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The drilling and blasting method is widely used in tunnel engineering. The accompanying airblast may damage structures and annoy nearby occupants. The prediction of airblast overpressure (poa) outside the tunnel is necessary to improve the safety of blasting works. A study of propagation characteristics of airblasts induced by tunnel blasting was carried out through experimental and numerical studies. The results indicate that the distributions of the poa outside the tunnel were anisotropic, which does not conform to the decay law of an explosion in free-field. The propagation of airblasts induced by tunnel blasting is related to the airblast shape. The phenomenon that the poa along the axial direction of the tunnel was higher than along other directions can be explained by the numerical results of the process of airblasts. The airblasts outside the tunnel traveled as a spherical wave, but the pressure was not uniformly distributed. After an airblast plane wave with high speed and high pressure inside the tunnel was transmitted out of the tunnel, its inertia strengthened the pressure in the axial direction. The airblast outside the tunnel is related to the propagation distance Rout, the angle from the measurement to the tunnel axis α, and the pressure intensity p0 at the tunnel portal. Subsequently, an ellipsoidal contour curve of the poa outside the tunnel was plotted, and therefore a new prediction equation was validated by numerical results and field data. Finally, the newly proposed methodology guided the blast design.

Cemiplimab may significantly increase overall survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with a PD-L1 level of at least 50%. Therefore, there is a need to consider the cost-effectiveness of using this therapy for this indication. This Markov model was built to estimate the cost and effectiveness of cemiplimab vs. chemotherapy in the first-line treatment of advanced NSCLC based on the data from the EMPOWER-Lung 1 trial. Life-years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. Treatment of advanced NSCLC with cemiplimab added 0.546 QALYs (1.492 LYs) and resulted in an incremental cost of $22,069.804 compared with chemotherapy, which was associated with an incremental cost-effectiveness ratio of $40,390.412 per QALY gained. The results of one-way sensitivity analysis found that the cost of cemiplimab was the most sensitive factor in our study. The probabilistic sensitivity analysis showed that the probability of cemiplimab being cost-effective was 100%. The subgroup analysis demonstrated that high PD-L1 expression (≥ 90%, > 60 to

The effectiveness of nivolumab plus ipilimumab with two cycles of chemotherapy (NIC) for advanced non-small cell lung cancer (NSCLC) has been demonstrated. We aimed to evaluate the cost-effectiveness of NIC for advanced NSCLC from the US payer perspective. A Markov model has been established to predict the disease course of previously untreated advanced NSCLC. The clinical data were derived from the CheckMate 9LA trial. Cost and utility were obtained from the literature. Model outputs included the incremental cost-effectiveness ratios (ICERs), incremental monetary benefit (INMB), and incremental net-health benefit (INHB). A series of sensitivity analyses were performed to analyze the uncertainty of the model. Our results showed that NIC versus chemotherapy alone cost $264,278 and yielded an additional 0.80 quality-adjusted life-years (QALYs), which led to an ICER of $202,275/QALY gained. The INHB was − 0.28 QALY, and the INMB was − $41,865 at the threshold of $150,000/QALY. The results of one-way sensitivity analysis showed that the hazard ratio of overall survival was the most sensitive parameter. NIC was unlikely to be cost-effective as a first-line treatment for patients with advanced NSCLC.

The ALCYONE trial found that daratumumab in combination with bortezomib, melphalan, and prednisone (D-VMP) can significantly improve progression-free survival (PFS) and overall survival (OS) for patients with transplant-ineligible, newly diagnosed multiple myeloma (MM) in China. In the present study, we evaluated the cost-effectiveness of D-VMP versus VMP for patients with newly diagnosed MM in China. A Markov model was used to estimate the cost-effectiveness of frontline D-VMP versus VMP for MM. The life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER) were calculated. A series of sensitivity analyses was performed to assess the robustness of the model and address uncertainties in variable estimates. Subgroup analysis was also performed. D-VMP provided an additional 2.99 LYs and 1.67 QALYs compared with VMP, with incremental $64,920 per LY and $116,015 per QALY gained. The results of the univariable sensitivity analysis showed that the parameter that had the greatest impact on the ICER was the cost of subsequent treatment and daratumumab. When the cost of daratumumab was 100%, 70%, 50%, and 30% of the current price, the probability of D-VMP being cost-effective was 2.49%, 16.11%, 39.09%, and 70.73% at the willingness-to-pay (WTP) threshold of $30,950/QALY, respectively. The results demonstrated that the ICER in all subgroups remained > $30,950/QALY. D-VMP versus VMP is likely to exceed the commonly accepted values of cost-effectiveness in patients with transplant-ineligible, newly diagnosed MM in China.

Self-consolidating concrete (SCC) with manufactured sand (MSCC) is crucial to guarantee the quality of concrete construction technology and the associated property. The properties of MSCC with different microlimestone powder (MLS) replacements of retreated manufactured sand (TMsand) are investigated in this study. The result indicates that high-performance SCC, made using TMsand (TMSCC), achieved high workability, good mechanical properties, and durability by optimizing MLS content and adding fly ash and silica fume. In particular, the TMSCC with 12% MLS content exhibits the best workability, and the TMSCC with 4% MLS content has the highest strength in the late age, which is even better than that of SCC made with the river sand (Rsand). Though MLS content slightly affects the hydration reaction of cement and mainly plays a role in the nucleation process in concrete structures compared to silica fume and fly ash, increasing MLS content can evidently have a significant impact on the early age hydration progress. TMsand with MLS content ranging from 8% to 12% may be a suitable alternative for the Rsand used in the SCC as fine aggregate. The obtained results can be used to promote the application of SCC made with manufactured sand and mineral admixtures for concrete-based infrastructure.

The dynamic splitting tensile behaviour of hybrid basalt‒polypropylene fibre-reinforced concrete (HBPRC) was investigated, and the reinforcing mechanism of the fibres was explored. The results indicate that the dynamic splitting tensile strength and dynamic energy dissipation capacity of HBPRC increased with strain rate. The effects of fibre type and content on the strain rate sensitivity of dynamic splitting tensile strength were consistent with that of dynamic dissipation energy. Furthermore, the dynamic splitting tensile strength of concrete was improved by adding appropriate content of basalt fibre (BF) and polypropylene fibre (PF), and the improving effect of hybrid BF and PF was the most significant. Excess fibres reduced the dynamic splitting tensile strength at low strain rates but improved it at high strain rates. The addition of fibres improved the dynamic dissipation energy and the impact resistance of concrete. With an increase in the strain rate, the pull-out lengths of BF and PF decreased gradually. When using hybrid BF and PF, the failure morphology of BF did not change considerably, although PF underwent more severe damage. Based on the weakest-link theory, a calculation model for the statistical scaling law of dynamic splitting tensile strength considering the strain rate effect was established.

A trial-based assessment was completed to evaluate the cost-effectiveness of ceritinib as a first-line treatment for advanced non-small cell lung cancer (NSCLC) with rearrangement of anaplastic lymphoma kinase. Based on the disease situation of advanced NSCLC, a Markov model was constructed to estimate the costs and benefits of ceritinib and platinum-based chemotherapy. The cost information and health utilities were obtained from published literature. The incremental cost-effectiveness ratio was calculated. The stability of the model was verified by sensitivity analyses. The base case analysis results indicated that compared with platinum-based chemotherapy, ceritinib therapy would increase benefits in a 5-, 10- and 15-year time horizon, with extra costs of $230,661.61, $149,321.52 and $136,414.43 per quality-adjusted life-year gained, respectively. The most sensitive parameter in the model analysis was the cost of ceritinib. Probabilistic sensitivity analysis suggested that at the current price of ceritinib, the chance of ceritinib being cost-effective was 0 at the willingness-to-pay threshold of $27,142.85 per quality-adjusted life-year (three times the per capita gross domestic product of China). As a first-line treatment for advanced NSCLC with rearrangement of anaplastic lymphoma kinase, ceritinib is unlikely to be cost-effective at the current price from the Chinese healthcare perspective. To meet the treatment demands of patients, it may be a better option to reduce the price or provide appropriate drug assistance policies.

In first-line treatment of advanced renal cell carcinoma (aRCC), the KEYNOTE-426 study demonstrated a significant progression-free survival and overall survival for pembrolizumab plus axitinib in comparison with sunitinib. The objective of the current study was to evaluate the cost effectiveness of pembrolizumab plus axitinib versus sunitinib for previously untreated patients with aRCC in China. A Markov model was used to estimate the costs and health outcomes of treatment of aRCC with sunitinib or pembrolizumab plus axitinib. Univariable and probabilistic sensitivity analyses were performed to determine the robustness of the model outcomes. Additional subgroup analyses were also performed. The primary outputs of the model included the total cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Pembrolizumab plus axitinib provided an additional 2.461 LYs (1.650 QALYs). The total cost per patient was US$178,725 for pembrolizumab plus axitinib and US$87,693 for sunitinib. The ICER for pembrolizumab plus axitinib was US$55,185/QALY versus sunitinib. Sensitivity analyses found the results to be most sensitive to pembrolizumab cost and overall hazard ratio. The results of subgroup analyses showed that the ICER remained greater than US$32,000/QALY across the all patient subgroups. Pembrolizumab plus axitinib is not likely to be cost effective versus sunitinib for patients with previously untreated aRCC at a threshold value of US$29,306/QALY.

Lipase-catalyzed esterification of conjugated linoleic acid (CLA) with L-carnitine in solvent-free system and acetonitrile was studied. Three lipases (Novzym 435, Amamo AY30 and Amano AYS) have been assayed as suitable biocatalysts in the reaction. It was found that Amano AY30 was the most effective biocatalyst in both solvent-free system and acetonitrile. The conversion rate varied from 8.05 to 60.9% in terms of reaction conditions such as the amount of lipase, the presence of water, the amount of molecular sieves and reaction time. The conversions of substrate in solvent-free system were higher than that in acetonitrile. When the substrates were 1 mmol CLA and 1 mmol L-carnitine, the maximum conversion (60.9%) was obtained in solvent-free system with 150 mg lipase AY30, 50% water content and 150 mg molecular sieves at the reaction time of 24 h. A novel CLA ester product was successfully isolated and characterized by ESI-MS and (1)H NMR.

It is demonstrated that when tension leg platform (TLP) moves with finite amplitude in waves, the inertia force, the drag force and the buoyancy acting on the platform are nonlinear functions of the response of TLP. The tensions of the tethers are also nonlinear functions of the displacement of TLP. Then the displacement, the velocity and the acceleration of TLP should be taken into account when loads are calculated. In addition, equations of motions should be set up on the instantaneous position. A theoretical model for analyzing the nonlinear behavior of a TLP with finite displacement is developed, in which multifold nonlinearities are taken into account, i.e., finite displacement, coupling of the six degrees of freedom, instantaneous position, instantaneous wet surface, free surface effects and viscous drag force. Based on the theoretical model, the comprehensive nonlinear differential equations are deduced. Then the nonlinear dynamic analysis of ISSC TLP in regular waves is performed in the time domain. The degenerative linear solution of the proposed nonlinear model is verified with existing published one. Furthermore, numerical results are presented, which illustrate that nonlinearities exert a significant influence on the dynamic responses of the TLP.