Outcomes of sequential treatment with sorafenib followed by regorafenib for HCC: Additional analyses from the phase III RESORCE trial.

Background & Aims: The RESORCE trial showed that regorafenib improves overall survival (OS) in patients with hepatocellular carcinoma progressing during sorafenib treatment (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.50-0.

Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial.

Background: There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment.

Methods: In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (≥400 mg/day for ≥20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled.

Ultrafast, sensitive and large-volume on-chip real-time PCR for the molecular diagnosis of bacterial and viral infections.

To control future infectious disease outbreaks, like the 2014 Ebola epidemic, it is necessary to develop ultrafast molecular assays enabling rapid and sensitive diagnoses. To that end, several ultrafast real-time PCR systems have been previously developed, but they present issues that hinder their wide adoption, notably regarding their sensitivity and detection volume. An ultrafast, sensitive and large-volume real-time PCR system based on microfluidic thermalization is presented herein.

Distinctive role of KV1.1 subunit in the biology and functions of low threshold K(+) channels with implications for neurological disease.

The diversity of pore-forming subunits of KV1 channels (KV1.1-KV1.8) affords their physiological versatility and predicts a range of functional impairments resulting from genetic aberrations.

Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial.

Background & Aims: Transarterial chemoembolization with doxorubicin-eluting beads (DC Bead®; DEB-TACE) is effective in patients with Barcelona clinic liver cancer stage B hepatocellular carcinoma (HCC). The multikinase inhibitor sorafenib enhances overall survival (OS) and time-to-tumor progression (TTP) in patients with advanced HCC. This exploratory phase II trial tested the efficacy and safety of DEB-TACE plus sorafenib in patients with intermediate stage HCC.

SEARCH: a phase III, randomized, double-blind, placebo-controlled trial of sorafenib plus erlotinib in patients with advanced hepatocellular carcinoma.

Purpose: To compare the clinical outcomes of sorafenib plus either erlotinib or placebo in patients with advanced hepatocellular carcinoma (HCC) in a multicenter, multinational, randomized, phase III trial.

Patients And Methods: Patients with advanced HCC and underlying Child-Pugh class A cirrhosis, who were naive to systemic treatment (N = 720), were randomly assigned to sorafenib plus either erlotinib (n = 362) or placebo (n = 358). The primary end point was overall survival (OS).

Completion of the full-length genome sequence of the infectious salmon anemia virus, an aquatic orthomyxovirus-like, and characterization of mAbs.

We report here the first full-length sequence of the eight ssRNA genome segments of the infectious salmon anemia virus (ISAV, Glesvaer/2/90 isolate), a salmonid orthomyxovirus-like. Comparison of ISAV genome sequence with those of others orthomyxovirus reveals low identity values, and a remarkable feature is the extremely long 5' end UTR of ISAV segments, which all contain an additional conserved motif of unknown function. In addition to the genome nucleotide sequence determination, specific mAbs have been produced through mice immunization with sucrose-purified ISAV.

Mitochondrial antiviral signaling protein plays a major role in induction of the fish innate immune response against RNA and DNA viruses.

Viral infection triggers host innate immune responses through cellular sensor molecules which activate multiple signaling cascades that induce the production of interferons (IFN) and other cytokines. The recent identification of mammalian cytoplasmic viral RNA sensors, such as retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and their mitochondrial adaptor, the mitochondrial antiviral signaling protein (MAVS), also called IPS-1, VISA, and Cardif, highlights the significance of these molecules in the induction of IFN. Teleost fish also possess a strong IFN system, but nothing is known concerning the RLRs and their downstream adaptor.

Recovery of a recombinant salmonid alphavirus fully attenuated and protective for rainbow trout.

Sleeping disease virus (SDV) is a member of the new Salmonid alphavirus genus within the Togaviridae family. The single-stranded RNA genome of SDV is 11,894 nucleotides long, excluding the 3' poly(A) tail. A full-length cDNA has been generated; the cDNA was fused to a hammerhead ribozyme sequence at the 5' end and inserted into a transcription plasmid (pcDNA3) backbone, yielding pSDV.

Bioluminescence imaging of live infected salmonids reveals that the fin bases are the major portal of entry for Novirhabdovirus.

Although Novirhabdovirus viruses, like the Infectious hematopietic necrosis virus (IHNV), have been extensively studied, limited knowledge exists on the route of IHNV entry during natural infection. A recombinant IHNV (rIHNV) expressing the Renilla luciferase gene was generated and used to infect trout. A noninvasive bioluminescence assay was developed so that virus replication in live fish could be followed hours after infection.

Characterization and mapping of monoclonal antibodies against the Sleeping disease virus, an aquatic alphavirus.

Sleeping disease virus (SDV) is an emerging pathogen in salmonid aquacultures, the impact of which is underestimated to date due to the lack of efficient diagnostic tools. To better characterize this new aquatic alphavirus and to make molecular tools available, a panel of monoclonal antibodies (mAbs) directed against SDV non-structural and structural proteins has been generated by immunizing mice with SDV-specific recombinant proteins overexpressed in Escherichia coli as antigens. So far, mAbs against nsP1, nsP3, E2 and E1 SDV proteins have been produced and their reactivity has been characterized by Western blot, radioimmunoprecipitation and indirect immunofluorescence assays.

Comparison of the efficacy and safety of moxifloxacin and trovafloxacin for the treatment of acute, bacterial maxillary sinusitis in adults.

In this multicentre, multinational, comparative, double-blind clinical trial, out-patients with both symptoms and radiographic evidence of acute sinusitis were randomly assigned to receive either a seven-day, once daily (o.d.) oral regimen of moxifloxacin (400 mg) or a 10-day o.

Observation of continuous-wave on-resonance "self-focusing".

We report what to our knowledge are the first observations of an increase in the on-axis intensity of an intense cw on-resonance beam resulting from nonlinear absorption and diffraction during its propagation through a highly absorbing medium (sodium vapor). This "self-focusing" is not a self-lensing; instead it is modeled well by placing an aperture part way through the cell: The stripping by the aperture approximates the effect of the nonlinear absorption, and then Fresnel diffraction results in on-axis minima and maxima.