9,648 research outputs found

    NVVC/NHJ Durrer prizes 2014

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    Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi

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    Limited data address the impact of HIV co-infection on the pharmacokinetics of anti-tuberculosis drugs in Sub-Saharan Africa. 47 Malawian adults underwent rich pharmacokinetic sampling at 0-0.5-1-2-3-4-6-8 and 24 hours post-dose. 51% were male; mean age was 34 years. 65% were HIV-positive with a mean CD4 count of 268 cells/μL. Anti-tuberculosis drugs were administered as fixed-dose combinations (rifampicin150mg/isoniazid75mg/pyrazinamide400mg/ethambutol275mg) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampicin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analysed by non-compartmental methods and analysis of variance of log-transformed summary parameters. Pharmacokinetic parameters were: rifampicin Cmax 4.129 (2.474-5.596)μg/mL, AUC0-24 21.32 (13.57-28.60)μg/mL*h, half-life 2.45 (1.86-3.08)h; isoniazid Cmax 3.97 (2.979-4.544)μg/mL, AUC0-24 22.5 (14.75-34.59)μg/mL*h, half-life 3.93 (3.18-4.73)h.; pyrazinamide Cmax 34.21 (30.00-41.60)μg/mL, AUC0-24 386.6 (320.0-463.7)μg/mL*h, half-life 6.821 (5.71-8.042)h; ethambutol Cmax 2.278 (1.694-3.098)μg/mL, AUC0-24 20.41 (16.18-26.27)μg/mL*h, half-life 7.507 (6.517-8.696)h. Isoniazid PK data analysis suggested that around two-thirds were slow acetylators. Dose, weight and weight-adjusted dose were not significant predictors of PK exposure probably due to weight-banded dosing. In this first pharmacokinetic study of tuberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with other studies for all first line drugs except for rifampicin, for which Cmax and AUC0-24 were notably lower. Contrary to some earlier observations, HIV status did not significantly affect AUC of any of the drugs. Increasing the dose of rifampicin could be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in half-life of isoniazid of 41% (p=0.022). Possible competitive interactions between isoniazid and sulphamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further

    On the Use of Quantum Algebras in Rotation-Vibration Spectroscopy

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    A two-parameter deformation of the Lie algebra u2_2 is used, in conjunction with the rotor system and the oscillator system, to generate a model for rotation-vibration spectroscopy of molecules and nuclei.Comment: 10 pages, Latex File, published in Modern Group Theoretical Methods in Physics, J. Bertrand et al. (eds.), Kluwer Academic Publishers (1995), 27-3

    Survey of H-alpha emission from thirty nearby dwarf galaxies

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    Measurements of the H-alpha flux from 30 neighboring dwarf galaxies are presented. After correction for absorption, these fluxes are used to estimate the star formation rate (SFR). The SFR for 18 of the galaxies according to the H-alpha emission are compared with estimates of the SFR from FUV magnitudes obtained with the GALEX telescope. These are in good agreement over the range log[SFR] = [-3,0]M sun/yr.Comment: 18 pages, 10 figures, 3 table

    Energy input and response from prompt and early optical afterglow emission in gamma-ray bursts

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    The taxonomy of optical emission detected during the critical first few minutes after the onset of a gamma-ray burst (GRB) defines two broad classes: prompt optical emission correlated with prompt gamma-ray emission, and early optical afterglow emission uncorrelated with the gamma-ray emission. The standard theoretical interpretation attributes prompt emission to internal shocks in the ultra-relativistic outflow generated by the internal engine; early afterglow emission is attributed to shocks generated by interaction with the surrounding medium. Here we report on observations of a bright GRB that, for the first time, clearly show the temporal relationship and relative strength of the two optical components. The observations indicate that early afterglow emission can be understood as reverberation of the energy input measured by prompt emission. Measurements of the early afterglow reverberations therefore probe the structure of the environment around the burst, whereas the subsequent response to late-time impulsive energy releases reveals how earlier flaring episodes have altered the jet and environment parameters. Many GRBs are generated by the death of massive stars that were born and died before the Universe was ten per cent of its current age, so GRB afterglow reverberations provide clues about the environments around some of the first stars.Comment: 13 pages, 4 figures, 1 table. Note: This paper has been accepted for publication in Nature, but is embargoed for discussion in the popular press until formal publication in Natur

    Stimulus Motion Propels Traveling Waves in Binocular Rivalry

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    State transitions in the nervous system often take shape as traveling waves, whereby one neural state is replaced by another across space in a wave-like manner. In visual perception, transitions between the two mutually exclusive percepts that alternate when the two eyes view conflicting stimuli (binocular rivalry) may also take shape as traveling waves. The properties of these waves point to a neural substrate of binocular rivalry alternations that have the hallmark signs of lower cortical areas. In a series of experiments, we show a potent interaction between traveling waves in binocular rivalry and stimulus motion. The course of the traveling wave is biased in the motion direction of the suppressed stimulus that gains dominance by means of the wave-like transition. Thus, stimulus motion may propel the traveling wave across the stimulus to the extent that the stimulus motion dictates the traveling wave's direction completely. Using a computational model, we show that a speed-dependent asymmetry in lateral inhibitory connections between retinotopically organized and motion-sensitive neurons can explain our results. We argue that such a change in suppressive connections may play a vital role in the resolution of dynamic occlusion situations

    Tau PET and relative cerebral blood flow in Dementia with Lewy bodies: A PET study

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    Purpose: Alpha-synuclein often co-occurs with Alzheimer’s disease (AD) pathology in Dementia with Lewy Bodies (DLB). From a dynamic [18F]flortaucipir PET scan we derived measures of both tau binding and relative cerebral blood flow (rCBF). We tested whether regional tau binding or rCBF differed between DLB patients and AD patients and controls and examined their association with clinical characteristics of DLB. / Methods: Eighteen patients with probable DLB, 65 AD patients and 50 controls underwent a dynamic 130-minute [18F]flortaucipir PET scan. DLB patients with positive biomarkers for AD based on cerebrospinal fluid or amyloid PET were considered as DLB with AD pathology(DLB-AD+). Receptor parametric mapping(cerebellar gray matter reference region) was used to extract regional binding potential (BPND) and R1, reflecting (AD-specific) tau pathology and rCBF, respectively. First, we performed regional comparisons of [18F]flortaucipir BPND and R1 between diagnostic groups. In DLB patients only, we performed regression analyses between regional [18F]flortaucipir BPND, R1 and performance on ten neuropsychological tests. / Results: Regional [18F]flortaucipir BPND in DLB was comparable with tau binding in controls (p>0.05). Subtle higher tau binding was observed in DLB-AD+ compared to DLB-AD- in the medial temporal and parietal lobe (both p<0.05). Occipital and lateral parietal R1 was lower in DLB compared to AD and controls (all p<0.01). Lower frontal R1 was associated with impaired performance on digit span forward (standardized beta, stβ=0.72) and category fluency (stβ=0.69) tests. Lower parietal R1 was related to lower delayed (stβ=0.50) and immediate (stβ=0.48) recall, VOSP number location (stβ=0.70) and fragmented letters (stβ=0.59) scores. Lower occipital R1 was associated to worse performance on VOSP fragmented letters (stβ=0.61), all p<0.05. / Conclusion: The amount of tau binding in DLB was minimal and did not differ from controls. However, there were DLB-specific occipital and lateral parietal relative cerebral blood flow reductions compared to both controls and AD patients. Regional rCBF, but not tau binding, was related to cognitive impairment. This indicates that assessment of rCBF may give more insight into disease mechanisms in DLB than tau PET
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