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Aim: To explore the risk of major adverse cardiovascular events (MACE) associated with exposure to bexagliflozin. Methods: The analysis included 4090 participants with type 2 diabetes (T2D) enrolled in nine phase 2 and 3 double‐blind randomized controlled trials. All potential MACE were adjudicated by a blinded committee. The primary endpoint for the meta‐analysis was the hazard ratio (HR) for the time to first occurrence of non‐fatal stroke, non‐fatal myocardial infarction (MI), cardiovascular (CV) death or hospitalization for unstable angina (MACE+), tested for non‐inferiority to a ratio of 1.8. The secondary endpoints were time to first occurrence of (i) non‐fatal stroke, non‐fatal MI or CV death (MACE), tested for non‐inferiority to a ratio of 1.3; and (ii) CV death or hospitalization for heart failure, tested for superiority. Results: The HR for the primary endpoint of MACE+ was 0.80 (95% confidence interval [CI] 0.58, 1.09), which fulfilled the non‐inferiority objective with a P value of less than 0.0001. Non‐inferiority for the first key secondary endpoint of MACE was also shown (HR = 0.82; 95% CI 0.59, 1.13; P = 0.0023). Superiority for time to CV death or first hospitalization for heart failure was not shown. Conclusions: Bexagliflozin did not increase the risk of MACE in participants with T2D when compared with placebo or active control. Both the preapproval and postapproval thresholds for CV safety were met and bexagliflozin has been approved by the US Food and Drug Administration. [ABSTRACT FROM AUTHOR]

This paper designs a highly parallel Nested Factorization (NF) to solve large linear equations generated in reservoir numerical simulation problems. The NF method is a traditional linear solution preprocessing method for reservoir numerical simulation problems, and has regained attention in recent years due to its potential to extend to parallel architectures such as GPUs (Graphics Processor Units). The parallel algorithm of this paper is based on the MPNF (Massively Parallel Nested Factorization) framework proposed by Appleya (Appleyard, Appleyard, Wakefield, & Desitter, 2011). The MPNF algorithm designed in this paper focuses on its efficient implementation on the GPU parallel architecture. Its features include: using a custom matrix structure to achieve merge access, improving access bottlenecks and improving the efficiency of the SpMV algorithm. It is also applicable to the two-stage preprocessing method CPR. (Constrain Pressure Residual) pressure solution and global preprocessing stage; the MPNF method is extended to the solution of 2.5-dimensional unstructured grid problem. The parallel algorithm in this paper has been integrated into the reservoir numerical simulator. For the SPE10 (million grid, highly heterogeneous) standard example, the GPU-based parallel NF algorithm is in the structured grid model and the equivalent 2.5-dimensional non- On the structured grid model, compared with the serial version of the NF method, the acceleration ratios of 19.8 and 17.0 times were obtained respectively; compared with the mainstream serial solution method, the efficiency was also improved by 2 to 3 times.

Abstract The horizontal wells and multi-stage hydraulic fracturing technologies play a significantly important role in developing unconventional reservoirs. Due to the nanopore effects and stress deformation in tight formations, the fluid equilibrium and thermodynamics become more complex and the conventional reservoir simulation models cannot accurately handle these mechanisms. Hence, the objective of this work is to propose a comprehensive simulation model considering the effects of confined space and stress-dependent deformation. We first evaluated the phase envelope and fluid properties in the confined nanopores. Results show that bubble-point pressure and oil viscosity decrease, while formation volume factor and gas-oil ratio increase. The heavy components cause large deviation on the P-T phase envelope at the reservoir condition. Subsequently, a reservoir simulation model of the Bakken tight oil reservoir was built including the effect of stress-dependent deformation. The proposed phase behavior model was applied into the reservoir simulator to predict the hydrocarbon production from the Bakken tight oil reservoir. Finally, the role of the confined space and the stress-dependent deformation on the production are examined in detail. This novel simulation approach can shed light on the better understanding of the key parameters affecting well production of in developing tight oil reservoirs in the future.

In this study, a label-free sensing method based on a functionalized nanopipette is proposed for detection of alkaline phosphatase (ALP) activity. This method is based on the unique charge transport properties of nanopores in which the ionic current can be modulated by variation in the charge on the inner surface of the nanopipette. A phosphorylated peptide, O-phospho-l-tyrosine (p-Tyr), was used as a model substrate and to functionalize the nanopipette. The covalent functionalization procedures were characterized by measuring the current-voltage (IV) curves and extracting the ionic current rectification status. On ALP catalysis, the removal of the p-Tyr phosphate group induces a decrease in the negative surface charge, subsequently leading to a sensitive response in the ionic current change. An ANOVA test confirmed a linear relationship between the normalized ionic current change and ALP activity. The functionalized nanopipettes demonstrated a directly measured detection limit of 0.1 mU/mL, and excellent selectivity against four common interfering proteins. Furthermore, this nanopore-based method has potential for use in characterizing or sensing the activities of other enzymes with a similar biochemical process to ALP. Keywords: Nanopipette, Alkaline phosphatase activity, Surface charge variation, Ionic current, De-phosphorylation

The pore sizes in tight reservoirs are nanopores, where the phase behavior deviates significantly from that of bulk fluids in conventional reservoirs. The phase behavior for fluids in tight reservoirs is essential for a better understanding of the mechanics of fluid flow. A novel methodology is proposed to investigate the phase behavior of carbon dioxide (CO2)/hydrocarbons systems considering nanopore confinement. The phase equilibrium calculation is modified by coupling the Peng-Robinson equation of state (PR-EOS) with capillary pressure, fluid-wall interaction, and molecule adsorption. The proposed model has been validated with CMG-Winprop and experimental results with bulk and confined fluids. Subsequently, one case study for the Bakken tight oil reservoir was performed, and the results show that the reduction in the nanopore size causes noticeable difference in the phase envelope and the bubble point pressure is depressed due to nanopore confinement, which is conductive to enhance oil recovery with a higher possibility of achieving miscibility in miscible gas injection. As the pore size decreases, the interfacial tension (IFT) decreases whereas the capillary pressure increases obviously. Finally, the recovery mechanisms for CO2 injection are investigated in terms of minimum miscibility pressure (MMP), solution gas-oil ratio, oil volume expansion, viscosity reduction, extraction of lighter hydrocarbons, and molecular diffusion. Results indicate that nanopore confinement effect contributes to decrease MMP, which suppresses to 650 psi (65.9% smaller) as the pore size decreases to 2 nm, resulting in the suppression of the resistance of fluid transport. With the nanopore confinement effect, the CO2 solution gas-oil ratio and the oil formation volume factor of the oil increase with the decrease of pore size. In turn, the oil viscosity reduces as the pore size decreases. It indicates that considering the nanopore confinement effect, the amount of gas dissolved into crude oil increases, which will lead to the increase of the oil volume expansion and the decrease of the viscosity of crude oil. Besides, considering nanopore confinement effect seems to have a slightly reduced effect on extraction of lighter hydrocarbons. On the contrary, it causes an increase in the CO2 diffusion coefficient for liquid phase. Generally, the nanopore confinement appears to have a positive effect on the recovery mechanisms for CO2 injection in tight oil reservoirs. The developed novel model could provide a better understanding of confinement effect on the phase behavior of nanoscale porous media in tight reservoirs. The findings of this study can also help for better understanding of a flow mechanism of tight oil reservoirs especially in the case of CO2 injection for enhancing oil recovery.

Abstract Background Ag2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation. Results 200 nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50 μg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15 days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal. Conclusions Ag2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.

This paper describes the design of a low-noise, high-speed readout-integrated circuit for use in InGaAs infrared focal plane arrays, and analyzes the working principle and noise index of the pixel circuit in detail. The design fully considers the dynamic range, noise, and power consumption of the pixel circuit in which a capacitance transimpedance amplifier structure is adopted as the input stage circuit, and chip fabrication via an XFAB 0.18 µm CMOS process is successfully realized. The ROIC adopts monolithic integration and implements various functions, such as windowing, subsampling, and different integration and readout modes. The ROIC reached an array scale of 32 × 32, a frame rate of 100 Hz, and a readout rate of 20 Mbps with an analog power consumption of less than 52 mW. The measurement results show that the input reference noise can be reduced to 143 e- via the CDS, and the fully customized scheme has certain advantages in the research of high-performance ROICs. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the relative safety and effectiveness of bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes mellitus. Methods: In total, 317 participants were randomized to receive bexagliflozin or placebo plus metformin. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24, with secondary endpoints for systolic blood pressure (SBP), fasting plasma glucose and weight loss. An open label arm enrolled participants with HbA1c >10.5% and was analysed separately. Results: The mean change in HbA1c was −1.09% (95% CI −1.24%, −0.94%) in the bexagliflozin arm and −0.56% (−0.71%, −0.41%) in the placebo arm, a difference of −0.53% (−0.74%, −0.32%; p <.0001). Excluding observations after rescue medication, the intergroup difference was −0.70% (−0.92, −0.48; p <.0001). The open label group change in HbA1c was −2.82% (−3.23%, −2.41%). Placebo‐adjusted changes from baseline SBP, fasting plasma glucose and body mass were −7.07 mmHg (−9.83, −4.32; p <.0001), −1.35 mmol/L (−1.83, −0.86; p <.0001) and −2.51 kg (−3.45, −1.57; p <.0001). Adverse events affected 42.4% and 47.2% of subjects in the bexagliflozin and placebo arms, respectively; fewer subjects in the bexagliflozin arm experienced serious adverse events. Conclusions: Bexagliflozin produced clinically meaningful improvement in glycaemic control, estimated glomerular filtration rate and SBP when added to metformin in a population of adults with diabetes. [ABSTRACT FROM AUTHOR]

Follow-up experimental designs are widely used in various scientific investigations and industrial applications to discuss the relationship between inputs and outputs at various stages. Due to the limitation of run size, the desired experimental purpose may not be achieved through one stage of the experiment, so additional runs should be considered in the follow-up stage. By taking all possible level permutation of the factors into consideration, the uniformity of row augmented designs with mixed four- and five-level is discussed under the average mixture discrepancy, and new lower bounds of average mixture discrepancy for row augmented designs with mixed four- and five-level are obtained in this paper. Accordingly, the algorithm for the construction of uniform row augmented designs with mixed four- and five-level is proposed. Numerical examples show that the constructed uniform row augmented designs with mixed four- and five-level are highly efficient and can be used in practice. [ABSTRACT FROM AUTHOR]