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Longitudinal monitoring for the emergence of epidermal growth factor C797S resistance mutations in non-small cell lung cancer using blood-based droplet digital PCR

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Cancer Drug Resistance 2019年第3期2卷 912-916页

作者： mark bowling Hyder Arastu Victoria Edwards Leisa Jackson Scott Thurston Jordan Reese Hestia Mellert Gary Pestano Paul Walker East Carolina University Mail Stop 628Internal Medicine-Hematology/OncologyGreenvilleNC 27834USA Biodesix Inc.2970 Wilderness PlaceBoulderCO 80301USA.

Validation of assays for the C797S mutation as a biomarker for osimertinib resistance is promising in guiding treatment decision-making for multidrug resistant non-small cell lung cancer. A newly developed droplet digital PCR (ddPCR) assay was used to retrospectively evaluate the emergence of the C797S mutation in six remnant plasma samples in this case report. It was found that the detected emergence of C797S clearly correlated with clinical signs of treatment resistance. Had these data been available to aid treatment selection in real time, there would have been hope for recaptured disease response and control instead of treatment cessation. The results of this study show that highly sensitive ddPCR methods can be used for the monitoring of emergent epidermal growth factor somatic variant mutations in circulation.

关键词： Epidermal growth factor non-small cell lung cancer C797S drug resistance

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Avulsion Dynamics in a River with Alternating Bedrock and Alluvial Reaches, Huron River, Northern Ohio (USA)

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Open Journal of Modern Hydrology 2019年第1期9卷 20-39页

作者： mark J. Potucek James E. Evans Arizona Department of Water Resources Phoenix AZ USA Department of Geology Bowling Green State University Bowling Green OH USA

The Huron River consists of alternating bedrock reaches and alluvial reaches. Analysis of historical aerial photography from 1950-2015 reveals six major channel avulsion events in the 8-km study area. These avulsions occurred in the alluvial reaches but were strongly influenced by the properties of the upstream bedrock reach (“inherited characteristics”). The bedrock reaches aligned with the azimuth of joint sets in the underlying bedrock. One inherited characteristic in the alluvial reach downstream is that the avulsion channels diverged only slightly from the orientation of the upstream bedrock channel (range 2 °- 38 °, mean and standard deviation 12.1 °± 13.7 °). A second inherited characteristic is that avulsion channels were initiated from short distances downstream after exiting the upstream bedrock channel reach (range 62 - 266 m, mean and standard deviation 143.7 ± 71.0 m), which is a fraction of the meander wavelength (1.2 km). Field evidence shows that some avulsion channel sites were re-occupied episodically. In addition, two properties were necessary for channel avulsions: 1) avulsion events were triggered by channel-forming hydrologic events (5-year recurrence interval flows), but not every channel-forming hydrologic event resulted in an avulsion, and 2) channel sinuosity (P) increased to 1.72 - 1.77 prior to an avulsion then decreased to 1.65 - 1.70 following an avulsion, suggesting that P ≥ 1.72 is the “critical sinuosity” or triggering value for avulsions on the Huron River. In summary, for this river consisting of alternating bedrock and alluvial reaches, the bedrock reaches impose certain parameters on downstream alluvial reaches (including sediment supply, channel direction and avulsion channel position downstream after exiting a bedrock reach) while adjustments in sinuosity and sediment storage occur in the alluvial reaches.

关键词： Avulsion Bedrock Channels Alluvial Channels Cut-Offs Historical Changes Fluvial Sediment Budgets

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