The Spitzer Infrared Nearby Galaxies Survey: A High-Resolution Spectroscopy Anthology

High resolution mid-infrared spectra are presented for 155 nuclear and extranuclear regions from the Spitzer Infrared Nearby Galaxies Survey (SINGS). The fluxes for nine atomic forbidden and three molecular hydrogen mid-infrared emission lines are also provided, along with upper limits in key lines for infrared-faint targets. The SINGS sample shows a wide range in the ratio of [SIII]18.71um/[SIII]33.48um, but the average ratio of the ensemble indicates a typical interstellar electron density of 300-400 cm^{-3} on ~23"x15" scales and 500-600 cm^{-3} using ~11"x9" apertures, independent of whether the region probed is a star-forming nuclear, a star-forming extranuclear, or an AGN environment. Evidence is provided that variations in gas-phase metallicity play an important role in driving variations in radiation field hardness, as indicated by [NeIII]15.56um/[NeII]12.81um, for regions powered by star formation. Conversely, the radiation hardness for galaxy nuclei powered by accretion around a massive black hole is independent of metal abundance. Furthermore, for metal-rich environments AGN are distinguishable from star-forming regions by significantly larger [NeIII]15.56um/[NeII]12.81um ratios. Finally, [FeII]25.99um/[NeII]12.81um versus [SiII]34.82um/[SIII]33.48um also provides an empirical method for discerning AGN from normal star-forming sources. However, similar to [NeIII]15.56um/[NeII]12.81um, these mid-infrared line ratios lose their AGN/star-formation diagnostic powers for very low metallicity star-forming systems with hard radiation fields.Comment: Accepted for publication in Ap

CardioClassifier: disease- and gene-specific computational decision support for clinical genome interpretation

Purpose Internationally adopted variant interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) are generic and require disease-specific refinement. Here we developed CardioClassifier (http://www.cardioclassifier.org), a semiautomated decision-support tool for inherited cardiac conditions (ICCs). Methods CardioClassifier integrates data retrieved from multiple sources with user-input case-specific information, through an interactive interface, to support variant interpretation. Combining disease- and gene-specific knowledge with variant observations in large cohorts of cases and controls, we refined 14 computational ACMG criteria and created three ICC-specific rules. Results We benchmarked CardioClassifier on 57 expertly curated variants and show full retrieval of all computational data, concordantly activating 87.3% of rules. A generic annotation tool identified fewer than half as many clinically actionable variants (64/219 vs. 156/219, Fisher’s P = 1.1  ×  10−18), with important false positives, illustrating the critical importance of disease and gene-specific annotations. CardioClassifier identified putatively disease-causing variants in 33.7% of 327 cardiomyopathy cases, comparable with leading ICC laboratories. Through addition of manually curated data, variants found in over 40% of cardiomyopathy cases are fully annotated, without requiring additional user-input data. Conclusion CardioClassifier is an ICC-specific decision-support tool that integrates expertly curated computational annotations with case-specific data to generate fast, reproducible, and interactive variant pathogenicity reports, according to best practice guidelines

Physical Conditions in the Ionized Gas of 30 Doradus

We present a mid-infrared spectroscopic data cube of the central part of 30 Doradus, observed with Spitzer's IRS and MIPS/SED mode. Aromatic dust emission features and emission lines from molecular and atomic hydrogen are detected but not particularly strong. The dominant spectral features are emission lines from moderately ionized species of argon, neon, and sulphur, which are used to determine the physical conditions in the ionized gas. The ionized gas excitation shows strong variations on parsec scales, some of which can plausibly be associated with individual hot stars. We fit the ionic line strengths with photoionization and shock models, and find that photoionization dominates in the region. The ionization parameter U traces the rim of the central bubble, as well as highlighting isolated sources of ionization, and at least one quiescent clump. The hardness of the ionizing radiation field T_rad reveals several "hot spots" that are either the result of individual very hot stars or trace the propagation of the diffuse ionizing field through the surrounding neutral cloud. Consistent with other measurements of giant molecular hydrogen regions, log(U) ranges between -3 and -0.75, and T_rad between 30000 and 85000K.Comment: 32 pages, 26 figures, ApJ accepted. A version with high-resolution images can be found at http://www.astro.virginia.edu/~ged3j/indebetouw20090125.pd

Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction

Background—Current guidelines only recommend the use of an implantable cardioverter defibrillator (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF)35%. Patients with a LVEF>35% also have low competing risks of death from non-sudden causes. Therefore, those at high-risk of SCD may gain longevity from successful ICD therapy. We investigated whether late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) identified patients with DCM without severe LV systolic dysfunction at high-risk of SCD. Methods—We prospectively investigated the association between mid-wall late gadolinium enhancement (LGE) and the pre-specified primary composite outcome of SCD or aborted SCD amongst consecutive referrals with DCM and a LVEF≥40% to our center between January 2000 and December 2011, who did not have a pre-existing indication for ICD implantation. Results—Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9-21.8; p5% compared to those without LGE were 10.6 (95%CI 3.9-29.4), 4.9 (95% CI 1.3-18.9) and 11.8 (95% CI 4.3-32.3) respectively. Conclusions—Mid-wall LGE identifies a group of patients with DCM and LVEF≥40% at increased risk of SCD and low-risk of non-sudden death who may benefit from ICD implantation

Gemini GMOS spectroscopy of HeII nebulae in M33

We have carried out a narrow-band survey of the Local Group galaxy, M33, in the HeII4686 emission line, to identify HeII nebulae in this galaxy. With spectroscopic follow-up observations, we confirm three of seven candidate objects, including identification of two new HeII nebulae, BCLMP651, HBW673. We also obtain spectra of associated ionizing stars for all the HII regions, identifying two new WN stars. We demonstrate that the ionizing source for the known HeII nebula, MA 1, is consistent with being the early-type WN star MC8 (M33-WR14), by carrying out a combined stellar and nebular analysis of MC8 and MA1. We were unable to identify the helium ionizing sources for HBW 673 and BCLMP 651, which do not appear to be Wolf-Rayet stars. According to the [OIII]5007/Hbeta vs [NII]6584/Halpha diagnostic diagram, excitation mechanisms apart from hot stellar continuum are needed to account for the nebular emission in HBW 673, which appears to have no stellar source at all.Comment: Accepted for publication in Astronomy and Astrophysics. 22 pages, 10 figure

Melatonin inhibira lipidnu peroksidaciju u jetri štakora uzrokovanu benzenom

We studied the antioxidative role of melatonin against benzene toxicity in rat liver. The inhibition of mitochondrial and microsomal lipid peroxidation differed between 24-hour (single-dose), 15-day, and 30-day treatments. Inhibition of mitochondrial lipid peroxidation was the highest after the single dose of melatonin, whereas highest microsomal inhibition was recorded after 30 days of melatonin treatment. No signifi cant difference was recorded between 15-day and 30-day treatments. Cytochrome P4502E1 (CYP4502E1) activity declined after the single-dose and 15-day melatonin treatment in the benzenetreated group, but it rose again, though not signifi cantly after 30 days of treatment. Liver histopathology generally supported these fi ndings. Phenol concentration in the urine samples declined in melatonin and benzene-treated rats. Our results show that melatonin affects CYP4502E1, which is responsible for benzene metabolism. Inhibition of its metabolism correlated with lower lipid peroxidation. In conclusion, melatonin was found to be protective against lipid peroxidation induced by benzene.Istražena je antioksidacijska uloga melatonina u zaštiti protiv toksičnoga djelovanja benzena u jetri štakora. Utvrđeno je da kratkoročno odnosno dugoročnije liječenje štakora melatoninom u različitoj mjeri štiti štakore istodobno izložene benzenu. Inhibicija lipidne peroksidacije mitohondrija i mikrosoma bila je različita nakon 24 h, 15 dana, odnosno 30 dana liječenja melatoninom. Najveća inhibicija lipidne peroksidacije mitohondrija zamijećena je nakon primjene jednokratne doze melatonina, dok je najizraženija inhibicija u mikrosomima zamijećena nakon 30 dana liječenja melatoninom. Slična istraživanja pokazuju da razina glutationa (GSH) najviše raste nakon 24 h liječenja melatoninom. Nije zamijećena razlika između liječenja u trajanju od 15 odnosno 30 dana. U štakora koji su uz benzen istodobno primali i melatonin razine citokroma P4502E1 pale su nakon 24 h odnosno 15 dana izloženosti. U štakora koji su primali samo melatonin te su razine nakon 30 dana statistički neznačajno porasle u odnosu na skupinu izloženu samo benzenu. Histopatološka analiza jetre načelno je potvrdila ove nalaze. Koncentracije fenola u mokraći bile su niže u štakora koji su istodobno primali melatonin i benzen. Ovi rezultati pokazuju da melatonin utječe na citokrom P4502E1, koji je odgovoran za metabolizam benzena. Inhibira li se njegov metabolizam, smanjuje se lipidna peroksidacija. Zaključak je da melatonin štiti od lipidne peroksidacije uzrokovane benzenom

Titin truncating variants affect heart function in disease cohorts and the general population

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease

Review article: Use of ultrasound in the developing world

As portability and durability improve, bedside, clinician-performed ultrasound is seeing increasing use in rural, underdeveloped parts of the world. Physicians, nurses and medical officers have demonstrated the ability to perform and interpret a large variety of ultrasound exams, and a growing body of literature supports the use of point-of-care ultrasound in developing nations. We review, by region, the existing literature in support of ultrasound use in the developing world and training guidelines currently in use, and highlight indications for emergency ultrasound in the developing world. We suggest future directions for bedside ultrasound use and research to improve diagnostic capacity and patient care in the most remote areas of the globe