SEARCH · Search PubMed

Results for “Uncertainty Quantification”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1995

Evaluation of the US pharmacopeia adsorption tests for activated charcoals and proposals for changes.

The current USP adsorption tests for activated charcoals, involving methylene blue (MB) and strychnine sulfate (SS), were conducted for 6 activated charcoals having surface areas ranging from 600 to 2000 m2/g. The MB test is relatively complex and tedious, and uses a pass/fail criterion which is of such small magnitude that substantial uncertainties are likely. The SS test is only qualitative. Modification, using quantification of the turbidities, permitted quantitative interpretation. The test was failed by 2 charcoals of surface area 660 m2/g or less, and was passed by 4 charcoals of 720 m2/g surface area or higher. Neither test was able to reflect the substantial drug adsorption differences which exist for charcoals of average, above average, and high surface areas. Alternative tests for MB and SS were developed and evaluated using 6 charcoals. These tests, which are proposed for consideration by the US Pharmacopeial Convention, are simpler and faster than the current tests and yield precise values for the percentages of the 2 compounds adsorbed. Moreover, they clearly reflect the wide differences in adsorption performance of charcoals having widely different surface areas. Minimum percent adsorption values that must be attained for a charcoal to qualify as "USP grade" are proposed for both alternative tests (these would not exclude any current USP grade charcoal). Performance classifications of charcoals into categories of Low, Average, Above Average, and High are also proposed for both tests. These are shown to correspond to surface area ranges of < 700, 700-950, 950-1200, and > 1200 m2/g, respectively.

Adsorption↗

PubMed2001

Identification and quantification of major bovine milk proteins by liquid chromatography.

In the field of food quality, bovine milk products are of particular interest due to the social and economic importance of the dairy products market. However, the risk of fraudulent manipulation is high in this area, for instance, replacing milk powder by whey is very interesting from an economic point of view. Therefore, there is a need to have suitable analytical methods available for the determination of all milk components, which is currently not the case, especially for the main proteins. The detection of potential manipulations requires then a clear analytical characterisation of each type of bovine milk, what constitutes the goal of this work. The separation of the major milk proteinic components has been carried out by ion-pair reversed-phase HPLC with photodiode array detection, using a C4 column. The overall optimisation has been achieved using a statistical experimental design procedure. The identification of each protein was ascertained using retention times, peak area ratios and second derivative UV spectra. Quantification was based on calibration curves drawn using purified proteins. Major sources of uncertainty were identified and the full uncertainty budget was established. The procedure was initially developed using the skimmed milk powder certified reference material CRM 063R and then applied to various types of commercial milks as well as to raw milk. The method is able to separate and quantify the seven major proteins (K-casein, alphas2-casein, alphas1-casein, beta-casein, alpha-lactalbumin, beta-lactoglobulin B and beta-lactoglobulin A) in one run and also to provide precise determinations of the total protein concentration. These are important results towards the further development of a reference method for major proteins in milk. In addition, the use of a certified material reference is suggested in order to make comparisons of method performances possible.

Animals↗

PubMed1997

Polymerase chain reaction compared with dot blotting for the determination of N-myc gene amplification in neuroblastoma.

The magnitude of N-myc amplification (NMA) influences the treatment strategy of localized neuroblastomas. Reliable assays are therefore needed for all types of tumor samples. The aim of this comparative study of 119 tumor samples was to determine whether a polymerase chain reaction (PCR)-based assay could replace the current dot blot assay as a routine and reliable means of determining NMA. The 2 assays exhibited comparable sensitivity and were completely concordant for samples containing at least 20% neuroblastoma cells. In their present state, both assays remain semi-quantitative since an absolute quantification of the N-myc copy number in clinical samples is limited by uncertainty about the amplification level of reference cell lines and by the estimation of the proportion of malignant cells. However, PCR offers several advantages over dot blotting, such as feasibility on minute samples, simplicity, standardization, rapidity and cost effectiveness.

Cost-Benefit Analysis↗

PubMed2001

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty.

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty Although several articles on the methodological aspects of mitotic counting have been published, the effects of macroscopic sampling and tumour heterogeneity have not been discussed in any detail. In this review the essential elements for a standardized mitotic counting protocol are described, including microscopic calibration, specific morphological criteria, macroscopic selection, counting procedure, effect of biological variation, threshold, and the setting of an area of uncertainty ('grey area'). We propose that the use of a standard area for mitotic quantification and of a grey area in mitotic counting protocols will facilitate the application of mitotic counting in diagnostic and prognostic pathology.

Data Interpretation, Statistical↗

PubMed2001

Analytical aspects of the CEEM soil project.

In the past, exercises aiming at an assessment of data uncertainty in environmental analysis were usually restricted to the analysis step, while sampling and pre-analytical sample treatment was largely ignored. Collaborative studies on the quantification of sampling errors require, besides a suitable and well characterized test site, the availability of a reference laboratory for the analysis of all of the samples taken in the context of the study by all participants and also test methods which do not contribute large and variable uncertainties due to long and complex analytical methodologies. Here we summarize the major analytical aspects of a European project on the identification and quantification of sampling influences on the determination of lead, cadmium, copper and zinc in soil. The participant group included the leading soil analysis laboratories in Europe; the test site at Dornach (CH) was well suited for the purpose and showed high metal gradients and differentiated land use. The analytical methods (wavelength-dispersive X-ray fluorescence spectrometry and solid-state Zeeman AAS) used in the study showed stable performance characteristics within the confidence interval of the certified reference materials used for the measurement quality control over the entire project period. Additionally, double-blind tests on split samples showed agreement of data in very narrow limits thus demonstrating the reliability of the reference database.

Databases, Factual↗

PubMed2002

Quasi-independent monitor unit calculation for intensity modulated sequential tomotherapy.

The number of linac monitor units (MU) from intensity modulated sequential tomotherapy (IMST) is substantially larger than the MU delivered in conventional radiation therapy, and the relation between MU and dose is obscure due to complicated variation of the beam intensities. The purpose of this work was to develop a practical method of verifying the MU and dose from IMST so that the MU of each arced beam could be double-checked for accuracy. MU calculations for 41 arced beams from 14 IMST patients were performed using the variables of vane open fraction time, field size, target depth, output factor, TMR, and derived intensity distribution. Discrepancy between planned and checked MU was quantified as 100 (MU(cal)-MU(plan))/MU(plan) percent. All 41 discrepancies were clustered between -5% to +4%, illustrated in a Gaussian-shaped histogram centered at -1.0+/-3.5% standard deviation indicating the present MU calculations are in agreement with the planned expectations. To confirm the correctness of the present calculated MUs of the IMST plans, eight of the calculated IMST plans are performed dose verifications using their hybrid plans, which are created by transporting patient's IMST plan beams onto a spherical polystyrene Phantom for dose distribution within the Phantom. The dose was measured with a 0.07 cc ionization chamber inserted in the spherical Phantom during the hybrid plan irradiation. Average discrepancy between planned and measured doses was found to be 0.6+/-3.4% with single standard deviation uncertainty. The spread of the discrepancies of present calculated MUs relative to their planned ones are attributed to uncertainties of effective field size, effective planned dose corresponding to each arc, and inaccuracy of quantification of scattered dose from adjacent arced beams. Overall, the present calculation of MUs is consistent with what derived from treatment plans. Since the MUs are verified by actual dose measurements, therefore the present MU calculation technique is considered adequate for double-checking planned IMST MUs.

Humans↗

PubMed1994

Future research needs associated with the assessment of potential human health risks from exposure to toxic ambient air pollutants.

This paper presents key conclusions and future research needs from a Workshop on the Risk Assessment of Urban Air, Emissions, Exposure, Risk Identification, and Quantification, which was held in Stockholm during June 1992 by 41 participants from 13 countries. Research is recommended in the areas of identification and quantification of toxics in source emissions and ambient air, atmospheric transport and chemistry, exposure level assessment, the development of improved in vitro bioassays, biomarker development, the development of more accurate epidemiological methodologies, and risk quantification techniques. Studies are described that will be necessary to assess and reduce the level of uncertainties associated with each step of the risk assessment process. International collaborative research efforts between industry and government organizations are recommended as the most effective way to carry out this research.

Air Pollutants↗

PubMed1994

Quantifying local lung perfusion and ventilation using correlated SPECT and CT data.

UNLABELLED: A clinically applicable method for quantifying lung perfusion and ventilation on a subregional (local) scale from SPECT scans in order to estimate local lung function in patients with pre-existing pulmonary disease and to monitor local treatment effects was developed and evaluated. METHODS: SPECT 99mTc perfusion and 81mKr ventilation images were corrected for photon attenuation and scatter effect with a postreconstruction correction method incorporating a variable-effective linear-attenuation coefficient calculated from spatially-correlated CT data. A new algorithm was developed to quantify local ventilation from the SPECT data, which, in contrast with other algorithms, makes no assumptions on ventilation homogeneity over the lung. The quantification procedure was applied to clinical data from patients with a normal lung function and from patients suffering from radiation-induced pulmonary dysfunction. RESULTS: The calculated attenuation correction factors on the observed number of counts in the lung range from 2.0 to 3.0 and 2.3 to 3.5 for 81mKr and 99mTc, respectively, showing a systematic increase from the diaphragm to the lung apex. As a result of this correction, the values of local perfusion and ventilation differ 10%-15% from values calculated without attenuation correction. The calculated values of the local ventilation are 10%-50% lower than those found by quantification algorithms which assume homogeneous ventilation. CONCLUSIONS: The methods presented here are robust with respect to uncertainties in the input parameters and yield realistic values for perfusion and ventilation distribution in the lung with an intrinsic accuracy (largely determined by count statistics) of about 10%.

Algorithms↗

PubMed2002

Quantitative nuclear magnetic resonance (QNMR) spectroscopy for assessing the purity of technical grade agrochemicals: 2,4-dichlorophenoxyacetic acid (2,4-D) and sodium 2,2-dichloropropionate (Dalapon sodium).

Comparison of quantitative NMR spectroscopy (QNMR) with chromatographic methods such as gas chromatography (GC) or high-pressure liquid chromatography (HPLC) for the determination of the purity of and impurities in technical grade agrochemicals, 2,4-dichlorophenoxyacetic acid (2,4-D), 1, and Dalapon sodium (sodium 2,2-dichloropropionate), 10, has revealed that QNMR is more precise and accurate than the chromatographic methods. Quantitative impurity profiling of technical grade 1 is rapid and accurate using 600 MHz (1)H NMR. Extra dispersion at the relatively high frequency allowed full assignment of the NMR spectrum of 1 and its related organic impurities in technical samples. The percentage purity of 1 was measured by the difference QNMR method, which involves summing the amounts of impurities and subtracting from 100%. Results are superior in consistency to those obtained by chromatographic methods. The percentage purity of Dalapon sodium, 10, in technical grade batches is readily obtained by (1)H QNMR, using either the difference method or the internal standard method, using dimethyl sulfone (DMSO2) internally as a reference material, that is chemically unrelated to the analyte. The latter method also allows the simultaneous identification and quantification of impurities, many of which are either not accessible to or detectable by the chromatographic methods. Uncertainty budgets for the QNMR method are presented and demonstrate that the major contributors to uncertainty lie in the weighing of the chemicals and in purity of the standard reference material prior to the QNMR experiment.

2,4-Dichlorophenoxyacetic Acid↗

PubMed1997

A methodology for specifying PET VOI's using multimodality techniques.

Volume-of-interest (VOI) extraction for radionuclide and anatomical measurements requires correct identification and delineation of the anatomical feature being studied. We have developed a toolset for specifying three-dimensional (3-D) VOI's on a multislice positron emission tomography (PET) dataset. The software is particularly suited for specifying cerebral cortex VOI's which represent a particular gyrus or deep brain structure. A registered 3-D magnetic resonance image (MRI) dataset is used to provide high-resolution anatomical information, both as oblique two-dimensional (2-D) sections and as volume renderings of a segmented cortical surface. VOI's are specified indirectly in two dimensions by drawing a stack of 2-D regions on the MRI data. The regions are tiled together to form closed triangular mesh surface models, which are subsequently transformed into the observation space of the PET scanner. Quantification by this method allows calculation of radionuclide activity in the VOI's, as well as their statistical uncertainties and correlations. The methodology for this type of analysis and validation results are presented.

Brain↗

PubMed2003

A 2-year dose-response study of lesion sequences during hepatocellular carcinogenesis in the male B6C3F(1) mouse given the drinking water chemical dichloroacetic acid.

Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed.

Adenoma, Acidophil↗

PubMed1989

Dysmorphism of urinary red blood cells--value in diagnosis.

To aid investigation into the clinical problem of hematuria, assessment of abnormalities in the shape of red cells in the urine (dysmorphism) is gaining popularity in nephrology. However, there is uncertainty in the literature regarding both the number of red blood cells (RBC) in normal urine, as well as the quantification of dysmorphism. We have shown that in normal urine (N = 27) the number of RBC is less than 2,000/ml as assessed by scanning electron microscopy of filtered urine specimens from normal volunteers without known renal disease, which compared to less than 1,000/ml by centrifugation and phase contrast microscopy of the same specimen. To determine whether dysmorphism of urinary red blood cells was a significant predictor of glomerular disease we compared the number of dysmorphic cells in the urine of patients with biopsy proven glomerulonephritis (GN), before and immediately after renal biopsy. We also compared the number of dysmorphic cells in patients with glomerulonephritis to those with lower urinary tract bleeding. Renal biopsy caused significant dysmorphic hematuria, indicating that dysmorphism suggests renal rather than glomerular bleeding. Although patients with GN had significantly more dysmorphic urinary RBC when compared to those with lower tract urinary bleeding, the overlap was such that one could only be confident of renal hematuria if they accounted for greater than 75% of the total number of RBC. Non renal hematuria is present if number of dysmorphic cells is less than 17% of total RBC. Thus dysmorphism of urinary RBC is a useful diagnostic tool, but only if strict criteria established for each laboratory are adhered to.

Erythrocyte Count↗

PubMed2002

Risk and uncertainty analysis in government safety decisions.

Probabilistic risk analysis (PRA) can be an effective tool to assess risks and uncertainties and to set priorities among safety policy options. Based on systems analysis and Bayesian probability, PRA has been applied to a wide range of cases, three of which are briefly presented here: the maintenance of the tiles of the space shuttle, the management of patient risk in anesthesia, and the choice of seismic provisions of building codes for the San Francisco Bay Area. In the quantification of a risk, a number of problems arise in the public sector where multiple stakeholders are involved. In this article, I describe different approaches to the treatments of uncertainties in risk analysis, their implications for risk ranking, and the role of risk analysis results in the context of a safety decision process. I also discuss the implications of adopting conservative hypotheses before proceeding to what is, in essence, a conditional uncertainty analysis, and I explore some implications of different levels of "conservatism" for the ranking of risk mitigation measures.

Journal Article↗

PubMed2026

Global disparities in COVID-19 vaccine coverage associated with trajectories of SARS-CoV-2 adaptation.

BACKGROUND: Vaccination serves as an effective intervention for health promotion and disease prevention across the socioecological systems and has played an important role during the COVID-19 pandemic. However, global disparities in vaccine coverage have increased uncertainty about the trajectories of viral adaptation, and the potential interplay between SARS-CoV-2 adaptation and vaccine rollout warrants further quantification. METHODS: Using over 13 million SARS-CoV-2 genomes across 86 countries from March 2020 to September 2022, we analyzed nonlinear associations between SARS-CoV-2 adaptation and vaccination coverage, considering public health and social measures, international travel, and infection dynamics, before and after the emergence of Omicron. Additionally, we examined the relationship between SARS-CoV-2 adaptation and COVID-19 mortality. RESULTS: During the pre-Omicron period, we found positive associations between nonsynonymous to synonymous divergence (dN/dS) ratios in the S1 subunit and medium levels of adjusted vaccine coverage (effect size: 0.96 [95% CI 0.47, 1.45]), while the association became insignificant at high levels (effect size: -1.89 [95% CI -4.20, 0.43]). However, no significant associations were found when Omicron dominated, possibly due to the immune escape ability of Omicron variants and the complex immune landscape shaped by mass hybrid immunity. Moreover, we observed evidence of dynamic interdependence and positive correlations between COVID-19 mortality and SARS-CoV-2 adaptation, with COVID-19 mortality interpreted as a proxy for uncontrolled viral spread. CONCLUSIONS: Our findings suggest a complex nonlinear relationship between vaccine-induced immunity and SARS-CoV-2 adaptation, with high vaccine coverage potentially linked to lower positive selection. We also observed directional coupling between COVID-19 mortality and SARS-CoV-2 adaptation. This may have implications for fair and fast vaccination in pandemic preparedness and response. CLINICAL TRIAL NUMBER: Not applicable.

Humans↗

PubMed2002

The regulation of ammonium translocation in plants.

Much controversy exists about whether or not NH(+)(4) is translocated in the xylem from roots to shoots. In this paper it is shown that such translocation can indeed take place, but that interference from other metabolites such as amino acids and amines may give rise to large uncertainties about the magnitude of xylem NH(+)(4) concentrations. Elimination of interference requires sample stabilization by, for instance, formic acid or methanol. Subsequent quantification of NH(+)(4) should be done by the OPA-fluorometric method at neutral pH with 2-mercaptoethanol as the reducing agent since this method is sensitive and reliable. Colorimetric methods based on the Berthelot reaction should never be used, as they are prone to give erroneous results. Significant concentrations of NH(+)(4), exceeding 1 mM, were measured in both xylem sap and leaf apoplastic solution of oilseed rape and tomato plants growing with NO(-)(3) as the sole N source. When NO(-)(3) was replaced by NH(+)(4), xylem sap NH(+)(4) concentrations increased with increasing external concentrations and with time of exposure to NH(+)(4). Up to 11% of the translocated N was constituted by NH(+)(4). Glutamine synthetase (GS) incorporates NH(+)(4) into glutamine, but root GS activity and expression were repressed when high levels of NH(+)(4) were supplied. Ammonium concentrations measured in xylem sap sampled just above the stem base were highly correlated with NH(+)(4) concentrations in apoplastic solution from the leaves. Young leaves tended to have higher apoplastic NH(+)(4) concentrations than older non-senescing leaves. The flux of NH(+)(4) (concentration multiplied by transpirational water flow) increased with temperature despite a decline in xylem NH(+)(4) concentration. Retrieval of leaf apoplastic NH(+)(4) involves both high and low affinity transporters in the plasma membrane of mesophyll cells. Current knowledge about these transporters and their regulation is discussed.

Amines↗

PubMed1991

Cancer risks related to electricity production.

The International Agency for Research on Cancer has previously evaluated the cancer risks associated with fossil fuel-based industrial processes such as coal gastification and coke production, substances and mixtures such as coal tars, coal tar pitch and mineral oils, and a number of substances emitted from fossil-fuelled plants such as benzo[a]pyrene and other polycyclic aromatic hydrocarbons, arsenic, beryllium, cadmium, chromium, nickel, lead and formaldehyde. Based on these evaluations and other evidence from the literature, the carcinogenic risks to the general population and occupational groups from the fossil fuel cycle, the nuclear fuel cycle and renewable cycles are reviewed. Cancer risks from waste disposal, accidents and misuses, and electricity distribution are also considered. No cycle appears to be totally free from cancer risk, but the quantification of the effects of such exposures (in particular of those involving potential exposure to large amounts of carcinogens, such as coal, oil and nuclear) requires the application of methods which are subject to considerable margins of error. Uncertainties due to inadequate data and unconfirmed assumptions are discussed. Cancer risks related to the operation of renewable energy sources are negligible, although there may be some risks from construction of such installations. The elements of knowledge at our disposal do not encourage any attempt toward a quantitative comparative risk assessment. However, even in the absence of an accurate quantification of risk, qualitative indication of carcinogenic hazards should lead to preventive measures.

Accidents, Occupational↗

PubMed2000

Three-dimensional echocardiography: assessment of inter- and intra-operator variability and accuracy in the measurement of left ventricular cavity volume and myocardial mass.

Accurate left ventricular (LV) volume and mass estimation is a strong predictor of cardiovascular morbidity and mortality. We propose that our technique of 3D echocardiography provides an accurate quantification of LV volume and mass by the reconstruction of 2D images into 3D volumes, thus avoiding the need for geometric assumptions. We compared the accuracy and variability in LV volume and mass measurement using 3D echocardiography with 2D echocardiography, using in vitro studies. Six operators measured the LV volume and mass of seven porcine hearts, using both 3D and 2D techniques. Regression analysis was used to test the accuracy of results and an ANOVA test was used to compute variability in measurement. LV volume measurement accuracy was 9.8% (3D) and 18.4% (2D); LV mass measurement accuracy was 5% (3D) and 9.2% (2D). Variability in LV volume quantification with 3D echocardiography was %SEMinter = 13.5%, %SEMintra = 11.4%, and for 2D echocardiography was %SEMinter = 21.5%, %SEMintra = 19.1%. We derived an equation to predict uncertainty in measurement of LV volume and mass using 3D echocardiography, the results of which agreed with our experimental results to within 13%. 3D echocardiography provided twice the accuracy for LV volume and mass measurement and half the variability for LV volume measurement as compared with 2D echocardiography.

Analysis of Variance↗

PubMed1989

[A new quantitative method for quantifying left heart jets by Doppler color imaging].

Quantification of valvular lesions by Color Doppler is based on jet measurements. The aim of this new method is to reduce some of the errors in these measurements: uncertainty in delimiting the colored areas of the jets; spontaneous beat-to-beat variations of the jets entailing interpretative difficulties. The first step was to determine the correlations between the colored areas and previously established single-gated Doppler criteria, retaining spectral criteria to define the borders of the jets, so overcoming some of the limitations of color Doppler. The association of these methods resulted in better discrimination between grades and a better correlation in 45 angiographically controlled mitral and aortic regurgitations than with color Doppler alone. In stenotic lesions, spectral criteria from single-gated associated exploration enabled localisation of the level for planimetry of the section of the jet at its origin visualised by color Doppler. Satisfactory correlations were obtained with the Gorlin surface area in a group of 43 patients with mitral and aortic stenosis. A coefficient of variation of 13 to 14 per cent was found with planimetry of the regurgitant jet in the upstream cardiac chamber. Uni-dimensional measurement decreased this variation to 6 to 11 per cent in the same patients. The largest decrease in variability (6 to 8 per cent) was observed in stenotic and regurgitant lesions with planimetry of the section of jet at its origin performed in held mid-expiration and so this would appear to be the best method. The guide lines and technological improvement associated with the physiopathological information provided by color Doppler should refine the quantification of valvular heart lesions.

Adult↗