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PubMedDate not supplied

A model for planning optimal follow-up for outpatients on warfarin anticoagulation. Warfarin Optimal Outpatient Follow-up Study Group.

Patients taking warfarin for long-term anticoagulation require frequent clinic visits to monitor the prothrombin time ratio (PTR), a measure of blood clotting. A dynamic stochastic model using nonlinear optimization was developed to select follow-up visit intervals that minimize the overall costs of patient care. Assuming that fluctuations in a patient's PTR behave as a random diffusion process, future PTR fluctuations are unknown, except as revealed by past PTRs. To determine the incidence and costs of complications in relation to PTR, the authors reviewed the charts of 216 patients who had 719 patient-years of follow-up with 695 trivial, significant, life-threatening, or fatal complications. They modeled the relationship between costs of complications and deviation of the PTR from the therapeutic target as a fourth-order convex polynomial. The model is used to compute the interval to the next follow-up visit to minimize accumulated potential costs. Variables in the optimization are the cost of a monitoring visit and the expected costs of complications. The latter are derived from the current PTR, the variability of the patient's past PTR values, the number of past PTRs available, and the target PTR for the patient. No attempt is made to predict the level of the next PTR or suggest adjustments in the warfarin dose. Shorter follow-up is recommended for patients who have histories of large fluctuations in past PTRs and for patients with few prior PTR determinations. As visits accumulate, the patient's degree of variability can be estimated more accurately and visit intervals adjusted accordingly. The scheduling method balances costs to the health care system of monitoring each patient against the expected costs of complications. This approach has the potential to reduce the number of monitoring visits necessary for safe management of anticoagulated patients with stable PTRs and to improve control among unstable patients.

Aged↗
PubMed1990

Studies on the optimal immunization schedule of experimental animals. IV. The optimal age and sex of mice, and the influence of booster injections.

To establish the optimal condition for preparing mouse antiserum specific to a drug, the optimal age and sex of mice for the immune response were studied by measuring the mouse serum levels of total immunoglobulin G (IgG) and specific antibody to viomycin, as well as the changes in weight of mice immunized with a viomycin immunogen. It was observed that age was a more important factor than sex, and strongly affected productions of both total and specific IgGs of mice. The mice aged 8 weeks yielded the highest levels of both total IgG and the specific antibody. In the study on the influence of booster schedule, the number of boosters given had a larger influence on the immune response than the interval between priming and boosters. The greater the number of booster shots given, the less was the production of total and specific antibodies. The decrease in the weight of mice after immunization was also studied in more detail; it was found that it only occurred in the first week after priming but not after a booster injection. The mice aged eight weeks showed the largest weight loss.

Aging↗
PubMedDate not supplied

[Means of optimizing conversion of light energy in the primary stages of photosynthesis. I. The need for optimizing the structure of a photosynthetic unit and calculation of its efficiency].

It is shown, that the photosynthetic unit structure is to be strongly optimized in vivo to operate with a 90% quantum yield of primary charge separation in reaction centers, which means that a macroscopic photosynthetic unit is neither uniform nor isotropic. Some requirements for optimization of photosynthetic unit structure are determined. The modified probability matrix method to simulate the excitation energy transfer in photosynthesis is proposed. The method is adapted to excitation trapping time (but not to excitation jumps number) calculation. The calculations assume a Förster inductive resonance mechanism for energy transfer within light-harvesting antenna and pairwise dipolar interactions.

Light↗
PubMed1996

Some optimal and non-optimal two-stage designs using an alpha-spending function.

While designing a group sequential clinical trial in the pharmaceutical industry setting, we often face a problem of determining the time for an interim analysis. For a two-stage trial we compute the sample sizes n and N per treatment group for the interim and final analyses, respectively, that minimize the average trial size for a specified overall power. We consider this optimization when we monitor the trial using a Lan-DeMets alpha-spending function. Two additional problems considered in this context are (i) finding the sample sizes that maximize the overall power for a specified average trial size, and (ii) finding the sample sizes that achieve specified powers at the interim and final analyses.

Algorithms↗
PubMed2006

An optimal range of transcription potency is necessary for efficient cell transformation by c-Rel to ensure optimal nuclear localization and gene-specific activation.

c-Rel is overexpressed in several B-cell lymphomas and c-rel gene overexpression can transform primary chicken lymphoid cells and induce tumors in animals. Although c-Rel is generally a stronger transcriptional activator than its viral derivative v-Rel, its oncogenic activity is significantly weaker. Among the mutations acquired during c-Rel's evolution into v-Rel are deletion of c-Rel's transactivation domain 2 (cTAD2) and mutations in cTAD1. Given the critical role of the Rel TADs in cell transformation, we investigated how mutations in c-Rel's cTAD1 and cTAD2 contribute to its oncogenicity and that of v-Rel. Mutations in cTAD2 noticeably increased c-Rel's transforming activity by promoting its nuclear localization and gene-specific transactivation, despite an overall decrease in kappaB site-dependent transactivation potency. Conversely, substitution of vTAD by cTAD1 increased v-Rel's transactivation and transforming efficiencies, whereas its substitution by the stronger cTAD2 compromised activation of mip-1beta but not irf-4 and was detrimental to cell transformation. These results suggest that the Rel TADs differentially contribute to gene-specific activation and that an optimal range of transcription potency is necessary for efficient transformation. These findings may have important implications for understanding how Rel TAD mutations can lead to a more oncogenic phenotype.

Amino Acid Sequence↗
PubMed2006

Optimized effective potential from a correlated wave function: optimized effective potential-generalized valence bond (OEP-GVB).

The optimized effective potential (OEP) method allows orbital-dependent functionals to be used in density functional theory. Traditionally the orbital-dependent functional of interest has been the Hartree-Fock energy, leading to exact exchange density functional theory. Here we present results that use a generalized valence-bond (GVB) wave function, a multiconfigurational wave function that includes static correlation and dissociates to the proper limits. We demonstrate the effectiveness of the OEP-GVB method by showing the dissociation of H2 and the excitation spectrum of He.

Journal Article↗
PubMedDate not supplied

Cardiac resynchronization therapy: optimizing the device, optimizing the patient.

Heart failure is a major health problem in the United States, associated with high morbidity, mortality, and economic burden. Despite recent advances in pharmacological treatments to attenuate disease progression, medications become relatively ineffective, resulting in worsening congestive symptoms and increased exercise intolerance. Cardiac resynchronization therapy provides a new adjunct for heart failure patients who remain symptomatic despite optimized medical therapies. This article discusses cardiac resynchronization therapy and measures that should be considered to ensure proper functioning of the device and improved quality of life for patients.

Activities of Daily Living↗
PubMedDate not supplied

Optimal selection of a battery of tests: a multiobjective optimization methodology.

The general problem of selecting a battery of tests for diagnostic purposes is discussed and multiobjective optimization methodology is applied to solve it, with battery selection being based on performance indices such as sensitivity, specificity, and the cost of testing. For a battery of tests, the extended majority rule is developed and used to interpret the compound test results. The major advantage of the model developed in this paper is that it can generate a set of noninferior batteries without requiring the calculation of all possible combinations of tests. An example in which the method is applied to a real problem--the selection of short-term tests to detect the carcinogenicity of chemicals--is discussed.

Algorithms↗
PubMed1995

Collaborative work to determine an optimal administration period and optimal parameters for detection of effects on male fertility in rats--male reproductive toxicity study of haloperidol.

Haloperidol, a neuroleptic, was orally administered at 0, 3, 10, 30 and 60 mg/kg/day in a 4-week dosing study, and 0, 3, 10 and 30 mg/kg/day in a 9-week dosing study, to Sprague-Dawley male rats which were then sacrificed for histopathological examination or mated with untreated females. The males in the mating groups were continuously treated during the mating period. Sperm positive females were sacrificed on day 20 of gestation. The males in the histopathology groups were sacrificed after 4- or 9-week dosing and their testes were fixed in Bouin's fluid and sections stained with HE or PAS. The mated males were sacrificed and reproductive organ weights were determined. At 3 mg/kg or more, reduced spontaneous motor activity was observed and body weights were lowered. The absolute weight of testes was decreased with 60 mg/kg in the 4-week dosing study, and was decreased with 10 and 30 mg/kg in the 9-week dosing study. However, the relative weight was increased or showed a tendency to increase. In the 4-week dosing study, decrease in the fertility index with 60 mg/kg and increase in pre-implantation loss with 30 mg/kg or more were noted. However, there were no adverse effects on the copulation index in any of the treated groups. The males given 60 mg/kg showed slight changes in the testes (necrosis of pachytene spermatocytes in seminiferous tubules of stage VII, exfoliation of round spermatids in the lumina and atrophy of Leydig cells) and seminal vesicles (atrophy of epithelial cells). Atrophy of Leydig cells was also observed at 30 mg/kg in the 4-week dosing study. In the 9-week dosing study, neither male reproductive ability nor histopathological parameters were affected by haloperidol up to 30 mg/kg. From the results detailed above, it may be concluded that 4-weeks dosing before mating is suitable for detection of effects of haloperidol on male reproductive ability, and that histopathological changes together provide an optimal parameter for predicting male reproductive disorders.

Animals↗
PubMed2001

Partnering for optimal respiratory home care: physicians working with respiratory therapists to optimally meet respiratory home care needs.

The need for respiratory care services continues to increase, reimbursement for those services has decreased, and cost-containment measures have increased the frequency of home health care. Respiratory therapists are well qualified to provide home respiratory care, reduce misallocation of respiratory services, assess patient respiratory status, identify problems and needs, evaluate the effect of the home setting, educate the patient on proper equipment use, monitor patient response to and complications of therapy, monitor equipment functioning, monitor for appropriate infection control procedures, make recommendations for changes to therapy regimen, and adjust therapy under the direction of the physician. Teamwork benefits all parties and offers cost and time savings, improved data collection and communication, higher job satisfaction, and better patient monitoring, education, and quality of life. Respiratory therapists are positioned to optimize treatment efficacy, maximize patient compliance, and minimize hospitalizations among patients receiving respiratory home care.

Health Services Needs and Demand↗
PubMed2002

Rapid optimization: strategies for optimal care of decompensated congestive heart-failure patients in the emergency department.

Sooner or later all heart failure patients will present to the emergency department for medical attention. The American demographic trend of a skyrocketing elderly population coupled with the current heart-failure epidemic means that strategies optimizing emergency department care of heart failure are needed. Safe and effective management has the potential to decrease hospitalizations and intensive care unit admissions, prevent readmissions, and improve the quality of life in the heart-failure patient, as well as relieving some of the economic burden of heart-failure management from the U.S. medical care system. The emergency department observation unit provides a successful venue for the management of decompensated heart failure, and nesiritide offers the promise of shorter hospitalizations, improved quality of life, and better symptom resolution than standard therapy.

Atrial Natriuretic Factor↗
PubMed1992

Optimization of high-performance liquid chromatographic assay for catecholamines. Determination of optimal mobile phase composition and elimination of species-dependent differences in extraction recovery of 3,4-dihydroxybenzylamine.

This paper describes the application of a window diagram technique to optimize the four components of eluent (sodium acetate, sodium heptanesulfonate, acetonitrile and pH adjusted by monochloroacetic acid), for complete separation of five catecholamine compounds and the internal standard (3,4-dihydroxybenzylamine, DHBA). In addition, studies were performed to address the problem of the variable recovery of DHBA from dog plasma due to a time-dependent loss of DHBA. We found that this phenomenon can be prevented by pH adjustment prior to addition of DHBA, allowing development of an accurate high-performance liquid chromatographic assay for plasma catecholamines in dogs.

Animals↗
PubMedDate not supplied

[The evolutionarily optimal rates of body development. The age of onset of sexual maturity and species-specific longevity as the parameters optimized during evolution].

Dynamics of biological community of the "resource--consumer" type considering age structure of consumer population is described by a system of differential equations with special derivatives. On the basis of such a model, a competition model for non-crossing populations with different individual development rates is elaborated. It is shown that only a population with development rates maximizing the Malthusian function (reaching zero value at the equilibrium state of the system) is able to survive under competition for food resources. Equilibrium density of the resources is provided being minimal. Thus maximum energy influx into the population is gained. Search algorithm of evolutionary values of puberty, age and maximal longevity of individuals belonging to the consumer population is proposed. Analytic dependence of maximal longevity on environmental factors and some other parameters are found. Aging is considered to be mechanism leading to death while individual approaches evolutionary optimal longevity.

Animals↗
PubMed1995

[Inhaled beclomethasone in long-term management of asthma: optimal dose and optimal duration of treatment].

We studied the usefulness of 24 weeks of therapy with inhaled beclomethasone dipropionate (BDP) in the management of mild and moderately severe asthma in adults. To determine the optimal dose and treatment duration, the patients were divided into three groups. Patients in group I (n = 10) were treated with bronchodilators but no BDP. Patients in group II (n = 12) received bronchodilators and 450 micrograms/day of BDP. Patients in group III (n = 17) received bronchodilators and 900 micrograms/day of BDP. BDP was inhaled via a large spacer (Volumatic). Asthma scores were measured before treatment began, and again every 2 weeks for the duration of the study (26 weeks). Peak expiratory flows (PEF) were measured before treatment began, 2 weeks after treatment had begun, and again every four weeks until the end of the study. Vital capacity, FEV1, and bronchial reactivity to methacholine were measured before treatment began, and again 12 weeks and 24 weeks after it had begun. Adrenocortical function in patients in group III was measured with a rapid ACTH test, at the same time as the pulmonary functions were measured. The results were: 1) Asthma scores decreased more in patients who received the higher dose of BDP than in those who received the lower dose, especially during the second 12 weeks. 2) After two weeks of treatment, %PEF had increased significantly in both groups that received BDP, but after six weeks of treatment there was no further improvement. %PEF did not improve in the group given bronchodilators only. 3) In the patients whose baseline %PEF was less than 80%, only the higher dose of BDP significantly increased %PEF. 4) Only the higher dose of BDP increased the %VC, the FEV1%, and the PD20 for methacholine. 5) Asthma type and severity were not related to the usefulness of BDP therapy. 6) Results of the rapid ACTH test indicated that the higher dose of BDP did not suppress adrenocortical function. These data indicate that 900 micrograms of BDP per day is more effective than 450 micrograms/day as initial therapy for long-term management of mild or moderate asthma in adults, and that the dose of BDP should be reviewed after 3 months of treatment. Patients in whom asthma is well-controlled may tolerate a reduction in dose, and those in whom asthma is not well-controlled may require a higher dose.

Administration, Inhalation↗
PubMed1996

Age, time, entropy, and biological optimality--some remarks on the general problem of biological optimization.

The purpose of this paper is to look from a very general viewpoint to the interaction of factors which contribute to the process of aging. Life time is the most significant period for an individual. Several theories try to explain the process of aging by genetic determinants, by genetic or metabolic defects, by immunologic failure or by other reasons. It is noteworthy that the duration of life is correlated to the size of the body of different animals. This fact indicates a close relation to metabolism. It can be assumed that under optimal conditions of life, defects in function or structure are repaired by special maintenance functions. During the process of aging these functions lose effectuality.

Aging↗
PubMed1996

Hypertension optimal treatment: the Israeli HOT Study Group. Hypertension Optimal Treatment.

A total of 411 patients were recruited in the Israeli cohort of the Hypertension Optimal Treatment (HOT) Study, a multinational study conducted to assess the effect on cardiovascular morbidity and mortality in hypertensive patients of three levels of target diastolic blood pressure: < 90, < 85, and < 80 mm Hg. Initial treatment with felodipine in all patients was supplemented with other drugs as needed. When compared to the subjects in the rest of the world, the percentage of Israeli patients getting previous antihypertensive treatment was higher, reflecting a higher proportion of hospital-recruited patients. This accounted for the lower percentage of Israeli patients ending up with low-dose felodipine: 50% vs 56% in other countries. The percentage of patients getting high-dose felodipine plus additional drugs was also higher: 3.8% vs 2.9% for other countries. Felodipine was remarkably well tolerated, and most of the patients were able to continue this drug regimen.

Aged↗
PubMed1977

[Principles for optimizing and guaging several processes in the technology of vaccine production. I. Several problems in guaging and optimizing thermal sterilization of fluids].

Thermal sterilization of fluids--one of the widespread operations in microbiological laboratories and in vaccine production--solves two tasks: provides sterility and maximal preservation of biological value of the sterilized fluid. A possibility and expediency of using some indices for the quantitative assessment of the efficacy of the sterilization regimens, including measurement of the sterilization processes is considered in this work. A possible way of the regimen optimization on the basis of known values of the activation energies of the processes of decomposition of thermolabile components and inactivation of foreign microbial flora is assessed.

Hot Temperature↗