Le rôle fondamental de l’observation directe dans la décision de confier une responsabilité professionnelle

Background: Entrustment decisions may be retrospective (based on past experiences with a trainee) or real-time (based on direct observation). We investigated judgments of entrustment based on assessor prior knowledge of candidates and based on systematic direct observation, conducted in an objective structured clinical exam (OSCE). Methods: Sixteen faculty examiners provided 287 retrospective and real-time entrustment ratings of 16 cardiology trainees during OSCE stations in 2019 and 2020. Reliability and validity of these ratings were assessed by comparing correlations across stations as a measure of reliability, differences across postgraduate years as an index of construct validity, correlation to standardized in-training exam (ITE) as a measure of criterion validity, and reclassification of entrustment as a measure of consequential validity. Results: Both retrospective and real-time assessments were highly reliable (all intra-class correlations >0.86). Both increased with year of postgraduate training. Real-time entrustment ratings were significantly correlated with standardized ITE scores; retrospective ratings were not. Real-time ratings explained 37% (2019) and 46% (2020) of variance in examination scores vs. 21% (2019) and 7% (2020) for retrospective ratings. Direct observation resulted in a different level of entrustment compared with retrospective ratings in 44% of cases (p = <0.001). Conclusions: Ratings based on direct observation made unique contributions to entrustment decisions.Contexte : La décision de confier une activité peut être rétrospective (basée sur les expériences antérieures avec un apprenant) ou en temps réel (basée sur l’observation directe). Nous avons étudié les évaluations de niveaux de confiance fondées sur des interactions antérieures des candidats par les évaluateurs et celles fondées sur l’observation directe systématique, dans le cadre d’un examen clinique objectif structuré (ECOS). Méthodes : Seize évaluateurs du corps professoral ont fourni 287 évaluations rétrospectives et en temps réel du niveau de confiance faites lors des stations d’ECOS en 2019 et 2020 concernant 16 stagiaires en cardiologie. La fiabilité et la validité de ces évaluations ont été analysées en comparant les corrélations entre les stations comme mesure de la fiabilité, les différences entre les années d’études postdoctorales comme indice de la validité de construit, la corrélation avec l’examen normalisé en cours de formation (ITE) comme mesure de la validité de critère, et le reclassement des évaluations de la confiance comme mesure de la validité corrélative. Résultats : Les évaluations rétrospectives et en temps réel étaient toutes les deux très fiables (toutes les corrélations intra-classes >0,86). Les deux augmentaient avec le niveau de formation postdoctorale. Les évaluations de la confiance en temps réel étaient significativement corrélées aux scores de l’examen normalisé en cours de formation; les évaluations rétrospectives ne l’étaient pas. Les évaluations en temps réel expliquaient 37 % (2019) et 46 % (2020) de la variance des notes d’examen, contre 21 % (2019) et 7 % (2020) pour les évaluations rétrospectives. L’observation directe a permis de reclasser 44 % des évaluations rétrospectives de la confiance (p=<0,001 dans les deux cas). Conclusion : Les évaluations basées sur l’observation directe contribuent de façon importante à la décision de confier une activité

A gene-rich linkage map in the dioecious species Actinidia chinensis (kiwifruit) reveals putative X/Y sex-determining chromosomes

<p>Abstract</p> <p>Background</p> <p>The genus <it>Actinidia </it>(kiwifruit) consists of woody, scrambling vines, native to China, and only recently propagated as a commercial crop. All species described are dioecious, but the genetic mechanism for sex-determination is unknown, as is the genetic basis for many of the cluster of characteristics making up the unique fruit. It is, however, an important crop in the New Zealand economy, and a classical breeding program would benefit greatly by knowledge of the trait alleles carried by both female and male parents. The application of marker assisted selection (MAS) in seedling populations would also aid the accurate and efficient development of novel fruit types for the market.</p> <p>Results</p> <p>Gene-rich female, male and consensus linkage maps of the diploid species <it>A. chinensis </it>have been constructed with 644 microsatellite markers. The maps consist of twenty-nine linkage groups corresponding to the haploid number n = 29. We found that sex-linked sequence characterized amplified region (SCAR) markers and the 'Flower-sex' phenotype consistently mapped to a single linkage group, in a subtelomeric region, in a section of inconsistent marker order. The region also contained markers of expressed genes, some of unknown function. Recombination, assessed by allelic distribution and marker order stability, was, in the remainder of the linkage group, in accordance with other linkage groups. Fully informative markers to other genes in this linkage group identified the comparative linkage group in the female map, where recombination ratios determining marker order were similar to the autosomes.</p> <p>Conclusion</p> <p>We have created genetic linkage maps that define the 29 linkage groups of the haploid genome, and have revealed the position and extent of the sex-determining locus in <it>A. chinensis</it>. As all <it>Actinidia </it>species are dioecious, we suggest that the sex-determining loci of other <it>Actinidia </it>species will be similar to that region defined in our maps. As the extent of the non-recombining region is limited, our result supports the suggestion that the subtelomeric region of an autosome is in the early stages of developing the characteristics of a sex chromosome. The maps provide a reference of genetic information in <it>Actinidia </it>for use in genetic analysis and breeding programs.</p

ceritinib plus nivolumab in patients with advanced alk rearranged non small cell lung cancer results of an open label multicenter phase 1b study

Abstract Introduction Induction of programmed death ligand 1 (PD-L1) expression due to constitutive oncogenic signaling has been reported in NSCLC models harboring echinoderm microtubule associated protein like 4 gene (EML4)–ALK receptor tyrosine kinase gene (ALK) rearrangements. We assessed the safety and activity of ceritinib plus nivolumab in these patients. Methods In this open-label, phase 1B, multicenter, dose escalation and expansion study, previously treated (with ALK receptor tyrosine kinase [ALK] inhibitor [ALKI]/chemotherapy) or treatment-naive patients with stage IIIB or IV ALK-rearranged NSCLC received nivolumab, 3 mg/kg intravenously every 2 weeks, plus ceritinib, 450 mg/300 mg daily, with a low-fat meal. Results In total, 36 patients were treated (a 450-mg cohort [n=14] and a 300-mg cohort [n=22]). In the 450-mg cohort, four patients experienced dose-limiting toxicities. In the 300-mg cohort, two patients experienced dose-limiting toxicities. Among ALKI-naive patients, the overall response rate (ORR) was 83% (95% confidence interval [CI]: 35.9–99.6) in the 450-mg cohort and 60% (95% CI: 26.2–87.8) in the 300-mg cohort. Among ALKI-pretreated patients, the ORR was 50% (95% CI: 15.7–84.3) in the 450-mg cohort and 25% (95% CI: 5.5–57.2) in the 300-mg cohort. The ORR point estimate was observed to be greater in patients who were positive for PD-L1 than in those who were negative for PD-L1, with overlapping CIs (e.g., at a cutoff ≥1% PD-L1, 64% of patients [95% CI: 35.1–87.2] had confirmed responses as compared with those with negative PD-L1 staining (31% [95% CI: 11.0–58.7]). The most frequently reported grade 3 or 4 adverse events were increased alanine aminotransferase level (25%), increased gamma-glutamyl transferase level (22%), increased amylase level (14%), increased lipase level (11%), and maculopapular rash (11%). The incidence of all-grade rash (grouped term) was 64% in both cohorts; grade 3 rash was reported in 29% and 14% of patients in the 450-mg and 300-mg cohorts, respectively; no grade 4 rash was reported. Conclusion Ceritinib plus nivolumab has activity; ORR appears to correlate with PD-L1 at baseline. Toxicity, especially rash, is more common than with either single agent

European registry of type A aortic dissection (ERTAAD) - rationale, design and definition criteria

Correction: Volume16 Issue1 Article Number225 DOI10.1186/s13019-021-01606-8Background: Acute Stanford type A aortic dissection (TAAD) is a life-threatening condition. Surgery is usually performed as a salvage procedure and is associated with significant postoperative early mortality and morbidity. Understanding the patient's conditions and treatment strategies which are associated with these adverse events is essential for an appropriate management of acute TAAD. Methods: Nineteen centers of cardiac surgery from seven European countries have collaborated to create a multicentre observational registry (ERTAAD), which will enroll consecutive patients who underwent surgery for acute TAAD from January 2005 to March 2021. Analysis of the impact of patient's comorbidities, conditions at referral, surgical strategies and perioperative treatment on the early and late adverse events will be performed. The investigators have developed a classification of the urgency of the procedure based on the severity of preoperative hemodynamic conditions and malperfusion secondary to acute TAAD. The primary clinical outcomes will be in-hospital mortality, late mortality and reoperations on the aorta. Secondary outcomes will be stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. Discussion: The analysis of this multicentre registry will allow conclusive results on the prognostic importance of critical preoperative conditions and the value of different treatment strategies to reduce the risk of early adverse events after surgery for acute TAAD. This registry is expected to provide insights into the long-term durability of different strategies of surgical repair for TAAD.Peer reviewe

Effects of Electrical and Structural Remodeling on Atrial Fibrillation Maintenance: A Simulation Study

Atrial fibrillation, a common cardiac arrhythmia, often progresses unfavourably: in patients with long-term atrial fibrillation, fibrillatory episodes are typically of increased duration and frequency of occurrence relative to healthy controls. This is due to electrical, structural, and contractile remodeling processes. We investigated mechanisms of how electrical and structural remodeling contribute to perpetuation of simulated atrial fibrillation, using a mathematical model of the human atrial action potential incorporated into an anatomically realistic three-dimensional structural model of the human atria. Electrical and structural remodeling both shortened the atrial wavelength - electrical remodeling primarily through a decrease in action potential duration, while structural remodeling primarily slowed conduction. The decrease in wavelength correlates with an increase in the average duration of atrial fibrillation/flutter episodes. The dependence of reentry duration on wavelength was the same for electrical vs. structural remodeling. However, the dynamics during atrial reentry varied between electrical, structural, and combined electrical and structural remodeling in several ways, including: (i) with structural remodeling there were more occurrences of fragmented wavefronts and hence more filaments than during electrical remodeling; (ii) dominant waves anchored around different anatomical obstacles in electrical vs. structural remodeling; (iii) dominant waves were often not anchored in combined electrical and structural remodeling. We conclude that, in simulated atrial fibrillation, the wavelength dependence of reentry duration is similar for electrical and structural remodeling, despite major differences in overall dynamics, including maximal number of filaments, wave fragmentation, restitution properties, and whether dominant waves are anchored to anatomical obstacles or spiralling freely

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment