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- Lind, Lars, et al.
(författare)
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Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
- 2021
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Ingår i: eLife. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)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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6. |
- Adrian-Martinez, S., et al.
(författare)
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A first search for coincident gravitational waves and high energy neutrinos using LIGO, Virgo and ANTARES data from 2007
- 2013
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Ingår i: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :6
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Tidskriftsartikel (refereegranskat)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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7. |
- Bixby, H., et al.
(författare)
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Rising rural body-mass index is the main driver of the global obesity epidemic in adults
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 569:7755, s. 260-4
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Tidskriftsartikel (refereegranskat)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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- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)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. |
- Adrian-Martinez, S., et al.
(författare)
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The First Combined Search For Neutrino Point-Sources In The Southern Hemisphere With The Antares And Icecube Neutrino Telescopes
- 2016
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 823:1
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Tidskriftsartikel (refereegranskat)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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13. |
- Barausse, Enrico, et al.
(författare)
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Prospects for fundamental physics with LISA
- 2020
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Ingår i: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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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14. |
- Bousquet, J., et al.
(författare)
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Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
- 2017
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
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Tidskriftsartikel (refereegranskat)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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- Wortman, J. R., et al.
(författare)
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The 2008 update of the Aspergillus nidulans genome annotation: A community effort
- 2009
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Ingår i: Fungal Genetics and Biology. - : Elsevier BV. - 1096-0937 .- 1087-1845. ; 46, s. S2-S13
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Tidskriftsartikel (refereegranskat)abstract
- The identification and annotation of protein-coding genes is one of the primary goals of whole-genome sequencing projects, and the accuracy of predicting the primary protein products of gene expression is vital to the interpretation of the available data and the design of downstream functional applications. Nevertheless, the comprehensive annotation of eukaryotic genomes remains a considerable challenge. Many genomes submitted to public databases, including those of major model organisms, contain significant numbers of wrong and incomplete gene predictions. We present a community-based reannotation of the Aspergillus nidulans genome with the primary goal of increasing the number and quality of protein functional assignments through the careful review of experts in the field of fungal biology. (C) 2009 Elsevier Inc. All rights reserved.
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- Vermunt, L., et al.
(författare)
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Duration of preclinical, prodromal, and dementia stages of Alzheimer's disease in relation to age, sex, and APOE genotype
- 2019
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Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 15:7, s. 888-898
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Tidskriftsartikel (refereegranskat)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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24. |
- de Graauw, Th., et al.
(författare)
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The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI)
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518, s. L6-
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Tidskriftsartikel (refereegranskat)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.
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25. |
- Heard, J. M., et al.
(författare)
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Availability, accessibility and delivery to patients of the 28 orphan medicines approved by the European Medicine Agency for hereditary metabolic diseases in the MetabERN network
- 2020
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Ingår i: Orphanet Journal of Rare Diseases. - : Springer Science and Business Media LLC. - 1750-1172. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The European Medicine Agency granted marketing approval to 164 orphan medicinal products for rare diseases, among which 28 products intended for the treatment of hereditary metabolic diseases. Taking advantage of its privileged connection with 69 healthcare centres of excellence in this field, MetabERN, the European Reference Network for hereditary metabolic diseases, performed a survey asking health care providers from 18 European countries whether these products are available on the market, reimbursed and therefore accessible for prescription, and actually delivered in their centre. Results Responses received from 52 centres (75%) concerned the design of treatment plans, the access to marketed products, and the barriers to delivery. Treatment options are always discussed with patients, who are often involved in their treatment plan. Most products (26/28) are available in most countries (15/18). Among the 15 broadly accessible products (88.5% of the centres), 9 are delivered to most patients (mean 70.1%), and the others to only few (16.5%). Among the 10 less accessible products (40.2% of the centres), 6 are delivered to many patients (66.7%), and 4 are rarely used (6.3%). Information was missing for 3 products. Delay between prescription and delivery is on average one month. Beside the lack of availability or accessibility, the most frequent reasons for not prescribing a treatment are patients' clinical status, characteristic, and personal choice. Conclusions Data collected from health care providers in the MetabERN network indicate that two-third of the orphan medicines approved by EMA for the treatment of hereditary metabolic diseases are accessible to treating patients, although often less than one-half of the patients with the relevant conditions actually received the approved product to treat their disease. Thus, in spite of the remarkable achievement of many products, patients concerned by EMA-approved orphan medicinal products have persistent unmet needs, which deserve consideration. The enormous investments made by the companies to develop products, and the high financial burden for the Member States to purchase these products emphasize the importance of a scrupulous appreciation of treatment value involving all stakeholders at early stage of development, before marketing authorization, and during follow up.
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- Benz, A. O., et al.
(författare)
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Hydrides in young stellar objects : Radiation tracers in a protostar-disk-outflow system
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L35-
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Tidskriftsartikel (refereegranskat)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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28. |
- Bergin, E. A., et al.
(författare)
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Sensitive limits on the abundance of cold water vapor in the DM Tauri protoplanetary disk
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L33-
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Tidskriftsartikel (refereegranskat)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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29. |
- Davies, J. I., et al.
(författare)
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Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report
- 2021
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Ingår i: Plos Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 18:8
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Tidskriftsartikel (refereegranskat)abstract
- Background Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. Methods and findings The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. Conclusions To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.
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31. |
- Feng, Shaohong, et al.
(författare)
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Dense sampling of bird diversity increases power of comparative genomics
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 587:7833
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Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity(1-4). Sparse taxon sampling has previously been proposed to confound phylogenetic inference(5), and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species. A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.
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32. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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33. |
- Kristensen, L. E., et al.
(författare)
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Water in low-mass star-forming regions with Herschel . HIFI spectroscopy of NGC 1333
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L30-
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Tidskriftsartikel (refereegranskat)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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36. |
- Yildiz, U. A., et al.
(författare)
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Herschel/HIFI observations of high-J CO lines in the NGC 1333 low-mass star-forming region
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L40-
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Tidskriftsartikel (refereegranskat)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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41. |
- Marseille, M. G., et al.
(författare)
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Water abundances in high-mass protostellar envelopes : Herschel observations with HIFI
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L32-
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Tidskriftsartikel (refereegranskat)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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43. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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44. |
- Schiava, M., et al.
(författare)
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Genotype-phenotype correlations in valosin-containing protein disease: a retrospective muticentre study
- 2022
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 93:10, s. 1099-1111
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Tidskriftsartikel (refereegranskat)abstract
- Background Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations. Methods Descriptive retrospective international study collecting clinical and genetic data of patients with mutations in the VCP gene. Results Two hundred and fifty-five patients (70.0% males) were included in the study. Mean age was 56.8 +/- 9.6 years and mean age of onset 45.6 +/- 9.3 years. Mean diagnostic delay was 7.7 +/- 6 years. Symmetric lower limb weakness was reported in 50% at onset progressing to generalised muscle weakness. Other common symptoms were ventilatory insufficiency 40.3%, PDB 28.2%, dysautonomia 21.4% and FTD 14.3%. Fifty-seven genetic variants were identified, 18 of these no previously reported. c.464G>A (p.Arg155His) was the most frequent variant, identified in the 28%. Full time wheelchair users accounted for 19.1% with a median time from disease onset to been wheelchair user of 8.5 years. Variant c.463C>T (p.Arg155Cys) showed an earlier onset (37.8 +/- 7.6 year) and a higher frequency of axial and upper limb weakness, scapular winging and cognitive impairment. Forced vital capacity (FVC) below 50% was as risk factor for being full-time wheelchair user, while FVC Conclusion This study expands the knowledge on the phenotypic presentation, natural history, genotype-phenotype correlations and risk factors for disease progression of VCP disease and is useful to improve the care provided to patient with this complex disease.
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45. |
- Stolk, Lisette, et al.
(författare)
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Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
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Tidskriftsartikel (refereegranskat)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.
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46. |
- van der Tak, F. F. S., et al.
(författare)
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Water abundance variations around high-mass protostars: HIFI observations of the DR21 region
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L107
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Tidskriftsartikel (refereegranskat)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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47. |
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48. |
- Bruderer, S., et al.
(författare)
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Herschel/HIFI detections of hydrides towards AFGL 2591. Envelope emission versus tenuous cloud absorption
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L44-
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Tidskriftsartikel (refereegranskat)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
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49. |
- Caselli, P., et al.
(författare)
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Water vapor toward starless cores : The Herschel view
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L29-
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Tidskriftsartikel (refereegranskat)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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50. |
- Chavarria, L., et al.
(författare)
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Water in massive star-forming regions : HIFI observations of W3 IRS5
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L37-
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Tidskriftsartikel (refereegranskat)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.
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