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Background Ramucirumab-an IgG1 vascular endothelial growth factor receptor 2 antagonistplus docetaxel was previously reported to improve progression-free survival in platinum-refractory, advanced urothelial carcinoma. Here, we report the secondary endpoint of overall survival results for the RANGE trial.Methods We did a randomised, double-blind, phase 3 trial in patients with advanced or metastatic urothelial carcinoma who progressed during or after platinum-based chemotherapy. Patients were enrolled from 124 investigative sites (hospitals, clinics, and academic centres) in 23 countries. Previous treatment with one immune checkpoint inhibitor was permitted. Patients were randomly assigned (1:1) using an interactive web response system to receive intravenous ramucirumab 10 mg/kg or placebo 10 mg/kg volume equivalent followed by intravenous docetaxel 75 mg/m 2 (60 mg/m 2 in Korea, Taiwan, and Japan) on day 1 of a 21-day cycle. Treatment continued until disease progression, unacceptable toxicity, or other discontinuation criteria were met. Randomisation was stratified by geographical region, Eastern Cooperative Oncology Group performance status at baseline, and visceral metastasis. Progression-free survival (the primary endpoint) and overall survival (a key secondary endpoint) were assessed in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT02426125; patient enrolment is complete and the last patient on treatment is being followed up for safety issues.Findings Between July 20, 2015, and April 4, 2017, 530 patients were randomly allocated to ramucirumab plus docetaxel (n=263) or placebo plus docetaxel (n=267) and comprised the intention-to-treat population. At database lock (March 21, 2018) for the final overall survival analysis, median follow-up was 7.4 months (IQR 3.5-13.9). In our sensitivity analysis of investigator-assessed progression-free survival at the overall survival database lock, median progression-free survival remained significantly improved with ramucirumab compared with placebo (4.1 months [95% CI 3.3-4.8] vs 2.8 months [2.6-2.9]; HR 0.696 [95% CI 0.573-0.845]; p=0.0002). Median overall survival was 9.4 months (95% CI 7.9-11.4) in the ramucirumab group versus 7.9 months (7.0-9.3) in the placebo group (stratified HR 0.887 [95% CI 0.724-1.086]; p=0.25). Grade 3 or worse treatment-related treatment-emergent adverse events in 5% or more of patients and with an incidence more than 2% higher with ramucirumab than with placebo were febrile neutropenia (24 [9%] of 258 patients in the ramucirumab group vs 16 [6%] of 265 patients in the placebo group) and neutropenia (17 [7%] of 258 vs six [2%] of 265). Serious adverse events were similar between groups (112 [43%] of 258 patients in the ramucirumab group vs 107 [40%] of 265 patients in the placebo group). Adverse events related to study treatment and leading to death occurred in eight (3%) patients in the ramucirumab group versus five (2%) patients in the placebo group.Interpretation Additional follow-up supports that ramucirumab plus docetaxel significantly improves progression-free survival, without a significant improvement in overall survival, for patients with platinum-refractory advanced urothelial carcinoma. Clinically meaningful benefit might be restricted in an unselected population. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

In this work a possibility of formation of supramolecular structures based on carbon nanotubes and coordinate molecules – cyclic hydrocarbons (including aromatic) was studied by means of molecular dynamics method. Model supramolecular structures were defined as arrays of nanotubes, coordinated by hydrocarbon molecules mainly in triangular package. A correlation between the sizes of coordinate molecules and average distances between nanotubes in the structures was defined as well as conditions of porosity development between the nanotubes while maintaining their ordered arrangement. Maximal adsorption of methane and hydrogen in model structures was estimated in space between the nanotubes as well as inside them

The goal of this work is to try to figure out the role of water in catalytic and non-catalytic aquathermolysis by using isotope tracing techniques. For this purpose, heavy water (deuterium oxide, D2O) was used to replace the ordinary water (H2O) for catalytic and non-catalytic aquathermolysis processes of extra-heavy oil with high sulfur content in autoclave. The donating and upgrading performance of D2O were deeply investigated by analyzing the upgraded (deuterated) oil and their SARA (saturates, aromatics, resins and asphaltenes) fractions using different tracing techniques (FTIR, isotope and elemental analysis), evolved gases by GC, and change in physical-chemical properties of upgraded (deuterated) oils by viscosity measurement, SARA analysis, elemental analysis and GC, etc. The results proved the chemical role of water as a green and environmental hydrogen-donor solvent during aquathermolysis process, verified by considerable deuterium substitution (deuteration) obtained from isotope analysis both in upgraded oil and SARA fractions. The results are further supported by significant deuterium exchanges (deuteration) of aliphatic and aromatics parts in the initial and deuterated oil samples and their individual SARA fractions in FTIR spectra. Simultaneously, introducing Ni-tallate as an oil-soluble catalyst promoted the donating capacity of water, thus significantly improving the upgrading performance. The important finding about the role of water in catalytic and non-catalytic aquathermolysis not only enriches the theoretical basis in this area, but also provides a strong support for the use of catalysts in aquathermolysis for improving in-situ heavy oil upgrading performance.

A novel hybrid material was prepared by the direct growth technique starting from metal-organic framework HKUST-1 (Cu3(BTC)2, BTC = benzene-1,3,5-tricarboxylate) and mesoporous silica matrix (MMS). MMS acts as a structure-directing agent, which assists to the formation of very small HKUST-1 nanoparticles (4–8 nm) are dispersed homogeneously in the silica matrix. To evaluate the field of the potential exploitation of HKUST-1@MMS hybrid, it was examined as a heterogeneous catalyst with Lewis and Bronsted acid sites in demanding organic transformations widely used for fine chemicals production, i.e. in the Friedlӓnder reaction between 2-amino-5-chlorobenzophenone and acetylacetone and Henry reaction (nitroaldol condensation) between nitromethane and 4-nitrobenzaldehyde. The cooperative effect between Lewis acid sites as Cu2+ ions in the HKUST-1 framework and acid sites of MMs silica in the HKUST-1@MMS catalytic material relevant to the Henry reaction between 4-nitrobenzaldehyde and nitromethane was found for the first time. According to adsorption tests, the novel hybrid features an hierarchical micro-/mesoporous structure and can also find application as an adsorbent with molecular-sieving properties.

A new approach was developed for the formation of an adsorbent from solid residual products of carbon dioxide reforming of Fe-containing lignin. The key stages of this approach are: (1) etching of residual products with dilute HCl; (2) carbon dioxide treatment with microwave plasma induction at 950–1000 ○С; and (3) thermal shock. The sequential application of procedures (1)–(3) to the residual products of carbon dioxide reforming of Fe-containing lignin affords a carbon adsorbent with a specific surface area of ~578 m2/g and comparable volumes of micro- and mesopores.

Deformations of organo-substituted laminar silicates (Pyzhevsk montmorillonite and synthetic fluorohectorite) upon hexane and benzene vapor sorption have been studied. To solve this problem, a dilatometer was used. Its main part was a line differential transformer, the core of which was connected to the sorbent by means of a rod. Any changes in the sorbent height caused a change in the core position in the transformer, which influenced the signal recorded from its secondary winding. The calibrated dilatometer was located in a liquid thermostat with a given temperature and was connected with the measurement unit (frequency meter, voltmeter, and generator). Montmorillonite and synthetic fluorohectorite were modified by cetylpyridinium bromide and used in the form of tablets. As a result of the samples preparation conditions, the modified clay silicates swelled isotropically. These results were compared with the sorption isotherms obtained gravimetrically. High sensitivity of the dilatometric method to the structural changes of the organo-substituted laminar silicates has been shown. The dilatometer used allowed the measurement of absolute deformations in the range 1×10−4 to 3 mm. Also, the dilatometric method was used for the first time to study the sorptive deformation hysteresis of sorbents. On the basis of the results obtained, it was suggested that sorbent deformation may be the universal cause of sorptive hysteresis.

It is shown that the known Dubinin–Radushkevich (DR) equation, which is widely used in engineering calculations of different technological processes and, in particular, in the field of chemical protection, follows from an earlier equation representing the interphase equilibrium condition for certain model prerequisites. A physical justification of the DR equation and its refinement is presented.

Deformations of cation-substituted vermiculite (Na, Ca, and Ba forms) upon water vapor sorption have been studied. To solve this problem a dilatometer was used. Its main part was a line differential transformer, the core of which was connected to the sorbent by means of a rod. Any changes of the sorbent height caused a change in the core position in the transformer, which influenced the signal recorded from its secondary winding. The sorbents used were plate-formed, anisotropic, and swelled only in the direction perpendicular to the plane of the plates. The results obtained were compared with the adsorption, calorimetry (a Calvet-type microcalorimeter with a microbalance attachment was used) and X-ray data. High sensitivity of the dilatometric method to the structural changes of the laminated silicates whose cell structures expand upon hydration has been shown.

A differential microcalorimetric technique for the investigation of high-pressure adsorption of fluids on microporous solids is developed. The thermodynamic analysis of the experimental scheme and the relationship between isosteric and calorimetric differential heats of adsorption are given. These values are obtained for the system Xe-zeolite Na X at pressures of 1 × 10 -5 -22 MPa and temperatures of 299-467 K. The strong dependence of differential calorimetric heats on adsorption on temperature observed at sufficiently high loadings is interpreted in terms of cooperative adsorbate-adsorbate interactions and adsorption deformation of the adsorbent. The notion of the area of thermodynamic inertness of the adsorbent is introduced and its frontiers are established for the system under question. In this region of comparatively low pressures and temperatures, the differential calorimetric heats and the isosteric heats of adsorption determined under the assumption of an inert adsorbent are in good agreement. Beyond this region, considerable differences between these values are shown to be due to adsorption deformation of adsorbent.

A combined experimental approach comprising up-to-date high-sensitivity methods was used to reveal the factors causing the sorptive hysteresis that occurs in sorption. The dilatometric method was used for the first time to study the sorptive deformation hysteresis of sorbents. On the basis of the results obtained, it was suggested that sorbent deformation may be the universal cause of sorptive hysteresis.