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Central nervous system (CNS) involvement is seen across a variety of rheumatic diseases. Common CNS manifestations include cerebrovascular events (such as ischemic and hemorrhagic strokes, cerebral venous sinus thrombosis), seizures, headaches, demyelinating lesions (such as optic neuritis, myelitis, parenchymal lesions), meningeal disease (leptomeningeal and pachymeningeal involvement, meningitis), and others. While most patients have other systemic symptoms of their rheumatic disease at the time of developing neurologic complications, some may present with CNS disease as the first symptom of their rheumatic disease. This review discusses rheumatic diseases with CNS manifestations and provides neuroimaging findings observed among affected individuals.

While there has been a trend in the last decades for publishing large-scale and highly-interconnected Knowledge Graphs (KGs), their users often get overwhelmed by the task of understanding their content as a result of their size and complexity. Data profiling approaches have been proposed to summarize large KGs into concise and meaningful representations, so that they can be better explored, processed, and managed. Profiles based on schema patterns represent each triple in a KG with its schema-level counterpart, thus covering the entire KG with profiles of considerable size. In this paper, we provide empirical evidence that profiles based on schema patterns, if explored with suitable mechanisms, can be useful to help users understand the content of big and complex KGs. ABSTAT provides concise pattern-based profiles and comes with faceted interfaces for profile exploration. Using this tool we present a user study based on query completion tasks. We demonstrate that users who look at ABSTAT profiles formulate their queries better and faster than users browsing the ontology of the KGs. The latter is a pretty strong baseline considering that many KGs do not even come with a specific ontology to be explored by the users. To the best of our knowledge, this is the first attempt to investigate the impact of profiling techniques on tasks related to knowledge graph understanding with a user study.

Objective: Brain metastasis (BM) from bone and soft tissue sarcomas (STS) is very rare and mostly predicts dismal prognosis. Owing to its' rarity, data on optimal therapy including surgical management, chemotherapy, and radiotherapy is scarce. We sought to assess the prevalence, disease characteristics, and outcomes of BM in bone and STS patients treated at a single institution. Methods: A retrospective chart review was performed for consecutive bone and STS patients treated at King Hussein Cancer Center from 2007 to 2020. Patients with BM were identified. Survival was estimated by the Kaplan-Meier method. Factors of possible effect on OS was examined in univariate analysis. Survival comparisons were carried out by the log-rank test. Results: A total of 1,548 bone and STS patients were treated at our center during the eligibility period. We identified 18 patients (1.1) who had BM at initial presentation (n = 16, 1.0) or during follow up (n = 2; 0.1). Fourteen patients (77.8) were male. The median age was 29.5 years (range: 0.1-60 years). The primary tumor was most commonly located in the extremities (61). Ten different histopathological subtypes were encountered; Ewing sarcoma (ES) was the most common (n = 4; 28). Twelve patients (67) had lung metastasis as the first site of metastatic disease. BM was detected at a median time of 12 months following sarcoma diagnosis (range: 1-71 months). A total of 10 patients (56) had solitary metastasis and 4 patients (22.2) had hemorrhagic metastasis. The most common location of brain metastatic lesions was the occipital lobe (n = 4; 22.2). Thirteen patients received treatment for metastatic brain sarcoma. The most common treatment modality was radiotherapy, received by a total of 10 patients (55.5), followed by surgical intervention performed in a total of 5 patients (27.7), The other treatment modalities included combined chemo-radiotherapy (n = 2), targeted therapy plus chemotherapy, and targeted therapy plus radiotherapy (n = 1, each). At a median follow up of 10 months following detection of BM, the median OS was 4.0 months; (95 CI: 2.54-5.46). We did not identify any factor that influenced OS in univariate analysis. Conclusion: Sarcoma BM is exceedingly rare and herald's dismal prognosis. ES was a major histological subtype accounting for BM metastasis in our series. Keywords: Brain metastasis, sarcoma, sarcomatous brain metastasis, surgical resection, Author(s): Hazim Sameer Ababneh [1]; Baha'eddin Muhsen (corresponding author) [1]; Ahmad Salah Fares [3]; Hawazen Hirbawi [4]; Tala Al Awabdeh [2]; Maysa Al Hussaini [5]; Rula Amarin [2]; Abdlatif Al [...]

The pathogenesis of age-related macular degeneration (AMD) involves aberrant complement activation and is a leading cause of vision loss worldwide. Complement aberrations are also implicated in many systemic immune-mediated inflammatory diseases (IMIDs), but the relationship between AMD and these conditions remains undescribed. The aim of this study is to first assess the association between AMD and IMIDs, and then assess the risk of AMD in patients with specific IMIDs associated with AMD.

This study examined the level of adherence to the recommended cervical cancer screening guidelines among Garifuna women residing in New York City, and screening practice association with demographic factors, access to healthcare services, perceptions/barriers to cervical cancer screening, acculturation, identity, and level of screening guideline knowledge. Four hundred Garifuna women were surveyed. The study results reveal low self-reported cervical cancer screening rates (60%), increased age, visiting a Garifuna healer in the past year, perceived benefits of receiving the screening test, and knowledge of the Pap test as having the highest predictive variability for receiving cervical cancer screening. The odds of having a Pap test were significantly lower in older women (age 65 years and above) and those visiting a traditional healer within the past year. The study findings provide several implications for developing culturally appropriate interventions aimed to increase the level of cervical cancer screening in this unique immigrant group.

This study delves into the complex prioritization process for Autism Spectrum Disorder (ASD), focusing on triaged patients at three urgency levels. Establishing a dynamic prioritization solution is challenging for resolving conflicts or trade-offs among ASD criteria. This research employs fuzzy multi-criteria decision making (MCDM) theory across four methodological phases. In the first phase, the study identifies a triaged ASD dataset, considering 19 critical medical and sociodemographic criteria for the three ASD levels. The second phase introduces a new Decision Matrix (DM) designed to manage the prioritization process effectively. The third phase focuses on the new extension of Fuzzy-Weighted Zero-Inconsistency (FWZIC) to construct the criteria weights using Single-Valued Neutrosophic 2-tuple Linguistic (SVN2TL). The fourth phase formulates the Multi-Attributive Border Approximation Area Comparison (MABAC) method to rank patients within each urgency level. Results from the SVN2TL-FWZIC weights offer significant insights, including the higher criteria values "C12 = Laughing for no reason" and "C16 = Notice the sound of the bell" with 0.097358 and 0.083832, indicating their significance in identifying potential ASD symptoms. The SVN2TL-FWZIC weights offer the base for prioritizing the three triage levels using MABAC, encompassing medical and behavioral dimensions. The methodology undergoes rigorous evaluation through sensitivity analysis scenarios, confirming the consistency of the prioritization results with critical analysis points. The methodology compares with three benchmark studies, using four distinct points, and achieves a remarkable 100% congruence with these prior investigations. The implications of this study are far-reaching, offering a valuable guide for clinical psychologists in prioritizing complex cases of ASD patients.

This study aims to assess the small ruminant value chain in Al-Ruwaished District, Jordan, to identify the potential intervention areas that could improve the production efficiency and guarantee the sustainability of the small ruminant sector in this area. Sheep breeding is the source of livelihood for most of the people in Al-Ruwaished District, which is characterized by the large number of sheep and goats. We surveyed 5.0% of the small ruminant holders in the study area and conducted individual interviews and surveys with the potential actors in the value chain to undertake a small ruminant value chain analysis. From the survey, we found that the small ruminant value chain consists of five core functions, namely, input supply, production management, marketing, processing, and consumption. Despite the large number of holdings that gives an impression of the stability to the small ruminant sector, the surveyed results show a clear fragility in the value chain of small ruminants in this area. The small ruminant production system is negatively impacted by climate change, especially continuous drought. In addition, the high prices of feed that the farmer cannot afford with clear and real absence of the governmental and non-governmental support activities also impact the development of the value chain. The results of strengths, weaknesses, opportunities, and threats (SWOT) analysis reveal that the major constraints faced by this value chain could be divided into external and internal threats. Specifically, the most prominent external threats are the nature of the desert land and continuous drought, while the major internal threats are the absence of appropriate infrastructure, shortage of inputs, and weakness in the production management and marketing. We proposed solutions to these challenges to ensure the sustainability and effectiveness of the sector, such as the formulation of emergency response plans to severe weather, qualifying farmers’ skills, and establishment of agricultural cooperative societies.

Central nervous system vasculitis (CNSV) is a group of disorders leading to inflammatory vasculopathy within the brain, spinal cord, and leptomeninges. CNSV is divided into primary angiitis of the central nervous system (PACNS) and secondary CNSV based on the underlying etiology. PACNS is a rare inflammatory disorder with poorly understood pathophysiology and heterogeneous and highly variable clinical features. The diagnosis depends on a combination of clinical and laboratory variables, multimodal imaging, and histopathological examination as well as exclusion of mimics. Several systemic vasculitides, infectious etiologies and connective tissue disorders have been shown to cause secondary CNSV and require prompt recognition.

Vapor pressure deficit (VPD) shows a gradually increasing trend that forces trees to produce ecological memory with time-delay characteristics to drought year by year. The reversible stem diameter variation of trees can serve as an indicator for tree water status. In the context of global warming, these variations can dynamically monitor the response of stem water to the change of environmental water, especially to VPD. In this study, stem diameter variations of Larix gmeliniiRupr. and environmental factors were measured at high temporal resolution. We analyzed the tree water deficit–induced stem shrinkage (TWD) response to VPD variations. The results showed that variation of TWD lagged behind that of VPD to a certain extent, by about 3–5.5 h. Environmental water supply of trees under natural conditions can be divided into water deficit and adequate water supply. The division of the two water conditions was helpful to study the correlation between TWD and VPD. Observing the response of changes of stem diameter to the time lag of VPD is helpful to accurately represent the relationship of changes between moisture in the tree body and moisture in the air and to identify the stress effect of the lag in a short period of time.Study Implications: Stem diameter changes with change in moisture in the environment and usually reversibly shrinks under water deficits. Such reversible change in stem diameter is closely related to change in vapor pressure deficit, which is an environmental factor. Tree water deficit–induced trunk shrinkage, an index reflecting the change in stem diameter affected by moisture, had a time lag correlation with vapor pressure deficit in terms of variation characteristics. The time lag of the tree water deficit–induced trunk shrinkage response to vapor pressure deficit was 3–5.5 h. Just as the phenomenon of ecological memory cannot be ignored in an observational study with the year as the time scale, the phenomenon of time lag should not be ignored during an observational study of moisture stress at small time scales.

•BCR signaling is inhibited by pirtobrutinib in vitro and in vivo regardless of BTK C481S mutation but is reactivated in vivo at progression.•BTK mutations at the gatekeeper site T474 and second-site kinase-dead mutations lead to resistance to pirtobrutinib.

Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hocanalysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hocstudy of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

In the context of autism spectrum disorder (ASD) triage, the robustness of machine learning (ML) models is a paramount concern. Ensuring the robustness of ML models faces issues such as model selection, criterion importance, trade-offs, and conflicts in the evaluation and benchmarking of ML models. Furthermore, the development of ML models must contend with two real-time scenarios: normal tests and adversarial attack cases. This study addresses this challenge by integrating three key phases that bridge the domains of machine learning and fuzzy multicriteria decision-making (MCDM). First, the utilized dataset comprises authentic information, encompassing 19 medical and sociodemographic features from 1296 autistic patients who received autism diagnoses via the intelligent triage method. These patients were categorized into one of three triage labels: urgent, moderate, or minor. We employ principal component analysis (PCA) and two algorithms to fuse a large number of dataset features. Second, this fused dataset forms the basis for rigorously testing eight ML models, considering normal and adversarial attack scenarios, and evaluating classifier performance using nine metrics. The third phase developed a robust decision-making framework that encompasses the creation of a decision matrix (DM) and the development of the 2-tuple linguistic Fermatean fuzzy decision by opinion score method (2TLFFDOSM) for benchmarking multiple-ML models from normal and adversarial perspectives, accomplished through individual and external group aggregation of ranks. Our findings highlight the effectiveness of PCA algorithms, yielding 12 principal components with acceptable variance. In the external ranking, logistic regression (LR) emerged as the top-performing ML model in terms of the 2TLFFDOSM score (1.3370). A comparative analysis with five benchmark studies demonstrated the superior performance of our framework across all six checklist comparison points.

Single-cell combinatorial indexing RNA sequencing (sci-RNA-seq) is a powerful method for recovering gene expression data from an exponentially scalable number of individual cells or nuclei. However, sci-RNA-seq is a complex protocol that has historically exhibited variable performance on different tissues, as well as lower sensitivity than alternative methods. Here, we report a simplified, optimized version of the sci-RNA-seq protocol with three rounds of split-pool indexing that is faster, more robust and more sensitive and has a higher yield than the original protocol, with reagent costs on the order of 1 cent per cell or less. The total hands-on time from nuclei isolation to final library preparation takes 2–3 d, depending on the number of samples sharing the experiment. The improvements also allow RNA profiling from tissues rich in RNases like older mouse embryos or adult tissues that were problematic for the original method. We showcase the optimized protocol via whole-organism analysis of an E16.5 mouse embryo, profiling ~380,000 nuclei in a single experiment. Finally, we introduce a ‘Tiny-Sci’ protocol for experiments in which input material is very limited.

This study attempts to gain insight into what factor influence on customer engagement and organisational performance. The research model of this study comprises e-marketing and organisational capability factors to investigate customer engagement. Additionally, the moderating role of market orientation was studied between customer engagement and organisational performance. Data were analysed with latest statistical approach namely structural equation modelling (SEM). Results revealed substantial variance R253.2% in customer engagement and R255.1% variance in organisational performance. The effect size analysis (f2) indicates that customer engagement has large effect size in predicting organisational performance. The predictive relevance of the model was tested with Q2indicated substantial power to predict market orientation and organisational performance. For managerial implications, this study is suggested that constructs like customer engagement, e-marketing, market orientation, learning capability and innovation capability are the most important constructs that managers should take into consideration in order to enhance the organisational performance.

A new framework for explainable artificial intelligence in the context of multimodal triage for autism spectrum disorders (ASD) using a fuzzy approach-based multi-criteria decision-making (MCDM) is proposed in this study. The framework consists of five phases. In the first phase, a real ASD dataset of 538 autistic patients is obtained and diagnosed based on 42 medical and sociodemographic criteria. In the second phase, an ASD methodology for triaging the 538 autistic patients into three levels (i.e., minor, moderate, and urgent) is presented using fuzzy approach-based MCDM techniques, namely, fuzzy Delphi method and fuzzy-weighted zero-inconsistency, followed by the processes for triaging autism patients. In the third phase, cost-sensitive learning is employed to balance two ASD datasets: one labeled based on the ASD triage methodology and the other labeled by specialized psychologists. Two multimodal of artificial intelligence are developed in the fourth phase using nine machine-learning algorithms for the balanced ASD datasets. The evaluation of the two multimodal setups is carried out using nine metrics. In the fifth phase, the local interpretable model-agnostic explanations (LIME) model is used to interpret the models using two scenarios. Four new algorithms are presented in the developed framework.

Hybridised classification and prioritisation of patients with chronic heart diseases (CHDs) can save lives by categorising them on the basis of disease severity and determining priority patients. Such hybridisation is challenging and thus has not been reported in the literature on telemedicine. This paper presents an intelligent classification and prioritisation framework for patients with CHDs who engage in telemedicine. The emergency status of 500 patients with CHDs was evaluated on the basis of multiple heterogeneous clinical parameters, such as electrocardiogram, oxygen saturation, blood pressure and non-sensory measurements (i.e. text frame), by using wearable sensors. In the first stage, the patients were classified according to Dempster–Shafer theory and separated into five categories, namely, at high risk, requires urgent care, sick, in a cold state and normal. In the second stage, hybridised multi-criteria decision-making models, namely, multi-layer analytic hierarchy process (MLAHP) and technique for order performance by similarity to ideal solution (TOPSIS), were used to prioritise patients according to their emergency status. Then, the priority patients were queued in each emergency category according to the results of the first stage. Results demonstrated that Dempster–Shafer theory and the hybridised MLAHP and TOPSIS model are suitable for classifying and prioritising patients with CHDs. Moreover, the groups’ scores in each category showed remarkable differences, indicating that the framework results were identical. The proposed framework has an advantage over other benchmark classification frameworks by 33.33% and 50%, and an advantage over earlier benchmark prioritisation by 50%. This framework should be considered in future studies on telemedicine architecture to improve healthcare management.

Klatskin tumor, also known as hilar cholangiocarcinoma, was clearly demonstrated in this case report by contrasting 68Ga-FAPI and 18F-FDG PET/CT in the same patient. This instance exemplifies a false-negative 18F-FDG PET/CT for the main tumor site, despite positive 68Ga-FAPI uptake at the same location.

The synthesis of activated carbon (AC) from pine fruit shells (PFS) biomass (BM) is described in this paper. AC was made from BM by gradual pyrolysis at 600°C. AC was also chemically activated with H3PO4(BC-H3PO4) and pyrolyzed at 600°C. BM, BC, and BC-H3PO4adsorbents were characterized by Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermal gravimetric analysis, and elemental analysis. The batch system was used to apply the BM, BC, and BC-H3PO4to the adsorption of paracetamol (PCM) from aqueous solution. Adsorption was evaluated in relation to adsorbent dosage, ionic strength, initial pH solution, contact time, and temperature. Based on their coefficient of determination (R2), chi-square (χ2) and error function (Ferror%) values, equilibrium and kinetic PCM adsorption data revealed that the process obeys the Langmuir, Dubinin–Radushkevich, and pseudo-second-order kinetic equations, respectively. According to the Langmuir model, the highest adsorption capacity for PCM by BM, BC, and BC-H3PO4was 99.010, 166.667, and 256.10 mg/g, respectively. Thermodynamic analysis revealed that PCM adsorption by the adsorbents is spontaneous and exothermic.

•All used selective serotonin reuptake inhibitors have antifungal activity against C. glabratastrains tested.•Combinations of fluconazole with sertraline showed promising synergistic effect (fractional inhibitory concentration index [FICI] ≤0.5) against all resistant and susceptible dose-dependent strains, including those known to express efflux pumps. This synergistic effect was confirmed by time-kill curve assay.•Combination of fluconazole with fluoxetine or fluvoxamine showed indifferent effects (FICI in all strains >1 but <4).•Paroxetine-fluconazole combination showed additive effect against DSY565 and CBS138, known to express efflux pumps as well as on ATCC strain (0.5 < FIC < 1) with indifferent effect on other strains used.•The data suggest that blocking active efflux pumps by sertraline may be considered the probable mechanism of synergism with fluconazole.•Combination of sertraline with fluconazole could be a promising remedy for treatment of infections caused by resistant C. glabrata.

2′-O-(N-(Aminoethyl)carbamoyl)methyl (2′-O-AECM)-modified oligonucleotides (ONs) and their mixmers with 2′-O-methyl oligonucleotides (2′-OMe ONs) with phosphodiester linkers as well as with partial and full phosphorothioate (PS) inclusion were synthesized and functionally evaluated as splice-switching oligonucleotides in several different reporter cell lines originating from different tissues. This was enabled by first preparing the AECM-modified A, C, G and U, which required a different strategy for each building block. The AECM modification has previously been shown to provide high resistance to enzymatic degradation, even without PS linkages. It is therefore particularly interesting and unprecedented that the 2′-O-AECM ONs are shown to have efficient splice-switching activity even without inclusion of PS linkages and found to be as effective as 2′-OMe PS ONs. Importantly, the PS linkages can be partially included, without any significant reduction in splice-switching efficacy. This suggests that AECM modification has the potential to be used in balancing the PS content of ONs. Furthermore, conjugation of 2′-O-AECM ONs to an endosomal escape peptide significantly increased splice-switching suggesting that this effect could possibly be due to an increase in uptake of ON to the site of action.

Hydrothermal alkaline treatment (HALT) can effectively degrade per- and polyfluoroalkyl substances (PFASs) present in aqueous film-forming foam (AFFF). However, information is lacking regarding the treatment of PFASs in actual groundwater and soil from AFFF-impacted sites, especially for complex soil matrices. Given the lack of studies on direct soil treatment for PFAS destruction, we herein applied HALT to two groundwater samples and three soil samples from AFFF-impacted sites and characterized the destruction of PFASs using high-resolution mass spectrometry. Results showed that the 148 PFASs identified in all collected field samples, including 10 cationic, 98 anionic, and 40 zwitterionic PFASs, were mostly degraded to nondetectable levels within 90 min when treated with 5 M NaOH at 350 °C. The near-complete defluorination, as evidenced by fluoride release measurements, confirmed the complete destruction of PFASs. While many structures, including perfluoroalkyl carboxylic acids and polyfluorinated substances, were readily degraded, perfluoroalkyl sulfonates (PFSAs, CnF2n+1–SO3–), most notably with short chain lengths (n= 3–5), were more recalcitrant. Rates of PFSA destruction in groundwater samples were similar to those measured in laboratory water solutions, but reactions in soil were slow, presumably due to base-neutralizing properties of the soil. Further, the degradation of PFASs in groundwaters and soils was found to be a function of reaction temperature, NaOH concentration, and reaction time. These findings have important implications for the remediation of AFFF-impacted sites.

We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1–13 of the pandemic. Sixty patients (median age 71 y, range 43–97) were identified. Median CIRS was eight (4–20). Patients had indolent CLL (n= 38), had completed (n= 12) or ongoing therapy (n= 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p< 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1–6 vs 7–13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents.

BackgroundRapid time to reperfusion is essential to minimize morbidity and mortality in acute ischemic stroke due to large vessel occlusion (LVO). We aimed to evaluate the workflow times when utilizing a direct-to-angiography suite (DTAS) pathway for patients with suspected stroke presenting at a comprehensive stroke center compared with a conventional CT pathway.MethodsWe developed a discrete-event simulation (DES) model to evaluate DTAS workflow timelines compared with a conventional CT pathway, varying the admission NIHSS score treatment eligibility criteria. Model parameters were estimated based on 2 year observational data from our institution. Sensitivity analyses of simulation parameters were performed to assess the impact of patient volume and baseline utilization of angiography suites on workflow times utilizing DTAS.ResultsSimulation modeling of stroke patients (SimStroke) demonstrated door-to-reperfusion time savings of 0.2–3.5 min (p=0.05) for a range of DTAS eligibility criteria (ie, last known well to arrival <6 hours and National Institutes of Health Stroke Scale ≥6–11), when compared with the conventional stroke care pathway. Sensitivity analyses revealed that DTAS time savings is highly dependent on baseline utilization of angiography suites.ConclusionsThe results of the SimStroke model showed comparable time intervals for door-to-reperfusion for DTAS compared with a conventional stroke care pathway. However, the DTAS pathway was very sensitive to baseline angiography suite utilization, with even a 10% increase eliminating the advantages of DTAS compared with the conventional pathway. Given the minimal time savings modeled here, further investigation of implementing the DTAS pathway in clinical care is warranted.

In recent years, Cyber Physical Production Systems and Digital Threads opened the vision on the importance of data modelling and management to lead the smart factory towards a full-fledged vertical and horizontal integration. Vertical integration refers to the full connection of smart factory levels from the work centers on the shop floor up to the business layer. Horizontal integration is realised when a single smart factory participates in multiple interleaved supply chains with different roles (e.g., main producer, supplier), sharing data and services and forming a Cyber Physical Production Network. In such an interconnected world, data and services become fundamental elements in the cyberspace to implement advanced data-driven applications such as production scheduling, energy consumption optimisation, anomaly detection, predictive maintenance, change management in Product Lifecycle Management, process monitoring and so forth. In this paper, we propose a methodology that guides the design of a portfolio of data-oriented services in a Cyber Physical Production Network. The methodology starts from the goals of the actors in the network, as well as their requirements on data and functions. Therefore, a data model is designed to represent the information shared across actors according to three interleaved perspectives, namely, product, process and industrial assets. Finally, multi-perspective data-oriented services for collecting, monitoring, dispatching and displaying data are built on top of the data model, according to the three perspectives. The methodology also includes a set of access policies for the actors in order to enable controlled access to data and services. The methodology is tested on a real case study for the production of valves in deep and ultra-deep water applications. Experimental validation in the real case study demonstrates the benefits of providing a methodological support for the design of multi-perspective data-oriented services in Cyber Physical Production Networks, both in terms of usability of the data navigation through the services and in terms of service performances in presence of Big Data.

Low health literacy disproportionately affects adults from culturally and linguistically diverse backgrounds. This study investigated the health literacy of adults attending outpatient allied health services in western Sydney, a highly diverse region in Sydney with residents from a range of cultural and linguistic backgrounds. A cross‐sectional survey was undertaken between March and April 2017 using the Health Literacy Questionnaire (HLQ). Participants, aged over 18 years and with a primary language of English, Arabic, Chinese or Hindi, were recruited from outpatient allied health clinics at Westmead Hospital. Means (standard deviation) for each of the nine HLQ domains were calculated and associations with demographic variables were investigated using analysis of variance (ANOVA). Two hundred and thirty people were included with mean age of 45.1 years (SD = 19.0), the majority were female (75.5%), over half were born overseas (55.7%) and 77.6% reported speaking English at home. The highest mean score on a HLQ domain (out of 5) was “Understanding health information well enough to know what to do” (M = 4.19; SD = 0.67), and the lowest mean score (out of 4) was “Appraisal of health information” (M = 2.97; SD = 0.54). Participants who did not speak English at home had significantly lower scores on seven of the nine HLQ domains. Important health literacy strengths and limitations of a diverse sample of adults attending outpatient allied health services in western Sydney were identified. Findings should be considered in the light of the cross‐sectional survey methodology with non‐random sampling. Data will inform future interventions to improve health literacy and health outcomes among vulnerable population groups in western Sydney.

A newly distributed fault-tolerant mHealth framework-based Internet of things (IoT) is proposed in this study to resolve the essential problems of healthcare service provision during the occurrence of frequent failures in a telemedicine architecture. Two models are presented to support the telehealth development of chronic heart disease (CHD) in a distant environment. In model-1, a new local multisensor fusion triage algorithm known as three-level localisation triage (3LLT) is proposed. In 3LLT, a group of heterogeneous sources is applied to triage patients as a clinical process, and the emergency levels inside/outside the home of a patient with CHD are determined. Failures related to sensor fusion can also be detected. In model-2, a centralised IoT connection towards distributed smart hospitals is employed by mHealth based on two attributes: (1) healthcare service packages and (2) time of arrival of a patient at a hospital. Three decision matrices have been used to overcome several issues on hospital selection based on multi-criteria decision-making by using an analytic hierarchy process. Two datasets are utilised: (1) a clinical CHD dataset, which includes 572 patients for testing model-1, and (2) a nonclinical dataset, which includes hospital healthcare service packages for testing model-2. Consequently, patients with CHD can be triaged into different emergency levels (risk, urgent and sick) with mHealth, and a final decision is made by selecting an appropriate hospital. Results are obtained through the clinical triage of patients, and different scenarios are provided for hospital selection. The verification of statistical results indicates that the proposed mHealth framework is systematically valid. The contribution of the mHealth framework is presented to provide an improved triage process, afford timely services and treatment for CVD patients and minimise the chances of error. These health sectors and policymakers can also recognise the evaluation benefits of smart hospitals by using the presented framework and move forward to fully automated mHealth applications.

The formation of salts is considered a simple strategy to modify the physicochemical properties of active pharmaceutical ingredients. In this study, seven novel binary and ternary organic salts of ciprofloxacin (CP) were prepared with benzoic acid (BA), acetylsalicylic acid (ASA), p-coumaric acid (PCMA) and p-aminosalicylic acid (PASA). They were characterized by spectroscopic techniques and differential scanning calorimetry. Solubility and partition coefficients values were also measured. Evaluation of the antimicrobial activity of the organic salts against Staphylococcus aureusand Staphylococcus epidermidisrevealed that most of the new salts had higher antimicrobial activity than CPHCl against both strains. The most active compounds against S. epidermidisand S. aureuswere CP-PASA and CPPCMA, resp., which were up to fourteen times more potent than parent CP-HCl. Our findings indicated a strong correlation between the lipophilicity of the formed salts and their antimicrobial activity and showed that an optimum value of lipophilicity (log P= 0.75) seemed to be necessary to maximize the antimicrobial activity. These findings highlighted the improved physical, thermal and antimicrobial properties of the new salts of CP that can aid in providing higher bioavailability than CP-HCl.

ABSTRACTHPV vaccination rates have improved in recent years, but remain suboptimal in the United States. Physician recommendation is associated with increased uptake; however, specific strategies used by physicians to recommend the vaccine and address hesitancy are underexplored. We iteratively conducted qualitative in-depth interviews with family medicine and pediatrics/adolescent medicine physicians recruited from four primary care settings (federally qualified health centers and hospital-affiliated practices) within a large academic-hospital system in New Jersey. Interviews aimed to understand factors influencing physician recommendations. Transcripts were analyzed iteratively using a team-based, thematic content analysis approach. All physicians reported strong support for HPV vaccination, intention to recommend for target age groups, and providing factsheets to parents. Many physicians used electronic medical records and/or the state immunization registry for monitoring vaccinations, but few were able to report their own clinic-level rates. The majority said they needed to overcome both hesitancy for at least 10–30% of parents and misinformation from the internet. Most cited having their own children vaccinated for HPV as a first-line strategy for addressing parental hesitancy. Other strategies included using data or professional authority to address safety concerns, linking HPV to cervical cancer, highlighting only needing two doses if vaccinated younger, and normalizing the vaccine. While our findings indicate physicians are knowledgeable about HPV vaccination and recommend it to parents, strategies to overcome parental hesitancy varied. Physician, clinic, and health-system-based strategies need to be adopted to overcome parental hesitancy for HPV vaccination.

Introduction:Anti-glomerular basement membrane (anti-GBM) disease is characterized by rapidly progressive glomerular nephritis with or without pulmonary hemorrhage with disease severity correlating with antibody titer. Following treatment, relapse is rare but has been reported in the literature. The objective of this study was to assess for clinical, serologic, and histologic differences associated with disease relapse in patients with anti-GBM disease. Methods:Patients seen at our facility between 1997 and 2017 were screened for anti-GBM disease by ICD 9/10 codes. They were included if the diagnosis was confirmed by a board-certified rheumatologist or nephrologist and had positive antibodies and/or biopsy results consistent with anti-GBM disease. Relapsing disease was defined as recurrence of pulmonary or renal manifestations after achieving remission following the initial presentation. All charts were reviewed for baseline demographics, clinical manifestations, and antibody positivity and compared between groups. Results:40 patients were confirmed as having anti-GBM disease. Mean follow-up from disease onset to the date of last follow-up was 56.2 months. 8 patients had relapsing disease and 32 patients had nonrelapsing disease. Baseline characteristics and clinical manifestations were similar between groups. Patients with relapsing disease had a high incidence of anti-neutrophilic cytoplasmic antibody (ANCA) co-positivity as compared to nonrelapsing patients (50 vs. 15.6%, respectively, p= 0.059), but this did not reach statistical significance. In patients with relapsing disease, only one had positive anti-GBM antibodies at time of relapse. Conclusions:In this study, patients with relapsing disease had a high incidence of ANCA co-positivity (50%). In patients with newly diagnosed anti-GBM disease, ANCAs should be obtained to assess for the risk of relapse and to help guide long-term follow-up and treatment.

<> Rula Ghani, première dame d'Afghanistan, qui a l'intention de jouer un rôle actif pendant le mandat de son mari, Ashraf Ghani [...]

COVID-19 vaccines are being produced using different platforms by different companies, some of which are entering Phase 3 and 4 trials. Due to the pandemic, this production has been accelerated, which leaves a window for speculation on the method of production and safety. Pharmacists are familiar with vaccination; however, COVID-19 vaccines are still new and further work is needed to clarify many aspects, including side effects, methods of storage, and number of doses. Prioritization of vaccination has been implemented to a certain extent, but no clear strategy is available. A comprehensive overview on immunity and immunological principles for the design of COVID-19 vaccine strategies is provided in this narrative review and the current COVID-19 vaccine landscape is discussed, in addition to exploring the principles for prioritization of vaccination using data from articles available in PubMed and from health organizations. Pharmacists should have a better understanding of COVID-19 vaccines and their manufacture. This would also allow better counseling of the public on COVID 19, immunization, and explaining prioritization basis and vaccination programs.

Irreversible inhibitors of Bruton tyrosine kinase (BTK), pioneered by ibrutinib, have become breakthrough drugs in the treatment of leukemias and lymphomas. Resistance variants (mutations) occur, but in contrast to those identified for many other tyrosine kinase inhibitors, they affect less frequently the “gatekeeper” residue in the catalytic domain. In this study we carried out variation scanning by creating 11 substitutions at the gatekeeper amino acid, threonine 474 (T474). These variants were subsequently combined with replacement of the cysteine 481 residue to which irreversible inhibitors, such as ibrutinib, acalabrutinib and zanubrutinib, bind. We found that certain double mutants, such as threonine 474 to isoleucine (T474I) or methionine (T474M) combined with catalytically active cysteine 481 to serine (C481S), are insensitive to ≥16-fold the pharmacological serum concentration, and therefore defined as super-resistant to irreversible inhibitors. Conversely, reversible inhibitors showed a variable pattern, from resistance to no resistance, collectively demonstrating the structural constraints for different classes of inhibitors, which may affect their clinical application.

The widespread use of aqueous film-forming foam (AFFF) for firefighting activities (e.g., fire training to extinguish fuel-based fires at aircraft facilities) has led to extensive groundwater and soil contamination by per- and polyfluoroalkyl substances (PFASs) that are highly recalcitrant to destruction using conventional treatment technologies. This study reports on the hydrothermal alkaline treatment of diverse PFASs present in AFFFs. Quantitative and semiquantitative high-resolution mass spectrometry analyses of PFASs demonstrate a rapid degradation of all 109 PFASs identified in two AFFFs (sulfonate- and fluorotelomer-based formulations) in water amended with an alkali (e.g., 1–5 M NaOH) at near-critical temperature and pressure (350 °C, 16.5 MPa). This includes per- and polyfluoroalkyl acids and a range of acid precursors. Most PFASs were degraded to nondetectable levels within 15 min, and the most recalcitrant perfluoroalkyl sulfonates were degraded within 30 min when treated with 5 M NaOH. 19F NMR spectroscopic analysis and fluoride ion analysis confirm the near-complete defluorination of PFASs in both dilute and concentrated AFFF mixtures, and no stable volatile organofluorine species were detected in reactor headspace gases by the gas chromatography–mass spectrometry analysis. These findings indicate a significant potential for application of hydrothermal treatment technologies to manage PFAS waste streams, including on-site treatment of unused AFFF chemical stockpiles, investigation-derived wastes, and concentrated source zone materials.

We developed and evaluated a health literacy training program for allied health professionals, and explored the feasibility of a train‐the‐trainer model to support dissemination. The program combined didactic and experiential teaching methods and behaviour change techniques, with a focus on teach‐back and developing easy‐to‐understand written materials. Outcomes included participant reactions, confidence (range: 6‐30), behavioural intentions (range: 6‐42), and dissemination of training content. Implementation outcomes were evaluated using the Normalization MeAsure Development (NoMAD) tool, assessing the constructs of coherence (range: 4‐20), cognitive participation (range: 4‐20), collective action (range: 7‐35) and reflexive monitoring (range: 5‐25). Of the 29 allied health professionals who participated, 90% rated the program as ‘excellent’/‘very good’, and 97% said the information was ‘extremely’/‘very’ helpful for their everyday practice. We observed increases in confidence (mean difference [MD] = 6.3, standard deviation [SD] = 2.7, t25= 11.87, P< .001) and intentions (MD = 3.6, SD = 8.1, t23= 2.2, P= .04) related to health literacy practices after 6 weeks. Improved confidence was retained over 6 months (MD = 7.1, SD = 5.2, t18= 5.96, P< .001). After 6 months, 95% of participants (n = 19) reported using teach‐back and 50% (n = 10) reported having used a readability formula. Eight‐five per cent of participants (17/20) had trained others in health literacy, reaching n = 201 allied health professionals and students. NoMAD scores were highest in relation to cognitive participation (/20) (M = 18.2, SD = 2.1) and lowest in relation to collective action (/35) (M = 25.4, SD = 3.0). A train‐the‐trainer model appears to be a feasible method to disseminate health literacy training, but additional work may be needed to improve the collective work done to enable health literacy practices in real‐world clinical contexts. Staff training is particularly important in highly diverse areas where patients are disproportionately affected by low health literacy.

An excerpt from the novel "Camera Obscura" by Rula Jurdi, translated by Maia Tabet, is presented.

The COVID-19 pandemic has drastically changed healthcare systems and training around the world. The Training Committee of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition sought to understand how COVID-19 has affected pediatric gastroenterology fellowship training. A 21 question survey was distributed to all 77 pediatric gastroenterology fellowship program directors (PDs) in the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition program director database via email on April 7. Responses collected through April 19, 2020 were analyzed using descriptive statistics. Fifty-one of 77 (66%) PDs from the United States, Canada, and Mexico responded to the survey. Forty-six of 51 (90%) PDs reported that they were under a “stay-at-home” order for a median of 4 weeks at the time of the survey. Two of the 51 (4%) programs had fellows participating in outpatient telehealth before COVID-19 and 39 of 51 (76%) at the time of the survey. Fellows stopped participating in outpatient clinics in 22 of 51 (43%) programs and endoscopy in 26 of 51 (52%) programs. Changes to inpatient care included reduced fellow staffing, limiting who entered patient rooms, and rounding remotely. Fellows in 3 New York programs were deployed to adult medicine units. Didactics were moved to virtual conferences in 47 of 51 (94%) programs, and fellows used various online resources. Clinical research and, disproportionately, bench research were restricted. This report provides early information of the impact of COVID-19 on pediatric fellowship training. Rapid adoption of telehealth and reduced clinical and research experiences were important changes. Survey information may spur communication and innovation to help educators adapt.

Pharmacological inhibitors of Bruton tyrosine kinase (BTK) have revolutionized treatment of B-lymphocyte malignancies and show great promise for dampening autoimmunity. The predominant BTK inhibitors tether irreversibly by covalently binding to cysteine 481 in the BTK catalytic domain. Substitution of cysteine 481 for serine (C481S) is the most common mechanism for acquired drug resistance. We generated a novel C481S knock-in mouse model and, using a battery of tests, no overt B-lymphocyte phenotype was found. B lymphocytes from C481S animals were resistant to irreversible, but sensitive to reversible, BTK inhibitors. In contrast, irreversible inhibitors equally impaired T-lymphocyte activation in mice, mimicking the effect of treatment in patients. This demonstrates that T-lymphocyte blockage is independent of BTK. We suggest that the C481S knock-in mouse can serve as a useful tool for the study of BTK-independent effects of irreversible inhibitors, allowing for the identification of novel therapeutic targets and pinpointing potential side effects.