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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

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.

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.

Axial fans play a pivotal role in the road tunnel ventilation system. Qualified performance of the axial fan is important for both safety and air quality maintenance reasons. Axial fans performance in situ test of Qinling Zhongnan Mountain highway tunnel, the second longest road tunnel in the world, is presented in this research. Performance test items and the qualification criterion, as well as a general framework for the road tunnel axial fan assessment, are recommended. Log-Tchebycheff method is suggested to confirm the location for the measuring lines and points. The precision of the log-Tchebycheff method in air flow rate measuring is verified by comparing with the biharmonic spline interpolation fitting result. The research shows that the log-Tchebycheff method has high precision and good efficiency in the air flow rate measurement of the road tunnel air duct. What is more, the biharmonic spline interpolation fitting method can be applied to obtain a more accurate result. The number of interpolation points of the biharmonic spline interpolation fitting method should be bigger than 2000 to provide quality results.

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.

During the Wenchuan Earthquake, with a magnitude of 5.12, collapses and rockfall hazards persisted for a long time after the initial investigations carried out by research fellow S. M. He and his team at the scene of the disaster in October 2008. It is possible that additional incidents of rockfalls in large quantities may continue in the same areas over the next ten to fifteen years. Furthermore, in the vast mountainous region of western China, the topographic relief is evident, and earthquakes occur frequently. Therefore, it is difficult to effectively defend against rockfall hazards. When designing protective structures, the key issue is the analysis of the mechanical response mechanism of the soil cushion layer of the upper cushion when subjected to the impact of rockfall. As such, a theoretical method was used to perform such an analysis. The cavity expansion and energy conservation model were adopted. Analytical solutions for the impact force and penetration depth were then derived. Furthermore, the impact force and penetration depth of rockfall were studied with the LS-DYNA software to obtain values for the impact forces and the penetration depth. Finally, the reliability of the theoretical method was evaluated using the cavity expansion, energy conservation, numerical simulation, Hertz, Japanese, Swiss, Australian, B. S. Guan, tunnel manual, and subgrade methods based on an engineering model. The results show that the cavity expansion and the energy conservation methods yielded consistent results. Meanwhile, the cavity expansion and the energy conservation methods also yielded consistent results with the numerical simulation, Japanese (obtained by laboratory experiment), Swiss (obtained by laboratory experiment), and Australian (obtained by field experiment) methods. The relevant methods and conclusions shall therefore be applied to the design of rockfall protection structure in future investigations.

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

OBJECTIVE This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 μg lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naïve type 2 diabetes on metformin. RESEARCH DESIGN AND METHODS Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 μg and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI ≤0.4%) of LixiLan in reducing HbA1c; if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety. RESULTS Baseline characteristics (mean age 57 years, diabetes duration 6–7 years, BMI 32 kg/m2) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squared mean [95% CI] difference: −0.17% [−0.31, −0.04] {−1.9 mmol/mol [−3.4, −0.4]}; P = 0.01). HbA1c CONCLUSIONS LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin.

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.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/mGreater reductions in HbAiGlarLixi complemented iGlar and Lixi effects to achieve meaningful HbA