Background Postprocedural aortic regurgitations following transcatheter aortic valve implantation （TAVI） procedures remain an is- sue. Benefit of oversizing strategies to prevent them isn＇t well established. We com...Background Postprocedural aortic regurgitations following transcatheter aortic valve implantation （TAVI） procedures remain an is- sue. Benefit of oversizing strategies to prevent them isn＇t well established. We compared different level of oversizing in our cohort of con- secutive patients to address if severe oversizing compared to normal sizing had an impact on post-procedural outcomes. Methods From January 2010 to August 2013, consecutive patients were referred for TAVI with preoperative Multislice-CT （MSCT） and the procedures were achieved using Edwards Sapien~ or Corevalve devices~. Retrospectively, according to pre-procedural MSCT and the valve size, pa- tients were classified into three groups： normal, moderate and severe oversizing; depending on the ratio between the prosthesis area and the annulus area indexed and measured on MSCT. Main endpoint was mid-term mortality and secondary endpoints were the Valve Academic Research Consortium （VARC-2） endpoints. Results Two hundred and sixty eight patients had a MSCT and underwent TAVI procedure, with mainly Corevalve~. While all-cause and cardiovascular mortality rates were similar in all groups, post-procedural new pacemaker （PM） implantation rate was significantly higher in the severe oversizing group （P = 0.03）, while we observed more in-hospital congestive heart-failure （P = 0.02） in the normal sizing group. There was a trend toward more moderate to severe aortic regurgitation （AR） in the normal sizing group （P = 0.07）. Conclusions Despite a higher rate of PM implantation, oversizing based on this ratio reduces aortic leak with lower rates of post-procedural complications and a similar mid-term survival.展开更多
Objective: To solve the problem of parameter estimate in the regression analysis of non-random sample. Methods: Calculating residuals according to the regression function based on original data. Modifying residuals an...Objective: To solve the problem of parameter estimate in the regression analysis of non-random sample. Methods: Calculating residuals according to the regression function based on original data. Modifying residuals and correcting them with mean. Adding mean-corrected residuals on original response and bootstrapping them to get 1000 samples. Fitting regression functions of 1000 resampling samples and calculating the 2.5th percentile and 97.5th percentile of corresponding coefficient. Results: The interval estimates deriving from bootstrap method had more statistical significance than that from usual method. Conclusion: Bootstrapping a regression with residuals is a valid method for estimating parameter in regression analysis.展开更多
Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage ...Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage of the specificity of these interactions, we postulate an "affinity-guided covalent conjugation" strategy to lock binding ligands through covalent reactions between the ligand and the receptor protein. The presence of a nucleophile close to the ligand binding site of a protein is sine qua none of this reaction. Specific noncovalent interaction of a ligand derivative(which contains an electrophile at a designed position) to the ligand binding site of the protein brings the electrophile to the close proximity of the nucleophile. Subsequently, a conjugation reaction spontaneously takes place between the nucleophile and the electrophile, and leads to an intermolecular covalent linkage. This strategy was first showcased in coiled coil peptides which include a cysteine mutation at a selected position. The short peptide sequence was used for covalent labeling of cell surface receptors. The same strategy was then used to guide the design of a set of protein Lego bricks for covalent assembly of protein complexes of unnatural geometry. We finally made "reactive peptides" for natural adaptor proteins that play significant roles in signal transduction. The peptides were designed to react with a single domain of the multidomain adaptor protein, delivered into the cytosol of neurons, and re-directed the intracellular signal of neuronal migration. The trilogy of protein labeling, assembly, and inhibition of intracellular signals, all through a specific covalent bond, fully demonstrated the generality and versatility of "affinity-guided covalent conjugation" in various applications.展开更多
文摘Background Postprocedural aortic regurgitations following transcatheter aortic valve implantation （TAVI） procedures remain an is- sue. Benefit of oversizing strategies to prevent them isn＇t well established. We compared different level of oversizing in our cohort of con- secutive patients to address if severe oversizing compared to normal sizing had an impact on post-procedural outcomes. Methods From January 2010 to August 2013, consecutive patients were referred for TAVI with preoperative Multislice-CT （MSCT） and the procedures were achieved using Edwards Sapien~ or Corevalve devices~. Retrospectively, according to pre-procedural MSCT and the valve size, pa- tients were classified into three groups： normal, moderate and severe oversizing; depending on the ratio between the prosthesis area and the annulus area indexed and measured on MSCT. Main endpoint was mid-term mortality and secondary endpoints were the Valve Academic Research Consortium （VARC-2） endpoints. Results Two hundred and sixty eight patients had a MSCT and underwent TAVI procedure, with mainly Corevalve~. While all-cause and cardiovascular mortality rates were similar in all groups, post-procedural new pacemaker （PM） implantation rate was significantly higher in the severe oversizing group （P = 0.03）, while we observed more in-hospital congestive heart-failure （P = 0.02） in the normal sizing group. There was a trend toward more moderate to severe aortic regurgitation （AR） in the normal sizing group （P = 0.07）. Conclusions Despite a higher rate of PM implantation, oversizing based on this ratio reduces aortic leak with lower rates of post-procedural complications and a similar mid-term survival.
文摘Objective: To solve the problem of parameter estimate in the regression analysis of non-random sample. Methods: Calculating residuals according to the regression function based on original data. Modifying residuals and correcting them with mean. Adding mean-corrected residuals on original response and bootstrapping them to get 1000 samples. Fitting regression functions of 1000 resampling samples and calculating the 2.5th percentile and 97.5th percentile of corresponding coefficient. Results: The interval estimates deriving from bootstrap method had more statistical significance than that from usual method. Conclusion: Bootstrapping a regression with residuals is a valid method for estimating parameter in regression analysis.
基金supported by the University Grants Committee of Hong Kong (ECS grant CUHK 404812, GRF grants 403711 and 404413, and Ao E/M-09/12)
文摘Specific and dynamic biological interactions pave the blueprint of signal networks in cell. For example, a great variety of specific protein-ligand interactions define how intracellular signals flow. Taking advantage of the specificity of these interactions, we postulate an "affinity-guided covalent conjugation" strategy to lock binding ligands through covalent reactions between the ligand and the receptor protein. The presence of a nucleophile close to the ligand binding site of a protein is sine qua none of this reaction. Specific noncovalent interaction of a ligand derivative(which contains an electrophile at a designed position) to the ligand binding site of the protein brings the electrophile to the close proximity of the nucleophile. Subsequently, a conjugation reaction spontaneously takes place between the nucleophile and the electrophile, and leads to an intermolecular covalent linkage. This strategy was first showcased in coiled coil peptides which include a cysteine mutation at a selected position. The short peptide sequence was used for covalent labeling of cell surface receptors. The same strategy was then used to guide the design of a set of protein Lego bricks for covalent assembly of protein complexes of unnatural geometry. We finally made "reactive peptides" for natural adaptor proteins that play significant roles in signal transduction. The peptides were designed to react with a single domain of the multidomain adaptor protein, delivered into the cytosol of neurons, and re-directed the intracellular signal of neuronal migration. The trilogy of protein labeling, assembly, and inhibition of intracellular signals, all through a specific covalent bond, fully demonstrated the generality and versatility of "affinity-guided covalent conjugation" in various applications.
