Digital Euro A stronaut

1. Stanislav Matousek, M.D. Digital EuroAstronaut Creative Connections s.r.o. in cooperation with Charles University in Prague and Czech Technical University

2. Why computer simulation models ? USA Extended cosmic flight Re-adaptation to gravity Overburdening Microgravity 1980’s Ever increasing times of human stay in space Physiological data available for shorter term Need to make all the possible use of the available data for extrapolation of physiological reactions Answer of both USA and USSR: Large-scale simulation models USSR

3. Complex simulation models of human physiology Why complex? • Influence of long stays in space on cardiovascular system • Influence on other systems – muscle, distribution of fluids, endocrine • The function of these physiological systems is connected and even intertwined; individual systems cannot be studies separately

4. Methods of System Analysis in Space Biology and Medicine Use of great-scale models of human physiology in USSR USSR

5. USA Mathematical Modeling of Acute and Chronic Cardiovascular Changes during Extended Duration Orbiter (EDO) Flights Use of great-scale models of human physiology in the USA USA USSR

6. Concrete outcomes in the past • pathogenesis of circulatory changes explained • Endorsed the importance of muscle exercise during space stays. • Helped to choose appropriate testing mechanisms for selection of suitable individuals.

7. thirst non-muscles oxygen delivery vascular stress relaxation muscle blood flow and PO2 kidney ADH control non-muscles blood flow capillary membrane dynamics angiotensin control Circulatory dynamics aldosterone control autonomic control tissue fluids, pressures, gel red cells, viscosity electrolytes & cell water heart rate, stroke volume pulmonary dynamics heart hypertrophy

8. New millennium: Digital Astronaut Project USA

9. New millennium: Digital Astronaut Project USA

10. Benefits of the project Digital EuroAstronaut for European Space Research

11. Should Europe have a similar project as United States? If not, are Americans going to SHARE their simulation results with European partners? If yes, the project should be started now - the new technological tools are available, knowledge has advanced and new human crew flights considered New millennium: Digital EuroAstronaut Project? USA

12. Digital EuroAstronaut ProjectGOALS: • Physiologic adaptation of human to the microgravity environment • Computer simulations using the model with predict microgravity induced changes and induced physiological adaptation • Identification and meaningful interpretation of the medical and physiological research required for human space exploration • Determination of the effectiveness of specific individual human countermeasures in reducing risk and meeting health and performance goals on challenging exploration • Evaluation of the appropriateness of various medical interventions during mission emergencies, accidents and illness.

13. Digital EuroAstronautOther research benefits: • Improved knowledge of quantitative human physiology • Development of new medical simulators (e.g. intensive care) • Use and further development of modern Europe-based modelling tools (e.g. Modelica)

14. “Digital EuroAstronaut”SUMMARY • Great potential in Europe • New technological tools available • Several groups concerned with large-scale physiology modelling • Cooperation could be established. • If long-term human crew space flights are to be considered, it is time to start

15. HOW SHOULD BE LARGE- SCALE SIMULATION MODEL OF “EUROASTRONAUT” BUILT?

16. POSSIBLE PROBLEMS • Physiological knowledge has advanced significantly since 1980’s. • The detailed structure of large-scale models has generally never been published! – Example: complex model of human physiologyby Guyton and Coleman (underlying structure of Americal Digital Astronaut.) • What has been published contains errors! • The 1980’s or even current models are implemented in old and surpassed modelling software (Fortran…).

17. Research Team Principal investigator: Jiří Kofránek, M.D., PhD. • 30 years of experience with modeling great-scale physiological systems • Current projects: • e-Golem: Intensive care simulator of human physiology as basis for e-learning” (Creative Connections) • National Virtual Laboratory of educational simulation models” (Charles Universityin Prague + Czech Technical University)

18. Research Team Principal investigator: Dr, Jiří Kofránek, CSc. In 1980’s part of the USSR space research

19. Research Team Creative Connections s.r.o. research/development company, founded in 1992 (former name BAJT servis s.r.o.) Project e-Golem Close cooperates with Charles University and Czech Technical University Currently starting cooperation on Quantitative HumanPhysiology part of European project Open Modelica Charles University in Prague, Czech Technical University Project : “National virtual laboratory of educational simulators. Cooperating with European simulation institutes Together: Education of Biomedical Engineering Students

20. Our Simulink implementation 260 VIE VIE OSV 1.5 1.5 7 337 0.000920 337 0.000920 259 Error 5 6 3.257 Z7 QAO HKM DVS HKM VVS + 5 5 0 HM2 1600 1600 + + Error HM2 336 HMK 336 VBD 258 HMK QVO - 40 + 186 Error 40 0 HM 1 260 AHC 40 - ò ò ò ò ò ò ò ò ò ò OSV + AH1 185 7 158A 40 RC1 259 HM RC1 .0785 5 331 6 3.257 331 + QAO Z7 DVS VVS + + .14 .3333 + - 5 - 0 - 5 - - 183 + + 184 Error VBD AH 1 QVO 258 RCD RCD 332 - 332 + 186 Error 1 AHC 185 AH1 VRC VRC 333 .0000058 333 .0000058 .0785 RCK RCK 158A .3333 183 .14 .0000116 1 AH .0000116 RC2 RC2 184

21. Great-scale model • Is not same as small scale • Correct hierarchy • Possible use of hierarchical state automata • Scalability • Model equations

22. Model Structure and Equations Thomas Coleman – Author of QHP model. Principal researchers of American Digital Astronaut We are probably the only team in Europe to have access to the commented structure of QHP

23. Modelling Environment • Very strong new simulation environment: • Math.Modelica • Dymola • Open Modelica Modelica .NET as web service Creation of web models visual editor and compiler Causality is solved automatically with bond-graph theory

24. Local reach publication activity • Kofránek, J. - Rusz, J.: Od obrázkových schémat k modelům pro výuku. Československá fyziologie. 2007, roč. 2007, č. 2, s. 69-78. ISSN 1210-6313. • Kofránek, J. - Rusz, J. - Matoušek, S.: Guytons Diagram Brought to Life - from Graphic Chart to Simulation Model for Teaching Physiology. In Technical Computing Prague 2007. Prague: HUMUSOFT, 2007, p. 1-14. ISBN 978-80-7080-658-6. • Kofránek, J. - Rusz, J. - Matoušek, S.: Vzkříšení Guytonova diagramu – od obrázku k simulačnímu modelu. In MEDSOFT 2008. Praha: Agentura Action M, 2008, s. 57-62. ISBN 978-80-86742-22-9. • Cited publication: Thomas SR, Baconnier P, Fontecave J, Francoise JP, Guillaud F, Hannaert P, Hernandez A, Le Rolle V: SAPHIR: a physiome core model of body fluid homeostasis and blood pressure regulation. PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES. ISSN 1364-503X.

25. Potential needs of Digital EuroAstronaut project

26. Digital EuroAstronaut Project NEEDS Data – all available physiological measurements Long-term co-operation with physitians directry involved with astronauts (fitting to individual parameters) Cooperation with USA Funding: e.g. People, SW, preparation of European team

27. ANNOTATION GOALS Modern implementation of adapted QHP and Golem (.NET Modelica) Compilator – Editor European team established Digital Astronaut Project e-Golem: complex circulatory-dynamics model Tools for cooperative web model creation

28. Contact: • MUDr. Jiří Kofránek, Ph.D. • Creative Connections s.r.o., Krasnojarská 14, Praha 10, DIČ 48039713 • 1. Faculty of Medicine Charles University in Prague, Praha 2, Kateřinská 32 • kofranek@gmail.com