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1.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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3.
  • Naghavi, Mohsen, et al. (författare)
  • Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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4.
  • Vos, Theo, et al. (författare)
  • Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
  • 2015
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 386:9995, s. 743-800
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. Methods Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. Findings Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2.4 billion and 1.6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537.6 million in 1990 to 764.8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114.87 per 1000 people to 110.31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21.1% in 1990 to 31.2% in 2013. Interpretation Ageing of the world's population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
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5.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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6.
  • Cosentino, Giuliana, et al. (författare)
  • Interstellar Plunging Waves: ALMA Resolves the Physical Structure of Nonstationary MHD Shocks
  • 2019
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 881:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Magnetohydrodynamic (MHD) shocks are violent events that inject large amounts of energy in the interstellar medium dramatically modifying its physical properties and chemical composition. Indirect evidence for the presence of such shocks has been reported from the especial chemistry detected toward a variety of astrophysical shocked environments. However, the internal physical structure of these shocks remains unresolved since their expected spatial scales are too small to be measured with current instrumentation. Here we report the first detection of a fully spatially resolved, MHD shock toward the infrared dark cloud (IRDC) G034.77-00.55. The shock, probed by silicon monoxide (SiO) and observed with the Atacama Large Millimeter/submillimeter Array (ALMA), is associated with the collision between the dense molecular gas of the cloud and a molecular gas flow pushed toward the IRDC by the nearby supernova remnant (SNR) W44. The interaction is occurring on subparsec spatial scales thanks to the enhanced magnetic field of the SNR, making the dissipation region of the MHD shock large enough to be resolved with ALMA. Our observations suggest that molecular flow-flow collisions can be triggered by stellar feedback, inducing shocked molecular gas densities compatible with those required for massive star formation.
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7.
  • Andersen, M., et al. (författare)
  • The Stellar Content of the Infalling Molecular Clump G286.21+0.17
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 850:1, s. 12-19
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017. The American Astronomical Society. All rights reserved. The early evolution during massive star cluster formation is still uncertain. Observing embedded clusters at their earliest stages of formation can provide insight into the spatial and temporal distribution of the stars and thus probe different star cluster formation models. We present near-infrared imaging of an 8′ × 13′ (5.4 pc × 8.7 pc) region around the massive infalling clump G286.21+0.17 (also known as BYF73). The stellar content across the field is determined and photometry is derived in order to obtain stellar parameters for the cluster members. We find evidence for some sub-structure (on scales less than a parsec in diameter) within the region with apparently at least three different sub-clusters associated with the molecular clump based on differences in extinction and disk fractions. At the center of the clump we identify a deeply embedded sub-cluster. Near-infrared excess is detected for 39%-44% in the two sub-clusters associated with molecular material and 27% for the exposed cluster. Using the disk excess as a proxy for age, this suggests the clusters are very young. The current total stellar mass is estimated to be at least 200 M o . The molecular core hosts a rich population of pre-main-sequence stars. There is evidence for multiple events of star formation both in terms of the spatial distribution within the star-forming region and possibly from the disk frequency.
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8.
  • Banik, Nilanjan, et al. (författare)
  • The formation of supermassive black holes from Population III.1 seeds. I. Cosmic formation histories and clustering properties
  • 2019
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 483:3, s. 3592-3606
  • Tidskriftsartikel (refereegranskat)abstract
    • We calculate cosmic distributions in space and time of the formation sites of the first, 'Pop III.1' stars, exploring a model in which these are the progenitors of all supermassive black holes (SMBHs), seen in the centres of most large galaxies. Pop III.1 stars are defined to form from primordial composition gas in dark matter minihaloes with similar to 10(6) M-circle dot that are isolated from neighbouring astrophysical sources by a given isolation distance, d(iso). We assume Pop III.1 sources are seeds of SMBHs, based on protostellar support by dark matter annihilation heating that allows them to accrete a large fraction of their minihalo gas, i.e. similar to 10(5) M-circle dot. Exploring d(iso) from 10 to 100 kpc (proper distances), we predict the redshift evolution of Pop III.1 source and SMBH remnant number densities. The local, z = 0 density of SMBH sconstrains d(iso) less than or similar to 100 kpc (i.e. 3 Mpc comoving distance at z similar or equal to 30). In our simulated (similar to 60 Mpc)(3) comoving volume, Pop III.1 stars start forming just after z = 40. Their formation is largely complete by z similar or equal to 25-20 for d(iso) = 100-50 kpc. We follow source evolution to z = 10, by which point most SMBHs reside in haloes with greater than or similar to 10(8) M-circle dot. Over this period, there is relatively limited merging of SMBHs for these values of d(iso). We also predict SMBH clustering properties at z = 10: feedback suppression of neighbouring sources leads to relatively flat angular correlation functions.
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9.
  • Bisbas, T.G., et al. (författare)
  • GMC Collisions as Triggers of Star Formation. V. Observational Signatures
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 850:1, s. 23-32
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017. The American Astronomical Society. All rights reserved.. We present calculations of molecular, atomic, and ionic line emission from simulations of giant molecular cloud (GMC) collisions. We post-process snapshots of the magnetohydrodynamical simulations presented in an earlier paper in this series by Wu et al. of colliding and non-colliding GMCs. Using photodissociation region (PDR) chemistry and radiative transfer, we calculate the level populations and emission properties of the transitions of 12 CO J = 1-0, [C i] at 609 μm, [C ii] 158 μm, and [O i] at 63 μm. From emission maps of integrated intensity and position-velocity diagrams, we find that fine-structure lines, particularly [C ii] 158 μm, can be used as a diagnostic tracer for cloud-cloud collision activity. These results hold even in more evolved systems in which the collision signature in molecular lines has been diminished.
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10.
  • Bisbas, T. G., et al. (författare)
  • The inception of star cluster formation revealed by [C ii] emission around an Infrared Dark Cloud
  • 2018
  • Ingår i: Monthly Notices of the Royal Astronomical Society: Letters. - : Oxford University Press (OUP). - 1745-3925 .- 1745-3933. ; 478:1, s. L54-L59
  • Tidskriftsartikel (refereegranskat)abstract
    • We present SOFIA-upGREAT observations of [C ii] emission of Infrared Dark Cloud (IRDC) G035.39-00.33, designed to trace its atomic gas envelope and thus test models of the origins of such clouds. Several velocity components of [C ii] emission are detected, tracing structures that are at a wide range of distances in the Galactic plane. We find a main component that is likely associated with the IRDC and its immediate surroundings. This strongest emission component has a velocity similar to that of the 13CO(2-1) emission of the IRDC, but offset by ∼3 km s-1 and with a larger velocity width of ∼9 km s-1. The spatial distribution of the [C ii] emission of this component is also offset predominantly to one side of the dense filamentary structure of the IRDC. The C ii column density is estimated to be of the order of ∼1017-1018 cm-2. We compare these results to the [C ii] emission from numerical simulations of magnetized, dense gas filaments formed from giant molecular cloud (GMC) collisions, finding similar spatial and kinematic offsets. These observations and modellingof [C ii] add further to the evidence that IRDC G035.39-00.33 has been formed by a process of GMC-GMC collision, which may thus be an important mechanism for initiating star cluster formation.
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11.
  • Cheng, Yu, et al. (författare)
  • The Core Mass Function in the Massive Protocluster G286.21+0.17 Revealed by ALMA
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 853:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the core mass function (CMF) of the massive protocluster G286.21+0.17 with the Atacama Large Millimeter/submillimeter Array via 1.3 mm continuum emission at a resolution of 1.″0 (2500 au). We have mapped a field of 5.′3 × 5.′3 centered on the protocluster clump. We measure the CMF in the central region, exploring various core detection algorithms, which give source numbers ranging from 60 to 125, depending on parameter selection. We estimate completeness corrections due to imperfect flux recovery and core identification via artificial core insertion experiments. For masses M 1 M o , the fiducial dendrogram-identified CMF can be fit with a power law of the form dN/dlog M ∝ M -α with α ≃ 1.24 ± 0.17, slightly shallower than, but still consistent with, the index of the Salpeter stellar initial mass function of 1.35. Clumpfind-identified CMFs are significantly shallower with α ≃ 0.64 ± 0.13. While raw CMFs show a peak near 1 M o , completeness-corrected CMFs are consistent with a single power law extending down to ∼0.5 M o , with only a tentative indication of a shallowing of the slope around ∼1 M o . We discuss the implications of these results for star and star cluster formation theories.
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12.
  • Christie, D., et al. (författare)
  • GMC Collisions as Triggers of Star Formation. IV. the Role of Ambipolar Diffusion
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 848:1, s. 50-63
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017. The American Astronomical Society. All rights reserved.. We investigate the role of ambipolar diffusion (AD) in collisions between magnetized giant molecular clouds (GMCs), which may be an important mechanism for triggering star cluster formation. Three-dimensional simulations of GMC collisions are performed using a version of the Enzo magnetohydrodynamics code that has been extended to include AD. The resistivities are calculated using the 31-species chemical model of Wu et al. (2015). We find that in the weak-field, 10 μG case, AD has only a modest effect on the dynamical evolution during the collision. However, for the stronger-field, case involving near-critical clouds, AD results in the formation of dense cores in regions where collapse is otherwise inhibited. The overall efficiency of formation of cores with n H ≥ 10 6 cm -3 in these simulations is increases from about 0.2% to 2% once AD is included, comparable to observed values in star-forming GMCs. The gas around these cores typically has relatively slow infall at speeds that are a modest fraction of the free-fall speed.
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13.
  • Concepcion Gil-Rodriguez, Maria, et al. (författare)
  • De Novo Heterozygous Mutations in SMC3 Cause a Range of Cornelia de Lange Syndrome-Overlapping Phenotypes
  • 2015
  • Ingår i: Human Mutation. - : Wiley: 12 months. - 1059-7794 .- 1098-1004. ; 36:4, s. 454-462
  • Tidskriftsartikel (refereegranskat)abstract
    • Cornelia de Lange syndrome (CdLS) is characterized by facial dysmorphism, growth failure, intellectual disability, limb malformations, and multiple organ involvement. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), account for at least 70% of patients with CdLS or CdLS-like phenotypes. To date, only the clinical features from a single CdLS patient with SMC3 mutation has been published. Here, we report the efforts of an international research and clinical collaboration to provide clinical comparison of 16 patients with CdLS-like features caused by mutations in SMC3. Modeling of the mutation effects on protein structure suggests a dominant-negative effect on the multimeric cohesin complex. When compared with typical CdLS, many SMC3-associated phenotypes are also characterized by postnatal microcephaly but with a less distinctive craniofacial appearance, a milder prenatal growth retardation that worsens in childhood, few congenital heart defects, and an absence of limb deficiencies. While most mutations are unique, two unrelated affected individuals shared the same mutation but presented with different phenotypes. This work confirms that de novo SMC3 mutations account for approximate to 1%-2% of CdLS-like phenotypes.
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14.
  • Csengeri, T., et al. (författare)
  • Search for high-mass protostars with ALMA revealed up to kilo-parsec scales (SPARKS): I. Indication for a centrifugal barrier in the environment of a single high-mass envelope
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
  • Tidskriftsartikel (refereegranskat)abstract
    • The conditions leading to the formation of the most massive O-type stars are still an enigma in modern astrophysics. To assess the physical conditions of high-mass protostars in their main accretion phase, here we present a case study of a young massive clump selected from the ATLASGAL survey, G328.2551-0.5321. The source exhibits a bolometric luminosity of 1.3 × 104L·, which allows us to estimate that its current protostellar mass lies between ∼11 and 16 M·. We show high angular resolution observations with ALMA that reach a physical scale of ∼400 au. To reveal the structure of this high-mass protostellar envelope in detail at a ∼0.17′′ resolution, we used the thermal dust continuum emission and spectroscopic information, amongst others from the CO (J = 3-2) line, which is sensitive to the high-velocity molecular outflow of the source. We also used the SiO (J = 8-7) and SO2(J = 82,6-71,7) lines, which trace shocks along the outflow, as well as several CH3OH and HC3N lines that probe the gas of the inner envelope in the closest vicinity of the protostar. Our observations of the dust continuum emission reveal a single high-mass protostellar envelope, down to our resolution limit. We find evidence for a compact, marginally resolved continuum source that is surrounded by azimuthal elongations that could be consistent with a spiral pattern. We also report on the detection of a rotational line of CH3OH within its vt= 1 torsionally excited state. This shows two bright emission peaks that are spatially offset from the dust continuum peak and exhibit a distinct velocity component ±4.5 km s-1offset from the systemic velocity of the source. Rotational diagram analysis and models based on local thermodynamic equilibrium assumption require high CH3OH column densities that reach N(CH3OH) = 1.2-2 × 1019cm-2, and kinetic temperatures of the order of 160-200 K at the position of these peaks. A comparison of their morphology and kinematics with those of the outflow component of the CO line and the SO2line suggests that the high-excitation CH3OH spots are associated with the innermost regions of the envelope. While the HC3N v7= 0 (J = 37-36) line is also detected in the outflow, the HC3N v7= 1e (J = 38-37) rotational transition within the first vibrationally excited state of the molecule shows a compact morphology. We find that the velocity shifts at the position of the observed high-excitation CH3OH spots correspond well to the expected Keplerian velocity around a central object with 15 M·consistent with the mass estimate based on the bolometric luminosity of the source. We propose a picture where the CH3OH emission peaks trace the accretion shocks around the centrifugal barrier, pinpointing the interaction region between the collapsing envelope and an accretion disc. The physical properties of the accretion disc inferred from these observations suggest a specific angular momentum several times higher than typically observed towards low-mass protostars. This is consistent with a scenario of global collapse setting on at larger scales that could carry a more significant amount of kinetic energy compared to the core-collapse models of low-mass star formation. Furthermore, our results suggest that vibrationally excited HC3N emission could be a new tracer for compact accretion discs around high-mass protostars.
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15.
  • Farias Osses, Juan Pablo, 1987, et al. (författare)
  • On the formation of runaway stars BN and x in the Orion Nebula Cluster
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
  • Tidskriftsartikel (refereegranskat)abstract
    • We explore scenarios for the dynamical ejection of stars BN and x from source I in the Kleinmann-Low nebula of the Orion Nebula Cluster (ONC), which is important because it is the closest region of massive star formation. This ejection would cause source I to become a close binary or a merger product of two stars. We thus consider binary-binary encounters as the mechanism to produce this event. By running a large suite of N-body simulations, we find that it is nearly impossible to match the observations when using the commonly adopted masses for the participants, especially a source I mass of 7 M-circle dot. The only way to recreate the event is if source I is more massive, that is, similar to 20 M-circle dot. However, even in this case, the likelihood of reproducing the observed system is low. We discuss the implications of these results for understanding this important star-forming region.
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16.
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17.
  • Farias Osses, Juan Pablo, 1987, et al. (författare)
  • Star cluster formation from turbulent clumps. II. Gradual star cluster formation
  • 2019
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 483:4, s. 4999-5019
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate the dynamical evolution of star clusters during their formation, assuming that they are born from a turbulent starless clump of a given mass that is embedded within a parent self-gravitating molecular cloud characterized by a particular mass surface density. In contrast to the standard practice of most N-body studies, we do not assume that all stars are formed at once. Rather, we explore the effects of different star formation rates on the global structure and evolution of young embedded star clusters, also considering various primordial binary fractions and mass segregation levels. Our fiducial clumps studied in this paper have initial masses of M cl = 3000M ⊙ , are embedded in ambient cloud environments of σ cloud = 0.1 and 1 g cm -2 , and gradually form stars with an overall efficiency of 50 per cent until the gas is exhausted. We investigate star formation efficiencies per free-fall time in the range ϵ ff = 0.01-1, and also compare to the instantaneous case (ϵ ff = α) of Paper I. We show that most of the interesting dynamical processes that determine the future of the cluster, happen during the early formation phase. In particular, the ejected stellar population is sensitive to the duration of star cluster formation: for example, clusters with longer formation times produce more runaway stars, since these clusters remain in a dense state for longer, thus favouring occurrence of dynamical ejections. We also show that the presence of radial age gradients in star clusters depends sensitively on the star formation efficiency per free-fall time, with observed values being matched best by our slowest forming clusters with ϵ ff ≲0.03.
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18.
  • Fedriani, R., et al. (författare)
  • Measuring the ionisation fraction in a jet from a massive protostar
  • 2019
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • It is important to determine if massive stars form via disc accretion, like their low-mass counterparts. Theory and observation indicate that protostellar jets are a natural consequence of accretion discs and are likely to be crucial for removing angular momentum during the collapse. However, massive protostars are typically rarer, more distant and more dust enshrouded, making observational studies of their jets more challenging. A fundamental question is whether the degree of ionisation in jets is similar across the mass spectrum. Here we determine an ionisation fraction of ~5–12% in the jet from the massive protostar G35.20-0.74N, based on spatially coincident infrared and radio emission. This is similar to the values found in jets from lower-mass young stars, implying a unified mechanism of shock ionisation applies in jets across most of the protostellar mass spectrum, up to at least ~10 solar masses.
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19.
  • Feitosa, Mary F., et al. (författare)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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20.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
  •  
21.
  • Fontani, F., et al. (författare)
  • Fragmentation properties of massive protocluster gas clumps: an ALMA study
  • 2018
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 1432-0746 .- 0004-6361. ; 615
  • Tidskriftsartikel (refereegranskat)abstract
    • Fragmentation of massive dense molecular clouds is the starting point in the formation of rich clusters and massive stars. Theory and numerical simulations indicate that the population of the fragments (number, mass, diameter, and separation) resulting from the gravitational collapse of such clumps is probably regulated by the balance between the magnetic field and the other competitors of self-gravity, in particular, turbulence and protostellar feedback. We have observed 11 massive, dense, and young star-forming clumps with the Atacama Large Millimeter Array (ALMA) in the thermal dust continuum emission at similar to 1 mm with an angular resolution of 0 ''.25 with the aim of determining their population of fragments. The targets have been selected from a sample of massive molecular clumps with limited or absent star formation activity and hence limited feedback. We find fragments on sub-arcsecond scales in 8 out of the 11 sources. The ALMA images indicate two different fragmentation modes: a dominant fragment surrounded by companions with much lower mass and smaller size, and many (>= 8) fragments with a gradual change in masses and sizes. The morphologies are very different, with three sources that show filament-like distributions of the fragments, while the others have irregular geometry. On average, the largest number of fragments is found towards the warmer and more massive clumps. The warmer clumps also tend to form fragments with higher mass and larger size. To understand the role of the different physical parameters in regulating the final population of the fragments, we simulated the collapse of a massive clump of 100 and 300 M-circle dot with different magnetic support. The 300 M-circle dot case was also run for different initial temperatures and Mach numbers M to evaluate the separate role of each of these parameters. The simulations indicate that (1) fragmentation is inhibited when the initial turbulence is low (M similar to 3), independent of the other physical parameters. This would indicate that the number of fragments in our clumps can be explained assuming a high (M similar to 6) initial turbulence, although an initial density profile different to that assumed can play a relevant role. (2) A filamentary distribution of the fragments is favoured in a highly magnetised clump. We conclude that the clumps that show many fragments distributed in a filament-like structure are likely characterised by a strong magnetic field, while the other morphologies are also possible in a weaker magnetic field.
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22.
  • Fresard, Laure, et al. (författare)
  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
  • 2019
  • Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
  • Tidskriftsartikel (refereegranskat)abstract
    • It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
  •  
23.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
  •  
24.
  • Indriolo, Nick, et al. (författare)
  • High Spectral Resolution Observations toward Orion BN at 6 μm: No Evidence for Hot Water
  • 2018
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 865:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The Becklin-Neugebauer (BN) object in Orion has a large proper motion and radial velocity with respect to the gas and other stars in the region where it is presumed to have formed. Multiple dynamical interaction scenarios have been proposed to explain this motion. In one case BN is thought to have interacted with stars in the Trapezium cluster, while in another it is thought to have interacted with source I while deeply embedded in molecular gas. If there is dense gas that has been retained in close proximity to BN, it may be evidence that the latter scenario is favored. We observed BN at high spectral resolution in three windows near 6 mu m using the Echelon-Cross-Echelle Spectrograph on board the Stratospheric Observatory for Infrared Astronomy targeting the nu(2) vibrational band of H2O. Absorption from only three transitions of H2O is detected, and through kinematic analysis is associated with cool, dense foreground gas, not BN itself. We find no evidence for H2O absorption or emission at the systemic velocity of BN.
  •  
25.
  • Jaehnig, K., et al. (författare)
  • IN-SYNC. VII. Evidence for a Decreasing Spectroscopic Binary Fraction (from 1 to 100 Myr) within the IN-SYNC Sample
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 851:1, s. 14-31
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017. The American Astronomical Society. All rights reserved. We study the occurrence of spectroscopic binaries in young star-forming regions using the INfrared Spectroscopy of Young Nebulous Clusters (IN-SYNC) survey, carried out in SDSS-III with the APOGEE spectrograph. Multi-epoch observations of thousands of low-mass stars in Orion A, NGC 2264, NGC 1333, IC 348, and the Pleiades have been carried out, yielding H-band spectra with a nominal resolution of R = 22,500 for sources with H
  •  
26.
  • Kong, Shuo, et al. (författare)
  • Core Emergence in a Massive Infrared Dark Cloud: A Comparison between Mid-IR Extinction and 1.3 mm Emission
  • 2018
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 855:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Stars are born from dense cores in molecular clouds. Observationally, it is crucial to capture the formation of cores in order to understand the necessary conditions and rate of the star formation process. The Atacama Large Millimeter/submillimeter Array (ALMA) is extremely powerful for identifying dense gas structures, including cores, at millimeter wavelengths via their dust continuum emission. Here, we use ALMA to carry out a survey of dense gas and cores in the central region of the massive (∼10 5 M o ) infrared dark cloud (IRDC) G28.37+0.07. The observation consists of a mosaic of 86 pointings of the 12 m array and produces an unprecedented view of the densest structures of this IRDC. In this first Letter about this data set, we focus on a comparison between the 1.3 mm continuum emission and a mid-infrared (MIR) extinction map of the IRDC. This allows estimation of the "dense gas" detection probability function (DPF), i.e., as a function of the local mass surface density, Σ, for various choices of thresholds of millimeter continuum emission to define "dense gas." We then estimate the dense gas mass fraction, f dg , in the central region of the IRDC and, via extrapolation with the DPF and the known Σ probability distribution function, to the larger-scale surrounding regions, finding values of about 5% to 15% for the fiducial choice of threshold. We argue that this observed dense gas is a good tracer of the protostellar core population and, in this context, estimate a star formation efficiency per free-fall time in the central IRDC region of ff ∼ 10%, with approximately a factor of two systematic uncertainties.
  •  
27.
  • Kong, Shuo, et al. (författare)
  • Widespread Molecular Outflows in the Infrared Dark Cloud G28.37+0.07: Indications of Orthogonal Outflow-filament Alignment
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 874:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present ALMA CO(2-1) observations toward a massive infrared dark cloud G28.37+0.07. The ALMA data reveal numerous molecular (CO) outflows with a wide range of sizes throughout the cloud. Sixty-two 1.3 mm continuum cores were identified to be driving molecular outflows. We have determined the position angle in the plane-of-sky of 120 CO outflow lobes and studied their distribution. We find that the distribution of the plane-of-sky outflow position angles peaks at about 100 degrees, corresponding to a concentration of outflows with an approximately east-west direction. For most outflows, we have been able to estimate the plane-of-sky angle between the outflow axis and the filament that harbors the protostar that powers the outflow. Statistical tests strongly indicate that the distribution of outflow-filament orientations is consistent with most outflow axes being mostly orthogonal to their parent filament in three dimensions. Such alignment may result from filament fragmentation or continuous mass transportation from the filament to the embedded protostellar core. The latter is suggested by recent numerical studies with moderately strong magnetic fields.
  •  
28.
  • Kong, Shuo, et al. (författare)
  • Zooming in to Massive Star Birth
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 867:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present high-resolution (0 2, 1000 au) 1.3 mm ALMA observations of the massive infrared dark cloud clump, G028.37+00.07-C1, thought to harbor the early stages of massive star formation. Using N2D +(3-2), we resolve the previously identified C1-S core, separating the bulk of its emission from two nearby protostellar sources. C1-S is thus identified as a massive (∼50M⊙), compact (∼0.1 pc diameter) starless core, e.g., with no signs of outflow activity. Being highly deuterated, this is a promising candidate for a pre-stellar core on the verge of collapse. An analysis of its dynamical state indicates a sub-virial velocity dispersion compared to a trans-Alfvenic turbulent core model. However, virial equilibrium could be achieved with sub-Alfvenic conditions involving magnetic field strengths of ∼2 mG.
  •  
29.
  • Leebens-Mack, James H., et al. (författare)
  • One thousand plant transcriptomes and the phylogenomics of green plants
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
  • Tidskriftsartikel (refereegranskat)abstract
    • Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
  •  
30.
  • Liu, Mengyao, et al. (författare)
  • The Core Mass Function across Galactic Environments. II. Infrared Dark Cloud Clumps
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 862:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the core mass function (CMF) within 32 dense clumps in seven infrared dark clouds (IRDCs) with the Atacama Large Millimeter/submillimeter Array via 1.3 mm continuum emission at a resolution of similar to 1 ''. We have identified 107 cores with the dendrogram algorithm, with a median radius of about 0.02 pc. Their masses range from 0.261 to 178 M-circle dot. After applying completeness corrections, we fit the combined IRDC CMF with a power law of the form dN/d log M proportional to M(-alpha)and derive an index of alpha similar or equal to 0.86 +/- 0.11 for M >= 0.79 M-circle dot and alpha similar or equal to 0.70 +/- 0.13 for M >= 1.26 M-circle dot, which is a significantly more top-heavy distribution than the Salpeter stellar initial mass function index of 1.35. We also make a direct comparison of these IRDC clump CMF results to those measured in the more evolved protocluster G286 derived with similar methods, which have alpha similar or equal to 1.29 +/- 0.19 and 1.08 +/- 0.27 in these mass ranges, respectively. These results provide a hint that, especially for the M >= 1.26 M-circle dot range where completeness corrections are modest, the CMF in high pressure, early-stage environments of IRDC clumps may be top-heavy compared to that in the more evolved, global environment of the G286 protoclusters. However, larger samples of cores probing these different environments are needed to better establish the robustness of this potential CMF variation.
  •  
31.
  • Liu, Mengyao, et al. (författare)
  • The SOFIA Massive (SOMA) Star Formation Survey. II. High Luminosity Protostars
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 874:1
  • Forskningsöversikt (refereegranskat)abstract
    • We present multiwavelength images observed with SOFIA-FORCAST from similar to 10 to 40 mu m of seven high luminosity massive protostars, as part of the SOFIA Massive Star Formation Survey. Source morphologies at these wavelengths appear to be influenced by outflow cavities and extinction from dense gas surrounding the protostars. Using these images, we build spectral energy distributions (SEDs) of the protostars, also including archival data from Spitzer, Herschel, and other facilities. Radiative transfer (RT) models of Zhang & Tan, based on Turbulent Core Accretion theory, are then fit to the SEDs to estimate key properties of the protostars. Considering the best five models fit to each source, the protostars have masses m* similar to 12-64 M circle dot accreting at rates of m* similar to 10(-4) -10(-3) M circle dot yr(-1) inside cores of initial masses M-c similar to 100-500 M circle dot embedded in clumps with mass surface densities Sigma(cl) similar to 0.1-3 g cm(-2) and span a luminosity range of 10(4) -10(6) L circle dot. Compared with the first eight protostars in Paper I, the sources analyzed here are more luminous and, thus, likely to be more massive protostars. They are often in a clustered environment or have a companion protostar relatively nearby. From the range of parameter space of the models, we do not see any evidence that Sigma(cl) needs to be high to form these massive stars. For most sources, the RT models provide reasonable fits to the SEDs, though the cold clump material often influences the long wavelength fitting. However, for sources in very clustered environments, the model SEDs may not be such a good description of the data, indicating potential limitations of the models for these regions.
  •  
32.
  • Lloyd-Price, Jason, et al. (författare)
  • Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 569:7758, s. 655-661
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammatory bowel diseases, which include Crohn's disease and ulcerative colitis, affect several million individuals worldwide. Crohn's disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study's infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi'omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities in inflammatory bowel diseases.
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33.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
  •  
34.
  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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35.
  • Rosero, Viviana, et al. (författare)
  • The SOMA Radio Survey. I. Comprehensive SEDs of High-mass Protostars from Infrared to Radio and the Emergence of Ionization Feedback
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 873:1
  • Forskningsöversikt (refereegranskat)abstract
    • We study centimeter continuum emission of eight high- and intermediate-mass protostars that are part of the SOFIA Massive Star Formation Survey, thus building extended spectral energy distributions (SEDs) from the radio to the infrared. We discuss the morphology seen in the centimeter continuum images, which are mostly derived from archival Very Large Array data, and the relation to infrared morphology. We use the SEDs to test new models of high-mass star formation including radiative and disk-wind feedback and associated free-free and dust continuum emission. We show that interferometric data of the centimeter continuum flux densities provide additional, stringent tests of the models by constraining the ionizing luminosity of the source; they also help to break degeneracies encountered when modeling the infrared-only SEDs, especially for the protostellar mass. Our derived parameters are consistent with physical parameters estimated by other methods, such as dynamical protostellar masses. We find a few examples of additional stellar sources in the vicinity of the high-mass protostars, which may be low-mass young stellar objects. However, the stellar multiplicity of the regions, at least as traced by radio continuum emission, appears to be relatively low.
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36.
  • Ruetz, Tyson, et al. (författare)
  • Constitutively Active SMAD2/3 Are Broad-Scope Potentiators of Transcription-Factor-Mediated Cellular Reprogramming
  • 2017
  • Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; , s. 9-805
  • Tidskriftsartikel (refereegranskat)abstract
    • Reprogramming of cellular identity using exogenous expression of transcription factors (TFs) is a powerful and exciting tool for tissue engineering, disease modeling, and regenerative medicine. However, generation of desired cell types using this approach is often plagued by inefficiency, slow conversion, and an inability to produce mature functional cells. Here, we show that expression of constitutively active SMAD2/3 significantly improves the efficiency of induced pluripotent stem cell (iPSC) generation by the Yamanaka factors. Mechanistically, SMAD3 interacts with reprogramming factors and co-activators and co-occupies OCT4 target loci during reprogramming. Unexpectedly, active SMAD2/3 also markedly enhances three other TF-mediated direct reprogramming conversions, from B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons, highlighting broad and general roles for SMAD2/3 as cell-reprogramming potentiators. Our results suggest that co-expression of active SMAD2/3 could enhance multiple types of TF-based cell identity conversion and therefore be a powerful tool for cellular engineering. Ruetz et al. show that constitutively active SMAD2/3 has a surprising ability to boost the efficiency of cell reprogramming both to iPSCs and across lineages and may therefore be a general factor that can enhance transcription-factor-mediated reprogramming in a variety of contexts.
  •  
37.
  • Scarlett, Jonathan, 1990, et al. (författare)
  • The dispersion of nearest-neighbor decoding for additive non-Gaussian channels
  • 2017
  • Ingår i: IEEE Transactions on Information Theory. - 0018-9448 .- 1557-9654. ; 63:1, s. 81-92
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the second-order asymptotics of information transmission using random Gaussian codebooks and nearest neighbor decoding over a power-limited stationary memoryless additive non-Gaussian noise channel. We show that the dispersion term depends on the non-Gaussian noise only through its second and fourth moments, thus complementing the capacity result (Lapidoth, 1996), which depends only on the second moment. Furthermore, we characterize the second-order asymptotics of point-to-point codes over K -sender interference networks with non-Gaussian additive noise. Specifically, we assume that each user's codebook is Gaussian and that NN decoding is employed, i.e., that interference from the K-1 unintended users (Gaussian interfering signals) is treated as noise at each decoder. We show that while the first-order term in the asymptotic expansion of the maximum number of messages depends on the power of the interfering codewords only through their sum, this does not hold for the second-order term.
  •  
38.
  • Scarlett, Jonathan, 1990, et al. (författare)
  • The Dispersion of Nearest-Neighbor Decoding for Additive Non-Gaussian Channels
  • 2016
  • Ingår i: IEEE International Symposium on Information Theory - Proceedings. - 2157-8095. ; 2016-August, s. 2664-2668
  • Konferensbidrag (refereegranskat)abstract
    • We study the second-order asymptotics of information transmission using random Gaussian codebooks and nearest neighbor (NN) decoding over a power-limited additive stationary memoryless non-Gaussian channel. We show that the dispersion term depends on the non-Gaussian noise only through its second and fourth moments. We also characterize the second-order performance of point-to-point codes over Gaussian interference networks. Specifically, we assume that each user’s codebook is Gaussian and that NN decoding is employed, i.e., that interference from unintended users is treated as noise at each decoder.
  •  
39.
  • Sokolov, V., et al. (författare)
  • Temperature structure and kinematics of the IRDC G035.39-00.33
  • 2017
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 606
  • Tidskriftsartikel (refereegranskat)abstract
    • © ESO, 2017. Aims. Infrared dark clouds represent the earliest stages of high-mass star formation. Detailed observations of their physical conditions on all physical scales are required to improve our understanding of their role in fueling star formation. Methods. We investigate the large-scale structure of the IRDC G035.39-00.33, probing the dense gas with the classical ammonia thermometer. This allows us to put reliable constraints on the temperature of the extended, pc-scale dense gas reservoir and to probe the magnitude of its non-Thermal motions. Available far-infrared observations can be used in tandem with the observed ammonia emission to estimate the total gas mass contained in G035.39-00.33. Results. We identify a main velocity component as a prominent filament, manifested as an ammonia emission intensity ridge spanning more than 6 pc, consistent with the previous studies on the Northern part of the cloud. A number of additional line-of-sight components are found, and a large-scale linear velocity gradient of ~ 0.2km s -1 pc -1 is found along the ridge of the IRDC. In contrast to the dust temperature map, an ammonia-derived kinetic temperature map, presented for the entirety of the cloud, reveals local temperature enhancements towards the massive protostellar cores. We show that without properly accounting for the line of sight contamination, the dust temperature is 2-3 K larger than the gas temperature measured with NH 3 . Conclusions. While both the large-scale kinematics and temperature structure are consistent with that of starless dark filaments, the kinetic gas temperature profile on smaller scales is suggestive of tracing the heating mechanism coincident with the locations of massive protostellar cores.
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40.
  • Staff, Jan E., et al. (författare)
  • Disk Wind Feedback from High-mass Protostars
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 882:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We perform a sequence of 3D magnetohydrodynamic (MHD) simulations of the outflow-core interaction for a massive protostar forming via collapse of an initial cloud core of 60 M-circle dot. This allows us to characterize the properties of disk-wind-driven outflows from massive protostars, which can allow testing of different massive star formation theories. It also enables us to assess quantitatively the impact of outflow feedback on protostellar core morphology and overall star formation efficiency (SFE). We find that the opening angle of the flow increases with increasing protostellar mass, in agreement with a simple semianalytic model. Once the protostar reaches similar to 24 M-circle dot, the outflow's opening angle is so wide that it has blown away most of the envelope, thereby nearly ending its own accretion. We thus find an overall SFE, of similar to 50%, similar to that expected from low-mass protostellar cores. Our simulation results therefore indicate that the MHD disk wind outflow is the dominant feedback mechanism for helping to shape the stellar initial mass function from a given prestellar core mass function.
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41.
  • Tan, Jonathan, 1973 (författare)
  • Fire from Ice - Massive Star Birth from Infrared Dark Clouds
  • 2017
  • Ingår i: Proceedings of the International Astronomical Union. - 1743-9213 .- 1743-9221. ; 13:S332, s. 139-152
  • Konferensbidrag (refereegranskat)abstract
    • I review massive star formation in our Galaxy, focussing on initial conditions in Infrared Dark Clouds (IRDCs), including the search for massive pre-stellar cores (PSCs), and modeling of later stages of massive protostars, i.e., hot molecular cores (HMCs). I highlight how developments in astrochemistry, coupled with rapidly improving theoretical/computational and observational capabilities are helping to improve our understanding of the complex process of massive star formation.
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42.
  • Tan, Xiao, et al. (författare)
  • Aiding sleep in type 2 diabetes : therapeutic considerations
  • 2018
  • Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 6:1, s. 60-68
  • Forskningsöversikt (refereegranskat)abstract
    • Insomnia and obstructive sleep apnoea (OSA) are more prevalent in patients with type 2 diabetes than in the general population. Both insomnia and OSA have been linked to cardiometabolic alterations (eg, hypertension, increased activity of the sympathetic nervous system, and systemic insulin resistance) that can exacerbate the pathophysiology of type 2 diabetes. Improvement of sleep in patients with diabetes could therefore aid the treatment of diabetes. To help health practitioners choose the best clinical tool to improve their patients' sleep without detrimentally affecting glucose regulation, this Review critically analyses the effects of common treatments for insomnia and OSA on both sleep and glucose metabolism in patients with type 2 diabetes. These treatments include pharmaceutical sleep aids (eg, benzodiazepine receptor agonists, melatonin) and cognitive behavioural therapy for insomnia, continuous positive airway pressure for OSA, and lifestyle interventions.
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43.
  • Tan, Xiao, et al. (författare)
  • Association between long sleep duration and increased risk of obesity and type 2 diabetes : A review of possible mechanisms
  • 2018
  • Ingår i: Sleep Medicine Reviews. - : Elsevier BV. - 1087-0792 .- 1532-2955. ; 40, s. 127-134
  • Forskningsöversikt (refereegranskat)abstract
    • For the last two decades research has revealed an alarming association between short sleep duration and metabolic disorders. In tandem, the hormonal, behavioral, and genetic mechanisms underlying this relationship have been extensively investigated and reviewed. However, emerging evidence is revealing that excessive sleep duration has remarkably similar deleterious effects. Unfortunately, to date there has been little attention to what drives this connection. This narrative review therefore aims to summarize existing epidemiological findings, experimental work, and most importantly putative molecular and behavioral mechanisms connecting excessive sleep duration with both obesity and type 2 diabetes mellitus. It will also address recent findings suggesting a worrisome bidirectional effect such that metabolic disorders create a positive feedback loop which further perpetuates excessive sleep.
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44.
  •  
45.
  • Tan, Xiao, et al. (författare)
  • Lack of association between self-reported insomnia symptoms and clamp-derived insulin sensitivity in elderly men
  • 2019
  • Ingår i: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 102, s. 256-260
  • Tidskriftsartikel (refereegranskat)abstract
    • Insomnia-related sleep disruptions, such as short and disturbed sleep, have been tied to systemic insulin resistance in young adult populations. We therefore sought to confirm these findings in a cohort of elderly men. To this aim, we utilized variables from 980 men who participated in the investigation at age 70 of the Uppsala Longitudinal Study of Adult Men. Self-reported insomnia symptoms were assessed by questions about difficulty initiating sleep, early final awakening, and regular use of hypnotics. All participants also underwent the gold standard hyperinsulinemic-euglycemic clamp technique to assess the insulin sensitivity index (M/I). Finally, fasting blood was collected to measure free fatty acids (FFAs) and adiponectin. Differences in blood parameters between men with and those without insomnia were determined by ANCOVA, and were adjusted for lifestyle and cardio-metabolic risk factors. Our analysis yielded no differences in M/I, FFAs, and adiponectin between men with and those without insomnia symptoms. Analyses in non-diabetic and diabetic subsamples confirmed these negative findings. Our cross-sectional results therefore suggest that insomnia symptoms may have a minimal effect, if any, on measures of insulin sensitivity in elderly men. Given the observational design of our study, future studies are needed to determine whether experimental sleep manipulations influence systemic insulin sensitivity in elderly humans, as has previously been shown in young adult populations.
  •  
46.
  • Tan, Xiao, et al. (författare)
  • Self-reported sleep disturbances and prostate cancer morbidity and mortality in Swedish men : A longitudinal study over 40 years
  • 2018
  • Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 27:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study, with an observational period of about 40 years, examined the association between self-reported sleep disturbances (i.e. problems with falling and staying asleep; use of hypnotics) and prostate cancer morbidity and mortality in initially 2322 men (all 50 years old at baseline). Self-reported sleep disturbances and established risk factors (e.g. age, lower urinary tract symptoms, smoking and family history of cancer) were measured at ages 50 and 70 years. Information about prostate cancer diagnosis and deaths as a result of prostate cancer was available from the National Cancer Registry and the Swedish Civil Registry of Morbidity. During the observational period, 263 participants developed prostate cancer (11% of the total cohort); 146 of them died as a result of prostate cancer. There was no association between sleep disturbances and prostate cancer morbidity or mortality (hazard ratio 1.09, 95% confidence interval (CI) 0.79, 1.52, and hazard ratio 1.21, 95% CI 0.77, 1.91, respectively). Similar findings were observed when examining associations between single sleep disturbance parameters and prostate cancer morbidity and mortality. Our study does not provide evidence that reports of sleep disturbances increase the risk of prostate cancer morbidity or mortality in middle to older-aged men. Therefore, assessing subjective sleep problems may not meaningfully help to identify men at risk of developing prostate cancer or dying of this devastating condition.
  •  
47.
  • Tanaka, Kei E. I., et al. (författare)
  • Multiple Feedback in Low-Metallicity Massive Star Formation
  • 2019
  • Ingår i: Proceedings of the International Astronomical Union. - 1743-9213 .- 1743-9221. ; 14:S344, s. 190-194
  • Konferensbidrag (refereegranskat)abstract
    • We theoretically investigate the impact of feedback and its metallicity dependence in massive star formation from prestellar cores at all metallicity range. We include the feedback by MHD disk winds, radiation pressure, and photoevaporation solving the evolution of protostars and accretion flows self-consistently. Interestingly, we find that the feedback does not set the upper mass limit of stellar birth mass at any metallicity. At the solar metallicity, the MHD disk wind is the dominant feedback to set the star formation efficiencies (SFEs) from the prestellar cores similar to low-mass star formation. The SFE is found to be lower at lower surface density environment. The photoevaporation becomes significant at the low metallicity of Z < 10(-2) Z(circle dot). Considering this efficient photoevaporation, we conclude that the IMF slope is steeper, i.e., massive stars are rarer at the extremely metal-poor environment of 10(-5)-10(-3)Z(circle dot). Our study raises a question on the common assumption of the universal IMF with a truncated at 100M(circle dot). Since the total feedback strength in the cluster/galaxy scale is sensitive to the number fraction of massive stars, the re-evaluations of IMF at various environments are necessary.
  •  
48.
  • Tanaka, K.E.I., et al. (författare)
  • Outflow-confined H II Regions. II. The Early Break-out Phase
  • 2017
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 849:2, s. 133-141
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2017. The American Astronomical Society. All rights reserved. In this series of papers, we model the formation and evolution of the photoionized region and its observational signatures during massive star formation. Here, we focus on the early breakout of the photoionized region into the outflow cavity. Using results of 3D magnetohydrodynamic-outflow simulations and protostellar evolution calculations, we perform a post-processing radiative transfer. The photoionized region first appears at a protostellar mass of m∗ = 10 M ⊙ in our fiducial model and is confined to within 10-100 au by the dense inner outflow, which is similar to some of the observed very small hypercompact H II regions. Since the ionizing luminosity of the massive protostar increases dramatically as the Kelvin-Helmholtz (KH) contraction proceeds, the photoionized region breaks out to the entire outflow region in ≲10,000 year. Accordingly, the radio free-free emission brightens significantly in this stage. In our fiducial model, the radio luminosity at 10 GHz changes from 0.1 mJy kpc 2 at m∗ = 11 M ⊙ to 100 mJy kpc 2 at m∗ = 16 M ⊙ , while the infrared luminosity increases by less than a factor of two. The radio spectral index also changes in the break-out phase from the optically thick value of ∼2 to the partially optically thin value of ∼0.6. Additionally, we demonstrate that short-timescale variation in the free-free flux would be induced by an accretion burst. The outflow density is enhanced in the accretion burst phase, which leads to a smaller ionized region and weaker free-free emission. The radio luminosity may decrease by one order of magnitude during such bursts, while the infrared luminosity is much less affected because internal protostellar luminosity dominates over accretion luminosity after the KH contraction starts. Such a variability may be observable on timescales as short 10-100 year if accretion bursts are driven by disk instabilities.
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49.
  • Tanaka, Kei E.I., et al. (författare)
  • The Impact of Feedback in Massive Star Formation. II. Lower Star Formation Efficiency at Lower Metallicity
  • 2018
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 861:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We conduct a theoretical study of the formation of massive stars over a wide range of metallicities from 10-5to and evaluate the star formation efficiencies (SFEs) from prestellar cloud cores taking into account multiple feedback processes. Unlike for simple spherical accretion, feedback processes in the case of disk accretion do not set upper limits on stellar masses. At solar metallicity, launching of magneto-centrifugally driven outflows is the dominant feedback process to set SFEs, while radiation pressure, which has been regarded as pivotal, makes only a minor contribution even in the formation of stars over 100 M⊙. Photoevaporation becomes significant in the formation of stars over 20 M⊙at low metallicities of ≲ 10-2Z⊙, where dust absorption of ionizing photons is inefficient. We conclude that if initial prestellar core properties are similar, then massive stars are rarer in extremely metal-poor environments of 10-5-10-3Z⊙. Our results give new insight into the high-mass end of the initial mass function and its potential variation with galactic and cosmological environments.
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50.
  • Tejada, Thor, et al. (författare)
  • IGF-1 degradation by mouse mast cell protease 4 promotes cell death and adverse cardiac remodeling days after a myocardial infarction
  • 2016
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:25, s. 6949-6954
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in post-ischemic heart disease.
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