Search

The Awakening is a story about women awakening, and it is also a story about extramarital affairs. By using feminist narration theory to analyze the relationship between Edna and the four men, namely Mr. Pontellier, Edna’s father, Arobin and Robert, we can have a deeper understanding of Edna’s emotional attitudes and values, and reflect on the relationship between people and the choice of life path.

Water splitting is catalyzed by photosystem II, which comprises an inorganic core (CaMn

The crystallization blockage of the tunnel drainage pipes in karst areas often threatens the normal construction of tunnels and affects operation of drainage systems. Based on basic theory of CaCO3 crystallization, this study analyses the law of the crystalline scale formation rate of tunnel drainage pipes in karst areas through three mass transfer mechanisms: convective mass transfer, molecular diffusion and wall ion reactions, obtains the calculation model of crystalline scale formation rate of drainage pipes, and verifies model by simulating crystalline scale formation tests of tunnel drainage pipes. The results show that factors such as the flow rate of karst water, the inner diameters of tunnel drainage pipes, the molecular diffusion coefficient, the dynamic viscosity of karst water, the molecular diffusion coefficient of calcium carbonate, the temperature of karst water, and the slopes of tunnel drainage pipes have certain influences on the crystallization of the tunnel drainage pipes in karst areas, and they promote or inhibit the formation of scale layers on the inner walls of the tunnel drainage pipes in karst areas by affecting the efficiency of convective mass transfer, molecular diffusion and wall ion reactions; under different test conditions, the average relative errors between the calculated results of the crystalline scale formation rate of drainage pipes and those of the pipes in the test group are 9.1%, 13.7%, 14.2% and 16.1% respectively. Considering the scouring effect of water flow on crystalline scale layers, although there are certain errors in the results, this does not affect the overall results

This paper aims at the problem of finite-time prescribed performance adaptive fuzzy control for a class of unknown nonlinear systems. An adjustable finite-time performance function with faster convergence rate is applied to the procedure of the controller design, whose parameters can be adjusted in real time on the basis of the tracking error. Furthermore, a finite-time prescribed performance adaptive fuzzy tracking controller is designed by the backstepping method, which can guarantee that all the signals in the closed-loop system are bounded. Simultaneously, the output tracking error always stays within an adjustable boundary and converges to a fixed region at finite-time settling time. Besides, the tracking performance in transient state is slightly optimized. Simulation results demonstrate the effectiveness of the proposed controller.

Background and ObjectivesPompe disease is a rare, progressive neuromuscular disorder caused by deficiency of lysosomal acid α-glucosidase (GAA) and subsequent glycogen accumulation. Avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy designed for increased cellular uptake and glycogen clearance, has been studied for long-term efficacy and safety in patients with late-onset Pompe disease (LOPD). Here, we report up to 6.5 years' experience with avalglucosidase alfa during the NEO1 and NEO-EXT studies.MethodsNEO1 participants with LOPD, either treatment naive (Naive Group) or receiving alglucosidase alfa for ≥9 months (Switch Group), received avalglucosidase alfa (5, 10, or 20 mg/kg every other week [qow]) for 6 months before entering NEO-EXT and continued their NEO1 dose until all proceeded with 20 mg/kg qow. Safety and efficacy, a prespecified exploratory secondary outcome, were assessed; slopes of change for efficacy outcomes were calculated from a repeated mixed-measures model.ResultsTwenty-four participants enrolled in NEO1 (Naive Group, n = 10; Switch Group, n = 14); 21 completed and 19 entered NEO-EXT; in February 2020, 17 participants remained in NEO-EXT, with data up to 6.5 years. Avalglucosidase alfa was generally well tolerated during NEO-EXT, with a safety profile consistent with that in NEO1. No deaths or treatment-related life-threatening serious adverse events occurred. Eighteen participants developed antidrug antibodies without apparent effect on clinical outcomes. No participants who were tested developed immunoglobulin E antibodies. Upright forced vital capacity %predicted remained stable in most participants, with slope estimates (95% CIs) of −0.473 per year (−1.188 to 0.242) and −0.648 per year (−1.061 to −0.236) in the Naive and Switch Groups, respectively. Six-minute walk test (6MWT) %predicted was also stable for most participants, with slope estimates of −0.701 per year (−1.571 to 0.169) and −0.846 per year (−1.567 to −0.125) for the Naive and Switch Groups, respectively. Improvements in 6MWT distance were observed in most participants aged DiscussionAvalglucosidase alfa was generally well tolerated for up to 6.5 years in adult participants with LOPD either naive to alglucosidase alfa or who had previously received alglucosidase alfa for ≥9 months.Classification of EvidenceThis study provides Class IV evidence of long-term tolerability and sustained efficacy of avalglucosidase alfa in patients with LOPD after up to 6.5 years.Trial Registration InformationNCT01898364 (NEO1 first posted: July 12, 2013; clinicaltrials.gov/ct2/show/NCT01898364); NCT02032524 (NEO-EXT first posted: January 10, 2014; clinicaltrials.gov/ct2/show/NCT02032524). First participant enrollment: NEO1—August 19, 2013; NEO-EXT—February 27, 2014.

In a seamless phase II/III/IIIb trial, K (K ≥ 2) doses versus placebo control are evaluated at phase II. Based on phase II results, one dose will be selected for phases III and IIIb. Pre-specified ...

The triple-shelled hollow CuCo2O4 (T-CuCo2O4) microspheres were synthesized by a solvothermal/calcination method. The unique structure with a large internal void volume and porous distribution shortened the ions/electrons transport distance and strengthened the electrochemical reaction. The triple-shelled architecture buffered the volume expansion/contraction to enhance structural stability due to the reduced stress and strain during the charge/discharge process. As a three-electrode cell, the T-CuCo2O4 electrode demonstrated a specific capacitance of 691 F/g (current density: 1 A/g), rate capability of 470 F/g (current density: 20 A/g) and capacitance retention of 93% after 6000 cycles. The all-solid-state asymmetrical supercapacitor achieved an energy density of 25.2 W h/kg at a power density of 1.05 kW/kg, using activated carbon as a negative electrode. The specific capacitance can still maintain 80.3 F/g at a current density of 2 A/g with 6% capacity loss after 2000 cycles.

In order to obtain the accurate B340LA material parameter, in this paper, a dynamic optimization approach was proposed to inverse determine the material parameters in bending springback process. After the inverse determination for material parameters, the finite element simulation result indicates a close agreement with actual experiment, and the relative errors between inverse determined and actual material parameters are also very small. It can be concluded that proposed optimization approach to inverse determine the material parameters is efficient and accurate.

OBJECTIVE To evaluate efficacy and safety of LixiLan (iGlarLixi), a novel titratable fixed-ratio combination of insulin glargine (iGlar) and lixisenatide (Lixi), compared with both components, iGlar and Lixi, given separately in type 2 diabetes inadequately controlled on metformin with or without a second oral glucose-lowering drug. RESEARCH DESIGN AND METHODS After a 4-week run-in to optimize metformin and stop other oral antidiabetic drugs, participants (N = 1,170, mean diabetes duration ∼8.8 years, BMI ∼31.7 kg/m2) were randomly assigned to open-label once-daily iGlarLixi or iGlar, both titrated to fasting plasma glucose RESULTS Greater reductions in HbA1c from baseline (8.1% [65 mmol/mol]) were achieved with iGlarLixi compared with iGlar and Lixi (−1.6%, −1.3%, −0.9%, respectively), reaching mean final HbA1c levels of 6.5% (48 mmol/mol) for iGlarLixi versus 6.8% (51 mmol/mol) and 7.3% (56 mmol/mol) for iGlar and Lixi, respectively (both P < 0.0001). More subjects reached target HbA1c CONCLUSIONS iGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA1c reductions, close to near normoglycemia without increases in either hypoglycemia or weight, compared with iGlar, and had low gastrointestinal adverse effects compared with Lixi.

An oriented nanograss array consisting of CuCo

Honeycomb-like nickel cobalt sulfide (NiCo

AimsTo assess efficacy and safety of lixisenatide once-daily versus placebo in Type 2 diabetes mellitus (T2DM) patients inadequately controlled on sulfonylurea (SU)±metformin.MethodsIn this randomized, double-blind, two-arm, parallel-group, multicenter study, patients received lixisenatide 20μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs±metformin. Primary outcome was change in HbA1c from baseline to Week 24.ResultsLixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo (LS mean: −0.85% vs. −0.10%; p

Maximum likelihood is a widely used estimation method in statistics. This method is model dependent and as such is criticized as being non robust. In this article, we consider using weighted likelihood method to make robust inferences for linear mixed models where weights are determined at both the subject level and the observation level. This approach is appropriate for problems where maximum likelihood is the basic fitting technique, but a subset of data points is discrepant with the model. It allows us to reduce the impact of outliers without complicating the basic linear mixed model with normally distributed random effects and errors. The weighted likelihood estimators are shown to be robust and asymptotically normal. Our simulation study demonstrates that the weighted estimates are much better than the unweighted ones when a subset of data points is far away from the rest. Its application to the analysis of deglutition apnea duration in normal swallows shows that the differences between the weighted ...

Linear mixed models based on the normality assumption are widely used in health related studies. Although the normality assumption leads to simple, mathematically tractable, and powerful tests, violation of the assumption may easily invalidate the statistical inference. Transformation of variables is sometimes used to make normality approximately true. In this paper we consider another approach by replacing the normal distributions in linear mixed models by skew-t distributions, which account for skewness and heavy tails for both the random effects and the errors. The full likelihood-based estimator is often difficult to use, but a 3-step estimation procedure is proposed, followed by an application to the analysis of deglutition apnea duration in normal swallows. The example shows that skew-t models often entail more reliable inference than Gaussian models for the skewed data.

An oriented nanograss array consisting of CuCo2S4 nanocrystallines was directly prepared on Ni foam by a hydrothermal method. The uniform arrays with a single blade diameter of ∼100 nm and length of ∼4 μm can grow tightly on Ni foam without any binders. The ordered one-dimensional structure facilitates the electron transport to Ni substrates along the axial direction. The electrochemical properties were presented in three- and two-electrode configurations, demonstrating an enhanced specific capacitance and a long-term cycling stability. As a practical all-solid-state device, it achieved a high energy density of 31.88 W h kg-1 at a power density of 3.20 kW kg-1. Even at a higher power density of 15.23 W h kg-1, the device still had an energy density of 16.5 kW kg-1. After 5000 cycles, the retention ratio was higher than 99% at high current density of 11.36 A g-1.

Honeycomb-like nickel cobalt sulfide (NiCo2S4) nanosheets were directly deposited on fluorine-doped tin oxide substrate by a rapid voltammetric deposition method. The method was also controllable and feasible for preparing NiCo2S4 on flexible Ti foil without any heating processes. Compared with Pt, CoS and NiS, NiCo2S4 exhibited low charge-transfer resistances and excellent electrocatalytic activity for [Formula: see text] reduction, acting as a counter electrode for a dye-sensitized solar cell. The NiCo2S4-based solar cell showed higher power conversion efficiency (7.44%) than that of Pt-based solar cell (7.09%) under simulated illumination (AM 1.5 G, 100 mW cm-2). The device based on the flexible NiCo2S4/Ti foil achieved a power conversion efficiency of 5.28% under the above illumination conditions. This work can be extended to flexible and wearable technologies due to its facile technique.

Intravascular ultrasound (IVUS) is a clinical imaging procedure used to assess drug effects on the progression of coronary atherosclerosis in clinical trials. It is an invasive medical procedure of measuring coronary artery atheroma (plaque) volume, and leads to high missing rates (often over 30%). This paper uses an IVUS Phase II clinical trial data to explore the missing mechanism of IVUS endpoint, the percent atheroma volume (PAV). We proposed a moving-window method to examine the relationship between continuous covariates such as lipid endpoint and the probability of missing IVUS values, which provides a general approach for missing mechanism exploration. The moving-window method is more intuitive and provides a fuller picture about the relationship. In the example, some covariates such as lipid measures also have high missing rates after 12 months because of compliance issues probably caused by fatigue of blood drawing. We found that if the method of last observation carried forward (LOCF) is used to impute the lipid endpoints, it leads to biologically unexplainable results. Using the multiple imputation approach for the missing covariates results in a more reasonable conclusion about the IVUS missing mechanism. Age, race, and baseline PAV are identified as key potential contributors to the probability of missing IVUS endpoint. This finding can be used to reduce missing values in future IVUS trials by setting up appropriate inclusion and exclusion criteria at the trial design stages.