Dihydroartemisinin-Piperaquine and Artemether-Lumefantrine for Treating Uncomplicated Malaria in African Children: A Randomised, Non-Inferiority Trial

BACKGROUND: Artemisinin combination therapies (ACTs) are currently the preferred option for treating uncomplicated malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising fixed-dose ACT with limited information on its safety and efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: The non-inferiority of DHA-PQP versus artemether-lumefantrine (AL) in children 6-59 months old with uncomplicated P. falciparum malaria was tested in five African countries (Burkina Faso, Kenya, Mozambique, Uganda and Zambia). Patients were randomised (2:1) to receive either DHA-PQP or AL. Non-inferiority was assessed using a margin of -5% for the lower limit of the one-sided 97.5% confidence interval on the treatment difference (DHA-PQP vs. AL) of the day 28 polymerase chain reaction (PCR) corrected cure rate. Efficacy analysis was performed in several populations, and two of them are presented here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 1553 children were randomised, 1039 receiving DHA-PQP and 514 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% (ePP) in the AL group. The lower limits of the one-sided 97.5% CI of the difference between the two treatments were -2.80% and -2.96%, in the ITT and ePP populations, respectively. In the ITT population, the Kaplan-Meier estimate of the proportion of new infections up to Day 42 was 13.55% (95% CI: 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: DHA-PQP is as efficacious as AL in treating uncomplicated malaria in African children from different endemicity settings, and shows a comparable safety profile. The occurrence of new infections within the 42-day follow up was significantly lower in the DHA-PQP group, indicating a longer post-treatment prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com ISRCTN16263443

Advances in modelling of biomimetic fluid flow at different scales

The biomimetic flow at different scales has been discussed at length. The need of looking into the biological surfaces and morphologies and both geometrical and physical similarities to imitate the technological products and processes has been emphasized. The complex fluid flow and heat transfer problems, the fluid-interface and the physics involved at multiscale and macro-, meso-, micro- and nano-scales have been discussed. The flow and heat transfer simulation is done by various CFD solvers including Navier-Stokes and energy equations, lattice Boltzmann method and molecular dynamics method. Combined continuum-molecular dynamics method is also reviewed

Optical determination of temperature and species concentration for homogeneous turbulent gas medium

In this study, we present an inverse calculation model to reconstruct time-averaged temperature, species concentration and their root mean square (rms) values from optical synthetic measurements for a homogeneous turbulent gaseous medium. The model is based on line-of-sight spectral transmissivity synthetic measurements, and time-averaged transmissivities and their rms values are successfully related to time-averaged temperatures, species concentrations and their rms values by considering interaction between turbulence and radiation (TRI). The turbulence length scale is also retrieved simultaneously with the turbulent scalars. In order to validate the model, a stochastic approach is used to generate synthetic turbulent fields (fluctuations of temperature and species concentration), and measured spectra are synthesized through calculations from HITEMP 2010 for different spectral bands of CO2, H2O and CO

Advanced differential approximation formulation of the PN method for radiative transfer

The spherical harmonics (P ) method, especially its lowest order, i.e., the P1 or differential approximation, enjoys great popularity because of its relative simplicity and compatibility with standard models for the solution of the (overall) energy equation. Low-order PN approximations perform poorly in the presence of strongly nonisotropic intensity distributions, especially in optically thin situations within nonisothermal enclosures (due to variation in surface radiosities across the enclosure surface, causing rapid change of irradiation over incoming directions). A previous modification of the PN approximation, i.e., the modified differential approximation (MDA), separates wall emission from medium emission to reduce the nonisotropy of intensity. Although successful, the major drawback of this method is that the intensity at the walls is set to zero into outward directions, while incoming intensity is nonzero, resulting in a discontinuity at grazing angles. To alleviate this problem, a new approach, termed here the advanced differential approximation (ADA)is developed, in which the directional gradient of the intensity at the wall is minimized. This makes the intensity distribution continuous for the P1 method and mostly continuous for higher-order PN methods. The new method is tested for a 1D slab and concentric spheres and for a 2D medium. Results are compared with the exact analytical solutions for the 1D slab as well as the Monte Carlo-based simulations for 2D media.

Two-dimensional axisymmetric formulation of high order spherical harmonics methods for radiative heat transfer

The spherical harmonics (PN) method is a radiative transfer equation solver, which approximates the radiative intensity as a truncated series of spherical harmonics. For general 3-D configurations, N(N+1)/2 intensity coefficients must be solved from a system of coupled second-order elliptic PDEs. In 2-D axisymmetric applications, the number of equations and intensity coefficients reduces to (N+1)2/4 if the geometric relations of the intensity coefficients are taken into account. This paper presents the mathematical details for the transformation and its implementation on the OpenFOAM finite volume based CFD software platform. The transformation and implementation are applicable to any arbitrary axisymmetric geometry, but the examples to test the new formulation are based on a wedge grid, which is the most common axisymmetric geometry in CFD simulations, because OpenFOAM and most other platforms do not have true axisymmetric solvers. Two example problems for the new axisymmetric PN formulation are presented, and the results are verified with that of the general 3-D PN solver, a Photon Monte Carlo solver and exact solutions

Eulerian-Eulerian multi-fluid methods for pulverized coal flames with nongray radiation

A new Favre averaging method based on gas phase density applied to Eulerian-Eulerian simulations of turbulent multiphase reacting flows is proposed. The new Favre averaging method can reproduce turbulent dispersions of mass, momentum, heat and species of solid phases from their averaged transport equations. A new radiation model that can account for nongray gas-solid mixtures is developed for pulverized coal flames. The new models are validated against a pulverized coal ignition flame. Predictions of velocity, temperature and gas major species are found in good agreement with experiments. Pyrometer measurements of temperature are predicted by a radiation transport calculation. It is found that radiation cooling effects can lead to a 500K temperature decline in solid phases. Radiation also has indirect influence on CO predictions through the slow yet strongly temperature-dependent char reaction rates. The consideration of radiation improves predictions of both temperature and CO concentrations. Effects of devolatilization model and number of phases are also discussed. 2