ALMA resolves the torus of NGC 1068: continuum and molecular line emission

We have used the Atacama Large Millimeter Array (ALMA) to map the emission of the CO(6-5) molecular line and the 432 {\mu}m continuum emission from the 300 pc-sized circumnuclear disk (CND) of the nearby Seyfert 2 galaxy NGC 1068 with a spatial resolution of ~4 pc. These observations spatially resolve the CND and, for the first time, image the dust emission, the molecular gas distribution, and the kinematics from a 7-10 pc-diameter disk that represents the submillimeter counterpart of the putative torus of NGC 1068. We fitted the nuclear spectral energy distribution of the torus using ALMA and near and mid-infrared (NIR/MIR) data with CLUMPY models. The mass and radius of the best-fit solution for the torus are both consistent with the values derived from the ALMA data alone: Mgas_torus=(1+-0.3)x10^5 Msun and Rtorus=3.5+-0.5 pc. The dynamics of the molecular gas in the torus show non-circular motions and enhanced turbulence superposed on the rotating pattern of the disk. The kinematic major axis of the CO torus is tilted relative to its morphological major axis. By contrast with the nearly edge-on orientation of the H2O megamaser disk, we have found evidence suggesting that the molecular torus is less inclined (i=34deg-66deg) at larger radii. The lopsided morphology and complex kinematics of the torus could be the signature of the Papaloizou-Pringle instability, long predicted to likely drive the dynamical evolution of active galactic nuclei (AGN) tori.Comment: Final version accepted by the Astrophysical Journal Letters (ApJLetters) on April 27th 2016, 6 pages, 5 figure

Molecular line emission in NGC1068 imaged with ALMA. I An AGN-driven outflow in the dense molecular gas

We investigate the fueling and the feedback of star formation and nuclear activity in NGC1068, a nearby (D=14Mpc) Seyfert 2 barred galaxy, by analyzing the distribution and kinematics of the molecular gas in the disk. We have used ALMA to map the emission of a set of dense molecular gas tracers (CO(3-2), CO(6-5), HCN(4-3), HCO+(4-3) and CS(7-6)) and their underlying continuum emission in the central r ~ 2kpc of NGC1068 with spatial resolutions ~ 0.3"-0.5" (~ 20-35pc). Molecular line and dust continuum emissions are detected from a r ~ 200pc off-centered circumnuclear disk (CND), from the 2.6kpc-diameter bar region, and from the r ~ 1.3kpc starburst (SB) ring. Most of the emission in HCO+, HCN and CS stems from the CND. Molecular line ratios show dramatic order-of-magnitude changes inside the CND that are correlated with the UV/X-ray illumination by the AGN, betraying ongoing feedback. The gas kinematics from r ~ 50pc out to r ~ 400pc reveal a massive (M_mol ~ 2.7 (+0.9, -1.2) x 10^7 Msun) outflow in all molecular tracers. The tight correlation between the ionized gas outflow, the radio jet and the occurrence of outward motions in the disk suggests that the outflow is AGN-driven. The outflow rate estimated in the CND, dM/dt ~ 63 (+21, -37) Msun yr^-1, is an order of magnitude higher than the star formation rate at these radii, confirming that the outflow is AGN-driven. The power of the AGN is able to account for the estimated momentum and kinetic luminosity of the outflow. The CND mass load rate of the CND outflow implies a very short gas depletion time scale of <=1 Myr.Comment: Version accepted for publication in A&A (June 4th). Accepted version. References (3) added and minor typos corrected. 24 pages, 20 figure

ALMA images the many faces of the NGC 1068 torus and its surroundings

Aims. We investigate the fueling and the feedback of nuclear activity in the nearby (D = 14 Mpc) Seyfert 2 barred galaxy NGC 1068 by studying the distribution and kinematics of molecular gas in the torus and its connections to the host galaxy disk. Methods.We used the Atacama Large Millimeter Array (ALMA ) to image the emission of a set of molecular gas tracers in the circumnuclear disk (CND) and the torus of the galaxy using the CO(2-1), CO(3-2), and HCO+(4-3) lines and their underlying continuum emission with high spatial resolutions (0:0300 0:0900 \u27 26 pc). These transitions, which span a wide range of physical conditions of molecular gas (n(H2) 103107 cm3), are instrumental in revealing the density radial stratification and the complex kinematics of the gas in the torus and its surroundings. Results. The ALMA images resolve the CND as an asymmetric ringed disk of D \u27 400 pc in size and \u271:4 108 M in mass. The CND shows a marked deficit of molecular gas in its central \u27130 pc region. The inner edge of the ring is associated with the presence of edge-brightened arcs of NIR polarized emission, which are identified with the current working surface of the ionized wind of the active galactic nucleus (AGN). ALMA proves the existence of an elongated molecular disk/torus in NGC 1068 of Mgas torus \u27 3 105 M, which extends over a large range of spatial scales D \u27 1030 pc around the central engine. The new observations evidence the density radial stratification of the torus: the HCO+(4-3) torus, with a full size DHCO+(43) = 11 0:6 pc, is a factor of between two and three smaller than its CO(2-1) and CO(3-2) counterparts, which have full sizes of DCO(32) = 26 0:6 pc and DCO(21) = 28 0:6 pc, respectively. This result brings into light the many faces of the molecular torus. The torus is connected to the CND through a network of molecular gas streamers detected inside the CND ring. The kinematics of molecular gas show strong departures from circular motions in the torus, the gas streamers, and the CND ring. These velocity field distortions are interconnected and are part of a 3D outflow that reflects the eects of AGN feedback on the kinematics of molecular gas across a wide range of spatial scales around the central engine. In particular, we estimate through modeling that a significant fraction of the gas inside the torus (\u270:40:6 Mgas torus) and a comparable amount of mass along the gas streamers are outflowing. However, the bulk of the mass, momentum, and energy of the molecular outflow of NGC 1068 is contained at larger radii in the CND region, where the AGN wind and the radio jet are currently pushing the gas assembled at the Inner Lindblad Resonance (ILR) ring of the nuclear stellar bar. Conclusions. In our favored scenario a wide-angle AGN wind launched from the accretion disk of NGC1068 is currently impacting a sizable fraction of the gas inside the torus. However, a large gas reservoir (\u271:21:8 105 M), which lies close to the equatorial plane of the torus, remains unaected by the feedback of the AGN wind and can therefore continue fueling the AGN for at least \u2714 Myr. Nevertheless, AGN fueling currently seems thwarted on intermediate scales (15 pc r 50 pc)

The MLL recombinome of acute leukemias in 2017

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients

The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.

Myriapods (e.g., centipedes and millipedes) display a simple homonomous body plan relative to other arthropods. All members of the class are terrestrial, but they attained terrestriality independently of insects. Myriapoda is the only arthropod class not represented by a sequenced genome. We present an analysis of the genome of the centipede Strigamia maritima. It retains a compact genome that has undergone less gene loss and shuffling than previously sequenced arthropods, and many orthologues of genes conserved from the bilaterian ancestor that have been lost in insects. Our analysis locates many genes in conserved macro-synteny contexts, and many small-scale examples of gene clustering. We describe several examples where S. maritima shows different solutions from insects to similar problems. The insect olfactory receptor gene family is absent from S. maritima, and olfaction in air is likely effected by expansion of other receptor gene families. For some genes S. maritima has evolved paralogues to generate coding sequence diversity, where insects use alternate splicing. This is most striking for the Dscam gene, which in Drosophila generates more than 100,000 alternate splice forms, but in S. maritima is encoded by over 100 paralogues. We see an intriguing linkage between the absence of any known photosensory proteins in a blind organism and the additional absence of canonical circadian clock genes. The phylogenetic position of myriapods allows us to identify where in arthropod phylogeny several particular molecular mechanisms and traits emerged. For example, we conclude that juvenile hormone signalling evolved with the emergence of the exoskeleton in the arthropods and that RR-1 containing cuticle proteins evolved in the lineage leading to Mandibulata. We also identify when various gene expansions and losses occurred. The genome of S. maritima offers us a unique glimpse into the ancestral arthropod genome, while also displaying many adaptations to its specific life history.This work was supported by the following grants: NHGRIU54HG003273 to R.A.G; EU Marie Curie ITN #215781 “Evonet” to M.A.; a Wellcome Trust Value in People (VIP) award to C.B. and Wellcome Trust graduate studentship WT089615MA to J.E.G; Marine rhythms of Life” of the University of Vienna, an FWF (http://www.fwf.ac.at/) START award (#AY0041321) and HFSP (http://www.hfsp.org/) research grant (#RGY0082/2010) to KT-­‐R; MFPL Vienna International PostDoctoral Program for Molecular Life Sciences (funded by Austrian Ministry of Science and Research and City of Vienna, Cultural Department -­‐Science and Research to T.K; Direct Grant (4053034) of the Chinese University of Hong Kong to J.H.L.H.; NHGRI HG004164 to G.M.; Danish Research Agency (FNU), Carlsberg Foundation, and Lundbeck Foundation to C.J.P.G.; U.S. National Institutes of Health R01AI55624 to J.H.W.; Royal Society University Research fellowship to F.M.J.; P.D.E. was supported by the BBSRC via the Babraham Institute;This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pbio.100200

Persistent effects of pre-Columbian plant domestication on Amazonian forest composition

The extent to which pre-Columbian societies altered Amazonian landscapes is hotly debated. We performed a basin-wide analysis of pre-Columbian impacts on Amazonian forests by overlaying known archaeological sites in Amazonia with the distributions and abundances of 85 woody species domesticated by pre-Columbian peoples. Domesticated species are five times more likely to be hyperdominant than non-domesticated species. Across the basin the relative abundance and richness of domesticated species increases in forests on and around archaeological sites. In southwestern and eastern Amazonia distance to archaeological sites strongly influences the relative abundance and richness of domesticated species. Our analyses indicate that modern tree communities in Amazonia are structured to an important extent by a long history of plant domestication by Amazonian peoples

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 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p&lt;00001), age 70 years or older versus younger than 70 years (230 [165-322], p&lt;00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p&lt;00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). 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

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p&lt;0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p&lt;0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised