* ABSTRACT The United States Pharmacopeia (USP) has empanelled biological and statistical experts to develop chapters pertaining to the practice of biological assays. These include a rewrite of General Chapter Design and Analysis of Biological Assays h111i and the development of two new General Chapters, Design of Biological Assays h1032i and Validation of Biological Assays h1033i. These experts have come to realize a need for clear and uniform terminology in their discussions, throughout the three chapters, and, indeed, throughout all portions of USP-NF that relate to biological assays. Accordingly, they have developed a glossary pertinent to biological assays. The purpose of this Stimuli article is to share this nascent glossary with the USP audience and to resolve and/or clarify differences in measurement terminology for well- (small molecules) and poorly characterized (biologicals and biotechnological moieties), hereafter referred to collectively as drug substances. In many cases the terms developed herein have common usages or appear elsewhere, for example in contemporary references by the International Conferences on Harmonization (ICH, for example Guideline Q2A, Text on Validation of Analytical Procedures (1)), Food and Drug Administration (FDA), and USP. For some of the terms in this document, the derivation may be clear. Rather than claim originality, the authors seek to associate with this work a compendial perspective that will provide clarity going forward, consistency with previous authoritative usage, and a useful focus on the bioassay context.

Zebra mussels (Dreissena polymorpha) invaded the Great Lakes in 1986 and are considered to be a nuisance species, because of their rapid population growth and their strong byssal attachment to a variety of man-made and natural surfaces. Research on possible antifouling materials or coatings has revealed few nontoxic substrates that even retard attachment of mussels. The influence of several substrate characteristics in combination (material, texture, orientation, and sunlight) on zebra mussel settlement was examined. Settlement of post-veliger mussels on experimental plates indicated that the mussels attached in higher numbers on upper versus lower horizontal surfaces, textured versus smooth surfaces, shaded versus sunlit surfaces, PVC versus Plexiglas, and plastic (PVC and Plexiglas) versus glass. Zebra mussels did not show strong preferences among several additional substrate materials (wood, Fiberglas, concrete, limestone, aluminum, and raw steel) but they strongly avoided galvanized steel. These results confirm field observations of locations in which mussels are most likely to be found. Information about zebra mussel substrate preferences may enhance the design of monitoring programs and the integrated management of mussels in vulnerable areas.

Optical aggregometry, traditionally used to assess platelet function, is highly dependent on sample preparation and technical procedure; as a result, data from various laboratories can be quite variable. In a study designed to assess the sources of variation, it was determined that the total standard deviation ranged from 3.6% to 7.7%. The assay variation by one analyst on one aggregometer on a single day ranged from 1.7 to 4.6, Day-to-day variation contributed 42% to 63% of the total variation, between-operator variation contributed 1% to 33% of the total variation, and within [between repeat measurements for a given sample by a given operator on a single day] variation contributed 22% to 36% of the total variation. Because of the disadvantages associated with optical aggregometry, alternate platelet function assays were considered and their correspondence to optical aggregometry was evaluated: activated clotting time, whole blood aggregometry, platelet count ratio, Platelet Function Analyzer (PFA-100, Dade), and Rapid Platelet Function Assay (Accumetrics). Of those assays evaluated, activated clotting time and PFA-100 are assays that measure aspects of coagulation and hemostasis, whereas whole blood aggregometry, platelet count ratio, and RPFA are more closely related to platelet function. Each assay has value in monitoring various aspects of the coagulation process. The best method for monitoring safety and efficacy of various inhibitors of platelet function will ultimately be determined by clinical trials.

AbstractChanges in soil physical and chemical properties following conversion from conventional to low-input farming systems could alter root growth in com and hence aboveground growth and yield. The main hypothesis we tested is that low-input and conventional farming systems produce different amounts of corn roots. We compared low-input and conventional farming systems, row position (row and interrow), and soil depth for effects on root length density in a Comly silt loam (Typic Fragiudalf) at the Rodale Institute Research Center in Kutztown, Pennsylvania. On all sampling dates studied (two each in 1989 and 1990) root length density under low-input farming systems was significantly greater than under conventional farming systems. We used analysis of covariance to correct for soil factors that could not be directly controlled. Soil water and bulk density had no clear effect on root length density. In contrast, there was significant covariance of soil organic matter with root length density on two of the four sample dates. Root networks were more dense in soil pockets rich in organic matter for every farming system, row position, and depth. These findings indicate that low-input farmers may be manipulating root production of corn to allow com to absorb more nutrients and water when water in the topsail is limited.

DNA analysis by flow cytometry has been reported to be a useful prognostic technique for a variety of malignant tumors. The goal of this study was to examine DNA ploidy status and proliferation index as potential predictors of recurrence and survival for patients with squamous cell vulvar carcinomas. The DNA ploidy, percentage of cells in the S-phase of the cell cycle, stage, and histologic grade were analyzed in 42 patients. Flow cytometry was performed on archival paraffin-embedded tissue. The histologic specimens were reviewed by a single pathologist. Thirty-four tumors (81%) were diploid and eight (19%) demonstrated an aneuploid peak. The percentage of cells in the S-phase (proliferation index) was calculated for all patients. The 5-year survival rate was 68% for diploid tumors and was 75% for aneuploid tumors. The difference between these rates was not statistically significant (P < or = 0.65). S-phase fraction was also not a useful predictor for recurrence or overall survival. FIGO stage and histologic grade were accurate predictors for both recurrence and 5-year survival. Multiple predictor analysis using stage, grade, ploidy status, and proliferation index did not identify any subgroup which would predict recurrence better than FIGO stage and grade. DNA ploidy and S-phase fraction analysis do not appear to be clinically useful prognostic factors for vulvar squamous cell carcinomas.