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Background Epstein-Barr virus (EBV) represents an important pathogenic factor of lymphoma and is significantly associated with poor clinical outcome of diffuse large B-cell lymphoma (DLBCL). Circular RNAs (circRNAs) play an essential role in lymphoma progression. However, the underlying mechanism of circRNA on DLBCL progression related to EBV remains largely unknown. Methods CircRNA was screened by high-throughput sequencing in tumor samples of 12 patients with DLBCL according to EBV infection status. Expression of circEAF2, as well as the relationship with clinical characteristics and prognosis, were further analyzed in tumor samples of 100 DLBCL patients using quantitative real-time PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of circEAF2 both in vitro and in vivo. The underlying mechanism of circRNA on DLBCL progression were further determined by RNA sequencing, RNA pull down assay, dual-luciferase reporter assay, rescue experiments and western blotting. Results We identified a novel circRNA circEAF2, which was downregulated in EBV + DLBCL and negatively correlated with EBV infection and DLBCL progression. In EBV-positive B lymphoma cells, circEAF2 overexpression induced lymphoma cell apoptosis and sensitized lymphoma cells to epirubicin. As mechanism of action, circEAF2 specifically targeted EBV-encoded miR-BART19-3p, upregulated APC, and suppressed downstream β-catenin expression, resulting in inactivation of Wnt signaling pathway and inhibition of EBV + DLBCL cell proliferation. In EBV-positive B-lymphoma murine models, xenografted tumors with circEAF2 overexpression presented decreased Ki-67 positivity, increased cell apoptosis and retarded tumor growth. Conclusions CircEAF2 counteracted EBV + DLBCL progression via miR-BART19-3p/APC/β-catenin axis, referring circEAF2 as a potential prognostic biomarker. Therapeutic targeting EBV-encoded miRNA may be a promising strategy in treating EBV-associated lymphoid malignancies.

Si-modified Mn-Ce oxide catalysts were prepared by the co-precipitation method for the selective catalytic reduction of NOx with NH3 (NH3-SCR). The doping of Si can improve significantly the NOx conversion...

Background: Real-world evidence on the effectiveness of COVID-19 vaccines marketed in China against the Omicron BA.2 variant remains scarce. Methods: A case-control study was conducted to estimate the vaccine effectiveness (VE) of COVID-19 vaccines marketed in China, including inactivated vaccines, an Ad5-nCoV vaccine, and a recombinant protein vaccine. The study included 414 participants infected with SARS-CoV-2 as cases and 828 individuals in close contact with COVID-19 patients as controls during the outbreak of the Omicron variant in April 2022 in Lu’an City, Anhui Province, China. Controls were selected from core close contacts based on a random sampling method with consecutive negative test results. Each case corresponded to two controls. Results: A total of 414 cases and 828 controls were included in this study. Compared to unvaccinated participants, the overall VE against Omicron BA.2 variant infection in the vaccinated group with any COVID-19 vaccine was 35.0% (95% CI: −9.1–61.3%), whereas the VE for booster vaccination was 51.6% (95% CI: 15.2–72.4%). Subgroup analysis showed that the overall VE of the Ad5-nCoV vaccine (65.8%, 95% CI: 12.8–86.6%) during the outbreak was higher than that of the inactivated vaccine (35.5%, 95%CI:-8.6–61.7%) and recombinant protein vaccine (13.0%, 95%CI:-76.1–57%). COVID-19 vaccines offered 46.8% (95% CI: 9.5–68.7%) protection for infection within 6 months, and no protection after 6 months. The VE of heterologous booster vaccination (76.4%, 95% CI: 14.3–93.5%) was considerably higher than that of homologous booster vaccination (51.8%, 95% CI: 9.6–74.3%). Conclusion: Booster vaccination of COVID-19 vaccines marketed in China offered more protection than full vaccination. A booster vaccination campaign for a booster dose after three doses of a recombinant protein vaccine must be urgently conducted. Keywords COVID-19 vaccines; Omicron; vaccine effectiveness; inactivated vaccine; Ad5-nCoV vaccine; recombinant protein vaccine

Metallized polymer films (MPFs) with superior self-healing properties are extremely attractive for application in energy storage capacitors. Self-healing behaviors allow MPFs to keep insulating between the local electrical breakdown region and the electrode, thereby reserving long-term operational viability of the capacitors. Polyimide (PI) is a type of well-developed polymer material with excellent mechanical and thermal stabilities, but it is deficient in intrinsic self-healing capabilities. This work reports a facile surface engineering strategy to endow metalized PI films with self-healing capabilities. By simple immersion of bare PI films in the solution of epoxy resin (ER) accompanied by curing of ER, PI films impregnated with ER (P-E films) not only show enhanced dielectric characteristics but also obtain excellent self-healing abilities upon multiple cycles of electrical breakdowns, even at a high temperature. For example, in comparison to bare PI films, PI films impregnated in ER solution with a solid content of 1 wt % (P-1%E) display improved initial Weibull breakdown strength (α

Invasive fractional flow reserve (FFR) measured by a pressure wire is a reference standard for evaluating functional stenosis in coronary artery disease. Coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) uses advanced computational analysis methods to noninvasively obtain FFR results from a single conventional coronary computed tomography angiography data to evaluate the hemodynamic significance of coronary artery disease. More and more evidence has found good correlation between the results of noninvasive CT-FFR and invasive FFR. CT-FFR has proven its potential in optimizing patient management, improving risk stratification and prognosis, and reducing total health care costs. However, there is still a lack of standardized interpretation of CT-FFR technology in real-world clinical settings. This expert consensus introduces the principle, workflow, and interpretation of CT-FFR; summarizes the state-of-the-art application of CT-FFR; and provides suggestions and recommendations for the application of CT-FFR with the aim of promoting the standardized application of CT-FFR in clinical practice.

This study aims to establish a stochastic link-based fundamental diagram (FD) with explicit consideration of two available sources of uncertainty: speed heterogeneity, indicated by the speed variance within an interval, and rainfall intensity. A stochastic structure was proposed to incorporate the speed heterogeneity into the traffic stream model, and the random-parameter structures were applied to reveal the unobserved heterogeneity in the mean speeds at an identical density. The proposed stochastic link-based FD was calibrated and validated using real-world traffic data obtained from two selected road segments in Hong Kong. Traffic data were obtained from the Hong Kong Journey Time Indication System operated by the Hong Kong Transport Department during January 1 to December 31, 2017. The data related to rainfall intensity were obtained from the Hong Kong Observatory. A two-stage calibration based on Bayesian inference was proposed for estimating the stochastic link-based FD parameters. The predictive performances of the proposed model and three other models were compared using K-fold cross-validation. The results suggest that the random-parameter model considering the speed heterogeneity effect performs better in terms of both goodness-of-fit and predictive accuracy. The effect of speed heterogeneity accounts for 18%–24% of the total heterogeneity effects on the variance of FD. In addition, there exists unobserved heterogeneity across the mean speeds at an identical density, and the rainfall intensity negatively affects the mean speed and its effect on the variance of FD differs at different densities.

Extranodal natural killer/T-cell lymphoma, nasal-type (ENKTL) is a type of rare and distinct entity of non-Hodgkin lymphoma with poor prognosis. It is important to evaluate the early treatment response accurately to decide further treatment strategy. 18F-FDG PET/CT plays an important role in response evaluation and prognostic prediction in some kinds of lymphomas. However, data available regarding patients with ENKTL are limited. Thus, in this prospective study, we analyzed the prognostic value of 18F-FDG PET/CT in ENKTL. Thirty-four patients with newly diagnosed ENKTL were enrolled in this phase 2 study (NCT02825147, July 7, 2016). The patients received pre-, mid-, and end-treatment 18F-FDG PET/CT scans. Deauville score (DS), maximal standardized uptake values (SUVmax), and the change in SUVmax (ΔSUVmax) were recorded for response assessment. The median follow-up period was 42.2 months. The 2-year overall survival (OS) and progression-free survival (PFS) were 82.4% and 73.5%, respectively. Univariate analysis revealed that Ann Arbor stage (P < 0.002), mid-treatment DS (P = 0.005), mid-SUVmax (P = 0.001), mid-∆SUVmax (P = 0.004), end-treatment DS (P < 0.001), and end-SUVmax (P = 0.014) were prognostic factors for OS. Ann Arbor stage (P = 0.001), mid-treatment DS (P = 0.008), mid-SUVmax (P = 0.029), mid-∆SUVmax (P < 0.001), and end-treatment DS (P =0.021) were of prognostic significance for PFS. Multivariate analysis showed that mid-SUVmax (P = 0.042) and DS at the middle (P = 0.050) and end (P = 0.044) of treatment were significant independent predictors of PFS. 18F-FDG PET/CT is useful for predicting the prognosis of ENKTL.

Introduction High altitude polycythemia (HAPC) is a common chronic disease at high altitudes. It is characterized by excessive erythrocytosis (≥190 g·L-1 in females or ≥210 g·L-1 in males). HAPC severely jeopardizes the health status of plateau dwellers. The Qinghai-Tibet plateau, with an elevation above 4000 m, is the highest plateau in the world. Both Han and Tibetan populations residing there face the threat of HAPC. Therapeutic erythrocytapheresis (TE) was introduced to Tibet as an alternative to phlebotomy in 2015. Methods In this study, we retrospectively analyzed 155 patients with HAPC treated with TE in Tibet. Routine blood testing values before and after TE were compared to evaluate treatment efficacy. The efficiency rate, defined as the rate of increase in red blood cell depletion attained by TE compared with 450 mL whole blood phlebotomy, was calculated using whole blood volume and hematocrit before and after treatment and used to identify patients who maintained a normal hemoglobin level in the year after the TE procedure. Results On average, TE reduced red blood cell levels by 1.5×1012·L-1, hemoglobin concentration by 52 g·L-1, and hematocrit by 14% (P Conclusions TE is a feasible therapeutic method to treat HAPC on the Qinghai-Tibet plateau. The efficiency rate is a useful tool to predict the expected interval between TE procedures.

A sensitive and portable microfluidic electrochemical array device (μFED) was developed for the immunoassay of trace amounts of human cardiac troponin I (cTnI), which is an attractive biomarker for acute myocardial infarction (AMI). The classical "sandwich" method was adopted for the immunoassay. The capture antibody was immobilized using a self-assembled monolayer (SAM) technique, and the process was reorganized to be compatible with the bonding process. The detection antibody was labeled with alkaline phosphatase (AP) for signal amplification. The performance of the μFED was improved by eliminating the shielding effect of the microelectrode array (MEA) integrated in the μFED. The effects of the interstice and the width of the MEA on the response peak current were analyzed and simulated. The concentration gradient, about 3% of the gradient at the surface, was considered as the criterion for estimation of the optimal interstice between electrodes, and its effectiveness was proved. A stable and miniaturized reference electrode was integrated in the μFED, and its potential deviation was less than 5 mV in 15 min. These efforts resulted in the enhanced immunoassay performance of the μFED. A low limit of detection of about 5 pg/mL was obtained in serum samples, and the response current was proportional to the logarithm of concentration from 50 pg/mL to 1 μg/mL. The immunoassay process was accomplished in 15 min. The μFED was thus qualified and is a promising candidate for point-of-care immunoassay of cTnI. Graphical abstract.

Introduction: Although public buses have been demonstrated as a relatively safe mode of transport, the number of injuries to public bus passengers is far from negligible. Existing studies of public bus safety have focused primarily on injuries caused by collisions. Surprisingly, limited effort has been devoted to identifying factors that increase the severity of passenger injuries in non-collision incidents. Method: Our study therefore investigated the injury risk of public bus passengers involved in collision incidents and non-collision incidents comparatively, based on a police-reported dataset of 17,383 passengers injured on franchised public buses over a 10-year period in Hong Kong. A random parameters logistic model was established to estimate the likelihood of fatal and severe injuries to passengers as a function of various factors. Results: Our results indicated substantial inconsistences in the effects of risk factors between models of non-collision injuries and collision injuries. The severity of passenger injuries tended to increase significantly when non-collision incidents occurred due to excessive speed of bus drivers, on double-decker buses, in less urbanized areas, in winter, in heavy rains, during daytime, and at night without street lighting. Elderly female passengers were also found more likely to be fatally or severely injured in non-collision incidents if they lost their balance while boarding, alighting from, or standing on a bus. In comparison, the following factors were associated with a greater likelihood of fatal or severe injuries in collision incidents: elderly female passengers, standing passengers who lost balance, buses out of driver control, double-decker buses, collisions with vehicles or objects, and less urbanized areas. Practical Applications: Based on our comparative analysis, more targeted countermeasures, namely “4E” (engineering, enforcement, emergency, and education) and “3A” (awareness, appreciation, and assistance), were recommended to mitigate collision injuries and non-collision injuries to public bus passengers, respectively.

The diagnostic value of pretreatment 18F-FDG PET/CT in early-stage extranodal natural killer/T-cell lymphoma (ENKTL) is established, but its prognostic value is still unclear. We conducted 18F-FDG ...

The spreading of novel coronavirus (SARS-CoV-2) has gravely impacted the world in the last year and a half. Understanding the spatial and temporal patterns of how it spreads at the early stage and the effectiveness of a governments' immediate response helps our society prepare for future COVID-19 waves or the next pandemic and contain it before the spreading gets out of control. In this article, a susceptible-exposed-infectious-removed model is used to model the city-to-city spreading patterns of the disease at the early stage of its emergence in China (from December 2019 to February 2020). Publicly available reported case numbers in 312 Chinese cities and between-city mobility data are leveraged to estimate key epidemiological characteristics, such as the transmission rate and the number of infectious people for each city. It is discovered that during any given time period, there are always only a few cities that are responsible for spreading the disease to other cities. We term these few cities as transmission centers. The spatial and temporal changes in transmission centers demonstrate predictable patterns. Moreover, rigorously designed experiments show that in controlling the disease spread in a city, non-pharmaceutical interventions (NPIs) implemented at transmission centers are more effective than the NPI implemented in the city itself. These findings have implications on the control of an infectious disease at the early stage of its spreading: implementing NPIs at transmission centers at early stages is effective in controlling the spread of infectious diseases.

The aim of this study was to investigate the impact of nitroglycerin (NTG) on the assessment of computed tomography-derived fractional flow reserve (CT-FFR).Seventy-seven patients with suspected coronary artery disease were recruited, and they underwent computed tomography angiography (CCTA) before and after NTG administration. The CT-FFRs were compared at 2 CCTAs. The difference was compared using the Wilcoxon signed rank test. Patients were divided into normal and stenosis groups according to CCTA results. Vessels in the stenosis group were further divided into different groups based on coronary artery calcium score (CACS) and stenosis degree. The poststenotic CT-FFR differences before and after NTG (DCT-FFR) were calculated to evaluate the impact of stenosis degree and CACS. Terminal CT-FFRs derived from CCTAs before and after NTG in total and vessel-specific levels were compared in the normal group.Of 47 patients in the stenosis group, poststenotic CT-FFR was significantly increased after NTG at per-vessel level. By taking CT-FFR of 0.75 or lower as the threshold, 5 and 4 patients showed abnormal CT-FFR before and after NTG, respectively. No significant differences were noted among the various stenosis degree and CACS groups regarding DCT-FFR. Of 30 patients in the normal group, terminal CT-FFR was significantly increased after NTG in total level and vessel-specific level of left anterior descending and right coronary artery, but not in the left circumflex.Both post lesion and distal vessel CT-FFR significantly improved after the administration of GTN with the degree of change not affected by stenosis severity or CACS.

This paper concerns the fully nonlinear fluid–structure interaction (FSI) of Large-scale floating photovoltaics (LFPV) in waves. The Euler Bernoulli–von Kármán beam models the structure while potential flow represents the fluid. A set of coupled dynamical equations is established. The fully analytic solution is sought with the unified Stokes perturbation method. The characteristic equation is derived up to third order, which has not been reported in literature before. The expressions obtained from the solution are applied to two typical cases of a pontoon LFPV and a membrane LFPV, with physical parameters from literature. The comparison with literature demonstrates our methodology for the membrane-type in waters of arbitrary depth and pontoon-type in relatively deep waters.

The present research analyzes the nonlinear fluid–structure interaction (FSI) of free surface waves with large-scale polymer offshore floating photovoltaics (LPOFPV). The floating structure is modeled as a nonlinear Euler Bernoulli–von Kármán (EBVK) beam coupling with water beneath. The EBVK theory takes the in-plane force into consideration to account for the moderately large deflection slopes in LPOFPV. A multi-time-scale perturbation method leads to hierarchic partial differential equations by introducing the wave steepness squared as the perturbation. The analytical solution of the proposed nonlinear FSI model is obtained up to the second order. Pontoon structures and LPOFPV are studied and compared. The asymptotic solution provides the expressions of the propagating wave through the coupled system and its frequency–amplitude dispersion relation in a closed-form. A property of the solution is that the progressive plane wave through the coupled system remains linear for small dimensionless amplitudes, and features a second order correction for moderately large dimensionless amplitudes. Furthermore, it is also theoretically proven that no resonance occurs in the considered infinite problem. The proposed approach can be extended to the nonlinear coupling between a EBVK beam and Stokes waves.

The incidence of diffuse large B-cell lymphoma (DLBCL) increases by age and older DLBCL are commonly related to poor prognosis. However, the clinical and biological features of older DLBCL patients remain to be determined. A total of 2,445 patients with newly diagnosed DLBCL were enrolled for clinical data analysis according to age at diagnosis, with tumor samples of 1,150 patients assessed by DNA sequencing and 385 patients by RNA sequencing. Older DLBCL presented advanced disease stage, elevated serum lactate dehydrogenase, poor performance status, multiple extranodal involvement, high percentage of double expressor subtype, and adverse clinical outcome. According to molecular features, age was positively correlated with the oncogenic mutations of PIM1, MYD88, BTG2, CD79B, TET2, BTG1, CREBBP, TBL1XR1, and with the MYD88-like genetic subtype. These oncogenic mutations were involved in B-cell receptor/NF-κB signaling, B-cell differentiation, and histone acetylation based on biological functions. Older DLBCL also manifested reduction in CD4+ naïve T and CD8+ naïve T cells, and also increased recruitment of exhausted T cells and macrophages, leading to immunosuppressive tumor microenvironment. Our work thus contributes to the understanding of aging-related oncogenic mutations and tumor microenvironment alterations in lymphoma progression, and may provide new insights to mechanism-based targeted therapy in DLBCL.

Upper limb paralysis and movement disorders resulting from neurologic injuries can be treated with an upper limb exoskeleton robot that assists with movement retraining. Cable-driven exoskeletons have been widely studied because of their lightness, compact structure, and low cost. However, the problems of shoulder squeeze force and system stability have not been solved. In this article, we present a prototype parallel cable-driven shoulder mechanism with series springs. The theoretical analysis suggests that the stability of the mechanism is improved compared with that of the previous mechanism, and the effects of stiffness, upper limb weight, and mechanism parameters on the shoulder joint extrusion pressure are analyzed by simulation and experimental results. The results show that this mechanism plays an important role in reducing or eliminating the shoulder squeeze pressure and improving the stability of the mechanism. Moreover, the mechanism has good portability and can be combined with other exoskeletons to facilitate various robot-assisted upper limb rehabilitation training.

The carbon emissions growth in the construction industry hinders the achievement of global carbon-neutral target, especially in China. Studies suggest that developing low-carbon technologies is an effective means of achieving the low-carbon transition (LCT) in the construction industry. However, these studies ignore the fact that the LCT is a complex and systemic issue that needs to consider the interaction of technical and non-technical factors. Thus, based on the socio-technical system transition theory, this study identified the influencing factors and constructs a dynamics model to simulate the dynamic changes of the LCT in China's construction industry under different scenarios. The results showed that multi-level factors coordinated to drive the LCT of the construction industry. Environmental factors played a weak role and the effectiveness of government intervention decreased with the transition process. On the contrary, technological and market factors were indispensable drivers and especially played a dominant role during the later stages of the transition. Finally, the LCT pathway of China's construction industry was proposed based on the results. These findings expand the boundary of theoretical research on industrial transition and provide a decision-making reference for the advancement of international carbon-neutral work.

Smaller volume/weight and higher output power/energy density are always the goals of electrochemistry energy devices. Here, a simple strategy is proposed to prepare an integrated gas diffusion electrode (GDE) with high conductivity through skin electroplating. The skin electroplating is the combination of magnetron sputtering and spatial confinement electroplating. The electroplated metal obtained by skin electroplating is uniformly, continuously, and tightly attached to the surface of carbon paper like a layer of skin. Uniform and continuous electroplating metal layer endows the integrated electrode excellent conductivity with the square resistance as low as 27 mΩ sq

Assembly is an essential part of complex product manufacturing. Due to the complexity of assembly operations and rapidly changing market demands, it is a labor-intensive industry with insufficient automation improvement. Force control methods are developed to allow industrial robots to do Contact-Rich manipulation with force sensors fixed at the end-effect. Deep Reinforcement Learning (DRL) provides a method to learn assembly skills by trial and error. Nevertheless, the performance of the framework combining DRL and force control is sensitive to the hyper-parameters, which limits the application in manufacturing. In this work, we analyze the force control based on primary impedance control and propose a method that designs hyper-parameters according to task information, thus speeding up learning and making the process safer by adding a constraint to the exploration space.

PurposeThe aim of the study was to delineate the disease characteristics, the initial treatment patterns, and survival in patients with mantle cell lymphoma (MCL) managed in the real world.MethodsData of 518 MCL patients from 5 major Chinese Hematology Centers in the period from 2007 to 2017 were retrospectively analyzed.ResultsThe median age was 58 years. Of the patients, 88.6% had Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–1 and 80.7% had advanced-stage disease. Ki67 expression was n = 71) underwent consolidative autologous stem cell transplantation (ASCT), and 19.3% (n = 100) received novel agents containing first-line regimens. With a median follow-up time of 52 months, the 3- and 5-year overall survival (OS) rates were 73.7% and 61.4%, respectively. Age ≤60 years, ECOG PS 0–1, stages I–II, normal lactate dehydrogenase (LDH), absence of bone marrow involvement, Ki67 p vs. 55.2%, p = 0.076). High-dose cytarabine-containing chemotherapy showed significant clinical benefit in 5-year OS (72.1% vs. 55.9%, p = 0.010). Patients with ASCT had better 5-year OS in the younger (≤60 years) age group (87.2% vs. 64.8%, p = 0.002).ConclusionThis large retrospective dataset unequivocally confirmed the survival advantage afforded by cytarabine-containing regimen and ASCT in a first-line setting under real-world management in the rituximab era.

Purpose To develop a weakly supervised deep learning (WSDL) method that could utilize incomplete/missing survival data to predict the prognosis of extranodal natural killer/T cell lymphoma, nasal type (ENKTL) based on pretreatment 18F-FDG PET/CT results. Methods One hundred and sixty-seven patients with ENKTL who underwent pretreatment 18F-FDG PET/CT were retrospectively collected. Eighty-four patients were followed up for at least 2 years (training set = 64, test set = 20). A WSDL method was developed to enable the integration of the remaining 83 patients with incomplete/missing follow-up information in the training set. To test generalization, these data were derived from three types of scanners. Prediction similarity index (PSI) was derived from deep learning features of images. Its discriminative ability was calculated and compared with that of a conventional deep learning (CDL) method. Univariate and multivariate analyses helped explore the significance of PSI and clinical features. Results PSI achieved area under the curve scores of 0.9858 and 0.9946 (training set) and 0.8750 and 0.7344 (test set) in the prediction of progression-free survival (PFS) with the WSDL and CDL methods, respectively. PSI threshold of 1.0 could significantly differentiate the prognosis. In the test set, WSDL and CDL achieved prediction sensitivity, specificity, and accuracy of 87.50% and 62.50%, 83.33% and 83.33%, and 85.00% and 75.00%, respectively. Multivariate analysis confirmed PSI to be an independent significant predictor of PFS in both the methods. Conclusion The WSDL-based framework was more effective for extracting 18F-FDG PET/CT features and predicting the prognosis of ENKTL than the CDL method.

In this research, a new, innovative method of differential temperature rolling with induction heating was proposed to prepare CP-Ti/AA6061-Al laminated composites in an argon protective atmosphere. The homogeneous deformation of titanium and aluminium was obtained, and the effect of rolling reduction on the mechanical properties and microstructure of the laminated composites was investigated in detail. The results showed that the interfacial bonding strength gradually increased with the rolling reduction, which was attributed to the increased mechanical meshing area and the wider element diffusion layer, leading to the microstructure of shear surface changing from brittle fracture to ductile fracture. When the rolling reduction was 50.5%, the shear strength of the Ti/Al clad plates reached a peak value of 122 MPa, close to the shear strength of the aluminium matrix (131 MPa). Ti/Al composites could improve the ultimate tensile strength of a single aluminium sheet. After tensile failure, the interfacial delamination length decreased from 7.64 mm to 0.22 mm with the reduction ranging from 17.5% to 50.5%, indicating that the strong interface could effectively impede the expansion of the interfacial delamination cracks, resulting in the improved resistance to delamination of composites. In summary, through the unique form of assembly and heating, the Ti/Al laminated composites achieved satisfactory microstructure and mechanical properties.

Summary Background Anthracycline dose optimisation in the treatment of diffuse large B-cell lymphoma has rarely been tested. We aimed to find out whether R-CEOP70 was non-inferior to R-CHOP50 with less cardiotoxicity, and whether R-CEOP90 had a superior efficacy to R-CHOP50 or R-CEOP70 with acceptable toxic effects. Methods In this multicentre, phase 3, randomised, controlled study (NHL-001), patients with newly diagnosed diffuse large B-cell lymphoma or follicular lymphoma grade 3B were enrolled from 20 centres of the Multicenter Hematology–Oncology Programs Evaluation System in China. Young patients (16–60 years) were randomly assigned 1:1:1 (block size of six) to six courses of R-CHOP50, R-CEOP70, or R-CEOP90, and older patients (61–80 years) were assigned 1:1 (block size of four) to R-CHOP50 or R-CEOP70. Patients were randomly assigned using computer-assisted permuted-block randomisation. Investigators and patients were not masked to treatment assignment. In the R-CHOP50 group, patients were given rituximab 375 mg/m2 intravenously on day 0, cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1·4 mg/m2 (maximum dose 2 mg) intravenously on day 1, and prednisone 60 mg/m2 (maximum dose 100 mg) orally from day 1–5; in the R-CEOP70 group, epirubicin 70 mg/m2 replaced doxorubicin; and in the R-CEOP90 group, high dose epirubicin 90 mg/m2 replaced doxorubicin. All patients received two additional courses of rituximab 375 mg/m2 intravenously every 21 days. Consolidation radiotherapy was given to patients with bulky disease at diagnosis or residual disease at the end of treatment. The primary endpoint was 2-year progression-free survival. The non-inferiority margin for R-CEOP70 versus R-CHOP50 was defined by hazard ratio [HR] as the upper limit of its 95% CI being no greater than 1·50. Analysis of efficacy and safety were of the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT01852435 . Findings From May 15, 2013, to March 16, 2016, a total of 648 patients were enrolled, including 404 (62%) young patients (R-CHOP50 [n=135], R-CEOP70 [n=134], or R-CEOP90 [n=135]), and 244 (38%) older patients (R-CHOP50 [n=122] or R-CEOP70 [n=122]). Four patients were excluded from the study for consent withdrawal and one patient for misdiagnosis before treatment. The 2-year progression-free survival in the R-CHOP50 group was 72·5% (95% CI 66·6–77·6) and in the R-CEOP70 group was 72·4% ([66·5–77·5]; HR 1·00 [0·73–1·38]; p=0·99). The non-inferiority was met and adverse events were similar between the two groups. Fewer patients in the R-CEOP70 group (14 [13%] of 110) presented with over 10% decrease in left ventricular ejection fraction (LVEF) than those in the R-CHOP50 group (31 [29%] of 108) at 3 years after remission. For young patients, the 2-year progression-free survival in the R-CEOP90 group was 88·8% (82·1–93·1) and was significantly improved compared with the R-CHOP50 group (75·9% [67·7–82·3]; 0·44 [0·25–0·76]; p=0·0047) and the R-CEOP70 group (77·4% [69·4–83·7%]; 0·49 [0·27–0·86]; p=0·017). Grade 3–4 neutropenia occurred more frequently in the R-CEOP90 group (97 [72%] of 134) than in the R-CHOP50 group (87 [65%] of 133) and R-CEOP70 group (84 [63%] of 133) in young patients but without further increase of clinically significant infections. Fewer patients in the R-CEOP70 group (7 [11%] of 66) and in the R-CEOP90 group (10 [13%] of 79) presented with more than 10% decrease in LVEF than those in the R-CHOP50 group (17 [26%] of 66) at 3 years after remission. Interpretation R-CEOP70 could serve as an alternative regimen to R-CHOP50 with mild long-term cardiotoxicity. Young patients with diffuse large B-cell lymphoma might benefit from high-dose epirubicin. Epirubicin is an alternative drug to doxorubicin in regular R-CHOP with mild long-term cardiotoxicity. Funding National Natural Science Foundation of China, National Key Research and Development Program, Shanghai Commission of Science and Technology, Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support, Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine, Clinical Research Plan of Shanghai Hospital Development Center, and Chang Jiang Scholars Program.

Although the importance of human factors to crash occurrence has been demonstrated previously, the roles played by human factors in motorcycle killed and severely injured (KSI) crashes have remained unclear. One aim of our study is therefore to empirically determine the relative contribution of illegal behavior to motorcycle KSI crashes, conditional on real-world collisions between motorcycles and motor vehicles. Given that a crash is typically the synthetical result of human, vehicle, roadway, and environmental factors, another aim is to identify high-risk scenarios where inappropriate behavior is more likely to result in severe injuries for motorcyclists through interactions with other related factors. Based on a comprehensive dataset of 4587 police-reported crashes involving motorcycles during 2015–2017 in Hunan province, China, a data mining technique namely classification and regression tree was elaborately employed. Our results demonstrated the illegal behavior of the striking motor-vehicle drivers as one of the most dominant factors contributory to motorcycle KSI crashes, with a normalized importance value of 36.9%. We also confirmed collision object (i.e., collision with heavy or light vehicles) and helmet use of motorcyclists as determinants influencing motorcycle rider injury severities. Two types of extreme high-risk traffic scenarios were identified accordingly. A motorcycle rider was hit at weekends by a heavy motor-vehicle driver who was driving without license, driving a substantial vehicle, speeding, changing lanes illegally or driving in the wrong direction, and a motorcyclist was hit on weekdays by a heavy motor-vehicle driver aged 18–34 or 45–54, who was driving without license, driving a substantial vehicle, speeding, changing lanes illegally or driving in the wrong direction. Our findings are expected to shed more light on a deeper understanding of the illegal driving behavior as causation of motorcycle KSI crashes.

In previous studies, the safety-in-numbers effect has been found, which is a phenomenon that when the number of pedestrians or cyclists increases, their crash rates decrease. The previous studies used data from highly populated areas. It is questionable that the safety-in-numbers effect is still observed in areas with a low population density and small number of pedestrians. Thus, this study aims at analyzing pedestrian crashes in a suburban area in the United States and exploring if the safety-in-numbers effect is also observed. We employ a Bayesian random-parameter Poisson-lognormal model to evaluate the safety-in-numbers effects of each intersection, which can account for the heterogeneity across the observations. The results show that the safety-in-numbers effect were found only at 32 intersections out of 219. The intersections with the safety-in-numbers effect have relatively larger pedestrian activities whereas those without the safety-in-numbers effect have extremely low pedestrian activities. It is concluded that just encouraging walking might result in serious pedestrian safety issues in a suburban area without sufficient pedestrian activities. Therefore, it is plausible to provide safe walking environment first with proven countermeasures and a people-oriented policy rather than motor-oriented. After safe walking environments are guaranteed and when people recognize that walking is safe, more people will consider walking for short-distance trips. Eventually, increased pedestrian activities will result in the safety-in-numbers effects and walking will be even further safer.