SEARCH · PubMed Health

Results for “Calibration”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 397 records · Page 22Linked to original sources

PubMed2003

Calibration of immunohistochemistry for assessment of HER2 in breast cancer: results of the French multicentre GEFPICS study.

AIMS: HER2 protein is over-expressed in 15-30% of breast carcinomas. Immunohistochemistry (IHC) is a common and inexpensive method able to specifically detect HER2 protein. However, lack of standardization of IHC has been considered responsible for discrepancies in HER2 status assessment performed by IHC and fluorescence in-situ hybridization (FISH). This prompted us to perform a multicentric IHC calibration test to achieve a maximum accuracy of HER2-IHC compared with HER2-FISH taken as the reference method. METHODS AND RESULTS: Twelve French laboratories participated in this study, including 119 cases of invasive breast carcinomas for which both fixed and frozen tissues were available. HER2 expression was determined in fixed tissues by individual in-house IHC techniques, using either CB11 (Novocastra, Newcastle, UK) or A0485 (Dako, Glostrup, Denmark) anti-HER2 antibodies. Two cut-off values were used: 10% and 60% of immunostained cells. In 116 of the 119 cases, HER2 gene status could also be determined by FISH on frozen sections, performed in a single laboratory. Results were centralized and compared. When suboptimal concordance between IHC and FISH was observed, IHC was calibrated and a second run was performed. The specificity, sensitivity and accuracy of IHC compared with FISH were noted before and after calibration. Forty-four out of 116 (38%) tumours showed HER2 gene amplification. Accuracy of IHC was complete in the first run for 6/12 laboratories. Calibration, necessary for the six others, relied mainly on the combination of a heat-induced epitope retrieval step with an increase of dilution of the primary antibody. In the second run, HER2 over-expression was found in 46 (40%) and 44 (38%) of the 116 cases, using 10% or 60% of stained cells as cut-offs, respectively. The corresponding accuracy rates were 93% and 95%. CONCLUSIONS: This study showed that a high accuracy of IHC could be obtained for the determination of HER2 status in all laboratories using their in-house IHC technique, provided that a calibration process was performed. Antigen retrieval procedure, high dilutions of anti-HER2 antibody and the use of specific controls were crucial for HER2-IHC calibration. A 95% accuracy rate of IHC, using FISH as gold standard, was obtained by considering immunolabelling HER2-IHC results as a continuous variable, and taking 60% invasive stained cells as the cut-off for HER2 over-expression.

Adenocarcinoma↗

PubMed1996

Transmission ionization chambers for measurements of air collision kerma integrated over beam area. Factors limiting the accuracy of calibration.

Kerma-area product meters (KAP meters) are frequently used in diagnostic radiology to measure the integral of air-collision kerma over an area A (integral of A Kc,air dA) perpendicular to the x-ray beam. In this work, a precise method for calibrating a KAP meter to measure integral of A Kc,air dA is described and calibration factors determined for a broad range of tube potentials (40-200 kV). The integral is determined using a large number of TL dosimeters spread over and outside the nominal field area defined as the area within 50% of maximum Kc,air. The method is compared to a simplified calibration method which approximates the integral by multiplying the kerma in the centre of the field by the nominal field area Anom. While the calibration factor using the precise method is independent of field area and distance from the source, that using the simplified method depends on both. This can be accounted for by field inhomogeneities caused by the heel effect, extrafocal radiation and scattered radiation from the KAP meter. The deviations between the calibration factors were as large as +/- 15% for collimator apertures of 5-100 cm2 and distances from the source of 50-160 cm. The uncertainty in the calibration factor using the precise method was carefully evaluated and the expanded relative uncertainty estimated to be +/- 3% with a confidence level of 95%.

Equipment Design↗

PubMed1977

Calibration of densitometers for indicator dye dilution.

A systematic investigation was undertaken to determine which factors affect the calibration of a Gilford monochromatic densitometer used for recording indicator-dilution curves with indocyanine green. Calibration was not influenced by variation of withdrawal speeds from 6.4 to 20.6 cm3/min but varied with differing sampling systems. Variation in haemoglobin from 10 to 17.5 g-dl-1 or in haematocrit from 30 to 60% did not affect calibration. Calibration lines showed both curvature and hysteresis. The opitcal properties of indocyanine green were not affected by storage of diluted dye in the dark for 24 hours but were altered by the presence of contrast media used in angiography. No systematic error resulted from the substitution of stored ACD blood for patient's blood in calibration although random error was increased. Recommendations based on these findings are made for a simple calibration technique which avoids systematic error.

Blood Preservation↗

PubMed1994

Calibration in multi-centre cohort studies.

BACKGROUND: This paper is concerned with overcoming problems caused by measurement error in multi-centre studies of diet and disease. Measurement error causes differential bias, so the information on the diet-disease relationship from different cohorts is not directly comparable. Hence this information needs to be calibrated before the data are combined in an eventual meta-analysis. We consider the design of calibration substudies. We distinguish two forms of information from a multi-centre cohort study. The first is subject-level information, which comes from the variation of disease rate within cohorts. The second is cohort-level information, which comes from the variation of disease rate between cohorts. The requirements of the calibration study are different for these two forms of information. METHODS: Calibration is carried out by remeasuring diet in a subsample of each cohort using a standardized reference method. This reference measurement should yield unbiased estimates of habitual intake. RESULTS: Using a criterion of efficiency, relative to a perfectly calibrated study, we show that the sample size should be a multiple of the expected number of cases in each cohort. To control for confounding, each cohort should be stratified and the ratio of sample size to number of cases should be constant within strata. CONCLUSIONS: Since the required sample size is related not to the size of the cohort, but to the eventual number of cases of disease, calibration samples need not be prohibitively large. They should, however, be concentrated on those parts of the cohort, such as older age groups, which will yield most cases.

Bias↗

PubMed2006

Fossil calibration of molecular divergence infers a moderate mutation rate and recent radiations for pinus.

Silent mutation rate estimates for Pinus vary 50-fold, ranging from angiosperm-like to among the slowest reported for plants. These differences either reflect extraordinary genomic processes or inconsistent fossil calibration, and they have important consequences for population and biogeographical inferences. Here we estimate mutation rates from 4 Pinus species that represent the major lineages using 11 nuclear and 4 chloroplast loci. Calibration was tested at the divergence of Pinus subgenera with the oldest leaf fossil from subg. Strobus (Eocene; 45 MYA) or a recently published subg. Strobus wood fossil (Cretaceous; 85 MYA). These calibrations place the origin of Pinus 190-102 MYA and give absolute silent rate estimates of 0.70-1.31x10(-9) and 0.22-0.42x10(-9).site-1.year-1 for the nuclear and chloroplast genomes, respectively. These rates are approximately 4- to 20-fold slower than angiosperms, but unlike many previous estimates, they are more consistent with the high per-generation deleterious mutation rates observed in pines. Chronograms from nuclear and chloroplast genomes show that the divergence of subgenera accounts for about half of the time since Pinus diverged from Picea, with subsequent radiations occurring more recently. By extending the sampling to encompass the phylogenetic diversity of Pinus, we predict that most extant subsections diverged during the Miocene. Moreover, subsect. Australes, Ponderosae, and Contortae, containing over 50 extant species, radiated within a 5 Myr time span starting as recently as 18 MYA. An Eocene divergence of pine subgenera (using leaf fossils) does not conflict with fossil-based estimates of the Pinus-Picea split, but a Cretaceous divergence using wood fossils accommodates Oligocene fossils that may represent modern subsections. Because homoplasy and polarity of character states have not been tested for fossil pine assignments, the choice of fossil and calibration node represents a significant source of uncertainty. Based on several lines of evidence (including agreement with ages inferred using calibrations outside of Pinus), we conclude that the 85 MYA calibration at the divergence of pine subgenera provides a reasonable lower bound and that further refinements in age and mutation rate estimates will require a synthetic examination of pine fossil history.

Chloroplasts↗

PubMed1999

Objective calibration of bone conductors using otoacoustic emissions.

OBJECTIVE: To demonstrate a technique for objectively calibrating bone conductors on an individual basis using distortion product otoacoustic emissions (DPOAEs). DESIGN: Individual calibrations were obtained using DPOAEs recorded from a single ear of 21 normally hearing adults. Validity and robustness of the technique were investigated through subjective phase cancellation measurements and sensitivity analysis. RESULTS: Calibrations obtained using the DPOAE method were well supported by phase cancellation results. Intersession repeatability was good, and manipulation of the DPOAE data showed that the calculated calibration is relatively insensitive to small variations of emission magnitude. Bilateral stimulation through bone conduction did not display an apparent effect on emission magnitude in a single individual. CONCLUSION: Bone conductors can be accurately calibrated on an individual basis with good repeatability using DPOAEs. The technique is robust and offers an objective, noninvasive calibration method for research and specialized clinical applications. No training and only passive cooperation are required, making the procedure ideal for special groups such as children. A number of limitations will reduce the clinical utility of this technique. Important audiometric frequencies below 1 kHz cannot be tested because of noise, because individuals with significant hearing loss are unlikely to produce sufficient DPOAEs, and because commercial bone conductors typically have poor high-frequency response above 4 kHz.

Acoustic Stimulation↗

PubMed2004

Assessing the quality of molecular divergence time estimates by fossil calibrations and fossil-based model selection.

Estimates of species divergence times using DNA sequence data are playing an increasingly important role in studies of evolution, ecology and biogeography. Most work has centred on obtaining appropriate kinds of data and developing optimal estimation procedures, whereas somewhat less attention has focused on the calibration of divergences using fossils. Case studies with multiple fossil calibration points provide important opportunities to examine the divergence time estimation problem in new ways. We discuss two cross-validation procedures that address different aspects of inference in divergence time estimation. 'Fossil cross-validation' is a procedure used to identify the impact of different individual calibrations on overall estimation. This can identify fossils that have an exceptionally large error effect and may warrant further scrutiny. 'Fossil-based model cross-validation' is an entirely different procedure that uses fossils to identify the optimal model of molecular evolution in the context of rate smoothing or other inference methods. Both procedures were applied to two recent studies: an analysis of monocot angiosperms with eight fossil calibrations and an analysis of placental mammals with nine fossil calibrations. In each case, fossil calibrations could be ranked from most to least influential, and in one of the two studies, the fossils provided decisive evidence about the optimal molecular evolutionary model.

Animals↗

PubMed2006

Position and time-delay calibration of transducer elements in a sparse array for underwater ultrasound imaging.

This paper describes a novel method for the calibration of the position and time delay of transducer elements in a large, sparse array used for underwater, high-resolution ultrasound imaging. This method is based on the principles used in the global positioning system (GPS). However, unlike GPS, in which the wave propagation speed is generally assumed known, the sound propagation speed in the water usually is unknown and it is calibrated simultaneously in this method to achieve high calibration accuracy. In this method, a high-precision positioning system is used to scan a single hydrophone (used for transmission) in the imaging field of the array. The hydrophone transmits pulses at selected positions, and the transducer elements in the sparse array receive the transmitted signals. Time of flight (TOF) values between transducer elements and hydrophone positions then are measured. From a series of measured TOF values, the position and time delay values for each transducer element as well as the propagation speed can be calibrated. The performances of the calibration algorithm are theoretically analyzed and evaluated with numerical calculations and simulation studies. It is found that this method is capable of calibrating the positions and time delays of transducer elements with high accuracy.

Journal Article↗

PubMed2005

A multi-group model of Schistosoma japonicum transmission dynamics and control: model calibration and control prediction.

Previously we formulated a quantitative model to characterize site-specific schistosomiasis transmission. In this paper, we present a procedure to calibrate the model to data collected in endemic villages of south-western Sichuan, China, with the objective of reducing parametric uncertainty to allow the model to describe local transmission with relative confidence. A Bayesian approach using local epidemiological data and expert opinion is employed to calibrate the model. Results indicate that, after calibration, the output uncertainty is reduced substantially. The calibrated model is then used for prediction of the effects of different intervention options. Simulations reflect a bimodal transmission in both human (early summer and early fall) and snail (late summer and late fall) infections in this area, for which there is some field evidence. Also shown in the simulations are relatively high reinfection rates following chemotherapy in these endemic villages. These results suggest that a sustainable control strategy is essential in reducing transmission, and that transmission can be reduced by chemotherapy, focal snail (e.g. snail clusters) control, and egg control. Our work demonstrates the feasibility of characterizing site-specific schistosomiasis transmission using a mathematical model and a calibration approach that integrates diverse field data, and the use of the calibrated model to design control strategies.

Animals↗

PubMed2004

Monte Carlo calculation of the sensitivity of a commercial dose calibrator to gamma and beta radiation.

The detection process used in a commercial dose calibrator was modeled using the GEANT 3 Monte Carlo code. Dose calibrator efficiency for gamma and beta emitters, and the response to monoenergetic photons and electrons was calculated. The model shows that beta emitters below 2.5 MeV deposit energy indirectly in the detector through bremsstrahlung produced in the chamber wall or in the source itself. Higher energy beta emitters (E > 2.5 MeV) deposit energy directly in the chamber sensitive volume, and dose calibrator sensitivity increases abruptly for these radionuclides. The Monte Carlo calculations were compared with gamma and beta emitter measurements. The calculations show that the variation in dose calibrator efficiency with measuring conditions (source volume, container diameter, container wall thickness and material, position of the source within the calibrator) is relatively small and can be considered insignificant for routine measurement applications. However, dose calibrator efficiency depends strongly on the inner-wall thickness of the detector.

Beta Particles↗

PubMed1994

A comparison of methods for calibrating parallel-plate chambers/.

All dosimetry protocols for calibrating the output of electron beams recommend the use of parallel-plate ionization chambers, but the method of determining their value of Ngas is a matter of concern. The AAPM Protocol (TG 21) recommends a direct comparison with a calibrated cylindrical chamber in phantom at dmax with the highest available electron energy beam. This must be done by the user. Since all calibration laboratories traditionally use 60Co for megavoltage chamber calibrations, two alternate procedures based on exposures in-air, or in-phantom, have been proposed. All methods use correction factors in the data reduction. To verify the consistency of the three methods, we have measured Ngas using each of these techniques for six of the most commonly used and commercially-available parallel-plate ionization chambers. The paired cylindrical and parallel-plate ionization chambers, and phantom materials/buildup caps were matched to the wall composition of the plane chambers, as recommended in TG 39. A 22 MeV electron beam was used for the electron irradiations. The ionization chambers were then taken to an Accredited Dosimetry Calibration Laboratory (ADCL), where 60Co calibrations were performed. The results demonstrate that, by using the appropriate correction factors for the chambers described in this work, all three methods yield values for Ngas that are within 1% of each other.

Biophysical Phenomena↗

PubMed2000

Accuracy and precision of quantitative calibrated loops in transfer of bronchoalveolar lavage fluid.

Quantitative cultures of bronchoalveolar lavage (BAL) fluid are important in the diagnosis of ventilator-associated pneumonia, and calibrated loops are commonly used to set up these cultures. In this study, the performances of calibrated 0.010- and 0.001-ml loops in the transfer of BAL fluid were determined. Five loops of one lot from seven manufacturers were tested. Calibrations were performed by the gravimetric method (0.010-ml loops) and the colorimetric method (0.001-ml loops). Most of the 0.010-ml loops displayed a precision that was less than 10%, but six of them showed very poor accuracies as they transferred a deficiency (nichrome loops) or an excess (disposable loops) of BAL fluid that exceeded +/-10%. The mean maximum and minimum BAL fluid volumes delivered by the 0.010-ml loops differed by a factor 3. The 0.001-ml loops displayed acceptable precision. Five of them showed inaccuracies of </=+/-10%, and mean maximum and minimum BAL fluid volumes had a range of a factor of 2. For all loops, the volumes of BAL fluid sampled were larger than the volumes of reagent-grade water sampled. Results of the colony counting experiments confirmed these findings and revealed a high intra-assay variability for the 0.001-ml loops. We conclude that, when BAL fluid samples are cultured with calibrated loops, (i) proper verification of the calibration of these loops is mandatory, (ii) calibrations should be performed with BAL fluid as the test solution, and (iii) borderline quantitative culture results should be interpreted with knowledge of the inaccuracy values of these loops.

Bronchoalveolar Lavage Fluid↗

PubMedDate not supplied

Changes in retinal ganglion cell axons after optic nerve crush: neurofilament expression is not the sole determinant of calibre.

After injury in the central nervous system of adult mammals, many of the axons that remain attached to their intact cell bodies degenerate and decrease in calibre. To understand this process better, we have investigated the relationship between axonal loss, cell loss, and the time course of changes in axonal calibre. Optic nerves (ONs) were crushed and the numbers and sizes of axons remaining close to the cell bodies (2 mm from the eye) and near the site of the lesion (6 mm from the eye) were determined for nerves examined between 1 week and 3 months after injury. Comparison with the retinal ganglion cell (RGC) counts from the same animals revealed that axonal loss was concomitant with cell body loss for at least the first 2 weeks after injury. However, there was no significant change in the calibre of the surviving neurons until 1 month after injury. Thereafter, the axonal calibre was decreased equally along the ON. No progressive somatofugal atrophy was observed. These decreases in axonal calibre occur much later than the immediate drop in neurofilament (NF) expression that also follows injury. The late effect of injury on axonal calibre suggests that NF expression is not the sole determinant of axon size of the RGC fibers in the ON. Other factors are likely additional contributing factors, such as the decreased rate of axonal transport that would help maintain the axonal neurofilament content.

Animals↗

PubMed1996

Inadequacy of high K+/nigericin for calibrating BCECF. II. Intracellular pH dependence of the correction.

In the accompanying study [G. Boyarsky, C. Hanssen, and L.A. Clyne. Am. J. Physiol. 271 (Cell Physiol. 40): C1131-C1145, 1996], it was demonstrated that steady-state intracellular pH (pHi) determined using high K+/nigericin calibrations was systematically in error in vascular smooth muscle (VSM) cells by approximately 0.2 pH units. In this paper the possibility is explored that this correction (pHcor) to the nigericin-calibrated pHi (pHnig) might not be a constant but could vary as pHi varies. The range of pHi during exposures to "null solutions" designed to bracket pHi was extended to acidic and alkaline levels relative to the starting pHi in VSM cells. The pHcor necessary to correct pHnig was linearly dependent on pHnig, increasing from near zero at approximately 6.0 to approximately 0.2 at steady-state pHi, to approximately 0.3 at alkaline pHnig. It is shown how to retrieve previously acquired (tabulated) data using the linear relationship between pHcor and pHnig. Also examined were what corrections must be made to high K+/nigericin calibration curves to correct for this pHi-dependent pHcor. The following changes in the calibration parameters were found: the maximal fluorescence ratio increased from 16.75 to 17.28; the minimal fluorescence ratio decreased from 2.15 to 1.57; and the pK of 2',7'-bis (carboxy-ethyl)-5 (6)-carboxyfluorescein decreased from 7.13 to 6.93. Three potential explanations for these changes are discussed: external [K+] in the nigericin solutions could have been too low; internal [K+] changes during the calibration because of the finite buffering power of cells; and other acid-base transport/generation could have been contributing during the nigericin calibrations (i.e., nigericin does not overwhelm to insignificance other processes generating/consuming H+). The nonconstancy of pHcor is shown to have profound implications for measuring changes in pHi.

Animals↗

PubMed1993

Evaluation of various models for respiratory inductance plethysmography calibration.

We evaluated one nonlinear and two linear models of the ventilatory system while calibrating the respiratory inductance plethysmograph (RIP) against a pneumotachometer. A calibration method involving voluntary varying rib cage and abdominal contributions to tidal volume in a single body position was utilized. The influence on accuracy of the choice of respiratory phase during calibration was assessed. Both tidal and intratidal volumes were evaluated. Ten adults with no history of respiratory disorders went through RIP calibration and validation in the sitting and supine positions. A linear calibration model, relating lung volume changes from the start of inspiration or expiration to rib cage and abdominal excursions from initiation of respiratory motion, had the best accuracy. The choice of respiratory phase for calibration did not affect accuracy. RIP generally underestimated lung volume at the start of inspiration and overestimated lung volume at the end of inspiration. RIP was more accurate in the supine than the sitting position, probably because of limited spine flexion in the supine position.

Adult↗

PubMed1993

Comparison of thoracoabdominal calibration methods in normal human subjects.

In 19 normal subjects in the supine posture, we compared accuracy and precision of calibration methods that utilized different ranges of tidal volumes and thoracoabdominal partitioning: spontaneous quiet breathing (QB), isovolume maneuvers, and voluntary efforts to breathe with variable tidal volume and thoracoabdominal partitioning. Thoracic and abdominal movements were measured with the respiratory area fluxometer. Calibration methods utilizing one or more types of respiratory efforts were applied to three measurement situations: QB, variable breathing (volume and thoracoabdominal partitioning), and simulated obstructive apnea (isovolume efforts). Qualitative diagnostic calibration (QDC) included QB data only. The isovolume method (ISOCAL) included isovolumetric efforts at end expiration (functional residual capacity) and QB. Multilinear regression analyses were performed on data sets that included 1) voluntary efforts to breathe with variable volume and thoracoabdominal partitioning (CAL 1), 2) QB in addition to variable volume and partitioning (CAL 2), and 3) isovolume maneuvers in addition to QB and variable volume and partitioning efforts (CAL 3). When calibration data included a wide range of tidal volume, variable thoracoabdominal partitioning, and isovolume efforts (CAL 3), a stable calibration with small bias and scatter during all respiratory patterns was obtained. Excluding isovolume maneuvers (CAL 2) and QB (CAL 1) did not diminish accuracy. Limiting data to isovolume efforts at functional residual capacity plus QB (ISO-CAL) caused a significant increase in scatter during variable breathing patterns. Limiting calibration data to that portion of QB with small variation in the uncalibrated sum of thoracic and abdominal movements (QDC) caused significant increases in scatter in both isovolume efforts and variable breathing.

Abdomen↗

PubMed2006

Regression analysis with categorized regression calibrated exposure: some interesting findings.

BACKGROUND: Regression calibration as a method for handling measurement error is becoming increasingly well-known and used in epidemiologic research. However, the standard version of the method is not appropriate for exposure analyzed on a categorical (e.g. quintile) scale, an approach commonly used in epidemiologic studies. A tempting solution could then be to use the predicted continuous exposure obtained through the regression calibration method and treat it as an approximation to the true exposure, that is, include the categorized calibrated exposure in the main regression analysis. METHODS: We use semi-analytical calculations and simulations to evaluate the performance of the proposed approach compared to the naive approach of not correcting for measurement error, in situations where analyses are performed on quintile scale and when incorporating the original scale into the categorical variables, respectively. We also present analyses of real data, containing measures of folate intake and depression, from the Norwegian Women and Cancer study (NOWAC). RESULTS: In cases where extra information is available through replicated measurements and not validation data, regression calibration does not maintain important qualities of the true exposure distribution, thus estimates of variance and percentiles can be severely biased. We show that the outlined approach maintains much, in some cases all, of the misclassification found in the observed exposure. For that reason, regression analysis with the corrected variable included on a categorical scale is still biased. In some cases the corrected estimates are analytically equal to those obtained by the naive approach. Regression calibration is however vastly superior to the naive method when applying the medians of each category in the analysis. CONCLUSION: Regression calibration in its most well-known form is not appropriate for measurement error correction when the exposure is analyzed on a percentile scale. Relating back to the original scale of the exposure solves the problem. The conclusion regards all regression models.

Journal Article↗

PubMed2005

Radiometric validation of NASA's Ames Research Center's Sensor Calibration Laboratory.

The National Aeronautics and Space Administration's (NASA's) Ames Research Center's Airborne Sensor Facility (ASF) is responsible for the calibration of several airborne Earth-viewing sensor systems in support of NASA Earth Observing System (EOS) investigations. The primary artifact used to calibrate these sensors in the reflective solar region from 400 to 2500 nm is a lamp-illuminated integrating sphere source. In September 1999, a measurement comparison was made at the Ames ASF Sensor Calibration Facility to validate the radiometric scale, establish the uncertainties assigned to the radiance of this source, and examine its day-to-day repeatability. The comparison was one of a series of validation activities overseen by the EOS Calibration Program to ensure the radiometric calibration accuracy of sensors used in long-term, global, remote-sensing studies. Results of the comparison, including an evaluation of the Ames Sensor Calibration Laboratory (SCL) measurement procedures and assigned radiometric uncertainties, provide a validation of their radiometric scale at the time of the comparison. Additionally, the maintenance of the radiance scale was evaluated by use of independent, long-term, multiyear radiance validation measurements of the Ames sphere source. This series of measurements provided an independent assessment of the radiance values assigned to integrating sphere sources by the Ames SCF. Together, the measurements validate the SCF radiometric scale and assigned uncertainties over the time period from September 1999 through July 2003.

Journal Article↗