Aim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase. Methods: A... Show moreAim: This paper investigates the conditions for inclusive design of regenerative medicine interventions from a bioethical perspective, taking regenerative valve implants as a showcase. Methods: A value hierarchy is construed to translate the value of justice into norms and design requirements for inclusive design of regenerative valve implants. Results: Three norms are proposed and translated into design requirements: regenerative valve implants should be designed to promote equal opportunity to good health for all potential users; equal respect for all potential users should be shown; and the implants should be designed to be accessible to everyone in need. Conclusion: The norms and design requirements help to design regenerative valve implants that are appropriate, respectful and available for everyone in need. Show less
International trade has played a major role in defining the modern global economy. Trade, however, entangles the environmental pressures of economic sectors, giving the illusion of environmental... Show moreInternational trade has played a major role in defining the modern global economy. Trade, however, entangles the environmental pressures of economic sectors, giving the illusion of environmental improvements, while the opposite may be occurring. This dissertation explores the role of international trade on the environmental impacts of two sectors: the food system and the plastic waste system. For each system, this work finds that international trade leads to unwelcomed tradeoffs. Within the food system, in the form of consumption patterns that have been able to shift towards more land intensive diets. Adopting more autarkic food policies may help shift food consumption back towards diets that are more in line with planetary boundaries while also improving the efficiency of currently underdeveloped food supply chains. Within the plastic waste system, international trade has been detrimental by increasing plastic waste leaking to the aquatic environment, particularly from high-income countries. Recycling policies within these countries have amplified the quantities of plastic waste being exported to reach recycling metrics, ultimately highlighting the need for improved metrics to evaluate the environmental tradeoffs of plastic waste disposal. Show less
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
This thesis has found a balance between individual data protection rights and the free flow of data. On the one hand, this balance serves to protect the individual and his data. On the other hand,... Show moreThis thesis has found a balance between individual data protection rights and the free flow of data. On the one hand, this balance serves to protect the individual and his data. On the other hand, health care and health research must take place using personal data.A balanced approach can be found in the following four ways. Firstly, a broad(-er) interpretation of the lawful basis of consent can facilitate secondary health research. Secondly, the use of other lawful bases can be a solution for the legitimation of secondary health research. Furthermore, a separate legal ground for secondary research can be a solution to resolve the issue of a lawful basis for health research.Thirdly, a balance can be found in the individual’s autonomy vis-à-vis the accountability of the health institution and the attention drawn to the free flow of data. The focus is shifted from the individual’s control over his data towards the health institution with other lawful bases than consent and a fair balance between data protection rights and the free flow of data.Fourthly, a risk-based approach to monitoring compliance contributes to balancing the rights and interests of individuals with data sharing for health care and research. Show less
The studies described in this thesis investigate the effects of different pharmacotherapieson antinociception and ventilatory control. Additionally, inherent variabilities in patient phenotypes... Show moreThe studies described in this thesis investigate the effects of different pharmacotherapieson antinociception and ventilatory control. Additionally, inherent variabilities in patient phenotypes within the population were assessed to gain a deeper understanding of the individual effects of analgesics and the ventilatory effects of disease, particularly type 2 diabetes mellitus (T2DM). Show less
Dit onderzoek richt zich op steunverlenende overheden die in het kader van het EU-staatssteunrecht algemene belangenafwegingen verrichten. In de verbodsfase van staatssteun moeten overheden... Show moreDit onderzoek richt zich op steunverlenende overheden die in het kader van het EU-staatssteunrecht algemene belangenafwegingen verrichten. In de verbodsfase van staatssteun moeten overheden beoordelen of een steunmaatregel (zoals een subsidie) als staatssteun kwalificeert. De weging van het algemene belang van staatssteun (bijvoorbeeld milieubescherming of cultuur) is gereserveerd voor de verenigbaarheidsfase. Bij de staatssteunhandhaving betrekt de Unie in toenemende mate nationale actoren (overheden en rechters) bij de beoordeling van deze algemene belangen, zowel in de verbodsfase als in de verenigbaarheidsfase. Dit proefschrift onderzoekt de algemene belangenafwegingen die ongelijke behandeling van ondernemingen rechtvaardigen, diensten van algemeen economisch belang uitzonderen en expliciet erkende sportbelangen een voorkeursbehandeling geven. Aansluitend wordt de beleidsruimte ter toetsing van groepsvrijstellingen aan verenigbaarheidscriteria door nationale actoren geanalyseerd. Daartoe worden een aantal knelpunten geïdentificeerd. Allereerst leiden de belangenafwegingen tot een vervaging van het onderscheid tussen de verbodstoepassing en de verenigbaarheidstoepassing. Zij raken daarmee aan de bevoegdheidsverdeling tussen nationale actoren en de Europese Commissie. Voorts mist het rechtmatigheidskader voor ex ante belangenafwegingen rechts zekerheid en ontbeert de ex post rechtmatigheidscontrole hierop een doeltreffende rechtsbeschermingsfunctie. Ter versterking van een gedecentraliseerde handhaving en een doeltreffende rechtsbescherming biedt dit onderzoek aanbevelingen op grond waarvan de Commissie verdere (afgebakende) bevoegdheden aan nationale actoren kan toestaan. Show less
Proteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by... Show moreProteinuria is an independent risk factor for the progression of kidney injury, cardiovascular morbidity, and overall mortality. In this thesis, the pathways leading to proteinuria are explored by revisiting elements previously considered essential, investigating known pathways, and identifying new players in the field of proteinuria. First, a zebrafish embryo model for developing new therapeutic options for the rare but devastating disease of nephropathic cystinosis is presented. The studies presented in thesis also investigate loss of heparan sulphate glycosaminoglycans in a zebrafish embryo model and in multiple osteochondroma patients. These studies show that loss of heparan sulphate glycosaminoglycans does not always lead to proteinuria. Next, dynamin is described as a promising potential therapeutic target for treating proteinuria. The final study introduces transmembrane protein 14A as an essential factor in maintaining glomerular filtration barrier function. Overall, these studies contribute to elucidating the pathways to proteinuria in the hope to keep advancing the field towards targeted treatment of proteinuria for the benefit of our patients. Show less
The aim of the thesis was to contribute to a better understanding of the influence of differences in implant design and surgical techniques on the migration of total knee arthroplasties (TKAs) and,... Show moreThe aim of the thesis was to contribute to a better understanding of the influence of differences in implant design and surgical techniques on the migration of total knee arthroplasties (TKAs) and, more broadly, the effect of using Radiostereometric Analysis (RSA) and other markers to detect early loosening. In this thesis, we compared various types of TKAs in different randomized controlled trials. Additionally, we investigated whether the positioning of TKAs relative to the patient's specific leg axis (e.g., neutral, varus, or valgus alignment) affects the stability of the prosthesis. We also analyzed, by combining registry data with data from a meta-analysis, whether TKAs evaluated with migration analysis (radiostereometric analysis; RSA) yield better results than TKAs that have not been previously examined with RSA. Finally, we conducted a systematic review to explore whether there are markers that can indicate loosening/failure of a prosthesis. 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
Simonse, O.; Dijk, W. van; Dillen, L.F. van; Dijk, E. van 2024
The subjective experience of financial stress has profound implications for well-being, health, cognitive performance, and decision-making. In a sample of Dutch households (N = 1114), we studied... Show moreThe subjective experience of financial stress has profound implications for well-being, health, cognitive performance, and decision-making. In a sample of Dutch households (N = 1114), we studied the association of five economic factors - income, saving, debts, income volatility, and employment - with a four-factor measure of financial stress: 1) an appraisal of insufficient financial resources, 2) an appraisal of lack of control over one's financial situation, 3) financial worries and rumination, and 4) a short-term focus. This enabled us to examine the economic factors' relative contributions to predicting5 financial stress. We found that the combination of economic factors predicted financial stress better than income alone. Particularly, buffer savings had a large contribution to predicting financial stress. The number of debts had a smaller relative contribution to predicting financial stress, whereas we did not find support for debt amount as a predictor of financial stress. Employment was negatively associated with financial stress, but only for households with the lowest incomes. We found no support for income volatility predicting financial stress. These results imply that research and policy on financial stress should have a broader scope than income alone and should take a more integrative approach to households' financial situation, considering savings, number of debts, and unemployment. 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
This article studies the use of the Bare Aorist in the Berber variety of Figuig, an oasis at the border of Morocco and Algeria. Like elsewhere in Berber, the Bare Aorist isused as a form that is... Show moreThis article studies the use of the Bare Aorist in the Berber variety of Figuig, an oasis at the border of Morocco and Algeria. Like elsewhere in Berber, the Bare Aorist isused as a form that is neutral as to aspect, whose interpretation is provided by context. It is shown that the major types of occurrence that were established for other varieties (Mauri2017) are also represented in Figuig Bare Aorists. Framed Aorists are found in main clauses that are preceded by a temporal/aspectual clause that provides the framing for its aspectual interpretation. With Chained Aorists, the framing is provided by verbs in preceding main clauses. It is shown, however, that Chained Aorists are subtly different in Figuig from the way they have been described for other varieties, as they mainly occur to express continuity at points where such a continuity is less expected. 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
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
