To test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N = 951). DHWFS is a natural... Show moreTo test the hypothesis that early-life adversity accelerates the pace of biological aging, we analyzed data from the Dutch Hunger Winter Families Study (DHWFS, N = 951). DHWFS is a natural-experiment birth-cohort study of survivors of in-utero exposure to famine conditions caused by the German occupation of the Western Netherlands in Winter 1944 to 1945, matched controls, and their siblings. We conducted DNA methylation analysis of blood samples collected when the survivors were aged 58 to quantify biological aging using the DunedinPACE, GrimAge, and PhenoAge epigenetic clocks. Famine survivors had faster DunedinPACE, as compared with controls. This effect was strongest among women. Results were similar for GrimAge, although effect-sizes were smaller. We observed no differences in PhenoAge between survivors and controls. Famine effects were not accounted for by blood-cell composition and were similar for individuals exposed early and later in gestation. Findings suggest in-utero undernutrition may accelerate biological aging in later life. Show less
Oratie uitgesproken door Prof.dr. Maaike M. Kempes bij de aanvaarding van het ambt van bijzonder hoogleraar forensische neuropedagogiek aan de Universiteit Leiden op maandag 10 juni 2024
Oratie uitgesproken door Prof. dr. Ivo van Vulpen bij de aanvaarding van het ambt van bijzonder hoogleraar Wetenschapscommunicatie, in het bijzonder betreffende de natuurkunde aan de Universiteit... Show moreOratie uitgesproken door Prof. dr. Ivo van Vulpen bij de aanvaarding van het ambt van bijzonder hoogleraar Wetenschapscommunicatie, in het bijzonder betreffende de natuurkunde aan de Universiteit Leiden op vrijdag 7 juni 2024 Show less
The mid-sixteenth century was a time of rapidly intensifying interest in the study of living nature. Networks of experts described a rapidly growing number of species, complementing descriptions... Show moreThe mid-sixteenth century was a time of rapidly intensifying interest in the study of living nature. Networks of experts described a rapidly growing number of species, complementing descriptions with ad vivum depictions. Since the increase in the number of known species soon called for an organisation of this information, to keep this accessible and navigable, naturalists experimented with classifications and the presentation of information in text and image. This dissertation explores questions about the management of knowledge and information specifically in the context of natural history, looking at a subfield of zoology, the study of fishes and other aquatic animals, as an example, taking as a point of departure the works published by the naturalist Conrad Gessner (1516-1565). Gessner aimed to incorporate into his works an overview of the state of knowledge. As a result his work presents an ideal case study from which to approach questions such as: What happens when a field of knowledge experiences a sudden influx of information? How is information made accessible, how do researchers keep the overview of an increasing quantity of information? How is rudimentary and incomplete information processed and presented, how does it affect established interpretations and methods of working? Show less
Political theological explorations of the international have mounted an important challenge to standard secularization narratives by drawing attention to the manner in which modern international... Show morePolitical theological explorations of the international have mounted an important challenge to standard secularization narratives by drawing attention to the manner in which modern international political thought has taken up and refashioned theological notions. However, there exists a certain danger of reducing the political theological move to the level of intellectualism. Explorations would benefit from attention to theology understood as an embodied form of understanding, as a way of life, and more specifically to the manner in which desire shapes understanding of and action within the world of international politics. This chapter details the intellectualist danger in two prominent, recent interjections regarding the political theology of the international, those of Seán Molloy and William Bain. Next it flags how two key critics of the political theological move, Mark Lilla and Hans Blumenberg, actually recognize the centrality of desire in human thought and action, while also noting the inadequacies of their accounts. It then highlights how the work of Charles Taylor and Talal Asad might inspire a political theology of the international that avoids the intellectualist danger by giving attention to desire. Show less
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
Grewal, S.; Theijse, R.T.; Dunlop, G.; Deurzen, D.F.P. van; Bekerom, M.P.J. van den; Klautz, R.J.M.; ... ; Grewal, N. 2024
Background: Professional athletes navigate a multitude of unique challenges associated to sport-specific factors (e.g., training, travel and competition) and non-sport factors (e.g., performance... Show moreBackground: Professional athletes navigate a multitude of unique challenges associated to sport-specific factors (e.g., training, travel and competition) and non-sport factors (e.g., performance pressure, stress and anxiety) that can interfere with healthy sleep behaviors. Sleep plays a key role in proper biopsychosocial development as well as short- and long-term biological, physical, psychological, and cognitive health. As poor sleep quality is known to impair proper brain function, this study aimed to investigate the effect of sleep quality on a professional athlete's ability to train, recover, and perform, as well as their overall emotional and physical well-being. Methods: A cohort study was performed in 40 professional male cricket athletes from the Dutch national cricket team (mean age 26.5 ± 5.1 years). The athletes were monitored across a 22 weeks in-season training period. Sleep quality and overall emotional and physical well-being were assessed using daily sleep diaries and questionnaires which scored the readiness to train, stress levels, fatigue, muscle soreness and flu symptoms respectively. Quality of sleep and subsequent association with the consecutive elements of the well-being questionnaire were assessed through statistical using the student t-test and clinical differences with the methodology of Osoba and colleagues: 20% “very much change”. Results: The results demonstrated that the professional athletes assessed their sleep quality as average with a mean score of 3.4 out of 5. Lower perceived quality of sleep (<75th percentile) was correlated with a decreased readiness to train (mean score 3.2 [IQR: 3.0–4.0] vs. 3.5 [IQR: 3.0–5.0]; P < 0.001) and increased extent of muscle soreness (2.7 [IQR: 2.0–3.0] vs. 2.3 [IQR: 2–3]; P < 0.001), stress level (mean score 2.3 [IQR: 2.0–3.0] vs. 1.9 [IQR: 1.0–2.0]; P < 0.001) and perceived fatigue (mean score 2.9 [IQR: 2.0–3.0] vs. 2.3 [IQR: 2.0–3.0]; P < 0.001). Likewise, in patients with lower perceived quality of sleep, the proportion of players presenting with flu symptoms increased over 4-fold (4.1% vs. 17%; P < 0.001). 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
