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The Community Multiscale Air Quality (CMAQ) model has been used for regulatory purposes at the US EPA and in the research community for decades. In 2012, we released the WRF-CMAQ coupled model that enables aerosol information from CMAQ to affect meteorological processes through direct effects on shortwave radiation. Both CMAQ and WRF-CMAQ are considered limited area models. Recently, we have extended domain coverage to global scale linking the meteorological Model for Prediction Across Scales – Atmosphere (MPAS-A, hereafter referred simply to as MPAS) with CMAQ to form the MPASCMAQ global coupled model. To configure these three different models, i.e. CMAQ (offline), WRF-CMAQ, and MPASCMAQ, we have developed the Advanced Air Quality Modelling System (AAQMS) for constructing each of them effortlessly. We evaluate this newly-built MPAS-CMAQ coupled model using two global configurations: a 120 km uniform mesh and a 92–25 km variable mesh with the finer area over North America. Preliminary computational tests show good scalability and model evaluation, a three years simulation (2014–2016) for the uniform mesh case and a monthly simulation of January and July 2016 for the variable mesh case, on ozone and PM2.5, show reasonable performance with respect to observations. The 92–25 km configuration has a high bias in wintertime surface ozone across the United States and this bias is consistent with the 120 km result. Summertime surface ozone in the 92–25 km configuration is less biased than the 120 km case. The MPAS-CMAQ system reasonably reproduces the daily variability of daily average PM from the Air Quality System (AQS) network. [ABSTRACT FROM AUTHOR]

This paper examines the impact of data-driven innovation (DDI) on firm performance, based on an exploratory case study of a manufacturing firm in China's textile and apparel industry. It explores the influence of various contextual variables on the firm's DDI and suggests ways to enhance DDI and thereby firm performance. Extending the literature on DDI, the paper proposes and validates a theoretical framework that incorporates the influence of various contextual factors on firms' DDI. The findings show that (1) individual context is associated with DDI; (2) organizational context is associated with DDI; and (3) DDI is associated with firm performance. This paper extends our understanding of how firm performance can be improved through DDI and shows that DDI should match a firm's contextual environment. [ABSTRACT FROM AUTHOR]

Purpose: Only a small proportion of patients obtain survival benefit from PD-1 blockade immunotherapy due to the highly heterogeneous and suppressed immune micro-environment of GBM. We aimed at revealing the characteristics of tumor micro-environment (TME) of GBM related to response to PD-1 inhibitors and constructing a response prediction model for screening patients possibly benefit from PD-1 inhibitors. Methods: Based on the composition and expression profiles of cell subpopulations calculated by deconvoluting the GBM bulk RNA-seq, differentially expressed gene analysis and gene set enrichment analysis (GSEA) were performed to explore genes and pathways related to response to PD-1 inhibitors. Further by combining least absolute shrinkage and selection operator (LASSO) regression and expression correlation with PD-L1, the response prediction genes of PD-1 inhibitors were identified and the response prediction model was constructed through binary logistic regression. Results: The comparison of abundances of tumor infiltrating immune cells showed that the abundance of M0 macrophages of responders was lower, while the abundance of activated dendritic cells (DCs) was higher before PD-1 inhibitors treatment; the abundances of plasma cells and M0 macrophages of responders were lower after PD-1 inhibitors treatment. In addition, GSEA showed that the main up-regulation pathways in the tumor micro-environment of responders before PD-1 inhibitors treatment included the regulation of T-helper 1 type immune response, the positive regulation of natural killer cell-mediated cytotoxicity, p53 signaling pathway, homotypic cell–cell adhesion, etc., the main down-regulation pathways included the activation of microglia and myeloid leukocytes, Ras signaling pathway, etc. Afterward, ITGAX, LRRFIP1 and FMN1 were identified as the key response prediction genes of PD-1 inhibitors and the response prediction model based on them showed good predictive performance with potential value of clinical application in its validation and verification. Conclusions: ITGAX, LRRFIP1 and FMN1 were identified as the response prediction genes of PD-1 inhibitors and the response prediction model based on them was proved to have potential clinical value. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the pharmacokinetics and clinical safety of acetaminophen after oral administration of 40 mg/kg q 12 hours or 60 mg/kg q 24 hours for 14 days. ANIMALS. 12 healthy light-breed neonatal foals. PROCEDURES: 6 foals received acetaminophen at 40 mg/kg q 12 hours and 6 foals received 60 mg/kg q 24 hours for 14 days. The study dates were January 31 to April 15, 2023. Physical examinations were performed daily. Plasma disposition of acetaminophen was determined after the first, mid-point drug administration. Hematology and biochemistry analysis was performed before the study, day 7, and the last day of drug administration. Plasma acetaminophen concentrations were determined by high-performance liquid chromatography. Plasma pharmacokinetic parameters were estimated using noncompartmental analysis. RESULTS: No statistically significant changes occurred on hematology or biochemistry profiles. Elevations in γ-glutamyl transferase (GGT) and sorbitol dehydrogenase (SDH) were noted in 4 foals at various time points. The maximum plasma concentration (Cmax) occurred within 2 hours for both doses. The 60 mg/kg dose resulted in a larger median Cmax (range) at 28 µg/mL (22-32) than the 40 mg/kg dose at 23 µg/mL (19-27). The median area under the concentration-vs-time curve from 0 to 8 hours (AUC0-8 hour [range]) was 100 h•µg/mL (82-100) at 40 mg/kg and 128 h•µg/mL (120-168) for 60 mg/kg. Trough concentrations decreased over time for both regimens. CLINICAL RELEVANCE: Foals tolerate oral acetaminophen at 40 mg/kg q 12 hours or 60 mg/kg q 24 hours. Further analgesic and antipyretic studies will help to delineate optimal dosage regimens of acetaminophen to treat foals. [ABSTRACT FROM AUTHOR]

Purpose: Certain factors such as instrumental and sample processing errors may contribute to variability of ocular biofluid samples when they are run as replicates with multiplex assays. There is a paucity of literature on the variability of replicates in multiplex assays. This study aims to evaluate whether there is significant variability in replicate analyses of multiplex assays.Methods: A total of 152 human ocular biofluid samples (51 aqueous humor and 101 vitreous) were collected and assayed for 27 cytokine biomarker concentrations (pg/mL). Samples were evaluated as replicates (duplicate analysis) at four different time points. Statistical methods including paired samples t-test, 3-way ANOVA, intraclass correlation coefficient (ICC; < 0.5– 0.75=poor-moderate, 0.75-> 0.90 =good-excellent reliability), and coefficients of variation (CV) were employed to evaluate for statistical significance, with Bonferroni corrected P=0.002.Results: Among the 4104 biomarker replicate assays for aqueous humor and vitreous, two analytes (PDGF-BB and IL-7) had a statistically significant difference between the sampled concentrations of the replicates in vitreous samples (mean (diff)=2.05, P< 0.001, mean (diff)=1.56, P< 0.001, respectively). Majority of the ICC values fell within the good-excellent range (86% of samples) with a minority falling in the poor-moderate range (14% of samples). More variability was noted in the vitreous humour, with five analytes (IL-2, IL-10, IL-12(p70), IL-13, IL-17) demonstrating an average ICC of less than 0.5. The CV calculated for each set of replicates suggested that 93% of replicates had an acceptable level of quantitative assay variability (CV< 20%).Conclusion: This study demonstrates that the analysis of most biomarkers in ocular fluids may not require the use of replicates. However, certain analytes such as PDGF-BB and IL-7 may require the use of replicates to ensure reliable results. Caution should be taken when applying these findings to other laboratory settings as our study was conducted by an experienced technician using a standardized protocol. In less standardized settings, replicates may be required in order to ensure accuracy of results. These findings may guide researchers with the design of their studies on ophthalmic biomarker analysis. [ABSTRACT FROM AUTHOR]

Background: Bacterial sepsis is the leading cause of death in foals and is associated with hypothalamic‐pituitary‐adrenocortical axis (HPAA) dysfunction. HPAA function can be evaluated by an arginine‐vasopressin (AVP) stimulation test. Hypotheses/Objectives: Administration of AVP will stimulate a dose‐dependent rise in systemic adrenocorticotropin‐releasing hormone (ACTH) and cortisol in neonatal foals. There will be no response seen in corticotropin‐releasing hormone (CRH) and baseline AVP will be within reference interval. Animals: Twelve neonatal foals, <72 hours old. Methods: HPAA function was assessed in foals utilizing 3 doses of AVP (2.5, 5, and 7.5 IU), administered between 24 and 48 hours of age in this randomized cross‐over study. Cortisol, ACTH, CRH and AVP were measured at 0 (baseline), 15, 30, 60 and 90 minutes after AVP administration with immunoassays. The fold increase in cortisol and ACTH was calculated at 15 and 30 minutes compared to baseline. Results: All doses of AVP resulted in a significant increase in cortisol concentration over time, and a dose‐dependent increase in ACTH concentration over time. ACTH and cortisol were significantly increased at 15 and 30 minutes, respectively after all 3 doses of AVP compared to baseline (P <.01). There was no change in endogenous CRH after stimulation with AVP. Conclusion and Clinical Importance: Administration of AVP is safe and results in a significant rise in ACTH and cortisol in neonatal foals. A stimulation test with AVP (5 IU) can be considered for HPAA assessment in septic foals. [ABSTRACT FROM AUTHOR]

Each day, humans produce approximately 0.5 through 1.5 liters of saliva, a biofluid that is rich in biological omic constituents. Our lack of understanding how omic biomarkers migrate from diseased tissue to the saliva has impeded the clinical translation of saliva testing. Although such biomarkers must be conveyed via the vascular and lymphatic systems to the salivary glands, the molecular mechanisms that underlie this transport remain unclear. Although COVID-19 highlighted the need for rapid and reliable testing for infectious diseases, it represents only one of the many health conditions that potentially can be diagnosed using a saliva sample. The authors discuss salivaomics, saliva exosomics, and the mechanisms on which saliva diagnostics are based and introduce a novel electrochemical sensing technology that may be exploited for saliva liquid biopsy. The utility of saliva for screening for lung cancer is under investigation. Saliva testing may be used to stratify patients, monitor treatment response, and detect disease recurrence. The authors also highlight the landscapes of saliva-based SARS-CoV-2 testing and ultrashort cell-free DNA and outline how these fields are likely to evolve in the near future. Breakthroughs in the study of saliva research, therefore, will facilitate clinical deployment of saliva-based testing. [ABSTRACT FROM AUTHOR]

The present study investigated the preparation of 2,5‐furandicarboxylic acid (FDCA) via the Henkel reaction between furoic acid alkali metal salts and zinc chloride under a continuous CO2 flow at atmospheric pressure. The results obtained were compared with those of previous studies that used high‐pressure conditions or toxic cadmium catalysts. The pathways and rate‐determining steps of the reaction are revealed for the first time. Furthermore, the enhanced formation of FDCA through the promotion of carboxyl exchange and rearrangement during the reaction under a CO2 flow was examined. The CO2‐rich environment afforded a high FDCA yield of 86.30 %, which is the highest yield obtained to date using the Henkel reaction. The findings of this study offer economically improved conditions for large‐scale FDCA production. [ABSTRACT FROM AUTHOR]

Since the announcement and establishment of the Oversight Board (OB) by the technology company Meta as an independent institution reviewing Facebook and Instagram's content moderation decisions, the OB has been subjected to scholarly scrutiny ranging from praise to criticism. However, there is currently no overarching framework for understanding the OB's various strengths and weaknesses. Consequently, this article analyses, organises, and supplements academic literature, news articles, and Meta and OB documents to understand the OB's strengths and weaknesses and how it can be improved. Significant strengths include its ability to enhance the transparency of content moderation decisions and processes, to effect reform indirectly through policy recommendations, and its assertiveness in interpreting its jurisdiction and overruling Meta. Significant weaknesses include its limited jurisdiction, limited impact, Meta's control over the OB's precedent, and its lack of diversity. The analysis of a recent OB case in Ethiopia shows these strengths and weaknesses in practice. The OB's relationship with Meta and governments will lead to challenges and opportunities shaping its future development. Reforms to the OB should improve the OB's control over its precedent, apply OB precedent to currently disputed cases, and clarify the standards for invoking OB precedent. Finally, these reforms provide the foundation for an additional improvement to address the OB's institutional weaknesses, by involving users in determining whether the OB's precedent should be applied to decide current content moderation disputes. [ABSTRACT FROM AUTHOR]

Background: Bradykinesia is considered the fundamental motor feature of Parkinson's disease (PD). It is central to diagnosis, monitoring, and research outcomes. However, as a clinical sign determined purely by visual judgement, the reliability of humans to detect and measure bradykinesia remains unclear. Objective: To establish interrater reliability for expert neurologists assessing bradykinesia during the finger tapping test, without cues from additional examination or history. Methods: 21 movement disorder neurologists rated finger tapping bradykinesia, by Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Modified Bradykinesia Rating Scale (MBRS), in 133 videos of hands: 73 from 39 people with idiopathic PD, 60 from 30 healthy controls. Each neurologist rated 30 randomly-selected videos. 19 neurologists were also asked to judge whether the hand was PD or control. We calculated intraclass correlation coefficients (ICC) for absolute agreement and consistency of MDS-UPDRS ratings, using standard linear and cumulative linked mixed models. Results: There was only moderate agreement for finger tapping MDS-UPDRS between neurologists, ICC 0.53 (standard linear model) and 0.65 (cumulative linked mixed model). Among control videos, 53% were rated > 0 by MDS-UPDRS, and 24% were rated as bradykinesia by MBRS subscore combination. Neurologists correctly identified PD/control status in 70% of videos, without strictly following bradykinesia presence/absence. Conclusion: Even experts show considerable disagreement about the level of bradykinesia on finger tapping, and frequently see bradykinesia in the hands of those without neurological disease. Bradykinesia is to some extent a phenomenon in the eye of the clinician rather than simply the hand of the person with PD. [ABSTRACT FROM AUTHOR]

Graefe's Archive of Clinical & Experimental Ophthalmology is the oldest ophthalmology journal in Europe, established in 1854. The journal is edited by a team of leading ophthalmologists and articles undergo rigorous peer-review. The article discusses the potential impact of artificial intelligence (AI) on scientific discovery and communication. It explores the limitations of AI in areas such as clinical diagnoses and plagiarism detection, and raises concerns about the potential for AI to manipulate data and deceive editors and reviewers. The article emphasizes the importance of human judgment and skepticism in maintaining academic integrity and suggests that AI should be used as a tool to enhance efficiency rather than replace human involvement in the peer review process. [Extracted from the article]

The Community Multiscale Air Quality (CMAQ) model has been a vital tool for air quality research and management at the United States Environmental Protection Agency (US EPA) and at government environmental agencies and academic institutions worldwide. The CMAQ model requires a significant amount of disk space to store and archive input and output files. For example, an annual simulation over the contiguous United States (CONUS) with horizontal grid-cell spacing of 12 km requires 2–3 TB of input data and can produce anywhere from 7–45 TB of output data, depending on modeling configuration and desired post-processing of the output (e.g., for evaluations or graphics). After a simulation is complete, model data are archived for several years, or even decades, to ensure the replicability of conducted research. As a result, careful disk space management is essential to optimize resources and ensure the uninterrupted progress of ongoing research and applications requiring large-scale, air quality modeling. Proper disk-space management may include applying optimal data-compression techniques that are executed on input and output files for all CMAQ simulations. There are several (not limited to) such utilities that compress files using lossless compression, such as GNU Gzip (gzip) and Basic Leucine Zipper Domain (bzip2). A new approach is proposed in this study that reduces the precision of the emission input for air quality modeling to reduce storage requirements (after a lossless compression utility is applied) and accelerate runtime. The new approach is tested using CMAQ simulations and post-processed CMAQ output to examine the impact on the performance of the air quality model. In total, four simulations were conducted, and nine cases were post-processed from direct simulation output to determine disk-space efficiency, runtime efficiency, and model (predictive) accuracy. Three simulations were run with emission input containing only five, four, or three significant digits. To enhance the analysis of disk-space efficiency, the output from the altered precision emission CMAQ simulations were additionally post-processed to contain five, four, or three significant digits. The fourth, and final, simulation was run using the full precision emission files with no alteration. Thus, in total, 13 gridded products (4 simulations and 9 altered precision output cases) were analyzed in this study. Results demonstrate that the altered precision emission files reduced the disk-space footprint by 6 %, 25 %, and 48 % compared to the unaltered emission files when using the bzip2 compression utility for files containing five, four, or three significant digits, respectively. Similarly, the altered output files reduced the required disk space by 19 %, 47 %, and 69 % compared to the unaltered CMAQ output files when using the bzip2 compression utility for files containing five, four, or three significant digits, respectively. For both compressed datasets, bzip2 performed better than gzip, in terms of compression size, by 5 %–27 % for emission data and 15 %–28 % for CMAQ output for files containing five, four, or three significant digits. Additionally, CMAQ runtime was reduced by 2 %–7 % for simulations using emission files with reduced precision data in a non-dedicated environment. Finally, the model-estimated pollutant concentrations from the four simulations were compared to observed data from the US EPA Air Quality System (AQS) and the Ammonia Monitoring Network (AMoN). Model performance statistics were impacted negligibly. In summary, by reducing the precision of CMAQ emission data to five, four, or three significant digits, the simulation runtime in a non-dedicated environment was slightly reduced, disk-space usage was substantially reduced, and model accuracy remained relatively unchanged compared to the base CMAQ simulation, which suggests that the precision of the emission data could be reduced to more efficiently use computing resources while minimizing the impact on CMAQ simulations. [ABSTRACT FROM AUTHOR]

Background: Polypharmacy can be a consequence of overprescribing that is prevalent in older adults with multimorbidity. Polypharmacy can cause adverse reactions and result in hospital admission. This study predicted risks of adverse drug reaction (ADR)-related and emergency hospital admissions by medicine classes. Methods: We used electronic health record data from general practices of Clinical Practice Research Datalink (CPRD GOLD) and Aurum. Older patients who received at least five medicines were included. Medicines were classified using the British National Formulary sections. Hospital admission cases were propensity-matched to controls by age, sex, and propensity for specific diseases. The matched data were used to develop and validate random forest (RF) models to predict the risk of ADR-related and emergency hospital admissions. Shapley Additive eXplanation (SHAP) values were calculated to explain the predictions. Results: In total, 89,235 cases with polypharmacy and hospitalised with an ADR-related admission were matched to 443,497 controls. There were over 112,000 different combinations of the 50 medicine classes most implicated in ADR-related hospital admission in the RF models, with the most important medicine classes being loop diuretics, domperidone and/or metoclopramide, medicines for iron-deficiency anaemias and for hypoplastic/haemolytic/renal anaemias, and sulfonamides and/or trimethoprim. The RF models strongly predicted risks of ADR-related and emergency hospital admission. The observed Odds Ratio in the highest RF decile was 7.16 (95% CI 6.65–7.72) in the validation dataset. The C-statistics for ADR-related hospital admissions were 0.58 for age and sex and 0.66 for RF probabilities. Conclusions: Polypharmacy involves a very large number of different combinations of medicines, with substantial differences in risks of ADR-related and emergency hospital admissions. Although the medicines may not be causally related to increased risks, RF model predictions may be useful in prioritising medication reviews. Simple tools based on few medicine classes may not be effective in identifying high risk patients. [ABSTRACT FROM AUTHOR]

Background: The fecal bacterial microbiota of normal foals and foals with enterocolitis has been characterized using next‐generation sequencing technology; however, there are no reports investigating the gut microbiota in foals hospitalized for other perinatal diseases. Objective: To describe and compare the fecal bacterial microbiota in healthy and sick foals using next‐generation sequencing techniques. Animals: Hospitalized (17) and healthy foals (21). Methods: Case‐control study. Fecal samples were collected from healthy and sick foals on admission. Sick foals were further divided into sick nonseptic (SNS, n = 9) and septic (n = 8) foals. After extraction of DNA, the V4 region of the 16 S rRNA gene was amplified using a PCR assay, and the final product was sequenced with an Illumina MiSeq. Results: Diversity was significantly lower in healthy than sick foals (P <.05). The bacterial membership (Jaccard index) and structure (Yue & Clayton index) of the fecal microbiota of healthy, septic, and SNS foals were similar (AMOVA, P >.05). Bacterial membership (AMOVA, P =.06) and structure (AMOVA, P =.33) were not different between healthy and sick foals. Enterobacteriaceae, Enterococcus, and Streptococcus were among the 5 more abundant taxa identified in both groups. Conclusion and Clinical Importance: Higher fecal microbiota diversity in sick than healthy foals might suggest a high exposure to environmental microorganisms or an unstable colonic microbiota. The presence of microorganisms causing bacteremia in foals in a high relative abundance in the feces of foals suggests the intestine might play an essential role in the causation of bacteremia in foals. [ABSTRACT FROM AUTHOR]

To evaluate the knowledge, skills and barriers to evidence-based practice and the impact of evidence-based practice training for physical therapy clinicians. Physical therapists from a health district in Sydney, Australia were invited to participate. The primary outcome was the Assessing Competency in Evidence-based Medicine scale (range 0–15; 15 is high knowledge and skill) to quantify knowledge and skills. The secondary outcomes were the four subscales of the BARRIERS scale (range 1–4; 4 is high barrier) to quantify barriers. Outcomes were collected at baseline and post an evidence-based practice training program (flipped classroom approach that addressed the core competencies for teaching evidence-based practice) of 3 months duration. Registration: Australian and New Zealand Clinical Trial Register (ACTRN12619000038190). 104 participants completed baseline data and 94 completed post-training data. The mean score for the Assessing Competency in Evidence-based Medicine scale for knowledge and skills at baseline was 9.5 (standard deviation 1.6). The mean BARRIERS subscale scores at baseline were: Healthcare Provider 1.9 (0.5); Research 2.2 (0.5); Setting 2.6 (0.5); and Presentation 2.6 (0.5). On average, training increased the Assessing Competency in Evidence-based Medicine scale score by 0.1 points (95% confidence interval −0.2 to 0.5) and reduced barriers by −0.1 (−0.2 to 0.0; Setting subscale) to −0.2 (−0.3 to −0.1; Healthcare Provider subscale). Physical therapists have knowledge and skill in evidence-based practice that is comparable to other allied health professionals, medical students and medical doctors, and encountered barriers to using high-quality clinical research to guide practice. Training did not change knowledge and skills but did reduce barriers. [ABSTRACT FROM AUTHOR]

Age segregation adversely impacts health and wellbeing. Prior studies, although limited, report increasing age segregation of the US. However, these studies are dated, do not comprehensively examine the spatiotemporal patterns and the correlates of intergenerational segregation, or suffer from methodological limitations. To address these gaps, we assess the spatiotemporal patterns of age segregation between 1990 and 2010 using census-tract data to compute the dissimilarity index (D) at the national, state, and county levels. Results contradict previous findings, providing robust evidence of decreasing age segregation for most parts of the country and across geographical levels. We also examine factors explaining adult-older adult segregation across counties between 1990 and 2010. Higher levels of rurality indicated lower levels of adult-older adult segregation, but this association diminished over time. Percent of older adults and percent of population in group quarters were inversely related to adult-older adult segregation, contrary to results from previous decades. [ABSTRACT FROM AUTHOR]

This research examines how tourism development has impacted economic growth in a global city–Hong Kong. A large body of research has investigated national tourism-led growth in developed and developing countries. However, many such studies have overlooked how policies aimed at fostering the development of tourism affect the local economic development of global cities. The Chinese and Hong Kong governments liberalized their visa policies with the launch of the Individual Visit Scheme in 2003. Such liberalization has led to significantly more tourist arrival from China. Our autoregressive distributed lag model of tourism-related data from 2003 to 2019 provides strong evidence that more tourism can spur short-run economic growth. Yet, such tourism can lead to uncertain effects on local economic development in the longer run. Hong Kong's transient tourism-led growth has almost entered the stagnation stage of the Tourism Area Life Cycle model. During such stagnation, jurisdictions like Hong Kong can expect limited long-term economic growth from their tourist sector. Our findings thus sound a warning for global cities looking to tourism to sustain longer-term economic growth. [ABSTRACT FROM AUTHOR]

This research considers the effects of air transport on economic growth and asks how airport development affects regional convergence across three Chinese macro‐regions. A growing body of research has examined national aviation‐growth relationships in developing countries over the last decade. Yet few studies have sought to determine whether air transport boosts regional development, especially in developing and emerging economies. Using a dataset spanning from 2005 to 2017, and drawing on panel data regression and instrumental variable analyses, we provide empirical evidence that air transport drives economic growth in China and its macro‐regions. However, we find no major synergy across air, high‐speed rail, and waterway transport as drivers of economic growth at national and regional levels. Furthermore, air transport has a significant effect in widening China's per capita income disparity. On that basis, we suggest Chinese local governments should carefully consider equity‐efficiency trade‐offs and provincial and municipal conditions and regional contexts when planning new airports, increasing airport services, or extending aviation connectivity. Others elsewhere may derive insights from these findings. [ABSTRACT FROM AUTHOR]

Case Description: A 9‐year‐old Quarter Horse gelding was presented for lethargy, decreased appetite, polyuria and polydipsia (PU/PD), and severe muscle wasting suggestive of immune‐mediated myositis. Clinical Findings: The horse displayed lethargy, fever, tachyarrhythmia, inappetence, PU/PD, and severe epaxial and gluteal muscle wasting. Clinicopathologic findings were consistent with previously reported cases of systemic calcinosis in horses, including increased muscle enzyme activity, hyperphosphatemia, increased calcium‐phosphorus product, hypoproteinemia, and an inflammatory leukogram. A diagnosis of systemic calcinosis was established by histopathologic evaluation of biopsy specimens from skeletal muscle, lung, and kidney. Treatment and Outcome: Symptomatic treatment was complemented by IV treatment with sodium thiosulfate to reverse calcium‐phosphate precipitation in soft tissue and PO aluminum hydroxide to decrease intestinal phosphorus absorption and serum phosphorus concentration. Clinical Relevance: This is the first report in the veterinary literature of an antemortem diagnosis of systemic calcinosis in the horse that was successfully treated and had favorable long‐term outcome. [ABSTRACT FROM AUTHOR]

The Community Multiscale Air Quality Model (CMAQ) has been a vital tool for air quality research and management at the United States Environmental Protection Agency (U.S. EPA), and at government environmental agencies and academic institutions worldwide. CMAQ requires a significant amount of disk space to store and archive input and output. For example, an annual simulation over the contiguous United States with horizontal grid cell spacing of 12 km requires 2-3 TB of input data and can produce anywhere from 7-45 TB of output data, depending upon modelling configuration, and desired post-processing output (e.g., for evaluations or graphics). After a simulation is complete, model data are archived for several years, or even decades, to ensure the replicability of conducted research. As a result, careful disk space management is essential to optimize resources and ensure the uninterrupted progress of ongoing research and applications requiring large scale, air quality modelling. Proper disk space management may include applying optimal data compression techniques that are executed on input and output files for all CMAQ simulations. There are several (not limited to) such utilities that compress files using losslessness compression, such as GNU Gzip and Basic Leucine Zipper Domain (bzip2). A new approach is proposed in this study that reduces the precision of the air quality model emissions input to reduce storage requirements (after a losslessness compression utility is applied) and accelerate runtime. The new approach is tested using CMAQ simulations and post-processed CMAQ output to examine the impact on the air quality model performance. In total, four simulations were conducted, and nine cases were post-processed from direct simulation output to determine disk space efficiency, runtime efficiency, and model (predictive) accuracy. Three simulations were run with emissions input containing only five, four, or three significant digits. To enhance the analysis of disk space efficiency, altered emissions CMAQ simulations were additionally post-processed to contain five, four, or three significant digits. The fourth, and final, simulation was run using the full precision emissions files with no alteration. Thus, in total, 13 gridded products (four simulations and nine cases) were analysed in this study. [ABSTRACT FROM AUTHOR]

Objective: To determine the accuracy of 2 interstitial glucose-monitoring systems (GMSs) for use in horses compared with a point-of-care (POC) glucometer and standard laboratory enzymatic chemistry method (CHEM). Animals: 8 clinically normal adult horses. Procedures: One of each GMS device (Dexcom G6 and Freestyle Libre 14-day) was placed on each horse, and blood glucose concentration was measured via POC and CHEM at 33 time points and compared with simultaneous GMS readings. An oral glucose absorption test (OGAT) was performed on day 2, and glucose concentrations were measured and compared. Results: Glucose concentrations were significantly correlated with one another between all devices on days 1 to 5. Acceptable agreement was observed between Dexcom G6 and Freestyle Libre 14-day when compared with CHEM on days 1, 3, 4, and 5 with a combined mean bias of 10.45 mg/dL and 1.53 mg/dL, respectively. During dextrose-induced hyperglycemia on day 2, mean bias values for Dexcom G6 (10.49 mg/dL) and FreeStyle Libre 14-day (0.34 mg/dL) showed good agreement with CHEM. Clinical relevance: Serial blood glucose measurements are used to diagnose or monitor a variety of conditions in equine medicine; advances in near-continuous interstitial glucose monitoring allow for minimally invasive glucose assessment, thereby reducing stress and discomfort to patients. Data from this study support the use of the Dexcom G6 and Freestyle Libre 14-day interstitial glucose-monitoring systems to estimate blood glucose concentrations in horses. [ABSTRACT FROM AUTHOR]

The daily organisation of most mammalian cellular functions is attributed to circadian regulation of clock‐controlled protein expression, driven by daily cycles of CRYPTOCHROME‐dependent transcriptional feedback repression. To test this, we used quantitative mass spectrometry to compare wild‐type and CRY‐deficient fibroblasts under constant conditions. In CRY‐deficient cells, we found that temporal variation in protein, phosphopeptide, and K+ abundance was at least as great as wild‐type controls. Most strikingly, the extent of temporal variation within either genotype was much smaller than overall differences in proteome composition between WT and CRY‐deficient cells. This proteome imbalance in CRY‐deficient cells and tissues was associated with increased susceptibility to proteotoxic stress, which impairs circadian robustness, and may contribute to the wide‐ranging phenotypes of CRY‐deficient mice. Rather than generating large‐scale daily variation in proteome composition, we suggest it is plausible that the various transcriptional and post‐translational functions of CRY proteins ultimately act to maintain protein and osmotic homeostasis against daily perturbation. Synopsis: CRYPTOCHROMES regulate proteome composition but are not required for its circadian organisation. Loss of these global transcriptional regulators leads to proteotoxic stress, which impairs the daily organisation of physiology in both cells and mice. Circadian protein abundance, phosphorylation and ion transport do not require CRYPTOCHROMEs.CRYPTOCHROME‐deficient cells and tissues show increased proteotoxic stress.Proteotoxic stress impairs the robustness of circadian rhythms in cells and mice.CRYPTOCHROME primarily functions to suppress temporal variation in proteome composition. [ABSTRACT FROM AUTHOR]

In this new age of globalization, regions attempt to attract foreign direct investment (FDI) in order to achieve regionally balanced development. We revisit existing theories of regional development and FDI by analyzing recent data sets on FDI, employment, and trade in China, Southeast Asia, and South Asia. Using Chinese provincial data in 2004, 2008, and 2013 and applying panel estimations, our econometric results demonstrate that FDI remarkably influenced the concentration of employment in manufacturing, financial, and business services industries within the three Chinese macro‐regions. We also find that FDI is ever transient, always moving away from high‐cost to low‐cost production bases across different regions. This transient nature of FDI is spatially selective and biased, and not able to generate the trickle‐down effects to other neighboring regions. That is why FDI recently moved from China to Southeast and South Asia rather than from its coastal to inland regions. Furthermore, we show that this nature of FDI generally leads to polarization development for regions. As a synthesis or extension of the existing theories, we propose a leapfrog polarization pattern and strategy for vast developing countries in considering their regional development strategies. [ABSTRACT FROM AUTHOR]

These recommendations, produced by a group of Canadian retina experts, have been developed to assist both retina specialists and general ophthalmologists in the management of vision-threatening neovascular age-related macular degeneration (nAMD). The recommendations are based on published evidence as well as collective experience and expertise in routine clinical practice. We provide an update on practice principles for optimal patient care, focusing on identified imaging biomarkers, in particular retinal fluid, as well as current and emerging therapeutic approaches. Algorithms for delivering high-quality care and improving long-term patient outcomes are provided, with an emphasis on timely and appropriate treatment to preserve and maintain vision. In the context of nAMD, increasing macular fluid or leakage on fluorescein angiography (FA) may indicate disease activity regardless of its location. Early elimination of intraretinal fluid (IRF) is of particular relevance as it is a prognostic indicator of worse visual outcomes. Robust referral pathways for second opinion and peer-to-peer consultations must be in place for cases not responding to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. [ABSTRACT FROM AUTHOR]

Background: Monitoring blood glucose concentrations is common in critically ill neonatal foals, especially septic foals and those receiving naso‐esophageal feedings or IV parenteral nutrition. Glucose typically is measured using a point‐of‐care (POC) glucometer but requires repeated restraint and blood collections, which may cause irritation at venipuncture sites and increased demands on nursing staff. Continuous glucose monitoring systems (CGMS) may provide an accurate alternative for monitoring blood glucose concentration. Objectives: To determine the correlation and accuracy of a CGMS to monitor neonatal foals' blood glucose concentrations as compared to a POC glucometer and laboratory chemistry analysis (CHEM). Animals: Samples from 4 healthy and 4 ill neonatal foals. Methods: A CGMS was placed on each foal, and glucose measurements acquired from this device were compared to simultaneous measurements of blood glucose concentration using a POC glucometer and CHEM. Results: Two‐hundred matched glucose measurements were collected from 8 neonatal foals. The mean bias (95% limits of agreement) between CGMS and CHEM, CGMS and POC glucometer, and POC glucometer and CHEM was 3.97 mg/dL (−32.5 to 40.4), 18.2 mg/dL (−28.8 to 65.2), and 22.18 mg/dL (−9.3 to 53.67), respectively. The Pearson's correlation coefficient (r) was significantly correlated among all devices: GCMS and CHEM (r = 0.81), CGMS and POC glucometer (r = 0.77) and POC glucometer‐CHEM (r = 0.92). Conclusions and Clinical Importance: Within the blood glucose concentration ranges in this study (78‐212 mg/dL), CGMS measurements were significantly correlated with CHEM, suggesting that it is an acceptable method to provide meaningful, immediate, and continuous glucose concentration measurements in neonatal foals while eliminating the need for repeated restraint and blood collection. [ABSTRACT FROM AUTHOR]

Background: Sepsis is common in foals and several treatments are used to facilitate recovery. Evidence in people suggests an association between low blood concentrations of thiamine, ascorbic acid, and cortisol and sepsis, with further evidence suggesting that administration of hydrocortisone, thiamine, and ascorbic acid may improve outcome. No information is available with regard to these treatments in foals. Hypothesis/Objectives: To compare blood concentrations of thiamine, ascorbic acid, and cortisol in healthy and ill foals. Animals: Fifteen healthy and 27 ill (septic and sick‐nonseptic [SNS]) foals were evaluated at admission. Fewer healthy and ill foals were available for sampling at 72 and 120 hours. Methods: Prospective study. Blood was collected from healthy foals at 12 (n = 15), 72 (n = 11), and 120 (n = 9) hours of age and from ill foals <48 hours old at admission (n = 27), 72 (n = 8), and 120 (n = 8) hours after presentation. Thiamine, ascorbic acid, and cortisol concentrations were measured in blood samples and compared between groups of foals. Results: Blood concentrations of thiamine were significantly lower in septic compared to healthy foals at 72 (median, 1.72 ng/mL; P =.02) and 120 (median, 2.0 ng/mL; P =.04) hours after admission; blood concentrations of ascorbic acid also were significantly lower in septic compared to healthy foals at 72 (median, 4.4 μg/mL; P =.02) and 120 hours (median, 4.8 μg/mL; P =.03). Blood concentrations of ascorbic acid were lower in SNS compared to healthy foals at 72 (median, 6.9 μg/mL; P =.03) and 120 (median, 6.4 μg/mL; P =.04) hours after admission. Serum cortisol concentrations were significantly higher at admission in septic (median, 4.23 μg/dL) compared to SNS (median, 1.8 μg/dL; P =.01) and healthy (median, 2.2 μg/dL; P =.002) foals. Conclusions and Clinical Importance: A potential association exists between illness in foals and lower blood concentrations of thiamine and ascorbic acid during hospitalization. Additional studies are needed to examine a larger population of foals and determine the clinical impact of low vitamin concentrations, if any, on morbidity and mortality. [ABSTRACT FROM AUTHOR]

Summary A 15‐year‐old multiparous Quarter Horse mare with a pre‐existing (>1 year) prepubic tendon rupture was presented pregnant (approximately 310 days gestation) with mild signs of generalised discomfort and an advanced degree of cervical relaxation. The foal was declared to be the priority in an emergency situation; therefore, intravenous dexamethasone (0.1 mg/kg bwt i.v. q24h) was administered in an attempt to mature the fetus in case urgent induction of parturition was required. Within 36 h of admission, the mare developed a complete rupture of the caudoventral body wall and skin, from the anus to the cranial aspect of the mammary gland. Because eventration had occurred, the mare underwent immediate euthanasia and terminal caesarean section via a modified approach. The colt foal was euthanised on humane grounds, due to an inability to breathe without a ventilator, following 72 h of intensive care. Rebreeding mares with prepubic tendon rupture is not recommended, this case report presents important evidence that rebreeding mares with this condition can have fatal consequences. [ABSTRACT FROM AUTHOR]

[Display omitted] • A combined rich and lean vapor recompression process for aqueous ammonia-based CO 2 capture was proposed. • Total equivalent work of 0.123 kW h/kg-CO 2 can be obtained, which is close to the thermodynamic minimum of 0.11 kW h/kg-CO 2. • The need of reboiler can be completely eliminated. Post-combustion carbon capture (PCC) using a chemical solvent is the most mature and well-proven technology to mitigate carbon dioxide (CO 2) emission. However, substantial energy consumption for solvent regeneration is still a critical challenge for widespread deployment of this PCC. In this study, a novel low-energy, combined rich and lean vapor recompression (RLVR) process for the CO 2 capture process using dilute aqueous ammonia (NH 3) solvent was developed and optimized by integrating of rich vapor recompression (RVR) and lean vapor recompression (LVR) approaches. A parametric study showed that the minimum total equivalent work can be obtained when CO 2 loading and NH 3 concentration of lean solution are 0.275 mol CO 2 /mol NH 3 and 5.0 wt%, respectively and the pressures of stripper, rich and lean solvent flash drums are maintained at 10.5 bar, 4.62 bar and 6.93 bar, respectively. Under such operation conditions, the total equivalent work required for a CO 2 capture plant was remarkably reduced to 0.123 kW h/kg of CO 2 captured, which is equivalent to about 10% energy penalty. This amounts to 26–54% reduction from recent literature reports. Furthermore, this combined RLVR process can completely eliminate the need of reboiler, leads to improving the flexibility of the capture plant since it can be separated from power plant steam systems. [ABSTRACT FROM AUTHOR]

Agricultural modification is one of the main drivers of global biodiversity decline. Vegetation clearance, tillage, grazing, and the application of fertilisers and pesticides have significantly affected native plants and animals. Reptiles can be vulnerable to agricultural practices, and localised declines in reptile biodiversity have been detected. However, the causes of these declines are likely to be many and will vary among reptiles with different life histories. Fossorial reptiles (those that mainly live below ground) are likely to be particularly vulnerable to soil and ground cover disturbance and yet are little studied in the context of agricultural practices. Here, we test the proposition that habitat disturbance caused by agricultural modification is a good predictor of decline or absence of a fossorial lizard. Specifically, we used boosted regression trees to model the relationship between five habitat factors and site abundance of the threatened Pink‐tailed Worm‐lizard (Aprasia parapulchella; Pygopodidae). We found that vegetation characteristics were the best predictors of A. parapulchella abundance. In particular, the relative contributions to our model of percentage cover of native large tussock‐forming grasses and site floristic score were 46% and 33%, respectively. Other variables that contributed to the explanation of abundance were percentage cover of rocks (10%), number of turnable rocks (5%) and relative density of rocks occupied by ants of the size class known to occur with A. parapulchella (5%). Our findings suggest that agricultural management or restoration strategies that promote ground‐layer vegetation characteristic of low levels of modification are likely to be most beneficial for the conservation of this species. Our findings and methods may be applicable to understand and study the presence and abundance of other fossorial or semi‐fossorial reptiles with specialised habitat preferences. Further research is required to establish the generality of our findings with respect to other such species around the world. [ABSTRACT FROM AUTHOR]

Circadian rhythms are a pervasive property of mammalian cells, tissues and behaviour, ensuring physiological adaptation to solar time. Models of cellular timekeeping revolve around transcriptional feedback repression, whereby CLOCK and BMAL1 activate the expression of PERIOD (PER) and CRYPTOCHROME (CRY), which in turn repress CLOCK/BMAL1 activity. CRY proteins are therefore considered essential components of the cellular clock mechanism, supported by behavioural arrhythmicity of CRY‐deficient (CKO) mice under constant conditions. Challenging this interpretation, we find locomotor rhythms in adult CKO mice under specific environmental conditions and circadian rhythms in cellular PER2 levels when CRY is absent. CRY‐less oscillations are variable in their expression and have shorter periods than wild‐type controls. Importantly, we find classic circadian hallmarks such as temperature compensation and period determination by CK1δ/ε activity to be maintained. In the absence of CRY‐mediated feedback repression and rhythmic Per2 transcription, PER2 protein rhythms are sustained for several cycles, accompanied by circadian variation in protein stability. We suggest that, whereas circadian transcriptional feedback imparts robustness and functionality onto biological clocks, the core timekeeping mechanism is post‐translational. SYNOPSIS: CRYPTOCHROME (CRY) proteins are central regulators of the circadian clock transcription/translation feedback loop. The finding that circadian timekeeping persists, albeit with reduced robustness, in CRY‐deficient cells and mice suggests that clock gene activity is determined by evolutionarily‐conserved post‐translational timing mechanisms. CRY‐mediated transcriptional feedback is dispensable for circadian timekeeping in mammalian cells, but functions to make rhythms more robust.CRY knockout mice exhibit behavioural rhythmicity under specific environmental conditions.Circadian variation in the abundance of core clock component PER2 is amplified by, but does not require, rhythmic Per2 transcription.CK1 and GSK3 kinases regulate PER2 stability in the absence of CRY. [ABSTRACT FROM AUTHOR]

Tenofovir disoproxil fumarate (TDF) effectively suppresses viral replication in chronic hepatitis B (CHB), but occasionally leads to renal impairment. We evaluated the prevalence of viral and biochemical breakthrough and renal function kinetics in renally impaired patients with CHB on reduced and on full‐dose TDF. This clinic‐based longitudinal cohort study included patients receiving full and reduced dose TDF (due to eGFR [Cockcroft‐Gault] <60 mL/min/1.73 m2). Viral and biochemical breakthroughs were assessed 1 month after starting full and reduced TDF dose until the end‐of‐follow‐up. Breakthroughs were studied in full and reduced dose TDF, and renal function (MDRD) longitudinally before and after dose reduction within patients starting on full‐dose TDF. Of 750 patients on TDF, 78 (10%) had reduced dose and 672 (90%) full dose. At the time of dose reduction, 36 (46%) patients had chronic kidney disease stage G3B. A viral breakthrough occurred in one cirrhotic dialysis‐dependent patient (dosed 300 mg weekly) which resolved without signs of decompensation, and in one patient on full dose which resolved spontaneously. One biochemical breakthrough occurred during dose reduction and resolved naturally without viral breakthrough. The MDRD improved within the first year of dose reduction (+3.0 [2.5] mL/min per year; P <.005) and remained stable thereafter. Fifty‐three (79%) patients reached an MDRD >50 mL/min during dose reduction. Low dose TDF maintains renal function and viral suppression in most renally impaired patients with CHB, even in those with advanced liver disease. This useful, yet simple strategy could be particularly viable in resource‐constrained settings. [ABSTRACT FROM AUTHOR]

To facilitate community action toward health equity, the County Health Rankings & Roadmaps program (CHR&R) assigns health rankings to US counties. The CHR&R conceptual model considers White-Black and White-non-White dissimilarity values to represent residential segregation as part of the family and social support subcomponent. As the US is greying and becoming more multi-racial-ethnic, the two-group White-centered segregation measures are inadequate to capture segregation among population subgroups in the US. Thus, we evaluate the relevancy of segregation measures that consider multiple racial, ethnic, and age groups in assessing US county health. Besides using the two-group dissimilarity index to measure White-centered racial segregation as conceptualized by CHR&R, the study also uses the multi-group generalized dissimilarity index to measure racial-ethnic-age segregation by counties, employing both aspatial and spatial versions of these measures. These indices are computed for counties using the 2015–2019 American Community Survey data at the census tract level. Descriptive statistics and regressions controlling for sociodemographic factors and healthcare access are used to assess the contributions of individual segregation measures to mortality (life expectancy, years of potential life lost and premature mortality) and morbidity (frequent mental distress, frequent physical distress, and low birth weight) indicators representing county health. Overall, correlations between these indicators and most segregation measures are significant but weak. Regression results show that many segregation measures are not significantly related to mortality indicators, but most are significantly associated with morbidity indicators, with the magnitudes of these associations higher for the multi-group racial-ethnic-age segregation index and its spatial version. Results provide evidence that racial-ethnic-age segregation is associated with county-level morbidity and that spatial measures capturing segregation of multiple population axes should be considered for ranking county health. • The US is becoming increasingly racially-ethnically diverse and greyer. • Segregation should be measured using multigroup indices with race/ethnicity/age. • Association between county health and race-ethnic-age segregation were assessed. • County health rankings may include multigroup and spatial segregation indices. [ABSTRACT FROM AUTHOR]

Physical distancing has been argued as one of the effective means to combat the spread of COVID-19 before a vaccine or therapeutic drug becomes available. How far people can be spatially separated is partly behavioral but partly constrained by population density. Most models developed to predict the spread of COVID-19 in the U.S. do not include population density explicitly. This study shows that population density is an effective predictor of cumulative infection cases in the U.S. at the county level. Daily cumulative cases by counties are converted into 7-day moving averages. Treating the weekly averages as the dependent variable and the county population density levels as the explanatory variable, both in logarithmic scale, this study assesses how population density has shaped the distributions of infection cases across the U.S. from early March to late May, 2020. Additional variables reflecting the percentages of African Americans, Hispanic-Latina, and older adults in logarithmic scale are also included. Spatial regression models with a spatial error specification are also used to account for the spatial spillover effect. Population density alone accounts for 57% of the variation (R-squared) in the aspatial models and up to 76% in the spatial models. Adding the three population subgroup percentage variables raised the R-squared of the aspatial models to 72% and the spatial model to 84%. The influences of the three population subgroups were substantial, but changed over time, while the contributions of population density have been quite stable after the first several weeks, ascertaining the importance of population density in shaping the spread of infection in individual counties, and in their neighboring counties. Thus, population density and sizes of vulnerable population subgroups should be explicitly included in transmission models that predict the impacts of COVID-19, particularly at the sub-county level. [ABSTRACT FROM AUTHOR]

This study revisits region‐specific determinants of foreign direct investment (FDI) in Eastern, Central, and Western China using econometric and spatial analyses. It uses a data set covering 31 Chinese provinces and autonomous regions spanning the period 2005–15, together with panel data regression. Our statistical results show that in Eastern China, FDI is significantly associated with bilateral trade, orientation towards the service industry, industrialisation level, and availability of strategic assets in the region. In Central China, FDI is mainly pulled by availability of the domestic market and strategic assets in the region. In Western China, FDI inflows are mainly determined by natural resource endowment, industrialisation level, and regional innovation and production effectiveness in information and communication technology industries. Our analysis also reveals the impact of FDI in China's regional development and its capacity to hollow out the three Chinese macro‐regions. Our findings for China lead us to suggest that those governments seeking to attract FDI should not solely rely on it to facilitate local economic development and should make use of local circumstances in combination with FDI to boost their economies. [ABSTRACT FROM AUTHOR]

BACKGROUND Telemedicine is an emerging field with numerous applications within medicine. Previous review articles describe its use within plastic surgery and otolaryngology but none, to the authors' knowledge, within dermatologic surgery. OBJECTIVE To provide a review of the applications of telemedicine within dermatologic surgery. MATERIALS AND METHODS A PubMed search of articles published on teledermatology was conducted in July 2018. Articles were selected based on their relevance to dermatologic surgery and reviewed for their discussion of the applications of telemedicine in surgical and cosmetic dermatology. RESULTS The initial search resulted in 156 articles. Eleven ultimately met inclusion criteria: 2 in referral and consultation, 5 in telepathology, 2 in intraoperative uses, and 2 in postprocedural care. CONCLUSION For preoperative consultation, teledermatology enables the surgeon to plan ahead and increases access to care by reducing the number of clinic visits. Telepathology has the potential to allow intraoperative consultation with a dermatopathologist to achieve accurate tumor clearance without delay. Smartglasses represent a promising technology for greater care coordination and a teaching tool. Postprocedural monitoring via text messaging provides convenient access to expert advice and early detection of postoperative complications. With increasing technologic advancements, telemedicine holds great potential to augment the dermatologic surgeon's daily practice. [ABSTRACT FROM AUTHOR]

Background & Aims: Tenofovir disoproxil fumarate (TDF) is a first‐line treatment for chronic hepatitis B (CHB). We aimed to describe the efficacy and safety profiles of TDF treatment for up to 10 years in a well‐described cohort of CHB patients. Methods: Hepatitis B e antigen (HBeAg)‐negative and HBeAg‐positive patients from two randomised, double‐blind trials (ClinicalTrials.gov: NCT00117676 and NCT00116805) completed 48 weeks of randomised treatment with TDF or adefovir dipivoxil. A subset of these patients was then eligible to receive open‐label TDF treatment for up to 10 years. At Year 10, patients were assessed for virological suppression, alanine aminotransferase (ALT) normalisation, serological response, safety and tolerability. Results: Of 641 randomised and treated patients, 585 (91%) entered the open‐label extension phase with 203 (32%) patients completing Year 10 of the study. At Year 10, 118/118 (100%) of HBeAg‐negative patients and 78/80 (98%) of HBeAg‐positive patients with available data achieved hepatitis B virus (HBV) DNA < 69 IU/mL, while 88/106 (83%) and 60/77 (78%) patients achieved ALT normalisation, respectively. Of the 23 patients with HBeAg status available at Year 10, 12 (52%) and six (27%) experienced HBeAg loss and seroconversion, respectively. No resistance to TDF was documented up to Year 10. In the period between Year 8 and Year 10, the safety profile of TDF was similar to previous reports, with few patients experiencing renal‐ or bone‐related adverse events. Conclusions: Over 10 years, TDF had a favourable safety profile, was well tolerated, and resulted in continued maintenance of virological suppression with no documented resistance. [ABSTRACT FROM AUTHOR]

Objective: To identify salivary metabolite biomarkers to differentiate patients with oral squamous cell carcinoma and oral epithelial dysplasia (OSCC/OED) from those with persistent suspicious oral mucosal lesions (PSOML). Subjects and methods: Whole unstimulated saliva samples were collected from age-, sex-, and race-matched patients who had a lesion in the oral cavity and for whom open biopsies were performed. The patients included OSCC (n = 6), OED (n = 10), and PSOML (n = 32). Hydrophilic metabolites in saliva samples were comprehensively analyzed using capillary electrophoresis mass spectrometry. To evaluate the discrimination ability of a combination of multiple markers, a multiple logistic regression (MLR) model was developed to differentiate OSCC/OED from PSOML. Results: Six metabolites were significantly different in OSCC/OED compared with PSOML. From these six metabolites, ornithine, o-hydroxybenzoate, and ribose 5-phosphate (R5P) were used to develop the MLR model, which resulted in a high value for the area under receiver operating characteristic curve (AUC 0.871, 95% confidential interval (CI) 0.760–0.982; p < 0.001) to discriminate OSCC/OED from PSOML. Conclusions: This is the first study to identify salivary metabolites that discriminate OSCC/OED from PSOML rather than from healthy controls. The profiles of salivary metabolites were significantly different between OSCC/OED and PSOML. The ability to discriminate OSCC/OED from PSOML is important for dentists who are not oral surgery specialists. These salivary metabolites showed potential for non-invasive screening to discriminate OSCC/OED from PSOML. Clinical relevance: Salivary metabolites in this study showed potential for non-invasive screening to discriminate OSCC/OED from PSOML. [ABSTRACT FROM AUTHOR]

Assessing spatial autocorrelation (SA) of statistical estimates such as means is a common practice in spatial analysis and statistics. Popular SA statistics implicitly assume that the reliability of the estimates is irrelevant. Users of these SA statistics also ignore the reliability of the estimates. Using empirical and simulated data, we demonstrate that current SA statistics tend to overestimate SA when errors of the estimates are not considered. We argue that when assessing SA of estimates with error, one is essentially comparing distributions in terms of their means and standard errors. Using the concept of the Bhattacharyya coefficient, we proposed the spatial Bhattacharyya coefficient (SBC) and suggested that it should be used to evaluate the SA of estimates together with their errors. A permutation test is proposed to evaluate its significance. We concluded that the SBC more accurately and robustly reflects the magnitude of SA than traditional SA measures by incorporating errors of estimates in the evaluation. Key Words: American Community Survey, Geary ratio, Moran's I, permutation test, spatial Bhattacharyya coefficient. [ABSTRACT FROM AUTHOR]

Quantitative indices of segregation are powerful tools for summarising the spatial relationships between population groups and thereby providing the basis for analysis and public policy intervention. While the broad concept of segregation may be intuitive, measurement is challenging because of the complexity of varied dimensions and spatial arrangements. Many traditional measures can be criticised for over‐simplification or over‐reduction, not least in their treatment of geographical space. Over the last several decades, however, a series of measures has been developed to explicitly incorporate the spatial arrangement of population groups as well as their interactions. This paper reviews the development of spatial segregation measures, particularly focusing on the mathematical formulation of spatial arrangement/relations. In addition, several related issues are discussed, including representation of spatial interaction, spatial scale and statistical inferences. Also, this paper presents an overview of existing software tools that are readily available for calculating some of the reviewed measures. Finally, discussions on challenges and future research are provided. [ABSTRACT FROM AUTHOR]

Intermetallic compound (IMC) formation is important for the reliability of microelectronic devices. In this work, a generalized phenomenological model was developed to explain the effects of electromigration on IMC growth by considering reaction and diffusion of two species. When both reaction and mass transfer are important, the model predicts cathode enhancement and anode thinning if the electromigration effect on the dominant diffusion species is more pronounced. Cathode suppression and anode enhancement occur when the electromigration effect on the minor diffusion species is more pronounced. Simultaneous cathode and anode suppressions happen when there are two diffusion species and the diffusion and electromigration fluxes are comparable. Simultaneous cathode and anode enhancements occur when mass transfer is the limiting step and diffusion flux is negligible compared to electromigration. This model was found to be consistent with experiment data on IMC growth in the literature given the limited amount of information on effective charge of various species. [ABSTRACT FROM AUTHOR]

Context: Pain is one of the most devastating symptoms for cancer patients. One third of patients who experience pain do not receive effective treatment. A key barrier to effective pain management is lack of routine measurement and monitoring of pain. Patient‐reported outcome measures (PROMs) are recommended for measuring cancer pain. However, evidence to guide the selection of the most appropriate measure to identify and monitor cancer pain is limited. A systematic review of measurement properties of PROMs for pain in cancer patients is needed to identify the best validated measure for adoption to an electronic platform. Objectives: To systematically review measurement properties of PROMs used for adult cancer patients to measure pain and, as a secondary goal, to investigate the evidence of validated mobile health (mHealth) applications used to measure pain (registration number: CRD42017065575). Methods: Medline, Embase, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were systematically searched in March 2018 for studies examining measurement properties for PROMs for pain in adult cancer patients. The methodological quality of the studies and their results were appraised using the Consensus‐based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist and specific measurement properties criteria, respectively. Results: Sixteen studies evaluating 8 instruments were included. No studies using a PROM in an mHealth application were identified. The methodological quality of the measurement properties ranged between poor and fair. No instrument showed strong positive evidence for all the evaluated measurement properties. Based on the available evidence, the Brief Pain Inventory‐Short Form (BPI‐SF) had the strongest evidence to support its selection for the measurement of cancer pain. Conclusion: The BPI‐SF was the best performing measure across all properties evaluated through COSMIN. Better quality validation studies of PROMs for cancer pain are needed to explore the full range of measurement properties. Utilizing mHealth applications to measure pain in cancer patients is an innovative approach worthy of further investigation. [ABSTRACT FROM AUTHOR]

The process of congressional redistricting, delineating boundaries for districts in which voters elect members to the U.S. House of Representatives, has always been an expensive and controversial process. Congressional districts (CDs) are redrawn due to changes in population reflected by the decennial census to ensure equal representation. Laws and regulations literature identifies eight criteria that may be considered when determining the boundaries of CDs and this article focuses on one of those criteria, maintaining communities of interest (COIs). This criterion requires states to preserve these boundaries when delineating CDs but fails to define a COI. This research proposes and evaluates two approaches to define a COI and examines the extent to which this criterion has been adhered to. One definition uses Thiessen polygons and census designated places to delineate COIs based on known cultural places, whereas the other definition uses cluster analysis to group together people with similar sociodemographic characteristics. The results show that the two definitions are feasible for defining a COI. Furthermore, the states largely maintain the COI boundaries within their CDs by only splitting, at most, 17.1 percent of the COIs defined. Existing literature shows that maintaining COIs within CDs leads to higher voter participation and engagement, as well as better representation. The results show that if either definition was adopted, states could comply with this criterion with relative ease. Furthermore, a standard definition could help reduce the cost and controversy surrounding the redistricting process. [ABSTRACT FROM AUTHOR]

Background: Difficult airway management and obstructive sleep apnea may contribute to increased risk of perioperative morbidity and mortality. The objective of this systematic review and meta-analysis (SRMA) is to evaluate the evidence of a difficult airway being associated with obstructive sleep apnea (OSA) patients undergoing surgery. Methods: The standard databases were searched from 1946 to April 2017 to identify the eligible articles. The studies which included adult surgical patients with either suspected or diagnosed obstructive sleep apnea must report at least one difficult airway event [either difficult intubation (DI), difficult mask ventilation (DMV), failed supraglottic airway insertion or difficult surgical airway] in sleep apnea and non-sleep apnea patients were included. Results: Overall, DI was 3.46-fold higher in the sleep apnea vs non-sleep apnea patients (OSA vs. non-OSA: 13.5% vs 2.5%; OR 3.46; 95% CI: 2.32–5.16, p <0.00001). DMV was 3.39-fold higher in the sleep apnea vs non-sleep apnea patients (OSA vs. non-OSA: 4.4% vs 1.1%; OR 3.39; 95% CI: 2.74–4.18, p <0.00001). Combined DI and DMV was 4.12-fold higher in the OSA vs. non-OSA patients (OSA vs. non-OSA: 1.1% vs 0.3%; OR 4.12; 95% CI: 2.93–5.79, p <0.00001). There was no significant difference in the supraglottic airway failure rates in the sleep apnea vs non-sleep apnea patients (OR: 1.34; 95% CI: 0.70–2.59; p = 0.38). Meta-regression to adjust for various subgroups and baseline confounding factors did not impact the final inference of our results. Conclusion: This SRMA found that patients with obstructive sleep apnea had a three to four-fold higher risk of difficult intubation or mask ventilation or both, when compared to non-sleep apnea patients. [ABSTRACT FROM AUTHOR]

Area-based measures of neighborhood characteristics simply derived from enumeration units (e.g., census tracts or block groups) ignore the potential of spatial spillover effects, and thus incorporating such measures into multilevel regression models may underestimate the neighborhood effects on health. To overcome this limitation, we describe the concept and method of areal median filtering to spatialize area-based measures of neighborhood characteristics for multilevel regression analyses. The areal median filtering approach provides a means to specify or formulate "neighborhoods" as meaningful geographic entities by removing enumeration unit boundaries as the absolute barriers and by pooling information from the neighboring enumeration units. This spatializing process takes into account for the potential of spatial spillover effects and also converts aspatial measures of neighborhood characteristics into spatial measures. From a conceptual and methodological standpoint, incorporating the derived spatial measures into multilevel regression analyses allows us to more accurately examine the relationships between neighborhood characteristics and health. To promote and set the stage for informative research in the future, we provide a few important conceptual and methodological remarks, and discuss possible applications, inherent limitations, and practical solutions for using the areal median filtering approach in the study of neighborhood effects on health. [ABSTRACT FROM AUTHOR]

The geographical distribution of a species is limited by factors such as climate, resources, disturbances and species interactions. Environmental niche models attempt to encapsulate these limits and represent them spatially but do not always incorporate disturbance factors. We constructed MaxEnt models derived from a remotely sensed vegetation classification with, and without, an agricultural modification variable. Including agricultural modification improved model performance and led to more sites with native vegetation and fewer sites with exotic or degraded native vegetation being predicted suitable for A. parapulchella. Analysis of a relatively well-surveyed sub-area indicated that including agricultural modification led to slightly higher omission rates but markedly fewer likely false positives. Expert assessment of the model based on mapped habitat also suggested that including agricultural modification improved predictions. We estimate that agricultural modification has led to the destruction or decline of approximately 30-35% of the most suitable habitat in the sub-area studied and approximately 20-25% of suitable habitat across the entire study area, located in the Australian Capital Territory, Australia. Environmental niche models for a range of species, particularly habitat specialists, are likely to benefit from incorporating agricultural modification. Our findings are therefore relevant to threatened species planning and management, particularly at finer spatial scales. [ABSTRACT FROM AUTHOR]

Background & Aims Current guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in all patients with cirrhosis, regardless of etiology. However, HCC incidence is not well established for many causes of cirrhosis. We aimed to assess the disease-specific incidence of HCC in a large cohort of patients with cirrhosis and to develop a scoring system to predict HCC risk. Methods A derivation cohort of patients with cirrhosis diagnosed by biopsy or non-invasive measures was identified through retrospective chart review. The disease-specific incidence of HCC was calculated according to etiology of cirrhosis. Factors associated with HCC were identified through multivariable Cox regression and used to develop a scoring system to predict HCC risk. The scoring system was evaluated in an external cohort for validation. Results Of 2,079 patients with cirrhosis and ≥6 months follow-up, 226 (10.8%) developed HCC. The 10-year cumulative incidence of HCC varied by etiologic category from 22% in patients with viral hepatitis, to 16% in those with steatohepatitis and 5% in those with autoimmune liver disease ( p <0.001). By multivariable Cox regression, age, sex, etiology and platelets were associated with HCC. Points were assigned in proportion to each hazard ratio to create the Toronto HCC Risk Index (THRI). The 10-year cumulative HCC incidence was 3%, 10% and 32% in the low-risk (<120 points), medium-risk (120–240) and high-risk (>240) groups respectively, values that remained consistent after internal validation. External validation was performed on a cohort of patients with primary biliary cirrhosis, hepatitis B viral and hepatitis C viral cirrhosis (n = 1,144), with similar predictive ability (Harrell’s c statistic 0.77) in the validation and derivation cohorts. Conclusion HCC incidence varies markedly by etiology of cirrhosis. The THRI, using readily available clinical and laboratory parameters, has good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis. Lay summary HCC incidence varies markedly depending on the underlying cause of cirrhosis. Herein, using readily available clinical and laboratory parameters we describe a risk score, THRI, which has a good predictive ability for HCC in patients with cirrhosis, and has been validated in an external cohort. This risk score may help to guide recommendations regarding HCC surveillance among patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Localization along a route is an everyday necessity for in-vehicle navigation systems, and a vital task for automated driving technologies. Visual ego-localization promises reliable accuracy even in challenging urban environments where Global Positioning Systems (GPSs) can fail. Using cameras for localization against a pre-constructed database requires either the creation of a dense three-dimensional feature point map and pose estimation of a query camera relative to this map, or image matching along a database route to determine the capture position of the query camera based on the most similar database image. While the latter method is potentially less computationally intensive and can provide a more compact database, localization accuracy is limited by the discrete positioning information at database frame capture locations. In this paper we propose an image matching method that makes use of image features which are pre-matched during database construction, allowing linear regression coefficients for the relationship between capture position and feature scale to be calculated. The capture position of matched query features can then be estimated to sub-database spacing resolution. By incorporating the visual localization system into a Bayes estimator, we demonstrate an average monocular vision localization accuracy of 0.33 m in tests on actual vehicle image streams. [ABSTRACT FROM AUTHOR]

Delineating regional boundaries for places has a long tradition in geography, urban analysis and regional planning. Its theoretical basis may be traced back to the central place theory. The normative approach, using spatial interaction models, has been used, and the empirical approach, using commuting data, is also popular. While gathering commuting data using traditional methodologies (e.g., surveys) is costly, data capturing people's locations and their thoughts, are widely available through social media platforms. This article demonstrates that Twitter data can be used to delineate boundaries among competing places. A generic approach based on the density of place names mentioned in geo-tagged tweets was proposed to reflect the sphere of influence or dominance of places. Locations with the same levels of influence from competing places constitute the boundaries delineating the regions dominated by the respective places. The method was tested to determine the boundaries between two metropolitan regions, two local cities, and two neighborhoods or communities. Results from these simple case studies demonstrated the validity of the general approach for evaluating existing place boundaries and determining boundaries if they have not been delineated. The method is applicable to different levels of the place hierarchy and has practical values for planning of places of different sizes. [ABSTRACT FROM AUTHOR]

Objectives: We introduce a novel quantitative approach for evaluating the order of roll-out during phased introduction of clinical information systems. Such roll-outs are associated with unavoidable risk due to patients transferring between clinical areas using both the old and new systems.Methods: We proposed a simple graphical model of patient flow through a hospital. Using a simple instance of the model, we showed how a roll-out order can be generated by minimising the flow of patients from the new system to the old system.Results: The model was applied to admission and discharge data acquired from 37,080 patient journeys at the Churchill Hospital, Oxford between April 2013 and April 2014. The resulting order was evaluated empirically and produced acceptable orders.Discussion: The development of data-driven approaches to clinical Information system roll-out provides insights that may not necessarily be ascertained through clinical judgment alone. Such methods could make a significant contribution to the smooth running of an organisation during the roll-out of a potentially disruptive technology.Conclusion: Unlike previous approaches, which are based on clinical opinion, the approach described here quantitatively assesses the appropriateness of competing roll-out strategies. The data-driven approach was shown to produce strategies that matched clinical intuition and provides a flexible framework that may be used to plan and monitor Clinical Information System roll-out. [ABSTRACT FROM AUTHOR]