205 research outputs found

    Atrial Flutter in Infants

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    ObjectivesWe sought to characterize the clinical nature of atrial flutter (AFL) in a large cohort of infants.BackgroundThere are no large studies describing the natural history of AFL in infants. Previous studies vary in the therapy used and expected prognosis.MethodsWe reviewed the records of all children younger than 1 year of age who were diagnosed with AFL at our hospital during the past 25 years, excluding those with previous cardiac surgery.ResultsWe identified 50 infants with AFL. Most, 36 (72%), presented within the first 48 h of life. Congestive heart failure was evident in 10 infants, with 6 presenting at 1 day of age, and 4 presenting beyond 1 month of age. The remainder were asymptomatic. A large atrial septal defect was the only structural heart disease. Spontaneous conversion to sinus rhythm occurred in 13 (26%) infants. Sinus rhythm was restored in 20 of 23 (87%) attempts at direct current cardioversion and 7 of 22 (32%) attempts at transesophegeal pacing; 7 required antiarrhythmic therapy. An additional arrhythmia, all supraventricular, appeared in 11 (22%) infants. The recurrence of AFL developed in 6 infants; 5 of 6 of these incidents occurred within 24 h of the first episode. All patients with recurrence had an additional arrhythmia.ConclusionsInfants with AFL usually present within the first 2 days of life. No association was found with structural heart disease. Direct current cardioversion appears to be most effective at establishing sinus rhythm. Chronic AFL has the potential to cause cardiovascular compromise. Atrial flutter in the absence of other arrhythmias has a low risk of recurrence. Once in sinus rhythm, infants with AFL have an excellent prognosis and may not require chronic antiarrhythmic therapy

    Detection of CRISPR-mediated genome modifications through altered methylation patterns of CpG islands.

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    BACKGROUND: The development and application of CRISPR technologies for the modification of the genome are rapidly expanding. Advances in the field describe new CRISPR components that are strategically engineered to improve the precision and reliability of CRISPR editing within the genome sequence. Genome modification using induced genome breaks that are targeted and mediated by CRISPR components leverage cellular mechanisms for repair like homology directed repair (HDR) to incorporate genomic edits with increased precision. RESULTS: In this report, we describe the gain of methylation at typically hypomethylated CpG island (CGI) locations affected by the CRISPR-mediated incorporation of donor DNA using HDR mechanisms. With characterization of CpG methylation patterns using whole genome bisulfite sequencing, these CGI methylation disruptions trace the insertion of the donor DNA during the genomic edit. These insertions mediated by homology-directed recombination disrupt the generational methylation pattern stability of the edited CGI within the cells and their cellular lineage within the animal strain, persisting across generations. Our approach describes a statistically based workflow for indicating locations of modified CGIs and provides a mechanism for evaluating the directed modification of the methylome of the affected CGI at the CpG-level. CONCLUSIONS: With advances in genome modification technology comes the need to detect the level and persistence of methylation change that modifications to the genomic sequence impose upon the collaterally edited methylome. Any modification of the methylome of somatic or germline cells could have implications for gene regulation mechanisms governed by the methylation patterns of CGI regions in the application of therapeutic edits of more sensitively regulated genomic regions. The method described here locates the directed modification of the mouse epigenome that persists over generations. While this observance would require supporting molecular observations such as direct sequence changes or gene expression changes, the observation of epigenetic modification provides an indicator that intentionally directed genomic edits can lead to collateral, unintentional epigenomic changes post modification with generational persistence

    Impurity generation during intense lower hybrid heating experiments on the Alcator C tokamak

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    and disposal, in whole or in part by or for the United States govern-ment is permitted. By acceptance of this article, the publisher and/or recipient ac-knowledges the U.S. Government's right to retain a non-exclusive, royalty-free license in and to any copyright covering this paper. Experiments are underway on the Alcator C Tokamak with over 1 MW of RF power injected into the plasma at a frequency of 4.6 GHz to study both heating and current drive effects. During these studies, impurity genera-tion from limiter structures has been observed. The RF induced impurity influx is a strongly nonlinear function of net injected power. For Prf < 500 kW, only small effects are seen. As Prf approaches 1 MW, however, sharp increases in impurity influxes and Zeff are observed. Three different lim-iter materials have been used during these studies: molybdenum, graphite, and silicon-carbide coated graphite. In each case, the materials of the limiter structure are seen to dominate the increased impurity influx. In a typical case, with Prf = 1.0 MW e = 1.3 x 1014 cm- 3, and the SiC coated limiters, Zeff is seen to increase from 1.5 before the RF pulse to about 4 during the heating. At the same time, central Te increases from 2000 eV to 3000 eV and central Ti from 1200 eV to 1800 eV. Similar effects are seen in both H2 and D2 working gas discharges. The contribution to impurity genera-tion of nonthermal electrons, which are produced by the RF, is under investi-gation. Changes in edge plasma temperature and density, as well as the possibility that the particle transport is affected by the RF, are also being examined. Results of the experiments with the three different limiter materials are compared, and contributions of impurity radiation to the overall power balance are estimated
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