Academic articles

A multimethod computational simulation approach for investigating mitochondrial dynamics and dysfunction in degenerative aging

Research in biogerontology has largely focused on the complex relationship between mitochondrial dysfunction and biological aging. In particular, the mitochondrial free radical theory of aging (MFRTA) has been well accepted. However, this theory has been challenged by recent studies showing minimal increases in reactive oxygen species (ROS) as not entirely deleterious in nature, and even beneficial under the appropriate cellular circumstances. To assess these significant and nonintuitive observations in the context of a functional system, we have taken an in silico approach to expand the focus of the MFRTA by including other key mitochondrial stress response pathways, as they have been observed in the nematode Caenorhabditis elegans. These include the mitochondrial unfolded protein response (UPRmt), mitochondrial biogenesis and autophagy dynamics, the relevant DAF-16 and SKN-1 axes, and NAD+-dependent deacetylase activities. To integrate these pathways, we have developed a multilevel hybrid-modeling paradigm, containing agent-based elements among stochastic system-dynamics environments of logically derived ordinary differential equations, to simulate aging mitochondrial phenotypes within a population of energetically demanding cells.

Sustainable Development in Surgery: The Health, Poverty, and Equity Impacts of Charitable Surgery in Uganda

The recently adopted Sustainable Development Goals call for the end of poverty and the equitable provision of healthcare. These goals are often at odds, however: health seeking can lead to catastrophic spending, an outcome for which cancer patients and the poor in resource-limited settings are at particularly high risk. How various health policies affect the additional aims of financial wellbeing and equity is poorly understood. This paper evaluates the health, financial, and equity impacts of governmental and charitable policies for surgical oncology in a resource-limited setting. Three charitable platforms for surgical oncology delivery in Uganda were compared to six governmental policies aimed at improving healthcare access. An extended cost-effectiveness analysis using an agent-based simulation model examined the numbers of lives saved, catastrophic expenditure averted, impoverishment averted, costs, and the distribution of benefits across the wealth spectrum.

Evaluation of Outbreak Response Immunization in the Control of Pertussis Using Agent-based Modeling

Pertussis control remains a challenge due to recently observed effects of waning immunity to acellular vaccine and suboptimal vaccine coverage. Multiple outbreaks have been reported in different ages worldwide. For certain outbreaks, publichealth authorities can launch an outbreak response immunization (ORI) campaign to control pertussis spread. The authors developed an agent-based model to investigate effects of outbreak response immunization campaigns targeting young adolescents in averting pertussis cases. The experience proved that ABM offers a promising methodology to evaluate other public health interventions used in pertussis control. The authors also identified the strong need for further research into application of modeling to further our understanding of pertussis epidemiology.

Hybrid Simulation in Healthcare: New Concepts and New Tools

Until relatively recently, developing hybrid simulation models using more than one simulation paradigm was a challenging task which required a degree of ingenuity on behalf of the modeler. Generally speaking, such hybrid models either had to be coded from scratch in a programming language, or developed using two (or more) different off-the-shelf software tools which had to communicate with each other through a user-written interface. Nowadays a number of simulation tools are available which aim to make this task easier. This paper does not set out to be a formal review of such software, but it discusses the increasing popularity of hybrid simulation and the rapidly developing market in hybrid modeling tools, focusing specifically on applications in health and social care and using experience from the Care Life Cycle project and elsewhere.

Towards a Guide to Domain-specific Hybrid Simulation

The advantages of combined simulation techniques have been already frequently discussed and are well-covered by the recently published literature. In particular, many case studies have been presented solving similar domain-specific problems by different multi-paradigm simulation approaches. Moreover, a number of papers exist focusing on theoretical and conceptual aspects of hybrid simulation. However, it still remains a challenge to decide, whether combined methods are appropriate in certain situations and how they can be applied. Therefore, domain-specific user guides for multi-paradigm modeling are required combining general concepts and best practices to common steps. In this paper, we particularly outline three major processes targeting to define structured hybrid approaches in domain-specific contexts, and we focus on some practical issues aiming to a sustainable model development. Finally, an example hybrid methodology for problems in healthcare will be presented.

Agent-based population model used to identify and evaluate dog population management strategies

Developing countries are faced with finding novel and humane ways to permanently reduce and control their dog population. Agent-based models developed to describe dog populations represent a unique, platform for using computer based simulation to identify control strategies with the greatest potential for success, aid in the design of more effective control measures, and provide a means to evaluate the success of different interventions.

The Effect of Cellular Interactions on Cancer Cell Growth Using Evolutionary Game Theory

In this experiment, game theory was used to assess the interactions between three cell phenotypes usually found in cancer. The three defined cells were autonomous growth cells, invasive and motile malignant cells, and cells that performed anaerobic glycolysis. Based on preset variables in the payoff matrix, analytical equations were deduced that allowed for the analysis of the proportion of autonomous growth and malignant cells in a tumor. AnyLogic was also used to simulate the interactions between cancerous and normal cells.

Partial Paradigm Hiding and Reusability in Hybrid Simulation Modeling Using the Frameworks Health-DS and I7-Anyenergy

Many complex real-world problems which are difficult to understand can be solved by discrete or continuous simulation techniques, such as Discrete-Event-Simulation, Agent-Based-Simulation or System Dynamics. In recently published literature, various multilevel and large-scale hybrid simulation examples have been presented that combine different approaches in common environments.

A Tripartite Hybrid Model Architecture for Investigating Health and Cost Impacts and Intervention Tradeoffs for Diabetic End-stage Renal Disease

Like most countries, Canada faces rising rates of diabetes and diabetic ESRD, which adversely affect cost, morbidity/mortality and quality of life. These trends raise great challenges for financial, human resource and facility planning and place a premium on understanding tradeoffs between different intervention strategies. We describe here our hybrid simulation model built to inform such efforts.