Clopidogrel Plus Aspirin vs Aspirin Alone in Patients With Acute Mild to Moderate Stroke: The ATAMIS Randomized Clinical Trial.

Importance: Dual antiplatelet therapy has been demonstrated to be superior to single antiplatelet in reducing recurrent stroke among patients with transient ischemic attack or minor stroke, but robust evidence for its effect in patients with mild to moderate ischemic stroke is lacking. Objective: To evaluate whether dual antiplatelet therapy is superior to single antiplatelet among patients with mild to moderate ischemic stroke. Design, Setting, and Participants: This was a multicenter, open-label, blinded end point, randomized clinical trial conducted at 66 hospitals in China from December 20, 2016, through August 9, 2022. The date of final follow-up was October 30, 2022. The analysis was reported on March 12, 2023. Of 3065 patients with ischemic stroke, 3000 patients with acute mild to moderate stroke within 48 hours of symptom onset were enrolled, after excluding 65 patients who did not meet eligibility criteria or had no randomization outcome. Interventions: Within 48 hours after symptom onset, patients were randomly assigned to receive clopidogrel plus aspirin (n = 1541) or aspirin alone (n = 1459) in a 1:1 ratio. Main Outcomes and Measures: The primary end point was early neurologic deterioration at 7 days, defined as an increase of 2 or more points in National Institutes of Health Stroke Scale (NIHSS) score, but not as a result of cerebral hemorrhage, compared with baseline. The superiority of clopidogrel plus aspirin to aspirin alone was assessed based on a modified intention-to-treat population, which included all randomized participants with at least 1 efficacy evaluation regardless of treatment allocation. Bleeding events were safety end points. Results: Of the 3000 randomized patients, 1942 (64.6%) were men, the mean (SD) age was 65.9 (10.6) years, median (IQR) NIHSS score at admission was 5 (4-6), and 1830 (61.0%) had a stroke of undetermined cause. A total of 2915 patients were included in the modified intention-to-treat analysis. Early neurologic deterioration occurred in 72 of 1502 (4.8%) in the dual antiplatelet therapy group vs 95 of 1413 (6.7%) in the aspirin alone group (risk difference -1.9%; 95% CI, -3.6 to -0.2; P = .03). Similar bleeding events were found between 2 groups. Conclusions and Relevance: Among Chinese patients with acute mild to moderate ischemic stroke, clopidogrel plus aspirin was superior to aspirin alone with regard to reducing early neurologic deterioration at 7 days with similar safety profile. These findings indicate that dual antiplatelet therapy may be a superior choice to aspirin alone in treating patients with acute mild to moderate stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT02869009.

A Magnetic Field Canceling System Design for Diminishing Electromagnetic Interference to Avoid Environmental Hazard.

Electromagnetic interference is a serious and increasing form of environmental pollution, creating many issues in the areas of health care and industrial manufacturing. The performance of high-precision measurement equipment used in health care and the manufacturing industry is sensitive to electromagnetic interference. However, extremely low-frequency magnetic fields (ELFMF), with a frequency range from 3 to 30 Hz, generated by high-power lines have become the main interference source in high-tech foundries. This paper presents a magnetic cancelling system that works by combining active cancelling technology and passive cancelling technology to reduce the ELFMF around high-precision measurement equipment. The simulation and experimental results show the validity and feasibility of the proposed system.

Breakdown Behavior of Metal Contact Positions in GaN HEMT with Nitrogen-Implanted Gate Using TCAD Simulation.

In this study, the breakdown behavior of a calibrated depletion mode AlGaN/GaN transistor with a nitrogen-implanted gate region was simulated and analyzed using Sentaurus TCAD simulation, with particular emphasis on the metal contact design rule for a GaN-based high-electron-mobility transistor (HEMT) device with a variety of 2DEG concentrations grown on a silicon substrate. The breakdown behaviors for different source/drain contact schemes were investigated using Sentaurus simulation. The metal contact positions within the source and drain exhibited different piezoelectric effects and induced additional polarization charges for the 2DEG (two-dimensional electron gas). Due to the variation of source/drain contact schemes, electron density has changed the way to increase the electric field distribution, which in turn increased the breakdown voltage. The electric field distribution and 2DEG profiles were simulated to demonstrate that the piezoelectric effects at different metal contact positions considerably influence the breakdown voltage at different distances between drain metal contacts. When the contact position was far away from the AlGaN/GaN, the breakdown voltage of the nitrogen-implanted gated device decreased by 41% because of the relatively low electron density and weak induced piezoelectric effect. This reduction is significant for a 20 µm source-drain length. The minimum critical field used for the breakdown simulation was 4 MV/cm. The simulated AlGaN/GaN device exhibits different breakdown behaviors at different metal contact positions in the drain.

A Novel Nitrogen Ion Implantation Technique for Turning Thin Film "Normally On" AlGaN/GaN Transistor into "Normally Off" Using TCAD Simulation.

This study presents an innovative, low-cost, mass-manufacturable ion implantation technique for converting thin film normally on AlGaN/GaN devices into normally off ones. Through TCAD (Technology Computer-Aided Design) simulations, we converted a calibrated normally on transistor into a normally off AlGaN/GaN transistor grown on a silicon <111> substrate using a nitrogen ion implantation energy of 300 keV, which shifted the bandgap from below to above the Fermi level. In addition, the threshold voltage (Vth) was adjusted by altering the nitrogen ion implantation dose. The normally off AlGaN/GaN device exhibited a breakdown voltage of 127.4 V at room temperature because of impact ionization, which showed a positive temperature coefficient of 3 × 10-3 K-1. In this study, the normally off AlGaN/GaN device exhibited an average drain current gain of 45.3%, which was confirmed through an analysis of transfer characteristics by changing the gate-to-source ramping. Accordingly, the proposed technique enabled the successful simulation of a 100-µm-wide device that can generate a saturation drain current of 1.4 A/mm at a gate-to-source voltage of 4 V, with a mobility of 1487 cm2V-1s-1. The advantages of the proposed technique are summarized herein in terms of processing and performance.

Simulation of Onset of the Capillary Surface Wave in the Ultrasonic Atomizer.

The novel drug delivery system refers to the formulations and technologies for transporting a pharmaceutical compound in the body as it is needed to safely achieve its desired therapeutic effects. In this study, the onset vibrational amplitude of capillary surface waves for ultrasonic atomization spray is explained based on Faraday instability. Using ultrasonic frequency, the vibrational amplitude approached a critical point, and the liquid surface broke up into tiny drops. The micro-droplets were are steadily and continuously formed after the liquid feeding rate was optimized. The simulation study reported a minimum vibrational amplitude or onset value of 0.38 µm at 500 kHz frequency. The required minimum energy to atomize the drops was simulated by COMSOL Multiphysics simulation software. The simulation result agreed well with the numerical results of a subharmonic vibrational model that ocurred at 250 kHz frequency on the liquid surface. This newly designed single frequency ultrasonic atomizer showed its true physical characteristic of resonance on the fluid surface plane. Hence, this research will contribute to the future development of a single-frequency ultrasonic nebulizer and mechatronics for the generation of uniform atomized droplets.

Physics-Based TCAD Simulation and Calibration of 600 V GaN/AlGaN/GaN Device Characteristics and Analysis of Interface Traps.

This study proposes an analysis of the physics-based TCAD (Technology Computer-Aided Design) simulation procedure for GaN/AlGaN/GaN HEMT (High Electron Mobility Transistor) device structures grown on Si (111) substrate which is calibrated against measurement data. The presence of traps and activation energies in the device structure will impact the performance of a device, the source of traps and position of traps in the device remains as a complex exercise until today. The key parameters for the precise tuning of threshold voltage (Vth) in GaN transistors are the control of the positive fixed charges -5 × 1012 cm-2, donor-like traps -3 × 1013 cm-2 at the nitride/GaN interfaces, the energy of the donor-like traps 1.42 eV below the conduction band and the acceptor traps activation energy in the AlGaN layer and buffer regions with 0.59 eV below the conduction band. Hence in this paper, the sensitivity of the trap mechanisms in GaN/AlGaN/GaN HEMT transistors, understanding the absolute vertical electric field distribution, electron density and the physical characteristics of the device has been investigated and the results are in good agreement with GaN experimental data.

A Sensor Fusion Based Nonholonomic Wheeled Mobile Robot for Tracking Control.

In this paper, a detail design procedure of the real-time trajectory tracking for the nonholonomic wheeled mobile robot (NWMR) is proposed. A 9-axis micro electro-mechanical systems (MEMS) inertial measurement unit (IMU) sensor is used to measure the posture of the NWMR, the position information of NWMR and the hand-held device are acquired by global positioning system (GPS) and then transmit via radio frequency (RF) module. In addition, in order to avoid the gimbal lock produced by the posture computation from Euler angles, the quaternion is utilized to compute the posture of the NWMR. Furthermore, the Kalman filter is used to filter out the readout noise of the GPS and calculate the position of NWMR and then track the object. The simulation results show the posture error between the NWMR and the hand-held device can converge to zero after 3.928 seconds for the dynamic tracking. Lastly, the experimental results show the validation and feasibility of the proposed results.

Investigations of the Influences of Processing Conditions on the Properties of Spray Dried Chitosan-Tripolyphosphate Particles loaded with Theophylline.

The preparation of chitosan-tripolyphosphate (chitosan-TPP) particles by the spray drying had been reported word widely for a sustained release of drugs to prevent rapid drug metabolism. Although the spray drying is a straightforward procedure turning a liquid feed into a well-defined dry powder, seldom research works were focusing on how the processing parameters and liquid feeding constitutions of spray drying system might affect the properties of spray-dried chitosan particles loaded with drugs, such as the particle size and morphologies, which would be very important to drug encapsulation and dissolution of the drug delivery design. This study thus prepared the chitosan particles with theophylline (TH) loaded as a model drug and TPP as cross-linker at various spray drying conditions. Our results indicate the diameter of the TH/chitosan-TPP particles made by customized spray drying apparatus spans from 424 to 497 nm with a geometric standard deviation of less than 2. The corresponding release of TH was tunable by the chitosan-TPP matrix density under the selected spray drying temperature and the carrying air flow rate. These results suggest an indeed need for optimized spray drying processing conditions to make the ideal spray-dried TH/chitosan-TPP particles for the desired drug delivery.

Suspected drug-induced liver injury associated with iguratimod: a case report and review of the literature.

BACKGROUND: Iguratimod is a novel anti-rheumatic drug with the capability of anti-cytokines as report goes. It has been reported that iguratimod is effective and safe for rheumatoid arthritis and other rheumatisms. As side effects, iguratimod can cause gastrointestinal reactions, dizziness, headache and itchy. CASE PRESENTATION: In this case report, a 60-year-old female patient was admitted with suspected drug-induced liver injury (DILI) caused by iguratimod. The causality assessment was done by the updated RUCAM, and the possibility of the case in our paper diagnosed as highly probable for the score was 9 points. Iguratimod was discontinued immediately, and methylprednisolone was used for acute liver injury and Sjogren's syndrome. The data showed the patient has improved gradually, and she was discharged on day 27. The true incidence of iguratimod-related hepatotoxicity and its pathogenic mechanism are largely unknown. It is difficult to recognize and diagnose DILI, and there is no standard for diagnosis of DILI. At the same time, the DILI is still lack of specific treatment. CONCLUSIONS: Based on this rare case of severe liver injury, we recommend careful monitoring of liver function throughout iguratimod treatment for diseases.

[A method for assessing the total viable count of fresh meat based on hyperspectral scattering technique].

The objective of this study is to develop a hyperspectral imaging system to predict the bacteria total viable count in fresh pork. The hyperspectral scattering data were curvefitted by different fitting methods, and correlation differences of models were compared based on the bacteria total viable count of fresh pork, thus providing modeling basis of device for future study. Total 63 fresh pork samples which was used in the experiment were stored at 4 degrees C in the refrigerator of constant temperature. Experiment was performed everyday for 15 days. 4 or 5 random samples were used each day for the experiment. Hyperspectral scattering images and spectral scattering optical data in the wavelength region of 400 to 1 100 nm were acquired from the surface of all of the pork samples. Lorentz and Gompertz function and the modified function was applied to fit the scattering profiles of pork samples. Different parameters could be obtained by Lorentz and Gompertz fitting and the modified function fitting. The different parameters could represent the optical characteristic of the scattering profiles. The standard values of the bacteria total viable count of pork were obtained by classical microbiological plating methods. Because the standard value of the bacteria total viable count was big, log10 of the bacteria total viable count obtained by classical microbiological plating was used to simplify the calculation. Both individual parameters and integrated parameters were explored to develop the models. The multi-linear regression statistical approach was used to establish the models for predicting pork the bacteria total viable count. Both Lorentz and Gompertz function and the modified function included three and four parameters formula. The results showed that correlation coefficient of the models is higher with Lorentz three parameters combination, Lorentz four parameters combination and Gompertz four parameters combination than the individual parameters and other two or three integrated parameters. The three models' correction set and prediction set correlation coefficients were 0.93, 0.96, 0.96 and 0.90, 0.90, 0.92, and the corresponding standard deviation were 0.47, 0.44, 0.39 and 0.56, 0.46, 0.42. Correlation was best with Gompertz four parameters. The device system will select the best correlation and the best stability of the model as the final model.

A novel aerosol-mediated drug delivery system for inner ear therapy: intratympanic aerosol methylprednisolone can attenuate acoustic trauma.

We developed a novel aerosol-mediated drug delivery system for inner ear therapy by using a silicon-based multiple-Fourier horn nozzle. Intratympanic aerosol (ITA) methylprednisolone (MP) delivery can protect hearing after acoustic trauma. The highest concentration of MP (38.9 ± 5.47 ppm) appeared at 2 h and declined rapidly within 10 h. The concentrations of MP remained at a relatively low level for more than 10 h. Compared to the baseline, the auditory brainstem response (ABR) thresholds shifted markedly at 1 h after noise exposure in all groups (p < 0.05). From the cochleograms, it can be noted that the main lesions encompassed the 2-20 kHz frequency range. Significant differences ( ) were observed for the range between 5 and 8 kHz in the cell loss of outer hair cells (OHCs). The losses for IHCs were lower than for OHCs. The MP movement in the middle ear was simulated by a convection diffusion equation with a relaxation time. The relaxation time was 0.5 h, and the concentration threshold of MP on the round window membrane (RWM) in the middle ear (C T) was 8900 ppm. Using the unit hydrograph (UH) method, we obtained a proper boundary concentration on the RWM at the cochlea, which resulted in a well-fit concentration. Finally, a linking mechanism between the middle ear and the cochlea was established by the RWM. The adjustable permeability and concentration threshold provide the flexibility to match the peak times and peak values of the concentration on the RWM in the middle ear and the cochlea.

Modeling sound transmission of human middle ear and its clinical applications using finite element analysis.

We have developed a new finite element (FE) model of human right ear, including the accurate geometry of middle ear ossicles, external ear canal, tympanic cavity, and mastoid cavity. The FE model would be suitable to study the dynamic behaviors of pathological middle ear conditions, including changes of stapedial ligament stiffness, tensor tympani ligament (TTL), and tympanic membrane (TM) stiffness and thickness. Increasing stiffness of stapedial ligament has substantial effect on stapes footplate movement, especially at low frequencies, but less effect on umbo movement. Softer TTL will result in increasing umbo and stapes footplate displacement, especially at low frequencies (f<1000Hz). When the TTL was detached, the vibration amplitude of umbo increased by 6dB at 600Hz and two peaks (300 and 600Hz) were found in the vibration amplitude of stapes footplate. Increasing the stiffness of tensor tympani resulted in a slightly decreased umbo amplitude at very low frequencies (f<500Hz) and significantly decreased displacement up to 12dB at middle frequencies (1000Hz1500Hz. As (TM) thickness was increased, the umbo displacement was reduced, especially at very low frequencies (f<600Hz). Otherwise, the stapes displacement was reduced at all frequencies.

Novel device to measure critical point "Onset" of capillary wave and interpretation of Faraday instability wave by numerical analysis.

A capillary wave was created on a surface by vibrating from the bottom of a container. When the amplitude of the container vibration approached the critical point, called the onset state, the surface broke up and bursted into very small drops on the air. The numerical analysis was used to determine the amplitude of the onset. The onset point was found to be 0.349µm at f=500kHz. The critical amplitude h(cr) was determined by using a multi-Fourier horn nozzle (MFHN) device. The onset point was measured to be 0.37µm using a laser Doppler vibrometer (LDV) with the MFHN at f=486kHz. These drops indicate that particle size distributions of 10.8µm and 7.0µm were produced by the MFHN at f=289kHz and f=486kHz, respectively. These results agreed with those obtained using Kelvin's equation, which predicted D=0.34λ.

Registration of micro-computed tomography and histological images of the guinea pig cochlea to construct an ear model using an iterative closest point algorithm.

We present a practical and systematic method to reconstruct accurate physical models of the guinea pig ear (n = 1). The method uses a semi-automatic technique to create three-dimensional (3-D) models of the guinea pig cochlea by registration of micro-computed tomography (CT) and histological images. An iterative closest point algorithm was employed to minimize the sum of square errors with respect to the closest histological model and corresponding micro-CT model. This allowed creation of an accurate geometric ear model including external ear canal, tympanic membrane, middle ear cavity, auditory ossicles, and the cochlea. The characteristic cross-sectional areas of scala tympani, scala vestibuli, and scala media were measured. The length, thickness, and apex width of the guinea pig's basilar membrane were compared to the data found in literature. Some shape parameters were also compared among different species. The results confirmed that the geometric model created by this method was accurate. This method provides an effective way to visualize the 3-D structure and the detailed information about ear geometry required for finite element and multibody dynamic analysis.

Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end-stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high-fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin-eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in liver. The results showed that high-fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high-fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH-Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high-fat diet possibly through its antioxidant actions.

Transfection of mouse macrophage metalloelastase gene into murine CT-26 colon cancer cells suppresses orthotopic tumor growth, angiogenesis and vascular endothelial growth factor expression.

A cDNA fragment coding for domains I and II of mouse macrophage metalloelastase (MME) was transfected into murine CT-26 colon cancer cells that are MME deficient. An orthotopic implantation model was established by using MME-transfected cells. In MME-transfected primary tumors, it demonstrated that tumor growth and microvessel formation were significantly inhibited compared with the controls. The expression of vascular endothelial growth factor (VEGF) mRNA and protein was significantly lower in MME-transfected group compared with those in the controls. Our data show that both MME and VEGF gene expression is highly associated with the vascularity of tumors, which may depend on a balance between MME and VEGF expression.

Inhibitory effect of oxymatrine on serum hepatitis B virus DNA in HBV transgenic mice.

AIM: To study the inhibitory effect of oxymatrine on serum hepatitis B virus (HBV) DNA in HBV transgenic mice. METHODS: HBV transgenic mice model was established by microinjection, and identified by HBV DNA integration and replication. Transgenic mice with replicating HBV were divided into 3 groups, and injected with normal saline (group A, n=9), 50 mg/kg (group B, n=8) and 100 mg/kg (group C, n=9) oxymatrine intraperitoneally once a day for 30 d, respectively. Quantitation of serum HBV DNA in HBV transgenic mice was performed by competitive polymerase chain reaction (PCR) in combination with DNA hybridization quantitative detection technique before and after treatment. RESULTS: Compared with pre-treatment, the serum HBV DNA in group A (F=1.04, P=0.9612) and group B (F=1.13, P=0.8739) had no changes after treatment. However, in group C serum HBV DNA was significantly decreased (F=13.97, P=0.0012). The serum HBV DNA after treatment was lower in group C than in groups B and A (F=8.65, P=0.0068; F=12.35, P=0.0018; respectively). The serum HBV DNA after treatment was lower in group B than in group A, but there was no statistical significance (F=1.43, P=0.652). CONCLUSION: Oxymatrine has inhibitory effects on serum HBV DNA in HBV transgenic mice.