Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias

BACKGROUND-\u2014Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (ARDCM). We investigated the phenotype and natural history of patients with AR-DCM. METHODS AND RESULTS-\u2014Two hundred eighty-five patients with a recent diagnosis of DCM (median duration of the disease 1 month, range 0 to 7 months) and who had Holter monitoring at baseline were comprehensively evaluated and followed for 107 months (range 29 to 170 months). AR-DCM was defined by the presence of 651 of the following: unexplained syncope, rapid nonsustained ventricular tachycardia ( 655 beats, 65150 bpm), 651000 premature ventricular contractions/24 hours, and 6550 ventricular couplets/ 24 hours, in the absence of overt heart failure. The primary end points were sudden cardiac death (SCD), sustained ventricular tachycardia (SVT), or ventricular fibrillation (VF). The secondary end points were death from congestive heart failure or heart transplantation. Of the 285 patients, 109 (38.2%) met criteria for AR-DCM phenotype. AR-DCM subjects had a higher incidence of SCD/SVT/VF compared with non\u2013AR-DCM patients (30.3% vs 17.6%, P=0.022), with no difference in the secondary end points. A family history of SCD/SVT/VF and the AR-DCM phenotype were statistically significant and cumulative predictors of SCD/SVT/VF. CONCLUSIONS-\u2014One-third of DCM patients may have an arrhythmogenic phenotype associated with increased risk of arrhythmias during follow-up. A family history of ventricular arrhythmias in DCM predicts a poor prognosis and increased risk of SCD

Temperature and surgical wound heat loss during orthopedic surgery: computer simulations and measurements

No Abstrac

Selenoprotein gene nomenclature

The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates

Superconformal symmetry and maximal supergravity in various dimensions

In this paper we explore the relation between conformal superalgebras with 64 supercharges and maximal supergravity theories in three, four and six dimensions using twistorial oscillator techniques. The massless fields of N=8 supergravity in four dimensions were shown to fit into a CPT-self-conjugate doubleton supermultiplet of the conformal superalgebra SU(2,2|8) a long time ago. We show that the fields of maximal supergravity in three dimensions can similarly be fitted into the super singleton multiplet of the conformal superalgebra OSp(16|4,R), which is related to the doubleton supermultiplet of SU(2,2|8) by dimensional reduction. Moreover, we construct the ultra-short supermultiplet of the six-dimensional conformal superalgebra OSp(8*|8) and show that its component fields can be organized in an on-shell superfield. The ultra-short OSp(8*|8) multiplet reduces to the doubleton supermultiplet of SU(2,2|8) upon dimensional reduction. We discuss the possibility of a chiral maximal (4,0) six-dimensional supergravity theory with USp(8) R-symmetry that reduces to maximal supergravity in four dimensions and is different from six-dimensional (2,2) maximal supergravity, whose fields cannot be fitted into a unitary supermultiplet of a simple conformal superalgebra. Such an interacting theory would be the gravitational analog of the (2,0) theory.Comment: 54 pages, PDFLaTeX, Section 5 and several references added. Version accepted for publication in JHE

The maximum standardized uptake value in patients with recurrent or persistent prostate cancer after radical prostatectomy and PSMA-PET-guided salvage radiotherapy-a multicenter retrospective analysis

Purpose This study aims to evaluate the association of the maximum standardized uptake value (SUVmax) in positron-emission tomography targeting prostate-specific membrane antigen (PSMA-PET) prior to salvage radiotherapy (sRT) on biochemical recurrence free survival (BRFS) in a large multicenter cohort.Methods Patients who underwent (68) Ga-PSMA11-PET prior to sRT were enrolled in four high-volume centers in this retrospective multicenter study. Only patients with PET-positive local recurrence (LR) and/or nodal recurrence (NR) within the pelvis were included. Patients were treated with intensity-modulated-sRT to the prostatic fossa and elective lymphatics in case of nodal disease. Dose escalation was delivered to PET-positive LR and NR. Androgen deprivation therapy was administered at the discretion of the treating physician. LR and NR were manually delineated and SUVmax was extracted for LR and NR. Cox-regression was performed to analyze the impact of clinical parameters and the SUVmax-derived values on BRFS.Results Two hundred thirty-five patients with a median follow-up (FU) of 24 months were included in the final cohort. Two-year and 4-year BRFS for all patients were 68% and 56%. The presence of LR was associated with favorable BRFS (p = 0.016). Presence of NR was associated with unfavorable BRFS (p = 0.007). While there was a trend for SUVmax values >= median (p = 0.071), SUVmax values >= 75% quartile in LR were significantly associated with unfavorable BRFS (p = 0.022, HR: 2.1, 95%CI 1.1-4.6). SUVmax value in NR was not significantly associated with BRFS. SUVmax in LR stayed significant in multivariate analysis (p = 0.030). Sensitivity analysis with patients for who had a FU of > 12 months (n = 197) confirmed these results.Conclusion The non-invasive biomarker SUVmax can prognosticate outcome in patients undergoing sRT and recurrence confined to the prostatic fossa in PSMA-PET. Its addition might contribute to improve risk stratification of patients with recurrent PCa and to guide personalized treatment decisions in terms of treatment intensification or de-intensification. This article is part of the Topical Collection on Oncology-Genitourinary

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Validation of the surgical fear questionnaire in adult patients waiting for elective surgery

Objectives: Because existing instruments for assessing surgical fear seem either too general or too limited, the Surgical Fear Questionnaire (SFQ) was developed. The aim of this study is to assess the validity and reliability of the SFQ. Methods: Based on existing literature and expert consultation the ten-item SFQ was composed. Data on the SFQ were obtained from 5 prospective studies (N = 3233) in inpatient or day surgery patients. These data were used for exploratory factor analysis (EFA), confirmatory factor analysis (CFA), reliability analysis and validity analysis. Results: EFA in Study 1 and 2 revealed a two-factor structure with one factor associated with fear of the short-term consequences of surgery (SFQ-s, item 1-4) and the other factor with fear of the long-term consequences of surgery (SFQ-l, item 5-10). However, in both studies two items of the SFQ-l had low factor loadings. Therefore in Study 3 and 4 the 2-factor structure was tested and confirmed by CFA in an eight-item version of the SFQ. Across all studies significant correlations of the SFQ with pain catastrophizing, state anxiety, and preoperative pain intensity indicated good convergent validity. Internal consistency (Cronbach's alpha) was between 0.765-0.920 (SFQ-total), 0.766-0.877 (SFQ-s), and 0.628-0.899 (SFQ-l). The SFQ proved to be sensitive to detect differences based on age, sex, education level, employment status and preoperative pain intensity. Discussion: The SFQ is a valid and reliable eight-item index of surgical fear consisting of two subscales: fear of the short-term consequences of surgery and fear of the long-term consequences.This study was conducted with departmental funding and supported by a grant from The Netherlands Organisation for Scientific Research (Zon-MW, http://www.zonmw.nl/en/), grant no. 110000007. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye