This study introduces CNRM‐ESM2‐1, the Earth system (ES) model of second generation developed by CNRM‐CERFACS for the sixth phase of the Coupled Model Intercomparison Project (CMIP6). CNRM‐ESM2‐1 ...offers a higher model complexity than the Atmosphere‐Ocean General Circulation Model CNRM‐CM6‐1 by adding interactive ES components such as carbon cycle, aerosols, and atmospheric chemistry. As both models share the same code, physical parameterizations, and grid resolution, they offer a fully traceable framework to investigate how far the represented ES processes impact the model performance over present‐day, response to external forcing and future climate projections. Using a large variety of CMIP6 experiments, we show that represented ES processes impact more prominently the model response to external forcing than the model performance over present‐day. Both models display comparable performance at replicating modern observations although the mean climate of CNRM‐ESM2‐1 is slightly warmer than that of CNRM‐CM6‐1. This difference arises from land cover‐aerosol interactions where the use of different soil vegetation distributions between both models impacts the rate of dust emissions. This interaction results in a smaller aerosol burden in CNRM‐ESM2‐1 than in CNRM‐CM6‐1, leading to a different surface radiative budget and climate. Greater differences are found when comparing the model response to external forcing and future climate projections. Represented ES processes damp future warming by up to 10% in CNRM‐ESM2‐1 with respect to CNRM‐CM6‐1. The representation of land vegetation and the CO2‐water‐stomatal feedback between both models explain about 60% of this difference. The remainder is driven by other ES feedbacks such as the natural aerosol feedback.
Key Points
This study introduces CNRM‐ESM2‐1 and describes its set‐up for CMIP6
Represented Earth system processes further impact the model response to external forcing than the model performance over present‐day
Represented Earth system processes damp future warming by up to 10%
Pulmonary embolism in patients with COVID-19 pneumonia Bompard, Florian; Monnier, Hippolyte; Saab, Ines ...
European respiratory journal/The European respiratory journal,
07/2020, Letnik:
56, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Acute respiratory distress syndrome development in patients with coronavirus disease 2019 (COVID-19) pneumonia is associated with a high mortality rate and is the main cause of death in patients with ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 1. Myocardial injury has also been reported to be significantly associated with fatal outcome, with a 37% mortality rate in patients without prior cardiovascular disease but elevated troponin levels 2. A D-dimer level of >1 μg·mL
−1
has been clearly identified as a risk factor for poor outcome in SARS-Cov-2 infection 3, with recent reports highlighting a high incidence of thrombotic events in intensive care unit (ICU) patients 4. A normal D-dimer level allows the safe exclusion of pulmonary embolism (PE) in outpatients with a low or intermediate clinical probability of PE, but there is no recommendation to use D-dimer as a positive marker of thrombosis because of lack of specificity.
This study reports an overall 24% (95% CI 17–32%) cumulative incidence of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30–70%) in ICU and 18% (12–27%) in other patients
https://bit.ly/35s7hjm
Summary Background Multislice CT (MSCT) combined with D-dimer measurement can safely exclude pulmonary embolism in patients with a low or intermediate clinical probability of this disease. We ...compared this combination with a strategy in which both a negative venous ultrasonography of the leg and MSCT were needed to exclude pulmonary embolism. Methods We included 1819 consecutive outpatients with clinically suspected pulmonary embolism in a multicentre non-inferiority randomised controlled trial comparing two strategies: clinical probability assessment and either D-dimer measurement and MSCT (DD-CT strategy n=903) or D-dimer measurement, venous compression ultrasonography of the leg, and MSCT (DD-US-CT strategy n=916). Randomisation was by computer-generated blocks with stratification according to centre. Patients with a high clinical probability according to the revised Geneva score and a negative work-up for pulmonary embolism were further investigated in both groups. The primary outcome was the 3-month thromboembolic risk in patients who were left untreated on the basis of the exclusion of pulmonary embolism by diagnostic strategy. Clinicians assessing outcome were blinded to group assignment. Analysis was per protocol. This study is registered with ClinicalTrials.gov , number NCT00117169. Findings The prevalence of pulmonary embolism was 20·6% in both groups (189 cases in DD-US-CT group and 186 in DD-CT group). We analysed 855 patients in the DD-US-CT group and 838 in the DD-CT group per protocol. The 3-month thromboembolic risk was 0·3% (95% CI 0·1–1·1) in the DD-US-CT group and 0·3% (0·1–1·2) in the DD-CT group (difference 0·0% −0·9 to 0·8). In the DD-US-CT group, ultrasonography showed a deep-venous thrombosis in 53 (9% 7–12) of 574 patients, and thus MSCT was not undertaken. Interpretation The strategy combining D-dimer and MSCT is as safe as the strategy using D-dimer followed by venous compression ultrasonography of the leg and MSCT for exclusion of pulmonary embolism. An ultrasound could be of use in patients with a contraindication to CT. Funding Swiss National Research Foundation, Projets Hospitaliers de Recherche Clinique (France), Pneumologie Développement (France).
The role of multidetector-row computed tomography (CT) in the diagnosis of pulmonary embolism remains to be determined. In this study, the combined use of multidetector-row CT and D-dimer assays ...allowed pulmonary embolism to be excluded without the need for lower-extremity ultrasonography.
The combined use of multidetector-row CT and D-dimer assays allowed pulmonary embolism to be excluded without the need for lower-extremity ultrasonography.
Computed tomography (CT) is increasingly being used as the main thoracic imaging technique in suspected pulmonary embolism.
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First-generation single-detector–row helical CT scanners have a 90 percent specificity but only a 70 percent sensitivity for pulmonary embolism.
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In series in which venous-compression ultrasonography of the lower limbs and single-detector–row helical CT were performed in all patients with clinically suspected pulmonary embolism,
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the proportion of patients with deep venous thrombosis despite findings on CT that were negative for pulmonary embolism was 6 to 9 percent. The implication of this finding is that lower-limb ultrasonography must be combined with CT . . .
Diagnosis of pulmonary embolism requires clinical probability assessment. Implicit assessment is accurate but is not standardized, and current prediction rules have shortcomings.
To construct a ...simple score based entirely on clinical variables and independent from physicians' implicit judgment.
Derivation and external validation of the score in 2 independent management studies on pulmonary embolism diagnosis.
Emergency departments of 3 university hospitals in Europe.
Consecutive patients admitted for clinically suspected pulmonary embolism.
Collected data included demographic characteristics, risk factors, and clinical signs and symptoms suggestive of venous thromboembolism. The variables statistically significantly associated with pulmonary embolism in univariate analysis were included in a multivariate logistic regression model. Points were assigned according to the regression coefficients. The score was then externally validated in an independent cohort.
The score comprised 8 variables (points): age older than 65 years (1 point), previous deep venous thrombosis or pulmonary embolism (3 points), surgery or fracture within 1 month (2 points), active malignant condition (2 points), unilateral lower limb pain (3 points), hemoptysis (2 points), heart rate of 75 to 94 beats/min (3 points) or 95 beats/min or more (5 points), and pain on lower-limb deep venous palpation and unilateral edema (4 points). In the validation set, the prevalence of pulmonary embolism was 8% in the low-probability category (0 to 3 points), 28% in the intermediate-probability category (4 to 10 points), and 74% in the high-probability category (> or =11 points).
Interobserver agreement for the score items was not studied.
The proposed score is entirely standardized and is based on clinical variables. It has sustained internal and external validation and should now be tested for clinical usefulness in an outcome study.
Millimeter‐size beads of gelatin are manufactured by dripping process to give enzyme supports qualified for micropollutants biodegradation in alternative wastewater treatment. The bead diameter is ...dependent on the tip diameter, the gelatin solution viscosity and the swelling of polymer chains in the collecting bath. Chemical crosslinking was performed with glutaraldehyde using optimal concentration to give mechanical and thermal properties suitable for application in stirred reactor in aqueous medium. Laccases from Trametes versicolor are grafted on the gelatin beads with glutaraldehyde. Sixty percentage of the initial enzymatic activity, evaluated by the oxidation of 2′‐Azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid)diammonium salt (ABTS) is maintained after 10 successive cycles of reaction. Thermal stability at 60°C of immobilized biocatalysts is improved when compared to free enzymes (45% vs 10% of relative activity after 6 h of incubation). The simplicity of the procedure to form gelatin beads and their properties make them promising bio‐based and biodegradable support for enzyme immobilization.
IMPORTANCE: Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. ...OBJECTIVE: To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. INTERVENTIONS: Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. MAIN OUTCOMES AND MEASURES: Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. RESULTS: In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 95% CI, 0.51-7.89; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. CONCLUSIONS AND RELEVANCE: Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00457158
Plant cell walls are complex structures subject to dynamic remodeling in response to developmental and environmental cues and play essential functions in disease resistance responses. We tested the ...specific contribution of plant cell walls to immunity by determining the susceptibility of a set of
cell wall mutants (
) to pathogens with different parasitic styles: a vascular bacterium, a necrotrophic fungus, and a biotrophic oomycete. Remarkably, most
mutants tested (29/34; 85.3%) showed alterations in their resistance responses to at least one of these pathogens in comparison to wild-type plants, illustrating the relevance of wall composition in determining disease-resistance phenotypes. We found that the enhanced resistance of
plants to the necrotrophic and vascular pathogens negatively impacted
fitness traits, such as biomass and seed yield. Enhanced resistance of
plants is not only mediated by canonical immune pathways, like those modulated by phytohormones or microbe-associated molecular patterns, which are not deregulated in the
tested. Pectin-enriched wall fractions isolated from
plants triggered immune responses in wild-type plants, suggesting that wall-mediated defensive pathways might contribute to
resistance. Cell walls of
plants show a high diversity of composition alterations as revealed by glycome profiling that detect specific wall carbohydrate moieties. Mathematical analysis of glycome profiling data identified correlations between the amounts of specific wall carbohydrate moieties and disease resistance phenotypes of
plants. These data support the relevant and specific function of plant wall composition in plant immune response modulation and in balancing disease resistance/development trade-offs.
Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder that affects cognitive and motor abilities by primarily targeting the striatum and cerebral cortex. HD is caused by a ...mutation elongating the CAG repeats within the Huntingtin gene, resulting in HTT protein misfolding. Although the genetic cause of HD has been established, the specific susceptibility of neurons within various brain structures has remained elusive. Microglia, which are the brain's resident macrophages, have emerged as important players in neurodegeneration. Nevertheless, few studies have examined their implication in HD.
To provide novel insights, we investigated the maturation and dysfunction of striatal microglia using the R6/2 mouse model of HD. This transgenic model, which presents with 120+/-5 CAG repeats, displays progressive motor deficits beginning at 6 weeks of age, with full incapacitation by 13 weeks. We studied microglial morphology, phagocytic capacity, and synaptic contacts in the striatum of R6/2 versus wild-type (WT) littermates at 3, 10, and 13 weeks of age, using a combination of light and transmission electron microscopy. We also reconstructed dendrites and determined synaptic density within the striatum of R6/2 and WT littermates, at nanoscale resolution using focused ion beam scanning electron microscopy.
At 3 weeks of age, prior to any known motor deficits, microglia in R6/2 animals displayed a more mature morphological phenotype than WT animals. Microglia from R6/2 mice across all ages also demonstrated increased phagocytosis, as revealed by light microscopy and transmission electron microscopy. Furthermore, microglial processes from 10-week-old R6/2 mice made fewer contacts with synaptic structures than microglial processes in 3-week-old R6/2 mice and age-matched WT littermates. Synaptic density was not affected by genotype at 3 weeks of age but increased with maturation in WT mice. The location of synapses was lastly modified in R6/2 mice compared with WT controls, from targeting dendritic spines to dendritic trunks at both 3 and 10 weeks of age.
These findings suggest that microglia may play an intimate role in synaptic alteration and loss during HD pathogenesis.
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