Tarral A.,Drugs for Neglected Diseases initiative DNDi |
Blesson S.,Drugs for Neglected Diseases initiative DNDi |
Mordt O.V.,Drugs for Neglected Diseases initiative DNDi |
Torreele E.,Drugs for Neglected Diseases initiative DNDi |
And 7 more authors.
Clinical Pharmacokinetics | Year: 2014
Background and Objectives: Fexinidazole is a 5-nitroimidazole recently included in a clinical efficacy trial as an oral drug for the treatment of human African trypanosomiasis (HAT). Preclinical studies showed it acts as a pharmacologically active pro-drug with two key active metabolites: sulfoxide and sulfone (the most active metabolite). The present studies aimed to determine the best dose regimen for the treatment of stage 2 sleeping sickness patients, which could eventually also treat stage 1 patients. Methods: Fexinidazole was assessed in 154 healthy adult male subjects of sub-Saharan African origin. Three initial first-in-human studies and two additional studies assessed a single ascending dose and multiple ascending doses (both under fasted conditions), tablet versus suspension formulation and food effect (fasted vs. high-fat meal and field-adapted food), and multiple ascending doses with a loading dose regimen under fed conditions. Results: Fexinidazole was well-tolerated in a single dose from 100 to 3,600 mg, with quick absorption of the parent drug and rapid metabolism into sulfoxide [time to maximum concentration (t max) 2-5 h] and sulfone (t max 18-24 h). The tablet formulation was approximately 25 % less bioavailable than the suspension, and food intake increased drug absorption and plasma concentrations of fexinidazole and its two metabolites by approximately 200 %. Fourteen-day multiple ascending dosing administered up to 3,600 mg/day in fasted conditions showed that fexinidazole was generally well-tolerated (mild to moderate, spontaneously reversible drug-related adverse events). Following the high-fat food effect finding, another study was conducted to evaluate the impact of a low-fat regimen closer to that of the target population, showing that the type of meal does not influence fexinidazole absorption. The last study showed that a loading dose of 1,800 mg/day for 4 days followed by a 1,200 mg/day regimen for 6 days with a normal meal provided the desired exposure of fexinidazole and its metabolites, particularly sulfone, with good tolerability. Based on preclinical evidence from a chronic infection mouse model, systemic drug concentrations obtained are expected to be clinically effective in stage 2 HAT. Conclusions: These studies show that fexinidazole can be safely assessed in patients as a potential oral cure for both stages of HAT. © 2014 The Author(s).
Emam A.,Aswan University |
Zoheir B.,Benha University |
International Geology Review | Year: 2016
The Allaqi-Heiani suture is an ~250 km-long ophiolite-associated fold-and-thrust belt in the South Eastern Desert of Egypt. It comprises imbricate thrust sheets of ophiolites (serpentinite, amphibolite, metagabbro, and metabasalt) and island-arc metavolcanic/metasedimentary rocks. Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER)-based mafic-ultramafic indices are combined with band ratioing (BR) and relative absorption band-depth techniques to comprehensively map the ophiolitic rocks along the eastern part of the Allaqi-Heiani suture. The applied techniques are found efficient in delineating the ophiolitic rocks in the study area, despite their highly tectonized and variably carbonate-altered character. Identification and mapping of the exposed mafic-ultramafic rocks were possible using shortwave infrared (SWIR) band ratio 4/8 and thermal infrared (TIR) band ratio 12/14. The refined mafic index (MI) provides an efficient discrimination of the ophiolitic mafic rocks, while the mafic-ultramafic indices (M1 and M2) show high sensitivity to ophiolitic ultramafic units. The mafic-ultramafic indices enabled an efficient discrimination of mafic ophiolites from mafic island-arc rocks. Combining mafic indices and SWIR band ratio 4/8 allowed an enhanced delineation of the ophiolitic mafic-ultramafic rocks from other rock units in the area. Detailed mapping of the ophiolitic units in the ophiolitic terranes was obtained using the relative absorption band depth (RBD8) together with the MI and band ratio 4/8. This approach offers a quick method to discriminate among ophiolitic rock units and to map their structural contacts, i.e. in such hitherto poorly studied and hardly accessible areas. © 2015 Taylor & Francis.
Macura B.,Institute Of Ciencia I Tecnologia Ambientals |
Zorondo-Rodriguez F.,Institute Of Ciencia I Tecnologia Ambientals |
Grau-Satorras M.,Institute Of Ciencia I Tecnologia Ambientals |
Demps K.,French Institute of Pondicherry |
And 3 more authors.
Ecology and Society | Year: 2011
The success of long-term sustainable management of natural resources depends on local people's support. Assessing local people's attitudes, taking into account their needs, and respecting their opinions should become a management priority. In India, in the last 20 years, community needs and aspirations in forest management were handled through Joint Forest Management with varying degrees of success. Recently, the Forest Rights Act (2006) was passed to recognize and vest forest rights in forest dwelling communities. This major policy development is still in implementation, but little is known about how this devolution process will affect people's attitudes toward forests. In this paper, we analyze associations between attitudes toward state controlled forests (Reserved Forests) and (i) awareness about the Forest Right Act, (ii) attitudes toward the State Forest Department, and (iii) participation in forest management groups of mostly tribal forest dwellers in the district of Kodagu (Karnataka). We collected information with a structured questionnaire among 247 villagers living under three different land tenure and management regimes: (1) private coffee plantations, (2) Reserved Forest, and (3) National Park. The results of the multivariate analyses show that people are more likely to appreciate Reserved Forests if they have more knowledge about the Forest Rights Act and if they have positive attitudes toward the State Forest Department. A sobering result in our sample is that participation in formal forest management groups is negatively associated to attitudes toward Reserved Forests, suggesting the Joint Forest Management model doesn't necessarily help the transition from coercion to consent. Increasing local people awareness about their rights and improving their relations with the formal forest stewards remain priorities for sustainable forest management to emerge in India. © 2011 by the author(s).
Herrera C.N.L.,Antonio Narino University |
Vallejo M.F.M.,SGS |
Mueller J.L.,Colorado State University |
Lima R.G.,University of Sao Paulo
IEEE Transactions on Medical Imaging | Year: 2015
A novel direct D-bar reconstruction algorithm is presented for reconstructing a complex conductivity distribution from 2-D EIT data. The method is applied to simulated data and archival human chest data. Permittivity reconstructions with the aforementioned method and conductivity reconstructions with the previously existing nonlinear D-bar method for real-valued conductivities depicting ventilation and perfusion in the human chest are presented. This constitutes the first fully nonlinear D-bar reconstructions of human chest data and the first D-bar permittivity reconstructions of experimental data. The results of the human chest data reconstructions are compared on a circular domain versus a chest-shaped domain. © 2014 IEEE.
Geng P.,General Motors |
Furey R.,Furey and Associates LLC |
SAE International Journal of Fuels and Lubricants | Year: 2010
Ethanol for use in automotive fuels can be made from renewable feedstocks, which contributes to its increased use in recent years. There are many differences in physical and chemical properties between ethanol and petrochemicals refined from fossil oil. One of the differences is its energy content. The energy content, or heating value, is an important property of motor fuel, since it directly affects vehicle fuel economy. While the energy content can be measured by combustion of the fuel in a bomb, the test is time-consuming and expensive. It is generally satisfactory and more convenient to estimate that property from other commonlymeasured fuel properties. Several standardized empirical methods have been developed in the past for estimating the energy content of hydrocarbon fuels such as gasoline, diesel fuel, and jet fuel. However, the addition of ethanol to gasoline has become very common in some countries, and most of the estimation methods developed for hydrocarbon fuels are not satisfactory for use with gasoline-ethanol blends, especially blends containing more than about 10 volumepercent ethanol. This paper summarizes heating value test results from recently collected retail samples of gasolineethanol blends in the U.S. for E10 and E85 blends and in Brazil for E20 and E100 blends, as well as laboratory blends of different levels of fuel ethanol. The heating values obtained by different standardized test methods are compared and discussed. New empirical equations are proposed for gasoline fuel blends containing ethanol. © 2010 SAE International.