Vascular smooth muscle cell (VSMC) plasticity is implicated in extracellular matrix (ECM) turnover and arterial failure. The osteochondrocytic phenotypes of synthetic VSMCs are thought to drive glycosaminoglycan (GAG) accumulation and swelling typically seen in connective tissue disease and hypertension. A central question is whether this phenotype switching under non-homeostatic conditions is a cause or effect of those conditions. We implement a cause–effect association between ECM damage, lost cell mechanosensitivity, and cell phenotype modulation using the Constrained Mixture Model, to simulate the evolution of VSMC population over time. We modelled a cylindrical bi-layer of media and adventitia of a mouse common carotid artery and simulated remodelling in response to initially compromised ECM, concurrent with varying degrees of hypertension. In normo- and moderately hypertensive ECM disruption, physiological remodelling restores mechanical homeostasis to cells with slightly altered mechanical properties. Alternatively, severe hypertension yields complete medial degeneration. Complete loss of stored elastic energy is observed, with stiffened arteries yielding characteristically high pulse wave velocities (PWVs). Early intervention recovering hypertensive to normotensive pressure, as well as enhanced adventitial collagen turnover, are shown to prevent medial degeneration. Our model thus offers a tool to better understand the relationship between ECM damage, arterial failure, and hypertension.

Objective: Increasing healthcare expenditures require governments to make difficult prioritization decisions. Considering public preferences can help raise citizens’ support. Previous research has predominantly elicited preferences for the allocation of public resources towards specific treatments or patient groups and principles for resource allocation. This study contributes by examining public preferences for budget allocation over various healthcare purposes in the Netherlands. Methods: We conducted a Participatory Value Evaluation (PVE) choice experiment in which 1408 respondents were asked to allocate a hypothetical budget over eight healthcare purposes: general practice and other easily accessible healthcare, hospital care, elderly care, disability care, mental healthcare, preventive care by encouragement, preventive care by discouragement, and new and better medicines. A default expenditure was set for each healthcare purpose, based on current expenditures. Respondents could adjust these default expenditures using sliders and were presented with the implications of their adjustments on health and well-being outcomes, the economy, and the healthcare premium. As a constraint, the maximum increase in the mandatory healthcare premium for adult citizens was €600 per year. The data were analysed using descriptive statistics and a Latent Class Cluster Analysis (LCCA). Results: On average, respondents preferred to increase total expenditures on all healthcare purposes, but especially on elderly care, new and better medicines, and mental healthcare. Three preference clusters were identified. The largest cluster preferred modest increases in expenditures, the second a much higher increase of expenditures, and the smallest favouring a substantial reduction of the healthcare premium by decreasing the expenditure on all healthcare purposes. The analyses also demonstrated substantial preference heterogeneity between clusters for budget allocation over different healthcare purposes. Conclusions: The results of this choice experiment show that most citizens in the Netherlands support increasing healthcare expenditures. However, substantial heterogeneity was identified in preferences for healthcare purposes to prioritize. Considering these preferences may increase public support for prioritization decisions.

Personalized treatment informed by computational models has the potential to markedly improve the outcome for patients with a type B aortic dissection. However, existing computational models of dissected walls significantly simplify the characteristic false lumen, tears and/or material behavior. Moreover, the patient-specific wall thickness and stiffness cannot be accurately captured non-invasively in clinical practice, which inevitably leads to assumptions in these wall models. It is important to evaluate the impact of the corresponding uncertainty on the predicted wall deformations and stress, which are both key outcome indicators for treatment optimization. Therefore, a physiology-inspired finite element framework was proposed to model the wall deformation and stress of a type B aortic dissection at diastolic and systolic pressure. Based on this framework, 300 finite element analyses, sampled with a Latin hypercube, were performed to assess the global uncertainty, introduced by 4 uncertain wall thickness and stiffness input parameters, on 4 displacement and stress output parameters. The specific impact of each input parameter was estimated using Gaussian process regression, as surrogate model of the finite element framework, and a δ moment-independent analysis. The global uncertainty analysis indicated minor differences between the uncertainty at diastolic and systolic pressure. For all output parameters, the 4^th quartile contained the major fraction of the uncertainty. The parameter-specific uncertainty analysis elucidated that the material stiffness and relative thickness of the dissected membrane were the respective main determinants of the wall deformation and stress. The uncertainty analysis provides insight into the effect of uncertain wall thickness and stiffness parameters on the predicted deformation and stress. Moreover, it emphasizes the need for probabilistic rather than deterministic predictions for clinical decision making in aortic dissections.

Computational investigations of how soft tissues grow and remodel are gaining more and more interest and several growth and remodeling theories have been developed. Roughly, two main groups of theories for soft tissues can be distinguished: kinematic-based growth theory and theories based on constrained mixture theory. Our goal was to apply these two theories on the same experimental data. Within the experiment, a pulmonary artery was exposed to systemic conditions. The change in diameter was followed-up over time. A mechanical and microstructural analysis of native pulmonary artery and pulmonary autograft was conducted. Whereas the kinematic-based growth theory is able to accurately capture the growth of the tissue, it does not account for the mechanobiological processes causing this growth. The constrained mixture theory takes into account the mechanobiological processes including removal, deposition and adaptation of all structural constituents, allowing us to simulate a changing microstructure and mechanical behavior.