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PubMed2005

A psychometric analysis of the Intolerance of Uncertainty Scale among four racial groups.

Recent psychometric analyses examining the cross-cultural validity of key anxiety measures have suggested that some, such as the Anxiety Sensitivity Index (ASI), may hold different psychometric characteristics among different racial or national groups. The Intolerance of Uncertainty Scale (IUS) is a self-report measure that, like the ASI, appears to assess a predispositional risk for developing some anxiety and mood disorders. Despite its validation in both a French and English version, the majority of the research conducted on the IUS has used predominantly Caucasian samples. Given this, the purpose of this research was to examine and compare the psychometric properties of the IUS among non-clinical participants of four racial groups: African American, Caucasian, Hispanic/Latino, and Southeast Asian. The data suggested generally strong, and highly similar, estimates of reliability and validity across the four racial groups. The factor structure of the IUS, however, was poorly interpretable among any of the groups. Implications for use of the IUS with different racial groups are discussed.

Adolescent↗

PubMed2006

Ranking without valuing in the face of major uncertainty--the case of the promotion of biodegradable lubricants.

Major benefit uncertainties prevent monetary quantification of some environmental amenities. Replacing mineral lubricants with biodegradable substitutes is shown to be a case in point. However, it is possible to rank the social benefits of substituting mineral lubricants with regard to different applications and environments. As the private costs and benefits of substitution are mainly constant, only a policy that prioritizes full substitution in the applications with the greatest benefits can be efficient. It is shown that regulations requiring substitution in certain fields are likely to fulfil this criterion, while subsidies for production, processing, market introduction and research usually fail to meet the efficiency criterion.

Biodegradation, Environmental↗

PubMed2005

Stochastic analysis and prioritization of the influence of parameter uncertainty on the predicted pressure profile in heterogeneous, unsaturated soils.

This article utilizes a Monte Carlo stochastic framework to investigate the influence on the mean and variance of the predicted mean pressure head profile of statistical assumptions regarding the parameters that enter the mathematical description of the problem of infiltration in unsaturated, heterogeneous layers. The parameters are treated as random functions with an exponential auto-covariance function expressing their spatial continuity. Four different truncated distributions are taken to describe the parameters according to field observations and various phases of site characterization campaigns. The exponential distribution is seen to produce the largest (in absolute value) mean and variance in the pressure head profile. For all distributions the variance in pressure head increases with increasing mean pressure. A second topic of this article is to investigate, the relative importance of each parameter, in terms of the mean and the variance of the predicted pressure. For uniformly or triangularly distributed parameters the saturated hydraulic conductivity appears to dominate the mean-behavior and the uncertainty in the system's solution. For lognormally or exponentially distributed parameters another parameter, the van Genuchten pore-size distribution index, is the dominant factor.

Pressure↗

PubMed2006

Robustness testing of a chiral NACE method for R-timolol determination in S-timolol maleate and uncertainty assessment from quantitative data.

A robustness test of a capillary electrophoresis method for the chiral separation of timolol in nonaqueous acidified media was performed. A two-level Plackett-Burman design was applied in which one qualitative and six quantitative factors were examined. Resolution, migration times and relative migration times to pyridoxine (selected as internal standard) were examined as qualitative responses to evaluate electrophoretic performance. A quantitative response, the content of R-timolol in S-timolol maleate sample, was also considered. Even though some significant factor effects were observed on the qualitative responses, it was still possible to quantify the R-timolol in the S-timolol maleate samples properly. The quantitative response was not significantly affected by the selected factors, demonstrating the robustness of the procedure. However, the use of different HDMS-beta-CD batches seemed to affect both types of responses necessitating to introduce a warning in the procedure. Since the experiments of the Plackett-Burman design can be assimilated to laboratories in an interlaboratory study, uncertainty can be evaluated using the robustness test data. The robustness test was set-up in such a way that the required variances could be estimated.

Adrenergic beta-Antagonists↗

PubMed2005

Before and beyond the precautionary principle: epistemology of uncertainty in science and law.

The precautionary principle has become, in European regulation of science and technology, a general principle for the protection of the health of human beings, animals, plants, and the environment. It requires that "[w]here there are threats of serious or irreversible damage, lack of full scientific certainty shall not be used as a reason for postponing cost-effective measures to prevent environmental degradation". By focusing on situations of scientific uncertainty where data are lacking, insufficient, or inconclusive, the principle introduced a shift from a neutral legal attitude towards science to a bias in favor of safety, and a shift from the paradigm of science certain and objective to the awareness that the legal regulation of science involves decisions about values and interests. Implementation of the precautionary principle is highly variable. A crucial question still needs to be answered regarding the assumption that scientific certainty is a 'normal' characteristic of scientific knowledge. The relationship between technoscience and society has moved into a situation where uncertain knowledge is the rule. From this perspective, a more general framework for a democratic governance of science is needed. In democratic society, science may still have a special authoritative voice, but it cannot be the ultimate word on decisions that only the broader society may make. Therefore, the precautionary model of scientific regulation needs to be informed by an 'extended participatory model' of the relationship between science and society.

Models, Theoretical↗

PubMed2005

The cost-effectiveness of basiliximab induction in "old-to-old" kidney transplant programs: Bayesian estimation, simulation, and uncertainty analysis.

INTRODUCTION: Markov models are employed in economic analyses to evaluate all possible expectations in a dilemna. The introduction of a new clinical protocol (Basiliximab induction with calcineurin-sparing protocols) for a group of kidney transplant recipients receiving organs from marginal donors was validated with a Markov simulation model, demonstrating the usefulness of combining simulation with Bayesian estimation methods for analysis of cost-effectiveness data collected alongside a clinical trial. We sought to determine whether calcineurin-sparing protocols using anti-interleukin-2/antibody induction (Simulect) would show a beneficial effect on initial kidney function and reduce transplantation costs upon admission, clinical incidences, graft function, and complications during the first month after transplant. PATIENTS AND METHODS: A Markov Chain Monte Carlo (MCMC) was used to estimate a system of generalized linear models relating costs and outcomes to a kidney transplant process affected by treatment under alternative therapies. The Markov simulation model was established following three chains: a calcineurin-free regimen with Basiliximab induction (chain A); a calcineurin-sparing protocol with Basiliximab induction (chain B); and a conventional immunosuppressive regimen (chain C). The MCMC draws were used as parameters in simulations that yielded inferences about the relative cost-effectiveness of the novel therapy under a variety of scenarios. After designing the Markov chain and cohorts, 31 patients from the "old-to-old" program were assigned; eight to chain A; eight to chain B; and 15 to chain C. A year after transplantation a cost-benefit study was performed guided by the three branches of the Markov model. RESULTS: The Markov model showed a benefit of induction therapies in elderly patients. A cost-benefit model showed that after a year, there was a clear benefit from calcineurin-free plus Basiliximab induction therapies, with a slight benefit from calcineurin-sparing protocols. CONCLUSIONS: Markov models are extremely useful when introducing new clinical therapies. The approach allows flexibility in assessing treatment using various premises and quantifies the global effect of parametric uncertainty on a decision maker's confidence to adopt one therapy over another. In our transplant program, a cost-effective analysis of outcomes in old patients using the Markov model showed a clear benefit of calcineurin-sparing protocols with Basixilimab induction.

Age Factors↗

PubMed2004

Stopping the motion and sleuthing the flash-lag effect: spatial uncertainty is the key to perceptual mislocalization.

A moving object is perceived to lie beyond a static object presented at the same time at the same retinal location (flash-lag effect or FLE). Some studies report that if the moving stimulus stops moving (flash-terminated condition or FTC) the instant the flash occurs, a FLE does not occur. Other studies, using different stimuli, report that the FLE does, in fact, occur in the FTC. The FTC is thus a crucial turning point in theories of flash-lag. Unraveling the mystery of the FLE in the FTC will help unravel the mechanisms underpinning flash-lag and perhaps even perceptual localization in general. Our experiments show that eccentricity of the moving stimulus was a contributing factor, as were eccentricity of the flashed stimulus and spatial separation between the two stimuli. Other factors, such as contrast and offset of moving stimulus, also modulate the magnitude of the FLE in the FTC. We surmise that uncertainty in determining the position in space of a moving stimulus is a key requirement for the lag-effect. A lag-effect in the FTC challenges influential models, such as differential latency, motion extrapolation, and postdiction. Based partly on the notion of an asymmetric spread of activity that arises because of the sheer nature of motion and from a combination of established physiological mechanisms, we propose a schematic account of the present findings that subsumes previous psychological models and scaffolds past experimental findings.

Contrast Sensitivity↗

PubMed2006

The use of Markov chain Monte Carlo uncertainty analysis to support a Public Health Goal for perchloroethylene.

The current Public Health Goal (PHG) for perchloroethylene (PCE) was derived using upper-bound estimates of fractional PCE metabolism in humans. These estimates were in part obtained from a published evaluation of the uncertainty and variability in human PCE metabolism conducted using a physiologically-based pharmacokinetic (PBPK) model in a Markov chain Monte Carlo (MCMC) analysis; however, the data used in that analysis were limited to post-exposure PCE blood and exhaled air concentrations from a single study. A more recent study [Volkel, W., Friedewald, M., Lederer, E., Pahler, A., Parker, J., Dekant, W., 1998. Biotransformation of perchloroethene: dose-dependent excretion of trichloroacetic acid, dichloroacetic acid, and N-acetyl-S-(trichlorovinyl)-l-cysteine in rats and humans after inhalation. Toxicol. Appl. Pharmacol. 153(1), 20-27.] provides data on blood concentrations of PCE and its major metabolite, trichloroacetic acid (TCA), and urinary excretion of TCA following exposure of human subjects to lower concentrations of PCE (10-40ppm) than in previous studies. In the present effort, a new MCMC analysis was performed that focused on data from this study along with two others [Fernandez, J., Guberan, E., Caperos, J., 1976. Experimental human exposures to tetrachloroethylene vapor and elimination in breath after inhalation. Am. Ind. Hyg. Assoc. J. 37, 143-150; Monster, A., Boersma, G., Steenweg, H., 1979. Kinetics of tetrachloroethylene in volunteers; influence of exposure concentration and work load. Int. Arch. Occup. Environ. Health 42, 303-309.] providing data on PCE blood concentrations and urinary excretion of TCA. To provide an accurate prediction of TCA kinetics, the PBPK model used here includes a description of the metabolism of PCE to TCA in both the liver and kidney. The resulting upper 95th percentile estimates of fraction of PCE metabolized by inhalation and oral routes were 2.1 and 5.2%, respectively, compared to 58 and 79% used in the derivation of the PHG.

Carcinogens, Environmental↗

PubMed2003

Prejudice, clinical uncertainty and stereotyping as sources of health disparities.

Disparities in health can result from the clinical encounter between a doctor and a patient. This paper studies three possible mechanisms: prejudice of doctors in the form of being less willing to interact with members of minority groups, clinical uncertainty associated with doctors' differential interpretation of symptoms from minority patients or from doctor's distinct priors across races, and stereotypes doctors hold about health-related behavior of minority patients. Within a unified conceptual framework, we show how all three can lead to disparities in health and health services use. We also show that the effect of social policy depends critically on the underlying cause of disparities.

Benchmarking↗

PubMed2003

Revisiting the decision rule of cost-effectiveness analysis under certainty and uncertainty.

The classical decision rule of cost-effectiveness analysis uses a threshold cost-effectiveness ratio as a cut-off point for resources allocation. One assumption of this decision rule is complete divisibility of health care programs. In this article, we argue that health care programs cannot be completely divisible since individuals are not divisible. Consequently, instead of a linear programming approach, an integer programming approach to budget allocation is suggested. The integer programming framework can be extended to include uncertainty in the analysis. An objective function (expected aggregate effects) is maximised subject to the constraint that the probability of exceeding the budget is limited to an arbitrary level (e.g., 0.05). In case the budget is exceeded, the objective function is penalised in order to account for the opportunity costs of the additional resource requirements.

Budgets↗

PubMed2003

Polymorphic CYP2C19 and N-acetylation: human variability in kinetics and pathway-related uncertainty factors.

CYP2C19-mediated oxidation and N-acetylation constitute major phase I and phase II polymorphic pathways of xenobiotic metabolism in humans. Analysis of human variability in kinetics for these pathways has been carried out for compounds metabolised extensively (>60%) by these routes. Data for minor substrates for CYP2C19 metabolism (10-60%) have also been analysed. Published pharmacokinetic studies (after oral and intravenous dosing) in CYP2C19 non-phenotyped healthy adults (NPs), and phenotyped extensive (EMs), slow-extensive (SEMs) and poor metabolisers (PMs) have been analysed using data for parameters that relate primarily to chronic exposure (metabolic and total clearances, area under the plasma concentration-time curve) and primarily to acute exposure (peak concentration). Similar analyses were performed for the N-acetylation pathway using data for fast acetylators (FA) and slow acetylators (SA). Interindividual variability in the kinetics of CYP2C19 substrates after oral dosage was greater in EMs than in NPs (60 vs 43% for clearances and 54 vs 45% for Cmax). Lower variability was found for N-acetylation for both phenotypes (32 and 22% for FA and SA, respectively). The internal dose of CYP2C19 substrates in PM subjects would be 31-fold higher than in EMs, while for N-acetylated substrates there was a three-fold difference between SA and FA subjects. Pathway-related uncertainty factors were above the default safety factor of 3.16 for most subgroups and values of 52 and 5.2 would be necessary to cover to the 99th centile of the poor metaboliser phenotype for CYP2C19 and N-acetylation, respectively. An exponential relationship (R(2)=0.86) was found between the extent of CYP2C19 metabolism and the difference in internal dose between EMs and PMs. The kinetic default factor (3.16) would cover PMs for substrates for which CYP2C19 was responsible for up to 20-30% of the metabolism in EMs.

Acetylation↗

PubMed1996

The language of death: euthanatos et mors--the science of uncertainty.

This article proposes that the medical community has a responsibility to guide and to treat patients through death just as it guides and treats them through life. A number of misunderstood concepts relating to this responsibility are discussed. An approach to the management of death that requires an embracing of medical uncertainty is developed.

Attitude to Death↗

PubMed2006

The role of uncertainty in the systematic spatial mislocalization of moving objects.

It only makes sense to talk about the position of a moving object if one specifies the time at which its position is of interest. The authors here show that when a flash or tone specifies the moment of interest, subjects estimate the moving object to be closer to where it passes the fixation point and further in its direction of motion than it really is. The authors propose that these biases arise from a combination of a large temporal uncertainty, a temporal asymmetry related to sampling the moving object's position, and a bias toward believing that one is looking at what one sees.

Adult↗

PubMed2005

Effect of uncertainty components such as recalibration on the performance of quality control charts.

BACKGROUND: Uncertainty components (recalibration, new reagent lots, etc.) may be the source of random changes in the level of quality control (QC) values, thus causing false alarms. We propose a method for reducing false alarms. MATERIAL AND METHODS: Daily QC measurements of 22 biochemical quantities were recorded over 5 months, while methods and analyser showed no signs of malfunctioning. Each time series of QC values was subdivided according to reagent lot, electrolyte diluent or disposable electrode used. Analysis of variance (ANOVA) was used to examine whether mean levels changed significantly between subseries. For each quantity, the entire time series and each subseries were examined for autocorrelation. An X chart and an exponentially weighted moving average (EWMA) chart (or EWMAST [EWMA for stationary processes] in autocorrelated series) were calculated from the first 50 values of each series or subseries and applied to the whole series. Values falling outside the three standard deviation control limits were noted. RESULTS: In 22 out of 24 time series, the mean level differed significantly between subseries. These changes caused spurious autocorrelation. However, in 51.3 % of all subseries a significant autocorrelation could also be demonstrated. In total, 5.6 % and 29.1 % of all time series values fell outside the control limits of the X charts and the EWMA or EWMAST charts, respectively. These percentages were significantly reduced to 0.44 and 0.70 when the subseries-specific control charts were used. CONCLUSIONS: The mean level may change because of recalibrations or change of electrolyte diluent lot with subsequent false alarms. False alarms may be significantly reduced by revising QC charts when significant changes occur.

Albumins↗

PubMed2005

Governing genomics in the 21st century: between risk and uncertainty.

The paper reconstructs the governance of genomics by sketching the main features, modes of operation and tactics of the emerging genomics apparatus. Genomic governance in the 20th century is characterized by the simultaneous operation of a process of the stabilization of knowledge regimes, in particular via patenting. Furthermore, we observe a heterogenization and globalization of the actors and knowledge creating systems in genomics governance. A variety of different mechanisms and strategies of governance are mobilized simultaneously. The transition of governing via risk to governance by uncertainty is another important feature of contemporary genomics governance. The implications of these trends for the regulation of genomics are considerable and might lead to the emergence of new patterns and spaces of conflict and controversy. The governance of genomics in the 21st century could become a more complex challenge than currently anticipated by many policy makers and the scientific community.

Europe↗

PubMed1994

Uncertainty in delivered dose resulting from the distribution of source activities in a Selectron LDR afterloader.

The uncertainty in the delivered dose resulting from the distribution of 137Cs source activity in a clinical Selectron LDR unit has been studied. A comparison is made of the dose delivered to a point 'A' in an implant with sources of equal activity to the actual dose delivered in the same implant with source activities randomly chosen from the population in the afterloader.

Cesium Radioisotopes↗

PubMed2005

Anonymous versus confidential HIV testing: client and provider decision making under uncertainty.

Six intensive observational studies of HIV testing sites were undertaken in order to improve understanding of confidential and anonymous testing. Three sites offered only confidential testing (a large health maintenance organization's Urgent Care clinic, the same organization's HIV clinic, and a private medical practitioner's office), one offered only anonymous testing (a free clinic), and two offered a choice of confidential or anonymous testing (a thrift shop alternate testing site and a mobile testing unit). Multiple data collection strategies were used including direct field observation, semistructured interviews with clients and providers, and document and policy analysis. Using an organizational/interactional uncertainty framework, this study found that the choice between anonymous and confidential testing is a central aspect of the HIV testing process, that some clients are unclear about the differences between anonymous and confidential testing, that alternate testing sites' providers play a significant role in encouraging confidential rather than anonymous testing in order to further their organization's resource needs and public health goals, and that testing counselors' may consider that some clients prefer anonymous testing because of fear of stigma, discrimination, or loss of privacy.

AIDS Serodiagnosis↗

PubMed2006

Mired in the quagmire of uncertainty: The "catch-22" of embryonic stem cell research.

Pluripotent human embryonic stem (ES) cells hold remarkable therapeutic potential, but their use is fraught with moral, ethical, scientific, and political concerns. In this essay, I discuss how an odd combination of patent issues, presidential policy, market uncertainties, and evolving Food and Drug Administration regulations have together hindered the progress of ES cell research in the United States of America. This coalescence of issues is unique. I suggest that these factors explain why the United States has not been a dominant player in advancing ES research. I predict that small, noncontroversial changes would go far in ameliorating many of the roadblocks that now exist. Most of these changes would not require a change in policy or even action by the U.S. government; a simple clarification and definition would suffice. The reason these changes have met solid resistance is suggested to derive from financial rather than moral, ethical, or scientific issues.

Adult↗