Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-de...Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.展开更多
OBJECTIVE: To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES: The online PubMed database was searched for English articles d...OBJECTIVE: To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES: The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION: The following types of article were selected: (1) clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and (2) studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES: Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3+ or S4. RESULTS: Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries (P 〈 0.05), and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION: Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.展开更多
When repairing nerves with adhesives, most researchers place glue directly on the nerve stumps, but this method does not fix the nerve ends well and allows glue to easily invade the nerve ends. In this study, we estab...When repairing nerves with adhesives, most researchers place glue directly on the nerve stumps, but this method does not fix the nerve ends well and allows glue to easily invade the nerve ends. In this study, we established a rat model of completely transected sciatic nerve injury and re- paired it using a modified 1 cm-length conduit with inner diameter of 1.5 mm. Each end of the cylindrical conduit contains a short linear channel, while the enclosed central tube protects the nerve ends well Nerves were repaired with 2-octyl-cyanoacrylate and suture, which complement the function of the modified conduit. The results demonstrated that for the same conduit, the av- erage operation time using the adhesive method was much shorter than with the suture method. No significant differences were found between the two groups in sciatic function index, motor evoked potential latency, motor evoked potential amplitude, muscular recovery rate, number of medullated nerve fibers, axon diameter, or medullary sheath thickness. Thus, the adhesive method for repairing nerves using a modified conduit is feasible and effective, and reduces the operation time while providing an equivalent repair effect.展开更多
The application of metamorphic testing(MT)on automatic program repair(APR-MT)is used to generate a patch without test oracles by examining whether the input metamorphic relation(MR)is satisfied or not.However,the deli...The application of metamorphic testing(MT)on automatic program repair(APR-MT)is used to generate a patch without test oracles by examining whether the input metamorphic relation(MR)is satisfied or not.However,the delivered patch is plausible since it may satisfy the input MR but violate other MRs.This inspires us to propose an improved approach to enhance the effectiveness of APR-MT with metamorphic relation group.Ourapproach involves three major steps.First,we formally define the repair process of APR-MT by building the model of automatic program repair and metamorphic testing separately.Then,we propose the advanced model of automatic program repair based on metamorphic relation group,named METARO^(3),which takes several MRs as input while only one MR is used in APR-MT.We additionally present two kinds of selection strategies to rank MRs in descending order of the fault detection capability,which helps shorten the repair time of finding a patch.To demonstrate the feasibility and procedure of our approach,an illustration example was conducted.The results show that METARO^(3) can improve the effectiveness of APR-MT significantly.展开更多
This paper proposes a new method for service restoration of distribution network with the support of transportable power sources(TPSs)and repair crews(RCs).Firstly,a coupling model of distribution networks and vehicle...This paper proposes a new method for service restoration of distribution network with the support of transportable power sources(TPSs)and repair crews(RCs).Firstly,a coupling model of distribution networks and vehicle routing of TPSs and RCs is proposed,where the TPSs serve as emergency power supply sources,and the RCs are used to repair the faulted lines.Considering the uncertainty of traffic congestion,the probability distribution of the travel time spent on each road is derived based on the Nesterov user equilibrium model,and a two-stage stochastic program is formulated to determine the optimal routings of TPSs and RCs.To efficiently solve the proposed stochastic mixed-integer linear program(MILP),a two-phase scenario reduction method is then developed to scale down the problem size,and an adaptive progressive hedging algorithm is used for an efficient solution.The effectiveness of the proposed methods and algorithms has been illustrated in a modified IEEE 33-bus system.展开更多
Component reallocation(CR)is receiving increasing attention in many engineering systems with functionally interchangeable and unbalanced degradation components.This paper studies a CR and system replacement maintenanc...Component reallocation(CR)is receiving increasing attention in many engineering systems with functionally interchangeable and unbalanced degradation components.This paper studies a CR and system replacement maintenance policy of series repairable systems,which undergoes minimal repairs for each emergency failure of components,and considers constant downtime and cost of minimal repair,CR and system replacement.Two binary mixed integer nonlinear programming models are respectively established to determine the assignment of CR,and the uptime right before CR and system replacement with the objective of minimizing the system average maintenance cost and maximizing the system availability.Further,we derive the optimal uptime right before system replacement with maximization of the system availability,and then give the relationship between the system availability and the component failure rate.Finally,numerical examples show that the CR and system replacement maintenance policy can effectively reduce the system average maintenance cost and improve the system availability,and further give the sensitivity analysis and insights of the CR and system replacement maintenance policy.展开更多
In recent years,automatic program repair approaches have developed rapidly in the field of software engineering.However,the existing program repair techniques based on genetic programming suffer from requiring verific...In recent years,automatic program repair approaches have developed rapidly in the field of software engineering.However,the existing program repair techniques based on genetic programming suffer from requiring verification of a large number of candidate patches,which consume a lot of computational resources.In this paper,we propose a random search and code similarity based automatic program repair(RSCSRepair).First,to reduce the verification computation effort for candidate patches,we introduce test filtering to reduce the number of test cases and use test case prioritization techniques to reconstruct a new set of test cases.Second,we use a combination of code similarity and random search for patch generation.Finally,we use a patch overfitting detection method to improve the quality of patches.In order to verify the performance of our approach,we conducted the experiments on the Defects4J benchmark.The experimental results show that RSCSRepair correctly repairs up to 54 bugs,with improvements of 14.3%,8.5%,14.3%and 10.3%for our approach compared with jKali,Nopol,CapGen and Sim Fix,respectively.展开更多
基金sponsored by BeiGene.Third-party medical writing assistance was provided by Ghina Yaacoub,MSc,of Ashfield MedComms,an Inizio Company,and funded by BeiGene.
文摘Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)tumors.Methods:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were enrolled.Patients received tislelizumab 200 mg intravenously every 3 weeks.Objective response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at baseline.Most had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided P<0.0001]and ORR across tumor-specific subgroups[colorectal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete responses.Median DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety signals.Treatment-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to TRAEs.Conclusions:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.
基金supported by the National High-Technology Research and Development Program of China(863 Program),No.2012A A020507985 Program of Sun Yat-sen University,No.90035-3283312+1 种基金Specialized Research Fund for the Doctoral Program of Higher Education,No.20120171120075Doctoral Start-up Project of the Natural Science Foundation of Guangdong Province,No.S201204006336
文摘OBJECTIVE: To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES: The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION: The following types of article were selected: (1) clinical trials describ- ing the repair of median, ulnar, radial, and digital nerve injuries published in English; and (2) studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to in- vestigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES: Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3+ or S4. RESULTS: Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were inde- pendent predictors of outcome after the repair of nerve injuries (P 〈 0.05), and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION: Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up.
基金supported by the International Technology Cooperation Program,No.S2014ZR0393
文摘When repairing nerves with adhesives, most researchers place glue directly on the nerve stumps, but this method does not fix the nerve ends well and allows glue to easily invade the nerve ends. In this study, we established a rat model of completely transected sciatic nerve injury and re- paired it using a modified 1 cm-length conduit with inner diameter of 1.5 mm. Each end of the cylindrical conduit contains a short linear channel, while the enclosed central tube protects the nerve ends well Nerves were repaired with 2-octyl-cyanoacrylate and suture, which complement the function of the modified conduit. The results demonstrated that for the same conduit, the av- erage operation time using the adhesive method was much shorter than with the suture method. No significant differences were found between the two groups in sciatic function index, motor evoked potential latency, motor evoked potential amplitude, muscular recovery rate, number of medullated nerve fibers, axon diameter, or medullary sheath thickness. Thus, the adhesive method for repairing nerves using a modified conduit is feasible and effective, and reduces the operation time while providing an equivalent repair effect.
基金The work was supported by a grant from National Natural Science Foundation of China(No.61772423).
文摘The application of metamorphic testing(MT)on automatic program repair(APR-MT)is used to generate a patch without test oracles by examining whether the input metamorphic relation(MR)is satisfied or not.However,the delivered patch is plausible since it may satisfy the input MR but violate other MRs.This inspires us to propose an improved approach to enhance the effectiveness of APR-MT with metamorphic relation group.Ourapproach involves three major steps.First,we formally define the repair process of APR-MT by building the model of automatic program repair and metamorphic testing separately.Then,we propose the advanced model of automatic program repair based on metamorphic relation group,named METARO^(3),which takes several MRs as input while only one MR is used in APR-MT.We additionally present two kinds of selection strategies to rank MRs in descending order of the fault detection capability,which helps shorten the repair time of finding a patch.To demonstrate the feasibility and procedure of our approach,an illustration example was conducted.The results show that METARO^(3) can improve the effectiveness of APR-MT significantly.
基金supported by National Natural Science Foundation of China(No.72171026).
文摘This paper proposes a new method for service restoration of distribution network with the support of transportable power sources(TPSs)and repair crews(RCs).Firstly,a coupling model of distribution networks and vehicle routing of TPSs and RCs is proposed,where the TPSs serve as emergency power supply sources,and the RCs are used to repair the faulted lines.Considering the uncertainty of traffic congestion,the probability distribution of the travel time spent on each road is derived based on the Nesterov user equilibrium model,and a two-stage stochastic program is formulated to determine the optimal routings of TPSs and RCs.To efficiently solve the proposed stochastic mixed-integer linear program(MILP),a two-phase scenario reduction method is then developed to scale down the problem size,and an adaptive progressive hedging algorithm is used for an efficient solution.The effectiveness of the proposed methods and algorithms has been illustrated in a modified IEEE 33-bus system.
基金supported by the National Natural Science Foundation of China(72101025,72271049)the Fundamental Research Funds for the Central Universities(FRF-TP-20-073A1)the China Postdoct oral Science Foundation(2021M690349)。
文摘Component reallocation(CR)is receiving increasing attention in many engineering systems with functionally interchangeable and unbalanced degradation components.This paper studies a CR and system replacement maintenance policy of series repairable systems,which undergoes minimal repairs for each emergency failure of components,and considers constant downtime and cost of minimal repair,CR and system replacement.Two binary mixed integer nonlinear programming models are respectively established to determine the assignment of CR,and the uptime right before CR and system replacement with the objective of minimizing the system average maintenance cost and maximizing the system availability.Further,we derive the optimal uptime right before system replacement with maximization of the system availability,and then give the relationship between the system availability and the component failure rate.Finally,numerical examples show that the CR and system replacement maintenance policy can effectively reduce the system average maintenance cost and improve the system availability,and further give the sensitivity analysis and insights of the CR and system replacement maintenance policy.
基金the Cultivation Programme for Young Backbone Teachers in Henan University of Technology,the Key Scientific Research Project of Colleges and Universities in Henan Province(No.22A520024)the Major Public Welfare Project of Henan Province(No.201300311200)the National Natural Science Foundation of China(Nos.61602154 and 61340037)。
文摘In recent years,automatic program repair approaches have developed rapidly in the field of software engineering.However,the existing program repair techniques based on genetic programming suffer from requiring verification of a large number of candidate patches,which consume a lot of computational resources.In this paper,we propose a random search and code similarity based automatic program repair(RSCSRepair).First,to reduce the verification computation effort for candidate patches,we introduce test filtering to reduce the number of test cases and use test case prioritization techniques to reconstruct a new set of test cases.Second,we use a combination of code similarity and random search for patch generation.Finally,we use a patch overfitting detection method to improve the quality of patches.In order to verify the performance of our approach,we conducted the experiments on the Defects4J benchmark.The experimental results show that RSCSRepair correctly repairs up to 54 bugs,with improvements of 14.3%,8.5%,14.3%and 10.3%for our approach compared with jKali,Nopol,CapGen and Sim Fix,respectively.