Writing Committee for the REMAP-CAP Investigators IMPORTANCE The evidence for benefit of convalescent plasma for critically ill patients with COVID-19 is inconclusive.OBJECTIVE To determine whether convalescent plasma would improve outcomes for critically ill adults with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThe ongoing Randomized, Embedded, Multifactorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) enrolled and randomized 4763 adults with suspected or confirmed COVID-19 between March 9, 2020, and January 18, 2021, within at least 1 domain; 2011 critically ill adults were randomized to open-label interventions in the immunoglobulin domain at 129 sites in 4 countries. Follow-up ended on April 19, 2021. INTERVENTIONSThe immunoglobulin domain randomized participants to receive 2 units of high-titer, ABO-compatible convalescent plasma (total volume of 550 mL ± 150 mL) within 48 hours of randomization (n = 1084) or no convalescent plasma (n = 916). MAIN OUTCOMES AND MEASURESThe primary ordinal end point was organ support-free days (days alive and free of intensive care unit-based organ support) up to day 21 (range, −1 to 21 days; patients who died were assigned -1 day). The primary analysis was an adjusted bayesian cumulative logistic model. Superiority was defined as the posterior probability of an odds ratio (OR) greater than 1 (threshold for trial conclusion of superiority >99%). Futility was defined as the posterior probability of an OR less than 1.2 (threshold for trial conclusion of futility >95%). An OR greater than 1 represented improved survival, more organ support-free days, or both. The prespecified secondary outcomes included in-hospital survival; 28-day survival; 90-day survival; respiratory support-free days; cardiovascular support-free days; progression to invasive mechanical ventilation, extracorporeal mechanical oxygenation, or death; intensive care unit length of stay; hospital length of stay; World Health Organization ordinal scale score at day 14; venous thromboembolic events at 90 days; and serious adverse events. RESULTS Among the 2011 participants who were randomized (median age, 61 [IQR, 52 to 70] years and 645/1998 [32.3%] women), 1990 (99%) completed the trial. The convalescent plasma intervention was stopped after the prespecified criterion for futility was met. The median number of organ support-free days was 0 (IQR, -1 to 16) in the convalescent plasma group and 3 (IQR, -1 to 16) in the no convalescent plasma group. The in-hospital mortality rate was 37.3% (401/1075) for the convalescent plasma group and 38.4% (347/904) for the no convalescent plasma group and the median number of days alive and free of organ support was 14 (IQR, 3 to 18) and 14 (IQR, 7 to 18), respectively. The median-adjusted OR was 0.97 (95% credible interval, 0.83 to 1.15) and the posterior probability of futility (OR <1.2) was 99.4% for the convalescent plasma group compared with the no convalescent plasma group. The treatment effects were consistent across the primary outcome and the 11...

BackgroundCoral reefs face increasing pressures particularly when on the edge of their distributions. The Houtman Abrolhos Islands (Abrolhos) are the southernmost coral reef system in the Indian Ocean, and one of the highest latitude reefs in the world. These reefs have a unique mix of tropical and temperate marine fauna and flora and support 184 species of coral, dominated by Acropora species. A significant La Niña event during 2011 produced anomalous conditions of increased temperature along the whole Western Australian coastline, producing the first-recorded widespread bleaching of corals at the Abrolhos.Methodology/ Principal FindingsWe examined long term trends in the marine climate at the Abrolhos using historical sea surface temperature data (HadISST data set) from 1900–2011. In addition in situ water temperature data for the Abrolhos (from data loggers installed in 2008, across four island groups) were used to determine temperature exposure profiles. Coupled with the results of coral cover surveys conducted annually since 2007; we calculated bleaching thresholds for monitoring sites across the four Abrolhos groups.Conclusions/ Significance In situ temperature data revealed maximum daily water temperatures reached 29.54°C in March 2011 which is 4.2°C above mean maximum daily temperatures (2008–2010). The level of bleaching varied across sites with an average of ∼12% of corals bleached. Mortality was high, with a mean ∼50% following the 2011 bleaching event. Prior to 2011, summer temperatures reached a mean (across all monitoring sites) of 25.1°C for 2.5 days. However, in 2011 temperatures reached a mean of 28.1°C for 3.3 days. Longer term trends (1900–2011) showed mean annual sea surface temperatures increase by 0.01°C per annum. Long-term temperature data along with short-term peaks in 2011, outline the potential for corals to be exposed to more frequent bleaching risk with consequences for this high latitude coral reef system at the edge of its distribution.

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Sponges are abundant, diverse and functionally important components of aquatic biotopes with crucial associations for many reef fish and invertebrates. Sponges have strict temperature optima, and mass mortality events have occurred after unusually high temperatures. To assess how sponges may adapt to thermal stress associated with a changing climate, we applied gene expression profiling to both stages of their bipartite life cycles. Adult Rhopaloeides odorabile are highly sensitive to thermal stress (32 °C), yet their larvae can withstand temperatures up to 36 °C. Here, we reveal the molecular mechanisms that underpin these contrasting thermal tolerances, which may provide sponges with a means to successfully disperse into cooler waters. Heat shock protein 70 was induced by increasing temperature in adult sponges, and genes involved in important biological functions including cytoskeleton rearrangement, signal transduction, protein synthesis/degradation, oxidative stress and detoxification were all negatively correlated with temperature. Conversely, gene expression in larvae was not significantly affected until 36 °C when a stress response involving extremely rapid activation of heat shock proteins occurred. This study provides the first transcriptomic assessment of thermal stress on both life history stages of a marine invertebrate facilitating better predictions of the long-term consequences of climate change for sponge population dynamics.

The production of salicylihalamide A by the marine sponge Haliclona sp. was investigated. Samples of the two morphologies (green and brown) were collected from four locations covering approximately 1,200 km of coastline. Temporal variation between winter and summer was also examined at Bremer Bay. Chemical profiling by using liquid chromatography coupled with ultra violet detection and mass spectrometry showed that salicylihalamide A was produced only by the green morphology. Salicylihalamide A concentration was significantly correlated to water temperature but not to the size or depth of the sponge. Salicylihalamide A concentration was found to differ significantly among locations (Bremer Bay 13.5 microg g(-1), Hamelin Bay 11 microg g(-1), Rottnest Island 9.9 microg g(-1), and Jurien Bay 8.5 microg g(-1)) partially accounted for by the influence of water temperature. A difference between seasons was also observed in Bremer Bay (summer concentration of 13.5 microg g(-1) vs. winter concentration of 8.2 microg g(-1)). Environmental and physiological factors appear to be important in the production of salicylihalamide A by the green morphology. Additionally, the brown morphology does not produce salicylihalamide A, thus adding to the evidence that this morphology may be a different species.

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Twenty-five years of Australian marine bioresources collecting and research by the Australian Institute of Marine Science (AIMS) has explored the breadth of latitudinally and longitudinally diverse marine habitats that comprise Australia’s ocean territory. The resulting AIMS Bioresources Library and associated relational database integrate biodiversity with bioactivity data, and these resources were mined to retrospectively assess biogeographic, taxonomic and phylogenetic patterns in cytotoxic, antimicrobial, and central nervous system (CNS)-protective bioactivity. While the bioassays used were originally chosen to be indicative of pharmaceutically relevant bioactivity, the results have qualified ecological relevance regarding secondary metabolism. In general, metazoan phyla along the deuterostome phylogenetic pathway (eg to Chordata) and their ancestors (eg Porifera and Cnidaria) had higher percentages of bioactive samples in the assays examined. While taxonomy at the phylum level and higher-order phylogeny groupings helped account for observed trends, taxonomy to genus did not resolve the trends any further. In addition, the results did not identify any biogeographic bioactivity hotspots that correlated with biodiversity hotspots. We conclude with a hypothesis that high-level phylogeny, and therefore the metabolic machinery available to an organism, is a major determinant of bioactivity, while habitat diversity and ecological circumstance are possible drivers in the activation of this machinery and bioactive secondary metabolism. This study supports the strategy of targeting phyla from the deuterostome lineage (including ancestral phyla) from biodiverse marine habitats and ecological niches, in future biodiscovery, at least that which is focused on vertebrate (including human) health.

The reproductive biology of 2 haliclonid sponges was examined over a 2 yr period. Histological samples of Haliclona sp. 1 (green Haliclona) and Haliclona sp. 2 (brown Haliclona) from tagged and haphazardly sampled individuals of both species were examined using light microscopy. Interest in these 2 sympatric species is high, due to the potent and unique bioactive compound (salicylihalamide A) they produce, hence the need to understand the reproductive biology of both species to ensure their proper conservation and management. Green Haliclona is viviparous, with both gonochoric and hermaphroditic individuals in the sponges sampled. Brown Haliclona is also viviparous and is clearly a gonochoric species. Only decreasing wave height showed a significant correlation to gametogenesis, but the onset and progression of reproduction in both species coincided with increases in water temperature and photoperiod. Oogenesis for both species extended from November to April. Spermatogenesis extended over 3 mo for green Haliclona (January to March) and 4 mo for brown Haliclona (January to April). Embryogenesis within brood chambers started in January and extended over 4 mo in green Haliclona and 5 mo in brown Haliclona. The parenchymellae larvae of green Haliclona were observed in tissue samples for 2 mo compared to 4 mo for brown Haliclona. The reproductive output of each species was similar; however, female reproductive output at 2.9% (green Haliclona) and 2.4% (brown Haliclona) of the mesohyl was much lower than that of other viviparous species. Male reproductive output (2.3 and 2.4% for green and brown Haliclona, respectively) compares favourably to that of oviparous species. The high reproductive output of males and the timing of reproduction in both species of sponge appears to help in reducing the risk of unsuccessful fertilisation and lower the probability of larvae being released into unfavourable conditions. KEY WORDS: Haliclona · Sexual · Fecundity · GametogenesisResale or republication not permitted without written consent of the publisher OPEN PEN ACCESS CCESS