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Performance characteristics of 5 automated thyroglobulin autoantibody and thyroid peroxidase autoantibody assays.

BACKGROUND: Measurement of thyroid peroxidase autoantibodies (TPOAb) is useful in diagnosing patients with autoimmune thyroid disease. Measurement of thyroglobulin autoantibodies (TgAb) is used to detect potential interferences with thyroglobulin immunoassays and in limited situations for the diagnosis of autoimmune thyroid disease. METHODS: The limit of detection, imprecision, reference interval, method comparison and diagnostic concordance for the ADVIA Centaur, ARCHITECT i2000, AxSYM, Immulite 2000, Modular E170 (TPOAb only), and UniCel DxI 800 (TgAb only) methods were evaluated. The Advantage was used as the comparison method. RESULTS: Total imprecision ranged from 2.6% to 14.9% for TgAb and 2.1% to 15.8% for TPOAb. Passing-Bablok slopes ranged from 0.51 to 10.4 (TgAb) and 1.05 to 7.12 (TPOAb) with correlation coefficients of 0.48 to 0.82 (TgAb) and 0.66 to 0.78 (TPOAb). Assay cutoffs were adjusted using a common set of reference interval samples. Concordance with the Advantage assay using the new cutoffs was found to be improved and ranged from 68.5% to 84.7% (TgAb) and 77.5% to 84.7% (TPOAb). CONCLUSIONS: Although all assays generally performed well, assay concordance for a negative or positive result ranged from 54.2 to 84.7%. Quantitative agreement between methods was generally poor and methods could not be used interchangeably. Additional standardization efforts are required to improve inter-method agreement.

Autoantibodies↗

Two high performance liquid chromatographic methods for the determination of alpha-tocopherol in serum compared to isotope dilution-gas chromatography-mass spectrometry.

Two high performance liquid chromatographic methods (HPLC) with isocratic reversed-phase separation are presented for the determination of alpha-tocopherol (vitamin E) in serum. In the first method alpha-tocopherol acetate is used as internal standard, detection of absorbance is performed at 284 nm. In the second method tocol is used as internal standard, detection of fluorescence is performed with an excitation wavelength of 292 nm and emission wavelength of 325 nm. Both methods require a liquid-liquid extraction as sample preparation. The results of both HPLC methods have been tested by method comparison for n = 25 serum samples versus an isotope dilution-gas chromatography-mass spectrometry (ID-GC-MS) method using alpha-tocopherol-d6 as internal standard. The imprecision within-run was lower than 2.5% for the UV method and lower than 1% for the fluorescence method for both standards and serum pools. The between-run imprecision, obtained for serum pools, was below 5% for the UV method and not higher than 1.5% for the fluorescence method and not higher 1.8% for the ID-GC-MS. Recovery experiments performed by spiking pool sera with alpha-tocopherol showed recoveries between 98.5% and 100.6% for all methods studied. The result of the method comparison was a coefficient of correlation of r = 0.998 for the HPLC method with fluorescence detection to the ID-GC-MS reference method and a coefficient of correlation of r = 0.981 for the HPLC method with UV detection to the ID-GC-MS reference method. Both methods presented are useful for the analysis of alpha-tocopherol in patient samples. If detection of fluorescence is used, imprecision and inaccuracy of the HPLC method are comparable to the ID-GC-MS chosen as reference method.

Adolescent↗

Results of the multicenter evaluation of the CEDIA Phenytoin assay.

Thirteen clinical evaluation sites in Europe and U.S.A. investigated the CEDIA Phenytoin assay on Boehringer Mannheim/Hitachi analyzers with respect to imprecision, recovery of control sera, interlaboratory survey, linearity and method comparisons using patient samples. The linear dose-response relationship up to 40 micrograms/mL was confirmed by all participants. Imprecision at therapeutic analyte concentrations equalled that of other routine methods. Recovery of controls was found in a +/- 6% range for target values assigned by the CEDIA assay. The good interlaboratory transferability of the CEDIA assay was confirmed with control material and human samples. The reconstituted reagent can be used up to one month using weekly recalibration. In method comparison studies good correlations to other routine methods were obtained. Results in analyte-free human sera did not deviate systematically from the zero-point. Thus, the accuracy in patient sera has been shown for the CEDIA Phenytoin assay.

Dose-Response Relationship, Drug↗

A comparison between methods for linkage disequilibrium fine mapping of quantitative trait loci.

We present a maximum likelihood method for mapping quantitative trait loci that uses linkage disequilibrium information from single and multiple markers. We made paired comparisons between analyses using a single marker, two markers and six markers. We also compared the method to single marker regression analysis under several scenarios using simulated data. In general, our method outperformed regression (smaller mean square error and confidence intervals of location estimate) for quantitative trait loci with dominance effects. In addition, the method provides estimates of the frequency and additive and dominance effects of the quantitative trait locus.

Chromosome Mapping↗

A comparison of methods for concentrating mutagens in drinking water--recovery aspects and their implications for the chemical character of major unidentified mutagens.

A comparison of techniques for concentrating mutagenic compounds in drinking water has shown that XAD-2 adsorption and dichloromethane extraction have acceptable and almost identical enrichment properties, while purging at an elevated temperature is inappropriate in this context. Quantitatively, the most important drinking water mutagens could only be adsorbed (extracted) after acidification of the water, and even then recovery was far from complete. Recovery experiments with known mutagens from pulp mill effluents have shown that none of the major chlorination-stage mutagens identified thus far can explain the mutagenic activity of extracts from neutral or acidified chlorinated drinking water.

Adsorption↗

Real world performance of approximate string comparators for use in patient matching.

Medical record linkage is becoming increasingly important as clinical data is distributed across independent sources. To improve linkage accuracy we studied different name comparison methods that establish agreement or disagreement between corresponding names. In addition to exact raw name matching and exact phonetic name matching, we tested three approximate string comparators. The approximate comparators included the modified Jaro-Winkler method, the longest common substring, and the Levenshtein edit distance. We also calculated the combined root-mean square of all three. We tested each name comparison method using a deterministic record linkage algorithm. Results were consistent across both hospitals. At a threshold comparator score of 0.8, the Jaro-Winkler comparator achieved the highest linkage sensitivities of 97.4% and 97.7%. The combined root-mean square method achieved sensitivities higher than the Levenshtein edit distance or long-est common substring while sustaining high linkage specificity. Approximate string comparators increase deterministic linkage sensitivity by up to 10% compared to exact match comparisons and represent an accurate method of linking to vital statistics data.

Algorithms↗

Cobalt-60 dose calibration: a comparison of methods.

Cobalt-60 dose determination can be accomplished by a variety of methods. This study investigates dose determination by actual "at-depth" measurement for the depths and field sizes desired as well as by "in-air" or "in-water" calibration measurements for both constant SSD and isocentric techniques. Comparison of the above dose determination methods reveals the existence of both depth-dependent and field size-dependent dose discrepancies between the individual methods studied. For many teletherapy units, the source of these discrepancies lies in the inapplicability of the tabulated percent depth dose and tissue-air ratio values employed. Appropriate percent depth dose and tissue-air ratios can be obtained by performing a series of at-depth dose determinations for a variety of depths and field sizes. When the appropriate values are employed, excellent agreement is found between all of the dose determination methods investigated.

Cobalt Radioisotopes↗

[Ligature and excision method with diathermy for haemorrhoidectomy: in comparison with conventional method].

The usefulness of ligature and excision method with diathermy (group D) for haemorrhoidectomy was evaluated in comparison with conventional ligature and excision method with scalpel and scissors (group S) from several parameters. Intraoperative bloodloss and hospitalization days in group D were significantly smaller than those in group S. Moreover, post-operative woundal bleeding and edema in group D were significantly smaller than those in group S. As regards post-operative pain, although there were no significant differences between the two groups, the values in group D were slightly improved as compared with group S. These results indicate the usefulness of diathermic method for haemorrhoidectomy because of its better cost-efficacy as compared with conventional method with scalpel and scissors.

Adult↗

Comparison of methods based on diversity and similarity for molecule selection and the analysis of drug discovery data.

The concepts of diversity and similarity of molecules are widely used in quantitative methods for designing (selecting) a representative set of molecules and for analyzing the relationship between chemical structure and biological activity. We review methods and algorithms for design of a diverse set of molecules in the chemical space using clustering, cell-based partitioning, or other distance-based approaches. Analogous cell-based and clustering methods are described for analyzing drug-discovery data to predict activity in virtual screening. Some performance comparisons are made. The choice of descriptor variables to characterize chemical structure is also included in the comparative study. We find that the diversity of a selected set is quite sensitive to both the statistical selection method and the choice of molecular descriptors and that, for the dataset used in this study, random selection works surprisingly well in providing a set of data for analysis.

Algorithms↗

High-density-lipoprotein cholesterol in heparin-MnCl2 supernates determined with the Dow enzymic method after precipitation of Mn2+ with HCO3-.

Manganese interferes with enzymic cholesterol methods. In this study, we enzymically measured high-density-lipoprotein (HDL) cholesterol in heparin-Mn2+ supernates that had been treated with NaHCO3 (91 mmol/L) to precipitate Mn2+, and compared results with those by an automated Liebermann- Burchard method. For untreated supernates of 96 fresh plasma samples, the enzymic values were 10.4% higher than comparison-method values, a bias that declined to +2.3% for treated supernates. For 72 sera promptly frozen and stored after collection, the enzymic values for untreated and treated supernates were, respectively, 6.0% and 0.5% higher than comparison-method values. In all cases, the magnitude of the bias was independent of the concentrations of cholesterol, triglyceride, and HDL-cholesterol. Enzymic HDL-cholesterol measurements in NaHCO3-treated heparin-Mn2+ supernates prepared from four pooled serum controls agreed within 21 mg/L with values established for these pools by the Centers for Disease Control. We conclude that the accuracy of enzymic HDL cholesterol measurements in heparin-Mn2+ supernates in considerably increased by treatment with NaHCO3.

Bicarbonates↗

Hemodynamic analysis of cephalothoracopagus by the color doppler method. A comparison to normal fetuses via a longitudinal study.

In a case of cephalothoracopagus, the umbilical artery (UA) was observed with color Doppler method, and the findings were compared with the hemodynamics of 46 normal fetuses. The patient was a 25-year-old primigravida who had appeared for routine prenatal visits since her 6th week of pregnancy. At a later time, the patient was examined after an interval of 4 weeks. Although an ultrasonography was also conducted, unfortunately, any findings of cephalothoracopagus were not detected. In the 25th week of gestation, we hospitalized her for marked polyhydramnios (amniotic fluid index: 280 mm), at which time an ultrasound examination revealed cephalothoracopagus. In the UA, the V(max) was 30.3 cm/s (normal fetus at 25-28 weeks: 33.5 +/- 3.9 cm/s). The UA hemodynamics fell below the normal range. At 26 weeks, the UA V(max) was 56.5 cm/sec, a level which significantly exceeded the normal range. The patient underwent a cesarean section at 27 weeks of gestation; the indication was fetal distress. This is caused by the condition in which the fetal heart beats decreases to 90 beats per minute 3 times during a 10-min period as measured on the cardiotocograms. She delivered a 1,392-gram female with an Apgar score of 2 points (respiratory 1 point and heart rate 1 point). The infant was a cephalothoracopagus, with one head, two hearts, four upper limbs, and four lower limbs. The neonate died from circulatory failure 56 min after birth.

Adult↗

A comparison of methods for determining genotypes at the tumour necrosis factor-alpha-308, interleukin (IL)-1beta+3953, IL-6 -174 and IL-10 -1082/-819/-592 polymorphic loci.

Induced heteroduplex genotyping (IHG) is one of many methods that can be used to determine single nucleotide polymorphisms (SNPs). It is relatively new in comparison to other polymerase chain reaction (PCR)-based techniques. The aim of this study was to compare the results of genotyping using IHG with the results of genotyping using either polymerase chain reaction-sequence-specific primers (PCR-SSP) or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for SNPs in the tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6 and IL-10 genes. Ninety patients who consented to participate in the study had their genotypes determined by IHG and either PCR-SSP (TNF-alpha-308 and IL-10 -1082/-819/-592) or PCR-RFLP (IL-1beta +3953 and IL-6 -174). Results for each locus were compared between techniques by calculating the Kappa statistic as a measure of agreement. The IHG and more traditional genotyping methods produced very similar results at all loci. The Kappa statistics for each locus were as follows: TNF-alpha -308, K = 0.727; IL-1beta +3953, K = 0.886; IL-6 -174, K = 0.909; IL-10 -1082, K = 0.876; IL-10 -592, K = 0.920. IHG is a valid method for the determination of genotypes at the loci examined in this study and produces comparable results to those of more traditional methods of genotyping.

Cytokines↗

[Measuring coronary circulation using an inert gas method--a comparison of common indicator gases].

Validation studies of inert gas techniques are limited in number and usually have not included circumstances with marked heterogeneity of flow. This study was intended to investigate the validity of the method in experimental animals under various hemodynamic conditions by parallel application of helium, argon, krypton and xenon as indicators and by comparison with direct flow measurements. Gases were applied by single breath inhalation. In order to avoid the limitations of conventional methods arising from the systemic recirculation of tracer and from shortened measuring periods we used continuous mass spectrometric recording and numeric deconvolution of the dilution curves in arterial and coronary venous blood. When the transit times are evaluated by "stochastic" analysis and commonly used tissue/blood partition-coefficients (lambda He = 0.95, lambda Ar = 1.1) the helium and argon values are found in reasonable agreement with reference flows. The effects of a shortening of measurements that are based on single integrated samples (Argon method) are shown under control conditions, adenosin infusion and elevated ventricular filling pressure. With xenon (lambda Xe = 0.7) coronary blood flow above 100 ml/min X 100 g is underestimated by the "stochastic" and by the "initial slope technique"; parallel measurements with argon suggest that in the initial slope technique a lambda Xe between 0.8 and 0.9 might be more adequate.

Animals↗

Use of viral pathogens and indicators to differentiate between human and non-human fecal contamination in a microbial source tracking comparison study.

Assays for the detection and typing of adenoviruses, enteroviruses and F+ specific coliphages were performed on samples created as part of a national microbial source tracking methods comparison study. The samples were created blind to the researchers, and were inoculated with a variety of types of fecal contamination source (human, sewage, dog, seagull and cow) and mixtures of sources. Viral tracer and pathogen assays demonstrated a general ability to discriminate human from non-human fecal contamination. For example, samples inoculated with sewage were correctly identified as containing human fecal contamination because they contained human adenovirus or human enterovirus. In samples containing fecal material from individual humans, human pathogen analysis yielded negative results probably because the stool samples were taken from healthy individuals. False positive rates for the virus-based methods (0-8%) were among the lowest observed during the methods comparison study. It is suggested that virus-based source tracking methods are useful for identification of sewage contamination, and that these methods may also be useful as an indication of the public health risk associated with viral pathogens. Overall, virus-based source tracking methods are an important approach to include in the microbial source tracking 'toolbox'.

Adenoviridae↗

Evaluation of Glucocard Memory 2 and Accutrend sensor blood glucose meters.

The performance and practicability of 2 blood glucose meters (Glucocard Memory 2 and Accutrend sensor) were evaluated. Both glucose meters produced acceptably precise results in the hyper- and normoglycaemic concentration ranges. In the hypoglycaemic concentration range, the imprecision of Accutrend sensor was much higher than recommended by the American Diabetes Association. Within-run coefficients of variation for Glucocard Memory 2 were 6.3%, 3.9% and 2.4% at glucose concentrations of 1.7 mmol/l, 5.8 mmol/l and 11.7 mmol/l, respectively: for Accutrend sensor these were 15.2%, 5.0% and 1.2% at respective concentrations of 0.9 mmol/l, 4.2 mmol/l and 19.6 mmol/l. Between-day coefficients of variation for Glucocard Memory 2 were 4.8% and 3.5% at glucose concentrations of 3.9 mmol/l and 17.2 mmol/l, respectively and for Accutrend sensor they were 3.8% and 2.9% at glucose concentrations of 3.8 mmol/l and 18.7 mmol/l, respectively. Results were linear over a range of 1.6 mmol/l -29.7 mmol/l for Glucocard Memory 2 and 1.6 mmol/l -33.3 mmol/l for Accutrend sensor. Results of both blood glucose meters correlated closely with the hexokinase/glucose-6-phosphate dehydrogenase laboratory method. Ninety-eight percent of both Glucocard Memory 2 and Accutrend sensor results were within 20% of the comparison method values. Ninety-three percent of the Glucocard Memory 2 and 96% of the Accutrend sensor results were within 15% of the comparison method results. An inverse relation between the glucose readings and haematocrit values was observed for both blood glucose meters in the hyperglycaemic range and this effect was more pronounced for Accutrend sensor. In the normo- and hypoglycaemic ranges the effect was insignificant and absent, respectively. Minimum sample volume for Glucocard Memory 2 was 3 microliters and for Accutrend sensor it was 9 microliters. Lower sample volumes gave erroneous results. Presenting more than the required volume had no effect on results.

Analysis of Variance↗

Comparison of methods to estimate non-milk extrinsic sugars and their application to sugars in the diet of young adolescents.

Consistent information on the non-milk extrinsic sugars (NMES) content of foods and the NMES intake by the population is required in order to allow comparisons between dietary surveys. A critical appraisal of methods of NMES estimation was conducted to investigate whether the different published methods for estimating the NMES content of foods lead to significantly different values for the dietary intake of NMES by children and to consider the relative practicality of each method. NMES values of foods were calculated using three different published descriptions of methods of NMES estimation, and the values were compared within food groups. Dietary intake values for English children aged 11-12 years were calculated using each method and compared in terms of overall NMES intake and the contribution of different food groups to NMES intake. There was no significant difference in the dietary intake of NMES in children between the method used in the National Diet and Nutrition Surveys (NDNS) (81.9 g/d; 95 % CI 79.0, 84.7) and a method developed by the Human Nutrition Research Centre (84.3 g/d; 95 % CI 81.4, 87.2) at Newcastle University, UK, although the latter gave slightly higher values. An earlier method used by the Ministry of Agriculture, Food and Fisheries gave significantly higher values than the other two methods (102.5 g/d; 95 % CI 99.3, 105.6; P<0.05). The method used in the NDNS surveys and the method used by the Human Nutrition Research Centre at Newcastle University are both thorough and detailed methods that give consistent results. However, the method used in the NDNS surveys was more straightforward to apply in practice and is the best method for a single uniform approach to the estimation of NMES.

Candy↗