The efficacy of halofantrine in the treatment of acute malaria in nonimmune travelers

A multicenter prospective trial was performed to investigate the efficacy and the tolerability of halofantrine in nonimmune patients with malaria imported from areas with drug-resistant falciparum parasites (mainly Africa). Forty-five of the 74 subjects were treated with a one-day regimen (3 x 500 mg) of halofantrine, and the other 29 received the same regimen with an additional treatment on day 7. In the second group, a 100% efficacy rate was demonstrated, but in the group receiving the one-day regimen, four recrudescences were observed in patients with falciparum malaria. Only five mild adverse reactions were seen, which disappeared spontaneously after the end of the treatment. We conclude that halofantrine is highly effective in curing malaria in nonimmune subjects. The treatment scheme for such persons should include an additional treatment on day 7 for nonimmune individuals. This drug was well tolerated in our patients, indicating that halofantrine will be useful in the treatment of multidrug-resistant malaria in nonimmune persons

On the completeness of impulsive gravitational wave space-times

We consider a class of impulsive gravitational wave space-times, which generalize impulsive pp-waves. They are of the form $M=N\times\mathbb{R}^2_1$, where $(N,h)$ is a Riemannian manifold of arbitrary dimension and $M$ carries the line element $ds^2=dh^2+ 2dudv+f(x)\delta(u)du^2$ with $dh^2$ the line element of $N$ and $\delta$ the Dirac measure. We prove a completeness result for such space-times $M$ with complete Riemannian part $N$.Comment: 13 pages, minor changes suggested by the referee

High omega arachidonic acid/docosahexaenoic acid ratio induces mitochondrial dysfunction and altered lipid metabolism in human hepatoma cells

Background Non-alcoholic fatty liver disease (NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in the development of NAFLD. However, the inflicted cellular pathology remains unknown. A high ratio may promote lipogenic pathways and contribute to ROS-mediated damage, perhaps leading to mitochondrial dysfunction. Therefore, these parameters were investigated to understand their contribution to NAFLD development. Aim To examine the effect of increasing ratios of omega-6:3 fatty acids on mitochondrial function and lipid metabolism mediators. Methods HepG2-derived VL-17A cells were treated with normal (1:1, 4:1) and high (15:1, 25:1) ratios of omega-6: omega-3 fatty acids (arachidonic (AA): docosahexaenoic (DHA)) at various time points. Mitochondrial activity and function was examined via MTT assay and Seahorse XF24 analyzer, respectively. Triglyceride accumulation was determined by using EnzyChrom™ and levels of ROS were measured by fluorescence intensity. Protein expression of the mediators of lipogenic, lipolytic and endocannabinoid pathways was assessed by Western blotting. Results High AA:DHA ratio decreased mitochondrial activity (p<0.01; upto 80%) and promoted intracellular triglyceride accumulation (p<0.05; 40-70%). Mechanistically, it altered the mediators of lipid metabolism; increased the expression of stearoyl-CoA desaturase (p<0.05; 22-35%), decreased the expression of peroxisome proliferator-activated receptor-alpha (p<0.05; 30-40%) and increased the expression of cannabinoid receptor 1 (p<0.05; 31%). Furthermore, the high ratio increased ROS production (p<0.01; 74-115%) and reduced mitochondrial respiratory functions such as basal and maximal respiration, ATP production, spare respiratory capacity and proton leak (p<0.01; 35-68%). Conclusion High AA:DHA ratio induced triglyceride accumulation, increased oxidative stress and disrupted mitochondrial functions. Stimulation of lipogenic and steroidal transcription factors may partly mediate these effects and contribute to NAFLD development

Intranasal dexmedetomidine in elderly subjects with or without beta blockade:a randomised double-blind single-ascending-dose cohort study

BACKGROUND: The aim of this double-blind, placebo-controlled, single-ascending-dose study was to determine the safety and tolerability of intranasal dexmedetomidine in the elderly.; METHODS: We randomly assigned 48 surgical patients ≥ ¥65 yr of age to receive single intranasal doses of dexmedetomidine or placebo (5:1 ratio) in four sequential dose cohorts: 0.5, 1.0, 1.5, and 2.0 mug kg-1. Each dose cohort comprised two groups of six subjects: a group of subjects using beta-blockers and a group not taking beta-blockers. Vital signs and sedation depth (Modified Observer's Assessment of Alertness and Sedation [MOAA/S] and bispectral index) were measured for 2 h after administration. Blood samples were taken to determine dexmedetomidine plasma concentrations.; RESULTS: One subject (1.0 mug kg-1) had acute hypotension requiring ephedrine. Systolic arterial BP decreased >30% in 15 of 40 subjects (37.5%) receiving dexmedetomidine, lasting longer than 5 min in 11 subjects (27.5%). The MAP decreased >30% (>5 min) in 10%, 20%, 50%, and 30% of subjects receiving dexmedetomidine 0.5, 1.0, 1.5, and 2.0 mug kg-1, respectively, irrespective of beta-blocker use. HR decreased 10-26%. MOAA/S score ≤ 3 occurred in 18 (45%) subjects; eight (20%) subjects receiving dexmedetomidine showed no signs of sedation. Tmax was 70 min. Cmax was between 0.15 ng ml-1 (0.5 mug kg-1) and 0.46 ng ml-1 (2.0 mug kg-1).; CONCLUSIONS: Intranasal dexmedetomidine in elderly subjects had a sedative effect, but caused a high incidence of profound and sustained hypotension irrespective of beta-blocker use. The technique is unsuitable for routine clinical use.; CLINICAL TRIAL REGISTRATION: NTR5513 (The Netherlands Trial Registry 5513)

Validation of frequency and mode extraction calculations from time-domain simulations of accelerator cavities

The recently developed frequency extraction algorithm [G.R. Werner and J.R. Cary, J. Comp. Phys. 227, 5200 (2008)] that enables a simple FDTD algorithm to be transformed into an efficient eigenmode solver is applied to a realistic accelerator cavity modeled with embedded boundaries and Richardson extrapolation. Previously, the frequency extraction method was shown to be capable of distinguishing M degenerate modes by running M different simulations and to permit mode extraction with minimal post-processing effort that only requires solving a small eigenvalue problem. Realistic calculations for an accelerator cavity are presented in this work to establish the validity of the method for realistic modeling scenarios and to illustrate the complexities of the computational validation process. The method is found to be able to extract the frequencies with error that is less than a part in 10^5. The corrected experimental and computed values differ by about one parts in 10^$, which is accounted for (in largest part) by machining errors. The extraction of frequencies and modes from accelerator cavities provides engineers and physicists an understanding of potential cavity performance as it depends on shape without incurring manufacture and measurement costs

Tracing the evolution of nearby early-type galaxies in low density environments. The Ultraviolet view from GALEX

We detected recent star formation in nearby early-type galaxies located in low density environments, with GALEX Ultraviolet (UV) imaging. Signatures of star formation may be present in the nucleus and in outer rings/arm like structures. Our study suggests that such star formation may be induced by different triggering mechanisms, such as the inner secular evolution driven by bars, and minor accretion phenomena. We investigate the nature of the (FUV-NUV) color vs. Mg2 correlation, and suggest that it relates to "downsizing" in galaxy formation.Comment: Conference "UV Universe 2010" S. Petersburg 31 May - 3 June, 2010 Accepted for publication in Astrophysics & Space Science . The final publication is available at http://www.springerlink.co

System engineering toolbox for design-oriented engineers

This system engineering toolbox is designed to provide tools and methodologies to the design-oriented systems engineer. A tool is defined as a set of procedures to accomplish a specific function. A methodology is defined as a collection of tools, rules, and postulates to accomplish a purpose. For each concept addressed in the toolbox, the following information is provided: (1) description, (2) application, (3) procedures, (4) examples, if practical, (5) advantages, (6) limitations, and (7) bibliography and/or references. The scope of the document includes concept development tools, system safety and reliability tools, design-related analytical tools, graphical data interpretation tools, a brief description of common statistical tools and methodologies, so-called total quality management tools, and trend analysis tools. Both relationship to project phase and primary functional usage of the tools are also delineated. The toolbox also includes a case study for illustrative purposes. Fifty-five tools are delineated in the text

Discovery of optical pulsations in V2116 Ophiuchi/GX 1+4

We report the detection of pulsations with $\sim 124$ s period in V2116 Oph, the optical counterpart of the low-mass X-ray binary GX 1+4. The pulsations are sinusoidal with modulation amplitude of up to 4% in blue light and were observed in ten different observing sessions during 1996 April-August using a CCD photometer at the 1.6-m and 0.6-m telescopes of Laborat\'orio Nacional de Astrof\'{\i}sica, in Brazil. The pulsations were also observed with the $UBVRI$ fast photometer. With only one exception the observed optical periods are consistent with those observed by the BATSE instrument on board the Compton Gamma Ray Observatory at the same epoch. There is a definite correlation between the observability of pulsations and the optical brightness of the system: V2116~Oph had $R$ magnitude in the range $15.3-15.5$ when the pulsed signal was detected, and $R = 16.0-17.7$ when no pulsations were present. The discovery makes GX 1+4 only the third of $\sim 35$ accretion-powered X-ray pulsars to be firmly detected as a pulsating source in the optical. The presence of flickering and pulsations in V2116 Oph adds strong evidence for an accretion disk scenario in this system. The absolute magnitude of the pulsed component on 1996 May 27 is estimated to be $M_V \sim -1.5$. The implied dimensions for the emitting region are 1.1 R_{\sun}, 3.2 R_{\sun}, and 7.0 R_{\sun}, for black-body spectral distributions with $T = 10^5$ K, $2 \times 10^4$ K, and $1 \times 10^4$ K, respectively.Comment: 9 pages, 3 figures in PostScript, latex, accepted for publication on the Astrophysical Journal Letter

Quasar Candidates in the Hubble Deep Field

We focus on the search for unresolved faint quasars and AGN in the crude combine images using a multicolor imaging analysis that has proven very successful in recent years. Quasar selection was carried out both in multicolor space and in "profile space," defined as the multi-parameter space formed by the radial profiles of the objects in the different images. By combining the dither frames available for each filter, we were able to obtain well-sampled radial profiles of the objects and measure their deviation from that of a stellar source. We also generated synthetic quasar spectra in the range 1.0 < z < 5.5 and computed expected quasar colors. We determined that the data are 90% complete for point sources at 26.2, 28.0, 27.8, 26.8 in the F300W, F450W, F606W and F814W filters, respectively. We find 41 compact objects in the HDF: 8 pointlike objects with colors consistent with quasars or stars, 18 stars, and 15 slightly resolved objects, 12 of which have colors consistent with quasars or stars. We estimate the upper limit of unresolved and slightly resolved quasars/AGNs with V < 27.0 and z < 3.5 to be 20 objects (16,200 per deg^2). We find good agreement among authors on the number of stars and the lack of quasar candidates with z > 3.5. We find more quasar candidates than previous work because of our more extensive modeling and use of all of the available color information. (abridged)Comment: We have clarified our discussion and conclusions, added some references and removed the appendix, which is now available from the first author. 37 pages including 10 embedded postscript figures and 6 tables. To appear in the Feb. 99 issue of A