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Gamified learning is an instructional strategy that motivates students to learn, and the use of multiple representations assists learning by promoting students' thinking and advanced mathematical problem-solving skills. In particular, emergency distance learning caused by the COVID-19 pandemic may result in a lack of motivation and effectiveness in learning. This study designed an online gamified learning activity incorporating multi-representational scaffolding and compared the differences in the learning achievement and motivation for the gamified activity and general synchronous distance learning. In addition, for the group that conducted the gamified learning activity, we measured the participants' flow, anxiety, and emotion during the activity. A total of 36 high school students participated in the experiment. The results indicated that the gamified learning activity was not significantly effective in terms of enhancing learning achievement. In terms of learning motivation, a significant decrease in motivation was found for the group using general synchronous learning, while a significant increase in motivation was found for the group using synchronous gamified learning. This indicates that despite the negative impact of the pandemic on learning, gamified learning still enhances students' learning motivation. The results of flow, anxiety, and emotion showed that the participants had a positive and engaged experience. Participants provided feedback that the multi-representational scaffolding facilitates learning.
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The orange-spotted grouper (Epinephelus coioides) is an important marine farmed fish in China. It is affected by the bacterial pathogen Vibrio alginolyticus, which causes high mortality and substantial economic losses. We studied the transcriptional changes of the IgZ gene in E. coioides following V. alginolyticus stimulation and investigated the distribution of IgZ in different tissues. The highest expression level of IgZ occurred in the head kidney. When fish were stimulated with live and inactivated V. alginolyticus, the expression levels of IgZ in the head kidney, spleen, intestine, gills and blood cells were significantly upregulated. In an in situ hybridization study, IgZ mRNA-positive cells were detected in the head kidney, spleen and gill, but positive signals were not detected in the liver and intestine. IgZ-labelled cells increased in the head kidney, spleen and gills post-infection with V. alginolyticus for 21 days. The present study provides additional evidence that IgZ is involved in mucosal immune responses and helps explain the role of IgZ in E. coioides defence against V. alginolyticus infection.
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Bass , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Perfilação da Expressão Gênica/veterinária , Vacinação/veterinária , Vibrioses/veterinária , Vibrio alginolyticus/fisiologia , Animais , Vacinas Bacterianas/administração & dosagem , Vacinas Bacterianas/imunologia , Doenças dos Peixes/microbiologia , Proteínas de Peixes/metabolismo , Cadeias Pesadas de Imunoglobulinas/genética , Cadeias Pesadas de Imunoglobulinas/metabolismo , Distribuição Aleatória , Vibrioses/imunologia , Vibrioses/microbiologiaRESUMO
Laser ablation in liquid has proven to be a universal and green method to synthesize nanocrystals and fabricate functional nanostructures. This study demonstrates the superiority of femtosecond laser-mediated plasma in enhancing photoredox of metal cations for controllable fabrication of plasmonic nanostructures in liquid. Through employing upstream high energetic plasma during laser-induced microexplosions, single/three-electron photoreduction of metallic cations can readily occur without chemical reductants or capping agents. Experimental evidences demonstrate that this process exhibits higher photon utilization efficiency in yield of colloidal metal nanoparticles than direct irradiation of metallic precursors. Photogenerated hydrated electrons derived from strong ionization of silicon and water are responsible for this enhanced consequences. Furthermore, these metallic nanoparticles are accessible to self-assemble into nanoplates for silver and nanospheres for gold, favored by surface-tension gradients between laser irradiated and unirradiated regions. These metallic nanostructures exhibit excellent surface-enhanced Raman spectroscopy performance in trace detection of Rhodamine 6G (R6G), 4-mercaptobenzoic acid (4-MBA), and mercapto-5-nitrobenzimidazole molecules with high sensitivity (down to 10-12 mol L-1 , 30 × 10-15 m for R6G), good reproducibility (relative standard deviation < 7%), and good dual-analyte detection ability with mixture ratios of R6G to 4-MBA ranging from 20 to 0.025. The conceptual importance of this plasma-enhanced-photochemical process may provide exciting opportunities in photochemical reactions, plasmofluidics, and material synthesis.
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PURPOSE: The risk of anemia due to bevacizumab-based chemotherapy has not been well described, and new randomized controlled trials (RCTs) have been reported in recent years. We therefore conducted an up-to-date meta-analysis of RCTs to fully characterize the risk of anemia with bevacizumab. METHODS: We carried out an electronic search of Medline, Embase, and The Cochrane Central Register of Controlled Trials to investigate the effects of RCTs on bevacizumab treatment on cancer patients up to October 2014, and random or fixed-effect meta-analytical models were used to assess the risk ratio (RR) of anemia due to the use of bevacizumab according to the heterogeneity of included studies. RESULTS: A total of 13,173 patients were included in this analysis from 18 RCTs. Among those patients receiving bevacizumab and chemotherapy, the incidences of all-grade and high-grade (grade 3 and above) anemia were 24% (95% confidence interval (CI) 13-41%) and 4.0% (95% CI 3.0-6.0%), respectively. Bevacizumab-containing therapy did not significantly decreased the risk of developing all-grade anemia (RR 0.872, 95% CI 0.739-1.029, P = 0.104) and high-grade anemia (RR 0.850, 95% CI 0.720-1.002, P = 0.053), which is not in agreement with previous meta-analysis. On subgroup analysis, we did not find significant risk differences based on bevacizumab dosage, tumor types, and concomitant drugs. When stratified by dose level, a significantly decreased risk of high-grade anemia with bevacizumab was obtained in a lower dose level (2.5 mg/kg/week, RR 0.773, 95% CI 0.611-0.978, P = 0.031) compared to control group. CONCLUSIONS: Bevacizumab did not significantly reduce the risk of anemia with chemotherapy in cancer patients.
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Anemia/epidemiologia , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Anemia/etiologia , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Humanos , Incidência , Neoplasias/tratamento farmacológico , RiscoRESUMO
In the technical route for the synthesis of avanafil, 1-ethyl-(3-dimethylaminopropyl)carbamyldiimide hydrochloride (EDCI) and 1-hydroxybenzotriazole (HOBT) are used as reactive acid-amine binding agents. HOBT contains trace amounts of hydrazine residue, and there is a risk of introducing potentially mutagenic impurities with hydrazide-containing structures. The potentially genotoxic impurities E (Imp-E) and F (Imp-F) of avanafil with altering hydrazide-structure were synthesized by chemical method; subsequently, the impurities were evaluated and classified according to ICH M7 guidelines. Two complementary quantitative structure-activity relationship (QSAR) evaluation systems (Derek and Sarah) based on expert rules and statistics were used to preliminarily predict the genotoxicity of Imp-E and Imp-F, and the prediction result of E was suspected to be positive. In the Ames test of Imp-E and Imp-F, in the dose range of 62.5-1000 µg per plate, with or without the presence of metabolic activation system S9, the number of revertant colonies did not exceed 2 times the number of colonies in the solvent control group and did not show a dose-response relationship, and the test results were negative. Imp-E and Imp-F were determined to be negative for genotoxicity, which could be controlled as class 5 in ICH M7, that is, non mutagenic impurity.
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Property-structure reconfigurable nanoparticles (NPs) provide additional flexibility for effectively and flexibly manipulating light at the nanoscale. This has facilitated the development of various multifunctional and high-performance nanophotonic devices. Resonant NPs based on dielectric active materials, especially phase change materials, are particularly promising for achieving reconfigurability. However, the on-demand control of the properties, especially the morphology, in individual dielectric resonant NP remains a significant challenge. In this study, we present an all-optical approach for one-step fabrication of Ge2Sb2Te5 (GST) hemispherical NPs, integrated active reversible phase-state switching, and morphology reshaping. Reversible optical switching is demonstrated, attributed to reversible phase-state changes, along with unidirectional modifications to their scattering intensity resulting from morphology reshaping. This novel technology allows the precise adjustment of each structural pixel without affecting the overall functionality of the switchable nanophotonic device. It is highly suitable for applications in single-pixel-addressable active optical devices, structural color displays, and information storage, among others.
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Carbon fiber reinforced polymer (CFRP), a highly engineered lightweight material with superior properties, is widely used in industrial fields, such as aerospace, automobile, and railway transportation, as well as medical implants and supercapacitor. This work presents an effective surface treatment method for the controllable fabrication of hydrophilic surface micro/nanostructures of CFRP through femtosecond laser processing. Selective removal of the epoxy resin and leaving the carbon fibers exposed are achieved when CFRP is weakly ablated by a femtosecond laser. The diameters and structures of the carbon fibers can be controlled by adjusting the laser processing parameters. Three-dimensional surface micro/nanostructures are processed when CFRP is strongly ablated by a femtosecond laser. Meanwhile, the transformation of the sp2 orbitals to sp3 orbitals of graphitic carbons of carbon fibers is induced by a femtosecond laser. Moreover, the investigation of surface roughness and wettability of femtosecond laser-processed CFRP indicates increased roughness and excellent hydrophilicity (a contact angle of 28.1°). This work reveals the effect of femtosecond laser processing on the regulation of the physicochemical properties of CFRP, which can be applicable to surface treatment and performance control of other fiber-resin composites. The excellent hydrophilicity will be conducive to the combination of CFRP with other materials or to reducing the friction resistance of CFRP used in medical implants.
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Ultra-thin 2D materials have great potential as electrodes for micro-supercapacitors (MSCs) because of their facile ion transport channels. Here, a high-precision controllable photonic-synthesis strategy that provided 1 inch wafer-scale ultra-thin film arrays of alloyed WxMo2xSy with sulfur vacancies and expanded interlayer (13.2 Å, twice of 2H MoS2) is reported. This strategy regulates the nucleation and growth of transition metal dichalcogenides (TMDs) on the picosecond or even femtosecond scale, which induces Mo-W alloying, interlayer expansion, and sulfur loss. Therefore, the diffusion barrier of WxMo2xSy is reduced, with charge transfer and ion diffusion enhancing. The as-prepared symmetric MSCs with the size of 100 × 100 µm2 achieve ultrahigh specific capacitance (242.57 mF cm-2 and 242567.83 F cm-3), and energy density (21.56 Wh cm-3 with power density of 485.13 W cm3). The established synthesis strategy fits numerous materials, which provides a universal method for the flexible synthesis of electrodes in microenergy devices.
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Laser transmission welding (LTW) is an excellent process for joining plastics and is widely used in industry. Numerical simulation is an important method and area for studying LTW. It can effectively shorten the experimental time and reduce research costs, aid in understanding the welding mechanism, and enable the acquisition of ideal process parameters. To enhance understanding of numerical simulation studies on LTW and facilitate research in this area, this paper presents a comprehensive overview of the progress made in numerical simulation of LTW, covering the following aspects: (a) characteristics of the three heat source models for LTW temperature field simulation, including surface heat source model, volumetric heat source model, and hybrid heat source model, along with the methods, results, and applications of temperature field simulation based on these models and experimental validation; (b) numerical simulation of thermal and residual stresses based on the temperature field; (c) numerical simulation of the melt flow field; and (d) predictive simulation of material degradation. The conclusion of the review and the prospects for further research work are eventually addressed.
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Over the past several years, resonance energy transfer involving noble metallic nanoparticles has received considerable attention. The aim of this review is to cover advances in resonance energy transfer, widely exploited in biological structures and dynamics. Due to the presence of surface plasmons, strong surface plasmon resonance absorption and local electric field enhancement are generated near noble metallic nanoparticles, and the resulting energy transfer shows potential applications in microlasers, quantum information storage devices and micro-/nanoprocessing. In this review, we present the basic principle of the characteristics of noble metallic nanoparticles, as well as the representative progress in resonance energy transfer involving noble metallic nanoparticles, such as fluorescence resonance energy transfer, nanometal surface energy transfer, plasmon-induced resonance energy transfer, metal-enhanced fluorescence, surface-enhanced Raman scattering and cascade energy transfer. We end this review with an outlook on the development and applications of the transfer process. This will offer theoretical guidance for further optical methods in distance distribution analysis and microscopic detection.
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In recent years, metallic nanoparticle (NP)-two-dimensional material hybrids have been widely used for photocatalysis and photoreduction. Here, we introduce a femtosecond laser reduction approach that relies on the repetitive ablation of recast layers by usi-ng temporally shaped pulses to achieve the fast fabrication of metallic NP-two-dimensional material hybrids. We selectively deposited silver-reduced graphene oxide (Ag-rGO) hybrids on different substrates under various fabrication conditions. The deposition of the hybrids was attributed to the redistribution of the cooling ejected plume after multiple radiation pulses and the exchange of carriers with ejected plume ions containing activated species such as small carbon clusters and H2O. The proposed one-step in situ fabrication method is a competitive fabrication process that eliminates the additive separation process and exhibits morphological controllability. The Ag-rGO hybrids demonstrate considerable potential for chemomolecular and biomolecular detection because the surface-enhanced Raman scattering signal of the enhancement factor reached 4.04 × 108.
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Ultratransparent electrodes have attracted considerable attention in optoelectronics and energy technology. However, balancing energy storage capability and transparency remains challenging. Herein, an in situ strategy employing a temporally and spatially shaped femtosecond laser is reported for photochemically synthesizing of MXene quantum dots (MQDs) uniformly attached to laser reduced graphene oxide (LRGO) with exceptional electrochemical capacitance and ultrahigh transparency. The mechanism and plasma dynamics of the synthesis process are analyzed and observed at the same time. The unique MQDs loaded on LRGO greatly improve the specific surface area of the electrode due to the nanoscale size and additional edge states. The MQD/LRGO supercapacitor has high flexibility and durability, ultrahigh energy density (2.04 × 10-3 mWh cm-2 ), long cycle life (97.6% after 12 000 cycles), and excellent capacitance (10.42 mF cm-2 ) with both high transparency (transmittance over 90%) and high performance. Furthermore, this method provides a means of preparing nanostructured composite electrode materials and exploiting quantum capacitance effects for energy storage.
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TiO2 is popular in photocatalytic degradation dye pollutants due to its abundance and its stability under photochemical conditions. Au loaded TiO2 can achieve efficient absorption of visible light and deal with the problem of low conversion efficiency for solar energy of TiO2. This work presents a new strategy to prepare Au nanoparticles-loaded TiO2 composites through electric-field-assisted temporally-shaped femtosecond laser liquid-phase ablation of Au3+ and amorphous TiO2. By adjusting the laser pulse delay and electric field parameters, gold nanoparticles with different structures can be obtained, such as nanospheres, nanoclusters, and nanostars (AuNSs). AuNSs can promote the local crystallization of amorphous TiO2 in the preparation process and higher free electron density can also be excited to work together with the mixed crystalline phase, hindering the recombination between carriers and holes to achieve efficient photocatalytic degradation. The methylene blue can be effectively degraded by 86% within 30 min, and much higher than the 10% of Au nanoparticles loaded amorphous TiO2. Moreover, the present study reveals the crystallization process and control methods for preparing nanoparticles by laser liquid ablation, providing a green and effective new method for the preparation of high-efficiency photocatalytic materials.
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Ubiquitous biological processes exhibit the ability to achieve spontaneous directionally guided droplet transport. Maskless three-dimensional (3D) fabrication of various miniature bionic structures, a method applicable to various materials, is subject to processing method limitations. This remains a large obstacle to realizing self-driven, continuous, and controllable unidirectional liquid spreading. Thus, we present a flexible maskless 3D method for fabricating bionic unidirectional liquid spreading surfaces by using a phase spatially shaped femtosecond laser. The laser can be transformed from having Gaussian distributions to having 3D bionic structure field distributions. Furthermore, we fabricated Syntrichia caninervis bionic structures with a spiculate end for unidirectional water spreading; 1 µL droplets had a 16 mm flow length on Si surfaces when the S. caninervis single structure was 34 (length), 8 (width), and 12 µm (height). Furthermore, various bionic structures-Nepenthes, cactus, and moth structures-were fabricated on Si, SiO2, and Ti. We also demonstrated the measurability of two-dimensional (S-shaped) curved flows on Si wafers as well as 3D curved flows on a Ti pipe turning 120° within 2320 ms. Our method can realize high-efficiency maskless 3D processing of various materials and structures (especially asymmetric structures); it is both flexible and fast, effectively expanding the processing capacity of micro-/nanostructures on patterned surfaces. This is of great significance to various domains such as microfluids, fog collection, and chemical reaction control.
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Materiais Biomiméticos/química , Nanoestruturas/química , Dióxido de Silício/química , Silício/química , Titânio/química , Anisotropia , Biônica , Briófitas/química , Lasers , Microfluídica , Nanoestruturas/ultraestrutura , Propriedades de Superfície , Água/químicaRESUMO
Previous research has demonstrated that trait self-control is related to a range of positive romantic relationship processes, suggesting that trait self-control should be positively and robustly linked to relationship satisfaction in both partners in a romantic relationship. However, the existing empirical evidence is limited and mixed, especially regarding partner effects (i.e., the effect of one's self-control on the partner's relationship satisfaction). With three datasets of heterosexual couples (S1: N = 195 newlyweds, longitudinal; S2: N = 249 couples who transition into first parenthood, longitudinal; S3: N = 929 couples, cross-sectional), the present pre-registered studies examined: (1) the dyadic associations between trait self-control and relationship satisfaction both cross-sectionally and longitudinally, and (2) whether these effects hold when controlling for both partners' relationship commitment. The results indicated a cross-sectional positive actor effect, some support for a positive cross-sectional partner effect, and only little support for a longitudinal actor (but not partner) effect. After controlling for relationship commitment, all effects of trait self-control on satisfaction diminished except for a longitudinal actor effect among women in Study 2. Potential explanations for the current results, and implications for theory and practice, are discussed.
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Blood-contacting medical devices that directly inhibit thrombosis and bacterial infection without using dangerous anticoagulant and antibacterial drugs can save countless lives but have proved extremely challenging. Here, a useful methodology is proposed that employs temporally shaped femtosecond laser ablation combined with fluorination to fabricate multifunctional three-dimensional (3D) micro-nanostructures with excellent hemocompatibility, zero cytotoxicity, outstanding biocompatibility, bacterial infection prevention, and long-term effectiveness on NiTi alloys. These multifunctional 3D micro-nanostructures present 0.1% hemolysis ratio and almost no platelet adhesion and activation, repel blood to inhibit blood coagulation in vitro, maintain 100% cell viability, and have exceptional stability over 6 months. Moreover, the multifunctional 3D micro-nanostructures simultaneously suppress bacterial colonization to form biofilm and kill 100% colonized Pseudomonas aeruginosa (P. aeruginosa) and 95.6% colonized Staphylococcus aureus (S. aureus) after 24 h of incubation, and bacterial residues can be easily removed. The fabrication method in this work has the advantages of simple processing, high efficiency, high quality, and high repeatability, and the new multifunctional 3D micro-nanostructures can effectively prevent thrombosis and bacterial infection, which can be widely applied to various clinical needs such as biomedical devices and implants.
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Ligas/química , Materiais Biocompatíveis/química , Lasers , Nanoestruturas/química , Animais , Aderência Bacteriana/efeitos dos fármacos , Infecções Bacterianas/prevenção & controle , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Biofilmes/efeitos dos fármacos , Coagulação Sanguínea/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana , Humanos , Níquel/química , Agregação Plaquetária/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Coelhos , Staphylococcus aureus/fisiologia , Trombose/tratamento farmacológico , Titânio/químicaRESUMO
Micro-supercapacitors are promising miniaturized energy storage devices that have attracted considerable research interest. However, their widespread use is limited by inefficient microfabrication technologies and their low energy density. Here, a flexible, designable micro-supercapacitor can be fabricated by a single pulse laser photonic-reduction stamping. A thousand spatially shaped laser pulses can be generated in one second, and over 30,000 micro-supercapacitors are produced within 10 minutes. The micro-supercapacitor and narrow gaps were dozens of microns and 500 nm, respectively. With the unique three-dimensional structure of laser-induced graphene based electrode, a single micro-supercapacitor exhibits an ultra-high energy density (0.23 Wh cm-3), an ultra-small time constant (0.01 ms), outstanding specific capacitance (128 mF cm-2 and 426.7 F cm-3) and a long-term cyclability. The unique technique is desirable for a broad range of applications, which surmounts current limitations of high-throughput fabrication and low energy density of micro-supercapacitors.
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Molybdenum disulfide (MoS2) micro/nanostructures are desirable for tuning electronic properties, developing required functionality, and improving the existing performance of multilayer MoS2 devices. This work presents a useful method to flexibly microprocess multilayer MoS2 flakes through femtosecond laser pulse direct writing, which can directly fabricate regular MoS2 nanoribbon arrays with ribbon widths of 179, 152, 116, 98, and 77 nm, and arbitrarily pattern MoS2 flakes to form micro/nanostructures such as single nanoribbon, labyrinth array, and cross structure. This method is mask-free and simple and has high flexibility, strong controllability, and high precision. Moreover, numerous oxygen molecules are chemically and physically adsorbed on laser-processed MoS2, attributed to roughness defect sites and edges of micro/nanostructures that contain numerous unsaturated edge sites and highly active centers. In addition, electrical tests of the field-effect transistor fabricated from the prepared MoS2 nanoribbon arrays reveal new interesting features: output and transfer characteristics exhibit a strong rectification (not going through zero and bipolar conduction) of drain-source current, which is supposedly attributed to the parallel structures with many edge defects and p-type chemical doping of oxygen molecules on MoS2 nanoribbon arrays. This work demonstrates the ability of femtosecond laser pulses to directly induce micro/nanostructures, property changes, and new device properties of two-dimensional materials, which may enable new applications in electronic devices based on MoS2 such as logic circuits, complementary circuits, chemical sensors, and p-n diodes.
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Defect/active site control is crucial for tuning the chemical, optical, and electronic properties of MoS2, which can adjust the performance of MoS2 in application areas such as electronics, optics, catalysis, and molecular sensing. This study presents an effective method of inducing defect/active sites, including micro/nanofractured structures and S atomic vacancies, on monolayer MoS2 flakes by using femtosecond laser pulses, through which physical-chemical adsorption and charge transfer between foreign molecules (O2 or R6G molecules) and MoS2 are enhanced. The enhanced charge transfer between foreign molecules (O2 or R6G) and femtosecond laser-treated MoS2 can enhance the electronic doping effect between them, hence resulting in a photoluminescence photon energy shift (reaching 0.05 eV) of MoS2 and Raman enhancement (reaching 6.4 times) on MoS2 flakes for R6G molecule detection. Finally, photoluminescence control and micropatterns on MoS2 and surface-enhanced-Raman-scattering (SERS) enhancement of MoS2 for organic molecule detection are achieved. The proposed method, which can control the photoluminescence properties and arbitrary micropatterns on MoS2 and enhance its chemicobiological sensing performance for organic/biological molecules, has advantages of simplicity, maskless processing, strong controllability, high precision, and high flexibility, highlighting the superior ability of femtosecond laser pulses to achieve the property control and functionalization of two-dimensional materials.
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BACKGROUND: Evolocumab (AMG 145), a PCSK9 inhibitor, has been shown to decrease low-density lipoprotein cholesterol (LDL-C) levels. Doses of 140mg administered every 2weeks (Q2W) and 420mg administered every 4weeks (Q4W) are widely used, and both dosing schedules were effective in clinical trials. However, some researchers have speculated that 140mg Q2W administration has equal or even greater efficacy. This meta-analysis was performed to assess the differences in efficacy and safety between the two doses. METHODS: We searched the PubMed, EMBASE, and Web of Science databases to identify relevant clinical trials published before January 2016. A total of 2403 patients from 8 randomized controlled trials were identified and included in the analysis. RESULTS: Evolocumab administered at 140mg Q2W resulted in a greater percent change from baseline in LDL-C concentration (-7.27; 95% confidence interval (CI), -10.36 to -4.18) and had greater efficacy in achieving the treatment goal of LDL-C ≤1.8mmol/L with an relative risk (RR) of 1.09 (95% CI, 1.00 to 1.18) compared with 420mg Q4W in patients who were concomitantly treated with statins. These findings were not significantly different between the 140mg Q2W and 420mg Q4W groups when evolocumab was administered as monotherapy. There was no difference in the rate of occurrence of the main treatment-related adverse events between the two doses. CONCLUSIONS: Evolocumab administered at 140mg Q2W was more effective than the 420mg Q4W dosage at lowering lipid concentrations, especially in patients who concomitantly received stable statin therapy.