International Migration, Integration and Social Cohesion online publications
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Optimizing pain management:Transition from acute to chronic pain
Get PDFThe aim of this thesis was to contribute to advancements in pain management within the perioperative setting. In part I, an overview of the literature was provided, focusing on innovative, multidisciplinary, and patient-tailored approaches to prevent the development of chronic postsurgical pain (CPSP). Furthermore, the TRUSt study with 176 patients showed that a Transitional Pain Service (TPS) did not impact immediate recovery after surgery, but long-term outcomes, including opioid reduction, and reduced disability, could benefit from TPS involvement. Healthcare providers expressed satisfaction and desired continued TPS implementation.Part II examined the use of perioperative peripheral nerve blocks, reviewing literature on the most common nerve blocks and their effectiveness on acute postoperative pain. In addition, two randomized controlled trials were conducted. The initial trial showed comparable readiness for discharge in patients undergoing anterior cruciate ligament reconstruction irrespective of whether they received a femoral nerve block or adductor canal block. Subsequently, the CAREFREE trial demonstrated that ambulatory continuous popliteal sciatic nerve blockade was non-inferior to standard of care with single shot popliteal sciatic nerve blockade on patient-reported overall benefit of analgesia. Finally, part III explored the unique pain experiences and treatment options for specific patient populations. First, potential age-related risk factors associated with acute postoperative pain were explored in older patients, revealing no difference between patients with and without disability. Second, neuraxial analgesia seems to be the most effective strategy in reducing acute postoperative pain in pediatric patients undergoing major abdominal surgery for intractable functional constipation. Last, the implementation of the multimodal pain protocol was feasible and enabled prompt administration of opioids in patients with sickle cell disease who experienced severe episodes of pain during vaso-occlusive crisis
Characterization of unknown <i>Bacillus subtilis </i>genes with transposon sequencing
Get PDFThe exact essentials for maintaining a living bacterial cell are still unclear. out of over 4000 genes in the model bacteria Bacillus subtilis and Escherichia coli, only approximately 260 genes have been identified as essential. However, this number does not accurately reflect the bacterial requirements due to the presence of many redundant pathways. To overcome this problem, we utilizes a genome-reduced strain of B. subtilis, PG10, that lacks 35% of the original chromosome, and likely many redundant pathways. Through extensive Tn-seq analysis, described in Chapter 2, we revealed 133 new essential genes in PG10, 69 of which remain functionally uncharacterized. In this thesis we describe the functional characterization of the unknown genes ytiB, ywnA, and ywgA. Chapter 3 reveals that the absence of ytiB leads to the overexpression of mtlR and subsequent upregulation of the mtlA operon involved in mannitol utilization. In Chapter 4, we explore the role of YwnA in oxidative stress response, and its regulatory impact on the ywnAB operon. Chapter 5 describes the discovery of a new dNTP triphosphatase that is controlled by YwgA. Finally, Chapter 6 investigates a phenomenon that we encountered throughout our research; a possible confounding effect on the transcriptome due to presence of the erythromycin resistance marker ermC. In conclusion, this PhD thesis elucidates the activity of several unknown genes in B. subtilis, thereby further our understanding of this important bacterial model system, and provides useful insights in the use of genome reduction to help uncover the minimal necessities for a bacterial cell
The interplay between epicardial adipose tissue and atrial fibrillation
Get PDFAtriumfibrilleren (AF), ook bekend als boezemfibrilleren, heeft een aanzienlijke invloed op het welzijn van patiënten en ons gezondheidszorgsysteem. Momenteel richt AF-management zich op algemene aritmogene mechanismen. Toespitsing van AF-management op het patiënt-specifieke substraat heeft de potentie om de lasten die geassocieerd zijn met AF te verminderen.Adipositas, overtollig vet, is een belangrijke risicofactor voor AF. In dit proefschrift onderzochten we de relatie tussen adipositas, vooral cardiale adipositas (epicardiaal vet), en het AF-substraat. We bestudeerden morfologische en biochemische verschillen van epicardiaal vetweefsel tussen mensen met en zonder AF, en of geïdentificeerde eiwitten en processen ook al meetbaar zijn voordat AF ontstaat. Verder onderzochten we of inflammatie van epicardiaal vet in AF niet-invasief klinisch meetbaar is op CT-scans.Onze bevindingen tonen aan dat het epicardiale vet-secretoom van AF-patiënten atriale fibroblasten sterker activeert dan van patiënten zonder AF. Ook vonden we dat neutrofielactiviteit, met myeloperoxidase als kerneiwit, verhoogd is in epicardiaal vet van patiënten met AF, maar ook bij patiënten die later pas AF ontwikkelen. Bovendien bestaat er een positieve relatie tussen de dichtheid van epicardiaal vet op de CT-scan en het aantal neutrofielen in dit vet. Ons systematische review toont aan dat CT-dichtheid van epicardiaal vet hoger is in patiënten mét dan zonder AF, maar alleen bij consistent gebruik van buisspanning of correctie hiervoor. Onze bevindingen suggereren dat inflammatie, met name neutrofielactiviteit, een belangrijke rol speelt in de relatie tussen epicardiaal vetweefsel en AF. Hoewel verdere klinische validatie nodig is, is CT-scan dichtheid een veelbelovende parameter voor het detecteren van deze vetinflammatie bij AF
Continuous blood pressure monitoring:The pulse of hemodynamics
Get PDFCritical illnesses and surgical procedures can impede the continuous blood flow to vital organs, potentially resulting in inadequate oxygen supply to meet their metabolic demands. Monitoring tools to assess organ perfusion are not readily available at the patient's bedside. Therefore, blood pressure measurements currently serve as a surrogate to estimate a patient's circulatory state. The first part of this thesis offers an overview of how critically low arterial blood pressure, also known as hypotension, is defined, monitored, and treated in intensive care units (ICUs) across various countries worldwide. Additionally, it provides insight into the effects of hypotension exposure during an ICU stay on patient outcomes. To prevent hypotension-related organ injury, blood pressure is often continuously monitored in critically ill patients, allowing for immediate alarms and prompt treatment if hypotension occurs. However, hypotension, and therefore organ injury, already occurred at that point. Moreover, selecting the appropriate treatment can be challenging as the cause of the blood pressure drop may be unclear. The final part of this thesis focuses on the prediction and prevention of hypotensive events during cardiac surgery and postoperative intensive care unit stay using continuous blood pressure monitoring and machine learning
Optimization of systemic treatments for patients with biliary tract cancer
Get PDFBiliary tract cancer (BTC) is a malignancy of the intrahepatic and extrahepatic bile ducts, including the gallbladder. BTC is diagnosed in approximately 1,000 patients annually in the Netherlands. The majority of patients are diagnosed at an advanced stage. Before the publication of the landmark ABC-02 trial in 2010, there were no standard systemic treatments for BTC. Over the past decade, there has been a substantial increase in the number of conducted clinical trials for BTC. Despite this, limited treatment options are available, all of which provide limited survival benefits. Real-world data is highly relevant to validate the results of clinical trials in daily practice and to monitor the quality of care in daily practice. The main aim of this thesis was to evaluate the effectiveness of available systemic treatments in daily practice using population-based data, and to identify subgroups of patients that may benefit most from these treatments. Additionally, we aimed to study the feasibility and efficacy of fluorouracil, leucovorin, irinotecan plus oxaliplatin (FOLFIRINOX) as a second-line treatment for biliary tract cancer
The complement system in COVID-19
Get PDFIn this thesis, complement activation in COVID-19 was described and the effect of targeting complement factor C5a with the monoclonal antibody vilobelimab in severely and critically ill COVID-19 patients. The aim was to determine the effect of vilobelimab on mortality and safety in critically ill COVID-19 patients, to assess its effects on biomarkers of inflammation and coagulation in severely and critically ill COVID-19 patients, and to analyse its pharmacokinetics. In this thesis, it was shown that vilobelimab improved survival in critically ill, mechanically ventilated COVID-19 patients. Vilobelimab was found to efficiently inhibit C5a in severely and critically ill COVID-19 patients, without evidence of immunogenicity in critically ill COVID-19 patients. Finally, vilobelimab was shown to decrease the inflammatory response by lowering concentrations of CXCL8 over time. Further research should investigate whether different subphenotypes in COVID-19 respond differently to vilobelimab treatment and focus on the role of C5a and C5a inhibition in other viral infections that lead to ARDS
Supramolecular strategies for the templated synthesis of confined nanoparticles and their application in catalysis
Get PDFNanoparticles (NPs) and Nanoclusters (NCs, NPs with a diameter of <2 nm) have become invaluable assets in various scientific disciplines. The dimensions, surface environment and composition of nanoparticles are essential to their distinctive properties and catalytic features. Hence, developing methods to gain precise synthetic control over these features is of considerable interest. Motivated by the challenges involved in NP and NC synthesis and inspired by supramolecular metal catalyst pre-organisation strategies developed in our group, we were curious if we could employ self-assembled [M12L24] nanospheres as templates for controlled nanocluster and nanoparticle synthesis. The goal of the research in this thesis was to explore and develop new synthetic methods for the precise preparation of (mixed) metal nanoparticles and nanoclusters through supramolecular pre-organisation. We herein describe a new synthetic strategy involving the pre-organisation and subsequent hydrogenation of organometallic complexes within [M12L24] nanospheres, leading to the templated formation of encapsulated nanoclusters or nanoparticles that reside in a unique microenvironment
The documentation of historical facts in trial judgments of the international criminal court:A constitutional theory of international criminal proceedings
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Poetic understanding and political community:Actualizing plurality through poetry
Get PDFCan poems show us a way to be part of a many-voiced history, to be with, a part of, despite being an outsider? What complex kinds of understanding do we need to sustain solidarities across the dividing lines of race, coloniality, caste, and class, and to create processes of sharing that do not undermine social difference or the particularity of individual experience? And can we look towards poetry, towards the dynamic between poems and readers, to offer us a model for such understanding? Where instituted racial and colonial hierarchies obstruct complex understandings of some ‘others’ as who they are and not what they are, can poetry help us? In this project, I propose an intersubjective pragmatist framework for reading poetry that takes the actualization of a decolonial and anti-identitarian political plurality as the basis of poetry’s politicality. At its core is the concept of ‘poetic understanding’: a transformative quality of understanding that is a necessarily dynamic, contingent, non-hierarchical, and anti-identitarian process of transformation and constitution, where who I am comes to be constituted in my process of understanding, as does who the other is. I develop this framework by bringing together four distinct conceptual fields: I build on Hannah Arendt’s theory of political plurality, Édouard Glissant’s concepts of relation and opacity, John Dewey’s pragmatist theory of aesthetic experience, and Sylvia Wynter’s model of decipherment to examine poetry as a site of intersubjective transformation, where a genuine plurality of relation in interaction, divested of discriminatory and hierarchizing mechanics, can be actualized. In such a conceptualization of poetic understanding, I argue, lies an as-yet-underestimated cornerstone of solidary understanding, and the crux of poetry’s political contribution