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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.

Aims Treatment of patients with heart failure (HF) relies on measurement of LVEF. However, the extent to which EF is recorded varies markedly. We sought to characterize the patient group that is missing a measure of EF, and to explore the association between missing EF and outcome. Methods and results Individual data on 30 445 patients from 28 observational studies in the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) project were used to compare the prevalence of co-morbidities and outcome across three groups of HF patients: those with missing EF (HF-mEF), reduced EF (HF-REF), and preserved EF (HF-PEF). A total of 29% had HF-mEF, 52% HF-REF, and 19% HF-PEF. Compared with patients in whom EF was known, patients with HF-mEF were older, had a greater prevalence of COPD and previous stroke, and were smokers. Patients with HF-mEF were less likely to receive evidence-based treatment than those with HF-REF. Adjusted mortality in HF-mEF was similar to that in HF-REF and greater than that in HF-PEF at 3 years [HF-REF, hazard ratio (HR) 1.03, 95% confidence interval (CI) 0.95–1.12); HF-PEF, HR 0.78, 95% CI 0.71–0.86]. Conclusion Missing EF is common. The short- and long-term outcome of patients with HF-mEF is poor and they exhibit different co-morbidity profiles and treatment patterns compared with patients with known EF. HF patients with missing EF represent a high risk group.

The condition and survival of Antarctic krill (Euphausia superba) strongly depends on sea ice conditions during winter. How krill utilize sea ice depends on several factors such as region and developmental stage. A comprehensive understanding of sea ice habitat use by krill, however, remains largely unknown. The aim of this study was to improve the understanding of the krill’s interaction with the sea ice habitat during winter/early spring by conducting large-scale sampling of the ice–water interface (0–2 m) and comparing the size and developmental stage composition of krill with the pelagic population (0–500 m). Results show that the population in the northern Weddell Sea consisted mainly of krill that were <1 year old (age class 0; AC0), and that it was comprised of multiple cohorts. Size per developmental stage differed spatially, indicating that the krill likely were advected from various origins. The size distribution of krill differed between the two depth strata sampled. Larval stages with a relatively small size (mean 7–8 mm) dominated the upper two metre layer of the water column, while larger larvae and AC0 juveniles (mean 14–15 mm) were proportionally more abundant in the 0- to 500-m stratum. Our results show that, as krill mature, their vertical distribution and utilization of the sea ice appear to change gradually. This could be the result of changes in physiology and/or behaviour, as, e.g., the krill’s energy demand and swimming capacity increase with size and age. The degree of sea ice association will have an effect on large-scale spatial distribution patterns of AC0 krill and on predictions of the consequences of sea ice decline on their survival over winter.

Background: Northern Ontario, Canada has a larger elder population, more resource-based employment, and limited access to physicians and specialists compared to southern Ontario. Given these important differences, it is possible that work disability rates will vary between the two Ontario jurisdictions. Objective: To determine the association between time lost due to workplace injuries and illnesses occurring in northern vs southern Ontario and work disability duration from 2006– 2011. Methods: The study base included all lost-time claims approved by the Workplace Safety and Insurance Board in Ontario, Canada for workplace injury or illness compensation occurring between January 1, 2006 and December 31, 2011. All eligible participants had to be 18 years of age or older at the time of making the claim and participants were excluded if one of the three variables used to determine location (claimant home postal code, workplace geographical code, and WSIB firm location) were missing. Multivariable proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals adjusted for sex, age, occupation, part of body, and nature of injury relating Ontario geographical location to compensated time off work. Results: A total of 156 453 lost-time claims were approved over the study period. Injured and ill workers from northern Ontario were 16% less likely to return to work than those from southern Ontario. Adjustment for potential confounding factors had no effect. Conclusion: The disability duration in northern Ontario is longer than that in southern Ontario. Future research should focus on assessing the relevant factors associated with this observation to identify opportunities for intervention.

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.