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Results for “sensitivity analysis”

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At least 325 records · Page 18Linked to original sources

Optimal-sensitivity analysis of ion channel gating kinetics.

We propose a new approach to analysis of kinetic models for ion channel gating, based on application of fluctuating voltages through a voltage clamp, in addition to conventional techniques. We show that the channel kinetics can be probed in a much more sensitive way, leading to more efficient model selection and more reliable estimates of model parameters. We use wavelet transform as an analytic tool for fluctuating currents and parametric dispersion plots as a measure of model compatibility with experimental data.

Algorithms↗

Calculations of protein volumes: sensitivity analysis and parameter database.

MOTIVATION: The precise sizes of protein atoms in terms of occupied packing volume are of great importance. We have previously presented standard volumes for protein residues based on calculations with Voronoi-like polyhedra. To understand the applicability and limitations of our set, we investigated, in detail, the sensitivity of the volume calculations to a number of factors: (i) the van der Waals radii set, (ii) the criteria for including buried atoms in the calculations or atom selection, (iii) the method of positioning the dividing plane in polyhedra construction, and (iv) the set of structures used in the averaging. RESULTS: We find that different radii sets have only moderate affects to the distribution and mean of volumes. Atom selection and dividing plane methods cause larger changes in protein atoms volumes. More significantly, we show how the variation in volumes appears to be clearly related to the quality of the structures analyzed, with higher quality structures giving consistently smaller average volumes with less variance.

Algorithms↗

[Decision tree sensitivity analysis for cost-effectiveness of chest FDG-PET in patients with a pulmonary tumor (non-small cell carcinoma)].

Decision tree analysis was used to assess cost-effectiveness of chest FDG-PET in patients with a pulmonary tumor (non-small cell carcinoma, < or = Stage IIIB), based on the data of the current decision tree. Decision tree models were constructed with two competing strategies (CT alone and CT plus chest FDG-PET) in 1,000 patient population with 71.4% prevalence. Baselines of FDG-PET sensitivity and specificity on detection of lung cancer and lymph node metastasis, and mortality and life expectancy were available from references. Chest CT plus chest FDG-PET strategy increased a total cost by 10.5% when a chest FDG-PET study costs 0.1 million yen, since it increased the number of mediastinoscopy and curative thoracotomy despite reducing the number of bronchofiberscopy to half. However, the strategy resulted in a remarkable increase by 115 patients with curable thoracotomy and decrease by 51 patients with non-curable thoracotomy. In addition, an average life expectancy increased by 0.607 year/patient, which means increase in medical cost is approximately 218,080 yen/year/patient when a chest FDG-PET study costs 0.1 million yen. In conclusion, chest CT plus chest FDG-PET strategy might not be cost-effective in Japan, but we are convinced that the strategy is useful in cost-benefit analysis.

Adult↗

Sensitivity analysis and potential uses of a novel gamma interferon release assay for diagnosis of tuberculosis.

Sputum smears for acid-fast bacilli (AFB) are the primary methods for diagnosis of tuberculosis (TB) in many countries. The tuberculin skin test (TST) is the primary method for diagnosis of latent TB infection (LTBI) worldwide. The poor sensitivity of the former and the poor specificity of the latter warrant the development of new tests and strategies to enhance diagnostic capabilities. We evaluated the sensitivity of an "in-tube" gamma interferon release assay (IGRA) using TB-specific antigens in comparison to the TST and the sputum smear for AFB in TB cases in South Africa. The sensitivity of the IGRA for TB was considered a surrogate of sensitivity in LTBI. Among 154 patients with a positive culture for Mycobacterium tuberculosis, the sensitivity of the IGRA for the diagnosis of TB varied by clinical subgroup from 64% to 82%, that of the TST varied from 85% to 94%, and that of two sputum smears for AFB varied from 35% to 53%. The sensitivity of the IGRA in human immunodeficiency virus (HIV)-infected TB cases was 81%. HIV-infected TB patients were significantly more likely to have indeterminate IGRA results and produced quantitatively less gamma interferon in response to TB-specific antigens than HIV-negative TB patients. The overall sensitivity of the TST in all TB cases was higher than that of the IGRA (90% versus 76%, respectively). The combined sensitivities of the TST plus IGRA and TST plus a single sputum smear were 96% and 93%, respectively. The TST combined with IGRA or with a single sputum smear may have a role in excluding the diagnosis of TB in some settings.

Adult↗

Sensitivity analysis of the diagnostic value of endoscopies in cross-sectional studies in the absence of a gold standard.

OBJECTIVES: The evaluation of the diagnostic value of endoscopic procedures usually lacks a gold standard when performed in cross-sectional studies. The objective is to demonstrate an easily applicable method to assess the possible range of sensitivity, specificity, and predictive values of endoscopic procedures in the absence of a gold standard method. METHODS: Data from a study of 328 endoscopies comparing two different methods to diagnose superficial bladder cancer were used as a numerical example. Both endoscopic procedures were performed in the same patients in one session. Under the assumption of a systematic misclassification process, a model to correct sensitivity estimates is developed. RESULTS: The lowest possible sensitivity estimate for a new fluorescence endoscopy technique (FE) was 78%, the maximum 97.5%. Depending on realistic assumptions made upon the misclassification, a reasonable estimate for sensitivity was 93.4% (95% confidence interval [CI]: 90%-97.3%) for the FE technique. The sensitivity of the traditional white-light endoscopy method ranged from 47.2% to 53%, with a reasonable estimate of 46.7% (95% CI: 39.4%-54.3%). CONCLUSIONS: This method to determine the theoretically possible range of sensitivity estimates in endoscopic procedures is helpful in cross-sectional studies with a missing gold standard method. It is easily applicable for a variety of endoscopic procedures, including upper and lower gastro-intestinal tract, urogenital tract, or diagnostic laparoscopic surgery.

Aminolevulinic Acid↗

Nonlinear response of ozone to emissions: source apportionment and sensitivity analysis.

For secondary air pollutants, precursor emissions may impact concentrations in nonlinear and interdependent manners. We explore the nonlinear responses of one such pollutant, ozone, to emissions of its precursors, nitrogen oxides (NOx) and volatile organic compounds. Modeling is conducted for a high ozone episode in the southeastern United States, applying a second-order direct sensitivity method in a regional air quality model. As applied here, the sensitivity method neglects most aerosol and aqueous chemistry processes. Inclusion of second-order sensitivities is shown to enable accurate characterization of response to large perturbations in emissions. An index is introduced to characterize the nonlinearity of ozone response to NOx emitted from each source region. Nonlinearity is found to increase with the tonnage and emission density of the source region. Interactions among the impacts of emission sources are shown to lead to discrepancies between source contribution attributed to an ensemble of emitters and the sum of the contributions attributed to each component. A method is introduced for applying these "cross-sensitivity" interactions to assess the uncertainty of sensitivity and source apportionment estimates arising from uncertainty in an emissions inventory. For ozone response to NOx, underestimates in emission rates lead to underprediction of total source contribution but overprediction of per-ton sensitivity.

Air Pollutants↗

Dynamic model comparing the bionomics of two isolated Culex tarsalis (Diptera: Culicidae) populations: sensitivity analysis.

A simulation model described (Eisenberg et al. 1994a) was used to compare the population dynamics of Culex tarsalis Coquillett in the Coachella and southern portion of the San Joaquin Valleys of California. Model outputs were classified as a pass if they met criteria that defined typical seasonal abundance patterns established by CO2 and New Jersey light trap data. The sensitivity of this classification to the model parameters was assessed by running multiple simulations for each valley site. Parameter sets associated with a pass were first analyzed separately for each valley and then compared. The two study sites were distinguished by the distributional characteristics of two parameters associated with temperature dependency. One of these parameters described the temperature dependence of larval mortality and the other the temperature dependence of adult egg development. We hypothesize that these isolated Cx. tarsalis populations evolved separately to maximize survival in their respective temperature regimes by adapting to different optimal larval survival temperatures and egg-development rates.

Analysis of Variance↗

Sensitivity analysis of a biofilm model describing a one-stage completely autotrophic nitrogen removal (CANON) process.

A mathematical model for nitrification and anaerobic ammonium oxidation (ANAMMOX) processes in a single biofilm reactor (CANON) was developed. This model describes completely autotrophic conversion of ammonium to dinitrogen gas. Aerobic ammonium and nitrite oxidation were modeled together with ANAMMOX. The sensitivity of kinetic constants and biofilm and process parameters to the process performance was evaluated, and the total effluent concentrations were, in general, found to be insensitive to affinity constants. Increasing the amount of biomass by either increasing biofilm thickness and density or decreasing porosity had no significant influence on the total effluent concentrations, provided that a minimum total biomass was present in the reactor. The ANAMMOX process always occurred in the depth of the biofilm provided that the oxygen concentration was limiting. The optimal dissolved oxygen concentration level at which the maximum nitrogen removal occurred is related to a certain ammonium surface load on the biofilm. An ammonium surface load of 2 g N/m2. d, associated with a dissolved oxygen concentration level of 1.3 g O2/m3 in the bulk liquid and with a minimum biofilm depth of 1 mm seems a proper design condition for the one-stage ammonium removal process. Under this condition, the ammonium removal efficiency is 94% (82% for the total nitrogen removal efficiency) (30 degrees C). Better ammonium removal could be achieved with an increase in the dissolved oxygen concentration level, but this would strongly limit the ANAMMOX process and decrease total nitrogen removal. It can be concluded that a one-stage process is probably not optimal if a good nitrogen effluent is required. A two-stage process like the combined SHARON and ANAMMOX process would be advised for complete nitrogen removal.

Anaerobiosis↗

High sensitivity analysis of nitrite and nitrate in biological samples by capillary zone electrophoresis with transient isotachophoretic sample stacking.

Tissue level of nitrate and nitrite are established indicators of altered nitric oxide metabolism under various pathological conditions. Determination of these anions in biological samples, in the presence of high chloride concentration, using capillary zone electrophoresis suffers from poor detection sensitivity. Separation conditions providing excellent resolution and submicromolar detection sensitivity of nitrate and nitrite have been developed and validated. Simple sample preparation was applied that maintains nitrite stability in tissue extracts and at the same time allows transient isotachophoresis stacking of the analytes. Nitrate and nitrite concentrations in rat brain and liver tissue samples were determined in control and lipopolysaccharide treated animals.

Animals↗

Method for the sensitive analysis of individual molecular species of phosphatidylcholine by high-performance liquid chromatography using post-column fluorescence detection.

Conditions are described for the efficient resolution by reversed-phase high-performance liquid chromatography on octadecylsilica stationary phases of individual molecular species of phosphatidylcholine on the basis of their fatty acyl composition. The effects are described of varying stationary phase carbon loading, mobile phase polarity and column temperature. Eluted peaks were detected by a sensitive post-column fluorescence system using the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene. This detection system permitted direct quantitation of phosphatidylcholine species irrespective of the degree of acyl unsaturation and eliminated the need for elaborate pre-column derivatization. The techniques were applied to the analysis of phosphatidylcholine isolated from rat liver and lung.

Animals↗

Sensitive analysis of 1alpha,25-dihydroxyvitamin D3 in biological fluids by liquid chromatography-tandem mass spectrometry.

A liquid chromatographic-tandem mass spectrometric assay using 5% bovine serum albumin as the calibration matrix has been developed for the quantitative analysis of 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3] in biological fluids. The analyte was extracted from the matrix after protein precipitation using an automated solid-phase extraction procedure involving both a reversed-phase and normal-phase procedure on a single C18 cartridge. The analytical chromatography was performed using a Symmetry C8 50 x 2.1 mm, 3.5 microm column. The mobile phase was a linear gradient from 75 to 99% methanol with a constant concentration of 2 mM ammonium acetate. 1alpha,25(OH)2D3 and the internal standard [2H6]1alpha,25(OH)2D3 were detected by using MS-MS. The ion source was operated in the positive electrospray ionisation mode. The assay is specific, sensitive, and has a capacity of more than 100 samples per day, with a limit of quantitation of 20 pg ml(-1) for a 1.0-ml sample aliquot. The assay has been used for the analysis of 1alpha,25(OH)2D3 in serum from rats and pigs simultaneously with the analysis of the vitamin D analog seocalcitol.

Animals↗

Sensitivity analysis of kinematic approximations in dynamic medusan swimming models.

Models of medusan swimming typically rely on kinematic approximations to observed animal morphology to make such investigations tractable. The effect of these simplifications on the accuracy of predicted dynamics has not been examined in detail. We conduct a case study of the scyphozoan jellyfish Chrysaora fuscescens to isolate and quantify the sensitivity of dynamic models to common kinematic approximations. It is found that dynamic models exhibit strong dependence on the nature of some approximations and the context in which they are implemented. Therefore it is incorrect and potentially misleading to assume that achieving kinematic similarity in models of measured animal locomotion will necessarily provide dynamically correct models.

Animals↗

Dentine lead and intelligence prior to school entry: a statistical sensitivity analysis.

The relationship between circumpulpal dentine lead and IQ at age 4 years 10 months was examined in 164 urban children. Negative correlations were observed between dentine lead and IQ scores, but were reduced in magnitude after adjustment for social covariates. Analyses using errors-in-variables regression models indicated that the degree of this reduction depended on difficult-to-verify assumptions regarding the magnitudes of (i) measurement error in the lead variable and the covariates, and (ii) possible changes in the caretaking environment resulting from conjectured effect of lead on the child's cognitive and behavioral development. Sensitivity analyses were conducted in which estimates of the lead effect were repeatedly computed and compared for a range of possible values for factors (i) and (ii). It was found that the statistical significance of the lead effect on Full Scale IQ depended on the relative magnitudes of these factors, and that failure to incorporate measurement error in the analysis would have led to gross overestimation of the precision of the findings.

Bias↗

Sensitivity analysis for trend tests: application to the risk of radiation exposure.

Trend tests are used to assess the relationship between multiple level treatment X and binary response R. In observational studies, however, there may be a confounder U that is associated with treatment X and causally related to response R. When the data for the confounder U are not observed, an approach for assessing the sensitivity of test results to U is provided. Its use is illustrated by examining data from a study of mutation rate after the Chernobyl accident.

Chernobyl Nuclear Accident↗

Combination of cationic surfactant-assisted solid-phase extraction with field-amplified sample stacking for highly sensitive analysis of chlorinated acid herbicides by capillary zone electrophoresis.

This report describes a novel online field-amplified sample stacking (FASS) procedure to analyze 16 chlorinated acid herbicides. By using a poly(vinyl alcohol) (PVA)-coated capillary to reduce electroosmotic flow and introducing a methanol-water plug before sample loading, the sample injection time could be very long without loss of sample and separation efficiency. Under the optimized condition, the FASS procedure could provide great sensitivity enhancement (5000-10 000-fold) and satisfactory reproducibility (relative standard deviations of migration times less than 2.4%, relative standard deviations of peak areas less than 8.0%). Combined with cationic surfactant-assisted solid-phase extraction (CSA-SPE), the limit of detection of the herbicides ranged from 0.269 to 20.3 ppt, which are two orders lower than those of the US Environmental Protection Agency standard method 515.1. The CSA-SPE-FASS-CE method was successfully applied to the analysis of local pond water.

2-Hydroxypropyl-beta-cyclodextrin↗

Sensitivity analysis of cost factors for various therapy options in the treatment of follicular lymphoma.

BACKGROUND: In Germany, patients with relapsed follicular non-Hodgkin's lymphoma do not all receive the same treatment. In this study, 3 therapy regimens were analyzed which were considered to be similar. With the goal of determining the treatment option with the lowest direct costs whilst maintaining the same degree of effectiveness, a cost analysis model was established and applied by way of example to the existing illness constellation. METHODS: The German doctors' fee scale (Einheitlicher Bewertungsmassstab, EBM) valid until 2005 served as the basis for the calculation of medical services within the scope of the present statutory health insurance guidelines. A virtual standard patient was constructed for the cost model and treated with the different therapy regimens. The incidences of individual adverse events described in literature served as the basis for the characterization of the average toxicity of the respective treatment methods. RESULT: The overall costs result from the sum of the treatment costs and the toxicity-related costs. The effect of additional interventions on the overall cost was also examined. CONCLUSION: Whereas the accompanying documentation of costs in clinical studies is organizationally complex and very tedious, the model applied here offers a reliable method of quantifying the costs of the different therapy regimens. It permits the comparison of different treatment alternatives, and it enables, by means of a cost variance analysis, the identification of cost drivers and less expensive measures within a therapy method.

Antibodies, Monoclonal↗

Alpha 2-macroglobulin: fast and sensitive analysis with monoclonal antibodies.

Monoclonal antibodies specific for human alpha 2-macroglobulin (alpha 2-M) have been produced. The antibodies were used in conjunction with commercially available rabbit antibody to alpha 2-M in a sandwich enzyme immunoassay. With incubation times of only 2 h with sample and 30 min with enzyme substrate, the useful range was 10-200 micrograms alpha 2-M per litre; longer incubation time increased the sensitivity. The intra-assay coefficient of variation (CV) was 5%; the inter-assay CV was 7%. The assay does not discriminate between native, methylamine-inactivated, and trypsin-treated alpha 2-M. The monoclonal antibodies are also useful for immunocytochemistry and for immunoprecipitation of alpha 2-M.

Animals↗