We present an isogeometric thin shell formulation for multi-patches based on rational splines over hierarchical T-meshes (RHT-splines). Nitsche’s method is employed to efficiently couple the patches. ...The RHT-splines have the advantages of allowing a computationally feasible local refinement, are free from linear dependence, possess high-order continuity and satisfy the partition of unity and non-negativity. In addition, the C1 continuity of the RHT-splines avoids the rotational degrees of freedom. The good performance of the present method is demonstrated by a number of numerical examples.
•We present a multi-patch isogeometric large deformation thin shell formulation based on RTH splines. It is an extension of our previous work on RHT-spline shells to large deformations and multiple patches. The coupling is based on Nitsche’s method and allows also coupling of a shell to a solid model.•Furthermore, we present a stress recovery technique to drive the adaptive h-refinement procedure in isogeometric thin structures.•The method is validated for several linear and non-linear benchmark problems including the pinched cylinder and hemispherical shell, a wind turbine rotor accounting for large deformations, a hemispherical shell with a stiffener and a pinched cylinder considering large deformations.
The search continues for nickel oxide-based materials with electronic properties similar to cuprate high-temperature superconductors
. The recent discovery of superconductivity in the doped ...infinite-layer nickelate NdNiO
(refs.
) has strengthened these efforts. Here, we use X-ray spectroscopy and density functional theory to show that the electronic structure of LaNiO
and NdNiO
, while similar to the cuprates, includes significant distinctions. Unlike cuprates, the rare-earth spacer layer in the infinite-layer nickelate supports a weakly interacting three-dimensional 5d metallic state, which hybridizes with a quasi-two-dimensional, strongly correlated state with Formula: see text symmetry in the NiO
layers. Thus, the infinite-layer nickelate can be regarded as a sibling of the rare-earth intermetallics
, which are well known for heavy fermion behaviour, where the NiO
correlated layers play an analogous role to the 4f states in rare-earth heavy fermion compounds. This Kondo- or Anderson-lattice-like 'oxide-intermetallic' replaces the Mott insulator as the reference state from which superconductivity emerges upon doping.
Aims/hypothesis Our recent studies suggest that activation of the wingless-type MMTV integration site (WNT) pathway plays pathogenic roles in diabetic retinopathy and age-related macular ...degeneration. Here we investigated the causative role of oxidative stress in retinal WNT pathway activation in an experimental model of diabetes. Methods Cultured retinal pigment epithelial cells and retinal capillary endothelial cells were treated with a lipid peroxidation product, 4-hydroxynonenal (HNE), and an antioxidant, N-acetyl-cysteine (NAC). In vivo, rats with streptozotocin-induced diabetes were treated by NAC for 8 weeks. Activation of the canonical WNT pathway was measured by TOPFLASH assay and by western blot analysis of WNT pathway components and a WNT target gene, Ctgf. Oxidative stress in the retina was evaluated by immunostaining of HNE and 3-nitrotyrosine. Results Levels of phosphorylated and total LDL receptor-related protein (LRP)6, and cytosolic β-catenin, as well as transcriptional activity of T cell factor (TCF)/β-catenin were significantly increased by HNE. The production of connective tissue growth factor (CTGF) was also upregulated by HNE. NAC blocked the WNT pathway activation induced by HNE. Furthermore, LRP6 stability was increased by HNE and decreased by NAC. Retinal levels of HNE and 3-nitrotyrosine were significantly increased in diabetic rats, compared with those in non-diabetic rats. In the same diabetic rat retinas, levels of LRP6, cytosolic β-catenin and CTGF were significantly increased. NAC treatment reduced HNE and 3-nitrotyrosine levels and attenuated the upregulation of LRP6, β-catenin and CTGF in diabetic rat retina. Conclusions/interpretation Lipid peroxidation products activate the canonical WNT pathway through oxidative stress, which plays an important role in the development of retinal diseases.
The crystal plane of ceria plays an essential role in determining its catalytic oxidation properties. In this study, single-crystalline CeO
2 nanorods with well-defined crystal planes have been ...synthesized by a facile solution-based hydrothermal method. HRTEM studies reveal that the predominantly exposed planes are the unusually reactive {001} and {110} in the CeO
2 nanorods rather than the stable {111} in the irregular nanoparticles. Consequently, it is demonstrated that the CeO
2 nanorods are more reactive for CO oxidation than their counterparts, irregular nanoparticles. The present results indicate that catalysts with well-defined reactive sites may be “designed” because of the recent development of morphology-controlled synthesis of nanostructured materials.
Abstract
We report the X-ray timing results of the black hole candidate MAXI J1820+070 during its 2018 outburst using the Hard X-ray Modulation Telescope (Insight-HXMT) and Neutron Star Interior ...Composition Explorer Mission (NICER) observations. Low-frequency quasi-periodic oscillations (LFQPOs) are detected in the low/hard state and the hard intermediate state, which lasted for ∼90 days. Thanks to the large effective area of Insight-HXMT at high energies and NICER at low energies, we are able to present the energy dependence of the LFQPO characteristics and phase lags from 0.2 to 200 keV, which has never been explored by previous missions. We find that the centroid frequency of the LFQPOs does not change significantly with energy, while the full width at half maximum and fractional rms show a complex evolution with energy. The LFQPO phase lags at high energies and low energies show consistent energy-dependence relations taking the ∼2 keV as reference. Our results suggest that the LFQPOs from high energy come from the LT precession of the relativistic jet, while the low-energy radiation is mainly from the perpendicular innermost regions of the accretion disk.
Purpose
The aim of the study was to evaluate the cost-effectiveness of capecitabine plus bevacizumab compared with capecitabine alone in elderly patients with metastatic colorectal cancer (CRC) from ...a Chinese societal perspective.
Methods
A decision-analytic Markov model was conducted to simulate the process of metastatic CRC. Three distinct health states: progression-free survival (PFS), progressive disease and death were included. Clinical data were derived from the AVEX trial. Health effectiveness was denoted in quality-adjusted life years (QALYs) and health utilities were derived from previously published studies. Incremental cost-effectiveness ratio (ICER) was regarded as the primary endpoint and willingness-to-pay (WTP) threshold was set at $26,753.37/QALY (3 × per capita GDP of China, 2017). One-way sensitivity analyses and probabilistic sensitivity analysis were also performed to explore the parameters uncertainty in the study.
Results
Over a 10-year life horizon, capecitabine plus bevacizumab gained 1.14 QALYs at an average cost of $21,609.48, while the effectiveness and cost of capecitabine group were 0.99 QALYs and $7274.83, respectively. The ICER between the two groups was $95,564.33/QALY. Parameters that mostly influenced the results of the model were utility of PFS state, duration of PFS state for capecitabine plus bevacizumab, total cost of PFS state for capecitabine plus bevacizumab and price of bevacizumab. The probabilities of capecitabine plus bevacizumab and capecitabine as the dominant option were 0% and 100% at the WTP threshold of $26,753.37/QALY.
Conclusions
The results of the study showed that capecitabine plus bevacizumab is unlikely to be a cost-effective treatment option for elderly patients with metastatic CRC.
•Scratch injury, starvation and LPS stimulation induce reactive astrogliosis.•Ski expression is up-regulated during the activation of astrocytes.•Knockdown of Ski by siRNA decreases astrocytes’ ...proliferation and migration.
Ski, as an evolutionarily conserved protein, is a versatile transcriptional regulator which widely distributes in various tissues and species. Recently, we have demonstrated for the first time that Ski was strikingly up-regulated in reactive astrocytes after spinal cord injury (SCI) in vivo, which indicates that maybe Ski is a new molecule that controls astrocytes’ biological properties after SCI. However, the accurate distributions and functions of Ski in astrocytes after central nervous system (CNS) injury are still unclear. Astrocytes were collected from rats’ cerebral cortex. To elucidate the expression and role of Ski in reactive astrocytes, we performed an activated astrocytes model induced by LPS and scratch injury in vitro. Our results showed that Ski gradually increased and reached a peak at 4days, then declined at 6days after induction by LPS. Up-regulation of Ski was accompanied with the increase in proliferation-related proteins including PCNA, CDK4 and CyclinD1. Furthermore, immunofluorescent staining analysis also demonstrated a highly positive relationship between Ski and GFAP, PCNA in astrocytes. These results indicated that Ski might play an important role in astrocyte proliferation. To further explore the role of Ski, astrocytes were transfected with Ski-specific small interfering RNA (siRNA). We found that the primary activated astrocytes’ proliferation decreased significantly after transfection with Ski-specific siRNA. Surprisingly, Ski knockdown also weakened the primary astrocyte migration. Based on the above, we could conclude that Ski might play a crucial role in astrocyte proliferation and migration. This discovery might contribute to a promising therapeutic intervention in CNS injury.
To uncover the clinical course of fetal isolated non-immune mediated second-degree AVB and determine the factors associated with the spontaneous recovery for fetal non-immune second-degree ...atrioventricular block (AVB).
A total of 20 fetuses with isolated, non-immune mediated second-degree AVB were prospectively recruited between 2014 and 2022. These fetuses were divided into the spontaneous recovery group (n=12) and the non-spontaneous recovery group (n=8). Maternal and fetal basic characteristics, intrauterine and postnatal outcomes were compared between groups.
Twelve fetuses restored 1:1 atrioventricular conduction in utero and did not recur during the postnatal follow-up period. The residual eight fetuses maintained as second-degree AVB and six of them were aborted due to parental request in utero. Of the two live children with second-degree AVB, one of them progressed to complete AVB at the latest follow up at the age of 34 months, but without any symptoms, heart enlargement or dysfunction. The residual one progressed to complete AVB and was finally diagnosed with type 2 long-QT syndrome. Fetuses in the spontaneous recovery group presented with earlier gestational age at diagnosis (20.017.0-26.0 vs. 24.518.0-35.0 weeks, p=0.004) and higher atrial rate (147130-160 vs 138.00125.00-149.00 bpm, p=0.006) in comparison with the non-spontaneous recovery group. A cut-off value of 22.5 weeks of gestational age and 144 bpm of atrial rate at diagnosis could predict the failure of spontaneous recovery, with sensitivities of 87.5%, 75%, and specificities of 92.0%, 87.5%, respectively.
The outcome of fetal non-immune second-degree AVB was favorable. Earlier gestational age at diagnosis and higher atrial rate were related to spontaneous reversion for isolated non-immune-mediated second-degree AVB. However, prenatal gene test should be performed for those with persistent AVB to exclude the heritable disorders including LQTS. These findings may provide important references for clinical management and prenatal counseling. This article is protected by copyright. All rights reserved.
Summary
Background
Carbon dioxide (CO2) insufflation has been proposed as an alternative to air insufflation to distend the lumen in gastrointestinal (GI) endoscopy.
Aim
To perform a systematic ...review with meta‐analysis of randomised controlled trials (RCTs) in which CO2 insufflation was compared with room air insufflation in GI endoscopy.
Methods
Electronic and manual searches were combined to search RCTs. After methodological quality assessment and data extraction, the efficacy and safety of CO2 insufflation were systematically assessed.
Results
Twenty‐one RCTs 13 on colonoscopy, four on endoscopic retrograde cholangiopancreatography (ERCP), two on double‐balloon enteroscopy (DBE), one on oesophagogastroduodenoscopy, and one on flexible sigmoidoscopy were identified. For colonoscopy, CO2 insufflation resulted lower postprocedural pain intensity, and increased the proportion of patient without pain at 1 h (RR: 1.84, 95% CI: 1.37–2.47) and 6 h (RR: 1.28; 95% CI: 1.14–1.44) postprocedure. For ERCP, the pain‐releasing effect of CO2 insufflation was not obvious (SMD: −1.48, 95% CI: −3.56, 0.59). CO2 insufflation revealed no consistent advantages in the RCTs of DBE, but was shown as safe as air insufflation in oesophagus/stomach endoscopic submucosal dissection in one study. pCO2 level showed no significant variation during these procedures.
Conclusions
Compared with air insufflation, CO2 insufflation during colonoscopy causes lower postprocedural pain and bowel distension without significant pCO2 variation. More RCTs are needed to assess its advantages in other GI endoscopic procedures.
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