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| 5. |
- 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. |
- 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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| 7. |
- 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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| 8. |
- 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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| 16. |
- 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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| 17. |
- 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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| 19. |
- 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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| 20. |
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| 21. |
- Underwood, J, et al.
(författare)
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Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
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Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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| 24. |
- 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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| 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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| 26. |
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| 27. |
- Spronk, H. M. H., et al.
(författare)
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Atherothrombosis and Thromboembolism : Position Paper from the Second Maastricht Consensus Conference on Thrombosis
- 2018
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Ingår i: Thrombosis and Haemostasis. - : SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN. - 0340-6245 .- 2567-689X. ; 118:2, s. 229-250
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Forskningsöversikt (refereegranskat)abstract
- Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in) stability; proteomic and metabolomics data are to be added to genetic information.2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; diseasemechanism-based biomarkers need to be identified; experimental systems are needed that incorporatewhole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin-angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet-fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis a vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia-reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novelmodified activated protein C-based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor.
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| 31. |
- 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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| 32. |
- 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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| 33. |
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| 34. |
- Frisoni, G. B., et al.
(författare)
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Dementia prevention in memory clinics: recommendations from the European task force for brain health services
- 2023
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Ingår i: Lancet Regional Health-Europe. - : Elsevier BV. - 2666-7762. ; 26
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Tidskriftsartikel (refereegranskat)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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| 35. |
- 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. |
- van Dishoeck, E. F., et al.
(författare)
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Water in Star-forming Regions with the Herschel Space Observatory (WISH). I. Overview of Key Program and First Results
- 2011
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 123:900, s. 138-170
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Tidskriftsartikel (refereegranskat)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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| 37. |
- 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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| 38. |
- Bauermeister, S, et al.
(författare)
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The Dementias Platform UK (DPUK) Data Portal
- 2020
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Ingår i: European journal of epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 35:6, s. 601-611
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Tidskriftsartikel (refereegranskat)abstract
- The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
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| 39. |
- 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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| 40. |
- 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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| 41. |
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| 42. |
- van Kempen, T. A., et al.
(författare)
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Origin of the hot gas in low-mass protostars Herschel-PACS spectroscopy of HH 46
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L121
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Tidskriftsartikel (refereegranskat)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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| 43. |
- 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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| 44. |
- Gurvits, L. I., et al.
(författare)
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The science case and challenges of spaceborne sub-millimeter interferometry: the study case of TeraHertz Exploration and Zooming-in for Astrophysics (THEZA)
- 2021
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Ingår i: Proceedings of the International Astronautical Congress, IAC. - 0074-1795. ; A7
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Konferensbidrag (refereegranskat)abstract
- Ultra-high angular resolution in astronomy has always been an important vehicle for making fundamental discoveries. Recent results in direct imaging of the vicinity of the super-massive black hole in the nucleus of the radio galaxy M87 by the millimeter VLBI system Event Horizon Telescope (EHT) and various pioneering results of the Space VLBI mission RadioAstron provided new momentum in high angular resolution astrophysics. In both mentioned cases, the angular resolution reached the values of about 10−20 microrcseconds (0.05−0.1 nanoradian). Angular resolution is proportional to the observing wavelength and inversely proportional to the interferometer baseline length. In the case of Earth-based EHT, the highest angular resolution was achieved by combining the shortest possible wavelength of 1.3 mm with the longest possible baselines, comparable to the Earth’s diameter. For RadioAstron, operational wavelengths were in the range from 92 cm down to 1.3 cm, but the baselines were as long as ∼350,000 km. However, these two highlights of radio astronomy, EHT and RadioAstron do not”saturate” the interest to further increase in angular resolution. Quite opposite: the science case for further increase in angular resolution of astrophysical studies becomes even stronger. A natural and, in fact, the only possible way of moving forward is to enhance mm/sub-mm VLBI by extending baselines to extraterrestrial dimensions, i.e. creating a mm/sub-mm Space VLBI system. The inevitable move toward space-borne mm/sub-mm VLBI is a subject of several concept studies. In this presentation we will focus on one of them called TeraHertz Exploration and Zooming-in for Astrophysics (THEZA), prepared in response to the ESA’s call for its next major science program Voyage 2050 (Gurvits et al. 2021). The THEZA rationale is focused at the physics of spacetime in the vicinity of super-massive black holes as the leading science drive. However, it will also open up a sizable new range of hitherto unreachable parameters of observational radio astrophysics and create a multi-disciplinary scientific facility and offer a high degree of synergy with prospective “single dish” space-borne sub-mm astronomy (e.g., Wiedner et al. 2021) and infrared interferometry (e.g., Linz et al. 2021). As an amalgam of several major trends of modern observational astrophysics, THEZA aims at facilitating a breakthrough in high-resolution high image quality astronomical studies.
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| 45. |
- Wampfler, S. F., et al.
(författare)
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Herschel observations of the hydroxyl radical (OH) in young stellar objects
- 2010
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 521, s. L36-
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Tidskriftsartikel (refereegranskat)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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| 46. |
- 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
-
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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| 47. |
- Cozen, W., et al.
(författare)
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A meta-analysis of Hodgkin lymphoma reveals 19p13.3 TCF3 as a novel susceptibility locus
- 2014
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 5, s. 3856-
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR) = 0.81, 95% confidence interval (95% CI) = 0.76-0.86, P-combined 3.5 x 10(-10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B-and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
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| 48. |
- 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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| 49. |
- Elks, Cathy E, et al.
(författare)
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Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
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Tidskriftsartikel (refereegranskat)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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| 50. |
- 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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