Next Generation Traffic Signal Performance Measures: Leveraging Connected Vehicle Data

High-resolution connected vehicle (CV) trajectory and event data has recently become commercially available. With over 500 billion vehicle position records generated each month in the United States, these data sets provide unique opportunities to build on and expand previous advances on traffic signal performance measures and safety evaluation. This report is a synthesis of research focused on the development of CV-based performance measures. A discussion is provided on data requirements, such as acquisition, storage, and access. Subsequently, techniques to reference vehicle trajectories to relevant roadways and movements are presented. This allows for performance analyses that can range from the movement- to the system-level. A comprehensive suite of methodologies to evaluate signal performance using vehicle trajectories is then provided. Finally, uses of CV hard-braking and hard-acceleration event data to assess safety and driver behavior are discussed. To evaluate scalability and test the proposed techniques, performance measures for over 4,700 traffic signals were estimated using more than 910 million vehicle trajectories and 14 billion GPS points in all 50 states and Washington, D.C. The contents of this report will help the industry transition towards a hybrid blend of detector- and CV-based signal performance measures with rigorously defined performance measures that have been peer-reviewed by both academics and industry leaders

Metabolism and hepatotoxicity of morphine, codeine and pholcodeine

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Development and application of an enantioselective liquid chromatography – tandem mass spectrometry method for the quantification of enantiomers to evaluate in vivo chiral inversion in beagle dog

To assess whether a suspected metabolic chiral inversion of a new chemical entity (NCE) with a single chiral centre occurred in an in vivo pharmacokinetic (PK) study of UCB-1, a quantitative enantioselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated. Chromatographic screening of authentic standards of the two enantiomers was carried out using a range of Phenomenex Lux chiral columns under various isocratic conditions to achieve optimum chromatographic resolution. Protein precipitation was used for analyte extraction from 40 µL of dog plasma. The subjects were given a po dose of either 1, 3 or 10 mg/kg followed by blood sample collection at timepoints over a 72-hour period. For the analysis, a Shimadzu liquid chromatography system was coupled to a Sciex QTRAP 5500 mass spectrometer operated using multiple reaction monitoring (MRM) in positive ion mode. The regression for the two enantiomers was (R2 ≥ 0.999) over the range of 10 – 20,000 ng/mL while employing a quadratic fit, with a lower limit of quantification (LLOQ) of 10 ng/ml. The method was validated for intra- and inter-day precision and accuracy, which were within +/- 20%. The enantiomers were stable in dog plasma at room temperature for 4 h and after three freeze-thaw cycles. The method was successfully applied to a pharmacokinetic study in dog, after po administration of UCB-1 where a significant level of chiral inversion was observed in plasma

Industry Perspective of International Consortium for Innovation through Quality in Pharmaceutical Development: Complementary LBA and LC-MS Strategies for Large Molecule Protein Bioanalysis and Biotransformation

Increasingly diverse large molecule modalities have driven the need for complex bioanalysis involving both traditional ligand binding assays (LBA) and more recent hybrid immunoaffinity liquid chromatography-mass spectrometry (LC-MS) platforms. Given the scientific expertise in LBA and LCMS typically resides in different functions within the industry, this has presented operational challenges for an integrated approach for bioanalysis. Encouragingly, over time, the industry has recognized the complementary value. This has not been an easy transition as organizational structures vary widely within the industry. However, there are tremendous benefits in adopting fully integrated strategies for biopharma. This paper highlights the technical and operational challenges in current large molecule bioanalysis, value of collaborations across LBA and LC-MS platforms, and scientific expertise for fully integrated strategies