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Abstract Acute ischemic stroke (AIS) is a leading global cause of mortality and morbidity. Improving long-term outcome predictions after thrombectomy can enhance treatment quality by supporting clinical decision-making. With the advent of interpretable deep learning methods in recent years, it is now possible to develop trustworthy, high-performing prediction models. This study introduces an uncertainty-aware, graph deep learning model that predicts endovascular thrombectomy outcomes using clinical features and imaging biomarkers. The model targets long-term functional outcomes, defined by the three-month modified Rankin Score (mRS), and mortality rates. A sample of 220 AIS patients in the anterior circulation who underwent endovascular thrombectomy (EVT) was included, with 81 (37%) demonstrating good outcomes (mRS $$\le$$ ≤ 2). The performance of the different algorithms evaluated was comparable, with the maximum validation under the curve (AUC) reaching 0.87 using graph convolutional networks (GCN) for mRS prediction and 0.86 using fully connected networks (FCN) for mortality prediction. Moderate performance was obtained at admission (AUC of 0.76 using GCN), which improved to 0.84 post-thrombectomy and to 0.89 a day after stroke. Reliable uncertainty prediction of the model could be demonstrated.

Purpose: Small Medium and Micro Enterprises (SMMEs) often struggle with performance measurement which can result in a high failure rate. This study aimed to examine the role of owner-managers in understanding performance management, the implementation processes of Performance Management System (PMS), and what challenges associated with applying PMS within SMMEs they faced. SMMEs will greatly benefit from a reliable PMS that can streamline day-to-day operations and facilitate effective decision-making through Key Performance Indicators (KPIs). Design/Methodology/Approach: A qualitative approach was applied for the research methodology to understand the perspectives of owner-managers within SMMEs. The study employed a purposive, non-purposeful sampling technique to select twelve (12) participants. Semi-structured, face-to-face interviews were conducted with the participants’ consent to collect data. Findings: The collected data was subsequently analyzed using content analysis to scrutinize and interpret the findings. The research findings of this study found that owner-managers hold a general understanding of PMSs. Implications/Originality/Value: The implementation of PMSs in SMMEs presents a significant challenge, particularly in identifying pertinent KPIs.

Timbre is a central aspect of music that allows listeners to identify musical sounds and conveys musical emotion, but also allows for the recognition of actions and is an important structuring property of music. The former functions are known to be implemented in a ventral auditory stream in processing musical timbre. While the latter functions are commonly attributed to areas in a dorsal auditory processing stream in other musical domains, its involvement in musical timbre processing is so far unknown. To investigate if musical timbre processing involves both dorsal and ventral auditory pathways, we carried out an activation likelihood estimation (ALE) meta-analysis of 18 experiments from 17 published neuroimaging studies on musical timbre perception. We identified consistent activations in Brodmann areas (BA) 41, 42, and 22 in the bilateral transverse temporal gyri, the posterior superior temporal gyri and planum temporale, in BA 40 of the bilateral inferior parietal lobe, in BA 13 in the bilateral posterior Insula, and in BA 13 and 22 in the right anterior insula and superior temporal gyrus. The vast majority of the identified regions are associated with the dorsal and ventral auditory processing streams. We therefore propose to frame the processing of musical timbre in a dual-stream model. Moreover, the regions activated in processing timbre show similarities to the brain regions involved in processing several other fundamental aspects of music, indicating possible shared neural bases of musical timbre and other musical domains.

Mountains are perceived as places of biodiversity, as attractive places with breathtaking aesthetic views and epitomized by their unique landscape features. As mountains are the second most demanded outdoor destination category at a global level after beaches and islands, the steady growth of tourism places high pressure on sensitive mountain ecosystems. As can be observed from tourism practice in mountain environments, the distribution of tourism activities is highly uneven. In the Alps, one of the best-known regions with relentless tourism growth, a substantial concentration of tourism intensity can be traced to specific locations and valleys, whereas other parts have to cope with trends of marginalization. In this situation, many concerned stakeholders have long advocated for more balanced economic and tourism development. The initiative of “Mountaineering Villages” promoted by the Alpine Convention is one of a few respective actions to shift perspectives and persuade tourists to engage in sustainable tourism activities. The paper explores how these activities are linked to the balanced use of cultural landscapes and the narratives that are exposed as convincing development models in these regions.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with liver and cardiovascular morbidity and mortality. Recently published NAFLD Quality Standards include 11 key performance indicators (KPIs) of good clinical care. This national study, endorsed by British Association for the Study of the Liver (BASL) and British Society of Gastroenterology (BSG), aimed to benchmark NAFLD care in UK hospitals against these KPIs. Methods: This study included all new patients with NAFLD reviewed in the outpatient clinic in the months of March 2019 and March 2022. Participating UK hospitals self-registered for the study through BASL/BSG. KPI outcomes were compared using Fisher’s exact or Chi-square tests. Results: Data from 776 patients with NAFLD attending 34 hospitals (England [25], Scotland [four], Wales [three], Northern Ireland [two]) were collected. A total of 85.3% of hospitals reported established local liver disease assessment pathways, yet only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment documented at the point of referral to secondary care. In secondary care, 79.1% of patients had fibrosis assessment. Assessment of cardiometabolic risk factors including obesity, type 2 diabetes, hypertension, and smoking were conducted in 73.2%, 33.0%, 19.3%, and 54.9% of all patients, respectively. There was limited documentation of diet (35.7%) and exercise advice (55.1%). Excluding those on statins, only 9.1% of patients with NAFLD at increased cardiovascular risk (T2DM and/or QRISK-3 >10%) had documented discussion of statin treatment. Significant KPI improvements from 2019 to 2022 were evident in use of non-invasive fibrosis assessment before secondary care referral, statin recommendations, and diet and exercise recommendations. Conclusions: This national study identified substantial variation in NAFLD management in the UK with clear areas for improvement, particularly fibrosis risk assessment before secondary care referral and management of associated cardiometabolic risk factors. Impact and implications: This study identified significant variation in the management of NAFLD in the UK. Only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment performed to identify those at greater risk of advanced liver disease before specialist referral. Greater emphasis is needed on the management of associated cardiometabolic risk factors in individuals with NAFLD. Hospitals with multidisciplinary NAFLD service provision had higher rates of fibrosis evaluation and assessment and management of cardiometabolic risk than hospitals without multidisciplinary services. Further work is needed to align guideline recommendations and real-world practice in NAFLD care.

Abstract Deep learning (DL) shows notable success in biomedical studies. However, most DL algorithms work as black boxes, exclude biomedical experts, and need extensive data. This is especially problematic for fundamental research in the laboratory, where often only small and sparse data are available and the objective is knowledge discovery rather than automation. Furthermore, basic research is usually hypothesis‐driven and extensive prior knowledge (priors) exists. To address this, the Self‐Enhancing Multi‐Photon Artificial Intelligence (SEMPAI) that is designed for multiphoton microscopy (MPM)‐based laboratory research is presented. It utilizes meta‐learning to optimize prior (and hypothesis) integration, data representation, and neural network architecture simultaneously. By this, the method allows hypothesis testing with DL and provides interpretable feedback about the origin of biological information in 3D images. SEMPAI performs multi‐task learning of several related tasks to enable prediction for small datasets. SEMPAI is applied on an extensive MPM database of single muscle fibers from a decade of experiments, resulting in the largest joint analysis of pathologies and function for single muscle fibers to date. It outperforms state‐of‐the‐art biomarkers in six of seven prediction tasks, including those with scarce data. SEMPAI's DL models with integrated priors are superior to those without priors and to prior‐only approaches.

Accumulation of cytoplasmic inclusions of TAR-DNA binding protein 43 (TDP-43) is seen in both neurons and glia in a range of neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD) and Alzheimer's disease (AD). Disease progression involves non-cell autonomous interactions among multiple cell types, including neurons, microglia and astrocytes. We investigated the effects in Drosophila of inducible, glial cell type-specific TDP-43 overexpression, a model that causes TDP-43 protein pathology including loss of nuclear TDP-43 and accumulation of cytoplasmic inclusions. We report that TDP-43 pathology in Drosophila is sufficient to cause progressive loss of each of the 5 glial sub-types. But the effects on organismal survival were most pronounced when TDP-43 pathology was induced in the perineural glia (PNG) or astrocytes. In the case of PNG, this effect is not attributable to loss of the glial population, because ablation of these glia by expression of pro-apoptotic reaper expression has relatively little impact on survival. To uncover underlying mechanisms, we used cell-type-specific nuclear RNA sequencing to characterize the transcriptional changes induced by pathological TDP-43 expression. We identified numerous glial cell-type specific transcriptional changes. Notably, SF2/SRSF1 levels were found to be decreased in both PNG and in astrocytes. We found that further knockdown of SF2/SRSF1 in either PNG or astrocytes lessens the detrimental effects of TDP-43 pathology on lifespan, but extends survival of the glial cells. Thus TDP-43 pathology in astrocytes or PNG causes systemic effects that shorten lifespan and SF2/SRSF1 knockdown rescues the loss of these glia, and also reduces their systemic toxicity to the organism.

Abstract Recently, algorithms capable of assessing the severity of Coronary Artery Disease (CAD) in form of the Coronary Artery Disease-Reporting and Data System (CAD-RADS) grade from Coronary Computed Tomography Angiography (CCTA) scans using Deep Learning (DL) were proposed. Before considering to apply these algorithms in clinical practice, their robustness regarding different commonly used Computed Tomography (CT)-specific image formation parameters—including denoising strength, slab combination, and reconstruction kernel—needs to be evaluated. For this study, we reconstructed a data set of 500 patient CCTA scans under seven image formation parameter configurations. We select one default configuration and evaluate how varying individual parameters impacts the performance and stability of a typical algorithm for automated CAD assessment from CCTA. This algorithm consists of multiple preprocessing and a DL prediction step. We evaluate the influence of the parameter changes on the entire pipeline and additionally on only the DL step by propagating the centerline extraction results of the default configuration to all others. We consider the standard deviation of the CAD severity prediction grade difference between the default and variation configurations to assess the stability w.r.t. parameter changes. For the full pipeline we observe slight instability (± 0.226 CAD-RADS) for all variations. Predictions are more stable with centerlines propagated from the default to the variation configurations (± 0.122 CAD-RADS), especially for differing denoising strengths (± 0.046 CAD-RADS). However, stacking slabs with sharp boundaries instead of mixing slabs in overlapping regions (called true stack ± 0.313 CAD-RADS) and increasing the sharpness of the reconstruction kernel (± 0.150 CAD-RADS) leads to unstable predictions. Regarding the clinically relevant tasks of excluding CAD (called rule-out; AUC default 0.957, min 0.937) and excluding obstructive CAD (called hold-out; AUC default 0.971, min 0.964) the performance remains on a high level for all variations. Concluding, an influence of reconstruction parameters on the predictions is observed. Especially, scans reconstructed with the true stack parameter need to be treated with caution when using a DL-based method. Also, reconstruction kernels which are underrepresented in the training data increase the prediction uncertainty.

Abstract Background Bats (Mammalia: Chiroptera) serve as natural reservoirs for many zoonotic pathogens worldwide, including vector-borne pathogens. However, bat-associated parasitic arthropods and their microbiota are thus far not thoroughly described in many regions across the globe, nor is their role in the spillover of pathogens to other vertebrate species well understood. Basic epidemiological research is needed to disentangle the complex ecological interactions among bats, their specific ectoparasites and microorganisms they harbor. Some countries, such as Ukraine, are particularly data-deficient in this respect as the ectoparasitic fauna is poorly documented there and has never been screened for the presence of medically important microorganisms. Therefore, the aims of this study were to provide first data on this topic. Methods A total of 239 arthropod specimens were collected from bats. They belonged to several major groups of external parasites, including soft ticks, fleas, and nycteribiid flies from six chiropteran species in Northeastern Ukraine. The ectoparasites were individually screened for the presence of DNA of Rickettsia spp., Anaplasma/Ehrlichia spp., Bartonella spp., Borrelia spp., and Babesia spp. with conventional PCRs. Positive samples were amplified at several loci, sequenced for species identification, and subjected to phylogenetic analysis. Results Rickettsia DNA was detected exclusively in specimens of the soft tick, Carios vespertilionis (7 out of 43 or 16.3%). Sequencing and phylogenetic analysis revealed high similarity to sequences from Rickettsia parkeri and several other Rickettsia species. Bacteria from the family Anaplasmataceae were detected in all groups of the ectoparasites (51%, 122/239 samples), belonging to the genera Anaplasma, Ehrlichia, and Wolbachia. The detection of Bartonella spp. was successful only in fleas (Nycteridopsylla eusarca) and bat flies (Nycteribia koleantii, N. pedicularia), representing 12.1% (29/239) of the collected ectoparasites. No DNA of Babesia or Borrelia species was identified in the samples. Conclusions We report for the first time in Ukraine the molecular detection of several bacterial agents in bat ectoparasites collected from six species of bats. The data presented extend the knowledge on the distribution of ectoparasite species in bats and their involvement in potentially circulating agents pathogenic for humans and vertebrate animals. Graphical Abstract

Purpose: This study delves into the issues faced by investment firms in financing small businesses formally as Small, Medium and Micro Enterprise (SMME). Despite being the backbone of the economy, small businesses have been struggling to attract investment, and the challenges faced by investment firms have not been thoroughly examined. Design/Methodology/Approach: The research method utilized in this study was qualitative, with data gathered from a non-probability sample of 12 participants using purposive sampling technique. Semi-structured interviews were conducted, and inductive thematic analysis was used to analyze the data. Findings: The study reveals that investment firms have specific requirements when it comes to financing SMMEs, such as compliance with rules and regulations. The study recommends credit reporting systems and investment in high return projects to address these challenges. Implications/Originality/Value: The research concludes that investment companies face difficulties in financing small and medium enterprises due to lack or low credit scores and the maturity gap in these enterprises.

The environmental gains of dietary change are often assessed in relation to average national diets, overlooking differences in individual consumption habits and people’s willingness to change. This study combines microdata on food intake and consumer behaviour to elicit the likely environmental gains of dietary shifts. We focus on the Netherlands owing to the country’s ambition to halve its dietary footprint by 2050. Linking food recall survey data from a cross-section of the population ( n = 4313), life cycle inventory analysis for 220 food products, and behavioural survey data ( n = 1233), we estimate the dietary footprints of consumer groups across water, land, biodiversity and greenhouse gas (GHG). We find that meat and dairy significantly contribute to the dietary GHG footprint (59%), land footprint (54%), and biodiversity footprint (59%) of all consumer groups and that male consumers impose a 30%–32% greater burden than women across these impact areas. Our scenario analysis reveals that simply replacing cow milk with soy milk could reduce the GHG, land and biodiversity footprints by ≈8% if widely adopted by the Dutch adult population. These footprints could be further reduced to ≈20% with full adoption of the EAT-Lancet diet but with a significantly increased blue water footprint. However, when incorporating gender- and age-specific willingness to reduce meat and dairy consumption, the environmental gains resulting from partial adoption of the No-Milk diet and EAT diet diminish to a mere ≈0.8% and ≈4.5%, respectively. Consequently, consumer motivation alone is insufficient to realise the significant environmental gains often promised by dietary change. Yet, substituting high-impact food products offers a near-term opportunity to accelerate a rapid sustainable dietary transition. Future studies on sustainable dietary transition must incorporate consumer behaviour to fully comprehend the lock-in of food consumption patterns and targeted policy action required to secure a sustainable food future.

Introduction: In high-income settings, vasopressor administration to treat haemodynamic instability through a central venous catheter (CVC) is the preferred standard. However, due to lack of availability and potential for complications, CVCs are not widely used in low- and middle-income countries. This prospective cohort study evaluated the use of peripheral vasopressors and associated incidence of extravasation events in patients with haemodynamic instability at the Centre Hospitalier Universitaire Kigali, Rwanda. Methods: Patients ≥18 years of age receiving peripheral vasopressors in the emergency centre (EC) or intensive care unit (ICU) for >1 hour were eligible for inclusion. The primary outcome was extravasation events. Patients were followed hourly until extravasation, medication discontinuation, death, or CVC placement. Extravasation incidence with 95% confidence intervals (CI) were calculated using Poisson exact tests. Results: 64 patients were analysed. The median age was 49 (Interquartile Range [IQR]:33-65) and 55% were female. Distributive shock was the most frequent aetiology (47%). Intravenous (IV) location was most commonly antecubital fossa/upper arm (31%) and forearm/hand (43%). IV gauges ≤18 were used in 58% of locations. Most patients were treated with adrenaline (66%) and noradrenaline (41%), and 11% received multiple vasopressors. The median treatment duration was 19 hours (IQR:8.5-37). Treatment discontinuation was predominantly due to mortality (41%) or resolution of instability (36%). There were two extravasation events (2.9%), both limited to soft tissue swelling. Extravasation incidence was 0.8 events per 1000 patient-hours (95% CI:0.2-2.2). Conclusion: Extravasation incidence with peripheral vasopressors was low, even with long use durations, suggesting peripheral infusions may be an acceptable approach when barriers exist to CVC placement.

(1) Background: to test the diagnostic performance of a fully convolutional neural network-based software prototype for clot detection in intracranial arteries using non-enhanced computed tomography (NECT) imaging data. (2) Methods: we retrospectively identified 85 patients with stroke imaging and one intracranial vessel occlusion. An automated clot detection prototype computed clot location, clot length, and clot volume in NECT scans. Clot detection rates were compared to the visual assessment of the hyperdense artery sign by two neuroradiologists. CT angiography (CTA) was used as the ground truth. Additionally, NIHSS, ASPECTS, type of therapy, and TOAST were registered to assess the relationship between clinical parameters, image results, and chosen therapy. (3) Results: the overall detection rate of the software was 66%, while the human readers had lower rates of 46% and 24%, respectively. Clot detection rates of the automated software were best in the proximal middle cerebral artery (MCA) and the intracranial carotid artery (ICA) with 88–92% followed by the more distal MCA and basilar artery with 67–69%. There was a high correlation between greater clot length and interventional thrombectomy and between smaller clot length and rather conservative treatment. (4) Conclusions: the automated clot detection prototype has the potential to detect intracranial arterial thromboembolism in NECT images, particularly in the ICA and MCA. Thus, it could support radiologists in emergency settings to speed up the diagnosis of acute ischemic stroke, especially in settings where CTA is not available.

Abstract Background Ixodid ticks from the Northern Hemisphere have registered a northward expansion in recent years, and Dermacentor reticulatus is such an example in Europe, its expansion being considered a result of climate change alongside other factors. The aim of this study was to identify the composition of questing tick species and the associated pathogens at different sites near the German Baltic coast. Methods Questing ticks were collected monthly at four sites (May–November, 2020), mainly grasslands, and in October and November 2020 at a fifth site. Molecular screening of ticks for pathogens included RT-qPCR for the tick-borne encephalitis virus (TBEV), qPCR for Anaplasma phagocytophilum, PCR for Babesia species and Rickettsia species, and nested PCR for Borrelia species. Results Altogether 1174 questing ticks were collected: 760 Ixodes ricinus, 326 D. reticulatus and 88 Haemaphysalis concinna. The highest activity peak of I. ricinus and D. reticulatus was in May, in June for H. concinna while a second peak was observed only for I. ricinus and D. reticulatus in September and October, respectively. All samples tested negative for TBEV. For A. phagocytophilum, 1.5% of I. ricinus adults tested positive while the minimum infection rate (MIR) in nymphs was 1.3%. This pathogen was found in 0.6% of D. reticulatus. Babesia spp. were detected in I. ricinus (18.2% adults, 2.1% MIR in nymphs) and H. concinna (13.3% adults, 9.7% MIR in nymphs). Borrelia spp. were present only in I. ricinus (49.1% adults, 11.9% MIR in nymphs), while Rickettsia spp. were detected in I. ricinus (14% adults, 8.9% MIR in nymphs) and D. reticulatus (82%). Co-detection of pathogens was observed in 26.6% and 54.8% of positive I. ricinus adults and nymph pools, respectively, while one D. reticulatus tested positive for A. phagocytophilum and Rickettsia spp. The most common co-infection in I. ricinus adults was Babesia microti and Borrelia afzelii (12.3% of positive ticks). Conclusions The results of this study confirm the northern expansion of D. reticulatus and H. concinna in Germany. The detailed data of the infection levels at each location could be useful in assessing the risk of pathogen acquisition following a tick bite. Graphical Abstract

The study examines the relationship between the stock market and exchange rate in South Africa for the period from 1980 to 2020. Quarterly data was used employing the Autoregressive Distributed Lag (ARDL) model given the order of integration of the variables. The empirical results revealed that there is a long-term relationship between the variables of interest. The results also revealed that there is a negative relationship between the stock market and exchange rate movement. The results also show that there is a negative relationship between the stock market and the interest rate as well as inflation as measured by CPI. These results imply that innovations in the exchange rate do have an impact on what happens to the stock market. The impact of exchange rates on stock market can be positive in the short run and negative in the long run and so policymakers can use our findings to avoid making unnecessary monetary or fiscal policy decisions. Policy makers may be able to know when to intervene in influencing the markets using monetary or fiscal policies. Investors and portfolio managers can apply the findings of this study to hedge against exchange rate risk, efficiently diversify their portfolios and predict future stock market movements by observing the exchange rate market.

In recent years, mobile applications (apps) have been increasingly used and investigated as a vocabulary learning approach. Despite the extensive use of commercial English as a Foreign Language (EFL) vocabulary learning apps in China, there is a lack of a review of these apps for a systematic understanding of the components and usefulness of app-assisted vocabulary learning. To fill this knowledge gap, this study presents a systematic review of 15 EFL vocabulary learning apps that were most downloaded in China, focusing on how these apps help students develop word knowledge. The results of this study showed that most apps enabled students to access word knowledge through translating words into their native language. Notably, word knowledge was usually presented through text-plus-image and text-plus-image-plus-audio. Most of these mobile apps provided sentence examples as vocabulary learning materials. Many of these apps were integrated with game elements, especially in interactivity or feedback systems and reward systems. Based on the review results, we have provided three recommendations to vocabulary learning app developers concerning the use of video for the input of word knowledge, the efficiency of vocabulary learning, and the integration of more game elements.

Abstract Background Dental implant placement is safe and predictable, yet optimal management of anticoagulated patients remains controversial. Whilst cessation of anticoagulation pre-operatively should decrease risks of bleeding, risk of thrombosis increases. We aim to define risk of bleeding in patients on oral anticoagulation who are undergoing dental implant placement, in order to establish best management. Methods This systematic review is registered with the National Institute for Health Research (NIHR) PROSPERO database (Registration No: CRD42021233929). We performed a systematic review as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Studies were identified using an agreed search strategy within the OVID Gateway (this included Pubmed, MEDLINE, Cochrane Collaborative). Studies assessing bleeding complications in patients who were undergoing dental implant placement were selected. The primary outcome was bleeding events in anticoagulated patients undergoing dental implant placement. Secondary outcomes included any complication requiring further intervention. Results We identified 182 studies through screening, and after review of titles and abstracts reduced this to 8 studies. In these studies, 1467 participants received at least 2366 implants. Studies were analysed for quality using the ROBINS-I risk of bias tool. Four studies were retrospective case reviews, and four were prospective reviews, three of which also blinded the operator to anticoagulation status. There was significant heterogeneity between the included studies. Meta-analysis showed an increased risk of bleeding (RR, 2.30; 95% CI, 1.25-4.24 p = 0.37 I = 7%) when implants were placed in the presence of anticoagulation however these were not clinically significant haemorrhagic events. Conclusion The continuation of anticoagulants peri-operatively during dental implant surgery does increase the risk of clinically non-significant peri- and post-operative bleeding. Dental implant surgery encompasses a broad spectrum of procedures ranging from minor to more invasive surgery with simple local haemostatic measures mitigating the risk of bleeding. The decision to discontinue anticoagulants prior to dental implant surgery must consider patient and surgical factors with the clinician undertaking a risk-balance assessment.

Background & Aims: The truncating mutations in tight junction protein 2 (TJP2) cause progressive cholestasis, liver failure, and hepatocyte carcinogenesis. Due to the lack of effective model systems, there are no targeted medications for the liver pathology with TJP2 deficiency. We leveraged the technologies of patient-specific induced pluripotent stem cells (iPSC) and CRISPR genome-editing, and we aim to establish a disease model which recapitulates phenotypes of patients with TJP2 deficiency. Methods: We differentiated iPSC to hepatocyte-like cells (iHep) on the Transwell membrane in a polarized monolayer. Immunofluorescent staining of polarity markers was detected by a confocal microscope. The epithelial barrier function and bile acid transport of bile canaliculi were quantified between the two chambers of Transwell. The morphology of bile canaliculi was measured in iHep cultured in the Matrigel sandwich system using a fluorescent probe and live-confocal imaging. Results: The iHep differentiated from iPSC with TJP2 mutations exhibited intracellular inclusions of disrupted apical membrane structures, distorted canalicular networks, altered distribution of apical and basolateral markers/transporters. The directional bile acid transport of bile canaliculi was compromised in the mutant hepatocytes, resembling the disease phenotypes observed in the liver of patients. Conclusions: Our iPSC-derived in vitro hepatocyte system revealed canalicular membrane disruption in TJP2 deficient hepatocytes and demonstrated the ability to model cholestatic disease with TJP2 deficiency to serve as a platform for further pathophysiologic study and drug discovery. Lay summary: We investigated a genetic liver disease, progressive familial intrahepatic cholestasis (PFIC), which causes severe liver disease in newborns and infants due to a lack of gene called TJP2. By using cutting-edge stem cell technology and genome editing methods, we established a novel disease modeling system in cell culture experiments. Our experiments demonstrated that the lack of TJP2 induced abnormal cell polarity and disrupted bile acid transport. These findings will lead to the subsequent investigation to further understand disease mechanisms and develop an effective treatment.

Abstract Background Anaplasma marginale is an obligate intracellular bacterium and the main cause of bovine anaplasmosis in tropical and subtropical regions. In Egypt, data regarding the prevalence of A. marginale in ruminant hosts and of the circulating genotypes is lacking. This study therefore aimed to (i) investigate the presence, epidemiology and genotypes of A. marginale in cattle and buffaloes in Egypt, (ii) to evaluate suitable diagnostic tools and (iii) to identify co-infections of A. marginale with other selected tick-borne pathogens. Methods Blood samples were collected from 394 animals (309 cattle and 85 buffaloes) from three different areas in Egypt. For the detection of A. marginale infection, several tests were compared for their sensitivity and specificity: blood smear analysis, enzyme-linked immunosorbent assay (ELISA), PCR, real-time PCR and reverse line blot (RLB) assay. Co-infections with A. marginale, piroplasms and other Anaplasmataceae were surveyed by RLB while A. marginale genotypes were identified by amplifying and sequencing the partial msp1α gene. Results Anaplasma marginale DNA was amplified by qPCR in 68.3% of cattle and 29.4% of buffaloes. RLB showed infection with A. marginale in 50.2% of cattle and 42.5% of buffaloes. Blood smear analysis detected this agent in 16.2% of cattle and 2.4% of buffaloes. ELISA showed specific antibodies against A. marginale in 54.9% of cattle. Anaplasma marginale was associated, in cattle and buffaloes, with several tick-borne pathogens (Theileria annulata, Babesia bovis, Babesia bigemina, Babesia occultans and Anaplasma platys). A significant difference of A. marginale infection level was noticed in cattle, where animals between 3–5-years-old had a higher prevalence (79.2%) compared to those older than 5 years (36.4%) and younger than 3 years (59.7%) and one year (64.5%), respectively (P = 0.002281). Microsatellite analysis identified 15 different genotypes. Conclusions The epidemiological findings revealed high prevalence of A. marginale in cattle and buffaloes in all the investigated areas. The circulation of diverse genotypes was observed, most of these A. marginale genotypes being specific for Egypt. The qPCR assay was confirmed to be the most sensitive tool for detection of A. marginale in cattle and buffaloes even in the carrier state, highlighting the importance of using suitable diagnostic tests.

Abstract Background Ticks are hematophagous arthropods responsible for maintenance and transmission of several pathogens of veterinary and medical importance. Current knowledge on species diversity and pathogens transmitted by ticks infesting camels in Nigeria is limited. Therefore, the aim of this study was to unravel the status of ticks and tick-borne pathogens of camels in Nigeria. Methods Blood samples (n = 176) and adult ticks (n = 593) were collected from one-humped camels (Camelus dromedarius) of both sexes in three locations (Kano, Jigawa and Sokoto states) in north-western Nigeria and screened for the presence of Rickettsia spp., Babesia spp., Anaplasma marginale, Anaplasma spp. and Coxiella-like organisms using molecular techniques. All ticks were identified to species level using a combination of morphological and molecular methods. Results Ticks comprised the three genera Hyalomma, Amblyomma and Rhipicephalus. Hyalomma dromedarii was the most frequently detected tick species (n = 465; 78.4%) while Amblyomma variegatum (n = 1; 0.2%) and Rhipicephalus evertsi evertsi (n = 1; 0.2%) were less frequent. Other tick species included H. truncatum (n = 87; 14.7%), H. rufipes (n = 19; 3.2%), H. impeltatum (n = 18; 3.0%) and H. impressum (n = 2; 0.3%). The minimum infection rates of tick-borne pathogens in 231 tick pools included Rickettsia aeschlimannii (n = 51; 8.6%); Babesia species, (n = 4; 0.7%) comprising of B. occultans (n = 2), B. caballi (n = 1) and Babesia sp. (n = 1); Coxiella burnetii (n = 17; 2.9%); and endosymbionts in ticks (n = 62; 10.5%). We detected DNA of “Candidatus Anaplasma camelli” in 40.3% of the blood samples of camels. Other tick-borne pathogens including Anaplasma marginale were not detected. Analysis of risk factors associated with both tick infestation and infection with Anaplasma spp. in the blood indicated that age and body condition scores of the camels were significant (P

This study presents a systematic review of previous research on e-book-based language learning. E-book-based language learning has been increasingly investigated in the field of language education, whereas previous review studies of relevant literature were relatively low in volume and incomprehensive from aspects of research participants and research perspectives. In the present study, we identified 52 relevant journal articles on e-book-based language learning published in the recent decade, coding them from three dimensions: methodology, e-book devices and features, and research issues and findings. The results indicated that: (a) most studies on e-book-based language learning were of a large sample size and one-session investigation; (b) pre-school children and university students were the most frequently investigated sample groups; (c) computers and tablets were the most frequently used devices; (d) multimedia, feedback giving, gamification and personalisation were the four features most frequently applied in enhancing the efficiency of e-book-based language learning; (e) researchers collected and processed data mainly through pre- and post-tests and group comparisons; (f) learning outcomes, learning behaviours and learners’ psychological states were investigated in most studies, whereby the findings indicated overall positive effects of e-book on language learning.

Abstract Background Ixodes ricinus is the most common tick species in Europe and the main vector for Borrelia burgdorferi (sensu lato) and tick-borne encephalitis virus (TBEV). It is involved also in the transmission of Borrelia miyamotoi, a relapsing fever spirochete that causes health disorders in humans. Little is known regarding the circulation of Borrelia species and the natural foci of TBEV in north-eastern Germany. The goal of this study was to investigate the infection rates of Borrelia spp. and of TBEV in I. ricinus ticks from north-eastern Germany. Methods Ticks were collected by flagging from 14 forest sites in Mecklenburg-Western Pomerania between April and October 2018. RNA and DNA extraction was performed from individual adult ticks and from pools of 2–10 nymphs. Real time reverse transcription PCR (RT-qPCR) targeted the 3′ non-coding region of TBEV, while DNA of Borrelia spp. was tested by nested PCR for the amplification of 16S-23S intergenic spacer. Multilocus sequence typing (MLST) was performed on B. miyamotoi isolates. Results In total, 2407 ticks were collected (239 females, 232 males and 1936 nymphs). Female and male I. ricinus ticks had identical infection rates (both 12.1%) for Borrelia spp., while nymphal pools showed a minimum infection rate (MIR) of 3.3%. Sequencing revealed four Borrelia species: B. afzelii, B. garinii, B. valaisiana and B. miyamotoi. Borrelia afzelii had the highest prevalence in adult ticks (5.5%) and nymphs (MIR of 1.8%). Borrelia miyamotoi was identified in 3.0% of adults and registered the MIR of 0.8% in nymphs. Borrelia valaisiana was confirmed in 2.5% adult ticks and nymphs had the MIR of 0.7%, while B. garinii was present in 1.1% of adults and showed a MIR of 0.1% in nymphs. The MLST of B. miyamotoi isolates showed that they belong to sequence type 635. No tick sample was positive after RT-qPCR for TBEV RNA. Conclusions The prevalence of B. miyamotoi in I. ricinus ticks registered similar levels to other reports from Europe suggesting that this agent might be well established in the local tick population. The detection of B. burgdorferi (s.l.) indicates a constant circulation in tick populations from this region.

Purpose - The purpose of this paper is to make a correlation analysis between students’ online learning behavior features and course grade, and to attempt to build some effective prediction model based on limited data.Design/methodology/approach - The prediction label in this paper is the course grade of students, and the eigenvalues available are student age, student gender, connection time, hits count and days of access. The machine learning model used in this paper is the classical three-layer feedforward neural networks, and the scaled conjugate gradient algorithm is adopted. Pearson correlation analysis method is used to find the relationships between course grade and the student eigenvalues. Findings - Days of access has the highest correlation with course grade, followed by hits count, and connection time is less relevant to students’ course grade. Student age and gender have the lowest correlation with course grade. Binary classification models have much higher prediction accuracy than multi-class classification models. Data normalization and data discretization can effectively improve the prediction accuracy of machine learning models, such as ANN model in this paper. Originality/value - This paper may help teachers to find some clue to identify students with learning difficulties in advance and give timely help through the online learning behavior data. It shows that acceptable prediction models based on machine learning can be built using a small and limited data set. However, introducing external data into machine learning models to improve its prediction accuracy is still a valuable and hard issue.

Purpose: The study analyses the effects of sovereign credit ratings on financial development in South Africa. This became important considering that the country has been receiving negative ratings of late. Design/Methodology/Approach: Quarterly data for the period 1994-2017 was analysed using the Auto-Regressive Distributed Lag (ARDL) cointegration model and its associated statistics. The Error Correction Model (ECM) was implemented to augment the results of ARDL analysing the short run dynamics. The model was chosen given the order of integration of the variables. Financial development was selected since it influences financial conditions and financial sector stability. Findings: The statistical results revealed that sovereign ratings positively influence financial variables that is in other words higher ratings are found to contribute positively to the growth of the financial development sector. Negative ratings are likely to affect the financial system as due to low access to external funding and exodus of investors, financial development is halted or decreased. Implications/Originality/Value: The results suggest that authorities need to consider the factors which are targeted by rating agencies and ensure that they perform as expected. Governments should focus on raising sovereign ratings and avoiding downgrades to boost financial development.

Discussing socio-scientific issues in a secondary chemistry classroom poses a challenge to traditional classroom practice because students and teachers need to think more broadly about chemical processes. Allowing students to create open-ended maps to generate and represent their understanding of socio-scientific issues while also learning chemistry theory can develop Systems Thinking capacity in students. This manuscript presents three vignettes of the classroom use of mapping exercises within separate action research studies, involving diverse school types, curricula, chemistry topics and student groups. The mapping exercises were effective to engage students in the development of Systems Thinking and were readily integrated into different curricula. Sequential student-generated maps for chemical processes illustrate increasing sophistication in their Systems Thinking approaches.

Abstract Background Real-time cardiovascular magnetic resonance (CMR) assessment of ventricular volumes and function enables data acquisition during free-breathing. The requirement for high spatiotemporal resolution in children necessitates the use of highly accelerated imaging techniques. Methods A novel real-time balanced steady state free precession (bSSFP) spiral sequence reconstructed using Compressed Sensing (CS) was prospectively validated against the breath-hold clinical standard for assessment of ventricular volumes in 60 children with congenital heart disease. Qualitative image scoring, quantitative image quality, as well as evaluation of biventricular volumes was performed. Standard BH and real-time measures were compared using the paired t-test and agreement for volumetric measures were evaluated using Bland Altman analysis. Results Acquisition time for the entire short axis stack (~ 13 slices) using the spiral real-time technique was ~ 20 s, compared to ~ 348 s for the standard breath hold technique. Qualitative scores reflected more residual aliasing artefact (p

A green economic recovery from Covid-19 cannot be built in the image of a pre-Covid era. Green growth must be abandoned.

Since Sundqvist introduced the term "extramural English" in 2009, empirical research on extramural language learning has continued to expand. However, the expanding empirical research has yet yielded incommensurate review studies. To present a timely picture of the field of extramural language learning, this study conducts a review of 33 relevant articles retrieved from Scopus and Web of Science databases. The results showed the five types of target languages frequently investigated in this field (i.e., English, German, French, Chinese, and Japanese) and seven main types of extramural learning activities (i.e., playing digital games, watching videos, reading, listening to audios, having technology-enhanced socialisation, having face-to-face socialisation, and writing compositions). People's engagement in extramural language learning was overall high, especially listening to audios and playing digital games, mediated by the relationship between the difficulty of the activities and people's target language proficiency levels, gender, and the interactive environment. Extramural language learning was overall effective for language development and enhancing affective states in language learning. The effectiveness may be influenced by the involvement of language inputs and outputs and the amount of engagement time. Implications for practitioners were suggested concerning encouraging digital gameplay, emphasising formal language instruction, and creating positive interactive environments for extramural language learning.

Top-N personalized recommendation has been extensively studied in assisting learners in finding interesting courses in MOOCs. Although existing Top-N personalized recommendation methods have achieved comparable performance, these models have two major shortcomings. First, these models seldom learn an explicit representation of the structural relation of items. Second, most of these models typically obtain a user’s general preference and neglect the recency of items. This paper proposes a Top-N personalized Recommendation with Graph Neural Network (TP-GNN) in the Massive Open Online Course (MOOCs) as a solution to tackle this problem. We explore two different aggregate functions to deal with the user’s sequence neighbors and then use an attention mechanism to generate the final item representations. The experiments on a real-world course dataset demonstrated that TP-GNN could improve the performances. Furthermore, the system developed based on our method obtains positive feedback from the participants, which denotes that our method effectively predicts learners’ preferences and needs.

Stimulants play a central role in modern human society. Consumption of stimulants transcends culture, demography, and income group. As cash crops, stimulants (such as cocoa, coffee, tea and tobacco) also act as a source of economic security for producers in low-income countries. However, satisfying the demand for stimulants entails a potentially large environmental cost. This burden demands careful attention given the potentially negative impact of stimulant production on local food security. To date, stimulants have been peripheral to the research and policy agenda on sustainable food systems. We undertake the first global assessment of water, land and fertiliser use associated with cocoa, coffee, tea and tobacco production, consumption and trade, across 254 countries, between 2002 and 2017. Globally, resource use associated with these stimulants (except for tobacco) grew substantially over this period. In 2017, the stimulant economy required i) land use equivalent to the total land area of Italy; ii) green and blue water equivalent to the food sectors of Brazil and Portugal, respectively; and iii) fertiliser use equivalent to India's total fertiliser demand in the same year. We show that the main centres of resource use and demand associated with stimulants implicate a few major countries, presenting management opportunities through supply chain screening of resource-intensive production sources and targeted demand-side policies. Differences between stimulant's resource use also highlights the potential for substitution of consumption to reduce environmental pressures across this system.

This study is an empirical analysis of sovereign credit ratings (SCR) in South Africa (SA) using Logistic Regression (LR) to identify their determinants and forecast SCRs. Data of macroeconomic indicators including SCRs from 1999 to 2020 in quarterly format were classified and analyzed to identify indicators utilized by Credit Rating Agencies (CRAs) and then predict future ratings CRAs take various information from political, infrastructure, financial, economic, regional, local, and other factors pertaining to a country and assess the ability of that country to pay its debt. This information is then presented through a grading scale termed rating, with the highest rating country being highly creditworthy and lowest rating likely to default. There are three major CRAs, namely, Fitch, Moodys and Standard and Poors. The study identified the use of different macroeconomic indicators by CRAs as well as different techniques in assessing and assigning sovereign credit ratings. The study points out that Household Debt to Disposable Income Ratio (HDDIR) was the most influential variable on SCRs. HDDIR, exchange rates and the inflation rate were the most crucial variables for guessing credit ratings. Policymakers should aim to reduce household debt in relation to disposable income, implement policies that strengthen the local currency and stabilize as well as lower inflation. Investors should watch out on nations that have high household debt levels as this may spill over into credit risk.

The aim of this article is to illustrate how visions of the future—sociotechnical imaginaries— mediate and thus shape sociotechnical practices involving educational robots in a Danish school context. In the analysis I show how imaginaries are manifested both in technological artefacts, teachers’ discourse and in policy documents from political bodies such as the OECD and the Danish Agency for Digitisation (DIGST). To show this manifestation, I apply two concepts: The Science and Technology Studies (STS) concept of ‘sociotechnical imaginaries’ as formulated by Sheila Jasanoff (2015) and the concept of ‘mediation’ known from postphenomenological tradition. I develop an analytical framework based on these two concepts and coin a third — ‘symbolic mediation’ — to present and analyse a case study based on an ethnographic field study that included semi-structured interviews conducted in a Danish school setting. The case study shows how the use of the robot NAO—an educational technology—is driven by two related imaginaries that both serve as arguments for implementing and using the robot—the imaginary of the digital future and the imaginary of educational optimization.

If widely adopted, the ‘planetary health diet’ (PHD), proposed by the EAT-Lancet Commission, would help to meet ambitious sustainability goals currently jeopardised by excessive and resource intensive food demand. To date, convergence of nations to the PHD has been assessed using average food consumption patterns, overlooking the influence of different consumers within this context. Using self-reported dietary intake data from a snapshot survey of the US we reveal the differentiated responsibilities of US citizens within the country’s adoption of the PHD otherwise hidden by use of country averaged dietary intake data. We show how such a granular analysis of food consumption patterns is critical to identify levers in the sustainable food transition of nations. By combining 7418 individual food intake reports from a representative cross section of the United States (US) with commodity-level impact data we estimate the overshoot of US dietary patterns in relation to the PHD and their impacts across the climate, water and land system. The net environmental impacts of PHD adoption across the US population are quantified based on realistic dietary shifts. We estimate that US overshoot of the PHD is responsible for 70% of the US dietary greenhouse gas (GHG) footprint. However, over 60% of this burden could be eliminated by just 10% of the US population following the PHD. Although we estimate PHD adoption will more than half the US dietary GHG footprint and land footprint, we find it may have unintended consequences on water demand due to increased tree nut consumption. Across almost all food categories, we show that the food choices of the top tier of consumers in the US create, and must bridge the PHD gap. As such, actions by these consumers will be of major consequences to the speed and direction of the country’s sustainable dietary transition. To avoid environmental trade-offs, dietary policies must be scrutinised across multiple sustainability criteria.

Die technische Infrastruktur, die zum Erstellen, Teilen und Remixen von freien Bildungsmaterialien genutzt wird, kann erheblichen Einfluss auf die Gestaltung derselben haben und verdient eine stärkere Betrachtung als bisher. Der «Action Plan» des zweiten OER-Weltkongresses scheint diese Aussage zu stützen. So werden in ihm an mehreren Stellen zu bearbeitende Felder genannt werden, die direkt oder indirekt von der technischen Infrastruktur abhängen – ohne sie jedoch selbst zum Ziel von Bemühungen zu machen. Die Infrastruktur ist jedoch nicht lediglich ein Werkzeug, das didaktischen Überlegungen Wirkung verleiht, sondern gleichsam unterschwelliges Vehikel für zu transportierende Werte. Da Open-Source-Software viele Werte mit der OER-Bewegung teilt, sollte ihr trotz der immer wieder auftretenden Unbequemlichkeiten im Vergleich zu ‹unfreier› Software der Vorzug gegeben werden. Der Beitrag versteht sich als Plädoyer, das exemplarisch anhand der offenen Software H5P zeigt, wie sich mit ihr zahlreiche Tätigkeiten unterstützen lassen, die der Öffnung der Lehre dienen. Ferner wird argumentiert, dass die Kongruenz der Werte von offener Bildung und offener Software mehr ist als reine Ästhetik, sondern im besten Fall zur Verbreitung dieser Werte beitragen kann.

Purpose - The purpose of this paper is to identify the success factors and challenges for students studying in an open and distance learning (ODL) mode and recommend strategies for student persistence based on the findings. Design/methodology/approach - Three groups of ODL students with various levels of study performance – nine high-level, nine mid-level and eight low-level students – were invited to participate in three focus group interviews. They were asked about their motivation, success factors and challenges in their studies. Findings - The different groups of participants showed observable variations in their response. The mid-level students believed that word-by-word rote memorisation was their best strategy in preparing for examinations. The low-level students believed that they needed to master multitasking to learn well in tight schedules. All these weak student participants considered quitting at some points, but no high-level student did so. To improve student persistence, the authors focus on meeting the needs of weak students and recommend the following actions for student persistence: add a time management and study skills component to existing courses for students to practise; appoint advisors to distance learning students to help them create an appropriate study plan and acquire a sense of belonging; make learning videos short and engaging; consider adopting student leaders or peer tutors that have been used successfully in full-time study; and conduct focus periodically with students to hear their views. Originality/value - This study revealed the factors contributing to student persistence in ODL for the students of various levels of study performance. The results help in formulating measures to meet the diverse needs of ODL students for persistence in their studies.

CAG/CTG trinuncleotide repeats are fragile sequences that when expanded form DNA secondary structures and cause human disease. We evaluated CAG/CTG repeat stability and repair outcomes in histone H2 mutants in S. cerevisiae. Although the two copies of H2A are nearly identical in amino acid sequence, CAG repeat stability depends on H2A copy 1 (H2A.1) but not copy 2 (H2A.2). H2A.1 promotes high-fidelity homologous recombination, sister chromatid recombination (SCR), and break-induced replication whereas H2A.2 does not share these functions. Both decreased SCR and the increase in CAG expansions were due to the unique Thr126 residue in H2A.1 and hta1Δ or hta1-T126A mutants were epistatic to deletion of the Polδ subunit Pol32, suggesting a role for H2A.1 in D-loop extension. We conclude that H2A.1 plays a greater repair-specific role compared to H2A.2 and may be a first step towards evolution of a repair-specific function for H2AX compared to H2A in mammalian cells.

Knowledge on the occurrence of pathogenic tick-borne bacteria Anaplasma phagocytophilum and Anaplasma ovis is scarce in sheep from Germany. In 2020, owners from five flocks reported ill thrift lambs and ewes with tick infestation. Out of 67 affected sheep, 55 animals were clinically examined and hematological values, blood chemistry and fecal examinations were performed to investigate the underlying disease causes. Serological tests (cELISA, IFAT) and qPCR were applied to all affected sheep to rule out A. phagocytophilum and A. ovis as a differential diagnosis. Ticks were collected from selected pastures and tested by qPCR. Most animals (n = 43) suffered from selenium deficiency and endoparasites were detected in each flock. Anaplasma spp. antibodies were determined in 59% of examined sheep. Seventeen animals tested positive for A. phagocytophilum by qPCR from all flocks and A. phagocytophilum was also detected in eight pools of Ixodes ricinus. Anaplasma phagocytophilum isolates from sheep and ticks were genotyped using three genes (16S rRNA, msp4 and groEL). Anaplasma ovis DNA was identified in six animals from one flock. Clinical, hematological and biochemical changes were not significantly associated with Anaplasma spp. infection. The 16S rRNA analysis revealed known variants of A. phagocytophilum, whereas the msp4 and groEL showed new genotypes. Further investigations are necessary to evaluate the dissemination and health impact of both pathogens in the German sheep population particularly in case of comorbidities.

Objective Critical care capabilities needed for the management of septic patients, such as continuous vital sign monitoring, are largely unavailable in most emergency departments (EDs) in low- and middle-income country (LMIC) settings. This study aimed to assess the feasibility and accuracy of using a wireless wearable biosensor device for continuous vital sign monitoring in ED patients with suspected sepsis in an LMIC setting. Methods This was a prospective observational study of pediatric (≥2 mon) and adult patients with suspected sepsis at the Kigali University Teaching Hospital ED. Heart rate, respiratory rate and temperature measurements were continuously recorded using a wearable biosensor device for the duration of the patients’ ED course and compared to intermittent manually collected vital signs. Results A total of 42 patients had sufficient data for analysis. Mean duration of monitoring was 32.8 h per patient. Biosensor measurements were strongly correlated with manual measurements for heart rate (r = 0.87, p < 0.001) and respiratory rate (r = 0.75, p < 0.001), although were less strong for temperature (r = 0.61, p < 0.001). Mean (SD) differences between biosensor and manual measurements were 1.2 (11.4) beats/min, 2.5 (5.5) breaths/min and 1.4 (1.0)°C. Technical or practical feasibility issues occurred in 12 patients (28.6%) although were minor and included biosensor detachment, connectivity problems, removal for a radiologic study or exam, and patient/parent desire to remove the device. Conclusions Wearable biosensor devices can be feasibly implemented and provide accurate continuous heart rate and respiratory rate monitoring in acutely ill pediatric and adult ED patients with sepsis in an LMIC setting.

With the increasing number of users and the emergence of different types of network services, a multi-server architecture has emerged in recent years. In order to ensure the secure communication of Internet participants in an open network environment, the authentication and key agreement protocol for multi-server architectures were proposed in the past. In 2018, Chatterjee et al. put forward a lightweight three-factor authentication and key agreement protocol for a multi-server environment, and they claimed that all known security features with satisfactory performance could be realized in their protocol. However, it is found that their scheme is vulnerable to user impersonation attacks and cannot achieve user un-traceability and three-factor security through our cryptanalysis. In order to solve these shortcomings, we propose a new lightweight and anonymous three-factor authentication scheme for the multi-server environment in this article. Furthermore, the proposed protocol is proved to be AKE secure theoretically, and we use BAN-logic to prove that our protocol realizes mutual authentication between communication participants. Finally, we show that our proposed scheme is practical and efficient through the comparison of security features and performance.

West Nile virus (WNV) is a mosquito-borne agent that has also been isolated from several tick species. Vector competence of Ixodes ricinus, one of the most common tick species in Europe, has been poorly investigated for WNV to date. As such, to evaluate the vector competence, laboratory reared Ixodes ricinus nymphs were in vitro fed with WNV lineage 1 infectious blood, allowed to molt, and the resulting females artificially fed to study the virus transmission. Furthermore, we studied the kinetics of WNV replication in ticks after infecting nymphs using an automatic injector. Active replication of WNV was detected in injected nymphs from day 7 post-infection until 28 dpi. In the nymphs infected by artificial feeding, the transstadial transmission of WNV was confirmed molecularly in 46.7% of males, while virus transmission during in vitro feeding of I. ricinus females originating from infected nymphs was not registered. The long persistence of WNV in I. ricinus ticks did not correlate with the transmission of the virus and it is unlikely that I. ricinus represents a competent vector. However, there is a potential reservoir role that this tick species can play, with hosts potentially acquiring the viral agent after ingesting the infected ticks.

We report a new locality for Rueppel’s Snake-eyed skink (Ablepharus rueppellii) in Southern Israel – near Shivta Junction. This record extends the known distribution of this species in Israel by ~25km. We examined all known localities of this species in Israel and the adjacent Sinai Peninsula (Egypt), and discuss some discrepancies between them and currently published range maps, including the one produced by the IUCN.

Specialized endoscopic evaluation for patients with Barrett’s esophagus (BE) is well supported; however, no studies have shown that centers with expertise provide better quality care for BE with high-grade dysplasia or early adenocarcinoma. In this study, the investigators aimed to evaluate the management and clinical course for patients treated in a community practice versus a specialized BE center. Methods. A retrospective analysis of referrals from the community to our specialized center for evaluation of BE at St Paul’s Hospital Division of Gastroenterology between January 2007 and February 2014 was performed. Subjects were patients who were referred for BE and dysplasia and subsequently reevaluated by endoscopy. The pathology and endoscopy reports from the community and our center were reviewed. Inclusion criteria were as follows: being ≥ 19 years old and pathologic diagnosis of BE or dysplasia in the community. Exclusion criteria were as follows: incomplete pathology data or incomplete endoscopy reports from the community physicians. Results. A total of 77 patients were reviewed. The staging of 28.9% of patients referred from the community was changed from the initial pathological diagnosis. 18.4% of these patients were upstaged. Using Fischer’s exact test, we showed that, in our specialized center, endoscopic impressions correlated significantly with pathology results (p

Objective. The Canadian Association of Gastroenterology Wait Time Consensus Group recommends that patients with symptoms associated with colorectal cancer (CRC) should have an endoscopic examination within 2 months. However, in a recent survey of Canadian gastroenterologists, wait-times for endoscopy were considerably longer than the current guidelines recommend. The purpose of this study was to evaluate wait-times for colonoscopy in patients who were subsequently found to have CRC through the Division of Gastroenterology at St. Paul’s Hospital (SPH). Methods. This study was a retrospective chart review of outpatients seen for consultation and endoscopy ultimately diagnosed with CRC. Subjects were identified through the SPH pathology database for the inclusion period 2010 through 2013. Data collected included wait-times, subject characteristics, cancer characteristics, and outcomes. Results. 246 subjects met inclusion criteria for this study. The mean wait-time from primary care referral to first office visit was 63 days; the mean wait-time to first endoscopy was 94 days. Patients with symptoms waited a mean of 86 days to first endoscopy, considerably longer than the national recommended guideline of 60 days. There was no apparent effect of length of wait-time on node positivity or presence of distant metastases at the time of diagnosis. Conclusion. Wait-times for outpatient consultation and endoscopic evaluation at the St. Paul’s Hospital Division of Gastroenterology exceed current guidelines.

Arabinogalactan proteins (AGP) are a diverse family of proteoglycans associated with the cell surfaces of plants. AGP have been implicated in a wide variety of plant cell processes, including signaling in symbioses. This study investigates the existence of putative AGP in free-living cyanobacterial cultures of the nitrogen-fixing, filamentous cyanobacteria Nostoc punctiforme and Nostoc sp. strain LBG1 and at the symbiotic interface in the symbioses between Nostoc spp. and two host plants, the angiosperm Gunnera manicata (in which the cyanobacterium is intracellular) and the liverwort Blasia pusilla (in which the cyanobacterium is extracellular). Enzyme-linked immunosorbent assay, immunoblotting, and immunofluorescence analyses demonstrated that three AGP glycan epitopes (recognized by monoclonal antibodies LM14, MAC207, and LM2) are present in free-living Nostoc cyanobacterial species. The same three AGP glycan epitopes are present at the Gunnera–Nostoc symbiotic interface and the LM2 epitope is detected during the establishment of the Blasia–Nostoc symbiosis. Bioinformatic analysis of the N. punctiforme genome identified five putative AGP core proteins that are representative of AGP classes found in plants. These results suggest a possible involvement of AGP in cyanobacterial–plant symbioses and are also suggestive of a cyanobacterial origin of AGP.