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PubMedDate not supplied

Changes in health status and quality of life and the impact of uncertainty in patients who survive life-threatening arrhythmias.

OBJECTIVE: The purpose of this study was to describe the changes in perception of health status and quality of life from before treatment to 6 months after and the impact of uncertainty on these variables in survivors of life-threatening arrhythmia. DESIGN AND SETTING: A descriptive correlational design at a large urban teaching hospital. MEASURES: We measured health status, quality of life, and uncertainty before treatment and 6 months after a life-threatening arrhythmia. RESULTS: Survivors included 66 men and 15 women, 41 of whom received pharmacologic therapy and 36 of whom received an implantable cardioverter defibrillator (ICD), completed the Medical Outcomes Survey (SF-36), Ferrans and Powers Quality of Life Index (QLI), and the Mishel Uncertainty in Illness Scale (MUIS-C) before treatment and 6 months after. There were significant improvements in the mental and physical health composite summaries as measured by the SF36 (P <.01). Conversely, there were significant reductions in the overall score and specifically in socioeconomic and psychological/spiritual quality of life domains as measured by the QLI (P <.05). An increased perception of uncertainty was related to decreased perception of health status and quality of life at both measurement times, with higher correlations 6 months later. CONCLUSIONS: Survivors demonstrated improvements in perceived health status, although this did not appear to translate into improvements in the subjective domains of quality of life. The overall quality of life and the domains of psychological/spiritual state and socioeconomic status were lower 6 months after a life-threatening arrhythmia. Uncertainty had a significant impact on these perceptions, identifying an area for nursing interventions.

Adaptation, Psychological↗

PubMed2002

Margins for geometric uncertainty around organs at risk in radiotherapy.

BACKGROUND AND PURPOSE: ICRU Report 62 suggests drawing margins around organs at risk (ORs) to produce planning organ at risk volumes (PRVs) to account for geometric uncertainty in the radiotherapy treatment process. This paper proposes an algorithm for drawing such margins, and compares the recommended margin widths with examples from clinical practice and discusses the limitations of the approach. METHOD: The use of the PRV defined in this way is that, despite the geometric uncertainties, the dose calculated within the PRV by the treatment planning system can be used to represent the dose in the OR with a certain confidence level. A suitable level is where, in the majority of cases (90%), the dose-volume histogram of the PRV will not under-represent the high-dose components in the OR. In order to provide guidelines on how to do this in clinical practice, this paper distinguishes types of OR in terms of the tolerance doses relative to the prescription dose and suggests appropriate margins for serial-structure and parallel-structure ORs. RESULTS: In some instances of large and parallel ORs, the clinician may judge that the complication risk in omitting a margin is acceptable. Otherwise, for all types of OR, systematic, treatment preparation uncertainties may be accommodated by an OR-->PRV margin width of 1.3Sigma. Here, Sigma is the standard deviation of the combined systematic (treatment preparation) uncertainties. In the case of serial ORs or small, parallel ORs, the effects of blurring caused by daily treatment execution errors (set-up and organ motion) should be taken into account. Near a region of high dose, blurring tends to shift the isodoses away from the unblurred edge as shown on the treatment planning system by an amount that may be represented by 0.5sigma. This margin may be used either to increase or to decrease the margin already calculated for systematic uncertainties, depending upon the size of the tolerance dose relative to the detailed planned dose distribution. Where the detailed distribution is unknown before the OR is delineated, then the overall margin for serial or small parallel ORs should be 1.3Sigma+0.5sigma. Examples are given where the application of this algorithm leads to margin widths around ORs similar to those in use clinically. CONCLUSIONS: Using PRVs is appropriate both for forward and inverse planning. Dose-volume histograms of PRVs for serial- and parallel-structure ORs require careful interpretation. Nevertheless, use of the proposed algorithms for drawing margins around both serial and parallel ORs can alert the dosimetrist/radiation oncologist to the possibility of high-dose complications in individual treatment plans, which might be missed if no such margins were drawn.

Algorithms↗

PubMedDate not supplied

Uncertainties in coupled thermal-hydrological processes associated with the Drift Scale Test at Yucca Mountain, Nevada.

Understanding thermally driven coupled hydrological, mechanical, and chemical processes in unsaturated fractured tuff is essential for evaluating the performance of the potential radioactive waste repository at Yucca Mountain, Nevada. The Drift Scale Test (DST), intended for acquiring such an understanding of these processes, has generated a huge volume of temperature and moisture redistribution data. Sophisticated thermal-hydrological (TH) conceptual models have yielded a good fit between simulation results and those measured data. However, some uncertainties in understanding the TH processes associated with the DST still exist. This paper evaluates these uncertainties and provides quantitative estimates of the range of these uncertainties. Of particular interest for the DST are the uncertainties resulting from the unmonitored loss of vapor through an open bulkhead of the test. There was concern that the outcome from the test might have been significantly altered by these losses. Using alternative conceptual models, we illustrate that predicted mean temperatures from the DST are within 1 degrees C of the measured mean temperatures through the first 2 years of heating. The simulated spatial and temporal evolution of drying and condensation fronts is found to be qualitatively consistent with measured saturation data. Energy and mass balance computation shows that no more than 13% of the input energy is lost because of vapor leaving the test domain through the bulkhead. The change in average saturation in fractures is also relatively small. For a hypothetical situation in which no vapor is allowed to exit through the bulkhead, the simulated average fracture saturation is not qualitatively different enough to be discerned by measured moisture redistribution data. This leads us to conclude that the DST, despite the uncertainties associated with open field testing, has provided an excellent understanding of the TH processes.

Forecasting↗

PubMed2000

Uncertainty in compartmental models for hazardous materials - a case study.

Performing uncertainty analysis on compartmental models is the main topic of this article. Elements of the methodology developed during a joint CEC/USNRC accident consequence code uncertainty analysis are introduced. The uncertainty is quantified using structured expert judgment. Experts are queried about physically observable quantities. Many code input parameters of the accident consequence codes are not physically observable but are used to predict observable quantities. Therefore, a probabilistic inversion technique was developed which 'transfers' the uncertainty from the physically observable quantities to the code input parameters. The probabilistic inversion technique is illustrated using the compartmental model of systemic retention of Sr in the human body. The article is concluded with a discussion on capturing uncertainty via compartmental models.

Hazardous Substances↗

PubMed2001

The effect of setup uncertainty on normal tissue sparing with IMRT for head-and-neck cancer.

PURPOSE: Intensity-modulated radiotherapy (IMRT) is being evaluated in the management of head-and-neck cancers at several institutions, and a Radiation Therapy Oncology Group study of its utility in parotid sparing is under development. There is an inherent risk that the sharper dose gradients generated by IMRT amplify the potentially detrimental impact of setup uncertainty. The International Commission on Radiation Units and Measurements Report 62 (ICRU-62) defined planning organ-at-risk volume (PRV) to account for positional uncertainties for normal tissues. The purpose of this study is to quantify the dosimetric effect of employing PRV for the parotid gland and to evaluate the use of PRV on normal-tissue sparing in the setting of small clinical setup errors. METHODS AND MATERIALS: The optimized nine-beam IMRT plans for three head-and-neck cancer patients participating in an institutional review board approved parotid-sparing protocol were used as reference plans. A second optimized plan was generated for each patient by adding a PRV of 5 mm for the contralateral parotid gland. The effect of these additions on the quality of the plans was quantified, in terms of both target coverage and normal-tissue sparing. To test the value of PRV in a worst-case scenario, systematic translational setup uncertainties were simulated by shifting the treatment isocenter 5 mm superiorly, inferiorly, left, right, anteriorly, and posteriorly, without altering optimized beam profiles. At each shifted isocenter, dose distributions were recalculated, producing a total of six shifted plans without PRV and six shifted plans with PRV for each patient. The effect of setup uncertainty on parotid sparing and the value of PRV in compensating for the uncertainty were evaluated. RESULTS: The addition of the PRV and reoptimization did not significantly affect the dose to gross tumor volume, spinal cord, or brainstem. In contrast, without any shift, the PRV did increase parotid sparing and reduce coverage of the nodal region adjacent to the parotid gland. As expected, when the plans were shifted, the greatest increase in contralateral parotid irradiation was noted with shifts toward the contralateral parotid gland. With these shifts, the average volume of contralateral parotid receiving greater than 30 Gy was reduced from 22% to 4% when a PRV was used. This correlated with a reduction in the average normal-tissue complication probability (NTCP) from 22% to 7%. CONCLUSIONS: The use of PRV may limit the volume of normal tissue structures, such as the parotid gland, exceeding tolerance dose as a result of setup errors. Consequently, it will be important to incorporate the nomenclature of ICRU-62 into the design of future IMRT studies, if the clinical gains of increased normal-tissue sparing are to be realized.

Aged↗

PubMed2003

The impact of geometric uncertainty on hypofractionated external beam radiation therapy of prostate cancer.

PURPOSE: Recent publications indicate alpha/beta for prostate carcinoma could be lower than assumed. Therefore, hypofractionation might increase the therapeutic ratio. However, patient repositioning and organ motion may affect hypofractionated treatments more than conventional treatments. Our purpose is to evaluate the potential impact of geometric uncertainties on hypofractionated treatments. METHODS AND MATERIALS: Tumor control probability (TCP) and normal tissue complication probability (NTCP) are calculated for simulated conventional and hypofractionated treatments, assuming alpha/beta of 1.5 Gy for prostate and 3.0 Gy for rectum. A Monte Carlo simulation randomly samples systematic and random displacements and produces the cumulative dose distribution for the prostate and rectum. The limiting number of fractions and the impact of different alpha/beta values are also explored. RESULTS: A consistent but small reduction in TCP is seen with hypofractionation (generally <1%) as a result of geometric uncertainties. Escalated hypofractionation seems to allow large TCP gains ( approximately 20%) without increasing NTCP. Treatments of five fractions seem to affect outcome minimally. The alpha/beta value has a much greater impact on TCP than geometric uncertainties. CONCLUSION: The potential increased influence of geometric uncertainties on hypofractionation seems small. Limited knowledge of radiobiologic response is likely a greater obstacle to prostate hypofractionation than geometric uncertainties.

Algorithms↗

PubMed2003

Measurement uncertainty from validation and duplicate analysis results in HPLC analysis of multivitamin preparations and nutrients with different galenic forms.

An approach to calculate the measurement uncertainty in the HPLC analysis of several hydro- and liposoluble vitamins in multivitamin preparations with different galenic composition and properties is described. In the first instance it is examined if duplicate analysis results, obtained with a fully validated analysis method on different lots of an effervescent tablet preparation spread over several points of time, might contribute to calculate the measurement uncertainty of the HPLC method used and if the established uncertainty is acceptable in the assessment of compliance with the legal content limits. Analysis of variance (ANOVA) and precision calculations, based on the ISO 5725-2 norm are applied on the analysis results obtained to estimate precision components, necessary to derive the measurement uncertainty. In the second instance it is demonstrated to which extent the fully validated method of analysis for effervescent tablets is applicable to other galenic forms as e.g. capsules with oily emulsions, tablets, coated tablets, oral solutions, em leader and which specific modifications in the analysis steps are involved. By means of duplicate analysis results, acquired from a large series of real samples over a considerable period of time and classified according to their similarity in content, galenic forms and matrices, estimations of measurement uncertainty calculations are shown.

Chromatography, High Pressure Liquid↗

PubMed1993

Coping with the uncertainty of uncontrolled epilepsy.

Parents of children with uncontrolled epilepsy experience chronic uncertainty in relation to their child's condition. In this study the author sought to explore the levels and dimensions of uncertainty experienced by parents of children with Lennox-Gastaut syndrome; the relationship between parental uncertainty and stress; and the range of cognitive and behavioural coping responses employed by parents. The population is drawn from a self-help group for parents of children with L.G.S. coordinated by the author. Data was collected through questionnaires as well as in-depth interviews with parents. The findings revealed five key dimensions of uncertainty: in respect to (1) diagnosis, (2) aetiology, (3) seizure activity, (4) treatment, and (5) prognosis. The study highlights the importance of information, contact with other parents of children with uncontrolled epilepsy and diary writing as aids to reducing uncertainty and enhancing coping for parents. The paper concludes by calling for a re-evaluation of the role of parents of children with epilepsy which moves away from the notion of parents as a source of pathology for their children to parents as part of a family unit attempting to cope as best it can with a chronic illness.

Adaptation, Psychological↗

PubMed2006

Balancing certainty and uncertainty in clinical medicine.

Nothing in clinical medicine is one hundred per cent certain. Part of a doctor's education involves learning how to cope with the anxiety that uncertainty in decisions affecting life and death inevitably produces. This paper examines: (1) the role of anxiety -- both rational and irrational -- in the provision of health care; (2) the effects of uncertainty upon the doctor-patient relationship; (3) the threat uncertainty poses to medical authority (and the assumption of infallibility that props it up); (4) the contribution of clinical uncertainty to the rising popularity of alternative therapies; and (5) the clash between the medical and the legal understanding of how certainty should be defined, particularly as it affects the paediatric community. It concludes by suggesting some strategies that might facilitate successful navigation between the opposing and ever-present forces of certainty and uncertainty.

Anxiety↗

PubMed1996

The consequences of uncertainty for the prediction of the effects of schistosomiasis control programmes.

Progress in the development of schistosomiasis models for use in control programmes is limited by the considerable uncertainty in many of the biological parameters. In this paper, this problem is addressed by a comprehensive sensitivity analysis of a schistosomiasis model using the Latin Hypercube method. Fifty simulations with different parameter contributions are run for 50 years with treatment during the first 20 years and reinfection thereafter. The analysis shows only a relatively small divergence between simulations during the chemotherapy treatment programme but considerable divergence in reinfection levels after treatment is stopped. A skewed distribution of outcomes was seen with most simulations showing effective control and a few where control had less impact. The most important uncertainty source was due to the unknown levels of acquired immunity and also uncertainty in the true worm burden. In particular, the strength of the immune response was most important in determining whether control was effective with higher immunity leading to less effective control. Among those simulations in which control was not very effective, those in which the mean worm burden was high showed the least effective control. Since both these are areas of genuine uncertainty, it is proposed that uncertainty analysis should be an integral part of any projection of control programmes.

Humans↗

PubMed2002

Species-specific isotope dilution-based calibration for trace element speciation and its combined uncertainty evaluation: determination of tributyltin in sediment by HPLC-ICPMS.

A method is described for the determination of tributyltin (TBT) in NRCC sediment CRM PACS-2 by isotope dilution (ID) analysis using HPLC-ICPMS. Reverse spike ID analysis was performed to determine the accurate concentration of a 117Sn-enriched TBT spike using a well-characterized natural abundance TBT standard. The accuracy of the latter is critical for obtaining reliable results. A unique approach, using hydride generation GC/MS, was developed to quantify the inorganic Sn and dibutyltin impurities in the natural abundance TBT standard. The true natural abundance TBT standard concentration was obtained following correction for these impurities. The total Sn concentration in the natural abundance TBT standard was determined by ID analysis using an enriched inorganic 117Sn following closed vessel mixed-acid digestion. Calibration of the enriched inorganic 117Sn standard was achieved by reverse ID analysis against a natural abundance inorganic tin standard prepared from the high-purity metal. An overall uncertainty associated with the present method was estimated, to which the uncertainties arising from measurement of the natural abundance TBT concentration, from the measurement of the isotope ratio in the spiked sample and in the reverse ID calibration solutions, and from estimation of the extraction efficiency were the main contributors. A concentration of 1.018 +/- 0.054 mg kg(-1) (expanded uncertainty, k = 2) as tin was obtained for TBT in PACS-2 using the present method, in excellent agreement with the certified value of 0.98 +/- 0.13 mg kg(-1) (95% confidence interval). A TBT concentration of 0.97 +/- 0.11 mg kg(-1) (expanded uncertainty, k = 2) as tin in PACS-2 was determined using the standard additions technique. Much smaller expanded uncertainty was obtained with ID, clearly demonstrating its superiority in providing more accurate and precise results over the method of additions. A detection limit (3sigma) of 0.02 mg kg(-1) for TBT, based on a 0.5-g subsample, was obtained.

Journal Article↗

PubMed2003

Evaluation of incremental reactivity and its uncertainty in Southern California.

The incremental reactivity (IR) and relative incremental reactivity (RIR) of carbon monoxide and 30 individual volatile organic compounds (VOC) were estimated for the South Coast Air Basin using two photochemical air quality models: a 3-D, grid-based model and a vertically resolved trajectory model. Both models include an extended version of the SAPRC99 chemical mechanism. For the 3-D modeling, the decoupled direct method (DDM-3D) was used to assess reactivities. The trajectory model was applied to estimate uncertainties in reactivities due to uncertainties in chemical rate parameters, deposition parameters, and emission rates using Monte Carlo analysis with Latin hypercube sampling. For most VOC, RIRs were found to be consistent in rankings with those produced by Carter using a box model. However, 3-D simulations show that coastal regions, upwind of most of the emissions, have comparatively low IR but higher RIR than predicted by box models for C4-C5 alkenes and carbonyls that initiate the production of HOx radicals. Biogenic VOC emissions were found to have a lower RIR than predicted by box model estimates, because emissions of these VOC were mostly downwind of the areas of primary ozone production. Uncertainties in RIR of individual VOC were found to be dominated by uncertainties in the rate parameters of their primary oxidation reactions. The coefficient of variation (COV) of most RIR values ranged from 20% to 30%, whereas the COV of absolute incremental reactivity ranged from about 30% to 40%. In general, uncertainty and variability both decreased when relative rather than absolute reactivity metrics were used.

Air Pollutants↗

PubMed2004

Optimization under variability and uncertainty: a case study for NOx emissions control for a gasification system.

Methods for optimization of process technologies considering the distinction between variability and uncertainty are developed and applied to case studies of NOx control for Integrated Gasification Combined Cycle systems. Existing methods of stochastic optimization (SO) and stochastic programming (SP) are demonstrated. A comparison of SO and SP results provides the value of collecting additional information to reduce uncertainty. For example, an expected annual benefit of 240,000 dollars is estimated if uncertainty can be reduced before a final design is chosen. SO and SP are typically applied to uncertainty. However, when applied to variability, the benefit of dynamic process control is obtained. For example, an annual savings of 1 million dollars could be achieved if the system is adjusted to changes in process conditions. When variability and uncertainty are treated distinctively, a coupled stochastic optimization and programming method and a two-dimensional stochastic programming method are demonstrated via a case study. For the case study, the mean annual benefit of dynamic process control is estimated to be 700,000 dollars, with a 95% confidence range of 500,000 dollars to 940,000 dollars. These methods are expected to be of greatest utility for problems involving a large commitment of resources, for which small differences in designs can produce large cost savings.

Air Pollution↗

PubMed2004

Balancing measurement uncertainty against financial benefits: comparison of in situ and ex situ analysis of contaminated land.

The uncertainty of measurements taken for the purpose of characterizing contaminated land can subsequently cause decision errors, which can produce significant, financial consequences. Given the site-specific costs, such as those associated with the measurements or with site misclassification, the important question addressed is "Are the measurements of acceptable quality for that given objective or fit-for-purpose"? It is often considered by investigators that using a standard operating procedure (SOP) with an approved analytical method will give an acceptable level of uncertainty. This is despite evidence that sampling is usually the predominant source of uncertainty, not the chemical analyses, mainly as a result of the contaminant heterogeneity within sampling locations at a site. One in situ and one ex situ measurement technique were used to represent these two contrasting approaches to characterizing a site contaminated with lead in topsoil. The measurement uncertainty, from both sampling and analyses, was estimated for the two techniques, and its fitness-for-purpose was assessed using the innovative optimized contaminated land investigation (OCLI) method. It is objectively demonstrated by the OCLI method that the in situ method (portable X-ray fluorescence) was three times more cost-effective than the ex situ (AAS) method at characterizing a contaminated site, despite generating higher uncertainty on individual measurements.

Cost-Benefit Analysis↗

PubMed1999

Estimating noncancer uncertainty factors: are ratios NOAELs informative?

The prominent role of animal bioassay evidence in environmental regulatory decisions compels a careful characterization of extrapolation uncertainties. In noncancer risk assessment, uncertainty factors are incorporated to account for each of several extrapolations required to convert a bioassay outcome into a putative subthreshold dose for humans. Measures of relative toxicity taken between different dosing regimens, different endpoints, or different species serve as a reference for establishing the uncertainty factors. Ratios of no observed adverse effect levels (NOAELs) have been used for this purpose; statistical summaries of such ratios across sets of chemicals are widely used to guide the setting of uncertainty factors. Given the poor statistical properties of NOAELs, the informativeness of these summary statistics is open to question. To evaluate this, we develop an approach to "calibrate" the ability of NOAEL ratios to reveal true properties of a specified distribution for relative toxicity. A priority of this analysis is to account for dependencies of NOAEL ratios on experimental design and other exogenous factors. Our analysis of NOAEL ratio summary statistics finds (1) that such dependencies are complex and produce pronounced systematic errors and (2) that sampling error associated with typical sample sizes (50 chemicals) is nonnegligible. These uncertainties strongly suggest that NOAEL ratio summary statistics cannot be taken at face value; conclusions based on such ratios reported in well over a dozen published papers should be reconsidered.

Algorithms↗

PubMed2001

Compensatory conviction in the face of personal uncertainty: going to extremes and being oneself.

Study 1 participants' self-integrity (C. M. Steele. 1988) was threatened by deliberative mind-set (S. E. Taylor & P. M. Gollwitzer, 1995) induced uncertainty. They masked the uncertainty with more extreme conviction about social issues. An integrity-repair exercise after the threat, however, eliminated uncertainty and the conviction response. In Study 2, the same threat caused clarified values and more self-consistent personal goals. Two other uncertainty-related threats, mortality salience and temporal discontinuity, caused similar responses: more extreme intergroup bias in Study 3, and more self-consistent personal goals and identifications in Study 4. Going to extremes and being oneself are seen as 2 modes of compensatory conviction used to defend against personal uncertainty. Relevance to cognitive dissonance and authoritarianism theories is discussed, and a new perspective on terror managenment theory (J. Greenberg, S. Solomom, & T. Pyszczynski, 1997) is proposed.

Adaptation, Psychological↗

PubMed2002

Method optimisation with the use of uncertainty budgets.

Uncertainty budgets can be used for a variety of situations, e.g. reporting the total uncertainty, calculating tolerance limits or method optimisation. In this paper it is demonstrated how the use of uncertainty budgets can help in reducing the total uncertainty of an analytical method, i.e. method optimisation. In this example it has been possible to reduce the total uncertainty of a concentration determination of hydrogen peroxide (by titration) from 2.7 x 10(-2) M to 3.93 x 10(-3) M (or to about a 1/7) by changing the traceability chain and working with more pure reagents.

Journal Article↗

PubMed2002

Optimised uncertainty in food analysis: application and comparison between four contrasting 'analyte-commodity' combinations.

The optimised uncertainty (OU) methodology is applied across a range of analyte-commodity combinations. The commodities and respective analytes under investigation were chosen to encompass a range of input factors: measurement costs (sampling and analytical), sampling uncertainties, analytical uncertainties and potential consequence costs which may be incurred as a result of misclassification. Two types of misclassification are identified-false compliance and false non-compliance. These terms can be used across a wide range of foodstuffs that have regulations requiring either minimum compositional requirements, maximum contaminant allowances or compositional specifications. The latter refers to foodstuffs with regulations that state an allowable tolerance around the compositional specification, i.e. the upper specification limit (USL) and the lower specification limit (LSL). The traditional OU methodology has been adapted so that it is applicable in these cases and has been successfully applied in practice. The Newton-Raphson method has been used to determine the optimal uncertainty value for the two case studies in which analyte concentration is assessed against a 'single threshold' regulatory requirement. This numerical method was shown to give a value of the optimal uncertainty that is practically identical to that given by the previously used method of visual inspection. The expectation of financial loss was reduced by an average of 65% over the four commodities by the application of the OU methodology, showing the benefit of the method.

Food Analysis↗