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Sökning: WFRF:(Sexton C. E.)

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1.
  • Bravo, L, et al. (författare)
  • 2021
  • swepub:Mat__t
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2.
  • Tabiri, S, et al. (författare)
  • 2021
  • swepub:Mat__t
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3.
  • Aaltonen, T., et al. (författare)
  • Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
  • 2010
  • Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
  • Tidskriftsartikel (refereegranskat)abstract
    • We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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4.
  • Adare, A., et al. (författare)
  • Measurements of Elliptic and Triangular Flow in High-Multiplicity He-3 + Au Collisions at root s(NN)=200 GeV
  • 2015
  • Ingår i: Physical Review Letters. - 1079-7114. ; 115:14
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the first measurement of elliptic (v(2)) and triangular (v(3)) flow in high-multiplicity He-3 + Au collisions at root s(NN) = 200 GeV. Two-particle correlations, where the particles have a large separation in pseudorapidity, are compared in He-3 + Au and in p + p collisions and indicate that collective effects dominate the second and third Fourier components for the correlations observed in the He-3 + Au system. The collective behavior is quantified in terms of elliptic v(2) and triangular v(3) anisotropy coefficients measured with respect to their corresponding event planes. The v(2) values are comparable to those previously measured in d + Au collisions at the same nucleon-nucleon center-of-mass energy. Comparisons with various theoretical predictions are made, including to models where the hot spots created by the impact of the three He-3 nucleons on the Au nucleus expand hydrodynamically to generate the triangular flow. The agreement of these models with data may indicate the formation of low-viscosity quark-gluon plasma even in these small collision systems.
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5.
  • Adare, A., et al. (författare)
  • Search for dark photons from neutral meson decays in p plus p and d plus Au collisions at root s(NN)=200 GeV
  • 2015
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 91:3
  • Tidskriftsartikel (refereegranskat)abstract
    • The standard model (SM) of particle physics is spectacularly successful, yet the measured value of the muon anomalous magnetic moment (g - 2)mu deviates from SM calculations by 3.6 sigma. Several theoretical models attribute this to the existence of a "dark photon," an additional U(1) gauge boson, which is weakly coupled to ordinary photons. The PHENIX experiment at the Relativistic Heavy Ion Collider has searched for a dark photon, U, in pi(0), eta -> gamma e(+)e(-) decays and obtained upper limits of O(2 x 10(-6)) on U-gamma mixing at 90% C.L. for the mass range 30 < m(U) < 90 MeV/c(2). Combined with other experimental limits, the remaining region in the U-gamma mixing parameter space that can explain the (g - 2)(mu) deviation from its SM value is nearly completely excluded at the 90% confidence level, with only a small region of 29 < m(U) < 32 MeV/c(2) remaining.
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6.
  • Adare, A., et al. (författare)
  • Measurement of K-S(0) and K*(0) in p plus p, d plus Au, and Cu plus Cu collisions at root s(NN)=200 GeV
  • 2014
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX experiment at the Relativistic Heavy Ion Collider has performed a systematic study of K-S(0) and K*(0) meson production at midrapidity in p + p, d + Au, and Cu + Cu collisions at root s(NN) = 200 GeV. The K-S(0) and K*(0) mesons are reconstructed via their K-S(0) -> pi(0)(-> gamma gamma) pi(0)(-> gamma gamma) and K*(0) -> K-+/-pi(-/+) decay modes, respectively. The measured transverse-momentum spectra are used to determine the nuclear modification factor of K-S(0) and K*(0) mesons in d + Au and Cu + Cu collisions at different centralities. In the d + Au collisions, the nuclear modification factor of K-S(0) and K*(0) mesons is almost constant as a function of transverse momentum and is consistent with unity, showing that cold-nuclear-matter effects do not play a significant role in the measured kinematic range. In Cu + Cu collisions, within the uncertainties no nuclear modification is registered in peripheral collisions. In central collisions, both mesons show suppression relative to the expectations from the p + p yield scaled by the number of binary nucleon-nucleon collisions in the Cu + Cu system. In the p(T) range 2-5 GeV/c, the strange mesons (K-S(0), K*(0)) similarly to the phi meson with hidden strangeness, showan intermediate suppression between the more suppressed light quark mesons (pi(0)) and the nonsuppressed baryons (p, (p) over bar). At higher transverse momentum, p(T) > 5 GeV/c, production of all particles is similarly suppressed by a factor of approximate to 2.
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7.
  • Adare, A., et al. (författare)
  • Low-mass vector-meson production at forward rapidity in p plus p collisions at root s=200 GeV
  • 2014
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX experiment at the Relativistic Heavy Ion Collider has measured low-mass vector-meson ,omega, rho, and phi, production through the dimuon decay channel at forward rapidity (1.2 < vertical bar y vertical bar < 2.2) in p + p collisions at root s = 200 GeV. The differential cross sections for these mesons are measured as a function of both p(T) and rapidity. We also report the integrated differential cross sections over 1 < p(T) < 7 GeV/c and 1.2 < vertical bar y vertical bar < 2.2: d sigma/dy(omega + rho rho -> mu mu) = 80 +/- 6(stat) +/- 12(syst)nb and d sigma/dy(phi -> mu mu) = 27 +/- 3(stat) +/- 4(syst)nb. These results are compared with midrapidity measurements and calculations.
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8.
  • Adare, A., et al. (författare)
  • Systematic study of charged-pion and kaon femtoscopy in Au plus Au collisions at root s(NN)=200 GeV
  • 2015
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a systematic study of charged-pion and kaon interferometry in Au + Au collisions at root s(NN) = 200 GeV. The kaon mean source radii are found to be larger than pion radii in the outward and longitudinal directions for the same transverse mass; this difference increases for more central collisions. The azimuthal-angle dependence of the radii was measured with respect to the second-order event plane and similar oscillations of the source radii were found for pions and kaons. Hydrodynamic models qualitatively describe the similar oscillations of the mean source radii for pions and kaons, but they do not fully describe the transverse-mass dependence of the oscillations.
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  • Adare, A., et al. (författare)
  • Cross section and transverse single-spin asymmetry of eta mesons in p up arrow plus p collisions at root s=200 GeV at forward rapidity
  • 2014
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 90:7
  • Tidskriftsartikel (refereegranskat)abstract
    • We present a measurement of the cross section and transverse single-spin asymmetry (AN) for. mesons at large pseudorapidity from root s = 200 GeV p up arrow + p collisions. The measured cross section for 0.5 < p(T) < 5.0 GeV/c and 3.0 < vertical bar eta vertical bar < 3.8 is well described by a next-to-leading-order perturbative-quantum-chromodynamics calculation. The asymmetries A(N) have been measured as a function of Feynman-x (x(F)) from 0.2 < vertical bar x(F)vertical bar < 0.7, as well as transverse momentum (p(T)) from 1.0 < p(T) < 4.5 GeV/c. The asymmetry averaged over positive x(F) is < A(N)> = 0.061 +/- 0.014. The results are consistent with prior transverse single-spin measurements of forward eta and pi(0) mesons at various energies in overlapping x(F) ranges. Comparison of different particle species can help to determine the origin of the large observed asymmetries in p up arrow + p collisions.
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11.
  • Adare, A., et al. (författare)
  • phi meson production in d plus Au collisions at root s(NN)=200 GeV
  • 2015
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 92:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The PHENIX Collaboration has measured phi meson production in d + Au collisions at root s(NN) = 200 GeV using the dimuon and dielectron decay channels. The phi meson is measured in the forward (backward) d-going (Au-going) direction, 1.2 < y < 2.2 (-2.2 < y < -1.2) in the transverse-momentum (pT) range from 1-7 GeV/c and at midrapidity vertical bar y vertical bar < 0.35 in the p(T) range below 7 GeV/c. The phi meson invariant yields and nuclear-modification factors as a function of p(T), rapidity, and centrality are reported. An enhancement of phi meson production is observed in the Au-going direction, while suppression is seen in the d-going direction, and no modification is observed at midrapidity relative to the yield in p + p collisions scaled by the number of binary collisions. Similar behavior was previously observed for inclusive charged hadrons and open heavy flavor, indicating similar cold-nuclear-matter effects.
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12.
  • Figlioli, G, et al. (författare)
  • The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
  • 2019
  • Ingår i: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
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13.
  • Adare, A., et al. (författare)
  • Inclusive cross section and double-helicity asymmetry for pi(0) production at midrapidity in p plus p collisions at root s=510 GeV
  • 2016
  • Ingår i: Physical Review D (Particles, Fields, Gravitation and Cosmology). - 1550-2368. ; 93:1
  • Tidskriftsartikel (refereegranskat)abstract
    • PHENIX measurements are presented for the cross section and double-helicity asymmetry (A(LL)) in inclusive pi(0) production at midrapidity from p + p collisions at root s = 510 GeV from data taken in 2012 and 2013 at the Relativistic Heavy Ion Collider. The next-to-leading-order perturbative-quantum-chromodynamics theory calculation is in excellent agreement with the presented cross section results. The calculation utilized parton-to-pion fragmentation functions from the recent DSS14 global analysis, which prefer a smaller gluon-to-pion fragmentation function. The pi(0)A(LL) results follow an increasingly positive asymmetry trend with p(T) and root s with respect to the predictions and are in excellent agreement with the latest global analysis results. This analysis incorporated earlier results on pi(0) and jet A(LL) and suggested a positive contribution of gluon polarization to the spin of the proton Delta G for the gluon momentum fraction range x > 0.05. The data presented here extend to a currently unexplored region, down to x similar to 0.01, and thus provide additional constraints on the value of Delta G.
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14.
  • Adare, A., et al. (författare)
  • Nuclear matter effects on J/psi production in asymmetric Cu plus Au collisions at root S-NN=200 GeV
  • 2014
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 90:6
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on J/psi production from asymmetric Cu + Au heavy-ion collisions at root S-NN = 200 GeV at the Relativistic Heavy Ion Collider at both forward (Cu-going direction) and backward (Au-going direction) rapidities. The nuclear modification of J/psi yields in Cu + Au collisions in the Au-going direction is found to be comparable to that inAu + Au collisions when plotted as a function of the number of participating nucleons. In the Cu-going direction, J/psi production shows a stronger suppression. This difference is comparable in magnitude and has the same sign as the difference expected from shadowing effects due to stronger low-x gluon suppression in the larger Au nucleus.
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16.
  • Kloske, C. M., et al. (författare)
  • APOE and immunity: Research highlights
  • 2023
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 19:6, s. 2677-2696
  • Forskningsöversikt (refereegranskat)abstract
    • INTRODUCTIONAt the Alzheimer's Association's APOE and Immunity virtual conference, held in October 2021, leading neuroscience experts shared recent research advances on and inspiring insights into the various roles that both the apolipoprotein E gene (APOE) and facets of immunity play in neurodegenerative diseases, including Alzheimer's disease and other dementias. METHODSThe meeting brought together more than 1200 registered attendees from 62 different countries, representing the realms of academia and industry. RESULTSDuring the 4-day meeting, presenters illuminated aspects of the cross-talk between APOE and immunity, with a focus on the roles of microglia, triggering receptor expressed on myeloid cells 2 (TREM2), and components of inflammation (e.g., tumor necrosis factor alpha [TNF alpha]). DISCUSSIONThis manuscript emphasizes the importance of diversity in current and future research and presents an integrated view of innate immune functions in Alzheimer's disease as well as related promising directions in drug development.
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17.
  • Thompson, B.A., et al. (författare)
  • Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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18.
  • Polettini, M., et al. (författare)
  • Decay studies in the A∼225 Po-Fr region from the DESPEC campaign at GSI in 2021
  • 2022
  • Ingår i: Il Nuovo Cimento. - : Società Italiana di Fisica. - 2037-4909. ; 45:5
  • Tidskriftsartikel (refereegranskat)abstract
    • The HISPEC-DESPEC collaboration aims at investigating the structure of exotic nuclei formed in fragmentation reactions with decay spectroscopy measurements, as part of the FAIR Phase-0 campaign at GSI. This paper reports on first results of an experiment performed in spring 2021, with a focus on beta-decaystudies in the Po-Fr nuclei in the 220 < A <230 island of octupole deformation exploiting the DESPEC setup. Ion-beta correlations and fast-timing techniques are being employed, giving an insight into this difficult-to-reach region.
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  • Sawcer, Stephen, et al. (författare)
  • Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
  • 2011
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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21.
  • Sexton, C. E., et al. (författare)
  • Alzheimer's disease research progress in Australia: The Alzheimer's Association International Conference Satellite Symposium in Sydney
  • 2022
  • Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:1, s. 178-190
  • Tidskriftsartikel (refereegranskat)abstract
    • The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the understanding of and treatment developments for Alzheimer's disease (AD) and other dementias. This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations. Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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22.
  • Sexton, Claire E., et al. (författare)
  • Novel avenues of tau research
  • 2024
  • Ingår i: Alzheimer's and Dementia. - 1552-5260. ; 20:3, s. 2240-2261
  • Forskningsöversikt (refereegranskat)abstract
    • INTRODUCTION: The pace of innovation has accelerated in virtually every area of tau research in just the past few years. METHODS: In February 2022, leading international tau experts convened to share selected highlights of this work during Tau 2022, the second international tau conference co-organized and co-sponsored by the Alzheimer's Association, CurePSP, and the Rainwater Charitable Foundation. RESULTS: Representing academia, industry, and the philanthropic sector, presenters joined more than 1700 registered attendees from 59 countries, spanning six continents, to share recent advances and exciting new directions in tau research. DISCUSSION: The virtual meeting provided an opportunity to foster cross-sector collaboration and partnerships as well as a forum for updating colleagues on research-advancing tools and programs that are steadily moving the field forward.
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  • Sexton, C. C., et al. (författare)
  • The overlap of storage, voiding and postmicturition symptoms and implications for treatment seeking in the USA, UK and Sweden: EpiLUTS
  • 2009
  • Ingår i: BJU International. - 1464-410X. ; 103:Suppl 3, s. 12-23
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess the (i) the overlap between voiding, storage, and postmicturition symptoms; and (ii) the relative effect of bother and implications for treatment seeking within these symptom groups, using data from the EpiLUTS study. SUBJECTS AND METHODS: This cross-sectional population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Participants were asked to rate the frequency and symptom-specific bother of individual LUTS. Descriptive statistics were used to examine differences in International Continence Society LUTS subgroups. Logistc regressions were used with treatment seeking as the dependent variable and the bother of individual symptoms as predictors. RESULTS: The survey response rate was 59%. The sample included 30,000 participants (14,139 men and 15,861 women); 71% of men and 75% of women reported at least one LUTS, and about half reported LUTS from more than one symptom group. Rates of bother were greatest for those who reported multiple storage, voiding and postmicturition LUTS (men 83%, women 89%). Less than a third of participants with LUTS from all three groups reported seeking treatment. Consistent correlates of treatment seeking across genders included bother due to weak stream, incomplete emptying, perceived daytime frequency, nocturia and urgency. There were also significant associations for several types of incontinence, most commonly stress incontinence in women and leaking during sexual activity in men. Despite high rates of symptom overlap and symptom-specific bother, few participants sought treatment for LUTS. CONCLUSION: Common conditions such as BPH and OAB are treatable, and clinicians should proactively ask patients about urinary symptoms. Given the many types of LUTS that patients experience, it is imperative that clinicians assess all LUTS to ensure that appropriate treatments are prescribed.
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27.
  • Chu, V H, et al. (författare)
  • Coagulase-negative staphylococcal prosthetic valve endocarditis--a contemporary update based on the International Collaboration on Endocarditis: prospective cohort study.
  • 2009
  • Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 95:7, s. 570-6
  • Tidskriftsartikel (refereegranskat)abstract
    • To describe the contemporary features of coagulase-negative staphylococcal (CoNS) prosthetic valve endocarditis (PVE).Observational study of prospectively collected data from a multinational cohort of patients with infective endocarditis. Patients with CoNS PVE were compared to patients with Staphylococcus aureus and viridans streptococcal (VGS) PVE.The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) is a contemporary cohort of patients with infective endocarditis from 61 centres in 28 countries.Adult patients in the ICE-PCS with definite PVE and no history of injecting drug use from June 2000 to August 2005 were included.None.Heart failure, intracardiac abscess, death.CoNS caused 16% (n = 86) of 537 cases of definite non-injecting drug use-associated PVE. Nearly one-half (n = 33/69, 48%) of patients with CoNS PVE presented between 60 days and 365 days of valve implantation. The rate of intracardiac abscess was significantly higher in patients with CoNS PVE (38%) than in patients with either S aureus (23%, p = 0.03) or VGS (20%, p = 0.05) PVE. The rate of abscess was particularly high in early (50%) and intermediate (52%) CoNS PVE. In-hospital mortality was 24% for CoNS PVE, 36% for S aureus PVE (p = 0.09) and 9.1% for VGS PVE (p = 0.08). Meticillin resistance was present in 68% of CoNS strains.Nearly one-half of CoNS PVE cases occur between 60 days and 365 days of prosthetic valve implantation. CoNS PVE is associated with a high rate of meticillin resistance and significant valvular complications.
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  • Cordtz, R, et al. (författare)
  • RISK OF HAEMATOLOGICAL MALIGNANCY IN PATIENTS WITH PSORIATIC ARTHRITIS, OVERALL AND IN RELATION TO TNF INHIBITORS - A NORDIC COHORT STUDY
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 169-170
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Several autoimmune inflammatory diseases, including rheumatoid arthritis (RA), are associated with increased risk of malignant lymphomas. There is also a longstanding concern of lymphoma development with tumour necrosis factor inhibitor (TNFi) treatment, but most studies in RA to date do not indicate an additionally increased risk. Corresponding studies in psoriatic arthritis (PsA), both with respect to the underlying risks, and risks in relation to treatment with TNFi, are limited. Data on myeloid malignancies in PsA are scarce.ObjectivesTo estimate the risk of haematological malignancy overall and by lymphoid and myeloid types in TNFi treated versus (vs.) biologics-naïve patients with PsA across the five Nordic countries. Additionally, we investigated the underlying risk of haematological malignancies in PsA as compared to the general population.MethodsWe identified patients with PsA starting a first ever TNFi from the clinical rheumatology registers (CRR) in Sweden (SE), Denmark (DK), Norway (NO), Finland (FI), and Iceland (ICE) from 2006 through 2019 (n=10 621). We identified biologics-naïve patients with PsA from a) the CRR (n=18 705, all countries) and b) the national patient registers (NPR, n=27 286, SE and DK only). To estimate the underlying risk of haematological malignancy in PsA, we randomly sampled general population comparators in SE and DK matched on year of birth, sex, and calendar year at start of follow-up, to the patients with PsA.Through linkage to the mandatory national cancer registers in all five countries, we collected information on haematological malignancy overall, and categorised into lymphoid or myeloid types. By applying a modified Poisson regression, we estimated pooled incidence rate ratio (IRR) with 95% confidence intervals (CI) for TNFi treated vs. biologics-naïve PsA and for PsA vs. the general population, adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ResultsWe observed 40 events of haematological malignancies (during 59 827 person-years) among TNFi treated PsA, resulting in a crude incidence rate (IR) of 67 per 100 000 person-years. The corresponding IR was 91 (63 events) for biologics-naïve PsA from the CRR, and 118 (172 events) for biologics-naïve PsA from NPR. This resulted in a pooled IRR of 0.97 (0.69 to 1.37) for TNFi-treated vs. biologics-naïve PsA patients from the CRR, and 0.84 (0.64 to 1.10) vs. biologics-naïve PsA patients from the NPR. The pooled IRR of haematological malignancies in PsA overall vs. the general population was 1.35 (1.17 to 1.55). Throughout, the estimates were largely similar for lymphoid and myeloid malignancies (Figure 1). The crude IR of haematological malignancies were substantially akin across different TNFi agents.Figure 1.Pooled incidence rate ratios (IRRs) (95% CI) of haematological malignancy overall and by lymphoid and myeloid types, in first ever TNFi treated versus biologics-naïve patients with PsA, and versus general population comparators. Legend: Lymphoid malignancies include international classification of diseases (ICD) 10 codes C81-86, C88, C90-91. Myeloid malignancies include ICD10 codes C92-95, D45-D46, D47.1, D47.3-5. Incidence rate ratios adjusted for age (18-55, 56-65, 66-70, >70 years), sex, calendar period (2006-2010, 2011-2019) and country, and using robust standard errors.ConclusionIn this large five-country cohort study, we did not observe any increased risk of haematological malignancies overall, nor for lymphoid and myeloid types, in patients with PsA treated with TNFi. By contrast, there were signals of a moderately increased underlying risk of haematological malignancies, both of lymphoid and myeloid types, in patients with PsA overall as compared to the general population. The findings are of importance from a patient information perspective.AcknowledgementsWe would like to acknowledge the NordForsk and FOREUM, and especially the patient representatives of the NordForsk collaboration for their valuable contribution to this study.Disclosure of InterestsRené Cordtz: None declared, Johan Askling Consultant of: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Grant/research support from: Abbvie, Astra-Zeneca, BMS, Eli Lilly, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB, Bénédicte Delcoigne: None declared, Karin Ekström Smedby: None declared, Eva Baecklund: None declared, Christine Ballegaard: None declared, Pia Isomäki Speakers bureau: AbbVie, Eli Lilly and Pfizer, Consultant of: AbbVie, Eli Lilly, Pfizer, Roche and ViforPharma, Grant/research support from: Pfizer, Kalle Aaltonen: None declared, Björn Gudbjornsson Speakers bureau: Novartis, not related to this work, Consultant of: Novartis, not related to this work, Thorvardur Love Speakers bureau: Celgene, Sella Aa. Provan: None declared, Brigitte Michelsen Grant/research support from: Novartis, not related to this work, Joe Sexton: None declared, Lene Dreyer Speakers bureau: Eli Lilly, Galderma and Janssen, Grant/research support from: BMS not related to this work, Karin Hellgren: None declared
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31.
  • Fjell, Anders M., et al. (författare)
  • No phenotypic or genotypic evidence for a link between sleep duration and brain atrophy
  • 2023
  • Ingår i: Nature Human Behaviour. - : Springer Nature. - 2397-3374. ; 7:11, s. 2008-2022
  • Tidskriftsartikel (refereegranskat)abstract
    • Short sleep is held to cause poorer brain health, but is short sleep associated with higher rates of brain structural decline? Analysing 8,153 longitudinal MRIs from 3,893 healthy adults, we found no evidence for an association between sleep duration and brain atrophy. In contrast, cross-sectional analyses (51,295 observations) showed inverse U-shaped relationships, where a duration of 6.5 (95% confidence interval, (5.7, 7.3)) hours was associated with the thickest cortex and largest volumes relative to intracranial volume. This fits converging evidence from research on mortality, health and cognition that points to roughly seven hours being associated with good health. Genome-wide association analyses suggested that genes associated with longer sleep for below-average sleepers were linked to shorter sleep for above-average sleepers. Mendelian randomization did not yield evidence for causal impacts of sleep on brain structure. The combined results challenge the notion that habitual short sleep causes brain atrophy, suggesting that normal brains promote adequate sleep duration—which is shorter than current recommendations.
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32.
  • Fjell, Anders M., et al. (författare)
  • Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium
  • 2021
  • Ingår i: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:4, s. 1953-1969
  • Tidskriftsartikel (refereegranskat)abstract
    • We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
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33.
  • Fjell, Anders M., et al. (författare)
  • Self-reported sleep relates to hippocampal atrophy across the adult lifespan : results from the Lifebrain consortium
  • 2020
  • Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 43:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.Methods: Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18–90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank.Results: No cross-sectional sleep—hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.Conclusions: Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.
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34.
  • Kalaria, Raj, et al. (författare)
  • The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.
  • 2024
  • Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - 1552-5279.
  • Tidskriftsartikel (refereegranskat)abstract
    • Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
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35.
  • Malkani, Sherina, et al. (författare)
  • Circulating miRNA Spaceflight Signature Reveals Targets for Countermeasure Development
  • 2020
  • Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 33:10
  • Tidskriftsartikel (refereegranskat)abstract
    • We have identified and validated a spaceflight-associated microRNA (miRNA) signature that is shared by rodents and humans in response to simulated, short-duration and long-duration spaceflight. Previous studies have identified miRNAs that regulate rodent responses to spaceflight in low-Earth orbit, and we have confirmed the expression of these proposed spaceflight-associated miRNAs in rodents reacting to simulated spaceflight conditions. Moreover, astronaut samples from the NASA Twins Study confirmed these expression signatures in miRNA sequencing, single-cell RNA sequencing (scRNA-seq), and single-cell assay for transposase accessible chromatin (scATAC-seq) data. Additionally, a subset of these miRNAs (miR-125, miR-16, and let-7a) was found to regulate vascular damage caused by simulated deep space radiation. To demonstrate the physiological relevance of key spaceflight-associated miRNAs, we utilized antagomirs to inhibit their expression and successfully rescue simulated deep-space-radiation-mediated damage in human 3D vascular constructs.
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36.
  • McDonald, J R, et al. (författare)
  • Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database.
  • 2005
  • Ingår i: The American journal of medicine. - : Elsevier BV. - 0002-9343. ; 118:7, s. 759-66
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.
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