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Diplomatic propaganda in the Dutch Republic and France, 1609-1674
No full textThis dissertation investigates the practices and theories of printed propaganda among seventeenth-century Dutch and French diplomats. It argues that early modern diplomats had more developed and explicit understandings of propaganda than has so far been assumed. The dissertation shows that these diplomats drew from contemporary political philosophy and theories of mind to formulate their publication strategies, and demonstrates how this knowledge was put into practice using a series of case studies. The first two chapters investigate two major diplomatic crises between the Dutch Republic and France to understand how French diplomats evaluated the political effects of pamphleteering within these conflicts. The third and fourth chapters focus on the role of embassy secretaries in coordinating international pamphleteering campaigns in early modern Europe and transferring knowledge about past campaigns within diplomatic circles. The fifth chapter investigates how diplomats understood the psychological effects of propaganda, focusing in particular on contemporary notions of the soul, the animal spirits, and the faculties of reason and will. It argues that subtle differences within diplomats’ understanding of these faculties influenced their views on the desirability and feasibility of particular approaches to propaganda. The dissertation argues the use of and need for a sustained dialogue between studies on early modern public politics and propaganda studies
Dynamically driven-dissipative phases of matter
Get PDFThis thesis is a theoretical study of low dimensional non-equilibrium quantum many-body systems undergoing dynamical drive and dissipation. Thus, the models in this thesis host explicit time-dependent parameters while in thermal contact with an environment. The formal description of these models is approximated using a time-dependent Lindblad equation. Multiple methods are employed, such as numerical simulations, by means of exact diagonalization and direct differential equation solving, mean-field approximations, algebraic disentanglement of time-ordered exponents and integrability.Three different dissipative models are investigated: (I) a system of free, translationally invariant fermions with dissipation, (II) driven-dissipative bosons in with a Kerr non-linearity (III) and finally noisy, driven-dissipative spins whose correlation functions are described by a non-Hermitian Richardson-Gaudin Hamiltonian. This thesis reports among others an exact solution for the wave functions of the free fermions in terms of coupled Riccati equations obtained through algebraic disentanglement. Furthermore, time-crystalline phases and chaos are identified in in the bosons.The noisy spins cannot be investigated directly, rather requiring an in-depth study of the formal solution to the time-dependent Richardson-Gaudin Hamiltonian. This study revealed a connection between integrable (hyperbolic) Landau-Zener models and the Richardson-Gaudin Hamiltonian and its solutions. Long-time expressions for specific wavefunctions of the time-dependent Richardson-Gaudin Hamiltonian are found. A time-dependent phase transition can subsequently be observed in the spins’ correlation functions where the transient behavior of the system ultimately reduces to a power law. Furthermore, using exact results for two-point correlation functions a temporal phase transition is identified
Systemic treatment in breast cancer:Towards a golden ratio
No full textBreast cancer affects over 2 million patients worldwide annually. Systemic treatment options for breast cancer are ample, and vary from endocrine treatment to chemotherapy and targeted therapies. Systemic therapies hold great promise for patients, but also come with a risk of toxicity for patients (in terms of side effects) as well as societies (in terms of resource use). This thesis describes several studies aimed at optimizing different types of systemic treatment for patients with breast cancer. The main findings include: - The use of aromatase inhibitors in early breast cancer is not associated with early markers for cardiovascular disease (carotid intima media thickness, advanced glycation end products and dyslipidemia) - Patients with limited metastatic burden, so-called oligometastatic disease, have a favorable prognosis compared to patients with more widespread disease- Intensified alkylating chemotherapy does not improve clinical outcome compared to standard chemotherapy regimens in patients with oligometastatic breast cancer, whose tumor harbors homologous recombination deficiency - Using CDK4/6 inhibitors in first- versus second-line does not provide clinical benefit (in terms of progression-free nor overall survival) and is associated with an increase in toxicity for patients and higher drug expenditures for societies- Efficiency clinical trials are essential for affordable and sustainable health car
Rescue alkaline phosphatase in ischemic kidney damage:Target then treat
No full textThis thesis centers exploring kidney transplantation and acute kidney injury (AKI), with a particular focus on the therapeutic potential of alkaline phosphatase (AP) to mitigate ischemia-reperfusion injury (IRI) by modulating the host and injury response. To better understand AKI following transplantation, we investigated early graft dysfunction across donor types using data from the Dutch National Transplant Registry. The analysis compared delayed graft function (DGF), slow graft function (SGF), and immediate graft function (IGF) in kidneys from donation after brain death (DBD) and donation after circulatory death (DCD). While long-term graft survival was similar, early dysfunction patterns and clinical implications varied, underscoring the need for tailored post-transplant care.In two biomarker studies, we examined AKI in critically ill patients with COVID-19 and sepsis. Findings suggest that these are distinct entities, with urinary CCL14 serving as a potential marker of severe host-response dysregulation closely tied to AKI development. We also explored AP’s therapeutic potential in a narrative review, particularly for sepsis-associated AKI, where preclinical studies showed promise, though clinical efficacy remains unproven.To explore clinical translation, we administered AP in a porcine model of donor kidney storage to assess its capacity to preserve cellular metabolism and reduce injury. Finally, in a pilot study, we administered bovine-derived AP (bRESCAP) to living donor kidney transplant recipients, evaluating its safety, feasibility, and impact on graft function one year post-transplant, using measured glomerular filtration rate (mGFR) and kidney injury biomarkers
Exploring the outflows and evolution of accreting neutron stars:A multi-wavelength approach
No full textNeutron stars and black holes (i.e. compact objects) are the evolutionary end states of massive stars, when these collapse and undergo a spectacular supernova explosion. These massive stars often form in binary systems, where mass transfer (accretion) can occur. When one of the stars in a binary system evolves into a compact object, its immense gravity causes accreted material to release vast amounts of energy, primarily emitted as X-rays. These systems are hence called “X-ray binaries”. X-ray binaries can also produce powerful outflows such as collimated jets, as well as winds launched from the accretion disc. This thesis is devoted to multi-wavelength observational studies of neutron stars in X-ray binaries, in particular to characterize their outflows and to understand certain aspects of their evolution. I combine X-ray and radio measurements to trace the coupling between the accretion inflow (via X-rays) and jet outflow (via radio), and investigate the role of additional X-ray emission from the neutron star surface in deriving the inflow-outflow behaviour. Furthermore, I use X-ray to near-infrared data to study accretion disc winds. I show that neutron star X-ray binaries can launch disc winds in much smaller systems than previously expected, and discuss the implications for the evolution of these systems. Finally, I present a study on the formation channel of a peculiar neutron star X-ray binary, and the impactful discovery of an unexpected velocity kick in its formation. I show that an uncommon supernova mechanism might impart velocity kicks, which was not previously realised
Coagulopathy assessment by rotational thromboelastometry and current treatment practices in cardiac surgery and critical care
Get PDFThis thesis investigated the role of viscoelastic testing, specifically rotational thromboelastometry (ROTEM), in guiding coagulation management for patients undergoing cardiac with cardiopulmonary bypass (CPB) and patients supported by extracorporeal membrane oxygenation (ECMO). It also reviewed current coagulation correction strategies in cardiac surgery, critically ill patients, and ECMO-supported patients, aiming to improve diagnostics and treatment outcomes.In Part I, the thesis identified that ROTEM reference ranges for cardiac surgery patients differ from manufacturer standards, indicating a somewhat hypercoagulable state without clinical symptoms. Female patients showed a slightly more hypercoagulable profile preoperatively. ROTEM interpretation showed high reliability among experts, though discrepancies between expert decisions and local transfusion protocols highlight a need for refined clinical decision tools. The transition from ROTEM Delta to ROTEM Sigma devices was explored, revealing differences in clotting time measurements in the EXTEM channel that might require local transfusion protocol adjustments. Preoperative ROTEM profiles helped identify distinct coagulopathy subphenotypes in acute type A aortic dissection patients, with hypocoagulability linked to worse outcomes. No significant preoperative coagulation differences were found between bicuspid and tricuspid aortic valve patients. In patients supported by ECMO, ROTEM cannot predict a bleeding event better than conventional coagulation tests (all models performed poor to moderate), and combining them did not significantly improve performance. Part II reviewed coagulation management practices, highlighting limited available evidence supporting intravenous hemostatic agents in particularly thoracic aortic surgery, and noted variable clinical approaches to reversing antithrombotic agents in critically ill patients, often lacking specific protocols. Plasma transfusions were frequently given without active bleeding or guideline-based indications in critically ill and ECMO-supported patients, underscoring the need for improved guideline adherence and targeted research to optimize coagulation management
Rare treatment, real barriers:A critical appraisal of cholic acid treatment
No full textThe thesis Rare Treatment, Real Barriers: A Critical Appraisal of Cholic Acid Treatment, explores the pharmaceutical, regulatory, and clinical dimensions of cholic acid (CA) therapy for patients with rare bile acid synthesis disorders (BASDs). While CA is an authorized orphan drug in the EU and US, its evidence base is limited and access in the Netherlands has been unavailable. To address this gap, the Amsterdam UMC developed a pharmacy-compounded CA formulation to enable both patient care and clinical research.The work demonstrates how pharmacists can bridge the gap between unavailable commercial medicines and patient needs by developing safe, high-quality compounded formulations under Good Manufacturing Practice (GMP) conditions. The thesis evaluates the analytical quality of CA as an active pharmaceutical ingredient, validates the compounded formulation, and confirms its stability and safety. A prospective clinical study further assesses long-term biochemical and clinical effects in patients with AMACR and 3β-HSD deficiency, showing biochemical improvement and good tolerability.Beyond its clinical findings, the thesis highlights the broader role of pharmacy compounding as an instrument of pharmaceutical innovation, access, and personalized medicine. It underscores the societal and ethical responsibility of pharmacists to ensure continuity of care when industrial supply fails or becomes unaffordable.By integrating pharmaceutical science, clinical research, and policy analysis, this work illustrates how the pharmacist’s expertise remains essential in safeguarding access to effective treatment for patients with rare diseases.<br/
The making of the global indigenous movement and its relation to Bolivian indigeneity today:Anthropology, development and transnationalism (1930-2012)
No full textThis dissertation documents how discourses and legal frameworks regarding global indigeneity influenced Bolivia’s polity and laws. From a historical approach, it attempts to answer the question regarding how international legal instruments for ‘indigenous peoples’, such as the ILO Convention 169 and the Declaration for United Nations Declaration on the Rights of Indigenous Peoples (UNDRIP), became major references for the modification of the Bolivian Constitutions in 1994 and 2009. These constitutional changes converted the country first into a ‘multi-ethnic and pluricultural’ state, and later into a ‘plurinational’ one.The study specifically explores the role of anthropology, international development and transnationalism in this transformation. By exploring the making of the global indigenous movement and Bolivian current indigeneity through a geneaology, the research seeks to unravel how the West, and generally people who do not consider themselves ‘indigenous’, have constructed ‘the other’ over time. Following this, it analyzes the influence of the development industry (which includes NGOs, churches and all types of international development organisations) in the construction of a range of indigeneities within a transnational and historical perspective
Molecular regulation of neural stem cell quiescence by FoxO transcription factors
Get PDFNeural stem cells (NSCs) are the origin of new neurons in the adult brain. The majority of NSCs reside in a state outside of the cell cycle known as quiescence, which helps to limit exhaustion of the NSC population. During aging, however, NSCs decline in number and grow increasingly quiescent, which both impair adult neurogenesis. Only finely tuned regulation of their cell cycle can ensure lifelong neurogenesis. We discovered that transcription factor FoxO6 is a novel regulator of NSC fates. In contrast to FoxO3, FoxO6 suppresses NSC quiescence during aging.Interestingly, NSCs lacking FoxO6 exhibit a glioma-like molecular signature whereas FoxO6 expression is a prognostic factor for glioma patients. This indicates a role for FoxO6 in the oncogenic transformation of neural stem cells towards brain cancer stem cells. In addition, these FoxO6-deficient NSCs show strongly reduced expression of Hmgn2, an epigenetic regulator of the NSC lineage and which we identified to be a transcriptional target of FoxO3. An emerging role of NSC regulation is the circadian control over their cell cycle entry. We found that FoxO3 controls the cellular circadian clock in NSCs and is necessary for the correct timing of their proliferation in the hippocampus. Together, this shows that an interplay between FoxO3 and FoxO6 regulates NSC quiescence and is required for healthy aging
Mechanistic insights and novel treatments for trauma-induced coagulopathy
Get PDFBleeding after trauma is a leading cause of mortality worldwide and is exacerbated by trauma-induced coagulopathy (TIC). Early on, TIC is characterised by platelet dysfunction, coagulation factor depletion and hyperfibrinolysis. Despite its clinical importance, the pathophysiology of TIC is not fully understood, and effective treatment options are limited. Therefore, we aimed to investigate the mechanisms underlying TIC and explore novel treatments using a translational approach.First, we studied the effect of shock duration on TIC, using a murine trauma model. Next, we reviewed the mechanisms and treatment options for trauma-induced platelet dysfunction. Using an experimental model of trauma and shock, we explored the relationship between high mobility group box 1 (HMGB1) and TIC. We investigated whether inhibition of HMGB1 would improve platelet dysfunction and TIC.Reduced coagulation factor activity is one of the key features of TIC. Previously it was shown that Factor V activity is most severely depleted. In an international cohort of trauma patients, we explored the relationship between Factor V activity and mortality. Next, we used an in vitro model of TIC to investigate whether supplementing FV(a) would improve coagulation. TIC with hyperfibrinolysis has the highest mortality when compared to other TIC phenotypes. The mechanisms are however incompletely understood. In the final part of this thesis, we studied the effect of ADAMTS13 degradation in hyperfibrinolytic trauma patients and explored whether ADAMTS13 has a causal role in hyperfibrinolysis. In this study, we combined clinical data from severely injured trauma patients, with a mechanistic in vitro study. These results were further supported in an experimental trauma model, using ADAMTS13 knock-out mice