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Background:. In this observational study, we describe the medium-term outcomes of total joint arthroplasty (TJA) in human immunodeficiency virus (HIV)-positive patients in Malawi, a low-income country. With a high prevalence of HIV and increasing arthroplasty rates in low and middle-income countries, understanding the outcomes of TJA in this unique cohort of patients is essential to ensure that surgical practice is evidence-based. Methods:. Data for all HIV-positive patients who had TJA from January 2005 to March 2020 were extracted from the National Arthroplasty Registry of the Malawi Orthopaedic Association (NARMOA). From January 2005 to March 2020, a total of 102 total hip arthroplasties (THAs) and 20 total knee arthroplasties (TKAs) were performed in 97 patients who were HIV-positive and without hemophilia or a history of intravenous drug use. The mean length of follow-up was 4 years and 3 months (range, 6 weeks to 15 years) in the THA group and 4 years and 9 months (range, 6 weeks to 12 years) in the TKA group. The mean patient age was 50 years (range, 21 to 76 years) and 64 years (range, 48 to 76 years) at the time of THA and TKA, respectively. Results:. The primary indication for THA was osteonecrosis (66 hips). In the THA group, the mean preoperative Oxford Hip Score and Harris hip score were 14.0 (range, 2 to 33) and 29.4 (range, 1 to 64), respectively, and improved to 46.6 (range, 23 to 48) and 85.0 (range, 28 to 91) postoperatively. The primary indication for TKA was osteoarthritis (19 knees). The mean preoperative Oxford Knee Score was 14.9 (range, 6 to 31) and increased to 46.8 (range, 40 to 48) postoperatively. In patients who underwent THA, there was 1 deep infection (1 of 102 procedures), and 6 patients developed aseptic loosening (6 of 102). There was 1 postoperative superficial infection following TKA (1 of 20 procedures), and 1 patient developed aseptic loosening (1 of 20). Postoperative 6-week mortality among all patients was zero. Conclusions:. To our knowledge this is the largest medium-term follow-up of HIV-positive patients, without hemophilia or a history of intravenous drug use, who have had TJA in a low-income country. This study demonstrated good medium-term results among HIV-positive patients undergoing TJA, low complication rates, and improvements in patient-reported outcome measures. Level of Evidence:. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

The external mucosal surfaces of the fish harbor complex microbial communities, which may play pivotal roles in the physiological, metabolic, and immunological status of the host. Currently, little is known about the composition and role of these communities, whether they are species and/or tissue specific and whether they reflect their surrounding environment. Co-culture of fish, a common practice in semi-intensive aquaculture, where different fish species cohabit in the same contained environment, is an easily accessible and informative model toward understanding such interactions. This study provides the first in-depth characterization of gill and skin microbiomes in co-cultured Nile tilapia (Oreochromis niloticus) and grey mullet (Mugil capito) in semi-intensive pond systems in Egypt using 16S rRNA gene-based amplicon sequencing. Results showed that the microbiome composition of the external surfaces of both species and pond water was dominated by the following bacterial phyla: Proteobacteria, Fusobacteriota, Firmicutes, Planctomycetota, Verrucomicrobiota, Bacteroidota, and Actinobacteriota. However, water microbial communities had the highest abundance and richness and significantly diverged from the external microbiome of both species; thus, the external autochthonous communities are not a passive reflection of their allochthonous communities. The autochthonous bacterial communities of the skin were distinct from those of the gill in both species, indicating that the external microbiome is likely organ specific. However, gill autochthonous communities were clearly species specific, whereas skin communities showed higher commonalities between both species. Core microbiome analysis identified the presence of shared core taxa between both species and pond water in addition to organ-specific taxa within and between the core community of each species. These core taxa included possibly beneficial genera such as Uncultured Pirellulaceae, Exiguobacterium, and Cetobacterium and opportunistic potential pathogens such as Aeromonas, Plesiomonas, and Vibrio. This study provides the first in-depth mapping of bacterial communities in this semi-intensive system that in turn provides a foundation for further studies toward enhancing the health and welfare of these cultured fish and ensuring sustainability.

AIMS OF THE STUDY: In Switzerland, there has been a boom in the market for cannabidiol (CBD) products in recent years. However, little is known on the prevalence, modes of administration and motives for use of CBD products. The aim of the present study was to fill this gap using recent (2019) data from the Cohort Study on Substance Use Risk Factors (C-SURF). METHODS: Between April and December 2019, an unselected sample of 5233 Swiss young men from the French- and German-speaking regions (mean age 28.2 years, standard deviation 1.3) completed a self-report questionnaire covering measures of use of CBD products, modes of administration and motives to use of CBD, tetrahydrocannabinol (THC) and cigarettes. Descriptive statistics were used to estimate prevalence of self-reported use, modes of administration and motives to use CBD, whereas logistic regression models were used to test the associations of linguistic region, THC and tobacco use with use of CBD. RESULTS: Lifetime and 12-month prevalence of self-reported use of CBD were 32.4% and 18.5%, respectively. Among past 12-month CBD users, 79.4% used CBD once a month or less often, whereas 20.6% used it more than once a month. The most often reported modes of administration of CBD were in association with tobacco: flowers mixed with tobacco (67.5%), and CBD cigarettes with tobacco (37.1%), while 18.6% used flowers without tobacco. The three most reported reasons for using CBD were: out of curiosity (74.0%), to feel the effects of THC (38.1%) and for well-being and health (37.5%). In multivariable models, CBD use was associated with use of THC (odds ratio [OR] 9.85, 95% confidence interval [CI] 8.28–11.73), cigarettes (OR 2.74, 95% CI 2.28–3.29) or e-cigarettes (OR 1.5795% CI 1.27–1.95), as well as for the linguistic region (French-speaking vs German-speaking region OR 1.3895% CI 1.15–1.65). CONCLUSIONS: Self-reported use of CBD is common among young Swiss men: about one third used CBD in their life and about one in five in the previous 12 months. However, the vast majority of CBD users used it infrequently and out of curiosity. CBD use was particularly prevalent among users of THC and cigarette smokers. CBD was most often used in combination with tobacco, thus exposing users to risks associated with smoking tobacco products.

No consensus has been reached on the optimal antibiotic regimen to treat Cutibacterium acnes PJIs (Ca-PJIs). In vitro studies showed excellent rifampicin efficacy against biofilm-associated C. acnes infections, but clinical studies did not confirm the superiority of rifampicin-combined therapy over monotherapy. This prospective cohort study was undertaken to analyze the outcomes of 70 patients who underwent exchange arthroplasty for chronic monomicrobial Ca-PJI and were treated with rifampicin or without between 2004 and 2019. The 37 patients treated from January 2004 to August 2014 were prescribed rifampicin-combination therapy and the 33 treated from September 2014 to December 2019 received monotherapy without rifampicin. The primary endpoint was the 2-year Kaplan–Meier-estimated reinfection-free probability, including relapses and new-pathogen PJIs. The 2-year reinfection-free rate was high and not different for patients who had received rifampicin or not (89.2% vs. 93.8%, respectively; p = 0.524). None of the patients relapsed and six developed new-pathogen PJIs. Our results do not support a benefit of rifampicin-combination therapy for patients who underwent exchange arthroplasty for chronic Ca-PJIs.

Different processes have been proposed to meet the global need for renewable fuel. The Biomass to Liquid process (BtL) converts biomass via the Fischer-Tropsch route to hydrocarbon chains that can be refined to transport fuel. With the addition of electrolytic hydrogen to the Power and Biomass to Liquid process (PBtL), the carbon efficiency can be increased relative to the BtL process. It was shown in previous studies that the PBtL concept has an economic edge over BtL when cheap electricity is available to maximize the fuel yield. In this study, a techno-economic analysis is conducted for a hybrid process concept which can switch operation modes from electrolysis enhanced to only biomass conversion. In case studies the effect of the Fischer-Tropsch conversion, H2/CO ratio of the Fischer-Tropsch feed and the biomass feed rate in the electrolysis enhanced mode are analyzed. Every process configuration is modeled based on experimentally validated unit models from literature in the commercial software Aspen Plus and analyzed using DLR’s software tool TEPET. For a 200 MWth biomass input plant, production costs of 1.08 €2019/L for the hybrid concept with a carbon efficiency of 53.3% compared to 0.66 €2019/L for BtL with 35.4% and 1 €2019/L for PBtL with 61.1% were found based on the Finnish day-ahead market for the base case. The net production cost for the hybrid concept can be decreased by 0.07 €2019/L when a Fischer-Tropsch H2/CO ratio of 1.6 instead of 2.05 is used.

Abstract Lightning strikes can be routinely observed by the radio receivers that measure electromagnetic signals in the very low frequency range. The acquired pulses called atmospherics provide valuable details about source lightning discharges and also about the Earth‐ionosphere waveguide where they can propagate thousands of kilometers. The automatic acquisition of the events requires also automatic methods for extraction of atmospherics' details to confirm the observed trends with statistical significance. For this purpose, we have developed a method based on a deep learning approach to automatically obtain the type of atmospherics, their exact time, and the frequency range from the frequency‐time spectrograms. The method that employs convolutional neural networks is designed to be adaptable to scientific needs and provide reliable results according to the requirements on the sensitivity to events, computation performance, and precision of extracted details. The efficiency and specific steps of our method are demonstrated for data recorded by the ELMAVAN‐G instrument. The comprehensive description of the method allows its usage for regular characterization of the ionospheric D‐layer or for other similar applications in the future.

Background: The retina has gained increasing attention in non-ophthalmological research in recent years. The pattern electroretinogram (PERG), a method to evaluate retinal ganglion cell function, has been used to identify objective correlates of the essentially subjective state of depression. A reduction in the PERG contrast gain was demonstrated in patients with depression compared to healthy controls with normalization after remission. PERG responses are not only modulated by stimulus contrast, but also by check size and stimulation frequency. Therefore, the rationale was to evaluate potentially more feasible procedures for PERG recordings in daily diagnostics in psychiatry.Methods: Twenty-four participants (12 patients with major depression (MDD) and 12 age- and sex-matched healthy controls) were examined in this pilot study. We investigated PERG amplitudes for two steady-state pattern reversal frequencies (12.5/18.75 rps) and four sizes of a checkerboard stimulus (0.8°, 1.6°, 3.2°, and 16°) to optimize the PERG recordings in MDD patients.Results: Smaller PERG amplitudes in MDD patients were observed for all parameters, whereby the extent of the reduction appeared to be stimulus-specific. The most pronounced decline in the PERG of MDD patients was observed at the higher stimulation frequency and the finest pattern, whilst responses for the largest check size were less affected. Following the PERG ratio protocol for early glaucoma, where similar stimulus dependent modulations have been reported, we calculated PERG ratios (0.8°/16°) for all participants. At the higher frequency (18.75 rps), significantly reduced ratios were observed in MDD patients.Conclusion: The “normalization” of the PERG responses—via building a ratio—appears to be a very promising approach with regard to the development of an objective biomarker of the depressive state, facilitating inter-individual assessments of PERG recordings in patients with psychiatric disorders.

Background: The COVID-19 pandemic and its countermeasures may have had a significant impact on the psychological well-being of specific population subgroups. The present study investigated whether sexual minority men (defined here as attracted partly or exclusively to men) from an ongoing cohort study of young Swiss men experienced different psychological impacts, levels of substance use and addictive behaviors, and to which degree pre-existing vulnerabilities and participants experiences during the crisis might explain these differences.Methods: An ongoing cohort sample based on the general population of young Swiss men (mean age = 29.07 years; SD = 1.27) was assessed before and during the COVID-19 crisis for depression, stress, sleep quality, substance use and addictive behaviors. Additionally, during the crisis, we assessed its impact in form of fear, isolation and traumatic experiences. Potential associations between these outcomes and sexual orientation (sexual minority vs. heterosexual) were tested using linear regression models. It was additionally estimated to which degree these associations were attenuated if adjusted for differences in mental health, personality and socioeconomic status before the crisis, as well as the experience of the COVID-19 crisis (infection with the virus and changes to work situation).Results: Compared to heterosexual men, sexual minority men showed higher levels of psychological trauma (b = 0.37 [0.25, 0.49]), fear (b = 0.18 [0.06, 0.30]) and isolation (b = 0.32 [0.20, 0.44]) due to the COVID-19 pandemic as well as higher levels of depression (b = 0.31 [0.20, 0.41]) and lower sleep quality (b = −0.13 [−0.24, −0.02]) during the crisis. These differences were to a large degree explained by higher pre-crisis levels of mental health problems and the personality dimension of neuroticism-anxiety. Sexual minority men showed higher overall levels of substance use and addictive behaviors, but these differences were already present before the crisis.Conclusion: The COVID-19 crisis may have worsened pre-existing vulnerabilities in sexual minority men, leading to its greater psychological impact on them than on heterosexual men. Reducing minority stress due to sexual orientation may help not only to improve mental health among important proportions of the population but also to reduce their vulnerability to crises. Services offering psychological support to sexual minorities may need to be reinforced during crises.

In this work, the techno-economic and exergy analyses of two gasification technologies with integration into heat and power combined cycles are presented: i). Circulating fluidized bed (CFB) and ii). Dual fluidized bed (DFB) systems. As feedstock, lignocellulosic biomass (sugarcane bagasse, SCB) was considered. The gasification process of the fluidized-bed systems (circulating and dual bed) and the syngas conversion were performed using Aspen Plus® software. The process design includes biomass drying and gasification, syngas cleaning, combustion, power generation, and heat recovery. The SCB-DFB system has the lowest irreversibility rate and, as a result, the highest overall performance and power generation (achieving 32% in the gasification system and 53% of exergy efficiency when coupled with the combined cycle). From the techno-economic assessment, the SCB-DFB system has the lowest total production costs per unit of energy. Hence, the dual fluidized bed systems could be a more competitive technology for the agro-industrial sector to generate power from lignocellulosic materials.

Loss of T cell immunogenicity due to mutations in virally encoded epitopes is a well-described adaptation strategy to limit host anti-viral immunity. Another described, but less understood, adaptation strategy involves the selection of mutations within epitopes that retain immune recognition, suggesting a benefit for the virus despite continued immune pressure (termed non-classical adaptation). To understand this adaptation strategy, we utilized a single cell transcriptomic approach to identify features of the HIV-specific CD8+ T cell responses targeting non-adapted (NAE) and adapted (AE) forms of epitopes containing a non-classical adaptation. T cell receptor (TCR) repertoire and transcriptome were obtained from antigen-specific CD8+ T cells of chronic (n=7) and acute (n=4) HIV-infected subjects identified by either HLA class I tetramers or upregulation of activation markers following peptide stimulation. CD8+ T cells were predominantly dual tetramer+, confirming a large proportion of cross-reactive TCR clonotypes capable of recognizing the NAE and AE form. However, single-reactive CD8+ T cells were identified in acute HIV-infected subjects only, providing the potential for the selection of T cell clones over time. The transcriptomic profile of CD8+ T cells was dependent on the autologous virus: subjects whose virus encoded the NAE form of the epitope (and who transitioned to the AE form at a later timepoint) exhibited an ‘effective’ immune response, as indicated by expression of transcripts associated with polyfunctionality, cytotoxicity and apoptosis (largely driven by the genes GZMB, IFNɣ, CCL3, CCL4 and CCL5). These data suggest that viral adaptation at a single amino acid residue can provide an alternative strategy for viral survival by modulating the transcriptome of CD8+ T cells and potentially selecting for less effective T cell clones from the acute to chronic phase.

Objectives To describe the relations between baseline clinical characteristics of the Applied Public-Private Research enabling OsteoArthritis Clinical Headway (IMI-APPROACH) participants and their predicted probabilities for knee osteoarthritis (OA) structural (S) progression and/or pain (P) progression.Methods Baseline clinical characteristics of the IMI-APPROACH participants were used for this study. Radiographs were evaluated according to Kellgren and Lawrence (K&L grade) and Knee Image Digital Analysis. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Numeric Rating Scale (NRS) were used to evaluate pain. Predicted progression scores for each individual were determined using machine learning models. Pearson correlation coefficients were used to evaluate correlations between scores for predicted progression and baseline characteristics. T-tests and χ2 tests were used to evaluate differences between participants with high versus low progression scores.Results Participants with high S progressions score were found to have statistically significantly less structural damage compared with participants with low S progression scores (minimum Joint Space Width, minJSW 3.56 mm vs 1.63 mm; p

Abstract Geophysical analysis of the Earth's lower mantle has revealed the presence of two superstructures characterized by low shear wave velocities on the core‐mantle boundary. These Large Low Shear Velocity Provinces (LLSVPs) play a crucial role in the dynamics of the lower mantle and act as the source region for deep‐seated mantle plumes. However, their origin, and the characteristics of the surrounding deep mantle, remain enigmatic. Mantle plumes located above the margins of the LLSVPs display evidence for the presence of this deep‐seated, thermally and/or chemically heterogeneous mantle material ascending into the melting region. As a result, analysis of the spatial geochemical heterogeneity in ocean island basalts provides constraints on the structure of the Earth's lower mantle and the origin of the LLSVPs. In this study, we focus on the Galápagos Archipelago in the eastern Pacific, where bilateral asymmetry in the radiogenic isotopic composition of erupted basalts has been linked to the presence of LLSVP material in the underlying plume. We show, using spatial variations in the major element contents of high‐MgO basalts, that the isotopically enriched south‐western region of the Galápagos mantle—assigned to melting of LLSVP material—displays no evidence for lithological heterogeneity in the mantle source. As such, it is unlikely that the Pacific LLSVP represents a pile of subducted oceanic crust. Clear evidence for a lithologically heterogeneous mantle source is, however, found in the north‐central Galápagos, indicating that a recycled crustal component is present near the eastern margin of the Pacific LLSVP, consistent with seismic observations.

AIMS: The COVID-19 pandemic caused many disturbances to daily life worldwide and may also have significantly affected people’s psychological well-being. The present study aimed to describe the psychological impact of the crisis on our sample of young Swiss men and to examine differences due to their linguistic region, experiencing COVID-19 symptoms and living arrangements. METHODS: Based on an ongoing cohort study, we assessed a general-population sample of young Swiss men (n = 2345; average 29 years old) shortly before (from April 2019) and early on during the COVID-19 crisis (between 13 May and 8 June 2020). This was a unique opportunity to estimate the crisis’ psychological impact in the form of depression, perceived stress and sleep quality (assessed before and during COVID-19), and any crisis-induced fears, isolation or psychological trauma. Associations of psychological impact with living arrangements, experiencing COVID-19 symptoms and linguistic region (German-speaking vs French-speaking) were investigated using linear regression models. FINDINGS: By the time participants responded to our questionnaire, less than 1% had been tested positive for COVID-19, 2.6% had been tested negative and 14.7% had had some COVID-19 symptoms but had not been tested. About 8.2% of the sample reported at least some symptoms of psychological trauma (≥24 points on the Impact of Event Scale). On average, participants reported higher levels of fear for others (43.6% at least moderate) and economic fear (12.7% at least moderate) than fear for themselves (5.8% at least moderate). Those living alone and those who reported having COVID-19 symptoms themselves, or knowing someone with symptoms, reported higher overall psychological impact in the form of depression, perceived stress, sleep quality, psychological trauma, fear and isolation. Associations with linguistic region varied by outcome, with higher levels of depression and fear in French-speaking regions and higher levels of perceived stress and isolation in German-speaking regions. INTERPRETATION: The crisis had a considerable impact on the psychological well-being of our sample of young Swiss men, and some groups were more affected than others: those living alone and those who had shown COVID-19 symptoms themselves or had known someone with symptoms may have felt a greater psychological impact from the crisis. Supporting those at a higher risk of psychological consequences in such crises, whether through structural measures or via individual support, should be an important aspect of crisis management and could help reduce the overall impact of the current pandemic on Switzerland’s population.

Abstract Background The aim of the study is to investigate how well patients remember the radiologist’s name after a radiological examination, and whether giving the patient a business card improves the patient’s perception of the radiologist’s professionalism and esteem. Methods In this prospective and randomized two-centre study, a total of 141 patients with BI-RADS 1 and 2 scores were included. After screening examination comprising mammography and ultrasound by a radiologist, 71 patients received a business card (group 1), while 70 received no business card (group 2). Following the examination, patients were questioned about their experiences. Results The patients in group 1 could remember the name of the radiologist in 85% of cases. The patients in group 2, in contrast, could only remember the name in 7% of cases (p

A new version of the Australian Community Climate and Earth System Simulator coupled model, ACCESS-CM2, has been developed for a wide range of climate modelling research and applications. In particular, ACCESS-CM2 is one of Australia's contributions to the World Climate Research Programme's Coupled Model Intercomparison Project Phase 6 (CMIP6). Compared with the ACCESS1.3 model used for our CMIP5 submission, all model components have been upgraded as well as the coupling framework (OASIS3-MCT) and experiment control system (Rose/Cylc). The component models are: UM10.6 GA7.1 for the atmosphere, CABLE2.5 for the land surface, MOM5 for the ocean, and CICE5.1.2 for the sea ice. This paper describes the model configuration of ACCESS-CM2, documents the experimental set up, and assesses the model performance for the preindustrial spin-up simulation in comparison against (reconstructed) observations and ACCESS1.3 results. While the performance of the two generations of the ACCESS coupled model is largely comparable, ACCESS-CM2 shows better global hydrological balance, more realistic ocean water properties (in terms of spatial distribution) and meridional overturning circulation in the Southern Ocean but a poorer simulation of the Antarctic sea ice and a larger energy imbalance at the top of atmosphere. This energy imbalance reflects a noticeable warming trend of the global ocean over the spin-up period.

We collect here recent results covering various aspects of the dynamical properties of interacting particle systems. In Section 1 we study the hydrodynamic limit of a facilitated exclusion process. Section 2 evidences a cutoff phenomenon for the mixing time of the weakly asymmetric exclusion process. Section 3 presents a study of the infection time in the Duarte model. Finally, Section 4 presents the study of a front propagation in the FA-If model.

El objetivo de este estudio es comprobar la evolución de las especificaciones de la prestación analítica (EPA) utilizadas en programas de garantía externa de la calidad (EQA) y el papel de un programa de categoría 1 en la vigilancia de la estandarización de la prestación de los laboratorios clínicos en España.

On social media, there is a very large number of audiovisual publications. This represents a considerable analytical material that can be studied from multiple angles. In addition to analyzing the contents themselves, taking into account comments related to audiovisual publications makes it possible to understand their reception. It also allows us to grasp the social dynamics that are being set up on online exchange platforms. Focusing on data collected on Facebook, this article shows how this methodology makes it possible to approach a topic as sensitive as the Israeli-Palestinian conflict. It is specifically aimed at presenting how the reference to Nazism serves as a means of delegitimizing the adversary, whether pro-Palestinian or pro-Israeli. The author observes that the comment sections on Facebook are above all spaces of self-assertion and exchange between people who share the same opinions. Little room is left for intergroup exchanges that could lead to the development of a true dialogue. Hate speech is frequently found and is sometimes based on references to Nazism. In the end, in-depth analysis of the comments makes it possible to delimit four types of discursive strategies of (de)legitimation.

Abstract Background Grain yield of wheat is greatly associated with the population of wheat spikes, i.e., $$spike~number~\text {m}^{-2}$$ spikenumberm-2 . To obtain this index in a reliable and efficient way, it is necessary to count wheat spikes accurately and automatically. Currently computer vision technologies have shown great potential to automate this task effectively in a low-end manner. In particular, counting wheat spikes is a typical visual counting problem, which is substantially studied under the name of object counting in Computer Vision. TasselNet, which represents one of the state-of-the-art counting approaches, is a convolutional neural network-based local regression model, and currently benchmarks the best record on counting maize tassels. However, when applying TasselNet to wheat spikes, it cannot predict accurate counts when spikes partially present. Results In this paper, we make an important observation that the counting performance of local regression networks can be significantly improved via adding visual context to the local patches. Meanwhile, such context can be treated as part of the receptive field without increasing the model capacity. We thus propose a simple yet effective contextual extension of TasselNet—TasselNetv2. If implementing TasselNetv2 in a fully convolutional form, both training and inference can be greatly sped up by reducing redundant computations. In particular, we collected and labeled a large-scale wheat spikes counting (WSC) dataset, with 1764 high-resolution images and 675,322 manually-annotated instances. Extensive experiments show that, TasselNetv2 not only achieves state-of-the-art performance on the WSC dataset ($$91.01\%$$ 91.01% counting accuracy) but also is more than an order of magnitude faster than TasselNet (13.82 fps on $$912\times 1216$$ 912×1216 images). The generality of TasselNetv2 is further demonstrated by advancing the state of the art on both the Maize Tassels Counting and ShanghaiTech Crowd Counting datasets. Conclusions This paper describes TasselNetv2 for counting wheat spikes, which simultaneously addresses two important use cases in plant counting: improving the counting accuracy without increasing model capacity, and improving efficiency without sacrificing accuracy. It is promising to be deployed in a real-time system with high-throughput demand. In particular, TasselNetv2 can achieve sufficiently accurate results when training from scratch with small networks, and adopting larger pre-trained networks can further boost accuracy. In practice, one can trade off the performance and efficiency according to certain application scenarios. Code and models are made available at: https://tinyurl.com/TasselNetv2.

Abstract Background Chest tubes are routinely used to evacuate shed mediastinal blood in the critical care setting in the early hours after heart surgery. Inadequate evacuation of shed mediastinal blood due to chest tube clogging may result in retained blood around the heart and lungs after cardiac surgery. The objective of this study was to compare if active chest tube clearance reduces the incidence of retained blood complications and associated hospital resource utilization after cardiac surgery. Methods Propensity matched analysis of 697 consecutive patients who underwent cardiac surgery at a single center. 302 patients served as a baseline control (Phase 0), 58 patients in a training and compliance verification period (Phase 1) and 337 were treated prospectively using active tube clearance (Phase 2). The need to drain retained blood, pleural effusions, postoperative atrial fibrillation, ICU resource utilization and hospital costs were assessed. Results Propensity matched patients in Phase 2 had a reduced need for drainage procedures for pleural effusions (22% vs. 8.1%, p

Abstract Three fluorescent organic compounds—furocoumarin (FC), dansyl aniline (DA), and 7-hydroxycoumarin-3-carboxylic acid (CC)—are mixed to produce almost pure white light emission (WLE). This novel mixture is immobilised in silica aerogel and applied as a coating to a UV LED to demonstrate its applicability as a low-cost, organic coating for WLE via simultaneous emission. In ethanol solution and when immobilised in silica aerogel, the mixture exhibits a Commission Internationale d’Eclairage (CIE) chromaticity index of (0.27, 0.33). It was observed that a broadband and simultaneous emission involving coumarin carboxylic acid, furocoumarin and dansyl aniline played a vital role in obtaining a CIE index close to that of pure white light.

Abstract We present a system for the removal of objects from videos. As input, the system only needs a user to draw a few strokes on the first frame, roughly delimiting the objects to be removed. To the best of our knowledge, this is the first system allowing the semi-automatic removal of objects from videos with complex backgrounds. The key steps of our system are the following: after initialization, segmentation masks are first refined and then automatically propagated through the video. Missing regions are then synthesized using video inpainting techniques. Our system can deal with multiple, possibly crossing objects, with complex motions, and with dynamic textures. This results in a computational tool that can alleviate tedious manual operations for editing high-quality videos.

Background: Cytochrome P450 (CYP) enzymes are essential in the metabolism of most drugs used today. Single nucleotide polymorphism(s) occurring in CYP genes can adversely affect drug pharmacokinetics, efficacy, and safety. Individuals carrying the CYP2C8*2 c.805A > T (CYP2C8*2; rs11572103) allele have impaired amodiaquine metabolism, increased risk of amodiaquine-related adverse events, and may promote the selection of drug-resistant parasite strains. This study investigated the distribution of the CYP2C8*2 allele in Brazzaville, Republic of Congo, where artesunate + amodiaquine is used as the second-line treatment for uncomplicated Plasmodium falciparum malaria. Methods: A total of 285 febrile children visiting the Marien Ngouabi paediatric hospital were genotyped for CYP2C8*2 using PCR-restriction fragment length polymorphism (PCR-RFLP). The allele frequencies and genotype distribution were determined. Results: The CYP2C8*2 allele was successfully genotyped in 75% (213/285) of the study participants. The CYP2C8*2A allele had a frequency of 63%, whereas the CYP2C8*2T allele had a frequency of 37%. Genotypes CYP2C8*2AA (rapid metabolizer), CYP2C8*2AT (intermediate metabolizer), and CYP2C8*2TT (poor metabolizer) were observed in 44%, 38%, and 18% of the investigated participants, respectively. Conclusions: This study gives the first description of CYP2C8*2 allele distribution in the Republic of Congo and highlights the potential risk of amodiaquine-related adverse events. Information from this study will be beneficial during pharmacovigilance investigations. Keywords: Cytochrome P450, CYP2C8, Brazzaville, Republic of Congo, Pharmacogenetics

Renal transplant recipients (RTRs) are highly susceptible to infections, and antimicrobial resistance is an increasing problem with limited treatment options. Faecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection and may be used for patients with intestinal carriage of multidrug-resistant (MDR) microorganisms. We present a RTR who suffered from recurrent urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase-producing (ESBL+) Klebsiella pneumoniae. Blood and urinary isolates revealed the same antibiotic susceptibility pattern, and whole-genome sequencing confirmed identical isolates in blood and urine. Despite several treatments with meropenem, the patient experienced recurrent infections that caused hospitalisation. ESBL+ K. pneumoniae was isolated in faeces. In an attempt to decolonise the gut, FMT was performed. A few days after nasojejunal infusion of donor faeces, the patient experienced a single relapse of UTI. During the subsequent 12 months, no further episodes of UTI occurred. Absence of ESBL+ K. pneumoniae in urine and faeces was demonstrated during follow-up. We conclude that FMT may be an effective treatment in RTRs with recurrent UTIs caused by intestinal colonisation with MDR organisms.

Abstract Background Sibling relation over chosen STR loci and localized database is yet to be developed in Indonesia like into many other countries despite the demand of varied ethnic population, catastrophes and civil conflict that call forensic preparedness. The targeted application includes human genomic typing and profile, kinship/sibship relation, forensic applications, individual identification, and or claneology tracing. Consequently, this study devotes on sibship in assessing and establishing preferable STR loci and allelic sharing extent amongst Madurese full sibling. Materials and methods One hundred blood samples were used to examine sibling relationship among 50 full siblings (25 pairs) assigned from a total of 100 individuals of 25 Madura families. Sibship relation was done by STR technique profile by 12 loci (CSF1PO, F13B, FES, TH01, TPOX, vWA, D5S818, D7S820, D8S1179, D13S317, D16S539, and D18S51) and a sex-typing amelogenin gene locus Results From 300 observations (25 pairs of full-sibling × 12 loci) of genotyped STR allele, of allele sharing, has found 4 STR loci: FES, CSF1PO, F13, and D8S1179 with high-shared allelic frequency in two alleles sharing among twelve STR loci by 52%, 52%, 44%, and 40% respectively. As for the four main loci of full sibling with one allele sharing, i.e, D7S820, D18S51, vWA, and THO1, have a sequence of percentages from large to small as follows: 76%, 76%, 72%, and 60%, respectively. Furthermore, STR locus VWA expressed null shared allele in 24 allele-sharing category. Likewise, F13 and FES both typed null allele in zero allele-sharing category among these full sibling Conclusion Through the use of 12 autosomal STR loci, the study has signified the strength of 2 shared allele evidence by 51.2% in establishing sibship and recommend D7S820, VWA, TH01, and D18S51 as STR loci of choice when typing sibling among Madurese.

Abstract Background Low‐molecular‐weight heparin has been the preferred treatment of cancer‐associated thrombosis (CAT); however, emerging data support the use of direct oral anticoagulants (DOACs). Objectives The Memorial Sloan Kettering Cancer Center Clinical Pathway has served as the institutional guideline for the use of rivaroxaban to treat CAT since 2014. Key elements are to recommend against use of a DOAC in patients with active gastrointestinal (GI) or genitourinary tract lesions, and a prespecified dose reduction in the elderly (75+ years old). We present our institutional experience for treatment of CAT. Methods From January 2014 through September 2016, 1072 patients began rivaroxaban treatment for CAT; 91.9% had a solid tumor, 8.1% had hematologic malignancies, and 75% of patients with solid tumors had metastatic disease. All patients with CAT treated with rivaroxaban were included in this analysis, regardless of adherence to the Clinical Pathway. Results The 6‐month cumulative incidence of recurrent venous thromboembolism and major bleeding were 4.2% (95% confidence interval [CI], 2.7%‐5.7%) and 2.2% (95% CI, 1.1%‐3.2%), respectively. The incidence of clinically relevant non–major bleeding leading to discontinuation of rivaroxaban for at least 7 days was 5.5% (95% CI, 3.7%‐7.1%), and 73.3% of major bleeds occurred in the GI tract. The 6‐month cumulative mortality rate was 22.2% (95% CI, 19.4%‐24.9%). The elderly had similar rates of recurrent thrombosis and bleeding as those aged under 75 years. Conclusion Our institutional experience suggests that in appropriately selected patients, rivaroxaban may be used for treatment of CAT with promising safety and efficacy.

Background: The cytochrome P450 CYP2B6*6 (CYP2B6 c.516G>T; rs3745274) is one of the genetic factors that alters the drug metabolism in antimalarial, antiretroviral and TB first-line drugs. In Central African populations, the distribution of the CYP2B6*6 variant is poorly documented. This study investigated the distribution of CYP2B6 c.516G>T variant among Congolese individuals. Methods: A total of 418 patients with HIV-1 mono-infection, HIV-1 and Tuberculosis coinfection and symptomatic P. falciparum malaria were genotyped for the CYP2B6 c.516G>T SNP using Restriction Fragment Length Polymorphism (RFLP). The allele frequencies and genotype distributions were determined. Results: The CYP2B6 c.516G>T was successfully analysed in 69% (288/418) of the study participants. Among the investigated individuals, the distribution of the major allele CYP2B6*G was 45% and the minor CYP2B6*T allele was 55%. Significant differences in genotype distribution were also observed among the studied individuals. The CYP2B6*GG (rapid metabolizer) genotype was observed in 17% (49/288) followed by CYP2B6*GT (intermediate metabolizer) 55% (159/288) and CYP2B6*TT (poor metabolizers) 28% (80/288). Conclusion: This study contributes to increasing understanding on population pharmacogenetics and may help policy makers regulate treatment guidelines in the Congolese population with a high burden of HIV, Malaria and TB. Keywords: CYP2B6, Cytochrome P 450, HIV, Malaria, Tuberculosis, Republic of Congo

Abstract We present a detailed study of a combined singlet-doublet fermion and triplet scalar model for dark matter. These models have only been studied separately in the past. Together, they form a simple extension of the Standard Model that can account for dark matter and explain the existence of neutrino masses, which are generated radiatively. This holds even if singlet-doublet fermions and triplet scalars never contribute simultaneously to the dark matter abundance. However, this also implies the existence of lepton flavour violating processes. In addition, this particular model allows for gauge coupling unification. The new fields are odd under a new ℤ2 symmetry to stabilise the dark matter candidate. We analyse the dark matter, neutrino mass and lepton flavour violation aspects both separately and in conjunction, exploring the viable parameter space of the model. This is done using a numerical random scan imposing successively the neutrino mass and mixing, relic density, Higgs mass, direct detection, collider and lepton flavour violation constraints. We find that dark matter in this model is fermionic for masses below about 1 TeV and scalar above. The narrow mass regions found previously for the two separate models are enlarged by their coupling. While coannihilations of the weak isospin partners are sizeable, this is not the case for fermions and scalars despite their often similar masses due to the relatively small coupling of the two sectors, imposed by the small neutrino masses. We observe a high degree of complementarity between direct detection and lepton flavour violation experiments, which should soon allow to fully probe the fermionic dark matter sector and at least partially the scalar dark matter sector.

Abstract Background Externally controlling and monitoring drug release at a desired time and location is currently lacking in the gastrointestinal tract. The aim of the study was to develop a thermoresponsive wax-coated capsule and to trigger its release upon applying a magnetic resonance imaging (MRI)-guided high-intensity focused ultrasound (HIFU) pulse. Methods Capsules containing a lyophilised gadolinium-based contrast agent (GBCA) were coated with a 1:1 (mass/mass) mixture of lanolin and cetyl alcohol (melting point ≈43 °C) and exposed to simulated gastric and intestinal fluids (United States Pharmacopoeia) at 37 °C for 2 and 24 h, respectively. In a HIFU gel phantom, wax-coated capsules (n = 3) were tracked based on their T1- and T2-hypointensity by 1.5-T T1- and T2-weighted MRI pre- and post-exposure to an MRI-guided HIFU pulse. Results Lanolin/cetyl alcohol-coated capsules showed high resistance to simulated gastrointestinal fluids. In a gel phantom, an MRI-guided HIFU pulse punctured the wax coating, resulting in the hydration and release of the encapsulated lyophilised GBCA and yielding a T1-hyperintense signal close to the wax-coated capsule. Conclusion We provide the proof-of-concept of applying a non-invasive MRI-guided HIFU pulse to actively induce the disintegration of the wax-coated capsule, and a method to monitor the release of the cargo via T1-weighted MRI based on the hydration of an encapsulated lyophilised GBCA. The wax-coated capsule platform enables temporally and spatially supertargeted drug release via the oral route and promises to address a currently unmet clinical need for personalised local therapy in gastrointestinal diseases such as inflammatory bowel diseases and cancer.

Azo compounds such as the Sudan dyes I–IV are frequently used illegally as colorants and added to a wide range of foods. These compounds have been linked to a number of food safety hazards. Several methods have been proposed to detect food contamination by azo compounds and most of these are laboratory based; however, the development of reliable and portable methods for the detection and quantification of food contaminated by these chemicals in low concentration is still needed due to their potentially carcinogenic properties. In this study, we investigated the ability of surface enhanced Raman scattering (SERS) combined with chemometrics to quantify Sudan I–IV dyes. SERS spectra were acquired using a portable Raman device and gold nanoparticles were employed as the SERS substrate. As these dyes are hydrophobic, they were first dissolved in water: acetonitrile (1:10, v/v) as single Sudan dyes (I–IV) at varying concentrations. SERS was performed at 785 nm and the spectra were analyzed by using partial least squares regression (PLS-R) with double cross-validations. The coefficient of determination (Q2) were 0.9286, 0.9206, 0.8676 and 0.9705 for Sudan I to IV, respectively; the corresponding limits of detection (LOD) for these dyes were estimated to be 6.27 × 10−6, 5.35 × 10−5, 9.40 × 10−6 and 1.84 × 10−6 M. Next, quadruplex mixtures were made containing all four Sudan dyes. As the number of possible combinations needed to cover the full concentration range at 5% intervals would have meant collecting SERS spectra from 194,481 samples (214 combinations) we used a sustainable solution based on Latin hypercubic sampling and reduced the number of mixtures to be analyzed to just 90. After collecting SERS spectra from these mixture PLS-R models with bootstrapping validations were employed. The results were slightly worse in which the Q2 for Sudan I to IV were 0.8593, 0.7255, 0.5207 and 0.5940 when PLS1 models (i.e., one model for one dye) was employed and they changed to 0.8329, 0.7288, 0.5032 and 0.5459 when PLS2 models were employed (i.e., four dyes were modelled simultaneously). These results showed the potential of SERS to be used as a high-throughput, low-cost, and reliable methods for detecting and quantifying multiple Sudan dyes in low concentration from illegally adulterated samples.

A population PK model of clindamycin orally administered to patients with prosthetic joint infections (PJIs) was developed using NONMEM 7.5. Monte-Carlo simulations were run to determine the probability of obtaining bone clindamycin concentrations equal to at least the MIC or four times the MIC for several MIC values and dosing regimens. One hundred and forty plasma concentrations prospectively obtained from 20 patients with PJIs were used. A one-compartment model with first-order absorption and elimination appropriately described the data. Mean PK-parameter estimates (F being the bioavailability) were: apparent clearance, CL/F = 23 L/h, apparent distribution volume, V/F = 103 l and absorption rate constant, Ka = 3.53/h, with respective interindividual variabilities (coefficients of variation) of 14.4%, 8.2% and 59.6%. Neither goodness-of-fit curves nor visual predictive checks indicated bias. The currently recommended 600 mg q8h regimen provided a high probability of obtaining concentrations equal to at least the MIC, except for MIC ≥ the clinical breakpoint for Staphylococcus spp. (0.25 mg/L). For such MIC values, higher daily doses and q6h regimens could be considered.

Background: This study investigates the correlation and discriminative diagnostic accuracy of dual-energy CT (DECT)-derived imaging biomarkers in patients with acute pancreatitis of varying severity. Methods: In this retrospective study, we included 51 patients with acute pancreatitis who had undergone portal-venous phase DECT of the abdomen. Three blinded readers independently performed region-of-interest measurements on DECT images in the inflammatory pancreatic parenchyma. The correlation between modified CT severity index (CTSI) and quantitative imaging parameters was investigated using Pearson correlation coefficient. We performed receiver operator curve (ROC) analysis to assess diagnostic accuracy of the quantitative image parameters for the differentiation between mild/moderate versus severe acute pancreatitis. The optimal discriminative cut-off value to diagnose severe acute pancreatitis was determined using the Youden index. Results: Moderate correlations were found between CTSI scores and iodine density (Pearson’s correlation coefficient r = −0.65; p < 0.001), as well as attenuation (r = −0.55; p < 0.001) and normalized iodine uptake (r = −0.50; p < 0.001). ROC curve analysis revealed highest ability to differentiate mild/moderate from severe acute pancreatitis for iodine density (AUC = 0.86, 95% confidence interval 0.75 to 0.97). An optimal iodine density threshold of ≤1.63 mg/mL was found to indicate severe acute pancreatitis with a sensitivity of 81.3% and specificity of 77.1%. Conclusion: DECT-derived iodine density correlates with acute pancreatitis severity and may facilitate prediction of severe acute pancreatitis.

Background and Objectives: We developed a predictive statistical model to identify donor–recipient characteristics related to kidney graft survival in the Chilean population. Given the large number of potential predictors relative to the sample size, we implemented an automated variable selection mechanism that could be revised in future studies as more national data is collected. Materials and Methods: A retrospective multicenter study was conducted to analyze data from 822 adult kidney transplant recipients from adult donors between 1998 and 2018. To the best of our knowledge, this is the largest kidney transplant database to date in Chile. A procedure based on a cross-validated regularized Cox regression using the Elastic Net penalty was applied to objectively identify predictors of death-censored graft failure. Hazard ratios were estimated by adjusting a multivariate Cox regression with the selected predictors. Results: Seven variables were associated with the risk of death-censored graft failure; four from the donor: age (HR = 1.02, 95% CI: 1.00–1.03), male sex (HR = 0.64, 95% CI: 0.46–0.90), history of hypertension (HR = 1.49, 95% CI: 0.98–2.28), and history of diabetes (HR = 2.04, 95% CI: 0.97–4.29); two from the recipient: years on dialysis log-transformation (HR = 1.29, 95% CI: 0.99–1.67) and history of previous solid organ transplantation (HR = 2.02, 95% CI: 1.18–3.47); and one from the transplant: number of HLA mismatches (HR = 1.13, 95% CI: 0.99–1.28). Only the latter is considered for patient prioritization in deceased kidney allocation in Chile. Conclusions: A risk model for kidney graft failure was developed and trained for the Chilean population, providing objective criteria which can be used to improve efficiency in deceased kidney allocation.

There is growing evidence that peptides encoded by small open-reading frames (sORF or smORF) can fulfill various cellular functions and define a novel class regulatory molecules. To which extend transcripts encoding only smORF peptides compare with canonical protein-coding genes, yet remain poorly understood. In particular, little is known on whether and how smORF-encoding RNAs might need tightly regulated expression within a given tissue, at a given time during development. We addressed these questions through the analysis of Drosophila polished rice (pri, a.k.a. tarsal less or mille pattes), which encodes four smORF peptides (11–32 amino acids in length) required at several stages of development. Previous work has shown that the expression of pri during epidermal development is regulated in the response to ecdysone, the major steroid hormone in insects. Here, we show that pri transcription is strongly upregulated by ecdysone across a large panel of cell types, suggesting that pri is a core component of ecdysone response. Although pri is produced as an intron-less short transcript (1.5 kb), genetic assays reveal that the developmental functions of pri require an unexpectedly large array of enhancers (spanning over 50 kb), driving a variety of spatiotemporal patterns of pri expression across developing tissues. Furthermore, we found that separate pri enhancers are directly activated by the ecdysone nuclear receptor (EcR) and display distinct regulatory modes between developmental tissues and/or stages. Alike major developmental genes, the expression of pri in a given tissue often involves several enhancers driving apparently redundant (or shadow) expression, while individual pri enhancers can harbor pleiotropic functions across tissues. Taken together, these data reveal the broad role of Pri smORF peptides in ecdysone signaling and show that the cis-regulatory architecture of the pri gene contributes to shape distinct spatial and temporal patterns of ecdysone response throughout development.

Background: Faecal microbiota transplantation (FMT) is an effective treatment of recurrent Clostridioides difficile infection (rCDI) and is being applied experimentally in other diseases. Encapsulated administration may be equivalent in efficacy to delivery through other routes. Methods: A systematic review was undertaken of studies using encapsulated FMT up to 26 October 2020. Data on indication, clinical outcomes, safety, treatment protocol and capsule preparation were collected and reported. Pooled rates of clinical efficacy in rCDI were calculated using random-effects meta-analysis. The impact of single variables on clinical efficacy was evaluated using univariate meta-regression. Results: A total of 35 studies reporting the treatment of 960 patients with encapsulated FMT for eight different indications met the inclusion criteria. Most studies ( n = 18, 51%) and patients ( n = 755, 79%) were from studies on rCDI. Cure rates after single and multiple courses of treatments with encapsulated FMT in rCDI were 85% (95% CI: 82%-88%) and 93% (95% CI: 88%-96%) respectively. The treatment outcome was not significantly affected by dose, number of delivered capsules, anaerobic/aerobic processing, single/multi-donor treatment, lyophilisation, or any other single factor in the production or delivery of encapsulated FMT. Promising but non-comparable results from the treatment of ulcerative colitis and multidrug-resistant organisms were reported. Conclusions: Encapsulated FMT is an effective and safe treatment of rCDI, with cure rates comparable to FMT delivered through other routes. The treatment is effective despite variations in donor screening, preparation and treatment protocol. For other indications, the role of FMT capsules is still not sufficiently examined, although some studies show promising results. Plain Language Summary Transfer of faecal material through capsules in the treatment of various diseases. Evidence for clinical efficacy The bacteria and other microorganisms of the gut is different in patient with various diseases in comparison with healthy subjects. Therefore, ways to change the microorganisms of the gut in a beneficial direction has been the subject of various research projects within recent years. Faecal microbiota transplantation often referred as FMT is a method of transferring microorganisms from healthy donors to patients with various diseases and is seen as one way to change the microbial community of the gut in a beneficial direction. Faecal microbiota transplantation can be performed in different ways such as through endoscopy, enemas or capsules. The transfer through capsules is preferred by the patients and has advantages since it can be administered long-term and can be delivered to the patients in their home. In this paper, we evaluated all accessible research reporting treatment with encapsulated faecal microbiota transplantation in the treatment of various diseases. We report the following major findings: -Treatment with capsules is safe when guidelines for screening donors and testing faecal material is followed. -The treatment is highly effective in the treatment of recurrent C. difficile infection, a disease with high mortality often caused by repeated antibiotic treatments. The treatment was effective in 596 of 723 patients following one course of capsule treatment. -Faecal microbiota transplantation delivered through capsules is as effective as treatment delivered through other routes in the treatment of C. difficile infection. -The treatment is effective in the treatment of C. difficile infection across studies and countries, despite great differences in the ways the capsules were prepared and delivered. -Increasing the amount of faecal material used in the production did not affect the efficacy of the treatment. -There are promising results in the treatment of other diseases such as liver disease, inflammatory bowel disease and the treatment of multi-drug resistant bacteria.

Finding new sustainable means of diagnosing and treating diseases is one of the most pressing issues of our time. In recent years, several endogenous peptides have been found to be both excellent biomarkers for many diseases and to possess important physiological roles which may be utilized in treatments. The detection of peptides has been facilitated by the rapid development of biological mass spectrometry and now the combination of fast and sensitive high resolution MS instruments and stable nano HP-LC equipment sequences thousands of peptides in one single experiment. In most research conducted with these advanced systems, proteolytically cleaved proteins are analyzed and the specific peptides are identified by software dedicated for protein quantification using different proteomics workflows. Analysis of endogenous peptides with peptidomics workflows also benefit from the novel sensitive and advanced instrumentation, however, the generated peptidomic data is vast and subsequently laborious to visualize and examine, creating a bottleneck in the analysis. Therefore, we have created Peptimetric, an application designed to allow researchers to investigate and discover differences between peptidomic samples. Peptimetric allows the user to dynamically and interactively investigate the proteins, peptides, and some general characteristics of multiple samples, and is available as a web application at https://peptimetric.herokuapp.com. To illustrate the utility of Peptimetric, we’ve applied it to a peptidomic dataset of 15 urine samples from diabetic patients and corresponding data from healthy subjects.

The COVID-19 epidemic has forced most countries to impose contact-limiting restrictions at workplaces, universities, schools, and more broadly in our societies. Yet, the effectiveness of these unprecedented interventions in containing the virus spread remain largely unquantified. Here, we develop a simulation study to analyze COVID-19 outbreaks on three real-life contact networks stemming from a workplace, a primary school and a high school in France. Our study provides a fine-grained analysis of the impact of contact-limiting strategies at workplaces, schools and high schools, including: (1) Rotating strategies, in which workers are evenly split into two shifts that alternate on a daily or weekly basis; and (2) On-Off strategies, where the whole group alternates periods of normal work interactions with complete telecommuting. We model epidemics spread in these different setups using a stochastic discrete-time agent-based transmission model that includes the coronavirus most salient features: super-spreaders, infectious asymptomatic individuals, and pre-symptomatic infectious periods. Our study yields clear results: the ranking of the strategies, based on their ability to mitigate epidemic propagation in the network from a first index case, is the same for all network topologies (workplace, primary school and high school). Namely, from best to worst: Rotating week-by-week, Rotating day-by-day, On-Off week-by-week, and On-Off day-by-day. Moreover, our results show that below a certain threshold for the original local reproduction number [Formula: see text] within the network (< 1.52 for primary schools, < 1.30 for the workplace, < 1.38 for the high school, and < 1.55 for the random graph), all four strategies efficiently control outbreak by decreasing effective local reproduction number to [Formula: see text] < 1. These results can provide guidance for public health decisions related to telecommuting.

Innsbruck Medical University Hospital, Austria, provides the highest level of care for a region of approximately 1.8 million people. During the early COVID-19 outbreak in spring 2020 surgical activity was drastically reduced with the prime goal of preserving hospital capacities, especially intensive care beds. We conducted a retrospective analysis of surgical activities performed at Innsbruck Medical University Hospital during the lockdown period from March 15 to April 14, 2020 and compared these activities to the same period during the previous 5 years. Total surgical activity was reduced by 65.4% compared to the same period during the previous 5 years (p < 0.001); elective surgeries were reduced by 88.7%, acute surgeries by 35.3% and oncological surgeries by 47.8% compared to the previous 5 years (all p < 0.001). This dramatic decrease in acute and oncological surgeries can most likely be ascribed to the fact that many patients avoided health care facilities because of the strict stay-at-home policy and/or the fear of contracting SARS-CoV-2 in the hospital. In view of future waves, the population should be encouraged to seek medical help for acute symptoms and to attend cancer screening programs.

Background: Genetic variations across the SARS-CoV-2 genome may influence transmissibility of the virus and the host’s anti-viral immune response, in turn affecting the frequency of variants over time. In this study, we examined the adjacent amino acid polymorphisms in the nucleocapsid (R203K/G204R) of SARS-CoV-2 that arose on the background of the spike D614G change and describe how strains harboring these changes became dominant circulating strains globally. Methods: Deep-sequencing data of SARS-CoV-2 from public databases and from clinical samples were analyzed to identify and map genetic variants and sub-genomic RNA transcripts across the genome. Results: Sequence analysis suggests that the 3 adjacent nucleotide changes that result in the K203/R204 variant have arisen by homologous recombination from the core sequence of the leader transcription-regulating sequence (TRS) rather than by stepwise mutation. The resulting sequence changes generate a novel sub-genomic RNA transcript for the C-terminal dimerization domain of nucleocapsid. Deep-sequencing data from 981 clinical samples confirmed the presence of the novel TRS-CS-dimerization domain RNA in individuals with the K203/R204 variant. Quantification of sub-genomic RNA indicates that viruses with the K203/R204 variant may also have increased expression of sub-genomic RNA from other open reading frames. Conclusions: The finding that homologous recombination from the TRS may have occurred since the introduction of SARS-CoV-2 in humans, resulting in both coding changes and novel sub-genomic RNA transcripts, suggests this as a mechanism for diversification and adaptation within its new host.

Background and Aims: Internet gambling has recently grown in popularity, but relatively little is known about how online and the combination of online and offline (mixed) gambling are associated with gambling disorder (GD) and related problems. The present research examined in a cohort study sample of young Swiss men how their gambling activities and gambling-related problems differed across the spectrum from offline to online gambling.Sample: A general-population based sample from the Cohort Study on Substance Use Risk Factors (C-SURF), consisting of 5,352 young Swiss men (mean age 28.26 years old).Measures: The spectrum from exclusively offline to almost exclusively online (>90% of gambling money spent online) gambling was measured using one question about the proportion of gambling money spent online. Total money gambled and time spent on gambling were also assessed. GD severity (range 0–9) was measured using items reflecting the nine DSM-5 GD criteria. The number of gambling-related problems (e.g., financial difficulties, range 0–10), other addictive disorders and mental health problems were also inquired about.Methods: We estimated a generalised linear model using a count model (negative binomial link function) for GD severity and gambling-related problems associated with the amounts and proportions of money gambled online and offline.Results: The number of GD criteria were associated with money gambled online (IRR [95%CI] = 2.81 [2.43, 3.24]) and offline (IRR = 2.68 [2.40, 3.00]). This was also found for the number of gambling-related problems (IRR = 2.43 [2.13, 2.79] and IRR = 2.89 [2.59, 3.23]). Compared with exclusively-offline gamblers, mixed gamblers (26–90% of money gambled online) showed the highest levels of GD symptoms and gambling-related problems, followed by the almost-exclusively-online gamblers (≥91% money gambled online) and, overall, these associations were still significant after adjustment for overall involvement in gambling (time spent and money gambled). Levels of other addictive disorders and mental health problems were higher among mixed gamblers than among offline-only gamblers, but levels among almost-exclusively-online gamblers were not.Conclusions: Symptoms of gambling disorder and gambling related problems are highest among gamblers engaging in both offline and online gambling. Prevention efforts need to target the combination of offline and online gambling.

Introduction Knee osteoarthritis (OA) is associated with chronic knee pain and functional disability that negatively affect the ability to carry out normal daily activities. Patients are offered a large variety of non-surgical treatments, often not in accordance with clinical guidelines. This observational study will provide a comprehensive overview of treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon, including timing and order of treatment modalities, predictors of treatment outcomes, cost-effectiveness of treatment pathways and patients’ views on different treatment pathways.Methods and analysis Patients with primary referrals to an orthopaedic surgeon due to knee OA are consecutively invited to participate and fill out a questionnaire prior to their consultation with an orthopaedic surgeon. Follow-up questionnaires will be obtained at 6 and 24 months after inclusion. Based on a prospective cohort study design, including questionnaires and register data, we will (1) describe treatment pathways for knee OA during the first 2 years after consulting an orthopaedic surgeon; (2) describe the characteristics of patients choosing different treatment pathways; (3) develop predictive models for patient-self-determined classifications of good and poor treatment outcomes; (4) evaluate the cost-effectiveness of treatment pathways that live up to clinical guidelines versus pathways that do not; based on a qualitative study design using semistructured individual interviews, we will (5) describe the patients’ perspectives on treatment pathways for knee OA.Ethics and dissemination The study is approved by the Danish regional ethical committee (journal number H-17017295) and the Danish Data Protection Agency (journal number AHH-2017–072). Data will be anonymised and handled in line with the General Data Protection Regulation and the Danish Data Protection Act. The study results will be submitted to international open-access peer-reviewed journals and disseminated at conferences.Trial registration number NCT03746184, pre-results.

The Social Sciences and Humanities (SSH) have a key role to play in understanding which factors and policies would motivate, encourage and enable different actors to adopt a wide range of sustainable energy behaviours and support the required system changes and policies. The SSH can provide critical insights into how consumers could be empowered to consistently engage in sustainable energy behaviour, support and adopt new technologies, and support policies and changes in energy systems. Furthermore, they can increase our understanding of how organisations such as private and public institutions, and groups and associations of people can play a key role in the sustainable energy transition. We identify key questions to be addressed that have been identified by the Platform for Energy Research in the Socio-economic Nexus (PERSON, see person.eu), including SSH scholars who have been studying energy issues for many years. We identify three main research themes. The first research theme involves understanding which factors encourage different actors to engage in sustainable energy behaviour. The second research theme focuses on understanding which interventions can be effective in encouraging sustainable energy behaviour of different actors, and which factors enhance their effects. The third research theme concerns understanding which factors affect public and policy support for energy policy and changes in energy systems, and how important public concerns can best be addressed as to reduce or prevent resistance.

Type B adverse drug reactions (ADRs) are iatrogenic immune-mediated syndromes with mechanistic etiologies that remain incompletely understood. Some of the most severe ADRs, including delayed drug hypersensitivity reactions, are T-cell mediated, restricted by specific human leukocyte antigen risk alleles and sometimes by public or oligoclonal T-cell receptors (TCRs), central to the immunopathogenesis of tissue-damaging response. However, the specific cellular signatures of effector, regulatory, and accessory immune populations that mediate disease, define reaction phenotype, and determine severity have not been defined. Recent development of single-cell platforms bringing together advances in genomics and immunology provides the tools to simultaneously examine the full transcriptome, TCRs, and surface protein markers of highly heterogeneous immune cell populations at the site of the pathological response at a single-cell level. However, the requirement for advanced bioinformatics expertise and computational hardware and software has often limited the ability of investigators with the understanding of diseases and biological models to exploit these new approaches. Here we describe the features and use of a state-of-the-art, fully integrated application for analysis and visualization of multiomic single-cell data called Visual Genomics Analysis Studio (VGAS). This unique user-friendly, Windows-based graphical user interface is specifically designed to enable investigators to interrogate their own data. While VGAS also includes tools for sequence alignment and identification of associations with host or organism genetic polymorphisms, in this review we focus on its application for analysis of single-cell TCR–RNA–Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE)-seq, enabling holistic cellular characterization by unbiased transcriptome and select surface proteome. Critically, VGAS does not require user-directed coding or access to high-performance computers, instead incorporating performance-optimized hidden code to provide application-based fast and intuitive tools for data analyses and production of high-resolution publication-ready graphics on standard specification laptops. Specifically, it allows analyses of comprehensive single-cell TCR sequencing (scTCR-seq) data, detailing (i) functional pairings of α–β heterodimer TCRs, (ii) one-click histograms to display entropy and gene rearrangements, and (iii) Circos and Sankey plots to visualize clonality and dominance. For unbiased single-cell RNA sequencing (scRNA-seq) analyses, users extract cell transcriptome signatures according to global structure via principal component analysis, t-distributed stochastic neighborhood embedding, or uniform manifold approximation and projection plots, with overlay of scTCR-seq enabling identification and selection of the immunodominant TCR-expressing populations. Further integration with similar sequence-based detection of surface protein markers using oligo-labeled antibodies (CITE-seq) provides comparative understanding of surface protein expression, with differential gene or protein analyses visualized using volcano plot or heatmap functions. These data can be compared to reference cell atlases or suitable controls to reveal discrete disease-specific subsets, from epithelial to tissue-resident memory T-cells, and activation status, from senescence through exhaustion, with more finite transcript expression displayed as violin and box plots. Importantly, guided tutorial videos are available, as are regular application updates based on the latest advances in bioinformatics and user feedback.

Sibling indices can be used as a comparison through alleles Short Tandem Repeats [STR] loci. This is an observational study among Maduranese with 4 STR loci (CSF1PO, THOI, TPOX, vWA) obtained from their blood samples. The percentage of alleles shared: 82.5% [33 times] with 2 allele sharing, 12.5% [5 times] with 1 allele sharing, and 5 % [2 times] with 0 sharing alleles. Sibling indices (SI) calculation results: 65% of sibling indices pairs have SI greater than 100 and 15% of them were between 10-100 (strong and very strong). Sibling indices interpretation is supported; therefore, the claimed sibling indices relationships were indeed true among Maduranese ethnic group in Surabaya.

RESUMEN El deporte es una actividad que se práctica de forma recreativa o profesional. Quienes lo hacen profesionalmente en ocasiones reciben aportes económicos y logran estudiar una carrera profesional, lo que se conoce como carrera dual. No obstante, hay quienes presentan esta actividad como su trabajo. El objetivo general del estudio fue analizar los argumentos de los deportistas chilenos para referirse a la práctica deportiva como una actividad laboral; el objetivo específico fue reflexionar críticamente sobre el desarrollo de la carrera dual en Chile. Para comprender estos argumentos, se realizó un estudio cualitativo por medio de entrevistas activas semiestructuradas a deportistas de alto rendimiento (DAR) y recreativos, olímpicos y paralímpicos. Los resultados muestran que los atletas demandan reconocimiento como trabajadores públicos por medio de tres argumentos: económico, subordinación y dependencia e identidad. Las conclusiones y discusiones sugieren debatir el reconocimiento de ellos y ellas como trabajadores públicos.

The delegation of decisions to machines has revived the debate on whether and how technology should and can embed fundamental legal values within its design. While these debates have predominantly been occurring within the philosophical and legal communities, the computer science community has been eager to provide tools to overcome some challenges that arise from ‘hardwiring’ law into code. What emerged is the formation of different approaches to code that adapts to legal parameters. Within this article, we discuss the translational, system-related, and moral issues raised by implementing legal principles in software. While our findings focus on data protection law, they apply to the interlinking of code and law across legal domains. These issues point towards the need to rethink our current approach to design-oriented regulation and to prefer ‘soft’ implementations, where decision parameters are decoupled from program code and can be inspected and modified by users, over ‘hard’ approaches, where decisions are taken by opaque pieces of program code.

Abstract Severe space weather was identified as a risk to the UK in 2010 as part of a wider review of natural hazards triggered by the societal disruption caused by the eruption of the Eyjafjallajökull volcano in April of that year. To support further risk assessment by government officials, and at their request, we developed a set of reasonable worst‐case scenarios and first published them as a technical report in 2012 (current version published in 2020). Each scenario focused on a space weather environment that could disrupt a particular national infrastructure such as electric power or satellites, thus, enabling officials to explore the resilience of that infrastructure against severe space weather through discussions with relevant experts from other parts of government and with the operators of that infrastructure. This approach also encouraged us to focus on the environmental features that are key to generating adverse impacts. In this paper, we outline the scientific evidence that we have used to develop these scenarios, and the refinements made to them as new evidence emerged. We show how these scenarios are also considered as an ensemble so that government officials can prepare for a severe space weather event, during which many or all of the different scenarios will materialize. Finally, we note that this ensemble also needs to include insights into how public behavior will play out during a severe space weather event and hence the importance of providing robust, evidence‐based information on space weather and its adverse impacts.