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    Burth, M., Verghese, G.C. & Velez-Reyes, M. Subset selection for improved parameter estimation in on-line identification of a synchronous generator 1999 #IEEE_J_PWRS#
    Vol. 14(1), pp. 218-225 
    article DOI  
      author = {Burth, M. and Verghese, G. C. and Velez-Reyes, M. },
      title = {Subset selection for improved parameter estimation in on-line identification of a synchronous generator},
      journal = {#IEEE_J_PWRS#},
      year = {1999},
      volume = {14},
      number = {1},
      pages = {218--225},
      doi = {http://dx.doi.org/10.1109/59.744536}
    Cao, H., Eshelman, L., Chbat, N., Nielsen, L., Gross, B. & Saeed, M. Predicting ICU hemodynamic instability using continuous multiparameter trends. 2008 Conf Proc IEEE Eng Med Biol Soc
    Vol. 2008, pp. 3803-3806 
    article DOI URL 
    Abstract: Identifying hemodynamically unstable patients in a timely fashion in intensive care units (ICUs) is crucial because it can lead to earlier interventions and thus to potentially better patient outcomes. Current alert algorithms are typically limited to detecting dangerous conditions only after they have occurred and suffer from high false alert rates. Our objective was to predict hemodynamic instability at least two hours before a major clinical intervention (e.g., vasopressor administration), while maintaining a low false alert rate.From the MIMIC II database, containing ICU minute-by-minute heart rate (HR) and invasive arterial blood pressure (BP) monitoring trend data collected between 2001 and 2005, we identified 132 stable and 104 unstable patients that met our stability-instability criteria and had sufficient data points.We first derived additional physiological parameters of shock index, rate pressure product, heart rate variability, and two measures of trending based on HR and BP. Then we developed 220 statistical features and systematically selected a small set to use for classification. We applied multi-variable logistic regression modeling to do classification and implemented validation via bootstrapping.Area under receiver-operating curve (ROC) 0.83+/-0.03, sensitivity 0.75+/-0.06, and specificity 0.80+/-0.07; if the specificity is targeted at 0.90, then the sensitivity is 0.57+/-0.07. Based on our preliminary results, we conclude that the algorithms we developed using HR and BP trend data may provide a promising perspective toward reliable predictive alerts for hemodynamically unstable patients.
      author = {Hanqing Cao and Larry Eshelman and Nicolas Chbat and Larry Nielsen and Brian Gross and Mohammed Saeed},
      title = {Predicting ICU hemodynamic instability using continuous multiparameter trends.},
      journal = {Conf Proc IEEE Eng Med Biol Soc},
      year = {2008},
      volume = {2008},
      pages = {3803--3806},
      url = {http://dx.doi.org/10.1109/IEMBS.2008.4650037},
      doi = {http://dx.doi.org/10.1109/IEMBS.2008.4650037}
    Eshelman, L.J., Lee, K.P., Frassica, J.J., Zong, W., Nielsen, L. & Saeed, M. Development and evaluation of predictive alerts for hemodynamic instability in ICU patients. 2008 AMIA Annu Symp Proc, pp. 379-383  article  
    Abstract: This paper describes an algorithm for identifying ICU patients that are likely to become hemodynamically unstable. The algorithm consists of a set of rules that trigger alerts. Unlike most existing ICU alert mechanisms, it uses data from multiple sources and is often able to identify unstable patients earlier and with more accuracy than alerts based on a single threshold. The rules were generated using a machine learning technique and were tested on retrospective data in the MIMIC II ICU database, yielding a specificity of approximately 0.9 and a sensitivity of 0.6.
      author = {Larry J Eshelman and K. P. Lee and Joseph J Frassica and Wei Zong and Larry Nielsen and Mohammed Saeed},
      title = {Development and evaluation of predictive alerts for hemodynamic instability in ICU patients.},
      journal = {AMIA Annu Symp Proc},
      year = {2008},
      pages = {379--383}
    Heldt, T., Chang, J.L., Chen, J.J.S., Verghese, G.C. & Mark, R.G. Cycle-averaged dynamics of a periodically driven, closed-loop circulation model. 2005 Control Eng Pract
    Vol. 13(9), pp. 1163-1171 
    Abstract: Time-varying elastance models have been used extensively in the past to simulate the pulsatile nature of cardiovascular waveforms. Frequently, however, one is interested in dynamics that occur over longer time scales, in which case a detailed simulation of each cardiac contraction becomes computationally burdensome. In this paper, we apply circuit-averaging techniques to a periodically driven, closed-loop, three-compartment recirculation model. The resultant cycle-averaged model is linear and time invariant, and greatly reduces the computational burden. It is also amenable to systematic order reduction methods that lead to further efficiencies. Despite its simplicity, the averaged model captures the dynamics relevant to the representation of a range of cardiovascular reflex mechanisms.
      author = {T. Heldt and J. L. Chang and J. J S Chen and G. C. Verghese and R. G. Mark},
      title = {Cycle-averaged dynamics of a periodically driven, closed-loop circulation model.},
      journal = {Control Eng Pract},
      year = {2005},
      volume = {13},
      number = {9},
      pages = {1163--1171}
    Heldt, T., Long, B., Verghese, G.C., Szolovits, P. & Mark, R.G. Integrating data, models, and reasoning in critical care. 2006 Conf Proc IEEE Eng Med Biol Soc
    Vol. 1, pp. 350-353 
    article DOI URL 
    Abstract: Modern intensive care units (ICUs) employ an impressive array of technologically sophisticated instrumentation to provide detailed measurements of the pathophysiological state of each patient. Providing life support in the ICU is becoming an increasingly complex task, however, because of the growing volume of relevant data from clinical observations, bedside monitors, mechanical ventilators, and a wide variety of laboratory tests and imaging studies. The enormous amount of ICU data and its poor organization makes its integration and interpretation time-consuming and inefficient. There is a critical need to integrate the disparate clinical information into a single, rational framework and to provide the clinician with hypothesis-driven displays that succinctly summarize a patient's trajectory over time. In this paper, we present our recent efforts towards the development of such an advanced patient monitoring system that aims to improve the efficiency, accuracy, and timeliness of clinical decision making in intensive care.
      author = {Thomas Heldt and Bill Long and George C Verghese and Peter Szolovits and Roger G Mark},
      title = {Integrating data, models, and reasoning in critical care.},
      journal = {Conf Proc IEEE Eng Med Biol Soc},
      year = {2006},
      volume = {1},
      pages = {350--353},
      url = {http://dx.doi.org/10.1109/IEMBS.2006.259734},
      doi = {http://dx.doi.org/10.1109/IEMBS.2006.259734}
    Heldt, T., Shim, E.B., Kamm, R.D. & Mark, R.G. Computational modeling of cardiovascular response to orthostatic stress. 2002 J Appl Physiol
    Vol. 92(3), pp. 1239-1254 
    article DOI URL 
    Abstract: The objective of this study is to develop a model of the cardiovascular system capable of simulating the short-term (< or = 5 min) transient and steady-state hemodynamic responses to head-up tilt and lower body negative pressure. The model consists of a closed-loop lumped-parameter representation of the circulation connected to set-point models of the arterial and cardiopulmonary baroreflexes. Model parameters are largely based on literature values. Model verification was performed by comparing the simulation output under baseline conditions and at different levels of orthostatic stress to sets of population-averaged hemodynamic data reported in the literature. On the basis of experimental evidence, we adjusted some model parameters to simulate experimental data. Orthostatic stress simulations are not statistically different from experimental data (two-sided test of significance with Bonferroni adjustment for multiple comparisons). Transient response characteristics of heart rate to tilt also compare well with reported data. A case study is presented on how the model is intended to be used in the future to investigate the effects of post-spaceflight orthostatic intolerance.
      author = {Thomas Heldt and Eun B Shim and Roger D Kamm and Roger G Mark},
      title = {Computational modeling of cardiovascular response to orthostatic stress.},
      journal = {J Appl Physiol},
      year = {2002},
      volume = {92},
      number = {3},
      pages = {1239--1254},
      url = {http://dx.doi.org/10.1152/japplphysiol.00241.2001},
      doi = {http://dx.doi.org/10.1152/japplphysiol.00241.2001}
    Heldt, T. & Verghese, G.C. Model-based data integration in clinical environments. 2010 Conf Proc IEEE Eng Med Biol Soc
    Vol. 2010, pp. 5209-5212 
    article DOI URL 
    Abstract: As a result of improved hospital information-technology infrastructure and declining costs of storage media, vast amounts of physiological waveform and trend data can now be continuously collected and archived from bedside monitors in operating rooms, intensive care units, or even regular hospital rooms. The real-time or off-line processing of such volumes of high-resolution data, in attempts to turn raw data into clinically actionable information, poses significant challenges. However, it also presents researchers - and eventually clinicians - with unprecedented opportunities to move beyond the traditional individual-channel analysis of waveform data, and towards an integrative patient-monitoring framework, with likely improvements in patient care and safety. We outline some of the challenges and opportunities, and propose strategies for model-based integration of physiological data to improve patient monitoring.
      author = {Thomas Heldt and George C Verghese},
      title = {Model-based data integration in clinical environments.},
      journal = {Conf Proc IEEE Eng Med Biol Soc},
      year = {2010},
      volume = {2010},
      pages = {5209--5212},
      url = {http://dx.doi.org/10.1109/IEMBS.2010.5626101},
      doi = {http://dx.doi.org/10.1109/IEMBS.2010.5626101}
    Hoi, Y., Wasserman, B.A., Lakatta, E.G. & Steinman, D.A. Carotid bifurcation hemodynamics in older adults: effect of measured versus assumed flow waveform. 2010 J Biomech Eng
    Vol. 132(7), pp. 071006 
    article DOI URL 
    Abstract: Recent work has illuminated differences in carotid artery blood flow rate dynamics of older versus young adults. To what degree flow waveform shape, and indeed the use of measured versus assumed flow rates, affects the simulated hemodynamics of older adult carotid bifurcations has not been elucidated. Image-based computational fluid dynamics models of N=9 normal, older adult carotid bifurcations were reconstructed from magnetic resonance angiography. Subject-specific hemodynamics were computed by imposing each individual's inlet and outlet flow rates measured by cine phase-contrast magnetic resonance imaging or by imposing characteristic young and older adult flow waveform shapes adjusted to cycle-averaged flow rates measured or allometrically scaled to the inlet and outlet areas. Despite appreciable differences in the measured versus assumed flow conditions, the locations and extents of low wall shear stress and elevated relative residence time were broadly consistent; however, the extent of elevated oscillatory shear index was substantially underestimated, more by the use of assumed cycle-averaged flow rates than the assumed flow waveform shape. For studies of individual vessels, use of a characteristic flow waveform shape is likely sufficient, with some benefit offered by scaling to measured cycle-averaged flow rates. For larger-scale studies of many vessels, ranking of cases according to presumed hemodynamic or geometric risk is robust to the assumed flow conditions.
      author = {Yiemeng Hoi and Bruce A Wasserman and Edward G Lakatta and David A Steinman},
      title = {Carotid bifurcation hemodynamics in older adults: effect of measured versus assumed flow waveform.},
      journal = {J Biomech Eng},
      year = {2010},
      volume = {132},
      number = {7},
      pages = {071006},
      url = {http://dx.doi.org/10.1115/1.4001265},
      doi = {http://dx.doi.org/10.1115/1.4001265}
    Hoi, Y., Wasserman, B.A., Xie, Y.J., Najjar, S.S., Ferruci, L., Lakatta, E.G., Gerstenblith, G. & Steinman, D.A. Characterization of volumetric flow rate waveforms at the carotid bifurcations of older adults. 2010 Physiol Meas
    Vol. 31(3), pp. 291-302 
    article DOI URL 
    Abstract: While it is widely appreciated that volumetric blood flow rate (VFR) dynamics change with age, there has been no detailed characterization of the typical shape of carotid bifurcation VFR waveforms of older adults. Toward this end, retrospectively gated phase contrast magnetic resonance imaging was used to measure time-resolved VFR waveforms proximal and distal to the carotid bifurcations of 94 older adults (age 68 +/- 8 years) with little or no carotid artery disease, recruited from the BLSA cohort of the VALIDATE study of factors in vascular aging. Timings and amplitudes of well-defined feature points from these waveforms were extracted automatically and averaged to produce representative common, internal and external carotid artery (CCA, ICA and ECA) waveform shapes. Relative to young adults, waveforms from older adults were found to exhibit a significantly augmented secondary peak during late systole, resulting in significantly higher resistance index (RI) and flow augmentation index (FAI). Cycle-averaged VFR at the CCA, ICA and ECA were 389 +/- 74, 245 +/- 61 and 125 +/- 49 mL min(-1), respectively, reflecting a significant cycle-averaged outflow deficit of 5 which peaked at around 10% during systole. A small but significant mean delay of 13 ms between arrivals of ICA versus CCA/ECA peak VFR suggested differential compliance of these vessels. Sex and age differences in waveform shape were also noted. The characteristic waveforms presented here may serve as a convenient baseline for studies of VFR waveform dynamics or as suitable boundary conditions for models of blood flow in the carotid arteries of older adults.
      author = {Yiemeng Hoi and Bruce A Wasserman and Yuanyuan J Xie and Samer S Najjar and Luigi Ferruci and Edward G Lakatta and Gary Gerstenblith and David A Steinman},
      title = {Characterization of volumetric flow rate waveforms at the carotid bifurcations of older adults.},
      journal = {Physiol Meas},
      year = {2010},
      volume = {31},
      number = {3},
      pages = {291--302},
      url = {http://dx.doi.org/10.1088/0967-3334/31/3/002},
      doi = {http://dx.doi.org/10.1088/0967-3334/31/3/002}
    Migliavacca, F., Pennati, G., Dubini, G., Fumero, R., Pietrabissa, R., Urcelay, G., Bove, E.L., Hsia, T.Y. & de Leval, M.R. Modeling of the Norwood circulation: effects of shunt size, vascular resistances, and heart rate. 2001 Am J Physiol Heart Circ Physiol
    Vol. 280(5), pp. H2076-H2086 
    Abstract: Hypoplastic left heart syndrome is the most common lethal cardiac malformation of the newborn. Its treatment, apart from heart transplantation, is the Norwood operation. The initial procedure for this staged repair consists of reconstructing a circulation where a single outlet from the heart provides systemic perfusion and an interpositioning shunt contributes blood flow to the lungs. To better understand this unique physiology, a computational model of the Norwood circulation was constructed on the basis of compartmental analysis. Influences of shunt diameter, systemic and pulmonary vascular resistance, and heart rate on the cardiovascular dynamics and oxygenation were studied. Simulations showed that 1) larger shunts diverted an increased proportion of cardiac output to the lungs, away from systemic perfusion, resulting in poorer O2 delivery, 2) systemic vascular resistance exerted more effect on hemodynamics than pulmonary vascular resistance, 3) systemic arterial oxygenation was minimally influenced by heart rate changes, 4) there was a better correlation between venous O2 saturation and O2 delivery than between arterial O2 saturation and O2 delivery, and 5) a pulmonary-to-systemic blood flow ratio of 1 resulted in optimal O2 delivery in all physiological states and shunt sizes.
      author = {F. Migliavacca and G. Pennati and G. Dubini and R. Fumero and R. Pietrabissa and G. Urcelay and E. L. Bove and T. Y. Hsia and M. R. de Leval},
      title = {Modeling of the Norwood circulation: effects of shunt size, vascular resistances, and heart rate.},
      journal = {Am J Physiol Heart Circ Physiol},
      year = {2001},
      volume = {280},
      number = {5},
      pages = {H2076--H2086}
    Parlikar, T. & Verghese, G. A simple cycle-averaged model for cardiovascular dynamics. 2005 Conf Proc IEEE Eng Med Biol Soc
    Vol. 5, pp. 5490-5494 
    article DOI URL 
    Abstract: Lumped-parameter time-varying electrical circuit analogs for cardiovascular systems are frequently used in computational models for simulating and analyzing hemodynamics. These pulsatile models provide details of the beat-by-beat or intracycle dynamics. In other settings, however, such as when tracking a hospital patient's hemodynamic state over time, it is more useful to track trends in the intercycle dynamics. In this paper, we apply a cycle-averaging method to a simple pulsatile cardiovascular model to derive a cycle-averaged model for cardiovascular dynamics. The resulting cycle-averaged model captures the intercycle dynamics with relatively small approximation errors for a large range of perturbations in parameters such as systemic vascular resistance.
      author = {Tushar Parlikar and George Verghese},
      title = {A simple cycle-averaged model for cardiovascular dynamics.},
      journal = {Conf Proc IEEE Eng Med Biol Soc},
      year = {2005},
      volume = {5},
      pages = {5490--5494},
      url = {http://dx.doi.org/10.1109/IEMBS.2005.1615726},
      doi = {http://dx.doi.org/10.1109/IEMBS.2005.1615726}
    Roberts, J.M., Parlikar, T.A., Heldt, T. & Verghese, G.C. Bayesian networks for cardiovascular monitoring. 2006 Conf Proc IEEE Eng Med Biol Soc
    Vol. 1, pp. 205-209 
    article DOI URL 
    Abstract: Bayesian Networks provide a flexible way of incorporating different types of information into a single probabilistic model. In a medical setting, one can use these networks to create a patient model that incorporates lab test results, clinician observations, vital signs, and other forms of patient data. In this paper, we explore a simple Bayesian Network model of the cardiovascular system and evaluate its ability to predict unobservable variables using both real and simulated patient data.
      author = {Jennifer M Roberts and Tushar A Parlikar and Thomas Heldt and George C Verghese},
      title = {Bayesian networks for cardiovascular monitoring.},
      journal = {Conf Proc IEEE Eng Med Biol Soc},
      year = {2006},
      volume = {1},
      pages = {205--209},
      url = {http://dx.doi.org/10.1109/IEMBS.2006.259985},
      doi = {http://dx.doi.org/10.1109/IEMBS.2006.259985}
    Singh, A., Liu, J. & Guttag, J. Discretization of continuous ECG based risk metrics using asymmetric and warped entropy measures 2010 Proc. Computers in Cardiology, pp. 473-476  inproceedings  
      author = {Singh, A and Liu, J and Guttag, JV},
      title = {Discretization of continuous ECG based risk metrics using asymmetric and warped entropy measures},
      booktitle = {Proc. Computers in Cardiology},
      year = {2010},
      pages = {473--476}
    Syed, Z., Stultz, C., Kellis, M., Indyk, P. & Guttag, J. Motif Discovery in Physiological Datasets: A Methodology for Inferring Predictive Elements. 2010 ACM Trans Knowl Discov Data
    Vol. 4(1), pp. 2 
    article DOI URL 
    Abstract: In this article, we propose a methodology for identifying predictive physiological patterns in the absence of prior knowledge. We use the principle of conservation to identify activity that consistently precedes an outcome in patients, and describe a two-stage process that allows us to efficiently search for such patterns in large datasets. This involves first transforming continuous physiological signals from patients into symbolic sequences, and then searching for patterns in these reduced representations that are strongly associated with an outcome.Our strategy of identifying conserved activity that is unlikely to have occurred purely by chance in symbolic data is analogous to the discovery of regulatory motifs in genomic datasets. We build upon existing work in this area, generalizing the notion of a regulatory motif and enhancing current techniques to operate robustly on non-genomic data. We also address two significant considerations associated with motif discovery in general: computational efficiency and robustness in the presence of degeneracy and noise. To deal with these issues, we introduce the concept of active regions and new subset-based techniques such as a two-layer Gibbs sampling algorithm. These extensions allow for a framework for information inference, where precursors are identified as approximately conserved activity of arbitrary complexity preceding multiple occurrences of an event.We evaluated our solution on a population of patients who experienced sudden cardiac death and attempted to discover electrocardiographic activity that may be associated with the endpoint of death. To assess the predictive patterns discovered, we compared likelihood scores for motifs in the sudden death population against control populations of normal individuals and those with non-fatal supraventricular arrhythmias. Our results suggest that predictive motif discovery may be able to identify clinically relevant information even in the absence of significant prior knowledge.
      author = {Zeeshan Syed and Collin Stultz and Manolis Kellis and Piotr Indyk and John Guttag},
      title = {Motif Discovery in Physiological Datasets: A Methodology for Inferring Predictive Elements.},
      journal = {ACM Trans Knowl Discov Data},
      year = {2010},
      volume = {4},
      number = {1},
      pages = {2},
      url = {http://dx.doi.org/10.1145/1644873.1644875},
      doi = {http://dx.doi.org/10.1145/1644873.1644875}
    Syed, Z., Sung, P., Scirica, B.M., Morrow, D.A., Stultz, C.M. & Guttag, J.V. Spectral energy of ECG morphologic differences to predict death. 2009 Cardiovasc Eng
    Vol. 9(1), pp. 18-26 
    article DOI URL 
    Abstract: Unstable conduction system bifurcations following ischemia and infarction are associated with variations in the electrocardiographic activity spanning the heart beat. In this paper, we investigate a spectral energy measure of morphologic differences (SE-MD) that quantifies aspects of these changes. Our measure uses a dynamic time-warping approach to compute the time-aligned morphology differences between pairs of successive sinus beats in an electrocardiographic signal. While comparing beats, the entire heart beat signal is analyzed in order to capture changes affecting both depolarization and repolarization. We show that variations in electrocardiographic activity associated with death can be distinguished by their spectral characteristics. We developed the SE-MD metric on holter data from 764 patients from the TIMI DISPERSE2 dataset and tested it on 600 patients from the TIMI MERLIN dataset. In the test population, high SE-MD was strongly associated with death over a 90 day period following non-ST-elevation acute coronary syndrome (HR 10.45, p < 0.001) and showed significant discriminative ability (c-statistic 0.85). In comparison with heart rate variability and deceleration capacity, SE-MD was also the most significant predictor of death in the study population. Furthermore, SE-MD had low correlation with these other measures, suggesting that complementary use of the risk variables may allow for more complete assessment of cardiac health.
      author = {Zeeshan Syed and Phil Sung and Benjamin M Scirica and David A Morrow and Collin M Stultz and John V Guttag},
      title = {Spectral energy of ECG morphologic differences to predict death.},
      journal = {Cardiovasc Eng},
      year = {2009},
      volume = {9},
      number = {1},
      pages = {18--26},
      url = {http://dx.doi.org/10.1007/s10558-009-9066-3},
      doi = {http://dx.doi.org/10.1007/s10558-009-9066-3}
    Torii, R., Keegan, J., Wood, N.B., Dowsey, A.W., Hughes, A.D., Yang, G.-Z., Firmin, D.N., Thom, S.A.M. & Xu, X.Y. The effect of dynamic vessel motion on haemodynamic parameters in the right coronary artery: a combined MR and CFD study. 2009 Br J Radiol
    Vol. 82 Spec No 1, pp. S24-S32 
    article DOI URL 
    Abstract: Human right coronary artery (RCA) haemodynamics is investigated using computational fluid dynamics (CFD) based on subject-specific information from magnetic resonance (MR) acquisitions. The dynamically varying vascular geometry is reconstructed from MR images, incorporated in CFD in conjunction with pulsatile flow conditions obtained from MR velocity mapping performed on the same subject. The effects of dynamic vessel motion on instantaneous and cycle-averaged haemodynamic parameters, such as wall shear stress (WSS), time-averaged WSS (TAWSS) and oscillatory shear index (OSI), are examined by comparing an RCA model with a time-varying geometry and those with a static geometry, corresponding to nine different time-points in the cardiac cycle. The results show that the TAWSS is similar for the dynamic and static wall models, both qualitatively and quantitatively (correlation coefficient 0.89-0.95). Conversely, the OSI shows much poorer correlations (correlation coefficient 0.38-0.60), with the best correspondence being observed with the static models constructed from images acquired in late diastole (at t = 0 and 800 ms, the cardiac cycle is 900 ms). These findings suggest that neglecting dynamic motion of the RCA is acceptable if TAWSS is the primary focus but may result in underestimation of haemodynamic parameters related to the oscillatory nature of the blood flow.
      author = {R. Torii and J. Keegan and N. B. Wood and A. W. Dowsey and A. D. Hughes and G-Z. Yang and D. N. Firmin and S. A. Mcg Thom and X. Y. Xu},
      title = {The effect of dynamic vessel motion on haemodynamic parameters in the right coronary artery: a combined MR and CFD study.},
      journal = {Br J Radiol},
      year = {2009},
      volume = {82 Spec No 1},
      pages = {S24--S32},
      url = {http://dx.doi.org/10.1259/bjr/62450556},
      doi = {http://dx.doi.org/10.1259/bjr/62450556}

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