Effects of An Acute Increase in Atrial Pressure on Atrial Refractoriness in Humans

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73199/1/j.1540-8159.1992.tb02954.x.pd

The role of genetics in cardiovascular disease: arrhythmogenic cardiomyopathy

Arrhythmogenic cardiomyopathy (ACM) is a heritable cardiomyopathy characterized by frequent ventricular arrhythmias and progressive ventricular dysfunction. Risk of sudden cardiac death is elevated in ACM patients and can be the presenting symptom particularly in younger individuals and athletes. This review describes current understanding of the genetic architecture of ACM and molecular mechanisms of ACM pathogenesis. We consider an emerging threshold model for ACM inheritance in which multiple factors including pathogenic variants in known ACM genes, genetic modifiers, and environmental exposures, particularly exercise, are required to reach a threshold for disease expression. We also review best practices for integrating genetics—including recent discoveries—in caring for ACM families and emphasize the utility of genotype for both management of affected individuals and predictive testing in family members

Management of Nonsustained Ventricular Tachycardia Guided By Electrophysiological Testing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73206/1/j.1540-8159.1993.tb04578.x.pd

Contemporary and Future Approaches to Precision Medicine in Inherited Cardiomyopathies: JACC Focus Seminar 3/5

Inherited cardiomyopathies are commonly occurring myocardial disorders that are associated with substantial morbidity and mortality. Clinical management strategies have focused on treatment of heart failure and arrhythmic complications in symptomatic patients according to standardized guidelines. Clinicians are now being urged to implement precision medicine, but what does this involve? Advances in understanding of the genetic underpinnings of inherited cardiomyopathies have brought new possibilities for interventions that are tailored to genes, specific variants, or downstream mechanisms. However, the phenotypic variability that can occur with any given pathogenic variant suggests that factors other than single driver gene mutations are often involved. This is propelling a new imperative to elucidate the nuanced ways in which individual combinations of genetic variation, comorbidities, and lifestyle may influence cardiomyopathy phenotypes. Here, Part 3 of a 5-part precision medicine Focus Seminar series reviews the current status and future opportunities for precision medicine in the inherited cardiomyopathies

Strongly Variable z=1.48 FeII and MgII Absorption in the Spectra of z=4.05 GRB 060206

We report on the discovery of strongly variable FeII and MgII absorption lines seen at z=1.48 in the spectra of the z=4.05 GRB 060206 obtained between 4.13 to 7.63 hours (observer frame) after the burst. In particular, the FeII line equivalent width (EW) decayed rapidly from 1.72+-0.25 AA to 0.28+-0.21 AA, only to increase to 0.96+-0.21 AA in a later date spectrum. The MgII doublet shows even more complicated evolution: the weaker line of the doublet drops from 2.05+-0.25 AA to 0.92+-0.32 AA, but then more than doubles to 2.47+-0.41 AA in later data. The ratio of the EWs for the MgII doublet is also variable, being closer to 1:1 (saturated regime) when the lines are stronger and becoming closer to 2:1 (unsaturated regime) when the lines are weaker, consistent with expectations based on atomic physics. We have investigated and rejected the possibility of any instrumental or atmospheric effects causing the observed strong variations. Our discovery of clearly variable intervening FeII and MgII lines lends very strong support to their scenario, in which the characteristic size of intervening patches of MgII ``clouds'' is comparable to the GRB beam size, i.e, about 10^16 cm. We discuss various implications of this discovery, including the nature of the MgII absorbers, the physics of GRBs, and measurements of chemical abundances from GRB and quasar absorption lines.Comment: 14 pages, 3 figures, 1 table; ApJ Letters, accepte

Two 'b's in the Beehive: The Discovery of the First Hot Jupiters in an Open Cluster

We present the discovery of two giant planets orbiting stars in Praesepe (also known as the Beehive Cluster). These are the first known hot Jupiters in an open cluster and the only planets known to orbit Sun-like, main-sequence stars in a cluster. The planets are detected from Doppler shifted radial velocities; line bisector spans and activity indices show no correlation with orbital phase, confirming the variations are caused by planetary companions. Pr0201b orbits a V=10.52 late F dwarf with a period of 4.4264 +/- 0.0070 days and has a minimum mass of 0.540 +/- 0.039 Mjup, and Pr0211b orbits a V=12.06 late G dwarf with a period of 2.1451 +/- 0.0012 days and has a minimum mass of 1.844 +/- 0.064 Mjup. The detection of 2 planets among 53 single members surveyed establishes a lower limit on the hot Jupiter frequency of 3.8 (+5.0)(-2.4) % in this metal-rich open cluster. Given the precisely known age of the cluster, this discovery also demonstrates that, in at least 2 cases, giant planet migration occurred within 600 Myr after formation. As we endeavor to learn more about the frequency and formation history of planets, environments with well-determined properties -- such as open clusters like Praesepe -- may provide essential clues to this end.Comment: 5 pages, 3 tables, 2 figures. Published in ApJ Letter

Deep Photometry of GRB 041006 Afterglow: Hypernova Bump at Redshift z=0.716

We present deep optical photometry of the afterglow of gamma-ray burst (GRB) 041006 and its associated hypernova obtained over 65 days after detection (55 R-band epochs on 10 different nights). Our early data (t<4 days) joined with published GCN data indicates a steepening decay, approaching F_nu ~t^{-0.6} at early times (<<1 day) and F_nu ~t^{-1.3} at late times. The break at t_b=0.16+-0.04 days is the earliest reported jet break among all GRB afterglows. During our first night, we obtained 39 exposures spanning 2.15 hours from 0.62 to 0.71 days after the burst that reveal a smooth afterglow, with an rms deviation of 0.024 mag from the local power-law fit, consistent with photometric errors. After t~4 days, the decay slows considerably, and the light curve remains approximately flat at R~24 mag for a month before decaying by another magnitude to reach R~25 mag two months after the burst. This ``bump'' is well-fitted by a k-corrected light curve of SN1998bw, but only if stretched by a factor of 1.38 in time. In comparison with the other GRB-related SNe bumps, GRB 041006 stakes out new parameter space for GRB/SNe, with a very bright and significantly stretched late-time SN light curve. Within a small sample of fairly well observed GRB/SN bumps, we see a hint of a possible correlation between their peak luminosity and their ``stretch factor'', broadly similar to the well-studied Phillips relation for the type Ia supernovae.Comment: ApJ Letters, accepted. Additional material available at ftp://cfa-ftp.harvard.edu/pub/kstanek/GRB041006

How often should we monitor for reliable detection of atrial fibrillation recurrence? Efficiency considerations and implications for study design

OBJECTIVE: Although atrial fibrillation (AF) recurrence is unpredictable in terms of onset and duration, current intermittent rhythm monitoring (IRM) diagnostic modalities are short-termed and discontinuous. The aim of the present study was to investigate the necessary IRM frequency required to reliably detect recurrence of various AF recurrence patterns. METHODS: The rhythm histories of 647 patients (mean AF burden: 12±22% of monitored time; 687 patient-years) with implantable continuous monitoring devices were reconstructed and analyzed. With the use of computationally intensive simulation, we evaluated the necessary IRM frequency to reliably detect AF recurrence of various AF phenotypes using IRM of various durations. RESULTS: The IRM frequency required for reliable AF detection depends on the amount and temporal aggregation of the AF recurrence (p<0.0001) as well as the duration of the IRM (p<0.001). Reliable detection (>95% sensitivity) of AF recurrence required higher IRM frequencies (>12 24-hour; >6 7-day; >4 14-day; >3 30-day IRM per year; p<0.0001) than currently recommended. Lower IRM frequencies will under-detect AF recurrence and introduce significant bias in the evaluation of therapeutic interventions. More frequent but of shorter duration, IRMs (24-hour) are significantly more time effective (sensitivity per monitored time) than a fewer number of longer IRM durations (p<0.0001). CONCLUSIONS: Reliable AF recurrence detection requires higher IRM frequencies than currently recommended. Current IRM frequency recommendations will fail to diagnose a significant proportion of patients. Shorter duration but more frequent IRM strategies are significantly more efficient than longer IRM durations. CLINICAL TRIAL REGISTRATION URL: Unique identifier: NCT00806689

Dietary Restraint in Adolescence Predicts Diet Quality in Young Adulthood

Establishing a diet that follows the Dietary Guidelines for Americans has been associated with lower risk of mortality from cardiovascular disease and cancer. Some research has shown that individuals’ desire for weight control is an important factor in determining food choices. The aims of this study were to 1) examine dietary restraint in adolescence as a predictor of overall diet quality in young adulthood and 2) compare selected dietary components by levels of restraint

Generation of degenerate, factorizable, pulsed squeezed light at telecom wavelengths

We characterize a periodically poled KTP crystal that produces an entangled, two-mode, squeezed state with orthogonal polarizations, nearly identical, factorizable frequency modes, and few photons in unwanted frequency modes. We focus the pump beam to create a nearly circular joint spectral probability distribution between the two modes. After disentangling the two modes, we observe Hong-Ou-Mandel interference with a raw (background corrected) visibility of 86 % (95 %) when an 8.6 nm bandwidth spectral filter is applied. We measure second order photon correlations of the entangled and disentangled squeezed states with both superconducting nanowire single-photon detectors and photon-number-resolving transition-edge sensors. Both methods agree and verify that the detected modes contain the desired photon number distributions