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2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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3. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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4. |
- Khatri, C, et al.
(författare)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Tidskriftsartikel (refereegranskat)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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5. |
- Abazov, M, et al.
(författare)
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Evidence of WW and WZ Production with lepton plus jets Final States in pp Collisions at root s=1.96 TeV
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:16, s. 161801-
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Tidskriftsartikel (refereegranskat)abstract
- We present first evidence for WW+WZ production in lepton+jets final states at a hadron collider. The data correspond to 1.07 fb(-1) of integrated luminosity collected with the D0 detector at the Fermilab Tevatron in pp collisions at root s=1.96 TeV. The observed cross section for WW+WZ production is 20.2 +/- 4.5 pb, consistent with the standard model and more precise than previous measurements in fully leptonic final states. The probability that background fluctuations alone produce this excess is < 5.4x10(-6), which corresponds to a significance of 4.4 standard deviations.
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- Abazov, M, et al.
(författare)
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Search for Long-Lived Charged Massive Particles with the D0 Detector
- 2009
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:16, s. 161802-
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Tidskriftsartikel (refereegranskat)abstract
- We search for long-lived charged massive particles using 1.1 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron pp Collider. Time-of-flight information is used to search for pair produced long-lived tau sleptons, gauginolike charginos, and Higgsino-like charginos. We find no evidence of a signal and set 95% C.L. cross section upper limits for staus, which vary from 0.31 to 0.04 pb for stau masses between 60 and 300 GeV. We also set lower mass limits of 206 GeV (171 GeV) for pair produced charged gauginos (Higgsinos).
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7. |
- Abazov, V. M., et al.
(författare)
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Measurement of the top quark pair production cross section in the lepton plus jets channel in proton-antiproton collisions at root s=1.96 TeV
- 2011
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 84:1, s. 012008-
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Tidskriftsartikel (refereegranskat)abstract
- We present a measurement of the inclusive top quark pair production cross section in p (p) over bar collisions at root s = 1.96 TeV utilizing data corresponding to an integrated luminosity of 5.3 fb(-1) collected with the D0 detector at the Fermilab Tevatron Collider. We consider final states containing one high-p(T) isolated electron or muon and at least two jets, and we perform three analyses: one exploiting specific kinematic features of t (t) over bar events, the second using b-jet identification, and the third using both techniques to separate the t (t) over bar signal from the background. In the third case, we determine simultaneously the t (t) over bar cross section and the ratio of the production rates of W + heavy flavor jets and W + light flavor jets, which reduces the impact of the systematic uncertainties related to the background estimation. Assuming a top quark mass of 172.5 GeV, we obtain sigma(t (t) over bar) = 7.78(-0.64)(-0.77)pb. This result agrees with predictions of the standard model.
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8. |
- Abazov, V. M., et al.
(författare)
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Muon reconstruction and identification with the Run II D0 detector
- 2014
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Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 737, s. 281-294
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Tidskriftsartikel (refereegranskat)abstract
- We present an overview of the muon reconstruction and identification methods employed by the DO collaboration to analyze the Run II (2001-2011) p (p) over bar data of the Fermilab Tevatron collider at root s = 1.96 TeV. We discuss the performance of these methods, how it is measured using DO data, and how it is properly modeled by the DO simulation program. In its pseudorapidity acceptance, vertical bar eta vertical bar < 2, the muon system identifies high-p(T) muons (p(T) greater than or similar to 10 GeV) with efficiencies ranging from 72% to 89%. Muons tracks are reconstructed in the DO central tracking system with efficiencies ranging from 85% to 92% and with a typical relative momentum resolution of 10% for p(T) = 40 GeV. Isolation criteria reject multijet background with efficiencies of 87-99%.
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11. |
- Jin, S. C., et al.
(författare)
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Mutations disrupting neuritogenesis genes confer risk for cerebral palsy
- 2020
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:10
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Tidskriftsartikel (refereegranskat)abstract
- Whole-exome sequencing of 250 parent-offspring trios identifies an enrichment of rare damaging de novo mutations in individuals with cerebral palsy and implicates genetically mediated dysregulation of early neuronal connectivity in the etiology of this disorder. In addition to commonly associated environmental factors, genomic factors may cause cerebral palsy. We performed whole-exome sequencing of 250 parent-offspring trios, and observed enrichment of damaging de novo mutations in cerebral palsy cases. Eight genes had multiple damaging de novo mutations; of these, two (TUBA1AandCTNNB1) met genome-wide significance. We identified two novel monogenic etiologies,FBXO31andRHOB, and showed that theRHOBmutation enhances active-state Rho effector binding while theFBXO31mutation diminishes cyclin D levels. Candidate cerebral palsy risk genes overlapped with neurodevelopmental disorder genes. Network analyses identified enrichment of Rho GTPase, extracellular matrix, focal adhesion and cytoskeleton pathways. Cerebral palsy risk genes in enriched pathways were shown to regulate neuromotor function in aDrosophilareverse genetics screen. We estimate that 14% of cases could be attributed to an excess of damaging de novo or recessive variants. These findings provide evidence for genetically mediated dysregulation of early neuronal connectivity in cerebral palsy.
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- Feroci, M., et al.
(författare)
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LOFT - The large observatory for x-ray timing
- 2012
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE - International Society for Optical Engineering. - 9780819491442 ; , s. 84432D-
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Konferensbidrag (refereegranskat)abstract
- The LOFT mission concept is one of four candidates selected by ESA for the M3 launch opportunity as Medium Size missions of the Cosmic Vision programme. The launch window is currently planned for between 2022 and 2024. LOFT is designed to exploit the diagnostics of rapid X-ray flux and spectral variability that directly probe the motion of matter down to distances very close to black holes and neutron stars, as well as the physical state of ultradense matter. These primary science goals will be addressed by a payload composed of a Large Area Detector (LAD) and a Wide Field Monitor (WFM). The LAD is a collimated (<1 degree field of view) experiment operating in the energy range 2-50 keV, with a 10 m2 peak effective area and an energy resolution of 260 eV at 6 keV. The WFM will operate in the same energy range as the LAD, enabling simultaneous monitoring of a few-steradian wide field of view, with an angular resolution of <5 arcmin. The LAD and WFM experiments will allow us to investigate variability from submillisecond QPO's to yearlong transient outbursts. In this paper we report the current status of the project.
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14. |
- Feroci, M., et al.
(författare)
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The large observatory for x-ray timing
- 2014
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 9780819496126
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Konferensbidrag (refereegranskat)abstract
- The Large Observatory For x-ray Timing (LOFT) was studied within ESA M3 Cosmic Vision framework and participated in the final downselection for a launch slot in 2022-2024. Thanks to the unprecedented combination of effective area and spectral resolution of its main instrument, LOFT will study the behaviour of matter under extreme conditions, such as the strong gravitational field in the innermost regions of accretion flows close to black holes and neutron stars, and the supranuclear densities in the interior of neutron stars. The science payload is based on a Large Area Detector (LAD, 10 m2 effective area, 2-30 keV, 240 eV spectral resolution, 1° collimated field of view) and a Wide Field Monitor (WFM, 2-50 keV, 4 steradian field of view, 1 arcmin source location accuracy, 300 eV spectral resolution). The WFM is equipped with an on-board system for bright events (e.g. GRB) localization. The trigger time and position of these events are broadcast to the ground within 30 s from discovery. In this paper we present the status of the mission at the end of its Phase A study.
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15. |
- Kennicutt, M. C., et al.
(författare)
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Delivering 21st century Antarctic and Southern Ocean science
- 2016
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Ingår i: Antarctic Science. - 0954-1020 .- 1365-2079. ; 28, s. 407-423
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Tidskriftsartikel (refereegranskat)abstract
- © Antarctic Science Ltd 2016.The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process 'big data' collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together.
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- Fretwell, P., et al.
(författare)
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Bedmap2 : improved ice bed, surface and thickness datasets for Antarctica
- 2013
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Ingår i: The Cryosphere. - : Copernicus GmbH. - 1994-0416 .- 1994-0424. ; 7:1, s. 375-393
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Tidskriftsartikel (refereegranskat)abstract
- We present Bedmap2, a new suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60 degrees S. We derived these products using data from a variety of sources, including many substantial surveys completed since the original Bedmap compilation (Bedmap1) in 2001. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1. In most parts of Antarctica the subglacial landscape is visible in much greater detail than was previously available and the improved data-coverage has in many areas revealed the full scale of mountain ranges, valleys, basins and troughs, only fragments of which were previously indicated in local surveys. The derived statistics for Bedmap2 show that the volume of ice contained in the Antarctic ice sheet (27 million km(3)) and its potential contribution to sea-level rise (58 m) are similar to those of Bedmap1, but the mean thickness of the ice sheet is 4.6% greater, the mean depth of the bed beneath the grounded ice sheet is 72m lower and the area of ice sheet grounded on bed below sea level is increased by 10 %. The Bedmap2 compilation highlights several areas beneath the ice sheet where the bed elevation is substantially lower than the deepest bed indicated by Bedmap1. These products, along with grids of data coverage and uncertainty, provide new opportunities for detailed modelling of the past and future evolution of the Antarctic ice sheets.
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21. |
- Al-Khan, A., et al.
(författare)
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IFPA Meeting 2010 Workshops Report II: Placental pathology; Trophoblast invasion; Fetal sex; Parasites and the placenta; Decidua and embryonic or fetal loss; Trophoblast differentiation and syncytialisation
- 2011
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 32:Suppl. 2, s. 90-99
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb.4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications. (C) 2011 Published by IFPA and Elsevier Ltd.
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22. |
- Barthelmy, S D, et al.
(författare)
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An origin for short gamma-ray bursts unassociated with current star formation
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 438, s. 994-996
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Tidskriftsartikel (refereegranskat)abstract
- Two short (< 2 s) gamma-ray bursts (GRBs) have recently been localized(1-4) and fading afterglow counterparts detected(2-4). The combination of these two results left unclear the nature of the host galaxies of the bursts, because one was a star-forming dwarf, while the other was probably an elliptical galaxy. Here we report the X-ray localization of a short burst (GRB 050724) with unusual gamma-ray and X-ray properties. The X-ray afterglow lies off the centre of an elliptical galaxy at a redshift of z = 0.258 (ref. 5), coincident with the position determined by ground-based optical and radio observations(6-8). The low level of star formation typical for elliptical galaxies makes it unlikely that the burst originated in a supernova explosion. A supernova origin was also ruled out for GRB 050709 ( refs 3, 31), even though that burst took place in a galaxy with current star formation. The isotropic energy for the short bursts is 2 - 3 orders of magnitude lower than that for the long bursts. Our results therefore suggest that an alternative source of bursts - the coalescence of binary systems of neutron stars or a neutron star-black hole pair - are the progenitors of short bursts.
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29. |
- Ek, Weronica E, et al.
(författare)
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Germline genetic contributions to risk for esophageal adenocarcinoma, barrett's esophagus, and gastroesophageal reflux
- 2013
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 105:22, s. 1711-1718
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Tidskriftsartikel (refereegranskat)abstract
- Background Esophageal adenocarcinoma (EA) is an increasingly common cancer with poor survival. Barrett's esophagus (BE) is the main precursor to EA, and every year 0.12% to 0.5% of BE patients progress to EA. BE typically arises on a background of chronic gastroesophageal reflux (GERD), one of the risk factors for EA. Methods We used genome-wide association data to investigate the genetic architecture underlying GERD, BE, and EA. We applied a method to estimate the variance explained (array heritability, h2 g) and the genetic correlation (rg) between GERD, BE, and EA by considering all single nucleotide polymorphisms (SNPs) simultaneously. We also estimated the polygenic overlap between GERD, BE, and EA using a prediction approach. All tests were twosided, except in the case of variance-explained estimation where one-sided tests were used. Results We estimated a statistically significant genetic variance explained for BE (h2 g = 35%; standard error [SE] = 6%; one-sided P = 1 × 10-9) and for EA (h2 g = 25 %; SE = 5%; one-sided P = 2 × 10-7). The genetic correlation between BE and EA was found to be high (rg = 1.0; SE = 0.37). We also estimated a statistically significant polygenic overlap between BE and EA (one-sided P = 1 × 10-6), which suggests, together with the high genetic correlation, that shared genes underlie the development of BE and EA. Conversely, no statistically significant results were obtained for GERD. Conclusions We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases. © The Author 2013.
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30. |
- Ek, Weronica E, et al.
(författare)
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Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma
- 2016
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 138:5, s. 1146-1152
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Tidskriftsartikel (refereegranskat)abstract
- The strong male predominance in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p=0.002) and in males (p=0.003), but not in females separately (p=0.3). This association was found in tobacco smokers (p=0.003) and in BE patients without reflux (p=0.004), but not in nonsmokers (p=0.2) or those with reflux (p=0.036). SNPs within JMJD1C were associated with risk of EAC in females (p=0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.
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31. |
- Feroci, M., et al.
(författare)
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The Large Observatory for X-ray Timing (LOFT)
- 2012
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Ingår i: Experimental Astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 34:2, s. 415-444
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Tidskriftsartikel (refereegranskat)abstract
- High-time-resolution X-ray observations of compact objects provide direct access to strong-field gravity, to the equation of state of ultradense matter and to black hole masses and spins. A 10 m(2)-class instrument in combination with good spectral resolution is required to exploit the relevant diagnostics and answer two of the fundamental questions of the European Space Agency (ESA) Cosmic Vision Theme "Matter under extreme conditions", namely: does matter orbiting close to the event horizon follow the predictions of general relativity? What is the equation of state of matter in neutron stars? The Large Observatory For X-ray Timing (LOFT), selected by ESA as one of the four Cosmic Vision M3 candidate missions to undergo an assessment phase, will revolutionise the study of collapsed objects in our galaxy and of the brightest supermassive black holes in active galactic nuclei. Thanks to an innovative design and the development of large-area monolithic silicon drift detectors, the Large Area Detector (LAD) on board LOFT will achieve an effective area of similar to 12 m(2) (more than an order of magnitude larger than any spaceborne predecessor) in the 2-30 keV range (up to 50 keV in expanded mode), yet still fits a conventional platform and small/medium-class launcher. With this large area and a spectral resolution of < 260 eV, LOFT will yield unprecedented information on strongly curved spacetimes and matter under extreme conditions of pressure and magnetic field strength.
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32. |
- Gerber, Evgeny, et al.
(författare)
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The missing pieces of the PuO2 nanoparticle puzzle
- 2020
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Ingår i: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 12:35, s. 18039-18048
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Tidskriftsartikel (refereegranskat)abstract
- The nanoscience field often produces results more mystifying than any other discipline. It has been argued that changes in the plutonium dioxide (PuO2) particle size from bulk to nano can have a drastic effect on PuO2 properties. Here we report a full characterization of PuO2 nanoparticles (NPs) at the atomic level and probe their local and electronic structures by a variety of methods available at the synchrotron, including extended X-ray absorption fine structure (EXAFS) at the Pu L-3 edge, X-ray absorption near edge structure (XANES) in high energy resolution fluorescence detection (HERFD) mode at the Pu L-3 and M-4 edges, high energy X-ray scattering (HEXS) and X-ray diffraction (XRD). The particles were synthesized from precursors with different oxidation states of plutonium (III, IV, and V) under various environmentally and waste storage relevant conditions (pH 8 and pH > 10). Our experimental results analyzed with state-of-the-art theoretical approaches demonstrate that well dispersed, crystalline NPs with a size of similar to 2.5 nm in diameter are always formed in spite of diverse chemical conditions. Identical crystal structures and the presence of only the Pu(IV) oxidation state in all NPs, reported here for the first time, indicate that the structure of PuO2 NPs is very similar to that of the bulk PuO2. All methods give complementary information and show that investigated fundamental properties of PuO2 NPs, rather than being exotic, are very similar to those of the bulk PuO2.
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34. |
- Grossmann, Igor, et al.
(författare)
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Insights into the accuracy of social scientists' forecasts of societal change
- 2023
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Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7, s. 484-501
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Tidskriftsartikel (refereegranskat)abstract
- How well can social scientists predict societal change, and what processes underlie their predictions? To answer these questions, we ran two forecasting tournaments testing the accuracy of predictions of societal change in domains commonly studied in the social sciences: ideological preferences, political polarization, life satisfaction, sentiment on social media, and gender-career and racial bias. After we provided them with historical trend data on the relevant domain, social scientists submitted pre-registered monthly forecasts for a year (Tournament 1; N = 86 teams and 359 forecasts), with an opportunity to update forecasts on the basis of new data six months later (Tournament 2; N = 120 teams and 546 forecasts). Benchmarking forecasting accuracy revealed that social scientists' forecasts were on average no more accurate than those of simple statistical models (historical means, random walks or linear regressions) or the aggregate forecasts of a sample from the general public (N = 802). However, scientists were more accurate if they had scientific expertise in a prediction domain, were interdisciplinary, used simpler models and based predictions on prior data. How accurate are social scientists in predicting societal change, and what processes underlie their predictions? Grossmann et al. report the findings of two forecasting tournaments. Social scientists' forecasts were on average no more accurate than those of simple statistical models.
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35. |
- Lagergren, K., et al.
(författare)
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Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
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Tidskriftsartikel (refereegranskat)abstract
- Background The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed.
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36. |
- Law, Philip J., et al.
(författare)
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Association analyses identify 31 new risk loci for colorectal cancer susceptibility
- 2019
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.
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- Searle, Stephanie Y, et al.
(författare)
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Leaf respiration and alternative oxidase in field-grown alpine grasses respond to natural changes in temperature and light
- 2011
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 189:4, s. 1027-1039
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Tidskriftsartikel (refereegranskat)abstract
- • We report the first investigation of changes in electron partitioning via the alternative respiratory pathway (AP) and alternative oxidase (AOX) protein abundance in field-grown plants and their role in seasonal acclimation of respiration. • We sampled two alpine grasses native to New Zealand, Chionochloa rubra and Chionochloa pallens, from field sites of different altitudes, over 1 yr and also intensively over a 2-wk period. • In both species, respiration acclimated to seasonal changes in temperature through changes in basal capacity (R₁₀) but not temperature sensitivity (E₀). In C. pallens, acclimation of respiration may be associated with a higher AOX : cytochrome c oxidase (COX) protein abundance ratio. Oxygen isotope discrimination (D), which reflects relative changes in AP electron partitioning, correlated positively with daily integrated photosynthetically active radiation (PAR) in both species over seasonal timescales. Respiratory parameters, the AOX : COX protein ratio and D were stable over a 2-wk period, during which significant temperature changes were experienced in the field. • We conclude that respiration in Chionochloa spp. acclimates strongly to seasonal, but not to short-term, temperature variation. Alternative oxidase appears to be involved in the plant response to both seasonal changes in temperature and daily changes in light, highlighting the complexity of the function of AOX in the field.
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