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 km 2 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. BATES ET AL.

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Background There is an urgent need for an effective tuberculosis (TB) vaccine. Heterologous prime–boost regimens induce potent cellular immunity. MVA85A is a candidate TB vaccine. This phase I clinical trial was designed to evaluate whether alternating aerosol and intradermal vaccination routes would boost cellular immunity to the Mycobacterium tuberculosis antigen 85A (Ag85A). Methods and findings Between December 2013 and January 2016, 36 bacille Calmette-Guérin–vaccinated, healthy UK adults were randomised equally between 3 groups to receive 2 MVA85A vaccinations 1 month apart using either heterologous (Group 1, aerosol–intradermal; Group 2, intradermal–aerosol) or homologous (Group 3, intradermal–intradermal) immunisation. Bronchoscopy and bronchoalveolar lavage (BAL) were performed 7 days post-vaccination. Adverse events (AEs) and peripheral blood were collected for 6 months post-vaccination. The laboratory and bronchoscopy teams were blinded to treatment allocation. One participant was withdrawn and was replaced. Participants were aged 21–42 years, and 28/37 were female. In a per protocol analysis, aerosol delivery of MVA85A as a priming immunisation was well tolerated and highly immunogenic. Most AEs were mild local injection site reactions following intradermal vaccination. Transient systemic AEs occurred following vaccination by both routes and were most frequently mild. All respiratory AEs following primary aerosol MVA85A (Group 1) were mild. Boosting an intradermal MVA85A prime with an aerosolised MVA85A boost 1 month later (Group 2) resulted in transient moderate/severe respiratory and systemic AEs. There were no serious adverse events and no bronchoscopy-related complications. Only the intradermal–aerosol vaccination regimen (Group 2) resulted in modest, significant boosting of the cell-mediated immune response to Ag85A ( p = 0.027; 95% CI: 28 to 630 spot forming cells per 1 × 10 6 peripheral blood mononuclear cells). All 3 regimens induced systemic cellular immune responses to the modified vaccinia virus Ankara (MVA) vector. Serum antibodies to Ag85A and MVA were only induced after intradermal vaccination. Aerosolised MVA85A induced significantly higher levels of Ag85A lung mucosal CD4+ and CD8+ T cell cytokines compared to intradermal vaccination. Boosting with aerosol-inhaled MVA85A enhanced the intradermal primed responses in Group 2. The magnitude of BAL MVA-specific CD4+ T cell responses was lower than the Ag85A-specific responses. A limitation of the study is that while the intradermal–aerosol regimen induced the most potent cellular Ag85A immune responses, we did not boost the last 3 participants in this group because of the AE profile. Timing of bronchoscopies aimed to capture peak mucosal response; however, peak responses may have occurred outside of this time frame. Conclusions To our knowledge, this is the first human randomised clin...