关键词： Virtual environment   Wayfinding   Co-presence   Decision-making   Pre-occupancy  

摘要： The effect of the social aspects on wayfinding behavior has been largely overlooked and left to designers' predictions. This research expands the understanding of wayfinding behavior in social contexts, common to real-world scenarios, proposing an experimental approach to assess and study the impact of co-presence on wayfinding decisions. Individual and paired (dyads) participants used player-controlled characters (PCs) to interact with identical T-shaped interior virtual environments inhabited by non-player-controlled characters (NPCs) in varying social scenarios. The results indicate a correlation between co-presence and wayfinding decision-making. Individual participants' favorable decisions differed from those of dyads due to social role-taking and social empowerment. The results also indicate that co-presence affected how participants viewed physical navigation aids such as signs and lighting, highlighting the importance of co-presence as a necessary backdrop for wayfinding studies. Designing with co-presence in mind would help architects anticipate wayfinding performances in their designs pre-occupancy and facilitate new design solutions.

关键词： Biodegradable polymer   Polyester   Alkylenedionic acid   1,4-Butanediol   Clear zone formation   Hydrolysis  

摘要： Poly(butylene n-alkylenedionate)s (PBADs), which are polymers that are potentially biodegradable in various environments, exhibit excellent thermal and mechanical properties similar to those of polyethylene because of their long alkyl chains. However, although it has not yet been experimentally verified, it is known that differences in the alkyl chain length affect the biodegradability of PBADs. In this study, we synthesized PBADs with alkylene diacid units, with the number of methylene chains ranging from 11 to 14. We subsequently investigated the relationship between their biodegradability via clear-zone formation and BOD-biodegradation testing and their physical properties, including their structural characteristics, using instrumental analysis. Although the monomers 1,4-butanediol (BD) and alpha,omega-dicarboxylic acids (DCA) exhibited good biochemical oxygen demand (BOD)-biodegradability, PBADs did not, indicating that PBADs with 11-14 methylene chains do not readily degrade in natural environments. (C) 2021 Elsevier Ltd. All rights reserved.

摘要： RNA N-6-methyladenosine (m(6)A) modification plays important roles in multiple aspects of RNA regulation. m(6)A is installed cotranscriptionally by the METTL3/14 complex, but its direct roles in RNA processing remain unclear. Here, we investigate the presence of m(6)A in nascent RNA of mouse embryonic stem cells. We find that around 10% of m(6)A peaks are located in alternative introns/exons, often close to 5' splice sites. m(6)A peaks significantly overlap with RBM15 RNA binding sites and the histone modification H3K36me3. Acute depletion of METTL3 disrupts inclusion of alternative introns/exons in the nascent transcriptome, particularly at 5' splice sites that are proximal to m(6)A peaks. For terminal or variable-length exons, m(6)A peaks are generally located on or immediately downstream from a 5' splice site that is suppressed in the presence of m(6)A and upstream of a 5' splice site that is promoted in the presence of m(6)A. Genes with the most immediate effects on splicing include several components of the m(6)A pathway, suggesting an autoregulatory function. Collectively, our findings demonstrate crosstalk between the m(6)A machinery and the regulation of RNA splicing.

关键词： alternative splicing   polyploid   evolution   embryogenesis   wheat   grain development  

摘要： Among polyploid species with complex genomic architecture, variations in the regulation of alternative splicing (AS) provide opportunities for transcriptional and proteomic plasticity and the potential for generating trait diversities. However, the evolution of AS and its influence on grain development in diploid grass and valuable polyploid wheat crops are poorly understood. To address this knowledge gap, we developed a pipeline for the analysis of alternatively spliced transcript isoforms, which takes the high sequence similarity among polyploid wheat subgenomes into account. Through analysis of synteny and detection of collinearity of homoeologous subgenomes, conserved and specific AS events across five wheat and grass species were identified. A global analysis of the regulation of AS in diploid grass and polyploid wheat grains revealed diversity in AS events not only between the endosperm, pericarp and embryo overdevelopment, but also between subgenomes. Analysis of AS in homoeologous triads of polyploid wheats revealed evolutionary divergence between gene-level and transcript-level regulation of embryogenesis. Evolutionary age analysis indicated that the generation of novel transcript isoforms has occurred in young genes at a more rapid rate than in ancient genes. These findings, together with the development of comprehensive AS resources for wheat and grass species, advance understanding of the evolution of regulatory features of AS during embryogenesis and grain development in wheat.

摘要： INTRODUCTION: Direct-acting antivirals (DAAs) are curative treatments for hepatitis C. However, initiation of these treatments requires adequate healthcare access. Coronavirus 2019 (COVID-19) resulted in restrictions to healthcare services in March 2020. We examined the impact of COVID-19 on the number of individuals dispensed DAAs. METHODS: This is a cross-sectional study examining the number of individuals dispensed DAAs in Ontario, Canada, from 2018 to 2020. Time-series models determined the impact of healthcare restrictions on DAA dispensations. RESULTS: Healthcare restrictions resulted in a 49.3% decrease in DAA dispensations (P = 0.026). DISCUSSION: COVID-19-related healthcare restrictions significantly affected access to DAAs. Studies exploring the long-term effects on reduced treatment are needed.

关键词： COVID-19   Vaccine-preventable   Traveler   Emerging infections   Re-emerging infections  

摘要： The role of the emergency provider lies at the forefront of recognition and treatment of novel and re-emerging infectious diseases in children. Familiarity with disease presentations that might be considered rare, such as vaccine-preventable and non-endemic illnesses, is essential in identifying and controlling outbreaks. As we have seen thus far in the novel coronavirus pandemic, susceptibility, severity, transmission, and disease presentation can all have unique patterns in children. Emergency providers also have the potential to play a public health role by using lessons learned from the phenomena of vaccine hesitancy and refusal.

关键词： Replacement   Sacha inchi meal   Soybean meal   Growth performance   Red hybrid tilapia  

摘要： A 10-week feeding trial was conducted to examine the effect of dietary sacha inchi meal (SIM) as a soybean meal (SBM) replacer on growth performance, feed utilization, whole-body fatty acid composition, blood biochemistry, and histological changes in red hybrid tilapia, Oreochromis niloticus x O. mossambicus. Five isonitrogenous and isolipidic diets were formulated with 0 (control diet), 110, 220, 320, and 420 g/kg replacement of SBM with SIM (referred to as SIM0. 420). Each diet was randomly assigned to one of five fish groups in a 100 L indoor tank (n = 15 each, average initial weight 9.36 +/- 0.02 g) with four replicates. During the last 2 weeks of the feeding trial, 5 g/kg chromic oxide (Cr2O3) was added to the diet to determine the apparent digestibility coefficient (ADC). The results showed that SIM inclusion significantly increased growth performance, feed utilization, and ADC of dry matter in a quadratic manner with the highest final weight observed in the SIM110 group. Survival rates were not significantly affected by SIM inclusion levels (P > 0.05). The amount of n-3 fatty acids in the whole-body fish, particularly that of C18:3n-3, was linearly and quadratically increased (P < 0.001) with increasing dietary SIM inclusions. Total cholesterol and triglycerides (TGs) were linearly and quadratically decreased in the fish fed the SIM inclusion diets (P < 0.05), but no linear or quadratic effects of dietary treatments were observed on levels of total protein, albumin, globulin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). Liver histology showed a significant increase in cytoplasmic vacuolization with increasing SIM inclusion in diets, and fish fed the SIM420 diet showed hepatocyte swelling and displacement of hepatocyte nuclei toward the periphery. Similarly, intestine histology detected a significant linear reduction in villi height and villi thickness with increasing level of dietary SIM (P < 0.001). Overal

摘要： INTRODUCTION: Regular endoscopic surveillance is the gold standard Barrett's esophagus (BE) surveillance, yet harms of surveillance for some patients may outweigh the benefits. We sought to characterize physicians' BE surveillance cessation recommendations. METHODS: We surveyed gastroenterologists about their BE surveillance recommendations varying patient age, comorbidity, and BE length. RESULTS: Clinicians varied in recommendations for repeat surveillance. Patient age showed the largest variation among decisions, whereas BE length varied the least. DISCUSSION: Age and comorbidities seem to influence BE surveillance cessation decisions, but with variation. Clear cessation guidelines balancing the risks and benefits for BE surveillance are warranted.

关键词： TDM   noninvasive   matrix   saliva   therapeutic drug monitoring  

摘要： Background: Historically, pharmacokinetic (PK) studies and therapeutic drug monitoring (TDM) have relied on plasma as a sampling matrix. Noninvasive sampling matrices, such as saliva, can reduce the burden on pediatric patients. The variable plasma-saliva relationship can be quantified using population PK models (nonlinear mixed-effect models). However, criteria regarding acceptable levels of variability in such models remain unclear. In this simulation study, the authors aimed to propose a saliva TDM evaluation framework and evaluate model requirements in the context of TDM, with gentamicin and lamotrigine as model compounds. Methods: Two population pharmacokinetic models for gentamicin in neonates and lamotrigine in pediatrics were extended with a saliva compartment including a delay constant (k(SALIVA)), a saliva:plasma ratio, and between-subject variability (BSV) on both parameters. Subjects were simulated using a realistic covariate distribution. Bayesian maximum a posteriori TDM was applied to assess the performance of an increasing number of TDM saliva samples and varying levels of BSV and residual variability. Saliva TDM performance was compared with plasma TDM performance. The framework was applied to a known voriconazole saliva model as a case study. Results: TDM performed using saliva resulted in higher target attainment than no TDM, and a residual proportional error <25% on saliva observations led to saliva TDM performance comparable with plasma TDM. BSV on k(SALIVA) did not affect performance, whereas increasing BSV on saliva:plasma ratios by >25% for gentamicin and >50% for lamotrigine reduced performance. The simulated target attainment for voriconazole saliva TDM was >90%. Conclusions: Saliva as an alternative matrix for noninvasive TDM is possible using nonlinear mixed-effect models combined with Bayesian optimization. This article provides a workflow to explore TDM performance for compounds measured in saliva and can be used for evaluation during m

关键词： Anemometer   Venturi   ANSYS  

摘要： This paper states that there might have around 1000 small size business jets (until nine occupants) flying across the world equipped with flow control and regulating shut-off valves that uses hot wire anemometer devices to regulate massflow rate from the bleed airflow to supply the air-conditioning and pressurization systems. However, these valves present low reliability in the field. The purpose of this paper is to evaluate the implications of a flow control and regulating shut-off valve with a non-intrusive airflow measurer device under the perspective of fluid mechanics. The Venturi technology that is commonly used technology, given its construction simplicity, precision, and broad use in the industry, is selected to substitute the flow control and regulating shut-off valves with hot wire anemometer of the mentioned small size business jets applications. This paper has adopted a numeric simulation approach utilizing the ANSYS-CFX computational fluid dynamics software to verify both the differential pressure at the Venturi device and its correspondent mass flow rate to supply the air conditioning systems of some small size business jets, considering the mass-flow rate as requested by the FAA certification requirement (0.55 lb/min per occupant). This paper shows that a mass-flow rate control and regulating shut-off valve with a Venturi device, of 1 inch and beta of 0.67, is compliant with the minimum fresh air flow requested by the FAA certification requirement to operate in some small size business jets. Besides that, the software ANSYS-CFX is also effective to support the engineering analysis of flow field characteristics inherent to the applications of internal compressible flow. The numeric simulation utilizing the ANSYS-CFX computational fluid dynamics software outlined herein can lay the basis for further research related to the design of a flow control and regulating shut-off valves with a Venturi device.