| 1. |
- Bjerner, Johan, et al.
(författare)
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Non-parametric estimation of reference intervals in small non-Gaussian sample sets
- 2009
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Ingår i: ACCREDITATION AND QUALITY ASSURANCE. - : Springer Science and Business Media LLC. - 0949-1775 .- 1432-0517. ; 14:4, s. 185-192
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed at validating common bootstrap algorithms for reference interval calculation.We simulated 1500 random sets of 50-120 results originating from eight different statistical distributions. In total, 97.5 percentile reference limits were estimated from bootstrapping 5000 replicates, with confidence limits obtained by: (a) normal, (b) from standard error, (c) bootstrap percentile (as in RefVal) (d) BCa, (e) basic, or (f) student methods. Reference interval estimates obtained with ordinary bootstrapping and confidence intervals by percentile method were accurate for distributions close to normality and devoid of outliers, but not for log-normal distributions with outliers. Outlier removal and transformation to normality improved reference interval estimation, and the basic method was superior in such cases. In conclusions, if the neighborhood of the relevant percentile contains non-normally distributed results, bootstrapping fails. The distribution of bootstrap estimates should be plotted, and a non-normal distribution should warrant transformation or outlier removal.
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| 2. |
- Fischer, C.P, et al.
(författare)
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Vitamin E isoform-specific inhibition of the exercise-induced heat shock protein 72 expression in humans
- 2006
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 100:5, s. 1679-1687
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of reactive oxygen and nitrogen species, as seen in response to exercise, challenge the cellular integrity. Important protective adaptive changes include induction of heat shock proteins (HSPs). We hypothesized that supplementation with antioxidant vitamins C (ascorbic acid) and E (tocopherol) would attenuate the exercise-induced increase of HSP72 in the skeletal muscle and in the circulation. Using randomization, we allocated 21 young men into three groups receiving one of the following oral supplementations: RRR-α-tocopherol 400 IU/ day + ascorbic acid (AA) 500 mg/day (CEα), RRR-α-tocopherol 290 IU/day + RRR-γ-tocopherol 130 IU/day + AA 500 mg/day (CEαγ), or placebo (Control). After 28 days of supplementation, the subjects performed 3 h of knee extensor exercise at 50% of the maximal power output. HSP72 mRNA and protein content was determined in muscle biopsies obtained from vastus lateralis at rest (0 h), postexercise (3 h), and after a 3-h recovery (6 h). In addition, blood was sampled for measurements of HSP72, α-tocopherol, γ-tocopherol, AA, and 8-isoprostaglandin-F2α (8-PGF2α). Postsupplementation, the groups differed with respect to plasma vitamin levels. The marker of lipid peroxidation, 8-iso-PGF2α, increased from 0 h to 3 h in all groups, however, markedly less (P < 0.05) in CEα. In Control, skeletal muscle HSP72 mRNA content increased 2.5-fold (P < 0.05) and serum HSP72 protein increased 4-fold (P < 0.05) in response to exercise, whereas a significant increase of skeletal muscle HSP72 protein content was not observed (P = 0.07). In CEα, skeletal muscle HSP72 mRNA, HSP72 protein, and serum HSP72 were not different from Control in response to exercise. In contrast, the effect of exercise on skeletal muscle HSP72 mRNA and protein, as well as circulating HSP72, was completely blunted in CEαγ. The results indicate that γ-tocopherol comprises a potent inhibitor of the exercise-induced increase of HSP72 in skeletal muscle as well as in the circulation.
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| 3. |
- Forsum, Urban, 1946-, et al.
(författare)
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The impact of qualitative analysis in laboratory medicine
- 2005
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier BV. - 0165-9936 .- 1879-3142. ; 24:6, s. 546-555
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Tidskriftsartikel (refereegranskat)abstract
- Laboratory medicine is a challenge for the metrologically and terminologically inclined scientist. One main reason is the need for a sound theory that can be applied in a systematic way to cover all aspects of examinations, i.e., those procedures whose results are reported on an ordinal scale and those reported on more primitive scales (e.g., classifications and narratives). Validation of procedures for examinations involving properties on a nominal scale is especially difficult to achieve because it is hard to find gold standards, in the conventional sense, against which to validate and which combine performance characteristics and clinically relevant specificity and sensitivity. We present a systematic, unambiguously defined terminology (the C-NPU coding scheme) for metrologically derived terms for expressing properties, and present some examples of how to attain diagnostic goals. If the analytic process in the laboratory can be subsumed into medical contexts in a systematic way, many pitfalls in reporting results can be avoided. © 2005 Elsevier Ltd. All rights reserved.
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| 4. |
- Greiser, Anne, et al.
(författare)
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The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population
- 2017
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 50:18, s. 1198-1202
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Determination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI.DESIGN & METHODS: CTnI and cTnT were determined in parallel by means of the AQT90 FLEX analyzer in about 2250 plasma samples from individuals with known health status. Results were compared to previously determined performance data of three CLT.RESULTS: The 99th percentile of cTnI in the POCT was determined at 19ng/L, the lowest concentration with an imprecision of 10% was reached at 22ng/L while an imprecision of 20% was reached at 13ng/L. Age, sex, or physical activity did not affect the 99th percentile of cTnI. Compared to CLT the AQT90 cTnI POCT the analytical performance was equivalent. The cTnT POCT could not be assessed due a considerable number of high values and an inadequate imprecision profile.CONCLUSION: While the cTnI POCT showed analytical performance comparable to CLT, the results of the cTnT assay on the same device did not suffice to determine a reliable 99th percentile. The present evaluation supports the usage of the cTnI POCT, but application of the cTnT POCT needs further evaluation.
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| 5. |
- Kallner, Anders, et al.
(författare)
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An experimental study of methods for the analysis of variance components in the inference of laboratory information
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 80:1, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Measurement uncertainty (MU) can be estimated and calculated by different procedures, representing different aspects and intended use. It is appropriate to distinguish between uncertainty determined under repeatability and reproducibility conditions, and to distinguish causes of variation using analysis of variance components. The intra-laboratory MU is frequently determined by repeated measurements of control material(s) of one or several concentrations during a prolonged period of time. We demonstrate, based on experimental results, how such results can be used to identify the repeatability, pure reproducibility and intra-laboratory variance as the sum of the two. Native patient material was used to establish repeatability using the Dahlberg formula for random differences between measurements and an expanded Dahlberg formula if a non-random difference, e.g. bias, was expected. Repeatability and reproducibility have different clinical relevance in intensive care compared to monitoring treatment of chronic diseases, comparison with reference intervals or screening.
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| 6. |
- Kallner, Anders, et al.
(författare)
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Measurement repeatability profiles of eight frequently requested measurands in clinical chemistry determined by duplicate measurements of patient samples
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 80:3, s. 202-209
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Tidskriftsartikel (refereegranskat)abstract
- Measurement uncertainties in clinical chemistry are commonly regarded as heteroscedastic - having a constant relative standard deviation irrespective of the concentration of the measurand. The uncertainty is usually determined at two concentrations using stabilized control materials and assumed to represent the analytical goal. The purpose of the present study was to use duplicates of unselected patient samples to calculate the absolute and relative repeatability component of the intra-laboratory measurement uncertainty from duplicates, using the Dahlberg formula and analysis of variance components. Estimates were made at five different concentration intervals of ALT, AST, Calcium, Cholesterol, Creatinine, CRP, Triglycerides and TSH covering the entire concentration interval of the patient cohort. This partioning allows detailing their repeatability profiles. The calculations of the profiles were based on randomly selected results from sets of duplicates ranging from 12,000 to 65,000 pairs. The repeatability of the measurands showed substantial variability within the measuring interval. Therefore, characterizing imprecision profiles as purely homo- or heteroscedastic or by a single number may not be optimal for the intended use. The present data make a case for nuancing the evaluation of analytical goals and minimal differences of measurement results by establishing uncertainty profiles under repeatability conditions, using natural patient samples.
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| 7. |
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| 8. |
- Kallner, Anders, et al.
(författare)
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Repeatability imprecision from analysis of duplicates of patient samples and control materials
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : TAYLOR & FRANCIS LTD. - 0036-5513 .- 1502-7686. ; 80:3, s. 210-214
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Tidskriftsartikel (refereegranskat)abstract
- Measurement imprecision is usually calculated from measurement results of the same stabilized control material(s) obtained over time, and is therefore, principally, only valid at the concentration(s) of the selected control material(s). The resulting uncertainty has been obtained under reproducibility conditions and corresponds to the conventional analytical goals. Furthermore, the commutability of the control materials used determines whether the imprecision calculated from the control materials reflects the imprecision of measuring patient samples. Imprecision estimated by measurements of patient samples uses fully commutable samples, freely available in the laboratories. It is commonly performed by calculating the results of routine patient samples measured twice each. Since the duplicates are usually analysed throughout the entire concentration interval of the patient samples processed in the laboratory, the result will be a weighted average of the repeatability imprecision measured in the chosen measurement intervals or throughout the entire interval of concentrations encountered in patient care. In contrast, the uncertainty derived from many measurements of control materials over periods of weeks is usually made under reproducibility conditions. Consequently, the repeatability and reproducibility imprecision play different roles in the inference of results in clinical medicine. The purpose of the present review is to detail the properties of the imprecision calculated by duplicates of natural samples, to explain how it differs from imprecision calculated from single concentrations of control materials, and to elucidate what precautions need to be taken in case of bias, e.g. due to carry-over effects.
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| 9. |
- Kallner, Anders, et al.
(författare)
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Response to Dr. Sadlers comments
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 80:6, s. 448-449
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
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| 10. |
- Oosterhuis, Wytze P., et al.
(författare)
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The use of error and uncertainty methods in the medical laboratory
- 2018
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : WALTER DE GRUYTER GMBH. - 1434-6621 .- 1437-4331. ; 56:2, s. 209-219
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Tidskriftsartikel (refereegranskat)abstract
- Error methods - compared with uncertainty methods - offer simpler, more intuitive and practical procedures for calculating measurement uncertainty and conducting quality assurance in laboratory medicine. However, uncertainty methods are preferred in other fields of science as reflected by the guide to the expression of uncertainty in measurement. When laboratory results are used for supporting medical diagnoses, the total uncertainty consists only partially of analytical variation. Biological variation, pre- and postanalytical variation all need to be included. Furthermore, all components of the measuring procedure need to be taken into account. Performance specifications for diagnostic tests should include the diagnostic uncertainty of the entire testing process. Uncertainty methods may be particularly useful for this purpose but have yet to show their strength in laboratory medicine. The purpose of this paper is to elucidate the pros and cons of error and uncertainty methods as groundwork for future consensus on their use in practical performance specifications. Error and uncertainty methods are complementary when evaluating measurement data.
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