Object-based tracking of precipitation systems in western Canada: the importance of temporal resolution of source data
Authors: Li, Lintao; Li, Yanping; Li, Zhenhua
Object-based algorithm provides additional spatiotemporal information of precipitation, besides traditional aspects such as amount and intensity. Using the Method for Object-based Diagnostic Evaluation with Time Dimension (MODE-TD, or MTD), precipitation features in western Canada have been analyzed comprehensively based on the Canadian Precipitation Analysis, North American Regional Reanalysis, Multi-Source Weighted-Ensemble Precipitation, and a convection-permitting climate model. We found light precipitation occurs frequently in the interior valleys of western Canada while moderate to heavy precipitation is rare there. The size of maritime precipitation system near the coast is similar to the continental precipitation system on the Prairies for moderate to heavy precipitation while light precipitation on the Prairies is larger in size than that occurs near the coast. For temporal features, moderate to heavy precipitation lasts longer than light precipitation over the Pacific coast, and precipitation systems on the Prairies generally move faster than the coastal precipitation. For annual cycle, the west coast has more precipitation events in cold seasons while more precipitation events are identified in warm seasons on the Prairies due to vigorous convection activities. Using two control experiments, the way how the spatiotemporal resolution of source data influences the MTD results has been examined. Overall, the spatial resolution of source data has little influence on MTD results. However, MTD driven by dataset with coarse temporal resolution tend to identify precipitation systems with relatively large size and slow propagation speed. This kind of precipitation systems normally have short track length and relatively long lifetime. For a typical precipitation system (0.7 similar to 2 x 10(4) km(2)in size) in western Canada, the maximum propagation speed that can be identified by 6-h data is approximately 25 km h(-1), 33 km h(-1) for 3-h, and 100 km h(-1) for hourly dataset. Since the propagation speed of precipitation systems in North America is basically between 0 and 80 km h(-1), we argue that precipitation features can be identified properly by MTD only when dataset with hourly or higher temporal resolution is used.
Safety and Pharmacokinetics of CXCR4 Peptide Antagonist, LY2510924, in Combination with Durvalumab in Advanced Refractory Solid Tumors
JOURNAL OF PANCREATIC CANCER
Authors: O'Hara, Mark H.; Messersmith, Wells; Kindler, Hedy; Zhang, Wei; Pitou, Celine; Szpurka, Anna M.; Wang, Dan; Peng, Sheng-Bin; Vangerow, Burkhard; Khan, Anis A.; Koneru, Mythili; Wang-Gillam, Andrea
Purpose: This was an open-label phase 1a study assessing the maximum tolerated dose (MTD), safety, and tolerability of CXCR4 peptide antagonist, LY2510924, administered in combination with durvalumab in patients with advanced refractory solid tumors. Methods: Patients received LY2510924 at 20, 30, or 40 mg subcutaneous (SC) once daily in combination with durvalumab at 1500 mg intravenously (IV) on day 1 of each 28-day cycle. The primary objective was to assess the MTD and safety of LY2510924 SC daily in combination with durvalumab in patients with advanced (metastatic and/or unresectable) solid tumors. Secondary objectives included pharmacokinetics (PK) and the antitumor activity of LY2510924 in combination with durvalumab. Exploratory objectives were biomarker analysis, including pharmacodynamic markers, relevant to LY2510924 and durvalumab, including immune functioning, drug targets, cancer-related pathways, and the disease state. Results: Nine patients (three each at 20, 30, and 40 mg) were enrolled in the study (eight patients with pancreatic cancer and one patient with rectal cancer). The majority of patients completed one or two cycles (100.0% >= 1 cycle; 88.9% >= 2 cycles) of LY2510924 and durvalumab. No dose limiting toxicities were reported. Most common (>10%) treatment-emergent adverse events were injection-site reaction (44.4%), fatigue (33.3%), and increased white blood cell count (33.3%). PK parameters for combination were similar to those reported in previous studies when given as monotherapy. Best overall response of stable disease was observed in four (44.4%) patients and one patient had unconfirmed partial response. Conclusion: The recommended phase 2 dose is 40 mg SC once-daily LY2510924 in combination with durvalumab 1500 mg IV and showed acceptable safety and tolerability in patients with advanced refractory tumors.