This phase 3, placebo-controlled platform trial evaluated a single infusion of casirivimab and imdevimab (REGEN-COV) at 2400-mg and 1200-mg doses in outpatients with acute SARS-CoV-2 infection. The ...incidence of Covid-19–related hospitalization was lower and recovery was faster among patients who received the antibody combination than among those who received placebo.
The evolution of ocean temperature measurement systems is presented with a focus on the development and accuracy of two critical devices in use today (expendable bathythermographs and ...conductivity‐temperature‐depth instruments used on Argo floats). A detailed discussion of the accuracy of these devices and a projection of the future of ocean temperature measurements are provided. The accuracy of ocean temperature measurements is discussed in detail in the context of ocean heat content, Earth's energy imbalance, and thermosteric sea level rise. Up‐to‐date estimates are provided for these three important quantities. The total energy imbalance at the top of atmosphere is best assessed by taking an inventory of changes in energy storage. The main storage is in the ocean, the latest values of which are presented. Furthermore, despite differences in measurement methods and analysis techniques, multiple studies show that there has been a multidecadal increase in the heat content of both the upper and deep ocean regions, which reflects the impact of anthropogenic warming. With respect to sea level rise, mutually reinforcing information from tide gauges and radar altimetry shows that presently, sea level is rising at approximately 3 mm yr−1 with contributions from both thermal expansion and mass accumulation from ice melt. The latest data for thermal expansion sea level rise are included here and analyzed.
Key Points
Oceanographic techniques and analysis have improved over many decades
These improvements allow more accurate Earth‐energy balance estimates
Understanding of ocean heat content and sea‐level rise has also increased
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We study the evolution of tropospheric ozone over the period 1979–2010 using a chemistry‐climate model employing a stratosphere‐troposphere chemistry scheme. By running with specified dynamics, the ...key feedback of composition on meteorology is suppressed, isolating the chemical response. By using historical forcings and emissions, interactions between processes are realistically represented. We use the model to assess how the ozone responds over time and to investigate model responses and trends. We find that the chlorofluorocarbon (CFC)‐driven decrease in stratospheric ozone plays a significant role in the tropospheric ozone burden. Over the period 1979–1994, the decline in transport of ozone from the stratosphere, partially offsets an emissions‐driven increase in tropospheric ozone production. From 1994–2010, despite a leveling off in emissions, increased stratosphere‐to‐troposphere transport of ozone drives a small increase in the tropospheric ozone burden. These results have implications for the impact of future stratospheric ozone recovery on air quality and radiative forcing.
Plain Language Summary
We use a modeling approach to study the effect of stratospheric ozone depletion on the composition of the troposphere. We focus on the period 1979–2010 and use a chemistry‐climate model employing historical emissions, climate forcing, and meteorology. Our model has a good description of both stratospheric and tropospheric ozone chemistry and allows us to calculate the effect of exchange between stratosphere and troposphere. We show that stratospheric ozone depletion over the period 1979–2010 has a critical effect on tropospheric composition – with less ozone in the lower stratosphere, there is less transport to the troposphere, and this offsets an emissions‐driven increase in ozone production in the troposphere. Such combined studies are important to quantify the future effects of stratospheric ozone recovery on the evolution of tropospheric composition.
Key Points
We show that stratospheric ozone recovery has an affect on tropospheric ozone levels
Stratospheric ozone loss over the period 1979–1994 offset an emissions‐driven increase in tropospheric ozone
Future stratospheric ozone recovery and changes to the rate of stratosphere‐to‐troposphere transport will be important in the future
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
•Advanced biorefineries are seen as key to implement a sustainable biobased economy.•Total valorization of biomass can boost the industrial implementation of biorefineries.•Tailor-made enzymes may ...increase process performance, reducing loadings and costs.•Big Data Analytics will enable better decision-making in biorefineries.•Interdisciplinary collaboration efforts are essential to develop sustainable biorefineries.
Advanced biorefineries, which aim at valorizing biomass (from agriculture, forestry, aquaculture, among others) into a wide spectrum of products and bioenergy, are seen today as key to implement a sustainable biobased economy. Although different concepts of biorefinery are currently under development, further research and improvement are still required to obtain environmentally friendly and economically feasible commercial scale biorefineries. Valorization of all biomass components and integration of different disciplines are some of the strategies that have been considered to improve the economic and environmental performance. This paper summarizes and discusses the most recent innovations and strategic orientations for the development of advanced biorefineries. Focus is given on the valorization of non-carbohydrate components of biomass (protein, acetic acid and lignin), on-site and tailor-made production of enzymes, big data analytics, and interdisciplinary efforts. The idea is to provide new insights and directions to support the development and large-scale implementation of biorefineries.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
With contributions from around the world, the editors have pulled together a tightly curated set of chapters which showcase how polysaccharide-based materials are employed in a range of biomedical ...systems.
The US Food and Drug Administration (FDA) is currently developing a guidance for industry to replace a previous guidance, “Pharmacokinetics in Patients With Impaired Renal Function—Study Design, Data ...Analysis, and Impact on Dosing and Labeling” (renal guidance) issued in May 1998. The impact of the 1998 renal guidance was assessed following a survey of 94 new drug applications (NDAs) for small‐molecule new molecular entities (NMEs) approved over the past 5 years (2003–2007). The survey results indicate that 57% of these NDAs included renal impairment study data, that 44% of those with renal data included evaluation in patients on hemodialysis, and that 41% of those with renal data resulted in recommendation of dose adjustment in renal impairment. In addition, the survey results provided evidence that renal impairment can affect the pharmacokinetics of drugs that are predominantly eliminated by nonrenal processes such as metabolism and/or active transport. The latter finding supports our updated recommendation to evaluate pharmacokinetic/pharmacodynamic alterations in renal impairment for those drugs that are mainly eliminated by nonrenal processes, in addition to those that are mainly excreted unchanged by the kidney.
Clinical Pharmacology & Therapeutics (2009); 85, 3, 305–311 doi:10.1038/clpt.2008.208
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Summary Background Acetabular dysplasia is a major predisposing factor for development of hip osteoarthritis (OA), and may result from alterations to chondrolabral loading. Subject-specific finite ...element (FE) modeling can be used to evaluate chondrolabral mechanics in the dysplastic hip, thereby providing insight into mechanics that precede OA. Objective To evaluate chondrolabral contact mechanics and congruency in dysplastic hips and normal hips using a validated approach to subject-specific FE modeling. Methods FE models of ten subjects with normal acetabula and ten subjects with dysplasia were constructed using a previously validated protocol. Labrum load support, and labrum and acetabular cartilage contact stress and contact area were compared between groups. Local congruency was determined at the articular surface for two simulated activities. Results The labrum in dysplastic hips supported 2.8–4.0 times more of the load transferred across the joint than in normal hips. Dysplastic hips did not have significantly different congruency in the primary load-bearing regions than normal hips, but were less congruent in some unloaded regions. Normal hips had larger cartilage contact stress than dysplastic hips in the few regions that had significant differences. Conclusions The labrum in dysplastic hips has a far more significant role in hip mechanics than it does in normal hips. The dysplastic hip is neither less congruent than the normal hip, nor subjected to elevated cartilage contact stresses. This study supports the concept of an outside–in pathogenesis of OA in dysplastic hips and that the labrum in dysplastic hips should be preserved during surgery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Clinical islet transplantation achieves insulin independence in selected patients, yet current methods for extracting islets from their surrounding pancreatic matrix are suboptimal. The islet ...basement membrane (BM) influences islet function and survival and is a critical marker of islet integrity following rodent islet isolation. No studies have investigated the impact of islet isolation on BM integrity in human islets, which have a unique duplex structure. To address this, samples were taken from 27 clinical human islet isolations (donor age 41–59, BMI 26–38, cold ischemic time < 10 h). Collagen IV, pan‐laminin, perlecan and laminin‐α5 in the islet BM were significantly digested by enzyme treatment. In isolated islets, laminin‐α5 (found in both layers of the duplex BM) and perlecan were lost entirely, with no restoration evident during culture. Collagen IV and pan‐laminin were present in the disorganized BM of isolated islets, yet a significant reduction in pan‐laminin was seen during the initial 24 h culture period. Islet cytotoxicity increased during culture. Therefore, the human islet BM is substantially disrupted during the islet isolation procedure. Islet function and survival may be compromised as a consequence of an incomplete islet BM, which has implications for islet survival and transplanted graft longevity.
This study characterizes the human islet basement membrane before and after islet isolation, demonstrating that substantial disruption of both layers of the duplex basement membrane occurs during the procedure, potentially compromising islet survival.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Naturally produced very short-lived substances (VSLS) account for almost a quarter of the current stratospheric inorganic bromine, Bry. Following VSLS oxidation, bromine radicals (Br and BrO) can ...catalytically destroy ozone. The extent to which possible increases in surface emissions or transport of these VSLS bromocarbons to the stratosphere could counteract the effect of halogen reductions under the Montreal Protocol is an important policy question. Here, by using a chemistry–climate model, UM-UKCA, we investigate the impact of a hypothetical doubling (an increase of 5 ppt Bry) of VSLS bromocarbons on ozone and how the resulting ozone changes depend on the background concentrations of chlorine and bromine. Our model experiments indicate that for the 5 ppt increase in Bry from VSLS, the ozone decrease in the lowermost stratosphere of the Southern Hemisphere (SH) may reach up to 10% in the annual mean; the ozone decrease in the Northern Hemisphere (NH) is smaller (4–6%). The largest impact on the ozone column is found in the Antarctic spring. There is a significantly larger ozone decrease following the doubling of the VSLS burden under a high stratospheric chlorine background than under a low chlorine background, indicating the importance of the inter-halogen reactions. For example, the decline in the high-latitude, lower-stratospheric ozone concentration as a function of Bry is higher by about 30–40% when stratospheric Cly is ~ 3 ppb (present day), compared with Cly of ~ 0.8 ppb (a pre-industrial or projected future situation). Bromine will play an important role in the future ozone layer. However, even if bromine levels from natural VSLS were to increase significantly later this century, changes in the concentration of ozone will likely be dominated by the decrease in anthropogenic chlorine. Our calculation suggests that for a 5 ppt increase in Bry from VSLS, the Antarctic ozone hole recovery date could be delayed by approximately 6–8 years, depending on Cly levels.
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