The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting FFR (MEMENTO-FFR) Study.

AIMS: Adenosine administration is needed for the achievement of maximal hyperaemia fractional flow reserve (FFR) assessment. The objective was to test the accuracy of Pd/Pa ratio registered during submaximal hyperaemia induced by non-ionic contrast medium (contrast FFR [cFFR]) in predicting FFR and comparing it to the performance of resting Pd/Pa in a collaborative registry of 926 patients enrolled in 10 hospitals from four European countries (Italy, Spain, France and Portugal). METHODS AND RESULTS: Resting Pd/Pa, cFFR and FFR were measured in 1,026 coronary stenoses functionally evaluated using commercially available pressure wires. cFFR was obtained after intracoronary injection of contrast medium, while FFR was measured after administration of adenosine. Resting Pd/Pa and cFFR were significantly higher than FFR (0.93±0.05 vs. 0.87±0.08 vs. 0.84±0.08, p<0.001). A strong correlation and a close agreement at Bland-Altman analysis between cFFR and FFR were observed (r=0.90, p<0.001 and 95% CI of disagreement: from -0.042 to 0.11). ROC curve analysis showed an excellent accuracy (89%) of the cFFR cut-off of ≤0.85 in predicting an FFR value ≤0.80 (AUC 0.95 [95% CI: 0.94-0.96]), significantly better than that observed using resting Pd/Pa (AUC: 0.90, 95% CI: 0.88-0.91; p<0.001). A cFFR/FFR hybrid approach showed a significantly lower number of lesions requiring adenosine than a resting Pd/Pa/FFR hybrid approach (22% vs. 44%, p<0.0001). CONCLUSIONS: cFFR is accurate in predicting the functional significance of coronary stenosis. This could allow limiting the use of adenosine to obtain FFR to a minority of stenoses with considerable savings of time and costs.info:eu-repo/semantics/publishedVersio

EROS variable stars: discovery of a slow nova in the SMC

We report the discovery of a slow nova found in the core of the Small Magellanic Cloud by the EROS microlensing survey. Nova SMC 1994 is a classical nova with a DQ Her type lightcurve characterized by a deep minimum. Low amplitude variations occuring on time-scales of hours and days are also detected at maximum light. Spectra collected during the nebular phase indicate that Nova SMC 1994 is similar to Galactic novae of the same class. Large helium enhancement in the shell is found and O and N enrichments are suspected. Based on observations collected at the European Southern Observatory, Chile

Relationship between the COVID-19 pandemic and structural inequalities within the pediatric trauma population

BACKGROUND: The COVID-19 pandemic disrupted social, political, and economic life across the world, shining a light on the vulnerability of many communities. The objective of this study was to assess injury patterns before and after implementation of stay-at-home orders (SHOs) between White children and children of color and across varying levels of vulnerability based upon children\u27s home residence. METHODS: A multi-institutional retrospective study was conducted evaluating patients \u3c 18 years with traumatic injuries. A Control cohort from an averaged March-September 2016-2019 time period was compared to patients injured after SHO initiation-September 2020 ( COVID cohort). Interactions between race/ethnicity or social vulnerability index (SVI), a marker of neighborhood vulnerability and socioeconomic status, and the COVID-19 timeframe with regard to the outcomes of interest were assessed using likelihood ratio Chi-square tests. Differences in injury intent, type, and mechanism were then stratified and explored by race/ethnicity and SVI separately. RESULTS: A total of 47,385 patients met study inclusion. Significant interactions existed between race/ethnicity and the COVID-19 SHO period for intent (p \u3c 0.001) and mechanism of injury (p \u3c 0.001). There was also significant interaction between SVI and the COVID-19 SHO period for mechanism of injury (p = 0.01). Children of color experienced a significant increase in intentional (COVID 16.4% vs. Control 13.7%, p = 0.03) and firearm (COVID 9.0% vs. Control 5.2%, p \u3c 0.001) injuries, but no change was seen among White children. Children from the most vulnerable neighborhoods suffered an increase in firearm injuries (COVID 11.1% vs. Control 6.1%, p = 0.001) with children from the least vulnerable neighborhoods having no change. All-terrain vehicle (ATV) and bicycle crashes increased for children of color (COVID 2.0% vs. Control 1.1%, p = 0.04 for ATV; COVID 6.7% vs. Control 4.8%, p = 0.02 for bicycle) and White children (COVID 9.6% vs. Control 6.2%, p \u3c 0.001 for ATV; COVID 8.8% vs. Control 5.8%, p \u3c 0.001 for bicycle). CONCLUSIONS: In contrast to White children and children from neighborhoods of lower vulnerability, children of color and children living in higher vulnerability neighborhoods experienced an increase in intentional and firearm-related injuries during the COVID-19 pandemic. Understanding inequities in trauma burden during times of stress is critical to directing resources and targeting intervention strategies

Discovery and characterization of potent, efficacious, orally available antimalarial Plasmepsin X inhibitors and preclinical safety assessment of UCB7362

Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development of functional liver merozoites (prophylactic activity), and blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization of an aspartyl protease binding scaffold and the discovery of potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation of safety evaluation early in the characterization of PMX inhibitors precluded compounds with a long human half-life

The Chlamydomonas Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Local failure events in prostate cancer treated with radiotherapy: A pooled analysis of 18 randomized trials from the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium (LEVIATHAN)

CONTEXT: The prognostic importance of local failure after definitive radiotherapy (RT) in National Comprehensive Cancer Network intermediate- and high-risk prostate cancer (PCa) patients remains unclear. OBJECTIVE: To evaluate the prognostic impact of local failure and the kinetics of distant metastasis following RT. EVIDENCE ACQUISITION: A pooled analysis was performed on individual patient data of 12 533 PCa (6288 high-risk and 6245 intermediate-risk) patients enrolled in 18 randomized trials (conducted between 1985 and 2015) within the Meta-analysis of Randomized Trials in Cancer of the Prostate Consortium. Multivariable Cox proportional hazard (PH) models were developed to evaluate the relationship between overall survival (OS), PCa-specific survival (PCSS), distant metastasis-free survival (DMFS), and local failure as a time-dependent covariate. Markov PH models were developed to evaluate the impact of specific transition states. EVIDENCE SYNTHESIS: The median follow-up was 11 yr. There were 795 (13%) local failure events and 1288 (21%) distant metastases for high-risk patients and 449 (7.2%) and 451 (7.2%) for intermediate-risk patients, respectively. For both groups, 81% of distant metastases developed from a clinically relapse-free state (cRF state). Local failure was significantly associated with OS (hazard ratio [HR] 1.17, 95% confidence interval [CI] 1.06-1.30), PCSS (HR 2.02, 95% CI 1.75-2.33), and DMFS (HR 1.94, 95% CI 1.75-2.15, p \u3c 0.01 for all) in high-risk patients. Local failure was also significantly associated with DMFS (HR 1.57, 95% CI 1.36-1.81) but not with OS in intermediate-risk patients. Patients without local failure had a significantly lower HR of transitioning to a PCa-specific death state than those who had local failure (HR 0.32, 95% CI 0.21-0.50, p \u3c 0.001). At later time points, more distant metastases emerged after a local failure event for both groups. CONCLUSIONS: Local failure is an independent prognosticator of OS, PCSS, and DMFS in high-risk and of DMFS in intermediate-risk PCa. Distant metastasis predominantly developed from the cRF state, underscoring the importance of addressing occult microscopic disease. However a second wave of distant metastases occurs subsequent to local failure events, and optimization of local control may reduce the risk of distant metastasis. PATIENT SUMMARY: Among men receiving definitive radiation therapy for high- and intermediate-risk prostate cancer, about 10% experience local recurrence, and they are at significantly increased risks of further disease progression. About 80% of patients who develop distant metastasis do not have a detectable local recurrence preceding it