Rationale and design of the RESOLVE trial: lanreotide as a volume reducing treatment for polycystic livers in patients with autosomal dominant polycystic kidney disease

Contains fulltext : 109282.pdf (publisher's version ) (Open Access)BACKGROUND: A large proportion of patients with autosomal dominant polycystic kidney disease (ADPKD) suffers from polycystic liver disease. Symptoms arise when liver volume increases. The somatostatin analogue lanreotide has proven to reduce liver volume in patients with polycystic liver disease. However, this study also included patients with isolated polycystic liver disease (PCLD). The RESOLVE trial aims to assess the efficacy of lanreotide treatment in ADPKD patients with symptomatic polycystic livers. In this study we present the design of the RESOLVE trial. METHODS/DESIGN: This open-label clinical trial evaluates the effect of 6 months of lanreotide in ADPKD patients with symptomatic polycystic livers. Primary outcome is change in liver volume determined by computerised tomography-volumetry. Secondary outcomes are changes in total kidney volume, kidney intermediate volume and renal function. Furthermore, urinary (NGAL, alpha1-microglobulin, KIM-1, H-FABP, MCP-1) and serum (fibroblast growth factor 23) biomarkers associated with ADPKD disease severity are assessed to investigate whether these biomarkers predict treatment responses to lanreotide. Moreover, safety and tolerability of the drug in ADPKD patients will be assessed. DISCUSSION: We anticipate that lanreotide is an effective therapeutic option for ADPKD patients with symptomatic polycystic livers and that this trial aids in the identification of patient related factors that predict treatment response. TRIAL REGISTRATION NUMBER: Clinical trials.gov NCT01354405

Direct observation of the thermal demagnetization of magnetic vortex structures in non-ideal magnetite recorders

The thermal demagnetization of pseudo-single-domain (PSD) magnetite (Fe3O4) particles, which govern the magnetic signal in many igneous rocks, is examined using off-axis electron holography. Visualization of a vortex structure held by an individual Fe3O4 particle (~ 250 nm in diameter) during in situ heating is achieved through the construction and examination of magnetic-induction maps. Step-wise demagnetization of the remanence-induced Fe3O4 particle upon heating to above the Curie temperature, performed in a similar fashion to bulk thermal demagnetization measurements, revealed its vortex state remains stable under heating close to its unblocking temperature, and is recovered upon cooling with the same or reversed vorticity. Hence, the PSD Fe3O4 particle exhibits thermomagnetic behavior comparable to a single-domain carrier, and thus vortex-states are considered reliable magnetic recorders for paleomagnetic investigations

Aspiration–sclerotherapy Results in Effective Control of Liver Volume in Patients with Liver Cysts

Purpose To study the extent to which aspiration–sclerotherapy reduces liver volume and whether this therapy results in relief of symptoms. Results Four patients, group I, with isolated large liver cysts, and 11 patients, group II, with polycystic livers, underwent aspiration–sclerotherapy. Average volume of aspirated cyst fluid was 1,044 ml (range 225–2,000 ml) in group I and 1,326 ml (range 40–4,200 ml) in group II. Mean liver volume before the procedure was 2,157 ml (range 1,706–2,841 ml) in group I and 4,086 ml (range 1,553–7,085 ml) in group II. This decreased after the procedure to 1,757 ml (range 1,479–2,187 ml) in group I. In group II there was a statistically significant decrease to 3,347 ml (range 1,249–6,930 ml, P = 0.008). Volume reduction was 17.1% (range −34.7% to −4.1%) and 19.2% (range −53.9% to +2.4%) in groups I and II, respectively. Clinical severity of all symptoms decreased, except for involuntary weight loss and pain in group II. Conclusion Aspiration–sclerotherapy is an effective means of achieving liver volume reduction and relief of symptoms

LOFAR Detection of 110-188 MHz Emission and Frequency-Dependent Activity from FRB 20180916B

FRB 20180916B is a well-studied repeating fast radio burst source. Its proximity (~150 Mpc), along with detailed studies of the bursts, have revealed many clues about its nature -- including a 16.3-day periodicity in its activity. Here we report on the detection of 18 bursts using LOFAR at 110-188 MHz, by far the lowest-frequency detections of any FRB to date. Some bursts are seen down to the lowest-observed frequency of 110 MHz, suggesting that their spectra extend even lower. These observations provide an order-of-magnitude stronger constraint on the optical depth due to free-free absorption in the source's local environment. The absence of circular polarization and nearly flat polarization angle curves are consistent with burst properties seen at 300-1700 MHz. Compared with higher frequencies, the larger burst widths (~40-160 ms at 150 MHz) and lower linear polarization fractions are likely due to scattering. We find ~2-3 rad/m^2 variations in the Faraday rotation measure that may be correlated with the activity cycle of the source. We compare the LOFAR burst arrival times to those of 38 previously published and 22 newly detected bursts from the uGMRT (200-450 MHz) and CHIME/FRB (400-800 MHz). Simultaneous observations show 5 CHIME/FRB bursts when no emission is detected by LOFAR. We find that the burst activity is systematically delayed towards lower frequencies by ~3 days from 600 MHz to 150 MHz. We discuss these results in the context of a model in which FRB 20180916B is an interacting binary system featuring a neutron star and high-mass stellar companion.Comment: Accepted for publication by ApJ

The 999th Swift gamma-ray burst: Some like it thermal: A multiwavelength study of GRB 151027A

We present a multiwavelength study of GRB 151027A. This is the 999th GRB detected by the Swift satellite and it has a densely sampled emission in the X-ray and optical band and has been observed and detected in the radio up to 140 days after the prompt. The multiwavelength light curve from 500 s to 140 days can be modelled through a standard forward shock afterglow but requires an additional component to reproduce the early X-ray and optical emission. We present TNG and LBT optical observations performed 19.6, 33.9 and 92.3 days after the trigger which show a bump with respect to a standard afterglow flux decay and are possibly interpreted as due to the underlying SN and host galaxy (of 0.4 uJy in the R band). Radio observations, performed with SRT, Medicina, EVN and VLBA between day 4 and 140, suggest that the burst exploded in an environment characterised by a density profile scaling with the distance from the source (wind profile). A remarkable feature of the prompt emission is the presence of a bright flare 100 s after the trigger, lasting 70 seconds in the soft X-ray band, which was simultaneously detected from the optical band up to the MeV energy range. By combining Swift-BAT/XRT and Fermi-GBM data, the broadband (0.3-1000 keV) time resolved spectral analysis of the flare reveals the coexistence of a non-thermal (power law) and thermal blackbody components. The BB component contributes up to 35% of the luminosity in the 0.3-1000 keV band. The gamma-ray emission observed in Swift-BAT and Fermi-GBM anticipates and lasts less than the soft X-ray emission as observed by Swift-XRT, arguing against a Comptonization origin. The BB component could either be produced by an outflow becoming transparent or by the collision of a fast shell with a slow, heavy and optically thick fireball ejected during the quiescent time interval between the initial and later flares of the burst