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Improving medication safety in patients on antithrombotic therapy
No full textEvery hour, 11 people in the Netherlands develop thrombosis, a blood clot in a blood vessel. Blood thinners are used to prevent and treat thrombosis, but they can also cause bleeding. Their use requires a careful balance between the risk of bleeding and the risk of thrombosis.After thrombosis, some patients use two blood thinners at the same time. After a few weeks or months, one of these blood thinners should be stopped. In daily practice, this does not always happen.The aim of this thesis is to explore how blood thinners can be used more safely.In a study in three hospitals, we found that 41.2% of patients using two blood thinners should have stopped one blood thinner earlier. Because they did not stop the blood thinner in time, they unnecessarily had a higher risk of bleeding. After advice from a pharmacist, this percentage dropped to 2.2%.Community pharmacists need the right information to prevent patients from using two blood thinners for too long, but this information is often missing. Therefore, we developed a questionnaire that helps pharmacists ask the right questions to patients to decide if using two blood thinners is really needed.We also sent pharmaceutical discharge letters to community pharmacies. These letters explained why patients must use blood thinners and for how long. As a result, patients stopped the blood thinner that needed to be stopped more often on time. The percentage of patients using two blood thinners for too long decreased from 22.1% to 9.3%
Optogenetic tools for cell cycle control and cell growth regulation in budding yeast
No full textCell cycle progression and cell growth are governed by complex regulatory networks that integrate internal state and environmental cues. In budding yeast, these processes are tightly controlled by cyclin-dependent regulation of the cell cycle and nutrient-sensing pathways including the Target of Rapamycin Complex 1 (TORC1) pathway. Traditional approaches to perturb these systems, such as gene deletions, overexpression strategies, or pharmacological inhibitors, have been fundamental in elucidating their function, but they are often limited by poor temporal resolution, irreversibility, or off-target effects. This thesis explores optogenetics as an alternative experimental paradigm, aiming to establish light-controlled, reversible, and minimally invasive tools to interrogate cell cycle and nutrient signaling dynamics in Saccharomyces cerevisiae
Learning to move, moving to improve:Applying motor learning principles to reduce ACL injury risk
No full textSuccess in sports depends not only on talent and training, but also on staying healthy. For young athletes, especially in sports like soccer and basketball, knee injuries are a serious concern. An ACL rupture is among the most severe injuries, often keeping athletes off the field for long periods. This dissertation presents research on how principles of motor learning can be applied to reduce ACL injury risk.While traditional training focuses on detailed instructions and quick improvements, the results of this dissertation demonstrate that an alternative approach can be more effective. Using ideas from motor learning research, athletes can improve how they move in a more natural and motivating way. For example, instead of overthinking instructions, athletes can learn implicitly, by watching skilled athletes on video and seeing recordings of their own performance. This helps them adjust their movements without having to consciously think about every detail. Giving athletes more control also matters. Letting them decide when they want feedback increases motivation and the quality of movement. Additionally, positive expectations encourage athletes to try different ways of moving and find what works best for their bodies.Over 130 male and female team-sport athletes (12-35 years), ranging from recreational to talent level, participated in intervention studies. Simply watching a skilled role model led to short-term changes. However, athletes could also imitate suboptimal movements, which can increase injury risk. In contrast, lasting improvements required the combination of video instruction with video feedback of the athletes themselves. These improvements included bending the hips and knees more and reducing harmful sideways knee motion, changes that are known to lower ACL injury risk. Additionally, wearable sensors proved reliable for measuring movement outside the lab, such as on a soccer field. This enables future research in realistic sports environments and development of on‑field interventions to further reduce ACL injury risk
Complications of microaxial flow pump and VA-ECMO in infarct-related cardiogenic shock:Insights from the Netherlands heart registration
No full textBackground: Active mechanical circulatory support (MCS) is associated with high complication rates. Reducing device-related complications may improve outcomes in patients with infarct-related cardiogenic shock (AMI-CS). This study aims to provide in-depth insight in the occurrence, specification and timing of complications in patients receiving active MCS, providing valuable starting points for clinical practice and future studies to reduce complications.Methods: This real-world, multicentre study, using data from the Netherlands Heart Registration PCI-Registry, describes AMI-CS patients that underwent PCI and received MCS between 2017 and 2021 across 9 Dutch hospitals.Results: This registry included 241 patients with a mean age of 59.7 years and predominantly male (78.0 %). Microaxial flow pump (MFP), VA-ECMO and MFP + VA-ECMO were used in 93 (38.6 %), 121 (50.2 %) and 27 (11.2 %) patients. MFP + VA-ECMO was associated with highest complication rates, particularly bleeding events (67 % vs. MFP: 33 % vs. VA-ECMO: 40 %). Differences in bleeding events persisted while accounting for competing risk of death (subdistribution hazard ratio (SHR) MFP + VA-ECMO vs. MFP: 2.33 [1.33–4.07]; SHR MFP + VA-ECMO vs. VA-ECMO: 2.00 [1.19–3.36]). SHR for VA-ECMO vs. MFP was 1.18 [0.74–1.90]). Bleeding events were observed within the first days of support, but also on the day of explant and thereafter. Access-site related bleeding events accounted for 51 % of all bleeding events.Conclusions: Combined use of MFP and VA-ECMO was associated with higher complication rates, particularly bleeding events, compared to single device use. Complication rates between MFP and VA-ECMO were not significantly different. Importantly, patients are still at risk for bleeding events during and after explant of MCS devices.</p
ZnO Nanoparticles Synthesized via a Supercritical-CO<sub>2</sub>-Assisted Method as Photocatalysts for the Degradation of Water Pollutants
No full textZinc oxide (ZnO) is a widely studied photocatalyst for the degradation of organic pollutants in water, yet its conventional sol–gel synthesis often suffers from low yield and produces materials with low specific surface area. In this study, we tackled these limitations by synthesizing ZnO nanoparticles using a supercritical-CO2-assisted sol–gel method (ZnO-scCO2). The influence of the calcination temperature, precursor concentration, and solvent type on the synthesis of ZnO was systematically investigated, and the materials were characterized with a combination of techniques (XRD, SEM, N2 physisorption, UV-Vis-DRS spectroscopy). The photocatalytic performance of the ZnO-scCO2 materials was evaluated in the degradation of two probe pollutants (phenol and rhodamine B, 200 ppm), under UV and visible radiation. The scCO2-assisted method in ethanol as the solvent allowed achieving at least a four-fold higher ZnO yield and two-fold higher surface area compared to the materials prepared with a conventional sol–gel route without scCO2. These ZnO-scCO2 nanoparticles consistently showed enhanced photocatalytic activity in the removal of phenol and rhodamine B compared to their counterparts synthesized without scCO2 and compared to commercial ZnO. Among the screened synthetic parameters, the solvent in which ZnO was prepared proved to be the one with the strongest influence in determining the ZnO yield and its photocatalytic activity. The optimum results were obtained using 0.50 M zinc acetate as the precursor in 1-butanol as the solvent, and calcination at 300 °C.</p
Parameterized Argumentation-based Reasoning Tasks for Benchmarking Generative Language Models
No full textGenerative large language models as tools in the legal domain have the potential to improve the justice system. However, the reasoning behavior of current generative models is brittle and poorly understood, hence cannot be responsibly applied in the domains of law and evidence. This paper presents reasoning benchmarks that are dynamically varied, scalable in their complexity, and have formally unambiguous interpretations. In this study, we illustrate the approach on the basis of witness testimony, focusing on the underlying argument attack structure. We dynamically generate both linear and non-linear argument attack graphs of varying complexity and translate these into reasoning puzzles about witness testimony expressed in natural language. We show that state-of-the-art large language models often fail in these reasoning puzzles, already at low complexity. Obvious mistakes are made by the models, and their inconsistent performance indicates that their reasoning capabilities are brittle. Furthermore, at higher complexity, even state-of-the-art models specifically designed for reasoning make mistakes. We show the viability of using a parametrized benchmark with varying complexity to evaluate the reasoning capabilities of generative language models, which contribute to a better understanding of the limitations of the reasoning capabilities of generative models.</p
High riverine metal oxide input provides substrates for metal-dependent methane oxidation in Baltic Sea sediments
No full textThis a dataset for thesis manuscript "High riverine metal oxide input provides substrates for metal-dependent methane oxidation in Baltic Sea sediments".
Back to basics:Bile acids in fat absorption
No full textUsing innovative methods to modify bile acid pool size and composition in mice, Chan et al. delineate that the "classical" function of bile acids, the body's endogenous soaps, in mediating intestinal fat absorption involves a delicate interplay between bile acid and fatty acid structures, with important metabolic implications.</p
Physics meets tradition:An ethnophysics study of the Perahu Jong in developing students' science literacy
No full textThe present study investigates the impact of the Perahu Jong cultural festival on students' cultural literacy and their understanding of physics concepts on Rupat Island, Indonesia. Utilizing a convergent mixed-methods approach, the research combined qualitative data from interviews and observations with quantitative data from a validated survey, involving 109 students from six schools. The instrument validation process included an expert panel and reliability analysis to ensure methodological rigor. The findings indicated that students' understanding of physics concepts related to the festival included Newton's Laws, Waves, Equilibrium, Pressure, Static Fluids, and Dynamic Fluids. Despite a generally low level of cultural literacy, Spearman's correlation analysis revealed a statistically significant. However, the correlation was categorized as weakly positive (rs = .266, p = .005) between cultural literacy and physics conceptual literacy, indicating that cultural understanding is related to academic achievement but explains only a limited proportion of the variance in physics literacy.266, p < .001) between cultural literacy and physics conceptual literacy, underscoring the critical role of cultural understanding in academic achievement. This study makes a unique contribution by quantitatively demonstrating the relationship between cultural literacy and physics conceptual literacy, particularly in coastal communities with strong ties to the Perahu Jong tradition, and presents a validated model for culturally responsive pedagogy.</p