Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings.

Water samples from several ponds in Minnesota were evaluated for their capacity to induce malformations in embryos of Xenopus laevis. The FETAX assay was used to assess the occurrence of malformations following a 96-hr period of exposure to water samples. These studies were conducted following reports of high incidences of malformation in natural populations of frogs in Minnesota wetlands. The purpose of these studies was to determine if a biologically active agent(s) was present in the waters and could be detected using the FETAX assay. Water samples from ponds with high incidences of frog malformations (affected sites), along with water samples from ponds with unaffected frog populations (reference sites), were studied. Initial experiments clearly showed that water from affected sites induced mortality and malformation in Xenopus embryos, while water from reference sites had little or no effect. Induction of malformation was dose dependent and highly reproducible, both with stored samples and with samples taken at different times throughout the summer. The biological activity of the samples was reduced or eliminated when samples were passed through activated carbon. Limited evidence from these samples indicates that the causal factor(s) is not an infectious organism nor are ion concentrations or metals responsible for the effects observed. Results do indicate that the water matrix has a significant effect on the severity of toxicity. Based on the FETAX results and the occurrence of frog malformations observed in the field, these studies suggest that water in the affected sites contains one or more unknown agents that induce developmental abnormalities in Xenopus. These same factors may contribute to the increased incidence of malformation in native species.

In recent studies, a high incidence of amphibian mortality and malformation has been reported in the field, suggesting that toxic and/or bioactive agents are present in the environment of the affected amphibians. This study provides evidence for this hypothesis, because it applies to several affected ponds in Minnesota and Vermont, USA. Three developmental bioassays were carried out on samples from three reference and three test sites in Minnesota and one reference and three test sites, in Vermont. The bioassays utilized Xenopus as a model system, measuring altered developmental patterns during the first 4 d of development (frog embryo teratogenesis assay-Xenopus [FETAX]), hind-limb development over a 30-d period, and tail length resorption over a 14-d period. Strong correlations were observed among the results for all three in vitro bioassays, as well as between adverse developmental effects in vitro and in the field.

Insulin pump therapy in pediatric type 1 diabetes has been associated with better glycemic control than multiple daily injections. However, insulin pump use remains limited. This article describes an initiative from the T1D Exchange Quality Improvement Collaborative aimed at increasing insulin pump use in patients aged 12-26 years with type 1 diabetes from a baseline of 45% in May 2018 to >50% by February 2020. Interventions developed by participating centers included increasing in-person and telehealth education about insulin pump technology, creating and distributing tools to assist in informed decision-making, facilitating insulin pump insurance approval and onboarding processes, and improving clinic staff knowledge about insulin pumps. These efforts yielded a 13% improvement in pump use among the five participating centers, from 45 to 58% over 22 months.