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Handelsman D.J.,University of Sydney | Newman J.D.,Southern Cross Pathology Australia | Jimenez M.,University of Sydney | McLachlan R.,Monash Institute of Medical Research | And 2 more authors.
Clinical Chemistry | Year: 2014

BACKGROUND: Steroid immunoassays originally required solvent extraction, chromatography, and structurally authentic tracers to avoid interference from steroid cross-reactivity and matrix effects. The demand for steroid assays has driven assay simplification, bypassing this triplet of validity criteria to allow use of unextracted serum, which has introduced bias and nonspecificity at low steroid concentrations. We aimed to evaluate the performance of commercial direct estradiol (E2) immunoassays relative to the reference method of LC-MS and compared serum E2 measurements from each assay with biomarkers of estrogen action. METHODS: We measured serum E2 in duplicate using 5 commercial direct immunoassays and LC-MS in a nested cohort of 101 healthy, asymptomatic men <40 years old from the Healthy Man Study. For each immunoassay, we evaluated the detectability and distribution of serum E2 measurements, CV, and bias (relative to LC-MS) by Passing-Bablok regression and deviance plots. RESULTS: Three assays detected E2 in all samples, whereas E2 was detected in only 53% and 72% of samples by 2 other assays. All 5 assays had positive biases, ranging from 6% to 74%, throughout their ranges. CVs were lower with 4 immunoassays than with LC-MS. LC-MS, but none of the direct immunoassays, correlated with serum testosterone and sex steroid-binding globulin. CONCLUSIONS: The positive bias of direct E2 immunoassays throughout their working range reflects the nonspecific effects of steroid cross-reactivity and/or matrix interference arising from the violation of the triplet validity criteria for steroid immunoassay. © 2013 American Association for Clinical Chemistry. Source

Stark D.,SydPath | Barratt J.,University of Technology, Sydney | Chan D.,University of Technology, Sydney | Ellis J.T.,University of Technology, Sydney
Clinical Microbiology Reviews | Year: 2016

Dientamoeba fragilis is a protozoan parasite of the human bowel, commonly reported throughout the world in association with gastrointestinal symptoms. Despite its initial discovery over 100 years ago, arguably, we know less about this peculiar organism than any other pathogenic or potentially pathogenic protozoan that infects humans. The details of its life cycle and mode of transmission are not completely known, and its potential as a human pathogen is debated within the scientific community. Recently, several major advances have been made with respect to this organism’s life cycle and molecular biology. While many questions remain unanswered, these and other recent advances have given rise to some intriguing new leads, which will pave the way for future research. This review encompasses a large body of knowledge generated on various aspects of D. fragilis over the last century, together with an update on the most recent developments. This includes an update on the latest diagnostic techniques and treatments, the clinical aspects of dientamoebiasis, the development of an animal model, the description of a D. fragilis cyst stage, and the sequencing of the first D. fragilis transcriptome. © 2016, American Society for Microbiology. All Rights Reserved. Source

Jones G.R.D.,SydPath
Annals of Clinical Biochemistry | Year: 2016

Background: Average of normals is a tool used to control assay performance using the average of a series of results from patients’ samples. Delta checking is a process of identifying errors in individual patient results by reviewing the difference from previous results of the same patient. This paper introduces a novel alternate approach, average of delta, which combines these concepts to use the average of a number of sequential delta values to identify changes in assay performance. Methods: Models for average of delta and average of normals were developed in a spreadsheet application. The model assessed the expected scatter of average of delta and average of normals functions and the effect of assay bias for different values of analytical imprecision and within- and between-subject biological variation and the number of samples included in the calculations. The final assessment was the number of patients’ samples required to identify an added bias with 90% certainty. Results: The model demonstrated that with larger numbers of delta values, the average of delta function was tighter (lower coefficient of variation). The optimal number of samples for bias detection with average of delta was likely to be between 5 and 20 for most settings and that average of delta outperformed average of normals when the within-subject biological variation was small relative to the between-subject variation. Conclusions: Average of delta provides a possible additional assay quality control tool which theoretical modelling predicts may be more valuable than average of normals for analytes where the group biological variation is wide compared with within-subject variation and where there is a high rate of repeat testing in the laboratory patient population. © 2015, The Author(s) 2015. Source

Dientamoeba fragilis is an inhabitant of the human bowel and is associated with gastrointestinal illness. Despite its discovery over a century ago, the details of Dientamoeba's life cycle are unclear and its mode of transmission is unknown. Several theories exist which attempt to explain how Dientamoeba may be transmitted. One theory suggests that animals are responsible for the transmission of Dientamoeba. However, reports of Dientamoeba in animals are sporadic and most are not supported by molecular evidence. Another theory suggests that Dientamoeba may be transmitted via the ova of a helminth. Given that the closest relative of Dientamoeba is transmitted via the ova of a helminth, this theory seems plausible. It has also been suggested that Dientamoeba could be transmitted directly between humans. This theory also seems plausible given that other relatives of Dientamoeba are transmitted in this way. Despite numerous investigations, Dientamoeba's mode of transmission remains unknown. This review discusses the strengths and weaknesses of theories relating to Dientamoeba's mode of transmission and, by doing so, indicates where gaps in current knowledge exist. Where information is lacking, suggestions are made as to how future research could improve our knowledge on the life cycle of Dientamoeba. Source

Jones G.R.D.,SydPath
Clinica Chimica Acta | Year: 2014

Common reference intervals for numerical pathology tests have been proposed for many years as an improvement over the common situation where individual laboratories establish or select and validate their own intervals. However it is important that any intervals that are developed for common use are themselves validated for use in individual laboratories. There are three main aspects to consider, the appropriateness of the interval, methodological factors and population factors. Techniques for assessing method biases are reasonably straightforward with the use of shared samples and appropriate external quality assurance schemes. Validating the local population, which also encompasses the laboratory's method, can be done using a number of healthy subjects, the more the better, or by various "data mining" techniques using the results of tests performed on routine patients. In any of these methods there is the need to consider the selection of subjects, the statistical approach and the acceptance criteria. Only if a proposed common reference interval can be shown to be appropriate in routine laboratories can it become widely adopted and become truly "common". © 2013 Elsevier B.V. Source

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