Biotic carbon feedbacks in a materially-closed soil-vegetation-atmosphere system

The magnitude and direction of the coupled feedbacks between the biotic and abiotic components of the terrestrial carbon cycle is a major source of uncertainty in coupled climate–carbon-cycle models1, 2, 3. Materially closed, energetically open biological systems continuously and simultaneously allow the two-way feedback loop between the biotic and abiotic components to take place4, 5, 6, 7, but so far have not been used to their full potential in ecological research, owing to the challenge of achieving sustainable model systems6, 7. We show that using materially closed soil–vegetation–atmosphere systems with pro rata carbon amounts for the main terrestrial carbon pools enables the establishment of conditions that balance plant carbon assimilation, and autotrophic and heterotrophic respiration fluxes over periods suitable to investigate short-term biotic carbon feedbacks. Using this approach, we tested an alternative way of assessing the impact of increased CO2 and temperature on biotic carbon feedbacks. The results show that without nutrient and water limitations, the short-term biotic responses could potentially buffer a temperature increase of 2.3 °C without significant positive feedbacks to atmospheric CO2. We argue that such closed-system research represents an important test-bed platform for model validation and parameterization of plant and soil biotic responses to environmental changes

Myocardial Perfusion Imaging After Severe COVID-19 Infection Demonstrates Regional Ischemia Rather Than Global Blood Flow Reduction

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis. Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients. Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF. Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54-71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29-146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p< 0.01). Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment

Accurate diagnosis of apical hypertrophic cardiomyopathy using explainable advanced electrocardiogram analysis.

AIMS: Typical electrocardiogram (ECG) features of apical hypertrophic cardiomyopathy (ApHCM) include tall R waves and deep or giant T-wave inversion in the precordial leads, but these features are not always present. The ECG is used as the gatekeeper to cardiac imaging for diagnosis. We tested whether explainable advanced ECG (A-ECG) could accurately diagnose ApHCM. METHODS AND RESULTS: Advanced ECG analysis was performed on standard resting 12-lead ECGs in patients with ApHCM [n = 75 overt, n = 32 relative (<15 mm hypertrophy); a subgroup of which underwent cardiovascular magnetic resonance (n = 92)], and comparator subjects (n = 2449), including healthy volunteers (n = 1672), patients with coronary artery disease (n = 372), left ventricular electrical remodelling (n = 108), ischaemic (n = 114) or non-ischaemic cardiomyopathy (n = 57), and asymmetrical septal hypertrophy HCM (n = 126). Multivariable logistic regression identified four A-ECG measures that together discriminated ApHCM from other diseases with high accuracy [area under the receiver operating characteristic (AUC) curve (bootstrapped 95% confidence interval) 0.982 (0.965-0.993)]. Linear discriminant analysis also diagnosed ApHCM with high accuracy [AUC 0.989 (0.986-0.991)]. CONCLUSION: Explainable A-ECG has excellent diagnostic accuracy for ApHCM, even when the hypertrophy is relative, with A-ECG analysis providing incremental diagnostic value over imaging alone. The electrical (ECG) and anatomical (wall thickness) disease features do not completely align, suggesting that future diagnostic and management strategies may incorporate both features

The Diversity of Religious Diversity. Using Census and NCS Methodology in Order to Map and Assess the Religious Diversity of a Whole Country

Religious diversity is often captured in “mapping studies” that use mostly qualitative methods in order to map and assess the religious communities in a given area. While these studies are useful, they often present weaknesses in that they treat only limited geographic regions, provide limited possibilities for comparing across religious groups and cannot test theories. In this article, we show how a census and a quantitative national congregations study (NCS) methodology can be combined in order to map and assess the religious diversity of a whole country (Switzerland), overcoming the problems mentioned above. We outline the methodological steps and selected results concerning organizational, geographic, structural, and cultural diversity

Tectono-stratigraphic evolution and crustal architecture of the Orphan Basin during North Atlantic rifting

The Orphan Basin is located in the deep offshore of the Newfoundland margin, and it is bounded by the continental shelf to the west, the Grand Banks to the south, and the continental blocks of Orphan Knoll and Flemish Cap to the east. The Orphan Basin formed in Mesozoic time during the opening of the North Atlantic Ocean between eastern Canada and western Iberia–Europe. This work, based on well data and regional seismic reflection profiles across the basin, indicates that the continental crust was affected by several extensional episodes between the Jurassic and the Early Cretaceous, separated by events of uplift and erosion. The preserved tectono-stratigraphic sequences in the basin reveal that deformation initiated in the eastern part of the Orphan Basin in the Jurassic and spread towards the west in the Early Cretaceous, resulting in numerous rift structures filled with a Jurassic–Lower Cretaceous syn-rift succession and overlain by thick Upper Cretaceous to Cenozoic post-rift sediments. The seismic data show an extremely thinned crust (4–16 km thick) underneath the eastern and western parts of the Orphan Basin, forming two sub-basins separated by a wide structural high with a relatively thick crust (17 km thick). Quantifying the crustal architecture in the basin highlights the large discrepancy between brittle extension localized in the upper crust and the overall crustal thinning. This suggests that continental deformation in the Orphan Basin involved, in addition to the documented Jurassic and Early Cretaceous rifting, an earlier brittle rift phase which is unidentifiable in seismic data and a depth-dependent thinning of the crust driven by localized lower crust ductile flow

P2 receptor-mediated modulation of neurotransmitter release—an update

Presynaptic nerve terminals are equipped with a number of presynaptic auto- and heteroreceptors, including ionotropic P2X and metabotropic P2Y receptors. P2 receptors serve as modulation sites of transmitter release by ATP and other nucleotides released by neuronal activity and pathological signals. A wide variety of P2X and P2Y receptors expressed at pre- and postsynaptic sites as well as in glial cells are involved directly or indirectly in the modulation of neurotransmitter release. Nucleotides are released from synaptic and nonsynaptic sites throughout the nervous system and might reach concentrations high enough to activate these receptors. By providing a fine-tuning mechanism these receptors also offer attractive sites for pharmacotherapy in nervous system diseases. Here we review the rapidly emerging data on the modulation of transmitter release by facilitatory and inhibitory P2 receptors and the receptor subtypes involved in these interactions

Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.

BACKGROUND: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4-12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. METHODS: We present data from three single-blind randomised controlled trials-one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)-and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 1010 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). FINDINGS: Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4-74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12 282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11 962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3-85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59-0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3-91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0-69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18-55 years (GMR 2·32 [2·01-2·68]). INTERPRETATION: The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. FUNDING: UK Research and Innovation, National Institutes of Health Research (NIHR), The Coalition for Epidemic Preparedness Innovations, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D'Or, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS