Extension of the Test-Area methodology for calculating solid-fluid interfacial tensions in cylindrical geometry

We extend the well-known Test-Area methodology of Gloor et al. [J. Chem. Phys. 123, 134703 (2005)], originally proposed to evaluate the surface tension of planar fluid-fluid interfaces along a computer simulation in the canonical ensemble, to deal with the solid-fluid interfacial tension of systems adsorbed on cylindrical pores. The common method used to evaluate the solid-fluid interfacial tension invokes the mechanical relation in terms of the tangential and normal components of the pressure tensor relative to the interface. Unfortunately, this procedure is difficult to implement in the case of cylindrical geometry, and particularly complex in case of nonspherical molecules. Following the original work of Gloor et al., we perform free-energy perturbations due to virtual changes in the solid-fluid surface. In this particular case, the radius and length of the cylindrical pore are varied to ensure constant-volume virtual changes of the solid-fluid surface area along the simulation. We apply the modified methodology for determining the interfacial tension of a system of spherical Lennard-Jones molecules adsorbed inside cylindrical pores that interact with fluid molecules through the generalized 10-4-3 Steele potential recently proposed by Siderius and Gelb [J. Chem. Phys. 135, 084703 (2011)]. We analyze the effect of pore diameter, density of adsorbed molecules, and fluid-fluid cutoff distance of the Lennard-Jones intermolecular potential on the solid-fluid interfacial tension. This extension, as the original Test-Area formulation, offers clear advantages over the classical mechanical route of computational efficiency, easy of implementation, and generality.The authors would like to acknowledge helpful discussions with A. I. Moreno-Ventas Bravo, M. M. Piñeiro, and J. M. Míguez. This work was supported by Acción Integrada España-Francia from Ministerio de Ciencia e In- novación and Picasso Project (Project Nos. FR2009-0056 and PHC PICASSO2010). Further financial support from Proyecto de Excelencia from Junta de Andalucía (Project No. P07-FQM02884), Ministerio de Ciencia e Innovación (Project No. FIS2010-14866), and Universidad de Huelva are also acknowledged

An accurate density functional theory for the vaporliquid interface of chain molecules based on the statistical associating fluid theory for potentials of variable range for Mie chainlike fluids

A new Helmholtz free energy density functional is presented to predict the vapor-liquid interface of chainlike molecules. The functional is based on the last version of the statistical associating fluid theory for potentials of variable range for homogeneous Mie chainlike fluids (SAFT-VR Mie). Following the standard formalism, the density functional theory (SAFT-VR Mie DFT) is constructed using a perturbative approach in which the free energy density contains a reference term to describe all the short-range interactions treated at the local level, and a perturbative contribution to account for the attractive perturbation which incorporates the long-range dispersive interactions. In this first work, we use a mean-field version of the theory in which the pair correlations are neglected in the attractive term. The SAFT-VR Mie DFT formalism is used to examine the effect of molecular chain length and the repulsive exponent of the intermolecular potential on density profiles and surface tension of linear chains made up to six Mie (lr6) segments with different values of the repulsive exponent of the intermolecular potential. Theoretical predictions from the theory are compared directly with molecular simulation data for density profiles and surface tension of Mie chainlike molecules taken from the literature. Agreement between theory and simulation data is good for short-chain molecules at all thermodynamic conditions of coexistence considered. Once the theory has proven that is able to predict the interfacial properties, and particularly interfacial tension, the SAFT-VR Mie DFT formalism is used to predict the interfacial behavior of two new coarse-grained models for carbon dioxide and water recently proposed in the literature. In particular, the theoretical formalism, in combination with the coarse-grained models for carbon dioxide and water, is able to predict the interfacial properties of these important substances in a reasonable way.The authors thank helpful discussions with Carlos Avendaño andJosé Matías Garrido. We also acknowledge Centro de Supercom-putación de Galicia (CESGA, Santiago de Compostela, Spain) andMCIA (Mésocentre de Calcul Intensif Aquitain) of the Universitésde Bordeaux and Pau et Pays de l’Adour (France), for providingaccess to computing facilities and Ministerio de Economía, In-dustria y Competitividad through Grant with reference FIS2017-89361-C3-1-P co-financed by EU FEDER funds. Further financialsupport from Junta de Andalucía and Universidad de Huelva isalso acknowledged. J.A., J.M.M., and F.J.B. thankfully acknowl-edge the computer resources at Magerit and the technical supportprovided by the Spanish Supercomputing Network (RES) (ProjectQCM-2018-2-0042)

Sequential versus combination chemotherapy for the treatment of advanced colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial

BACKGROUND: The optimum use of cytotoxic drugs for advanced colorectal cancer has not been defined. Our aim was to investigate whether combination treatment is better than the sequential administration of the same drugs in patients with advanced colorectal cancer. METHODS: In this open-label, randomised, phase 3 trial, we randomly assigned patients (1:1 ratio) with advanced, measurable, non-resectable colorectal cancer and WHO performance status 0-2 to receive either first-line treatment with bolus (400 mg/m(2)) and infusional (2400 mg/m(2)) fluorouracil plus leucovorin (400 mg/m(2)) (simplified LV5FU2 regimen), second-line LV5FU2 plus oxaliplatin (100 mg/m(2)) (FOLFOX6), and third-line LV5FU2 plus irinotecan (180 mg/m(2)) (FOLFIRI) or first-line FOLFOX6 and second-line FOLFIRI. Chemotherapy was administered every 2 weeks. Randomisation was done centrally using minimisation (minimisation factors were WHO performance status, previous adjuvant chemotherapy, number of disease sites, and centre). The primary endpoint was progression-free survival after two lines of treatment. Analyses were by intention-to-treat. This trial is registered at ClinicalTrials.gov, NCT00126256. FINDINGS: 205 patients were randomly assigned to the sequential group and 205 to the combination group. 161 (79%) patients in the sequential group and 161 (79%) in the combination group died during the study. Median progression-free survival after two lines was 10·5 months (95% CI 9·6-11·5) in the sequential group and 10·3 months (9·0-11·9) in the combination group (hazard ratio 0·95, 95% CI 0·77-1·16; p=0·61). All six deaths caused by toxic effects of treatment occurred in the combination group. During first-line chemotherapy, significantly fewer severe (grade 3-4) haematological adverse events (12 events in 203 patients in sequential group vs 83 events in 203 patients in combination group; p<0·0001) and non-haematological adverse events (26 events vs 186 events; p<0·0001) occurred in the sequential group than in the combination group. INTERPRETATION: Upfront combination chemotherapy is more toxic and is not more effective than the sequential use of the same cytotoxic drugs in patients with advanced, non-resectable colorectal cancer. FUNDING: Sanofi-Aventis France

Br J Nutr

The Optimising treatment for acute MAlnutrition (OptiMA) strategy trains mothers to use mid upper arm circumference (MUAC) bracelets for screening and targets treatment to children with MUAC 75 %). A single-arm proof-of-concept trial was conducted in 2017 in Yako district, Burkina Faso including children aged 6–59 months in outpatient health centres with MUAC < 125 mm or oedema. Outcomes were stratified by MUAC category at admission. Multivariate survival analysis was carried out to identify variables predictive of recovery. Among 4958 children included, 824 (16·6 %) were admitted with MUAC < 115 mm or oedema, 1070 (21·6 %) with MUAC 115–119 mm and 3064 (61·8 %) with MUAC 120–124 mm. The new dosage was correctly implemented at all visits for 75·9 % of children. Global recovery was 86·3 (95 % CI 85·4, 87·2) % and 70·5 (95 % CI 67·5, 73·5) % for children admitted with MUAC < 115 mm or oedema. Average therapeutic food consumption was 60·8 sachets per child treated. Recovery was positively associated with mothers trained to use MUAC prior to child’s admission (adjusted hazard ratio 1·09; 95 % CI 1·01, 1·19). OptiMA was successfully implemented at the scale of an entire district under ‘real-life’ conditions. Programme outcomes exceeded SPHERE standards, but further study is needed to determine if increasing therapeutic food dosages for the most severely malnourished will improve recovery

On interfacial properties of tetrahydrofuran : atomistic and coarse-grained models from molecular dynamics simulation

We have determined the interfacial properties of tetrahydrofuran (THF) from direct simulation of the vapor-liquid interface. The molecules are modeled using six di↵erent molecular models, three of them based on the united-atom approach and the other three based on a coarse-grained (CG) approach. In the first case, THF is modeled using the transferable parameters potential functions approach proposed by Chandrasekhar and Jorgensen [J. Chem. Phys. 77, 5073 (1982)] and a new parametrization of the TraPPE force fields for cyclic alkanes and ethers [S. J. Keasler et al., J. Phys. Chem. B 115, 11234 (2012)]. In both cases, dispersive and coulombic intermolecular interactions are explicitly taken into account. In the second case, THF is modeled as a single sphere, a diatomic molecule, and a ring formed from three Mie monomers according to the SAFT-! Mie top-down approach [V. Papaioannou et al., J. Chem. Phys. 140, 054107 (2014)]. Simulations were performed in the molecular dynamics canonical ensemble and the vapor-liquid surface tension is evaluated from the normal and tangential components of the pressure tensor along the simulation box. In addition to the surface tension, we have also obtained density profiles, coexistence densities, critical temperature, density, and pressure, and interfacial thickness as functions of temperature, paying special attention to the comparison between the estimations obtained from di↵erent models and literature experimental data. The simulation results obtained from the three CG models as described by the SAFT-! Mie approach are able to predict accurately the vapor-liquid phase envelope of THF, in excellent agreement with estimations obtained from TraPPE model and experimental data in the whole range of coexistence. However, Chandrasekhar and Jorgensen model presents significant deviations from experimental results.We also compare the predictions for surface tension as obtained from simulation results for all the models with experimental data. The three CG models predict reasonably well (but only qualitatively) the surface tension of THF, as a function of temperature, from the triple point to the critical temperature. On the other hand, only the TraPPE united-atoms models are able to predict accurately the experimental surface tension of the system in the whole temperature rangeWe thank Dr. Andres Mejia (Universidad de Concepcion, Chile) for stimulating discussions. This work was supported by Ministerio de Economia and Competitividad (MINECO, Spain) through Grant Nos. FIS2013-46920-C2-1-P and FIS2015-68910-P, both cofinanced with EU FEDER funds. We also acknowledge CESGA (www.cesga.es) in Santiago de Compostela, Spain, and MCIA (Mesocentre de Calcul Intensif Aquitain) of the Universites de Bordeaux and Pau et Pay de l'Adour, France, for providing access to computing facilities. J.M.G. acknowledges the doctoral scholarship from Conicyt (Chile) and from Red Doctoral REDOC. CTA, MINEDUC Project No. UCO1202 at U. de Concepcion. J.M.M. acknowledges Xunta de Galicia (Spain) for the Postdoctoral Grant. J.A.F. acknowledges Contrato Predoctoral de Investigacion from XIX Plan Propio de Investigacion de la Universidad de Huelva. Further financial support from Junta de Andalucia, Universidad de Huelva, and Carnot Institure (ISIFoR, France) are also acknowledged