Population pharmacokinetics of orally administered mefloquine in healthy volunteers and patients with uncomplicated Plasmodium falciparum malaria

Background The determination of dosing regimens for the treatment of malaria is largely empirical and thus a better understanding of the pharmacokinetic/pharmacodynamic properties of antimalarial agents is required to assess the adequacy of current treatment regimens and identify sources of suboptimal dosing that could select for drug-resistant parasites. Mefloquine is a widely used antimalarial, commonly given in combination with artesunate. Patients and methods Mefloquine pharmacokinetics was assessed in 24 healthy adults and 43 patients with Plasmodium falciparum malaria administered mefloquine in combination with artesunate. Population pharmacokinetic modelling was conducted using NONMEM. Results A two-compartment model with a single transit compartment and first-order elimination from the central compartment most adequately described mefloquine concentration-time data. The model incorporated population parameter variability for clearance (CL/F), central volume of distribution (VC/F) and absorption rate constant (KA) and identified, in addition to body weight, malaria infection as a covariate for VC/F (but not CL/F). Monte Carlo simulations predict that falciparum malaria infection is associated with a shorter elimination half-life (407 versus 566 h) and T>MIC (766 versus 893 h). Conclusions This is the first known population pharmacokinetic study to show falciparum malaria to influence mefloquine disposition. Protein binding, anaemia and other factors may contribute to differences between healthy individuals and patients. As VC/F is related to the earlier portion of the concentration-time profiles, which occurs during acute malaria, and CL/F is more related to the terminal phase during convalescence after treatment, this may explain why malaria was found to be a covariate for VC/F but not CL/

Weakly Interacting, Dilute Bose Gases in 2D

This article surveys a number of theoretical problems and open questions in the field of two-dimensional dilute Bose gases with weak repulsive interactions. In contrast to three dimensions, in two dimensions the formation of long-range order is prohibited by the Bogoliubov-Hohenberg theorem, and Bose-Einstein condensation is not expected to be realized. Nevertheless, first experimental indications supporting the formation of the condensate in low dimensional systems have been recently obtained. This unexpected behaviour appears to be due to the non-uniformity, introduced into a system by the external trapping potential. Theoretical predictions, made for homogeneous systems, require therefore careful reexamination. We survey a number of popular theoretical treatments of the dilute weakly interacting Bose gas and discuss their regions of applicability. The possibility of Bose-Einstein condensation in a two-dimensional gas, the validity of perturbative t-matrix approximation and diluteness condition are issues that we discuss in detail.Comment: Survey, 25 pages RMP style, revised version, refs added, some changes made, accepted for publication in Rev. Mod. Phy

The temperature dependent bandstructure of a ferromagnetic semiconductor film

The electronic quasiparticle spectrum of a ferromagnetic film is investigated within the framework of the s-f model. Starting from the exact solvable case of a single electron in an otherwise empty conduction band being exchange coupled to a ferromagnetically saturated localized spin system we extend the theory to finite temperatures. Our approach is a moment-conserving decoupling procedure for suitable defined Green functions. The theory for finite temperatures evolves continuously from the exact limiting case. The restriction to zero conduction band occupation may be regarded as a proper model description for ferromagnetic semiconductors like EuO and EuS. Evaluating the theory for a simple cubic film cut parallel to the (100) crystal plane, we find some marked correlation effects which depend on the spin of the test electron, on the exchange coupling, and on the temperature of the local-moment system.Comment: 11 pages, 9 figure

Bulbos úmidos a partir da irrigação por gotejamento subsuperficial com água de abastecimento e efluente de esgoto tratado

The use of treated sewage effluent (TSE) combined with the subsurface drip irrigation (SDI) method in agriculture can decrease the costs of agricultural production, in attempts to fertigate crops more efficiently. In this study it was compared the dimensions of the wet bulb formed by the application of TSE and municipal water supply (MWS) in an Oxisoil. We have evaluated the effect of water quality and discharge between drippers used in sugarcane crop. Three trenches were opened and 21 three-rod TDR probes were setup in a mesh and a dripper was buried at 0.30 m, for each constant discharge of 1.0 L h-1and 1.6 L h-1. Comparing results from different wetted soil profiles it was observed that the vertical and horizontal dimensions of the wet bulb are similar for both MWS and TSE, being peculiars according to the discharges used and volume applied. Regardless the water quality, an increase of 60% in discharge decreased the deepest infiltration.352242253O uso de efluente de esgoto tratado (EET), combinado com o método de irrigação por gotejamento subsuperfical (IGS) na agricultura, pode reduzir os custos de produção agrícola, fertirrigando de maneira eficiente as culturas. Neste artigo, compararam-se as dimensões do bulbo úmido formado pela aplicação de EET e água de abastecimento municipal (AAM), em um Latossolo Vermelho distroférrico. Avaliou-se o efeito da qualidade da água e da vazão entre gotejadores utilizados na cultura da cana-de-açúcar. Três trincheiras foram abertas e 21 sondas de TDR com três hastes foram instaladas em malha, e um gotejador foi enterrado a 0,30 m, para cada vazão constante de 1,0 Lh-1 e 1,6 Lh-1. Comparando os resultados de diferentes perfis de umidade do solo, sugere-se que as dimensões vertical e horizontal do bulbo úmido sejam similares para a AAM e para o EET, sendo peculiares de acordo com as vazões utilizadas e o volume aplicado. Independentemente da qualidade da água, o aumento de 60% na vazão reduziu a infiltração em profundidade

Simulating secondary organic aerosol from missing diesel-related intermediate-volatility organic compound emissions during the Clean Air for London (ClearfLo) campaign

We present high-resolution (5g kmg × g 5g km) atmospheric chemical transport model (ACTM) simulations of the impact of newly estimated traffic-related emissions on secondary organic aerosol (SOA) formation over the UK for 2012. Our simulations include additional diesel-related intermediate-volatility organic compound (IVOC) emissions derived directly from comprehensive field measurements at an urban background site in London during the 2012 Clean Air for London (ClearfLo) campaign. Our IVOC emissions are added proportionally to VOC emissions, as opposed to proportionally to primary organic aerosol (POA) as has been done by previous ACTM studies seeking to simulate the effects of these missing emissions. Modelled concentrations are evaluated against hourly and daily measurements of organic aerosol (OA) components derived from aerosol mass spectrometer (AMS) measurements also made during the ClearfLo campaign at three sites in the London area. According to the model simulations, diesel-related IVOCs can explain on average ∼30g % of the annual SOA in and around London. Furthermore, the 90th percentile of modelled daily SOA concentrations for the whole year is 3.8g μg-3, constituting a notable addition to total particulate matter. More measurements of these precursors (currently not included in official emissions inventories) is recommended. During the period of concurrent measurements, SOA concentrations at the Detling rural background location east of London were greater than at the central London location. The model shows that this was caused by an intense pollution plume with a strong gradient of imported SOA passing over the rural location. This demonstrates the value of modelling for supporting the interpretation of measurements taken at different sites or for short durations

Three-body correlations in the Nagaoka state on the square lattice

A three-body scattering theory previously proposed by one of the present authors is developed to be applied to the saturated ferromagnetic state in the two-dimensional Hubbard model. The single-particle Green's function is calculated by taking account of the multiple scattering between two electrons and one hole. Several limiting cases are discussed and the relation to the variational principle is examined. The importance of the three-body correlation is demonstrated in comparison with the results of the ladder approximation. A possible phase boundary for the Nagaoka ground state is presented for the square lattice, which improves the previous variational results.Comment: 13 pages, 8 Postscript figures, submitted to Phys.Rev.

Dark solitons in atomic Bose-Einstein condensates: from theory to experiments

This review paper presents an overview of the theoretical and experimental progress on the study of matter-wave dark solitons in atomic Bose-Einstein condensates. Upon introducing the general framework, we discuss the statics and dynamics of single and multiple matter-wave dark solitons in the quasi one-dimensional setting, in higher-dimensional settings, as well as in the dimensionality crossover regime. Special attention is paid to the connection between theoretical results, obtained by various analytical approaches, and relevant experimental observations.Comment: 82 pages, 13 figures. To appear in J. Phys. A: Math. Theor