Biomedical subjects

Manfred Morari

Publications and source records attributed to Manfred Morari.

6 recordsLinked to original sources

PubMed2006

The well-being model: a new drug interaction model for positive and negative effects.

BACKGROUND: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account. METHODS: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs. RESULTS: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed. CONCLUSIONS: The model is consistent with clinical knowledge and supports previously published experimental results on optimal drug combinations. This new framework improves understanding of the characteristics of drug combinations used in clinical practice and can be used in clinical research to identify optimal drug dosing.

Drug Interactions↗

PubMed2005

Optimizing control of simulated moving beds--experimental implementation.

The operation of simulated moving beds (SMBs) at their optimal operating conditions is difficult and not robust. Therefore, it is common practice to operate SMB units far from their economic optimum in order to tolerate uncertainties in the system and minimize the effect of disturbances. Recently, we have proposed an on-line optimization based SMB control scheme that allows to exploit the full economic potential of SMB technology. The goal of this work is two-fold. Firstly, to experimentally evaluate and demonstrate the capability of the controller to optimize and operate the SMB units, thus delivering the products with maximum productivity and minimum solvent consumption. Secondly, to show the suitability of the controller even using a minimum of system information, thus making the detailed isotherm measurements redundant and saving time in the separation design phase. This paper reports and discusses the first experimental implementation of the control concept on a high purity separation of nucleosides (uridine, guanosine) with an eight-column four-section SMB where the species to be separated are retained on the source 30RPC stationary phase according to a linear isotherm.

Chromatography, Liquid↗

PubMed2005

Energy-optimal electrical excitation of nerve fibers.

We derive, based on an analytical nerve membrane model and optimal control theory of dynamical systems, an energy-optimal stimulation current waveform for electrical excitation of nerve fibers. Optimal stimulation waveforms for nonleaky and leaky membranes are calculated. The case with a leaky membrane is a realistic case. Finally, we compare the waveforms and energies necessary for excitation of a leaky membrane in the case where the stimulation waveform is a square-wave current pulse, and in the case of energy-optimal stimulation. The optimal stimulation waveform is an exponentially rising waveform and necessitates considerably less energy to excite the nerve than a square-wave pulse (especially true for larger pulse durations). The described theoretical results can lead to drastically increased battery lifetime and/or decreased energy transmission requirements for implanted biomedical systems.

Action Potentials↗

PubMed2004

Optimizing control of simulated moving beds--linear isotherm.

A new optimization based adaptive control strategy for simulated moving beds (SMBs) is proposed. A linearized reduced order model, which accounts for the periodic nature of the SMB process, is used for online optimization and control. The manipulated variables are the four inlet flow rates, the outputs are the raffinate and extract concentrations. Concentration measurements at the raffinate and extract outlets are used as the feedback information. The state estimate from the periodic Kalman filter is used for the prediction of the outlet concentrations over a chosen horizon. Predicted outlet concentrations are the basis for the calculation of the optimal input adjustments, which maximize the productivity and minimize the desorbent consumption subject to constraints on product purities. The realization of this concept is discussed and the implementation on a virtual eight column SMB platform is assessed, in the case of binary linear systems. For a whole series of typical plant disturbances it is shown that the proposed approach is effective in minimizing off-spec products and in achieving optimal SMB operation, also in the case where there are significant model uncertainties.

Models, Theoretical↗

PubMed2002

A new paradigm for the closed-loop intraoperative administration of analgesics in humans.

We present a new paradigm for the closed-loop administration of analgesics during general anesthesia. The manipulated variable in the control system is the infusion rate of the opiate alfentanil, administered intravenously through a computer-controlled infusion pump (CCIP). The outputs to be controlled are the patient's mean arterial pressure (MAP) and the drug concentration in the plasma. Maintaining MAP within appropriate ranges provides optimal treatment of the patient's reactions to surgical stimuli. Maintaining plasma drug concentrations close to a reference value specified by the anesthesiologist allows to titrate analgesic administration to qualitative clinical end-points of insufficient analgesia. MAP is acquired invasively through a catheter cannula. Since plasma drug concentrations cannot be measured on-line, they are estimated via a pharmacokinetic model. We describe an explicit model-predictive controller which achieves the above-mentioned objectives. An upper constraint on drug concentrations is maintained to avoid overdosing. Constraints on the MAP are introduced to trigger a prompt controller reaction during hypertensive and hypotensive periods. Measurement artifacts in the MAP signal are rejected to prevent harmful misbehavior of the controller. We discuss the results of the clinical validation of the controller on humans.

Alfentanil↗

PubMed1999

Identification of low order manifolds: Validating the algorithm of Maas and Pope.

The algorithm of Maas and Pope (1992) is presented as a method for identification of invariant reduced-order manifolds for stable systems which exhibit dynamics with a time-scale separation. While this method has been published previously in the literature, theoretical justification for the algorithm was not presented in the original work. Here, it will be shown rigorously that the algorithm correctly identifies the slow manifold. Before the theoretical results are presented, a brief background on the behavior of singularly perturbed systems is presented. The algorithm of Maas and Pope (1992) is then introduced. This method will be applied to two different examples, a distillation column and a two-phase chemical reactor. For each of these examples, the resulting reduced-order description will be compared to other standard methods of producing reduced-order models. In addition, some preliminary thoughts on how this method can be used to form reduced-order models are presented. (c) 1999 American Institute of Physics.

Journal Article↗