The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data.

BACKGROUND: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. METHODS: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. FINDINGS: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). INTERPRETATION: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. FUNDING: Bill & Melinda Gates Foundation.

Aortic blood pressure measured via EIT: investigation of different measurement settings.

Electrical impedance tomography (EIT) allows the measurement of intra-thoracic impedance changes related to cardiovascular activity. As a safe and low-cost imaging modality, EIT is an appealing candidate for non-invasive and continuous haemodynamic monitoring. EIT has recently been shown to allow the assessment of aortic blood pressure via the estimation of the aortic pulse arrival time (PAT). However, finding the aortic signal within EIT image sequences is a challenging task: the signal has a small amplitude and is difficult to locate due to the small size of the aorta and the inherent low spatial resolution of EIT. In order to most reliably detect the aortic signal, our objective was to understand the effect of EIT measurement settings (electrode belt placement, reconstruction algorithm). This paper investigates the influence of three transversal belt placements and two commonly-used difference reconstruction algorithms (Gauss-Newton and GREIT) on the measurement of aortic signals in view of aortic blood pressure estimation via EIT. A magnetic resonance imaging based three-dimensional finite element model of the haemodynamic bio-impedance properties of the human thorax was created. Two simulation experiments were performed with the aim to (1) evaluate the timing error in aortic PAT estimation and (2) quantify the strength of the aortic signal in each pixel of the EIT image sequences. Both experiments reveal better performance for images reconstructed with Gauss-Newton (with a noise figure of 0.5 or above) and a belt placement at the height of the heart or higher. According to the noise-free scenarios simulated, the uncertainty in the analysis of the aortic EIT signal is expected to induce blood pressure errors of at least ± 1.4 mmHg.

A MORTE PRECOCE DO PESSEGUEIRO ASSOCIADA À FERTILIDADE DO SOLO

RESUMO A morte precoce do pessegueiro é uma síndrome caracterizada por um colapso das plantas ao final do período de dormência, cujas causas envolvem diversos fatores bióticos e abióticos. Objetivou-se avaliar a associação da morte precoce do pessegueiro com à fertilidade do solo. Amostraram-se a rizosfera, para análise química, sob a copa de plantas sintomáticas e assintomáticas, com idade entre dois e oito anos, em nove pomares comerciais localizados nos municípios de Pelotas e Canguçu, no Rio Grande do Sul, totalizando 108 amostras. De acordo com os resultados, a obtenção de uma função discriminante para classificar as plantas em duas categorias, como sintomáticas ou assintomáticas, não proporcionou resultado satisfatório, pois a taxa de classificação errônea superou 40%. A análise de variância individual mostrou que, univariadamente, não existe diferença significativa na fertilidade do solo entre os dois grupos de plantas amostradas. Embora a fertilidade do solo, na maioria dos pomares amostrados, esteja aquém do recomendado para a cultura do pessegueiro, a ocorrência da morte precoce do pessegueiro não apresentou relação com os atributos químicos de fertilidade do solo. O resultado sugere que outros fatores, como os aspectos físicos do solo e o uso de misturas varietais de cultivares-copa como porta-enxerto, possam estar envolvidos na ocorrência de morte precoce do pessegueiro.

TEORES DE NUTRIENTES FOLIARES DE PESSEGUEIRO EM CINCO PORTA-ENXERTOS

RESUMO Teores de nutrientes foliares indicam o estado nutricional da planta, auxiliam na recomendação de adubação e, em plantas frutíferas enxertadas, podem indicar combinações de copa/porta-enxerto incompatíveis. O objetivo do presente trabalho foi avaliar os teores de nutrientes foliares na cv. Maciel de pessegueiro, enxertada em cinco porta-enxertos (‘Aldrighi’, ‘Capdeboscq’, ‘Flordaguard’, ‘Nemaguard’ e ‘Okinawa’). Dois pomares experimentais, localizados no município de Pelotas-RS, foram avaliados no 2° e no 3° anos após o plantio, respectivamente, nos anos de 2012 e 2013. Conclui-se que os porta-enxertos ‘Aldrighi’, ‘Capdeboscq’, ‘Flordaguard’, ‘Nemaguard’ e ‘Okinawa’ não influenciaram nos teores foliares de P e de Mn da cv. Maciel, em ambos os pomares e anos de avaliação; o porta-enxerto ‘Nemaguard’ reduz os teores foliares de Mg da cv. Maciel, sem alterar a classe de interpretação agronômica; embora os teores foliares de N, Fe, Zn e B tenham sido abaixo do normal ou insuficientes, em praticamente todas as amostras de ambos os pomares e anos de avaliação, os porta-enxertos testados não influenciaram nestas interpretações.

DESCRIÇÃO DA CURVA DE CRESCIMENTO DE FRUTOS DO CAJUEIRO POR MODELOS NÃO LINEARES

RESUMO O objetivo do trabalho foi avaliar o ajuste dos modelos Gompertz e Logístico, com estrutura de erros independentes e autoregressivos, no desenvolvimento de frutos de caju, com base em medidas de comprimento e largura do fruto, tomados ao longo do tempo. A estimação dos parâmetros foi feita por meio de rotinas no software R, utilizando-se o método dos mínimos quadrados e o processo iterativo de Gauss- Newton. Os modelos foram comparados pelos critérios: coeficiente de determinação ajustado (R2 aj), desvio padrão residual (DPR), critério de informação Akaike (AIC) ecritériobayesiano de Schwarz (BIC). Para os dois modelos, os dados apresentaram autocorrelação residual positiva, tanto para a variável comprimento como para a largura do fruto, descrita por processo autoregressivo de primeiraordem. Em geral, por todos critérios de avaliação da qualidade de ajuste, os dados se ajustaram ao modelo Logístico com uma estrutura autoregressiva da primeira ordem, havendo no entanto superestimação do tamanhodo fruto nas últimas idades, tanto no crescimento em comprimento (cm) e largura (cm).

Reliable computation of robust response tori on the verge of breakdown

We prove the existence and local uniqueness of invariant tori on the verge of breakdown for two systems: the quasi-periodically driven logistic map and the quasi-periodically forced standard map. These systems exemplify two scenarios: the Heagy-Hammel route for the creation of strange non- chaotic attractors and the nonsmooth bifurcation of saddle invariant tori. Our proofs are computer- assisted and are based on a tailored version of the Newton-Kantorovich theorem. The proofs cannot be performed using classical perturbation theory because the two scenarios are very far from the perturbative regime, and fundamental hypotheses such as reducibility or hyperbolicity either do not hold or are very close to failing. Our proofs are based on a reliable computation of the invariant tori and a careful study of their dynamical properties, leading to the rigorous validation of the numerical results with our novel computational techniques.

Studying the non-thermal lobes of IRAS 16547-4247 through a multi-wavelength approach

In recent years, massive protostars have turned out to be a possible population of high-energy emitters. Among the best candidates is IRAS 16547-4247, a protostar that presents a powerful outflow with clear signatures of interaction with its environment. This source has been revealed to be a potential high-energy source because it displays non-thermal radio emission of synchrotron origin, which is evidence of relativistic particles. To improve our understanding of IRAS 16547-4247 as a high-energy source, we analyzed XMM-Newton archival data and found that IRAS 16547-4247 is a hard X-ray source. We discuss these results in the context of a refined one-zone model and previous radio observations. From our study we find that it may be difficult to explain the X-ray emission as non-thermal radiation coming from the interaction region, but it might be produced by thermal Bremsstrahlung (plus photo-electric absorption) by a fast shock at the jet end. In the high-energy range, the source might be detectable by the present generation of Cherenkov telescopes, and may eventually be detected by Fermi in the GeV range.

El proyecto Science of the city. Territorio de encuentro entre arte, ciencia y ciudad

El objetivo de este artículo es presentar la experiencia colaborativa entre el proyecto Science of the city y el grupo de investigación"Metamétodo. Metodologías compartidas y procesos artísticos en la sociedad del conocimiento" de la Facultad de Bellas Artes de la UB y La Mandarina de Newton, empresa emergente en el ámbito de la divulgación científica, interesada en nuevas estrategias y formas de pensar la ciencia que reviertan en la transmisión del conocimiento. Las cuestiones ¿Qué es ciencia? y ¿Qué es ciudad? o ¿Dónde encontramos la ciencia en la ciudad? fueron el punto de partida del proyecto Science of the city, ideado por La Mandarina de Newton. Los organizadores lanzaron una convocatoria a través de la red, en formato de concurso internacional de vídeos que debían tratar estas cuestiones. El propósito era acercar la ciencia a las experiencias cotidianas de los habitantes de la ciudad y a su vez, obtener una respuesta en formato de vídeo que nos sirviera como punto de partida para los artistas integrantes de nuestro grupo de investigación para elaborar nuestras propias obras. Los vídeos ganadores y las obras resultantes de esta experiencia conformaron la exposición Science of the City, proyecto financiado por el FECYT. La exposición pudo verse en el espacio Arts Santa Mònica de Barcelona en mayo del pasado 2012. Los procesos de trabajo y las reflexiones quedaron recopilados en una publicación multilingüe.

Efeito da aplicação foliar de ácidos graxos na "Via das Lipoxigenases" de plantas de soja

The involvement of lipoxygenase isozymes in several physiological processes of plants has been described but their role is not well understood and more biochemical studies are needed to elucidate the role of the "Lipoxygenase Pathway" in plant physiology. Thus, the biochemical and kinetic characterization of a lipoxygenases "pool" from soybean leaves was carried out. Two genotypes were used: IAC-100 (a normal variety having lipoxygenases in the seeds) and IAC-100 TN (genetically modified genotype, which is devoid of lipoxygenases in the seeds). The plants were submitted to the application of fatty acids (lipoxygenase substrates) on leaves. The results of the biochemical and kinetic studies of lipoxygenase isozymes from leaves of the two genotypes analysed showed that genetic removal of lipoxygenase from seeds did not affect the response of the plant to the treatment, since both genotypes showed similar results.

On the Connectivity of the Julia sets of meromorphic functions

We prove that every transcendental meromorphic map $f$ with disconnected Julia set has a weakly repelling fixed point. This implies that the Julia set of Newton's method for finding zeroes of an entire map is connected. Moreover, extending a result of Cowen for holomorphic self-maps of the disc, we show the existence of absorbing domains for holomorphic self-maps of hyperbolic regions, whose iterates tend to a boundary point. In particular, the results imply that periodic Baker domains of Newton's method for entire maps are simply connected, which solves a well-known open question.

Non-thermal emission from microquasar/ISM interaction

Context. The interaction of microquasar jets with their environment can produce non-thermal radiation as in the case of extragalactic outflows impacting on their surroundings. Significant observational evidence of jet/medium interaction in galactic microquasars has been collected in the past few years, although little theoretical work has been done regarding the resulting non-thermal emission. Aims. In this work, we investigate the non-thermal emission produced in the interaction between microquasar jets and their environment, and the physical conditions for its production. Methods. We developed an analytical model based on those successfully applied to extragalactic sources. The jet is taken to be a supersonic and mildly relativistic hydrodynamical outflow. We focus on the jet/shocked medium structure in its adiabatic phase, and assume that it grows in a self-similar way. We calculate the fluxes and spectra of the radiation produced via synchrotron, inverse Compton, and relativistic bremsstrahlung processes by electrons accelerated in strong shocks. A hydrodynamical simulation is also performed to investigate further the jet interaction with the environment and check the physical parameters used in the analytical model. Results. For reasonable values of the magnetic field, and using typical values of the external matter density, the non-thermal particles could produce significant amounts of radiation at different wavelengths, although they do not cool primarily radiatively, but by adiabatic losses. The physical conditions of the analytical jet/medium interaction model are consistent with those found in the hydrodynamical simulation. Conclusions. Microquasar jet termination regions could be detectable at radio wavelengths for current instruments sensitive to ~arcminute scales. At X-ray energies, the expected luminosities are moderate, although the emitter is more compact than the radio one. The source may be detectable by XMM-Newton or Chandra, with 1-10 arcsec of angular resolution. The radiation at gamma-ray energies may be within the detection limits of the next generation of satellite and ground-based instruments.

A química newtoniana

The work of Newton exerted a profound influence on the development of science. In chemistry this newtonian influence was present in Query 31 of Newton's Optics. However, the incursion of Newton's thought into chemistry brought upon the chemists an epistemological question, that of the nature of their discipline. Would chemistry be a discipline in its own right, or simply a branch of physics? In this work we present the newtonian program for chemistry, as well as the reaction of traditional chemists to it. We conclude by proposing that Lavoisier carried through a synthesis between newtonian methodology and the singularity of traditional chemistry.

A Practical Micro Mechanical Model Based Local Approach Methodology for the Analysis of Ductile Fracture of Welded T-Joints

This thesis concentrates on developing a practical local approach methodology based on micro mechanical models for the analysis of ductile fracture of welded joints. Two major problems involved in the local approach, namely the dilational constitutive relation reflecting the softening behaviour of material, and the failure criterion associated with the constitutive equation, have been studied in detail. Firstly, considerable efforts were made on the numerical integration and computer implementation for the non trivial dilational Gurson Tvergaard model. Considering the weaknesses of the widely used Euler forward integration algorithms, a family of generalized mid point algorithms is proposed for the Gurson Tvergaard model. Correspondingly, based on the decomposition of stresses into hydrostatic and deviatoric parts, an explicit seven parameter expression for the consistent tangent moduli of the algorithms is presented. This explicit formula avoids any matrix inversion during numerical iteration and thus greatly facilitates the computer implementation of the algorithms and increase the efficiency of the code. The accuracy of the proposed algorithms and other conventional algorithms has been assessed in a systematic manner in order to highlight the best algorithm for this study. The accurate and efficient performance of present finite element implementation of the proposed algorithms has been demonstrated by various numerical examples. It has been found that the true mid point algorithm (a = 0.5) is the most accurate one when the deviatoric strain increment is radial to the yield surface and it is very important to use the consistent tangent moduli in the Newton iteration procedure. Secondly, an assessment of the consistency of current local failure criteria for ductile fracture, the critical void growth criterion, the constant critical void volume fraction criterion and Thomason's plastic limit load failure criterion, has been made. Significant differences in the predictions of ductility by the three criteria were found. By assuming the void grows spherically and using the void volume fraction from the Gurson Tvergaard model to calculate the current void matrix geometry, Thomason's failure criterion has been modified and a new failure criterion for the Gurson Tvergaard model is presented. Comparison with Koplik and Needleman's finite element results shows that the new failure criterion is fairly accurate indeed. A novel feature of the new failure criterion is that a mechanism for void coalescence is incorporated into the constitutive model. Hence the material failure is a natural result of the development of macroscopic plastic flow and the microscopic internal necking mechanism. By the new failure criterion, the critical void volume fraction is not a material constant and the initial void volume fraction and/or void nucleation parameters essentially control the material failure. This feature is very desirable and makes the numerical calibration of void nucleation parameters(s) possible and physically sound. Thirdly, a local approach methodology based on the above two major contributions has been built up in ABAQUS via the user material subroutine UMAT and applied to welded T joints. By using the void nucleation parameters calibrated from simple smooth and notched specimens, it was found that the fracture behaviour of the welded T joints can be well predicted using present methodology. This application has shown how the damage parameters of both base material and heat affected zone (HAZ) material can be obtained in a step by step manner and how useful and capable the local approach methodology is in the analysis of fracture behaviour and crack development as well as structural integrity assessment of practical problems where non homogeneous materials are involved. Finally, a procedure for the possible engineering application of the present methodology is suggested and discussed.