Finding the optimal dose combination in two-agent dose-finding trials is challenging due to limited sample sizes and the extensive range of potential doses.Unlike traditional chemotherapy or radiotherapy,which primari...Finding the optimal dose combination in two-agent dose-finding trials is challenging due to limited sample sizes and the extensive range of potential doses.Unlike traditional chemotherapy or radiotherapy,which primarily focuses on identifying the maximum tolerated dose(MTD),therapies involving targeted and immune agents facilitate the identifica-tion of an optimal biological dose combination(OBDC)by simultaneously evaluating both toxicity and efficacy.Cur-rently,most approaches to determining the OBDC in the literature are model-based and require complex model fittings,making them cumbersome and challenging to implement.To address these challenges,we developed a novel model-as-sisted approach called uTPI-Comb.This approach refines the established utility-based toxicity probability interval design by integrating a strategically devised zone-based local and global candidate set searching strategy,which can effectively optimize the decision-making process for two-agent dose escalation or de-escalation in drug combination trials.Extensive simulation studies demonstrate that the uTPI-Comb design speeds up the dose-searching process and provides substantial improvements over existing model-based methods in determining the optimal biological dose combinations.展开更多
The seminal report ofα-diimine palladium and nickel catalysts in 1995 represented a major breakthrough in the preparation of functionalized polyolefin materials.Owing to the high abundance and low cost of nickel,nick...The seminal report ofα-diimine palladium and nickel catalysts in 1995 represented a major breakthrough in the preparation of functionalized polyolefin materials.Owing to the high abundance and low cost of nickel,nickel-based catalysts have great application prospects in the industrialization process of olefin coordination polymerization.In this work,various N-aryl substituents with different electronic effects were synthesized and introduced intoα-diimine ligands.The aspreparedα-diimine nickel catalysts showed high polymerization activity(0.9×10^(7)–3.0×10^(7)g·mol^(−1)·h^(−1))in ethylene polymerization,generating polyethylene products with adjustable molecular weights(Mn values:7.4×10^(4)–146.9×10^(4)g·mol^(−1))and branching densities(31/1000 C–68/1000 C).The resulting polyethylene products showed excellent mechanical properties,with high tensile strength(up to 25.0 MPa)and high strain at break values(up to 3890%).The copolymerization of ethylene and polar monomers can also be achieved by these nicekel complexes,ultimately preparing functionalized polyolefins.展开更多
基金This work was supported by the Natural Science Foundation of Anhui Province(2022AH050703)the National Natural Science Foundation of China(11671375).
文摘Finding the optimal dose combination in two-agent dose-finding trials is challenging due to limited sample sizes and the extensive range of potential doses.Unlike traditional chemotherapy or radiotherapy,which primarily focuses on identifying the maximum tolerated dose(MTD),therapies involving targeted and immune agents facilitate the identifica-tion of an optimal biological dose combination(OBDC)by simultaneously evaluating both toxicity and efficacy.Cur-rently,most approaches to determining the OBDC in the literature are model-based and require complex model fittings,making them cumbersome and challenging to implement.To address these challenges,we developed a novel model-as-sisted approach called uTPI-Comb.This approach refines the established utility-based toxicity probability interval design by integrating a strategically devised zone-based local and global candidate set searching strategy,which can effectively optimize the decision-making process for two-agent dose escalation or de-escalation in drug combination trials.Extensive simulation studies demonstrate that the uTPI-Comb design speeds up the dose-searching process and provides substantial improvements over existing model-based methods in determining the optimal biological dose combinations.
基金supported by the National Key R&D Program of China(2021YFA1501700)Fundamental Research Funds for the Central Universities(WK9990000142).
文摘The seminal report ofα-diimine palladium and nickel catalysts in 1995 represented a major breakthrough in the preparation of functionalized polyolefin materials.Owing to the high abundance and low cost of nickel,nickel-based catalysts have great application prospects in the industrialization process of olefin coordination polymerization.In this work,various N-aryl substituents with different electronic effects were synthesized and introduced intoα-diimine ligands.The aspreparedα-diimine nickel catalysts showed high polymerization activity(0.9×10^(7)–3.0×10^(7)g·mol^(−1)·h^(−1))in ethylene polymerization,generating polyethylene products with adjustable molecular weights(Mn values:7.4×10^(4)–146.9×10^(4)g·mol^(−1))and branching densities(31/1000 C–68/1000 C).The resulting polyethylene products showed excellent mechanical properties,with high tensile strength(up to 25.0 MPa)and high strain at break values(up to 3890%).The copolymerization of ethylene and polar monomers can also be achieved by these nicekel complexes,ultimately preparing functionalized polyolefins.
