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PubMed2006

Uncertainty-based internal quality control. Harmonization considerations.

Three main quality aspects for analytical laboratories are internal method validation, internal quality control (IQC), and sample result uncertainty. Unfortunately, in the past they have been used in a nonharmonized way. The most universal IQC tool is the mean chart, but some criteria used to fix their control limits do not fit the real nature of analytical results. A new approach for fixing these limits is proposed (the u-approach). The key is the combined uncertainty, u, obtained from the method validation information, also used for estimating the sample result uncertainty. A comparative study on "in-control" simulated, bibliographic, and real laboratory data suggests that the u-approach is more reliable than other well-established criteria. In addition, the u-approach mean chart emerges as an IQC tool, consistent with chemical assays, which harmonizes the validation-control-uncertainty process.

Journal Article↗
PubMed2001

Uncertainties of Monod kinetic parameters nonlinearly estimated from batch experiments.

Monod kinetic parameters (Ks, micromax, and Y) that are estimated from batch experimental data can have large uncertainties due to linear correlations between them. The degree of correlation and the resulting uncertainties of the Monod parameters are functions of the initial experimental conditions, the values of the parameters, the type and magnitude of measurement errors, and the sampling number. Careful manipulation of experimental conditions can reduce the correlations between Monod parameters allowing for the estimation of Monod kinetic parameters with the lowest degree of uncertainty. By dimensionless analysis, the correlation and relative standard deviations of Monod parameters were found to be functions of a few dimensionless variables involving the initial substrate (S0) and cell (X0) concentrations. Quantitative relationships were analyzed between the dimensionless variables and the correlation and the uncertainties of the Monod parameters. This analysis allowed for identification of the optimal experimental conditions for estimating Monod parameters under both no growth and growth conditions coupled with two kinds of measurement errors: those with constant absolute standard deviation and those with constant relative standard deviation. Examples involving the microbial reduction of iron(III) as an electron acceptor are used to illustrate the application of the developed technique.

Cell Division↗
PubMed2004

Propagation of uncertainty in hourly utility NOx emissions through a photochemical grid air quality model: a case study for the Charlotte, NC, modeling domain.

One of the major hypothesized sources of uncertainties in air quality model inputs is the emission inventory. A probabilistic hourly NOx emission inventory for 32 units of nine coal-fired power plants in the Charlotte domain for the year 1995 was propagated through the Multiscale Air Quality Simulation Platform (MAQSIP). The inventory was developed using time series techniques. Time series for a 4-d episode were simulated and propagated through the air quality model 50 times in order to represent the ranges of uncertainty in hourly emissions and predicted ozone levels. Intra-unit autocorrelation in emissions and inter-unit dependence were accounted for. The range of uncertainty in predicted ozone was greater when inter-unit dependence was included as compared to when units were treated as statistically independent. Uncertainties in maximum ozone hourly or 8-h concentrations at a specific location could be attributed to a specific power plant based upon regression analysis. Out of 3969 grid cells in the modeling domain, there were 43 and 1654 grid cells with a probability greater than 0.9 of exceeding a 1-h 120 ppb standard and an 8-h 80 ppb standard, respectively. The time series of predicted ozone values had similar autocorrelation as compared to monitored data. The implications of these results for air quality management are addressed.

Air Pollutants↗
PubMed2004

Quantification of variability and uncertainty for air toxic emission inventories with censored emission factor data.

Probabilistic emission inventories were developed for urban air toxic emissions of benzene, formaldehyde, chromium, and arsenic for the example of Houston. Variability and uncertainty in emission factors were quantified for 71-97% of total emissions, depending upon the pollutant and data availability. Parametric distributions for interunit variability were fit using maximum likelihood estimation (MLE), and uncertainty in mean emission factors was estimated using parametric bootstrap simulation. For data sets containing one or more nondetected values, empirical bootstrap simulation was used to randomly sample detection limits for nondetected values and observations for sample values, and parametric distributions for variability were fit using MLE estimators for censored data. The goodness-of-fit for censored data was evaluated by comparison of cumulative distributions of bootstrap confidence intervals and empirical data. The emission inventory 95% uncertainty ranges are as small as -25% to +42% for chromium to as large as -75% to +224% for arsenic with correlated surrogates. Uncertainty was dominated by only a few source categories. Recommendations are made for future improvements to the analysis.

Air Pollutants↗
PubMed1999

Parameter uncertainty and variability in evaluative fate and exposure models.

The human toxicity potential, a weighting scheme used to evaluate toxic emissions for life cycle assessment and toxics release inventories, is based on potential dose calculations and toxicity factors. This paper evaluates the variance in potential dose calculations that can be attributed to the uncertainty in chemical-specific input parameters as well as the variability in exposure factors and landscape parameters. A knowledge of the uncertainty allows us to assess the robustness of a decision based on the toxicity potential; a knowledge of the sources of uncertainty allows us to focus our resources if we want to reduce the uncertainty. The potential dose of 236 chemicals was assessed. The chemicals were grouped by dominant exposure route, and a Monte Carlo analysis was conducted for one representative chemical in each group. The variance is typically one to two orders of magnitude. For comparison, the point estimates in potential dose for 236 chemicals span ten orders of magnitude. Most of the variance in the potential dose is due to chemical-specific input parameters, especially half-lives, although exposure factors such as fish intake and the source of drinking water can be important for chemicals whose dominant exposure is through indirect routes. Landscape characteristics are generally of minor importance.

Animals↗
PubMed2001

Uncertainty management in integrated assessment modeling: towards a pluralistic approach.

Integrated Assessment (IA) is an evolving research community that aims to address complex societal issues through an interdisciplinary process. The most-widely used method in Integrated Assessment is modeling. The state of the art in Integrated Assessment modeling is described in this paper in terms of history, general features, classes of models, and in terms of the strengths and weaknesses, and the dilemmas and challenges modelers face. One of the key challenges is the issue of uncertainty management. The paper outlines the sources and types of uncertainty modelers are confronted with. It then discusses how uncertainties are currently managed in Integrated Assessment modeling, on which evaluation it is argued that complementary methods are needed that allow for pluralistic uncertainty management. The paper finalises with discussing pluralistic concepts and approaches that are currently explored in the IA community and that seem promising in view of the challenge to incorporate explicitly more than one hidden perspective in models.

Animals↗
PubMed1997

Thurstonian and Brunswikian origins of uncertainty in judgment: a sampling model of confidence in sensory discrimination.

As a preliminary step towards the presentation of a model of confidence in sensory discrimination, the authors propose a distinction between 2 different origins of uncertainty named after 2 of the great probabilists in the history of psychology, L.L. Thurstone and Egon Brunswik. The authors review data that suggest that there are empirical as well as conceptual differences between the 2 modes of uncertainty and thus that separate models of confidence are needed in tasks dominated by Thurstonian and Brunswikian uncertainty. The article presents a computational model for 1 class of tasks dominated by Thurstonian uncertainty: sensory discrimination with pair comparisons. The sensory sampling model predicts decisions, confidence assessments, and the complex pattern of response times in simple psychophysical discrimination tasks (J.V. Baranski and W.M. Petrusic, 1994). The model also accounts for the disposition towards underconfidence often observed in sensory discrimination with pair comparisons.

Adult↗
PubMed2005

Coping with employment uncertainty: a comparison of employed and unemployed workers.

This study examined coping with stress associated with employment uncertainty for comparable samples of laid-off and employed high-technology workers. It was expected that different coping strategies would be associated with perceived stress for employed vs. unemployed people. Although unemployed participants reported higher levels of stress compared with employed participants, employment uncertainty mediated the association between employment status and perceived stress. Emotion-focused coping strategies were related to higher perceived stress, whereas problem-focused coping strategies were related to lower perceived stress. The use of emotional avoidance as a strategy moderated the effect of employment uncertainty on perceived stress, such that a greater propensity to endorse avoidance coping strategies was associated with higher levels of stress particularly under low uncertainty conditions.

Adaptation, Psychological↗
PubMed1977

Uncertainty, as defined by the contingency between environmental events, and the adrenocortical response of the rat to electric shock.

The pituitary-adrenal system is thought to be sensitive to the degree of uncertainty in a situation. In addition, there is some question whether the pituitary-adrenal system can be conditioned in a Pavlovian sense. Three experiments are reported here. The first and third sought to define uncertainty in terms of conditioned stimulus-unconditioned stimulus (CB-US) and US-US contingencies, which vary the amount of information that can be used to predict the occurrence of discrete shocks. The second experiment examined the possibility that the adrenocortical system was subject to the laws of Pavlovian conditioning, by using a conditioned emotional response paradigm. The results showed that the magnitude of the Pituitary-adrenal response varied in a curvilinear manner along the dimension of uncertainty. Very low and very high degrees of uncertainty resulted in greater corticosterone elevations than did moderate levels. No evidence for Pavlovian conditioning of the adrencortical system was found, although behavioral measures showed fear conditioning. The data presented were supportive of the hypothesis that the pituitary-adrenal response reflects the operation of an arousal system.

Animals↗
PubMed1997

Modulation of neuronal activity by target uncertainty.

Visual scenes are composed of many elements and although we can appreciate a scene as a whole, we can only move our eyes to one element of the scene at a time. As visual scenes become more complex, the number of potential targets in the scene increases, and the uncertainty that any particular one will be selected for an eye movement also increases. How motor systems accommodate this target uncertainty remains unknown. The activities of neurons in both the cerebral cortex and superior colliculus are modulated by this selection process. We reasoned that activity associated with target uncertainty should be evident in the saccadic motor system at the final stages of neural processing, in the superior colliculus. By systematically changing the number of stimuli from which a selection must be made and recording from superior colliculus neurons, we found that as the target uncertainty increased, the neural activity preceding target selection decreased. These results indicate that neurons within the final common pathway for movement generation are active well in advance of the selection of a particular movement. This early activity varies with the probability that a particular movement will be selected.

Animals↗
PubMed2001

Inter-organisational sampling trials for the uncertainty estimation of landfill gas measurements.

Inter-organisational sampling trials were performed at a reclaimed landfill site in Bedfont, West London, UK, to assess the uncertainty in measured concentrations of landfill gas. Eight participants independently measured concentrations of methane, carbon dioxide and oxygen, each on one occasion, over a two week period in February 1999. The organisers monitored the natural variability of the gas concentration over this sampling period using a control borehole in order to separate the variance that arose as a result of the sampling procedure from that caused by natural geochemical variation. A collaborative trial in sampling showed the extent of agreement between participants' results when they measured gases using the same, nominal protocol and equipment. The protocol was identified as fit for the purpose of estimating the mean concentration of methane, carbon dioxide and oxygen in a single borehole to within 21%, 15% and 321% of their assigned values, respectively (at 95% confidence). A realistic estimate of uncertainty in measurements of concentration from different protocols was estimated by the use of a sampling proficiency test, in which participants collected measurements using a protocol selected on the basis of their own professional judgement. Each participant's performance was compared with the consensus mean for each of the three gases using the z-score assessment proposed by the International Harmonised Protocol. This test highlighted the potentially large uncertainty in measured gas concentrations that can arise (91% relative uncertainty for CH4 in one borehole), and identified that an improved sampling protocol is required if misclassification of the explosive potential of methane is to be avoided.

Air Pollution↗
PubMed2001

Expression of results with uncertainty for the determination of pesticides in melon--experience in a proficiency test.

The expression of results with an uncertainty through the "bottom-up" approach, involving the estimation and combination of all the sources of uncertainty, represents a challenge when the analytical method includes mass transfer steps (MTS). These steps (e.g. extraction, evaporation, digestion, etc.) with inherently different from 100% recoveries lack models capable of describing their precision and efficiency. Recently, a new methodology was published aimed at the estimation of the performance of these critical steps. Comparison of the experimental dispersion from the replicated analysis of spiked samples with the combination of the uncertainty associated with gravimetric, volumetric and instrumental quantification steps (described by well established models) allows the estimation of the MTS uncertainty. Evaluation of the behaviour of the MTS within the analytical range supports the use of developed estimations over a wide concentration range. This methodology was applied, with success, to the determination of pesticide residues in melon in one particular proficiency test organised by the Food Analysis Performance Assessment Scheme (FAPAS) between November 2000 and February 2001.

Chromatography, Gas↗
PubMed2002

Worst case uncertainty estimates for routine instrumental analysis.

A methodology for the worst case measurement uncertainty estimation for analytical methods which include an instrumental quantification step, adequate for routine determinations, is presented. Although the methodology presented should be based on a careful evaluation of the analytical method, the resulting daily calculations are very simple. The methodology is based on the estimation of the maximum value for the different sources of uncertainty and requires the definition of limiting values for certain analytical parameters. The simplification of the instrumental quantification uncertainty estimation involves the use of the standard deviation obtained from control charts relating to the concentrations estimated from the calibration curves for control standards at the highest calibration level. Three levels of simplification are suggested, as alternatives to the detailed approach, which can be selected according to the proximity of the sample results to decision limits. These approaches were applied to the determination of pesticide residues in apples (CEN, EN 12393), for which the most simplified approach showed a relative expanded uncertainty of 37.2% for a confidence level of approximately 95%.

Journal Article↗
PubMed1997

Analysis of the clinical behaviour of anaesthetists: recognition of uncertainty as a basis for practice.

The dynamic complexity of anaesthesia sets specific requirements for the activity of anaesthetists. By exploring the significance given by anaesthetists to their work we have demonstrated a new conceptual framework and confirmed our hypothesis that there are differences in the orientations of anaesthetists, and that these become manifest in different types of clinical behaviour. We describe methods the anaesthetists use in framing the focus of their work, the patient in anaesthesia. The patient's uniqueness and uncertainty in anaesthesia were recognized in the 'realistic' orientation, which is characterized by an extensive use of situational information and an aim to construct a cumulative interpretation of a patient's physiological state. In the objectivistic orientation the patient was treated as a natural object and uncertainty was not recognized. This orientation is typified by a reactive habit of action which seemed to be based on a preoperative plan, and its deterministic implementation. Our results point to the need for a new strategy to cope with the uniqueness and uncertainty of actual problems. This has implications for education and practice in anaesthetic practice, since uncertainty is increasing with the ageing patient population and with implementation of new technology.

Anesthesia↗
PubMed2002

Reviewing intuitive decision-making and uncertainty: the implications for medical education.

CONTEXT: Intuition and uncertainty are inescapable conditions of many instances of clinical decision- making. Under such conditions biases and heuristics may operate, distorting the decision-making process. Physicians and students are generally unaware of these influences. PURPOSE: To review the extant literature regarding the role of uncertainty and intuition and associated biases on medical decision-making, to highlight the implications this holds for medical education. CONTENT: Using literature identified via Medline and Bioethicsline searches of the past 3 decades, this paper reviews the sources of uncertainty in clinical practice and the role of intuitive decision-making. A detailed description of associated heuristics and biases is provided, and linked with demonstrable examples from medical decision-making. CONCLUSIONS: It is argued that although uncertainty can be reduced, it can never be completely eliminated from decision-making. Therefore most decision-making performed in medicine contains an irreducible intuitive element and is thus vulnerable to these biases and heuristics. Given that few medical curricula overtly address the process of medical decision-making, both medical students and physicians remain vulnerable to these effects on their own (and their patients') decision-making. Insight via education appears the major means in which to avoid distorting decision-making processes.

Clinical Competence↗
PubMed2005

[How about the uncertainty in the haplotypes in the population-based KORA studies?].

In the KORA surveys, numerous candidate genes in the context of type 2 diabetes, myocardial infarction, atherosclerosis or obesity are under investigation. Current focus is on genotyping single nucleotide polymorphism (SNPs). Haplotypes are also of increasing interest: haplotypes are combinations of alleles within a certain section of one chromosome. Analysing haplotypes in genetic association studies is often more efficient than studying the SNPs separately. A statistical problem in this context is the reconstruction of the phase: genotyping the SNPs determines the alleles of an individual at one particular locus of the DNA, but does not reveal which allele is located on which one of the two chromosomes. This information is required when talking about haplotypes. There are statistical approaches to identify the most likely two haplotypes of an individual given the genotypes. However, a certain error in prognosis is unavoidable. There are also errors in the genotypes. These errors are assumed to be small for one SNP but can accumulate over the SNPs involved in one haplotype and thus can induce further uncertainty in the haplotype. It is therefore the aim of our project to quantify the uncertainties in the haplotypes particularly for genes investigated in the KORA surveys. We conduct computer simulations based on the haplotypes and their frequencies observed in the KORA individuals and compare the results with simulations based on mathematical modelling of the evolutionary process ("coalescent models"). The uncertainties in the haplotypes have an impact on the search for association between genes and disease: an association may not be detected as the haplotype uncertainty obscures the haplotype frequency differences between cases and controls. It is a further aim of our project to elucidate the extent of this problem and to develop strategies for reducing it.

Adult↗
PubMed1976

Temporal uncertainty, anticipation time, and cognitive coping under threat.

The effects of temporal uncertainty, anticipation time, and coping orientations on anticipatory reactions to an inevitable electric shock were investigated. One hundred eight male subjects were randomly assigned to the experimental conditions: they knew or did not know (temporal uncertainty) exactly when shock would occur; they waited either 1, 3, or 12 minutes for the shock, and were given either a vigilance, avoidance, or no orientation for preparing for the shock. Physiological measures were recorded continuously and pre- and post-trial questionnaires were completed to assess thoughts and feelings. Temporal uncertainty and anticipation time interacted to affect stress reactivity--i.e., as shock became imminent, temporal uncertainty led to the increased use of avoidant (as opposed to vigilant) modes of coping and was associated with a progressive lowering of reactivity, especially under the longer anticipation times. The results are consistent with the theory that coping processes mediate stress reactions under conditions of threat.

Adaptation, Psychological↗
PubMed1999

'In an important way, I did die': uncertainty and revival in persons living with HIV or AIDS.

This study reports the revival experiences of persons who once were reconciled to their death from HIV/AIDS but who, as a result of dramatic treatment responses, now believe they may survive (popularly known as the Lazarus Syndrome). A purposive sample of men and women living with HIV infection or AIDS were interviewed in six focus groups. As part of a larger study of uncertainty in HIV illness, participants described their uncertainty accompanying renewed health and a return to the joys and problems of continued life. While new discoveries about the disease and exciting antiretroviral therapies hold the promise of improved survival, ambiguity about the durability of treatment response and ultimate survival contribute to the level of uncertainty with which a patient must cope. The experience of uncertainty in the narratives about revival involved renegotiation. Participants described physical renewal as an unexpected new stressor forcing them to renegotiate: (a) feelings of hope and future orientation, (b) social roles and identities, (c) interpersonal relations, and (d) the quality of their lives. Implications for prevention, practice, research and theory are presented and suggestions for education and assistance are offered.

Acquired Immunodeficiency Syndrome↗