Authors: Chan, Alice; Breton, Marc; Kovatchev, Boris

Abstract: Type 1 diabetes mellitus (T1DM) patients relies exclusively on exogenous insulin to maintain safe blood glucose levels. It has been recently demonstrated that insulin promotes its own action by enhancing capillary recruitment which occurs 15-20 minutes before increase in glucose uptake. In this study, we examine insulin-induced capillary recruitment in T1DM patients with various levels of insulin sensitivity. Eleven hyperinsulinemic euglycemic clamps were performed on nine T1DM patients during which capillary recruitment was assessed at basal insulin concentration levels and at hyperphysiological levels 30 min after the start of the clamp using contrast-enhance ultrasound (CEU) imaging. A systematic procedure was developed to select regions of interest (ROI) in the sequences of ultrasound images, thus bypassing the subjectivity of a selection done ''by hand''. The replenishment curves were then obtained and fitted with exponential curves which parameters provide measures of microvascular blood volume (MBV) and microvascular flow (MF). Higher basal MBV and MF were observed in high insulin sensitive subjects compared to low SI subjects. Hyperphysiological insulin concentrations induced by the clamp yielded opposite effects in low insulin sensitivity (SI) and high SI patients: capillary recruitment and derecruitment was observed respectively. It was hypothesized that insulin-induced capillary recruitment occurs at a subject-specific level of insulin concentration, and that this level is low (below basal) for sensitive patients and higher (above basal) for more resitant patients. Furthermore, diabetic microvascular complications significantly correlated with the effect of hyperphysiological insulin levels on the capillary recruitment/derecruitment in the two groups.

Keywords: Pharmacokinetics and drug delivery,; Biomedical imaging systems; Quantification of physiological parametes for diagnosis assessment

Identifier: 10.3182/20090812-3-DK-2006.00011

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Pretty, Christopher; Chase, J. Geoffrey; Lin, Jessica; Shaw, Geoffrey M; Le Compte, Aaron; Razak, Normy; Parente, Jacquelyn Dawn

Abstract: Corticosteroids reduce insulin sensitivity in healthy individuals by 30- 62-percent. The aim of this research was to use model-based methods to determine whether this reduction is also true in critically ill patients and how it may affect tight glycaemic control. A clinically validated model-based measure of insulin sensitivity was used to quantify changes between two matched cohorts of 40 intensive care unit (ICU) patients from Christchurch hospital. A 9-percent reduction in median insulin sensitivity was seen between the control cohort and patients receiving corticosteroids (per patient dose equivalent to 160mg/d of hydrocortisone). On a per-patient basis 11- 22-percent reductions were observed with higher percentile patients having greater suppression of insulin sensitivity. This research has shown that corticosteroids cause a much lower reduction in insulin sensitivity for critically ill patients compared to healthy controls and may thus have far less impact than suspected on glycaemic control in the ICU setting.

Keywords: Critical care and decision support systems; Quantification of physiological parametes for diagnosis assessment; Control of physiological and clinical variables,

Identifier: 10.3182/20090812-3-DK-2006.00005

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Andreassen, Steen; Zalounina, Alina; Paul, Mical; Leibovici, Leonard

Abstract: The results from the in vitro susceptibility tests are usually available only for a limited set of antibiotics. This paper provides a practical method for prediction of a posteriori probability for coverage for all relevant antibiotics. The method combines susceptibility results for a limited set of antibiotics with data on cross-resistance between antibiotics. The Brier distance was used to measure the accuracy of the predicted coverages. Across all pathogen/antibiotic combinations in the derivation database, the Brier distances for a priori coverages was 39%, reduced to 25% for predicted a posteriori coverages, indicating that there is a significant advantage to the method proposed (p<10 99).

Keywords: Decision support and control of biomedical systems; Pharmacokinetics and drug delivery,

Identifier: 10.3182/20090812-3-DK-2006.00055

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Lin, Jessica; Parente, Jacquelyn Dawn; Chase, J. Geoffrey; Shaw, Geoffrey M; Blakemore, Amy; Le Compte, Aaron; Pretty, Christopher; Razak, Normy; Lee, Dominic; Hann, Christopher E; Wang, Sheng-Hui

Abstract: Sepsis occurs frequently in the intensive care unit (ICU) and is a leading cause of admission, mortality, and cost. Treatment guidelines recommend early intervention, however positive blood culture results may take up to 48 hours. Insulin sensitivity (SI) is known to decrease with worsening condition and could thus be used to aid diagnosis. Some glycemic control protocols are able to accurately identify insulin sensitivity in real-time. Receiver operator characteristic (ROC) curves and cut-off SI values for sepsis diagnosis were calculated for real-time model-based insulin sensitivity from glycemic control data of 36 patients with sepsis. Patients were identified as having sepsis based on a clinically validated sepsis score (ss) of 2 or higher (ss = 0-4 for increasing severity). A clinical biomarker was calculated from patient clinical data to maximize the discrimination between cohorts. Insulin sensitivity as a sepsis biomarker for diagnosis of severe sepsis achieves a 50% sensitivity, 76% specificity, 4.8% PPV, and 98.3% NPV at a SI cut-off value of 0.00013 L*mU min-1. A clinical biomarker combining SI, temperature, heart rate, respiratory rate, blood pressure, and their respective hourly rates of change achieves 73% sensitivity, 80% specificity, 8.4% PPV, and 99.2% NPV. Thus, a clinical biomarker provides an effective real-time negative predictive diagnostic for severe sepsis. Examination of both inter- and intra-patient statistical distribution of this biomarker and sepsis score show potential avenues to improve the positive predictive value.

Keywords: Quantification of physiological parametes for diagnosis assessment; Critical care and decision support systems; Disease control and critical care,

Identifier: 10.3182/20090812-3-DK-2006.00003

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Hann, Christopher E; Chase, J. Geoffrey; Revie, James A; Hewett, Darren; Shaw, Geoffrey M

Abstract: Diabetic Retinopathy (DR) is one of the main causes of blindness and visual impairment in developed countries, stemming solely from diabetes mellitus. Current screening methods using fundus images rely on the experience of the operator as they are manually examined. Automated methods based on neural networks and other approaches have not provided sensitivity or specificity above 85%. This work presents a computer vision based method that directly identifies hard exudates and dot haemorrhages (DH) from 100 digital fundus images from a graded database of images using standard computer vision techniques, and clinical observation and knowledge. Sensitivity and specificity in diagnosis are 95-100% in both cases. Positive and negative prediction values (PPV, NPV) were 95-100% for both cases. The overall method is general, computationally efficient and suitable for further clinical trials to test both accuracy and the ability to the track DR status over time.

Keywords: Biomedical imaging systems; Endocrine and metabolic systems; Quantification of physiological parametes for diagnosis assessment

Identifier: 10.3182/20090812-3-DK-2006.00052

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Docherty, Paul D; Chase, J. Geoffrey; Lotz, Thomas; Hann, Christopher E; Shaw, Geoffrey M; Berkeley, Juliet E; J I, Mann; McAuley, Kirsten A

Abstract: Knowing insulin sensitivity (SI) can optimise glycaemic control, assess metabolic drug therapy, or define diabetes risk. The DISTq is a short, low dose IM-IVGTT that generates an estimate of SI immediately after a 40 minute test using only glucose measurements, subjects physical attributes, and population parameter estimations. In this article, the DISTq is evaluated in clincial and in silics trials. In clinical trials, the test has shown a very strong correlation to the fully sampled DIST SI (R=0.91), (which also uses insulin and c-peptide assays) and a strong correlation to the euglycemic hyperinsulinaemic clamp (EIC) in in silico virtual trials (R=0.81). This study shows that population estimates can reduce the need for expensive insulin and c-peptide assays in obtaining an accurate, realtime estimation of SI.

Keywords: Functional imaging and data modelling; Disease control and critical care,; Endocrine and metabolic systems

Identifier: 10.3182/20090812-3-DK-2006.00016

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Wen, Lingfeng; Eberl, Stefan; Feng, David Dagan; Stalley, Paul; Huang, Gang; Fulham, Michael

Abstract: Kinetic modeling in functional imaging can derive quantitative rate constants and macroparameters, which can facilitate clinical evaluation. 18F-fluoride is a suitable tracer for quantifying bone metabolism. This study employed a three-compartment and four-parameter kinetic model for 18F-fluoride to analysis dynamic 18F-fluoride PET studies of eight patients with bone grafts. Kinetic parameters were estimated for bone graft, ilium, rib, femur and lumbar vertebra regions with non-linear least square fitting. Parametric images of the influx rate constant were constructed by the Patlak graphical analysis for comparison. Differences in net influx rate constant between bone graft and normal bone regions could be detected by the technique and the technique shows promise in providing quantitative assessment of the viability of bone grafts.

Keywords: Quantification of physiological parametes for diagnosis assessment; Kinetic modelling and system control; Biomedical imaging systems

Identifier: 10.3182/20090812-3-DK-2006.00048

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Heinke, Stefanie; Finocchiaro, Thomas; Steinseifer, Ulrich; Schmitz-Rode, Thomas; Walter, Marian; Leonhardt, Steffen

Abstract: A new tool for the development process of total artificial hearts (TAH) dedicated for the long-term use is presented. The focus is on the modelling of a dynamic Mock Circulatory Loop, which can adapt to different physiological conditions and simulates a natural transient behaviour in between. This is important for the development of adaptive control algorithms which are able to respond to the physiological demand. After an introduction of the clinical problem, the Mock Circulatory Loop is described. The concept for the simulation process of the TAH with the Mock Circulatory Loop and with the hardware to realize Hardware-in-the-Loop (HIL) simulation is introduced. Finally, some results of the first measurements with a component of the Mock Circulatory Loop are presented.

Keywords: Circulatory and respiratory systems; Control of physiological and clinical variables,

Identifier: 10.3182/20090812-3-DK-2006.00045

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Csercsik, Dávid; Szederkenyi, Gabor; Hangos, Katalin M.; Farkas, Imre

Abstract: GnRH neurons, as key elements of the reproductive neuroendocrine system, have important central regulating role in the dynamics of the hormonal cycle. A Hodgkin-Huxley type neural model is proposed in this paper, that takes into account up-to-date biological literature data related to ion channels. The proposed neuron model is highly nonlinear in parameters and the evaluation of the objective function is computationally expensive, therefore the asynchronous parallel pattern search (APPS) procedure has been used for identification. The model with high number of estimated parameters provides a qualitatively good fit of both voltage clamp and current clamp traces.

Keywords: Neurosystems; Kinetic modelling and system control; Endocrine and metabolic systems

Identifier: 10.3182/20090812-3-DK-2006.00074

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Salido Ruiz, Ricardo Antonio; Ranta, Radu; Louis Dorr, Valérie

Abstract: Blind source separation (BSS) is a relatively recent technique, more and more applied in electroencephalographic (EEG) signal processing. Still, the classical mixing model of the BSS does not take into account the real recording set-up. In fact, a major problem in electrophysiological recording systems (e.g. ECG, EEG, EMG) is to find a region in the human body whose bio-potential activity can be considered as neutral as possible i.e., a quasi-inactive reference place. Nowadays, it is well known that it is impossible to find a “zero-potential” site on the human body. In particular, the most common way of performing EEG recordings is by using as a common reference an electrode placed somewhere on the head. Starting from this Common Reference Montage (CRM), several other montages can be constructed for interpretation or processing purposes. Regardless of the chosen montage, the reference electrode intervenes in the mixing model of the BSS. The objective of this work is to analyse the influence of the montage on the mixing matrix and the quality of the BSS solution. This communication proposes to formalize the source separation problem in a non zero-potential reference context and shows that the Average Reference Montage (ARM), augmented by a virtual “average measure”, leads to better source separation results (separability index IS). This conclusion is supported by simulated EEGs using the most common montages i.e. Common Reference Montage, Average Reference Montage and Bipolar-Longitudinal Montage, as well as by real EEG examples.

Keywords: Biomedical signal processing

Identifier: 10.3182/20090812-3-DK-2006.00068

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Sundaresan, Ashwath; Hann, Christopher E; Chase, J. Geoffrey; Shaw, Geoffrey M

Abstract: Acute Respiratory Distress Syndrome (ARDS) results in collapse of alveolar units and loss of lung volume at end of expiration. Mechanical ventilation (MV) is used on patients with ARDS or Acute Lung Injury (ALI), with the end objective being to increase the end expiratory volume (EEV) and hence increasing overall functional residual capacity (FRC). Simple methods to estimate EEV at a given positive end expiratory pressure (PEEP) level in patients with ARDS/ ALI currently do not exist. Current viable methods are time consuming, relatively invasive and not model based. Previous studies have found a constant linear relationship between the global stress and strain in the lung independent of lung condition. This study utilizes the constant stress strain ratio and an individual patient’s volume responsiveness to PEEP to estimate EEV. The estimation model identifies two global parameters that can be used to estimate EEV in a patient, β and mβ. The parameter β captures physiological parameters of FRC, lung and respiratory elastance, and varies depending on the PEEP level used, and mβ is the gradient of β vs PEEP. EEV was estimated at different PEEP values and compared to the measured EEV for 12 different patients with different levels of lung injury. The median percentage error is 18% (IQR: 6,49) for PEEP = 5 cm H2O, 10% (IQR: 9,18) for PEEP = 7 cm H2O, 28% (IQR: 12,33) for PEEP = 10 cm H2O, 3% (IQR: 2,10) for PEEP = 12 cm H2O and 10% (IQR: 9,11) for PEEP = 15 cm H2O. The results were further validated using a cross correlation test and a linear regression was performed between the estimated and measured EEV with a median R2 of 0.948 (IQR: 0.915,0.968 ; 90% CI: 0.814,0.984). This simple approach can be done at the bedside with minimal intervention to provide an estimate with reasonable accuracy to track patient condition.

Keywords: Circulatory and respiratory systems; Critical care and decision support systems; Healthcare management

Identifier: 10.3182/20090812-3-DK-2006.00039

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Gurses, Senih; Kenyon, Robert; Keshner, Emily

Abstract: To examine the evolution of inter-segmental coordination over time, a previously developed multi-variate model of postural coordination during quiet stance (Kuo et al. 1998) has been extended. In the original model, postural coordination was treated as an eigenvalue-eigenvector problem between two segmental degrees of freedom represented by angular displacements of the trunk and lower limb. Strategies of postural coordination were then identified using the sign of the covariance between the two segments’ angular displacements. In contrast to the original model, the current model first subdivided the entire trial into smaller time segments, comprising four cycles of perturbation, i.e., a 16 sec window. This window marched along the data advancing in 8.3 ms steps, each time performing the computation from the original model on the terms of the covariance matrix. The resulting time-segment-dependent postural strategies estimated the changes in posture control that took place over the course of the experiment. In addition to the statistical modeling, the auto-power spectrums and cross-spectral density function estimates for the entire trial, as well as for the individual time-segments, were analyzed. In these experiments subjects experienced a 0.25 Hz sinusoidal perturbation of a platform while exposed to a virtual reality environment. The data we collected showed that the statistical and spectral characteristics across the entire trial may differ from individual time segments of the same trial indicating time varying postural behavior. Comparison of these results from young and elderly subjects revealed that the time dependency observed in postural behavior was sensitive to aging. The young population managed to be consistent in their postural behavior throughout the entire trial and responded to the perturbation frequency with an out-of-phase response between the postural segments. Elderly subjects, however, demonstrated inconsistent postural behaviors as they switched back and forth between different postural coordination patterns within a trial.

Keywords: Neurosystems; Rehabilitation engineering and healthcare delivery; Biomedical signal processing

Identifier: 10.3182/20090812-3-DK-2006.00065

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Debril, Jean-François; Pudlo, Philippe; Gorce, Philippe; Lepoutre, François Xavier

Abstract: Several times per day, manual wheelchair (MW) users perform weight relief lifting or sitting pivot transfer movements using only their upper limbs. These motions generate significant articular constraints that could lead to musculo-skeletal disorders. The geometry of the hardware configurations of manual wheelchairs influence the movements produced by these MW users. To evaluate this influence, it was necessary to design an instrumented and adjustable experimental platform that would allow the articular efforts of the weight relief lifting and sitting pivot transfer movements to be estimated. The experimental platform that we have developed is composed of 5 adjustable modules: 2 seat modules, 2 armrest modules, and 1 footrest module. These modules are instrumented to allow the effort exerted by the subjects on their environment to be measured, while a motion capture system records the position of reflective markers positioned on the subject. The measured data, coupled with kinematic, anthropometric and dynamic models, make it possible to estimate the articular effort. The results reported in the literature confirm our results, thus validating our method and our instrumentation.

Keywords: Quantification of physiological parametes for diagnosis assessment; Rehabilitation engineering and healthcare delivery; Control of voluntary movements, respiration,

Identifier: 10.3182/20090812-3-DK-2006.00073

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Bai, Er-Wei; Cai, Zhijun

Abstract: Electrical muscle stimulation demonstrates potential for restoring functional movement and for preventing muscle atrophy after spinal cord injury (SCI). To optimize delivery of electrical stimulation protocols, an accurate and easy-to-implement mathematical skeletal muscle model is essential. The existing models are either accurate but complex, making them hard to implement, such as the Hill-Huxley-type model, or simple but inaccurate, such as second order model. In this paper, we propose a Wiener-Hammerstein system to model the paralyzed skeletal muscle dynamics under electrical stimulus conditions. The proposed model has substantial advantages in identification algorithm analysis and implementation including computational complexity and convergence. Experimental data sets were collected on soleus muscles under 15 Hz frequency stimulation for fourteen subjects with SCI. The simulation results show that the proposed model outperforms the Hill-Huxley-type model not only in peak force prediction, but also in fitting performance for force output of each individual stimulation train.

Keywords: Biomedical signal processing; Rehabilitation engineering and healthcare delivery; Neurosystems

Identifier: 10.3182/20090812-3-DK-2006.00064

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Haidegger, Tamas; Kovacs, Levente; Benyo, Balazs; Benyo, Zoltan

Abstract: Surgical robotics is one of the most dynamically developing areas of biomedical engineering. In the past few decades, Computer Integrated Interventional Medicine has gained significance internationally in the field of surgical procedures. More recently, mechatronic devices have been used for prostatectomy, neurosurgery, nephrectomy, cholecystectomy, orthopedics and radiosurgery. The paper both introduces surgical robotics and the basics of force control. It also provides a review on the different algorithms and control paradigms developed for interventional systems. The application of force sensors and force based control algorithms gives a natural extension to these systems allowing for higher quality human-machine interaction, more realistic sensory feedback and telepresence. Precise and effective control of robotic devices in a changing environment can be realized with force control. Beyond, it can apply important safety features. Different methods are presented to overcome the physical limitations of instrument sensorization, and force control algorithms tailored to medical robotic applications.

Keywords: Kinetic modelling and system control; Rehabilitation engineering and healthcare delivery; Biomedical imaging systems

Identifier: 10.3182/20090812-3-DK-2006.00070

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: None

Abstract:

Keywords:

Identifier: 10.3182/20090812-3-DK-2006.90001

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Zambrano, Darine; Garcia-Gabin, Winston; Bondia Company, Jorge; Vehi, Josep

Abstract: This paper presents a sliding mode controller for blood glucose control in critically ill patients. Most of the critically ill patients require an insulin infusion to regulate the elevated glucose levels mainly produced by counter-regulatory hormone secretion and insulin resistance. Sliding mode control can successfully handle problems with parameter uncertainties and nonlinearities. Robust differentiators have been incorporated in order to approximate the derivatives that appear in the resulting control law, and to avoid the abrupt changes in the control signal that are produced by the presence of noise and set point changes. The controller has been tested in silico with a literature model. Validation scenarios include parameter uncertainties, sensor noise and set point changes.

Keywords: Control of physiological and clinical variables,; Critical care and decision support systems; Disease control and critical care,

Identifier: 10.3182/20090812-3-DK-2006.00013

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Morain-Nicolier, Frédéric; Landré, Jérôme; Ruan, Su

Abstract: In order to evaluate performance quality of coding techniques, it is needed to have a good global index and a local index allowing the localisation of the distortions. In this study, a local dissimilarity map is presented for gray-level images. Its application to the comparison of a compressed image and its reference allows an excellent visual detection of the distortions. A global dissimilarity index is computed from the local dissimilarity map. These new measures are compared to the structural similarity index (SSIM). The results of the global measure are as good as the SSIM. The results of the local measure are quite superior to the SSIM computed in a local window. We claim these good results come from the consistency of the proposed index. It is more consistent to compute a global measure from a local one, than a local measure from a global one.

Keywords: Biomedical imaging systems

Identifier: 10.3182/20090812-3-DK-2006.00049

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Thursky, Karin; Robertson, Marion; Luu, Susan; Black, James; Richards, Michael; Buising, Kirsty

Abstract: We describe a web-based drug approval and clinical decision support system called Guidance DS. The system was developed by a multidisciplinary team of clinicians, pharmacists, software developers and epidemiologist at the Royal Melbourne Hospital (RMH). Its design was informed by contextual enquiry and formative evaluation processes. Guidance DS has role based workflows for clinicians, senior prescribers, pharmacists, administrators and auditors. Its primary use has been antimicrobial stewardship, and the system has demonstrated significant improvements in antibiotic use and antimicrobial resistance since its deployment at the RMH in 2005 and at the Peter MacCallum Cancer Centre in 2007. The technology is suited to any clinical algorithm, guideline or other class of drug that requires surveillance or monitoring.

Keywords: Disease control and critical care,

Identifier: 10.3182/20090812-3-DK-2006.00062

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: McGuinness, Ed; Ruskin, Heather J.; Crane, Martin

Abstract: As knowledge of HIV and factors governing its progression to AIDS has increased, this has driven development of mathematical models, with improved biological realism. Typically, multi-cell versions have replaced simple, initial models of single-cell ordinary differential equation (ODE) type, but at the cost of tractability. This paper shows how dimensional analysis can be used to pare models down to essential components, while retaining key functionality. Further, while the delay between a cell becoming infected and releasing replicated virus particles, has attracted little attention to date, we explicitly incorporate this into the model forms, and assess impact on disease progression.

Keywords: Kinetic modelling and system control; Functional imaging and data modelling; Cellular and molecular systems

Identifier: 10.3182/20090812-3-DK-2006.00056

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Matousek, Stanislav; Kofranek, Jiri; Rees, Stephen Edward

Abstract: Several approaches have been taken to modelling of the acid-base chemistry of blood. The Stewart approach includes three independent variables (SID, PCO2, Atot), which are postulated to completely describe causal mechanisms behind changes in acid-base status. This paper explores this postulate, simulating typical clinical examples using an online modeling tool. For changes in alveolar ventilation, production of strong acid, and selective removal of non-charged protein buffers, this postulate is true. However for non-selective protein buffer removal SID and Atot cannot be seen as independent. The paper discusses the implication of this on diagnosis of acid-base disturbances in patients with abnormal protein concentration.

Keywords: Quantification of physiological parametes for diagnosis assessment; Circulatory and respiratory systems; Control of physiological and clinical variables,

Identifier: 10.3182/20090812-3-DK-2006.00042

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Perez-Velazquez, Judith; Hattersley, John Glenn; Chappell, Michael; Bearup, Daniel; Roper, David; Dowson, Chris; Bugg, Timothy; Evans, Neil D.

Abstract: An important question in Systems Biology is the design of experiments to allow discrimination between two (or more) competing pathway models or biological mechanisms. In chemical kinetics a common assumption when studying reactions which release several products is to assume that they are all released in one step. A structural indistinguishability analysis is performed between two different models describing the kinetic mechanism of the Mur C reaction in the cytoplasmic phase of peptidoglycan biosynthesis. One model involves ordered substrate binding and ordered release of the three products; the competing model also assumes ordered substrate binding, but with fast release of the three products. The two versions are shown to be distinguishable both in the full version and under quasi-steady-state assumptions. A structural identifiability analysis is carried out for both models to ensure that the model output uniquely determines the unknown parameters. Similar analyses (indistinguishability and identifiability) are performed using other model simplifications (using conservation equations) and comparisons made with the results of the full model. The analysis forms an integrated step towards the modelling of the full pathway of the cytoplasmic phase of peptidoglycan biosynthesis.

Keywords: Kinetic modelling and system control

Identifier: 10.3182/20090812-3-DK-2006.00018

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Kovacs, Levente; Kulcsar, Balazs; Benyo, Balazs; Benyo, Zoltan

Abstract: Using induced L2-norm minimization, a robust controller was developed for insulin delivery in Type I diabetic patients. The high-complexity nonlinear diabetic patient Sorensen-model was considered and Linear Parameter Varying methodology was used to develop open loop model and robust controller. Considering the normoglycemic set point (81.1 mg/dL), a polytopic set was created over the physiologic boundaries of the glucose-insulin interaction of the Sorensen-model. In this way, Linear Parameter Varying model formalism was defined. The robust control was developed considering input and output multiplicative uncertainties with two additional uncertainties from those used in the literature: sensor noise and worst case design for meal disturbance (60 g carbohydrate).

Keywords: Control of physiological and clinical variables,; Disease control and critical care,; Kinetic modelling and system control

Identifier: 10.3182/20090812-3-DK-2006.00010

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: None

Abstract:

Keywords:

Identifier: 10.3182/20090812-3-DK-2006.90005

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009

Authors: Atari, Mohammed I.; Chappell, Michael; Errington, Rachel; Smith, Paul; Evans, Neil D.

Abstract: A compartmental model for the in vitro uptake kinetics of the anti-cancer agent topotecan (TPT) has been extended from a previously published model. The extended model describes the drug activity and delivery of the pharmacologically active form to the DNA target as well as the catalysis of the aldehyde dehydrogenase (ALDH) enzyme and the elimination of drug from the cytoplasm via the active pump. Verification of the proposed model is achieved using scanning-laser microscopy data from live human breast cancer cells. Before estimating the unknown model parameters from the collected data it is essential to determine parameter uniqueness (or otherwise) from this imposed output structure. This is formally performed as a structural identifiability analysis, which demonstrates that all of the unknown model parameters are uniquely determined by the output structure corresponding to the real experiment.

Keywords: Pharmacokinetics and drug delivery,; Kinetic modelling and system control; Control of physiological and clinical variables,

Identifier: 10.3182/20090812-3-DK-2006.00019

Conference: 7th IFAC Symposium on Modelling and Control in Biomedical Systems

Location: Hvide Hus, Denmark

Start Date: Wed Aug 12 2009 - End Date: Fri Aug 14 2009