Circadian Rhythms of Atrioventricular Conduction Properties in Chronic Atrial Fibrillation With and Without Heart Failure

AbstractObjectives. We examined the circadian variations in atrioventricular (AV) conduction properties during atrial fibrillation (AF) by a technique based on the Lorenz plot of successive ventricular response (VR) intervals and analyzed their relations with clinical features.Background. The VR interval in chronic AF shows circadian variation, which is attenuated in patients with an increased risk of death. Although the VR interval is determined by the dynamic processes in the AV node randomly stimulated by rapid atrial activity, the circadian variations of the AV conduction properties related to this mechanism are unknown.Methods. In 48 patients with chronic AF, Lorenz plots were generated on overlapping sequential segments of 512 VR intervals in 24-h ambulatory electrocardiograms. For each scatter plot, the 1.0-s intercept of the lower envelope (LE1.0) of the plot and the degree of scatter above the envelope (root mean square difference from the envelope [scattering index]) were measured for estimating AV node refractoriness and concealed AV conduction, respectively.Results. In all patients, a significant circadian rhythm was observed for the average VR interval, LE1.0and scattering index, with an acrophase occurring at night. The mesor, amplitude and acrophase of LE1.0and the scattering index closely and independently correlated with the corresponding rhythm variables of the average VR interval (partial r20.98, 0.86 and 0.68 for LE1.0and 0.98, 0.92 and 0.92 for scattering index). The amplitudes of these measures were lower in patients with congestive heart failure (CHF) even after adjustment for the effects of age, duration of AF, medications, left atrial diameter and blood pressure (p < 0.01 for all).Conclusions. These results suggest that 1) both AV node refractoriness and the degree of concealed AV conduction during AF may show a circadian rhythm; 2) the circadian rhythms of these properties may independently contribute to the circadian variation of the VR interval; and 3) these circadian rhythms may be attenuated in patients with CHF

Development of a frequency-detuned interferometer as a prototype experiment for next-generation gravitational-wave detectors

We report on our prototype experiment that uses a 4-m detuned resonant sideband extraction interferometer with suspended mirrors, which has almost the same configuration as the next-generation, gravitational-wave detectors. We have developed a new control scheme and have succeeded in the operation of such an interferometer with suspended mirrors for the first time ever as far as we know. We believe that this is the first such instrument that can see the radiation pressure signal enhancement, which can improve the sensitivity of next-generation gravitational-wave detectors

Measurement of optical response of a detuned resonant sideband extraction gravitational wave detector

We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) interferometer with power recycling. The purpose of the detuned RSE configuration is to manipulate and optimize the optical response of the interferometer to differential displacements (induced by gravitational waves) as a function of frequency, independently of other parameters of the interferometer. The design of our interferometer results in an optical gain with two peaks: an RSE optical resonance at around 4 kHz and a radiation pressure induced optical spring at around 41 Hz. We have developed a reliable procedure for acquiring lock and establishing the desired optical configuration. In this configuration, we have measured the optical response to differential displacement and found good agreement with predictions at both resonances and all other relevant frequencies. These results build confidence in both the theory and practical implementation of the more complex optical configuration being planned for Advanced LIGO

Measurement of Optical Response of a Detuned Resonant Sideband Extraction Interferometer

We report on the optical response of a suspended-mass detuned resonant sideband extraction (RSE) interferometer with power recycling. The purpose of the detuned RSE configuration is to manipulate and optimize the optical response of the interferometer to differential displacements (induced by gravitational waves) as a function of frequency, independently of other parameters of the interferometer. The design of our interferometer results in an optical gain with two peaks: an RSE optical resonance at around 4 kHz and a radiation pressure induced optical spring at around 41 Hz. We have developed a reliable procedure for acquiring lock and establishing the desired optical configuration. In this configuration, we have measured the optical response to differential displacement and found good agreement with predictions at both resonances and all other relevant frequencies. These results build confidence in both the theory and practical implementation of the more complex optical configuration being planned for Advanced LIGO.Comment: 6 pages, 4 figures, for submission to Phys Rev Letter

Sensing and control of the advanced LIGO optical configuration

The LIGO Laboratory 40m prototype interferometer at Caltech is being commissioned to prototype an optical configuration for Advanced LIGO. This optical configuration has to control five length degrees of freedom, and its control topology will be significantly more complicated than any other present interferometers. This paper explains the method of sensing, controls and lock acquisition

The latest update on individual external doses in an early stage after the Fukushima nuclear accident

Following the Fukushima Daiichi Nuclear Power Plant accident, a survey for estimating individual external doses for the first 4 months after the accident was started, and it remains ongoing. Since the authors' previous paper, 44 605 new dose estimates have been made. The new dose estimates increase the number of dose estimates to 465 999 and are reported in this note. Since the previous paper, most of the recently collected responses have been gotten through public relations activities to encourage responses across the prefecture. Thus, recent respondents might be biased ('selection bias'). Also, the dose estimates were based on self-administered responses about personal behaviour, which relied on memories of residents. In this respect, incorrect behaviour records possibly resulted as memories have faded over time ('recall bias'). However, the effects of these biases on dose distribution on a whole-prefecture basis seemed to be small

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases

Aims The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. Methods and Results We performed WES of 23 probands diagnosed with early-onset (&amp;lt;65 years) CCSD and analyzed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency &amp;lt; 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as “pathogenic” by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that 2 variants in KCNH2 and SCN5A, 4 variants in SCN10A, and 1 variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from “Uncertain significance” to “Likely pathogenic” in 6 probands. Conclusions Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD. Translational Perspective Whole-exome sequencing (WES) may be helpful in determining the causes of cardiac conduction system disease (CCSD), however, the identification of pathogenic variants remains a challenge. We performed WES of 23 probands diagnosed with early-onset CCSD, and identified 12 pathogenic or likely pathogenic variants in 11 of these probands (48%) according to the 2015 ACMG standards and guidelines. In this context, functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants, and SCN10A may be one of the major development factors in CCSD

An influential factor for external radiation dose estimation for residents after the Fukushima Daiichi Nuclear Power Plant accident-time spent outdoors for residents in Iitate Village

Many studies have been conducted on radiation doses to residents after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Time spent outdoors is an influential factor for external dose estimation. Since little information was available on actual time spent outdoors for residents, different values of average time spent outdoors per day have been used in dose estimation studies on the FDNPP accident. The most conservative value of 24 h was sometimes used, while 2.4 h was adopted for indoor workers in the UNSCEAR 2013 report. Fukushima Medical University has been estimating individual external doses received by residents as a part of the Fukushima Health Management Survey by collecting information on the records of moves and activities (the Basic Survey) after the accident from each resident. In the present study, these records were analyzed to estimate an average time spent outdoors per day. As an example, in Iitate Village, its arithmetic mean was 2.08 h (95% CI: 1.64-2.51) for a total of 170 persons selected from respondents to the Basic Survey. This is a much smaller value than commonly assumed. When 2.08 h is used for the external dose estimation, the dose is about 25% (23-26% when using the above 95% CI) less compared with the dose estimated for the commonly used value of 8 h