A comparative evaluation of open loop and closed loop drug administration strategies in the treatment of AIDS.

In recent years, many researchers in the field of biomedical sciences have made successful use of mathematical models to study, in a quantitative way, a multitude of phenomena such as those found in disease dynamics, control of physiological systems, optimization of drug therapy, economics of the preventive medicine and many other applications. The availability of good dynamic models have been providing means for simulation and design of novel control strategies in the context of biological events. This work concerns a particular model related to HIV infection dynamics which is used to allow a comparative evaluation of schemes for treatment of AIDS patients. The mathematical model adopted in this work was proposed by Nowak & Bangham, 1996 and describes the dynamics of viral concentration in terms of interaction with CD4 cells and the cytotoxic T lymphocytes, which are responsible for the defense of the organism. Two conceptually distinct techniques for drug therapy are analyzed: Open Loop Treatment, where a priori fixed dosage is prescribed and Closed Loop Treatment, where the doses are adjusted according to results obtained by laboratory analysis. Simulation results show that the Closed Loop Scheme can achieve improved quality of the treatment in terms of reduction in the viral load and quantity of administered drugs, but with the inconvenience related to the necessity of frequent and periodic laboratory analysis.

Efficiency: a key ingredient towards sustainable supply chains

This edition of the FAL Bulletin aims to help industry and policy makers see and embrace the direct link between sustainability and efficiency, so that action to make supply chains and businesses more efficient and sustainable can be taken.

“Eco-innovations in more sustainable supply chains for a low-carbon economy: A multiple case study of human critical success factors in Brazilian leading companies”

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Extending lean manufacturing in supply chains: a successful case in Brazil

Purpose – The purpose of this paper is to present the results of a success story involving the extending of lean manufacturing practices between a focal firm and its supplier, both located in Brazil, thereby configuring a case of excellence. Design/methodology/approach – An in-depth case study was conducted involving two companies: Company A, focal, leader in its segment, located in Brazil; and Company B, Company A's supplier, also located in Brazil. Findings – Results indicate there are several mechanisms for extending lean manufacturing practices in the supply chain, such as workshops, training, and integrated teams. These mechanisms are shown and guidelines are also introduced for companies seeking to successfully extend lean manufacturing practices. Originality/value – An original use of define, measure, analyze, improve, control for structuring the extending of lean manufacturing practices to suppliers and, consequently, the importance of the lean six-sigma relationship in this context. Furthermore, the guidelines introduced serve as a benchmark for other companies interested in the topic.

Closed-loop stable model predictive control of integrating systems with dead time

Model predictive control (MPC) applications in the process industry usually deal with process systems that show time delays (dead times) between the system inputs and outputs. Also, in many industrial applications of MPC, integrating outputs resulting from liquid level control or recycle streams need to be considered as controlled outputs. Conventional MPC packages can be applied to time-delay systems but stability of the closed loop system will depend on the tuning parameters of the controller and cannot be guaranteed even in the nominal case. In this work, a state space model based on the analytical step response model is extended to the case of integrating time systems with time delays. This model is applied to the development of two versions of a nominally stable MPC, which is designed to the practical scenario in which one has targets for some of the inputs and/or outputs that may be unreachable and zone control (or interval tracking) for the remaining outputs. The controller is tested through simulation of a multivariable industrial reactor system. (C) 2012 Elsevier Ltd. All rights reserved.

Closed-loop investigation of the dynamical properties of cardiomyocyte electrophysiology by means of Dynamic clamp and Mathematical modelling

The research field of my PhD concerns mathematical modeling and numerical simulation, applied to the cardiac electrophysiology analysis at a single cell level. This is possible thanks to the development of mathematical descriptions of single cellular components, ionic channels, pumps, exchangers and subcellular compartments. Due to the difficulties of vivo experiments on human cells, most of the measurements are acquired in vitro using animal models (e.g. guinea pig, dog, rabbit). Moreover, to study the cardiac action potential and all its features, it is necessary to acquire more specific knowledge about single ionic currents that contribute to the cardiac activity. Electrophysiological models of the heart have become very accurate in recent years giving rise to extremely complicated systems of differential equations. Although describing the behavior of cardiac cells quite well, the models are computationally demanding for numerical simulations and are very difficult to analyze from a mathematical (dynamical-systems) viewpoint. Simplified mathematical models that capture the underlying dynamics to a certain extent are therefore frequently used. The results presented in this thesis have confirmed that a close integration of computational modeling and experimental recordings in real myocytes, as performed by dynamic clamp, is a useful tool in enhancing our understanding of various components of normal cardiac electrophysiology, but also arrhythmogenic mechanisms in a pathological condition, especially when fully integrated with experimental data.

High-quality lung fixation by controlled closed loop perfusion for stereological analysis in a large animal model

Stereology is an essential method for quantitative analysis of lung structure. Adequate fixation is a prerequisite for stereological analysis to avoid bias in pulmonary tissue, dimensions and structural details. We present a technique for in situ fixation of large animal lungs for stereological analysis, based on closed loop perfusion fixation.

Closed-loop control of mean arterial blood pressure during surgery with alfentanil: clinical evaluation of a novel model-based predictive controller

BACKGROUND: In contrast to hypnosis, there is no surrogate parameter for analgesia in anesthetized patients. Opioids are titrated to suppress blood pressure response to noxious stimulation. The authors evaluated a novel model predictive controller for closed-loop administration of alfentanil using mean arterial blood pressure and predicted plasma alfentanil concentration (Cp Alf) as input parameters. METHODS: The authors studied 13 healthy patients scheduled to undergo minor lumbar and cervical spine surgery. After induction with propofol, alfentanil, and mivacurium and tracheal intubation, isoflurane was titrated to maintain the Bispectral Index at 55 (+/- 5), and the alfentanil administration was switched from manual to closed-loop control. The controller adjusted the alfentanil infusion rate to maintain the mean arterial blood pressure near the set-point (70 mmHg) while minimizing the Cp Alf toward the set-point plasma alfentanil concentration (Cp Alfref) (100 ng/ml). RESULTS: Two patients were excluded because of loss of arterial pressure signal and protocol violation. The alfentanil infusion was closed-loop controlled for a mean (SD) of 98.9 (1.5)% of presurgery time and 95.5 (4.3)% of surgery time. The mean (SD) end-tidal isoflurane concentrations were 0.78 (0.1) and 0.86 (0.1) vol%, the Cp Alf values were 122 (35) and 181 (58) ng/ml, and the Bispectral Index values were 51 (9) and 52 (4) before surgery and during surgery, respectively. The mean (SD) absolute deviations of mean arterial blood pressure were 7.6 (2.6) and 10.0 (4.2) mmHg (P = 0.262), and the median performance error, median absolute performance error, and wobble were 4.2 (6.2) and 8.8 (9.4)% (P = 0.002), 7.9 (3.8) and 11.8 (6.3)% (P = 0.129), and 14.5 (8.4) and 5.7 (1.2)% (P = 0.002) before surgery and during surgery, respectively. A post hoc simulation showed that the Cp Alfref decreased the predicted Cp Alf compared with mean arterial blood pressure alone. CONCLUSION: The authors' controller has a similar set-point precision as previous hypnotic controllers and provides adequate alfentanil dosing during surgery. It may help to standardize opioid dosing in research and may be a further step toward a multiple input-multiple output controller.

Real-time closed-loop electrophysiology: towards new frontiers in in vitro investigations in the neurosciences

Reflected at any level of organization of the central nervous system, most of the processes ranging from ion channels to neuronal networks occur in a closed loop, where the input to the system depends on its output. In contrast, most in vitro preparations and experimental protocols operate autonomously, and do not depend on the output of the studied system. Thanks to the progress in digital signal processing and real-time computing, it is now possible to artificially close the loop and investigate biophysical processes and mechanisms under increased realism. In this contribution, we review some of the most relevant examples of a new trend in in vitro electrophysiology, ranging from the use of dynamic-clamp to multi-electrode distributed feedback stimulation. We are convinced these represents the beginning of new frontiers for the in vitro investigation of the brain, promising to open the still existing borders between theoretical and experimental approaches while taking advantage of cutting edge technologies.

Use of a computerized closed-loop sodium nitroprusside titration system for antihypertensive treatment after open heart surgery

This study evaluates the clinical applicability of administering sodium nitroprusside by a closed-loop titration system compared with a manually adjusted system. The mean arterial pressure (MAP) was registered every 10 and 30 sec during the first 150 min after open heart surgery in 20 patients (group 1: computer regulation) and in ten patients (group 2: manual regulation). The results (16,343 and 2,912 data points in groups 1 and 2, respectively), were then analyzed in four time frames and five pressure ranges to indicate clinical efficacy. Sixty percent of the measured MAP in both groups was within the desired +/- 10% during the first 10 min. Thereafter until the end of observation, the MAP was maintained within +/- 10% of the desired set-point 90% of the time in group 1 vs. 60% of the time in group 2. One percent and 11% of data points were +/- 20% from the set-point in groups 1 and 2, respectively (p less than .05, chi-square test). The computer-assisted therapy provided better control of MAP, was safe to use, and helped to reduce nursing demands.