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PubMed1985

Stimulus offset P3 and temporal resolution of uncertainty.

Stimulus offset evoked potentials were recorded to short (1 250 ms) and long (2 500 ms) tones in the context of the odd-ball paradigm. In one condition, the short tone was presented frequently with a probability of 0.85 and the long tone with a probability of 0.15, and in a second condition, the probabilities of tone presentation were reversed. Offset P3s were obtained only to short and not to long rare tones, indicating that resolution of uncertainty rather than stimulus probability or task relevance is responsible for eliciting this late positive component in the context of this experiment.

Adult↗
PubMed1989

Validity and uncertainty in the calculation of an emission inventory for ammonia arising from agriculture in Great Britain.

Emissions of ammonia have received increasing attention recently, following concern about the environmental consequences, especially in The Netherlands where levels are high due to intensive livestock farming. Direct local effects and more widespread consequences for a range of ecosystems have been attributed to ammonia emissions. As the most prevalent alkaline gas in the atmosphere, ammonia interacts with acidic species, changing their characteristics, chemical and physical behaviour, and enhancing their potential for acidification of soils. Ammonia also forms an important component of the nitrogen cycle and of nitrogen deposition. In the UK, as in many other European countries, there has been a considerable increase in the emission of ammonia within the last 30 years, estimated at about 50%. This results mainly from increases in agricultural production based on the steadily rising number of livestock and increasing fertilizer consumption. This paper discusses the various sources to emissions of ammonia from agricultural sources in the United Kingdom, and some of the uncertainties involved in constructing a national emissions inventory.

Journal Article↗
PubMed1994

Uncertainties in radiation effect predictions for the natural radiation environments of space.

Future manned missions beyond low earth orbit require accurate predictions of the risk to astronauts and to critical systems from exposure to ionizing radiation. For low-level exposures, the hazards are dominated by rare single-event phenomena where individual cosmic-ray particles or spallation reactions result in potentially catastrophic changes in critical components. Examples might be a biological lesion leading to cancer in an astronaut or a memory upset leading to an undesired rocket firing. The risks of such events appears to depend on the amount of energy deposited within critical sensitive volumes of biological cells and microelectronic components. The critical environmental information needed to estimate the risks posed by the natural space environments, including solar flares, is the number of times more than a threshold amount of energy for an event will be deposited in the critical microvolumes. These predictions are complicated by uncertainties in the natural environments, particularly the composition of flares, and by the effects of shielding. Microdosimetric data for large numbers of orbits are needed to improve the environmental models and to test the transport codes used to predict event rates.

Cosmic Radiation↗
PubMed1985

Uncertainty factors and interindividual variation.

Human variation in response to environmental agents appears often greater than a factor of 10, sometimes even up to several orders of magnitude. However, the vast majority of people studied to date respond within a factor of 10. The implications of these findings for the current use of uncertainty factors in regulatory toxicology is discussed.

Acetylation↗
PubMed1989

Reducing uncertainty in risk assessment.

This article presents a summary of the proceedings of the Symposium and Workshop on Reducing Uncertainty in Risk Assessment, held at Michigan State University, on May 18-19, 1987. Participants addressed four topic areas: safety factors in noncarcinogen risk assessment; relevance of biological data in risk assessment; upper and lower bounds in carcinogenic risk assessment; and exposure assessment. One additional issue, risk communication, was discussed as a result of participant interest. Consensus recommendations in these five areas, resulting from the deliberations of the workshop groups, are presented. In addition to the specific recommendations, some general conclusions could be drawn. One was that the increased understanding of underlying mechanisms of toxicity, gained in the last decade, should be incorporated as much as possible into the risk assessment process. A second conclusion was that more effort should be devoted to increasing this understanding and developing the best methods for applying this knowledge to risk assessment. Last, more effort should be made to improve the communication of these assessments to the public and to policy makers so that the best and most complete information is utilized in risk management decisions.

Animals↗
PubMed1992

Does the animal-to-human uncertainty factor incorporate interspecies differences in surface area?

Risk assessment practices for noncarcinogens typically employ an uncertainty factor (UF) for animal-to-human extrapolation when defining acceptable levels for humans based on animal studies. EPA has interpreted the use of this factor as addressing interspecies differences due to dose normalization via surface area (exposure-dose relationships) and to innate differences in species susceptibility (dose-response relationships). Thus EPA has concluded that dose normalization via surface area is not necessary when using animal studies to define acceptable levels for noncarcinogens for humans. In this report we challenge this position on both theoretical and practical grounds. It is recommended that the UF for animal-to-human extrapolation for noncarcinogens in the risk assessment process and the technique for dose normalization be considered distinctly.

Animals↗
PubMed1992

Uncertainty in risk assessment: exceedence frequencies, acceptable risk, and risk-based decision making.

The use of "exceedence frequencies" is proposed as a means of evaluating the acceptability of uncertain environmental risks. A survey was conducted of U.S. Environmental Protection Agency personnel. When respondents were requested to identify preferred "acceptable" exceedence frequencies at four different regulatory risk thresholds (10(-3) to 10(-6), three general response patterns were found: "absolutist" responses in which no level of exceedence was deemed acceptable; "fixed" responses in which respondents felt that the level of exceedence should remain constant at all risk levels; and "outcome sensitive" responses in which preferred exceedence frequencies were inversely related to the risk level. This last group's responses were based on the rationale that the "marginal cost" of risk (in terms of expected mortalities) increases as the risk threshold increases. Although the majority of respondents accepted the concept of an acceptable risk exceedence frequency, the low exceedence frequencies selected as being "acceptable" by survey respondents (generally 5% or less) appear to be overly conservative given the degree of uncertainty inherent in risk assessments. Finally, two regulatory uses of exceedence frequencies are proposed as a tool for streamlined risk ranking.

Attitude of Health Personnel↗
PubMed1989

Professional uncertainty and physician medical decision-making in a multiple treatment framework.

This paper develops a new microanalytic approach to physician medical decision-making treatment setting. Physician medical decision-making is modelled as a two-stage sequential process. In Stage 1, the patient's illness is diagnosed and the health outcomes for all illness-related restoration options are identified. In Stage 2, an "optimal" restoration option is selected. This model provides new insights into physician medical decision-making and the complexity of proving physician-induced demand in a medical care market where professional uncertainty and consumer heterogeneity exist.

Clinical Competence↗
PubMed1995

Dealing with uncertainty: will science solve the problems of resource allocation in the U.K. NHS?

In spite of the huge efforts which internationally address the development and assessment of health technologies, the majority of health care interventions have not been formally evaluated for their effectiveness and their likely impact upon health status is largely unknown. This has led to a situation where it is unclear on what basis a health care system might be judged, or for that matter on what basis decisions on the specification of individual services might be made. It has frequently been argued that the only way to build an adequate understanding of the effectiveness of different interventions is through systematically locating and synthesising the available evidence from research, and such systematic overviews are increasingly available in many areas. However, such overviews produce few clear conclusions, and even when the results of systematic overviews show unequivocal benefits for patients, implementing the findings of such reviews remains problematic. Research evidence provides useful information on marginal benefits for patients, though areas where the absolute benefit is high appear to be very rare. The most common finding appears to be uncertainty. Interpreting research evidence is complex, and even very clear findings may prove hard to operationalise. Good quality research will help, but will not solve, the problems of resource allocation in the NHS or in other health systems.

Adrenal Cortex Hormones↗
PubMed1976

Psychophysical judgment: electro-cortical and heart rate correlates of accuracy and uncertainty.

The relationship between perceptual accuracy and physiological response amplitude was investigated in an auditory pitch discrimination experiment. Confidence ratings were obtained from all subjects following each trial. The stimulus set consisted of three tones of different frequencies spaced in a manner to provide both easy and difficult discriminations. Heart rate, EEG and vertical eye movement were recorded throughout the experiment. The results of the experiment indicated that the largest evoked cardiac rate response was elicited by the stimulus which produced the fewest errors in judgment; larger auditory evoked potentials, particularly the late positive component (P300), were associated with the 'easy' stimulus; greater cortical negativity was associated with the difficult stimuli. Eye activity was found to covary with judgmental accuracy; cortical slow wave activity was particularly sensitive to the confidence, or 'uncertainty' parameter. A 'decision tree' model was hypothesized to describe the processing mechanism involved in solving the discrimination problem.

Acoustic Stimulation↗
PubMed1983

Sources of uncertainty and psychophysiological state changes under conditions of noxious stimulus anticipation.

The main aim of the experiment was to compare the effect of the two variables (regarded here as different sources of subjective uncertainty) - probability of stimulus occurrence and ambiguity of the message about this probability - upon changes in heart rate (HR) and skin resistance (SR) during anticipation of a noxious stimulus. Three other independent variables - the type of stimulus (shock vs. sound), repetition of trials (two series of trials), and time-within-trial - were controlled as well. Results indicate that ambiguity as compared to probability has a more pronounced effect upon SR changes. Effects of the two variables upon HR changes are not significant. Moreover, in the shock group, the effect of repetition of trials was found to have a habituation effect for HR changes and a dishabituation effect for SR changes.

Acoustic Stimulation↗
PubMedDate not supplied

Force uncertainty of voluntary movement and human movement-related potentials.

Five movement related potentials, the Bereitschaftspotential (BP), the pre-motion positivity (PMP), the motor potential (MP), the first negative potential during the movement (N1) and the late positive component (LPC) were recorded from human subjects performing right index finger flexions under conditions when the resistive forces (70 N/cm or 10 N/cm) were predictable and when they were unpredictable. The BP was larger prior to the larger force in the certain condition. In the uncertain condition, the BP was similar to that associated with the larger force in the certain condition suggesting that the subjects tended to prepare for the heavy resistance when confronted with force uncertainty. The MP revealed enhanced negativity over the left parietal cortex when the force was unpredictable. The N1 was significantly larger during the high force movement, especially in the uncertain condition. The results support the view that pre-movement compensation for force unpredictability does exist as reflected by the MP over the parietal areas.

Adolescent↗
PubMed1995

An evaluation of setup uncertainties for patients treated to pelvic sites.

PURPOSE: Successful delivery of conformal fields requires stringent immobilization and treatment verification, as well as knowledge of the setup reproducibility. The purpose of this study was to compare the three-dimensional distribution of setup variations for patients treated to pelvic sites with electronic portal imaging devices (EPID) and portal film. METHODS AND MATERIALS: Nine patients with genitourinary and gynecological cancers immobilized with custom casts and treated with a four-field whole-pelvis technique were imaged daily using an EPID and filmed once every five to seven treatments. The three-dimensional translational and rotational setup errors were determined using a technique that relies on anatomical landmarks identified on simulation and treatment images. The distributions of the translational and rotational variations in each dimension as well as the total displacement of the treatment isocenter from the simulation isocenter were determined. RESULTS: Grouped analysis of all patients revealed average unidirectional translational deviations of less than 2 mm and a standard deviation of 5.3 mm. The average total undirected distance between the treatment and simulated isocenters was 8.3 mm with a standard deviation of 5 mm. Individual patient analysis revealed eight of nine patients had statistically significant nonzero mean translational variations (p < 0.05). Translational variations measured with film were an average of 1.4 mm less than those measured with EPID, but this difference was not statistically significant. CONCLUSION: Translational variations measured in this study are in general agreement with previous studies. The use of the EPID in this study was less intrusive and may have resulted in less additional attention being given each imaging setup. This may explain the slightly larger average translational variations observed with EPID vs. film, and suggests that the use of EPIDs is a superior method for assessing the true extent of setup displacements. Although no statistically significant translational variations for the patient group overall were observed, 90% of patients had significant translational variations in at least one direction when analyzed separately. The margin to be added to the clinical target volume (CTV) to account for setup uncertainties will depend on whether it is possible to identify patients with significant translational variations, and to eliminate these displacements from routine treatments. The choice to eliminate these variations and to use a smaller CTV margin will have to be accompanied by stringent frequent position verification methods and repositioning.

Female↗
PubMed1989

Diagnosis deferred--the clinical spectrum of diagnostic uncertainty.

This study attempts to define the term "Diagnosis Deferred" (DD) and determine its natural history and outcome. It is suggested that such a "non-diagnosis" should be used when the clinical and laboratory picture cannot be explained by any known disease entity after a minimum of 5 days hospitalization. During a 9 year period (1972-1980) 250 patients (1.8%) were identified as warranting the term DD from a total of 14,098 admissions to a department of Internal Medicine. Their average stay in hospital was 11.5 days. There was no sex difference between the patients, whose average age was 42.8 +/- 17.6 years (mean +/- SD; range 14-93). Three complaints predominated: joint pains (21.6%), abdominal pain (20.4%) and chest pain (16.8%). In 103 of the patients, there was follow-up information until the diagnosis was made or for at least 24 months (average 53.0 +/- 40.0 months, range 2-186). These patients were representative of the original cohort in both age, sex and classification of symptoms. Forty-three patients (42%) were subsequently diagnosed. 58% of these patients were diagnosed as a result of a change in or appearance of a clinical symptom during the follow-up period. "The survival of diagnostic uncertainty" in 50% of the patients was 84.5 months (7 years) with a range of 2-13 years. This time was significantly shorter for chest pain than for abdominal pain (33 months vs 87 months) (p = 0.003). In patients with "Diagnosis Deferred", a diagnosis was reached in 42%; in 22% the symptoms disappeared leaving 36% undiagnosed, and a continuing clinical challenge.

Abdomen, Acute↗
PubMed2006

Opioid contracts in chronic nonmalignant pain management: objectives and uncertainties.

In this article, we review the principal objectives and ideal elements of opioid contracts, as articulated by proponents of the practice. We examine the limited empirical evidence for the effectiveness of opioid contracts in achieving their intended objectives and identify areas of uncertainty and of ethical concern regarding their implementation. We argue that the challenge in deciding about implementing opioid contracts in clinical practice relates to the multiplicity of potential objectives they might serve, to a lack of empirical evidence regarding their effectiveness, and to ethical concerns over their implementation. Specialty and primary care clinicians contemplating the use of opioid contracts in treating patients with chronic nonmalignant pain need to be sensitive to these considerations, and further debate and research is necessary to establish the proper objectives, elements, effectiveness, and ethical justifications of opioid contracts in clinical practice.

Analgesics, Opioid↗
PubMed2005

137Cs measurement uncertainties and detection limits for airborne gamma spectrometry (AGS) data analysed using a spectral windows method.

The uncertainties associated with airborne gamma spectrometry (AGS) measurements analysed using a spectral windows method, and associated detection limits, have been investigated. For individual short measurements over buried 137Cs activity detection limits of 10 kBq m(-2) are achieved. These detection limits are reduced for superficial activity and longer integration times. For superficial activity, detection limits below 1 kBq m(-2) are achievable. A comparison is made with the detection limits for other data processing methods.

Journal Article↗
PubMed2006

Nonaqueous capillary electrophoresis method for the enantiomeric purity determination of S-timolol using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin: validation using the accuracy profile strategy and estimation of uncertainty.

Nonaqueous capillary electrophoresis (NACE) was successfully applied to the enantiomeric purity determination of S-timolol maleate using heptakis(2,3-di-O-methyl-6-O-sulfo)-beta-cyclodextrin (HDMS-beta-CD) as chiral selector. With a background electrolyte made up of a methanolic solution of 0.75 M formic acid, 30 mM potassium camphorsulfonate and containing 30 mM HDMS-beta-CD, the determination of 0.1% of R-timolol in S-timolol could be performed with an enantiomeric resolution of 8.5. Pyridoxine was selected as internal standard. The NACE method was then fully validated by applying a novel strategy using accuracy profiles. It is based on beta-expectation tolerance intervals for the total measurement error which includes trueness and intermediate precision. The uncertainty of measurements derived from beta-expectation tolerance intervals was estimated at each concentration level of the validation standards. To confirm the suitability of the developed and validated method, several real samples of S-timolol maleate containing R-timolol maleate at different concentrations were analysed and the results were compared to those obtained by liquid chromatography.

Antihypertensive Agents↗
PubMed2006

Prediction of measurement uncertainty in isotope dilution gas chromatography/mass spectrometry.

An equation is theoretically derived which describes the relative standard deviation (RSD) of the amount ratios of analyte to its isotope-labeled variant in gas chromatography/mass spectrometry (GC/MS) using the stable isotope dilution method. The determination of methyltestosterone is taken as an example. The uncertainty equation proposed is justified by comparing the theoretical RSD values with the experimental RSD values obtained by replication over a wide range of analyte amount. The detection limit and quantitation limit are estimated from the continuous plot (precision profile) of the theoretical RSD against analyte amount.

Deuterium↗