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Evaluation of nonlinear optimization for scheduling of follow-up cystoscopies to detect recurrent bladder cancer. The Bladder Cancer follow-up Group.

Standard recommendations for patients who have had superficial bladder cancer are inspection by cystoscopy quarterly for a year or two after tumor removal, then half-yearly and yearly. The authors assessed the potential for improvement in scheduling cystoscopies according to probabilistic optimization techniques. Eight hypothetical practices were created, based on retrospective analysis of 918 bladder-cancer-patient charts. Standard and alternative recommendations for the interval to next cystoscopy were compared. The alternatives were derived from patient-specific predictions of future tumor risks (based on the patient's prior recurrence rate and tumor stage and grade) and a nonlinear optimization approach to allocation of the same number of cystoscopies as were available for standard follow-up. The optimization proposed longer intervals between visits for low-risk patients and shorter intervals for high-risk patients. Overall, optimization reduced expected tumor detection delays by 30%, from 12.6 to 8.7 weeks. When optimization intervals were shorter than standard, cancer was found more often at subsequent cystoscopies (34% vs 27%, p less than 0.05), suggesting that the optimization was a better predictor of cancer recurrence. If reduction in tumor-detection delay is the goal of follow-up for recurrent cancers, then urologists can improve monitoring by using probabilistic optimization methods for scheduling cystoscopies. Further understanding of the accuracy of predictive models for bladder-cancer recurrence rates is desirable. Subsequently, the optimization method developed here may be tested prospectively.

Aftercare↗

Optimal wave-front reconstruction strategies for multiconjugate adaptive optics.

We propose an optimal approach for the phase reconstruction in a large field of view (FOV) for multiconjugate adaptive optics. This optimal approach is based on a minimum-mean-square-error estimator that minimizes the mean residual phase variance in the FOV of interest. It accounts for the C2n profile in order to optimally estimate the correction wave front to be applied to each deformable mirror (DM). This optimal approach also accounts for the fact that the number of DMs will always be smaller than the number of turbulent layers, since the C2n profile is a continuous function of the altitude h. Links between this optimal approach and a tomographic reconstruction of the turbulence volume are established. In particular, it is shown that the optimal approach consists of a full tomographic reconstruction of the turbulence volume followed by a projection onto the DMs accounting for the considered FOV of interest. The case where the turbulent layers are assumed to match the mirror positions [model-approximation (MA) approach], which might be a crude approximation, is also considered for comparison. This MA approach will rely on the notion of equivalent turbulent layers. A comparison between the optimal and MA approaches is proposed. It is shown that the optimal approach provides very good performance even with a small number of DMs (typically, one or two). For instance, good Strehl ratios (greater than 20%) are obtained for a 4-m telescope on a 150-arc sec x 150-arc sec FOV by using only three guide stars and two DMs.

Journal Article↗

Geometric optimization of a tissue pattern for semilunar valve reconstruction.

BACKGROUND AND AIM OF THE STUDY: A novel geometric trefoil pattern has been suggested for semilunar valve reconstruction. Optimization of the geometry must rely on an appreciation of normal anatomy and knowledge of the mechanical properties of the tissue used for the reconstruction. METHODS: Computer-assisted design (CAD) was used to create an optimized leaflet geometry based on published dimensions for normal human aortic valves. The optimized leaflet geometry was subjected to finite element analysis (FEA) to study stress distribution with pressure loading of the leaflet. In vitro function of the optimized trefoil tissue pattern is being studied by static testing initially, with physiological saline. RESULTS: An optimized leaflet geometry has been developed by CAD, and further refined by FEA. Static testing of the optimized trefoil tissue pattern shows near-normal anatomy, with no prolapse or pin wheeling, and full valve competence to 90 mmHg pressure. CONCLUSIONS: An initial optimized geometry has been developed for a two-dimensional tissue pattern that can be used to reconstruct diseased semilunar heart valves with human pericardium. Optimization studies are based on the mechanical properties of the tissue, CAD to mimic normal anatomy, FEA to study stress distribution, and static load testing to confirm function.

Animals↗

Optimizing replacement decisions for Finnish dairy herds.

The purposes of the study were to determine how "an optimal herd" would be structured with respect to its calving pattern, average herdlife and calving interval, and to evaluate how sensitive the optimal solution was to changes in input prices, which reflected the situation in Finland in 1998. The study used Finnish input values in an optimization model developed for dairy cow insemination and replacement decisions. The objective of the optimization model was to maximize the expected net present value from present and replacement cows over a given decision horizon. In the optimal solution, the average net revenues per cow were highest in December and lowest in July, due to seasonal milk pricing. Based on the expected net present value of a replacement heifer over the decision horizon, calving in September was optimal. In the optimal solution, an average calving interval was 363 days and average herdlife after first calving was 48.2 months (i.e., approximately 4 complete lactations). However, there was a marked seasonal variation in the length of a calving interval (it being longest in spring and early summer) that can be explained by the goal of having more cows calving in the fall. This, in turn, was due to seasonal milk pricing and higher production in the fall. In the optimal solution, total replacement percentage was 26, with the highest frequency of voluntary culling occurring at the end of the year. Seasonal patterns in calving and replacement frequencies by calendar month and variation in calving interval length or herdlife did not change meaningfully (< 1%-2% change in the output variables) with changes in calf, carcass or feed prices. When the price of a replacement heifer decreased, average herdlife was shorter and replacement percentage increased. When the price increased, the effect was the opposite.

Animal Feed↗

Radiation dose and image quality in diagnostic radiology. Optimization of the dose-image quality relationship with clinical experience from scoliosis radiography, coronary intervention and a flat-panel digital detector.

UNLABELLED: X-rays are known to cause malignancies, skin damage and other side effects and they are thus potentially dangerous. Therefore, it is essential and in fact mandatory to reduce the radiation dose in diagnostic radiology as far as possible. This is also known as the ALARA (as low as reasonably achievable) principle. However, the dose is linked to image quality and the image quality may not be lowered so far that it jeopardizes the diagnostic outcome of a radiographic procedure. The process of reaching this balance between dose and image quality is called optimization. The aim of this thesis was to propose and evaluate methods for optimizing the radiation dose-image quality relationship in diagnostic radiography with a focus on clinical usefulness. The work was performed in three main parts. OPTIMIZATION OF SCOLIOSIS RADIOGRAPHY: In the first part, two recently developed methods for digital scoliosis radiography (digital exposure and pulse fluoroscopy) were evaluated and compared to the standard screen-film method. Radiation dose was measured as kerma area-product (KAP), entrance surface dose (ESD) and effective dose; image quality was assessed with a contrast-detail phantom and through visual grading analysis. Accuracy in angle measurements was also evaluated. The radiation dose for digital exposure was nearly twice as high as the screen-film method at a comparable image quality while the dose for pulsed fluoroscopy was very low but with a considerably lower image quality. The variability in angle measurements was sufficiently low for all methods. Then, the digital exposure protocol was optimized to a considerably lower dose with a slightly lower image quality compared to the baseline. FLAT-PANEL DETECTOR: In the second part, an amorphous-silicon direct digital flat-panel detector was evaluated using a contrast-detail phantom, measuring dose as entrance dose. The flat-panel detector yielded a superior image quality at a lower dose than both storage phosphor plates and screen-film. Equivalent image quality compared to storage phosphor plates was reached at about one-third of the dose. OPTIMIZATION OF PERCUTANEOUS CORONARY INTERVENTION (PCI): In the third part, influence of various settings on radiation dose and image quality in coronary catheterisation and PCI was investigated. Based on these findings, the dose rate for fluoroscopy was reduced to one-third. The dose reduction was evaluated in a clinical series of 154 PCI procedures before and 138 after the optimization. Through this optimization, the total KAP was significantly reduced to two-thirds of the original value. IN SUMMARY: This thesis indicates the possibility of dose reduction in diagnostic radiology through optimization of the radiographic process.

Coronary Angiography↗

Genetic algorithms-based design and optimization of statistical quality-control procedures.

In general, one cannot use algebraic or enumerative methods to optimize a quality-control (QC) procedure for detecting the total allowable analytical error with a stated probability with the minimum probability for false rejection. Genetic algorithms (GAs) offer an alternative, as they do not require knowledge of the objective function to be optimized and can search through large parameter spaces quickly. To explore the application of GAs in statistical QC, I developed two interactive computer programs based on the deterministic crowding genetic algorithm. Given an analytical process, the program "Optimize" optimizes a user-defined QC procedure, whereas the program "Design" designs a novel optimized QC procedure. The programs search through the parameter space and find the optimal or near-optimal solution. The possible solutions of the optimization problem are evaluated with computer simulation.

Algorithms↗

[The role of the atrium and optimal values of AV intervals in sequentially paced patients].

In 1995, 2249 dual chamber pacemakers were implanted in the Czech Republic. These pacemakers make it possible to set an optimal AV delay between the atrial and ventricular impulse. Although the optimization of the AV interval has its well defined physiologic advantages, it does not seem to be necessary in otherwise healthy individuals with a good atrial and ventricular function. In these patients the default value, usually about 170 ms, is acceptable. However, AV interval optimization--i.e. finding the interval at which the atrial contribution to ventricular filling is maximal--should be done in all patients with left ventricular dysfunction, indicated for pacing because of bradyarrhthmia. In this subset of patients, even a small improvement in ventricular filling is believed to be clinically useful. Moreover, it has been documented, that in some types of ventricular dysfunction the so-called "primary optimization" (i.e. optimization of the AV interval in patients, in whom the pacemaker is not indicated for bradyarrhthmia but for ventricular dysfunction that might be improved by AV interval optimization) may be clinically useful. It is the case in patients with hypertrophic obstructive cardiomyopathy, dilated cardiomyopathy with presystolic regurgitation and AV interval prolongation, and perhaps even in some patients with impairment of ventricular systolic function and substantial prolongation of the AV interval. Despite all that, optimization of the AV interval is not routinely performed because even the best available optimization procedures (stroke volume measurements at different AV intervals by aortic Doppler echography) is observer dependent, time-consuming and costly.

Arrhythmias, Cardiac↗

Optimism, coping and long-term recovery from coronary artery surgery in women.

Optimism, coping strategies, and psychological and functional outcomes were measured in 55 women undergoing coronary artery surgery. Data were collected in-hospital and at 1, 6, and 12 months after surgery. Optimism was related to positive moods and life satisfaction, and inversely related to negative moods. Few relationships were found between optimism and functional ability. Cognitive coping strategies accounted for a mediating effect between optimism and negative mood. Optimists were more likely to accept their situation, and less likely to use escapism. In turn, these coping strategies were inversely related to negative mood and mediated the relationship between optimism and this outcome. Optimism was not related to problem-focused coping strategies; this, these coping strategies cannot explain the relationship between optimism and outcomes.

Adaptation, Psychological↗

Optimal cryogen spray cooling parameters for pulsed laser treatment of port wine stains.

BACKGROUND AND OBJECTIVE: In dermatologic laser therapy, cryogen spray cooling (CSC) is a means to protect the epidermis while leaving dermal structures susceptible to thermal damage. The purpose of this study was to determine optimal spurt duration, tau(s), and optimal delay, tau(d), between the cryogen spurt and laser pulse when using CSC in treatment of port wine stain birthmarks. STUDY DESIGN/MATERIALS AND METHODS: A finite difference method is used to compute temperature distributions in human skin in response to CSC. Optimal tau(s) and tau(d) are determined by maximizing the temperature difference between a modeled basal layer and an imaginary target chromophore. RESULTS: The model predicts an optimal tau(s) of 170-300 msec and approximately 400 msec for shallow (150 microm) and deeper (400 microm) targets, respectively. Spraying for longer than the optimal tau(s) does not critically impair cooling selectivity. For a spurt duration of 100 msec, optimal delays are 5-10 msec and 25-70 msec for a shallow and deep basal layer, respectively. CONCLUSION: In the absence of knowledge about the lesion anatomy, using a tau(s) of 100-200 msec and no delay is a good compromise. A delay is justified only when basal layer and target chromophore are relatively deep and the optimal spurt duration cannot be applied, e.g., to avoid frostbite.

Cryotherapy↗

Framework for online optimization of recombinant protein expression in high-cell-density Escherichia coli cultures using GFP-fusion monitoring.

A framework for the online optimization of protein induction using green fluorescent protein (GFP)-monitoring technology was developed for high-cell-density cultivation of Escherichia coli. A simple and unstructured mathematical model was developed that described well the dynamics of cloned chloramphenicol acetyltransferase (CAT) production in E. coli JM105 was developed. A sequential quadratic programming (SQP) optimization algorithm was used to estimate model parameter values and to solve optimal open-loop control problems for piecewise control of inducer feed rates that maximize productivity. The optimal inducer feeding profile for an arabinose induction system was different from that of an isopropyl-beta-D-thiogalactopyranoside (IPTG) induction system. Also, model-based online parameter estimation and online optimization algorithms were developed to determine optimal inducer feeding rates for eventual use of a feedback signal from a GFP fluorescence probe (direct product monitoring with 95-minute time delay). Because the numerical algorithms required minimal processing time, the potential for product-based and model-based online optimal control methodology can be realized.

Algorithms↗

Optimal temperature policy for immobilized enzyme packed bed reactor performing reversible Michaelis-Menten kinetics using the disjoint policy.

The optimal temperature policy that maximizes the time-averaged productivity of a continuous immobilized enzyme packed bed reactor is determined. This optimization study takes into consideration the enzyme thermal deactivation with substrate protection during the reactor operation. The general case of reversible Michaelis-Menten kinetics under constant reactor feed flow rate is assumed. The corresponding nonlinear optimization problem is solved using the calculus of variations by applying the disjoint policy. This policy reduces the optimization problem into a differential-algebraic system, DAE. This DAE system defines completely the optimal temperature-time profiles. These profiles depend on the kinetic parameters, feed substrate concentration, operating period, and the residence time and are characterized by increasing form with time. Also, general analytical expressions for the slopes of the temperature and residual enzyme activity profiles are derived. An efficient solution algorithm is developed to solve the DAE system, which results into a one-dimensional optimization problem with simple bounds on the initial feed temperature. The enzymatic isomerization of glucose into fructose is selected as a case study. The computed productivities are very close to that obtained by numerical nonlinear optimization with simpler problem to solve. Moreover, the computed conversion profiles are almost constant over 90% of the operating periods, thus producing a homogeneous product.

Algorithms↗

Application of modified Rosenbrock's method for optimization of nutrient media used in microorganism culturing.

The Rosenbrock's procedure has been modified for optimization of nutrient medium composition and has been found to be less tedious than the Box-Wilson method, especially for larger numbers of optimized parameters. Its merits are particularly obvious with multiparameter optimization where the gradient method, so far the only one employed in microbiology from a variety of optimization methods (e.g., refs, 9 and 10), becomes impractical because of the excessive number of experiments required. The method suggested is also more stable during optimization than the gradient methods which are very sensitive to the selection of steps in the direction of the gradient and may thus easily shoot out of the optimized region. It is also anticipated that other direct search methods, particularly simplex design, may be easily adapted for optimization of medium composition. It is obvious that direct search methods may find an application in process improvement in antibiotic and related industries.

Culture Media↗

Geometry optimization with QM/MM, ONIOM, and other combined methods. I. Microiterations and constraints.

Hybrid energy methods such as QM/MM and ONIOM, that combine different levels of theory into one calculation, have been very successful in describing large systems. Geometry optimization methods can take advantage of the partitioning of these calculations into a region treated at a quantum mechanical (QM) level of theory and the larger, remaining region treated by an inexpensive method such as molecular mechanics (MM). A series of microiterations can be employed to fully optimize the MM region for each optimization step in the QM region. Cartesian coordinates are used for the MM region and are chosen so that the internal coordinates of the QM region remain constant during the microiterations. The coordinates of the MM region are augmented to permit rigid body translation and rotation of the QM region. This is essential if any atoms in the MM region are constrained, but it also improves the efficiency of unconstrained optimizations. Because of the microiterations, special care is needed for the optimization step in the QM region so that the system remains in the same local valley during the course of the optimization. The optimization methodology with microiterations, constraints, and step-size control are illustrated by calculations on bacteriorhodopsin and other systems.

Journal Article↗

Optimization of parameter values for complex pulse sequences by simulated annealing: application to 3D MP-RAGE imaging of the brain.

A number of pulse sequence techniques, including magnetization-prepared gradient echo (MP-GRE), segmented GRE, and hybrid RARE, employ a relatively large number of variable pulse sequence parameters and acquire the image data during a transient signal evolution. These sequences have recently been proposed and/or used for clinical applications in the brain, spine, liver, and coronary arteries. Thus, the need for a method of deriving optimal pulse sequence parameter values for this class of sequences now exists. Due to the complexity of these sequences, conventional optimization approaches, such as applying differential calculus to signal difference equations, are inadequate. We have developed a general framework for adapting the simulated annealing algorithm to pulse sequence parameter value optimization, and applied this framework to the specific case of optimizing the white matter-gray matter signal difference for a T1-weighted variable flip angle 3D MP-RAGE sequence. Using our algorithm, the values of 35 sequence parameters, including the magnetization-preparation RF pulse flip angle and delay time, 32 flip angles in the variable flip angle gradient-echo acquisition sequence, and the magnetization recovery time, were derived. Optimized 3D MP-RAGE achieved up to a 130% increase in white matter-gray matter signal difference compared with optimized 3D RF-spoiled FLASH with the same total acquisition time. The simulated annealing approach was effective at deriving optimal parameter values for a specific 3D MP-RAGE imaging objective, and may be useful for other imaging objectives and sequences in this general class.

Adipose Tissue↗

The ability of preoperative serum CA-125 to predict optimal primary tumor cytoreduction in stage III epithelial ovarian carcinoma.

PURPOSE: The aim of this study was to determine the ability of preoperative serum CA-125 to predict optimal primary tumor cytoreduction in patients with Stage III epithelial ovarian carcinoma. METHODS: We performed a retrospective chart review of 100 consecutive patients with Stage III ovarian carcinoma who had a serum CA-125 drawn prior to primary cytoreductive surgery. We used a receiver operating characteristic curve to determine the CA-125 level with the maximal prognostic power in predicting optimal versus suboptimal cytoreduction. RESULTS: The median CA-125 level for the 100 patients was 819 U/ml (range 5.6-26,200 U/ml). Optimal cytoreduction (diameter of largest residual tumor nodule < or =1 cm) was obtained in 45 cases (45%). The probability of performing optimal cytoreduction decreased with increasing CA-125 levels. A preoperative CA-125 level of 500 U/ml was identified as the value with the most predictive power. Optimal cytoreduction was achieved in 33 of the 45 cases (73%) with a CA-125 less than 500 U/ml compared to only 12 of the 55 cases (22%) with a CA-125 greater than 500 U/ml. Using a threshold level of 500 U/ml, the preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 78%, specificity of 73%, positive predictive value of 78%, and negative predictive value of 73%. CONCLUSION: The probability of performing optimal cytoreduction in patients with Stage III ovarian carcinoma and a preoperative CA-125 greater than 500 U/ml was approximately one in five. These patients may be candidates for initial laparoscopic evaluation to obtain a confirmatory tissue diagnosis and to determine resectability.

Adult↗

Optimal cytoreductive surgery is an independent prognostic indicator in stage IV epithelial ovarian cancer with hepatic metastases.

OBJECTIVES: The aim of this study was to determine the value of optimal cytoreduction in stage IV epithelial ovarian cancer. METHODS: A retrospective review was performed of 37 women with stage IV epithelial ovarian cancer treated by radical surgery. RESULTS: Optimal surgery to less than 2 cm tumor deposits was performed in 16 of the 37 cases (43%) and tumor debulking to less than 1 cm tumor deposits in 6 cases (16.2%). Twenty-three cases (62%) were designated stage IV because of the presence of liver metastases alone. Although no patients died within 2 weeks of surgery, 7 of the 37 cases (22%) failed to survive more than 50 days after primary surgery. The overall median survival was 11 months with overall 2- and 5-year survivals of 23 and 9%, respectively. On multivariate analysis comparing age, histological type, tumor grade, place of surgery, secondary surgical procedure, performance of bowel surgery, presence of liver metastases, and optimal cytoreduction, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained highly significant (P = 0.0029 and 0.0086, respectively). Even when assessing only the 27 cases who were designated as having stage IV disease because of the presence of liver metastases, by multivariate analysis, only optimal surgery and residual tumor deposits of less than 2 cm, or less than 1 cm, remained significant (P = 0.023 and 0.036, respectively). Site of metastases designating stage IV status was not associated with a reduced likelihood of achieving optimal debulking (P = 0.18). CONCLUSION: Optimal cytoreduction in women with stage IV epithelial ovarian cancer with or without hepatic metastases is associated with a more favorable outcome survival.

Adenocarcinoma↗

Time optimality in the control of human movements.

In a simulation study the control of maximally fast goal directed movements has been analyzed. For a simple linear model it is shown that the presence of a third input block reduces the movement duration. The time optimal size of the third block depends on the ratio of a neuromuscular time constant (first-order lag) and movement time. As a second step a non-linear muscle model was simulated. By an optimization of input parameters it was found that the time optimal input, as expected, switches between maximal agonist and maximal antagonist activation. As for the linear model, a third phase was required for an optimal movement. It was found that the third phase serves to compensate the slowly decaying antagonist force. Also an input similar to experimentally found activation patterns was simulated. This input contains a silent period between the first two bursts and the second and the third burst have submaximal amplitudes. This input led to a near time optimal movement with a duration 9% larger than the minimal duration but with largely reduced muscle forces. This suggests that a criterion is minimized which also takes into account the effort spent. Including gravity in the model indicates optimality of a silent period between the third phase and a final agonist activity to resist gravity. When assuming different dynamics for agonist and antagonist, the optimal switch times for agonist and antagonist no longer coincide, also after the three block pattern some extra activity is required to obtain a cancellation of the slowly decaying force in agonist and antagonist.

Biological Clocks↗

A variable target intensity-restrained global optimization (VARTIGO) procedure for determining three-dimensional structures of polypeptides from NOESY data: application to gramicidin-S.

A global optimization method for intensity-restrained structure refinement, based on variable target function (VTF) analysis, is illustrated using experimental data on a model peptide, gramicidin-S (GS) dissolved in DMSO. The method (referred to as VARTIGO for variable target intensity-restrained global optimization) involves minimization of a target function in which the range of NOE contacts is gradually increased in successive cycles of optimization in dihedral angle space. Several different starting conformations (including all-trans) have been tested to establish the validity of the method. Not all optimizations were successful, but these were readily identifiable from their large NOE R-factors. We also show that it is possible to simultaneously optimize the rotational correlation time along with the dihedral angles. The structural features of GS thus obtained from the successful optimizations are in excellent agreement with the available experimental data. A comparison is made with structures generated from an intensity-restrained single target function (STF) analysis. The results on GS suggest that VARTIGO refinement is capable of yielding better quality structures. Our work also underscores the need for a simultaneous analysis of different NOE R-factors in judging the quality of optimized structures. The NOESY data on GS in DMSO appear to provide evidence for the presence of two orientations for the ornithine side chain, in fast exchange. The NOESY spectra for this case were analyzed using a relaxation rate matrix which is a weighted average of the relaxation rate matrices for the individual conformations.

Amino Acid Sequence↗