34 research outputs found

    Numerical simulation and first-order hazard analysis of large co-seismic tsunamis generated in the Puerto Rico trench: near-field impact on the North shore of Puerto Rico and far-field impact on the US East Coast

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    We perform numerical simulations of the coastal impact of large co-seismic tsunamis, initiated in the Puerto Rican trench, both in far-field areas along the upper US East coast (and other Caribbean islands), and in more detail in the near-field, along the Puerto Rico North Shore (PRNS). We first model a magnitude 9.1 extreme co-seismic source and then a smaller 8.7 magnitude source, which approximately correspond to 600 and 200 year return periods, respectively. In both cases, tsunami generation and propagation (both near- and far-field) are first performed in a coarse 2′ basin scale grid, with ETOPO2 bathymetry, using a fully nonlinear and dispersive long wave tsunami model (FUNWAVE). Coastal runup and inundation are then simulated for two selected areas, using finer coastal nested grids. Thus, a 15″ (450 m) grid is used to calculate detailed far-field impact along the US East Coast, from New Jersey to Maine, and a 3″ (90 m) grid (for the finest resolution), encompassing the entire PRNS, is used to compute detailed near-field impact along the PRNS (runup and inundation). To perform coastal simulations in nested grids, accurate bathymetry/topography databases are constructed by combining ETOPO2 2′ data (in deep water) and USGS\u27 or NOAA\u27s 15″ or 3″ (in shallow water) data. In the far-field, runup caused by the extreme 9.1 source would be severe (over 10 m) for some nearby Caribbean islands, but would only reach up to 3 m along the selected section of the East coast. A sensitivity analysis to the bathymetric resolution (for a constant 3″ model grid) of runup along the PRNS, confirms the convergence of runup results for a topographic resolution 24″ or better, and thus stresses the importance of using sufficiently resolved bathymetric data, in order to accurately predict extreme runup values, particularly when bathymetric focusing is significant. Runup (10–22 m) and inundation are found to be very large at most locations for the extreme 9.1 source. Both simulated spatial inundation snapshots and time series indicate, the inundation would be particularly severe near and around the low-lying city of San Juan. For the 8.7 source, runup along the PRNS would be much less severe (3–6 m), but still significant, while inundation would only be significant near and around San Juan. This first-order tsunami hazard analysis stresses the importance of conducting more detailed and comprehensive studies, particularly of tsunami hazard along the PRNS, for a more complete and realistic selection of sources; such work is ongoing as part of a US funded (NTHMP) tsunami inundation mapping effort in Puerto Rico

    Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

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    Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

    Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

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    Zur Systematik der Trichomyceten

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