Inaccurate Test Results Research Articles

Assessing Viability of Prevariety Germplasm of Native Coreopsis Species

Dormancy issues and lack of approved protocols have led to increasing use of the pregermination tetrazolium test to assess whether seeds of premium-priced, prevariety germplasm of native wildflower species are living and have the potential to germinate and develop normally under field conditions, that is, whether seeds are viable. A major concern is the limited amount of industrywide training on how to conduct and interpret results of tetrazolium (TZ) tests for the multitude of native species. Precise methods that yield uniform results are especially critical for testing of prevariety germplasm of native species given their high value and economic consequences of inaccurate test results. In preliminary work, we observed that embryos extracted from intact seeds of native Coreopsis species subjected to TZ testing were viable if they were turgid and appeared normal and were stained pink, red, or were pure white with or without the radicle tip stained pink to red. In this study, we conducted an in-depth analysis of TZ testing of intact seeds of prevariety germplasm of four native Coreopsis species to: 1) verify our preliminary conclusions; and 2) to determine if staining could be improved by preconditioning or gibberellic acid (GA3) because relatively low percentages of embryos of intact seeds stained pink or red. In addition, we evaluated two other methods to assess viability: the excised embryo test and emergence tests in soil and a soilless medium under ambient conditions. We confirmed that embryos extracted from intact seeds subjected to TZ testing were viable provided that embryos were turgid and appeared normal and were stained pink, red, or were pure white ± a pink to red radicle tip. Embryo staining was not consistently improved by moist preconditioning or GA3. Results of pregermination TZ tests of intact seeds and/or germination plus postgermination TZ tests of intact, nongerminated seeds were not consistently accurate and/or uniform across all species and seed lots, issues usually encountered in seed lots that were relatively dormant or of poor quality, and in postgermination TZ testing of seed lots with relatively low dormancy. Moreover, these issues are likely to be encountered even with standard TZ testing protocols given the widely accepted challenges of accurately interpreting TZ tests of native species in general. The most precise, uniform method of assessing viability was the excised embryo germination test because all viable seeds germinated, results were easy to interpret so the likelihood of false-positives or -negatives was nil, and results were very uniform across replications. Emergence tests under ambient conditions substantially underestimated viability. In summary, the high cost of prevariety germplasm seeds of native Coreopsis species, inherent genetic and phenotypic variability, and unknown dormancy characteristics warrant the use of the embryo excision test for determining viability and for increased sample sizes, especially for any tests involving TZ.

Interlaboratory Validation of 1% Pluronic L92 Surfactant as a Suitable, Aqueous Vehicle for Testing Pesticide Formulations Using the Murine Local Lymph Node Assay

The mouse local lymph node assay (LLNA) has become the preferred test for evaluating the dermal sensitization potential of chemicals and requirements are now emerging for its use in the evaluation of their formulated products, especially in the European Union. However, despite its widespread use and extensive validation, the use of this assay for directly testing mixtures and formulated products has been questioned, which could lead to repeat testing using multiple animal models. As pesticide formulations are typically a specific complex blend of chemicals for use as aqueous-based dilutions, traditional vehicles prescribed for the LLNA may change the properties of these formulations leading to inaccurate test results and hazard identification. The objective of this study was to evaluate the effectiveness of an aqueous solution of Pluronic L92 block copolymer surfactant (L92) as a vehicle in the mouse LLNA across five laboratories. Three chemicals with known sensitization potential and four pesticide formulations for which the sensitization potential in guinea pigs and/or humans had previously been assessed were used. Identical LLNA protocols and test materials were used in the evaluation. Assessment of the positive control chemicals, hexylcinnamaldehyde, formaldehyde, and potassium dichromate revealed positive results when using 1% aqueous L92 as the vehicle. Furthermore, results for these chemicals were reproducible among the five laboratories and demonstrated consistent relative potency determinations. The four pesticide formulations diluted in 1% aqueous L92 also demonstrated reproducible results in the LLNA among the five laboratories. Results for these test materials were also consistent with those generated previously using guinea pigs or from human experience. These data support testing aqueous compatible chemicals or pesticide formulations using the mouse LLNA, and provide additional support for the use of 1% aqueous L92 as a suitable, aqueous-based vehicle.

Performance Standards for Allergen Skin Testing: An Approach to Proficiency Testing

The importance ascribed to clinical laboratory tests with respect to having well-defined and validated methodology, test that fall within acceptable limits for accuracy, precision, and sensitivity, and ongoing documentation that operators performing test are proficient are subject of federal regulations derived from Clinical Laboratory Improvement Amendments (CLIA) of 1988. 3 The Health Care Financing Administration (HCFA) operates CLIA laboratory certification program in conjunction with Center for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA). 3 CLIA defines laboratory testing as the examination of materials derived from human body for purpose of providing information for diagnosis, prevention, or treatment of any disease or impairment of, or assessment of health of human beings. 2 Under CLIA all entities providing laboratory testing are regulated and required by law to perform proficiency testing for specific tests. 2 Proficiency testing involves sending blind sample specimens with defined properties to each laboratory during year to evaluate whether laboratory's matches samples' defined properties. 2 Samples are required to be tested in same manner and by same individuals performing patient testing. 2 Results of proficiency test programs have been analyzed, 2 resulting in recognition that physician-operated testing laboratories experience a lower rate of successful test performance than traditional, previously regulated laboratories or physician-operated laboratories in which a laboratory professional provides supervision. The introduction of required proficiency testing has increased accuracy of test and quality of laboratory practice in physician-office laboratories, reflecting positive impact of CLIA over time. 2,15 FDA-licensed allergen vaccines approved for diagnostic use commonly are employed clinically to detect cutaneous immediate hypersensitivity to allergens of interest. Results of allergen skin tests impact clinical decisions. Positive test may indicate likelihood of life-threatening hypersensitivity to food, insect, or drug allergens or presence of environmental aeroallergens responsible for allergic disease. In each circumstance, there is an important impact on quality of life in terms of interventions designed to avoid exposure, pharmaco- and immunotherapeutic interventions indicated to reduce expected allergic response (if re-exposed), and psychosomatic sequelae and economic cost to patient associated with diagnosis. The adverse impact if test are falsely positive or negative should be considered, and attendent health and economic costs should be calculated. Similar considerations concerning adverse impact of inaccurate tests on quality of health care lead to passage of CLIA to increase patient and physician confidence in ability of tests to perform accurately according to objective standards, thus improving medical decisions and quality of care and decreasing economic burden of inaccurate test results. 2 Practice parameters for allergen skin testing 1 specify that the proficiency of skin tester should be validated by intrapatient and interpatient test results 1,11 and refer to proficiency tests and performance standards required by FDA for allergen standardization. 1 In latter context, investigators who submit allergen skin test data to FDA to define biologic potency of allergen vaccines for estimating US Standard of Potency 23 and to estimate cutaneous sensitivity of subjects 23 enrolled in clinical trials submitted to FDA in support of diagnostic or therapeutic efficacy of allergen vaccines are provided a skin test proficiency 22 The method is suitable for assessing proficiency of operator who is carrying out this technique and can be used to qualify personnel for submission of skin test data to CBER. 22 Before submitting allergen skin test data to FDA, Investigators should be familiar with Proficiency Method … and have submitted proficiency data qualifying their use of this method. 23 The allergen skin test Proficiency Method based on parallel line bioassay methodology described in 1982 24 has been subjected to international collaborative evaluation. 12,17,21 It has been used in support of skin test data submitted to FDA in support of licensure of standardized cat, housedust mite, and grass pollen extracts (see FDA-approved package inserts that reference use of FDA skin test methods). Test performance can be divided into two categories: analytical test performance and clinical test performance. 19 Analytical test performance refers to accuracy, precision, and sensitivity of a test to measure analyte of interest. 5 Clinical test performance is defined by clinical accuracy of test with respect to whether test accurately discriminates between disease and nondisease states. 25

A study to examine the accuracy of potassium measurements in clinical laboratories across Canada

Objective: To assess the accuracy of potassium measurements in clinical laboratories across Canada. Design and method: The flame atomic emission spectrophotometry reference method for the determination of potassium was established at the Canadian Reference Laboratory by using National Institute of Science and Technology standard reference materials. The method was subsequently used to assign target values for potassium to Canadian Reference Laboratory’s External Quality Assessment human-serum-based testing material. A total of 503 laboratories participated and 9,279 individual External Quality Assessment test results were included in the study. Bias was determined by using difference plots. Results: Clinically significant bias (>1.6%) was observed in 45.9% of the laboratories. Bias ranged from 0.34 mmol/L to −0.54 mmol/L. At low concentrations (<3.5 mmol/L) a positive bias was most frequently observed (14.7% of analytical systems). At high potassium concentrations (>5.1 mmol/L) a negative bias was most frequently observed (31.4% of analytical systems). Conclusion: Inaccuracy in potassium results can contribute to test redundancy and mismanagement of patients, while prohibiting the merger of laboratory data from disparate testing sites for the purpose of trending and consolidation within a “universal health record.” Inaccurate test results and the lack of standardization among laboratories adversely impact our ability to establish common reference intervals and critical limits. This inability has an adverse effect on medical decisions and patient care.

Assessing disease prevalence from inaccurate test results: teaching an old dog new tricks.

Estimates of disease prevalence are needed for the interpretation of test results as well as for public health decisions. Assessing prevalence may be difficult if a definitive test is unavailable, impractical, or expensive. A formula derived from Bayes' theorem can calculate the prevalence of disease in a population by incorporating test results with a knowledge of the sensitivity and specificity of a test. This paper reviews this formula and provides examples evaluating the prevalence of HIV disease, the usefulness of ventilation-perfusion scans in diagnosing pulmonary embolism, and settings where screening tests should not be applied. These examples demonstrate that precise yet inexpensive estimates of disease prevalence are possible by enhancing the usefulness of an inaccurate test.

An APL function for the asymptotic test of significance for Goodman and Kruskal’s gamma statistic

Goodman and Kruskal's (1954) gamma is a measure of association that is often used to measure the degree of association between two cross-elassified ordinal variables. Gamma is a symmetric measure of ordinal association that utilizes infonnation only from concordant and discordant (i.e., untied) object pairs; Somers' (1962) d, on the other hand, is an asymmetric measure of ordinal association that utilizes the infonnation from the concordant and discordant object pairs, but adjusts for additional object pairs that are tied on the dependent variable but not on the independent variable. Although these two measures examine somewhat different kinds of object pairs obtained from the two ordinal variables, they both estimate the degree to which knowledge of order on one variable predicts order on the other variable. Several APL routines exist to compute Goodman and Kruskal's (1954) symmetric measure of ordinal association, gamma, as well as Somers' (1962) asymmetric measures, dre , with row variable dependent, and den with column variable dependent (Berry & Mielke, 1986; Brennan, Nitz, & Daly, 1988). Unfortunately, none of these routines provides the probability value, under the null hypothesis, for any of the three measures. The function GAMMA is a noniterative APL function that calculates the three coefficients of ordinal association-gamma, drc> and der-the associated two-sided probability values, and the 95% and 99% confidence limits, under full multinomial sampling. The probability values and the confidence limits are computed using the asymptotic standard errors developed by Goodman and Kruskal (1963, 1972) and, specifically, do not use the approximate standard errors given in many textbooks. The approximate tests are based on the maximum standard error (Goodman & Kruskal, 1963), which yields a conservative test with a probability of falsely rejecting the null hypothesis known only to be less than some nominal value, or they assume unifonn marginals (Somers, 1980), which may yield inaccurate test results for cross classifications with severely skewed marginal distributions. Moreover, because the approximations introduced by Somers (1980) are based on null populations, they preclude the computation of confidence limits. Procedure. Consider a full multinomial sample of n discrete objects, which are cross classified by two ordi-

Some fuzzy set applications in mining geomechanics

Subjective judgement normally constitutes an important element in mining geomechanics decision processes. In most instances, subjectivity arises from the imprecise or fuzzy information which in turn results from descriptive data or inaccurate test results. The paper proposes the application of fuzzy set theory in assisting mining engineers in the geomechanics decision processes for which subjectivity plays an important role. In particular, the Bellman-Zadeh optimization procedure is used to synthesize a hazard index for mining excavations. The same procedure is used to evaluate a rock mass classification rating from Bieniawski's system with incorporation of expert knowledge. The extension principle of fuzzy sets is applied to evaluate Barton's quality index Q when information on various contributing indices is fuzzy. Basic principles of fuzzy set theory are described and numerical examples are used to illustrate applications of fuzzy set theory in mining geomechanics.