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Prevention of surgical site infections
No full textSurgical site infection (SSI) is a common and concerning healthcare-associated infection. The first part of this thesis explored the impact of SSI on both patient health and economic burden. Specifically, it evaluated the impact of SSI and anastomotic leakage on cost and quality of life. In addition, a qualitative study investigated the physical and emotional experiences of patients with negative pressure wound therapy with instillation. Last, a cross-sectional study examined patients’ experiences and preferences regarding surgical wound care education at discharge in the Netherlands.The second part of this thesis investigated the efficacy of individual interventions aimed at reducing SSI risk, addressing gaps in existing knowledge, and highlighting discrepancies in current guidelines. Systematic reviews and (network) meta-analyses were conducted to assess the effects of different preoperative skin antiseptics, incisional wound irrigation solutions, and incisional negative pressure wound therapy on SSI. Additionally, the potential effect of operating room door openings on SSI rates was investigated in a systematic review and individual patient data meta-analysis. The findings from four chapters of Part II have contributed to the development of recommendations for the Dutch guideline for the prevention of SSI, which was published in 2024
Multidisciplinary developments in rectal cancer care and lateral nodal disease
No full textGedurende de laatste decennia zijn de behandelopties voor rectumcarcinoom aanzienlijk verbeterd dankzij betere herkenning, selectieve radiotherapie en nieuwe chirurgische technieken. In dit proefschrift zijn de multidisciplinaire ontwikkelingen in kaart gebracht en hiaten geïdentificeerd waar mogelijkheden liggen voor verdere verbeteringen.Het eerste deel van dit proefschrift behandelt de incidentie, herkenning en klinische kenmerken van zowel primair als recidiverend rectumcarcinoom. Het blijkt dat de incidentie van mismatch-repair deficiënte (dMMR) tumoren laag is (2.8%), maar dat deze tumoren, in tegenstelling tot coloncarcinoom, goed reageren op neoadjuvante (chemo)radiatie. Daarnaast wordt beschreven dat aanwezigheid van extramurale veneuze invasie op MRI-scan een belangrijke prognostische factor is voor een slechtere overleving. Verder heeft een afname van het gebruik van neoadjuvante (chemo)radiatie bijgedragen aan een grotere kans op curatieve behandeling van lokaal recidiverend rectumcarcinoom.Deel twee onderzoekt de chirurgische behandelingen van het rectumcarcinoom. Lokale excisie bleek bij actieve opvolging een hoger risico op lokaal recidief te hebben, maar een lager stoma-risico. Bovendien zijn lokale recidieven na lokale excisie bijna altijd goed te behandelen. Verder blijkt dat de keuze voor chirurgische technieken, zoals TME met anastomose of lage Hartmann’s procedure, varieert tussen ziekenhuizen. Het derde deel richt zich op de behandeling van laterale lymfeklieren. Deze klieren zijn geassocieerd met een hoger risico op lokaal recidief, maar niet op afstandsmetastasen. Dit deel benadrukt ook het belang van nauwkeurige herkenning, risicoclassificatie en gestandaardiseerde bestraling voor betere behandelresultaten. Daarnaast wordt ook het protocol van de LaNoReC-trial beschreven, deze studie onderzoekt de effectiviteit van een multidisciplinaire aanpak bij patiënten met laterale lymfeklieren
Early nutritional strategies to modulate the early-life stress- and Alzheimer's disease-induced changes in the brain:Focus on microglia
No full textDit proefschrift onderzoekt de invloed van voedingsstoffen zoals omega-3 vetzuren (N-3 PUFAs) en koffiepolyfenolen op de hersenen en hun rol in het immuunsysteem, met een specifieke focus op microglia, de immuuncellen van de hersenen. Een belangrijk thema is de rol van deze voedingsstoffen in het verminderen van de negatieve gevolgen van vroege stress (early-life stress (ES)) en hun mogelijke bijdrage aan de ziekteprocessen van de ziekte van Alzheimer (AD).Uit eerder onderzoek blijkt dat vroege voedingsinterventies, bijvoorbeeld via verrijking met N-3 PUFAs, bescherming kunnen bieden tegen de schadelijke effecten van ES, waarbij microglia een belangrijke rol spelen. Deze interventies kunnen mogelijk de achteruitgang verminderen bij AD, zoals wordt waargenomen in individuelen blootgesteld aan ES. Dit proefschrift bespreekt hoe N-3 PUFA en hun derivaten, zoals oxylipines, de structuur en functies van microglia beïnvloeden in verschillende hersengebieden. Er wordt onderzocht hoe een dieet verrijkt met N-3 PUFAS de vorming van amyloïde plaques, een pathologisch kenmerk van AD, kan verminderen. Muizen die op jonge leeftijd een dergelijk dieet kregen, vertoonden een significante afname van amyloïde plaques in de hippocampus en de entorhinale cortex, hersengebieden die essentieel zijn voor geheugenfuncties. Deze vermindering van plaques werd in verband gebracht met veranderingen in de morfologie en functie van microglia. Microglia die zich dichter bij amyloïde plaques bevonden, vertoonden veranderingen in complexiteit en een toename van fagocytose—het vermogen om schadelijke stoffen zoals amyloïde plaques op te ruimen.Samengevat, dit proefschrift benadrukt het potentieel van (vroege) voedingsinterventies, met name N-3 PUFAs, om vroege negatieve programmering door stress te moduleren en de ontwikkeling van neurodegeneratieve ziekten zoals AD op latere leeftijd te beïnvloeden. Het onderzoek draagt bij aan een beter begrip van de complexe interacties tussen voeding, het immuunsysteem van de hersenen en ziekteprocessen zoals AD
Light-driven CO<sub>2 </sub>reduction in metal-organic frameworks:Strategies for catalyst immobilization
No full textThe increasing concentration of atmospheric CO₂ due to fossil fuel overreliance demands innovative solutions to mitigate climate change and transition toward a carbon-neutral society. This thesis focuses on the development of a hybrid catalytic platform for photocatalytic CO₂-to-CO reduction, combining the high activity and selectivity of molecular catalysts with the stability and recyclability of heterogeneous systems. In this work, we employed porous, tuneable, and hierarchical coordination polymers, known as Metal-Organic Frameworks (MOFs), to immobilize an active and selective CO₂ reduction molecular catalyst, creating a hybrid material. Initially, the optimal catalyst loading within the MOF was identified to balance porosity and catalytic performance to optimize CO₂-to-CO conversion. The study further explored different installation strategies for the catalyst within the MOF, revealing that the coordination linkage between the catalyst and MOF provides the most robust attachment, minimizing leaching and enhancing long-term stability. Next, a comparative analysis between 3D and 2D assemblies highlighted the trade-off between initial catalytic performance and durability, with MOFs demonstrating superior recyclability. Finally, the hybrid material was integrated into a dye-sensitized photoelectrochemical cell, where a redox mediator facilitated electron transfer from the photoelectrode to the catalytic sites within the MOF. The fabricated device achieved a stable photocurrent, leading to the formation of CO. This work advances the understanding of hybrid catalysts for solar fuels, emphasizing the importance of catalyst loading, immobilization strategy, and integration into functional devices. The findings offer a promising step toward scalable and sustainable artificial photosynthesis.
Visualizing, quantifying, and understanding nanowear of hard multi-asperity contacts
No full textWear takes place across the scale of contacts, involving different mechanisms, making predictive understanding difficult to build. At the macroscopic scale, the famous empirical Archard law predicts a linear relationship between the volume of material worn, the applied load and slid distance, normalized by the hardness of the softest material at the interface. This law describes wear extremely well in the context of debris formation, covering a wide range of wear mechanisms (fatigue, fracture, fretting, etc.) causing the softer material to wear down. For single asperity contacts, tribochemical (or stress-assisted) processes have been found to be the dominant mechanism driving wear. Derived from the Arrhenius equation governing chemical reaction rates, such processes describe the removal of single (or groups of) atoms by the supply of energy in the form of stress that enables the breaking of covalent bonds at the interface. On the one hand, attempts have been made to scale down the Archard law to single asperity context to understand how contact junction size is crucial in the transition from gradual to fracture type wear. On the other hand, efforts are made to observe tribochemical wear at multi-asperity contacts. In this thesis, we have experimentally studied promising systems to bridge the small-scale single asperity contact understanding to the large multi-asperity contact empirically understood. Our results indicate that tribochemical wear on hard, multi-asperity contacts can be detected but also understood (and manipulated) by changing the environmental conditions
Dramaturgie van het antropoceen:Theatraliteit in transitie(s)
No full textIn dit proefschrift heb ik onderzocht wat theater kan betekenen in een tijd van (klimaat)crises. Theatraliteit en dramaturgie staan centraal als creatieve concepten en praktijken om de kritiek op het antropoceen te doordenken. In vier hoofdstukken analyseer ik hoe vijf hedendaagse Nederlandse performances toekomstscenario’s voor leven en sterven in – en na - een instabiele en onzekere tijd vormgeven en aldus alternatieve narratieven voor klimaatverandering presenteren. De hoofdstukken verbind ik door drie Interludes, waarin als tussenspel theatraliteit en dramaturgie ingezet worden om te oefenen met een andersoortige taal voor een verstrengeld tijdperk
News in perspective:What is news to news users in the digital age?
No full textThe rise of new technologies has profoundly reshaped the news landscape, characterized by three intertwined elements: genre-blending news content, multifaceted digital platforms, and the prevalence of algorithmic recommendations. As news consumption evolves in this new landscape, users’ perception of news has naturally shifted. Historically, the question “What is news?” was defined by institutional journalism. But what is news to news users in the digital age? This dissertation explores users’ news perception through three empirical chapters, focusing on content, platforms, and algorithms. The first study measures news content on a spectrum along abstract dimensions, based on genre cues recognizable to news users. The second study investigates how varying definitions of news shape users’ news repertoires on digital platforms. The final study examines how genre cues contribute to user perception, particularly in the context of algorithmic news recommendations. Using innovative data collection methods, such as data donation and online field experiments, alongside advanced computational techniques, this dissertation offers both theoretical and methodological insights. By emphasizing the relevance of a user-centric focus in news research, it sheds light on how users navigate the new news landscape and broadly contributes to a more informed and democratic society
Self driving labs for the optimization of photochemical processes
No full textThe integration of automation, artificial intelligence (AI), and robotics into synthetic chemistry has ushered in a new era of self-driving laboratories (SDLs) capable of accelerating reaction optimization and chemical discovery. This thesis presents RoboChem, an advanced SDL platform designed for the optimization of photochemical processes. By leveraging Bayesian optimization and automated experimentation, RoboChem efficiently explores chemical space, reducing the number of required experiments while improving reproducibility and scalability.Chapter 1 introduces the field of SDLs, emphasizing their potential to overcome inefficiencies in traditional organic synthesis. Chapter 2 details the development of the RoboChem platform, including its hardware and software architecture, fluidic automation, and AI-driven decision-making. Chapter 3 applies RoboChem to synthetic photochemistry, demonstrating its capability for optimizing reaction conditions, light intensity, and catalyst loadings. Chapter 4 expands the platform’s utility to automated substrate selection and functional group tolerance testing, enabling high-throughput dataset generation for machine learning applications.By automating photochemical optimization, RoboChem enables rapid discovery of efficient reaction conditions, minimizes human intervention, and enhances safety. The findings in this thesis highlight the transformative role of SDLs in modern chemistry, paving the way for broader applications in reaction discovery, materials science, and beyond
The rheostats of the immune response:Post-transcriptional regulation of gene expression by RNA-binding proteins in adaptive immunity
No full textThe adaptive immune system protectsthe host from pathogens and cancer through the actions of B and T lymphocytes.B cells produce antibodies, while CD4⁺ and CD8⁺ T cells secrete effector molecules,including inflammatory cytokines such as Tumor Necrosis Factor (TNF),Interferon gamma (IFN-g), and Interleukin-2 (IL-2). To perform their functions, T and Bcells differentiate into specialized subsets, a process governed by geneexpression programs that are tightly regulated at both transcriptional andpost-transcriptional levels. RNA-binding proteins (RBPs) are keypost-transcriptional regulators that control gene expression by modulating mRNAsplicing, stability, translation, and localization.This thesis demonstrates that theRBP ZFP36L2 plays a crucial role in limiting IFN-g production duringprolonged T cell activation. ZFP36L2 binds AU-rich elements in the 3’UTR of IfngmRNA, promoting its degradation and thereby reducing IFN-g output. Incontrast, its paralog ZFP36L1 acts earlier during T cell activation, andcombined deletion of ZFP36L1 and ZFP36L2 induces superior cytokine productionin T cells. We further show that ZFP36L1 and ZFP36L2 cooperate to control cellcycle progression and survival in resting T cells. Furthermore, transcriptomicprofiling reveals that RBPs are highly expressed in T and B cells and undergodynamic changes during differentiation. Lastly, we performed a CRISPR-Cas9screen in primary human T cells to identify RBPs that modulate T cellactivation.Together, the contents of thisthesis underscore the central role of RBPs in T and B cell biology and highlightseveral RBPs as potential targets for modulating T cell function fortherapeutic purposes
Indulging in Paradise?:EU law and policy of holiday air travel through the lens of practice theory
No full textIn his doctoral thesis Yannick van den Berg researches how EU (consumer) law and policy have failed to reduce emissions from holiday air travel. In his thesis he argues that taking a social practice theoretical approach to holiday air travel can yield valuable insights into EU law and policy on sustainable consumption, in particular by giving new ways to frame problems of sustainability. Instead of focusing on individual choice, behaviour and green technologies, the thesis shows how it can be more fruitful to understand the problem of emissions of holiday air travel as one that requires us to recraft air travel to become more sustainable, substitute air travel by rail travel and finally to see how air travel can become less ‘locked in’ to other practices like holidaying. Taking a practice approach, Van den Berg also sheds a light on the limitations of law (and policy) in addressing unsustainable social practices