Amikacin use and therapeutic drug monitoring in adults : do dose regimens and drug exposures affect either outcome or adverse events? A systematic review

Objectives To identify the amikacin dosage regimens and drug concentrations consistent with good outcomes and to determine the drug exposures related to nephrotoxicity and ototoxicity. Methods A literature review was conducted in Medline, EMBASE and the Cochrane Central Register of Controlled Trials. Full journal articles of randomised controlled trials, controlled clinical trials, interrupted time series trials and controlled before and after studies involving amikacin TDM and dose adjustment were considered for inclusion. Results Seventeen included studies were identified, comprising 1677 participants. Amikacin doses ranged from 11-15 mg/kg/day with thirteen studies using 15 mg/kg/day. Studies were generally designed to compare different aminoglycosides rather than to assess concentration-effect relationships. Only eleven papers presented data on target concentrations, rate of clinical cure and toxicity. Target peak concentrations ranged from 15 – 40 mg/L and target troughs were typically <10 mg/L or <5 mg/L. It was not clear whether these targets were achieved. Measured peaks averaged 28 mg/L for twice daily dosing and 40-45 mg/L for once daily dosing; troughs averaged 5 mg/L and 1-2 mg/L, respectively. Fifteen of the included studies reported rates of nephrotoxicity; auditory and vestibular toxicities were reported in twelve and eight studies. Conclusions This systematic review found little published evidence to support an optimal dosage regimen or TDM targets for amikacin therapy. The use of alternative approaches, such as consensus opinion and a review of current practice, will be required to develop guidelines to maximise therapeutic outcomes and minimise toxicity with amikacin

LOFAR tied-array imaging and spectroscopy of solar S bursts

Context. The Sun is an active source of radio emission that is often associated with energetic phenomena ranging from nanoflares to coronal mass ejections (CMEs). At low radio frequencies (&lt;100 MHz), numerous millisecond duration radio bursts have been reported, such as radio spikes or solar S bursts (where S stands for short). To date, these have neither been studied extensively nor imaged because of the instrumental limitations of previous radio telescopes. Aims. Here, LOw Frequency ARray (LOFAR) observations were used to study the spectral and spatial characteristics of a multitude of S bursts, as well as their origin and possible emission mechanisms. Methods. We used 170 simultaneous tied-array beams for spectroscopy and imaging of S bursts. Since S bursts have short timescales and fine frequency structures, high cadence (~50 ms) tied-array images were used instead of standard interferometric imaging, that is currently limited to one image per second. Results. On 9 July 2013, over 3000 S bursts were observed over a time period of ~8 h. S bursts were found to appear as groups of short-lived (&lt;1 s) and narrow-bandwidth (~2.5 MHz) features, the majority drifting at ~3.5 MHz s-1 and a wide range of circular polarisation degrees (2−8 times more polarised than the accompanying Type III bursts). Extrapolation of the photospheric magnetic field using the potential field source surface (PFSS) model suggests that S bursts are associated with a trans-equatorial loop system that connects an active region in the southern hemisphere to a bipolar region of plage in the northern hemisphere. Conclusions. We have identified polarised, short-lived solar radio bursts that have never been imaged before. They are observed at a height and frequency range where plasma emission is the dominant emission mechanism, however, they possess some of the characteristics of electron-cyclotron maser emission

First LOFAR observations at very low frequencies of cluster-scale non-thermal emission: the case of Abell 2256

Abell 2256 is one of the best known examples of a galaxy cluster hosting large-scale diffuse radio emission that is unrelated to individual galaxies. It contains both a giant radio halo and a relic, as well as a number of head-tail sources and smaller diffuse steep-spectrum radio sources. The origin of radio halos and relics is still being debated, but over the last years it has become clear that the presence of these radio sources is closely related to galaxy cluster merger events. Here we present the results from the first LOFAR Low band antenna (LBA) observations of Abell 2256 between 18 and 67 MHz. To our knowledge, the image presented in this paper at 63 MHz is the deepest ever obtained at frequencies below 100 MHz in general. Both the radio halo and the giant relic are detected in the image at 63 MHz, and the diffuse radio emission remains visible at frequencies as low as 20 MHz. The observations confirm the presence of a previously claimed ultra-steep spectrum source to the west of the cluster center with a spectral index of -2.3 \pm 0.4 between 63 and 153 MHz. The steep spectrum suggests that this source is an old part of a head-tail radio source in the cluster. For the radio relic we find an integrated spectral index of -0.81 \pm 0.03, after removing the flux contribution from the other sources. This is relatively flat which could indicate that the efficiency of particle acceleration at the shock substantially changed in the last \sim 0.1 Gyr due to an increase of the shock Mach number. In an alternative scenario, particles are re-accelerated by some mechanism in the downstream region of the shock, resulting in the relatively flat integrated radio spectrum. In the radio halo region we find indications of low-frequency spectral steepening which may suggest that relativistic particles are accelerated in a rather inhomogeneous turbulent region.Comment: 13 pages, 13 figures, accepted for publication in A\&A on April 12, 201

LOFAR Sparse Image Reconstruction

Context. The LOw Frequency ARray (LOFAR) radio telescope is a giant digital phased array interferometer with multiple antennas distributed in Europe. It provides discrete sets of Fourier components of the sky brightness. Recovering the original brightness distribution with aperture synthesis forms an inverse problem that can be solved by various deconvolution and minimization methods Aims. Recent papers have established a clear link between the discrete nature of radio interferometry measurement and the "compressed sensing" (CS) theory, which supports sparse reconstruction methods to form an image from the measured visibilities. Empowered by proximal theory, CS offers a sound framework for efficient global minimization and sparse data representation using fast algorithms. Combined with instrumental direction-dependent effects (DDE) in the scope of a real instrument, we developed and validated a new method based on this framework Methods. We implemented a sparse reconstruction method in the standard LOFAR imaging tool and compared the photometric and resolution performance of this new imager with that of CLEAN-based methods (CLEAN and MS-CLEAN) with simulated and real LOFAR data Results. We show that i) sparse reconstruction performs as well as CLEAN in recovering the flux of point sources; ii) performs much better on extended objects (the root mean square error is reduced by a factor of up to 10); and iii) provides a solution with an effective angular resolution 2-3 times better than the CLEAN images. Conclusions. Sparse recovery gives a correct photometry on high dynamic and wide-field images and improved realistic structures of extended sources (of simulated and real LOFAR datasets). This sparse reconstruction method is compatible with modern interferometric imagers that handle DDE corrections (A- and W-projections) required for current and future instruments such as LOFAR and SKAComment: Published in A&A, 19 pages, 9 figure

Optimized Trigger for Ultra-High-Energy Cosmic-Ray and Neutrino Observations with the Low Frequency Radio Array

When an ultra-high energy neutrino or cosmic ray strikes the Lunar surface a radio-frequency pulse is emitted. We plan to use the LOFAR radio telescope to detect these pulses. In this work we propose an efficient trigger implementation for LOFAR optimized for the observation of short radio pulses.Comment: Submitted to Nuclear Instruments and Methods in Physics Research Section

The brightness and spatial distributions of terrestrial radio sources

Faint undetected sources of radio-frequency interference (RFI) might become visible in long radio observations when they are consistently present over time. Thereby, they might obstruct the detection of the weak astronomical signals of interest. This iss

LOFAR detections of low-frequency radio recombination lines towards Cassiopeia A

Cassiopeia A was observed using the low-band antennas of the LOw Frequency ARray (LOFAR) with high spectral resolution. This allowed a search for radio recombination lines (RRLs) along the line-of-sight to this source. Five carbon {$α$} RRLs were detected in absorption between 40 and 50 MHz with a signal-to-noise ratio of {gt}5 from two independent LOFAR data sets. The derived line velocities (v$_{LSR}$ ~{} - 50 km s$^{-1}$) and integrated optical depths (~{}13 s$^{-1}$) of the RRLs in our spectra, extracted over the whole supernova remnant, are consistent within each LOFAR data set and with those previously reported. For the first time, we are able to extract spectra against the brightest hotspot of the remnant at frequencies below 330 MHz. These spectra show significantly higher (15-80 percent) integrated optical depths, indicating that there is small-scale angular structure of the order of ~{}1 pc in the absorbing gas distribution over the face of the remnant. We also place an upper limit of 3 { imes} 10$^{-4}$ on the peak optical depths of hydrogen and helium RRLs. These results demonstrate that LOFAR has the desired spectral stability and sensitivity to study faint recombination lines in the decameter band