Strength, stiffness and ductility of concrete-filled steel columns under axial compression

YesExtensive experimental and theoretical studies have been conducted on the compressive strength of concrete-filled steel tubular (CFST) columns, but little attention has been paid to their compressive stiffness and deformation capacity. Despite this, strength prediction approaches in existing design codes still have various limitations. A finite element model, which was previously proposed by the authors and verified using a large amount of experimental data, is used in this paper to generate simulation data covering a wide range of parameters for circular and rectangular CFST stub columns under axial compression. Regression analysis is conducted to propose simplified models to predict the compressive strength, the compressive stiffness, and the compressive strain corresponding to the compressive strength (ductility) for the composite columns. Based on the new strength prediction model, the capacity reduction factors for the steel and concrete materials are recalibrated to achieve a target reliability index of 3.04 when considering resistance effect only

Concrete-filled bimetallic tubes under axial compression

YesThis paper presents the experimental results of axial compression tests on concrete-filled bimetallic tubes (CFBT). The cross section of the bimetallic tube is composed of an outer layer made of stainless steel and an inner layer made of carbon steel. A total of 12 specimens with a circular cross section were tested under axial compression. The test parameters included the thickness of the stainless steel tube layer (tss=0-1.36 mm) and the compressive strength of the infilled concrete (fcu=21.1-42.8 MPa). Test results showed that, the two layers of the bimetallic tube worked well together, and the CFBT specimens exhibited ductile characteristics. The influence of the parameters on the failure mode, load versus deformation relationship, axial compressive strength, and strain development of the tested specimens were investigated. Finally, the feasibility of three existing design codes for predicting the axial compressive strength of CFST under axial compression was evaluated.Tsinghua University Initiative Scientific Research Program, China Postdoctoral Science Foundatio

Phosphorus poisoning during wet oxidation of methane over Pd@CeO2/graphite model catalysts

10siThe influence of phosphorus and water on methane catalytic combustion was studied over Pd@CeO2 model catalysts supported on graphite, designed to be suitable for X-ray Photoelectron Spectroscopy/Synchrotron Radiation Photoelectron Spectroscopy (XPS/SRPES) analysis. In the absence of P, the catalyst was active for the methane oxidation reaction, although introduction of 15% H2O to the reaction mixture did cause reversible deactivation. In the presence of P, both thermal and chemical aging treatments resulted in partial loss of activity due to morphological transformation of the catalyst, as revealed by Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) analysis. At 600 °C the combined presence of PO43− and water vapor caused a rapid, irreversible deactivation of the catalyst. XPS/SRPES analysis, combined with operando X-ray Absorption Near Edge Structure (XANES) and AFM measurements, indicated that water induces severe aggregation of CeO2 nanoparticles, exposure of CePO4 on the outer layer of the aggregates and incorporation of the catalytic-active Pd nanoparticles into the bulk. This demonstrates a temperature-activated process for P-poisoning of oxidation catalysts in which water vapor plays a crucial role.partially_openembargoed_20171009Monai, Matteo; Montini, Tiziano; Melchionna, Michele; Duchoň, Tomáš; Kúš, Peter; Tsud, Nataliya; Prince, Kevin C.; Matolin, Vladimir; Gorte, Raymond J.; Fornasiero, PaoloMonai, Matteo; Montini, Tiziano; Melchionna, Michele; Duchoň, Tomáš; Kúš, Peter; Tsud, Nataliya; Prince, Kevin C.; Matolin, Vladimir; Gorte, Raymond J.; Fornasiero, Paol

Factors associated with diagnosis of stages I and II lung cancer: a multivariate analysis

OBJECTIVE To present the overall survival rate for lung cancer and identify the factors associated with early diagnosis of stage I and II lung cancer. METHODS This is a retrospective cohort study including individuals diagnosed with lung cancer, from January 2009 to December 2017, according to the cancer registry at UMass Memorial Medical Center. Five-year overall survival and its associated factors were identified by Kaplan–Meier curves and Cox’s proportional hazards model. Factors associated with diagnosing clinical stage I and II lung cancer were identified by bivariate and multivariate backward stepwise logistic regression (Log-likelihood ratio (LR)) at 95% confidence interval (CI). RESULTS The study was conducted with data on 2730 individuals aged 67.9 years on average, 51.5% of whom female, 92.3% white, and 6.6% never smoked. Five-year overall survival was 21%. Individuals diagnosed with early-stage disease had a 43% five-year survival rate compared to 8% for those diagnosed at late stages. Stage at diagnosis was the main factor associated with overall survival [HR = 4.08 (95%CI: 3.62–4.59)]. Factors associated with early diagnosis included patients older than 68 years [OR = 1.23 (95%CI: 1.04–1.45)], of the female gender [OR = 1.47 (95%CI: 1.24–1.73)], white [OR = 1.63 (95%CI: 1.16–2.30)], and never-smokers [OR = 1.37 (95%CI: 1.01–1.86)]; as well as tumors affecting the upper lobe [OR = 1.46 (95%CI: 1.24–1.73)]; adenocarcinoma [OR = 1.43 (95%CI: 1.21–1.69)]; and diagnosis after 2014 [OR = 1.61 (95%CI: 1.37–1.90)]. CONCLUSIONS Stage at diagnosis was the most decisive predictor for survival. Non-white and male individuals were more likely to be diagnosed at a late stage. Thus, promoting lung cancer early diagnosis by improving access to health care is vital to enhance overall survival for individuals with lung cancer

Phase 1 study of the MDM2 antagonist RO6839921 in patients with acute myeloid leukemia

In acute myeloid leukemia (AML), TP53 mutations and dysregulation of wild-type p53 is common and supports an MDM2 antagonist as a therapy. RO6839921 is an inactive pegylated prodrug of the oral MDM2 antagonist idasanutlin (active principle [AP]) that allows for IV administration. This phase 1 monotherapy study evaluated the safety, pharmacokinetics, and pharmacodynamics of RO6839921 in patients with AML. Primary objectives identified dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Secondary objectives assessed pharmacokinetic, pharmacodynamic, and antileukemic activity. A total of 26 patients received 120-300 mg AP of idasanutlin. The MTD was 200 mg, with DLTs at 250 (2/8 patients) and 300 mg (2/5). Treatment-related adverse events in \u3e20% of patients were diarrhea, nausea, vomiting, decreased appetite, and fatigue. Six deaths (23.1%) occurred, all unrelated to treatment. Pharmacokinetics showed rapid and near-complete conversion of the prodrug to AP and dose-proportional exposure across doses. Variability ranged from 30%-47% (22%-54% for idasanutlin). TP53 was 21 (87.5%) wild-type and 3 mutant (12.5%). The composite response rate (complete remission [CR], CR with incomplete hematologic recovery/morphological leukemia-free state [CRi/MLFS], or CR without platelet recovery [CRp]) was 7.7%. Antileukemic activity (CR, CRi/MLFS, partial response, hematologic improvement/stable disease) was observed in 11 patients (disease control rate, 42%): 10/11 were TP53 wild-type; 1 had no sample. p53 activation was demonstrated by MIC-1 induction and was associated with AP exposure. There was not sufficient differentiation or improvement in the biologic or safety profile compared with oral idasanutlin to support continued development of RO6839921. NCT02098967

Quality-adjusted Time Without Symptoms of disease or Toxicity (Q-TWiST) analysis of CPX-351 versus 7 + 3 in older adults with newly diagnosed high-risk/secondary AML

BACKGROUND: CPX-351 (United States: Vyxeos METHODS: Patients were randomized 1:1 between December 20, 2012 and November 11, 2014 to receive induction with CPX-351 or 7 + 3. Survival time for each patient was partitioned into 3 health states: TOX (time with any grade 3 or 4 toxicity or prior to remission), TWiST (time in remission without relapse or grade 3 or 4 toxicity), and REL (time after relapse). Within each treatment arm, Q-TWiST was calculated by adding the mean time spent in each health state weighted by its respective quality-of-life, represented by health utility. The relative Q-TWiST gain, calculated as the difference in Q-TWiST between treatment arms divided by the mean survival of the 7 + 3 control arm, was determined in order to evaluate results in the context of other Q-TWiST analyses. RESULTS: The relative Q-TWiST gain with CPX-351 versus 7 + 3 was 53.6% in the base case scenario and 39.8% among responding patients. Across various sensitivity analyses, the relative Q-TWiST gains for CPX-351 ranged from 48.0 to 57.6%, remaining well above the standard clinically important difference threshold of 15% for oncology. CONCLUSIONS: This post hoc analysis demonstrates that CPX-351 improved quality-adjusted survival, further supporting the clinical benefit in patients with newly diagnosed high-risk/secondary acute myeloid leukemia. Trial registration This trial was registered on September 28, 2012 at www.clinicaltrials.gov as NCT01696084 ( https://clinicaltrials.gov/ct2/show/NCT01696084 ) and is complete

Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination. During the expansion phase, additional patients received CPX-351 plus venetoclax at the identified RP2D. The primary end points were the RP2D and safety of CPX-351 combined with venetoclax. Secondary end points included preliminary efficacy and pharmacokinetics. Overall, 35 patients were enrolled in the study. A RP2D of CPX-351 30 units/m2 (daunorubicin 13.2 mg/m2 and cytarabine 30 mg/m2) plus venetoclax 400 mg was established. The safety profile of the combination was consistent with the known safety profiles of CPX-351 and venetoclax. Complete remission (CR)/CR with incomplete hematologic recovery (CRi) was achieved by 17 of 35 patients (49%), all after cycle 1; of these, 14 were negative for measurable residual disease. CR was achieved by 1 of 8 patients (13%) with a mutation in TP53, and CR/CRi was achieved by 15 of 26 patients (58%) with wild-type TP53. This study highlights that lower-intensity therapy of CPX-351 plus venetoclax as induction therapy provides a well-tolerated treatment option in adults with AML deemed unfit for intensive chemotherapy. This trial was registered at www.ClinicalTrials.gov as #NCT04038437