Comparing Strategies to Prevent Stroke and Ischemic Heart Disease in the Tunisian Population: Markov Modeling Approach Using a Comprehensive Sensitivity Analysis Algorithm.

Background. Mathematical models offer the potential to analyze and compare the effectiveness of very different interventions to prevent future cardiovascular disease. We developed a comprehensive Markov model to assess the impact of three interventions to reduce ischemic heart diseases (IHD) and stroke deaths: (i) improved medical treatments in acute phase, (ii) secondary prevention by increasing the uptake of statins, (iii) primary prevention using health promotion to reduce dietary salt consumption. Methods. We developed and validated a Markov model for the Tunisian population aged 35–94 years old over a 20-year time horizon. We compared the impact of specific treatments for stroke, lifestyle, and primary prevention on both IHD and stroke deaths. We then undertook extensive sensitivity analyses using both a probabilistic multivariate approach and simple linear regression (metamodeling). Results. The model forecast a dramatic mortality rise, with 111,134 IHD and stroke deaths (95% CI 106567 to 115048) predicted in 2025 in Tunisia. The salt reduction offered the potentially most powerful preventive intervention that might reduce IHD and stroke deaths by 27% (−30240 [−30580 to −29900]) compared with 1% for medical strategies and 3% for secondary prevention. The metamodeling highlighted that the initial development of a minor stroke substantially increased the subsequent probability of a fatal stroke or IHD death. Conclusions. The primary prevention of cardiovascular disease via a reduction in dietary salt consumption appeared much more effective than secondary or tertiary prevention approaches. Our simple but comprehensive model offers a potentially attractive methodological approach that might now be extended and replicated in other contexts and populations

Predictive Behavior of a Computational Foot/Ankle Model through Artificial Neural Networks

Computational models are useful tools to study the biomechanics of human joints. Their predictive performance is heavily dependent on bony anatomy and soft tissue properties. Imaging data provides anatomical requirements while approximate tissue properties are implemented from literature data, when available. We sought to improve the predictive capability of a computational foot/ankle model by optimizing its ligament stiffness inputs using feedforward and radial basis function neural networks. While the former demonstrated better performance than the latter per mean square error, both networks provided reasonable stiffness predictions for implementation into the computational model

Lattice and Continuum Modelling of a Bioactive Porous Tissue Scaffold

A contemporary procedure to grow artificial tissue is to seed cells onto a porous biomaterial scaffold and culture it within a perfusion bioreactor to facilitate the transport of nutrients to growing cells. Typical models of cell growth for tissue engineering applications make use of spatially homogeneous or spatially continuous equations to model cell growth, flow of culture medium, nutrient transport, and their interactions. The network structure of the physical porous scaffold is often incorporated through parameters in these models, either phenomenologically or through techniques like mathematical homogenization. We derive a model on a square grid lattice to demonstrate the importance of explicitly modelling the network structure of the porous scaffold, and compare results from this model with those from a modified continuum model from the literature. We capture two-way coupling between cell growth and fluid flow by allowing cells to block pores, and by allowing the shear stress of the fluid to affect cell growth and death. We explore a range of parameters for both models, and demonstrate quantitative and qualitative differences between predictions from each of these approaches, including spatial pattern formation and local oscillations in cell density present only in the lattice model. These differences suggest that for some parameter regimes, corresponding to specific cell types and scaffold geometries, the lattice model gives qualitatively different model predictions than typical continuum models. Our results inform model selection for bioactive porous tissue scaffolds, aiding in the development of successful tissue engineering experiments and eventually clinically successful technologies.Comment: 38 pages, 16 figures. This version includes a much-expanded introduction, and a new section on nonlinear diffusion in addition to polish throughou

Research and Education in Computational Science and Engineering

Over the past two decades the field of computational science and engineering (CSE) has penetrated both basic and applied research in academia, industry, and laboratories to advance discovery, optimize systems, support decision-makers, and educate the scientific and engineering workforce. Informed by centuries of theory and experiment, CSE performs computational experiments to answer questions that neither theory nor experiment alone is equipped to answer. CSE provides scientists and engineers of all persuasions with algorithmic inventions and software systems that transcend disciplines and scales. Carried on a wave of digital technology, CSE brings the power of parallelism to bear on troves of data. Mathematics-based advanced computing has become a prevalent means of discovery and innovation in essentially all areas of science, engineering, technology, and society; and the CSE community is at the core of this transformation. However, a combination of disruptive developments---including the architectural complexity of extreme-scale computing, the data revolution that engulfs the planet, and the specialization required to follow the applications to new frontiers---is redefining the scope and reach of the CSE endeavor. This report describes the rapid expansion of CSE and the challenges to sustaining its bold advances. The report also presents strategies and directions for CSE research and education for the next decade.Comment: Major revision, to appear in SIAM Revie

Addressing current challenges in cancer immunotherapy with mathematical and computational modeling

The goal of cancer immunotherapy is to boost a patient's immune response to a tumor. Yet, the design of an effective immunotherapy is complicated by various factors, including a potentially immunosuppressive tumor microenvironment, immune-modulating effects of conventional treatments, and therapy-related toxicities. These complexities can be incorporated into mathematical and computational models of cancer immunotherapy that can then be used to aid in rational therapy design. In this review, we survey modeling approaches under the umbrella of the major challenges facing immunotherapy development, which encompass tumor classification, optimal treatment scheduling, and combination therapy design. Although overlapping, each challenge has presented unique opportunities for modelers to make contributions using analytical and numerical analysis of model outcomes, as well as optimization algorithms. We discuss several examples of models that have grown in complexity as more biological information has become available, showcasing how model development is a dynamic process interlinked with the rapid advances in tumor-immune biology. We conclude the review with recommendations for modelers both with respect to methodology and biological direction that might help keep modelers at the forefront of cancer immunotherapy development.Comment: Accepted for publication in the Journal of the Royal Society Interfac