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Positional uncertainty in peripheral and amblyopic vision.

Three experiments were performed to examine positional acuity and the role of spatial sampling in central, peripheral and amblyopic vision. In the first experiment, 3-line bisection acuity was compared to grating acuity. In normal foveal vision bisection acuity represents a hyperacuity. In anisometropic amblyopes, bisection acuity is reduced in rough proportion to their grating acuity. In strabismic amblyopes, and in the normal periphery, bisection acuity is reduced to a greater extent than grating acuity. This result implies that reduced contrast sensitivity of the spatial filters is not sufficient to account for the increased positional uncertainty found in peripheral vision and in strabismic amblyopia. In order to test the hypothesis that the high degree of positional uncertainty evident in these visual systems is a consequence of sparse spatial sampling, bisection thresholds and width discrimination thresholds were measured with stimuli comprised of discrete samples. The results showed that normal foveal vision and the vision of anisometropic amblyopes show little benefit from adding discrete samples to the stimulus. In contrast, the normal periphery, and the central field of strabismic amblyopes demonstrate marked positional uncertainty which can be efficiently reduced in proportion to the square root of the number of samples (up to about 10) comprising the stimulus in the direction orthogonal to the discrimination cue. In aggregate the results suggest that anisometropic and strabismic amblyopia are fundamentally different. The positional uncertainty in anisometropic amblyopia is consistent with the reduced sensitivity of the spatial filters. The data of the normal periphery and of the central field of strabismic amblyopes suggest that the cortical sampling grain imposes a fundamental limit upon their positional acuity.

Amblyopia↗

Is the increased spatial uncertainty in the normal periphery due to spatial undersampling or uncalibrated disarray?

There are two possible causes for the elevated positional uncertainty of the peripheral field; undersampling by post receptoral arrays or uncalibrated disarray within post receptoral arrays. In order to assess the relative influences of these two factors to peripheral spatial uncertainty, we apply an approach which has enjoyed much success in the field of colour vision to examine the trade-off between position and contrast errors for spatial vision. We show that, if our positional uncertainty in the periphery is due to spatial undersampling, a correlated contrast inaccuracy should be present. We find no evidence for this expected linkage in the peripheral field at any spatial scale. We conclude that uncalibrated neural disarray rather than undersampling is the cause of peripheral positional uncertainty.

Awareness↗

Medical uncertainty and the autopsy: occult benefits for students.

The autopsy has been of great importance in educating students regarding medical uncertainty. The marked decline in the use of the autopsy in medical education and continuing education has contributed significantly to the current discomfort among physicians regarding medical uncertainty and medical errors, which, in turn, has furthered the decline of the autopsy. Inordinate guilt, denial, and other defensive behaviors that many physicians marshall in response to uncertainty and error prevent these individuals from learning from their mistakes. The autopsy experience during medical school, properly utilized, helps students to confront fallibility and sets the stage for later successful management of uncertainty and error.

Autopsy↗

Uncertainty and the demand for medical care.

This paper provides an analysis of the effects of uncertainty on the demand for medical care using a simplified version of Grossman's human capital model of the demand for health. Two types of uncertainty are analysed: the uncertainty surrounding the incidence of illness and the uncertainty surrounding the effectiveness of medical care. In the first the consumer's basic level of health is assumed to be a random variable; in the second the effectiveness of medical care is assumed to be random. Comparative static results are reported indicating the effects on the demand for medical care of both increases in the means of these distributions and mean-preserving spreads of the distributions.

Health Services↗

An approach for treating the uncertainties in the impact of climate change.

Past accumulated data supported by the predictions of climate models suggest that our world is getting warmer. Scientists are trying to construct mathematical models of both climate and crop systems to identify what types of climate changes could constitute a significant risk or benefit for agriculture. However, due to the many uncertainties regarding these models, it is impossible to make unequivocal predictions. At present, almost all the research in this area is carried out without considering the uncertain nature of the problem. The approach outlined here attempts to find a way to deal with the above uncertainty problem. Artificial intelligence techniques are being developed with the aim of performing inferences based on uncertain information. In our method, causal graphs are used for explicit representation of the relationships between climatic factors and yield. Probabilities are used to express the uncertainties associated with these links, and Bayes' theorem is applied to deal with uncertainty reasonings. This approach has the additional advantage of allowing the prediction to be readily updated as results from improved climate and crop models become available. These opportunities are being evaluated initially by using the model for potato growth developed at the Scottish Crop Research Institute.

Journal Article↗

Uncertainties in health-risk assessment: an integrated case study based on tetrachloroethylene in California groundwater.

Population risk to an environmental contaminant is represented as the product of a source term; the exposure function, which converts the source into a lifetime-equivalent contact rate in the population; the fraction metabolized; the toxic potency associated with the delivered dose; and the size of the exposed population. Using case studies for contamination of groundwater in California with tetrachloroethylene (PCE), the combined uncertainty in exposure and dose-response models is characterized. Three key issues are addressed: (a) uncertainty in quantifying pathway exposure factors that relate measured environmental concentrations to levels of contact in the exposed population; (b) the uncertainty in the human dose-response models derived from animal data; and (c) an overview of important contributors to the overall uncertainty in population risk estimates.

Administration, Inhalation↗

Statistical uncertainty in ultrasonic backscatter and attenuation coefficients determined with a reference phantom.

Uncertainties in measured attenuation and backscatter coefficients due to statistical fluctuations in echo signal data from a randomly scattering medium are estimated. The uncertainties are computed for the special case in which a reference phantom is employed to account for transducer and instrumentation factors when measuring attenuation and backscatter coefficients. The resultant uncertainty in the attenuation is inversely proportional to the 3/2 power of the depth range. The error in the backscatter coefficient arises both from the local fluctuation in the data and from the uncertainty in the attenuation estimate. The first of these is inversely proportional to the square root of the number of independent data points, while the second results in a contribution that is depth dependent. Predicted errors were tested by scanning tissue mimicking phantoms and estimating attenuation and backscatter coefficients for subsets of the digitized echo data. Standard deviations of the experimental results were in agreement with those predicted.

Models, Structural↗

A method for estimating the uncertainty of future bone mass.

The development of statistical models for estimating fracture probability is a promising method for quantitating and optimizing the clinical utility of bone mass measurements. Earlier models have assumed that future bone mass could be predicted exactly and were, therefore, limited to analyses that assume the loss rate is known in advance. Since bone loss rates may vary over time and cannot be predicted accurately, we have developed a new model, based on empirical data, that estimates the degree of uncertainty associated with predicted bone mass. Without a bone mass measurement, the population mean must be assumed for an individual. For the calcaneus, the standard deviation of the population distribution is about 60 mg/cm2. By measuring bone mass, one can determine how close or far from the mean an individual's true bone mass is, with a standard deviation (SD) of about 3 mg/cm2. Without a subsequent bone mass measurement, our model predicts that the uncertainty (standard deviation) in calcaneal bone mass will increase approximately sixfold (relative to the reproducibility at the initial measurement) over a period of five years for women under age 60, from 3 mg/cm2 to 19 mg/cm2. The five-year increase in uncertainty is approximately fourfold for women over age 60, from 3 to 13 mg/cm2. However, the uncertainty in bone mass for an individual five years after the initial measurement is still only one third to one fifth that of the entire population, and can be reduced to the initial level by obtaining another measurement. Furthermore, the predicted (or measured) values are usually much better estimates of an individual's true bone mass than simply assuming the population average.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Evaluation of uncertainty of the comprehensive interpretation of borehole logs by the multiple re-run statistical method.

Measurements of various physical quantities in a borehole by geophysical well logging tools are designed to determine these quantities for underground geological formations. Then, the raw data (logs) are combined in a comprehensive interpretation to obtain values of geological parameters. Estimating the uncertainty of calculated geological parameters, interpreted in such a way, is difficult, often impossible, when classical statistical methods are used. The method presented here permits an estimate of the uncertainty of a quantity to be obtained. The discussion of the dependence between the uncertainty of nuclear and acoustic tool responses, and the estimated uncertainty of the interpreted geological parameters (among others: porosity, water saturation, clay content) is presented.

Journal Article↗

Uncertainty in rate loss corrections based on counting a periodic pulser.

Tomographic gamma scanning of waste produces three-dimensional transmission and emission images. These are used to derive item-specific attenuation correction factors that improve the accuracy of non-destructive waste assay. For each vertical layer, data grabs of short duration are acquired as the waste item is rotated and translated. The image reconstruction demands accurate rate loss corrections to minimize assay bias. For this application a pulser was used to perform the necessary rate loss corrections. In this work, we summarize the benefits of the pulser approach and review the basic principles on which the method is based. We extend the treatment to include a derivation of the expression for the uncertainty in the net pulser peak area in the presence of an underlying continuum. We report experimental results, taken using a Canberra model WM2900 Tomographic Gamma Scanner, over a broad range of count-rates and peak-to-continuum ratios. Repeat counts under controlled conditions allowed the correction factor and its variance to be determined and compared against expectations. These results confirm the validity of the correction factor formula and the corresponding expression for its uncertainty. The rate loss analysis has been built into a Monte Carlo Replicate engine to allow the uncertainty to be propagated into the total measurement uncertainty of the final assay.

Gamma Rays↗

Volumetric uncertainty in radiotherapy.

The technologies available to identify anatomical structures (including radiotherapy target and normal tissue 'volumes'), and to deliver dose accurately to these volumes, have improved significantly in the past decade. However, the ability of clinicians to identify volumes accurately and consistently in patients still suffers from uncertainties that arise from human error, inadequate training, lack of consensus on the derivation of volumes and inadequate characterisation of the accuracy and specificity of imaging technologies. Inadequate volume definition of a target can result in treatment failure and, consequently, disease progression; excessive volume may also lead to unnecessary patient injury. This is a serious problem in routine clinical care. In the context of large multi-centre clinical trials, uncertainty and inconsistency in tissue-volume reporting will be carried through to the analysis of treatment effect on outcome, which will subsequently influence the treatment of future patients. Strategies need to be set in place to ensure that the abilities and consistency of clinicians in defining volumes are aligned with the ability of new technologies to present volumetric information. This review seeks to define the concept of volumetric uncertainty and propose a conceptual model that has these errors evaluated and responded to separately. Specifically, we will explore the major causes, consequences of, and possible remediation of volumetric uncertainty, from the point of view of a multidisciplinary radiotherapy clinical environment.

Humans↗

Human variability in xenobiotic metabolism and pathway-related uncertainty factors for chemical risk assessment: a review.

This review provides an account of recent developments arising from a database that defined human variability in phase I metabolism (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, hydrolysis, alcohol dehydrogenase), phase II metabolism (N-acetyltransferases, glucuronidation, glycine conjugation, sulphation) and renal excretion. This database was used to derive pathway-related uncertainty factors for chemical risk assessment that allow for human variability in toxicokinetics. Probe substrates for each pathway of elimination were selected on the basis that oral absorption was >95% and that the metabolic route was the primary route of elimination of the compound (60-100% of a dose). Intravenous data were used for compounds for which absorption was variable. Human variability in kinetics was quantified for each compound from published pharmacokinetic studies (after oral and intravenous dosing) in healthy adults and other subgroups of the population using parameters relating to chronic exposure (metabolic and total clearances, area under the plasma concentration-time curve (AUC)) and acute exposure (Cmax) (data not presented here). The pathway-related uncertainty factors were calculated to cover 95%, 97.5% and 99% of the population of healthy adults and of each subgroup. Pathway-related uncertainty factors allow metabolism data to be incorporated into the derivation of health-based guidance values. They constitute an intermediate approach between the general kinetic default factors (3.16) and a chemical-specific adjustment factor. Applications of pathway-related uncertainty factors for chemical risk assessment and future refinements of the approach are discussed. A knowledge-based framework to predict human variability in kinetics for xenobiotics showing a threshold dose below which toxic effects are not observed, is proposed to move away from default assumptions.

Age Factors↗

Lessons from the organization of a proficiency testing program in food microbiology by interlaboratory comparison: analytical methods in use, impact of methods on bacterial counts and measurement uncertainty of bacterial counts.

The proficiency testing program in food microbiology RAEMA (Réseau d'Analyses et d'Echanges en Microbiologie des Aliments), created in 1988, currently includes 450 participating laboratories. This interlaboratory comparison establishes proficiency in detection of Salmonella and Listeria monocytogenes, as well as enumeration of aerobic micro-organisms, Enterobacteriaceae, coliforms, beta-glucuronidase-positive Escherichia coli, anaerobic sulfito-reducing bacteria, Clostridium perfringens, coagulase-positive staphylococci, and L. monocytogenes. Twice a year, five units samples are sent to participants to assess their precision and trueness for enumeration and detection of micro-organisms. Most of participating laboratories use standard or validated alternative methods, they were 50-70% in 1994 and, for 5 years, they are 95%. An increasing use of alternative methods was also observed. This phenomenon is all the more significant as standard methods are laborious and time consuming; thus, 50% of the laboratories use alternative methods for the detection of Salmonella and L. monocytogenes. More and more laboratories use ready-to-use media and although the percentage is variable according to the microflora, we can consider that, today, 50-60% of the laboratories participating to the proficiency program only use ready-to-use media. The internal quality assurance programs lead also to an increasing use of media quality controls. The impact of analytical methods on bacterial counts was assessed by grouping together the results obtained by participating laboratories during the 10 last testing schemes from 1999 to 2003. The identified significant factors influencing enumeration results are variable from one microflora to another. Some of them significantly influence many microflora: the plating method (spiral plating or not) is influential for aerobic micro-organisms, Enterobacteriaceae, coliforms, and staphylococci, the type of culture medium and the medium manufacturer is influential for aerobic micro-organisms, Enterobacteriaceae, coliforms, E. coli, anaerobic sulfito-reducing bacteria, staphylococci, and L. monocytogenes. Others are specific of some micro-organisms: the resuscitation broth for L. monocytogenes, the mode of medium preparation for staphylococci and the incubation temperature for C. perfringens. These effects lead generally to small differences of about 0.1 log10 cfu g(-1), except for the enumeration of anaerobic sulfito-reducing bacteria, where the difference reaches 0.7 log10 cfu g(-1). These results, although difficult to extrapolate to all actual situations, which associate numerous food constituents and physiological states of bacteria to detect or numerate, allow nevertheless the quantification of interlaboratory variations linked to the methods in use. The analysis of bacterial counts obtained by the laboratories participating to the RAEMA proficiency testing program allowed also to validate a formula to calculate the repeatability of bacterial counts and to estimate the between-laboratory uncertainties for the majority of micro-organisms enumerated in food microbiology. The repeatability uncertainty is only indirectly affected by the method in use but depends essentially on the number of counted colonies. On the other hand, the between-laboratory uncertainty varies with the enumeration method in use, this variability is relatively small for the enumerations calling for methods without colony confirmation, i.e. for the enumeration of aerobic micro-organisms, Enterobacteriaceae, 'total' and thermotolerant coliforms, beta-glucuronidase-positive E. coli and coagulase-positive staphylococci with the technique using the rabbit-plasma fibrinogen agar. For these methods, the average between-laboratory standard deviation is 0.17 log10 cfu g(-1). The between-laboratory uncertainty is, on the contrary, larger for more complex techniques. For the enumeration of coagulase-positive staphylococci with the Baird-Parker agar, the between-laboratory standard deviation is equal to 0.23 log10 cfu g(-1), it is equal to 0.28 log10 cfu g(-1) for the enumeration of L. monocytogenes, to 0.34 log10 cfu g(-1) for the enumeration of C. perfringens, and to 0.47 log10 cfu g(-1) for the enumeration of anaerobic sulfito-reducing bacteria.

Bacteria↗

Effect of image uncertainty on the dosimetry of trigeminal neuralgia irradiation.

OBJECTIVE: Our objective was to quantify the uncertainty in localization of the trigeminal nerve (TGN) with magnetic resonance imaging (MRI) and computed tomography (CT) and to determine the effect of this uncertainty on gamma-knife dose delivery. METHODS: An MR/CT test phantom with 9, 0.6-mm diameter, copper rings was devised. The absolute ring positions in stereotactic space were determined by the angiographic module of the LGP software. The standard deviation, sigma, in the difference between the absolute and MR-measured or CT-measured coordinates of the rings was determined. The trigeminal nerve in 52 previously treated patients was contoured and expanded by 1sigma and 2sigma margins to model the uncertainty in the location of the nerve. For gamma-knife treatment, a single isocenter was used and was located at the distal cisternal portion of the trigeminal nerve root. Irradiation methods included a 4-mm collimator, 90 Gy to isocenter and a 4&8-mm collimator, 70 Gy to isocenter. A patient outcome survey that sampled pain relief and morbidity was done. RESULTS: The MR coordinate sigma was 0.7 mm left-right, 0.8 mm anterior-posterior, and 0.6 mm superior-inferior, and the CT coordinate sigma was 0.4 mm left-right, 0.2 mm anterior-posterior, and 0.2 mm superior-inferior. A 45% higher dose line covered the TGN with the 4&8-mm method. No significant increase in pain reduction or morbidity occurred. CONCLUSIONS: The uncertainty of target location by MRI is more than twice that found in CT imaging. The 4&8-mm collimator method covers the trigeminal root cross section with a higher isodose line than does the 4-mm method. This higher dose did not significantly reduce pain or increase morbidity.

Humans↗

Fearing the unknown: a short version of the Intolerance of Uncertainty Scale.

Intolerance of uncertainty is the tendency of an individual to consider the possibility of a negative event occurring unacceptable, irrespective of the probability of occurrence. It is a key component of worry, state anxiety, and related anxiety pathologies. The 27-item Intolerance of Uncertainty Scale (IUS) was developed to measure intolerance of uncertainty. Previous psychometric analyses of the IUS have suggested both four- and five-factor models. High inter-item correlations, factor instability, and previous theoretical research support the development of a reduced measure. The present study used two undergraduate samples and evaluated a psychometrically stable 12-item two-factor version of the IUS. The reduced measure (IUS-12) retained exemplary internal consistency, while correlating extremely well with the original IUS and related measures of anxiety and worry. The IUS-12 also demonstrated a stable two-factor structure, representing both anxious and avoidance components of intolerance of uncertainty. Directions for future research and potential applications for assessment are discussed.

Adolescent↗

Low uncertainty reverse isotope dilution ICP-MS applied to certifying an isotopically enriched Cd candidate reference material: a case study.

An analytical method is presented based on reverse isotope dilution single detector inductively coupled plasma magnetic sector mass spectrometry (ID-ICP-SMS) and applied to the specific case of the certification of a (111)Cd enriched candidate Cd spike calibration material (nominal mass fraction 10 mg kg(-1) in 5% HNO3 solution). Uncertainty propagation was used as a tool for both determining the analytical approach and validating it. The robustness of close to "exact matching" reverse IDMS to correction of measured isotope intensities for multiplicative (mass discrimination) and (semi)additive effects (dead time, instrumental background, and isobaric interference) is discussed. The very low experimental relative standard deviation of the mean (0.08%) of eight replicate determinations indicated that all significant sources of uncertainty had probably been taken into account for the estimation of the final combined uncertainty statement (U(c) = 0.17%, k = 1). IRMM-621 was used as comparator. Uncertainties on IUPAC isotopic abundances of 111Cd and 112Cd, for the natural Cd solution involved between the two enriched materials, formed nearly 60% of U(c). The repeatability of the isotope ratio measurements contributed less than 10%. Correction for procedural blank necessitated somewhat unusual calculations (potential contamination of an enriched material with natural Cd). The procedure also involved a quadrupole based ICP-MS judged to be appropriate for the characterization of the isotopic composition. For comparison purposes, direct IDMS results are simulated using identical experimental input data. Finally, a significant background signal in the 106-116 mass region, observed only with the magnetic sector instrument, was attributed to argon based isobaric interferences.

Belgium↗

Sensitivity of elastic properties to measurement uncertainties in laryngeal muscles with implications for voice fundamental frequency prediction.

This paper discusses the effects of measurement uncertainties when calculating elastic moduli of laryngeal tissue. Small dimensions coupled with highly nonlinear elastic properties exacerbate the uncertainties. The sensitivity of both tangent and secant Young's Modulus was quantified in terms of the coefficient of variation, which depended on measurement of reference length and cross-sectional area. Uncertainties in the measurement of mass, used to calculate cross-sectional area of a small tissue sample, affected Young's Modulus calculations when tissue absorption of the hydrating solution was not accounted for. Uncertainty in reference length had twice the effect on elasticity than other measures. The implication of these measurement errors on predicted fundamental frequency of vocalization is discussed. Refinements on isolated muscle experimental protocols are proposed that pay greatest attention to measures of highest sensitivity.

Elasticity↗

The uncertainty of the pendulum method for the determination of the moment of inertia.

The purpose of this study was to quantify the uncertainty of the pendulum method for determining the moment of inertia of an object using various suspension distances. Experimental data were collected on a known geometric solid and partial differential equations were derived to calculate the uncertainty. Repeated measures were used to estimate the errors of the mass, period of oscillation, and distance measurements from the axis to the centre of mass. The results showed that the pendulum method was relatively insensitive to measurement errors of mass but was quite sensitive to errors in the period of oscillation. It was also found that the uncertainty of the pendulum method could be drastically reduced to less than 3% by suspending the object with the axis located at the radius of gyration. Most studies using the pendulum method to determine limb inertial properties have adopted a proximal suspension, including the often cited work by Dempster [Dempster WT. Space requirements for the seated operator. W ADC Technical Report 55-159. Ohio: Aero Medical Laboratory, Wright Air Development Centre, Air Research and Development Council, Wright-Patterson Air Force Base; 1955]. The results suggest that validation of imaging techniques to determine inertial properties should use geometric solids in addition to the pendulum method where the object is suspended at a distance estimated to be the radius of gyration. It is further recommended that the uncertainty be reported whenever it is necessary to use the pendulum method.

Acceleration↗