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1.
  • Abbasi, R., et al. (författare)
  • Search for point sources of high energy neutrinos with final data from AMANDA-II
  • 2009
  • Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 79, s. 062001-
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a search for point sources of high energy neutrinos using 3.8 yr of data recorded by AMANDA-II during 2000-2006. After reconstructing muon tracks and applying selection criteria designed to optimally retain neutrino-induced events originating in the northern sky, we arrive at a sample of 6595 candidate events, predominantly from atmospheric neutrinos with primary energy 100 GeV to 8 TeV. Our search of this sample reveals no indications of a neutrino point source. We place the most stringent limits to date on E(-2) neutrino fluxes from points in the northern sky, with an average upper limit of E(2)Phi(nu mu)+nu(tau)<= 5.2x10(-11) TeV cm(-2) s(-1) on the sum of nu(mu) and nu(tau) fluxes, assumed equal, over the energy range from 1.9 TeV to 2.5 PeV.
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2.
  • Abbasi, R., et al. (författare)
  • The IceCube data acquisition system : Signal capture, digitization, and timestamping
  • 2009
  • Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 601:3, s. 294-316
  • Tidskriftsartikel (refereegranskat)abstract
    • IceCube is a km-scale neutrino observatory under construction at the South Pole with sensors both in the deep ice (InIce) and on the surface (IceTop). The sensors, called Digital Optical Modules (DOMs). detect, digitize and timestamp the signals from optical Cherenkov-radiation photons. The DOM Main Board (MB) data acquisition subsystem is connected to the central DAQ in the IceCube Laboratory (ICL) by a single twisted copper wire-pair and transmits packetized data on demand. Time calibration is maintained throughout the array by regular transmission to the DOMs of precisely timed analog signals, synchronized to a central GPS-disciplined clock. The design goals and consequent features, functional capabilities, and initial performance of the DOM MB, and the operation of a combined array of DOMs as a system, are described here. Experience with the first InIce strings and the IceTop stations indicates that the system design and performance goals have been achieved. (c) 2009 Elsevier B.V. All rights reserved.
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3.
  • Achterberg, A., et al. (författare)
  • The search for muon neutrinos from northern hemisphere gamma-ray bursts with AMANDA
  • 2008
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 674:1, s. 357-370
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results of the analysis of neutrino observations by the Antarctic Muon and Neutrino Detector Array (AMANDA) correlated with photon observations of more than 400 gamma-ray bursts (GRBs) in the northern hemisphere from 1997 to 2003. During this time period, AMANDA's effective collection area for muon neutrinos was larger than that of any other existing detector. After the application of various selection criteria to our data, we expect similar to 1 neutrino event and <2 background events. Based on our observations of zero events during and immediately prior to the GRBs in the data set, we set the most stringent upper limit on muon neutrino emission correlated with GRBs. Assuming a Waxman-Bahcall spectrum and incorporating all systematic uncertainties, our flux upper limit has a normalization at 1 PeV of E-2 Phi(nu) <= 6.3 x 10(-9) GeV cm(-2) s(-1) sr(-1), with 90% of the events expected within the energy range of similar to 10 TeV to similar to 3 PeV. The impact of this limit on several theoretical models of GRBs is discussed, as well as the future potential for detection of GRBs by next-generation neutrino telescopes. Finally, we briefly describe several modifications to this analysis in order to apply it to other types of transient point sources.
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4.
  • Ackermann, M., et al. (författare)
  • Search for ultra-high-energy neutrinos with amanda-II
  • 2008
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 675:2, s. 1014-1024
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for diffuse neutrinos with energies in excess of 10(5) GeV is conducted with AMANDA-II data recorded between 2000 and 2002. Above 10(7) GeV, the Earth is essentially opaque to neutrinos. This fact, combined with the limited overburden of the AMANDA-II detector ( roughly 1.5 km), concentrates these ultra-high-energy neutrinos at the horizon. The primary background for this analysis is bundles of downgoing, high-energy muons from the interaction of cosmic rays in the atmosphere. No statistically significant excess above the expected background is seen in the data, and an upper limit is set on the diffuse all-flavor neutrino flux of E-2 Phi(90%CL) < 2.7x10(-7) GeV cm(-2) s(-1) sr(-1) valid over the energy range of 2x10(5) to 10(9) GeV. A number of models that predict neutrino fluxes from active galactic nuclei are excluded at the 90% confidence level.
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8.
  • Achterberg, A., et al. (författare)
  • Multiyear search for a diffuse flux of muon neutrinos with AMANDA-II
  • 2007
  • Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:4, s. 042008-
  • Tidskriftsartikel (refereegranskat)abstract
    • A search for TeV-PeV muon neutrinos from unresolved sources was performed on AMANDA-II data collected between 2000 and 2003 with an equivalent live time of 807 days. This diffuse analysis sought to find an extraterrestrial neutrino flux from sources with nonthermal components. The signal is expected to have a harder spectrum than the atmospheric muon and neutrino backgrounds. Since no excess of events was seen in the data over the expected background, an upper limit of E-2 Phi(90%C.L.)< 7.4x10(-8) GeV cm(-2) s(-1) sr(-1) is placed on the diffuse flux of muon neutrinos with a Phi proportional to E-2 spectrum in the energy range 16 TeV to 2.5 PeV. This is currently the most sensitive Phi proportional to E-2 diffuse astrophysical neutrino limit. We also set upper limits for astrophysical and prompt neutrino models, all of which have spectra different from Phi proportional to E-2.
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9.
  • Achterberg, A., et al. (författare)
  • Detection of atmospheric muon neutrinos with the IceCube 9-string detector
  • 2007
  • Ingår i: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998. ; 76:2, s. 027101-
  • Tidskriftsartikel (refereegranskat)abstract
    • The IceCube neutrino detector is a cubic kilometer TeV to PeV neutrino detector under construction at the geographic South Pole. The dominant population of neutrinos detected in IceCube is due to meson decay in cosmic-ray air showers. These atmospheric neutrinos are relatively well understood and serve as a calibration and verification tool for the new detector. In 2006, the detector was approximately 10% completed, and we report on data acquired from the detector in this configuration. We observe an atmospheric neutrino signal consistent with expectations, demonstrating that the IceCube detector is capable of identifying neutrino events. In the first 137.4 days of live time, 234 neutrino candidates were selected with an expectation of 211 +/- 76.1(syst)+/- 14.5(stat) events from atmospheric neutrinos.
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12.
  • Wightman, D. P., et al. (författare)
  • A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
  • 2021
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
  • Tidskriftsartikel (refereegranskat)abstract
    • Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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14.
  • Bonham, LW, et al. (författare)
  • Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
  • Tidskriftsartikel (refereegranskat)abstract
    • The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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15.
  • Gao, YX, et al. (författare)
  • Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
  • 2020
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
  • Tidskriftsartikel (refereegranskat)abstract
    • We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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16.
  • Gordon, I.E., et al. (författare)
  • The HITRAN2020 molecular spectroscopic database
  • 2022
  • Ingår i: Journal of Quantitative Spectroscopy and Radiative Transfer. - : Elsevier. - 0022-4073 .- 1879-1352. ; 277
  • Tidskriftsartikel (refereegranskat)abstract
    • The HITRAN database is a compilation of molecular spectroscopic parameters. It was established in the early 1970s and is used by various computer codes to predict and simulate the transmission and emission of light in gaseous media (with an emphasis on terrestrial and planetary atmospheres). The HITRAN compilation is composed of five major components: the line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, experimental infrared absorption cross-sections (for molecules where it is not yet feasible for representation in a line-by-line form), collision-induced absorption data, aerosol indices of refraction, and general tables (including partition sums) that apply globally to the data. This paper describes the contents of the 2020 quadrennial edition of HITRAN. The HITRAN2020 edition takes advantage of recent experimental and theoretical data that were meticulously validated, in particular, against laboratory and atmospheric spectra. The new edition replaces the previous HITRAN edition of 2016 (including its updates during the intervening years). All five components of HITRAN have undergone major updates. In particular, the extent of the updates in the HITRAN2020 edition range from updating a few lines of specific molecules to complete replacements of the lists, and also the introduction of additional isotopologues and new (to HITRAN) molecules: SO, CH3F, GeH4, CS2, CH3I and NF3. Many new vibrational bands were added, extending the spectral coverage and completeness of the line lists. Also, the accuracy of the parameters for major atmospheric absorbers has been increased substantially, often featuring sub-percent uncertainties. Broadening parameters associated with the ambient pressure of water vapor were introduced to HITRAN for the first time and are now available for several molecules. The HITRAN2020 edition continues to take advantage of the relational structure and efficient interface available at www.hitran.org and the HITRAN Application Programming Interface (HAPI). The functionality of both tools has been extended for the new edition.
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17.
  • Van Deerlin, Vivian M, et al. (författare)
  • Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
  • Tidskriftsartikel (refereegranskat)abstract
    • Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
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18.
  • Ferrari, Raffaele, et al. (författare)
  • Frontotemporal dementia and its subtypes: a genome-wide association study.
  • 2014
  • Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
  • Tidskriftsartikel (refereegranskat)abstract
    • Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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19.
  • Langerak, A. W., et al. (författare)
  • EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations
  • 2012
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 26:10, s. 2159-2171
  • Forskningsöversikt (refereegranskat)abstract
    • PCR-based immunoglobulin (Ig)/T-cell receptor (TCR) clonality testing in suspected lymphoproliferations has largely been standardized and has consequently become technically feasible in a routine diagnostic setting. Standardization of the pre-analytical and post-analytical phases is now essential to prevent misinterpretation and incorrect conclusions derived from clonality data. As clonality testing is not a quantitative assay, but rather concerns recognition of molecular patterns, guidelines for reliable interpretation and reporting are mandatory. Here, the EuroClonality (BIOMED-2) consortium summarizes important pre- and post-analytical aspects of clonality testing, provides guidelines for interpretation of clonality testing results, and presents a uniform way to report the results of the Ig/TCR assays. Starting from an immunobiological concept, two levels to report Ig/TCR profiles are discerned: the technical description of individual (multiplex) PCR reactions and the overall molecular conclusion for B and T cells. Collectively, the EuroClonality (BIOMED-2) guidelines and consensus reporting system should help to improve the general performance level of clonality assessment and interpretation, which will directly impact on routine clinical management (standardized best-practice) in patients with suspected lymphoproliferations.
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20.
  • Lerner, M.S., et al. (författare)
  • A 100 GHZ map of 3C 446
  • 1993
  • Ingår i: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 280:1, s. 117-120
  • Tidskriftsartikel (refereegranskat)abstract
    • The first map made from 100 GHz VLBI observations of the quasar/BL Lac object 3C446 is presented. This map represents a 25-fold increase in resolution compared to earlier maps. Our main conclusions are that the core of 3C 446 is still almost unresolved (less than or similar to 30 muas) at this frequency and that a jet extends several hundred microarcseconds at position angle almost-equal-to -142-degrees. A comparison is also made with observations at other size scales.
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21.
  • Manzoni, Claudia, et al. (författare)
  • Genome-wide analyses reveal a potential role for the MAPT, MOBP, and APOE loci in sporadic frontotemporal dementia
  • 2024
  • Ingår i: American Journal of Human Genetics. - 0002-9297. ; 111:7, s. 1316-1329
  • Tidskriftsartikel (refereegranskat)abstract
    • Frontotemporal dementia (FTD) is the second most common cause of early-onset dementia after Alzheimer disease (AD). Efforts in the field mainly focus on familial forms of disease (fFTDs), while studies of the genetic etiology of sporadic FTD (sFTD) have been less common. In the current work, we analyzed 4,685 sFTD cases and 15,308 controls looking for common genetic determinants for sFTD. We found a cluster of variants at the MAPT (rs199443; p = 2.5 × 10−12, OR = 1.27) and APOE (rs6857; p = 1.31 × 10−12, OR = 1.27) loci and a candidate locus on chromosome 3 (rs1009966; p = 2.41 × 10−8, OR = 1.16) in the intergenic region between RPSA and MOBP, contributing to increased risk for sFTD through effects on expression and/or splicing in brain cortex of functionally relevant in-cis genes at the MAPT and RPSA-MOBP loci. The association with the MAPT (H1c clade) and RPSA-MOBP loci may suggest common genetic pleiotropy across FTD and progressive supranuclear palsy (PSP) (MAPT and RPSA-MOBP loci) and across FTD, AD, Parkinson disease (PD), and cortico-basal degeneration (CBD) (MAPT locus). Our data also suggest population specificity of the risk signals, with MAPT and APOE loci associations mainly driven by Central/Nordic and Mediterranean Europeans, respectively. This study lays the foundations for future work aimed at further characterizing population-specific features of potential FTD-discriminant APOE haplotype(s) and the functional involvement and contribution of the MAPT H1c haplotype and RPSA-MOBP loci to pathogenesis of sporadic forms of FTD in brain cortex.
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22.
  • Rantakyrö, F.T., et al. (författare)
  • 50 μas resolution VLBI images of AGN’s at λ3 mm
  • 1998
  • Ingår i: Astronomy and Astrophysics. - Berlin : Springer-Verlag. - 0004-6361 .- 1432-0746. ; 131, s. 451-467
  • Tidskriftsartikel (refereegranskat)abstract
    • We present 15 images from the global mm-VLBI sessions in 1990 April at 100 GHz and 1993 April at 86 GHz. These observations probe the central engines of the 16 observed AGN's with up to 50 mu as resolution. Among other sources previously observed with lambda 3 mm VLBI we present the first lambda 3 mm maps of 0735+178, 0748+126, 1055+018, 2145+067, and CTA102, in total we have been able to image 13 out of the 16 observed sources. 6 out of the 13 imaged sources observed exhibit curvature and rapid structural changes, although the low dynamic range in two thirds of the maps limits the detection of weak features. Most of the sources have unresolved cores even at this high resolution. There is substantial evidence that the observed sources can be grouped into two general groups: A misaligned population with parsec scale jets in the form of low pitch helices and an aligned population with straight jets with small changes in PA due to intrinsic bends.
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23.
  • Bååth, L.B. 1948-, et al. (författare)
  • The microarcsecond structure of 3C 273 at 3 MM
  • 1991
  • Ingår i: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 241:1, s. L1-L4
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent improvements in data analysis and receiver techniques have allowed us to produce a map of the 100GHz emission from the compact radio source 3C273 with the unsurpassed resolution of 50-mu-as (microarcseconds). Our map shows that the structure within 300-mu-as (approximately 1.5.10(18).h-1 cm) has a position angle significantly different from the position angle of the jet observed at lower frequencies. There are also indications in our map that the inner structure has a more pronounced wiggling structure than has been observed on larger scales. The observations were made about 60 days from the start of the outburst of 1988. Most of the flux from the outburst is concentrated in a component which is elongated approximately (56 x 5).10(16).h-1 cm perpendicular to the overall jet-axis. The distance between this component and the core is approximately 128-mu-as, which corresponds to the distance expected from an apparent velocity of approximately 800-mu-as year-1.
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24.
  • Bååth, L.B. 1948-, et al. (författare)
  • VLBI observations of active galactic nuclei at 3 MM
  • 1992
  • Ingår i: Astronomy and Astrophysics. - Les Ulis : EDP Sciences. - 0004-6361 .- 1432-0746. ; 257:1, s. 31-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent improvements in data analysis and receiver techniques have allowed us to produce maps of the 100 GHz emission from the compact cores of active galactic nuclei with the unsurpassed resolution of 50-mu-as (microarcseconds). We present here hybrid maps of a set of compact radio sources observed at two epochs with a global VLBI array. The high resolution enables us to show details of active galactic nuclei on size scales of 10(16)-10(17) cm. Jets are shown to be more curved in these inner parts than further out in the areas mapped with VLBI at lower frequencies. Our maps of the quasar 3C345 show that the curvature seen with lower resolution instruments continues very close to the core. New components are seen separating from the cores of 3C84 and BL Lac. We observe a component in 3C84 separating from the core with an apparent speed approximately 21000 km sec-1. The radio source OJ287 is still unresolved with our array, having a core size of less-than-or-similar-to 10(17) cm. There is no indication of any compact component in 3C279 which would be associated with the outburst in integrated flux density which happened some months before our observation. The flux density of the most compact component we observe in 3C279 agrees well with that of the quiet core as extrapolated from its radio spectrum at lower frequencies. The inner part of the radio jet of the giant elliptical galaxy M87 also shows a continuation of the structure on a larger size scale, with a structure we interpret as parts of a helical pattern. No fringes were found for 4C39.25 or Sgr A.
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26.
  • Shraim, M. A., et al. (författare)
  • Features and methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system: a Delphi expert consensus study
  • 2022
  • Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 163:9, s. 1812-1828
  • Tidskriftsartikel (refereegranskat)abstract
    • Classification of musculoskeletal pain based on underlying pain mechanisms (nociceptive, neuropathic, and nociplastic pain) is challenging. In the absence of a gold standard, verification of features that could aid in discrimination between these mechanisms in clinical practice and research depends on expert consensus. This Delphi expert consensus study aimed to: (1) identify features and assessment findings that are unique to a pain mechanism category or shared between no more than 2 categories and (2) develop a ranked list of candidate features that could potentially discriminate between pain mechanisms. A group of international experts were recruited based on their expertise in the field of pain. The Delphi process involved 2 rounds: round 1 assessed expert opinion on features that are unique to a pain mechanism category or shared between 2 (based on a 40% agreement threshold); and round 2 reviewed features that failed to reach consensus, evaluated additional features, and considered wording changes. Forty-nine international experts representing a wide range of disciplines participated. Consensus was reached for 196 of 292 features presented to the panel (clinical examination-134 features, quantitative sensory testing-34, imaging and diagnostic testing-14, and pain-type questionnaires-14). From the 196 features, consensus was reached for 76 features as unique to nociceptive (17), neuropathic (37), or nociplastic (22) pain mechanisms and 120 features as shared between pairs of pain mechanism categories (78 for neuropathic and nociplastic pain). This consensus study generated a list of potential candidate features that are likely to aid in discrimination between types of musculoskeletal pain.
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27.
  • Hodges, P. W., et al. (författare)
  • Building a Collaborative Model of Sacroiliac Joint Dysfunction and Pelvic Girdle Pain to Understand the Diverse Perspectives of Experts
  • 2019
  • Ingår i: PM&R. - : Wiley. - 1934-1482 .- 1934-1563. ; 11:Suppl. 1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Pelvic girdle pain (PGP) and sacroiliac joint (SIJ) dysfunction/pain are considered frequent contributors to low back pain (LBP). Like other persistent pain conditions, PGP is increasingly recognized as a multifactorial problem involving biological, psychological, and social factors. Perspectives differ between experts and a diversity of treatments (with variable degrees of evidence) have been utilized. Objective: To develop a collaborative model of PGP that represents the collective view of a group of experts. Specific goals were to analyze structure and composition of conceptual models contributed by participants, to aggregate them into a metamodel, to analyze the metamodel's composition, and to consider predicted efficacy of treatments. Design: To develop a collaborative model of PGP, models were generated by invited individuals to represent their understanding of PGP using fuzzy cognitive mapping (FCM). FCMs involved proposal of components related to causes, outcomes, and treatments for pain, disability, and quality of life, and their connections. Components were classified into thematic categories. Weighting of connections was summed for components to judge their relative importance. FCMs were aggregated into a metamodel for analysis of the collective opinion it represented and to evaluate expected efficacy of treatments. Results: From 21 potential contributors, 14 (67%) agreed to participate (representing six disciplines and seven countries). Participants' models included a mean (SD) of 22 (5) components each. FCMs were refined to combine similar terms, leaving 89 components in 10 categories. Biomechanical factors were the most important in individual FCMs. The collective opinion from the metamodel predicted greatest efficacy for injection, exercise therapy, and surgery for pain relief. Conclusions: The collaborative model of PGP showed a bias toward biomechanical factors. Most efficacious treatments predicted by the model have modest to no evidence from clinical trials, suggesting a mismatch between opinion and evidence. The model enables integration and communication of the collection of opinions on PGP.
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28.
  • Kemmer, D., et al. (författare)
  • Exploring the foundation of genomics : a Northern blot reference set for the comparative analysis of transcript profiling technologies
  • 2004
  • Ingår i: Comparative and functional genomics. - : Hindawi Limited. - 1531-6912 .- 1532-6268. ; 5:8, s. 584-595
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we aim to create a reference data collection of Northern blot results and demonstrate how such a collection can enable a quantitative comparison of modern expression profiling techniques, a central component of functional genomics studies. Historic ally, Northern blots were the de facto standard for determining RNA transcript levels. However, driven by the demand for analysis of large sets of genes in parallel, high-throughput methods, such as microarrays, dominate modern profiling efforts. To facilitate assessment of these methods, in comparison to Northern blots, we created a database of published Northern results obtained with a standardized commercial multiple tissue blot (dbMTN). In order to demonstrate the utility of the dbMTN collection for technology comparison, we also generated expression profiles for genes across a set of human tissues, using multiple profiling techniques. No method produced profiles that were strongly correlated with the Northern blot data. The highest correlations to the Northern blot data were determined with microarrays for the subset of genes observed to be specifically expressed in a single tissue in the Northern analyses. The database and expression profiling data are available via the project website (http://www.cisreg.ca). We believe that emphasis on multitechnique validation of expression profiles is justified, as the correlation results between platforms are not encouraging on the whole. Supplementary material for this article can be found at: http://www.interscience.wiley.com/jpages/1531-6912/suppmat
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30.
  • Retuerto, Maria, et al. (författare)
  • Pb2MnTeO6 Double Perovskite : An Antipolar Anti-ferromagnet
  • 2016
  • Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 55:9, s. 4320-4329
  • Tidskriftsartikel (refereegranskat)abstract
    • Pb2MnTeO6, a new double perovskite, was synthesized. Its crystal structure was determined by synchrotron X-ray and powder neutron diffraction. Pb2MnTeO6 is monoclinic (I2/m) at room temperature with a regular arrangement of all the cations in their polyhedra. However, when the temperature is lowered to similar to 120 K it undergoes a phase transition from I2/m to C2/c structure. This transition is accompanied by a displacement of the Pb atoms from the center of their polyhedra due to the 6s2 lone-pair electrons, together with a surprising off-centering of Mn2+ (d5) magnetic cations. This strong first-order phase transition is also evidenced by specific heat, dielectric, Raman, and infrared spectroscopy measurements. The magnetic characterizations indicate an anti-ferromagnetic (AFM) order below TN approximate to 20 K; analysis of powder neutron diffraction data confirms the magnetic structure with propagation vector k = (0 1 0) and collinear AFM spins. The observed jump in dielectric permittivity near similar to 150 K implies possible anti-ferroelectric behavior; however, the absence of switching suggests that Pb2MnTeO6 can only be antipolar. First-principle calculations confirmed that the crystal and magnetic structures determined are locally stable and that anti-ferroelectric switching is unlikely to be observed in Pb2MnTeO6.
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31.
  • Albert, F. W., et al. (författare)
  • Targeted resequencing of a genomic region influencing tameness and aggression reveals multiple signals of positive selection
  • 2011
  • Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 107:3, s. 205-214
  • Tidskriftsartikel (refereegranskat)abstract
    • The identification of the causative genetic variants in quantitative trait loci (QTL) influencing phenotypic traits is challenging, especially in crosses between outbred strains. We have previously identified several QTL influencing tameness and aggression in a cross between two lines of wild-derived, outbred rats (Rattus norvegicus) selected for their behavior towards humans. Here, we use targeted sequence capture and massively parallel sequencing of all genes in the strongest QTL in the founder animals of the cross. We identify many novel sequence variants, several of which are potentially functionally relevant. The QTL contains several regions where either the tame or the aggressive founders contain no sequence variation, and two regions where alternative haplotypes are fixed between the founders. A re-analysis of the QTL signal showed that the causative site is likely to be fixed among the tame founder animals, but that several causative alleles may segregate among the aggressive founder animals. Using a formal test for the detection of positive selection, we find 10 putative positively selected regions, some of which are close to genes known to influence behavior. Together, these results show that the QTL is probably not caused by a single selected site, but may instead represent the joint effects of several sites that were targets of polygenic selection.
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32.
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33.
  • Nijs, Jo, et al. (författare)
  • Nociceptive, neuropathic, or nociplastic low back pain? : The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations
  • 2024
  • Ingår i: The Lancet Rheumatology. - : Elsevier. - 2665-9913. ; 6:3, s. e178-e188
  • Tidskriftsartikel (refereegranskat)abstract
    • The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes.
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34.
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35.
  • Bennell, Kim L., et al. (författare)
  • Comparison of neuromuscular and quadriceps strengthening exercise in the treatment of varus malaligned knees with medial knee osteoarthritis: a randomised controlled trial protocol
  • 2011
  • Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Osteoarthritis of the knee involving predominantly the medial tibiofemoral compartment is common in older people, giving rise to pain and loss of function. Many people experience progressive worsening of the disease over time, particularly those with varus malalignment and increased medial knee joint load. Therefore, interventions that can reduce excessive medial knee loading may be beneficial in reducing the risk of structural progression. Traditional quadriceps strengthening can improve pain and function in people with knee osteoarthritis but does not appear to reduce medial knee load. A neuromuscular exercise program, emphasising optimal alignment of the trunk and lower limb joints relative to one another, as well as quality of movement performance, while dynamically and functionally strengthening the lower limb muscles, may be able to reduce medial knee load. Such a program may also be superior to traditional quadriceps strengthening with respect to improved pain and physical function because of the functional and dynamic nature. This randomised controlled trial will investigate the effect of a neuromuscular exercise program on medial knee joint loading, pain and function in individuals with medial knee joint osteoarthritis. We hypothesise that the neuromuscular program will reduce medial knee load as well as pain and functional limitations to a greater extent than a traditional quadriceps strengthening program. Methods/Design: 100 people with medial knee pain, radiographic medial compartment osteoarthritis and varus malalignment will be recruited and randomly allocated to one of two 12-week exercise programs: quadriceps strengthening or neuromuscular exercise. Each program will involve 14 supervised exercise sessions with a physiotherapist plus four unsupervised sessions per week at home. The primary outcomes are medial knee load during walking (the peak external knee adduction moment from 3D gait analysis), pain, and self-reported physical function measured at baseline and immediately following the program. Secondary outcomes include the external knee adduction moment angular impulse, electromyographic muscle activation patterns, knee and hip muscle strength, balance, functional ability, and quality-of-life. Discussion: The findings will help determine whether neuromuscular exercise is superior to traditional quadriceps strengthening regarding effects on knee load, pain and physical function in people with medial knee osteoarthritis and varus malalignment.
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36.
  • Bennell, Kim L., et al. (författare)
  • Neuromuscular Versus Quadriceps Strengthening Exercise in Patients With Medial Knee Osteoarthritis and Varus Malalignment
  • 2014
  • Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191. ; 66:4, s. 950-959
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. To compare the effects of neuromuscular exercise (NEXA) and quadriceps strengthening (QS) on the knee adduction moment (an indicator of medio-lateral distribution of knee load), pain, and physical function in patients with medial knee joint osteoarthritis (OA) and varus malalignment. Methods. One hundred patients with medial knee pain, mostly moderate-to-severe radiographic medial knee OA, and varus malalignment were randomly allocated to one of two 12-week exercise programs. Each program involved 14 individually supervised exercise sessions with a physiotherapist plus a home exercise component. Primary outcomes were peak external knee adduction moment (3-dimensional gait analysis), pain (visual analog scale), and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index). Results. Eighty-two patients (38 [76%] of 50 in the NEXA group and 44 [88%] of 50 in the QS group) completed the trial. There was no significant between-group difference in the change in the peak knee adduction moment (mean difference 0.13 Nm/[body weight x height]% [95% confidence interval (95% CI) -0.08, 0.33]), pain (mean difference 2.4 mm [95% CI -6.0, 10.8]), or physical function (mean difference -0.8 units [95% CI -4.0, 2.4]). Neither group showed a change in knee moments following exercise, whereas both groups showed similar significant reductions in pain and improvement in physical function. Conclusion. Although comparable improvements in clinical outcomes were observed with both neuromuscular and quadriceps strengthening exercise in patients with moderate varus malalignment and mostly moderate-to-severe medial knee OA, these forms of exercise did not affect the knee adduction moment, a key predictor of structural disease progression.
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37.
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38.
  • Hodges, Gethin W., et al. (författare)
  • Effect of simvastatin and ezetimibe on suPAR levels and outcomes
  • 2018
  • Ingår i: Atherosclerosis. - : ELSEVIER IRELAND LTD. - 0021-9150 .- 1879-1484. ; 272, s. 129-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.& para;& para;Methods: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).& para;& para;Results: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (p<0.001). In a multivariate 1-year analysis, 1-year suPAR was strongly associated with all-cause mortality, hazard ratio (HR) = 2.05 (1.17-3.61); MCE 1.40 (1.01-1.92); and AVE 1.42 (1.02-1.99) (all p<0.042) for each doubling of suPAR; but was not associated with ICE.& para;& para;Conclusions: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677). (C) 2018 Elsevier B.V. All rights reserved.
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39.
  • Huang, Q M, et al. (författare)
  • Postural control of the trunk in response to lateral support surface translations during trunk movement and loading.
  • 2001
  • Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 141:4, s. 552-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The postural response to translation of the support surface may be influenced by the performance of an ongoing voluntary task. This study was designed to test this proposal by applying lateral perturbations while subjects handled a load in the frontal plane. Measurements were made of medio-lateral displacement of the centre of pressure, angular displacement of the trunk and thigh in the frontal plane and intra-abdominal pressure. Subjects were translated randomly to the left and right in a variety of conditions that involved standing either quietly or with a 5 kg load in their left hand, which they were required either to hold statically or to lift or lower. The results indicate that when the perturbation occurred towards the loaded left side the subjects were able to return their centre of pressure, trunk and thigh rapidly and accurately to the initial position. However, when the perturbation occurred towards the right (away from the load) this correction was delayed and associated with multiple changes in direction of movement, suggesting decreased efficiency of the postural response. This reduced efficiency can be explained by a conflict between the motor commands for the ongoing voluntary task and the postural response, and/or by the mechanical effect of the asymmetrical addition of load to the trunk.
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40.
  • Jourdan, F., et al. (författare)
  • High-precision dating of the Kalkarindji large igneous province, Australia, and synchrony with the Early-Middle Cambrian (Stage 4-5) extinction
  • 2014
  • Ingår i: Geology. - 0091-7613. ; 42:6, s. 543-546
  • Tidskriftsartikel (refereegranskat)abstract
    • The voluminous Kalkarindji flood basalts erupted in Australia during the Cambrian and covered >2 x 10(6) km(2). New U-Pb and Ar-40/Ar-39 age data from intrusive rocks and lava flows yielded statistically indistinguishable ages at ca. 511 Ma, suggesting a relatively brief emplacement for this province. A zircon age of 510.7 +/- 0.6 Ma shows that this province is temporally indistinguishable at the few-hundred-thousand-year level from the Early-Middle Cambrian (Stage 4-5) boundary age of 510 +/- 1 Ma, which marks the first severe extinction of the Phanerozoic and an extended marine anoxia period. Sulfur concentration measurements ranging from < 50 to 1900 mu g/g, and fractal analysis of extensive explosive volcanic breccias, suggest that blasts and phreatomagmatic explosions have contributed to injection of large amounts of sulfur into the stratosphere. In addition, magma intrusions in oil, gas, and sulfate deposits may have generated significant emission of CH4 and SO2 which, along with volcanic gases, would have combined to cause an oscillation of the climate and led to the Cambrian extinction.
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41.
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42.
  • King, Siobhan M., et al. (författare)
  • Iridium Nanoparticles for Multichannel Luminescence Lifetime Imaging, Mapping Localization in Live Cancer Cells
  • 2018
  • Ingår i: Journal of the American Chemical Society. - 0002-7863 .- 1520-5126. ; 140, s. 10242-10249
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of long-lived luminescent nanoparticles for lifetime imaging is of wide interest as luminescence lifetime is environmentally sensitive detection independent of probe concentration. We report novel iridium-coated gold nanoparticles as probes for multiphoton lifetime imaging with characteristic long luminescent lifetimes based on iridium luminescence in the range of hundreds of nanoseconds and a short signal on the scale of picoseconds based on gold allowing multichannel detection. The tailor-made IrC6 complex forms stable, water-soluble gold nanoparticles (AuNPs) of 13, 25, and 100 nm, bearing 1400, 3200, and 22 000 IrC6 complexes per AuNP, respectively. The sensitivity of the iridium signal on the environment of the cell is evidenced with an observed variation of lifetimes. Clusters of iridium nanoparticles show lifetimes from 450 to 590 ns while lifetimes of 660 and 740 ns are an average of different points in the cytoplasm and nucleus. Independent luminescence lifetime studies of the nanoparticles in different media and under aggregation conditions postulate that the unusual long lifetimes observed can be attributed to interaction with proteins rather than nanoparticle aggregation. Total internal reflection fluorescence microscopy (TIRF), confocal microscopy studies and 3D luminescence lifetime stacks confirm the presence of bright, nonaggregated nanoparticles inside the cell. Inductively coupled plasma mass spectrometry (ICPMS) analysis further supports the presence of the nanoparticles in cells. The iridium-coated nanoparticles provide new nanoprobes for lifetime detection with dual channel monitoring. The combination of the sensitivity of the iridium signal to the cell environment together with the nanoscaffold to guide delivery offer opportunities for iridium nanoparticles for targeting and tracking in in vivo models.
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