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...
We describe oyster population trends in the James River, VA from 1993 through 2006 using quantitative fishery independent survey data collected using a stratified random design. The 23 reefs contained in the study area cover a total of 2.41 3 10 7 m 2 and vary in individual size from 1.26 3 10 4 m 2 to 4.98 3 10 6 m 2. There is a marked pattern in density of oysters among the reefs: during the study period a small group of reefs comprising 5.4% of the total area consistently contained between 25.7 and 55.5% by number and 35.8 and 54.8% by biomass of the total oyster population. The highest density reefs exhibit, with very few exceptions, mean densities well in excess of 200 oysters m-2 , typically between 300 and 500 m-2 , with a single maximum value of 773 oysters m-2 in 2002 coincident with the highest annual recruitment observed during the study period. Recruitment events were usually followed by very high mortality with very small percentages of the population reaching ages $3 y of age. A strong stockrecruit relationship is absent; rather population demographics appear to be dominated by periodic high recruitment events. Biomass maxima tended to lag one to two years after recruitment maxima. Standing stock for the total system varied between 1.07 3 10 8 g and 3.31 3 10 8 g (107 and 331 metric tonnes) in 2003 and 2005, respectively as the 2002 recruits grew and suffered mortality. Age-at-length relationships were estimated from demographics: using a July 1 birth date and a November 1 survey date giving lengths of 37.3 mm at 0.33 y, 58.9 mm at 1.33 y, 80.5 mm at 2.33 y, 102.1 mm at 3.33 y and 123.7 mm at 4.33 y Length demographics were recast as age demographics to estimate annual proportional mortality. Mean proportional mortality values for age 1 oysters range from a low of 0.2-0.4 to a high in excess of 0.7. Age 2 mean proportional mortality values range from a low of 0.41 to a high exceeding 0.75. The proportional mortality for age 3 and 4 y olds generally exceeded mean values of 0.6 with highest values approaching 0.95. In all cases, these values exceeded mortality estimates calculated using traditional box count methods by a considerable margin. The ability to accurately estimate age specific mortality allows the construction of shell (habitat) budgets for the individual reef systems. Shell half-life loss rate estimates in the most productive reefs is between 2 and 3 y, and the population is maintained by the continual and extraordinary recruitment in the face of high mortality-the latter driven by disease (predominantly Perkinsus marinus) epizootics. The shell resource, even on the most productive reefs, is modest, equivalent to little more than a monolayer several centimeters thick. Individual reefs demonstrate remarkable stability as either high shell density + high population density associations (high:high) or low shell density + low population density associations (low:low), even in the face of temporal population and demographic fluctuations associated with disease related mortality. The probabilit...
Estuaries around the world are in a state of decline following decades or more of overfishing, pollution, and climate change. Oysters (Ostreidae), ecosystem engineers in many estuaries, influence water quality, construct habitat, and provide food for humans and wildlife. In North America's Chesapeake Bay, once-thriving eastern oyster (Crassostrea virginica) populations have declined dramatically, making their restoration and conservation extremely challenging. Here we present data on oyster size and human harvest from Chesapeake Bay archaeological sites spanning ∼3,500 y of Native American, colonial, and historical occupation. We compare oysters from archaeological sites with Pleistocene oyster reefs that existed before human harvest, modern oyster reefs, and other records of human oyster harvest from around the world. Native American fisheries were focused on nearshore oysters and were likely harvested at a rate that was sustainable over centuries to millennia, despite changing Holocene climatic conditions and sea-level rise. These data document resilience in oyster populations under long-term Native American harvest, sea-level rise, and climate change; provide context for managing modern oyster fisheries in the Chesapeake Bay and elsewhere around the world; and demonstrate an interdisciplinary approach that can be applied broadly to other fisheries.historical baseline | archaeological shellfish | fossil shellfish | marine fisheries | environmental management
We describe oyster population trends in the Great Wicomico River, VA, from 2000 through 2009 using quantitative fishery independent survey data collected using a stratified random design. The seven public reefs examined cover a total of 2.8 3 10 5 m 2 and vary in individual size from 1.36 3 10 4 to 7.16 3 10 4 m 2. The river is functionally divided by a sand spit into upriver and downriver regions. Oyster densities on the upriver reefs were typically an order of magnitude higher than densities on the downriver reefs within the same time period. Throughout the system, the highest observed densities were coincident with high annual recruitment events (2002, 2006). Recruitment events were usually followed by high mortality, with small percentages of the population reaching $3 y of age. A predictive stock-recruit relationship is absent; rather, population demographics appear to be dominated by periodic high recruitment events. In the absence of seed removal, biomass maxima follow 1-2 y after recruitment maxima. Standing stock for the system varied between 1.56 3 10 6 g and 3.63 3 10 7 g in 2005 and 2006. Year-specific age-at-length relationships were estimated from demographics data. Length demographics were recast as age demographics to estimate mortality. Observed proportional mortality between young of the year and age 2 oysters was approximately 0.88 for the 2006-y class, which is slightly higher than the 0.62-0.71 observed for the 2007-y class. The ability to estimate age specific mortality accurately allows the construction of shell (habitat) budgets for the individual reef systems. The Great Wicomico oyster population appears to be maintained by episodic and extraordinary recruitment in the face of high mortality-the latter driven by disease (predominantly Perkinsus marinus) epizootics. The shell resource is modest, equivalent to little more than a monolayer several centimeters thick. Over short timescales (years), the available shell resource oscillates in concert with mortality. The shell accretion rate on upriver reefs is consistently 4-5 times greater than that observed on downriver reefs. Periodic modest shell planting has maintained the habitat base (the shell resource) throughout the system over decadal scales.
During the estrous cycle of the mare and several other species, the time of maximum
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