Blood pressure is a crucial parameter in haemodynamic monitoring, providing an indication of tissue perfusion in critical situations. Commonplace in (paediatric) intensive care units ((P)ICU) are arterial catheters, inserted in the radial artery, which are an invasive means of continuously measuring blood pressure. However, quantifying the degree to which arterial catheter geometries modify the pressure measurement, especially for paediatrics, remains seemingly unexplored in research, while discrepancies between non-invasive and invasive blood pressure monitoring methods have been observed in Erasmus MC (P)ICU departments.

Using FEBio, a computational fluid dynamics (CFD) model was developed to investigate the influence of catheter geometries on the pressure generated at the catheter tip (taken to be the measured pressure) for six age groups ranging from <2 years to 18 years of age. For three age groups (2-5 years, 12-14 years, and 15-18 years), simulations were run with two different catheter gauges (diameters).

Hence, a total of nine different sets of age and catheter gauge were investigated. Apart from comparison between simulations with and without a catheter, the effect of the position of the catheter in the vessel (eccentricity ratio) and changing catheter lengths in the vessel were studied. The results show that arterial catheters (substantially) influence the pressure measured by the catheter. In the worst-case scenarios simulated, namely that in which the catheter is in the centre of the vessel with an intraluminal catheter length equal to 80% of its total length, eight of the nine cases investigated showed systolic pressure values higher than the target values used in the
PICU. Thus, the results suggest that the presence of the catheter may be enough to modify a normal blood pressure into appearing elevated (hypertensive), potentially influencing patient treatment. Shorter catheter lengths were associated with lower pressure overestimations, as was moving the catheter towards the vessel wall. Consequently, these results are clinically significant, and may help physicians in making more informed haemodynamic assessments.

The airway epithelium plays a crucial role in respiratory defense by regulating cellular composition and related functions to maintain pulmonary homeostasis. This study investigates the impact of temperature variations (33°C and 37°C) on cellular differentiation, mucociliary function, and host defense responses of human primary bronchial and nasal epithelial cells (hPBECs and hPNECs) cultured at the air-liquid interface. A reduction of well-differentiated cell cultures from 37°C to 33°C
significantly increased goblet cell-related gene expression (MUC5AC) while decreasing ciliated cell-related gene expression (FOXJ1). Mucociliary clearance was generally impaired at 33°C, with ciliated cells displaying less organized ciliary alignment; however, donor variability made it challenging to establish consistent trends. Furthermore, cultures maintained at 33°C exhibited an enhanced antiviral response to Poly(I:C), as indicated by increased IFNL gene expression in both bronchial and nasal epithelial cells. In contrast, temperature had no effect on the inflammatory response to whole cigarette smoke in bronchial cultures but attenuated the oxidative stress response in nasal cultures,
as evidenced by reduced HMOX1 expression at 33°C. Analysis of Notch signaling revealed no significant alterations in the expression of key target genes (HES1, HEY1), with the exception of a transient decrease in HEY2 at 33°C, suggesting complex regulatory interactions. These findings
support the hypothesis that the temperature gradient along the airway tree influences the spatial distribution of airway epithelial cells, with potential implications for intervention with airway remodeling in chronic lung diseases, such as asthma and chronic obstructive pulmonary disease.
However, further studies are needed to confirm these results and explore their clinical relevance.

Introduction
Paediatric palliative care (PPC) aims to optimise the quality of life of children with life-limiting or life-threatening conditions by addressing physical, psychosocial, emotional and spiritual needs of children as well as their family members. Advance care planning (ACP) is a central element of PPC, as it helps children and family members formulate values, needs, and goals for future care. However, ACP documentation is time-consuming and burdensome for healthcare professionals (HCPs). Large Language Models (LLMs) may support this process by automatically extracting and structuring ACP outcomes. This study explored the support of open-source LLMs summarising ACP outcomes from Individual Care Plans (ICPs) in a Dutch PPC setting.

Methods
We constructed a pseudonymised dataset of 38 ICPs, with reference ACP summaries structured around three guiding questions: (1) Who are you?, (2) What is important to you?, and (3) What are your goals and wishes for future care and treatment? Two open-source decoder-only LLMs were selected: Llama-3.1-8B-instruct (Llama-3.1) and Fietje-2-instruct (Fietje-2). We evaluated their performance under zero-shot prompting, in-context learning (ICL) with up to eight examples, and QLoRA fine-tuning on 30 training samples. Outputs were assessed with automatic metrics (BLEU, ROUGE-L, BERTScore, MEDCON), complemented by textual analysis and a human reader study.

Results

Background: Computational musculoskeletal models are valuable for understanding finger biomechanics and aiding in medical applications such as postoperative therapy and surgical planning. These models simulate various scenarios and predict outcomes by representing the biomechanical system through equations of motion. However, the complex mechanics of the human finger, particularly the role of the Lateral Bands in coordinated joint flexion, have primarily been studied in static simulations. Their role in dynamic simulations, especially with the inclusion of other key tendons and ligaments, has not been researched.
Aim: This study aims to develop a musculoskeletal model to enhance our understanding of the contribution of Lateral Bands to coordinated finger flexion, by combining insights from previous research to address existing gaps in finger biomechanics. The model will replicate the anatomical joints and Lateral Band structures of an anthropomorphic mechanical finger, offering a simplified design to reduce simulation complexity and enhance verification reliability.
Method: An adapted anthropomorphic mechanical finger was created based on previous work, scaled down to reduce weight and required actuation force. The simulation model was developed in OpenSim, using bone geometries from CAD files and direct measurement attachment location of tendons and ligaments from the mechanical finger for improved accuracy. Model verification involved comparing the model’s behavior with the mechanical finger through experiments focusing on finger flexion under external deep flexor tendon load, using motion capture data, inverse kinematics (IK), and forward dynamics (FD). Results The simulation model accurately replicated the mechanical finger’s joint kinematics, with an average squared error ranging from 1.54e−3 mm to 9.55e−3 mm and an average marker RMSE of ±0.65 mm. Tendon displacement and moment arm were verified with average errors ±1 mm and ±1.23 mm, respectively, indicating that the model closely matches the mechanical finger’s tendon force and joint torque relationships. The model demonstrated that Lateral Bands are essential for interphalangeal joint (IPJ) coupling, as they adjust their tension by becoming taut or slack during finger flexion to distribute forces effectively. Without these Lateral Bands, finger flexion leads to unrealistic joint movements in mechanical finger models. Additionally, the Lateral Bands play a significant role in generating tension in the deep flexor tendon during IPJ coupling.
Conclusion: This study demonstrated the role of Lateral Bands during dynamic finger flexion by incorporating anatomically-based structures and replicating their behavior. The findings provide deeper insights into their function and set a new foundation for future research. Additional studies could further explore how Lateral Bands influence force distribution and joint mechanics, potentially leading to better understanding and treatment of finger injuries and disorders.

Achilles tendinopathy (AT) is a common Achilles tendon injury, yet its exact cause and the factors influencing progression of individuals remain unclear. Strain distribution is indicated to play a significant role in the progression, possibly linked to the twist of the subtendons. Pizzolato et al. (2020) proposed an integrated framework for studying Achilles tendon mechanics, including a finite element (FE) model estimating local displacements in the Achilles tendon. However, before im- plementing this in AT research, further testing and validation is necessary. Therefore, to make a start for future improvements, this study aims to build a foundational FE model of the Achilles tendon, verify it with in vivo local displacement data and assess the sensitivity to subtendon twist. 3D ultrasound and X-rays of the ankle provided the geometry and the moment arm of the Achilles tendon, respectively. By minimizing the error between the tendon’s elongation during contraction and the FE model prediction, the material properties were optimized. Local displacements in the sagittal and coronal plane were computed using estimated forces from in vivo studies. Simulated subtendon twists (11◦, 37◦, 65◦) examined the effect of the amount of twist on the displacement. Comparing the FE estimated local displacements to in vivo data indicated that additional substructure details are needed to accurately calculate the displacement behavior. Modifying fiber twist angles altered the uniformity of the displacements in the FE model. Therefore, further development of the FE model of the Achilles tendon is recommended before incorporating it into an Achilles tendon mechanics study.

This graduation project is part of a double degree program for the master’s in Biomedical Engineering and Communication Design for Innovation, conducted at the Cardio-Respiratory Engineering And TEchnology laboratory (CREATElab) in Melbourne, Australia.

Cardiovascular diseases remain the leading cause of death globally, with out-of-hospital cardiac arrests often resulting in poor outcomes due to prolonged periods of compromised blood flow. Prehospital extracorporeal cardiopulmonary resuscitation (pECPR) offers a promising rescue intervention to reduce treatment delays. This design study improved the RApidly DEployable (RADE) ECPR kit prototype 1.0, which demonstrates full ECPR equipment compatibility for prehospital settings while streamlining the treatment workflow. Based on clinical insights, prototype 2.0 aimed to optimize the RADE ECPR kit’s speed and performance. Testing with clinicians at the Alfred Hospital in Melbourne showed significant improvements in deployability, equipment organization, and overall usability compared to the conventional pECPR suitcase and prototype 1.0.

Additionally, this study examined the impact of leadership absence on innovative scientific performance. While the effects of leadership gaps on research teams remain underexplored, the departure of the CREATElab’s Director provided a unique opportunity to evaluate the challenges and consequences of such disruptions. Using a mixed-method approach, the findings revealed that leadership absence hindered collaboration and motivation, shifting lab dynamics toward task-oriented isolation. Shared decision-making and distributed leadership were identified as communication strategies to sustain innovation during such gaps, with The CREATElab Challenge offering a gamified solution to strengthen connectivity and morale.

The studies highlight the critical role of engineering design optimization in improving outcomes for cardiac arrest patients and underscore the importance of adaptive communication strategies in sustaining scientific innovation, particularly in challenging circumstances.

Critically ill patients in the Intensive Care Unit (ICU) are often comatose and thoroughly monitored. Neurological complications occur in up to 20% of these patients. Therefore, monitoring of the brain, which can be performed using electroencephalography (EEG), has the potential to significantly impact the outcomes of patients at the ICU. Despite the potential of EEG as a noninvasive method for monitoring the neurological status of critically ill patients, the labor-intensive and complex nature of its application and assessment has hindered widespread implementation. Therefore, the aim of this thesis was to identify the logistical and technical prerequisites for efficient and effective neuromonitoring using EEG in the ICU.

Chapter 1 provides an overview of neuromonitoring techniques in the critically ill patient. It delves into the neurophysiological background of the EEG, the techniques used for applying the EEG electrodes, and the EEG assessment.

In Chapter 2 we present a qualitative study on the optimal conditions for EEG monitoring in the ICU. Through 12 individual and 2 focus group interviews with employees from different departments within and outside of the hospital, the current workflow regarding neuromonitoring in the ICU is identified. Additionally, we evaluate the barriers and facilitators for change in this monitoring process through the Consolidated Framework for Implementation Research (CFIR). Factors such as motivation and willingness to change serve as facilitators, while a lack of interdepartmental communication and the high workload for various healthcare professionals involved can be significant barriers.

The qualitative research reveals that the largest group monitored using EEG in the ICU consists of patients suffering from postanoxic encephalopathy, which can be a complication of a cardiac arrest. Therefore, in Chapter 3, we examine the technical requirements for optimal EEG monitoring. Specifically, we focus on the necessary number of EEG electrodes for reliable automatic classification of the EEG background pattern in postanoxic encephalopathy. By training an Random Forest (RF) classifier with input from 12, 10, 8, 6, and 4 EEG electrodes, we develop a model with a micro-averaged One-vs-Rest (OvR) Area Under the Curve - Receiver Operating Characteristics (AUC-ROC) value of 0.923, 0.924, 0.924, 0.925, and 0.923 (p-value: 0.279) for the different numbers of electrodes respectively. The constant performance of the model suggests that a reduced number of electrodes may be sufficient for monitoring this patient group, potentially reducing the workload for EEG technicians. Automatic assessment of the EEG can also contribute to a decreased workload for clinical neurophysiologists.

In Chapter 4 we provide the conclusions and future perspectives of this thesis. We have demonstrated the potential for change in the EEG monitoring workflow at the ICU of the Erasmus MC, indicating that there is an opportunity to work towards more effective and efficient neuromonitoring. Future research should focus on a broader range of logistical and technical prerequisites - including effective interdepartmental collaboration and which EEG equipment to use - thereby creating opportunities to improve treatment and outcomes of critically ill patients.

DMD (Duchenne muscular dystrophy) is a genetic disorder characterized by progressive muscle weakness, leading to the eventual loss of muscle function. After losing lower extremity function, DMD patients lose the ability to use their arms. To assist individuals with DMD, an upper extremity exoskeleton is being developed to provide support.

The device is required to provide proper weight compensation for the weight of both the user and the support system. Previous literature review has highlighted three strategies for achieving compensation: Model, Calibration dynamic and Calibration static. However, the review lacks a conclusive understanding of the differences between these strategies. Thus, this study aims to validate a weight compensation model by comparing the joint torque with two different measurements: Calibration static and Calibration dynamic on non-disabled participants with a one DOF (Degree of freedom) elbow support system.

The weight compensation model was designed to accurately account for the weight of the user's arms and the exoskeleton device itself. It incorporates multiple inputs, including shoulder flexion, shoulder abduction, elbow joint angle, arm mass, and arm center of mass to calculate the required compensation torque for the motor located at the elbow joint.

The model was validated by a dead weight experiment. The weight compensation model was validated by comparing the joint torque measurements from Calibration dynamic and Calibration static results. Afterwards, experiments were performed on 12 male non-disabled participants. The weight compensation model results does not align well with the measurements from non-disabled participants. Analysis suggests that joint impedance caused these discrepancies. However, even after accounting for joint impedance, the weight compensation model still exhibits a tendency to overestimate the required compensation torque. A fitted model was used to decrease the product value of mass and center of mass to decrease overestimation. Furthermore, the comparative analysis indicates that dynamic and static measurements yielded similar mean values for joint torque.

While the weight compensation model demonstrates accuracy in a dead weight experiment under the assumption of an accurate estimation of its mass and center of mass, its performance is sub-optimal during the human experiment. This is attributed to the absence of joint impedance consideration and the overestimation of the forearm plus hand mass and center of mass for the user. Comparison between dynamic and static measurements the mean difference between dynamic and static measurements obtained from non-disabled participants indicates no substantial disparity in terms of joint torque.

Future plans for this research involve expanding the current one DOF configuration to a four DOF configuration and incorporating an inertial measurement unit (IMU) for more accurate angle measurements. Additionally, different compensation strategies will be compared in terms of task performance using metrics such as external interaction force or sEMG (surface electromyography). Lastly, the overestimation of forearm plus hand mass and center of mass will be further investigated.

This thesis investigates the ability of Bayesian EUCLID to retrieve a predictive approximate material model for the myocardium in the presence of heterogeneous deformation fields due to simulated biaxial stretch tests. The Holzapfel-Ogden material model is used as the ground-truth material model of the simulation, since it is capable of describing the orthotropic and hyperelastic behavior of the myocardium. In total, four material models were retrieved from Bayesian-EUCLID by considering two fiber orientations within the sample and two displacement measurement techniques. The two fiber directions included one in which the sheet-like structure of the sample lies within the test plane and one in which it lies perpendicular to the test plane. The displacement field measurements considered were a full displacement field measurement and an approximation thereof based on a stereo digital image correlation method. The results show that when the sheet-like structure of the myocardium lies within the test plane of the biaxial stretch test and the full displacement field is available, Bayesian EUCLID is capable of finding orthotropic and hyperelastic material models that correspond well to the ground truth. This shows that a biaxial stretch test can adequately characterize the material behavior of the myocardium.

Gastroschisis, a congenital abdominal wall defect located to the right of the intact umbilical cord (UC), results in the herniation of fetal abdominal organs into the amniotic cavity without a protective membrane covering these structures. Complex gastroschisis (CG), comprising approximately 10% of cases, is associated with significantly higher morbidity and mortality rates compared to simple gastroschisis. Fetoscopic repair of CG offers the potential to improve gastrointestinal health at birth, but thus far, no procedure has been successfully demonstrated as safe and feasible. Therefore, the goal of this graduation project was to provide a proof of principle for a novel dedicated method that enables the swift closure of the abdominal wall defect during a fetoscopic repair procedure for CG.

The development of this method began with an analysis of the clinical context, including the characteristics of the abdominal wall defect, the adjacent umbilical cord and vessels, and the fetoscopic surgical setup, which provided a clear design direction. After generating various concept solutions, the key concept — a silicone ring with membrane — was selected using the Harris Profile methodology. This concept was designed for insertion into the fetal abdominal cavity, with the membrane effectively covering the opening of the defect.

Eight configurations of the silicone ring with a membrane were then prototyped through injection molding of liquid silicone rubber in a 3D-printed mold. The rings varied in shape (round or rusk), diam- eter (20 mm and 30 mm), and stiffness (shore hardness A25 and A40). Additionally, a validation model simulating a 24-week-old fetus with CG was developed with input from medical experts.

The validation experiments demonstrated that the silicone ring with a membrane securely remained in place, effectively closing the abdominal wall defect under intra-abdominal pressure conditions ranging from 0 to 40 mmHg. These experiments, conducted using the validation model, simulated conditions during and immediately after fetal intervention in a 24-week-old fetus with CG following intestinal repositioning. These experiments provided proof of principle for the silicone ring with membrane as a novel method that enables the swift closure of the abdominal wall defect in CG during a fetoscopic repair procedure. Notably, round-shaped rings were favored, and larger diameters allowed for coverage of larger defects. However, it’s noteworthy that the 20 mm round ring effectively covered an oval-shaped defect measuring 13.5 × 12.7 mm, aligning with the reported mean defect size in CG. Furthermore, the experiments demonstrated the feasibility of introducing the rings through a 12 Fr (20 mm rings) or 14 Fr (30 mm rings) surgical port, aligning with the preferred surgical setup.

Future research is required to clinically investigate the defect diameter in CG and optimize the silicone ring with membrane’s design. Additionally, enhancing the validation model to serve dual purposes as both a validation and training model will facilitate user tests. Moreover, developing an instrument for introducing the ring into the uterus and refining the surgical technique for precise ring positioning will be essential steps toward the clinical application of this innovative approach.

An acute ischemic stroke is one of the leading causes of death and is caused by a thrombus that occludes a cerebral artery. This thrombus reduces the cerebral blood flow and causes irreversible brain tissue damage. Mechanical thrombectomy is a safe and effective technique to remove the thrombus from the cerebral arteries and restore the brain's blood flow. The mechanical properties of the thrombus highly influence the success rate of mechanical thrombectomy. To investigate the mechanical behavior of the thrombus under different loading conditions, numerical simulations could be performed. The aim of this thesis is to develop an in silico thrombus model to investigate the mechanical behavior of the thrombus under compressive and tensile loading conditions using finite element analysis software LS-DYNA. Experimental data collected from the lab is used to describe the mechanical behavior in the numerical thrombus models.

The building process of the in silico models in this study is organized in three parts. Part one is the cube model, where the material properties and numerical stable settings are investigated. Also, a combination of compression and tension is applied to the cube model to capture both the compressive and tensile forces present during mechanical thrombectomy. Part two includes geometry models that mimic the clot analog samples' geometry used during the experimental compression and tensile tests. Part three includes a clot analog with an initial hole in the middle to understand the fracture behavior of the thrombus. Different approaches to model fracture of the thrombus are investigated.

Three different parts characterize this thesis, and each includes a method, results, and discussion section. The discussion section of each part is dedicated to the decisions that have been made in that specific chapter. A discussion section is also included in the chapter Experiments. The general discussion at the end of this study will include the findings of each model and the comparison with literature. Recommendations for further research are given at the end.

In conclusion, this study provides a framework for modeling the thrombus under tensile and compressive loading, where the thrombus is modeled as a hyperelastic material. Future work is advised to extend and improve the models developed in this study.

In the Netherlands, over 12% of the population has chronic kidney damage resulting in about 2000 patients with renal failure each year. Replacement of the kidney function by transplantation is desired, but due to a shortage of donor kidneys, the waiting list for a transplant is long. Extending the criteria that donors must meet can reduce the waiting list, but it is necessary that these organs are still of sufficient quality. Initial studies indicate that using the normothermic machine perfusion (NMP) preservation method results in better transplant outcomes and possibly improves donor kidneys’ quality. The quality of the organ during NMP can be used as a potential biomarker for graft survival. However, what is still missing is a reliable way to test the quality during NMP. Laser speckle contrast imaging (LSCI) is a non-invasive, continuous, real-time imaging technique that can visualize tissue perfusion. In this study, a method is designed to visualize the perfusion over the entire surface of normothermic machine-perfused kidneys using LSCI. A three-dimensional (3D) perfusion model is developed based on two-dimensional (2D) LSCI images. This method can then be used to determine the quality of the perfusion of donor kidneys before they are transplanted.

A method is designed to obtain LSCI data of porcine kidneys undergoing NMP. Data is recorded during the first 100 minutes of NMP to evaluate the relationship between renal arterial blood flow and perfusion. The kidneys are then placed in six different positions from which LSCI data is collected. Using shape from silhouettes, a 3D model is made from each kidney. The 2D LSCI data is given depth using the 3D model by assigning each pixel a 3D coordinate. The perfusion model is validated by comparing the perfusion model for the situation where no ischemia is present in the kidney and the situation where ischemia is present in the kidney. 

The designed method and setup made it possible to obtain perfusion data over the vast majority of the surface of the kidneys. Further, the results show a positive linear correlation between measured perfusion and arterial blood flow in each kidney. With the collected perfusion data, a 3D visualization was made. 3D models from all kidneys could be used for this. The 3D visualization is represented as a point cloud and allows for easy and fast viewing of the perfusion over the entire surface.

Validating the model with induced ischemia showed that the 3D visualization can indicate significant perfusion differences caused by ischemia. This makes LSCI a promising method for determining perfusion quality.

Atherosclerosis is a cardiovascular disease in the arteries and a primary cause of death in the industrialized world. Most deaths due to atherosclerosis occur when the fibrous cap covering the necrotic core ruptures, leading to a blood clot. To determine whether an atherosclerotic plaque will rupture requires the development of accurate computational models. One of the key aspects for these models is the material model, in which collagen fibres play a major role. This study aims to contribute to the making of a numerical model which accurately represents atherosclerotic plaque by comparing the elastic and rupture behaviour of engineered collagenous micro tissues and their respective finite element models in ABAQUS. The Holzapfel-Gasser-Ogden material model of these computational models is based on a combination of global material parameters and local material parameters based on the local fibre organisation. A framework developed to measure the local fibre organisation using provided imagery of a nuclear stained tissue engineered sample shows the collagen fibres align along the loading direction and the edges of the geometry. The fibers are less dispersed along the edges of the geometry and on the left and right of a formed soft inclusion. A uniaxial tensile test was performed on four tissue engineered samples. The elastic and rupture behaviour of the samples during the uniaxial tensile tests is replicated in ABAQUS using both isotropic and homogeneous material parameters, and anisotropic heterogenous material parameters. The stresses measured in the simulations are highly dependent on both the material parameters and the geometry of the model. The strains are mostly dependent on the geometry, but are affected by the material model. Due to the higher stiffness at the edges of the geometry of the anisotropic samples, the stresses increased greatly, and the strains decreased slightly. The rupture behaviour of the cultured samples is replicated in the FEM simulations using extended finite element method (XFEM). The damage in the samples with isotropic material parameters initiates both from the soft inclusion as the left and right edges of the geometry. The damage in the samples with anisotropic material parameters initiates, similarly to the cultured samples, only from the sides of the soft inclusion. The damage in both the cultured and simulated samples propagate mostly horizontal and from the soft inclusion outward. In three out of four isotropic samples however, damage propagates to varying degrees from the edge of the geometry inward. Based on these findings it is concluded that implementing the local fibre organisation in the material model can improve the accuracy of finite element simulations of collagenous soft tissues, which includes atherosclerotic plaque, as the rupture behaviour of the simulations with anisotropic material parameters more accurately represents the rupture behaviour of the engineered fibrous tissues in comparison with simulations with isotropic material parameters.