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PubMed2006

Evaluation of uncertainty in quantitative real-time PCR.

Quantitative real-time PCR is one of the newer methods for measurement of the amount of nucleic material in biological systems. However, reliable measurement requires an appropriate estimation of uncertainty and this paper has developed the uncertainty budget associated with this procedure using as an example, data from a quantitative real-time PCR method for the enumeration of Campylobacter jejuni. This uncertainty is relatively large and for instance, a measured result of 151 units of DNA would have a 95% confidence interval of +/-84 units of DNA with the main sources of uncertainty being the measurement of the threshold cycle (Ct) value, the predicted DNA content of the unknown sample from the calibration line and the molar absorbance value for DNA.

Campylobacter jejuni↗
PubMed2005

The sensitivity of dose distributions for organ motion and set-up uncertainties in prostate IMRT.

BACKGROUND AND PURPOSE: To determine the effect of organ motion and set-up uncertainties on IMRT dose distributions for prostate. METHODS: For five patients, IMRT techniques were designed to irradiate the CTV (prostate plus seminal vesicles). Technique I delivered 78 Gy to PTV1 (CTV+10 mm margin). Technique II delivered 68 Gy to PTV1, and a 10 Gy boost to PTV2 (CTV+an anisotropic margin of 0 to 5 mm). Technique III delivered 68 Gy to PTV1 and simultaneously 78 Gy to PTV2. Uncertainties were simulated using population statistics of organ motion and set-up accuracy. The average TCP (TCPpop) of the CTV and average NTCP (NTCPpop) of the rectal wall were calculated. RESULTS: The planning TCP was a good predictor for TCPpop for Techniques I and II. Technique III was sensitive for geometrical uncertainties, reducing TCPpop by 0.8 to 2.4% compared to planning. NTCPpop was reduced for Technique III by a factor 2.6 compared to Technique I. For all plans, the planning NTCP was strongly correlated with NTCPpop. CONCLUSIONS: Dose distributions created with Techniques I and II are insensitive for geometrical uncertainties, while Technique III resulted in a reduction of TCPpop. This reduction can be compensated by a small dose escalation, while still resulting in an NTCPpop of the rectal wall that is lower or comparable to Technique I.

Humans↗
PubMed2006

Metabolic engineering under uncertainty. I: framework development.

Standard bioprocess conditions have been widely applied for the microbial conversion of raw material to essential industrial products. Successful metabolic engineering (ME) strategies require a comprehensive framework to manage the complexity embedded in cellular metabolism, to explore the impacts of bioprocess conditions on the cellular responses, and to deal with the uncertainty of the physiochemical parameters. We have recently developed a computational and statistical framework that is based on Metabolic Control Analysis and uses a Monte Carlo method to simulate the uncertainty in the values of the system parameters [Wang, L., Birol, I., Hatzimanikatis, V., 2004. Metabolic control analysis under uncertainty: framework development and case studies. Biophys. J. 87(6), 3750-3763]. In this work, we generalize this framework to incorporate the central cellular processes, such as cell growth, and different bioprocess conditions, such as different types of bioreactors. The framework provides the mathematical basis for the quantification of the interactions between intracellular metabolism and extracellular conditions, and it is readily applicable to the identification of optimal ME targets for the improvement of industrial processes [Wang, L., Hatzimanikatis, V., 2005. Metabolic engineering under uncertainty. II: analysis of yeast metabolism. Submitted].

Bioreactors↗
PubMed2000

Uncertainty in incident rates for trucks carrying dangerous goods.

This paper addresses the uncertainty associated with release and fire incident rates for trucks in transit carrying dangerous goods. The research extends the treatment of uncertainty beyond sensitivity analysis, low-best-high estimates and confidence intervals, and represents the uncertainty through probability density functions. The analysis uses Monte Carlo simulations to propagate the uncertainty in the input variables through to the resulting release and fire incident rates. The paper illustrates how we can combine information on accident and non-accident releases and fires to generate probability density functions for the total expected releases and fires per billion vehicle kilometres for trucks carrying dangerous goods.

Accidents, Traffic↗
PubMed1999

How well do elderly people cope with uncertainty in a learning task?

The relation between age, task complexity and learning performance in a Multiple Cue Probability Learning task was studied by systematically varying the level of uncertainty present in the task, keeping constant the direction of relationships. Four age groups were constituted: young adults (mean age = 21), middle-aged adults (45), elderly people (69) and very elderly people (81). Five uncertainty levels were considered: predictability = 0.96, 0.80, 0.64, 0.48, and 0.32. All relationships involved were direct ones. A strong effect of uncertainty on 'control', a measure of the subject's consistency with respect to a linear model, was found. This effect was essentially a linear one. To each decrement in predictability of the task corresponded an equal decrement in participants' level of control. This level of decrement was the same, regardless of the age of the participant. It can be concluded that elderly people cope with uncertainty in probability learning tasks as well as young adults.

Adaptation, Psychological↗
PubMed2001

Responding to uncertainty in nursing practice.

Uncertainty is a fact of life for practising clinicians and cannot be avoided. This paper outlines the model of uncertainty presented by Katz (1988, Cambridge University Press, Cambridge, UK. pp. 544-565) and examines the descriptive and normative power of three broad theoretical and strategic approaches to dealing with uncertainty: rationality, bounded rationality and intuition. It concludes that nursing research and development (R&D) must acknowledge uncertainty more fully in its R&D agenda and that good-quality evaluation studies which directly compare intuitive with rational-analytical approaches for given clinical problems should be a dominant feature of future R&D.

Adaptation, Psychological↗
PubMed1998

Numerical errors and uncertainties in finite-element modeling of trabecular bone.

Although micromechanical finite-element models are being increasingly used to help interpret the results of bio-mechanical tests, there has not yet been a systematic study of the numerical errors and uncertainties that occur with these methods. In this work, finite-element models of human L1 vertebra have been used to analyze the sensitivity of the calculated elastic moduli to resolution, boundary conditions, and variations in the Poisson's ratio of the tissue material. Our results indicate that discretization of the bone architecture, inherent in the tomography process, leads to an underestimate in the calculated elastic moduli of about 20% at 20 microm resolution; these errors vary roughly linearly with the size of the image voxels. However, it turns out that there is a cancellation of errors between the softening introduced by the discretization of the bone architecture and the excess bending resistance of eight-node hexahedral finite elements. Our empirical finding is that eight-node cubic elements of the same size as the image voxels lead to the most accurate calculation for a given number of elements, with errors of less than 5% at 20 microm resolution. Comparisons with mechanical testing are also hindered by uncertainties in the grip conditions: our results show that these uncertainties are of comparable magnitude to the systematic differences in mechanical testing methods. Both discretization errors and uncertainties in grip conditions have a smaller effect on relative moduli, used when comparing between different specimens or different load directions, than on an absolute modulus. The effects of variations in the Poisson's ratio of the bone tissue were found to be negligible.

Bone and Bones↗
PubMed2002

Effects of uncertainty, transmission type, driver age and gender on brake reaction and movement time.

PROBLEM: Braking time (BT) is a critical component in safe driving, and various approaches have been applied to minimize it. This study analyzed the components of BT in order to assess the effects of age, gender, vehicle transmission type, and event uncertainty, on its two primary components, perception-reaction time and brake-movement time. METHOD: Perception-reaction time and brake-movement time were measured at the onset of lights for 72 subjects in a simulator. The six experimental conditions were three levels of uncertainty conditions (none, some, and some + false alarms) and two types of transmission (manual and automatic). The 72 subjects, half male and half female, were further divided into three age groups (mean of 23, 30, and 62 years). Each subject had 10 trials in each of the three levels of uncertainty conditions. RESULTS: Transmission type did not significantly affect either perception-reaction time or brake-movement time. Perception-reaction time increased significantly from 0.32 to 0.42 s (P < .05) as uncertainty increased but brake-movement time did not change. Perception-reaction time increased (from 0.35 to 0.43 s) with age but brake-movement time did not change with age. Gender did not affect perception-reaction time but did affect brake-movement time (males 0.19 s vs. females 0.16 s). IMPACT ON INDUSTRY: At 90 km/h, a car travels 0.25 m in 0.01 s. Consequently, even such small effects multiplied by millions of vehicle-kilometers can contribute to significant savings in lives and damages.

Adolescent↗
PubMed2001

Uncertainty, attentional capacity and chromatic mechanisms in visual search.

Two general questions were investigated using a visual search task. First, we asked whether effects of target uncertainty on reaction time varied with the discriminability of the target and distractors. Second, a higher order chromatic mechanism model was tested against a flexible model in which the signals in cardinal color-opponent mechanisms are combined through an attentional process. The models were tested by measuring the effects of target uncertainty on search time. A regression analysis indicated that the magnitude of the uncertainty effect was approximately constant in logarithmic units as a function of the chromatic difference between the target and distractors. The constant magnitude of the uncertainty effect suggested that an attentional capacity limit was exceeded when observers were required to monitor several chromatic mechanisms at several locations. The results of experiments 3 and 4 suggested that search for chromatic targets among distractors was mediated by diagonally tuned higher order chromatic mechanisms, rather than by signals in cardinal color-opponent mechanisms that were combined through an attentional mechanism.

Adult↗
PubMed1998

Spatial uncertainty and sampling efficiency in amblyopic position acuity.

Spatial uncertainty and undersampling are two of the major hypotheses for the losses of amblyopic spatial vision. To test these two hypotheses, equivalent spatial uncertainty and spatial integration efficiency in spatial position judgments were quantified with a spatial perturbation paradigm. Specifically, three-line bisection thresholds were measured for the amblyopic eyes of two strabismic and two anisometropic amblyopes, and for normal controls. The horizontal stimulus lines comprised discrete dark dots distributed randomly around the mean line position according to a gaussian function. Line separation, the number of dots on each line (N), stimulus contrast (C), and the vertical standard deviation (sigma e) of the dot distribution were varied. An ideal observer analysis quantified the magnitude of equivalent spatial uncertainty (sigma s), the effective number of dots used (k), and spatial integration efficiency (k/N). At the optimal separation, equivalent spatial uncertainty (sigma s) is approximately ten-fold higher in both types of amblyopic visual systems than in control observers, even when stimulus visibility is accounted for. This apparent increase in sigma s is largely due to a shift in spatial scale of analysis in the amblyopic eye. Integration efficiency (k/N) increases in proportion to stimulus contrast or visibility (in units of detection threshold). Unlike sigma s, k/N is different between the two types of amblyopia. For the anisometropic observers, k/N is quantitatively similar to that of control observers. For the strabismic observers, on the other hand, k/N is reduced even after taking stimulus visibility into account. The decreased spatial integration efficiency in the strabismic visual system suggests that spatial undersampling may occur at a secondary stage of visual processing, beyond the detection stage.

Adult↗
PubMed2002

Copper complexation by dissolved organic matter and uncertainty assessment of their stability constants.

The interaction of Cu with dissolved organic matter (DOM, extracted from an organic forest floor) was investigated and the resulting data was evaluated in terms of their uncertainty. The speciation of Cu over 'free' Cu (as analysed by diffusive gradients in thin films (DGT)), dissolved Cu-DOM complexes and precipitated Cu-DOM was determined as a function of pH (3.5, 4.0 and 4.5) and Cu/C ratio. The dissolved organically bound fraction was highest at pH 4.5, but this fraction decreased with increasing Cu/C ratio, which was observed for all pH levels. In the range of Cu/C = 7 x 10(-5) -2.3 x 10(-2) (mol/mol) the precipitated fraction was very small. The speciation of both Al and Fe was not affected by increasing Cu concentrations. From a continuous distribution model using the Scatchard approach, we calculated the optimal fit and corresponding upper and lower 95% uncertainty bounds of the overall stability constants (K(o)) with the shuffled complex evolution Metropolis (SCEM) algorithm. Although the optimal equation fitted the data very well, the uncertainty of the, according to literature, most reliable approach to establish stability constants, was still large. Accordingly, the usually reported intrinsic stability constants exhibited large uncertainty ranging from log K(i) = 6.0-7.1 (optimal 6.7) for pH 3.5, log K(i) = 6.5-7.1 (optimal 6.8) for pH 4.0, and log K(i) = 6.4-7.2 (optimal 6.8) for pH 4.5 and showed only little effect of pH.

Chemical Precipitation↗
PubMed2002

Framework for the uncertainty assessment in the impact pathway analysis with an application on a local scale in Spain.

The estimation of damage estimates due to air emissions gives important basic knowledge for decision-making on the level of environmental politics and business strategies. Nowadays, a frequently applied method to estimate environmental damages is the Impact Pathway Analysis (IPA), which can be easily carried out using models such as EcoSense or PathWays. These models produce results in a relatively short term. However, there is a lack of reliability in the results. As in many other environmental software tools, the uncertainty is the key problem that makes it difficult to convince decision-makers by the outcomes of a study. Therefore, a framework that allows assessing the uncertainties within studies in which the IPA is applied on a local scale has been developed. In this assessment framework, the uncertainties of the used parameters, including their spatial and temporal variability, are taken into account. As the model is processing a huge quantity of data, one step of the assessment consists of a screening procedure to determine the parameters that are supposed to be fixed. For the other data, probability distributions have to be selected and classified into two groups: extensively available data for which average and standard deviation can be calculated and data based on little information. A quantification of the uncertainty can be completed by a stochastic model in the form of Monte Carlo (MC) simulation on the basis of the framework. As an illustration of the framework, we have applied it to a study on the installation of an advanced gas treatment in the municipal waste incinerator of Tarragona. It can be shown that the presented stochastic approach gives a lower geometric deviation than the analytical one and that the new gas treatment reduces the environmental damages without any doubt.

Costs and Cost Analysis↗
PubMed2001

A Web-based survey method for evaluating different components of uncertainty in relative health risk judgments.

Uncertainty permeates the process of risk assessment. It arises from recognized sources such as inadequacy of toxicological data, lack of exposure information, and imprecise identification of sensitive populations. In addition to these ambiguities, comparative risk exercises, which amount to risk assessment on a scale wider than that applied to single agents, also entail balancing community values, cost-benefit analyses, and other factors not directly tied to toxicology. Such exercises often convene evaluation panels to attempt a ranking of different stressors or stressor groups. The size of these panels is necessarily limited, and they usually strive to reach some form of consensus on ranking. Because ordinal assignments of risk are so difficult to achieve, they actually evolve into rating agendas in which stressors are categorized as high, medium, or low risks. Whether ranking or rating is its aim, this process, with its emphasis on agreement, usually overlooks two major components of uncertainty. One is variability among raters in assigning a score or category. The other is the degree of uncertainty they implicitly attach to their individual ratings. Both serve as guides to the scope and clarity of the available information. To gather more information about these critical but usually overlooked contributions to uncertainty, and, simultaneously, to query a broader sample of respondents, a survey method was designed to exploit the possibilities of electronic communication based on the World Wide Web. This method can secure risk ratings of selected stressors from many different samples of respondents. In addition, it can also provide information about the extent of ratings variability among risk assessors, individuals, or groups of respondents, about the bases of the ratings, and, concurrently, the confidence they place in their judgment. Comparative risk endeavors conducted in this format make their aims and content easy to modify. Data obtained by such a method can serve as pointers to new research initiatives, to regulator priorities, or to further iterations.

Data Collection↗
PubMed2003

Estimation of uncertainty and variability in bacterial growth using Bayesian inference. Application to Listeria monocytogenes.

The usefulness of risk assessment is limited by its ability or inability to model and evaluate risk uncertainty and variability separately. A key factor of variability and uncertainty in microbial risk assessment could be growth variability between strains and growth model parameter uncertainty. In this paper, we propose a Bayesian procedure for growth parameter estimation which makes it possible to separate these two components by means of hyperparameters. This model incorporates in a single step the logistic equation with delay as a primary growth model and the cardinal temperature equation as a secondary growth model. The estimation of Listeria monocytogenes growth parameters in milk using literature data is proposed as a detailed application. While this model should be applied on genuine data, it is highlighted that the proposed approach may be convenient for estimating the variability and uncertainty of growth parameters separately, using a complete predictive microbiology model.

Animals↗
PubMed2001

Modelling and simulation of variability and uncertainty in toxicokinetics and pharmacokinetics.

Two important methodological issues within the framework of the variability and uncertainty analysis of toxicokinetic and pharmacokinetic systems are discussed: (i) modelling and simulation of the existing physiologic variability in a population; and (ii) modelling and simulation of variability and uncertainty when there is insufficient or not well defined (e.g. small sample, semiquantitative, qualitative and vague) information available. Physiologically based pharmacokinetic models are especially suited for separating and characterising the physiologic variability from the overall variability and uncertainty in the system. Monte Carlo sampling should draw from multivariate distributions, which reflect all levels of existing dependencies in the intact organism. The population characteristics should be taken into account. A fuzzy simulation approach is proposed to model variability and uncertainty when there is semiquantitative, qualitative and vague information about the model parameters and their statistical distributions cannot be defined reliably.

Animals↗
PubMed2001

Neural activity in the human brain relating to uncertainty and arousal during anticipation.

We used functional magnetic resonance neuroimaging to measure brain activity during delay between reward-related decisions and their outcomes, and the modulation of this delay activity by uncertainty and arousal. Feedback, indicating financial gain or loss, was given following a fixed delay. Anticipatory arousal was indexed by galvanic skin conductance. Delay-period activity was associated with bilateral activation in orbital and medial prefrontal, temporal, and right parietal cortices. During delay, activity in anterior cingulate and orbitofrontal cortices was modulated by outcome uncertainty, whereas anterior cingulate, dorsolateral prefrontal, and parietal cortices activity was modulated by degree of anticipatory arousal. A distinct region of anterior cingulate was commonly activated by both uncertainty and arousal. Our findings highlight distinct contributions of cognitive uncertainty and autonomic arousal to anticipatory neural activity in prefrontal cortex.

Adult↗
PubMedDate not supplied

An approach to the assessment of overall uncertainty of determination of dose using an ESR technique.

An approach to the assessment of overall uncertainty of dose reconstruction by means of an ESR with additive dose technique is proposed. This approach takes account of uncertainties caused by different sources giving a quantitative measure of uncertainty of the determined dose. Dose is determined as an interval assessment rather than a deterministic value, allowing for the analytical estimation of both the mean value and the 95% confidence intervals. The effects of the number of additional irradiations and the value of dose increment on the uncertainty of dose determination are analyzed.

Dental Enamel↗
PubMed1999

Managing geometric uncertainty in conformal intensity-modulated radiation therapy.

The geometric precision of radiotherapy treatments must increase if the objectives of dose escalation and increased disease control are to be achieved. There are multiple strategies for increasing the geometric precision of a radiotherapy treatment system, including immobilization and setup aids for reducing random and systematic components of setup errors and organ motion alike. Alternatively, more complex strategies can be implemented based on additional information acquired over the course of treatment. Generally, these strategies can be divided into two categories: off-line and on-line. The strategies that are implemented in the clinic must consider the required geometric precision for a given treatment. From this specification, it is possible to select the appropriate strategies and approaches. The cost associated with each approach must also be considered. Once a system for delivery has been designed, the residual uncertainties must still be considered in the planning process. Parallel to the development of strategies for reducing uncertainty, progress is being made in better relating these residual uncertainties to margins for use in treatment planning. This article reviews advances in reducing uncertainty.

Cost-Benefit Analysis↗