(For conference participants.The content is password protected)
We are very pleased that the distinguished scientists, thought leaders and excellent speakers Denis Noble, Tom Kirkwood, Peter Hunter and Yoram Rudy will each open one of the four plenary sessions of the conference:
Professor Denis Noble, University of Oxford
Professor Tom Kirkwood, Newcastle University
Professor Peter Hunter, University of Auckland
Professor Yoram Rudy, Washington University in St. Louis
Organizer: Arun Holden, Multidisciplinary Cardiovascular Research Centre, University of Leeds
Grodins ( Quart Rev Biol 34 93-116 1959) began the integrated modelling of cardiovascular dynamics by volumes, pressures and flows using linear equations and analytical methods. However, nonlinearity is essential for explaining the phenomenology myocardial and vascular smooth muscle electrophysiology, calcium dynamics, and tissue mechanics.
Voltage-dependent channels produce cell threshold behaviour and allow autorhymicity. Myocytes types are widely modelled by multiple parameter, high order systems of ordinary differential equations. Propagation is modelled as nonlinear waves by partial differential systems. Dysrhythmias emerge via bifurcations (e.g. into alternans) or by conduction blocks, and unidirectional conduction block can lead to re-entrant tachyarrhythmias and fibrillatory activity. Detailed 3D reconstruction of cardiac activity can be partially validated by optical mapping of V and Ca++ on the surface of isolated hearts, and by clinical endo-, epi-cardial and body surface recordings, or cine- and tagged MRI. Cardiovascular tissue also includes the extracellular matrix, endothelial cells, and fibrocytes which may be coupled to myocytes. Vascular endothelial cells modulate vascular tone, mediate responses to oxidative stress, and endothelial dysfunction can lead to the development and progression of atherosclerosis. Endothelial damage leads to vascular smooth muscle proliferation and extracellular matrix synthesis and plaque formation.
The current challenge is to integrate these detailed electrophysiology, mechanics, fluid dynamics and biochemical signalling models into an overall model of the cardiovascular system under autonomic control, during normal sinus rhythm, ageing, and the development of pathologies.
Computational integration of organ physiology
Interoperability infrastructures bridging molecular- to organ-level data and models
Organizer: Bernard de Bono, CHIME Institute, University College London & Auckland Bioengineering Institute, University of Auckland
The practice and research of biomedicine generates considerable quantities of data and model resources. In particular, the organized archiving of high-throughput genomic and biochemical assays, as well as large scale biobanking and electronic health anonymization efforts, are starting to build a detailed, if patchy, multiscale record of tissue biology at both population and individual level. The VPH community is now faced with the challenge of interpreting this wealth of new information, and specifically to detect physiologically meaningful correlates between molecular-, subcellular-, cellular- and organ-level measurements of relevance to model construction and validation. What strategies are to be adopted to create a coherent VPH modeling framework that consistently interoperates across these levels? Do we need new forms of knowledge representation? Do we need new forms of knowledge management? This workshop draws upon real community efforts, and their solutions, to build interoperability infrastructures that address data-model integration, as well as the modular assembly of complex models, across the scale divide.
Make them run: modelling challenges identified by exercise physiology
Mathematical challenges of multiscale modelling
Metamodelling methodology for easing model construction and validation
Computational physiology models do in general contain a large number of parameters, numerous state variables, and intricate functional relationships between these state variables. Thus the parameter-to-phenotype map, i.e. the multidimensional mapping between model inputs and model outputs, can possess a very complex topography. Robust development and use of models require an explication of this topography. A metamodel of a given computational physiology model is a statistical prediction model that provides a description of the parameter-to-phenotype map. It is becoming increasingly clear that metamodels may become very useful for computational physiology in connection with model construction, model validation, parameter estimation, sensitivity analysis, model comparisons and computational compaction facilitating clinical use. The workshop will provide a state-of-the-art overview of metamodelling methodology and associated methodology for making use of metamodels in these application areas.
Model-guided medical device design and assessment
Organizer: Marco Viceconti, Department of Mechanical Engineering, University of Sheffield
Traditionally, bioengineers use computational approaches in the early phases of the design of a new medical device, primarily for exploratory purposes. Once a basic design is defined, prototypes are realised, and then tested first pre-clinically and then clinically, with multiple cycles of design revision as the product shortcomings become evident. But in the last few years pioneering efforts have been made to explore the possibility of making much more extensive use of computer simulation to improve the medical device design process. This opens up a number of very interesting possibilities, but also raises a number of concerns on the accuracy, reliability, and certification of these in silico medicine methods when used in the development and assessment of medical devices. Like many other industrial sectors virtual prototyping can improve the products and reduce the costs, but for medical devices this must be achieved with an extreme attention to the reliability of these simulations. The workshop will provide an overview of this pioneering work, explore innovative uses of advanced patient-specific models to guide device design, to improve the pre-clinical assessment phase and to reduce, refine and to some extent replace clinical experimentation, and discuss how to address associated model reliability issues.
Model-guided tissue engineering and stem cell therapy
Models for surgical decision support
Organizer: Kerstin Denecke, Innovation Center Computer Assisted Surgery (ICCAS), Medical Faculty, University of Leipzig
Improved clinical examination methods and developments towards personalized medicine lead increasingly to complex patient data to be considered within clinical decision making processes. Clinical decision support systems aim at making the optimum use of patient data and are supposed to support in this process of information management and interpretation. They should lead to high percentages of appropriate treatment and reduce mortality and complications. However, such systems did not yet arrived sufficiently in clinical practice, since approaches often lack relationships to scientific evidence and are poorly integrated with clinician's workflow. In the last years, the idea of model-based decision support came up that bases upon two assumptions: 1) Medical knowledge can be modelled including diagnosis, treatment, and decision making processes, i.e. it can be formally described which parameter characterize a specific diagnosis or which steps are performed within a decision-making process (domain theory). 2) The observations made during physical or other clinical assessment of a patient can be described and instantiates the formal patient model (situation description).
The workshop aims at providing an excellent opportunity for the presentation and discussion of state of the art in model-based decision support as well as for the presentation of models and concepts specifically designed for surgical decision support. The workshop further intends to collect requirements and key challenges to be addressed in future with respect to digital patient modeling for surgical decision support.
Multiscale modelling of cancer
A poster presentation is in many cases at least as valuable as an oral presentation in terms of getting people in touch with each other and conveying important results. The poster presentations therefore define a very important segment of VPH2014.We will use electronic posters (ePosters) at the VPH2014.
Hands on demonstrations
Share, discover and access biomedical resources: VPH-Share in action
Debora Testi, VPH-Share Platform
The VPH-Share is presenting the software platform currently released which allows biomedical researchers and clinicians to share data, and tools and to compose them in complex workflows to build new knowledge. The system is accessible via an easy to use web interface and allows searching for resources, the upload/creation of new resources, the remote execution of tools and workflows relying on an efficient cloud platform. The presentation will be a live demo of the system functionalities and use cases.
VPH tools from the Auckland Bioengineering Institute
Poul Michael Fonss Nielsen
This tutorial will highlight three VPH-compliant tools, PMR2, OpenCOR, and MAP Client. PMR2 is a software framework for providing data and knowledge repositories, with the data encapsulated in version controlled workspaces. OpenCOR is a tool for model editing, annotation, and simulation, initially based on CellML but extensible to other model encoding standards. The MAP Client is a workflow editor and execution tool being developed in order to capture the semantics of workflows.