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...

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The goal of this paper is the derivation and application of a direct characterization of the inverse of the covariance matrix central to portfolio analysis. Such a characterization, in terms of a few primitive constructs, provides the basis for new and illuminating expressions for key concepts as the optimal holding of a given risky asset and the slope of the risk-return efficiency frontier faced by the individual investor. The building blocks of the inverse turn out to be the regression coefficients and residual variance obtained by regressing the asset's excess return on the set of excess returns for all other risky assets. THE GOAL OF THIS PAPER is the derivation and application of a direct characterization of the inverse of the covariance matrix of asset returns, C ϭ @s ij # , central to portfolio analysis. As argued below, the specifications of C Ϫ1 in terms of a few primitive constructs provides new and illuminating expressions for such key concepts as the optimal holding of a given risky asset and the slope of the risk-return efficiency locus. The building blocks of the inverse turn out to be the regression coefficients and residual variance obtained by regressing the asset's excess return on the set of excess returns for all other risky assets.After setting up the problem in Section I, the desired characterization for C Ϫ1 is derived in Section II. Given this result, it is possible, as shown in Section III, to rewrite the familiar equation for the optimal holding of a given risky asset as proportional to the ratio of the intercept and residual variance of the aforementioned regression. The section provides intuitively appealing interpretations for these factors: the latter as that part of the asset's variance that is unhedgeable or nondiversifiable, the former as the asset's excess expected return over that of the linear combination of other assets that minimizes its unhedgeable variance. Section IV concludes the paper with a summary of its findings.

30Background. Increased interest in luxury products and Traditional Chinese Medicine, associated 31 with economic growth in China, has been linked to depletion of both terrestrial and marine 32 wildlife. Among the most rapidly emerging concerns with respect to these markets is the 33 relatively new demand for gill plates, or Peng Yu Sai ("Fish Gills"), from devil and manta rays 34 (subfamily Mobulinae). The high value of gill plates drives international trade supplied by largely 35 unmonitored and unregulated bycatch and target fisheries around the world. Devil and manta rays 36 are especially sensitive to overexploitation because of their exceptionally low productivity 37(maximum intrinsic rate of population increase). Scientific research, conservation campaigns, as 38 well as international and national protections that restrict fishing or trade have increased in recent 39 years. Many key protections, however, apply only to manta rays. 40Methods. We review the state of the development of scientific knowledge and capacity for these 41 species, and summarise the geographic ranges, fisheries and national and international protections 42 for these species. We use a conservation planning approach to develop the Global Devil and 43Manta Ray Conservation Strategy, specifying a vision, goals, objectives, and actions to advance 44 the conservation of both devil and manta rays. 45Results and Discussion. Generally, there is greater scientific attention and conservation focused 46on Manta compared to Devil Rays. We discuss how the successes in manta ray conservation can 47 be expanded to benefit devil rays. We also examine solutions for the two leading threats to both 48 devil and manta rays -bycatch and target fisheries. First, we examine how can the impact of 49 bycatch fisheries can be reduced through international measures and best-practice handling 50techniques. Second, we examine the role that responsible trade and demand can play in reducing 51 target fisheries for gill plates. Our paper suggests that given similarities in sensitivity and 52 appearance, particularly of the dried gill plate product, conservation measures may need to be 53 harmonised particularly for the larger species in this subfamily.