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Towards a Verified Artificial Pancreas: Challenges and Solutions for Runtime Verification

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Runtime Verification

Part of the book series: Lecture Notes in Computer Science ((LNPSE,volume 9333))

Abstract

In this paper, we briefly examine the recent developments in artificial pancreas controllers, that automate the delivery of insulin to patients with type-1 diabetes. We argue the need for offline and online runtime verification for these devices, and discuss challenges that make verification hard. Next, we examine a promising simulation-based falsification approach based on robustness semantics of temporal logics. These ideas are implemented in the tool S-Taliro that automatically searches for violations of metric temporal logic (MTL) requirements for Simulink(tm)/Stateflow(tm) models. We illustrate the use of S-Taliro for finding interesting property violations in a PID-based hybrid closed loop control system.

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Notes

  1. 1.

    S-Taliro stands for System TemporAl LogIc RObustness.

  2. 2.

    Cf. https://sites.google.com/a/asu.edu/s-taliro/s-taliro.

References

  1. Abbas, H., Fainekos, G., Sankaranarayanan, S., Ivancic, F.: Probabilistic temporal logic falsification of cyber-physical systems. Trans. Embedded Comput. Syst. (TECS) 12, 95 (2013)

    Google Scholar 

  2. Annapureddy, Y.S.R., Fainekos, G.E.: Ant colonies for temporal logic falsification of hybrid systems. In: Proceedings of the 36th Annual Conference of IEEE Industrial Electronics, pp. 91–96 (2010)

    Google Scholar 

  3. Annpureddy, Y., Liu, C., Fainekos, G., Sankaranarayanan, S.: S-TaLiRo: a tool for temporal logic falsification for hybrid systems. In: Abdulla, P.A., Leino, K.R.M. (eds.) TACAS 2011. LNCS, vol. 6605, pp. 254–257. Springer, Heidelberg (2011)

    Chapter  Google Scholar 

  4. Atlas, E., Nimri, R., Miller, S., Grunberg, E.A., Phillip, M.: MD-Logic artificial pancreas system: a pilot study in adults with type 1 diabetes. Diabetes Care 33(5), 1072–1076 (2010)

    Article  Google Scholar 

  5. Baier, C., Katoen, J.-P.: Principles of Model Checking. MIT Press, Cambridge (2008)

    MATH  Google Scholar 

  6. Buckingham, B., Wilson, D.M., Lecher, T., Hanas, R., Kaiserman, K., Cameron, F.: Duration of nocturnal hypoglycemia before seizures. Diabetes Care 31(11), 2110–2112 (2008)

    Article  Google Scholar 

  7. Cameron, F.: Explicitly minimizing clinical risk through closed-loop control of blood glucose in patients with type 1 diabetes mellitus. Ph.D. thesis, Stanford University (2010)

    Google Scholar 

  8. Cameron, F., Wayne Bequette, B., Wilson, D.M., Buckingham, B., Lee, H., Niemeyer, G.: Closed-loop artificial pancreas based on risk management. J. Diabetes Sci. Technol. 5(2), 36879 (2011)

    Article  Google Scholar 

  9. Cameron, F., Niemeyer, G., Wayne Bequette, B.: Extended multiple model prediction with application to blood glucose regulation. J. Process Control 22(8), 1422–1432 (2012)

    Article  Google Scholar 

  10. Cameron, F., Wilson, D.M., Buckingham, B.A., Arzumanyan, H., Clinton, P., Peter Chase, H., Lum, J., Maahs, D.M., Calhoun, P.M.: Inpatient studies of a kalman-filter-based predictive pump shutoff algorithm. J. Diabetes Sci. Technol. 6(5), 1142–1147 (2012)

    Article  Google Scholar 

  11. Peter Chase, H., Maahs, D.: Understanding Diabetes (Pink Panther Book), 12th edn. Children’s Diabetes Foundation, Denver (2011). Available online through CU Denver Barbara Davis Center for Diabetes

    Google Scholar 

  12. Chee, F., Fernando, T.: Closed-Loop Control of Blood Glucose. Springer, Heidelberg (2007)

    MATH  Google Scholar 

  13. Chen, X., Ábrahám, E., Sankaranarayanan, S.: Taylor model flowpipe construction for non-linear hybrid systems. In: Proceeding of the RTSS 2012, pp. 183–192. IEEE (2012)

    Google Scholar 

  14. Chen, X., Ábrahám, E., Sankaranarayanan, S.: Flow*: an analyzer for non-linear hybrid systems. In: Sharygina, N., Veith, H. (eds.) CAV 2013. LNCS, vol. 8044, pp. 258–263. Springer, Heidelberg (2013)

    Chapter  Google Scholar 

  15. Cobelli, C., et al.: First use of model predictive control in outpatient wearable artificial pancreas. Diabetes Care 37(5), 1212–1215 (2014)

    Article  Google Scholar 

  16. Cobelli, C., Dalla Man, C., Sparacino, G., Magni, L., De Nicolao, G., Kovatchev, B.P.: Diabetes: models, signals and control (methodological review). IEEE Rev. Biomed. Eng. 2, 54–95 (2009)

    Article  Google Scholar 

  17. Dall Man, C., Rizza, R.A., Cobelli, C.: Meal simulation model of the glucose-insulin system. IEEE Trans. Biomed. Eng. 1(10), 1740–1749 (2006)

    Google Scholar 

  18. Dang, T., Nahhal, T.: Coverage-guided test generation for continuous and hybrid systems. Formal Methods Syst. Des. 34(2), 183–213 (2009)

    Article  MATH  Google Scholar 

  19. Dassau, E., Zisser, H., Harvey, R.A., Percival, M.W., Grosman, B., Bevier, W., Atlas, E., Miller, S., Nimri, R., Jovanovic, L., Doyle, F.J.: Clinical evaluation of a personalized artificial pancreas. Diabetes Care 36(4), 8019 (2013)

    Article  Google Scholar 

  20. de Moura, L., Bjørner, N.S.: Z3: an efficient SMT solver. In: Ramakrishnan, C.R., Rehof, J. (eds.) TACAS 2008. LNCS, vol. 4963, pp. 337–340. Springer, Heidelberg (2008)

    Chapter  Google Scholar 

  21. Dokhanchi, A., Hoxha, B., Fainekos, G.: On-line monitoring for temporal logic robustness. In: Bonakdarpour, B., Smolka, S.A. (eds.) RV 2014. LNCS, vol. 8734, pp. 231–246. Springer, Heidelberg (2014)

    Google Scholar 

  22. Donzé, A.: Breach, a toolbox for verification and parameter synthesis of hybrid systems. In: Touili, T., Cook, B., Jackson, P. (eds.) CAV 2010. LNCS, vol. 6174, pp. 167–170. Springer, Heidelberg (2010)

    Chapter  Google Scholar 

  23. Donzé, A., Maler, O.: Robust satisfaction of temporal logic over real-valued signals. In: Chatterjee, K., Henzinger, T.A. (eds.) FORMATS 2010. LNCS, vol. 6246, pp. 92–106. Springer, Heidelberg (2010)

    Chapter  Google Scholar 

  24. Dreossi, T., Dang, T., Donzé, A., Kapinski, J., Jin, X., Deshmukh, J.V.: Efficient guiding strategies for testing of temporal properties of hybrid systems. In: Havelund, K., Holzmann, G., Joshi, R. (eds.) NFM 2015. LNCS, vol. 9058, pp. 127–142. Springer, Heidelberg (2015)

    Google Scholar 

  25. El-Khatib, F., Jiang, J., Damiano, E.R.: Adaptive closed-loop control provides blood-glucose regulation using dual subcutaneous insulin and glucagon infusion in diabetic swine. J. Diabetes Sci. Technol. 1(2), 18192 (2007)

    Article  Google Scholar 

  26. El-Khatib, F.H., Russell, S.J., Nathan, D.M., Sutherlin, R.G., Damiano, E.R.: A bihormonal closed-loop artificial panceras for type 1 diabetes. Sci. Transl. Med. 2, 27ra27 (2010)

    Article  Google Scholar 

  27. Fainekos, G., Pappas, G.J.: Robustness of temporal logic specifications for continuous-time signals. Theor. Comput. Sci. 410, 4262–4291 (2009)

    Article  MathSciNet  MATH  Google Scholar 

  28. Fainekos, G., Sankaranarayanan, S., Ueda, K., Yazarel, H.: Verification of automotive control applications using s-taliro. In: Proceedings of the American Control Conference (2012)

    Google Scholar 

  29. Forlenza, G.P., Sankaranarayanan, S., Maahs, D.M.: Refining the closed loop in the data age: research-to-practice transitions in diabetes technology. Diabetes Technol. Ther. 17(5), 304–306 (2015)

    Article  Google Scholar 

  30. Frehse, G., Le Guernic, C., Donzé, A., Cotton, S., Ray, R., Lebeltel, O., Ripado, R., Girard, A., Dang, T., Maler, O.: SpaceEx: scalable verification of hybrid systems. In: Gopalakrishnan, G., Qadeer, S. (eds.) CAV 2011. LNCS, vol. 6806, pp. 379–395. Springer, Heidelberg (2011)

    Chapter  Google Scholar 

  31. Gao, S., Kong, S., Clarke, E.M.: dReal: an SMT Solver for nonlinear theories over the reals. In: Bonacina, M.P. (ed.) CADE 2013. LNCS, vol. 7898, pp. 208–214. Springer, Heidelberg (2013)

    Chapter  Google Scholar 

  32. Grosman, B., Dassau, E., Zisser, H.C., Jovanovic, L., Doyle, F.J.: Zone model predictive control: a strategy to minimize hyper- and hypoglycemic events. J. Diabetes Sci. Technol. 4(4), 961–975 (2010)

    Article  Google Scholar 

  33. Hovorka, R., Allen, J.M., Elleri, D., Chassin, L.J., Harris, J., Xing, D., Kollman, C., Hovorka, T., Larsen, A.M., Nodale, M., De Palma, A., Wilinska, M., Acerini, C., Dunger, D.: Manual closed-loop delivery in children and adoloscents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet 375, 743–751 (2010)

    Article  Google Scholar 

  34. Hovorka, R., Canonico, V., Chassin, L.J., Haueter, U., Massi-Benedetti, M., Frederici, M.O., Pieber, T.R., Shaller, H.C., Schaupp, L., Vering, T., Wilinska, M.E.: Nonlinear model predictive control of glucose concentration in subjects with type 1 diabetes. Physiol. Measur. 25, 905–920 (2004)

    Article  Google Scholar 

  35. Hovorka, R., Shojaee-Moradie, F., Carroll, P.V., Chassin, L.J., Gowrie, I.J., Jackson, N.C., Tudor, R.S., Umpleby, A.M., Hones, R.H.: Partitioning glucose distribution/transport, disposal and endogenous production during IVGTT. Am. J. Physiol. Endocrinol. Metab. 282, 992–1007 (2002)

    Article  Google Scholar 

  36. Hovorka, R.: Continuous glucose monitoring and closed-loop systems. Diabetic Med. 23(1), 1–12 (2005)

    Article  Google Scholar 

  37. Hoxha, B., Bach, H., Abbas, H., Dokhanchi, A., Kobayashi, Y., Fainekos, G.: Towards formal specification visualization for testing and monitoring of cyber-physical systems. In: International Workshop on Design and Implementation of Formal Tools and Systems (2014)

    Google Scholar 

  38. Kovatchev, B., Cobelli, C., Renard, E., Anderson, S., Breton, M., Patek, S., Clarke, W., Bruttomesso, D., Maran, A., Costa, S., Avogaro, A., Dalla Man, C., Facchinetti, A., Magni, L., De Nicolao, G., Place, J., Farret, A.: Multinational study of subcutaneous model-predictive closed-loop control in type 1 diabetes mellitus: summary of the results. J. Diabetes Sci. Technol. 4(6), 137481 (2010)

    Article  Google Scholar 

  39. Kowalski, A.: Pathway to artificial pancreas revisited: moving downstream. Diabetes Care 38, 1036–1043 (2015)

    Article  Google Scholar 

  40. Koymans, R.: Specifying real-time properties with metric temporal logic. Real-Time Syst. 2(4), 255–299 (1990)

    Article  Google Scholar 

  41. LaValle, S.M.: Planning Algorithms. Cambridge University Press, New York (2006)

    Book  MATH  Google Scholar 

  42. Maahs, D., Mayer-Davis, E., Bishop, F., Wang, L., Mangan, M., McMurray, R.G.: Outpatient assessment of determinants of glucose excursions in adolescents with type-1 diabetes. Diabetes Technol. Ther. 14(8), 658–664 (2012)

    Article  Google Scholar 

  43. Maahs, D.M., Peter Chase, H., Westfall, E., Slover, R., Huang, S., Shin, J.J., Kaufman, F.R., Pyle, L., Snell-Bergeon, J.K.: The effects of lowering nighttime and breakfast glucose levels with sensor-augmented pump therapy on hemoglobin a1c levels in type 1 diabetes. Diabetes Technol. Ther. 16(5), 284–291 (2014)

    Article  Google Scholar 

  44. Magni, L., Raimondo, D.M., Bossi, L., Dalla Man, C., De Nicolao, G., Kovatchev, B., Cobelli, C.: Model predictive control of type 1 diabetes: an in silico trial. J. Diabetes Sci. Technol. 1(6), 804–812 (2007)

    Article  Google Scholar 

  45. DallaMan, C., Camilleri, M., Cobelli, C.: A system model of oral glucose absorption: validation on gold standard data. IEEE Trans. Biomed. Eng. 53(12), 2472–2478 (2006)

    Article  Google Scholar 

  46. Dalla Man, C., Micheletto, F., Lv, D., Breton, M., Kovatchev, B., Cobelli, C.: The UVA/PADOVA type 1 diabetes simulator: new features. J. Diabetes Sci. Technol. 8(1), 26–34 (2014)

    Article  Google Scholar 

  47. DallaMan, C., Raimondo, D.M., Rizza, R.A., Cobelli, C.: GIM, simulation software of meal glucose-insulin model. J. Diabetes Sci. Tech. 1(3), 323–330 (2007)

    Article  Google Scholar 

  48. Medtronic Inc. “paradigm” insulin pump with low glucose suspend system (2012). http://www.medtronicdiabetes.ca/en/paradigm_veo_glucose.html

  49. Nghiem, T., Sankaranarayanan, S., Fainekos, G.E., Ivančić, F., Gupta, A., Pappas, G.J.: Monte-carlo techniques for falsification of temporal properties of non-linear hybrid systems. In: Hybrid Systems: Computation and Control, pp. 211–220. ACM Press (2010)

    Google Scholar 

  50. Nimri, R., Muller, I., Atlas, E., Miller, S., Kordonouri, O., Bratina, N., Tsioli, C., Stefanija, M.A., Danne, T., Battelino, T., Phillip, M.: Night glucose control with md-logic artificial pancreas in home setting: a single blind, randomized crossover trial-interim analysis. Pediatr. Diabetes 15(2), 91–100 (2014)

    Article  Google Scholar 

  51. Palerm, C.C.: Physiologic insulin delivery with insulin feedback: a control systems perspective. Comput. Methods Programs Biomed. 102(2), 130–137 (2011)

    Article  MathSciNet  Google Scholar 

  52. Patek, S.D., Bequette, B.W., Breton, M., Buckingham, B.A., Dassau, E., Doyle III, F.J., Lum, J., Magni, L., Zisser, H.: In silico preclinical trials: methodology and engineering guide to closed-loop control in type 1 diabetes mellitus. J Diabetes Sci. Technol. 3(2), 269–282 (2009)

    Article  Google Scholar 

  53. Plaku, E., Kavraki, L.E., Vardi, M.Y.: Falsification of LTL safety properties in hybrid systems. In: Kowalewski, S., Philippou, A. (eds.) TACAS 2009. LNCS, vol. 5505, pp. 368–382. Springer, Heidelberg (2009)

    Chapter  Google Scholar 

  54. Plaku, E., Kavraki, L.E., Vardi, M.Y.: Hybrid systems: from verification to falsification. In: Damm, W., Hermanns, H. (eds.) CAV 2007. LNCS, vol. 4590, pp. 463–476. Springer, Heidelberg (2007)

    Chapter  Google Scholar 

  55. Plaku, E., Kavraki, L.E., Vardi, M.Y.: Falsification of ltl safety properties in hybrid systems. Int. J. Softw. Tools Technol. Transf. 15(4), 305–320 (2013)

    Article  MATH  Google Scholar 

  56. Rizk, A., Batt, G., Fages, F., Soliman, S.: On a continuous degree of satisfaction of temporal logic formulae with applications to systems biology. In: Heiner, M., Uhrmacher, A.M. (eds.) CMSB 2008. LNCS (LNBI), vol. 5307, pp. 251–268. Springer, Heidelberg (2008)

    Chapter  Google Scholar 

  57. Sankaranarayanan, S., Fainekos, G.: Simulating insulin infusion pump risks by In-Silico modeling of the insulin-glucose regulatory system. In: Gilbert, D., Heiner, M. (eds.) CMSB 2012. LNCS, vol. 7605, pp. 322–341. Springer, Heidelberg (2012)

    Chapter  Google Scholar 

  58. Sankaranarayanan, S., Fainekos, G.E.: Falsification of temporal properties of hybrid systems using the cross-entropy method. In: HSCC, pp. 125–134. ACM (2012)

    Google Scholar 

  59. Skyler, J.S. (ed.): Atlas of Diabetes, 4th edn. Springer Science+Business Media, New York (2012)

    Google Scholar 

  60. Steil, G.M.: Algorithms for a closed-loop artificial pancreas: the case for proportional-integral-derivative control. J. Diabetes Sci. Technol. 7, 1621–1631 (2013)

    Article  Google Scholar 

  61. Steil, G.M., Panteleon, A.E., Rebrin, K.: Closed-loop insulin delivery - the path to physiological glucose control. Adv. Drug Delivery Rev. 56(2), 125–144 (2004)

    Article  Google Scholar 

  62. Weinzimer, S., Steil, G., Swan, K., Dziura, J., Kurtz, N., Tamborlane, W.: Fully automated closed-loop insulin delivery versus semiautomated hybrid control in pediatric patients with type 1 diabetes using an artificial pancreas. Diabetes Care 31, 934–939 (2008)

    Article  Google Scholar 

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Acknowledgments

This material is based upon work supported by the US National Science Foundation (NSF) under grant numbers CPS-1446900, CNS-1319457, CPS-1446751, and CNS-1319560. All opinions expressed are those of the authors, and not necessarily of the NSF.

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Authors and Affiliations

  1. Department of Mechanical Engineering, University of Texas, El Paso, USA

    Fraser Cameron

  2. School of Computing, Informatics and Decision Systems Engineering, Arizona State University, Tempe, USA

    Georgios Fainekos

  3. Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver, USA

    David M. Maahs

  4. Department of Computer Science, University of Colorado, Boulder, USA

    Sriram Sankaranarayanan

Authors
  1. Fraser Cameron
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  2. Georgios Fainekos
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  3. David M. Maahs
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  4. Sriram Sankaranarayanan
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Corresponding author

Correspondence to Sriram Sankaranarayanan .

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Editors and Affiliations

  1. TU Wien, Vienna, Austria

    Ezio Bartocci

  2. Max Planck Institute for Software Systems, Kaiserslautern, Germany

    Rupak Majumdar

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Cameron, F., Fainekos, G., Maahs, D.M., Sankaranarayanan, S. (2015). Towards a Verified Artificial Pancreas: Challenges and Solutions for Runtime Verification. In: Bartocci, E., Majumdar, R. (eds) Runtime Verification. Lecture Notes in Computer Science(), vol 9333. Springer, Cham. https://doi.org/10.1007/978-3-319-23820-3_1

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  • DOI: https://doi.org/10.1007/978-3-319-23820-3_1

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