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Inverse optimization: functional and physiological considerations related to the force-sharing problem.

This paper is a review of the optimization techniques used for the solution of the force-sharing problem in biomechanics; that is, the distribution of the net joint moment to the force generating structures such as muscles and ligaments. The solution to this problem is achieved by the minimization (or maximization) of an objective function that includes the design variable (usually muscle forces) that are subject to certain constraints, and it is generally related to physiological or mechanical properties such as muscle stress, maximum force or moment, activation level, etc. The usual constraints require the sum of the exerted moments to be equal to the net joint moment and certain boundary conditions restrict the force solutions within physiologically acceptable limits. Linear optimization (objective and constraint functions are both linear relationships) has limited capabilities for the solution of the force sharing problem, although the use of appropriate constraints and physiologically realistic boundary conditions can improve the solution and lead to reasonable and functionally acceptable muscle force predictions. Nonlinear optimization provides more physiologically acceptable results, especially when the criteria used are related to the dynamics of the movement (e.g., instantaneous maximum force derived from muscle modeling based on length and velocity histories). The evaluation of predicted forces can be performed using direct measurements of forces (usually in animals), relationship with EMG patterns, comparisons with forces obtained from optimized forward dynamics, and by evaluating the results using analytical solutions of the optimal problem to highlight muscle synergism for example. Global objective functions are more restricting compared to local ones that are related to the specific objective of the movement at its different phases (e.g., maximize speed or minimize pain). In complex dynamic activities multiobjective optimization is likely to produce more realistic results.

Biomechanical Phenomena↗

Thirty-cycle temperature optimization of a closed-cycle capillary PCR machine.

The performance of a novel thermal cycler has been characterized in a 30-cycle PCR. The device consists of a microcapillary equipped with bidirectional pressure-driven flow and in situ optical position sensors. A 1-microL droplet of reaction mixture moves between three heat zones in a 1-mm i.d., oil-filled capillary using a multi-element scattered light detector and active feedback. The design permits time and number of cycles to be changed without hardware modification, unlike other flow-in-capillary PCR systems. Temperature optimization has been performed on the three PCR heat steps. The optimal denaturation temperature is 94 degrees C-96 degrees C, which is identical to commercial machines. The optimal extension temperature of 62 degrees C-66 degrees C is lower than reported for Taq DNA polymerase (70 degrees C-80 degrees C) because of the high enzyme concentration and/or the absence of detergent in the PCR mixture. The optimal annealing temperature seems to be the same as the optimal extension temperature. This is because extension occurs when the sample is inside of the annealing heat zone. Annealing takes place as the sample travels between heat zones. Device speed (23 minfor 30 cycles without time optimization) is competitive with other rapid PCR designs for efficiencies comparable to a commercial machine.

Bacteriophage lambda↗

Biopharmaceutic classification system: a scientific framework for pharmacokinetic optimization in drug research.

The tenets of biopharmaceutics, solubility and permeability, are of pivotal importance in new drug discovery and lead optimization due to the dependence of drug absorption and pharmacokinetics on these two properties. A classification system for drugs based on these two fundamental parameters, Biopharmaceutic Classification System (BCS), provides drug designer an opportunity to manipulate structure or physicochemical properties of lead candidates so as to achieve better "deliverability". Considering the facts for failure of NCEs, drug research, once concentrating on optimizing the efficacy and safety of the leads, dramatically transformed in the past two decades. With the enormous number of molecules being synthesized using combinatorial and parallel synthesis, high throughput methodologies for screening solubility and permeability has gained significant interest in pharmaceutical industry. Ultimate aim of the drug discovery scientist in pharmacokinetic optimization is to tailor the molecules so that they show the features of BCS class I without compromising on pharmacodynamics. Considerations to optimize drug delivery and pharmacokinetics right from the initial stages of drug design propelled need for "High Throughput Pharmaceutics" (HTP). In silico predictions and development of theoretical profiles for solubility and lipophilicity provides structure based biopharmaceutical optimization, while in vitro experimental models (microtitre plate assays and cell cultures) validate the predictions. Thus, biopharmaceutical characterization during drug design and early development helps in early withdrawal of molecules with insurmountable developmental problems associated with pharmacokinetic optimization.

Animals↗

Optimism, satisfaction and time perspective in the elderly.

In contrast to younger groups, research with the elderly suggest a predominantly present-focused temporal orientation. One aspect of satisfaction, optimism is conceptualized as a form of future perspective. Health psychology generally asserts that health-enhancing messages depend for effect on a person perceiving future benefits to actions taken in the present to enhance health or minimize ill-health risk. The extent to which the elderly perceive or value the future should impact on health maintenance behaviors. In a study of eighty-six elderly people, the dominant ways of viewing time coalesced around a variety of present time perspectives. Within-group differences revealed that as people aged, they became less satisfied with life relative to their level of optimism. For the young-old, optimism was positively correlated with satisfaction, but for the oldest-old the variables were negatively associated. Optimism increased with age while satisfaction decreased with age. The decrease in satisfaction is most probably related more to a sense of realism about the tasks of aging than a sense of "death anxiety," or avoidance of the future. As people age, temporal variables become less important in predicting optimism or satisfaction and optimism becomes less important as a predictor of satisfaction. Implications for developing models of health management in the elderly are discussed.

Aged↗

T2-weighted MR imaging of the uterus: comparison of optimized fast spin-echo and HASTE sequences with conventional fast spin-echo sequences.

OBJECTIVE: Our objective was to compare the value of a half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequence with optimized fast spin-echo and conventional fast spin-echo techniques in evaluation of the uterus. SUBJECTS AND METHODS: Optimized fast spin-echo imaging was compared with fast spin-echo and HASTE imaging, for both image quality and ability to assess the zonal anatomy of the uterus, in 40 volunteers. In optimized fast spin-echo imaging, the imaging time was reduced using partial-Fourier reconstruction, reducing the echo spacing, and increasing the echo train length. RESULTS: HASTE imaging offered the least motion artifact of all techniques. On optimized fast spin-echo imaging, motion artifacts were moderate to severe in 10% of patients. On fast spin-echo imaging, motion artifacts were moderate to severe in 40% of patients. Optimized fast spin-echo imaging was superior to the other two techniques in terms of anatomic sharpness and overall image quality. CONCLUSION: Although HASTE imaging offers the unique feature of providing images free of motion artifacts, optimized fast spin-echo imaging appears to be the preferred technique for T2-weighted imaging of the uterus.

Adolescent↗

Usefulness of optimized gadolinium-enhanced fast fluid-attenuated inversion recovery MR imaging in revealing lesions of the brain.

OBJECTIVE: The purpose of this study was to compare the contrast enhancement of lesions of the brain revealed by gadolinium-enhanced optimized fast fluid-attenuated inversion recovery (FLAIR) MR imaging with that of lesions on gadolinium-enhanced optimized T1-weighted spin-echo MR imaging. SUBJECTS AND METHODS: Using computer simulations, we optimized the fast FLAIR parameters (TR, TEeff, and inversion time) and the T1-weighted spin-echo parameters (TR and TE) to provide maximum difference in signal intensity between enhancing lesions of the brain and white matter. Seventy-six consecutive patients referred for single-dose gadolinium-enhanced MR imaging of the brain underwent both optimized techniques, which were matched for spatial resolution, bandwidth, and number of excitations. The gadolinium-enhanced fast FLAIR and T -weighted spin-echo MR images were evaluated independently by two observers for number and size of enhancing lesions and for the degree of gray-white matter differentiation. Contrast-to-noise ratios were measured for enhancing lesions 1.0 cm or larger in diameter using 8 x 8 pixel regions of interest in the enhancing lesions and normal white matter. RESULTS: The most revealing parameters for fast FLAIR MR imaging proved to be a TR of 1500 msec, an inversion time of 683 msec, and a TEeff of 16 msec. For T1-weighted spin-echo MR imaging, the optimized parameters were a TR of 550 msec and a TE of 16 msec. In 28 patients, we saw enhancing lesions of the brain with at least one MR imaging technique. More lesions were seen on the T1-weighted spin-echo sequence (n = 141) than on the fast FLAIR sequence (n = 94) (p < .03). Gray-white matter differentiation was significantly better on the fast FLAIR sequence (p < .001). Contrast-to-noise ratios of enhancing lesions were greater on the T1-weighted spin-echo sequence (p < .001). CONCLUSION: In this study, optimized gadolinium-enhanced conventional T1-weighted spin-echo MR imaging proved superior to gadolinium-enhanced fast FLAIR MR imaging in revealing lesions of the brain.

Adult↗

Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure.

OBJECTIVE: Three measures--heart rate, a global index of the influence of the autonomic nervous system on the heart; circulating concentrations of adiponectin, an adipose-specific protein; and C-reactive protein (CRP), a sensitive marker of inflammation--have been reported to be closely associated with insulin resistance. Patients with borderline hypertension are known to be more insulin resistant and dyslipidemic than those with normal blood pressure (BP). BP can be classified into three categories: optimal, normal, and high-normal. The present study examined whether those with high-normal BP have any of these three conditions as compared with those with optimal BP in young healthy men. RESEARCH DESIGN AND METHODS: Anthropometric, blood pressure, heart rate, and blood tests, including tests for adiponectin and CRP, were conducted in 198 male students, ages 18-26 years, who had fasted overnight. Insulin resistance (IR) and insulin secretion (beta-cell levels) were calculated using the homeostasis model assessment (HOMA), and LDL size was measured by PAGE. RESULTS: Compared with the 90 men who had optimal BP, the 46 men with high-normal BP had increased heart rate, BMI, percent body fat, and serum leptin levels. In addition, they had greater serum insulin, HOMA IR, and beta-cell levels, lower adiponectin levels, and comparable CRP levels. Furthermore, the 46 men with high-normal BP had higher serum triglyceride and apolipoprotein (apo) B levels, and smaller LDL size; however, there was no difference in LDL and HDL cholesterol and apoA-I between men with optimal and high-normal BP. After adjusting for BMI, differences were still significant in serum adiponectin, heart rate, and LDL particle size. As BP rose, there was an increase in heart rate (BMI-adjusted least square means were 63, 65, and 70 bpm in men with optimal, normal, and high-normal BP, respectively; P = 0.005), whereas serum adiponectin (7.5, 6.6, and 6.4 mg/l; P = 0.007) and LDL particle size (271, 269, and 269 A; P = 0.008) decreased. CONCLUSIONS: Young men with high-normal BP have a faster heart rate, lower serum adiponectin levels, and smaller LDL size than men with optimal BP, even after adjustment for BMI. These results suggest the necessity of preventing further development of cardiac and metabolic diseases in young people who have high-normal BP.

Adiponectin↗

Clinical evaluation of established optimal immobilizing doses of medetomidine-ketamine in captive reindeer (Rangifer tarandus tarandus).

OBJECTIVE: To evaluate clinical effects and repeatability of clinical effects for an optimal immobilizing dose of a combination of medetomidine hydrochloride (MED) and ketamine hydrochloride (KET) in reindeer (Rangifer tarandus tarandus). ANIMALS: 12 healthy 6- to 8-month old reindeer. PROCEDURE: Each reindeer was immobilized once with an initial dose (combination of 0.06 mg of MED/kg of body weight and 0.3 mg KET/kg) and twice with an optimal dose of MED-KET. Reversal was achieved with 5 mg of atipamezole/mg of MED injected 45 minutes after MED-KET administration. Observational variables were recorded. Oxygen saturation of arterial hemoglobin measured by pulse oximetry (Spo2), respiratory rate (RR), heart rate (HR), and rectal temperature (RT) were recorded 10, 25, and 40 minutes after immobilization. RESULTS: Mean time to first sign of sedation and time until a recumbent animal lifted its head were significantly reduced for reindeer given the optimal dose, compared with the initial dose. Mean Spo2 remained > 90% during initial immobilization; this value was significantly lower for the optimal dose, but increased during immobilization from 85 to 89%. At all doses, RR increased significantly throughout the recorded period; however, RT and HR were constant. Except for time until reindeer stood, all time variables, Spo2, RR, RT, and HR were repeatable. CONCLUSION AND CLINICAL RELEVANCE: mmobilization of captive reindeer achieved by use of the optimal dose established here is clinically acceptable, although Spo2 should be carefully monitored. Administration of the optimal dose produced the same clinical effect during repeated immobilization of the same reindeer.

Adrenergic alpha-Agonists↗

Stability of optimism and choice of coping strategy.

Dispositional optimism and choice of coping strategies were measured twice to test the hypothesis that optimists and pessimists routinely use different methods of coping with stressful events and that these choices are stable over time. 82 participants completed a measure of optimism (LOT) and of coping strategy choice (COPE) at each of two sessions, four weeks apart. Repeated-measures t tests showed that overall the self-reports of dispositional optimism and all 15 coping strategy factors were stable over the four-week period. In addition, all 16 scales were significantly related to the first administration at follow-up. Regarding the relation between the 15 coping factors and optimism, five remained significantly correlated with optimism at both testings, five remained uncorrelated with optimism at both testings, and five showed minor changes in magnitude of their correlation (and statistical significance) at both testings.

Adaptation, Psychological↗

Cognitive bias of optimism and its influence on psychological well-being.

An investigation of the cognitive bias observed in optimism and the influence of optimism on psychological well-being was conducted. The cognitive bias was assumed to be related to the repressive style of information processing, represented by the trait scale of the State-Trait Anxiety Inventory and the Social Desirability scale. Optimism and well-being were measured by the Life Orientation Test and the Social Optimism scale as well as by the Life Satisfaction and Depression scales, respectively. These scales were applied to a sample of 200 individuals. Trait Anxiety and Social Desirability led to a high multiple correlation with the Life Orientation Test (R = .54) and a moderate multiple correlation with the Social Optimism scale (R = .30). Higher correlations were obtained for the expectation of a positive than of a negative future. Both the Life Orientation Test and the Social Optimism scale contributed to the high multiple correlation with psychological well-being (R = .52).

Adult↗

Optimal beef cattle diets formulated by nonlinear programming.

A beef diet model based on National Research Council recommendations is significantly nonlinear for feed ingredients, daily gain and weight of cattle. Solving a diet model has been difficult, but advances in nonlinear programming now allow solutions that are quick and easy. This study developed a nonlinear programming method for optimally planning a feeding program by choosing feeds, daily gains and selling weight. Two types of diets are important for this purpose:optimal-return diets and least-cost-gain diets. For a given weight of cattle, an optimal-return diet chooses feeds and daily gain to maximize returns above feed costs. A least-cost-gain diet chooses feeds and daily gain to minimize feed plus yardage costs per kilogram of gain. In an optimal feeding program, a sequence of optimal-return diets is fed to increasing weights of cattle. Feed costs plus yardage per kilogram of gain rise to equal the actual selling price at the optimal selling weight, and the cattle are sold. Cattle feeders and researchers with access to a microcomputer can maximize net returns from a feeding program.

Animal Husbandry↗

Minimax optimization-based inverse treatment planning for interstitial thermal therapy.

The following work represents the development and evaluation of a minimax optimization-based inverse treatment planning approach for interstitial thermal therapy of cancer and benign disease. The goal is to determine a priori optimal applicator placements and power level settings to maintain the minimum tumour temperature, Tmin, and maximum normal tissue temperature, Tmax within a prescribed therapeutic temperature range. The temperature distribution is approximated by a finite element method (FEM) solution of a bioheat transfer equation on a nonuniform finite element mesh. Lower and upper therapeutic temperature thresholds are specified in the tumour and surrounding normal tissues. A constrained minimax optimization problem is formulated to determine optimal applicator positions and power level settings that minimize the maximum (rather than average) temperature errors in the target tumour region and surrounding normal tissues. The optimization problem is formulated for two general classes of interstitial heating applicators, those with and without a surface cooling mechanism. The viability and sensitivity of this approach is investigated in the two-dimensional setting for various tumour shapes and blood perfusion levels using surface-cooled and direct-coupled interstitial ultrasound applicator power deposition models. These preliminary results indicate the utility of this approach for meeting a prescribed Tmin/Tmax-based clinical objective criterion, and its potential for generating optimal treatment plans that can withstand variations or uncertainty in blood perfusion levels.

Energy Transfer↗

Whole-herd optimization with the Cornell Net Carbohydrate and Protein System. II. Allocating homegrown feeds across the herd for optimum nutrient use.

The objective of this paper was to develop a linear optimization procedure for allocating homegrown feeds across the herd to optimize use of their nutrients in whole farm nutrient management planning. The first step involved developing an optimal diet for each group by a linear programming (LP) procedure developed for the Cornell Net Carbohydrate and Protein System (CNCPS). Information (feed biological values, nutrient requirements, animal and environmental factors, nutrient excretion, and the optimal diet) for each group was exported to a whole farm worksheet, where another LP procedure was used to optimize the allocation of homegrown crops by satisfying the set requirements of each animal group while optimizing return over feed costs and nutrient excretion constraints. A sample evaluation shows how this model was used to reduce N, P, and K excretion by changing feeding strategies while maintaining return over feed costs.

Animal Feed↗

A nonlinear programming optimization model to maximize net revenue in cheese manufacture.

A nonlinear programming optimization model was developed to maximize net revenue in cheese manufacture and is described in this paper. The model identifies the optimal mix of milk resources together with the types of cheeses and co-products that maximize net revenue. It works in Excel while it takes the data specified by the user from a user-friendly interface created in Access. The user can specify any number of resources, cheese types, and co-products. To demonstrate the capabilities of the model, we determined the impact of variation in milk price and composition in the period 1998 to 2000 on the optimal mix of resources and optimal type of co-product for Cheddar and low-moisture, part-skim Mozzarella. It was also desired to determine the impact of variation in protein content of nonfat dry milk (NDM) on net revenue, and examine the effect of reconstitution of NDM with water versus milk on net revenue. The optimal mix of resources and the net revenue markedly varied as milk resource prices and composition varied. The net revenue for Mozzarella was much higher than for Cheddar when the price of cream was high. Cheese plants that did not optimize the use of resources in response to variations in prices and composition missed a significant profit opportunity. Whey powder was more profitable than 34% whey protein concentrate and lactose in most months. The use of high-protein NDM led to an appreciable increase in net revenue. When the value of the nonfat portion of raw milk was high, reconstitution of NDM with water rather than milk markedly raised net revenue.

Cheese↗

[Questionnaire of self-efficacy, optimism and pessimism: reconstruction, selection of items and validation of an instrument by means of examinations of clinical samples].

Self-efficacy and optimism are considered highly useful parameters in the context of therapeutic indication prognosis, and outcome evaluation. In our study, a combined questionnaire measuring "self-efficacy" (Schwarzer u. Jerusalem 1986) and "optimism" (Scheier u. Carver 1985) was restructured and reduced in length. The resulting instrument was compared with its original version in five different clinical samples comprising n = 726 inpatients. Factor analyses achieved the bidimensionality in the construct "optimism" as postulated by Scheier and Carver, this yielding the two factors "optimism" and "pessimism". The statistical validation resulted in good to optimal values. Factor analyses considering the different clinical groups showed that certain items failed to be invariably approprieted to one factor. Therefore, we decided in favor of an item reduction, resulting in half the original number: 5 items representing "self-efficacy" 2 for "optimism" and 2 for "pessimism". The scale values of the reduced version showed no relevant deviations compared to the original, and hence we conclude that the reduction does not result in a loss of information.

Humans↗

[Pareto-optimal alignment of biological sequences].

The problem of alignment of two symbol sequences is considered. The validity of the available algorithms for constructing optimal alignment depends on the weighting coefficients which are frequently difficult to choose. A new approach to the problem is proposed, which is based on the use of vector weighting functions (instead of tradionally used scalar ones) and Pareto-optimal alignment (an alignment that is optimal at any choice of weighting coefficient will always be Pareto-optimal). An efficient algorithm for constructing all Pareto-optimal alignments of two sequences is proposed. An approach to choosing a "biologically correct" alignment among all Pareto-optimal alignments is suggested.

Algorithms↗

Measurement of dopamine release with continuous infusion of [11C]raclopride: optimization and signal-to-noise considerations.

UNLABELLED: PET studies with [11C]raclopride provide an indirect measure of changes in synaptic dopamine. Previously, we used the bolus-plus-infusion (B/I) method to assess dopamine response from the percentage change in binding potential (deltaBP) before and after administration of amphetamine. The goal of this work is to optimize the measurement of changes in neurotransmitter with the B/I method by choosing the optimal timing for pre- and poststimulus scanning. METHODS: Two sources of variability in deltaBP were considered: within-subject and between-subject noise. A noise model based on a phantom study and human data was used to evaluate the within-subject noise. For between-subject noise, simulated time--activity curves were generated from measured [11C]raclopride input functions. Optimal timing to measure deltaBP was determined and applied to human data. RESULTS: According to the simulation study, the optimal scan times for pre-and poststimulus scans were 39-50 and 58-100 min, respectively. The optimal timing resulted in a 28% noise reduction compared with the original timing. By applying the optimal timing to human studies, the statistical significance of the difference in deltaBP between patients with schizophrenia and healthy volunteers increased from P = 0.038 to 0.012. CONCLUSION: Careful assessment of the sources of noise in receptor imaging studies can increase the sensitivity of the B/I method for the detection of biologic signals.

Adult↗

A practical algorithm for optimal inference of haplotypes from diploid populations.

The next phase of human genomics will involve large-scale screens of populations for significant DNA polymorphisms, notably single nucleotide polymorphisms (SNP's). Dense human SNP maps are currently under construction. However, the utility of those maps and screens will be limited by the fact that humans are diploid, and that it is presently difficult to get separate data on the two "copies". Hence genotype (blended) SNP data will be collected, and the desired haplotype (partitioned) data must then be (partially) inferred. A particular non-deterministic inference algorithm was proposed and studied before SNP data was available, and extensively applied more recently to study the first available SNP data. In this paper, we consider the question of whether we can obtain an efficient, deterministic variant of that method to optimize the obtained inferences. Although we have shown elsewhere that the optimization problem is NP-hard, we present here a practical approach based on (integer) linear programming. The method either returns the optimal answer, and a declaration that it is the optimal, or declares that it has failed to find the optimal. The approach works quickly and correctly, finding the optimal on all simulated data tested, data that is expected to be more demanding than realistic biological data.

Algorithms↗