2,217 research outputs found

    Phase III Open-Label Randomized Study of Eribulin Mesylate Versus Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer Previously Treated With an Anthracycline and a Taxane

    Get PDF
    Purpose: This phase III randomized trial (ClinicalTrials.gov identifier: NCT00337103) compared eribulin with capecitabine in patients with locally advanced or metastatic breast cancer (MBC). Patients and Methods: Women with MBC who had received prior anthracycline- and taxane-based therapy were randomly assigned to receive eribulin or capecitabine as their first-, second-, or third-line chemotherapy for advanced/metastatic disease. Stratification factors were human epidermal growth factor receptor-2 (HER2) status and geographic region. Coprimary end points were overall survival (OS) and progression-free survival (PFS). Results: Median OS times for eribulin (n = 554) and capecitabine (n = 548) were 15.9 and 14.5 months, respectively (hazard ratio [HR], 0.88; 95% CI, 0.77 to 1.00; P = .056). Median PFS times for eribulin and capecitabine were 4.1 and 4.2 months, respectively (HR, 1.08; 95% CI, 0.93 to 1.25; P = .30). Objective response rates were 11.0% for eribulin and 11.5% for capecitabine. Global health status and overall quality-of-life scores over time were similar in the treatment arms. Both treatments had manageable safety profiles consistent with their known adverse effects; most adverse events were grade 1 or 2. Conclusion: In this phase III study, eribulin was not shown to be superior to capecitabine with regard to OS or PFS

    CO observations of water-maser post-AGB stars and detection of a high-velocity outflow in IRAS 15452-5459

    Full text link
    Many aspects of the evolutionary phase in which Asymptotic Giant Branch stars (AGB stars) are in transition to become Planetary Nebulae (PNe) are still poorly understood. An important question is how the circumstellar envelopes of AGB stars switch from spherical symmetry to the axially symmetric structures frequently observed in PNe. In many cases there is clear evidence that the shaping of the circumstellar envelopes of PNe is linked to the formation of jets/collimated winds and their interaction with the remnant AGB envelope. Because of the short evolutionary time, objects in this phase are rare, but their identification provides valuable probes for testing evolutionary models. We have observed (sub)millimeter CO rotational transitions with the APEX telescope in a small sample of stars hosting high-velocity OH and water masers. These targets are supposed to have recently left the AGB, as indicated by the presence of winds traced by masers, with velocities larger than observed during that phase. We have carried out observations of several CO lines, ranging from J=2-1 up to J=7-6. In IRAS 15452-5459 we detect a fast molecular outflow in the central region of the nebula and estimate a mass-loss rate between 1.2x10^{-4} Msun yr^{-1} (assuming optically thin emission) and 4.9x10^{-4} Msun yr^{-1} (optically thick emission). We model the SED of this target taking advantage of our continuum measurement at 345 GHz to constrain the emission at long wavelengths. For a distance of 2.5 kpc, we estimate a luminosity of 8000 Lsun and a dust mass of 0.01 Msun. Through the flux in the [CII] line (158 um), we calculate a total mass of about 12 Msun for the circumstellar envelope, but the line is likely affected by interstellar contamination.Comment: 12 pages, 9 figures, accepted for publication on A&

    Modulating attentional load affects numerosity estimation: evidence against a pre-attentive subitizing mechanism

    Get PDF
    Traditionally, the visual enumeration of a small number of items (1 to about 4), referred to as subitizing, has been thought of as a parallel and pre-attentive process and functionally different from the serial attentive enumeration of larger numerosities. We tested this hypothesis by employing a dual task paradigm that systematically manipulated the attentional resources available to an enumeration task. Enumeration accuracy for small numerosities was severely decreased as more attentional resources were taken away from the numerical task, challenging the traditionally held notion of subitizing as a pre-attentive, capacity-independent process. Judgement of larger numerosities was also affected by dual task conditions and attentional load. These results challenge the proposal that small numerosities are enumerated by a mechanism separate from large numerosities and support the idea of a single, attention-demanding enumeration mechanism

    Expression of HIV transgene aggravates kidney injury in diabetic mice

    Get PDF
    With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy has decreased. Currently, HIV-infected patients live much longer and often suffer from comorbidities such as diabetes mellitus. Recent epidemiological studies suggest that concurrent HIV infection and diabetes mellitus may have a synergistic effect on the incidence of chronic kidney disease. To address this, we determined whether HIV-1 transgene expression accelerates diabetic kidney injury using a diabetic HIV-1 transgenic (Tg26) murine model. Diabetes was initially induced with low-dose streptozotocin in both Tg26 and wild-type mice on a C57BL/6 background, which is resistant to classic HIV-associated nephropathy. Although diabetic nephropathy is minimally observed on the C57BL/6 background, diabetic Tg26 mice exhibited a significant increase in glomerular injury compared with nondiabetic Tg26 mice and diabetic wild-type mice. Validation of microarray gene expression analysis from isolated glomeruli showed a significant upregulation of proinflammatory pathways in diabetic Tg26 mice. Thus, our study found that expression of HIV-1 genes aggravates diabetic kidney disease

    Parton energy loss limits and shadowing in Drell-Yan dimuon production

    Get PDF
    A precise measurement of the ratios of the Drell-Yan cross section per nucleon for an 800 GeV/c proton beam incident on Be, Fe and W targets is reported. The behavior of the Drell-Yan ratios at small target parton momentum fraction is well described by an existing fit to the shadowing observed in deep-inelastic scattering. The cross section ratios as a function of the incident parton momentum fraction set tight limits on the energy loss of quarks passing through a cold nucleus

    The N-terminal intrinsically disordered domain of mgm101p is localized to the mitochondrial nucleoid.

    Get PDF
    The mitochondrial genome maintenance gene, MGM101, is essential for yeasts that depend on mitochondrial DNA replication. Previously, in Saccharomyces cerevisiae, it has been found that the carboxy-terminal two-thirds of Mgm101p has a functional core. Furthermore, there is a high level of amino acid sequence conservation in this region from widely diverse species. By contrast, the amino-terminal region, that is also essential for function, does not have recognizable conservation. Using a bioinformatic approach we find that the functional core from yeast and a corresponding region of Mgm101p from the coral Acropora millepora have an ordered structure, while the N-terminal domains of sequences from yeast and coral are predicted to be disordered. To examine whether ordered and disordered domains of Mgm101p have specific or general functions we made chimeric proteins from yeast and coral by swapping the two regions. We find, by an in vivo assay in S.cerevisiae, that the ordered domain of A.millepora can functionally replace the yeast core region but the disordered domain of the coral protein cannot substitute for its yeast counterpart. Mgm101p is found in the mitochondrial nucleoid along with enzymes and proteins involved in mtDNA replication. By attaching green fluorescent protein to the N-terminal disordered domain of yeast Mgm101p we find that GFP is still directed to the mitochondrial nucleoid where full-length Mgm101p-GFP is targeted
    • …
    corecore