Everolimus and long acting octreotide as a volume reducing treatment of polycystic livers (ELATE): study protocol for a randomized controlled trial

Contains fulltext : 97893.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Polycystic liver disease (PLD) is defined as having more than 20 liver cysts and can present as a severe and disabling condition. Most symptoms are caused by the mass effect of the liver size and include abdominal pain and distension. The somatostatin analogues octreotide and lanreotide have proven to reduce polycystic liver volume. mTOR inhibitors such as everolimus inhibit cell proliferation and might thereby reduce growth of liver cysts. This trial aims to assess the benefit of combination therapy of everolimus and octreotide compared to octreotide monotherapy. In this study we present the structure of the trial and the characteristics of the included patients. METHODS/DESIGN: This is a randomized open-label clinical trial comparing the effect of 12 months of everolimus and octreotide to octreotide monotherapy in PLD patients. Primary outcome is change in liver volume determined by CT-volumetry. Secondary outcomes are changes in abdominal symptoms and quality of life. Moreover, safety and tolerability of the drugs will be assessed. DISCUSSION: This trial will compare the relative efficacy of combination therapy with octreotide and everolimus to octreotide monotherapy. Since they apply to different pathways of cystogenesis we expect that combining octreotide and everolimus will result in a cumulative reduction of polycystic liver volume. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01157858

The SFXC software correlator for Very Long Baseline Interferometry: Algorithms and Implementation

In this paper a description is given of the SFXC software correlator, developed and maintained at the Joint Institute for VLBI in Europe (JIVE). The software is designed to run on generic Linux-based computing clusters. The correlation algorithm is explained in detail, as are some of the novel modes that software correlation has enabled, such as wide-field VLBI imaging through the use of multiple phase centres and pulsar gating and binning. This is followed by an overview of the software architecture. Finally, the performance of the correlator as a function of number of CPU cores, telescopes and spectral channels is shown.Comment: Accepted by Experimental Astronom

The small FOXP1 isoform predominantly expressed in activated B cell-like diffuse large B-cell lymphoma and full-length FOXP1 exert similar oncogenic and transcriptional activity in human B cells

Proteomic

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

FOXP1 suppresses immune response signatures and MHC class II expression in activated B-cell-like diffuse large B-cell lymphomas.

The FOXP1 (forkhead box P1) transcription factor is a marker of poor prognosis in diffuse large B-cell lymphoma (DLBCL). Here microarray analysis of FOXP1-silenced DLBCL cell lines identified differential regulation of immune response signatures and major histocompatibility complex class II (MHC II) genes as some of the most significant differences between germinal center B-cell (GCB)-like DLBCL with full-length FOXP1 protein expression versus activated B-cell (ABC)-like DLBCL expressing predominantly short FOXP1 isoforms. In an independent primary DLBCL microarray data set, multiple MHC II genes, including human leukocyte antigen DR alpha chain (HLA-DRA), were inversely correlated with FOXP1 transcript expression (P<0.05). FOXP1 knockdown in ABC-DLBCL cells led to increased cell-surface expression of HLA-DRA and CD74. In R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL patients (n=150), reduced HLA-DRA (<90% frequency) expression correlated with inferior overall survival (P=0.0003) and progression-free survival (P=0.0012) and with non-GCB subtype stratified by the Hans, Choi or Visco-Young algorithms (all P<0.01). In non-GCB DLBCL cases with <90% HLA-DRA, there was an inverse correlation with the frequency (P=0.0456) and intensity (P=0.0349) of FOXP1 expression. We propose that FOXP1 represents a novel regulator of genes targeted by the class II MHC transactivator CIITA (MHC II and CD74) and therapeutically targeting the FOXP1 pathway may improve antigen presentation and immune surveillance in high-risk DLBCL patients

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

A direct localization of a fast radio burst and its host

Fast radio bursts are astronomical radio flashes of unknown physical nature with durations of milliseconds. Their dispersive arrival times suggest an extragalactic origin and imply radio luminosities orders of magnitude larger than any other kind of known short-duration radio transient. Thus far, all FRBs have been detected with large single-dish telescopes with arcminute localizations, and attempts to identify their counterparts (source or host galaxy) have relied on contemporaneous variability of field sources or the presence of peculiar field stars or galaxies. These attempts have not resulted in an unambiguous association with a host or multi-wavelength counterpart. Here we report the sub-arcsecond localization of FRB 121102, the only known repeating burst source, using high-time-resolution radio interferometric observations that directly image the bursts themselves. Our precise localization reveals that FRB 121102 originates within 100 mas of a faint 180 uJy persistent radio source with a continuum spectrum that is consistent with non-thermal emission, and a faint (25th magnitude) optical counterpart. The flux density of the persistent radio source varies by tens of percent on day timescales, and very long baseline radio interferometry yields an angular size less than 1.7 mas. Our observations are inconsistent with the fast radio burst having a Galactic origin or its source being located within a prominent star-forming galaxy. Instead, the source appears to be co-located with a low-luminosity active galactic nucleus or a previously unknown type of extragalactic source. [Truncated] If other fast radio bursts have similarly faint radio and optical counterparts, our findings imply that direct sub-arcsecond localizations of FRBs may be the only way to provide reliable associations.Comment: Nature, published online on 4 Jan 2017, DOI: 10.1038/nature2079