Low CO Luminosities in Dwarf Galaxies

[Abridged] We present maps of CO 2-1 emission covering the entire star-forming disks of 16 nearby dwarf galaxies observed by the IRAM HERACLES survey. The data have 13 arcsec angular resolution, ~250 pc at our average distance of 4 Mpc, and sample the galaxies by 10-1000 resolution elements. We apply stacking techniques to perform the first sensitive search for CO emission in dwarfs outside the Local Group ranging from single lines-of-sight, stacked over IR-bright regions of embedded star formation, and stacked over the entire galaxy. We detect 5 dwarfs in CO with total luminosities of L_CO = 3-28 1e6 Kkmspc2. The other 11 dwarfs remain undetected in CO even in the stacked data and have L_CO < 0.4-8 1e6 Kkmspc2. We combine our sample of dwarfs with a large literature sample of spirals to study scaling relations of L_CO with M_B and metallicity. We find that dwarfs with metallicities of Z ~ 1/2-1/10 Z_sun have L_CO about 1e2-1e4x smaller than spirals and that their L_CO per unit L_B is 10-100x smaller. A comparison with tracers of star formation (FUV and 24 micron) shows that L_CO per unit SFR is 10-100x smaller in dwarfs. One possible interpretation is that dwarfs form stars much more efficiently, however we argue that the low L_CO/SFR ratio is due to significant changes of the CO-to-H2 conversion factor, alpha_CO, in low metallicity environments. Assuming a constant H2 depletion time of 1.8 Gyr (as found for nearby spirals) implies alpha_CO values for dwarfs with Z ~ 1/2-1/10 Z_sun that are more than 10x higher than those found in solar metallicity spirals. This significant increase of alpha_CO at low metallicity is consistent with previous studies, in particular those which model dust emission to constrain H2 masses. Even though it is difficult to parameterize the metallicity dependence of alpha_CO, our results suggest that CO is increasingly difficult to detect at lower metallicities.Comment: Accepted for publication in the Astronomical Journal, 19 pages, 7 figure

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Embolic stroke of undetermined source (ESUS) – Classification of a new stroke entity

Kitsiou A, Zuhorn F, Wachter R, Israel CW, Schäbitz W-R, Rogalewski A. Embolischer Schlaganfall mit ungeklärter Emboliequelle (ESUS) – Klassifikation einer neuen Schlaganfallentität. DMW - Deutsche Medizinische Wochenschrift. 2021;146(06):403-409.Als embolischer Schlaganfall mit ungeklärter Emboliequelle (ESUS) wird eine Subgruppe kryptogener Schlaganfälle bezeichnet, welche durch ein embolisches Infarktmuster definiert werden, wenn gleichzeitig trotz einer sorgfältig durchgeführten Diagnostik keine eindeutige und spezifische Emboliequelle identifiziert werden kann. In diesem Übersichtsartikel werden die Grundlagen des ESUS-Konzepts analysiert und ein Überblick über die Evidenz jüngster Kohortenstudien gegeben. Es werden die Definition, Ätiologie und die Diagnostik eines ESUS neu bewertet. Durch eine gezielte Diagnostik bei ESUS-Patienten kann die Anzahl kryptogener Schlaganfälle durch Stellen einer spezifischen Diagnose reduziert werden

Detection of Atrial Fibrillation on Stroke Units: Comparison of Manual versus Automatic Analysis of Continuous Telemetry

Rogalewski A, Plümer J, Feldmann T, et al. Detection of Atrial Fibrillation on Stroke Units: Comparison of Manual versus Automatic Analysis of Continuous Telemetry. Cerebrovascular Diseases. 2020;49(6):647-655.Background: Detection of atrial fibrillation (AF) is one of the primary diagnostic goals for patients on a stroke unit. Physician-based manual analysis of continuous ECG monitoring is regarded as the gold standard for AF detection but requires considerable resources. Recently, automated computer-based analysis of RR intervals was established to simplify AF detection. The present prospective study analyzes both methods head to head regarding AF detection specificity, sensitivity, and overall effectiveness. Methods: Consecutive stroke patients without history of AF or proof of AF in the admission ECG were enrolled over the period of 7 months. All patients received continuous ECG telemetry during the complete stay on the stroke unit. All ECGs underwent automated analysis by a commercially available program. Blinded to these results, all ECG tracings were also assessed manually. Sensitivity, specificity, time consumption, costs per day, and cost-effectiveness were compared. Results: 216 consecutive patients were enrolled (70.7 ± 14.1 years, 56% male) and 555 analysis days compared. AF was detected by manual ECG analysis on 37 days (6.7%) and automatically on 57 days (10.3%). Specificity of the automated algorithm was 94.6% and sensitivity 78.4% (28 [5.0%] false positive and 8 [1.4%] false negative). Patients with AF were older and had more often arterial hypertension, higher NIHSS at admission, more often left atrial dilatation, and a higher CHA2DS2-VASc score. Automation significantly reduced human resources but was more expensive compared to manual analysis alone. Conclusion: Automatic AF detection is highly specific, but sensitivity is relatively low. Results of this study suggest that automated computer-based AF detection should be rather complementary to manual ECG analysis than replacing it

Detection of atrial fibrillation on stroke units

$\it Background:$ Detection of atrial fibrillation (AF) is one of the primary diagnostic goals for patients on a stroke unit. Physician-based manual analysis of continuous ECG monitoring is regarded as the gold standard for AF detection but requires considerable resources. Recently, automated computer-based analysis of RR intervals was established to simplify AF detection. The present prospective study analyzes both methods head to head regarding AF detection specificity, sensitivity, and overall effectiveness. $\it Methods:$ Consecutive stroke patients without history of AF or proof of AF in the admission ECG were enrolled over the period of 7 months. All patients received continuous ECG telemetry during the complete stay on the stroke unit. All ECGs underwent automated analysis by a commercially available program. Blinded to these results, all ECG tracings were also assessed manually. Sensitivity, specificity, time consumption, costs per day, and cost-effectiveness were compared. $\it Results:$ 216 consecutive patients were enrolled (70.7 ± 14.1 years, 56% male) and 555 analysis days compared. AF was detected by manual ECG analysis on 37 days (6.7%) and automatically on 57 days (10.3%). Specificity of the automated algorithm was 94.6% and sensitivity 78.4% (28 [5.0%] false positive and 8 [1.4%] false negative). Patients with AF were older and had more often arterial hypertension, higher NIHSS at admission, more often left atrial dilatation, and a higher CHA2DS2-VASc score. Automation significantly reduced human resources but was more expensive compared to manual analysis alone. $\it Conclusion:$ Automatic AF detection is highly specific, but sensitivity is relatively low. Results of this study suggest that automated computer-based AF detection should be rather complementary to manual ECG analysis than replacing it

Heracles: The HERA CO Line Extragalactic Survey

Original article can be found at: http://www.iop.org/EJ/journal/1538-3881 Copyright American Astronomical Society. DOI: 10.1088/0004-6256/137/6/4670 [Full text of this article is not available in the UHRA]We present the Heterodyne Receiver Array CO Line Extragalactic Survey, an atlas of CO emission from 18 nearby galaxies that are also part of The H I Nearby Galaxy Survey and the Spitzer Infrared Nearby Galaxies Survey. We used the HERA multipixel receiver on the IRAM 30-m telescope to map the CO J = 2 → 1 line over the full optical disk (defined by the isophotal radius r 25) of each target, at 13'' angular resolution and 2.6 km s–1 velocity resolution. Here we describe the observations and reduction of the data and show channel maps, azimuthally averaged profiles, integrated intensity maps, and peak intensity maps. The implied H2 masses range from 7 × 106 to 6 × 109 M , with four low metallicity dwarf irregular galaxies yielding only upper limits. In the cases where CO is detected, the integrated H2-to-H I ratios range from 0.02 to 1.13 and H2-to-stellar mass ratios from 0.01 to 0.25. Exponential scale lengths of the CO emission for our targets are in the range 0.8-3.2 kpc, or 0.2 ± 0.05r 25. The intensity-weighted mean velocity of CO matches that of H I very well, with a 1σ scatter of only 6 km s–1. The CO J = 2 → 1/J = 1 → 0 line ratio varies over a range similar to that found in the Milky Way and other nearby galaxies, ~0.6-1.0, with higher values found in the centers of galaxies. The typical line ratio, ~0.8, could be produced by optically thick gas with an excitation temperature of ~10 K.Peer reviewe

GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes.

Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field