Stocks of soil organic carbon represent a large component of the carbon cycle that may participate in climate change feedbacks, particularly on decadal and centennial timescales. For Earth system ...models (ESMs), the ability to accurately represent the global distribution of existing soil carbon stocks is a prerequisite for accurately predicting future carbon-climate feedbacks. We compared soil carbon simulations from 11 model centers to empirical data from the Harmonized World Soil Database (HWSD) and the Northern Circumpolar Soil Carbon Database (NCSCD). Model estimates of global soil carbon stocks ranged from 510 to 3040 Pg C, compared to an estimate of 1260 Pg C (with a 95% confidence interval of 890-1660 Pg C) from the HWSD. Model simulations for the high northern latitudes fell between 60 and 820 Pg C, compared to 500 Pg C (with a 95% confidence interval of 380-620 Pg C) for the NCSCD and 290 Pg C for the HWSD. Global soil carbon varied 5.9 fold across models in response to a 2.6-fold variation in global net primary productivity (NPP) and a 3.6-fold variation in global soil carbon turnover times. Model-data agreement was moderate at the biome level (R super(2) values ranged from 0.38 to 0.97 with a mean of 0.75); however, the spatial distribution of soil carbon simulated by the ESMs at the 1 degree scale was not well correlated with the HWSD (Pearson correlation coefficients less than 0.4 and root mean square errors from 9.4 to 20.8 kg C m super(-2)). In northern latitudes where the two data sets overlapped, agreement between the HWSD and the NCSCD was poor (Pearson correlation coefficient 0.33), indicating uncertainty in empirical estimates of soil carbon. We found that a reduced complexity model dependent on NPP and soil temperature explained much of the 1 degree spatial variation in soil carbon within most ESMs (R super(2) values between 0.62 and 0.93 for 9 of 11 model centers). However, the same reduced complexity model only explained 10% of the spatial variation in HWSD soil carbon when driven by observations of NPP and temperature, implying that other drivers or processes may be more important in explaining observed soil carbon distributions. The reduced complexity model also showed that differences in simulated soil carbon across ESMs were driven by differences in simulated NPP and the parameterization of soil heterotrophic respiration (inter-model R super(2) = 0.93), not by structural differences between the models. Overall, our results suggest that despite fair global-scale agreement with observational data and moderate agreement at the biome scale, most ESMs cannot reproduce grid-scale variation in soil carbon and may be missing key processes. Future work should focus on improving the simulation of driving variables for soil carbon stocks and modifying model structures to include additional processes.
Background
Several single‐site alcohol treatment clinical trials have demonstrated efficacy for immediate‐release (IR) gabapentin in reducing drinking outcomes among individuals with alcohol ...dependence. The purpose of this study was to conduct a large, multisite clinical trial of gabapentin enacarbil extended‐release (GE‐XR) (HORIZANT®), a gabapentin prodrug formulation, to determine its safety and efficacy in treating alcohol use disorder (AUD).
Methods
Men and women (n = 346) who met DSM‐5 criteria for at least moderate AUD were recruited across 10 U.S. clinical sites. Participants received double‐blind GE‐XR (600 mg twice a day) or placebo and a computerized behavioral intervention (Take Control) for 6 months. Efficacy analyses were prespecified for the last 4 weeks of the treatment period.
Results
The GE‐XR and placebo groups did not differ significantly on the primary outcome measure, percentage of subjects with no heavy drinking days (28.3 vs. 21.5, respectively, p = 0.157). Similarly, no clinical benefit was found for other drinking measures (percent subjects abstinent, percent days abstinent, percent heavy drinking days, drinks per week, drinks per drinking day), alcohol craving, alcohol‐related consequences, sleep problems, smoking, and depression/anxiety symptoms. Common side‐effects were fatigue, dizziness, and somnolence. A population pharmacokinetics analysis revealed that patients had lower gabapentin exposure levels compared with those in other studies using a similar dose but for other indications.
Conclusions
Overall, GE‐XR at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with AUD. It is possible that, unlike the IR formulation of gabapentin, which showed efficacy in smaller Phase 2 trials at a higher dose, GE‐XR is not effective in treating AUD, at least not at doses approved by the U.S. Food and Drug Administration for treating other medical conditions.
Gabapentin enacarbil extended‐release (GE‐XR) (HORIZANT) at 600 mg twice a day did not reduce alcohol consumption or craving in individuals with alcohol use disorder, including the primary outcome – the percentage of subjects with no heavy drinking days (PSNHDD). There was no significant difference between GE‐XR and placebo on PSNHDD across trial months and across the entire maintenance period (Weeks 2 to 25) (all ps > 0.05).
Tackling the role of syntactic constructions in text, thiscompanion brings out the connections between syntactic structures and semantics/pragmatics and the function of different clausal structures ...in written and spoken texts. It also draws attention to variation in standard written English, to the grammatical structures and discourse devices in spoken English, and to ongoing changes in English grammar. It focuses on the concepts of descriptive grammar as extended and refined over the last fifty years. * Encyclopedic format gives immediate access the most relevant topic Cross-referencing allows students to follow a thread and explore the interrelationships between syntactic structures * Innovative structure of the volume enables lecturers to decide the order in which they wish to discuss topics and to prescribe reading This is a practical yet flexible reference that you can return to again and again, whether it be for learning, research or teaching.
Injuries to articular cartilage and menisci can lead to cartilage degeneration that ultimately results in arthritis. Different forms of arthritis affect ~50 million people in the USA alone, and it is ...therefore crucial to identify methods that will halt or slow the progression to arthritis, starting with the initiating events of cartilage and meniscus defects. The surgical approaches in current use have a limited capacity for tissue regeneration and yield only short-term relief of symptoms. Tissue engineering approaches are emerging as alternatives to current surgical methods for cartilage and meniscus repair. Several cell-based and tissue-engineered products are currently in clinical trials for cartilage lesions and meniscal tears, opening new avenues for cartilage and meniscus regeneration. This Review provides a summary of surgical techniques, including tissue-engineered products, that are currently in clinical use, as well as a discussion of state-of-the-art tissue engineering strategies and technologies that are being developed for use in articular cartilage and meniscus repair and regeneration. The obstacles to clinical translation of these strategies are also included to inform the development of innovative tissue engineering approaches.
Abstract Pancreatic cancer has a very poor prognosis. While gemcitabine is the mainstay of therapy and improves quality of life, it has little impact on survival. More effective treatments are ...desperately needed for this disease. Frondoside A is a triterpenoid glycoside isolated from the Atlantic sea cucumber, Cucumaria frondosa . Frondoside A potently inhibits pancreatic cancer cell growth and induces apoptosis in vitro and in vivo . The aim of the present study was to investigate whether frondoside A could enhance the anti-cancer effects of gemcitabine. Effects of frondoside A and gemcitabine alone and in combination on proliferation were investigated in two human pancreatic cancer cell lines, AsPC-1 and S2013. To investigate possible synergistic effects, combinations of low concentrations of the two drugs were used for a 72 h treatment period in vitro . Growth inhibition was significantly greater with the drug combinations than their additive effects. Combinations of frondoside A and gemcitabine were tested in vivo using the athymic mouse model. Xenografts of AsPC-1 and S2013 cells were allowed to form tumours prior to treatment with the drugs alone or in combination for 30 days. Tumours grew rapidly in placebo-treated animals. Tumour growth was significantly reduced in all treatment groups. At the lowest dose tested, gemcitabine (4 mg/kg/dose), combined with frondoside A (100 μg/kg/day) was significantly more effective than with either drug alone. To conclude: The present data suggest that combinations of frondoside A and gemcitabine may provide clinical benefit for patients with pancreatic cancer.
Sulfidation of metallic nanoparticles such as silver nanoparticles (AgNPs) released to the environment may be an important detoxification mechanism. Two types of AgNPsan engineered polydisperse and ...aggregated AgNP powder, and a laboratory-synthesized, relatively monodisperse AgNP aqueous dispersionwere studied. The particles were sulfidized to varying degrees and characterized to determine the effect of initial AgNP polydispersity and aggregation state on AgNP sulfidation, and then exposed to Escherichia coli to determine if the degree of sulfidation of pristine AgNPs affects growth inhibition of bacteria. The extent of sulfidation was found to depend on the HS–/Ag ratio. However, for the same reaction times, the more monodisperse particles were fully transformed to Ag2S, and the polydisperse, aggregated particles were not fully sulfidized, thus preserving the toxic potential of Ag0 in the aggregates. A higher Ag2S:Ag0 ratio in the sulfidized nanoparticles resulted in less growth inhibition of E. coli over 6 h of exposure. These results suggest that the initial properties of AgNPs can affect sulfidation products, which in turn affect microbial growth inhibition, and that these properties should be considered in assessing the environmental impact of AgNPs.
Fresh waters are particularly vulnerable to climate change because (i) many species within these fragmented habitats have limited abilities to disperse as the environment changes; (ii) water ...temperature and availability are climate-dependent; and (iii) many systems are already exposed to numerous anthropogenic stressors. Most climate change studies to date have focused on individuals or species populations, rather than the higher levels of organization (i.e. communities, food webs, ecosystems). We propose that an understanding of the connections between these different levels, which are all ultimately based on individuals, can help to develop a more coherent theoretical framework based on metabolic scaling, foraging theory and ecological stoichiometry, to predict the ecological consequences of climate change. For instance, individual basal metabolic rate scales with body size (which also constrains food web structure and dynamics) and temperature (which determines many ecosystem processes and key aspects of foraging behaviour). In addition, increasing atmospheric CO2 is predicted to alter molar CNP ratios of detrital inputs, which could lead to profound shifts in the stoichiometry of elemental fluxes between consumers and resources at the base of the food web. The different components of climate change (e.g. temperature, hydrology and atmospheric composition) not only affect multiple levels of biological organization, but they may also interact with the many other stressors to which fresh waters are exposed, and future research needs to address these potentially important synergies.
Novel coronavirus disease 2019 (COVID-19) vaccine hesitancy is a barrier to achieving herd immunity, and thus, a prominent public health concern. This study aimed to identify the determinants of ...COVID-19 vaccine hesitancy based on the World Health Organization's '3Cs' model (i.e., confidence, complacency, and convenience) in the United States (U.S.) and Canada. Data from 7678 adults ages 18 or older were collected from the four most populous U.S. States, specifically New York, California, Florida, and Texas, and from English-speaking Canada at three timepoints, in May and July 2020, and March 2021 using a web-based survey (www.covid19-database.com). Sociodemographic information was collected, and comprehensive psychological assessments were administered. Univariate analyses were performed to identify the individual determinants of vaccine hesitancy, which were categorized as: 1) vaccine confidence, 2) vaccine complacency, 3) sociodemographic, and 4) other psychological factors. A series of models were computed using these categorizations. Mistrust of vaccine benefit (beta(SE) = 0.67(0.01), p<0.001, partial eta.sup.2 = 0.26) and lower perceived seriousness of COVID-19 (beta(SE) = 0.68(0.02), p<0.001, partial eta.sup.2 = 0.12) were the principal determinants of vaccine hesitancy. Right-wing political affiliation (beta(SE) = 0.32(0.02), p<0.001, partial eta.sup.2 = 0.03), higher risk propensity (beta(SE) = 0.24(0.02), p<0.001, partial eta.sup.2 = 0.03), and less negative mental health effects of the COVID-19 pandemic (beta(SE) = 0.20(0.01), p<0.001, partial eta.sup.2 = 0.03) were the main sociodemographic and psychological determinants. Other sociodemographic determinants included younger age, women, race, and employment status. Lack of vaccine confidence and complacency explained 38% and 21% of the variance in vaccine hesitancy, respectively; whereas, sociodemographic and psychological determinants explained 13% and 11% of the variance in vaccine hesitancy, respectively. Targeted and tailored public health interventions that enhance the public's confidence in vaccines and emphasize the risk and seriousness of COVID-19 may address COVID-19 vaccine hesitancy. Efforts directed toward specific marginalized and underserved groups may be required to promote vaccine confidence.
Pristine silver nanoparticles (AgNPs) are not chemically stable in the environment and react strongly with inorganic ligands such as sulfide and chloride once the silver is oxidized. Understanding ...the environmental transformations of AgNPs in the presence of specific inorganic ligands is crucial to determining their fate and toxicity in the environment. Chloride (Cl–) is a ubiquitous ligand with a strong affinity for oxidized silver and is often present in natural waters and in bacterial growth media. Though chloride can strongly affect toxicity results for AgNPs, their interaction is rarely considered and is challenging to study because of the numerous soluble and solid Ag–Cl species that can form depending on the Cl/Ag ratio. Consequently, little is known about the stability and dissolution kinetics of AgNPs in the presence of chloride ions. Our study focuses on the dissolution behavior of AgNPs in chloride-containing systems and also investigates the effect of chloride on the growth inhibition of E.coli (ATCC strain 33876) caused by Ag toxicity. Our results suggest that the kinetics of dissolution are strongly dependent on the Cl/Ag ratio and can be interpreted using the thermodynamically expected speciation of Ag in the presence of chloride. We also show that the toxicity of AgNPs to E.coli at various Cl– concentrations is governed by the amount of dissolved AgCl x (x–1)– species suggesting an ion effect rather than a nanoparticle effect.
We present an analysis of survey observations targeting the leading L4 Jupiter Trojan cloud near opposition using the wide-field Suprime-Cam CCD camera on the 8.2 m Subaru Telescope. The survey ...covered about 38 degsub 2 of sky and imaged 147 fields spread across a wide region of the L4 cloud. Each field was imaged in both the g' and the i' band, allowing for the measurement of g-i color. We detected 557 Trojans in the observed fields, ranging in absolute magnitude from H = 10.0 to H = 20.3. In the context of the less-red and red color populations, as classified in Wong et al. using photometric and spectroscopic data, we demonstrate that the observed trend in color for the faint Trojans is consistent with the expected trend derived from extrapolation of the best-fit color population magnitude distributions for bright cataloged Trojans. Finally, we interpret our results using collisional modeling and propose several hypotheses for the color evolution of the Jupiter Trojan population.
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