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Item ASGCT 2023—Gene therapy is becoming medicine(Elsevier, 2023) Herzog, Roland W.; Bricker-Anthony, Courtney; Pediatrics, School of MedicineItem Editorial: Furthering precision medicine and cancer prevention through novel insights in molecular and chemical carcinogenesis(Frontiers Media, 2024-10-08) Bisson, William H.; Liby, Karen T.; Bernard, Jamie J.; Medicine, School of MedicineItem Genome-wide circadian rhythm detection methods: systematic evaluations and practical guidelines(Oxford University Press, 2021-05-20) Mei, Wenwen; Jiang, Zhiwen; Chen, Yang; Chen, Li; Sancar, Aziz; Jiang, Yuchao; Medicine, School of MedicineCircadian rhythms are oscillations of behavior, physiology and metabolism in many organisms. Recent advancements in omics technology make it possible for genome-wide profiling of circadian rhythms. Here, we conducted a comprehensive analysis of seven existing algorithms commonly used for circadian rhythm detection. Using gold-standard circadian and non-circadian genes, we systematically evaluated the accuracy and reproducibility of the algorithms on empirical datasets generated from various omics platforms under different experimental designs. We also carried out extensive simulation studies to test each algorithm’s robustness to key variables, including sampling patterns, replicates, waveforms, signal-to-noise ratios, uneven samplings and missing values. Furthermore, we examined the distributions of the nominal equation M1-values under the null and raised issues with multiple testing corrections using traditional approaches. With our assessment, we provide method selection guidelines for circadian rhythm detection, which are applicable to different types of high-throughput omics data.Item Precision and accuracy of hyperglycemic clamps in a multicenter study(American Physiological Society, 2021) Mather, Kieren J.; Tjaden, Ashley H.; Hoehn, Adam; Nadeau, Kristen J.; Buchanan, Thomas A.; Kahn, Steven E.; Arslanian, Silva A.; Caprio, Sonia; Atkinson, Karen M.; Cree-Green, Melanie; Utzschneider, Kristina M.; Edelstein, Sharon L.; RISE Consortium; Medicine, School of MedicineApplication of glucose clamp methodologies in multicenter studies brings challenges for standardization. The Restoring Insulin Secretion (RISE) Consortium implemented a hyperglycemic clamp protocol across seven centers using a combination of technical and management approaches to achieve standardization. Two-stage hyperglycemic clamps with glucose targets of 200 mg/dL and >450 mg/dL were performed utilizing a centralized spreadsheet-based algorithm that guided dextrose infusion rates using bedside plasma glucose measurements. Clamp operators received initial and repeated training with ongoing feedback based on surveillance of clamp performance. The precision and accuracy of the achieved stage-specific glucose targets were evaluated, including differences by study center. We also evaluated robustness of the method to baseline physiologic differences and on-study treatment effects. The RISE approach produced high overall precision (3%–9% variance in achieved plasma glucose from target at various times across the procedure) and accuracy (SD < 10% overall). Statistically significant but numerically small differences in achieved target glucose concentrations were observed across study centers, within the magnitude of the observed technical variability. Variation of the achieved target glucose over time in placebo-treated individuals was low (<3% variation), and the method was robust to differences in baseline physiology (youth vs. adult, IGT vs. diabetes status) and differences in physiology induced by study treatments. The RISE approach to standardization of the hyperglycemic clamp methodology across multiple study centers produced technically excellent standardization of achieved glucose concentrations. This approach provides a reliable method for implementing glucose clamp methodology across multiple study centers. NEW & NOTEWORTHY: The Restoring Insulin Secretion (RISE) study centers undertook hyperglycemic clamps using a simplified methodology and a decision guidance algorithm implemented in an easy-to-use spreadsheet. This approach, combined with active management including ongoing central data surveillance and routine feedback to study centers, produced technically excellent standardization of achieved glucose concentrations on repeat studies within and across study centers.Item Precision of the virtual occlusal record(Allen Press, 2019-09) Botsford, Keyan P.; Frazier, Michael C.; Ghoneima, Ahmed A.M.; Utreja, Achint; Bhamidipalli, Surya S.; Stewart, Kelton T.; Orthodontics and Oral Facial Genetics, School of DentistryObjectives: To evaluate the precision of the virtual occlusal record using the Carestream CS3600 Intraoral Scanner (Carestream Dental, Atlanta, Ga). Materials and methods: A total of 20 participants were recruited for this prospective study using preestablished inclusion/exclusion criteria. A complete intraoral scan and two bite registrations were obtained. The participants were instructed to bite with normal pressure when bite registrations were acquired. Contact locations, size (circumference), and intensity were identified on the maxillary first molars and canines. Agreement between contact size and intensity was assessed with intraclass correlation coefficients. Kappa statistics evaluated agreement in contact locations. Statistical significance was set at P < .05. Results: All participant data were included for statistical analysis. Between the two bite registrations, nonstatistically significant differences were observed in the proportion of locations with contacts (P = .7681). A nonstatistically significant difference (-0.25 mm, P = .8416) in mean contact circumference size was observed. A statistically significant difference in mean contact intensity was observed (P = .0448). When evaluating agreement between the bite registrations, a weak correlation for size (intraclass correlation coefficient = 0.35) and intensity (intraclass correlation coefficient = 0.32) was observed as well as a moderate agreement for contact location (κ coefficient = 0.67). Conclusions: The findings suggest that the Carestream intraoral scanner software possesses adequate precision when acquiring the location and size of the contacts in bite registrations. The scanner failed to demonstrate adequate precision when acquiring contact intensities in bite registrations. Additional research is warranted to further investigate the precision of virtual occlusal records with currently available software systems.