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Properties of synergies arising from a theory of optimal motor behavior.

We consider the properties of motor components, also known as synergies, arising from a computational theory (in the sense of Marr, 1982) of optimal motor behavior. An actor's goals were formalized as cost functions, and the optimal control signals minimizing the cost functions were calculated. Optimal synergies were derived from these optimal control signals using a variant of nonnegative matrix factorization. This was done using two different simulated two--joint arms--an arm controlled directly by torques applied at the joints and an arm in which forces were applied by muscles--and two types of motor tasks-reaching tasks and via-point tasks. Studies of the motor synergies reveal several interesting findings. First, optimal motor actions can be generated by summing a small number of scaled and time-shifted motor synergies, indicating that optimal movements can be planned in a low-dimensional space by using optimal motor synergies as motor primitives or building blocks. Second, some optimal synergies are task independent--they arise regardless of the task context-whereas other synergies are task dependent--they arise in the context of one task but not in the contexts of other tasks. Biological organisms use a combination of task--independent and task--dependent synergies. Our work suggests that this may be an efficient combination for generating optimal motor actions from motor primitives. Third, optimal motor actions can be rapidly acquired by learning new linear combinations of optimal motor synergies. This result provides further evidence that optimal motor synergies are useful motor primitives. Fourth, synergies with similar properties arise regardless if one uses an arm controlled by torques applied at the joints or an arm controlled by muscles, suggesting that synergies, when considered in "movement space," are more a reflection of task goals and constraints than of fine details of the underlying hardware.

Animals↗

Optimal constant positive airway pressure assessed by arterial alveolar difference for CO2 in hyaline membrane disease.

In a group of infants with hyaline membrane disease, the level of optimal constant positive airway pressure (CPAP) was assessed by raising CPAP in small steps from an initial low value, and after each change measuring the arterial alveolar difference for CO2 (aADCO2) and transmission of airway pressure to the esophagus. Below optimal CPAP there was a progressive increase in mixed alveolar partial pressure of CO2 (PACO2) and no change in arterial partial pressure of CO2 (PaCO2), so that aADCO2 declined and reached a lowest value at optimal CPAP. Correspondingly, transmission of airway pressure increased progressively and reached a highest value at optimal CPAP. Between 1 step below and optimal CPAP, PACO2 rose from 30.9 to 34.0 torr, and aADCO2 declined from 16.6 to 12.7 torr. Between optimal and 1 step above optimal CPAP, PaCO2 increased from 46.7 to 51.0 torr, PACO2 rose slightly, and aADCO2 increased from 12.7 to 15.6 torr. Thus, the aADCO2 was an excellent index of optimal CPAP. In five patients with measurements of PaO2 at constant fractional inspired oxygen, calculated values for arterial oxygen saturation changed from 80.8 to 91.5 to 92.2%, and calculated values for venous admixture changed from 0.61 to 0.48 to 0.46 as CPAP was raised from 1 step below through optimal to 1 step above optimal CPAP. The results are interpreted to mean a progressive improvement in perfusion of well ventilated lung units as CPAP increased to optimal levels, but a significant reduction of both ventilation and perfusion above optimal CPAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗

Dynamic optimization of hybridoma growth in a fed-batch bioreactor.

This study addressed the problem of maximizing cell mass and monoclonal antibody production from a fed-batch hybridoma cell culture. We hypothesized that inaccuracies in the process model limited the mathematical optimization. On the basis of shaker flask data, we established a simple phenomenological model with cell mass and lactate production as the controlled variables. We then formulated an optimal control algorithm, which calculated the process-model mismatch at each sampling time, updated the model parameters, and re-optimized the substrate concentrations dynamically throughout the time course of the batch. Manipulated variables were feed rates of glucose and glutamine. Dynamic parameter adjustment was done using a fuzzy logic technique, while a heuristic random optimizer (HRO) optimized the feed rates. The parameters selected for updating were specific growth rate and the yield coefficient of lactate from glucose. These were chosen by a sensitivity analysis. The cell mass produced using dynamic optimization was compared to the cell mass produced for an unoptimized case, and for a one-time optimization at the beginning of the batch. Substantial improvements in reactor productivity resulted from dynamic re-optimization and parameter adjustment. We demonstrated first that a single offline optimization of substrate concentration at the start of the batch significantly increased the yield of cell mass by 27% over an unoptimized fermentation. Periodic optimization online increased yield of cell mass per batch by 44% over the single offline optimization. Concomitantly, the yield of monoclonal antibody increased by 31% over the off-line optimization case. For batch and fed-batch processes, this appears to be a suitable arrangement to account for inaccuracies in process models. This suggests that implementation of advanced yet inexpensive techniques can improve performance of fed-batch reactors employed in hybridoma cell culture.

Antibodies, Monoclonal↗

HIV treatments optimism among gay men: an international perspective.

OBJECTIVE: To examine HIV optimism (i.e., optimism in the light of highly active antiretroviral therapy [HAART]) among gay men in four industrialized countries using a standard scale. METHODS: Gay men were surveyed between January and December 2000 in Australia (Sydney and Melbourne, n = 3,120), Canada (Vancouver, n = 357), England (London, n = 690), and France (Paris, n = 1,715). Information was collected on HIV status, sexual behavior, and responses to a four-item HIV optimism scale. Possible responses to each item were as follows: strongly disagree, 1; disagree, 2; agree, 3; and strongly agree, 4. Agreement indicated optimism in the light of new HIV drug therapies. Total scores could range from a minimum of 4 (strongly disagree on all four items [i.e., not at all optimistic]) to a maximum of 16 (strongly agree on all four items [i.e., extremely optimistic]). RESULTS: In all cities, mean scores on the four-item scale were low (<7), indicating that for the most part men disagreed with the optimism statements. Mean scores were lowest in Paris (p <.001). There was no consistent relationship between mean optimism score and HIV status. In multivariate analysis, the association between mean optimism score and both city (p <.001) and HIV status (p =.05) was significant as was the interaction between city and HIV status (p =.02); the association between mean optimism score and age was not significant (p =.6). In London, Paris, and Sydney/Melbourne but not Vancouver, the mean optimism scores for men reporting high-risk sexual behavior were higher than scores for other men (p <.001). CONCLUSION: In the year 2000, only a few gay men in Australian, Canadian, and European cities were optimistic in the light of new HIV drug therapies. Although there was an association between HIV optimism and high-risk sexual behavior, causality could not be established. The lack of a consistent association between HIV optimism and HIV status across the cities suggests heterogeneity in gay men's response to HAART in different countries.

Adult↗

Piezoelectric transducer design via multiobjective optimization.

The design of piezoelectric transducers is usually based on single-objective optimization only. In most practical applications of piezoelectric transducers, however, there exist multiple design objectives that often are contradictory to each other by their very nature. It is impossible to find a solution at which each objective function gets its optimal value simultaneously. Our design approach is to first find a set of Pareto-optimal solutions, which can be considered to be best compromises among multiple design objectives. Among these Pareto-optimal solutions, the designer can then select the one solution which he considers to be the best one. In this paper we investigate the optimal design of a Langevin transducer. The design problem is formulated mathematically as a constrained multiobjective optimization problem. The maximum vibration amplitude and the minimum electrical input power are considered as optimization objectives. Design variables involve continuous variables (dimensions of the transducer) and discrete variables (the number of piezoelectric rings and material types). In order to formulate the optimization problem, the behavior of piezoelectric transducers is modeled using the transfer matrix method based on analytical models. Multiobjective evolutionary algorithms are applied in the optimization process and a set of Pareto-optimal designs is calculated. The optimized results are analyzed and the preferred design is determined.

Journal Article↗

Comparison of traditional low-dose-rate to optimized and nonoptimized high-dose-rate tandem and ovoid dosimetry.

PURPOSE: Few dose specification guidelines exist when attempting to perform high-dose-rate (HDR) dosimetry. The purpose of this study was to model low-dose-rate (LDR) dosimetry, using parameters common in HDR dosimetry, to achieve the "pear-shape" dose distribution achieved with LDR tandem and ovoid applications. METHODS AND MATERIALS: Radiographs of Fletcher-Suit LDR applicators and Nucletron "Fletcher-like" HDR applicators were taken with the applicators in an idealized geometry. Traditional Fletcher loadings of 3M Cs-137 sources and the Theratronics Planning System were used for LDR dosimetry. HDR dosimetry was performed using the Nucletron Microselectron HDR UPS V11.22 with an Ir-192 source. Dose optimization points were initially located along a line 2 cm lateral to the tandem, beginning at the tandem tip at 0.5-cm intervals, ending at the sail, and optimized to 100% of the point A dose. A single dose optimization point was also placed laterally from the center of each ovoid equal to the radius of the ovoid (ovoid surface dose). For purposes of comparison, dose was also calculated for points A and B, and a point located 1 cm superior to the tandem tip in the plane of the tandem, (point F). Four- and 6-cm tandem lengths and 2.0-, 2.5-, and 3.0-cm ovoid diameters were used for this study. Based on initial findings, dose optimization schemes were developed to best approximate LDR dosimetry. Finally, radiographs were obtained of HDR applications in two patients. These radiographs were used to compare the optimization schemes with "nonoptimized" treatment plans. RESULTS: Calculated doses for points A and B were similar for LDR, optimized HDR, and nonoptimized HDR. The optimization scheme that used tapered dose points at the tandem tip and optimized a single ovoid surface point on each ovoid to 170% of point A resulted in a good approximation of LDR dosimetry. Nonoptimized HDR resulted in higher doses at point F, the bladder, and at points lateral to the tandem tip than both the optimized plan or the LDR plan. CONCLUSION: Optimized HDR allows specification of dose to points of interest, can approximate LDR dosimetry, and appears superior to nonoptimized HDR treatment planning, at least at the tandem tip. An optimization scheme is presented that approximates LDR dosimetry.

Brachytherapy↗

Optimization of beam weights in conformal radiotherapy planning of stage III non-small cell lung cancer: effects on therapeutic ratio.

PURPOSE: To evaluate the effects of beam weight optimization for 3D conformal radiotherapy plans, with or without beam intensity modulation, in Stage III non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: Ten patients with Stage III NSCLC were planned using a conventional 3D technique and a technique involving noncoplanar beam intensity modulation (BIM). Two planning target volumes (PTVs) were defined: PTV1 included macroscopic tumor volume and PTV2 included macroscopic and microscopic tumor volume. Virtual simulation defined the beam shapes and incidences as well as the wedge orientations (3D) and segment outlines (BIM). Weights of wedged beams, unwedged beams, and segments were determined by human trial and error for the 3D-plans (3D-manual), by a standard weight table (SWT) for the BIM-plans (BIM-SWT) and by optimization (3D-optimized and BIM-optimized) using an objective function with a biological and a physical component. The resulting non-optimized and optimized dose distributions were compared, using physical endpoints, after normalizing the median dose of PTV1 to 80 Gy. RESULTS: Optimization improved dose homogeneity at the target for 3D- and BIM-plans and the minimum dose at PTV1. The minimum dose at PTV2 was decreased by optimization especially in 3D-plans. After optimization, the dose-volume histograms (DVHs) of lung and heart were shifted to lower doses for 80-90% of the organ volume. Since lung is the dose-limiting organ in Stage III NSCLC, an increased minimum dose at PTV1 together with a decreased dose at the main lung volume suggests an improved therapeutic ratio. Optimization allows 10% dose escalation for 3D-plans and 20% for BIM-plans at isotoxicity levels of lung and spinal cord. Upon dose escalation, esophagus may become the dose-limiting structure when PTV1 extends close to the esophagus. CONCLUSIONS: Optimization using a biophysical objective function allowed an increase of the therapeutic ratio of radiotherapy planning for Stage III NSCLC.

Algorithms↗

Optimization of individual and population designs using Splus.

We address the problem of design optimization for individual and population pharmacokinetic studies. We develop Splus generic functions for pharmacokinetic design optimization: IFIM, a function for individual design optimization similar to the ADAPT II software, and PFIM_OPT, a function for population design optimization which is an extension of the Splus function PFIM for population design evaluation. Both evaluate and optimise designs using the Simplex algorithm. IFIM optimizes the sampling times in continuous intervals of times; PFIM_OPT optimizes either, for a given group structure of the population design, only the sampling times taken in some given continuous intervals or, both the sampling times and the group structure, performing then statistical optimization. A combined variance error model can be supplied with the possibility to include parameters of the error model as parameters to be estimated. The performance of the optimization with the Simplex algorithm is demonstrated with two pharmacokinetic examples: by comparison of the optimized designs to those of the ADAPT II software for IFIM, and to those obtained using a grid search or the Fedorov-Wynn algorithm for PFIM_OPT. The influence of the variance error model on design optimization was investigated. For a given total number of samples, different group structures of a population design are compared, showing their influence on the population design efficiency. The functions IFIM and PFIM_OPT offer new efficient solutions for the increasingly important task of optimization of individual or population pharmacokinetic designs.

Algorithms↗

Absence of multiple local minima effects in intensity modulated optimization with dose-volume constraints.

This paper reports on the analysis of intensity modulated radiation treatment optimization problems in the presence of non-convex feasible parameter spaces caused by the specification of dose-volume constraints for the organs-at-risk (OARs). The main aim was to determine whether the presence of those non-convex spaces affects the optimization of clinical cases in any significant way. This was done in two phases: (1) Using a carefully designed two-dimensional mathematical phantom that exhibits two controllable minima and with randomly initialized beamlet weights, we developed a methodology for exploring the nature of the convergence characteristics of quadratic cost function optimizations (deterministic or stochastic). The methodology is based on observing the statistical behaviour of the residual cost at the end of optimizations in which the stopping criterion is progressively more demanding and carrying out those optimizations to very small error changes per iteration. (2) Seven clinical cases were then analysed with dose-volume constraints that are stronger than originally used in the clinic. The clinical cases are two prostate cases differently posed, a meningioma case, two head-and-neck cases, a spleen case and a spine case. Of the 14 different sets of optimizations (with and without the specification of maximum doses allowed for the OARs), 12 fail to show any effect due to the existence of non-convex feasible spaces. The remaining two sets of optimizations show evidence of multiple minima in the solutions, but those minima are very close to each other in cost and the resulting treatment plans are practically identical, as measured by the quality of the dose-volume histograms (DVHs). We discuss the differences between fluence maps resulting from those similar treatment plans. We provide a possible reason for the observed results and conclude that, although the study is necessarily limited, the annealing characteristics of a simulated annealing method may not be justified in clinical optimization in the presence of dose-volume constraints. The results of optimizations by the Newton gradient (NG) method with a quadratic cost function are reported in detail. An adaptive simulated annealing method, optimizing the same function, and the dynamically penalized likelihood method, optimizing a log likelihood function, have also been used in the study. The results of the latter two methods have only been discussed briefly, as they yielded the same conclusions as the NG method.

Algorithms↗

Optimism, distress, health-related quality of life, and change in cancer antigen 125 among patients with ovarian cancer undergoing chemotherapy.

OBJECTIVE: This study investigated whether situational and dispositional optimism were protective against dimensions of distress and aspects of health-related quality of life (HQoL) in patients with ovarian cancer undergoing chemotherapy. This study also evaluated whether optimism predicted a decrease in cancer antigen (CA) 125 levels during treatment. METHODS: Ninety women with epithelial ovarian cancer were assessed at the start and end of chemotherapy. Optimism, distress, and HQoL were measured by self-report; CA 125 levels were gathered from patients' medical charts. RESULTS: Both measures of optimism were inversely associated with baseline anxiety, perceived stress, and depression. In addition, situational optimism was positively associated with baseline social and physical well-being, and dispositional optimism was positively associated with baseline social and functional well-being. However, neither measure of optimism predicted domains of distress or HQoL at the follow-up assessment after controlling for baseline levels. Dispositional optimism predicted CA 125 at the end of treatment after controlling for baseline levels. However, neither situational nor dispositional optimism predicted CA 125 falling to normal levels (< or =35 U/mL). CONCLUSION: Consistent with prior research, optimism was inversely associated with distress and positively associated with HQoL in patients with ovarian cancer undergoing chemotherapy. Higher levels of dispositional optimism at the start of chemotherapy were associated with a greater decline in patients' CA 125 during treatment.

Adult↗

Iterative regularization in intensity-modulated radiation therapy optimization.

A common way to solve intensity-modulated radiation therapy (IMRT) optimization problems is to use a beamlet-based approach. The approach is usually employed in a three-step manner: first a beamlet-weight optimization problem is solved, then the fluence profiles are converted into step-and-shoot segments, and finally postoptimization of the segment weights is performed. A drawback of beamlet-based approaches is that beamlet-weight optimization problems are ill-conditioned and have to be regularized in order to produce smooth fluence profiles that are suitable for conversion. The purpose of this paper is twofold: first, to explain the suitability of solving beamlet-based IMRT problems by a BFGS quasi-Newton sequential quadratic programming method with diagonal initial Hessian estimate, and second, to empirically show that beamlet-weight optimization problems should be solved in relatively few iterations when using this optimization method. The explanation of the suitability is based on viewing the optimization method as an iterative regularization method. In iterative regularization, the optimization problem is solved approximately by iterating long enough to obtain a solution close to the optimal one, but terminating before too much noise occurs. Iterative regularization requires an optimization method that initially proceeds in smooth directions and makes rapid initial progress. Solving ten beamlet-based IMRT problems with dose-volume objectives and bounds on the beamlet-weights, we find that the considered optimization method fulfills the requirements for performing iterative regularization. After segment-weight optimization, the treatments obtained using 35 beamlet-weight iterations outperform the treatments obtained using 100 beamlet-weight iterations, both in terms of objective value and of target uniformity. We conclude that iterating too long may in fact deteriorate the quality of the deliverable plan.

Algorithms↗

Finite burn maneuver modeling for a generalized spacecraft trajectory design and optimization system.

The modeling, design, and optimization of finite burn maneuvers for a generalized trajectory design and optimization system is presented. A generalized trajectory design and optimization system is a system that uses a single unified framework that facilitates the modeling and optimization of complex spacecraft trajectories that may operate in complex gravitational force fields, use multiple propulsion systems, and involve multiple spacecraft. The modeling and optimization issues associated with the use of controlled engine burn maneuvers of finite thrust magnitude and duration are presented in the context of designing and optimizing a wide class of finite thrust trajectories. Optimal control theory is used examine the optimization of these maneuvers in arbitrary force fields that are generally position, velocity, mass, and are time dependent. The associated numerical methods used to obtain these solutions involve either, the solution to a system of nonlinear equations, an explicit parameter optimization method, or a hybrid parameter optimization that combines certain aspects of both. The theoretical and numerical methods presented here have been implemented in copernicus, a prototype trajectory design and optimization system under development at the University of Texas at Austin.

Journal Article↗

Effect of dietary optimization on growth, survival, tumor incidences and clinical pathology parameters in CD Sprague-Dawley and Fischer-344 rats: a 104-week study.

Controversy regarding the use of ad libitum feeding in chronic rodent toxicity studies will soon result in issue of a FDA Points to Consider document. Caloric intakes are now recognized to be important uncontrolled variables in bioassays because rodents chronically fed ad libitum become obese, reproductively senile and have increased incidences of age-related diseases, higher tumor burdens and decreased survival. The available literature suggests that ad libitum feeding neither optimizes the health and well-being of rodents nor provides the best model for use in evaluation of pharmacological and toxicological profiles. Use of an optimized diet, restricted in terms of caloric intakes, has been proposed for chronic toxicity and carcinogenicity studies in rodents. It is suggested that limiting caloric intakes to 50-80% of ad libitum consumption would result in lower body weights, decreased tumor incidences and prolonged survival in the controls. To evaluate the influence of diet on chronic toxicity and carcinogenicity studies in rats, two 104-week studies were conducted. These studies consisted of 280 CD Sprague-Dawley and 280 Fischer-344 rats fed ad libitum, and 140 CD Sprague-Dawley and 140 Fischer-344 rats fed a diet that was optimized by limiting caloric intakes by 15-35%. Both diets consisted of certified commercial diet in meal form. The optimized diet reduced weight gain approximately 50% after 100 weeks. Clinical chemistry and hematology parameters showed negligible effects of reduced diet, with the exception that serum triglycerides were lower in males and females in both strains at weeks 52 and 104. The ad libitum-fed animals had a higher incidence of pseudopregnancy, aggressiveness, foot sores and abscesses than the animals fed an optimized diet. These effects were more pronounced in the CD Sprague-Dawley rats than in the Fischer-344 rats. At the completion of the 104-week study, survival in the ad libitum fed CD Sprague-Dawley rats was approximately one-half that of the animals fed an optimized diet (39% versus 76%). The difference in survival between Fischer-344 rats fed ad libitum and those fed an optimized diet was less pronounced (78% versus 89%). A reduced incidence of palpable tissue masses in the ad libitum-fed CD Sprague-Dawley rats versus the animals fed an optimized diet reflected inability to detect small masses in the obese ad libitum-fed animals. In contrast, the leaner Fischer-344 ad libitum-fed animals had an increased incidence of palpable tissue masses. After 52 weeks, 40 animals from each strain and feeding regimen were killed and subjected to complete necropsy and histopathological examination; the remainder of the survivors was examined at the completion of the study (104 weeks). Use of an optimized diet substantially reduced the incidences of endocrine-mediated tumors in both rat strains and delayed the onset of leukemia in Fischer-344 rats. These results indicate the need to further investigate the relationship of increased caloric intakes and endocrine-mediated or strain specific tumors and support FDA's and others' positions that use of diet optimization in chronic toxicity and carcinogenicity rodent bioassays has the potential to remarkably improve the scientific quality and relevance of these studies. It also identified that the small increases in cost associated with diet optimization are far exceeded by the advantages of increased survival of animals, reduced intercurrent disease and rumor burdens, and increased ease of histopathological processing and evaluation.

Animals↗

Performance of the OptiMAL test for malaria diagnosis among suspected malaria patients at the rural health centers.

The OptiMAL test detects both Plasmodium falciparum and P. vivax malaria infections. In this study, we evaluated the performance of the OptiMAL test at the Basic Health Units (BHUs) and the District Health Quarter (DHQ) Center in rural villages of Punjab, Pakistan that provide minimal health services. Two sets of blood specimens obtained from 930 suspected malaria patients attending these BHUs were tested at BHUs and the DHQ Center by microscopy and the OptiMAL test. At the BHUs, 231 (25%) of the patients were positive by microscopy and 278 (30%) patients tested positive by the OptiMAL test. At the DHQ Center, microscopic analysis of a second set of specimens from the same patients confirmed the malaria infection in 386 (42%) patients and the OptiMAL test result was positive in 300 (32%) patients. To determine the performance of OptiMAL test at the BHUs and the DHQ Center, all data were compared with microscopy results obtained at the DHQ Center. The OptiMAL test results for P. falciparum at the BHUs were comparable to those of the OptiMAL test at the DHQ Center. However, the sensitivity, positive predictive value (PPV), and negative predictive value (NPV) of the OptiMAL test were considerably lower for P. vivax infections than for P. falciparum infections, irrespective of whether the test was performed at the BHUs or at the DHQ Center (P. falciparum: sensitivity = 78-85%, PPV = 89-97%, NPV = 96-98%; P. vivax: sensitivity = 61-76%, PPV = 88-95%, NPV = 90-93%). The OptiMAL test also detected a number of false-positive and false-negative results at both the BHUs and the DHQ Center. The false-positive results ranged from 1% to 2%; however, the number of false-negative results was much higher (BHUs: P. falciparum = 22%, P. vivax = 39%; DHQ Center: P. falciparum = 15%, P. vivax = 24%). In conclusion, these results, when combined with other advantages of the OptiMAL test, suggest that this test can be used by relatively inexperienced persons to diagnose malaria infection in rural areas where facilities for microscopy are not available.

Adolescent↗

[Fast optimization of stepwise gradient conditions for ternary mobile phase in reversed-phase high performance liquid chromatography].

In high performance liquid chromatography, it is necessary to apply multi-composition gradient elution for the separation of complex samples such as environmental and biological samples. Multivariate stepwise gradient elution is one of the most efficient elution modes, because it combines the high selectivity of multi-composition mobile phase and shorter analysis time of gradient elution. In practical separations, the separation selectivity of samples can be effectively adjusted by using ternary mobile phase. For the optimization of these parameters, the retention equation of samples must be obtained at first. Traditionally, several isocratic experiments are used to get the retention equation of solute. However, it is time consuming especially for the separation of complex samples with a wide range of polarity. A new method for the fast optimization of ternary stepwise gradient elution was proposed based on the migration rule of solute in column. First, the coefficients of retention equation of solute are obtained by running several linear gradient experiments, then the optimal separation conditions are searched according to the hierarchical chromatography response function which acts as the optimization criterion. For each kind of organic modifier, two initial linear gradient experiments are used to obtain the primary coefficients of retention equation of each solute. For ternary mobile phase, only four linear gradient runs are needed to get the coefficients of retention equation. Then the retention times of solutes under arbitrary mobile phase composition can be predicted. The initial optimal mobile phase composition is obtained by resolution mapping for all of the solutes. A hierarchical chromatography response function is used to evaluate the separation efficiencies and search the optimal elution conditions. In subsequent optimization, the migrating distance of solute in the column is considered to decide the mobile phase composition and sustaining time of the latter steps until all the solutes are eluted out. Thus the first stepwise gradient elution conditions are predicted. If the resolution of samples under the predicted optimal separation conditions is satisfactory, the optimization procedure is stopped; otherwise, the coefficients of retention equation are adjusted according to the experimental results under the previously predicted elution conditions. Then the new stepwise gradient elution conditions are predicted repeatedly until satisfactory resolution is obtained. Normally, the satisfactory separation conditions can be found only after six experiments by using the proposed method. In comparison with the traditional optimization method, the time needed to finish the optimization procedure can be greatly reduced. The method has been validated by its application to the separation of several samples such as amino acid derivatives, aromatic amines, in which satisfactory separations were obtained with predicted resolution.

Amino Acids↗

[Effect of the optimal neurohormonal blockade on long-term survival in patients with chronic heart failure].

BACKGROUND: In recent years large scale clinical trials have cleary shown that a number of pharmacological treatments can improve the outcomes of patients (pts) with chronic heart failure (CHF). AIM: The aim of this study was to assess the effect of optimal neurohormal blockade in pts with chronic heart failure on survival during 12 month follow-up. METHODS: We analyzed data on 489 pts in NYHA II-IV class of HF, referred to our Dept. (mean age was 69 +/- 12). We define doptimal neurohormonal therapy as beta-blocker and ACE-inhibitor in pts with NYHA II, and beta-blocker, ACE-Inhibitor and spironolactone in patients with NYHA III-IV class. Pts were divided into groups: group 1--optimal neurohormonal blockade (n = 232, mean age, 67 +/- 11), group 2--non-optimal neurohormonal blockade (n = 257, mean age, 70 +/- 13). Pts were followed for 12 month. RESULTS: Group with optimal therapy were frequent male gender, of ischemic aetiology, and NYHA class II (p < 0.05). Diabetes mellitus, hypertension, left ventricular ejection fraction did not differ the groups (p = NS). Pts with non-optimal therapy were more frequent with prior history of renal dysfunction and anemia at admission (p < 0.05). During 12 month follow-up 12% in optimal vs 40% in non-optimal therapy died (p < 0.005). The rehospitalisation rate during one-year was also significantly higher in pts receiving non-optimal therapy (69% vs 48%, p < 0.005). Cox multivariate analysis showed after adjusting for age, gender, etiology of HF, NYHA functional class, renal dysfunction, EF, had significantly 62% reduction in mortality and 41% reduction in cardiovascular rehospitalisation in pts receiving optimal therapy. CONCLUSIONS: The optimal neurohormonal therapy have favorable effects on outcomes in pts with CHF. This data strongly support that optimalization of care and evidence-based treatment of CHF pts can improve poor prognosis in this group.

Adrenergic beta-Antagonists↗

Optimal calcium intake.

The National Institutes of Health Consensus Development Conference on Optimal Calcium Intake brought together experts from many different fields including osteoporosis and bone and dental health, nursing, dietetics, epidemiology, endocrinology, gastroenterology, nephrology, rheumatology, oncology, hypertension, nutrition and public education, and biostatistics, as well as the public, to address the following questions: (1) What is the optimal amount of calcium intake? (2) What are the important cofactors for achieving optimal calcium intake? (3) What are the risks associated with increased levels of calcium intake? (4) What are the best ways to attain optimal calcium intake? (5) What public health strategies are available and needed to implement optimal calcium intake recommendations? and (6) What are the recommendations for future research on calcium intake? The consensus panel concluded that: A large percentage of Americans fail to meet currently recommended guidelines for optimal calcium intake. On the basis of the most current information available, optimal calcium intake is estimated to be 400 mg/day (birth-6 months) to 600 mg/day (6-12 months) in infants; 800 mg/day in young children (1-5 years) and 800-1,200 mg/day for older children (6-10 years); 1,200-1,500 mg/day for adolescents and young adults (11-24 years); 1,000 mg/day for women between 25 and 50 years; 1,200-1,500 mg/day for pregnant or lactating women; and 1,000 mg/day for postmenopausal women on estrogen replacement therapy and 1,500 mg/day for postmenopausal women not on estrogen therapy. Recommended daily intake for men is 1,000 mg/day (25-65 years). For all women and men over 65, daily intake is recommended to be 1,500 mg/day, although further research is needed for this age group. These guidelines are based on calcium from the diet plus any calcium taken in supplemental form. Adequate vitamin D is essential for optimal calcium absorption. Dietary constituents, hormones, drugs, age, and genetic factors influence the amount of calcium required for optimal skeletal health. Calcium intake, up to a total intake of 2,000 mg/day, appears to be safe in most individuals. The preferred source of calcium is through calcium-rich foods such as dairy products. Calcium-fortified foods and calcium supplements are other means by which optimal calcium intake can be reached in those who cannot meet this need by ingesting conventional foods. A unified public health strategy is needed to ensure optimal calcium intake in the American population. The full text of the consensus panel's statement follows.

Absorption↗

Optimal calcium intake. Sponsored by National Institutes of Health Continuing Medical Education.

The National Institutes of Health Consensus Development Conference on Optimal Calcium Intake brought together experts from many different fields including osteoporosis and bone and dental health, nursing, dietetics, epidemiology, endocrinology, gastroenterology, nephrology, rheumatology, oncology, hypertension, nutrition and public education, and biostatistics, as well as the public, to address the following questions: 1) What is the optimal amount of calcium intake? 2) What are the important cofactors for achieving optimal calcium intake? 3) What are the risks associated with increased levels of calcium intake? 4) What are the best ways to attain optimal calcium intake? 5) What public health strategies are available and needed to implement optimal calcium intake recommendations? and 6) What are the recommendations for future research on calcium intake? The consensus panel concluded that: A large percentage of Americans fail to meet currently recommended guidelines for optimal calcium intake. On the basis of the most current information available, optimal calcium intake is estimated to be 400 mg/day (birth-6 months) to 600 mg/day (6-12 months) in infants; 800 mg/day in young children (1-5 years) and 800-1,200 mg/day for older children (6-10 years); 1,200-1,500 mg/day for adolescents and young adults (11-24 years); 1,000 mg/day for women between 25 and 50 years; 1,200-1,500 mg/day for pregnant or lactating women; and 1,000 mg/day for postmenopausal women on estrogen replacement therapy and 1,500 mg/day for postmenopausal women not on estrogen therapy. Recommended daily intake for men is 1,000 mg/day (25-65 years). For all women and men over 65, daily intake is recommended to be 1,500 mg/day, although further research is needed for this age group. These guidelines are based on calcium from the diet plus any calcium taken in supplemental form. Adequate vitamin D is essential for optimal calcium absorption. Dietary constituents, hormones, drugs, age, and genetic factors influence the amount of calcium required for optimal skeletal health. Calcium intake, up to a total intake of 2,000 mg/day, appears to be safe in most individuals. The preferred source of calcium is through calcium-rich foods such as dairy products. Calcium-fortified foods and calcium supplements are other means by which optimal calcium intake can be reached in those who cannot meet this need by ingesting conventional foods. A unified public health strategy is needed to ensure optimal calcium intake in the American population.

Absorption↗