International Migration, Integration and Social Cohesion online publications
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Predictive algorithms in perioperative haemodynamic management
Get PDFDit proefschrift richt zich op de effectiviteit van de Hypotension Prediction Index (HPI), een voorspeller van lage bloeddruk, bij het verminderen van hypotensie tijdens hartchirurgie en intensivecare-opname (IC). Het evalueert de vergelijkbaarheid van invasieve en niet-invasieve HPI-modaliteiten, waarbij op groepsniveau grotendeels vergelijkbare prestaties werden gevonden, met kleine verschillen in voorspellende tijdvensters.Daarnaast worden zorgen besproken over de voorspellende nauwkeurigheid van eerdere HPI-validatiestudies. Hoewel HPI veelbelovend is, suggereren sommige bevindingen dat standaard bloeddrukparameters vergelijkbare resultaten kunnen bieden. Daarom werd in een nieuwe vergelijkende analyse gekozen voor een klinisch relevante benadering om deze suggesties te onderzoeken. Hierbij werd de vergelijking gemaakt tussen HPI-pop-upalarmen en de MAP-alarmen in veelgebruikte bloeddrukmonitoren, ingesteld op een drempelwaarde tussen 70 en 75 mmHg. Deze analyses tonen aan dat het machine-learning-gebaseerde HPI-algoritme voordelen biedt op het gebied van voorspellen en mogelijk voorkomen van hypotensie. Een belangrijke exploratieve analyse liet echter zien dat een kleine aanpassing aan de MAP-alarmen, door het toevoegen van een tijdsafhankelijke functie, de voorspellende prestaties vergelijkbaar maakte.Tot slot wordt een gerandomiseerde studie besproken die is uitgevoerd tijdens hartchirurgie en postoperatieve IC-verblijven om HPI-geleide zorg te vergelijken met standaardzorg. HPI bleek effectief in het verminderen van hypotensie zonder een toename van hypertensieve gebeurtenissen. De studie toont aan dat HPI minder onnodige alarmen genereert dan conventionele bloeddrukmonitoren en voordelen biedt in de klinische praktijk. De resultaten ondersteunen de haalbaarheid en effectiviteit van HPI bij complexe chirurgische procedures en benadrukken het potentieel van innovatieve technologieën om de hemodynamische zorg te verbeteren
Visualizing, quantifying, and understanding nanowear of hard multi-asperity contacts
Get PDFWear 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
Tissue-specific interactions between <i>Xanthomonas campestris</i> pv. <i>campestris</i> and its host plant
Get PDFThe work in this thesis focused on the interaction between the bacterial plant pathogen Xanthomonas campestris pv. campestris (Xcc) and the host plant Arabidopsis thaliana. As this pathogen displays an intricate infection process with multiple distinct phases, efforts were made to identify plant resistance mechanisms in the early phase of infection when the bacteria enter the plant hydathodes, which are organs involved in water homeostasis that are located at the leaf margins. An intracellular immune receptor was identified that confers resistance against Xcc early in hydathodes, but not in later stages of infection. To track progression of the bacteria through the plant, bioluminescence was applied to genetically modify the bacteria to emit light. Next, a high-throughput imaging method was developed to follow infection events Arabidopsis rosettes non-invasively over time. This method yielded insights in the infection process and allowed for phenotypic screening of large plant populations. Finally, a bacterial virulence factor was identified that contributed to the vascular phase of the bacteria, when they colonize the plant xylem vessels and spread systemically through the plant. Taken together, the findings in this thesis yielded insights on the tissue-specific interactions between Xcc and its host plant
Serotonin and dopamine:An updated investigation of neurochemical signals surrounding appetitive and aversive stimuli
Get PDFMany people believe that dopamine and serotonin are key players in experiencing reward and happiness, but this understanding oversimplifies the complex roles these neuromodulators play in influencing behavior. Our current understanding of dopamine and serotonin signaling remains incomplete, limiting the development of effective treatments for neuropsychiatric disorders such as obsessive-compulsive disorder (OCD), addiction, depression, and Parkinson’s disease. In this thesis, we employed high-precision techniques with high specificity, sensitivity, and temporal resolution to better characterize dopamine and serotonin signaling. By utilizing fast-scan cyclic voltammetry (FSCV) to measure real-time serotonin and dopamine release and optogenetics to selectively activate serotonergic neurons, we investigated how these neuromodulators respond to appetitive and aversive stimuli on behaviorally-relevant timescales. We found dopamine release is differentially regulated across striatal subregions and that, within the ventromedial striatum (VMS), value-based changes in dopamine signaling in response to rewards occur rapidly and incorporate both model-based and model-free reinforcement learning mechanisms. Additionally, we found that VMS dopamine tracks aversive stimulus duration and prediction but not value or prediction error. Lastly, we observed that serotonin mildly promotes voluntary actions and ongoing movement but does not influence instinctive or compulsive behaviors. Together, our findings provide new insights into how dopamine and serotonin influence behavior in response to appetitive and aversive stimuli. These insights offer promising avenues for improving therapeutic strategies for neuropsychiatric disorders
Appropriate care and sustainable anaesthesiology
Get PDFWith stagnating life expectancy in developed nations, rising incidence of chronic diseases and mounting costs of care, the call for transforming healthcare into an efficient and sustainable sector has never been more pressing. In this thesis, meta-research on appropriate care and sustainability was combined with qualitative research and guideline development. The overall aim of the thesis was to enable changes in clinical and scientific behaviour that promote appropriate and sustainable healthcare.The findings of this thesis indicate that methodological limitations, unrealistic expectations and the use of inappropriate outcomes measures may limit the translation of study results into clinical practice. Moreover, our results suggest that all those involved in research – researchers, funders, editors – are inclined to favour innovation above evaluation. These findings were translated into clinical practice by interviewing anaesthetists about clinical decision-making. Reported barriers to change included a prevailing lack of evidence for everyday interventions, patient and societal pressures and expectations, and financial incentives to ‘do more’. This thesis further focussed on the largest source of environmental pollution originating from anaesthesiology, which is the use of anaesthetic gases. These gases are potent greenhouse gases, ‘forever chemicals’ (PFAS) and cause ozone layer depletion. We performed two systematic reviews with meta-analyses and concluded that omitting anaesthetic gases from general anaesthesia is safe and effective, and actually improved postoperative recovery. To promote sustainable change among anaesthetists, we additionally collected qualitative data through questionnaires and interviews and combined these to create a national guideline in close collaboration with the Dutch Society for Anaesthesiology
Emerging fields:Their strategic implications and identification
Get PDFThis PhD dissertation explores the role of emerging fields, such as Artificial Intelligence (AI), for two key strategic decisions—entrepreneurial resource acquisition and alliance formation—and examines how these fields can be identified using computational methods. Chapter 2 examines the effects of being associated with an emerging field on initial venture financing from both scientists’ and investors’ perspectives. We demonstrate that increasing scientific involvement in a field positively influences capital raised, while increased investor involvement has a negative effect. This contrast likely arises because scientific interest signals innovation potential, whereas greater investor presence may indicate that the most lucrative opportunities have already been exploited. Chapter 3 investigates how the novelty of these fields—both to the firm making a decision and to its competitors—affects alliance formation. We further explore how the scientific background of alliance decision-makers shapes these strategic choices. Our findings show that only fields familiar to competitors of the focal firm positively impact alliance formation, while decision-makers with a scientific background tend to favor more novel solutions. Chapter 4 assesses the effectiveness of various computational methods in identifying fields, introducing a novel quantitative measure of overlap to compare their results. Our findings reveal that each method yields different insights, highlighting the need for careful interpretation as certain outputs may lack substantive meaning, necessitating human judgment. Chapter 5 extends traditional metrics, commonly applied to track topics over time within a single method, by using them to bridge topics, including fields, across different methods. We also assess the performance of traditional versus neural topic modeling in detecting emergence. Our results show that content-based metrics are particularly effective for cross-method matching, with traditional topic modeling demonstrating greater accuracy than neural topic modeling in identifying emerging fields
New insights into anastomotic leakage after rectal cancer resection
Get PDFAnastomotic leakage (AL) is a severe complication after rectal cancer surgery, occurring in 20-25% of cases, resulting in increased morbidity, mortality, extended recovery periods, additional interventions, and significant economic burdens. This dissertation provides new insights into the etiology, long-term outcomes, and economic impacts of AL, presenting innovative strategies for prevention and treatment.The first part investigates the gut microbiome's influence on anastomotic healing. Microbial dysbiosis, characterized by decreased diversity and increased facultative anaerobes like Enterococcus, negatively impacts recovery. Tranexamic acid, an inhibitor of plasminogen activation, effectively reduces collagen breakdown and AL incidence in mouse models without disturbing microbial balance. Additionally, brief dietary prehabilitation using a high-fiber diet enhances microbial diversity and reduces AL rates. Clinical translation through perioperative microbiome analyses within the IMARI study revealed significant microbial shifts postoperatively, including Enterococcus dominance and reduced alpha diversity, providing valuable insights into human perioperative microbiome dynamics.The second part assesses the long-term clinical outcomes of AL. The STOMA-score enables clinicians to better predict stoma risk one year post-leakage based on patient and leakage characteristics. Additionally, various AL treatment strategies are compared, emphasizing reactivation leakages after stoma reversal, an underestimated issue significantly affecting quality of life and surgical complexity.The third part addresses the financial implications of AL. Cost analyses reveal substantial variation internationally and methodologically. The IMARI study evaluates treatment strategy costs in the first postoperative year and another study highlights that persistent leakages significantly amplify financial burdens, emphasizing the need for preventive, cost-effective interventions
The complexity of post COVID-19 condition:Exploring long-term health effects
Get PDFThe main objective of this thesis is to enhance our understanding of post COVID-19 condition by exploring its long-term health effects, focusing on symptom development and progression. We used data from the P4O2 COVID-19 cohort, which included 95 patients aged 40-65 years with persistent symptoms 3-6 months after infection.We observed that diffusion capacity (DLCO) was below the lower limit of normal in 40.2% of the patients, with age and severe acute infection independently associated with this decrease. Fatigue was reported by 75.9% of patients at 3-6 months, decreasing to 57.1% at 12-18 months after infection. Post COVID-19 patients were grouped into 11 symptom-based clusters previously seen in an ME/CFS cohort. Three distinct trajectories were identified for fatigue and dyspnoea: decreasing, high persistent, and low persistent. Never smokers and participants in lifestyle interventions were more likely to show improvement. Similarly, moderate cases and lifestyle intervention participants had higher odds of decreasing dyspnoea compared to high persistent. We also found a decline in kidney function. The estimated glomerular filtration rate (eGFR) decreased over time from 85.3 ml/min/1.73m2 during acute phase to 80.9 ml/min/1.73m2 at 12-18 months after infection. Compared to controls, eGFR in post COVID-19 patients was 6.45 ml/min/1.73m2 lower at 3-6 months and 10.26 ml/min/1.73m2 lower at 12-18 months. These findings underscore the diverse and persistent nature of post COVID-19 symptoms and highlight the role of demographic and physiological factors. They emphasize the importance of personalized treatment strategies that consider the unique symptom profiles and backgrounds of patients.<br/
When the esophageal sphincter fails:New treatment strategies on achalasia and GERD
Get PDFThe first part of the thesis focuses on treatment of achalasia, comparing two methods: single series pneumatic dilation (PD) and peroral endoscopic myotomy (POEM). Our study of 133 patients showed that POEM was more effective than PD after five years was more effective than PD, with 81% of patients in remission, compared to 40% with PD.However, patients treated with POEM were more likely to use proton pump inhibitors.In addition, a phenomenon seen after treatment with POEM was described; a pseudodiverticulum or distal focal dilatation at the site of the myotomy, also called a 'blown-out myotomy' (BOM). This is seen in one-third of POEM patients five years after initial treatment. Patients who developed a BOMhad higher acid exposure time, more reflux complaints and symptoms of regurgitation. We concluded that the presence of a BOM could explain for certain symptoms that patients develop in the years following a myotomy.The second part of the thesis explores new treatments for gastro-esophageal reflux disease. The natural supplement benesco™ was investigated but found to be no more effective than a placebo in reducing reflux symptoms. Ziverel, a gel that forms a layer in the esophagus, offered no significant benefit for patients with persistent reflux symptoms who were taking concurrent proton pump inhibitors.A promising treatment is endoscopic anti-reflux mucosectomy (ARMS). In patients with therapy-resistant reflux symptoms, ARMS led to a significant reduction in reflux episodes and acid exposure, with no increase in swallowing problems.This technique may be an effective option for a certain group of patients who do not respond well respond to medication
Tissue-specific interactions between <i>Xanthomonas campestris</i> pv. <i>campestris</i> and its host plant
Get PDFThe work in this thesis focused on the interaction between the bacterial plant pathogen Xanthomonas campestris pv. campestris (Xcc) and the host plant Arabidopsis thaliana. As this pathogen displays an intricate infection process with multiple distinct phases, efforts were made to identify plant resistance mechanisms in the early phase of infection when the bacteria enter the plant hydathodes, which are organs involved in water homeostasis that are located at the leaf margins. An intracellular immune receptor was identified that confers resistance against Xcc early in hydathodes, but not in later stages of infection. To track progression of the bacteria through the plant, bioluminescence was applied to genetically modify the bacteria to emit light. Next, a high-throughput imaging method was developed to follow infection events Arabidopsis rosettes non-invasively over time. This method yielded insights in the infection process and allowed for phenotypic screening of large plant populations. Finally, a bacterial virulence factor was identified that contributed to the vascular phase of the bacteria, when they colonize the plant xylem vessels and spread systemically through the plant. Taken together, the findings in this thesis yielded insights on the tissue-specific interactions between Xcc and its host plant