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On the role of optimization in the cardiovascular system.

This essay discusses in a very simple manner several aspects of the meaning of optimization in general and, particularly, the role of optimization in relation to the work and action of the heart. Starting out with historical considerations the role of the properties of the heart as a pump, its relation to the arterial system, the problem of pulsatility and blood pressure and the role of time intervals and coronary perfusion is discussed. Mathematical methods permit the calculation of the time course of the cardiac ejection which, under certain constraints, minimizes the energy consumption of the heart. The saving of energy by this optimization compared with a nonoptimal ejection pattern is rather small--in the order of a few percent. It is therefore interesting and important to discuss the physiological meaning of small variations of the cost-effect function. It seems that unexplained phenomena like synchronization of heart beat and respiration have something to do with an optimization process. The most important conclusion is that any optimization has to be seen as a process related to the functioning of the organism as a whole.

Animals↗

The relationship of dispositional optimism, daily life stress, and domestic environment to coping methods used by cancer patients.

The relationship of dispositional optimism, daily life stress, and domestic environment to two types of coping methods was examined in a group of 94 cancer patients. As expected, dispositional optimism and domestic environment made significant contributions to the prediction of avoidance coping. Dispositional optimism contributed significantly to the prediction of active-behavioral coping. Specifically, a significant positive relationship was obtained between active-behavioral coping and optimism. A significant positive relationship also was found between avoidance coping and both daily stress and domestic environment. Avoidance coping was negatively related to dispositional optimism. In multivariate analyses, gender and disease-related variables did not make significant contributions to the prediction of coping method. Suggestions for future research were made.

Adaptation, Psychological↗

Do optimal dipoles obtained by the dipole tracing method always suggest true source locations?

Scalp potentials generated by a concentrated electric source in the brain are very similar to potentials generated by an electric dipole at the source position. In this sense a concentrated source in the brain is modelled as an electric dipole. When the source is diffuse such a dipole which best approximates the scalp potential is called an optimal dipole. Its position is calculated by the Dipole Tracing Method based on a realistic head model with homogeneous electric conductivity. There are 2 major difficulties inherent in this method: (1) The low electric conductivity of the skull causes systematic shifts of the optimal dipole positions from the true positions of concentrated sources; (2) the optimal dipoles cannot specify diffuse source positions. The first difficulty is overcome by using the numerical correction obtained by comparing the known dipole positions generated within a human head with their optimal ones. The second difficulty is removed to a certain extent by comparing the optimal dipole positions obtained with the 1-dipole and 2-dipole models together with their dipolarity. We have obtained criteria for the validity of the dipole approximation and source concentration.

Brain↗

Optimization of pulse train duration for the electrical stimulation of a skeletal muscle ventricle in the dog.

The optimal means of electrically stimulating a skeletal muscle to contract around a fluid-filled pouch (i.e., a skeletal muscle ventricle [SMV]) has not been determined. A SMV was made from the latissimus dorsi muscle in five dogs and the rectus abdominis muscle in five dogs, and each SMV was electrically stimulated via the motor nerve(s) to contract around a fluid-filled pouch, which was connected to a mock circulatory system. The pulse train duration (PTD) was varied from 100 ms to 800 ms in 100 ms increments to determine the effect of this variable upon SMV output. The pulse width of the electrical stimulus was kept constant at 100 microseconds and the pulse frequency was maintained at 50 s-1. For SMV contraction rates of 20, 30, and 40 min-1, the optimal PTD was 400 ms for both muscles. The peak output was 710 ml min-1 for the rectus SMV and 556 ml min-1 for the latissimus SMV. For an SMV contraction rate of 10 min-1, the optimal PTD was 800 ms for the rectus SMV and 600 ms for the latissimus SMV. Use of less than an optimal PTD caused reductions in SMV output of 25-50%. Although SMVs made from rectus abdominis and latissimus dorsi had similar values for the optimal PTD, the maximum SMV output was usually greater with the rectus abdominis in this acute study with untrained muscles. We conclude that PTD is an important variable to control, which can markedly affect results when studying the potential use of skeletal muscle power for cardiac assistance.

Animals↗

Uniqueness of optimal controllers during exercise.

The optimization hypothesis of respiratory control during exercise is based on the minimization of a function reflecting both chemical and mechanical costs. Both additive and multiplicative controllers have been derived as optimal from similar cost functions. The purpose of the present study was to explore the uniqueness of such predictions. Various formulations of controllers compatible with isocapnia were found to yield identical costs as controllers predicted to be optimal. It was concluded that controller predictions based on optimization theory are not unique. Optimization can occur with either an additive or multiplicative controller or any combination of the two which satisfies an isocapnic constraint. A general form of a combined additive-multiplicative controller was derived which was found to be compatible with previously reported experimental data collected during combined CO2 inhalation and exercise.

Exercise↗

Optimized acquisition and processing protocols for I-123 cardiac SPECT imaging.

BACKGROUND: Deconvolution of septal penetration (DSP) has been developed to improve quantification so as to allow the use of low-energy high-resolution collimators for iodine 123 cardiac single photon emission computed tomography (SPECT) imaging. The purpose of this study is to optimize its acquisition and processing protocols. METHODS AND RESULTS: Planar images of a 9-compartment phantom loaded with variable radioactive concentrations were acquired to derive optimal scatter compensation scaling factors for 20% and 15% photopeak energy window configurations, respectively. A cardiac phantom, loaded with high and low heart-to-calibration ratios (HCRs), respectively, was imaged with both configurations. Repeated acquisitions were done for medium-energy all-purpose collimators for comparison. Critical frequencies for Butterworth filtering were optimized by use of defect contrast and normal short-axis uniformity as selection indices. HCRs were calculated with planar projection and different reconstruction methods, respectively, and then compared with the true HCRs. SPECT produced more accurate HCRs than planar imaging. With the optimized parameters for scatter compensation and filtering, the 2 energy window configurations yielded similar results. Iterative reconstructions with DSP yielded more accurate HCRs than other reconstructions without DSP. CONCLUSION: The optimized protocols based on DSP show promise that quantification of I-123 cardiac SPECT imaging can be achieved with the widely available low-energy high-resolution collimators.

Algorithms↗

Optimization of nonviral transfection: variables influencing liposome-mediated gene transfer in proliferating vs. quiescent cells in culture and in vivo using a porcine restenosis model.

Cationic liposomes/DNA complexes are widely used vectors for delivering genes in clinical and experimental trials. Relatively low transfer efficiencies in vivo compared with viral gene transfer may be improved using local application. In addition, markedly increased transfer efficiency may be achieved in vitro and in vivo via optimization of known variables influencing liposomal transfection. Lipofection under different conditions was performed in various cell lines and primary porcine smooth muscle cells. Optimized conditions found in vitro were verified in vivo using a porcine restenosis model. Toxicity was monitored analyzing cell metabolism. Transfer efficiency and safety were determined using morphometry, histology, galactosidase assays, PCR, and RT-PCR. The most important variables enabling maximum transfer efficiency were firstly the appropriate selection of cationic lipids for the cell type to be transfected, secondly the DNA/liposome ratio chosen, which depended on the cell type and cationic lipids used, and thirdly the state of proliferation of the targeted cells. Transfection in vivo demonstrated two- to fivefold higher transfer efficiencies when transfer conditions were extrapolated from optimization experiments in stationary cells compared with the use of conditions established in proliferating cells. Application of the therapeutic gene for cecropin using optimized transfer conditions resulted in a significantly reduced neointima formation compared with the transfection using a control gene for ss-galactosidase. Thus, in this vascular model, initial optimization of lipofection in stationary cells in culture followed by local delivery in vivo and with selection of a suitable therapeutic gene led to markedly improved transfer efficiencies, gene expression, and biological effect. Stationary cell cultures simulate more realistically the in vivo situation and may therefore represent a better model for future in vivo experiments. In addition, the advantages of liposomes are easy handling, low toxicity, and the lack of carcinogenicity or immunogenic reactions.

Animals↗

Oxygenation index, an indicator of optimal distending pressure during high-frequency oscillatory ventilation?

OBJECTIVE: To test the hypothesis that, during high-frequency oscillatory ventilation (HFOV) of pigs with acute lung injury, the oxygenation index (OI = Paw*FIO(2)*100/PaO(2)) is minimal at the lowest continuous distending pressure (Paw), where the physiological shunt fraction is below 0.1 (Paw(optimal)). DESIGN AND SETTING: Prospective, observational study in a university research laboratory. SUBJECTS: Eight Yorkshire pigs weighing 12.0+/-0.5 kg, with lung injury induced by lung lavage. INTERVENTIONS: After initiation of HFOV, the pigs were subjected to a stepwise increase of Paw to obtain under-inflation, optimal inflation and over-distension of the lungs (inflation) in series, followed by a similar decrease of Paw (deflation). MEASUREMENTS AND RESULTS: At each Paw level, the OI and physiological shunt fraction were determined. The OI reached a minimum of 6.2+/-1.4 at Paw 30+/-4 cmH(2)O during inflation and a minimum of 2.4+/-0.3 at Paw 13+/-2 cmH(2)O during deflation. Paw(optimal) was 32+/-6 cmH(2)O on the inflation limb and 14+/-2 cmH(2)O on the deflation limb. The difference between the Paw at minimal OI and Paw(optimal) was -1.9+/-4.2 cmH(2)O (NS) during inflation and -1.5+/-1.6 cmH(2)O (p<0.05) during deflation. In 15 out of the 16 comparisons, the difference in Paw was within one step (+/-3 cmH(2)O). CONCLUSION: The minimal OI is indicative for the Paw where oxygenation is optimal during HFOV in surfactant-depleted pigs.

Animals↗

Interpretation and optimization of absorbance and fluorescence signals from voltage-sensitive dyes.

Voltage-sensitive dyes produce absorbance and fluorescence changes that can be used to image voltage. The present study develops a systematic approach to the optimization of these signals. A mathematical analysis assesses the dye optical density ( OD) that optimizes the signal-to-noise ratio in absorbance and fluorescence measurements. The signal-to-noise ratio is maximal for a dye OD of 2 (natural logarithm) in absorbance and ~1 in fluorescence. The fluorescence result is approximate because, in contrast to absorbance, the optimal dye OD varies with the amount of scattering and intrinsic absorbance of the tissue. The signal-to-noise ratio of absorbance is higher in thick preparations such as brain slices; fluorescence is superior in thin preparations such as cell culture. The optimal OD for absorbance and fluorescence, as well as the superiority of absorbance, were confirmed experimentally on hippocampal slices. This analysis also provided insight into the interpretation of signals normalized to resting light intensities. With both absorbance and fluorescence, the normalized signal (Delta I/I) varies with OD, and does not reflect the change in dye absorbance. In absorbance this problem is remedied by dividing Delta I/I by the dye OD to obtain the absorbance change. For fluorescence a correction is possible, but is more complicated. Because this analysis indicates that high levels of stain optimize the signal-to-noise, dyes were tested for pharmacological actions and phototoxicity. The absorbance dye RH155 was found to have pharmacological action at high staining levels. The fluorescent dye RH414 was phototoxic. Adverse effects could not be detected with the absorbance dye RH482.

Animals↗

Nitrogen source and mineral optimization enhance D: -xylose conversion to ethanol by the yeast Pichia stipitis NRRL Y-7124.

Nutrition-based strategies to optimize xylose to ethanol conversion by Pichia stipitis were identified in growing and stationary-phase cultures provided with a defined medium varied in nitrogen, vitamin, purine/pyrimidine, and mineral content via full or partial factorial designs. It is surprising to note that stationary-phase cultures were unable to ferment xylose (or glucose) to ethanol without the addition of a nitrogen source, such as amino acids. Ethanol accumulation increased with arginine, alanine, aspartic acid, glutamic acid, glycine, histidine, leucine, and tyrosine, but declined with isoleucine. Ethanol production from 150 g/l xylose was maximized (61+/-9 g/l) by providing C:N in the vicinity of approximately 57-126:1 and optimizing the combination of urea and amino acids to supply 40-80 % nitrogen from urea and 60-20 % from amino acids (casamino acids supplemented with tryptophan and cysteine). When either urea or amino acids were used as sole nitrogen source, ethanol accumulation dropped to 11 or 24 g/l, respectively, from the maximum of 46 g/l for the optimal nitrogen combination. The interaction of minerals with amino acids and/or urea was key to optimizing ethanol production by cells in both growing and stationary-phase cultures. In nongrowing cultures supplied with nitrogen as amino acids, ethanol concentration increased from 24 to 54 g/l with the addition of an optimized mineral supplement of Fe, Mn, Mg, Ca, Zn, and others.

Amino Acids↗

Medium optimization by combination of response surface methodology and desirability function: an application in glutamine production.

An optimization strategy based on desirability function approach (DFA) together with response surface methodology (RSM) has been used to optimize production medium in L-glutamine fermentation. Fermentation problems often force to reach a compromise between different experimental variables in order to achieve the most suitable strategy applying in industrial production. The importance of the use of multi-objective optimization methods lies in the ability to cope with this kind of problems. A sequential RSM with different combinations of glucose and (NH(4))(2)SO(4) was performed to attain the optimal medium (OM-1) in glutamine production. Based on the result of RSM and the evaluation of production cost, a more economical optimal medium (OM-2) was obtained with the aid of DFA. In DFA study, glutamate, the main by-product in glutamine fermentation as another response was considered. Compared with OM-1 in validated experiment, similar amounts of glutamine were obtained in OM-2 while the concentration of glutamate and the production cost decreased by 53.6 and 7.1%, respectively.

Biotechnology↗

Optimization of pyrene oxidation by Penicillium janthinellum using response-surface methodology.

At present, there is little information on the optimization of the degradation of polycyclic aromatic hydrocarbons (PAH) by deuteromycete filamentous fungi, a reaction catalyzed by cytochrome P450 monooxygenases. We utilized response-surface methodology to determine the optimal growth conditions for the oxidation of the PAH pyrene by Penicillium janthinellum SFU403, with respect to the variables glucose concentration, nitrate concentration and bioconversion time. Models were derived for the relationship between the variables tested and the level of the pyrene oxidation products. 1-pyrenol (1-PY) and pyrenequinones (PQ). Production of 1-PY and PQ were optimized by the same glucose and nitrate concentrations: 2.5% glucose and 1.5% sodium nitrate. The optimized 1-PY and PQ bioconversion times were 71 h and 73 h respectively. These conditions improved the yield of 1-PY by fivefold and PQ were more than 100-fold higher than the baseline levels obtained in this study. The optimized PQ yield represented 95% of the initial pyrene, thus the total optimised pyrene bioconversion to 1-PY and PQ was approximately 100%. Concentrations of glucose exceeding 4.0% repressed pyrene hydroxylation. Pyrene hydroxylation occurred almost exclusively during the deceleration phase of culture growth.

Biodegradation, Environmental↗

Optimization of the resources management in fighting wildfires.

Wildfires lead to important economic, social, and environmental losses, especially in areas of Mediterranean climate where they are of a high intensity and frequency. Over the past 30 years there has been a dramatic surge in the development and use of fire spread models. However, given the chaotic nature of environmental systems, it is very difficult to develop real-time fire-extinguishing models. This article proposes a method of optimizing the performance of wildfire fighting resources such that losses are kept to a minimum. The optimization procedure includes discrete simulation algorithms and Bayesian optimization methods for discrete and continuous problems (simulated annealing and Bayesian global optimization). Fast calculus algorithms are applied to provide optimization outcomes in short periods of time such that the predictions of the model and the real behavior of the fire, combat resources, and meteorological conditions are similar. In addition, adaptive algorithms take into account the chaotic behavior of wildfire so that the system can be updated with data corresponding to the real situation to obtain a new optimum solution. The application of this method to the Northwest Forest of Madrid (Spain) is also described. This application allowed us to check that it is a helpful tool in the decision-making process.

Climate↗

Development of an optimal pharmacokinetic sampling schedule for rubitecan administered orally in a daily times five schedule.

PURPOSE: Our aim was to develop an optimal sampling strategy for the description of the pharmacokinetics of rubitecan and its active metabolite 9-aminocamptothecin (9-AC) for use in phase II/III studies with oral rubitecan administered in a daily times five schedule. METHODS: Concentration-time data of rubitecan and 9-AC were obtained from 14 patients who had received 1.5 mg/m(2) per day rubitecan orally. Population pharmacokinetic analysis of both the parent and the metabolite was performed using the nonlinear mixed effect modelling program (NONMEM). Optimal sampling points were selected on the basis of the assessed population pharmacokinetic parameters using a D-optimality algorithm. RESULTS: The pharmacokinetics of both rubitecan and 9-AC were adequately described with a one-compartment model. The absorption rate constant, apparent volume of distribution and apparent clearance of rubitecan were 0.81 h(-1), 50 l and 1.7 l/h, respectively. For 9-AC the corresponding values of the apparent volume of distribution and the elimination rate constant were 51 l and 0.102 h(-1). Interindividual variability of the pharmacokinetic parameters ranged from 38% to 49%. For the first dose, optimal sampling points were 1, 3, 5, 8 and 24 h after dosing. Monte Carlo simulations indicated that the sampling schedule produced parameter estimates which were unbiased and precise. CONCLUSIONS: An optimal sampling schedule was derived which allowed assessment of the pharmacokinetic parameters of both the parent compound and its metabolite 9-AC after oral administration of rubitecan.

Administration, Oral↗

Mum, why do you keep on growing? Impacts of environmental variability on optimal growth and reproduction allocation strategies of annual plants.

In their 1990 paper Optimal reproductive efforts and the timing of reproduction of annual plants in randomly varying environments, Amir and Cohen considered stochastic environments consisting of i.i.d. sequences in an optimal allocation discrete-time model. We suppose here that the sequence of environmental factors is more generally described by a Markov chain. Moreover, we discuss the connection between the time interval of the discrete-time dynamic model and the ability of the plant to rebuild completely its vegetative body (from reserves). We formulate a stochastic optimization problem covering the so-called linear and logarithmic fitness (corresponding to variation within and between years), which yields optimal strategies. For "linear maximizers'', we analyse how optimal strategies depend upon the environmental variability type: constant, random stationary, random i.i.d., random monotonous. We provide general patterns in terms of targets and thresholds, including both determinate and indeterminate growth. We also provide a partial result on the comparison between ;"linear maximizers'' and "log maximizers''. Numerical simulations are provided, allowing to give a hint at the effect of different mathematical assumptions.

Algorithms↗

MR imaging of the ankle at 3 Tesla and 1.5 Tesla: protocol optimization and application to cartilage, ligament and tendon pathology in cadaver specimens.

The objective of this study was to optimize ankle joint MR imaging in volunteers at 1.5 Tesla (T) and 3.0 T, and to compare these optimized sequences concerning image quality and performance in assessing cartilage, ligament and tendon pathology in fresh human cadaver specimens. Initially our clinical ankle protocol consisting of T1-weighted (-w), fat-saturated (fs) T2-w, and short tau inversion-recovery fast spinecho (FSE) sequences was optimized at 1.5 T and 3.0 T by two radiologists. For dedicated cartilage imaging, fs-intermediate (IM)-w FSE, fs spoiled gradient echo, and balanced free-precession steady-state sequences were optimized. Using the optimized sequences, thirteen cadaver ankle joints were imaged. Four radiologists independently assessed these images concerning image quality and pathology. All radiologists consistently rated image quality higher at 3.0 T (all sequences p<0.05). For detecting cartilage pathology, diagnostic performance was significantly higher at 3.0 T (ROC-values up to 0.93 vs. 0.77; p<0.05); the fs-IM FSE sequence showed highest values among the different sequences. Average sensitivity for detecting tendon pathology was 63% at 3.0 T vs. 41% at 1.5 T and was significantly higher at 3.0 T for 2 out of 4 radiologists (p<0.05). Compared to 1.5 T, imaging of the ankle joint at 3.0 T significantly improved image quality and diagnostic performance in assessing cartilage pathology.

Aged↗

Estimation of optimal feeding strategies for fed-batch bioprocesses.

A generic methodology for feeding strategy optimization is presented. This approach uses a genetic algorithm to search for optimal feeding profiles represented by means of artificial neural networks (ANN). Exemplified on a fed-batch hybridoma cell cultivation, the approach has proven to be able to cope with complex optimization tasks handling intricate constraints and objective functions. Furthermore, the performance of the method is compared with other previously reported standard techniques like: (1) optimal control theory, (2) first order conjugate gradient, (3) dynamical programming, (4) extended evolutionary strategies. The methodology presents no restrictions concerning the number or complexity of the state variables and therefore constitutes a remarkable alternative for process development and optimization.

Algorithms↗

Structure-property relationships in the optimization of polysilicon thin films for electrical recording/stimulation of single neurons.

We had earlier demonstrated the use of polysilicon microelectrodes for recording electrical activity from single neurons in vivo. Good machinability and compatibility with CMOS processing further make polysilicon an attractive interface material between biological environments on one hand and MEMS technology and digital circuits on the other hand. In this study, we focus on optimizing the polysilicon thin films for (a) electrical recording and (b) stimulation of single neurons by minimizing its electrochemical impedance spectra and maximizing its charge storage/injection capacity respectively. The structure-property relationships in ion-implanted (phosphorus) LPCVD polysilicon thin films under different annealing and doping conditions were carefully assessed during this optimization process. A 2D model of the polysilicon thin film consisting of 4 grains and 3 grain boundaries was constructed and the effect of grain size and grain boundaries on dc resistivity was simulated using device simulator ATLAS. Optimal processing conditions and doping concentrations resulted in a 10-fold decrease in electrochemical impedance from 1.1 kOmega to 0.1 kOmega at 1 kHz (area of polysilicon interface = 4.8 mm(2)). Subsequent characterizations showed that evolution of secondary grains within the polysilicon thin films at optimal doping and annealing conditions (10(21)/cm(3) of phosphorus and annealed at 1200 degrees C) was responsible for decreasing the impedance. Cyclic voltammetry studies demonstrated that charge storage properties of low doped (10(15)/cm(3)) thin films was 111.4 microC/cm(2) in phosphate buffered saline which compares well with platinum wires (approximately 50 microC/cm(2)) and the double-layered capacitance (C(dl)) could be sustained between -1 to 1 V before breakdown and hydrolysis. We conclude that polysilicon can be optimized for recording and stimulating single neurons and can be a valuable interface material between neurons and CMOS or MEMS devices.

Action Potentials↗