Electrocardiographic safety evaluation of dihydroartemisinin piperaquine in the treatment of uncomplicated falciparum malaria.

Dihydroartemisinin-piperaquine (DP) could become a leading fixed combination malaria treatment worldwide. Although there is accumulating evidence of efficacy and safety from clinical trials, data on cardiotoxicity are limited. In two randomized controlled trials in Thailand, 56 patients had ECGs performed before treatment, 4 hours after the first dose, and 4 hours after the last dose. The mean (95% CI) changes in QTc interval (Bazett's correction) were 2 (-6 to 9) ms and 14 (7 to 21) ms, respectively. These small changes on the third day of treatment are similar to those observed elsewhere in the convalescent phase following antimalarial treatment with drugs known to have no cardiac effects and are therefore likely to result from recovery from acute malaria and not the treatment given. At therapeutic doses, DP does not have clinically significant effects on the electrocardiogram

Sound Propagation in Nematic Fermi Liquid

We study the longitudinal sound propagation in the electronic nematic Fermi liquid where the Fermi surface is distorted due to the spontaneously broken rotational symmetry. The behavior of the sound wave in the nematic ordered state is dramatically different from that in the isotropic Fermi liquid. The collective modes associated with the fluctuations of the Fermi surface distortion in the nematic Fermi liquid leads to the strong and anisotropic damping of the sound wave. The relevance of the nematic Fermi liquid in doped Mott insulator is discussed.Comment: 4 pages, no figur

Hidden spin liquid in an antiferromagnet: Applications to FeCrAs

The recently studied material FeCrAs exhibits a surprising combination of experimental signatures, with metallic, Fermi liquid like specific heat but resistivity showing strong non-metallic character. The Cr sublattice posseses local magnetic moments, in the form of stacked (distorted) Kagome lattices. Despite the high degree of magnetic frustration, anti-ferromagnetic order develops below ~125K suggesting the non-magnetic Fe sublattice may play a role in stabilizing the ordering. From the material properties we propose a microscopic Hamiltonian for the low energy degrees of freedom, including the non-magnetic Fe sublattice, and study its properties using slave-rotor mean field theory. Using this approach we find a spin liquid phase on the Fe sublattice, which survives even in the presence of the magnetic Cr sublattice. Finally, we suggest that the features of FeCrAs can be qualitatively explained by critical fluctuations in the non-magnetic sublattice Fe due to proximity to a metal-insulator transition.Comment: 9 pages, 8 figure

Thyroxine-Induced Changes in the Development of Neutral Α-Amino Acid Transport Systems of Rat Brain

Transport of representative neutral Α-amino acids was measured in brain slices after injecting thy-roxine into donor rats of various ages from 1 to 23 days old. The hormone did not alter uptake in slices from 1-day-old rats even when treatment was begun on pregnant rats as much as 10 days before delivery. Injecting thy-roxine until age 6 days, however, decreased the activity of transport system A (the major sodium-dependent system in most mammalian cells) and caused appearance of a new transport system used by the model amino acids, 2-aminoisobutyric acid and 2-(methylamino)isobutyric acid. Uptake at 6 days was similar to that found in slices from older, untreated rats (e.g., those 14 days old). These results strongly suggest that one action of thyroxine is to accelerate the development of neutral Α-amino acid transport systems of brain over the first six days after birth. Thyroxine treatment of rats from birth to age 14 days also appears to increase the activities of both system A and the second transport system used by the two model amino acids in brains from 14-day-old rats.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66252/1/j.1471-4159.1984.tb02781.x.pd

Developmental Changes in the Neutral Α-Amino Acid Transport Systems of Rat Brain Over the First Three Weeks After Birth

Transport of seven different amino acids into brain slices increased as donor rats aged from 1 to 6 days. Uptakes of 2-aminoisobutyric acid, 2-(methyl-amino)isobutyric acid, and L-alanine then decreased by day 14, while uptakes of other amino acids continued to increase or remained fairly constant. Neutral Α-amino acid transport systems were characterized by measuring inhibition of uptakes and kinetics for representative amino acids at different ages. Results indicate that 2-ami-noisobutyrate and 2-(methylamino)isobutyrate used only one (and the same) system in brain slices from 6-day-old rats, with characteristics of system A (the major sodium-dependent system in most mammalian cells). They used at least two systems at ages 1, 14, and 23 days, but, of these, only at 1 day did they use the same systems in the same proportions. Alanine and leucine used more than one system at all four ages, and somewhat different combinations than used by each other or by 2-aminoisobu-tyrate or 2-(methylamino)isobutyrate. Their transport characteristics showed they used mostly system ASC (a sodium-dependent system distinguished from A) and/or system L (sodium-independent). We conclude that system A increases as the brain ages from 1 to 6 days and declines thereafter. System L probably increases with aging from 1 to 23 days.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66235/1/j.1471-4159.1984.tb02780.x.pd

Mixed Effects Modeling of Proliferation Rates in Cell-Based Models: Consequence for Pharmacogenomics and Cancer

The International HapMap project has made publicly available extensive genotypic data on a number of lymphoblastoid cell lines (LCLs). Building on this resource, many research groups have generated a large amount of phenotypic data on these cell lines to facilitate genetic studies of disease risk or drug response. However, one problem that may reduce the usefulness of these resources is the biological noise inherent to cellular phenotypes. We developed a novel method, termed Mixed Effects Model Averaging (MEM), which pools data from multiple sources and generates an intrinsic cellular growth rate phenotype. This intrinsic growth rate was estimated for each of over 500 HapMap cell lines. We then examined the association of this intrinsic growth rate with gene expression levels and found that almost 30% (2,967 out of 10,748) of the genes tested were significant with FDR less than 10%. We probed further to demonstrate evidence of a genetic effect on intrinsic growth rate by determining a significant enrichment in growth-associated genes among genes targeted by top growth-associated SNPs (as eQTLs). The estimated intrinsic growth rate as well as the strength of the association with genetic variants and gene expression traits are made publicly available through a cell-based pharmacogenomics database, PACdb. This resource should enable researchers to explore the mediating effects of proliferation rate on other phenotypes.</p

On Measuring Condensate Fraction in Superconductors

An analysis of off-diagonal long-range order in superconductors shows that the spin-spin correlation function is significantly influenced by the order if the order parameter is anisotropic on a microscopic scale. Thus, magnetic neutron scattering can provide a direct measurement of the condensate fraction of a superconductor. It is also argued that recent measurements in high temperature superconductors come very close to achieving this goal.Comment: 4 pages, 1 eps figure, RevTex. A new possibility in the underdoped regime is added. Other corrections are mino