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Results for “sensitivity analysis”

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PubMed2005

Dissecting coherent vibrational spectra of small proteins into secondary structural elements by sensitivity analysis.

The response of proteins to sequences of femtosecond infrared pulses provides a multidimensional view into their equilibrium distribution of structures and snapshot pictures of fast-triggered dynamical events. Analyzing these experiments requires advanced computational tools for assigning regions in the resulting multi-dimensional correlation plots to specific secondary-structure elements and their couplings. A differential sensitivity analysis technique based on a perturbation of the local (real space) Hamiltonian is developed to achieve that goal. Application to the amide I region of a small globular protein reveals regions associated with the alpha-helix, beta-sheet, and their coupling. Comparison of signals generated in different directions shows that the double-quantum-coherence signal has a higher sensitivity to the couplings compared with the single-quantum-coherence (photon echo) technique.

Infrared Rays↗
PubMed2005

A sensitivity analysis of the fed-batch animal-cell bioreactor with respect to some control parameters.

Animal cell culture is widely used in the manufacture of valuable products, and this process is nowadays seeing a rapid expansion. The growth of animal cells is a complex process, because the cells are very sensitive to environmental changes (in, for example, nutrients, pH, temperature, oxygen and osmolarity) during this phase and to the toxic compounds produced by the cell itself. Ammonia and lactate are the two major waste materials of cell culture. They can have inhibitory effects on cell growth and product (monoclonal antibodies among others) formation. In order to model the behaviour of a fed-batch animal cell bioreactor producing monoclonal antibodies, it is necessary to use a complex kinetic model with optimal operating patterns ensuring high productivities. Good knowledge of such domains of operating parameters, together with the understanding of the response of this rather complex system to small modifications in the working conditions, are essential for on-line control to improve the quality of product and the yield of an animal cell culture. The present study focuses on the sensitivity analysis of a fed-batch animal cell bioreactor with respect to some candidate control parameters (substrate set-point concentrations, feeding time-step patterns and concentration of feeding solutions), emphasizing the influence of these on the overall performance of the system.

Animals↗
PubMed2001

A sensitivity analysis for subverting randomization in controlled trials.

In some randomized controlled trials, subjects with a better prognosis may be diverted into the treatment group. This subverting of randomization results in an unobserved non-compliance with the originally intended treatment assignment. Consequently, the estimate of treatment effect from these trials may be biased. This paper clarifies the determinants of the magnitude of the bias and gives a sensitivity analysis that associates the amount that randomization is subverted and the resulting bias in treatment effect estimation. The methods are illustrated with a randomized controlled trial that evaluates the efficacy of a culturally sensitive AIDS education video.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Multitoxin biosensor-mass spectrometry analysis: a new approach for rapid, real-time, sensitive analysis of staphylococcal toxins in food.

Biomolecular interaction analysis mass spectrometry (BIA-MS) was applied to detection of bacterial toxins in food samples. This two-step approach utilizes surface plasmon resonance (SPR) to detect the binding of the toxin(s) to antibodies immobilized on a surface of a sensor chip. SPR detection is then followed by identification of the bound toxin(s) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Staphylococcal enterotoxin B (SEB) was readily detected in milk and mushroom samples at levels of 1 ng/ml. In addition, non-specific binding of food components to the immobilized antibody and to the sensor chip surface was detected. To evaluate the applicability of BIA-MS in the analysis of materials containing multiple toxic components, sample containing both SEB and toxic-shock syndrome toxin-1 was analyzed. Both toxins were successfully and simultaneously detected through the utilization of multiaffinity sensor chip surfaces.

Enterotoxins↗
PubMed2026

High-Dimensional Sensitivity Analysis for Genomic Studies: An Adversarial Framework for Learning Worst-Case Latent Confounders.

High-dimensional genomics studies are frequently confounded by unmeasured biological processes that obscure disease-specific signals. While existing workflows can estimate these latent confounders, they fail to quantify how robust a discovery is to varying levels of hypothetical confounding. We introduce sensGAN, a deep-learning adversarial framework that systematically explores the confounding spectrum by learning "worst-case" latent variables that nullify the most gene associations under novel predictive-gain constraints. By identifying the minimum confounding strength required to explain away an observed effect, our method shifts the paradigm toward a formal, quantitative sensitivity analysis. In diverse simulations, sensGAN accurately recovers latent structures and outperforms existing methods in identifying confounder-sensitive genes. Applied to human Alzheimer's disease microglia, our framework prioritizes robust disease pathways while successfully isolating signals driven by unmeasured co-occurring neurodegenerative pathologies. Our method is publicly available, deposited at the GitHub repository yifanlinz/ADsensitivityICML.

Journal Article↗
PubMedDate not supplied

A pricing strategy to promote sales of lower fat foods in high school cafeterias: acceptability and sensitivity analysis.

Prices of four low fat foods were reduced about 25% and prices of three high fat foods were increased about 10% to determine the impact on food purchases in a Midwestern suburban high school cafeteria to explore the impact of price on purchases. Low fat foods averaged about 13% of total sales. Sensitivity analysis was used to estimate that low fat foods would probably have averaged about 9% of total sales without the reduced price.

Adolescent↗
PubMed2003

Risks of estrogen plus progestin therapy: a sensitivity analysis of findings in the Women's Health Initiative randomized controlled trial.

CONTEXT: The Women's Health Initiative (WHI) randomized controlled trial that compared estrogen plus progestin versus placebo was stopped because of a significantly increased risk of breast cancer in the active treatment group (reason 1), and because a global index supported a finding of overall harm (reason 2). The possibility that the findings could have been accounted for by bias was not considered. OBJECTIVE: The present analysis was undertaken to determine whether detection bias is a plausible alternative to causality as an explanation for those findings that contributed to the reasons for discontinuing the study. DESIGN: setting and participants: This work took the form of a sensitivity analysis of the published WHI data to determine the magnitude of the detection bias required to account for those findings that contributed to the two reasons for stopping the study. MAIN OUTCOME MEASURES: These were differences in incidence rates of breast cancer (reason 1), and breast cancer, coronary heart disease, stroke and pulmonary embolism (reason 2), among estrogen plus progestin and placebo recipients. RESULTS: In the WHI study, 44.4% of the women on active treatment, as against 6.8% of the placebo recipients, had their treatments unblinded (mainly because of vaginal bleeding). Among them, detection bias could not be excluded. For the three cardiovascular outcomes, bias became a strong likelihood after the women were twice cautioned about possible increased risks observed in the interim data among estrogen plus progestin recipients. On the null hypothesis, bias could have accounted for the observed associations if, on average, it augmented the detection of disease that would otherwise have gone undiagnosed by 0.7-0.8/1000 per year. CONCLUSIONS: For differences in incidence of the order of 0.7-0.8/1000 per year, it is not possible to discriminate between causation and detection bias as alternative explanations for the findings.

Bias↗
PubMed2000

Application of neural networks and sensitivity analysis to improved prediction of trauma survival.

The performance of trauma departments is widely audited by applying predictive models that assess probability of survival, and examining the rate of unexpected survivals and deaths. Although the TRISS methodology, a logistic regression modelling technique, is still the de facto standard, it is known that neural network models perform better. A key issue when applying neural network models is the selection of input variables. This paper proposes a novel form of sensitivity analysis, which is simpler to apply than existing techniques, and can be used for both numeric and nominal input variables. The technique is applied to the audit survival problem, and used to analyse the TRISS variables. The conclusions discuss the implications for the design of further improved scoring schemes and predictive models.

Analysis of Variance↗
PubMed2004

Sensitivity analysis for pattern mixture models.

Incomplete series of data is a common feature in quality-of-life studies, in particular in chronic diseases where attrition of patients is high. Two alternative approaches to modeling longitudinal data with incomplete measurements have frequently been proposed in the literature, selection models and pattern-mixture models. In this paper we focus on, by way of sensitivity analysis, extrapolating incomplete patterns using identifying restrictions. Perhaps the best known ones are so-called complete case missing value restrictions (CCMV), where for a given pattern, the conditional distribution of the missing data, given the observed data, is equated to its counterpart in the completers. Available case missing value (ACMV) restrictions equate this conditional density to the one calculated from the subgroup of all patterns for which all required components have been observed. Neighboring case missing value restrictions (NCMV) equate this conditional density to the one calculated from the the pattern with one additional measurement obtained. In this paper, these three identifying restriction strategies are used to multiply impute missing data in a study in metastatic prostate cancer. Multiple imputation is employed to reduce the uncertainty of single imputation. It is shown how hypothesis testing and sensitivity analyses are carried out in this setting.

Humans↗
PubMed1991

Lower extremity angle measurement with accelerometers--error and sensitivity analysis.

Closed-loop control techniques for the restoration of locomotion of paraplegic subjects are expected to improve the quality of functional neuromuscular stimulation (FNS). We investigated the use of accelerometers for the assessment of feedback parameters. Previously, the possibility of angle assessment of the lower extremities using accelerometers, but without integration, was demonstrated. The current paper evaluates and assesses this method by an error and sensitivity analysis using healthy subject data. Of three potential error sources, the reference system, the accelerometers, and the model assumptions, the last was found to be the most important. Model calculations based on data obtained by the Elite video motion analysis system showed the rigid-body assumption error to be dominant for high frequencies (greater than 10 Hz), with vibrations in the order of 1 mm resulting in errors of one radial or more. For low frequencies (less than 5 Hz), the imperfect fixation of the accelerometers combined with a nonhinge type knee joint gave an error contribution of +/- 0.03 rad. The walking pattern was assumed to be two-dimensional which was shown to result in an error of +/- 0.04 rad. Accelerations due to rotations of the segments could be neglected. The total error computed for low frequencies (+/- 0.07 rad) was comparable to the experimental difference between the current and the reference system.

Acceleration↗
PubMed1990

A mathematical model for insulin kinetics. III. Sensitivity analysis of the model.

A non-linear mathematical model involving four variables and several constants incorporating beta-cell kinetics, a glucose-insulin feedback system and a gastrointestinal absorption term had been applied in earlier papers to various forms of diabetes mellitus. In this paper, we examine the response of the system to variations in the parameters and to initial conditions using sensitivity analysis. It is found that such a method leads to results that are consistent with clinical findings. Further, it is suggested that such an analysis could help in making some predictions regarding future directions in the therapy of diabetes mellitus.

Diabetes Mellitus↗
PubMed1996

Basic methods for sensitivity analysis of biases.

BACKGROUND: Most discussions of statistical methods focus on accounting for measured confounders and random errors in the data-generating process. In observational epidemiology, however, controllable confounding and random error are sometimes only a fraction of the total error, and are rarely if ever the only important source of uncertainty. Potential biases due to unmeasured confounders, classification errors, and selection bias need to be addressed in any thorough discussion of study results. METHODS: This paper reviews basic methods for examining the sensitivity of study results to biases, with a focus on methods that can be implemented without computer programming. CONCLUSION: Sensitivity analysis is helpful in obtaining a realistic picture of the potential impact of biases.

Bias↗
PubMed2002

Aerosol scavenging: model application and sensitivity analysis in the Indian context.

Sulfate aerosols have been found to be the major contributors to precipitation acidity. Thus, in view of the long-term ecological repercussions they have on aquatic ecosystems and their acidity-potential, the present analysis focuses on a case study application of the layer-averaged aerosol-scavenging model (Okita et al., 1996) for predicting values of the wet scavenging coefficient and sulfate concentrations in precipitation samples on the basis of the information available for some selected Indian cities. Through sensitivity analysis (Pandey et al., 1997) the scavenging coefficient has been found to be very strongly dependent on precipitation intensity. Comparison of model predictions has been done with the measured values for Delhi, Mumbai, Calcutta and Chennai in India.

Acid Rain↗
PubMed2003

A distributed model of solid waste anaerobic digestion: sensitivity analysis.

A distributed model of anaerobic digestion of solid waste was developed to describe the balance between the rates of polymer hydrolysis and methanogenesis during the anaerobic conversion of rich and lean wastes in batch and continuous-flow reactors. Waste, volatile fatty acids (VFAs), methanogenic biomass and sodium concentrations are the model variables. Diffusion and advection of VFAs inhibiting both polymer hydrolysis and methanogenesis were considered. A sensitivity analysis by changing the key model parameter values was carried out. The model simulations showed that the effective distance between the areas of hydrolysis/acidogenesis and methanogenesis is very important. An initial spatial separation of rich waste and inoculum enhances the methane production and waste degradation at high waste loading if relatively low VFA diffusion into the methanogenic area is taking place. When both hydrolysis and methanogenesis are strongly inhibited by high levels of VFA, fluctuations in biomass concentration are thought to be responsible for initiating the expansion of methanogenic area over the reactor space.

Bacteria, Anaerobic↗
PubMed2000

Design of large metabolic responses. Constraints and sensitivity analysis.

Metabolic control analysis (Kacser & Burns (1973). Symp. Soc. Exp. Biol.27, 65-104; Heinrich & Rapoport (1974). Eur. J. Biochem.42, 89-95) has been extensively used to describe the response of metabolic concentrations and fluxes to small (infinitesimal) changes in enzyme concentrations and effectors. Similarly, metabolic control design (Acerenza (1993). J. theor. Biol.165, 63-85) has been proposed to design small metabolic responses. These approaches have the limitation that they were not devised to deal with large (non-infinitesimal) responses. Here we develop a strategy to design large changes in the metabolic variables. The only assumption made is that, for all the parameter values under consideration, the system has a unique stable steady state. The procedure renders the kinetic parameters of the rate equations that when embedded in the metabolic network produce the pattern of large changes in the steady-state variables that we aim to design. Structural and kinetic constraints impose restrictions on the type of responses that could be designed. We show that these conditions can be transformed into the language of mean-sensitivity coefficients and, as a consequence, a sensitivity analysis of large metabolic responses can be performed after the system has been designed. The mean-sensitivity coefficients fulfil conservation and summation relationships that in the limit reduce to the well-known theorems for infinitesimal changes. Finally, it is shown that the same procedure that was used to design metabolic responses and analyse their sensitivity properties can also be used to determine the values of kinetic parameters of the rate laws operating "in situ".

Animals↗
PubMed2001

Phylogenetics of the lizard genus Tropidurus (Squamata: Tropiduridae: Tropidurinae): direct optimization, descriptive efficiency, and sensitivity analysis of congruence between molecular data and morphology.

By use of the technique of direct optimization the phylogenetics of the cis-Andean lizard genus Tropidurus were examined on the basis of both molecular (ca. 1.04 kb of sequences from 12S rDNA, valine tDNA, and 16S rDNA) and morphological (93 characters) data. Although equal weighting of all parsimony cost functions logically must maximize descriptive efficiency and explanatory power of all evidence, a sensitivity analysis demonstrated that equal weighting of indels, transitions, transversions, and morphological change provided the most congruent solution between the molecular and the morphological data partitions. The position of Uranoscodon is resolved as the sister taxon of the remaining members of the Tropidurinae. Plica, Uracentron, and Strobilurus, previously considered synonyms of Tropidurus, are resurrected; the group of these three genera form the sister taxon of the former Tropidurus nanuzae group (herein named Eurolophosaurus) plus Tropidurus sensu stricto (composed of the T. bogerti, T. semitaeniatus, T. spinulosus, and T. torquatus groups, herein diagnosed).

Animals↗
PubMed2004

Sensitivity analysis of respiratory parameter estimates in the constant-phase model.

The constant-phase model is increasingly used to fit low-frequency respiratory input impedance (Zrs), highlighting the need for a better understanding of the use of the model. Of particular interest is the extent to which Zrs would be affected by changes in parameters of the model, and conversely, how reliable are parameters estimated from model fits to the measured Zrs. We performed sensitivity analysis on respiratory data from 6 adult mice, at functional residual capacity (FRC), total lung capacity (TLC), and during bronchoconstriction, obtained using a 1-25 Hz oscillatory signal. The partial derivatives of Zrs with respect to each parameter were first examined. The limits of the 95% confidence intervals, 2-dimensional pairwise and p-dimensional joint confidence regions were then calculated. It was found that airway resistance was better estimated at FRC, as determined by the confidence region limits, whereas tissue damping and elastance were better estimated at TLC. Airway inertance was poorly estimated at this frequency range, as expected. During methacholine-evoked pulmonary constriction, there was an increase in the uncertainty of airway resistance and tissue damping, but this can be compensated for by using the relative (weighted residuals) in preference over the absolute (unweighted residuals) fitting criterion. These results are consistent with experimental observation and physiological understanding.

Airway Resistance↗
PubMed2004

Clinical significance of a highly sensitive analysis for gene dosage and the expression level of MYCN in neuroblastoma.

BACKGROUND: The amplification of the MYCN gene is one of the most powerful adverse prognosis factors in neuroblastoma, but the clinical significance of an enhanced expression of MYCN remains controversial. To reassess the clinical implications of MYCN amplification and expression in neuroblastoma, the status of amplification and the expression level of the MYCN gene of primary neuroblastoma samples were analyzed using highly sensitive analyses. METHODS: Using a quantitative polymerase chain reaction (PCR) method (TaqMan), the gene dosages (MYCN/p53) of 66 primary neuroblastoma samples were determined. In all 66 samples, the status of MYCN amplification has been determined previously by the Southern blotting method. Of the 54 samples with a single copy of MYCN based on the Southern blotting method, 23 samples were analyzed for MYCN amplification using the fluorescence in situ hybridization (FISH) method. The expression levels (MYCN/GAPDH) of 56 samples were determined by a quantitative reverse transcriptase (RT)-PCR method. RESULTS: Of the 54 samples with a single copy of MYCN based on the Southern blotting method, 46 samples showed MYCN gene dosages of less than 2.0, whereas the remaining 8 samples with dosages of more than 2.0 were tumors from patients with advanced-stage disease. The results of FISH supported the fact that these 8 samples contained a small number of MYCN-amplified cells. The cases of MYCN gene dosages of more than 2.0 were significantly associated with all other unfavorable prognostic factors (an age of >1 year at diagnosis [P <.0001], nonmass screening [P =.0003], advanced stage [P <.0001], diploid or tetraploid [P <.0001], and a Shimada unfavorable histology [P <.0001]). MYCN gene dosages of more than 2.0 were significantly associated with a high expression of MYCN (P =.0459). However, the expression level of MYCN was not significantly associated with any other prognostic factors. CONCLUSIONS: Quantitative PCR may thus be a useful modality for performing a highly sensitive and accurate assessment of the amplification and expression levels of the MYCN gene. In particular, the combination of the quantitative PCR system and the FISH method is considered to be a highly effective method for evaluating the status of MYCN amplification. In this highly sensitive analysis, MYCN amplification (MYCN/p53 > or = 2.0) was reconfirmed to be a strongly unfavorable factor, whereas the expression level of MYCN does not appear to be an independently significant prognosis factor.

Child↗