A viscous damping model is proposed based on a simplified equation of fluid motion in a moonpool or the narrow gap formed by two fixed boxes. The model takes into account the damping induced by both ...flow separation and wall friction through two damping coefficients, namely, the local and friction loss coefficients. The local loss coefficient is determined through specifically designed physical model tests in this work, and the friction loss coefficient is estimated through an empirical formula found in the literature. The viscous damping model is implemented in the dynamic free-surface boundary condition in the gap of a modified potential flow model. The modified potential flow model is then applied to simulate the wave-induced fluid responses in a narrow gap formed by two fixed boxes and in a moonpool for which experimental data are available. The modified potential flow model with the proposed viscous damping model works well in capturing both the resonant amplitude and frequency under a wide range of damping conditions.
No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to ...compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM.
From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety.
After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 95% confidence interval (CI) 8.31-19.02 months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms hazard ratio (HR) 1.00; 95% CI 0.65-1.54. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients’ actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%).
Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.
•This is the first study to compare toripalimab versus HDI as adjuvant therapy for resected MM.•In PD-L1-positive patients, the median RFS was ∼6 months longer in the toripalimab arm than in the HDI arm.•The incidence of TEAEs with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm.•Both interventions have potential for MM; toripalimab might be the better treatment option.
We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would ...differ from primary mucosal melanomas at different anatomical sites.
Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites.
The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%,P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%,P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively.
The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.
Blood-circulating microRNAs (miRNAs) have been reported to be used as potential biomarkers in various cancers. MiR-101 has been found to act as a tumor suppressor in many tumor types, but little is ...known for osteosarcoma. The purpose of this study was to investigate miR-101 expression in osteosarcoma patients and assess its correlation with clinical features and prognosis. Serum samples from 152 osteosarcoma patients and 70 healthy controls were detected using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The data showed that miR-101 expression levels were remarkably underexpressed in serum samples from osteosarcoma patients compared to controls, and the post-treatment serum miR-101 expression was significantly higher than that in the pre-treatment expression. Low serum miR-101 expression was positively associated with advanced clinical stage and distant metastasis. Receiver operating characteristic (ROC) curve analysis showed that serum miR-101 could serve as a useful marker for osteosarcoma diagnosis, with a high sensitivity and specificity. Moreover, patients with high miR-101 expression had longer overall survival and recurrence free survival than those with low miR-101 expression. In addition, both univariate and multivariate analyses showed that serum miR-101 downregulation was associated with shorter overall survival and recurrence free survival. Our present results implicated serum miR-101 might be a useful biomarker for the clinical diagnosis and prognosis of osteosarcoma.
Creating oxide interfaces with precise chemical specificity at the atomic layer level is desired for the engineering of quantum phases and electronic applications, but highly challenging, owing ...partially to the lack of in situ tools to monitor the chemical composition and completeness of the surface layer during growth. Here we report the in situ observation of atomic layer-by-layer inner potential variations by analysing the Kikuchi lines during epitaxial growth of strontium titanate, providing a powerful real-time technique to monitor and control the chemical composition during growth. A model combining the effects of mean inner potential and step edge density (roughness) reveals the underlying mechanism of the complex and previously not well-understood reflection high-energy electron diffraction oscillations observed in the shuttered growth of oxide films. General rules are proposed to guide the synthesis of atomically and chemically sharp oxide interfaces, opening up vast opportunities for the exploration of intriguing quantum phenomena at oxide interfaces.
Summary
Background
A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi‐ancestral cohorts, but failed to find ...significant evidence for an association in the Han Chinese population.
Objectives
To explore the association between this locus and SLE using data from our previously published genome‐wide association study (GWAS).
Methods
Single‐nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large‐scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells.
Results
Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls.
Conclusions
This study found evidence for multiple associations with SLE in 5q31.1 at genome‐wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.
What's already known about this topic?
Systemic lupus erythematosus (SLE) is a prototype multisystem autoimmune inflammatory disease involving genetic and environmental predisposing factors.
Genome‐wide association studies have been performed to identify and confirm over 70 risk genes associated with SLE.
What does this study add?
This study confirmed two independent SLE association signals in 5q31.1, with genome‐wide levels of significance for the first time in a Han Chinese population.
Significant and suggestive associations were revealed between clinical manifestations and genetic variants.
Both TCF7 and PPP2CA are within the association interval and are very likely to be involved in the development of SLE.
What is the translational message?
The genetic variant in 5q31.1 contributes to the complex subphenotypes of SLE, which suggests that this variant can be a novel marker for SLE phenotypes.
The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased, which suggests that TCF7 and PPP2CA can be used as an auxiliary method for the diagnosis of SLE.
Linked Comment: Sarin. Br J Dermatol 2017; 177:620–621
This study comparatively examines the dividends behavior in state-controlled firms versus familycontrolled firms. With the sample of large industrial firms listed on the Main Board of Hong Kong Stock ...Exchange, we investigate the dividends payment rates, stability of dividends payment, the effects of firm size, profitability and growth opportunity on likelihood to pay dividends, as well as the concentration of dividend in state-controlled versus family-controlled firms. Based on the findings, we derive some ethical implications of dividends policy regarding the differences in business ethical behavior, corporate social responsibility, corporate governance, business sustainability, and shareholder activism in state-controlled versus family-controlled firms, as well as the improvement in these respects through cross-listing in Hong Kong.
Background
Soluble CD40 ligand (sCD40L) is associated with inflammation. This study aimed to assess the prognostic value of sCD40L for clinical outcomes of acute intracerebral hemorrhage (ICH) ...patients.
Materials and methods
The serum sCD40L levels of 110 patients and 110 age‐ and gender‐matched healthy controls were measured using sandwich immunoassays. The relationships between serum sCD40L levels and 1‐week mortality, 6‐month mortality, 6‐month overall survival, 6‐month unfavorable outcome (modified Rankin Scale score >2), and ICH severity including hematoma volume and National Institutes of Health Stroke Scale (NIHSS) score were assessed using multivariate analysis.
Results
Compared with healthy controls, ICH patients had higher serum sCD40L levels. Serum sCD40L levels were correlated positively with hematoma volumes and NIHSS scores using a multivariate linear regression. Multivariate analysis results indicated that sCD40L was identified an independent predictor of 1‐week mortality, 6‐month mortality, 6‐month unfavorable outcome and 6‐month overall survival. sCD40L also showed high predictive performances for 1‐week mortality, 6‐month mortality and 6‐month unfavorable outcome based on receiver operating characteristic curve.
Conclusions
Elevated serum sCD40L levels are independently associated with ICH severity and clinical outcomes. And sCD40L has potential to be a good prognostic biomarker of ICH.
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