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In super high-rise buildings with varying story heights, the wind-induced inter-story drifts might violate the specified limit. However, these effects have seldom been concerned in wind-induced response analysis. The theory and application of equivalent static wind load (ESWL) for wind-induced inter-story drifts of super high-rise buildings were studied in this paper. A spectral decomposition method suitable for multi-point excitation problems was firstly proposed. The formula of ESWL targeting for largest inter-story drift was derived. For more reasonable structural design, the ESWL for multiple targets including displacement atop of building and inter-story drifts at all story levels is put forward, in which the dominant modal inertial forces are adopted as the based load vectors. The presented methods were finally verified by its application for the wind-induced response analysis for a tallest super tall building in Guangzhou. The researched results showed that the proposed spectral decomposition method not only has the same precision as the complete quadratic combination method but also possesses higher computation efficiency. The ESWL for multiple targets produces the same static responses for all the specified wind-induced response, so it is much more rational for wind-resistant structural design. Meanwhile, it is more reasonable to select the wind-induced responses in the same direction simultaneously as the targeted values for obtaining the required ESWLs; however, the ESWL targeting for the wind-induced responses in all degrees of freedom would generate more queer and unrealistic ESWLs distribution. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

BackgroundUmbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSC) for transplantation of patients with hematologic malignancies or hereditary diseases.MethodsWe developed a provincial UCB bank in Guangzhou, China, using good manufacturing practices and standard operating procedures to address donor eligibility, collection, characterization, processing, storage and release from quarantine. The banking activities were analyzed.ResultsFrom June 1998 to May 2005, 8623 UCB units of Han ethnic origin were collected; 4147 (48.1%) were stored, while 4476 (51.9%) were discarded as a result of pre-determined exclusion criteria. A median volume of 95.5 mL (range 60–227.7) and 1.2×109 (0.8–9.3) nucleated cells were collected. The cell viability was 97.8% (90–100%). The CD34+ cell count of 3691 (89.0%) UCB units was 5.2×106 (0.3–131.6) and clonogenic assays of 4036 (97.3%) UCB units demonstrated 9.8×105 (0.04–135.8) CFU-GM, 0.3×105 (0.0–18.6) CFU-GEMM and 8.8×105 (0.0–74.2) BFU-E. A total of 0.4% (15/3863) UCB derived from babies known to have health problems at age 6 months was discarded. Up to May 2005, 151 units were issued for transplantation to 127 patients [90 (70.9%) children and 37 (29.1%) adults]. The infused nucleated cells in unrelated single-unit recipients were 3.4×107/kg (1.7–14.9) for adults (n=19) and 5.7×107/kg (2.0–20.5) for children (n=71), respectively. The numbers of days for the engraftment of neutrophils among 65 children and 22 adults were 17 (7–41) and 20 (10–42), respectively.DiscussionData of this study show that stringent procedures and comprehensive policies are requisite for pursuing the banking and release of quality UCB for successful transplantation. [ABSTRACT FROM AUTHOR]

Background Immune checkpoint blockade (ICB) therapy has been a pivotal treatment for lung cancer, yet predictive biomarkers are still lacking. PBRM1 mutation is associated with greater sensitivity to immunotherapy for clear cell renal cell carcinoma. To our knowledge, the frequency and clinical relevance of PBRM1 mutation in lung cancer remain unknown. Therefore, we conducted a retrospective study to evaluate the prevalence of PBRM1 mutation and its preliminary response to ICB therapy in NSCLC. Methods We analyzed the combined NSCLC cohort of 2767 patients, from 3 sources: (1) The Cancer Genome Atlas (TCGA) (N = 1144), (2) Memorial Sloan Kettering Cancer Center (MSKCC) (N = 1567), and (3) Dana Farber Cancer Institute (DFCI) (N = 56). We first estimated the prevalence of PBRM1 mutation in the whole NSCLC cohort. A subset of ICB-treated patients (N = 441) with annotated clinical records were further analyzed for association between PBRM1 mutation and response to ICB therapy. We also calculated the overall survival (OS) of 454 non-ICB treated patients. Institutional review board approval and informed consent were waived because all data were de-identified and publicly available. Results Of 2767 patients included in our study, PBRM1 mutation was identified in 75 NSCLC patients (2.70%). Among 39 PBRM1-mutant patients with annotated clinical records, 25 patients (64.1%) were treated with PD-1/PD-L1 inhibitor monotherapy. In the cohort of ICB-treated patients (N = 441, PBRM1 MT=25), the OS of the PBRM1-mutant patients was worse than that of those without mutation (P = 0.03, median OS 6 vs. 13 months). In total, 14 patients, all with PBRM1 mutation, were able to be evaluated for response to ICB therapy. The median PFS was 2.1 months. The ORR was 28.6%, the DCR was 50%, and the DCB was 14.29%. In the cohort of non-ICB-treated patients (N = 454, PBRM1 MT=14), there seems to be no difference between the OS of the PBRM1 mutation subgroup and PBRM1 wild type subgroup (P = 0.097). Conclusions Our findings suggested that PBRM1-mutant NSCLC patients might get less survival benefit from ICB therapy, unlike previously reported data in clear cell renal cell carcinoma. Further prospective research is warranted to confirm the negative predictive role of PBRM1 in NSCLC ICB therapy. Legal entity responsible for the study The authors. Funding This work was supported by: National Key R&D Program of China (Grant No. 2016YFC0905500, 2016YFC0905503), Chinese National Natural Science Foundation project (Grant No. 81872499, 81772476), Science and Technology Program of Guangdong (Grant No. 2017B020227001), and Science and Technology Program of Guangzhou (Grant No. 201607020031, 201704020072). Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background Reduced lung cancer incidence was observed after the use of metformin. However, previous reports from observational study can be biased by confounders, inverse causality and so on, keeping the causality between observed decreased lung cancer risk and metformin use uncertain. Mendelian randomization (MR) analysis is a novel approach for the estimation of causality, eliminating the effect of confounders by using single-nucleotide polymorphisms (SNPs) as instrument variables. Growth Differentiation Factor 15 (GDF 15) is a robust biomarker of metformin use. To verify the potential preventive effect of metformin on lung cancer, we aimed to assess the causality, using SNPs of GDP 15. Methods We utilized the genome-wide association study (GWAS) summary data of GDF 15 and lung cancer. Two-sample MR was used to investigate the causality. In detail, Inverse-Variance Weighted, MR-Egger and Weighted Median methods were conducted. Single SNP analysis and leave-one-out analysis were performed to assess whether the result was driven by a single SNP. We also conducted the MR-Egger regression to evaluate the pleiotropy. Results The result of this study did not support a causality between metformin use and lung cancer incidence (OR = 0.988, 95% CI = 0.914-1.069, P-value = 0.768), which was not driven by single SNP. (Table) Directional horizontal pleiotropy did not seem to exist in the MR-Egger regression (intercept β = −0.02, P = 0.69). Table: 460P Mendelian randomization estimates of the causality between metformin utilization and lung CaExpo Exposure  Outcome  Inverse variance weighted   MR Egger   Weighted median   OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  Metformin Utilization  Lung Cancer  0.988 (0.914-1.069)  0.768  1.049 (0.797-1.381)  0.754  0.982 (0.894-1.079)  0.705  Exposure  Outcome  Inverse variance weighted   MR Egger   Weighted median   OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  Metformin Utilization  Lung Cancer  0.988 (0.914-1.069)  0.768  1.049 (0.797-1.381)  0.754  0.982 (0.894-1.079)  0.705  # Odds ratio. * Confidence interval. Table: 460P Mendelian randomization estimates of the causality between metformin utilization and lung CaExpo Exposure  Outcome  Inverse variance weighted   MR Egger   Weighted median   OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  Metformin Utilization  Lung Cancer  0.988 (0.914-1.069)  0.768  1.049 (0.797-1.381)  0.754  0.982 (0.894-1.079)  0.705  Exposure  Outcome  Inverse variance weighted   MR Egger   Weighted median   OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  OR# (95%CI*)  P-value  Metformin Utilization  Lung Cancer  0.988 (0.914-1.069)  0.768  1.049 (0.797-1.381)  0.754  0.982 (0.894-1.079)  0.705  # Odds ratio. * Confidence interval. Conclusions This study indicated no causality between metformin and lung cancer. The potential use of metformin in lung cancer prevention need further verification in randomized controlled trials. Further studies are warranted to investigate the shared and modifiable risk factors of metformin use and lung cancer contributing to the observed reverse association, which will be beneficial to the control of lung cancer incidence. Legal entity responsible for the study The authors. Funding National Key R&D Program of China (2016YFC0905500, 2016YFC0905503); Science and Technology Program of Guangdong (2017B020227001); Science and Technology Program of Guangzhou (201704020072). Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]