2,737 research outputs found

    Expression of RUNX1 correlates with poor patient prognosis in triple negative breast cancer

    Get PDF
    The RUNX1 transcription factor is widely recognised for its tumour suppressor effects in leukaemia. Recently a putative link to breast cancer has started to emerge, however the function of RUNX1 in breast cancer is still unknown. To investigate if RUNX1 expression was important to clinical outcome in primary breast tumours a tissue microarray (TMA) containing biopsies from 483 patients with primary operable invasive ductal breast cancer was stained by immunohistochemistry. RUNX1 was associated with progesterone receptor (PR)-positive tumours (P<0.05), more tumour CD4+(P<0.05) and CD8+(P<0.01) T-lymphocytic infiltrate, increased tumour CD138+plasma cell (P<0.01) and more CD68+macrophage infiltrate (P<0.001). RUNX1 expression did not influence outcome of oestrogen receptor (ER)-positive or HER2-positive disease, however on univariate analysis a high RUNX1 protein was significantly associated with poorer cancer-specific survival in patients with ER-negative (P<0.05) and with triple negative (TN) invasive breast cancer (P<0.05). Furthermore, multivariate Cox regression analysis of cancer-specific survival showed a trend towards significance in ER-negative patients (P<0.1) and was significant in triple negative patients (P<0.05). Of relevance, triple negative breast cancer currently lacks good biomarkers and patients with this subtype do not benefit from the option of targeted therapy unlike patients with ER-positive or HER2-positive disease. Using multivariate analysis RUNX1 was identified as an independent prognostic marker in the triple negative subgroup. Overall, our study identifies RUNX1 as a new prognostic indicator correlating with poor prognosis specifically in the triple negative subtype of human breast cancer

    Surveilling the web, mobile, and language accessibility of Communication’s digital presence within institutions of higher education globally

    Get PDF
    This study aims to understand the general web accessibility of digital information networks which may serve as barriers for access to the global discipline of Communication through institutional and departmental websites, specifically for persons with disabilities and those with limited English proficiency (LEP). Our exploratory content analysis relies on computer-aided software to systematically analyze the departmental home pages of websites of institutional members of the International Communication Association (ICA), N = 77, representing 26 countries, globally. Findings from this study help us to: (1) better understand the general web, language, and mobile accessibility of discipline-related online information; (2) identify strengths and opportunities for improvement; and, (3) to reflect upon the anticipated barriers impacting persons with disabilities when accessing higher education information online

    A One-sided, Highly Relativistic Jet from Cygnus X-3

    Get PDF
    Very Long Baseline Array images of the X-ray binary, Cygnus X-3, were obtained 2, 4 and 7 days after the peak of a 10 Jy flare on 4 February 1997. The first two images show a curved one-sided jet, the third a scatter-broadened disc, presumably at the position of the core. The jet curvature changes from the first to the second epoch, which strongly suggests a precessing jet. The ratio of the flux density in the approaching to that in the (undetected) receding jet is > 330; if this asymmetry is due to Doppler boosting, the implied jet speed is > 0.81c. Precessing jet model fits, together with the assumptions that the jet is intrinsically symmetric and was ejected during or after the major flare, yield the following constraints: the jet inclination to the line of sight must be < 14 degrees; the cone opening angle must be < 12 degrees; and the precession period must be > 60 days.Comment: 12 pages 7 figures, accepted by Ap

    Feasibility of Dual-Task Gait to Estimate Alzheimer\u27s Related Cognitive Decline in Down Syndrome

    Get PDF
    Introduction: The striatum and frontal lobes have been shown to have early Alzheimer\u27s disease (AD) neuropathology and are critical for motor and cognitive function. We hypothesized gait would be associated with early-stage dementia in Down syndrome (DS), a cohort at risk for AD. Methods: Twenty-eight participants with DS were enrolled in the study. Participants walked at their self-selected pace and while completing a dual task (counting, obstacle, or counting+obstacle). Results: All participants were able to complete the self-paced condition and 78.57-96.42% completed the dual-task conditions. There was a trend for greater dual-task effects on gait velocity based on dementia diagnosis. Gait velocity had stronger associations with clinical dementia assessments than age or diagnosis. Discussion: A dual-task gait paradigm is feasible to conduct with adults with DS and is associated with age and cognitive impairment. Dual-task gait may serve as an indicator of early stage dementia in DS

    Born too soon: accelerating actions for prevention and care of 15 million newborns born too soon.

    Get PDF
    Preterm birth complication is the leading cause of neonatal death resulting in over one million deaths each year of the 15 million babies born preterm. To accelerate change, we provide an overview of the comprehensive strategy required, the tools available for context-specifi c health system implementation now, and the priorities for research and innovation. There is an urgent need for action on a dual track: (1) through strategic research to advance the prevention of preterm birth and (2) improved implementation and innovation for care of the premature neonate. We highlight evidence-based interventions along the continuum of care, noting gaps in coverage, quality, equity and implications for integration and scale up. Improved metrics are critical for both burden and tracking programmatic change. Linked to the United Nation’s Every Women Every Child strategy, a target was set for 50% reduction in preterm deaths by 2025. Three analyses informed this target: historical change in high income countries, recent progress in best performing countries, and modelling of mortality reduction with high coverage of existing interventions. If universal coverage of selected interventions were to be achieved, then 84% or more than 921,000 preterm neonatal deaths could be prevented annually, with antenatal corticosteroids and Kangaroo Mother Care having the highest impact. Everyone has a role to play in reaching this target including government leaders, professionals, private sector, and of course families who are aff ected the most and whose voices have been critical for change in many of the countries with the most progress

    Parapatric speciation of Meiothermus in serpentinite-hosted aquifers in Oman

    Get PDF
    The factors that control the distribution and evolution of microbial life in subsurface environments remain enigmatic due to challenges associated with sampling fluids from discrete depth intervals via boreholes while avoiding mixing of fluids. Here, using an inflatable packer system, fracture waters were isolated and collected from three discrete depth intervals spanning &gt;130 m in a borehole intersecting an ultramafic rock formation undergoing serpentinization in the Samail Ophiolite, Sultanate of Oman. Near surface aquifer waters were moderately reducing and had alkaline pH while deeper aquifer waters were reduced and had hyperalkaline pH, indicating extensive influence by serpentinization. Metagenomic sequencing and analysis of DNA from filtered biomass collected from discrete depth intervals revealed an abundance of aerobes in near surface waters and a greater proportion of anaerobes at depth. Yet the abundance of the putatively obligate aerobe, Meiothermus, increased with depth, providing an opportunity to evaluate the influence of chemical and spatial variation on its distribution and speciation. Two clades of Meiothermus metagenome assembled genomes (MAGs) were identified that correspond to surface and deep populations termed Types I (S) and II (D), respectively; both clades comprised an apparently Oman-specific lineage indicating a common ancestor. Type II (D) clade MAGs encoded fewer genes and were undergoing slower genome replication as inferred from read mapping. Further, single nucleotide variants (SNVs) and mobile genetic elements identified among MAGs revealed detectable, albeit limited, evidence for gene flow/recombination between spatially segregated Type I (S) and Type II (D) populations. Together, these observations indicate that chemical variation generated by serpentinization, combined with physical barriers that reduce/limit dispersal and gene flow, allowed for the parapatric speciation of Meiothermus in the Samail Ophiolite or a geologic precursor. Further, Meiothermus genomic data suggest that deep and shallow aquifer fluids in the Samail Ophiolite may mix over shorter time scales than has been previously estimated from geochemical data

    Acetyl-CoA synthetase 2 promotes acetate utilization and maintains cancer cell growth under metabolic stress

    Get PDF
    A functional genomics study revealed that the activity of acetyl-CoA synthetase 2 (ACSS2) contributes to cancer cell growth under low-oxygen and lipid-depleted conditions. Comparative metabolomics and lipidomics demonstrated that acetate is used as a nutritional source by cancer cells in an ACSS2-dependent manner, and supplied a significant fraction of the carbon within the fatty acid and phospholipid pools. ACSS2 expression is upregulated under metabolically stressed conditions and ACSS2 silencing reduced the growth of tumor xenografts. ACSS2 exhibits copy-number gain in human breast tumors, and ACSS2 expression correlates with disease progression. These results signify a critical role for acetate consumption in the production of lipid biomass within the harsh tumor microenvironment
    • …
    corecore