 |
Leiter der Forschungsgruppe |
Dr. med. Sven Zenker |
Adresse:
Klinik für Anästhesiologie und Operative Intensivmedizin
OPZ, 3. Etage
Sigmund-Freud-Str. 25
53105 Bonn
Die Arbeitsgruppe Angewandte Mathematische Physiologie (AMP AG) beschäftigt sich mit
der Nutzung mathematischer Modelle physiologischer und pathophysiologischer Prozesse
zur quantitativen Interpretation von akutmedizinischen Monitoringdaten,
mit dem mittelfristigen Ziel der quantitativen Prädiktion und optimierten therapeutischen
Beeinflussung der Entwicklung von intensivmedizinisch relevanten Krankheitsbildern
auf der Basis der Gesamtheit der über den Patienten verfügbaren Daten
im Sinne einer individualisierten Therapie.
The Applied Mathematical Physiology (AMP) lab, directed by Dr. Sven Zenker,
focuses on utilizing mathematical models of physiology and pathopyhsiology to
quantitatively interpret monitoring data from acute care settings.
The mid-term goal
is the fully individualized quantitative prediction and optimized therapeutic control
of critical illness treajectories exploiting all quantitative data available for a patient.
Methodisch liegt der Fokus neben der Entwicklung für die speziellen Anwendungsszenarien
optimierter mathematischer Modelle auf der vollständigen Quantifizierung der Unsicherheit
der praktisch relevanten Parameter- und Zustandsschätzungsprobleme sowie der aus
diesen aufbauenden Vorhersagen durch probabilistische Lösungsansätze für das
zugrundeliegende inverse Problem. Die Arbeit der Arbeitsgruppe wird durch die
Deutsche Forschungsgemeinschaft (DFG), die National Institutes of Health (NIH), USA,
und die German-Israeli-Foundation (GIF) gefördert.
In addition to developing mathematical models optimized for these application scenarios,
we focus on the complete quantification of uncertainty in the solutions of the practically
relevant parameter and state estimation problems and the resulting predictions arising
in this context by applying probabilistic solution techniques to the underlying inverse problem.
This work is supported by the Deutsche Forschungsgemeinschaft (DFG),
the National Institutes of Health (NIH), USA, and the German-Israeli-Foundation (GIF).
Doktorarbeiten / Stellenangebote:
1 Postdoc TVL E13, 100%, zunächst befristet auf 3 Jahre
Für ein DFG und GIF-gefördertes, hochgradig interdisziplinäres Projekt
suchen wir einen Postdoc (Physiker, Mathematiker, Informatiker oder
Ingenieur), der neben hervorragenden Programmierkenntnissen
(idealerweise MATLAB, C, C++, FORTRAN, Erfahrung mit MPI auf
HPC-Hardware) auch ein tiefgreifendes Verständnis für die Theorie und
Praxis der numerischen Simulation auf gewöhnlichen und verzögerten
Differentialgleichungen basierender mathematischer Modelle verfügt oder
alternativ Vorerfahrungen auf dem Gebiet der probabilistischen Inferenz
mittels Markov Chain Monte Carlo und Sequential Monte Carlo-Verfahren
mitbringt. Solide IT-Kenntnisse sind ebenfalls von Vorteil, da mit
mehreren Terabyte an Messdaten gearbeitet wird. Die Bereitschaft, sich
in klinische und pathophysiologische Zusammenhänge einzuarbeiten, wird
erwartet. Inhaltlich wird auf die klinische Anwendung mechanistischer
Modelle der menschlichen Pathophysiologie auf der Intensivstation
hingearbeitet, zu Details gibt Ihnen bei Interesse Herr Dr. Sven Zenker gerne
Auskunft.
Medizinische Doktoranden
Für unterschiedliche Projekte suchen wir medizinische Doktoranden.
Durchweg wird ein weit überdurchschnittliches Interesse für und
Verständnis von mathematischen Sachverhalten erwartet, idealerweise
verfügen Sie über eine Doppelqualifikation (z.B. Vordiplom in Physik
oder Mathematik), wobei dies bei entsprechendem Interesse keine
Voraussetzung ist. Bei gegebenen Voraussetzungen kann ein Stipendium
beantragt werden. Wir erwarten überdurchschnittliche
Einsatzbereitschaft, bieten im Gegenzug aber die Möglichkeit, zu
hochaktuellen Forschungsprojekten an der Schnittstelle zwischen
Mathematik und Klinik beizutragen. Bei Interesse nehmen Sie bitte mit
Dr. Sven Zenker Kontakt auf
Peer-reviewed Publications
Kiefer N, Theis J, Putensen-Himmer G, Hoeft A, Zenker S. Peristaltic pneumatic
compression of the legs reduces fluid demand and improves hemodynamic
stability during surgery: a randomized, prospective study. Anesthesiology
2011; 114(3):536-44.
Zenker, S. Parallel particle filters for online identification of mechanistic
mathematical models of physiology from monitoring data: performance and
real-time scalability in simulation scenarios. Journal of Clinical Monitoring
and Computing 2010;24:319-33
Namas, R., Ghuma, A., Torres, A., Polanco, P., Gomez, H., Barclay, D., Gordon, L.,
Zenker, S., Hermus, L., Zamora, R., Rosengart, M.R., Clermont, G., Peitzman,
A., Billiar, T.R., Ochoa, J., Pinsky, M.R., Puyana, J.C., Vodovotz, Y. An
Adequately Robust Early TNF-α Response is a Hallmark of Survival
following Trauma/Hemorrhage. PLoS ONE 2009; 4(12):e8406
Zenker, S., Polanco, P.M., Torres, A., Clermont, G., Kim, H.K., Vodovotz, Y., Pinsky,
M.R., Namas, R.A., Puyana, J.C. Very low frequecy variability in the
peripheral circulation: the possibility of plethysmographic quantification.
European Journal of Anaesthesiology 2009;26(6):522-4
Gómez, H., Torres, A., Polanco, P. Kim, H.K., Zenker, S., Puyana, J.C., Pinsky, M.R.
Use of non-invasive NIRS during a vascular occlusion test to assess dynamic
tissue O2 saturation response. Intensive Care Medicine 2008;34(9):1600-7.
Zenker, S., Rubin, J., Clermont, G. From Inverse Problems in Mathematical
Physiology to Quantitative Differential Diagnoses. PloS Computational
Biology 2007, Vol. 3, No. 11 (doi:10.1371/journal.pcbi.0030204)
Zenker, S., Polanco, P.M., Kim, H.K., Torres, A., Vodovotz, Y., Clermont, G., Pinsky,
M.R., Severyn, D.A., Puyana, J.C. Thresholded area over the curve (TAOC) of
spectrometric tissue oxygen saturation (StO2) as an indicator of volume
resuscitability in porcine hemorrhagic shock. Journal of Trauma-Injury
Infection & Critical Care 2007 63(3) 573-580.
Zenker, S., Haverkamp, F., Klingmüller, D. Growth hormone deficiency in pituitary
disease: relationship to depression, apathy and somatic complaints.
European Journal of Endocrinology 2002 147(2) 165-171.
Quade, G., Burde, B., Zenker, S., Goldschmidt, A. CancerNet online - ein Beitrag
zur Verbesserung der onkologischen Versorgung. Zentralblatt für
Gynäkologie 2000 122(12) 646-650.
Quade, G., Zenker, S., Burde, B., Riedel, R.R., Goldschmidt, A. Differences in
demographic data regarding physicians and patients in the US or abroad
using a medically oriented Internet information service. Studies in Health
Technology and Informatics 2000 77 668-672.
Conference Papers
Kiefer, N., Hoeft, A., Zenker, S. Non invasive oscillometric assessment of pulse
pressure variation – a feasibility study. Proceedings of the 11th World
Congress on Medical Physics and Biomedical Engineering 2009 (paper and
oral presentation)
Reviews, Commentaries, and Book Chapters
Kass, R., Rubin, J., Zenker, S. Discussion of Ramsay, J.O., et al., "Parameter
estimation for ordinary differential equations: a generalized smoothing
approach", Journal of the Royal Statistical Society B 2007 69(5) 785
Zenker, S., Clermont, G., Pinsky, M.R. Using mathematical models to improve the
utility of quantitative ICU data. In: Vincent JL, editors. Yearbook of Intensive
Care and Emergency Medicine 2007. Berlin Heidelberg New York: Springer.
pp. 479-492.
Quade, G., Burde, B., Zenker, S., Nagel, W., Goldschmidt, A.
Recherchefunktionalität/-algorithmen von Suchsystemen im Internet. In:
Victor, N., Blettner, M., Edler, L., Haux, R., Knaup-Gregori, P., Pritsch, M.,
Wahrendorf, J, Windeler, J. Ziegler, S. (Eds.): Medical Informatics,
Biostatistics and Epidemiology for Efficient Health Care and Medical
Research. Urban & Vogel Medien und Medizin-Verl., Müchen (1999):
329-332
Invited Presentations (International Conferences)
“Probabilistic approaches to solving the inverse problem of state and parameter
estimation for mechanistic models of physiology: from theory to practice.”
European Society for Computing and Technology in Anaesthesia and
Intensive Care (ESCTAIC) Annual Meeting 2010, Amsterdam, Netherlands.
“Probabilistic approaches to the inverse problem of state and parameter
estimation for mechanistic mathematical models of physiology. “, SIAM Life
Sciences 2010, Pittsburgh, PA, USA
“Probabilistic approaches to inverse problems in physiology, with applications to
intensive care medicine.” 9th International Conference on Complexity in
Acute Illness (ICCAI 2010), Atlanta, GA, USA
“Unbiased Representation of Population Variability in Mechanistic Ensemble
Models”, 6th International Conference on Complexity in Acute Illness (ICCAI
2007), Long Beach, CA, USA
“Mechanisms of Physiological Variability”, 7th World Congress on Trauma, Shock,
Inflammation, and Sepsis (TSIS 2007), Munich, Germany. Inflammation and
Research 2007, 56: Supplement 2, S230
“Models of the Cardiovascular System and its Control: Development to Clinical
Application”, with Sanjeev Shroff, 5th International Conference on
Complexity in Acute Illness (ICCAI 2006), Tyson's Corner, VA, USA
“Physiological Bases of Variability”, ICCAI 2006, Tyson's Corner, VA, USA
Conference Posters & Presentations
Zenker, S. Joint state and parameter estimation of an ordinary differential
equation model of the cardiovascular system from simulated monitoring
data using particle filters. Oral presentation, European Society for
Computing and Technology in Anaesthesia and Intensive Care (ESCTAIC)
Annual Meeting, Berlin, Germany, September 2009
Zenker, S. Echtzeit-Zustandsschätzung für Differentialgleichungsmodelle des
kardiovaskulären Systems aus Monitoringdaten mittels parallelisierter
Partikelfilter: eine Machbarkeitsstudie. Poster Presentation,
Hauptstadtkongress der DGAI für Anästhesiologie und Intensivtherapie,
Berlin, Germany, September 2009
Zenker, S., Hoeft, A. Using statistical model selection criteria to discriminate
nonsubjectively between hypotheses about physiologic mechanisms
underlying experimental observations: a practical example. Oral
Presentation, International Conference on Complexity in Acute Illness
(ICCAI), Palo Alto, CA, USA, August 2009. J. Crit Care 2009; 24(3):e20
Zenker, S., Gomez, H., Polanco, P., Namas, R., Torres, A., Clermont, G., Vodovotz,
Y., Pinsky, M., Puyana., J. Role of Pulmonary Resistance in Response to
Resuscitation of Porcine Shocked Trauma and Circulatory Collapse.
Poster Presentation SHOCK 2008, Cologne, Germany, June 2008, Shock.
29(7) Suppl 1:17
Conference Posters & Presentations
Namas, R., Torres, A., Gomez, H., Barclay, D., Zenker, S., Clermont, G., Puyana, J.C.,
Pinsky, M.R., Vodovotz, Y. Robustness of Early Inflammation may
Predispose to Survival: Studies in a Porcine Model of Hemorrhagic Shock.
Poster Presentation SHOCK 2008, Cologne, Germany, June 2008,Shock.
29(7) Suppl 1:74
Zenker, S. , Rubin, J., Clermont, G. Unbiased Inference of Parameter Distributions
for Nonlinear Models: the Underdetermined Case. Oral Presentation,
International Conference on Complexity in Acute Illness (ICCAI), Cologne,
Germany, June 2008. J Crit Care 2008;23(2):272
Zenker, S., Polanco, P.M., Torres, A., Clermont, G., Pinsky, M.R., Kim, H.K.,
Vodovotz, Y., Puyana, J.C. Quantifying Microcirculatory Variability Using
the Reflectance Intensity Signal of a Reflectance Pulse Oxymeter. Discussed
Poster, Society of Critical Care Medicine 37th Annual Congress, Honolulu,
Hawaii, February 2008, Crit Care Med 2007;12(Suppl):A28
Zenker, S., Rubin, J., Clermont, G. Towards differential diagnosis of critical illness
using mechanistic mathematical models: first application to clinical data.
Poster, International Conference on Complexity in Acute Illness (ICCAI),
Long Beach, CA, USA, October 2007, J Crit Care 2007; 21(4):349
Zenker, S., Rubin, J., Clermont, G. From Inverse Problems in Mathematical
Physiology to Quantitative Differential Diagnoses. Poster, Workshop on
Statistical Methods for Modeling Dynamic Systems, Montreal, Canada, July
2007
Zenker, S., Rubin, J., Clermont, G. The discriminatory power of the physical
examination: a theoretical analysis. Poster, 30th Annual Conference on
Shock, Baltimore, MD, USA, June 2007, Shock 27(7):Supplement 1:45
Zenker, S., Polanco, P.M., Kim, H., et al. Thresholded area over the curve (TAOC) of
spectrometric tissue oxygen saturation (StO2) as an indicator of volume
resuscitability in an acute porcine model of hemorrhagic shock.
Presentation, Eastern Association for the Surgery of Trauma (EAST) Annual
Meeting, Fort Myers, FL, USA, January 2007
Polanco, P.M., Zenker, S., Torres, A., Kim, H.K., Vodovotz, Y., Clermont, G., Pinsky,
M.R., Puyana, J.C. Correlation of Sublingual PCO2 with Base Excess and
Lactate during severe hemorrhagic shock and resuscitation. Poster, Eastern
Association for the Surgery of Trauma (EAST) Annual Meeting, Fort Myers,
FL, USA, January 2007
Zenker, S., Rubin, J., Clermont, G. Towards a model based medicine: integration of
probabilistic inference with mechanistic knowledge. Poster, International
Conference on Complexity in Acute Illness (ICCAI), Tyson's Corner, VA, USA,
October 2006, J Crit Care 2006; 21(4):350
Polanco, P.M., Zenker, S., Torres, A., Vodovotz, Y., Clermont, G., Pinsky, M.R.,
Puyana, J.C. Complex Systems approach to Irreversible Hemorrhagic Shock.
Poster, Advanced Technology Applications for Combat Casualty Care
(ATACCC), August 2006, St. Pete Beach, Florida
Zenker, S., Polanco, P., Torres, A., Vodovotz, Y., Puyana, J.C., Pinsky, M.R.,
Clermont, G. Continuous sublingual pCO2 as a rapid indicator of changes in
tissue perfusion in hemorrhagic shock: an experimental study. Poster, 29th
Annual Conference on Shock, Broomfield, Colorado, USA, June 2006, Shock
29:Supplement 1:57
Zenker, S., Rubin, J., Puyana, J.C., Clermont, G. The baroreflex feedback loop and
the low- frequency component of heart rate variability in sepsis: A
simulation study. Poster, International Conference of the American Thoracic
Society, San Diego, USA, May 2006, Proc Am Thorac Soc 3:A646
Zenker, S., Rubin, J., Torres, A., Polanco, P., Puyana, J.C., Clermont, G.
Determinants of the irreversibility of hemorrhagic shock: an exploratory
simulation study. Presentation & Poster, 4th International Conference on
Complexity in Acute Illness, Cologne, Germany, November 2005, Journal of
Critical Care 20:397-398 (Abst)
Zenker, S., Polpitiya, A.D., Rahaghi, F.N., Guikema, B. Interaction of
hemodynamics and fluid balance between intravascular and interstitial
compartments in septic shock: a mathematical model incorporating protein
shifts. Presentation & Poster, 3rd International Conference on Complexity in
Acute Illness, Pittsburgh, PA, November 2004
Zenker, S., Haverkamp, F., Klingmüller, D. Growth hormone after GHRH and
Insulin-like Growth factor-1 (IGF-1) in pituitary diseases and their
relationship to depression. Poster, 44th Symposion of the German Society of
Endocrinology, Munich, May/June 2000. Exp. Clin. Edocrinol. Diabetes
101:S193
Prizes & Awards
Best Free Paper Prize, European Society for Computing and Technology in
Anaesthesia and Intensive Care (ESCTAIC) Annual Meeting, Berlin, Germany,
September 2009
Finalist, Alexander Award of the Eastern Association for the Surgery of Trauma
(EAST), EAST Annual Meeting, Fort Myers, FL, USA, January 2007
Poster prize, 4th International Conference on Complexity in Acute Illness,
Cologne, NRW, Germany, November 2005
2nd prize, young investigators' competition, 3rd International Conference on
Complexity in Acute Illness, Pittsburgh, PA, November 2004
Research grants
Principal Investigator, DFG ZE 904/3, “Improving monitoring data utility in acute
care medicine using mechanistic mathematical models of physiological
processes.” 2011-2014
Principal Investigator, GIF Young Scientist Grant no. 2249, “Quantitative decision
support in the intensive care unit using mechanistic mathematical models
of physiology: interaction between fluid management, cardiovascular, and
renal function.” 2011-2012
Co-Investigator, NIH R21LM009936-01A1 “Quantitative, model-based medical
decision support by Bayesian inference”; 07/2009 - 07/2011
Principal Investigator, University of Bonn Faculty of Medicine Intramural Startup
grant mechanism 10. “Quantitative Interpretation akutmedizinischer
Monitoringdaten mittels mechanistischer mathematischer Modelle
physiologischer Prozesse”; 01/2009 – 12/2009
Principal Investigator, Teragrid DAC IBN080003N High Performance Computing
Startup grant for 30,000 CPU hours. “Probabilistic inference for
physiological data interpretation and prediction”; 05/2007-05/2009
Patents
Zenker, S., Rubin, J., Clermont, G., “Diagnosis of Medical Condition using
Mechanistic Mathematical Model“, U.S. Provisional Patent Application
#60/977,280, filed on October 3, 2007
International
Gilles Clermont, Dpt. of Critical Care Medicine, University of
Pittsburgh Medical Center, Pittsburgh, PA, USA
Jonathan Rubin, Dpt. of Mathematics, University of Pittsburgh Medical
Center, Pittsburgh, PA, USA
Idit Matot, Dpt. of Anesthesiology, Sourasky Medical Center, Tel Aviv,
Israel
National
Bernhard Thull, Darmstadt University of Applied Sciences, Darmstadt,
Germany
Intramural
Klaus Lehnertz, Neurophysics Group, Dpt. of Epileptology, University of
Bonn Medical Center
Anton Bovier, Institute for Applied Mathematics, University of Bonn
Medical Center
Intern
FG Prof. Dr. med. A. Hoeft, Klinik für Anästhesiologie und Operative Intensivmedizin,
Universität Bonn
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