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Ideal-observer performance under signal and background uncertainty.

We use the performance of the Bayesian ideal observer as a figure of merit for hardware optimization because this observer makes optimal use of signal-detection information. Due to the high dimensionality of certain integrals that need to be evaluated, it is difficult to compute the ideal observer test statistic, the likelihood ratio, when background variability is taken into account. Methods have been developed in our laboratory for performing this computation for fixed signals in random backgrounds. In this work, we extend these computational methods to compute the likelihood ratio in the case where both the backgrounds and the signals are random with known statistical properties. We are able to write the likelihood ratio as an integral over possible backgrounds and signals, and we have developed Markov-chain Monte Carlo (MCMC) techniques to estimate these high-dimensional integrals. We can use these results to quantify the degradation of the ideal-observer performance when signal uncertainties are present in addition to the randomness of the backgrounds. For background uncertainty, we use lumpy backgrounds. We present the performance of the ideal observer under various signal-uncertainty paradigms with different parameters of simulated parallel-hole collimator imaging systems. We are interested in any change in the rankings between different imaging systems under signal and background uncertainty compared to the background-uncertainty case. We also compare psychophysical studies to the performance of the ideal observer.

Algorithms↗

Boron tolerable intake: re-evaluation of toxicokinetics for data-derived uncertainty factors.

Boron, which is ubiquitous in the environment, causes developmental and reproductive effects in experimental animals. This observation has led to efforts to establish a Tolerable Intake value for boron. Although risk assessors agree on the use of fetal weight decreases observed in rats as an appropriate critical effect, consensus on the adequacy of toxicokinetic data as a basis for replacement of default uncertainty factors remains to be reached. A critical analysis of the existing data on boron toxicokinetics was conducted to clarify the appropriateness of replacing default uncertainty factors (10-fold for interspecies differences and 10-fold for intraspecies differences) with data-derived values. The default uncertainty factor for variability in response from animals to humans of 10-fold (default values of 4-fold for kinetics and 2.5-fold for dynamics) was recommended, since clearance of boron is 3- to 4-fold higher in rats than in humans and data on dynamic differences--in order to modify the default value--are unavailable. A data-derived adjustment of 6-fold (1.8 for kinetics and 3.1 for dynamics) rather than the default uncertainty factor of 10-fold was considered appropriate for intrahuman variability, based on variability in glomerular filtration rate during pregnancy in humans and the lack of available data on dynamic differences. Additional studies to investigate the toxicokinetics of boron in rats would be useful to provide a stronger basis for replacement of default uncertainty factors for interspecies variation.

Animals↗

Reliability and uncertainty in the estimation of pKa by least squares nonlinear regression analysis of multiwavelength spectrophotometric pH titration data.

When drugs are poorly soluble then, instead of the potentiometric determination of dissociation constants, pH-spectrophotometric titration can be used along with nonlinear regression of the absorbance response surface data. Generally, regression models are extremely useful for extracting the essential features from a multiwavelength set of data. Regression diagnostics represent procedures for examining the regression triplet (data, model, method) in order to check (a) the data quality for a proposed model; (b) the model quality for a given set of data; and (c) that all of the assumptions used for least squares hold. In the interactive, PC-assisted diagnosis of data, models and estimation methods, the examination of data quality involves the detection of influential points, outliers and high leverages, that cause many problems when regression fitting the absorbance response hyperplane. All graphically oriented techniques are suitable for the rapid estimation of influential points. The reliability of the dissociation constants for the acid drug silybin may be proven with goodness-of-fit tests of the multiwavelength spectrophotometric pH-titration data. The uncertainty in the measurement of the pK (a) of a weak acid obtained by the least squares nonlinear regression analysis of absorption spectra is calculated. The procedure takes into account the drift in pH measurement, the drift in spectral measurement, and all of the drifts in analytical operations, as well as the relative importance of each source of uncertainty. The most important source of uncertainty in the experimental set-up for the example is the uncertainty in the pH measurement. The influences of various sources of uncertainty on the accuracy and precision are discussed using the example of the mixed dissociation constants of silybin, obtained using the SQUAD(84) and SPECFIT/32 regression programs.

Antioxidants↗

Some aspects of the evaluation of measurement uncertainty using reference materials.

To ensure and to confirm the required traceability according to the definition given in the International Vocabulary of Basic and Standard Terms in Metrology, three main aspects need to be considered in practice: "stated reference", "unbroken chain of calibration" and "stated uncertainty". For a certain spectrochemical result, each of the aspects above mentioned is highly dependent on measurement uncertainty, both on its magnitude and how it was estimated. The paper describes the experience of the Romanian National Institute of Metrology (INM) in estimating measurement uncertainty during certification of reference materials, in metrological calibration and during specific analytical processes. Practical examples of the use of reference materials or certified reference materials issued by the INM to estimate measurement uncertainty are discussed for their applicability in spectrochemical and turbidity analysis. Some aspects of the use of analysis of variance (ANOVA) to obtain additional information on the components of measurement uncertainty and to identify the magnitude of individual random effects are presented.

Journal Article↗

Quantifying the measurement uncertainty of results from environmental analytical methods.

The Eurachem-CITAC Guide Quantifying Uncertainty in Analytical Measurement was put into practice in a public laboratory devoted to environmental analytical measurements. In doing so due regard was given to the provisions of ISO 17025 and an attempt was made to base the entire estimation of measurement uncertainty on available data from the literature or from previously performed validation studies. Most environmental analytical procedures laid down in national or international standards are the result of cooperative efforts and put into effect as part of a compromise between all parties involved, public and private, that also encompasses environmental standards and statutory limits. Central to many procedures is the focus on the measurement of environmental effects rather than on individual chemical species. In this situation it is particularly important to understand the measurement process well enough to produce a realistic uncertainty statement. Environmental analytical methods will be examined as far as necessary, but reference will also be made to analytical methods in general and to physical measurement methods where appropriate. This paper describes ways and means of quantifying uncertainty for frequently practised methods of environmental analysis. It will be shown that operationally defined measurands are no obstacle to the estimation process as described in the Eurachem/CITAC Guide if it is accepted that the dominating component of uncertainty comes from the actual practice of the method as a reproducibility standard deviation.

Journal Article↗

Testing for differentiation of microbial communities using phylogenetic methods: accounting for uncertainty of phylogenetic inference and character state mapping.

Comparative analyses of microbial communities increasingly involve the assay of 16S rRNA (or other gene) sequences from environmental DNA. Determining whether the composition of two or more communities differ in their phylogenetic composition involves testing for covariation between phylogeny and community type. This approach requires estimating the phylogenetic relationships among all sampled sequences and assessing whether the distribution of sequences among communities differs from the null expectation that sequences are randomly distributed. One method developed for implementing the phylogeny-based test of differentiation, referred to as the Phylogenetic test, relies on a single estimate of the phylogeny. However, for most data sets, many alternative phylogenetic trees provide statistically equivalent descriptions of the data. Because the actual phylogeny is unknown, phylogenetic tests of differentiation among microbial communities must account for phylogenetic uncertainty. In this article, we evaluate bootstrapping and Bayesian phylogenetic methods when implementing the Phylogenetic test using parsimony to map character states, and we investigate the effects of character mapping uncertainty by using a Bayesian approach to stochastically map character states on trees. Our approaches incorporate uncertainty into the tests of two closely related null hypotheses: (1) populations are panmictic, and (2) identical communities existed in both environments over the course of evolutionary history. We use two data sets previously implemented in tests for community differentiation: nitrite reductase genes sampled from marsh and upland soils and 16S rDNA sequences sampled from the human mouth and gut. We show that accounting for phylogenetic and mapping uncertainties can drastically affect results when implementing the Phylogenetic test. Accounting for phylogenetic and character mapping uncertainty provides a more conservative and robust test of covariation between phylogeny and environment when comparing microbial communities using DNA sequences.

Bacteria↗

Effect of exposure duration on spatial uncertainty in normal and amblyopic eyes.

Previous studies have found that the spatial uncertainty of amblyopes is critically dependent on temporal factors. These studies claim that the spatial uncertainty is much greater at short exposure durations. We have reassessed the effect of exposure duration on the spatial uncertainty of normal and amblyopic eyes using a task in which we can compensate for the loss in contrast sensitivity which inevitably occurs as exposure duration is shortened. Our task involved a three-element alignment task, where each of the elements were spatial Gabors at two different separations. We ensured that our stimuli were always displayed at a fixed ratio above contrast detection thresholds at each exposure duration. Our results show that for normal subjects, for well separated equivisible stimuli, there is only a weak effect of exposure duration. A similar dependence is found for the dominant and amblyopic eyes of a group of strabismic amblyopes. Dominant eyes of strabismic amblyopes show increased spatial uncertainty compared with normal subjects. Amblyopic eyes of strabismic amblyopes show increased spatial uncertainty compared with their dominant fellow eye which is invariant with exposure duration. Some subjects show a larger positional deficit at short durations when the stimuli are almost abutting.

Adolescent↗

Specific effects of spatial-frequency uncertainty and different cue types on contrast detection: data and models.

If the spatial-frequency of sinusoidal signals in a contrast-detection experiment varies randomly from trial to trial, then performance is decreased compared with that in a situation where it remains constant. This spatial-frequency uncertainty effect can more or less be compensated by presenting informative cues shortly before each trial. Single-band, as well as multiple-band models, have been proposed to explain the uncertainty and cuing effects. While the latter assume that under uncertainty multiple channels are monitored simultaneously, the former propose that in each trial a single, but sometimes inappropriate, channel is selected for monitoring. Until now it is open which of these models is valid. Therefore, psychometric functions were collected under different conditions of spatial-frequency uncertainty. It appears that the size of the uncertainty effect varies with spatial-frequency. This result can be explained by a multiple-band model, as computational analysis reveals.

Adult↗

Investigation of the impact of pharmacokinetic variability and uncertainty on risks predicted with a pharmacokinetic model for chloroform.

A sensitivity and uncertainty analysis was performed on the Reitz et al. (Toxicol. Appl. Pharmacol., 1990: 105, 443) physiologically based pharmacokinetic (PBPK) risk assessment model for chloroform. The analytical approach attempted to separately consider the impacts of interindividual variability and parameter uncertainty on the predicted values of the dose metrics in the model, as well as on liver cancer risk estimates obtained with the model. An important feature of the analytical approach was that an attempt was made to incorporate information on correlation between important parameters, for example, the observed correlation between total blood flow and alveolar ventilation rate. Using the published PBPK model for chloroform, the best estimate of the average population risk based on the preferred pharmacodynamic dose metric (PTDEAD), representing cell death, is 9.2 x 10(-7); this estimate is more than 500-fold lower than the risk estimate of 5.3 x 10(-4) based on an alternative pharmacokinetic dose metric (AVEMMB), which represents tissue adduct formation. However, when interindividual variability was considered the range of individual risks (from the 5th to the 95th percentile of the population) predicted with PTDEAD was extremely broad (from 3.0 x 10(-13) to 3.2 x 10(-4)), while individual risks predicted with AVEMMB only varied over a factor of four (from 1.9 x 10(-4) to 7.4 x 10(-4)). As a result, the upper 95th percentile of the distribution of individual risk estimates based on the preferred cell death metric were within a factor of three of the 95th percentile for the pharmacokinetic alternative. The crucial factor with respect to the much greater variability of chloroform risk estimates based on cell death is that the dose metric, PTDEAD, is exquisitely sensitive to variation of the parameters in the model defining the response of cells to the cytotoxicity of chloroform. Unfortunately, these key parameters are also highly uncertain, as well as strongly correlated. As a result it proved impossible to accurately quantify the additional impact of parameter uncertainty on the dose metrics and risk estimates for chloroform. In general, however, the approach used in this study should be useful for differentiating the impact of interindividual variability and parameter uncertainty on PBPK-based risk assessments of other chemicals where the sensitivity, uncertainty, and correlation of the key parameters are more limited.

Animals↗

The uncertainty principle as an evolutionary engine.

Heisenberg's uncertainty principle in quantum mechanics underlies the genesis of evolutionary variability. When the uncertainty principle is coupled with the incontrovertible principle of the conservation of energy and material resources, there appears an uncertainty relationship between local fluctuations in the quantities to be conserved on a global scale and the rate of their local variation. Since the local fluctuations are accompanied by the non-vanishing rate of variation because of the uncertainty relationship, they generate subsequent fluctuations. Generativity latent in the uncertainty relationship is non-random and ubiquitous all through various evolutionary stages from abiotic synthesis of monomers and polymers up to the emergence of behavior-induced variability of organisms.

Amino Acid Sequence↗

The effect of setup uncertainties on the treatment of nasopharynx cancer.

PURPOSE: As radiation treatment techniques become more complicated, the need to understand the effect of uncertainties on dose distributions increases. This study investigates the effect of positional uncertainities for patients with nasopharynx carcinoma treated with a multiple field conformal boost technique. Three dimensional setup errors were measured for six patients and the effect on patient dose was evaluated using dose volume histograms. METHODS AND MATERIALS: A method is presented for determining 3-dimensional translational and rotational setup errors by identifying anatomical landmarks on two treatment field images and their corresponding simulation images. Measurements were made on a daily basis for six patients undergoing conformal treatment. RESULTS: The average magnitude of the translational errors was between 1.5 and 3 mm while the average distance between simulation and treatment isocenters was 5 mm. Both systematic and random setup errors were observed. Dose volume histograms incorporating these uncertainties for standard parallel opposed and conformal techniques were generated for patients experiencing random and systematic setup errors. CONCLUSION: The data imply that positional uncertainties effect the daily dose distributions for target and critical structures differently and that the effect may be treatment technique dependent. These results demonstrate the need to measure setup uncertainties for all sites and to develop techniques for incorporating dose uncertainties in treatment plans.

Calibration↗

Different methodologies to quantify uncertainties of air emissions.

Characterization of the uncertainty associated with air emission estimates is of critical importance especially in the compilation of air emission inventories. In this paper, two different theories are discussed and applied to evaluate air emissions uncertainty. In addition to numerical analysis, which is also recommended in the framework of the United Nation Convention on Climate Change guidelines with reference to Monte Carlo and Bootstrap simulation models, fuzzy analysis is also proposed. The methodologies are discussed and applied to an Italian example case study. Air concentration values are measured from two electric power plants: a coal plant, consisting of two boilers and a fuel oil plant, of four boilers; the pollutants considered are sulphur dioxide (SO(2)), nitrogen oxides (NO(X)), carbon monoxide (CO) and particulate matter (PM). Monte Carlo, Bootstrap and fuzzy methods have been applied to estimate uncertainty of these data. Regarding Monte Carlo, the most accurate results apply to Gaussian distributions; a good approximation is also observed for other distributions with almost regular features either positive asymmetrical or negative asymmetrical. Bootstrap, on the other hand, gives a good uncertainty estimation for irregular and asymmetrical distributions. The logic of fuzzy analysis, where data are represented as vague and indefinite in opposition to the traditional conception of neatness, certain classification and exactness of the data, follows a different description. In addition to randomness (stochastic variability) only, fuzzy theory deals with imprecision (vagueness) of data. Fuzzy variance of the data set was calculated; the results cannot be directly compared with empirical data but the overall performance of the theory is analysed. Fuzzy theory may appear more suitable for qualitative reasoning than for a quantitative estimation of uncertainty, but it suits well when little information and few measurements are available and when distributions of data are not properly known.

Air Pollutants↗

Analysis and reduction of the uncertainty of the assessment of children's lead exposure around an old mine.

Exposure to lead is a special problem in children, because they are more highly exposed than adults and because this pollutant, which accumulates in the body, induces neurobehavioral and cognitive effects. The objective of this study was to determine the probability density of the lead exposure dose of a 2-year-old child around an old mine site and to analyze its uncertainties, especially those associated with the bioavailability of lead in soil. Children's exposure was estimated indirectly from environmental samples (soils, domestic dust, water, air) and parameters (volume inhaled, body weight, soil intake rate, water intake, dietary intake) from the literature. Uncertainty and variability were analyzed separately in a two-dimensional Monte Carlo simulation with Crystal Ball software. Exposure doses were simulated with different methods for accessing the bioavailability of lead in soil. The exposure dose per kilogram of body weight varied from 2 microg/kgday at the 5th percentile to 5.5 microg/kgday at the 95th percentile (and from 2 to 10 microg/kgday, respectively, when ignoring bioavailability). The principal factors of variation were dietary intake, soil concentrations, and soil ingestion. The principal uncertainties were associated with the level of soil ingestion and the bioavailability of lead. Reducing uncertainty about the bioavailability of lead in soil by taking into account information about the type of mineral made it possible to increase our degree of confidence (from 25% to more than 95%) that the median exposure dose does not exceed the Tolerable Daily Intake. Knowledge of the mineral very substantially increases the degree of confidence in estimates of children's lead exposure around an old mining site by reducing the uncertainty associated with lead's bioavailability.

Air Pollutants↗

Risk taking and tolerance of uncertainty: implications for surgeons.

BACKGROUND: Adherence to evidence-based adverse outcome prevention techniques is a critical factor in providing high-quality patient care, but many of these interventions are not used by physicians. It is unclear if surgeons' risk attitudes and reactions to uncertainty influence their use of these or other interventions. MATERIALS AND METHODS: A systematic review of the literature was conducted to identify studies evaluating the effects of physicians' risk attitudes, reactions to uncertainty or ambiguity, and personality traits on clinical decision making. RESULTS: A variety of instruments to assess risk attitude and reactions to uncertainty have been developed and tested among physicians involved in critical care and emergency medicine. Scoring systems distinguish risk averse and risk seeking practitioners. In many studies, these characteristics were related to clinical decision making in situations of uncertainty. For example, among patients evaluated in the emergency room for chest pain, "risk-seeking" physicians admitted significantly fewer patients who did not have acute myocardial infarction than risk-avoiding physicians (29% and 47% of patients admitted, respectively). In contrast, risk-seeking physicians were no more likely to discharge a patient who eventually was found to have an acute myocardial infarction. CONCLUSIONS: There are very limited data on the extent to which surgical decision making is linked to risk taking behavior and "comfort with uncertainty". Understanding the behaviors, attitudes and beliefs that make up surgical "judgment" remains a challenge for those interested in influencing behavior.

Attitude of Health Personnel↗

Pharmacogenetics and uncertainty: implications for policy makers.

Uncertainty for policy makers is not new but the pressure to make decisions under conditions of uncertainty is perhaps greater than ever. The arrival of new scientific developments such as pharmacogenetics offers potentially great benefits (as well as significant risks). They have passionate supporters as well as doubters. The evidence is often extensive but unclear and policy makers may find themselves under pressure to make decisions before they feel that the evidence is compelling. The UK is particularly well placed to play a leading role in the development of pharmacogenetics and is equally well placed to derive the benefits to both health and wealth that could flow from this. However, the uncertainties threaten to overwhelm the capacity of policy makers to act effectively. The uncertainties are both about the context within which the science and delivery of pharmacogenetics is being developed and about the interests that could be served. This paper maps these uncertainties and concludes with some suggestions, drawing on deliberative democracy and futures thinking, as to how policy makers might manage the tensions and dilemmas they face by moving from an unstable, emergent policy arena to a more stable one.

Administrative Personnel↗

A new nano-accuracy AFM system for minimizing Abbe errors and the evaluation of its measuring uncertainty.

A new AFM system was designed for the establishment of a standard technique of nano-length measurement in a 2D plane. In a long range (about several tens of micrometers), measurement uncertainty is dominantly affected by the Abbe error of the XY scanning stage. No linear stage is perfectly straight; in other words, every scanning stage is subject to tilting, pitch and yaw motions. In this paper, an AFM system with minimum offsets of XY sensing is designed. Moreover, the XY scanning stage is designed to minimize the rotation angle, as Abbe errors occur through multiple combination of the offset and the rotation angle. To minimize the rotation angle, an optimal design is performed by maximizing the ratio of the stiffness of the parasitic direction to the motion direction of each stage. This paper describes a design scheme of a full AFM system, in particular, the XY scanner. The full range of a fabricated XY scanner is 100 microm x 100 microm. The tilting, pitch and yaw motions are measured by an autocollimator to evaluate the performance of the XY stage. The results show that the XY scanner have a 0.75 arcsec parasitic rotation about the maximum range, thus the uncertainty in terms of the Abbe errors are very small relative to other standard equipment. Using this AFM system, a 3mum pitch specimen was measured. The measurement uncertainty of the total system was evaluated especially about pitch length. For a 1D evaluation, Abbe errors are the most dominant factor, and the expanded combined uncertainty (k = 2) of system was square root (4.13)(2)+(5.07 x 10(-5)xp)(2)(nm). For a 2D evaluation, mirror non-orthogonality and Abbe errors are dominant factors, and expanded combined uncertainty (k = 2) of the system was square root (4.13)(2)+(1.228 x 10(-4)xp)(2) in the X direction, and square root (6.28)(2)+(1.266 x 10(-4)xp)(2) in the Y direction (the unit is nanometers), where p is the measured length in nm.

Journal Article↗

Cognitive components of naming in children: effects of referential uncertainty and stimulus realism.

The ease of picture naming in children was assessed as a function of two stimulus characteristics: (a) the number of available correct names for a picture (referential uncertainty) and (b) the degree to which a picture realistically represents the depicted object (stimulus realism). Two experiments employing different methods demonstrated that: (a) children named low uncertainty objects (those with a single dominant name, e.g., key, elephant) faster than high uncertainty objects (those with multiple possible correct names, e.g., lamp/light, stove/oven) and (b) this uncertainty effect arose at a stage of naming subsequent to object identification. Possible underlying mechanisms for the uncertainty effect include passive diffusion of activation over multiple object-name pathways or active inhibition among competing candidate names. Stimulus realism (colored photographs vs uncolored line drawings) did not consistently influence naming performance. Implications for understanding children's naming behavior are discussed.

Attention↗

Eutrophication research of West Lake, Hangzhou, China: modeling under uncertainty.

The models such as the eutrophication ecosystem model of West Lake, Hangzhou (EEM), are always used to make policy decisions for eutrophication management. Thus it is important to know the uncertainty in the model predictions due to the combined effects of uncertainty in the full set of input variables, and the individual input parameters whose variations have the greatest effect on variations in model predictions. In this study, randomized methods based on Monte Carlo technique have been developed and applied to the model (EEM). The technique consists of parameter sensitivity analysis, randomly sampling from underlying probability distributions and multivariate regression analysis. With this technique, model uncertainties during modeling are clarified and their propagation evaluated. Results show that among the five input parameters selected for uncertainty analysis, the settling rate of algae SVS and water temperature TEM have the largest contribution to model prediction uncertainty of the model outputs (PC, PS and PHYT).

China↗