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Abstract Background Fibrosis regression has been associated with nucleoside analogue (NA) treatment in chronic hepatitis B (CHB) patients. Although non-invasive fibrosis markers have been evaluated in CHB, their utility for monitoring on-treatment histologic regression has not been evaluated. Aims To characterize improvements in disease severity and the utility of non-invasive biomarkers in CHB NA treated patients. Methods Histology, labs, AST-to-platelet ratio index, and Fibrosis-4 (Fib-4) from treatment-naive CHB patients were evaluated at baseline and longitudinally. Relative change from baseline to various time points during treatment were evaluated. Correlative analysis of APRI and Fib-4 with histology was performed longitudinally. Results 80 CHB patients (84% male, median age 45 (IQR 32, 54)) with histology up to 17 years (median 6(IQR 3.9, 8.0)) years were studied. Median baseline Ishak fibrosis was 3 (IQR 2, 4), histologic activity index (HAI) inflammation was 9 (IQR 7, 11), and AUROC of fibrosis markers for detecting cirrhosis (Ishak ≥ 5) was >0.64. HAI improved at a rate of 54% during year 1 and 37% in year 2, both greater than in the remaining follow-up periods. Within the first year, fibrosis improved by 35%, greater than all other time periods. Non-invasive biomarkers began to correlate with histology beyond 4 years (APRI: 4–6 years: r = 0.33, p = 0.03; ≥6 years: r = 0.41, p = 0.009; Fib-4: ≥6 years: r = 0.35, p = 0.03). Conclusion Early dynamic changes in histology occur in CHB patients on NA followed by linear improvements. Non-invasive fibrosis biomarkers do not capture these dynamic changes and may demonstrate clinical utility beyond 4 years of treatment.

Background Child survival initiatives historically prioritized efforts to reduce child morbidity and mortality from infectious diseases and maternal conditions. Little attention has been devoted to paediatric injuries in resource‐limited settings. This study aimed to evaluate the demographics and outcomes of paediatric injury in a sub‐Saharan African country in an effort to improve prevention and treatment. Methods A prospective trauma registry was established at the two university teaching campuses of the University of Rwanda to record systematically patient demographics, prehospital care, initial physiology and patient outcomes from May 2011 to July 2015. Univariable analysis was performed for demographic characteristics, injury mechanisms, geographical location and outcomes. Multivariable analysis was performed for mortality estimates. Results Of 11 036 patients in the registry, 3010 (27·3 per cent) were under 18 years of age. Paediatric patients were predominantly boys (69·9 per cent) and the median age was 8 years. The mortality rate was 4·8 per cent. Falls were the most common injury (45·3 per cent), followed by road traffic accidents (30·9 per cent), burns (10·7 per cent) and blunt force/assault (7·5 per cent). Patients treated in the capital city, Kigali, had a higher incidence of head injury (7·6 per cent versus 2·0 per cent in a rural town, P < 0·001; odds ratio (OR) 4·08, 95 per cent c.i. 2·61 to 6·38) and a higher overall injury‐related mortality rate (adjusted OR 3·00, 1·50 to 6·01; P = 0·019). Pedestrians had higher overall injury‐related mortality compared with other road users (adjusted OR 3·26, 1·37 to 7·73; P = 0·007). Conclusion Paediatric injury is a significant contributor to morbidity and mortality. Delineating trauma demographics is important when planning resource utilization and capacity‐building efforts to address paediatric injury in low‐resource settings and identify vulnerable populations. This study evaluated the demographics and outcomes of paediatric injury in Rwanda through a prospective trauma registry to inform capacity‐building for prevention and treatment. Patients treated in the capital city had a higher incidence of head injury and a higher overall injury‐related mortality than those in a rural town. Pedestrians had higher overall injury‐related mortality compared with other road‐users. Falls and road traffic accidents significant contributors to pediatric injury in Rwanda

In the last century, we have passed two severe pandemics; the 1957 influenza (Asian flu) pandemic and the 1918 influenza (Spanish flu) pandemic with a high fatality rate. In the last few months, we have been again facing a new epidemic (COVID-19), which is a frighteningly high-risk disease and is globally threatening human lives. Among all attempts and presented solutions to tackle the COVID-19, a publicly available dataset of radiological imaging using chest radiography, also called chest X-ray (CXR) images, could efficiently accelerate the detection process of patients infected with COVID-19 through presented abnormalities in their chest radiography images. In this study, we have proposed a deep neural network (DNN), namely RAM-Net, a new combination of MobileNet with Dilated Depthwise Separable Convolution (DDSC), Residual blocks, and Attention augmented convolution. The network has been learned and validated using the COVIDx dataset, one of the most popular public datasets comprising the chest X-ray (CXR) images. Using this model, we could accurately identify the positive cases of COVID-19 viral infection while a new suspicious chest X-ray image is shown to the network. Our network’s overall accuracy on the COVIDx test dataset was 95.33%, with a sensitivity and precision of 92% and 99% for COVID-19 cases, respectively, which are the highest results on the COVIDx dataset to date, to the best of our knowledge. Finally, we performed an audit on RAM-Net based on the Grad-CAM’s interpretation to demonstrate that our proposed architecture detects SARS-CoV-2 (COVID-19) viral infection by focusing on vital factors rather than relying on irrelevant information.

Abstract Discrete time-translational symmetry in a periodically driven many-body system can be spontaneously broken to form a discrete time crystal, an exotic new phase of matter. We present observations characteristic of discrete time crystalline order in a driven system of paramagnetic P-donor impurities in isotopically enriched 28Si cooled below 10 K. The observations exhibit a stable subharmonic peak at half the drive frequency which remains pinned even in the presence of pulse error, a signature of discrete time crystalline order. This signal has a finite lifetime of ∼100 Floquet periods, but this effect is long-lived relative to coherent spin–spin interaction timescales, lasting ∼104 times longer. We present simulations of the system based on the paradigmatic central spin model and show good agreement with experiment. We investigate the role of dissipation and interactions within this model, and show that both are capable of giving rise to discrete time crystal-like behaviour.

Endolysins are produced by (bacterio)phages to rapidly degrade the bacterial cell wall and release new viral particles. Despite sharing a common function, endolysins present in phages that infect a specific bacterial species can be highly diverse and vary in types, number, and organization of their catalytic and cell wall binding domains. While much is now known about the biochemistry of phage endolysins, far less is known about the implication of their diversity on phage–host adaptation and evolution. Using CRISPR-Cas9 genome editing, we could genetically exchange a subset of different endolysin genes into distinct lactococcal phage genomes. Regardless of the type and biochemical properties of these endolysins, fitness costs associated to their genetic exchange were marginal if both recipient and donor phages were infecting the same bacterial strain, but gradually increased when taking place between phage that infect different strains or bacterial species. From an evolutionary perspective, we observed that endolysins could be naturally exchanged by homologous recombination between phages coinfecting a same bacterial strain. Furthermore, phage endolysins could adapt to their new phage/host environment by acquiring adaptative mutations. These observations highlight the remarkable ability of phage lytic systems to recombine and adapt and, therefore, explain their large diversity and mosaicism. It also indicates that evolution should be considered to act on functional modules rather than on bacteriophages themselves. Furthermore, the extensive degree of evolvability observed for phage endolysins offers new perspectives for their engineering as antimicrobial agents.

REVIEW OBJECTIVE This review seeks to establish the current state of knowledge regarding physical assessment skills taught in nursing programs globally. It aims to explore the literature on physical assessment skills taught in nursing curricula globally, skills used by nurses in practice, skills used by students, and core physical assessment skills that are important to teach nursing students.

En 1968 en Ontario et en 1970 au Québec naissaient différents projets visant à établir une meilleure coordination des services et des ressources des bibliothèques universitaires. Un de ces projets, conçu en mai 1973, vise à la concrétisation d’une formule de télécatalogage en coopération entre les universités du Québec et de l’Ontario. Après avoir décrit le contexte historique qui a entraîné l’élaboration de ce projet, l’auteur en fait une description succincte (détails techniques d’opération, problèmes de bilinguisme, etc.). L’échéancier a été respecté puisque la deuxième étape devant conduire à l’installation des périphériques et à leur utilisation réelle sera, tel que prévu, complétée sous peu. Cette concertation des efforts devrait entraîner, à long terme, une amélioration considérable au plan de la qualité des services.

To study the binding mechanism of disparlure (7,8)-epoxy-2-methyloctadecane enantiomers with pheromone-binding proteins (PBPs) of the gypsy moth, oxygen-17 or 18 and 5,5,6,6-deuterium labelled disparlure enantiomers were prepared in an efficient, enantioselective route. Key steps involve the asymmetric α-chlorination of dodecanal by SOMO catalysis and Mitsunobu inversion of a 1, 2-chlorohydrin. The pheromone, (+)-disparlure (7R, 8S), was tested in two infested zones, demonstrating that it is very attractive towards male gypsy moths. Studies of the binding of (+)-disparlure and its antipode to gypsy moth PBPs by 2H &17O NMR at 600 MHz are reported. Chemical shifts, spin-lattice relaxation times and transverse relaxation times of deuterium atoms of disparlure enantiomers in 2H NMR show that binding of disparlure enantiomers to PBP1 differs from binding to PBP2, as expected from their opposite binding preferences (PBP1 binds (-)-disparlure, and PBP2 binds (+)-disparlure more strongly). Models of the disparlure enantiomers bound to one internal binding site and two external binding sites of both PBPs were constructed. The observed chemical shift changes of deuterated ligand signals, from non-bound to bound, T1 and T2 values are correlated with results from the simulations. Together these results suggest that the disparlure enantiomers adopt distinct conformations within the binding sites of the two PBPs and interact with residues that line the sites.

Limited data exist evaluating the effect of blood pressure (BP) on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with mechanical thrombectomy (MT). We sought to evaluate the association of BP levels on clinical outcomes among patients with acute ischemic stroke with large vessel occlusion treated with MT. Studies were identified that reported the association of systolic BP (SBP) or diastolic BP levels before, during, or after MT on the outcomes of patients with acute ischemic stroke treated with MT. Unadjusted and adjusted analyses of studies reporting odds ratios (OR adj ) per 10 mm Hg BP increment were performed. Our analysis included 25 studies comprising 6474 patients. Higher pre-MT mean SBP ( P =0.008) and post-MT maximum SBP ( P =0.009) levels were observed in patients who died within 3 months. Patients with 3-month functional independence were noted to have lower pre-MT ( P <0.001) and post-MT maximum SBP levels ( P <0.001). In adjusted analyses, increasing post-MT maximum SBP and diastolic BP levels were associated with 3-month mortality (OR adj , 1.19 [95% CI,1.00–1.43]; I 2 =78%, P value for Cochran Q test: 0.001) and symptomatic intracranial hemorrhage (OR adj , 1.65 [95% CI, 1.11–2.44]; I 2 =0%, P value for Cochran Q test: 0.80), respectively. Increasing pre- and post-MT mean SBP levels were associated with lower odds of 3-month functional independence (OR adj , 0.86 [95% CI, 0.77–0.96]; I 2 =18%, P value for Cochran Q test: 0.30) and (OR adj , 0.80 [95% CI, 0.72–0.89]; I 2 =0%, P value for Cochran Q test: 0.51), respectively. In conclusion, elevated BP levels before and after MT are associated with adverse outcomes among patients with acute ischemic stroke with large vessel occlusion.