Diagnostic laboratory standardization and validation of platelet transmission electron microscopy

<p>Platelet transmission electron microscopy (PTEM) is considered the gold standard test for assessing distinct ultrastructural abnormalities in inherited platelet disorders (IPDs). Nevertheless, PTEM remains mainly a research tool due to the lack of standardized procedures, a validated dense granule (DG) count reference range, and standardized image interpretation criteria. The aim of this study was to standardize and validate PTEM as a clinical laboratory test. Based on previously established methods, we optimized and standardized preanalytical, analytical, and postanalytical procedures for both whole mount (WM) and thin section (TS) PTEM. Mean number of DG/platelet (plt), percentage of plts without DG, platelet count (PC), mean platelet volume (MPV), immature platelet fraction (IPF), and plt light transmission aggregometry analyses were measured on blood samples from 113 healthy donors. Quantile regression was used to estimate the reference range for DG/plt, and linear regression was used to assess the association of DG/plt with other plt measurements. All PTEM procedures were standardized using commercially available materials and reagents. DG interpretation criteria were established based on previous publications and expert consensus, and resulted in improved operator agreement. Mean DG/plt was stable for 2 days after blood sample collection. The median within patient coefficient of variation for mean DG/plt was 22.2%; the mean DG/plt reference range (mid-95th %) was 1.2–4.0. Mean DG/plt was associated with IPF (<i>p </i>= .01, R² = 0.06) but not age, sex, PC, MPV, or plt maximum aggregation or primary slope of aggregation (<i>p </i>> .17, R² < 0.02). Baseline ultrastructural features were established for TS-PTEM. PTEM was validated using samples from patients with previously established diagnoses of IPDs. Standardization and validation of PTEM procedures and interpretation, and establishment of the normal mean DG/plt reference range and PTEM baseline ultrastructural features, will facilitate implementation of PTEM as a valid clinical laboratory test for evaluating ultrastructural abnormalities in IPDs.</p

Strengthening Biblical Historicity vis-à-vis Minimalism, 1992-2008 and Beyond, Part 2.1: The Literature of Perspective, Critique, and Methodology, First Half

This series of articles covers scholarly works in English which can, at least potentially, be associated with a positive view of biblical historicity regarding the periods preceding the Israelites’ return from exile. Part 2 covers works that treat the concepts and methodological issues at the center of the maximalist-minimalist debate. (Parts 3–5 will cover works on evidences.) This article, the first half of Part 2, focuses on works that provide a framework in which there exists the realistic possibility for large amounts of Hebrew Scripture to stand as valid historical source material— while still subject to comparison with other sources. These works are by J. Maxwell Miller and John H. Hayes, Megan Bishop Moore, Lester L. Grabbe, James Barr, Bob Becking, Amihai Mazar, Hans M. Barstad, Ronald S. Hendel, and Mark S. Smith. The article leads up to this focus by beginning with bibliographic selections in earlier works, works that offer long-term perspectives, and a summary of good effects and misguided aspects of minimalist publications. (Part 2.2 will treat works on methodology by authors who espouse biblical historicity unless it is proven wrong.