Prioritizing Stream Barrier Removal to Maximize Connected Aquatic Habitat and Minimize Water Scarcity

Instream barriers, such as dams, culverts, and diversions, alter hydrologic processes and aquatic habitat. Removing uneconomical and aging instream barriers is increasingly used for river restoration. Historically, selection of barrier removal projects used score‐and‐rank techniques, ignoring cumulative change and the spatial structure of stream networks. Likewise, most water supply models prioritize either human water uses or aquatic habitat, failing to incorporate both human and environmental water use benefits. Here, a dual‐objective optimization model identifies barriers to remove that maximize connected aquatic habitat and minimize water scarcity. Aquatic habitat is measured using monthly average streamflow, temperature, channel gradient, and geomorphic condition as indicators of aquatic habitat suitability. Water scarcity costs are minimized using economic penalty functions while a budget constraint specifies the money available to remove barriers. We demonstrate the approach using a case study in Utah\u27s Weber Basin to prioritize removal of instream barriers for Bonneville cutthroat trout, while maintaining human water uses. Removing 54 instream barriers reconnects about 160 km of quality‐weighted habitat and costs approximately US$10 M. After this point, the cost‐effectiveness of removing barriers to connect river habitat decreases. The modeling approach expands barrier removal optimization methods by explicitly including both economic and environmental water uses

Integrative and Comparative Genomic Analysis of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas

PURPOSE: The genetic differences between Human papilloma Virus (HPV)-positive and negative head and neck squamous cell carcinomas (HNSCC) remain largely unknown. In order to identify differential biology and novel therapeutic targets for both entities we determined mutations and copy number aberrations in a large cohort of locoregionally-advanced HNSCC. EXPERIMENTAL DESIGN: We performed massively parallel sequencing of 617 cancer-associated genes in 120 matched tumor/normal samples (42.5% HPV-positive). Mutations and copy number aberrations were determined and results validated with a secondary method. RESULTS: The overall mutational burden in HPV-negative and HPV-positive HNSCC was similar with an average of 15.2 versus 14.4 somatic exonic mutations in the targeted cancer-associated genes. HPV-negative tumors showed a mutational spectrum concordant with published lung squamous cell carcinoma analyses with enrichment for mutations in TP53, CDKN2A, MLL2, CUL3, NSD1, PIK3CA and NOTCH genes. HPV-positive tumors showed unique mutations in DDX3X, FGFR2/3 and aberrations in PIK3CA, KRAS, MLL2/3 and NOTCH1 were enriched in HPV-positive tumors. Currently targetable genomic alterations were identified in FGFR1, DDR2, EGFR, FGFR2/3, EPHA2 and PIK3CA. EGFR, CCND1, and FGFR1 amplifications occurred in HPV-negative tumors, while 17.6% of HPV-positive tumors harbored mutations in Fibroblast Growth Factor Receptor genes (FGFR2/3) including six recurrent FGFR3 S249C mutations. HPV-positive tumors showed a 5.8% incidence of KRAS mutations, and DNA repair gene aberrations including 7.8% BRCA1/2 mutations were identified. CONCLUSIONS: The mutational makeup of HPV-positive and HPV-negative HNSCC differs significantly, including targetable genes. HNSCC harbors multiple therapeutically important genetic aberrations, including frequent aberrations in the FGFR and PI3K pathway genes