Produção de forragem e potencial de utilização do capim faixa-branca submetido a frequências de desfolhação / Production of forage potential of utilization of digit grass subjected to high defoliation frequencies

O objetivo deste trabalho foi avaliar a produção de forragem e o potencial de utilização do capim faixa-branca submetido a frequências de desfolhação. Os tratamentos foram constituídos de quatro frequências de desfolhação: muito alta (25cm), alta (35cm), média (45cm) e baixa (55cm), avaliados em duas épocas do ano (maior e menor insolação), entre 2015 e 2016. Utilizou-se o delineamento em blocos ao acaso, com quatro repetições e medidas repetidas no tempo. A produção diária de folhas foi menor na frequência muito alta em relação às outras frequências. A redução das frequências de desfolhação aumentou a produção diária de colmo, senescência diária de folhas, produção total diária e acúmulo líquido diário de forragem e diminuiu o potencial de utilização da forragem. No período de maior insolação, a produção diária de colmos, o acúmulo líquido diário de forragem e o potencial de utilização de forragem foram maiores e a senescência diária de folhas foi menor. A frequência de desfolhação muito alta não proporcionou um bom desenvolvimento da planta, enquanto a frequência baixa apresentou elevada produção de colmos. As frequências de desfolhação alta e média são mais indicadas para a desfolhação do capim faixa-branca, promovendo uma melhor proporção de folhas em relação a colmos.(AU)

The objective of this study was to evaluate the production of forage and the potential of utilization of digit grass subjected to four defoliation frequencies: very high (25cm), high (35cm), medium (45cm), and low (55cm), evaluated at two times of the year (higher and lower insolation), from January 2015 to January 2016. A randomized-block design with four replicates was adopted and measures repeated over time. The daily production of leaves was lower at the very high frequency in relation to the other frequencies. The reduction in defoliation frequency increased the daily production of stems, the daily leaf senescence, the total daily forage production, and the daily forage accumulation, and decreased the potential of forage utilization. At the time of higher insolation, the daily production of stems, the daily forage accumulation, the potential of utilization of forage were higher, and the daily leaf senescence was lower. The very high frequency of defoliation did not provide a good development of the plan, while the lower frequency displayed a high production of stems. The high and medium frequencies of defoliation are more indicated to the defoliation of digit grass, enabling a better proportion of leaves in relation to stems.(AU)

Age-dependent hepatic alterations induced by a high-fat high-fructose diet.

OBJECTIVE: The present study aimed to evaluate and clarify how the age at which the intake of a high-fat and high-fructose diet begins can affect animals' livers. METHODS: Thirty-eight male wistar rats aged 6 and 12 weeks were fed a high-fat and high-fructose diet for 13 weeks. Inflammatory cytokines, hepatic glycogen, serum and hepatic triacylglycerol and pAkt protein content in the liver were assessed. Percentage of weight gained, and visceral adiposity were also evaluated. RESULTS: Young animal presented increased hepatic triacylglycerol and decreased glycogen, while adult animals had no significant alterations regarding its contents. IL6 and IL10 to IL6 ratio were also altered in young animals exposed to HFHF, while adult animals fed with HFHF had only increases in TNF-α. Both groups which received HFHF had increased serum triacylglycerol and visceral adiposity. However, only young animals gained more relative weight and had greater final body weight, gains which were related to alterations found in hepatic triacylglycerol and glycogen. CONCLUSION: Age of which consumption begins interferes in how the liver deals with an excess of nutrient and subsequent proinflammatory stimulation, leading to different phenotypes.

How Does the Addition of a Third Ion Affect the Molecular Interactions and the Thermodynamic Properties of Acetate-Based Ionic Liquids?

The effect of the addition of a third ion to the ionic liquid 1-butyl-3-methylimidazolium acetate [C4C1Im][OAc] was studied through the measurement of the enthalpy of mixing and of the excess molar volume of its mixtures with 1-butyl-3-methylimidazolium trifluoroacetate [C4C1Im][CF3CO2], 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [C4C1Im][NTf2], and tetrabutylphosphonium acetate [P4444][OAc]. Negative enthalpies of mixing (ΔmixH < 0) and positive excess molar volumes (VE > 0) were observed in all cases. The infrared and NMR studies of the pure ionic liquids and their mixtures show that the presence of a third ion with a weaker affinity with the common counterion contributes to prevailing the more favorable hydrogen-bond, herein always between the imidazolium cation and the acetate anion. Both radial and spatial distribution functions calculated by molecular simulation confirm this behavior. The remarkable enhancement of the viscosities of the [C4C1Im][OAc] + [P4444][OAc] mixtures could be discussed in light of the calculated friction coefficients.

Can the tricyanomethanide anion improve CO2 absorption by acetate-based ionic liquids?

Carbon dioxide absorption by mixtures of two ionic liquids with a common cation-1-butyl-3-methylimidazolium acetate, [C4C1Im][OAc], and 1-butyl-3-methylimidazolium tricyanomethanide, [C4C1Im][C(CN)3]-was determined experimentally at pressures below atmospheric pressure as a function of temperature between 303 K and 343 K, and at 303 K as a function of pressure up to 10 bar. It is observed that the absorption of carbon dioxide decreases with increasing tricyanomethanide anion concentration and with increasing temperature, showing a maximum of 0.4 mole fraction of carbon dioxide in pure [C4C1Im][OAc] at 303 K. At this temperature, the CO2 absorption in the mixtures [C4C1Im][OAc](1-x)[C(CN)3]x is approximately the mole-fraction average of that in the pure ionic liquids. By applying an appropriate thermodynamic treatment, after identification of the species in solution, it was possible to calculate both the equilibrium constant, Keq, and Henry's law constant, KH, in the different mixtures studied thus obtaining an insight into the relative contribution of chemical and physical absorption of the gas. It is shown that chemical sorption proceeds through a 1 : 2 stoichiometry between CO2 and acetate-based ionic liquid. The presence of the C(CN)3- anion does not significantly affect the chemical reaction of the gas with the solvent (Keq = 75 ± 2 at 303 K) but leads to lower Henry's law constants (from KH = 77.8 ± 0.6 bar to KH = 49.5 ± 0.5 bar at 303 K), thus pointing towards larger physical absorption of the gas. The tricyanomethanide anion considerably improves the mass transfer by increasing the fluidity of the absorbent as proven by the larger diffusivities of all the ions when the concentration of the C(CN)3- anion increases in the mixtures.

Zika in Rio de Janeiro: Assessment of basic reproduction number and comparison with dengue outbreaks.

Zika virus infection was declared a public health emergency of international concern in February 2016 in response to the outbreak in Brazil and its suspected link with congenital anomalies. In this study, we use notification data and disease natural history parameters to estimate the basic reproduction number (R 0) of Zika in Rio de Janeiro, Brazil. We also obtain estimates of R 0 of dengue from time series of dengue cases in the outbreaks registered in 2002 and 2012 in the city, when DENV-3 and DENV-4 serotypes, respectively, had just emerged. Our estimates of the basic reproduction number for Zika in Rio de Janeiro based on surveillance notifications (R 0 = 2·33, 95% CI: 1·97-2·97) were higher than those obtained for dengue in the city (year 2002: R 0 = 1·70 [1·50-2·02]; year 2012: R 0 = 1·25 [1·18-1·36]). Given the role of Aedes aegypti as vector of both the Zika and dengue viruses, we also derive R 0 of Zika as a function of both dengue reproduction number and entomological and epidemiological parameters for dengue and Zika. Using the dengue outbreaks from previous years allowed us to estimate the potential R 0 of Zika. Our estimates were closely in agreement with our first Zika's R 0 estimation from notification data. Hence, these results validate deriving the potential risk of Zika transmission in areas with recurring dengue outbreaks. Whether transmission routes other than vector-based can sustain a Zika epidemic still deserves attention, but our results suggest that the Zika outbreak in Rio de Janeiro emerged due to population susceptibility and ubiquitous presence of Ae. aegypti.

Influence of Fluorination on the Solubilities of Carbon Dioxide, Ethane, and Nitrogen in 1-n-Fluoro-alkyl-3-methylimidazolium Bis(n-fluoroalkylsulfonyl)amide Ionic Liquids.

The effect on gas solubilities of adding partially fluorinated alkyl side chains either on imidazolium-based cations or on bis(perfluoroalkylsulfonyl)amide anions was studied. The aim was to gain knowledge of the mechanisms of dissolution of gases in fluorinated ionic liquids and, if possible, to improve physical absorption of carbon dioxide in ionic liquids. We have determined experimentally, in the temperature range of 298-343 K and at pressures close to atmospheric pressure, the solubility and thermodynamics of solvation of carbon dioxide, ethane, and nitrogen in the ionic liquids 1-octyl-3-methylimidazolium bis[trifluoromethylsulfonyl]amide ([C8mim][NTf2]), 1-octyl-3-methylimidazolium bis[pentafluoroethylsulfonyl]amide ([C8mim][BETI]), 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[trifluoromethylsulfonyl]amide ([C8H4F13mim][NTf2]), and 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[pentafluoroethylsulfonyl]amide ([C8H4F13mim][BETI]). Ionic liquids with partial fluorination on the cation were found to exhibit higher carbon dioxide and nitrogen mole fraction solubilities but lower ethane solubilities, compared to those of their hydrogenated counterparts. Molecular simulation provided insights about the mechanisms of solvation of the different gases in the ionic liquids.

Tailoring the properties of acetate-based ionic liquids using the tricyanomethanide anion.

The equilibrium and transport properties of mixtures of two ionic liquids - [C4C1Im][OAc] and [C4C1Im][C(CN)3] - were determined and interpreted at the molecular level using vibration spectroscopy, NMR and molecular dynamics simulation. The non-ideality of the mixtures [C4C1Im][OAc](1-x)[C(CN)3]x was characterized by V(E) = +0.28 cm(3) mol(-1) (293 K, x = 0.65) and H(E) = -2.2 kJ mol(-1) for x = 0.5. These values could be explained by a rearrangement of the hydrogen-bond network of the mixture that favours the interaction of the acetate anion with the imidazolium cation at position C2. The dynamic properties of the mixture are also dramatically influenced by the composition with a decrease of the viscosity and an increase of self-diffusion coefficients of the ions when the amount of tricyanomethanide anion increases in the mixture.

Mixing Enthalpy for Binary Mixtures Containing Ionic Liquids.

A complete review of the published data on the mixing enthalpies of mixtures containing ionic liquids, measured directly using calorimetric techniques, is presented in this paper. The field of ionic liquids is very active and a number of research groups in the world are dealing with different applications of these fluids in the fields of chemistry, chemical engineering, energy, gas storage and separation or materials science. In all these fields, the knowledge of the energetics of mixing is capital both to understand the interactions between these fluids and the different substrates and also to establish the energy and environmental cost of possible applications. Due to the relative novelty of the field, the published data is sometimes controversial and recent reviews are fragmentary and do not represent a set of reliable data. This fact can be attributed to different reasons: (i) difficulties in controlling the purity and stability of the ionic liquid samples; (ii) availability of accurate experimental techniques, appropriate for the measurement of viscous, charged, complex fluids; and (iii) choice of an appropriate clear thermodynamic formalism to be used by an interdisciplinary scientific community. In this paper, we address all these points and propose a critical review of the published data, advise on the most appropriate apparatus and experimental procedure to measure this type of physical-chemical data in ionic liquids as well as the way to treat the information obtained by an appropriate thermodynamic formalism.

Homogenous demineralized dentin matrix and platelet-rich plasma for bone tissue engineering in cranioplasty of diabetic rabbits: biochemical, radiographic, and histological analysis.

This study evaluated the effects of homogenous demineralized dentin matrix (HDDM) slices and platelet-rich plasma (PRP) in surgical defects created in the parietal bones of alloxan-induced diabetic rabbits, treated with a guided bone regeneration technique. Biochemical, radiographic, and histological analyses were performed. Sixty adult New Zealand rabbits were divided into five groups of 12: normoglycaemic (control, C), diabetic (D), diabetic with a PTFE membrane (DM), diabetic with a PTFE membrane and HDDM slices (DM-HDDM), and diabetic with PTFE membrane and PRP (DM-PRP). The quantity and quality of bone mass was greatest in the DM-HDDM group (respective radiographic and histological analyses: at 15 days, 71.70 ± 16.50 and 50.80 ± 1.52; 30 days, 62.73 ± 16.51 and 54.20 ± 1.23; 60 days, 63.03 ± 11.04 and 59.91 ± 3.32; 90 days, 103.60 ± 24.86 and 78.99 ± 1.34), followed by the DM-PRP group (respective radiographic and histological analyses: at 15 days 23.00 ± 2.74 and 20.66 ± 7.45; 30 days 31.92 ± 6.06 and 25.31 ± 5.59; 60 days 25.29 ± 16.30 and 46.73 ± 2.07; 90 days 38.10 ± 14.04 and 53.38 ± 9.20). PRP greatly enhanced vascularization during the bone repair process. Abnormal calcium metabolism was statistically significant in the DM-PRP group (P<0.001) for all four time intervals studied, especially when compared to the DM-HDDM group. Alkaline phosphatase activity was significantly higher in the DM-HDDM group (P<0.001) in comparison to the C, D, and DM-PRP groups, confirming the findings of intense osteoblastic activity and increased bone mineralization. Thus, HDDM promoted superior bone architectural microstructure in bone defects in diabetic rabbits due to its effective osteoinductive and osteoconductive activity, whereas PRP stimulated angiogenesis and red bone marrow formation.

Amniotic membrane as a biological dressing for 5-fluoruracil-induced oral mucositis in rats.

Oral mucositis is a reaction to chemoradiation therapy during cancer treatment. The aim of this study was to investigate the use of amniotic membrane as a biological dressing for oral mucositis lesions in rats. Sixty Wistar rats were divided into three groups (n = 20): control, 5-fluoruracil (5-FU), 5-fluoruracil + amniotic membrane (5-FU+AM). Each group was subdivided (n = 5) according to the time interval to sacrifice (3, 7, 14, and 21 days). Histology (haematoxylin-eosin staining) and immunocytochemistry (anti-rat antibodies CD4, CD8, VEGF, and PCNA) were evaluated. Immunocytochemistry results were analyzed using one-way ANOVA and Tukey tests. The amniotic membrane (5FU+AM) played an important role in cell proliferation (PCNA 3 days 27.08 ± 4.65, 7 days 27.90 ± 3.34) and especially in neovascularization (VEGF 3 days 23.00 ± 1.40, 7 days 26.00 ± 0.95) for all time intervals, when compared to 5-FU (PCNA 3 days 23.12 ± 1.61, 7 days 37.21 ± 1.20; VEGF 3 days 17.05 ± 1.51, 7 days 8.45 ± 1.35) and control (PCNA 3 days 29.99 ± 0.92, 7 days 16.33 ± 2.88; VEGF 3 days 13.65 ± 0.55, 7 days 15.70 ± 1.39). It was biocompatible, showing significant differences compared to the other groups in CD4 (F = 40.72; P = 0.001) and CD8 (F = 69.99, P = 0.001) staining together, only during the inflammation phase (7 days). Amniotic membrane presented biocompatibility and stimulated cell proliferation and neovascularization, functioning as a promising biological dressing.

Thermodynamics of cellulose dissolution in an imidazolium acetate ionic liquid.

The heat of dissolution of cellulose in one imidazolium acetate ionic liquid was determined experimentally. The value of -132 ± 8 J g(-1) indicates that the dissolution is exothermal thus confirming energetically favourable cellulose-ionic liquid interactions but indicating that an increase in temperature does not thermodynamically favour the dissolution process.

Assessing the impact of travel restrictions on international spread of the 2014 West African Ebola epidemic.

The quick spread of an Ebola outbreak in West Africa has led a number of countries and airline companies to issue travel bans to the affected areas. Considering data up to 31 Aug 2014, we assess the impact of the resulting traffic reductions with detailed numerical simulations of the international spread of the epidemic. Traffic reductions are shown to delay by only a few weeks the risk that the outbreak extends to new countries.

Pressure effect on vibrational frequency and dephasing of 1-alkyl-3-methylimidazolium hexafluorophosphate ionic liquids.

Raman spectra in the range of the totally symmetric stretching mode of the [PF6](-) anion, νs(PF6), have been measured for 1-alkyl-3-methylimidazolium ionic liquids [CnC1im][PF6], for n = 4, 6, and 8, as a function of pressure at room temperature. The ionic liquids [C6C1im][PF6] and [C8C1im][PF6] remain in an amorphous phase up to 3.5 GPa, in contrast to [C4C1im][PF6], which crystallizes above ~0.5 GPa. Equations of state based either on a group contribution model or Carnahan-Starling-van der Waals model have been used to estimate the densities of the ionic liquids at high pressures. The shifts of the vibrational frequency of νs(PF6) with density observed in [C6C1im][PF6] and in [C8C1im][PF6] have been calculated by a hard-sphere model of a pseudo-diatomic solute under short-range repulsive interactions with the neighboring particles. The stochastic model of Kubo for vibrational dephasing has been used to obtain the amplitude of vibrational frequency fluctuation, <Δω(2)>, and the relaxation time of frequency fluctuation, τc, as a function of density by Raman band shape analysis of the νs(PF6) mode of [C6C1im][PF6] and [C8C1im][PF6].

Absorption of carbon dioxide, nitrous oxide, ethane and nitrogen by 1-alkyl-3-methylimidazolium (C(n)mim, n = 2,4,6) tris(pentafluoroethyl)trifluorophosphate ionic liquids (eFAP).

We measured the densities of 1-alkyl-3-methylimidazolium (C(n)mim, n = 2,4,6) tris(pentafluoroethyl)trifluorophosphate ionic liquids (eFAP) as a function of temperature and pressure and their viscosities as a function of temperature. These ionic liquids are less viscous than those based in the same cations but with other anions such as bis(trifluoromethylsulfonyl)imide. The ionic liquids studied are only partially miscible with water, their solubility increasing with the size of the alkyl side-chain of the cation and with temperature (from x(H(2)O) = 0.20 ± 0.03 for [C(4)mim][eFAP] at 303.10 K to x(H(2)O) = 0.49 ± 0.07 for [C(6)mim][eFAP] at 315.10 K). The solubility of carbon dioxide, nitrous oxide, ethane, and nitrogen in the three ionic liquids was measured as a function of temperature and at pressures close to atmospheric. Carbon dioxide and nitrous oxide are the more soluble gases with mole fraction solubilities of the order of 3 × 10(-2) at 303 K. The solubility of these gases does not increase linearly with the size of the alkyl-side chain of the cation. The solubilities of ethane and nitrogen are much lower than those of carbon dioxide and nitrous oxide (mole fractions 60% and 90% lower, respectively). The higher solubility of CO(2) and N(2)O can be explained by more favorable interactions between the solutes and the polar region of the ionic liquids as shown by the enthalpies of solvation determined experimentally and by the calculation of the site-site solute-solvent radial distribution functions using molecular simulation.

Characteristics of aggregation in aqueous solutions of dialkylpyrrolidinium bromides.

Three pyrrolidinium-based ionic liquids-N-dodecyl-N-methylpyrrolidinium bromide, N-butyl-N-octylpyrrolidinium bromide, and N-butyl-N-dodecylpyrrolodinium bromide-were synthesized and characterized by their decomposition temperatures (T(d)) measured by thermogravimetric analysis, and by their melting point (T(m)), glass transition (T(g)) and crystallization temperatures (T(cryst)) determined by differential scanning calorimetry. Their self-aggregation properties in aqueous solution were studied and their behavior is compared with that of analogous conventional cationic surfactants, namely tetra-alkylammonium bromide salts. The critical micellar concentration, cmcs were obtained by isothermal titration calorimetry (ITC); which were further validated by measurements of interfacial tension, fluorescence and NMR spectroscopy. Enthalpies of micellization were measured at three different temperatures using ITC. The Taylor dispersion method and DOSY NMR were used to determine diffusion coefficients of the ionic liquid surfactants in aqueous solution at 298.15K. Several correlations between structural features of the surfactant species, such as the number and size of their alkyl chains, and the thermodynamic quantities of micellization-expressed by experimental values of cmc, counter-ion binding fraction, Δ(mic)G°, Δ(mic)°, and Δ(mic)S°-are established. We could interpret the different contributions of the two alkyl side chains to the aggregation properties in terms of the balance of interactions in homogeneous and micellar phases, contributing to understanding the aggregation behavior of ionic liquids in water and the parallel between these systems and traditional ionic surfactants.

Effect of fluorination and size of the alkyl side-chain on the solubility of carbon dioxide in 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ionic liquids.

It is proven in this work that it is possible to significantly increase the carbon dioxide uptake by an ionic liquid relying on physical interactions only. The solubility and thermodynamics of solvation of carbon dioxide in the ionic liquids 1-octyl-3-methylimidazolium bis[trifluoromethylsulfonyl]amide [C(8)mim][Ntf(2)], 1-decyl-3-methylimidazolium bis[trifluoromethylsulfonyl]amide [C(10)mim][Ntf(2)], and 1-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-3-methylimidazolium bis[trifluoromethylsulfonyl]amide [C(8)H(4)F(13)mim][Ntf(2)] were determined experimentally between 298 and 343 K at pressures close to atmospheric. The solubility of carbon dioxide is significantly higher in the fluorine-substituted ionic liquid with Henry's law constants at 303 K of 33.3 and 30.7 bar for [C(8)mim][Ntf(2)] and [C(10)mim][Ntf(2)], respectively, and of 28.0 bar for [C(8)H(4)F(13)mim][Ntf(2)]. Molecular simulation was used for interpreting the molecular mechanisms of solvation of carbon dioxide in the studied ionic liquids and coherent molecular mechanisms of solvation are proposed in light of the solute-solvent radial distribution functions. It is shown that the increase of the size of the hydrogenated or fluorinated alkyl chain in the imidazolium cation does not lead to a steady augmentation of the gaseous uptake by the liquid probably due to an increase of the nonpolar domains of the ionic liquid, carbon dioxide being solvated preferentially in the charged regions of the solvent.

Intravenous immunoglobulin in lupus panniculitis.

Systemic lupus erythematosus (SLE) is a disease of unknown cause that may involve one or many organ or systems. Skin involvement is a major feature in this disease, and a wide variety of skin conditions may be present. Lupus erythematosus panniculitis (LEP) constitutes a rare form of cutaneous lupus characterized by recurrent nodular or plaque lesions that can vary from a benign and mild course to a more disfiguring disease. Initial therapy includes corticosteroids, antimalarials, and azathioprine and, in refractory cases, two antimalarials in association, mycophenolate mofetil, or other immunomodulators. Intravenous immuglobulin (IVIG) is used in many autoimmune disorders, like in SLE, although clinical trials have not yet taken place. In this report, we review skin manifestations of SLE and their treatment, IVIG, and finally a case of LEP successfully treated with IVIG when other therapy modalities failed.

Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial.

BACKGROUND: Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. METHODS: In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7-30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. RESULTS: Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2.5%vs 3.0%, p=0.1). Two versus 13 (0.03%vs 0.22%, p=0.0020) were permanently disabled; total dead or disabled: 156 versus 190 (2.6%vs 3.2%, p=0.0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1.6%] vs 82/4426 [1.9%], risk ratio 0.86 [95% CI 0.63-1.18], p=0.35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1.9%] vs 57/1519 [3.8%], risk ratio 0.49 [95% CI 0.32-0.77], p=0.0013). INTERPRETATION: If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. FUNDING: UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).