Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects

BACKGROUND\ud \ud Efforts to ease administration and enhance acceptability of the oral anti-malarial artemether-lumefantrine (A-L) crushed tablet to infants and children triggered the development of a novel dispersible tablet of A-L. During early development of this new formulation, two studies were performed in healthy subjects, one to evaluate the palatability of three flavours of A-L, and a second one to compare the bioavailability of active principles between the dispersible tablet and the tablet (administered crushed and intact).\ud \ud METHODS\ud \ud Study 1 was performed in 48 healthy schoolchildren in Tanzania. Within 1 day, all subjects tasted a strawberry-, orange- and cherry-flavoured oral A-L suspension for 10 seconds (without swallowing) in a randomized, single-blind, crossover fashion. The palatability of each formulation was rated using a visual analogue scale (VAS). Study 2 was an open, randomized crossover trial in 48 healthy adults given single doses of A-L (80 mg artemether + 480 mg lumefantrine) with food. The objectives were to compare the bioavailability of artemether, dihydroartemisinin (DHA) and lumefantrine between the dispersible tablet and the tablet administered crushed (primary objective) and intact (secondary objective).\ud \ud RESULTS\ud \ud Study 1 showed no statistically significant difference in VAS scores between the three flavours but cherry had the highest score in several ratings (particularly for overall liking). Study 2 demonstrated that the dispersible and crushed tablets delivered bioequivalent artemether, DHA and lumefantrine systemic exposure (area under the curve [AUC]); mean ± SD AUC0-tlast were 208 ± 113 vs 195 ± 93 h.ng/ml for artemether, 206 ± 81 vs 199 ± 84 h.ng/ml for DHA and 262 ± 107 vs 291 ± 106 h x μg/ml for lumefantrine. Bioequivalence was also shown for peak plasma concentrations (Cmax) of DHA and lumefantrine. Compared with the intact tablet, the dispersible tablet resulted in bioequivalent lumefantrine exposure, but AUC and Cmax values of artemether and DHA were 20-35% lower.\ud \ud CONCLUSIONS\ud \ud Considering that cherry was the preferred flavour, and that the novel A-L dispersible tablet demonstrated similar pharmacokinetic performances to the tablet administered crushed, a cherry-flavoured A-L dispersible tablet formulation was selected for further development and testing in a large efficacy and safety study in African children with malaria

Disturbi dello spettro autistico vs. disturbi genetici del neurosviluppo

vengono riviste le condizioni neurogenetiche il cui fenotipo include la presenza di un disturbo autistico o manifestano una spiccata diatesi autistic

Analysis of wall–flame interaction in laminar non-premixed combustion

The study is aimed at demonstrating a methodology for the time-scale characterization of the chemistry-wall-heat-transfer interaction. The driving chemical time-scale is estimated by means of the tangential stretching rate, and a proper thermal timescale for the temperature-time variation due to wall heat flux is presented. A thermal Damköhler number, Dath, is proposed as the ratio of the two. The methodology is applied on a prototypical laminar methane-oxygen diffusion flame impinging on an isothermal cold wall. Non-adiabatic effects are described qualitatively and a CSP-TSR analysis is performed to obtain topological information and physical insights. The thermal Damköhler number field is computed and discussed to highlight the interplay between chemical and diffusive processes and to a-priori assess the accuracy of the steady laminar flamelet assumption under non-adiabatic conditions

What Are Patients Seeking When They Turn to the Internet? Qualitative Content Analysis of Questions Asked by Visitors to an Orthopaedics Web Site

BACKGROUND: More people than ever are turning to the Internet for health-related information, and recent studies indicate that the information patients find online directly affects the decisions they make about their health care. Little is known about the information needs or actual search behavior of people who use the Internet for health information. OBJECTIVE: This study analyzes what people search for when they use a health-education Web site offering information about arthritis, orthopaedics, and sports-medicine topics. Additionally, it determines who is performing these searches: is it patients, friends or relatives of patients, or neither? Finally, it examines the similarities and differences among questions submitted by Web site visitors from different countries. METHODS: Content analysis was performed on 793 free-text search queries submitted to a patient-education Web site owned and operated by the Department of Orthopaedics and Sports Medicine at the University of Washington Medical Center. The 793-query data set was coded into 3 schemes: (1) the purpose of the query, (2) the topic of the query, and (3) the relationship between the asker of the query and the patient. We determined the country from which each query was submitted by analyzing the Internet Protocol addresses associated with the queries. RESULTS: The 5 most frequent reasons visitors searched the Web site were to seek: (1) information about a condition, (2) information about treatment, (3) information about symptoms, (4) advice about symptoms, and (5) advice about treatment. We were able to determine the relationship between the person submitting the query and the patient in question for 178 queries. Of these, the asker was the patient in 140 cases, and the asker was a friend or relative of the patient in 38 cases. The queries were submitted from 34 nations, with most coming from the United States, Australia, the United Kingdom, and Canada. When comparing questions submitted from the United States versus those from all other countries, the 3 most frequent types of questions were the same for both groups (and were the top 3 question types listed above). CONCLUSIONS: These results provide the University of Washington Department of Orthopaedics and Sports Medicine, as well as other organizations that provide health-information Web sites, with data about what people around the world are seeking when they turn to the Internet for health information. If Web site managers can adapt their health-information Web sites in response to these findings, patients may be able to find and use Internet-based health information more successfully, enabling them to participate more actively in their health care

Study on buoyant instabilities of high pressures laminar jet flames

Laminar diffusion jet flames are subjected to buoyant instabilities when the Froude number is lower than a critical value. In the present work, a numerical study on syngas laminar jet diffusion flames at elevated pressures (1, 2, 4, 8 and 12 bar) and buoyant instabilities is presented. Since the Reynolds number is kept constant, the velocity and Froude number diminish as pressure is increased. For pressures from 1 to 4 bar the flames display a steady behavior with a progressive reduction of the thickness, while for 8 and 12 bar the flames oscillate and pulsate. These predictions are consistent with experimental observations. Furthermore, for the unsteady flames, the pulsation of the flame thickness and spatial oscillations are quantified and analyzed

Large eddy simulation with flamelet progress variable approach via neural network acceleration

In the context of large eddy simulation of turbulent reacting flows, flamelet-based models are key to affordable simulations of large and complex systems. However, as the complexity of the problem increases, higher-dimensional look-up tables are required, rendering the conventional look-up procedure too demanding. This work focuses on accelerating the estimation of flamelet-based data for the flamelet/progress variable model via an artificial neural network. The neural network hyper-parameters are defined by a Bayesian optimization and two different architectures are selected for comparison against the classical look-up procedure on the well known Sandia flame D. The performance in terms of execution time and accuracy are analyzed, showing that the neural network model reduces the computational time by 30%, as compared to the traditional table look-up, while retaining comparable accuracy

Uncertainty quantification analysis of rans of spray jets

Parametric uncertainty is propagated through Reynolds-averaged Navier-Stokes (RANS) computations of a prototypical acetone/air aerosol stream flowing in a dry air environment. Two parameters are considered as uncertain: the inflow velocity dissipation and a coefficient that blends the discrete random walk and the gradient-based dispersion models. A Bayesian setting is employed to represent the degree of belief about the parameters of interest in terms of probability theory, such that uncertainty is described with probability density functions. Random variables are represented by means of polynomial chaos expansions. The sensitivity of mean axial velocity and mean vapor mass fraction to the uncertain parameters is discussed