Sensitive aerial hearing within a noisy nesting soundscape in a deep-diving seabird, the common murre Uria aalge

Diving seabirds face a combination of sound exposure in marine and terrestrial environments due to increasing human encroachment on coastal ecosystems. Yet the sound-sensitivity and sensory ecology of this threatened group of animals is largely unknown, complicating effective management and conservation. Here, we characterize aspects of the acoustic ecology of the common murre Uria aalge, one of the deepest diving alcid seabirds. Electrophysiological aerial hearing thresholds were measured for 12 wild, nesting individuals and compared to conspecific vocalizations and short-term aerial soundscape dynamics of their cliff nesting habitat. Auditory responses were measured from 0.5 to 6 kHz, with a lowest mean threshold of 30 dB at 2 kHz and generally sensitive hearing from 1 to 3.5 kHz. The short-term murre nesting soundscape contained biotic sounds from con- and heterospecific avifauna; broadband sounds levels of 56-69 dB re: 20 µPa rms (0.1-10 kHz) were associated with both diel and tidal-cycle factors. Five murre vocalization types showed dominant spectral emphasis at or below the region of best hearing. Common murre hearing appears to be less sensitive than a related alcid, the Atlantic puffin Fratercula arctica, but more sensitive than other non-alcid diving birds described to date, suggesting that adaptations for deep diving have not caused a loss of the species’ hearing ability above water. Overall, frequencies of common murre hearing and vocalization overlap with many anthropogenic noise sources, indicating that the species is susceptible to disturbance from a range of noise types

Living on a flammable planet: interdisciplinary, cross-scalar and varied cultural lessons, prospects and challenges: Table 1.

Living with fire is a challenge for human communities because they are influenced by socio-economic, political, ecological and climatic processes at various spatial and temporal scales. Over the course of 2 days, the authors discussed how communities could live with fire challenges at local, national and transnational scales. Exploiting our diverse, international and interdisciplinary expertise, we outline generalizable properties of fire-adaptive communities in varied settings where cultural knowledge of fire is rich and diverse. At the national scale, we discussed policy and management challenges for countries that have diminishing fire knowledge, but for whom global climate change will bring new fire problems. Finally, we assessed major fire challenges that transcend national political boundaries, including the health burden of smoke plumes and the climate consequences of wildfires. It is clear that to best address the broad range of fire problems, a holistic wildfire scholarship must develop common agreement in working terms and build across disciplines. We must also communicate our understanding of fire and its importance to the media, politicians and the general public. This article is part of the themed issue ‘The interaction of fire and mankind’

Anti-non-Gal-specific combination treatment with an anti-idiotypic Ab and an inhibitory small molecule mitigates the xenoantibody response

BACKGROUND: B cell depletion significantly extends survival of α-1,3-galactosyltranferase knockout (GTKO) porcine organs in pig-to-primate models. Our previous work demonstrated that the anti-nonGal xenoantibody response is structurally restricted. Selective inhibition of xenoantigen-xenoantibody interactions could prolong xenograft survival while preserving B cell-mediated immune surveillance. METHODS: The anti-idiotypic antibody, B4N190, was selected from a synthetic human phage display library after enrichment against a recombinant anti-nonGal xenoantibody followed by functional testing in vitro. The inhibitory small molecule, JMS022, was selected from the NCI diversity set III using virtual screening based on predicted xenoantibody structure. Three rhesus monkeys were pretreated with anti-nonGal specific single chain anti-idiotypic antibody, B4N190. A total of five monkeys, including two untreated controls, were then immunized with GTKO porcine endothelial cells to initiate an anti-non α-1,3-gal (nonGal) xenoantibody response. The efficacy of the inhibitory small molecule specific for anti-nonGal xenoantibody, JMS022, was tested in vitro. RESULTS: After the combination of in vivo anti-id and in vitro small molecule treatments, IgM xenoantibody binding to GTKO cells was reduced to pre-immunization levels in 2/3 animals, however, some xenoantibodies remained in the third animal. Furthermore, when treated with anti-id alone all three experimental animals displayed a lower anti-nonGal IgG xenoantibody response compared to controls. Treatment with anti-idiotypic antibody alone reduced IgM xenoantibody response intensity in only one of three monkeys injected with GTKO pig endothelial cells. In the one experimental animal which displayed reduced IgM and IgG responses select B cell subsets were also reduced by anti-id therapy alone. Furthermore, natural antibody responses, including anti-laminin, anti-ssDNA, and anti-throglobulin antibodies were intact despite targeted depletion of anti-nonGal xenoantibodies in vivo indicating that selective reduction of xenoantibodies can be accomplished without total B cell depletion. CONCLUSIONS: This preliminary study demonstrates the strength of approaches designed to selectively inhibit anti-nonGal xenoantibody. Both anti-nonGal specific xenoantibody and small molecules can be used to selectively limit xenoantibody responses

Long-term (180-Day) outcomes in critically Ill patients with COVID-19 in the REMAP-CAP randomized clinical trial

Importance The longer-term effects of therapies for the treatment of critically ill patients with COVID-19 are unknown. Objective To determine the effect of multiple interventions for critically ill adults with COVID-19 on longer-term outcomes. Design, Setting, and Participants Prespecified secondary analysis of an ongoing adaptive platform trial (REMAP-CAP) testing interventions within multiple therapeutic domains in which 4869 critically ill adult patients with COVID-19 were enrolled between March 9, 2020, and June 22, 2021, from 197 sites in 14 countries. The final 180-day follow-up was completed on March 2, 2022. Interventions Patients were randomized to receive 1 or more interventions within 6 treatment domains: immune modulators (n = 2274), convalescent plasma (n = 2011), antiplatelet therapy (n = 1557), anticoagulation (n = 1033), antivirals (n = 726), and corticosteroids (n = 401). Main Outcomes and Measures The main outcome was survival through day 180, analyzed using a bayesian piecewise exponential model. A hazard ratio (HR) less than 1 represented improved survival (superiority), while an HR greater than 1 represented worsened survival (harm); futility was represented by a relative improvement less than 20% in outcome, shown by an HR greater than 0.83. Results Among 4869 randomized patients (mean age, 59.3 years; 1537 [32.1%] women), 4107 (84.3%) had known vital status and 2590 (63.1%) were alive at day 180. IL-6 receptor antagonists had a greater than 99.9% probability of improving 6-month survival (adjusted HR, 0.74 [95% credible interval {CrI}, 0.61-0.90]) and antiplatelet agents had a 95% probability of improving 6-month survival (adjusted HR, 0.85 [95% CrI, 0.71-1.03]) compared with the control, while the probability of trial-defined statistical futility (HR >0.83) was high for therapeutic anticoagulation (99.9%; HR, 1.13 [95% CrI, 0.93-1.42]), convalescent plasma (99.2%; HR, 0.99 [95% CrI, 0.86-1.14]), and lopinavir-ritonavir (96.6%; HR, 1.06 [95% CrI, 0.82-1.38]) and the probabilities of harm from hydroxychloroquine (96.9%; HR, 1.51 [95% CrI, 0.98-2.29]) and the combination of lopinavir-ritonavir and hydroxychloroquine (96.8%; HR, 1.61 [95% CrI, 0.97-2.67]) were high. The corticosteroid domain was stopped early prior to reaching a predefined statistical trigger; there was a 57.1% to 61.6% probability of improving 6-month survival across varying hydrocortisone dosing strategies. Conclusions and Relevance Among critically ill patients with COVID-19 randomized to receive 1 or more therapeutic interventions, treatment with an IL-6 receptor antagonist had a greater than 99.9% probability of improved 180-day mortality compared with patients randomized to the control, and treatment with an antiplatelet had a 95.0% probability of improved 180-day mortality compared with patients randomized to the control. Overall, when considered with previously reported short-term results, the findings indicate that initial in-hospital treatment effects were consistent for most therapies through 6 months