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The flexible geometry configuration of the bistatic synthetic aperture radar (SAR) has many advantages. However, it causes serious measurement error in the bistatic SAR system, which degrades the quality of the SAR images and the ...
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The flexible geometry configuration of the bistatic synthetic aperture radar (SAR) has many advantages. However, it causes serious measurement error in the bistatic SAR system, which degrades the quality of the SAR images and the precision of the digital elevation model (DEM) obtained using stereoscopy bistatic SAR. In this paper, the influence of the scene height estimation error, trigger delay, transmitter position measurement error, receiver position measurement error, and transmission line length measurement error are analyzed. These analyses are very useful in bistatic SAR system design. The scene height estimation error, trigger delay, transmitter position measurement error, and synchronization receiver position measurement error affect both the quality of the images and the precision of the DEM obtained by stereoscopy bistatic SAR slightly. The echo receiver position measurement error and transmission line length measurement error affect the quality of the imaging only slightly, but seriously affect the precision of the DEM obtained by stereoscopy bistatic SAR. Luckily, their measurement precision can be quite satisfactory. Simulations and real bistatic experimental results verify the proposed theoretical analysis.
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Background: Previous studies have reported that patients who are medication naive in some medication classes have a higher risk of medication discontinuation during the first 30 days of treatment and shorter median times to discon...
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Background: Previous studies have reported that patients who are medication naive in some medication classes have a higher risk of medication discontinuation during the first 30 days of treatment and shorter median times to discontinuation than do medication-experienced patients. Objectives: This study compared the risk of discontinuation during the first 30 days after the index fill and the median time to discontinuation for medication-naive and medication-experienced patients who were prescribed drugs for asthma, diabetes mellitus, high cholesterol, cardiovascular disease, breast cancer, glaucoma, or osteoporosis. Methods: Deidentified outpatient pharmacy records from 4 large US retail chains were searched for patients who had obtained a prescription for one of the index medications between January 1, 2007, and January 31, 2007. Included medication classes were asthma inhalers, asthma pills, oral breast-cancer agents, cardiovascular medications, oral antidiabetic medications, insulin, glaucoma drops, osteoporosis medications, and statins. Patients were divided into 2 groups: those for whom an in-class medication was not dispensed in the previous 180 days were identified as medication naive, and those for whom an in-class medication was dispensed during this period were identified as medication experienced. Discontinuation was defined as being >30 days late for a scheduled refill. Time to discontinuation was measured using Kaplan-Meier analysis during a 360-day follow-up period. Results: Data for 2.17 million patients who received prescriptions from 3821 pharmacies were analyzed. During the first 30 days of therapy, rates of discontinuation for medication-naive patients were 17.4% to 42.6% higher than for medication-experienced patients, and their median times to discontinuation were 14.2% to 28.9% as long. The difference in persistence between medication-naive and medication-experienced patients emerged during the first 30 days of medication use, after which rates of discontinuation were relatively consistent. Patients prescribed nonoral medications for diabetes mellitus (insulin), asthma (inhalers), and glaucoma (drops) had an especially high risk of discontinuation during the first month of treatment. Conclusion: This study found that medicationnaive patients had a higher risk of discontinuation during the first 30 days of therapy than did medicationexperienced patients, regardless of the medication class prescribed, leading to shorter median times to discontinuation.
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Dear Editor,Large vestibular aqueduct syndrome was first described in 1978 by Valvassori and Clemis.1 Children with large vestibular aqueduct syndrome may have hearing in their childhood enabling the acquisition of normal speech a...
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Dear Editor,Large vestibular aqueduct syndrome was first described in 1978 by Valvassori and Clemis.1 Children with large vestibular aqueduct syndrome may have hearing in their childhood enabling the acquisition of normal speech and language development by using hearing aids. Typically, their hearing progressively deteriorates in association with an incident of minor head trauma, exercise or an upper respiratory tract infection. Surgical management including shunts and obliteration of the vestibular aqueduct has proven to be ineffective. When the hearing of these patients has progressed to the severe-to-profound level bilaterally, it has been proposed that cochlear implantation may be an effective treatment. Many reports have demonstrated that cochlear implantation is an effective method in providing hearing to children with severe-to-profound hearing loss caused by large vestibular aqueduct syndrome. However, most of these studies examined few cases and reported only short-term speech perception results in children. Therefore, the aim of this study was to report the long-term speech perception outcome of children with large vestibular aqueduct syndrome at an earlier implantation time and to compare the performance of a cochlear implant (given to the initially poorer hearing ear) to a contralateral hearing aid (better hearing ear).
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We study a pervasive fraudulent strategy, called “brushing,” employed by retailers operating in e-commerce platforms: Retailers place fake orders of their own products to inflate sales and boost the visibility of their store lin...
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We study a pervasive fraudulent strategy, called “brushing,” employed by retailers operating in e-commerce platforms: Retailers place fake orders of their own products to inflate sales and boost the visibility of their store links in search results. Using a duopolistic pricing game with heterogeneous consumer search behavior, we show that the retailer at a more prominent position in product listing enjoys greater profit as well as an advantage in future position allocation if the platform charges a per-sale commission fee and uses a sales-based ranking mechanism to display store-link positions. To fight for better visibility, retailers may employ brushing to boost their sales metrics. We characterize the equilibrium brushing behavior for the position competition game between the retailers. Under a sufficiently high commission rate, the game has a pure-strategy equilibrium and entails no-brushing outcome. Otherwise, retailers fully engage in brushing activity and the brushing equilibrium exists only in mixed strategies. Model extensions incorporating heterogeneities in wholesale cost and product quality show that retailers with cost and quality advantages are able to gain profit improvement at a less prominent position and thereby have less incentive to invest in brushing. Our results provide platform managers and retailers with economic insights to better understand the logic for brushing fraud and strategic decisions in online marketplaces.
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The aim of the study is to provide an up-to-date review of studies that used preclinical animal models for the evaluation of tissue engineering treatments for spinal cord injury (SCI), which involved the use of biomaterials with o...
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The aim of the study is to provide an up-to-date review of studies that used preclinical animal models for the evaluation of tissue engineering treatments for spinal cord injury (SCI), which involved the use of biomaterials with or without the addition of cells or biomolecules. Electronic search of the PubMed, Web of Science, and Embase databases was performed for relevant studies published between January 2009 and December 2019. In total, 1579 articles were retrieved, of which 58 studies were included for analysis. Among the included studies, rats were the most common species used for animal models of SCI, while complete transection was the most commonly used injury pattern. Immediate intervention after injury was conducted in the majority of studies, and 8 weeks was the most common final time point of outcome assessment. A wide range of natural and synthetic biomaterials with different morphologies were used as a part of tissue engineering treatments for SCI, including scaffolds, hydrogels, and particles. Experimental parameters in studies using SCI animal models to evaluate tissue engineering treatments should be carefully considered to match the purpose of the study. Biomaterials that have functional modifications or are applied in combination with cells and biomolecules can be effective in creating a permissive environment for SCI repair in preclinical animal models. This review provides an up-to-date summary of the preclinical landscape where tissue engineering treatments involving biomaterials were tested in animal models of spinal cord injury (SCI). Using studies published within the last 10 years, novel perspectives were presented on the animal species used, injury pattern, timing of intervention and outcome measurement, and biomaterials selection, as well as a summary of the individual findings of each study. This review provides unique insight into biomaterials-based tissue engineering strategies that have progressed to testing in animal models of SCI, which will help shape future research in the field and propel the clinical translation of discoveries. ? Copyright 2022, Mary Ann Liebert, Inc.
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While DNA methylation carries genetic signals and is instrumental in the evolution of organismal complexity, small RNAs (sRNAs), ~18–24 ribonucleotide (nt) sequences, are crucial mediators of methylation as well as gene silencing...
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While DNA methylation carries genetic signals and is instrumental in the evolution of organismal complexity, small RNAs (sRNAs), ~18–24 ribonucleotide (nt) sequences, are crucial mediators of methylation as well as gene silencing. However, scant study deals with sRNA evolution via featuring their expression dynamics coupled with species of different evolutionary time. Here we report an atlas of sRNAs and microRNAs (miRNAs, single-stranded sRNAs) produced over time at seed-set of two major spermatophytes represented by populations of Picea glauca and Arabidopsis thaliana with different seed-set duration. We applied diverse profiling methods to examine sRNA and miRNA features, including size distribution, sequence conservation and reproduction-specific regulation, as well as to predict their putative targets. The top 27 most abundant miRNAs were highly overlapped between the two species (e.g., miR166,?319 and?396), but in P. glauca, they were less abundant and significantly less correlated with seed-set phases. The most abundant sRNAs in libraries were deeply conserved miRNAs in the plant kingdom for Arabidopsis but long sRNAs (24-nt) for P. glauca. We also found significant difference in normalized expression between populations for population-specific sRNAs but not for lineage-specific ones. Moreover, lineage-specific sRNAs were enriched in the 21-nt size class. This pattern is consistent in both species and alludes to a specific type of sRNAs (e.g., miRNA, tasiRNA) being selected for. In addition, we deemed 24 and 9 sRNAs in P. glauca and Arabidopsis, respectively, as sRNA candidates targeting known adaptive genes. Temperature had significant influence on selected gene and miRNA expression at seed development in both species. This study increases our integrated understanding of sRNA evolution and its potential link to genomic architecture (e.g., sRNA derivation from genome and sRNA-mediated genomic events) and organismal complexity (e.g., association between different sRNA expression and their functionality).
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Background: Gout is the most common inflammatory arthritis, which, if left untreated or inadequately treated, will lead to joint destruction, bone erosion and disability due to the crystal deposition. Uric acid transporter 1 (URAT...
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Background: Gout is the most common inflammatory arthritis, which, if left untreated or inadequately treated, will lead to joint destruction, bone erosion and disability due to the crystal deposition. Uric acid transporter 1 (URAT1) was the promising therapeutic target for urate-lowering therapy. Objective: The goal of this work is to understand the structure-activity relationship (SAR) of a potent lesinurad-based hit, sodium 2-((5-bromo-4-((4-cyclopropyl-naphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1c), and based on that discover a more potent URAT1 inhibitor. Methods: The SAR of 1c was systematically explored and the in vitro URAT1 inhibitory activity of synthesized compounds 1a-1t was determined by the inhibition of URAT1-mediated [8-14C]uric acid uptake by human embryonic kidney 293 (HEK293) cells stably expressing human URAT1. Results: Twenty compounds 1a-1t were synthesized. SAR analysis was performed. Two highly active URAT1 inhibitors, sodium 2-((5-bromo-4-((4-n-propylnaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1j) and sodium 2-((5-bromo-4-((4-bromonaphth-1-yl)methyl)-4H-1,2,4-triazol-3-yl)thio)acetate (1m), were identified, which were 78- and 76-fold more active than parent lesinurad in in vitro URAT1 inhibitory assay, respectively (IC50 values for 1j and 1m were 0.092 μM and 0.094 μM, respectively, against human URAT1 vs 7.18 μM for lesinurad). Conclusion: Two highly active URAT1 inhibitors were discovered. The SAR exploration also identified more flexible naphthyltriazolylmethane as a novel molecular skeleton that will be valuable for the design of URAT1 inhibitors, as indicated by the observation that many of the synthesized naphthyltriazolylmethane-bearing derivatives (1b-1d, 1g, 1j and 1m) showed significantly improved UART1 inhibitory activity (sub-micromolar IC50 values) as compared with lesinurad which has the rigid naphthyltriazole skeleton
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Our investigation evaluates the extent of differences in the patient’s hospital experience due to variations among state strategies to adopt, or not adopt, their Medicaid plans to the 2010 ACA legislation. Using ten HCAHPS measur...
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Our investigation evaluates the extent of differences in the patient’s hospital experience due to variations among state strategies to adopt, or not adopt, their Medicaid plans to the 2010 ACA legislation. Using ten HCAHPS measures, we analyze patient hospital experience data for the 2009 - 2013 period for all 50 states and the District of Columbia grouped by those states that (1) did not expand, (2) expanded Medicaid through Section 1115 waivers, (3) expanders early, and (4) expanded Medicaid concurrent with the new ACA legislation.Our findings reveal that those states that opted out of Medicaid expansion typically started with higher patient experience scores in 2009 on all 10 HCAHPS hospital measures and maintained their higher scores levels for all five years over the other three state expansion strategies for most measures. While states that were early expanders and those that expanded concurrent with the ACA implementation generally show higher growth rates over the five-year period for most HCAHPS measures when compared to states that opted out of the Medicaid expansion, our multivariate results indicate that their rates of growth were not statistically superior to those states that opted out of the expansion.We conclude that while there have been concerns that the patients in opt-out states would experience lower levels of satisfaction from their state’s actions, the patient experience scores in these states show that they perform better or as well as those states that expanded early, expanded under waivers, and expanded with the implementation of the ACA legislation.
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Linearizability is an important correctness criterion for implementations of concurrent objects. Automatic checking of linearizability is challenging because it requires checking that: 1) All executions of concurrent operations ar...
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Linearizability is an important correctness criterion for implementations of concurrent objects. Automatic checking of linearizability is challenging because it requires checking that: 1) All executions of concurrent operations are serializable, and 2) the serialized executions are correct with respect to the sequential semantics. In this work, we describe a method to automatically check linearizability based on refinement relations from abstract specifications to concrete implementations. The method does not require that linearization points in the implementations be given, which is often difficult or impossible. However, the method takes advantage of linearization points if they are given. The method is based on refinement checking of finite-state systems specified as concurrent processes with shared variables. To tackle state space explosion, we develop and apply symmetry reduction, dynamic partial order reduction, and a combination of both for refinement checking. We have built the method into the PAT model checker, and used PAT to automatically check a variety of implementations of concurrent objects, including the first algorithm for scalable nonzero indicators. Our system is able to find all known and injected bugs in these implementations.
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Histone deacetylase 6 (HDAC6) has been shown to be involved in various pathological conditions, including cancer, neurodegenerative disorders and inflammatory diseases. Nonetheless, its specific role in drug-induced nephrotoxicity...
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Histone deacetylase 6 (HDAC6) has been shown to be involved in various pathological conditions, including cancer, neurodegenerative disorders and inflammatory diseases. Nonetheless, its specific role in drug-induced nephrotoxicity is poorly understood. Cisplatin (dichlorodiamino platinum) belongs to an inorganic platinum - fundamental chemotherapeutic drug utilized in the therapy of various solid malignant tumors. However, the use of cisplatin is extremely limited by obvious side effects, for instance bone marrow suppression and nephrotoxicity. In the present study, we utilized a murine model of cisplatin-induced acute kidney injury (AKI) and a highly selective inhibitor of HDAC6, tubastatin A (TA), to assess the role of HDAC6 in nephrotoxicity and its associated mechanisms. Cisplatin-induced AKI was accompanied by increased expression and activation of HDAC6; blocking HDAC6 with TA lessened renal dysfunction, attenuated renal pathological changes, reduced expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule 1, and decreased tubular cell apoptosis. In cultured human epithelial cells, TA or HDAC6 siRNA treatment also inhibited cisplatin-induced apoptosis. Mechanistic studies demonstrated that cisplatin treatment induced phosphorylation of AKT and loss of E-cadherin in the nephrotoxic kidney, and administration of TA enhanced AKT phosphorylation and preserved E-cadherin expression. HDAC6 inhibition also potentiated autophagy as evidenced by increased expression of autophagy-related gene (Atg) 7 (Atg7), Beclin-1, and decreased renal oxidative stress as demonstrated by up-regulation of superoxide dismutase (SOD) activity and down-regulation of malondialdehyde levels. Moreover, TAwas effective in inhibiting nuclear factor-?B (NF-築) phosphorylation and suppressing the expression of tumor necrosis factor-?(TNF-? and interleukin-6 (IL-6). Collectively, these data provide strong evidence that HDAC6 inhibition is protective against cisplatin-induced AKI and suggest that HDAC6 may be a potential therapeutic target for AKI treatment.
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