiotic combination treatment strategies to improve the... Show moreTuberculosis (TB) is associated with 1.5 million deaths annually. There is a need exists to optimize both current as well as novel antibiotic combination treatment strategies to improve the effectiveness and safety of treatments against TB. This PhD thesis has described how various quantitative pharmacology modeling approaches can contribute to the further development and optimization of both existing and novel therapies and treatment strategies against TB. Show less
This book focuses on the general right of suspension regulated in article 6:52 et seq. of the Dutch Civil Code. The author pays attention, among other things, to the requirements for the power to... Show moreThis book focuses on the general right of suspension regulated in article 6:52 et seq. of the Dutch Civil Code. The author pays attention, among other things, to the requirements for the power to suspend, including the coherence criterion (Dutch: samenhangcriterium), which is also the central requirement. The author explains that this criterion is not a measure of judgment or criterion to be judged by itself, but the existence of sufficient coherence between mutual obligations to justify suspension is rather a conclusion that follows the application of the coherence criterion. The author also discusses how the general right of suspension is exercised. Under circumstances, that exercise may be unacceptable. This involves weighing the interests involved in that exercise. Procedural aspects of the general right of suspension are also discussed, including the dictum. The author discusses that under circumstances an order for gradual performance fits a defense of suspension better than a rejection of the claim. The author makes this concrete using many examples mainly from case law. This book is therefore relevant for both law and legal practice. Show less
The fundamental research question in this dissertation is what the image of man - in the broadest sense of the word - entails within the classical and modern enlightenment points of view. This... Show moreThe fundamental research question in this dissertation is what the image of man - in the broadest sense of the word - entails within the classical and modern enlightenment points of view. This overarching question is considered with regard to the notions of man maintained by the ancients and moderns, with regard to their visions of society, and with regard to the worldview these theories entail. We also evaluate which of the two paradigms is the more convincing upon scrutiny. We have answered such questions by distilling the ideas of the classical philosopher Aristotle -and some ontological ideas from his teacher, Plato- on the one hand, and from the modern intellectual giant, Thomas Hobbes, on the other hand. This is premised on the belief that the essential features of the classical and modern idealtype are to be found within their thought and works.In order to answer our central question, we had to look into the values which underly each vision of man. After all, values are the ideas that motivate our actions as individuals and as a community. We found that the classical vision is guided by the value of Virtue/Duty, Hierarchy and the pursuit of Community in a world permeated with objective values, whilst the modern conception embraces Freedom, Equality and Individuality in a world that is set free of objective values. Show less
Lung cancer is the leading cause of cancer death in the Netherlands. For years chemotherapy was the only (palliative) treatment, with a short survival of only months. Since the introduction of... Show moreLung cancer is the leading cause of cancer death in the Netherlands. For years chemotherapy was the only (palliative) treatment, with a short survival of only months. Since the introduction of immunotherapy in 2015, this survival has increased significantly, with the first results showing a survival of even a few years. However, the response rate is relatively low, the treatment is expensive and the (low percentage of) side effects are severe. Therefore a biomarker is needed to predict which patients would benefit of immunotherapy.This thesis is about the search for a new biomarker. With the use of the RNA of platelets, proteins, tumor markers in blood and a an electronic nose for exhaled breath, we tried to find a non-invasive biomarker for the prediction of response on immunotherapy and for the (future) use in clinical practice, some of which are promising. Show less
