Leiden University Scholary Publications
Not a member yet
131438 research outputs found
Sort by
“A custome lothsome”: investigating the association between tobacco consumption and respiratory inflammation in two post-medieval English populations (c. CE 1500–1855)
Get PDF Despite current clinical knowledge of the risks associated with tobacco consumption, the bioarchaeological investigation of tobacco’s effect on health in past populations remains woefully underexamined. This study explores the potential respiratory health implications of the rapid incorporation of tobacco-use into the everyday lives of English citizens during the post-medieval period. Adult skeletons from urban post-medieval St James’s Gardens Burial Ground, Euston, London (N = 281; CE1789–1853) and rural post-medieval (N = 151; CE1500–1855) and medieval (N = 62; CE1150–1500) Barton-upon-Humber were examined. Individuals were assessed for tobacco consumption status using osteoarchaeological and biomolecular methods. Individuals were observed for bone changes related to inflammation within the maxillary sinuses and within the pleural/pulmonary regions. Statistical tests revealed a significant association between tobacco consumption and the presence of pulmonary/pleural inflammation in the Barton-upon-Humber post-medieval group. Tobacco consumers at Barton-upon-Humber were also more than twice as likely to present with maxillary sinusitis or pleural/pulmonary inflammation, although the results were not statistically significant. Differences between tobacco consumers and non-consumers in the London group were not apparent, but the odds of having maxillary sinusitis increased by two-fold in middle adults (compared to young adults) and lower socio-economic groups (compared to higher socio-economic groups). Significant differences in respiratory disease frequencies were apparent between rural and urban groups. The results highlight the complexity of factors affecting upper and lower respiratory disease, indicating the potential impacts of not only tobacco consumption, but household, environmental, and occupational air pollution, as well as poor water sanitation, on frequencies of respiratory disease in different population groups.NWOPGW.21.008Archaeological Science
Synthesis, structure and epitope mapping of well-defined Staphylococcus aureus capsular polysaccharides
Get PDFThis dissertation presents the synthesis and evaluation of antibody recognition for various capsular polysaccharide (CP) fragments of Staphylococcus aureus (S. aureus). Previous glycoconjugate vaccine candidates to combat S. aureus infections, that made use of isolated CP5 and CP8, have all failed in late-stage clinical trials, prompting the focus on well-defined synthetic materials. The synthesized CP fragments that have been studied include type 8, type 5, and type 1. To facilitate conjugation, all these saccharides were equipped with an amino-functionalized linker. All these CP-fragments were built up from rare monosaccharides, that were synthesized in effective multi-step routes from commercially available materials. A method for constructing longer saccharides was developed, utilizing a [3+3n] glycosylation approach that reduced the number of glycosylation steps. The synthetic oligosaccharides of CP5 and CP8 were shown to induce an antibody response and the recognition of the longer synthetic fragments were consistent with that of the natural polysaccharide, providing a model for further understanding the immunology of glycoconjugate vaccines against S. aureus.Bio-organic Synthesi
Tobler/Beglinger-Brevier zu den bilateralen Abkommen Schweiz – EU. Paketansatz und institutionelle Aspekte: Ausgabe 2025-05.1. Stand: 21. Mai 2025
Get PDFThe progression of EU law: Accommodating change and upholding value
Changes in physical activity and sedentary behaviour following geriatric rehabilitation in older adults with stroke
Get PDFBackgroundOlder adults recovering from stroke engage in low levels of physical activity and spend long periods in sedentary behaviour. Sedentary behaviour during geriatric rehabilitation is still poorly understood. The aims of this study were to quantify physical activity, sedentary behaviour and accompanying patterns of change during geriatric rehabilitation.MethodsOlder adults (>= 70 years) recovering from stroke in geriatric rehabilitation were included in this prospective cohort study. Patients wore an inertial measurement unit (IMU) on the ankle for 48 h, with data collected between 7am and 11 pm. Variables related to physical activity, sedentary behaviour and patterns of sedentary behaviour were calculated and analysed. Extracted principal components on admission and discharge were plotted in order to assess the individual degree of change.ResultsIn total, 53 patients with sufficient accelerometer wear time were included. The degree of change in physical activity and sedentary behaviour components was extremely diverse. Except for step count (P = 0.01), no significant changes were observed in any variable related to physical activity, sedentary behaviour or patterns of sedentary behaviour between admission and discharge.ConclusionsOlder adults recovering from stroke during geriatric rehabilitation improve their functional performance, but show little change in physical activity, sedentary behaviour or patterns of sedentary behaviour. The degree of change in physical activity and sedentary behaviour was highly diverse.Prevention, Population and Disease management (PrePoD)Geriatrics in primary carePublic Health and primary car
Integrating pharmacokinetics and quantitative systems pharmacology approaches in generative drug design
Get PDFIntegrated understanding of pharmacokinetics (PK) and pharmacodynamics (PD) is a key aspect of successful drug discovery. Yet in generative computational drug design, the focus often lies on optimizing potency. Here we integrate PK property predictions in DrugEx, a generative drug design framework and we explore the generated compounds' PD through simulations with a quantitative systems pharmacology (QSP) model. Quantitative structure-property relationship models were developed to predict molecule PK (clearance, volume of distribution and unbound fraction) and affinity for the Adenosine A2AR receptor (A2AR), a drug target in immuno-oncology. These models were used to score compounds in a reinforcement learning framework to generate molecules with a specific PK profile and high affinity for the A2AR. We predicted the expected tumor growth inhibition profiles using the QSP model for selected candidate molecules with varying PK and affinity profiles. We show that optimizing affinity to the A2AR, while minimizing or maximizing a PK property, shifts the type of molecular scaffolds that are generated. The difference in physicochemical properties of the compounds with different predicted PK parameters was found to correspond with the differences observed in the PK data set. We demonstrated the use of the QSP model by simulating the effect of a broad range of compound properties on the predicted tumor volume. In conclusion, our proposed integrated workflow incorporating affinity predictions with PKPD may provide a template for the next generation of advanced generative computational drug design.Medicinal Chemistr
‘Wat moeten wij, hoogleeraren, doen?’: Burgermoed in meervoud. bij de 80ste sterfdag van prof. mr. B.M. Telders
Get PDFThe Legitimacy and Effectiveness of Law & Governance in a World of Multilevel Jurisdiction
Survival of the littlest: navigating sepsis diagnosis beyond inflammation in preterm neonates
Get PDFAnalytical BioScience
Combining core cross-linking and π–π-interactions in polymer micelles based on polypept(o)ide AB3 miktoarm star polymers
Get PDFDrug Delivery Technolog
The European Central Bank in the international political economy
Get PDFCentral banks lie at the interface between domestic and international political economy. Powerful technocracies tasked with domestic and international macroeconomic governance functions are responsible for monetary policy, sometimes banking supervision, and to contribute to overall financial stability. On occasion, they supervise a variety of non-banking financial services and other functions, such as anti-money laundering. During economic and financial turmoil, central banks can be crisis managers of last resort, or actually crisis managers of first resort. Today, many central banks often enjoy independence from the political authorities. They are important actors in the international monetary and financial systems acting separately from government actors. Central banks contribute to shaping these systems, and are, in turn, affected by them. Major geopolitical developments pose significant challenges to central banks and thus to the scholars studying them. This forum takes stock of current academic and policy debates on the European Central Bank (ECB) and the euro. Individual contributions explore key aspects of the ECB and the euro: the ECB as an overstretched multi-tasking technocracy, struggling with multiple goals; the distributive effects of ECB’s policies; the ECB as a global normative and policy entrepreneur in combating climate change; and the geopolitics of the euro, in particular, the failed promise of the euro as a leading international currency. Together, these contributions tackle fundamental questions about the past, present, and future of the euro and the ECB; offer contending perspectives on the success (or otherwise) of this experiment; and point out what features would warrant further study. We reflect on how these analyses feed into the broader literature on central banks and international organizations in the global political economy more generally.SSHRC Connection Grant 611-2021-0074Institutions, Decisions and Collective Behaviou