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1.
  • 2017
  • swepub:Mat__t
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2.
  • Lind, Lars, et al. (author)
  • Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
  • 2021
  • In: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
  • Journal article (peer-reviewed)abstract
    • From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions.
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3.
  • Bixby, H., et al. (author)
  • Rising rural body-mass index is the main driver of the global obesity epidemic in adults
  • 2019
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
  • Journal article (peer-reviewed)abstract
    • Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities(.)(1,2) This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity(3-6). Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017-and more than 80% in some low- and middle-income regions-was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing-and in some countries reversal-of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.
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7.
  • Adrian-Martinez, S., et al. (author)
  • A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
  • 2013
  • In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
  • Journal article (peer-reviewed)abstract
    • We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.
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10.
  • Mishra, A., et al. (author)
  • Stroke genetics informs drug discovery and risk prediction across ancestries
  • 2022
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
  • Journal article (peer-reviewed)abstract
    • Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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12.
  • Barausse, Enrico, et al. (author)
  • Prospects for fundamental physics with LISA
  • 2020
  • In: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
  • Journal article (other academic/artistic)abstract
    • In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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13.
  • Bousquet, J., et al. (author)
  • Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
  • 2017
  • In: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
  • Journal article (peer-reviewed)abstract
    • The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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14.
  • Adrian-Martinez, S., et al. (author)
  • The First Combined Search For Neutrino Point-Sources In The Southern Hemisphere With The Antares And Icecube Neutrino Telescopes
  • 2016
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 823:1
  • Journal article (peer-reviewed)abstract
    • We present the results of searches for point-like sources of neutrinos based on the first combined analysis of data from both the ANTARES and IceCube neutrino telescopes. The combination of both detectors, which differ in size and location, forms a window in the southern sky where the sensitivity to point sources improves by up to a factor of 2 compared with individual analyses. Using data recorded by ANTARES from 2007 to 2012, and by IceCube from 2008 to 2011, we search for sources of neutrino emission both across the southern sky and from a preselected list of candidate objects. No significant excess over background has been found in these searches, and flux upper limits for the candidate sources are presented for E-2.5 and E-2 power-law spectra with different energy cut-offs.
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17.
  • Caselli, P., et al. (author)
  • Water vapor toward starless cores : The Herschel view
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L29-
  • Journal article (peer-reviewed)abstract
    • Aims: Previous studies by the satellites SWAS and Odin provided stringent upper limits on the gas phase water abundance of dark clouds (x(H2O) < 7 × 10-9). We investigate the chemistry of water vapor in starless cores beyond the previous upper limits using the highly improved angular resolution and sensitivity of Herschel and measure the abundance of water vapor during evolutionary stages just preceding star formation. Methods: High spectral resolution observations of the fundamental ortho water (o-H2O) transition (557 GHz) were carried out with the Heterodyne Instrument for the Far Infrared onboard Herschel toward two starless cores: Barnard 68 (hereafter B68), a Bok globule, and LDN 1544 (L1544), a prestellar core embedded in the Taurus molecular cloud complex. Detailed radiative transfer and chemical codes were used to analyze the data. Results: The RMS in the brightness temperature measured for the B68 and L1544 spectra is 2.0 and 2.2 mK, respectively, in a velocity bin of 0.59 km s-1. The continuum level is 3.5 ± 0.2 mK in B68 and 11.4 ± 0.4 mK in L1544. No significant feature is detected in B68 and the 3σ upper limit is consistent with a column density of o-H2O N(o-H2O) < 2.5 × 1013 cm-2, or a fractional abundance x(o-H2O) < 1.3 × 10-9, more than an order of magnitude lower than the SWAS upper limit on this source. The L1544 spectrum shows an absorption feature at a 5σ level from which we obtain the first value of the o-H2O column density ever measured in dark clouds: N(o-H2O) = (8 ± 4) × 1012 cm-2. The corresponding fractional abundance is x(o-H2O) ≃ 5 × 10-9 at radii >7000 AU and ≃2 × 10-10 toward the center. The radiative transfer analysis shows that this is consistent with a x(o-H2O) profile peaking at ≃10-8, 0.1 pc away from the core center, where both freeze-out and photodissociation are negligible. Conclusions: Herschel has provided the first measurement of water vapor in dark regions. Column densities of o-H2O are low, but prestellar cores such as L1544 (with their high central densities, strong continuum, and large envelopes) appear to be very promising tools to finally shed light on the solid/vapor balance of water in molecular clouds and oxygen chemistry in the earliest stages of star formation. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
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  • Fich, M., et al. (author)
  • Herschel-PACS spectroscopy of the intermediate mass protostar NGC 7129 FIRS 2
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L86
  • Journal article (peer-reviewed)abstract
    • Aims. We present preliminary results of the first Herschel spectroscopic observations of NGC 7129 FIRS2, an intermediate mass star-forming region. We attempt to interpret the observations in the framework of an in-falling spherical envelope. Methods. The PACS instrument was used in line spectroscopy mode ( R = 1000-5000) with 15 spectral bands between 63 and 185 mu m. This provided good detections of 26 spectral lines seen in emission, including lines of H2O, CO, OH, O I, and C II. Results. Most of the detected lines, particularly those of H2O and CO, are substantially stronger than predicted by the spherical envelope models, typically by several orders of magnitude. In this paper we focus on what can be learned from the detected CO emission lines. Conclusions. It is unlikely that the much stronger than expected line emission arises in the (spherical) envelope of the YSO. The region hot enough to produce such high excitation lines within such an envelope is too small to produce the amount of emission observed. Virtually all of this high excitation emission must arise in structures such as as along the walls of the outflow cavity with the emission produced by a combination of UV photon heating and/or non-dissociative shocks.
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21.
  • Kristensen, L. E., et al. (author)
  • Water in low-mass star-forming regions with Herschel . HIFI spectroscopy of NGC 1333
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L30-
  • Journal article (peer-reviewed)abstract
    • “Water In Star-forming regions with Herschel” (WISH) is a key programme dedicated to studying the role of water and related species during the star-formation process and constraining the physical and chemical properties of young stellar objects. The Heterodyne Instrument for the Far-Infrared (HIFI) on the Herschel Space Observatory observed three deeply embedded protostars in the low-mass star-forming region NGC 1333 in several H_216O, H_218O, and CO transitions. Line profiles are resolved for five H_216O transitions in each source, revealing them to be surprisingly complex. The line profiles are decomposed into broad (>20 km s-1), medium-broad (~5-10 km s-1), and narrow (<5 km s-1) components. The H_218O emission is only detected in broad 110-101 lines (>20 km s-1), indicating that its physical origin is the same as for the broad H_216O component. In one of the sources, IRAS4A, an inverse P Cygni profile is observed, a clear sign of infall in the envelope. From the line profiles alone, it is clear that the bulk of emission arises from shocks, both on small (⪉1000 AU) and large scales along the outflow cavity walls (~10 000 AU). The H2O line profiles are compared to CO line profiles to constrain the H2O abundance as a function of velocity within these shocked regions. The H2O/CO abundance ratios are measured to be in the range of ~0.1-1, corresponding to H2O abundances of ~10-5-10-4 with respect to H2. Approximately 5-10% of the gas is hot enough for all oxygen to be driven into water in warm post-shock gas, mostly at high velocities. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Tables 2 and 3 (page 6) are only available in electronic form at http://www.aanda.org
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22.
  • Marseille, M. G., et al. (author)
  • Water abundances in high-mass protostellar envelopes : Herschel observations with HIFI
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L32-
  • Journal article (peer-reviewed)abstract
    • Aims: We derive the dense core structure and the water abundance in four massive star-forming regions in the hope of understanding the earliest stages of massive star formation. Methods: We present Herschel/HIFI observations of the para-H2O 111-000 and 202-111 and the para-H_218O 111-000 transitions. The envelope contribution to the line profiles is separated from contributions by outflows and foreground clouds. The envelope contribution is modeled with Monte-Carlo radiative transfer codes for dust and molecular lines (MC3D and RATRAN), and the water abundance and the turbulent velocity width as free parameters. Results: While the outflows are mostly seen in emission in high-J lines, envelopes are seen in absorption in ground-state lines, which are almost saturated. The derived water abundances range from 5×10-10 to 4×10-8 in the outer envelopes. We detect cold clouds surrounding the protostar envelope, thanks to the very high quality of the Herschel/HIFI data and the unique ability of water to probe them. Several foreground clouds are also detected along the line of sight. Conclusions: The low H2O abundances in massive dense cores are in accordance with the expectation that high densities and low temperatures lead to freeze-out of water on dust grains. The spread in abundance values is not clearly linked to physical properties of the sources. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation of NASA.Appendix (pages 6 to 7) is only available in electronic form at http://www.aanda.org
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  • van der Tak, F. F. S., et al. (author)
  • Water abundance variations around high-mass protostars: HIFI observations of the DR21 region
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L107
  • Journal article (peer-reviewed)abstract
    • Context. Water is a key molecule in the star formation process, but its spatial distribution in star-forming regions is not well known. Aims. We study the distribution of dust continuum and H2O and (CO)-C-13 line emission in DR21, a luminous star-forming region with a powerful outflow and a compact H II region. Methods. Herschel-HIFI spectra near 1100 GHz show narrow (CO)-C-13 10-9 emission and H2O 1(11)-0(00) absorption from the dense core and broad emission from the outflow in both lines. The H2O line also shows absorption by a foreground cloud known from ground-based observations of low-J CO lines. Results. The dust continuum emission is extended over 36 '' FWHM, while the (CO)-C-13 and H2O lines are confined to approximate to 24 '' or less. The foreground absorption appears to peak further North than the other components. Radiative transfer models indicate very low abundances of similar to 2 x 10(-10) for H2O and similar to 8 x 10(-7) for (CO)-C-13 in the dense core, and higher H2O abundances of similar to 4 x 10(-9) in the foreground cloud and similar to 7 x 10(-7) in the outflow. Conclusions. The high H2O abundance in the warm outflow is probably due to the evaporation of water-rich icy grain mantles, while the H2O abundance is kept down by freeze-out in the dense core and by photodissociation in the foreground cloud.
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  • van Dishoeck, E. F., et al. (author)
  • Water in Star-forming Regions with the Herschel Space Observatory (WISH). I. Overview of Key Program and First Results
  • 2011
  • In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 123:900, s. 138-170
  • Journal article (peer-reviewed)abstract
    • Water In Star-forming regions with Herschel (WISH) is a key program on the Herschel Space Observatory designed to probe the physical and chemical structures of young stellar objects using water and related molecules and to follow the water abundance from collapsing clouds to planet-forming disks. About 80 sources are targeted, covering a wide ranee of luminosities-from low ( 10(5) L-circle dot)-and a wide range of evolutionary stages-from cold prestellar cores to warm protostellar envelopes and outflows to disks around young stars. Both the HIFI and PACS instruments are used to observe a variety of lines of H2O, (H2O)-O-18 and chemically related species at the source position and in small maps around the protostars and selected outflow positions. In addition, high-frequency lines of CO, (CO)-C-13, and (CO)-O-18 are obtained with Herschel and are complemented by ground-based observations of dust continuum, HDO, CO and its isotopologs, and other molecules to ensure a self-consistent data set for analysis. An overview of the scientific motivation and observational strategy of the program is given, together with the modeling approach and analysis tools that have been developed. Initial science results are presented. These include a lack of water in cold gas at abundances that are lower than most predictions, strong water emission from shocks in protostellar environments, the importance of UV radiation in heating the gas along outflow walls across the full range of luminosities, and surprisingly widespread detection of the chemically related hydrides OH+ and H2O+ in outflows and foreground gas. Quantitative estimates of the energy budget indicate that H2O is generally not the dominant coolant in the warm dense gas associated with protostars. Very deep limits on the cold gaseous water reservoir in the outer regions of protoplanetary disks are obtained that have profound implications for our understanding of grain growth and mixing in disks.
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  • van Kempen, T. A., et al. (author)
  • Origin of the hot gas in low-mass protostars Herschel-PACS spectroscopy of HH 46
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L121
  • Journal article (peer-reviewed)abstract
    • Aims. "Water In Star-forming regions with Herschel" (WISH) is a Herschel key programme aimed at understanding the physical and chemical structure of young stellar objects (YSOs) with a focus on water and related species. Methods. The low-mass protostar HH 46 was observed with the Photodetector Array Camera and Spectrometer (PACS) on the Herschel Space Observatory to measure emission in H2O, CO, OH, [O I], and [C II] lines located between 63 and 186 mu m. The excitation and spatial distribution of emission can disentangle the different heating mechanisms of YSOs, with better spatial resolution and sensitivity than previously possible. Results. Far-IR line emission is detected at the position of the protostar and along the outflow axis. The OH emission is concentrated at the central position, CO emission is bright at the central position and along the outflow, and H2O emission is concentrated in the outflow. In addition, [O I] emission is seen in low-velocity gas, assumed to be related to the envelope, and is also seen shifted up to 170 km s(-1) in both the red-and blue-shifted jets. Envelope models are constructed based on previous observational constraints. They indicate that passive heating of a spherical envelope by the protostellar luminosity cannot explain the high-excitation molecular gas detected with PACS, including CO lines with upper levels at >2500 K above the ground state. Instead, warm CO and H2O emission is probably produced in the walls of an outflow-carved cavity in the envelope, which are heated by UV photons and non-dissociative C-type shocks. The bright OH and [O I] emission is attributed to J-type shocks in dense gas close to the protostar. In the scenario described here, the combined cooling by far-IR lines within the central spatial pixel is estimated to be 2 x 10(-2) L-circle dot, with 60-80% attributed to J- and C-type shocks produced by interactions between the jet and the envelope.
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  • Wampfler, S. F., et al. (author)
  • Herschel observations of the hydroxyl radical (OH) in young stellar objects
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L36-
  • Journal article (peer-reviewed)abstract
    • Aims: “Water In Star-forming regions with Herschel” (WISH) is a Herschel key program investigating the water chemistry in young stellar objects (YSOs) during protostellar evolution. Hydroxyl (OH) is one of the reactants in the chemical network most closely linked to the formation and destruction of H2O. High-temperature (T ⪆ 250 K) chemistry connects OH and H2O through the OH + H2 Leftrightarrow H2O + H reactions. Formation of H2O from OH is efficient in the high-temperature regime found in shocks and the innermost part of protostellar envelopes. Moreover, in the presence of UV photons, OH can be produced from the photo-dissociation of H2O through H2O + γUV Rightarrow OH + H. Methods: High-resolution spectroscopy of the 163.12 μm triplet of OH towards HH 46 and NGC 1333 IRAS 2A was carried out with the Heterodyne Instrument for the Far Infrared (HIFI) on board the Herschel Space Observatory. The low- and intermediate-mass protostars HH 46, TMR 1, IRAS 15398-3359, DK Cha, NGC 7129 FIRS 2, and NGC 1333 IRAS 2A were observed with the Photodetector Array Camera and Spectrometer (PACS) on Herschel in four transitions of OH and two [O i] lines. Results: The OH transitions at 79, 84, 119, and 163 μm and [O i] emission at 63 and 145 μm were detected with PACS towards the class I low-mass YSOs as well as the intermediate-mass and class I Herbig Ae sources. No OH emission was detected from the class 0 YSO NGC 1333 IRAS 2A, though the 119 μm was detected in absorption. With HIFI, the 163.12 μm was not detected from HH 46 and only tentatively detected from NGC 1333 IRAS 2A. The combination of the PACS and HIFI results for HH 46 constrains the line width (FWHM ⪆ 11 km s-1) and indicates that the OH emission likely originates from shocked gas. This scenario is supported by trends of the OH flux increasing with the [O i] flux and the bolometric luminosity, as found in our sample. Similar OH line ratios for most sources suggest that OH has comparable excitation temperatures despite the different physical properties of the sources. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Appendices (page 6) are only available in electronic form at http://www.aanda.org
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  • Yildiz, U. A., et al. (author)
  • Herschel/HIFI observations of high-J CO lines in the NGC 1333 low-mass star-forming region
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L40-
  • Journal article (peer-reviewed)abstract
    • Herschel/HIFI observations of high-J lines (up to J(u) = 10) of (CO)-C-12, (CO)-C-13 and (CO)-O-18 are presented toward three deeply embedded low-mass protostars, NGC 1333 IRAS 2A, IRAS 4A, and IRAS 4B, obtained as part of the Water In Star-forming regions with Herschel (WISH) key program. The spectrally-resolved HIFI data are complemented by ground-based observations of lower-J CO and isotopologue lines. The (CO)-C-12 10-9 profiles are dominated by broad (FWHM 25-30 km s(-1)) emission. Radiative transfer models are used to constrain the temperature of this shocked gas to 100-200 K. Several CO and (CO)-C-13 line profiles also reveal a medium-broad component (FWHM5-10 km s(-1)), seen prominently in H2O lines. Column densities for both components are presented, providing a reference for determining abundances of other molecules in the same gas. The narrow (CO)-O-18 9-8 lines probe the warmer part of the quiescent envelope. Their intensities require a jump in the CO abundance at an evaporation temperature around 25 K, thus providing new direct evidence for a CO ice evaporation zone around low-mass protostars.
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  • Benz, A. O., et al. (author)
  • Hydrides in young stellar objects : Radiation tracers in a protostar-disk-outflow system
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L35-
  • Journal article (peer-reviewed)abstract
    • Context. Hydrides of the most abundant heavier elements are fundamental molecules in cosmic chemistry. Some of them trace gas irradiated by UV or X-rays. Aims: We explore the abundances of major hydrides in W3 IRS5, a prototypical region of high-mass star formation. Methods: W3 IRS5 was observed by HIFI on the Herschel Space Observatory with deep integration (≃2500 s) in 8 spectral regions. Results: The target lines including CH, NH, H3O+, and the new molecules SH+, H2O+, and OH+ are detected. The H2O+ and OH+ J = 1-0 lines are found mostly in absorption, but also appear to exhibit weak emission (P-Cyg-like). Emission requires high density, thus originates most likely near the protostar. This is corroborated by the absence of line shifts relative to the young stellar object (YSO). In addition, H2O+ and OH+ also contain strong absorption components at a velocity shifted relative to W3 IRS5, which are attributed to foreground clouds. Conclusions: The molecular column densities derived from observations correlate well with the predictions of a model that assumes the main emission region is in outflow walls, heated and irradiated by protostellar UV radiation. Herschel is an ESA space observatory with science instruments provided by a European-led Principal Investigator consortia and with important participation from NASA.Appendix (page 5) is only available in electronic form at http://www.aanda.org
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29.
  • Bergin, E. A., et al. (author)
  • Sensitive limits on the abundance of cold water vapor in the DM Tauri protoplanetary disk
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L33-
  • Journal article (peer-reviewed)abstract
    • We performed a sensitive search for the ground-state emission lines of ortho-and para-water vapor in the DM Tau protoplanetary disk using the Herschel/HIFI instrument. No strong lines are detected down to 3 sigma levels in 0.5 km s(-1) channels of 4.2 mK for the 1(10)-1(01) line and 12.6 mK for the 1(11)-0(00) line. We report a very tentative detection, however, of the 1(10)-1(01) line in the wide band spectrometer, with a strength of T-mb = 2.7 mK, a width of 5.6 km s(-1) and an integrated intensity of 16.0 mK km s(-1). The latter constitutes a 6 sigma detection. Regardless of the reality of this tentative detection, model calculations indicate that our sensitive limits on the line strengths preclude efficient desorption of water in the UV illuminated regions of the disk. We hypothesize that more than 95-99% of the water ice is locked up in coagulated grains that have settled to the midplane.
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30.
  • Bruderer, S., et al. (author)
  • Herschel/HIFI detections of hydrides towards AFGL 2591. Envelope emission versus tenuous cloud absorption
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L44-
  • Journal article (peer-reviewed)abstract
    • The Heterodyne Instrument for the Far Infrared (HIFI) onboard the Herschel Space Observatory allows the first observations of light diatomic molecules at high spectral resolution and in multiple transitions. Here, we report deep integrations using HIFI in different lines of hydrides towards the high-mass star forming region AFGL 2591. Detected are CH, CH+, NH, OH+, H2O+, while NH+ and SH+ have not been detected. All molecules except for CH and CH+ are seen in absorption with low excitation temperatures and at velocities different from the systemic velocity of the protostellar envelope. Surprisingly, the CH(JF,P = 3/22,- - 1/21,+ ) and CH+(J = 1-0, J = 2-1) lines are detected in emission at the systemic velocity. We can assign the absorption features to a foreground cloud and an outflow lobe, while the CH and CH+ emission stems from the envelope. The observed abundance and excitation of CH and CH+ can be explained in the scenario of FUV irradiated outflow walls, where a cavity etched out by the outflow allows protostellar FUV photons to irradiate and heat the envelope at larger distances driving the chemical reactions that produce these molecules. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.Apppendices and Table 1 (pages 6 to 7) are only available in electronic form at http://www.aanda.org
  •  
31.
  • Chavarria, L., et al. (author)
  • Water in massive star-forming regions : HIFI observations of W3 IRS5
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L37-
  • Journal article (peer-reviewed)abstract
    • We present Herschel observations of the water molecule in the massive star-forming region W3 IRS5. The o-(H2O)-O-17 1(10)-1(01), p-(H2O)-O-18 1(11)-0(00), p-H2O 2(02)-1(11), p-H2O 1(11)-0(00), o-H2O 2(21)-2(12), and o-H2O 2(12)-1(01) lines, covering a frequency range from 552 up to 1669 GHz, have been detected at high spectral resolution with HIFI. The water lines in W3 IRS5 show well-defined high-velocity wings that indicate a clear contribution by outflows. Moreover, the systematically blue-shifted absorption in the H2O lines suggests expansion, presumably driven by the outflow. No infall signatures are detected. The p-H2O 1(11)-0(00) and o-H2O 2(12)-1(01) lines show absorption from the cold material (T similar to 10 K) in which the high-mass protostellar envelope is embedded. One-dimensional radiative transfer models are used to estimate water abundances and to further study the kinematics of the region. We show that the emission in the rare isotopologues comes directly from the inner parts of the envelope (T greater than or similar to 100 K) where water ices in the dust mantles evaporate and the gas-phase abundance increases. The resulting jump in the water abundance (with a constant inner abundance of 10(-4)) is needed to reproduce the o-(H2O)-O-17 1(10)-1(01) and p-(H2O)-O-18 1(11)-0(00) spectra in our models. We estimate water abundances of 10(-8) to 10(-9) in the outer parts of the envelope (T less than or similar to 100 K). The possibility of two protostellar objects contributing to the emission is discussed.
  •  
32.
  • Benz, A. O., et al. (author)
  • Water in star-forming regions with Herschel (WISH): VI. Constraints on UV and X-ray irradiation from a survey of hydrides in low- to high-mass young stellar objects
  • 2016
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 590, s. Art. no. A105-
  • Journal article (peer-reviewed)abstract
    • Context. Hydrides are simple compounds containing one or a few hydrogen atoms bonded to a heavier atom. They are fundamental precursor molecules in cosmic chemistry and many hydride ions have become observable in high quality for the first time thanks to the Herschel Space Observatory. Ionized hydrides such as CH+ and OH+ (and also HCO+), which affect the chemistry of molecules such as water, provide complementary information on irradiation by far-UV (FUV) or X-rays and gas temperature. Aims. We explore hydrides of the most abundant heavier elements in an observational survey covering young stellar objects (YSOs) with different mass and evolutionary state. The focus is on hydrides associated with the dense protostellar envelope and outflows, contrary to previous work that focused on hydrides in diffuse foreground clouds. Methods. Twelve YSOs were observed with HIFI on Herschel in six spectral settings providing fully velocity-resolved line profiles as part of the Water in star-forming regions with Herschel (WISH) program. The YSOs include objects of low (Class 0 and I), intermediate, and high mass, with luminosities ranging from 4 L? to 2 × 105 L?. Results. The targeted lines of CH+, OH+, H2O+, C+, and CH are detected mostly in blue-shifted absorption. H3O+ and SH+ are detected in emission and only toward some high-mass objects. The observed line parameters and correlations suggest two different origins related to gas entrained by the outflows and to the circumstellar envelope. The derived column densities correlate with bolometric luminosity and envelope mass for all molecules, best for CH, CH+, and HCO+. The column density ratios of CH+/OH+ are estimated from chemical slab models, assuming that the H2 density is given by the specific density model of each object at the beam radius. For the low-mass YSOs the observed ratio can be reproduced for an FUV flux of 2-400 times the interstellar radiation field (ISRF) at the location of the molecules. In two high-mass objects, the UV flux is 20-200 times the ISRF derived from absorption lines, and 300-600 ISRF using emission lines. Upper limits for the X-ray luminosity can be derived from H3O+ observations for some low-mass objects. Conclusions. If the FUV flux required for low-mass objects originates at the central protostar, a substantial FUV luminosity, up to 1.5 L?, is required. There is no molecular evidence for X-ray induced chemistry in the low-mass objects on the observed scales of a few 1000 AU. For high-mass regions, the FUV flux required to produce the observed molecular ratios is smaller than the unattenuated flux expected from the central object(s) at the Herschel beam radius. This is consistent with an FUV flux reduced by circumstellar extinction or by bloating of the protostar.
  •  
33.
  • de Graauw, Th., et al. (author)
  • The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
  • Journal article (peer-reviewed)abstract
    • Aims: This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI) that was launched onboard ESA's Herschel Space Observatory in May 2009. Methods: The instrument is a set of 7 heterodyne receivers that are electronically tuneable, covering 480-1250 GHz with SIS mixers and the 1410-1910 GHz range with hot electron bolometer (HEB) mixers. The local oscillator (LO) subsystem comprises a Ka-band synthesizer followed by 14 chains of frequency multipliers and 2 chains for each frequency band. A pair of auto-correlators and a pair of acousto-optical spectrometers process the two IF signals from the dual-polarization, single-pixel front-ends to provide instantaneous frequency coverage of 2 × 4 GHz, with a set of resolutions (125 kHz to 1 MHz) that are better than 0.1 km s-1. Results: After a successful qualification and a pre-launch TB/TV test program, the flight instrument is now in-orbit and completed successfully the commissioning and performance verification phase. The in-orbit performance of the receivers matches the pre-launch sensitivities. We also report on the in-orbit performance of the receivers and some first results of HIFI's operations. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important participation from NASA.
  •  
34.
  • Elks, Cathy E, et al. (author)
  • Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
  • 2010
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
  • Journal article (peer-reviewed)abstract
    • To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
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35.
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36.
  • Johnstone, D., et al. (author)
  • Herschel/HIFI spectroscopy of the intermediate mass protostar NGC7129 FIRS 2
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L41-
  • Journal article (peer-reviewed)abstract
    • Herschel/HIFI observations of water from the intermediate mass protostar NGC 7129 FIRS 2 provide a powerful diagnostic of the physical conditions in this star formation environment. Six spectral settings, covering four (H2O)-O-16 and two (H2O)-O-18 lines, were observed and all but one (H2O)-O-18 line were detected. The four (H2O)-O-16 lines discussed here share a similar morphology: a narrower, approximate to 6kms(-1), component centered slightly redward of the systemic velocity of NGC7129 FIRS 2 and a much broader, approximate to 25 km s(-1) component centered blueward and likely associated with powerful outflows. The narrower components are consistent with emission from water arising in the envelope around the intermediate mass protostar, and the abundance of H2O is constrained to approximate to 10(-7) for the outer envelope. Additionally, the presence of a narrow self-absorption component for the lowest energy lines is likely due to self-absorption from colder water in the outer envelope. The broader component, where the H2O/CO relative abundance is found to be approximate to 0.2, appears to be tracing the same energetic region that produces strong CO emission at high J.
  •  
37.
  • Karska, A., et al. (author)
  • Water in star-forming regions with Herschel (WISH) III. Far-infrared cooling lines in low-mass young stellar objects
  • 2013
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 552
  • Journal article (peer-reviewed)abstract
    • Context. Understanding the physical phenomena involved in the earlierst stages of protostellar evolution requires knowledge of the heating and cooling processes that occur in the surroundings of a young stellar object. Spatially resolved information from its constituent gas and dust provides the necessary constraints to distinguish between different theories of accretion energy dissipation into the envelope.Aims. Our aims are to quantify the far-infrared line emission from low-mass protostars and the contribution of different atomic and molecular species to the gas cooling budget, to determine the spatial extent of the emission, and to investigate the underlying excitation conditions. Analysis of the line cooling will help us characterize the evolution of the relevant physical processes as the protostar ages.Methods. Far-infrared Herschel-PACS spectra of 18 low-mass protostars of various luminosities and evolutionary stages are studied in the context of the WISH key program. For most targets, the spectra include many wavelength intervals selected to cover specific CO, H2O, OH, and atomic lines. For four targets the spectra span the entire 55-200 mu m region. The PACS field-of-view covers similar to 47 '' with the resolution of 9.4 ''.Results. Most of the protostars in our sample show strong atomic and molecular far-infrared emission. Water is detected in 17 out of 18 objects (except TMC1A), including 5 Class I sources. The high-excitation H2O 8(18)-7(07) 63.3 mu m line (E-u/k(B) = 1071 K) is detected in 7 sources. CO transitions from J = 14-13 up to J = 49-48 are found and show two distinct temperature components on Boltzmann diagrams with rotational temperatures of similar to 350 K and similar to 700 K. H2O has typical excitation temperatures of similar to 150 K. Emission from both Class 0 and I sources is usually spatially extended along the outflow direction but with a pattern that depends on the species and the transition. In the extended sources, emission is stronger off source and extended on >= 10 000 AU scales; in the compact sample, more than half of the flux originates within 1000 AU of the protostar. The H2O line fluxes correlate strongly with those of the high-J CO lines, both for the full array and for the central position, as well as with the bolometric luminosity and envelope mass. They correlate less strongly with OH fluxes and not with [O I] fluxes. In contrast, [O I] and OH often peak together at the central position.Conclusions. The PACS data probe at least two physical components. The H2O and CO emission very likely arises in non-dissociative (irradiated) shocks along the outflow walls with a range of pre-shock densities. Some OH is also associated with this component, most likely resulting from H2O photodissociation. UV-heated gas contributes only a minor fraction to the CO emission observed by PACS, based on the strong correlation between the shock-dominated CO 24-23 line and the CO 14-13 line. [O I] and some of the OH emission probe dissociative shocks in the inner envelope. The total far-infrared cooling is dominated by H2O and CO, with the fraction contributed by [O I] increasing for Class I sources. Consistent with previous studies, the ratio of total far-infrared line emission over bolometric luminosity decreases with the evolutionary state.
  •  
38.
  • Kristensen, L., et al. (author)
  • Water in star-forming regions with Herschel (WISH) II. Evolution of 557 GHz 1(10)-1(01) emission in low-mass protostars
  • 2012
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 542
  • Journal article (peer-reviewed)abstract
    • Context. Water is a key tracer of dynamics and chemistry in low-mass star-forming regions, but spectrally resolved observations have so far been limited in sensitivity and angular resolution, and only data from the brightest low-mass protostars have been published. Aims. The first systematic survey of spectrally resolved water emission in 29 low-mass (L 10 km s(-1)). The water abundance in the outer cold envelope is low, greater than or similar to 10(-10). The different H2O profile components show a clear evolutionary trend: in the younger Class 0 sources the emission is dominated by outflow components originating inside an infalling envelope. When large-scale infall diminishes during the Class I phase, the outflow weakens and H2O emission all but disappears.
  •  
39.
  • Nisini, B., et al. (author)
  • Water cooling of shocks in protostellar outflows. Herschel-PACS map of L1157
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L120-
  • Journal article (peer-reviewed)abstract
    • Context. The far-IR/sub-mm spectral mapping facility provided by the Herschel-PACS and HIFI instruments has made it possible to obtain, for the first time, images of H2O emission with a spatial resolution comparable to ground based mm/sub-mm observations. Aims: In the framework of the Water In Star-forming regions with Herschel (WISH) key program, maps in water lines of several outflows from young stars are being obtained, to study the water production in shocks and its role in the outflow cooling. This paper reports the first results of this program, presenting a PACS map of the o-H2O 179 μm transition obtained toward the young outflow L1157. Methods: The 179 μm map is compared with those of other important shock tracers, and with previous single-pointing ISO, SWAS, and Odin water observations of the same source that allow us to constrain the H2O abundance and total cooling. Results: Strong H2O peaks are localized on both shocked emission knots and the central source position. The H2O 179 μm emission is spatially correlated with emission from H2 rotational lines, excited in shocks leading to a significant enhancement of the water abundance. Water emission peaks along the outflow also correlate with peaks of other shock-produced molecular species, such as SiO and NH3. A strong H2O peak is also observed at the location of the proto-star, where none of the other molecules have significant emission. The absolute 179 μm intensity and its intensity ratio to the H2O 557 GHz line previously observed with Odin/SWAS indicate that the water emission originates in warm compact clumps, spatially unresolved by PACS, having a H2O abundance of the order of 10-4. This testifies that the clumps have been heated for a time long enough to allow the conversion of almost all the available gas-phase oxygen into water. The total H2O cooling is ~10-1 L_ȯ, about 40% of the cooling due to H2 and 23% of the total energy released in shocks along the L1157 outflow. Herschel is an ESA space observatory with science instruments provided by European-led Principal Investigator consortia and with important partecipation from NASA.
  •  
40.
  • Wyrowski, F., et al. (author)
  • Variations in H2O+/H2O ratios toward massive star-forming regions
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L34-
  • Journal article (peer-reviewed)abstract
    • Early results from the Herschel Space Observatory revealed the water cation H2O+ to be an abundant ingredient of the interstellar medium. Here we present new observations of the H2O and H2O+ lines at 1113.3 and 1115.2 GHz using the Herschel Space Observatory toward a sample of high-mass star-forming regions to observationally study the relation between H2O and H2O+. Nine out of ten sources show absorption from H2O+ in a range of environments: the molecular clumps surrounding the forming and newly formed massive stars, bright high-velocity outflows associated with the massive protostars, and unrelated low-density clouds along the line of sight. Column densities per velocity component of H2O+ are found in the range of 10(12) to a few 10(13) cm(-2). The highest N(H2O+) column densities are found in the outflows of the sources. The ratios of H2O+/H2O are determined in a range from 0.01 to a few and are found to differ strongly between the observed environments with much lower ratios in the massive (proto) cluster envelopes (0.01-0.1) than in outflows and diffuse clouds. Remarkably, even for source components detected in H2O in emission, H2O+ is still seen in absorption.
  •  
41.
  • Mottram, J. C., et al. (author)
  • Water in star-forming regions with Herschel (WISH)
  • 2014
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 572
  • Journal article (peer-reviewed)abstract
    • Context. Outflows are an important part of the star formation process as both the result of ongoing active accretion and one of the main sources of mechanical feedback on small scales. Water is the ideal tracer of these effects because it is present in high abundance for the conditions expected in various parts of the protostar, particularly the outflow. Aims. We constrain and quantify the physical conditions probed by water in the outflow-jet system for Class 0 and I sources. Methods. We present velocity-resolved Herschel HIFI spectra of multiple water-transitions observed towards 29 nearby Class 0/I protostars as part of the WISH guaranteed time key programme. The lines are decomposed into different Gaussian components, with each component related to one of three parts of the protostellar system; quiescent envelope, cavity shock and spot shocks in the jet and at the base of the outflow. We then use non-LTE radex models to constrain the excitation conditions present in the two outflow-related components. Results. Water emission at the source position is optically thick but effectively thin, with line ratios that do not vary with velocity, in contrast to CO. The physical conditions of the cavity and spot shocks are similar, with post-shock H-2 densities of order 10(5) -10(8) cm(-3) and H2O column densities of order 10(16) -10(18) cm(-2). H2O emission originates in compact emitting regions: for the spot shocks these correspond to point sources with radii of order 10-200 AU, while for the cavity shocks these come from a thin layer along the outflow cavity wall with thickness of order 1-30 AU. Conclusions. Water emission at the source position traces two distinct kinematic components in the outflow; J shocks at the base of the outflow or in the jet, and C shocks in a thin layer in the cavity wall. The similarity of the physical conditions is in contrast to off-source determinations which show similar densities but lower column densities and larger filling factors. We propose that this is due to the differences in shock properties and geometry between these positions. Class I sources have similar excitation conditions to Class 0 sources, but generally smaller line-widths and emitting region sizes. We suggest that it is the velocity of the wind driving the outflow, rather than the decrease in envelope density or mass, that is the cause of the decrease in H2O intensity between Class 0 and I sources.
  •  
42.
  • Beecham, Ashley H, et al. (author)
  • Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
  • 2013
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
  • Journal article (peer-reviewed)abstract
    • Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
  •  
43.
  • Frisoni, G. B., et al. (author)
  • Dementia prevention in memory clinics: recommendations from the European task force for brain health services
  • 2023
  • In: Lancet Regional Health-Europe. - : Elsevier BV. - 2666-7762. ; 26
  • Journal article (peer-reviewed)abstract
    • Observational population studies indicate that prevention of dementia and cognitive decline is being accomplished, possibly as an unintended result of better vascular prevention and healthier lifestyles. Population aging in the coming decades requires deliberate efforts to further decrease its prevalence and societal burden. Increasing evidence sup-ports the efficacy of preventive interventions on persons with intact cognition and high dementia risk. We report recommendations for the deployment of second-generation memory clinics (Brain Health Services) whose mission is evidence-based and ethical dementia prevention in at-risk individuals. The cornerstone interventions consist of (i) assessment of genetic and potentially modifiable risk factors including brain pathology, and risk stratification, (ii) risk communication with ad-hoc protocols, (iii) risk reduction with multi-domain interventions, and (iv) cognitive enhancement with cognitive and physical training. A roadmap is proposed for concept validation and ensuing clinical deployment.
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44.
  •  
45.
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46.
  •  
47.
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48.
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49.
  • Stolk, Lisette, et al. (author)
  • Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
  • 2012
  • In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
  • Journal article (peer-reviewed)abstract
    • To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
  •  
50.
  • Vermunt, L., et al. (author)
  • Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype
  • 2019
  • In: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:7, s. 888-898
  • Journal article (peer-reviewed)abstract
    • Introduction: We estimated the age-specific duration of the preclinical, prodromal, and dementia stages of Alzheimer's disease (AD) and the influence of sex, setting, apolipoprotein E (APOE) genotype, and cerebrospinal fluid tau on disease duration. Methods: We performed multistate modeling in a combined sample of 6 cohorts (n = 3268) with death as the end stage and estimated the preclinical, prodromal, and dementia stage duration. Results: The overall AD duration varied between 24 years (age 60) and 15 years (age 80). For individuals presenting with preclinical AD, age 70, the estimated preclinical AD duration was 10 years, prodromal AD 4 years, and dementia 6 years. Male sex, clinical setting, APOE epsilon 4 allele carriership, and abnormal cerebrospinal fluid tau were associated with a shorter duration, and these effects depended on disease stage. Discussion: Estimates of AD disease duration become more accurate if age, sex, setting, APOE, and cerebrospinal fluid tau are taken into account. This will be relevant for clinical practice and trial design. (C) 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
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