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Optimization of the granulation process for designing tablets.

A computer optimization technique based on surface response methodology was applied to optimize the wet granulation process for designing tablets. Physical properties (mean granule size, granule size distribution, compressibility, granule strength) of a model granule formulation containing ethenzamide were accurately described by a second polynomial equation based on two independent variables (amounts of binder and binder solution). This regression equation also gave a good correlation for three physical properties of tablets (distintegration time, compactibility, compression force variance), but the correlation for tablet hardness and weight variation was poor. These results imply that not only the above physical properties of granules but also the rheological behavior and porous structure of granules are closely related to tablet properties. Using an optimization of five tablet properties using the generalized distance function, the predicted values of the physical properties of both granules and tablets agreed well with experimental values. This agreement indicates that the computer optimization technique is useful for optimizing the granulation process for designing tablets.

Computers↗

Constrained optimization of L-lysine production based on metabolic flux using a mathematical programming method.

Constrained optimization for microbial fermentation was studied. For optimization, we used not the maximum principle but a nonlinear programming method because of the need to consider many metabolic reactions. In the case of L-lysine fermentation, the optimization problem in L-lysine production was formulated as a nonlinear programming problem. In general, the state equations based on material balances are represented as differential equations, but such equations which are dependent on time can not be applied to a nonlinear programming problem. Therefore, the state equations were made discrete in a time base, and a new single vector which is not dependent on time was substituted. From these formulae, the objective function and the constraints using nonlinear programming problem were defined as the amount of L-lysine produced, and as a metabolic reaction model and empirical equations, respectively. Computer program was developed to solve this constrained nonlinear programming problem. The applied algorithm of the computer programming was a sequential quadratic programming method (SQP method). When the constrained nonlinear programming problem is solved using the SQP method, the maximum amount of L-lysine produced and the optimal feeding rate of L-threonine could be calculated. From the calculated results, it was clear that introduction of the equality and inequality constraints was easy. L-Lysine at a concentration up to 75.3 g/l could be produced when the fermentation was carried out under optimal conditions.

Journal Article↗

Optimism, hostility, and adjustment in the first year of high school.

BACKGROUND: The period of transition to high school is marked by large variations in student adjustment patterns. Many students make successful adjustments but others do not and are at risk of developing hostile attitudes towards their school environment. AIMS: This study sought to investigate the role of optimism and pessimism in predicting the extent of hostility students express towards school. SAMPLE: The sample consisted of 102 students who completed questionnaires at the beginning of the school year, and also in the last term of their first year at high school. METHODS: Students responded to questionnaires assessing their levels of (a) dispositional optimism and pessimism, (b) personal expectancies for the occurrence of specific negative events, and (c) depression and anxiety. Additional data concerning hostility to school, perceived classroom involvement, and student adjustment (self-reported and teacher-reported) to school measures were collected at the end of the year. RESULTS: In general, the girls reported greater levels of positive adjustment than boys. It was found that optimism together with expectations of negative events accounted for 21% of the variance in school hostility. In addition, optimism was significantly related to classroom involvement and to students' self-reported adjustment. Teachers' ratings of student adjustment were related only to gender. Only 15 (12 male, 3 female) of the 102 students were clearly hostile towards the school. CONCLUSIONS: We conclude that young people are vulnerable to adjustment problems when levels of dispositional optimism are not sufficiently strong to counteract high expectations about the possibility of specific negative events occurring.

Adaptation, Psychological↗

Optimism, coping style and emotional well-being in cardiac patients.

OBJECTIVE: Optimism is associated with superior emotional well-being in people with chronic and acute health problems, possibly because optimists are more likely to implement problem-focused coping. Another interpretation posits that optimism can be a defensive response designed to diminish affective reactions to health problems. The study objective is to investigate this possibility. DESIGN: A cross-sectional examination of relationships between dispositional and relative optimism, threat avoidance and emotional well-being in 85 cardiac patients. RESULTS: Blunting, a measure of threat avoidance, was found to be associated with both optimism and emotional well-being, and the common variance was predictive of positive affect. As expected, this link was stronger in people with low self-efficacy for problem-focused coping. CONCLUSION: These findings support a defensive interpretation of optimism amongst patients with recently-experienced cardiac disease, particularly as the effect was more pronounced in the low self-efficacy subsample. We discuss possible explanations for these findings and implications for the study of coping with serious illness.

Adaptation, Psychological↗

Optimization of a semianalytical ocean color model for global-scale applications.

Semianalytical (SA) ocean color models have advantages over conventional band ratio algorithms in that multiple ocean properties can be retrieved simultaneously from a single water-leaving radiance spectrum. However, the complexity of SA models has stalled their development, and operational implementation as optimal SA parameter values are hard to determine because of limitations in development data sets and the lack of robust tuning procedures. We present a procedure for optimizing SA ocean color models for global applications. The SA model to be optimized retrieves simultaneous estimates for chlorophyll (Chl) concentration, the absorption coefficient for dissolved and detrital materials [a(cdm)(443)], and the particulate backscatter coefficient [b(bp)(443)] from measurements of the normalized water-leaving radiance spectrum. Parameters for the model are tuned by simulated annealing as the global optimization protocol. We first evaluate the robustness of the tuning method using synthetic data sets, and we then apply the tuning procedure to an in situ data set. With the tuned SA parameters, the accuracy of retrievals found with the globally optimized model (the Garver-Siegel-Maritorena model version 1; hereafter GSM01) is excellent and results are comparable with the current Sea-viewing Wide Field-of-view sensor (SeaWiFS) algorithm for Chl. The advantage of the GSM01 model is that simultaneous retrievals of a(cdm)(443) and b(bp)(443) are made that greatly extend the nature of global applications that can be explored. Current limitations and further developments of the model are discussed.

Journal Article↗

Multireference binary phase-only filter optimized by regions of support.

A new formulation of a multiplex filter for filtering-based optical processors, based on the VanderLugt architecture, is presented. The multireference binary phase-only filter (MBPOF), optimized by regions of support (ROS), constitutes a formal rewriting of some multiplex or composite filters including optimization functions, such as the distribution function and the selection function. The first function optimizes the multiplexing of references into the multireference filter. The second function defines the ROS of an object's Fourier spectrum and can be independently used to optimize the conventional binary phase-only filter. Both functions result from a segmentation of the Fourier plane. The MBPOF with ROS can be optically implemented in a filtering-based optical processor owing to a binary-phase spatial light modulator. Simulation and optical results are given for different examples of the BPOF and the MBPOF, both with ROS optimizing different criteria of performance, such as peak-to-correlation energy, discrimination capability, and distortion sensitivity.

Journal Article↗

Design of short fiber Bragg gratings by use of optimization.

We demonstrate an optimization approach for designing fiber Bragg gratings. A layer-peeling inverse-scattering algorithm is used to produce an initial solution, which is optimized numerically with an iterative optimization method. To avoid problems with local minima, we use merit functions that are zero for wavelengths for which the predefined demands (acceptance limits) are fulfilled, making it possible to alter the local minima under the optimization process without disturbing the global minimum. Because short gratings are difficult to design with inverse scattering, and because the time consume of the optimization increases rapidly with the grating length, the method is particularly useful for designing short gratings. The method is also useful when the demands are complex and difficult to handle with inverse-scattering methods. Design examples are given, including a dispersionless bandpass filter suitable for dense wavelength-division multiplexing and a filter with linear reflectivity.

Journal Article↗

Zone-boundary optimization for direct laser writing of continuous-relief diffractive optical elements.

Enhancing the diffraction efficiency of continuous-relief diffractive optical elements fabricated by direct laser writing is discussed. A new method of zone-boundary optimization is proposed to correct exposure data only in narrow areas along the boundaries of diffractive zones. The optimization decreases the loss of diffraction efficiency related to convolution of a desired phase profile with a writing-beam intensity distribution. A simplified stepped transition function that describes optimized exposure data near zone boundaries can be made universal for a wide range of zone periods. The approach permits a similar increase in the diffraction efficiency as an individual-pixel optimization but with fewer computation efforts. Computer simulations demonstrated that the zone-boundary optimization for a 6 microm period grating increases the efficiency by 7% and 14.5% for 0.6 microm and 1.65 microm writing-spot diameters, respectively. The diffraction efficiency of as much as 65%-90% for 4-10 microm zone periods was obtained experimentally with this method.

Journal Article↗

Ethyl alcohol production optimization by coupling genetic algorithm and multilayer perceptron neural network.

In this present article, genetic algorithms and multilayer perceptron neural network (MLPNN) have been integrated in order to reduce the complexity of an optimization problem. A data-driven identification method based on MLPNN and optimal design of experiments is described in detail. The nonlinear model of an extractive ethanol process, represented by a MLPNN, is optimized using real-coded and binary-coded genetic algorithms to determine the optimal operational conditions. In order to check the validity of the computational modeling, the results were compared with the optimization of a deterministic model, whose kinetic parameters were experimentally determined as functions of the temperature.

Algorithms↗

Sequential and simultaneous statistical optimization by dynamic design of experiment for peptide overexpression in recombinant Escherichia coli.

The production of recombinant anti-HIV peptide, T-20, in Escherichia coli was optimized by statistical experimental designs (successive designs with multifactors) such as 2(4-1) fractional factorial, 2(3) full factorial, and 2(2) rotational central composite design in order. The effects of media compositions (glucose, NPK sources, MgSO4, and trace elements), induction level, induction timing (optical density at induction process), and induction duration (culture time after induction) on T-20 production were studied by using a statistical response surface method. A series of iterative experimental designs was employed to determine optimal fermentation conditions (media and process factors). Optimal ranges characterized by %T-20 (proportion of peptide to the total cell protein) were observed, narrowed down, and further investigated to determine the optimal combination of culture conditions, which was as follows: 9, 6, 10, and 1 mL of glucose, NPK sources, MgSO4, and trace elements, respectively, in a total of 100 mL of medium inducted at an OD of 0.55-0.75 with 0.7 mM isopropyl-beta-D-thiogalactopyranoside in an induction duration of 4 h. Under these conditions, up to 14% of T-20 was obtained. This statistical optimization allowed the production of T-20 to be increased more than twofold (from 6 to 14%) within a shorter induction duration (from 6 to 4 h) at the shake-flask scale.

Anti-HIV Agents↗

Optimization of a stochastically simulated gene network model via simulated annealing.

By rearranging naturally occurring genetic components, gene networks can be created that display novel functions. When designing these networks, the kinetic parameters describing DNA/protein binding are of great importance, as these parameters strongly influence the behavior of the resulting gene network. This article presents an optimization method based on simulated annealing to locate combinations of kinetic parameters that produce a desired behavior in a genetic network. Since gene expression is an inherently stochastic process, the simulation component of simulated annealing optimization is conducted using an accurate multiscale simulation algorithm to calculate an ensemble of network trajectories at each iteration of the simulated annealing algorithm. Using the three-gene repressilator of Elowitz and Leibler as an example, we show that gene network optimizations can be conducted using a mechanistically realistic model integrated stochastically. The repressilator is optimized to give oscillations of an arbitrary specified period. These optimized designs may then provide a starting-point for the selection of genetic components needed to realize an in vivo system.

Algorithms↗

Short and long period optimization of drug doses in the treatment of AIDS.

Numerical optimization techniques are useful in solving problems of computing the best inputs for systems described by mathematical models and when the objectives can be stated in a quantitative form. This work concerns the problem of optimizing the drug doses in the treatment of AIDS in terms of achieving a balance between the therapeutic response and the side effects. A mathematical model describing the dynamics of HIV viruses and CD4 cells is used to compute the short term optimal drug doses in the treatments of patients with AIDS by a direct method of optimization using a cost function of Bolza type. The model parameters were fitted to actual published clinical data. In order to simplify the numerical procedures, the control law is expressed as a series and the sub-optimal control is obtained by truncating the higher terms. When the patient reaches a clinically satisfactory state, the LQR - Linear Quadratic Regulator technique is used to determine the long period maintenance doses for the drugs. The doses computed using the LQR technique tend to be smaller than equivalent constant-dose therapy in terms of increase in the counts of CD4+T cells and reduction of the density of free viruses.

Acquired Immunodeficiency Syndrome↗

A comparative analysis of primary stenting and optimal balloon coronary angioplasty in acute myocardial infarction. Six month results from the STENT PAMI trial.

OBJECTIVE: To compare the outcome of balloon PTCA with final coronary stenosis diameter (SD) < or =30 %, with elective coronary stenting. METHODS: We performed a comparative analysis of the 6 month outcomes in patients treated with primary stenting and those who obtained an optimal balloon PTCA result treated during the first 12 hours of AMI onset included in the STENT PAMI randomized trial. RESULTS: The results were analysed into 3 groups: primary stenting (441 patients, SD=22+/-6 %), optimal PTCA (245 patients), and non-optimal PTCA (182 patients, SD= 37+/-5 %). At the end of the 6 months primary stent group presented with the lowest restenosis(23 vs. 31 vs. 45 %, p=0.001, respectively). Ischemia-driven target vessel revascularization rate (TVR) (7 vs. 15.5 vs. 19 %, p=0.001, respectively). CONCLUSION: At the 6 month follow-up, primary stenting offered the lowest restenosis and ischemia-driven TVR rates. Compared to optimal balloon PTCA. Non-optimal primary balloon PTCA pts (SD=31-50 %), had the worst late angiographic outcomes and should be treated more actively with coronary stent implantation.

Angioplasty, Balloon, Coronary↗

Shape optimization of plate with static and dynamic constraints via virtual laminated element.

The virtual laminated element method (VLEM) can resolve structural shape optimization problems with a new method. According to the characteristics of VLEM, only some characterised layer thickness values need be defined as design variables instead of boundary node coordinates or some other parameters determining the system boundary. One of the important features of this method is that it is not necessary to regenerate the FE(finite element) grid during the optimization process so as to avoid optimization failures resulting from some distortion grid elements. The thickness distribution in thin plate optimization problems in other studies before is of stepped shape. However, in this paper, a continuous thickness distribution can be obtained after optimization using VLEM, and is more reasonable. Furthermore, an approximate reanalysis method named "behavior model technique" can be used to reduce the amount of structural reanalysis. Some typical examples are offered to prove the effectiveness and practicality of the proposed method.

Computer Simulation↗

Optimization of block-floating-point realizations for digital controllers with finite-word-length considerations.

The closed-loop stability issue of finite-precision realizations was investigated for digital controllers implemented in block-floating-point format. The controller coefficient perturbation was analyzed resulting from using finite word length (FWL) block-floating-point representation scheme. A block-floating-point FWL closed-loop stability measure was derived which considers both the dynamic range and precision. To facilitate the design of optimal finite-precision controller realizations, a computationally tractable block-floating-point FWL closed-loop stability measure was then introduced and the method of computing the value of this measure for a given controller realization was developed. The optimal controller realization is defined as the solution that maximizes the corresponding measure, and a numerical optimization approach was adopted to solve the resulting optimal realization problem. A numerical example was used to illustrate the design procedure and to compare the optimal controller realization with the initial realization.

Analog-Digital Conversion↗

On stochastic optimal control of partially observable nonlinear quasi Hamiltonian systems.

A stochastic optimal control strategy for partially observable nonlinear quasi Hamiltonian systems is proposed. The optimal control forces consist of two parts. The first part is determined by the conditions under which the stochastic optimal control problem of a partially observable nonlinear system is converted into that of a completely observable linear system. The second part is determined by solving the dynamical programming equation derived by applying the stochastic averaging method and stochastic dynamical programming principle to the completely observable linear control system. The response of the optimally controlled quasi Hamiltonian system is predicted by solving the averaged Fokker-Planck-Kolmogorov equation associated with the optimally controlled completely observable linear system and solving the Riccati equation for the estimated error of system states. An example is given to illustrate the procedure and effectiveness of the proposed control strategy.

Algorithms↗

Initial results of the use of prescription order change forms to achieve dose form optimization (consolidation and tablet splitting) of SSRI antidepressants in a state Medicaid program.

BACKGROUND: One method to reduce drug costs is to promote dose form optimization strategies that take advantage of the flat pricing of some drugs, i.e., the same or nearly the same price for a 100 mg tablet and a 50 mg tablet of the same drug. Dose form optimization includes tablet splitting; taking half of a higher-strength tablet; and dose form consolidation, using 1 higher-strength tablet instead of 2 lower-strength tablets. Dose form optimization can reduce the direct cost of therapy by up to 50% while continuing the same daily dose of the same drug molecule. OBJECTIVE: To determine if voluntary prescription change forms for antidepressant drugs could induce dosing changes and reduce the cost of antidepressant therapy in a Medicaid population. METHODS: Specific regimens of 4 selective serotonin reuptake inhibitors (SSRIs)- citalopram, escitalopram, paroxetine, and sertraline- were identified for conversion to half tablets or dose optimization. Change forms, which served as valid prescriptions, were faxed to Oregon prescribers in October 2004. The results from both the returned forms and subsequent drug claims data were evaluated using a segmented linear regression. Citalopram claims were excluded from the cost analysis because the drug became available in generic form in October 2004. RESULTS: A total of 1,582 change forms were sent to 556 unique prescribers; 9.2% of the change forms were for dose consolidation and 90.8% were for tablet splitting. Of the 1,118 change forms (70.7%) that were returned, 956 (60.4% of those sent and 85.5% of those returned) authorized a prescription change to a lower-cost dose regimen. The average drug cost per day declined by 14.2%, from Dollars 2.26 to Dollars 1.94 in the intervention group, versus a 1.6% increase, from Dollars 2.52 to Dollars 2.56, in the group without dose consolidation or tablet splitting of the 3 SSRIs (sertraline, escitalopram, and immediate-release paroxetine). Total drug cost for the 3 SSRIs declined by 35.6%, from Dollars 333,567 to Dollars 214,794, as a result of a 24.8% decline in the total days of SSRI drug therapy and the 14.2% decline in average SSRI drug cost per day. The estimated monthly cost avoidance from this intervention, based on pharmacy claims data, was approximately Dollars 35,285, about 2% of the entire spending on SSRI drugs each month, or about Dollars 0.09 per member per month. Program administration costs, excluding costs incurred by prescribers and pharmacy providers, were about 2% of SSRI drug cost savings. CONCLUSIONS: Voluntary prescription change forms appear to be an effective and well-accepted tool for obtaining dose form optimization through dose form consolidation and tablet splitting, resulting in reduction in the direct costs of SSRI antidepressant drug therapy with minimal additional program administration costs.

Antidepressive Agents, Second-Generation↗

Influence of anaerobic digestion on particle surface charge and optimal polymer dosage.

Anaerobic digestion leads to significant changes of the sludge structural matrix, affecting particle size distribution and dewaterability. The surface charge, determined by means of streaming current, can be effectively used to monitor the complex phenomena of floc disruption, colloid formation and chemical conditioning. To study the relation between surface charge and optimal dosage, two different cationic polyelectrolytes were used: Praestol 644, polymer with high molecular weight and low charge density, and Poly Dadmac, with relatively low molecular weight but high charge density. The optimal Poly Dadmac dosage strictly met the value required to neutralise particle charge whereas the optimal dosage of Praestol 644 indicated that the relevant charge was considerably lower than the one required for charge neutralisation. Mechanisms of action are therefore clearly different. Another objective was to investigate the changes of dewatering characteristics of secondary sludge during anaerobic digestion tests at different inoculum content by determining charge density, and optimal polymer dosage. The optimal polyelectrolyte dosage remains almost constant during digestion at high inoculum, but a significant increase in the first period is observed at low inoculum, thus suggesting that the release of colloidal and supracolloidal material from sludge affects dewaterability, especially in the first days of digestion.

Anaerobiosis↗