ABSTRACT
We present sofia 2, the fully automated 3D source finding pipeline for the WALLABY extragalactic H i survey with the Australian SKA Pathfinder (ASKAP). sofia 2 is a reimplementation of parts ...of the original sofia pipeline in the c programming language and makes use of OpenMP for multithreading of the most time-critical algorithms. In addition, we have developed a parallel framework called sofia-X that allows the processing of large data cubes to be split across multiple computing nodes. As a result of these efforts, sofia 2 is substantially faster and comes with a much reduced memory footprint compared to its predecessor, thus allowing the large WALLABY data volumes of hundreds of gigabytes of imaging data per epoch to be processed in real time. The source code has been made publicly available to the entire community under an open-source licence. Performance tests using mock galaxies injected into genuine ASKAP data suggest that in the absence of significant imaging artefacts sofia 2 is capable of achieving near-100 per cent completeness and reliability above an integrated signal-to-noise ratio (SNR) of about 5–6. We also demonstrate that sofia 2 generally recovers the location, integrated flux, and w20 line width of galaxies with high accuracy. Other parameters, including the peak flux density and w50 line width, are more strongly biased due to the influence of the noise on the measurement. In addition, very faint galaxies below an integrated SNR of about 10 may get broken up into multiple components, thus requiring a strategy to identify fragmented sources and ensure that they do not affect the integrity of any scientific analysis based on the sofia 2 output.
Summary
Background
Adefovir and tenofovir are nucleotide analogues used as long‐term therapy of chronic hepatitis B. Side effects are few, but prolonged and high‐dose therapy has been associated with ...proximal renal tubular dysfunction (RTD).
Aim
To assess the incidence of RTD during long‐term nucleotide therapy of chronic hepatitis B.
Methods
A total of 51 patients being treated at the Clinical Center, National Institutes of Health were studied. Diagnosis of RTD required de novo appearance of at least three of five features: hypophosphataemia, hypouricaemia, serum creatinine elevation, proteinuria or glucosuria.
Results
Among 51 patients treated for 1–10 (mean 7.4) years with adefovir (n = 42), tenofovir (n = 4) or adefovir followed by tenofovir (n = 5), 7 (14%) developed RTD. Time to onset ranged from 22 to 94 (mean 49) months with an estimated 10‐year cumulative rate of 15%. All seven had low urinary percent maximal tubular reabsorption of phosphate (<82%). Patients with RTD were older (58 vs. 44 years; P = 0.01) and had lower baseline glomerular filtration rates (82 vs. 97 cc/min; P = 0.08) compared to those without; but did not differ in other features. Six patients with RTD were switched to entecavir, all subsequently had improvements in serum phosphate (2.0–3.0 mg/dL), creatinine (1.6–1.1 mg/dL), uric acid (2.7–3.8 mg/dL) and proteinuria.
Conclusions
Renal tubular dysfunction develops in 15% of patients treated with adefovir or tenofovir for 2–9 years and is partially reversible with change to other antivirals. Monitoring for serum phosphate, creatinine and urinalysis is prudent during long‐term adefovir and tenofovir therapy.
We present MeerKAT 1000 MHz and 1400 MHz observations of a bright radio galaxy in the southern hemisphere, ESO 137-006. The galaxy lies at the centre of the massive and merging Norma galaxy cluster. ...The MeerKAT continuum images (rms ∼0.02 mJy beam
−1
at ∼10″ resolution) reveal new features that have never been seen in a radio galaxy before: collimated synchrotron threads of yet unknown origin, which link the extended and bent radio lobes of ESO 137-006. The most prominent of these threads stretches in projection for about 80 kpc and is about 1 kpc in width. The radio spectrum of the threads is steep, with a spectral index of up to
α
≃ 2 between 1000 and 1400 MHz.
We present new observations of Fornax A taken at ∼1 GHz with the MeerKAT telescope and at ∼6 GHz with the Sardinia Radio Telescope (SRT). The sensitive (noise ∼16
μ
Jy beam
−1
), high-resolution ...(≲10″) MeerKAT images show that the lobes of Fornax A have a double-shell morphology, where dense filaments are embedded in a diffuse and extended cocoon. We study the spectral properties of these components by combining the MeerKAT and SRT observations with archival data between 84 MHz and 217 GHz. For the first time, we show that multiple episodes of nuclear activity must have formed the extended radio lobes. The modelling of the radio spectrum suggests that the last episode of injection of relativistic particles into the lobes started ∼24 Myr ago and stopped 12 Myr ago. More recently (∼3 Myr ago), a less powerful and short (≲1 Myr) phase of nuclear activity generated the central jets. Currently, the core may be in a new active phase. It appears that Fornax A is rapidly flickering. The dense environment around Fornax A has lead to a complex recent merger history for this galaxy, including mergers spanning a range of gas contents and mass ratios, as shown by the analysis of the galaxy’s stellar- and cold-gas phases. This complex recent history may be the cause of the rapid, recurrent nuclear activity of Fornax A.
Summary
Background
Chronic delta hepatitis virus (HDV) infection rapidly progresses to cirrhosis. Treatment with peginterferon for up to 2 years is often without durable response.
Aim
To examine the ...efficacy and safety of long‐term peginterferon in achieving a durable response.
Methods
Treatment was initiated with 180 μg/week of peginterferon alfa‐2a with titration to a maximal tolerable dose, for up to 5 years. Liver biopsies and hepatic venous pressure gradients (HVPG) were evaluated at baseline, 1, 3 and 5 years. The primary endpoint was histological improvement or loss of serum HDV and HBsAg at 3 years.
Results
Thirteen patients were treated for a median of 140 weeks (6–260) with an average peginterferon dose of 180 μg/week (90–270). At baseline, most had advanced disease (median Ishak fibrosis = 3) with portal hypertension (HVPG = 10.2 ± 6 mmHg). Five of 13 patients (39%) achieved the primary endpoint, with three seroconverting for HBsAg after 24, 37 and 202 weeks of treatment. Histological inflammation improved after 1 year, (median HAI: 10 vs. 7, P = 0.01) with persistence in 4/5 patients at 3 years (median HAI: 7.5). Greatest improvements occurred in the first year. Baseline bilirubin and HBsAg levels were significantly lower in virological responders than nonresponders. After 12 weeks, virological responders had a significant decline in HBsAg (1.5 log10 IU/mL, P = 0.05).
Conclusion
Despite increased doses and duration of therapy, treatment of chronic HDV with peginterferon remains unsatisfactory. Quantitative measures of HBsAg may be an important biomarker of early response to peginterferon therapy in chronic delta hepatitis virus infection.
Abstract
We report on neutral hydrogen (H i) observations of the NGC 7232 group with the Australian Square Kilometre Array Pathfinder (ASKAP). These observations were conducted as part of the ...Wide-field ASKAP L-Band Legacy All-sky Blind surveY (WALLABY) Early Science program with an array of 12 ASKAP antennas equipped with Phased Array Feeds, which were used to form 36 beams to map a field of view of 30 deg2. Analysing a subregion of the central beams, we detect 17 H i sources. Eleven of these detections are identified as galaxies and have stellar counterparts, of which five are newly resolved H i galaxy sources. The other six detections appear to be tidal debris in the form of H i clouds that are associated with the central triplet, NGC 7232/3, comprising the spiral galaxies NGC 7232, NGC 7232B, and NGC 7233. One of these H i clouds has a mass of MH i ∼ 3 × 108 M⊙ and could be the progenitor of a long-lived tidal dwarf galaxy. The remaining H i clouds are likely transient tidal knots that are possibly part of a diffuse tidal bridge between NGC 7232/3 and another group member, the lenticular galaxy IC 5181.
IL‐6‐type cytokines bind to plasma membrane receptor complexes containing the common signal transducing receptor chain gp130 that is ubiquitously expressed in most tissues including the heart. The ...two major signalling cascades activated by the gp130 receptor, SHP2/ERK and STAT pathways, have been demonstrated to play important roles in cardiac development, hypertrophy, protection and remodelling in response to physiological and pathophysiological stimuli. Experimental data, both in vivo and in vitro, imply beneficial effects of gp130 signalling on cardiomyocytes in terms of growth and survival. In contrast, it has been reported that elevated serum levels of IL‐6 cytokines and gp130 proteins are strong prognostic markers for morbidity and mortality in patients with heart failure or after myocardial infarction. Moreover, it has been shown that the local gp130 receptor system is altered in failing human hearts. In the present review, we summarize the basic principles of gp130 signalling, which requires simultaneous activation of STAT and ERK pathways under the tight control of positive and negative intracellular signalling modulators to provide a balanced biological outcome. Furthermore, we highlight the key role of the gp130 receptor and its major downstream effectors in the heart in terms of development and regeneration and in response to various physiological and pathophysiological stress situations. Finally, we comment on tissue‐specific diversity and challenges in targeted pharmacological interference with components of the gp130 receptor system.
British Journal of Pharmacology (2008) 153, S414–S427; doi:10.1038/bjp.2008.1; published online 4 February 2008
Summary
Background Non‐alcoholic steatohepatitis (NASH) is a form of progressive fatty liver disease that is strongly associated with insulin resistance, which suggests that insulin sensitizing ...agents such as metformin may be beneficial for NASH.
Aim To assess the effects of metformin on insulin sensitivity, body composition, serum alanine aminotransferase (ALT) levels and liver histology in patients with NASH.
Methods Patients underwent liver biopsy, metabolic profiling and imaging studies before and at the end 48 weeks of metformin (2000 mg/day) therapy. The primary endpoint was a three‐point improvement in the histological NASH activity index.
Results Of 28 patients enrolled, 26 (13 females; average age 44 years) completed 48 weeks of treatment and underwent repeat metabolic studies, imaging and liver biopsy. Thirty per cent achieved a histological response. Most patients lost weight, the average being 6 kg. There was a marked association between weight loss and improvements in NASH activity index and ALT levels (both, P < 0.01). Insulin sensitivity also improved, but the degree of change did not correlate with histological improvement.
Conclusion Metformin leads to improvements in liver histology and ALT levels in 30% of patients with NASH, probably by its effects in causing weight loss.
ABSTRACT
We present a Wide-field ASKAP L-Band Legacy All-sky Blind surveY (WALLABY) study of the nearby (vsys = 915 km s−1) spiral galaxy IC 5201 using the Australian Square Kilometre Array ...Pathfinder (ASKAP). IC 5201 is a blue, barred spiral galaxy that follows the known scaling relations between stellar mass, SFR, H i mass, and diameter. We create a four-beam mosaicked H i image cube from 175 h of observations made with a 12-antenna sub-array. The root mean square noise level of the cube is 1.7 mJy beam−1 per channel, equivalent to a column density of $N_{\rm H\, \small {I}}$ = 1.4 × 1020 cm−2 over 25 km s−1. We report nine extragalactic H i detections – five new H i detections including the first velocity measurements for two galaxies. These sources are IC 5201, three dwarf satellite galaxies, two galaxies, and a tidal feature belonging to the NGC 7232/3 triplet and two potential infalling galaxies to the triplet. There is evidence of a previous tidal interaction between IC 5201 and the irregular satellite AM 2220−460. A close fly-by is likely responsible for the asymmetric optical morphology of IC 5201 and warping its disc, resulting in the irregular morphology of AM 2220−460. We quantify the H i kinematics of IC 5201, presenting its rotation curve as well as showing that the warp starts at 14 kpc along the major axis, increasing as a function of radius with a maximum difference in position angle of 20°. There is no evidence of stripped H i, triggered or quenched star formation in the system as measured using DECam optical and GALEX UV photometry.
Circulating levels of interleukin (IL)-6 and related cytokines are elevated in patients with congestive heart failure and after myocardial infarction. Serum IL-6 concentrations are related to ...decreasing functional status of these patients and provide important prognostic information.Moreover, in the failing human heart, multiple components of the IL-6- glycoprotein (gp)130 receptor system are impaired, implicating an important role of this system in cardiac pathophysiology.Experimental studies have shown that the common receptor subunit of IL-6 cytokines is phosphorylated in response to pressure overload and myocardial infarction and that it subsequently activates at least three different downstream signaling pathways, the signal transducers and activators of transcription 1 and 3 (STAT1/3), the Src-homology tyrosine phosphatase 2 (SHP2)-Ras-ERK, and the PI3K-Akt system. Gp130 receptor mediated signaling promotes cardiomyocyte survival, induces hypertrophy, modulates cardiac extracellular matrix and cardiac function. In this regard, the gp130 receptor system and its main downstream mediator STAT3 play a key role in cardioprotection. This review summarizes the current knowledge of IL-6 cytokines, gp130 receptor and STAT3 signaling in the heart exposed to physiological (aging, pregnancy) and pathophysiological stress (ischemia, pressure overload, inflammation and cardiotoxic agents) with a special focus on the potential role of individual IL-6 cytokines.
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