Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. A warming climate can induce environmental changes that accelerate the microbial ...breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.
The use of intensive lipid-lowering therapy by means of statin medications is recommended after transient ischemic attack (TIA) and ischemic stroke of atherosclerotic origin. The target level for ...low-density lipoprotein (LDL) cholesterol to reduce cardiovascular events after stroke has not been well studied.
In this parallel-group trial conducted in France and South Korea, we randomly assigned patients with ischemic stroke in the previous 3 months or a TIA within the previous 15 days to a target LDL cholesterol level of less than 70 mg per deciliter (1.8 mmol per liter) (lower-target group) or to a target range of 90 mg to 110 mg per deciliter (2.3 to 2.8 mmol per liter) (higher-target group). All the patients had evidence of cerebrovascular or coronary-artery atherosclerosis and received a statin, ezetimibe, or both. The composite primary end point of major cardiovascular events included ischemic stroke, myocardial infarction, new symptoms leading to urgent coronary or carotid revascularization, or death from cardiovascular causes.
A total of 2860 patients were enrolled and followed for a median of 3.5 years; 1430 were assigned to each LDL cholesterol target group. The mean LDL cholesterol level at baseline was 135 mg per deciliter (3.5 mmol per liter), and the mean achieved LDL cholesterol level was 65 mg per deciliter (1.7 mmol per liter) in the lower-target group and 96 mg per deciliter (2.5 mmol per liter) in the higher-target group. The trial was stopped for administrative reasons after 277 of an anticipated 385 end-point events had occurred. The composite primary end point occurred in 121 patients (8.5%) in the lower-target group and in 156 (10.9%) in the higher-target group (adjusted hazard ratio, 0.78; 95% confidence interval, 0.61 to 0.98; P = 0.04). The incidence of intracranial hemorrhage and newly diagnosed diabetes did not differ significantly between the two groups.
After an ischemic stroke or TIA with evidence of atherosclerosis, patients who had a target LDL cholesterol level of less than 70 mg per deciliter had a lower risk of subsequent cardiovascular events than those who had a target range of 90 mg to 110 mg per deciliter. (Funded by the French Ministry of Health and others; Treat Stroke to Target ClinicalTrials.gov number, NCT01252875.).
As Arctic regions warm and frozen soils thaw, the large organic carbon pool stored in permafrost becomes increasingly vulnerable to decomposition or transport. The transfer of newly mobilized carbon ...to the atmosphere and its potential influence upon climate change will largely depend on the degradability of carbon delivered to aquatic ecosystems. Dissolved organic carbon (DOC) is a key regulator of aquatic metabolism, yet knowledge of the mechanistic controls on DOC biodegradability is currently poor due to a scarcity of long-term data sets, limited spatial coverage of available data, and methodological diversity. Here, we performed parallel biodegradable DOC (BDOC) experiments at six Arctic sites (16 experiments) using a standardized incubation protocol to examine the effect of methodological differences commonly used in the literature. We also synthesized results from 14 aquatic and soil leachate BDOC studies from across the circum-arctic permafrost region to examine pan-arctic trends in BDOC. An increasing extent of permafrost across the landscape resulted in higher DOC losses in both soil and aquatic systems. We hypothesize that the unique composition of (yedoma) permafrost-derived DOC combined with limited prior microbial processing due to low soil temperature and relatively short flow path lengths and transport times, contributed to a higher overall terrestrial and freshwater DOC loss. Additionally, we found that the fraction of BDOC decreased moving down the fluvial network in continuous permafrost regions, i.e. from streams to large rivers, suggesting that highly biodegradable DOC is lost in headwater streams. We also observed a seasonal (January-December) decrease in BDOC in large streams and rivers, but saw no apparent change in smaller streams or soil leachates. We attribute this seasonal change to a combination of factors including shifts in carbon source, changing DOC residence time related to increasing thaw-depth, increasing water temperatures later in the summer, as well as decreasing hydrologic connectivity between soils and surface water as the thaw season progresses. Our results suggest that future climate warming-induced shifts of continuous permafrost into discontinuous permafrost regions could affect the degradation potential of thaw-released DOC, the amount of BDOC, as well as its variability throughout the Arctic summer. We lastly recommend a standardized BDOC protocol to facilitate the comparison of future work and improve our knowledge of processing and transport of DOC in a changing Arctic.
Cardiovascular disease is a competing cause of death in patients with cancer with early-stage disease. This elevated cardiovascular disease risk is thought to derive from both the direct effects of ...cancer therapies and the accumulation of risk factors such as hypertension, weight gain, cigarette smoking, and loss of cardiorespiratory fitness. Effective and viable strategies are needed to mitigate cardiovascular disease risk in this population; a multimodal model such as cardiac rehabilitation may be a potential solution. This statement from the American Heart Association provides an overview of the existing knowledge and rationale for the use of cardiac rehabilitation to provide structured exercise and ancillary services to cancer patients and survivors. This document introduces the concept of cardio-oncology rehabilitation, which includes identification of patients with cancer at high risk for cardiac dysfunction and a description of the cardiac rehabilitation infrastructure needed to address the unique exposures and complications related to cancer care. In this statement, we also discuss the need for future research to fully implement a multimodal model of cardiac rehabilitation for patients with cancer and to determine whether reimbursement of these services is clinically warranted.
We present an approach to estimate the feedback from large-scale thawing of permafrost soils using a simplified, data-constrained model that combines three elements: soil carbon (C) maps and profiles ...to identify the distribution and type of C in permafrost soils; incubation experiments to quantify the rates of C lost after thaw; and models of soil thermal dynamics in response to climate warming. We call the approach the Permafrost Carbon Network Incubation-Panarctic Thermal scaling approach (PInc-PanTher). The approach assumes that C stocks do not decompose at all when frozen, but once thawed follow set decomposition trajectories as a function of soil temperature. The trajectories are determined according to a three-pool decomposition model fitted to incubation data using parameters specific to soil horizon types. We calculate litterfall C inputs required to maintain steady-state C balance for the current climate, and hold those inputs constant. Soil temperatures are taken from the soil thermal modules of ecosystem model simulations forced by a common set of future climate change anomalies under two warming scenarios over the period 2010 to 2100. Under a medium warming scenario (RCP4.5), the approach projects permafrost soil C losses of 12.2-33.4 Pg C; under a high warming scenario (RCP8.5), the approach projects C losses of 27.9-112.6 Pg C. Projected C losses are roughly linearly proportional to global temperature changes across the two scenarios. These results indicate a global sensitivity of frozen soil C to climate change (γ sensitivity) of −14 to −19 Pg C °C−1 on a 100 year time scale. For CH4 emissions, our approach assumes a fixed saturated area and that increases in CH4 emissions are related to increased heterotrophic respiration in anoxic soil, yielding CH4 emission increases of 7% and 35% for the RCP4.5 and RCP8.5 scenarios, respectively, which add an additional greenhouse gas forcing of approximately 10-18%. The simplified approach presented here neglects many important processes that may amplify or mitigate C release from permafrost soils, but serves as a data-constrained estimate on the forced, large-scale permafrost C response to warming.
Controls on the fate of ~277 Pg of soil organic carbon (C) stored in permafrost peatland soils remain poorly understood despite the potential for a significant positive feedback to climate change. ...Our objective was to quantify the temperature, moisture, organic matter, and microbial controls on soil organic carbon (SOC) losses following permafrost thaw in peat soils across Alaska. We compared the carbon dioxide (CO₂) and methane (CH₄) emissions from peat samples collected at active layer and permafrost depths when incubated aerobically and anaerobically at −5, −0.5, +4, and +20 °C. Temperature had a strong, positive effect on C emissions; global warming potential (GWP) was >3× larger at 20 °C than at 4 °C. Anaerobic conditions significantly reduced CO₂ emissions and GWP by 47% at 20 °C but did not have a significant effect at −0.5 °C. Net anaerobic CH₄ production over 30 days was 7.1 ± 2.8 μg CH₄‐C gC⁻¹ at 20 °C. Cumulative CO₂ emissions were related to organic matter chemistry and best predicted by the relative abundance of polysaccharides and proteins (R² = 0.81) in SOC. Carbon emissions (CO₂‐C + CH₄‐C) from the active layer depth peat ranged from 77% larger to not significantly different than permafrost depths and varied depending on the peat type and peat decomposition stage rather than thermal state. Potential SOC losses with warming depend not only on the magnitude of temperature increase and hydrology but also organic matter quality, permafrost history, and vegetation dynamics, which will ultimately determine net radiative forcing due to permafrost thaw.
Wetlands are the single largest natural source of atmospheric methane (CH4), a greenhouse gas, and occur extensively in the northern hemisphere. Large discrepancies remain between “bottom‐up” and ...“top‐down” estimates of northern CH4 emissions. To explore whether these discrepancies are due to poor representation of nongrowing season CH4 emissions, we synthesized nongrowing season and annual CH4 flux measurements from temperate, boreal, and tundra wetlands and uplands. Median nongrowing season wetland emissions ranged from 0.9 g/m2 in bogs to 5.2 g/m2 in marshes and were dependent on moisture, vegetation, and permafrost. Annual wetland emissions ranged from 0.9 g m−2 year−1 in tundra bogs to 78 g m−2 year−1 in temperate marshes. Uplands varied from CH4 sinks to CH4 sources with a median annual flux of 0.0 ± 0.2 g m−2 year−1. The measured fraction of annual CH4 emissions during the nongrowing season (observed: 13% to 47%) was significantly larger than that was predicted by two process‐based model ensembles, especially between 40° and 60°N (modeled: 4% to 17%). Constraining the model ensembles with the measured nongrowing fraction increased total nongrowing season and annual CH4 emissions. Using this constraint, the modeled nongrowing season wetland CH4 flux from >40° north was 6.1 ± 1.5 Tg/year, three times greater than the nongrowing season emissions of the unconstrained model ensemble. The annual wetland CH4 flux was 37 ± 7 Tg/year from the data‐constrained model ensemble, 25% larger than the unconstrained ensemble. Considering nongrowing season processes is critical for accurately estimating CH4 emissions from high‐latitude ecosystems, and necessary for constraining the role of wetland emissions in a warming climate.
The extensive wetlands in temperate, boreal, and tundra regions emit varying amounts of methane, a potent greenhouse gas, during the warmer growing season as well as the colder nongrowing season, but the importance of nongrowing season emissions is not well understood. Using existing data from 191 sites, we find that nongrowing season fluxes were significantly greater than zero and amounted to 10%–50% of annual emissions, depending on which ecosystem type and biome. Comparing observations and process‐based methane models indicated that nongrowing season emissions were under‐estimated by process‐based models; using a measurement‐informed model constraint leads to 25% larger annual methane emissions from northern latitudes.
RNA sequencing and genetic data support spleen tyrosine kinase (SYK) and high affinity immunoglobulin epsilon receptor subunit gamma (FCER1G) as putative targets to be modulated for Alzheimer's ...disease (AD) therapy. FCER1G is a component of Fc receptor complexes that contain an immunoreceptor tyrosine-based activation motif (ITAM). SYK interacts with the Fc receptor by binding to doubly phosphorylated ITAM (p-ITAM) via its two tandem SH2 domains (SYK-tSH2). Interaction of the FCER1G p-ITAM with SYK-tSH2 enables SYK activation via phosphorylation. Since SYK activation is reported to exacerbate AD pathology, we hypothesized that disruption of this interaction would be beneficial for AD patients. Herein, we developed biochemical and biophysical assays to enable the discovery of small molecules that perturb the interaction between the FCER1G p-ITAM and SYK-tSH2. We identified two distinct chemotypes using a high-throughput screen (HTS) and orthogonally assessed their binding. Both chemotypes covalently modify SYK-tSH2 and inhibit its interaction with FCER1G p-ITAM, however, these compounds lack selectivity and this limits their utility as chemical tools.
The magnitude of carbon (C) loss to the atmosphere via microbial
decomposition is a function of the amount of C stored in soils, the quality
of the organic matter, and physical, chemical, and ...biological factors that
comprise the environment for decomposition. The decomposability of C is
commonly assessed by laboratory soil incubation studies that measure
greenhouse gases mineralized from soils under controlled conditions. Here,
we introduce the Soil Incubation Database (SIDb) version 1.0, a compilation
of time series data from incubations, structured into a new, publicly
available, open-access database of C flux (carbon dioxide, CO2, or
methane, CH4). In addition, the SIDb project also provides a platform
for the development of tools for reading and analysis of incubation data as
well as documentation for future use and development. In addition to
introducing SIDb, we provide reporting guidance for database entry and the
required variables that incubation studies need at minimum to be included in
SIDb. A key application of this synthesis effort is to better characterize
soil C processes in Earth system models, which will in turn reduce our
uncertainty in predicting the response of soil C decomposition to a changing
climate. We demonstrate a framework to fit curves to a number of incubation
studies from diverse ecosystems, depths, and organic matter content using a
built-in model development module that integrates SIDb with the existing
SoilR package to estimate soil C pools from time series data. The database
will help bridge the gap between point location measurements, which are
commonly used in incubation studies, and global remote-sensed data or data
products derived from models aimed at assessing global-scale rates of
decomposition and C turnover. The SIDb version 1.0 is archived and publicly
available at https://doi.org/10.5281/zenodo.3871263 (Sierra et al., 2020), and the database is managed
under a version-controlled system and centrally stored in GitHub (https://github.com/SoilBGC-Datashare/sidb, last access: 26 June 2020).
Summary
Background
Comparative, real‐life and long‐term evidence on the effectiveness and safety of phototherapy and systemic therapy in moderate‐to‐severe atopic eczema (AE) is limited. Such data ...must come from well‐designed prospective patient registries. Standardization of data collection is needed for direct comparisons and data pooling.
Objectives
To reach a consensus on how and when to measure the previously defined domain items of the TREatment of ATopic eczema (TREAT) Registry Taskforce core dataset for research registries for paediatric and adult patients with AE.
Methods
Proposals for the measurement instruments were based on recommendations of the Harmonising Outcome Measures for Eczema (HOME) initiative, the existing AE database of TREATgermany, systematic reviews of the literature and expert opinions. The proposals were discussed at three face‐to‐face consensus meetings, one teleconference and via e‐mail. The frequency of follow‐up visits was determined by an expert survey.
Results
A total of 16 experts from seven countries participated in the ‘how to measure’ consensus process and 12 external experts were consulted. A consensus was reached for all domain items on how they should be measured by assigning measurement instruments. A minimum follow‐up frequency of initially 4 weeks after commencing treatment, then every 3 months while on treatment and every 6 months while off treatment was defined.
Conclusions
This core dataset for national AE research registries will aid in the comparability and pooling of data across centres and country borders, and enables international collaboration to assess the long‐term effectiveness and safety of phototherapy and systemic therapy used in patients with AE.
What's already known about this topic?
Comparable, real‐life and long‐term data on the effectiveness and safety of phototherapy and systemic therapy in patients with atopic eczema (AE) are needed.
There is a high diversity of outcomes and instruments used in AE research, which require harmonization to enhance comparability and allow data pooling.
What does this study add?
Our taskforce has reached international consensus on how and when to measure core domain items for national AE research registries.
This core dataset is now available for use by researchers worldwide and will aid in the collection of unified data.
What are the clinical implications of this work?
The data collected through this core dataset will help to gain better insights into the long‐term effectiveness and safety of phototherapy and systemic therapy in AE and will provide important information for clinical practice.
Standardization of such data collection at the national level will also allow direct data comparisons and pooling across country borders (e.g. in the analysis of treatment‐related adverse events that require large patient numbers).
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