This study reports a new and significantly enhanced analysis of US flood hazard at 30 m spatial resolution. Specific improvements include updated hydrography data, new methods to determine channel ...depth, more rigorous flood frequency analysis, output downscaling to property tract level, and inclusion of the impact of local interventions in the flooding system. For the first time, we consider pluvial, fluvial, and coastal flood hazards within the same framework and provide projections for both current (rather than historic average) conditions and for future time periods centered on 2035 and 2050 under the RCP4.5 emissions pathway. Validation against high‐quality local models and the entire catalog of FEMA 1% annual probability flood maps yielded Critical Success Index values in the range 0.69–0.82. Significant improvements over a previous pluvial/fluvial model version are shown for high‐frequency events and coastal zones, along with minor improvements in areas where model performance was already good. The result is the first comprehensive and consistent national‐scale analysis of flood hazard for the conterminous US for both current and future conditions. Even though we consider a stabilization emissions scenario and a near‐future time horizon, we project clear patterns of changing flood hazard (3σ changes in 100 years inundated area of −3.8 to +16% at 1° scale), that are significant when considered as a proportion of the land area where human use is possible or in terms of the currently protected land area where the standard of flood defense protection may become compromised by this time.
Plain Language Summary
We develop a method to estimate past, present, and future flood risk for all properties in the conterminous United States whether affected by river, coastal or rainfall flooding. The analysis accounts for variability within environmental factors including changes in sea level rise, hurricane intensity and landfall locations, precipitation patterns, and river discharge. We show that even for a conservative climate change trajectory we can expect locally significant changes in the land area at risk from floods by 2050, and by this time defenses protecting 2,200 km2 of land may be compromised. The complete dataset has been made available via a website (https://floodfactor.com/) created by the First Street Foundation in order to increase public awareness of the threat posed by flooding to safety and livelihoods.
Key Points
First complete high‐resolution flood hazard analysis of conterminous US flood risk from all major sources (fluvial, pluvial, and coastal)
In validation tests the model achieved Critical Success Index scores of 0.69–0.82, similar to many local custom‐built 2D models
By 2050, flood hazard increases for the Eastern seaboard and Western states, but decreases or changes little for the center and South‐West
The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between EGF receptor ...(EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs and increased markers of T-cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape and mechanistically link treatment response to PD-1 inhibition.
We show that autochthonous EGFR-driven lung tumors inhibit antitumor immunity by activating the PD-1/PD-L1 pathway to suppress T-cell function and increase levels of proinflammatory cytokines. These findings indicate that EGFR functions as an oncogene through non-cell-autonomous mechanisms and raise the possibility that other oncogenes may drive immune escape.
The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a population known as mucosal-associated invariant T (MAIT) cells. To understand whether ...different T cell subsets expressing CD161 have similar properties, we examined these populations in parallel using mass cytometry and mRNA microarray approaches. The analysis identified a conserved CD161++/MAIT cell transcriptional signature enriched in CD161+CD8+ T cells, which can be extended to CD161+ CD4+ and CD161+TCRγδ+ T cells. Furthermore, this led to the identification of a shared innate-like, TCR-independent response to interleukin (IL)-12 plus IL-18 by different CD161-expressing T cell populations. This response was independent of regulation by CD161, which acted as a costimulatory molecule in the context of T cell receptor stimulation. Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes and independent of both T cell receptor (TCR) expression and cell lineage.
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•CD161 expression defines specific T cell subsets, including CD8+, CD4+, and TCRγδ+•CD161-expressing lymphocytes possess a conserved transcriptional signature•CD161-expressing lymphocytes display a shared innate response to IL-12+18•CD161 can act as a costimulatory receptor
T lymphocytes are conventionally divided into subsets based on expression of coreceptors, cytokines, and surface molecules. Using CyTOF and mRNA microarray analysis, Fergusson et al. identify T lymphocytes that express the C-type lectin CD161 to share a transcriptional profile and innate function across these previously defined subsets.
Robust assessments of ecosystem stability are critical for informing conservation and management decisions. Tidal marsh ecosystems provide vital services, yet are globally threatened by anthropogenic ...alterations to physical and biological processes. A variety of monitoring and modeling approaches have been undertaken to determine which tidal marshes are likely to persist into the future. Here, we conduct the most robust comparison of marsh metrics to date, building on two foundational studies that had previously and independently developed metrics for marsh condition. We characterized pairs of marshes with contrasting trajectories of marsh cover across six regions of the United States, using a combination of remote-sensing and field-based metrics. We also quantified decadal trends in marsh conversion to mudflat/open water at these twelve marshes. Our results suggest that metrics quantifying the distribution of vegetation across an elevational gradient represent the best indicators of marsh trajectories. The unvegetated to vegetated ratio and flood-ebb sediment differential also served as valuable indicators. No single metric universally predicted marsh trajectories, and therefore a more robust approach includes a suite of spatially-integrated, landscape-scale metrics that are mostly obtainable from remote sensing. Data from surface elevation tables and marker horizons revealed that degrading marshes can have higher rates of vertical accretion and elevation gain than more intact counterparts, likely due to longer inundation times potentially combined with internal recycling of material. A high rate of elevation gain relative to local sea-level rise has been considered critical to marsh persistence, but our results suggest that it also may serve as a signature of degradation in marshes that have already begun to deteriorate. This investigation, with rigorous comparison and integration of metrics initially developed independently, tested at a broad geographic scale, provides a model for collaborative science to develop management tools for improving conservation outcomes.
Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die ...may permit more appropriate treatments to be deployed. We examined the clinical features and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would ultimately die differed markedly from those of patients who would survive. The different profiles of proteins and metabolites clustered into the following groups: fatty acid transport and β-oxidation, gluconeogenesis, and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of five metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis.
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