Automated analysis of atrial late gadolinium enhancement imaging that correlates with endocardial voltage and clinical outcomes: A 2-center study

This work was supported by the British Heart Foundation PG/10/37/28347, RG/10/11/28457, NIHR Biomedical Research Centre funding, and the ElectroCardioMaths Programme of the Imperial BHF Centre of Research Excellence

Co-activation of NF-κB and MYC renders cancer cells addicted to IL6 for survival and phenotypic stability

NF-κB and MYC are found co-deregulated in human B and plasma-cell cancers. In physiology, NF-κB is necessary for terminal B-to-plasma cell differentiation, whereas MYC repression is required. It is thus unclear if NF-κB/MYC co-deregulation is developmentally compatible in carcinogenesis and/or impacts cancer cell differentiation state, possibly uncovering unique sensitivities. Using a mouse system to trace cell lineage and oncogene activation we found that NF-κB/MYC co-deregulation originated cancers with a plasmablast-like phenotype, alike human plasmablastic-lymphoma and was linked to t(8;14)[MYC-IGH] multiple myeloma. Notably, in contrast to NF-κB or MYC activation alone, co-deregulation rendered cells addicted to IL6 for survival and phenotypic stability. We propose that conflicting oncogene-driven differentiation pressures can be accommodated at a cost in poorly-differentiated cancers. SIGNIFICANCE: Our studies improve the understanding of cancer pathogenesis by demonstrating that co-deregulation of NF-κB and MYC synergize in forming a cancer with a poorly-differentiated state. The cancers in the mouse system share features with human Plasmablastic lymphoma that has a dismal prognosis and no standard of care, and with t(8;14)[MYC-IGH] Multiple myeloma, which is in overall resistant to standard therapy. Notably, we found that NF-κB and MYC co-deregulation uniquely render cells sensitive to IL6 deprivation, providing a road-map for patient selection. Because of the similarity of the cancers arising in the compound mutant mouse model with that of human Plasmablastic lymphoma and t(8;14)[MYC-IGH] Multiple myeloma, this model could serve in preclinical testing to investigate novel therapies for these hard-to-treat diseases

Application of ripple mapping to visualize slow conduction channels within the infarct-related left ventricular scar

Background - Ripple mapping (RM) displays each electrogram at its 3-dimensional coordinate as a bar changing in length according to its voltage-time relationship with a fiduciary reference. We applied RM to left ventricular ischemic scar for evidence of slow-conducting channels that may act as ventricular tachycardia (VT) substrate. Methods and Results - CARTO-3(Biosense Webster Inc, Diamond Bar, CA) maps in patient undergoing VT ablation were analyzed on an offline MatLab RM system. Scar was assessed for sequential movement of ripple bars, during sinus rhythm or pacing, which were distinct from surrounding tissue and termed RM conduction channels (RMCC). Conduction velocity was measured within RMCCs and compared with the healthy myocardium (>1.5 mV). In 21 maps, 77 RMCCs were identified. Conduction velocity in RMCCs was slower when compared with normal left ventricular myocardium (median, 54 [interquartile range, 40-86] versus 150 [interquartile range, 120-160] cm/s; P<0.001). All 7 sites meeting conventional criteria for diastolic pathways coincided with an RMCC. Seven patients had ablation colocating to all identified RMCCs with no VT recurrence during follow-up (median, 480 [interquartile range, 438-841] days). Fourteen patients had \ue2\u89\ua51 RMCC with no ablation lesions. Five had recurrence during follow-up (median, 466 [interquartile range, 395-694] days). One of the 2 patients with no RMCC locations ablated had VT recurrence at 605 days post procedure. RMCCs were sensitive (100%; negative predictive value, 100%) for VT recurrence but the specificity (43%; positive predictive value, 35.7%) may be limited by blind alleys channels. Conclusions - RM identifies slow conduction channels within ischemic scar and needs further prospective investigation to understand the role of RMCCs in determining the VT substrate

The C-Band All-Sky Survey (C-BASS):Design and capabilities

The C-Band All-Sky Survey (C-BASS) is an all-sky full-polarisation survey at a frequency of 5 GHz, designed to provide complementary data to the all-sky surveys of WMAP and Planck, and future CMB B-mode polarization imaging surveys. The observing frequency has been chosen to provide a signal that is dominated by Galactic synchrotron emission, but suffers little from Faraday rotation, so that the measured polarization directions provide a good template for higher frequency observations, and carry direct information about the Galactic magnetic field. Telescopes in both northern and southern hemispheres with matched optical performance are used to provide all-sky coverage from a ground-based experiment. A continuous-comparison radiometer and a correlation polarimeter on each telescope provide stable imaging properties such that all angular scales from the instrument resolution of 45 arcmin up to full sky are accurately measured. The northern instrument has completed its survey and the southern instrument has started observing. We expect that C-BASS data will significantly improve the component separation analysis of Planck and other CMB data, and will provide important constraints on the properties of anomalous Galactic dust and the Galactic magnetic field.Comment: 21 pages, 9 figure