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Objective The aim of this study was to evaluate the efficacy and safety of the biosimilar candidate of adalimumab (HS016) compared with adalimumab (Humira) for the treatment of active ankylosing spondylitis. Methods A multicenter, randomized, double-blind, parallel, positive control, phase III clinical trial was conducted at 28 locations in China. Patients with active ankylosing spondylitis were randomized in a 2:1 ratio to subcutaneously receive 40 mg of either HS016 or adalimumab every other week for 24 weeks. The primary endpoint was to achieve at least a 20% improvement (ASAS20) in patients at 24 weeks according to the Assessment of Spondyloarthritis International Society criteria. The secondary endpoint included other efficacy assessment parameters, health evaluations, safety, pharmacokinetic, and immunogenicity parameters. Results Following the random assignment of 648 patients into HS016 (n = 416) and adalimumab (n = 232) groups, no significant difference was found in the ASAS20 response rates at 24 weeks between the HS016 (364/416, 87.5%) and adalimumab (209/232, 90.1%) treatments and the difference between the response rates (− 2.59%; 90% confidence interval [CI] − 6.77 to 1.60) was within the predefined equivalence margin (± 15%). There were also no significant differences when the secondary endpoints were compared (all p > 0.05). Similarly, the rates of treatment-emergent adverse events (TEAEs) were not significantly different between the two groups, with most TEAEs being mild to moderate. Only nine severe cases were found, including seven within the HS016 group, three (0.7%) of which were tuberculosis cases. Plasma concentrations of HS016 and adalimumab from weeks 12 to 14 were similar during the steady-state period and steady-state maximal concentration (Cmax,ss) was equivalent for HS016 (7356.6 ng/mL) and adalimumab (7600.3 ng/mL). The accumulated proportion of patients with positive human anti-human antibodies (HAHAs) at week 24 was 326/412 (79.1%) in the HS016 group and 183/229 (79.9%) in the adalimumab group (p > 0.05), while the accumulated proportion of patients with positive neutralizing antibody (NAb) tests were 72/412 (17.5%) in the HS016 group and 43/229 (18.8%) in the adalimumab group (p > 0.05). Conclusion HS016 resembled adalimumab in efficacy and safety over the 24-week treatment period. Trial registration number ChiCTR1900022520. Electronic supplementary material The online version of this article (10.1007/s40259-020-00408-z) contains supplementary material, which is available to authorized users.

Conversational recommender systems elicit user preference via interactive conversational interactions. By introducing conversational key-terms, existing conversational recommenders can effectively reduce the need for extensive exploration in a traditional interactive recommender. However, there are still limitations of existing conversational recommender approaches eliciting user preference via key-terms. First, the key-term data of the items needs to be carefully labeled, which requires a lot of human efforts. Second, the number of the human labeled key-terms is limited and the granularity of the key-terms is fixed, while the elicited user preference is usually from coarse-grained to fine-grained during the conversations. In this paper, we propose a clustering of conversational bandits algorithm. To avoid the human labeling efforts and automatically learn the key-terms with the proper granularity, we online cluster the items and generate meaningful key-terms for the items during the conversational interactions. Our algorithm is general and can also be used in the user clustering when the feedback from multiple users is available, which further leads to more accurate learning and generations of conversational key-terms. We analyze the regret bound of our learning algorithm. In the empirical evaluations, without using any human labeled key-terms, our algorithm effectively generates meaningful coarse-to-fine grained key-terms and performs as well as or better than the state-of-the-art baseline.

Immunoglobulin G4-related disease (IgG4-RD) is an autoimmune inflammatory disease characterized by infiltration of IgG4+ plasma cells that can simulate a tumor manifesting as a tumor-like mass. This disease involves the pancreas, biliary tract, kidneys, salivary glands, lymph nodes, aorta, and retroperitoneum amongst other organs. However, testicular involvement is a rare entity in this disease. The treatment of testicular involvement in IgG4-RD is currently controversial. We present the case of a 65-year-old man with swelling and pain in his right scrotum three months ago. On examination, a mobile mass of approximately 2 cm in diameter was found in the right scrotum. Serological tests showed elevated levels of IgG4 and negative for tumor markers. Enhanced computed tomography of the scrotum showed a nodular hyperdense shadow with a diameter of approximately 23 mm on the right epididymis. Pathological biopsy of the right epididymis showed infiltration of plasma cells, lymphocytes, and a few neutrophils. IgG4+ plasma cells stained positive, with an IgG4/IgG ratio of more than 40% and more than 30 IgG4+ plasma cells per high-power field. A diagnosis of IgG4-RD involving the testicles was made. Prednisone 30 mg/d was given for three weeks. No scrotum swelling or pain was observed at the follow-up after six months. IgG4-related disease should be considered whenever a mass-like lesion with typical histomorphologic features involving multiple organs/anatomical sites is encountered. The testicles are an important male reproductive organ, especially for young male patients with fertility requirements. For patients with IgG4-RD testicular involvement, surgical or medical treatment requires further study.

Background IL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population. Methods 989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods. Results A four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2). Conclusions Gene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

Objective The equivalence of the biosimilar HS016 to adalimumab (Humira) for the treatment of active ankylosing spondylitis (AS) patients has been previously validated. The aim was to compare the efficacy of HS016 and adalimumab in stratified subgroups at different time points using Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S) and short form 36 (SF-36) questionnaires. Methods We carried out a multicenter, randomized, double-blind, parallel, positive control, phase 3 trial of patients with active AS. They were selected randomly to be subcutaneously administered 40 mg HS016 or adalimumab every 2 weeks for a total treatment period of 24 weeks in a 2:1 ratio. A health surveys were used to assess mental and physical improvements of patients as well as other factors. Results HAQ-S revealed that changes in scores from baseline in both groups were time dependent until 14 weeks and that during the first 4 weeks of treatment the changes declined rapidly. The SF-36 health survey revealed that both HS016 and adalimumab produced rapid beneficial effects against AS during the first 2 weeks of therapy, which gradually declined between 2 and 12 weeks and flattened out after 12 weeks until 24 weeks. Conclusion This trial demonstrated that both HS016 and adalimumab produced rapid improvements in symptoms during the first 2 weeks of treatment. These findings suggest that HS016 is an alternative economical treatment for Chinese AS patients producing a rapid amelioration of symptoms, aiding them to recover their lifestyle satisfaction. Trial registration http://www.chictr.org.cn/enindex.aspx, ChiCTR1900022520, retrospectively registered. Key points • HS016 and adalimumab produced rapid AS symptom improvements during the first 2 weeks followed by a slowdown of improvements until week 4 with afterwards few improvements evaluated by HAQ-S • The improvements according to the short form of the 36 (SF-36) questionnaires revealed similar trends as for HAQ-S • There was no significant difference in HAQ-S and SF-36 scores between HS016 and adalimumab

Rationale: Hydroxychloroquine has excellent anti-inflammatory and immunomodulatory effects as one of the antimalarial drugs. In particular, hydroxychloroquine was once widely used as a treatment for the new coronavirus pneumonia epidemic in 2020. Retinopathy caused by hydroxychloroquine is normally irreversible, but little attention has been paid to it. Patient concerns: A 38-year-old young Chinese woman was taking oral hydroxychloroquine 400 mg daily to control lupus disease activity for six years after the diagnosis of systemic lupus erythematosus (SLE). She did not have any history of eye disease and was admitted to the hospital with a sudden blurring of both eyes. Diagnoses: The diagnosis of retinal macular degeneration caused by hydroxychloroquine was made after excluding other interfering diseases based on the patient's long-term use of hydroxychloroquine and the results of the eye examination. Interventions: The patient was discontinued from hydroxychloroquine. To control the recurrence of SLE, she was given intravenous methylprednisolone, oral tacrolimus and mycophenolate. Meanwhile, she was asked to take extra care of her eyes and to come to the hospital every three months to have her vision checked. Outcomes: The patient's blurred vision improved one week later. Three months later, her vision examination showed no further decline (0.4 in the right eye and 0.6 in the left eye). Meanwhile, the SLE disease activity index (SLEDAI) decreased from six points to five points currently. Lessons: Retinopathy caused by hydroxychloroquine is irreversible and there is no particularly effective treatment. Discontinuation of hydroxychloroquine, better daily eye protection, and regular vision checks are the keys to preventing retinopathy. Although hydroxychloroquine causing retinal toxicity was mentioned several years ago, the rate and severity of retinal toxicity require further research. How to get more patients to take care of their eyes requires continuous and increased education by doctors.

Background No reliable biological marker for the diagnosis of asthma in younger children is currently available. In this study, we analyzed the differences in basophil activation test (BAT) results among children with recurrent wheezing episodes who had different asthma outcomes. Results A prospective cohort study was conducted in children aged under 5 years who visited our pediatric respiratory clinic and ward for wheezing. After enrollment, the participants provided samples for a CD63-based BAT performed using an inhalant allergen mixture as a stimulant. Histories of personal allergic diseases and family allergic diseases were evaluated by using a questionnaire. All participants were followed up for 2 years, and their asthma outcomes were evaluated at the end of the follow-up period. The correlation between the BAT results and asthma outcomes was analyzed. Of the 45 originally enrolled children, 38 completed both the follow-up and a BAT. After stimulation with the inhalant mixture, the CD63 expression on basophils and the rate of positive CD63-based BAT results in children diagnosed with asthma were both significantly higher than those in children who were not diagnosed with asthma (p p Conclusions Our pilot study indicates that CD63-based BAT has potential clinical value for predicting asthma outcome in young children with wheezing episodes.

Objectives: A phase III, 24-weeks Chinese clinical trial demonstrated that efficacy and safety outcomes of treatments with 40 mg/0.8 ml HS016 (n = 416) or adalimumab (n = 232) for active ankylosing spondylitis (AS) patients was comparable. In the present study, a subanalysis of the clinical trial was conducted to determine whether also individual efficacy indicators were comparable between HS016 and adalimumab.Methods: The individual efficacy indicators total and nocturnal back pain, global assessment of disease activity, swollen joint count, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index, Bath AS Functional Index, Bath AS Metrology Index and chest expansion, were assessed at baseline and every 2 weeks during the treatment period.Results: This subanalysis revealed no significant difference between the patient groups treated with HS016 or adalimumab for any individual efficacy indicator investigated at any time point (all p > 0.05) beside faster total back pain score improvements in the adalimumab group on week 10, 12 and 22, which became equal at week 24. Among these indicators, chest expansion showed a significant increase at each time point compared with baseline, whereas all other efficacy indicators showed significant decreases compared with baseline at each time point (all p < 0.05). All efficacy indicators had increased or decreased rapidly by week 2, and the values continued to increase/decrease up to week 12, with subsequent smaller changes thereafter up to week 24 of treatment.Conclusion: The response trajectory of most individual efficacy indicators was comparable between HS016 and adalimumab at each time point during the 24 weeks of the trial.Clinical Trial Registration:http://www.chictr.org.cn/showproj.aspx?proj=37910, identifier [ChiCTR1900022520]

Background：Wheezing is an important respiratory symptom in the diagnosis of asthma. However, wheezing is common in children and often related to viral infection. This and the lack of reliable biological indicators for asthma create difficulty in diagnosing asthma early in children. Objective: In this study, the levels of CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children with different diagnostic outcomes were investigated to determine correlation with a diagnosis of asthma and to assess their potential clinical value as a biological indicator for this disease. Methods: A prospective study was performed with a cohort of wheezing children aged 3 months to 6 years hospitalized in the Division of Pulmonary Pediatrics at Shanghai Xinhua hospital and Shanghai children’s medical center affiliated to Shanghai Jiao Tong University School of Medicine from July 2017 to March 2018. After inclusion, the level of serum IgE, presence of allergen-specific serum IgE (sIgE) and proportion of circulating CD4+CCR6+CRTh2+ memory Th2 cells were counted. In addition, the patients’ personal and family histories of allergic disease were acquired by questionnaire. The children were followed up annually over 2 years by telephone call with a guardian to record whether the child had been diagnosed with asthma. The accuracy of an increased proportion of CD4+CCR6+CRTh2+ memory Th2 cells as an indicator of asthma was assessed. Results: A total of 43 children completed follow-up. The median of circulating CD4+CCR6+CRTh2+ memory Th2 cells in wheezing children diagnosed with or without asthma was 1.2%(0.8%~2.9%) and 0.6%(0.1%~0.9%), respectively, and was significantly higher in children diagnosed with asthma (P 0.05). Conclusion: Our exploratory study found that an increase in the level of circulating CD4+CCR6+CRTh2+ memory Th2 cells could be used as a biological indicator for early diagnosis of asthma, especially in predicting the risk of asthma in atopic children.

Osteoporosis is a metabolic bone disease that is characterized by low bone mass and micro-architectural deterioration of bones. The mechanism underlying this disease implicates an imbalance between bone resorption and bone remodeling. In 2002, the US Food and Drug Administration (FDA) approved Teriparatide for the treatment of osteoporosis, and so far, this compound is the only permitted osteoanabolic. However, as a structurally flexible linear peptide, this drug may be further optimized. In this study, we develop a series of novel N-acetyl glucosamine glycosylation derivatives of Teriparatide and examine their characteristics. Of the analyzed compounds, PTHG-9 exhibits enhanced helicity, greater protease stability, and increased osteoblast differentiation promoting ability compared with the original Teriparatide. Accordingly, PTHG-9 is suggested as a therapeutic candidate for postmenopausal osteoporosis (PMOP) and other related diseases. The successful development of an enhanced osteoporosis drug proves that the method proposed herein can be used to effectively enhance the chemical and biological properties of linear peptides with various biological functions.

Background: Caffeine citrate has been approved in China for the management of apnea of prematurity. This clinical trial was conducted as a condition of regulatory approval. The aim was to confirm the efficacy of caffeine citrate in the treatment of recurrent intermittent hypoxia and bradycardia in preterm newborns with primary apnea.Objectives: The primary outcome was the change from baseline in the number of apnea events after loading dose administration of caffeine citrate. Secondary efficacy outcomes included the change from baseline in apnea events after 2 and 4 weeks of maintenance doses.Methods: This was a multicenter, prospective longitudinal open-label, single-arm study. Neonates who had experienced at least four apnea events during a 24 h period received a loading dose of caffeine citrate 20 mg/kg; those who required additional maintenance doses received 5 mg/kg/day (titrated up to 10 mg/kg/day in case of insufficient response). The number of apnea events was recorded for 6–12 h prior to the loading dose (baseline), and for 12 h post-dose, following the loading dose and at Weeks 2 and 4 (during maintenance).Results: A total of 247 neonates received the loading dose, who had a significant reduction from baseline of 3.9 events (p < 0.001) in the mean number of apnea events. The subset of neonates who required maintenance doses also had significant reductions in the number of events at all visits (p < 0.001 for all). A total of 79.4% of participants had at least one adverse event, but only one non-serious and no serious events were considered related to treatment.Conclusions: In this large, prospective, open-label study, premature infants with a history of apnea who received caffeine citrate were significantly less likely to experience further apnea events.

This paper describes a rapid method for validation and visualization of agile Earth-observation satellites scheduling. Benefited from the previous work, various algorithms are proposed for scheduling the observations of agile satellites. However, the satellite maneuvers are three- dimensional, this characteristic makes it difficult for the operation engineers to validate and interpret the scheduled solutions. They have to plot these attitude data to analyze different situations such as an observing phase or a slew maneuver. Finally, one tries to imagine the three-dimensional situations from many one-dimensional plots, which is time-consuming and susceptible to errors. Moreover, now it is low-efficiency to deal with the data about ephemeris, targets, etc., because different software platforms are required. In this research, a validation and visualization method is suggested to overcome this barrier. It is successful to integrate the Satellite Tool Kit ActiveX and the C# programming language. Based on the embedded scheme, all the interaction and assessment can be visualized. Practical techniques for modelling satellite objects, sensor objects, target objects and satellite attitudes are presented. Such a method has been applied for Chinese agile satellites project, and a software interface has been developed. The simulation results indicate that the proposed method is intuitive and efficient. Note that this method is general, and thus it can be applied to other Earth observation missions. Enough details are provided for interested readers to develop the software interface.

High-quality water-soluble Ag-In-S/ZnS core/shell quantum dots have been successfully synthesized via a facile and green method, with mercaptosuccinic acid and sodium citrate as dual ligands in one pot. The fabricated quantum dots exhibit excellent optical characteristics, including photoluminescence quantum yield (PLQY) of up to 50%, and the obvious first excition absorption peak. The emission peak of Ag-In-S/ZnS core/shell quantum dots can be tuned from 507 to 580 nm which covers the most of the visible light. Finally, the as-prepared Ag-In-S core quantum dots can be used directly in ion probe, achieved the direct visual inspection of Pb2+.

Tumbling debris has become a great threat to orbit activities. Contactless interaction is a novel concept for active debris removal, through which the tumbling debris no longer rotates freely but is under control. The contactless interaction method aims to de-tumble the debris and then maintain desired relative states between the spacecraft and debris. The spacecraft is simultaneously stabilized through three-axis attitude control, which makes the de-tumbling and capture operation much safer, more effective and accurate. The dynamics and control for the contactless interaction have been little studied in the past years. This paper considers a generic dynamics and control problem for contactless interaction between a spacecraft and debris. A translational and rotational dynamics model of contactless interaction is proposed and the 6-DOF equations are established. The contactless interaction control law is designed with the backstepping method, and the spacecraft three-axis control law is designed with the PD control. Simulation results show that the angular momentum is transferred from the debris to the spacecraft and the debris is thus de-tumbled. The desired relative states are achieved efficiently. Significantly, the spacecraft and debris no longer rotate in the inertial frame and, hence, the safety and accuracy for capture operation are guaranteed.

Aim: To assess the cost–effectiveness of infliximab-containing therapy (ICT) for moderate-to-severe rheumatoid arthritis (RA) in a medium-sized Chinese city. Methods: A Chinese prospective cohort study comparing ICT (25 patients) versus conventional disease-modified antirheumatic drugs (24 patients) for RA was used to assess the cost–effectiveness of ICT. Results: The cohort study observed significantly reduced disease activity score of 28 joints (coefficient -2.718, p < 0.001), improved EQ-5D (coefficient 0.453, p < 0.001) and increased medical costs (coefficient 1.289, p < 0.001) associated with ICT. The incremental cost–effectiveness ratio per gained quality-adjusted life year for ICT versus disease-modified antirheumatic drugs was 1.897-times of the local gross domestic product per capita. Conclusion: Infliximab was a favorable cost-effective alternative option for moderate-to-severe RA in a medium-sized city of China.

Background: This study aimed to evaluate the cost-effectiveness of anbainuo (ABN) plus methotrexate (MTX) versus conventional disease-modifying antirheumatic drugs (cDMARDs) in Chinese rheumatoid arthritis (RA) patients. Methods: Ninety RA patients who underwent ABN+MTX (assigned as ABN+MTX group (N=47)) or cDMARDs (assigned as control group (N=43)) treatment were analyzed. Disease activity was assessed at baseline (M0), 3rd month (M3), 6th month (M6) and 12th month (M12) after treatment. Drug, other medical, indirect and total costs were calculated. Then pharmacoeconomic analyses were performed with the threshold of cost-effectiveness set as 3 times of the mean gross domestic product per capita in China during the study period.Results: Treatment response rate was similar, while disease remission and low disease activity rates were increased in ABN+MTX group compared to control group. Drug cost, other medical cost and total cost were higher in ABN+MTX group than control group, while indirect cost was similar between the two groups. Meanwhile, the quality-adjusted life years (QALY) in ABN+MTX group and control group were 0.72 and 0.48 years, respectively. The incremental cost-effectiveness ratios (ICER) of ABN+MTX group compared to control group in total patients, moderate-disease-activity patients and severe-disease-activity patients were ¥135486.7, ¥146450.4 and ¥124987.2/QALY, respectively, which were all below cost-effectiveness threshold. Further sensitivity analyses revealed that the cost-effectiveness of ABN+MTX versus cDMARDs was relative robust, while among all the indexes, ABN price and HAQ-DI score change for ABN+MTX group affected ICER most.Conclusions: ABN+MTX treatment presents acceptable cost-effectiveness compared to cDMARDs treatment in Chinese RA patients.

Flexible photodetectors based on two-dimensional (2D) transitional metal dichalcogenides (TMDCs) can be used in wearable photoelectronic devices, which have attracted a lot of attention for the last few years. However, most photodetectors based on single layer materials often have low light absorption, and it generally requires complicated and elaborate preparation processes. In this work, we synthesized MoS2 flower-like microspheres with a hydrothermal method, and then a flexible broadband photodetector was prepared by combining MoS2 with a flexible microporous filter membrane. The photodetectors show broad spectral response from 405 nm to 808 nm, with superior responsivity and detectivity reached 0.963 A W−1 and 2.9x1010 Jones respectively under a 405 nm light of 1.77 mW cm−2. Furthermore, these devices also exhibit stable photoelectric responsivity even under various bending conditions. We believe this work will inspire the future development of flexible wearable optoelectronic device.

High performance, flexible broadband photodetectors based on two-dimensional materials have attracted extensive research interest due to their potential applications. However, these reported flexible photodetectors are generally fabricated into micron-nano devices due to the limited size of two-dimension material, with a narrow spectrum detection range, which has seriously hindered their applications in large-area, broadband photodetector. Herein, we have prepared WS2 nanosheets film via typical hydrothermal intercalation and vacuum filtration methods to fabricate a large-area, flexible broadband photodetector. The fabricated devices respond to a broadband wavelength from visible light to near-infrared light (532–1064 nm), and exhibit a responsivity of 4.04 mA/W and a detectivity of 2.55 × 109 Jones at 532 nm irradiation. Moreover, even in an arbitrary bending condition, our fabricated photodetectors show consistently stable photoresponse characteristics. All the results indicate that our stratagem in this work will be a more convenient and practical guidance for the future flexible optoelectronic devices.

Summary Rationale: IL13, IL4, IL4RA, FCER1B, and ADRB2 are important inflammatory genes associated with immunoglobulin E levels. This study attempts to determine whether there are gene–gene interactions in the five genes among asthmatic children of Chinese Han nationality. Methods: Nine single-nucleotide polymorphisms (SNPs) in the five genes were genotyped in 1,000 asthmatic children and 1,000 healthy controls using TaqMan real-time quantitative polymerase chain reaction. Multifactor–dimensionality reduction method was applied for the analysis. Results: A four-way gene–gene interaction model consisting of IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108 was chosen as the optimal one for determining asthma susceptibility (testing balanced accuracy = 0.6089, cross-validation consistency = 10/10, P = 6.98E−05). Each of the four SNPs was identified to have an independent association with childhood asthma (G allele of rs20541, odds ratio (OR) = 1.24, P = 1.23E−03; T allele of rs2243250, OR = 1.25, P = 3.81E-03; A allele of rs1042713, OR = 1.29, P = 6.75E-05; G allele of rs569108, OR = 1.27, P = 3.86E−03). Individuals homozygous for the risk alleles at all the four loci (rs20541 GG, rs2243250 TT, rs1042713 AA, and rs569108 GG) had a significantly higher risk of asthma compared with those without any risk homozygotes (OR = 13.55, P = 4.28E−03), and also greater than those with less than four risk homozygotes (OR = 10.09, P = 6.51E−03). Conclusions: Our results suggest that IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713, and FCER1B rs569108, four SNPs with significant sole effect on asthma, interact to confer a higher risk for the disease in Chinese Han children. Pediatr Pulmonol. © 2015 Wiley Periodicals, Inc.

The lunar exploration phase III mission is a part of the China Aerospace Science and Technology Corporation’s lunar exploration program that will perform a soft-landing and sample return from the Moon to test the key technologies that are required for human lunar missions. This paper focuses primarily on the trajectory design and orbital launch window generation for a lunar probe that are consistent with the constraints imposed by third phase of lunar exploration. Two categories of trajectories are explored: Earth-to-Moon and Moon-to-Earth. With the patched conic technique, the analytical and modified analytical models of the transfer trajectories are developed. The requirement of high-latitude landing for the return phase trajectory is considered in the modified model. By varying the initial input conditions and with a fast convergence iteration scheme, different characteristics of the transfer trajectory are generated. The orbital launch windows are established to study the mission sensitivities to time and fuel consumption and to provide a launch timetable that is compatible with this mission’s requirements. The lunar surface stay time is analyzed for different conditions. The high-fidelity gravitational model is introduced to demonstrate the accuracy and convergence behavior of the analytical solution. The design method can also be used as a basis for the future human lunar missions.

A precise and convenient targeting architecture for accomplishing the rendezvous of a lunar lander with an orbiter in a near-circular lunar parking orbit is proposed in this paper. This procedure enables a systematic design and refinement of the number of thrust impulses, their application times, and the mission duration. The simplicity and accuracy of this targeting procedure makes it well suited for onboard use during real-time control and strategy reconstruction operations. A concise and revealing form of the linearized rendezvous equations is derived based on the Clohessy–Wiltshire model, as adopted to generate feasible initial solutions to satisfy the demands of rapid mission analysis and design. A three-step iterative procedure is adopted to determine the minimum-impulse control strategies for autonomous rendezvous, involving the progress of the solution from a linear model to a nonlinear, two-body model and finally to a high-fidelity model. The two-body model is introduced as an intermediary to ena...

This paper presents a method for designing a lunar orbit insertion (LOI) targeting sequence from a two-segment lunar free-return trajectory. To reduce the fuel consumption for lunar orbit targeting, the algorithm modifies the LOI sequence and simultaneously optimizes the midcourse lunar-targeting maneuver (LTM) time. The circular restricted three-body is used to construct the two-segment lunar free-return trajectories and to observe the trajectory characteristics during the midcourse transfer and lunar encounter. A high-fidelity lunar gravitational model is adopted to modify the initial estimates of the LTM time and LOI sequence. Numerical examples are presented to illustrate the fuel consumption for accomplishing the lunar global targeting from a specified two-segment lunar free-return trajectory. The result indicates the lunar global targeting can be achieved within a LOI budget of 2.6 km/s and LTM budget of 0.4 km/s. The use of the proposed method provides an accurate initial solution that can be further optimized rapidly on higher-fidelity models. The procedure is well suited for onboard, real-time control of lunar global access missions.

A precise and convenient procedure for designing the two-segment lunar free-return trajectory is presented in this paper. The trajectory characteristics are analyzed to support the lunar mission design associated with the higher inclination lunar approaches and safer returns from the moon. The concise procedure is established based on the matched conic model. An analytical algorithm is developed to compute the spacecraft state at the lunar sphere of influence to complete the conic matching. An iteration process is then adopted to generate favorable initial solutions that satisfy the constraints at injection, perilune, and Earth-entry interface. Orbital launch windows for departure from Earth, lunar encounter, and returns to Earth are established in the years 2024 and 2034. These years are chosen due to the moon’s inclination reaching a maximum in 2024 and it reaching a minimum in 2034 during a Metonic cycle. This novel trajectory enables greater lunar surface coverage than standard free-return trajectorie...

A Flywheel Energy Storage System (FESS) can solve the problem of randomness and fluctuation of new energy power generation. The flywheel energy storage as a DC power supply, the primary guarantee is to maintain the stability of output voltage in discharge mode, which will cause the variation of motor internal magnetic field. In this paper, taking a flywheel energy storage permanent magnet motor as the study object, constant pressure discharge DC voltage is stabilized at 310v, and then the rotation speed, electromagnetic torque, armature current, and the system output DC voltage are calculated for a FESS in discharge mode. Meanwhile, the change rule of electromagnetic field is given, which can provide reference for FESS design controller.

Safe and reliable of inverter is directly related to the normal operation of permanent magnet synchronous motor drive system. Therefore, in the paper, taking a 12.5kW Permanent Magnet Synchronous Motor (PMSM) as the research object, two-dimensional transient electromagnetic field calculation model based on vector control strategy is established, and the corresponding assumptions and boundary conditions are also given. By adopting field circuit coupled calculation method, electromagnetic field is theoretically calculated under inverter normal and short circuit fault (SCF) in the upper switch of phase A, respectively. Simultaneously, due to the SCF, DC components are produced in three phase current, and the influence of the magnetic field produced by DC components on air gap magnetic field is analyzed in detail. In order to validate the accuracy of the established calculation model, some relevant experiments have been conducted. The obtained conclusion can provide theoretical basis for drive system fault diagnosis of PMSM.

High-speed and high-capacity flywheel energy storage system with high-performance is a research focus in the energy field. A 200kW, 15000rpm high-speed permanent-magnet machine that used in flywheel energy storage system is investigated in this paper, and its discharge performance is analyzed through establishing a field-circuit coupling model. The relationship between the load and the performance of uncontrolled discharge process of the flywheel system are studied, and the computational results is compared with the experimental ones, which prove the model is correct. On the basis of the above study, the influence of the load and the control circuit on the constant voltage discharge performance of system is analyzed. The results could provide a reference for the design of high performance flywheel energy storage system.

Supplemental Digital Content is available in the text, The aim of this study was to evaluate the cost-effectiveness of Anbainuo (ABN) plus methotrexate (MTX) (ABN + MTX) versus conventional disease-modifying anti-rheumatic drugs (cDMARDs) in rheumatoid arthritis (RA) patients. Forty-eight moderate to severe RA patients underwent ABN + MTX or cDMARDs treatment were consecutively enrolled and assigned to ABN + MTX group (n = 26) and control group (n = 22). Patients were followed up and their disease activity and quality of life (QoL) were evaluated at 3rd month, 6th month and 12th month after initiation of treatment. Treatment costs of 2 groups were calculated, then pharmacoeconomic analysis was performed. ABN + MTX increased drug cost and total cost while decreased indirect cost compared with cDMARDs after 12-month treatment. ABN + MTX group gained additional 0.22 quality-adjusted life years (QALY) and yielded an incremental cost-effectiveness ratio (ICER) of ¥104,293.6 per QALY after treatment. Sensitivity analysis reveals that rising ABN price by 20% produced an ICER of ¥130,403.6 per QALY, which was still lower than 3 times of the mean gross domestic product (GDP) per capita during the same period in China (¥165,960). Besides, ABN + MTX was more cost-effective in severe RA patients compared to moderate RA patients. ABN + MTX is cost-effective in treating moderate to severe RA patients compared with cDMARDs, although the total cost of ABN + MTX is relatively higher.

To support the mission and trajectory design problems associated with the Earth-to-moon trajectories for a crewed vehicle, a multisegment lunar free-return trajectory is proposed. The multisegment free return differs from hybrid profiles in that it consists of free-return sections only; however, it maintains the advantages of hybrid returns. The analysis presented here is limited to a two-segment class of trajectories. In this profile, the translunar injection puts the spacecraft onto a free-return trajectory with a high perilune altitude; then, the spacecraft performs a transfer maneuver onto a new translunar coast trajectory that has an approximate perilune altitude of 100 km. This new translunar coast trajectory is also designed as a free-return trajectory that can perform a safe return. With a finite sphere of influence model, an analytical model of the multisegment free-return trajectories is developed by the matched-conic technique. Characteristics of the injection velocity, flight time, and lunar a...

This paper proposed a novel algorithm for forensic identification of electronic disguised voice based on supervector and statistical analysis. The supervector was stacked by mixtures of mean vector of Gaussian mixture model. SVM classifier was used to identify whether a testing voice was disguised or not. By comparing the difference of Mel-cepstrum coefficients statistical characteristics between normal and disguised voice, we studied the variation of voice parameters. Experimental results showed that we can get good detection performance with error identified rate lower than 7%.

Chinese text categorization differs from English text categorization due to its much larger term set (of words or character n -grams), which results in very slow training and working of modern high-performance classifiers. This study assumes that this high-dimensionality problem is related to the redundancy in the term set, which cannot be solved by traditional term selection methods. A greedy algorithm framework named “non-independent term selection” is presented, which reduces the redundancy according to string-level correlations. Several preliminary implementations of this idea are demonstrated. Experiment results show that a good tradeoff can be reached between the performance and the size of the term set.

The herbicide resistant bar gene has been widely used as selectable marker genes in the study on plant genetic transformation. Owing to the integration of the gene into rice genome, transgenic rice was resistant to the herbicide Basta. Therefore, selection of transgenic plant and genetic analysis became easier. In the studies, bar gene was introduced as a genetic marker gene into rice restore line variety of two-line or three-line. Combined with conventional breeding method, the good herbicide resistant individual plant was derived as the new restore line for hybrid combination. After sprayed with Basta at seedling phase, the real hybrid rice that had herbicide resistance could grow normally, while the fake hybrid rice and weeds, having no bar gene, were killed by herbicide. The method described above helped rapidly to examine and improve the purity of hybrid rice.

s: AACR Special Conference on Tumor Metastasis; November 30-December 3, 2015; Austin, TX Patients with Pancreatic Adenocarcinoma (PDA) often present with advanced stage disease including widespread metastasis and have dismal 5-year survival rates. The molecular mechanism promoting PDA progression and metastasis remain poorly understood. We have previously demonstrated that tumor cells undergo Epithelial-to-Mesenchymal Transition (EMT) in mouse models of PDA [Rhim et al., 2012]. EMT is a developmental process where cells loss epithelial characteristics and transdifferentiate into a mesenchymal-like state that is highly associated with increased invasion and metastasis. To better understand molecular mechanisms of PDA development and metastatic disease, we subjected tumors cells from a lineage labeled mouse model of PDA to RNA sequencing to identify global transcriptional changes. Interestingly, we discovered that there are at least two distinct subtypes of PDA based on transcriptome profiling. Comparison of gene expression profiles from mouse PDA subtypes to established subtypes from human PDA datasets [Collisson et al., 2011] revealed that mouse PDA is transcriptionally similar to the human disease. Differences in transcriptional profiling between PDA subtypes may dictate response to chemotherapeutics and metastatic competency. Citation Format: David Balli, Nicole Aiello, Robert Norgard, Jingyang Li, Amine Sahmoud, Ben Stanger. Transcriptome analysis of mouse PDA subtypes. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Metastasis; 2015 Nov 30-Dec 3; Austin, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(7 Suppl):Abstract nr B10.

This paper presents a new charge recovery logic structure called Complementary Pass-transistor Boost Logic (CPBL). CPBL is a low-power charge recovery logic structure powered by 2-phase non-overlap alternating power clocks and requires no DC power supply. To demonstrate the energy efficiency of CPBL, 4-bit counter is designed to show the energy comparison among CPBL, Complementary Pass-transistor Adiabatic Logic (CPAL) and the conventional static CMOS with 0.18µm process. The simulation results indicate that CPBL implementation reduces about 65% power dissipation compared with the static CMOS counterpart in a range from 50MHz to 500MHz and dissipates about 40% energy with respect to CPAL at 200MHz.

Words and character-bigrams are both used as features in Chinese text processing tasks, but no systematic comparison or analysis of their values as features for Chinese text categorization has been reported heretofore. We carry out here a full performance comparison between them by experiments on various document collections (including a manually word-segmented corpus as a golden standard), and a semi-quantitative analysis to elucidate the characteristics of their behavior; and try to provide some preliminary clue for feature term choice (in most cases, character-bigrams are better than words) and dimensionality setting in text categorization systems.

Because of the economic and technical advantages, laser processing technology has been developed rapidly in recent years. Jilin Province Laser Institute laser processing center set up a laser cutting production line, a laser heat- treatment production line, and a laser marking machine. In this paper we describe applied examples of laser cut, laser heat-treatment and laser marking.