Application of unmanned aircraft system (UAS) for monitoring bank erosion along river corridors

Excessive streambank erosion is a significant source of fine sediments and associated nutrients in many river systems as well as poses risk to infrastructure. Geomorphic change detection using high-resolution topographic data is a useful method for monitoring the extent of bank erosion along river corridors. Recent advances in an unmanned aircraft system (UAS) and structure from motion (SfM) photogrammetry techniques allow acquisition of high-resolution topographic data, which are the methods used in this study. To evaluate the effectiveness of UAS-based photogrammetry for monitoring bank erosion, a fixed-wing UAS was deployed to survey 20 km of river corridors in central Vermont, in the northeastern United States multiple times over a two-year period. Digital elevation models (DEMs) and DEMs of difference allowed quantification of volumetric changes along selected portions of the survey area where notable erosion occurred. Results showed that UAS was capable of collecting high-quality topographic data at fine resolutions even along vegetated river corridors provided that the surveys were conducted in early spring, after snowmelt but prior to summer vegetation growth. Longer term estimates of streambank movements using the UAS showed good comparison to previously collected airborne lidar surveys and allowed reliable quantification of significant geomorphic changes along rivers

Intermittent Surface Oxygenation Results in Similar Mitochondrial Protection and Maintenance of Aerobic Metabolism as Compared to Continuous Oxygenation during Hypothermic Machine Kidney Machine Perfusion

Short bubble and subsequent surface oxygenation is an innovative oxygenation technique and alternative for membrane oxygenation during hypothermic machine perfusion (HMP). The metabolic effect of the interruption of surface oxygenation for 4 h (mimicking organ transport) during HMP was compared to continuous surface and membrane oxygenation in a pig kidney ex situ preservation model. After 30 min of warm ischemia by vascular clamping, a kidney of a ±40 kg pig was procured and subsequently preserved according to one of the following groups: (1) 22-h HMP + intermittent surface oxygenation ( = 12); (2) 22-h HMP + continuous membrane oxygenation ( = 6); and (3) 22-h HMP + continuous surface oxygenation ( = 7). Brief perfusate O uploading before kidney perfusion was either obtained by direct bubble (groups 1, 3) or by membrane (group 2) oxygenation. Bubble oxygenation during minimum 15 min was as efficient as membrane oxygenation in achieving supraphysiological perfusate pO levels before kidney perfusion. Metabolic tissue analysis (i.e., lactate, succinate, ATP, NADH, and FMN) during and at the end of the preservation period demonstrated similar mitochondrial protection between all study groups. Short bubble and subsequent intermittent surface oxygenation of the perfusate of an HMP-kidney might be an effective and cheap preservation strategy to protect mitochondria, eliminating the need/costs of a membrane oxygenator and oxygen source during transport

Diabetes and Clinical Outcome in Patients With Metastatic Colorectal Cancer: CALGB 80405 (Alliance)

Background Diabetes is a prognostic factor for some malignancies, but its association with outcome in patients with advanced or metastatic colorectal cancer (CRC) is less clear. Methods This cohort study was nested within a randomized trial of first-line chemotherapy and bevacizumab and/or cetuximab for advanced or metastatic CRC. Patients were enrolled at 508 community and academic centers throughout the National Clinical Trials Network. The primary exposure was physician-documented diabetes at the time of enrollment. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS) and adverse events. Tests of statistical significance were two-sided. Results Among 2326 patients, 378 (16.3%) had diabetes. The median follow-up time was 6.0 years. We observed 1973 OS events and 2173 PFS events. The median time to an OS event was 22.7 months among those with diabetes and 27.1 months among those without diabetes (HR = 1.27, 95% CI = 1.13 to 1.44; P < .001). The median time to a PFS event was 9.7 months among those with diabetes and 10.8 months among those without diabetes (HR = 1.16, 95% CI = 1.03 to 1.30; P = .02). Patients with diabetes were more likely to experience no less than grade 3 hypertension (8.1% vs 4.4%; P = .054) but were not more likely to experience other adverse events, including neuropathy. Conclusions Diabetes is associated with an increased risk of mortality and tumor progression in patients with advanced or metastatic CRC. Patients with diabetes tolerate first-line treatment with chemotherapy and monoclonal antibodies similarly to patients without diabetes

Identification of a Genomic Region Between SLC29A1 and HSP90AB1 Associated With Risk of Bevacizumab-Induced Hypertension: CALGB 80405 (Alliance)

Purpose: Bevacizumab is a VEGF-specific angiogenesis inhibitor indicated as an adjunct to chemotherapy for the treatment of multiple cancers. Hypertension is commonly observed during bevacizumab treatment, and high-grade toxicity can limit therapy or lead to cardiovascular complications. The factors that contribute to interindividual variability in blood pressure rise during bevacizumab treatment are not well understood.Experimental Design: To identify genomic regions associated with bevacizumab-induced hypertension risk, sequencing of candidate genes and flanking regulatory regions was performed on 61 patients treated with bevacizumab (19 cases developed early-onset grade 3 hypertension and 42 controls had no reported hypertension in the first six cycles of treatment). SNP-based tests for common variant associations and gene-based tests for rare variant associations were performed in 174 candidate genes.Results: Four common variants in independent linkage disequilibrium blocks between SLC29A1 and HSP90AB1 were among the top associations. Validation in larger bevacizumab-treated cohorts supported association between rs9381299 with early grade 3+ hypertension (P = 0.01; OR, 2.4) and systolic blood pressure >180 mm Hg (P = 0.02; OR, 2.1). rs834576 was associated with early grade 3+ hypertension in CALGB 40502 (P = 0.03; OR, 2.9). These SNP regions are enriched for regulatory elements that may potentially increase gene expression. In vitro overexpression of SLC29A1 in human endothelial cells disrupted adenosine signaling and reduced nitric oxide levels that were further lowered upon bevacizumab exposure.Conclusions: The genomic region between SLC29A1 and HSP90AB1 and its role in regulating adenosine signaling are key targets for further investigation into the pathogenesis of bevacizumab-induced hypertension

Use of Bevacizumab for Elderly Patients With Stage IV Colon Cancer: Analysis of SEER-Medicare Data

Bevacizumab is used for the treatment of metastatic colon cancer in conjunction with first-line chemotherapy. In this study, we examined receipt of first-line bevacizumab and predictors of its use among older patients with stage IV colon cancer. We used data from the Surveillance, Epidemiology, and End Results-Medicare dataset to identify patients with stage IV colon cancer diagnosed from 2005 to 2013 who received FOLFOX (5-fluorouracil/leucovorin/oxaliplatin) or FOLFIRI (5-fluorouracil/leucovorin/irinotecan) as first-line therapy. We used multivariable regression analysis to determine demographic and clinical factors associated with use of concomitant bevacizumab. We identified 3785 patients with stage IV colon cancer who met our eligibility criteria. Of these, 2352 (62.1%) received bevacizumab. Bevacizumab use has decreased over time from 68.2% in 2005 to 57.6% in 2013 (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.91-0.97). Patients were less likely to receive bevacizumab if they were older (compared with 65-69 years, ≥ 80 years: OR, 0.64; 95% CI, 0.52-0.80), or had multiple comorbidities (compared with comorbidity score of 0, score of 1: OR, 0.73; 95% CI, 0.60-0.89). Over one-half of elderly patients received bevacizumab as part of their first-line therapy for stage IV colon cancer. Bevacizumab use has been slowly decreasing since 2005. Newer anti-epidermal growth factor receptor treatments have not been supplanting bevacizumab, as first-line biologic use in general has also decreased during this time period. In this study, we used the Surveillance, Epidemiology, and End Results-Medicare dataset to analyze the trends in prescription as well as characteristics associated with the use of first-line bevacizumab in patients with metastatic colon cancer. We found that bevacizumab is used 62% of the time as part of first-line therapy for stage IV colon cancer. However, since 2005, bevacizumab and first-line biologics use in general has been slowly decreasing. This study illustrates new practice patterns associated with first-line biologics receipt for treatment of metastatic colon cancer

Common variation in a long non-coding RNA gene modulates variation of circulating TGF-β2 levels in metastatic colorectal cancer patients (Alliance)

Background: Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous blood collected at baseline. A robust rank-based method was used to assess the statistical significance of each variant and protein pair against a strict genome-wide level. A given pQTL was tested for validation in two external datasets of prostate (CALGB 90401) and pancreatic cancer (CALGB 80303) patients. Bioinformatics analyses were conducted to further establish biological bases for these findings. Results: The final analysis was carried out based on data from 540,021 common typed genetic variants and 23 protein markers from 869 genetically estimated European patients with mCRC. Correcting for multiple testing, the analysis discovered a novel cis-pQTL in LINC02869, a long non-coding RNA gene, for circulating TGF-β2 levels (rs11118119; AAF = 0.11; P-value Conclusions: This study has provided evidence of a novel cis germline genetic variant that regulates circulating TGF-β2 levels in plasma of patients with advanced mCRC and prostate cancer. Moreover, the validation of previously identified pQTLs for VEGF-A, CD73, and VEGF-R3, potentiates the validity of these associations.</p

Response to Letter to the Editor: “Prevention of Adrenal Crisis: Cortisol Response to Major Stress Compared to Stress Dose Hydrocortisone Delivery”

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Association of Coffee Intake With Survival in Patients With Advanced or Metastatic Colorectal Cancer

Importance: Several compounds found in coffee possess antioxidant, anti-inflammatory, and insulin-sensitizing effects, which may contribute to anticancer activity. Epidemiological studies have identified associations between increased coffee consumption and decreased recurrence and mortality of colorectal cancer. The association between coffee consumption and survival in patients with advanced or metastatic colorectal cancer is unknown. Objective: To evaluate the association of coffee consumption with disease progression and death in patients with advanced or metastatic colorectal cancer. Design, setting, and participants: This prospective observational cohort study included 1171 patients with previously untreated locally advanced or metastatic colorectal cancer who were enrolled in Cancer and Leukemia Group B (Alliance)/SWOG 80405, a completed phase 3 clinical trial comparing the addition of cetuximab and/or bevacizumab to standard chemotherapy. Patients reported dietary intake using a semiquantitative food frequency questionnaire at the time of enrollment. Data were collected from October 27, 2005, to January 18, 2018, and analyzed from May 1 to August 31, 2018. Exposures: Consumption of total, decaffeinated, and caffeinated coffee measured in cups per day. Main outcomes and measures: Overall survival (OS) and progression-free survival (PFS). Results: Among the 1171 patients included in the analysis (694 men [59%]; median age, 59 [interquartile range, 51-67] years). The median follow-up time among living patients was 5.4 years (10th percentile, 1.3 years; IQR, 3.2-6.3 years). A total of 1092 patients (93%) had died or had disease progression. Increased consumption of coffee was associated with decreased risk of cancer progression (hazard ratio [HR] for 1-cup/d increment, 0.95; 95% CI, 0.91-1.00; P = .04 for trend) and death (HR for 1-cup/d increment, 0.93; 95% CI, 0.89-0.98; P = .004 for trend). Participants who consumed 2 to 3 cups of coffee per day had a multivariable HR for OS of 0.82 (95% CI, 0.67-1.00) and for PFS of 0.82 (95% CI, 0.68-0.99), compared with those who did not drink coffee. Participants who consumed at least 4 cups of coffee per day had a multivariable HR for OS of 0.64 (95% CI, 0.46-0.87) and for PFS of 0.78 (95% CI, 0.59-1.05). Significant associations were noted for both caffeinated and decaffeinated coffee. Conclusions and relevance: Coffee consumption may be associated with reduced risk of disease progression and death in patients with advanced or metastatic colorectal cancer. Further research is warranted to elucidate underlying biological mechanisms