3 research outputs found
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The establishment of Central American migratory corridors and the biogeographic origins of seasonally dry tropical forests in Mexico
Biogeography and community ecology can mutually illuminate the formation of a regional species pool or biome. Here, we apply phylogenetic methods to a large and diverse plant clade, Malpighiaceae, to characterize the formation of its species pool in Mexico, and its occupancy of the seasonally dry tropical forest (SDTF) biome that occurs there. We find that the ~162 species of Mexican Malpighiaceae represent ~33 dispersals from South America beginning in the Eocene and continuing until the Pliocene (~46.4–3.8 Myr). Furthermore, dispersal rates between South America and Mexico show a significant six-fold increase during the mid-Miocene (~23.9 Myr). We hypothesize that this increase marked the availability of Central America as an important corridor for Neotropical plant migration. We additionally demonstrate that this high rate of dispersal contributed substantially more to the phylogenetic diversity of Malpighiaceae in Mexico than in situ diversification. Finally, we show that most lineages arrived in Mexico pre-adapted with regard to one key SDTF trait, total annual precipitation. In contrast, these lineages adapted to a second key trait, precipitation seasonality, in situ as mountain building in the region gave rise to the abiotic parameters of extant SDTF. The timing of this in situ adaptation to seasonal precipitation suggests that SDTF likely originated its modern characteristics by the late Oligocene, but was geographically more restricted until its expansion in the mid-Miocene. These results highlight the complex interplay of dispersal, adaptation, and in situ diversification in the formation of tropical biomes. Our results additionally demonstrate that these processes are not static, and their relevance can change markedly over evolutionary time. This has important implications for understanding the origin of SDTF in Mexico, but also for understanding the temporal and spatial origin of biomes and regional species pools more broadly
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Corrigendum to: The establishment of Central American migratory corridors and the biogeographic origins of seasonally dry tropical forests in Mexico
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Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial
We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.
In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.
Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50–72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74–1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67–1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74–1·58]; BRII-196 plus BRII-198 1·00 [0·68–1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91–1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88–1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.
Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.
US National Institutes of Health and Operation Warp Spee