Fixed-Dose Artesunate-Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

BACKGROUND: Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. METHODS: This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop(R) (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. RESULTS: From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ group and for 85/190 (44x7%) in the CQ group. Both treatments had similar safety profiles. CONCLUSIONS: ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization

Growth and formation mechanism of shape-selective preparation of ZnO structures : correlation of structural, vibrational and optical properties

A shape-selective preparation method was used to obtain highly crystalline rod-, needle-, nut-, and doughnut-like ZnO morphologies with distinct particle sizes and surface areas. We study the nucleation and growth mechanism of those structures and the influence of physical–chemical parameters, such as the solvent and the pH of the solution, on the morphology, as well as the structural and optical properties. A clear correlation between the growth rate along the c-axis and surface defects was established. Our results suggest that the needle- and rod-like morphologies are formed due to the crystal growth orientation along the c-axis and the occurrence of crystalline defects, such as oxygen vacancies and interstitial Zn2+ located at the surface, whereas nuts and doughnuts are formed due to growth along all crystalline planes except those related to growth along the c-axis. Based on the experimental results, growth mechanisms for the formation of ZnO structures were proposed. We believe this synthetic route will be of guidance to prepare several materials whose shapes will depend on the desired applications

Implicações sobre a natureza das fontes mantélicas envolvidas na gênese da Província Magmática do Paraná

Neste estudo, buscou-se compreender os processos e materiais que contribuíram às fontes\ud mantélicas envolvidas na gênese da Província Magmática do Paraná (PMP). O papel que a\ud crosta, a litosfera e o manto terrestre (raso ou profundo) desempenham na geração de\ud assinaturas químicas e isotópicas em basaltos de derrames continentais e oceânicos tem\ud sido um tema intensamente pesquisado e muito debatido na literatura internacional (e.g.,\ud Sheth, 2005). Embora muitos estudos já tenham sido conduzidos na PMP, existe ainda uma\ud grande controvérsia com relação à natureza das regiões-fonte dos magmas (manto\ud litosférico continental ou manto sublitosférico), como também acerca dos mecanismos\ud geodinâmicos que provocam o início da fusão dessas regiões-fonte (e.g., Bellieni et al.,\ud 1984; Hawkesworth et al., 1992). Nesse contexto, uma grande quantidade de análises de\ud elementos traço (litófilos e siderófilos), como também dados isotópicos de quatro sistemas\ud de decaimento radioativo (Rb-Sr, Sm-Nd, U-Th-Pb e Re-Os), foram obtidos em basaltos que\ud ocorrem no norte e sul da PMP. A regionalização geoquímica e isotópica (Sr-Nd-Pb)\ud observada nas rochas basálticas da PMP tem sido frequentemente interpretada como\ud resultante da fusão de manto litosférico subcontinental heterogêneo. Entretanto, dados\ud geoquímicos de elementos altamente siderófilos e de razões isotópicas 187Os/188Os, obtidos\ud neste estudo, indicam uma fonte mantélica homogênea, já que os basaltos baixo-TiO2 e alto-\ud TiO2 possuem razões isotópicas de ósmio muito similares (187Os/188Osi = 0,1295±0,0018), as\ud quais são distintas daquelas de manto litosférico subcontinental antigo (Proterozoico ou\ud Arqueano; 187Os/188Os = 0,113). Os dados isotópicos Re-Os exibem uma tendência linear\ud (187Re/188Os versus 187Os/188Os), definindo uma isócrona de boa qualidade (idade = 131,6 ±\ud 2,3 Ma), consistente com as idades obtidas em trabalhos anteriores utilizando o método\ud 40Ar/39Ar. Comumente, a PMP tem sido geneticamente ligada ao hotspot Tristão da Cunha\ud via Rio Grande Rise e Walvis Ridge. No entanto, as razões isotópicas de ósmio\ud determinadas nas rochas da Ilha de Tristão da Cunha são muito distintas daquelas dos\ud basaltos da PMP, reforçando que essa pluma não deve ter contribuído com matéria na\ud gênese dessas rochas. Desta forma, para explicar todas as características isotópicas dos\ud basaltos da PMP é necessário o envolvimento de três componentes mantélicos (Marques et\ud al., 1999). Um deles, empobrecido e semelhante ao DMM, estaria presente na fonte dos\ud basaltos alto-TiO2 e baixo-TiO2, dominando as composições isotópicas de ósmio. Os outros\ud dois componentes enriquecidos (EM-I e EM-II) seriam responsáveis pelas variações nas\ud composições isotópicas de Sr-Nd-Pb. Na gênese dos basaltos alto-TiO2 provavelmente\ud ocorreu envolvimento de crosta continental inferior delaminada (EM-I), enquanto nas rochas\ud baixo-TiO2 há indicação de participação de crosta continental superior reciclada (EM-II). O\ud componente empobrecido possui composição semelhante à de peridotitos de arco, sendo\ud que essa assinatura isotópica pode ter sido gerada por processos metassomáticos\ud relacionados a processos de subducção neoproterozóicas, que teriam modificado o manto\ud astenosférico (DMM). No processo de aglutinação do Gondwana esse manto astenosférico\ud metassomatizado pode ter sido incorporado à base da litosfera, sofrendo posterior refusão,\ud por ocasião da atividade ígnea da PMP

Re-Os isotope and highly siderophile element systematics of the Parana continental flood basalts (Brazil)

Basalts of the Parana continental flood basalt (PCFB) province erupted through dominantly Proterozoic continental crust during the Cretaceous. In order to examine the mantle source(s) of this major flood basalt province, we studied Os, Sr, Nd, and Pb isotope systematics, and highly siderophile element (HSE) abundances in tholeiitic basalts that were carefully chosen to show the minimal effects of crustal contamination. These basalts define a precise Re-Os isochron with an age of 131.6 +/- 2.3 Ma and an initial Os-187/Os-188 of 0.1295 +/- 0.0018 (gamma Os-187 = +2.7 +/- 1.4). This initial Os isotopic composition is considerably more radiogenic than estimates of the contemporary Depleted Mantle (DM). The fact that the Re-Os data define a well constrained isochron with an age similar to Ar-40/Ar-39 age determinations, despite generally low Os concentrations, is consistent with closed-system behavior for the HSE. Neodymium, Sr, and Pb isotopic data suggest that the mantle source of the basalts had been variably hybridized by melts derived from enriched mantle components. To account for the combined Os, Nd, Sr, and Pb isotopic characteristics of these rocks, we propose that the primary melts formed from metasomatized asthenospheric mantle (represented by arc-mantle peridotite) that underwent mixing with two enriched components, EM-I and EM-II. The different enriched components are reflected in minor isotopic differences between basalts from southern and northern portions of the province. The Tristan da Cunha hotspot has been previously suggested to be the cause of the Parana continental flood basalt magmatism. However, present-day Tristan da Cunha lavas have much higher Os-187/Os-188 isotopic compositions than the source of the PCFB. These data, together with other isotopic and elemental data, preclude making a definitive linkage between the Tristan plume and the PCFB. (C) 2012 Elsevier B.V. All rights reserved.NSF [EAR-0946629]NSFCNPqCNPqCAPESCAPESFAPESPFAPES

Fixed-Dose Artesunate-Amodiaquine Combination vs Chloroquine for Treatment of Uncomplicated Blood Stage P. vivax Infection in the Brazilian Amazon: An Open-Label Randomized, Controlled Trial

BACKGROUND: Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination therapies (ACTs) in Latin America. METHODS: This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop(R) (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. RESULTS: From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41x6%) in the ASAQ group and for 85/190 (44x7%) in the CQ group. Both treatments had similar safety profiles. CONCLUSIONS: ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization