1. |
- Ademuyiwa, Adesoji O., et al.
(author)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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2. |
- Abelev, Betty, et al.
(author)
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Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :11
-
Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
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3. |
- Abelev, Betty, et al.
(author)
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Underlying Event measurements in pp collisions at root s=0.9 and 7 TeV with the ALICE experiment at the LHC
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :7
-
Journal article (peer-reviewed)abstract
- We present measurements of Underlying Event observables in pp collisions at root s = 0 : 9 and 7 TeV. The analysis is performed as a function of the highest charged-particle transverse momentum p(T),L-T in the event. Different regions are defined with respect to the azimuthal direction of the leading (highest transverse momentum) track: Toward, Transverse and Away. The Toward and Away regions collect the fragmentation products of the hardest partonic interaction. The Transverse region is expected to be most sensitive to the Underlying Event activity. The study is performed with charged particles above three different p(T) thresholds: 0.15, 0.5 and 1.0 GeV/c. In the Transverse region we observe an increase in the multiplicity of a factor 2-3 between the lower and higher collision energies, depending on the track p(T) threshold considered. Data are compared to PYTHIA 6.4, PYTHIA 8.1 and PHOJET. On average, all models considered underestimate the multiplicity and summed p(T) in the Transverse region by about 10-30%.
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4. |
- Lagou, Vasiliki, et al.
(author)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
-
In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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5. |
- Moro, Carlos Fernandez, et al.
(author)
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An idiosyncratic zonated stroma encapsulates desmoplastic liver metastases and originates from injured liver
- 2023
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
-
Journal article (peer-reviewed)abstract
- A perimetastatic capsule is a strong positive prognostic factor in liver metastases, but its origin remains unclear. Here, we systematically quantify the capsule's extent and cellular composition in 263 patients with colorectal cancer liver metastases to investigate its clinical significance and origin. We show that survival improves proportionally with increasing encapsulation and decreasing tumor-hepatocyte contact. Immunostaining reveals the gradual zonation of the capsule, transitioning from benign-like NGFR(high) stroma at the liver edge to FAP(high) stroma towards the tumor. Encapsulation correlates with decreased tumor viability and preoperative chemotherapy. In mice, chemotherapy and tumor cell ablation induce capsule formation. Our results suggest that encapsulation develops where tumor invasion into the liver plates stalls, representing a reparative process rather than tumor-induced desmoplasia. We propose a model of metastases growth, where the efficient tumor colonization of the liver parenchyma and a reparative liver injury reaction are opposing determinants of metastasis aggressiveness.
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6. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
-
Journal article (peer-reviewed)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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7. |
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8. |
- Abazov, M, et al.
(author)
-
Combination of t(t)over-bar cross section measurements and constraints on the mass of the top quark and its decays into charged Higgs bosons
- 2009
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 80, s. 071102-
-
Journal article (peer-reviewed)abstract
- We combine measurements of the top quark pair production cross section in p (p) over bar collisions in the l + jets, ll, and tau l final states ( where l is an electron or muon) at a center of mass energy of root s = 1.96 TeV in 1 fb(-1) of data collected with the D0 detector. For a top quark mass of 170 GeV/c(2), we obtain sigma(t (t) over bar) = 8.18(-0.87)(+0.98) pb in agreement with the theoretical prediction. Based on predictions from higher order quantum chromodynamics, we extract a mass for the top quark from the combined t (t) over bar cross section, consistent with the world average of the top quark mass. In addition, the ratios of t (t) over bar cross sections in different final states are used to set upper limits on the branching fractions B(t -> H(+)b -> tau(+) vb) and B(t -> H(+)b -> c (s) over barb) as a function of the charged Higgs boson mass.
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9. |
- Abazov, M, et al.
(author)
-
Evidence of WW and WZ Production with lepton plus jets Final States in pp Collisions at root s=1.96 TeV
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:16, s. 161801-
-
Journal article (peer-reviewed)abstract
- We present first evidence for WW+WZ production in lepton+jets final states at a hadron collider. The data correspond to 1.07 fb(-1) of integrated luminosity collected with the D0 detector at the Fermilab Tevatron in pp collisions at root s=1.96 TeV. The observed cross section for WW+WZ production is 20.2 +/- 4.5 pb, consistent with the standard model and more precise than previous measurements in fully leptonic final states. The probability that background fluctuations alone produce this excess is < 5.4x10(-6), which corresponds to a significance of 4.4 standard deviations.
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10. |
- Abazov, M, et al.
(author)
-
Measurement of gamma + b + X and gamma + c + X Production Cross Sections in pp > Collisions at s=1.96 TeV
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:19, s. 192002-
-
Journal article (peer-reviewed)abstract
- First measurements of the differential cross sections d(3)sigma/(dp(T)(gamma)dy(gamma)dy(jet)) for the inclusive production of a photon in association with a heavy quark (b, c) jet are presented, covering photon transverse momenta 30 < p(T)(gamma)< 150 GeV, photon rapidities |y(gamma)|< 1.0, jet rapidities |y(jet)|< 0.8, and jet transverse momenta p(T)(jet)> 15 GeV. The results are based on an integrated luminosity of 1 fb(-1) in pp collisions at s=1.96 TeV recorded with the D0 detector at the Fermilab Tevatron Collider. The results are compared with next-to-leading order perturbative QCD predictions.
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11. |
- Abazov, M, et al.
(author)
-
Measurement of the t(t)over-bar production cross section and top quark mass extraction using dilepton events in p(p)over-bar collisions
- 2009
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 679:3, s. 177-185
-
Journal article (peer-reviewed)abstract
- We present a measurement of the top quark pair production cross section in p (p) over bar collisions at root s = 1.96 TeV using approximately 1 fb(-1) collected with the DO detector. We consider decay channels containing two high p(T) charged leptons where one lepton is identified as an electron or a muon while the other lepton can be an electron, a muon or a hadronically decaying tau lepton. For a mass of the top quark of 170 GeV, the measured cross section is 7.5(-1.0)(+1.0)(stat)(-0.6)(+0.7)(syst)(-0.5)(+0.6)(lumi) pb. Using l tau events only, we measure: sigma(t (t) over bar) x B(t (t) over bar -> l tau b (b) over bar) = 0.13(-0.08)(+0.09)(stat)(-0.06)(+0.06)(syst)(-0.02)(+0.02)(lumi) pb. Comparing the measured cross section as a function of the mass of the top quark with a partial next-to-next-to leading order Quantum Chroniodynamics theoretical prediction, we extract a mass of the top quark of 171.5(-8.8)(+9-9) GeV, in agreement with direct measurements.
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12. |
- Abazov, M, et al.
(author)
-
Observation of Single Top-Quark Production
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 103:9, s. 092001-
-
Journal article (peer-reviewed)abstract
- We report observation of the electroweak production of single top quarks in pp collisions at s=1.96 TeV based on 2.3 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron Collider. Using events containing an isolated electron or muon and missing transverse energy, together with jets originating from the fragmentation of b quarks, we measure a cross section of sigma(pp -> tb+X,tqb+X)=3.94 +/- 0.88 pb. The probability to measure a cross section at this value or higher in the absence of signal is 2.5x10(-7), corresponding to a 5.0 standard deviation significance for the observation.
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13. |
- Abazov, M, et al.
(author)
-
Relative rates of B meson decays into psi(2S) and J/psi mesons
- 2009
-
In: Physical Review D. - 1550-7998 .- 1550-2368. ; 79, s. 111102-
-
Journal article (peer-reviewed)abstract
- We report on a study of the relative rates of B meson decays into psi(2S) and J/psi mesons using 1.3 fb(-1) of p (p) over bar collisions at root s = 1.96 TeV recorded by the D0 detector operating at the Fermilab Tevatron Collider. We observe the channels B-s(0) -> psi(2S)phi, B-s(0) -> J/psi phi, B-+/- -> psi(2S)K-+/-, and B-+/- -> J/psi K-+/- and we measure the relative branching fractions for these channels to be B(B-s(0) -> psi(2S)phi)/B(B-s(0) -> J/psi phi)=0.53 +/- 0.10(stat)+/- 0.07(syst)+/- 0.06(B), B(B+ -> psi(2S)K+)/B(B+ -> J/psi K+)=0.63 +/- 0.05(stat)+/- 0.03(syst)+/- 0.07(B), where the final error corresponds to the uncertainty in the J/psi and psi(2S) branching ratio into two muons.
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14. |
- Abazov, M, et al.
(author)
-
Search for associated production of charginos and neutralinos in the trilepton final state using 2.3 fb(-1) of data
- 2009
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 680:1, s. 34-43
-
Journal article (peer-reviewed)abstract
- We report the results of a search for associated production of charginos and neutralinos using a data set corresponding to an integrated luminosity of 2.3 fb(-1) collected with the Demptyset experiment during Run II of the Tevatron proton-antiproton collider. Final states containing three charged leptons and missing transverse energy are probed for a signal from supersymmetry with four dedicated trilepton event selections. No evidence for a signal is observed, and we set limits on the product of production cross section and leptonic branching fraction. Within minimal supergravity, these limits translate into bounds on m(0) and m(1/2) that are well beyond existing limits.
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15. |
- Abazov, M, et al.
(author)
-
Search for Charged Higgs Bosons Decaying into Top and Bottom Quarks in pp Collisions
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:19, s. 191802-
-
Journal article (peer-reviewed)abstract
- We describe a search for production of a charged Higgs boson, qq>-> H+, reconstructed in the tb final state in the mass range 180 <= M-H(+)<= 300 GeV. The search was undertaken at the Fermilab Tevatron collider with a center-of-mass energy s=1.96 TeV and uses 0.9 fb(-1) of data collected with the D0 detector. We find no evidence for charged Higgs boson production and set upper limits on the production cross section in the types I, II, and III two-Higgs-doublet models (2HDMs). An excluded region in the (M-H(+), tan beta) plane for type I 2HDM is presented.
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16. |
- Abazov, M, et al.
(author)
-
Search for Long-Lived Charged Massive Particles with the D0 Detector
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:16, s. 161802-
-
Journal article (peer-reviewed)abstract
- We search for long-lived charged massive particles using 1.1 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron pp Collider. Time-of-flight information is used to search for pair produced long-lived tau sleptons, gauginolike charginos, and Higgsino-like charginos. We find no evidence of a signal and set 95% C.L. cross section upper limits for staus, which vary from 0.31 to 0.04 pb for stau masses between 60 and 300 GeV. We also set lower mass limits of 206 GeV (171 GeV) for pair produced charged gauginos (Higgsinos).
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17. |
- Abazov, M, et al.
(author)
-
Search for Resonant Diphoton Production with the D0 Detector
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:23, s. 231801-
-
Journal article (peer-reviewed)abstract
- We present a search for a narrow resonance in the inclusive diphoton final state using similar to 2.7 fb(-1) of data collected with the D0 detector at the Fermilab Tevatron p (p) over bar Collider. We observe good agreement between the data and the background prediction, and set the first 95% C. L. upper limits on the production cross section times the branching ratio for decay into a pair of photons for resonance masses between 100 and 150 GeV. This search is also interpreted in the context of several models of electroweak symmetry breaking with a Higgs boson decaying into two photons.
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18. |
- Abazov, M, et al.
(author)
-
Search for the Standard Model Higgs Boson in Tau Final States
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:25, s. 251801-
-
Journal article (peer-reviewed)abstract
- We present a search for the standard model Higgs boson using hadronically decaying tau leptons, in 1 fb(-1) of data collected with the D0 detector at the Fermilab Tevatron pp collider. We select two final states: tau(+/-) plus missing transverse energy and b jets, and tau(+)tau(-) plus jets. These final states are sensitive to a combination of associated W/Z boson plus Higgs boson, vector boson fusion, and gluon-gluon fusion production processes. The observed ratio of the combined limit on the Higgs production cross section at the 95% C.L. to the standard model expectation is 29 for a Higgs boson mass of 115 GeV.
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19. |
- Abazov, V. M., et al.
(author)
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Evidence for production of single top quarks and first direct measurement of vertical bar V-tb vertical bar
- 2007
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:18, s. 181802-
-
Journal article (peer-reviewed)abstract
- The D0 Collaboration presents first evidence for the production of single top quarks at the Fermilab Tevatron < p(p)over bar > collider. Using a 0.9 fb(-1) dataset, we apply a multivariate analysis to separate signal from background and measure sigma(< p(p)over bar >-> tb+X,tqb+X)=4.9 +/- 1.4 pb. The probability to measure a cross section at this value or higher in the absence of a signal is 0.035%, corresponding to a 3.4 standard deviation significance. We use the cross section measurement to directly determine the Cabibbo-Kobayashi-Maskawa matrix element that describes the Wtb coupling and find 0.68 <= 1 at 95% C.L. within the standard model.
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20. |
- Abazov, V. M., et al.
(author)
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Experimental discrimination between charge 2e/3 top quark and charge 4e/3 exotic quark production scenarios
- 2007
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:4, s. 041801-
-
Journal article (peer-reviewed)abstract
- We present the first experimental discrimination between the 2e/3 and 4e/3 top quark electric charge scenarios, using top quark pairs (t (t) over bar) produced in p (p) over bar collisions at root s =1.96 TeV by the Fermilab Tevatron Collider. We use 370 pb(-1) of data collected by the D0 experiment and select events with at least one high transverse momentum electron or muon, high transverse energy imbalance, and four or more jets. We discriminate between b- and (b) over bar -quark jets by using the charge and momenta of tracks within the jet cones. The data are consistent with the expected electric charge, |q|=2e/3. We exclude, at the 92% C.L., that the sample is solely due to the production of exotic quark pairs Q (Q) over bar with |q|=4e/3. We place an upper limit on the fraction of Q (Q) over bar pairs rho < 0.80 at the 90% C.L.
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21. |
- Abazov, V. M., et al.
(author)
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Lifetime difference and CP-violating phase in the B-s(0) system
- 2007
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:12, s. 121801-
-
Journal article (peer-reviewed)abstract
- From an analysis of the decay B-s(0)-> J/psi phi, we obtain the width difference between the light and heavy mass eigenstates Delta Gamma equivalent to(Gamma(L)-Gamma(H))=0.17 +/- 0.09(stat)+/- 0.02(syst) ps(-1) and the CP-violating phase phi(s)=-0.79 +/- 0.56(stat)(-0.01)(+0.14)(syst). Under the hypothesis of no CP violation (phi(s)equivalent to 0), we obtain 1/Gamma=tau/(B-s(0))=1.52 +/- 0.08(stat)(-0.03)(+0.01)(syst) ps and Delta Gamma=0.12(-0.10)(+0.08)(stat)+/- 0.02(syst) ps(-1). The data sample corresponds to an integrated luminosity of about 1.1 fb(-1) accumulated with the D0 detector at the Fermilab Tevatron collider. This is the first direct measurement of the CP-violating mixing phase in the B-s(0) system.
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22. |
- Abazov, V. M., et al.
(author)
-
Measurement of the charge asymmetry in semileptonic B-s(0) decays
- 2007
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:15, s. 151801-
-
Journal article (peer-reviewed)abstract
- We have performed the first direct measurement of the time-integrated flavor untagged charge asymmetry in semileptonic B-s(0) decays A(SL)(s,unt) by comparing the decay rate of B-s(0) -> mu(+) D-s(-) nu X, where D-s(-) -> phi pi(-) and phi -> K+K-, with the charge-conjugate (B) over bar (0)(s) decay rate. This sample was selected from 1: 3 fb(-1) of data collected by the D0 experiment in run II of the Fermilab Tevatron collider. We obtain A(SL)(s,unt) = [1.23 +/- 0.97(stat) +/- 0.17(syst)] x 10(-2). Assuming that Delta m(s)/(Gamma) over bar (s) >> 1, this result can be translated into a measurement of the CP-violating phase in B-s(0) mixing: Delta Gamma(s)/Delta m(s) tan phi(s) = [2.45 +/- 1.93(stat) +/- 0.35(syst)] x 10(-2).
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23. |
- Abazov, V. M., et al.
(author)
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Measurement of the Lifetime of the B-c(+/-) Meson in the Semileptonic Decay Channel
- 2009
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In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:9, s. 092001-
-
Journal article (peer-reviewed)abstract
- Using approximately 1.3 fb(-1) of data collected by the D0 detector between 2002 and 2006, we measure the lifetime of the B-c(+/-) meson in the B-c(+/-)-> J/psi mu(+/-)+X final state. A simultaneous unbinned likelihood fit to the J/psi+mu invariant mass and lifetime distributions yields a signal of 881 +/- 80(stat) candidates and a lifetime measurement of tau(B-c(+/-))=0.448(-0.036)(+0.038)(stat)+/- 0.032(syst) ps.
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24. |
- Abazov, V. M., et al.
(author)
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Measurement of the top quark mass in final states with two leptons
- 2009
-
In: Physical Review D - Particles, Fields, Gravitation and Cosmology. - 1550-7998 .- 1550-2368. ; 80, s. 092006-
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Journal article (peer-reviewed)abstract
- We present measurements of the top quark mass (m(t)) in tt candidate events with two final state leptons using 1 fb(-1) of data collected by the D0 experiment. Our data sample is selected by requiring two fully identified leptons or by relaxing one lepton requirement to an isolated track if at least one jet is tagged as a b jet. The top quark mass is extracted after reconstructing the event kinematics under the tt hypothesis using two methods. In the first method, we integrate over expected neutrino rapidity distributions, and in the second we calculate a weight for the possible top quark masses based on the observed particle momenta and the known parton distribution functions. We analyze 83 candidate events in the data and obtain m(t)=176.2 +/- 4.8(stat)+/- 2.1(sys) GeV and m(t)=173.2 +/- 4.9(stat)+/- 2.0(sys) GeV for the two methods, respectively. Accounting for correlations between the two methods, we combine the measurements to obtain m(t)=174.7 +/- 4.4(stat)+/- 2.0(sys) GeV.
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25. |
- Abazov, V. M., et al.
(author)
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Model-independent measurement of the W-boson helicity in top-quark decays at D0
- 2008
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 100:6
-
Journal article (peer-reviewed)abstract
- We present the first model-independent measurement of the helicity of W bosons produced in top quark decays, based on a 1 fb(-1) sample of candidate t (t) over bar events in the dilepton and lepton plus jets channels collected by the D0 detector at the Fermilab Tevatron p (p) over bar Collider. We reconstruct the angle theta(*) between the momenta of the down-type fermion and the top quark in the W boson rest frame for each top quark decay. A fit of the resulting cos theta(*) distribution finds that the fraction of longitudinal W bosons f(0)=0.425 +/- 0.166(stat)+/- 0.102(syst) and the fraction of right-handed W bosons f(+)=0.119 +/- 0.090(stat)+/- 0.053(syst), which is consistent at the 30% C.L. with the standard model.
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26. |
- Abazov, V. M., et al.
(author)
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Search for Anomalous Top-Quark Couplings with the D0 Detector
- 2009
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:9, s. 092002-
-
Journal article (peer-reviewed)abstract
- Anomalous Wtb couplings modify the angular correlations of the top-quark decay products and change the single top-quark production cross section. We present limits on anomalous top-quark couplings by combining information from W boson helicity measurements in top-quark decays and anomalous coupling searches in the single top-quark final state. We set limits on right-handed vector couplings as well as left-handed and right-handed tensor couplings based on about 1 fb(-1) of data collected by the D0 experiment.
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27. |
- Abazov, V. M., et al.
(author)
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Search for single production of scalar leptoquarks in p(p)over-bar collisions decaying into muons and quarks with the D0 detector
- 2007
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 647:2-3, s. 74-81
-
Journal article (peer-reviewed)abstract
- lWe report on a search for second generation leptoquarks (LQ(2)) which decay into a muon plus quark in (p) over barp collisions at a center-of-mass energy of root s = 1.96 TeV in the DO detector using an integrated luminosity of about 300 pb(-1). No evidence for a leptoquark signal is observed and an upper bound on the product of the cross section for single leptoquark production times branching fraction into a quark and a muon was determined for second generation scalar leptoquaiks as a function of the leptoquark mass. This result has been combined with a previously published DO search for leptoquark pair production to obtain leptoquark mass limits as a function of the leptoquark-muon-quark coupling, lambda. Assuming lambda = 1, lower limits on the mass of a second generation scalar leptoquark coupling to a u quark and a muon are m(LQ2) > 274 GeV and m(LQ2) > 226 GeV for beta = 1 and beta = 1/2, respectively.
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28. |
- Abazov, V. M., et al.
(author)
-
Search for techniparticles in e plus jets events at D0
- 2007
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 98:22, s. 221801-
-
Journal article (peer-reviewed)abstract
- We search for the technicolor process p(p) over bar ->rho(T)/omega(T)-> W pi(T) in events containing one electron and two jets, in data corresponding to an integrated luminosity of 390 pb(-1), recorded by the D0 experiment at the Fermilab Tevatron. Technicolor predicts that technipions pi(T) decay dominantly into b(b) over bar, b(c) over bar, or (b) over barc, depending on their charge. In these events b and c quarks are identified by their secondary decay vertices within jets. Two analysis methods based on topological variables are presented. Since no excess above the standard model prediction was found, the result is presented as an exclusion in the pi(T) vs rho(T) mass plane for a given set of model parameters.
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29. |
- Abazov, V. M., et al.
(author)
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Study of the decay B-s(0)->(DsDs(*))-D-(*)
- 2007
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 99:24
-
Journal article (peer-reviewed)abstract
- We report a study of the decay B-s(0)->(DsDs(*))-D-(*) using a data sample corresponding to 1.3 fb(-1) of integrated luminosity collected by the D0 experiment in 2002-2006 during run II of the Fermilab Tevatron collider. One D-s((*)) meson was partially reconstructed in the decay D-s ->phi mu nu, and the other D-s((*)) meson was identified using the decay D-s ->phi pi where no attempt was made to distinguish D-s and D-s(*) states. For the branching fraction Br(B-s(0)->(DsDs(*))-D-(*)) we obtain a 90% C.L. range [0.002,0.080] and central value 0.039(-0.017)(+0.019)(stat)(-0.015)(+0.016)(syst). This was subsequently used to make the most precise estimate of the width difference Delta Gamma(CP)(s) in the B-s(0)-(B)over bar(s)(0) system: Delta Gamma(CP)(s)/Gamma(s)=0.079(-0.035)(+0.038)(stat)(-0.030)(+0.031)(syst).
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30. |
- Abelev, Betty, et al.
(author)
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Long-range angular correlations on the near and away side in p-Pb collisions at root S-NN=5.02 TeV
- 2013
-
In: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 719:1-3, s. 29-41
-
Journal article (peer-reviewed)abstract
- Angular correlations between charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV for transverse momentum ranges within 0.5 < P-T,P-assoc < P-T,P-trig < 4 GeV/c. The correlations are measured over two units of pseudorapidity and full azimuthal angle in different intervals of event multiplicity, and expressed as associated yield per trigger particle. Two long-range ridge-like structures, one on the near side and one on the away side, are observed when the per-trigger yield obtained in low-multiplicity events is subtracted from the one in high-multiplicity events. The excess on the near-side is qualitatively similar to that recently reported by the CMS Collaboration, while the excess on the away-side is reported for the first time. The two-ridge structure projected onto azimuthal angle is quantified with the second and third Fourier coefficients as well as by near-side and away-side yields and widths. The yields on the near side and on the away side are equal within the uncertainties for all studied event multiplicity and p(T) bins, and the widths show no significant evolution with event multiplicity or p(T). These findings suggest that the near-side ridge is accompanied by an essentially identical away-side ridge. (c) 2013 CERN. Published by Elsevier B.V. All rights reserved.
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31. |
- Abulaiti, Yiming, et al.
(author)
-
Centrality, rapidity, and transverse momentum dependence of isolated prompt photon production in lead-lead collisions at root S-NN=2.76 TeV measured with the ATLAS detector
- 2016
-
In: Physical Review C. - : American Physical Society. - 2469-9985. ; 93:3
-
Journal article (peer-reviewed)abstract
- Prompt photon production in root S-NN = 2.76-TeV Pb + Pb collisions has been measured by the ATLAS experiment at the Large Hadron Collider using data collected in 2011 with an integrated luminosity of 0.14 nb(-1). Inclusive photon yields, scaled by the mean nuclear thickness function, are presented as a function of collision centrality and transverse momentum in two pseudorapidity intervals, vertical bar eta vertical bar < 1.37 and 1.52 <= vertical bar eta vertical bar < 2.37. The scaled yields in the two pseudorapidity intervals, as well as the ratios of the forward yields to those at midrapidity, are compared to the expectations from next-to-leading-order perturbative QCD (pQCD) calculations. The measured cross sections agree well with the predictions for proton-proton collisions within statistical and systematic uncertainties. Both the yields and the ratios are also compared to two other pQCD calculations, one which uses the isospin content appropriate to colliding lead nuclei and another which includes nuclear modifications to the nucleon parton distribution functions.
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32. |
- Abulaiti, Yiming, et al.
(author)
-
Measurement of the centrality dependence of the charged-particle pseudorapidity distribution in proton-lead collisions at root s(NN)=5.02 TeV with the ATLAS detector
- 2016
-
In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 76:4
-
Journal article (peer-reviewed)abstract
- The centrality dependence of the mean charged-particle multiplicity as a function of pseudorapidity is measured in approximately 1 mu b(-1) of proton-lead collisions at a nucleon-nucleon centre-of-mass energy of root s(NN) = 5.02 TeV using the ATLAS detector at the Large Hadron Collider. Charged particles with absolute pseudorapidity less than 2.7 are reconstructed using the ATLAS pixel detector. The p + Pb collision centrality is characterised by the total transverse energy measured in the Pb-going direction of the forward calorimeter. The charged-particle pseudorapidity distributions are found to vary strongly with centrality, with an increasing asymmetry between the proton-going and Pb-going directions as the collisions become more central. Three different estimations of the number of nucleons participating in the p + Pb collision have been carried out using the Glauber model as well as two Glauber-Gribov inspired extensions to the Glauber model. Charged-particle multiplicities per participant pair are found to vary differently for these three models, highlighting the importance of including colour fluctuations in nucleon-nucleon collisions in the modelling of the initial state of p + Pb collisions.
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33. |
- Bahram, Fuad, et al.
(author)
-
Interferon-γ-induced p27KIP1 binds to and targets MYC for proteasome-mediated degradation.
- 2016
-
In: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:3, s. 2837-2854
-
Journal article (peer-reviewed)abstract
- The Myc oncoprotein is tightly regulated at multiple levels including ubiquitin-mediated protein turnover. We recently demonstrated that inhibition of Cdk2-mediated phosphorylation of Myc at Ser-62 pharmacologically or through interferon (IFN)-γ-induced expression of p27Kip1 (p27) repressed Myc's activity to suppress cellular senescence and differentiation. In this study we identified an additional activity of p27 to interfere with Myc independent of Ser-62 phosphorylation. p27 is required and sufficient for IFN-γ-induced turnover of Myc. p27 interacted with Myc in the nucleus involving the C-termini of the two proteins, including Myc box 4 of Myc. The C-terminus but not the Cdk2 binding fragment of p27 was sufficient for inducing Myc degradation. Protein expression data of The Cancer Genome Atlas breast invasive carcinoma set revealed significantly lower Myc protein levels in tumors with highly expressed p27 lacking phosphorylation at Thr-157 - a marker for active p27 localized in the nucleus. Further, these conditions correlated with favorable tumor stage and patient outcome. This novel regulation of Myc by IFN-γ/p27KIP1 potentially offers new possibilities for therapeutic intervention in tumors with deregulated Myc.
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34. |
- Barredo, José I., et al.
(author)
-
Mapping and assessment of forest ecosystems and their services : Applications and guidance for decision making in the framework of MAES
- 2015
-
Reports (other academic/artistic)abstract
- The aim of this report is to illustrate by means of a series of case studies the implementation of mapping and assessment of forest ecosystem services in different contexts and geographical levels. Methodological aspects, data issues, approaches, limitations, gaps and further steps for improvement are analysed for providing good practices and decision making guidance. The EU initiative on Mappingand Assessment of Ecosystems and their Services (MAES), with the support of all Member States, contributes to improve the knowledge on ecosystem services. MAES is one of the building-block initiatives supporting the EU Biodiversity Strategy to 2020.
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35. |
- Barthelmie, Rebecca, et al.
(author)
-
ENDOW: Efficient Development of Offshore Windfarms
- 2003
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In: Proceedings from Offshore Wind Energy in Meditteranean and Other Seas OWEMES2003, Naples, Italy, 10-12 April 2003.
-
Conference paper (other academic/artistic)
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36. |
- Berne, Olivier, et al.
(author)
-
PDRs4All : A JWST Early Release Science Program on Radiative Feedback from Massive Stars
- 2022
-
In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 134:1035
-
Journal article (peer-reviewed)abstract
- Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.
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37. |
- Bernhard, Irene, 1953-
(author)
-
E-government and E-governance : Local Implementation of E-government Polices in Sweden
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- It is recognized in international research that the public sector has been transformed into a networked, open and more flexible, informal and interactive governance structure. This is described as a transition from “government to governance”. Sweden is one of the international leaders with regards to e-government development. The objective of this thesis is to provide a deeper understanding of how e-government policies are implemented in an e-governance context, through empirical case studies in Sweden. The focus is on the local level. The overall research question is: How is e-government policy put into practice when focusing on the local level? This is reported in four articles.Case study methodology is used as research method, including interviews, focus group interviews, document studies, and some participatory observations. The analysis is partly based on an inductive methodological approach, since this is a new, emerging field of innovative policy and practice.The analysis arrives at three overarching conclusions: (1) In practice, when e-government policy is implemented and translated at the local level, it tends to happen in an e-governance setting conducted by policy entrepreneurs or promoted by entrepreneurial behaviour in public administration. E-government policies are implemented in relation to local cultures, norms and economic structures. (2) Implementation of e-government and e-governance initiatives requires trust in the service provision among public administrators as well as among citizens. Efficiency and citizen-centred approaches in the redesign of information relationships between public administration and citizens to create some sort of added value are crucial. (3) The thesis indicates that there are two main implications of municipal contact centres (CCs): they localize public services and they combine different services into a one-stop practice striving to provide “holistic” services to the individual citizen. However, although the use of ICT is essential for the organisational transformation, the results indicate that the organisational settings and internal anchoring are greater constraints than new technology for implementation of local e-government and e-governance initiatives in the form of contact centres. One example for potential added value is the source of information of citizens’ issues through the implementation of municipal contact centres, which may have a positive impact on the conditions for local planning.
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38. |
- Bernhard, Sara, et al.
(author)
-
Molecular pathogenesis of infections caused by Moraxella catarrhalis in children.
- 2012
-
In: Swiss Medical Weekly. - : SMW Supporting Association. - 1424-7860 .- 1424-3997. ; 142
-
Journal article (peer-reviewed)abstract
- Moraxella catarrhalis (M. catarrhalis) is a human-restricted commensal of the normal bacterial flora in the upper respiratory tract of children, and - during the previous two decades - has been recognised as a true human pathogen. M. catarrhalis is the third most common pathogen causing acute otitis media in children, which is the most common reason to visit a paediatrician during childhood. Acute otitis media thus causes a high clinical and economical burden. With the introduction of the conjugate pneumococcal vaccines the microbiomic pattern in the nasopharyngeal flora of children has changed, and the frequency of isolation of M. catarrhalis has increased. Compared to adults, children are more often colonised with M. catarrhalis. Over the last three decades there has been a dramatic increase in the acquisition of β-lactam resistance in M. catarrhalis. Today 95-100% of clinically isolated M. catarrhalis produce β-lactamase. It is thus desirable to reduce the burden of M. catarrhalis disease by developing a vaccine. There are several potential vaccine antigen candidates in different stages of development, but none of them has entered clinical trials at the present time.
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39. |
- Bernhard, Sara, et al.
(author)
-
The outer membrane protein OlpA contributes to Moraxella catarrhalis serum resistance via interaction with factor H and the alternative pathway.
- 2014
-
In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 210:8, s. 1306-1310
-
Journal article (peer-reviewed)abstract
- Factor H is an important complement regulator of the alternative pathway commonly recruited by pathogens for increased survival in the human host. The respiratory pathogen Moraxella catarrhalis that resides in the mucosa is highly serum resistant and causes otitis media in children and respiratory tract infections in individuals with underlying diseases. In this study, we show that M. catarrhalis binds factor H via the outer membrane protein OlpA. M. catarrhalis serum resistance was dramatically decreased in the absence of either OlpA or factor H, demonstrating that this inhibition of the alternative pathway significantly contributes to the virulence of M. catarrhalis.
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40. |
- Bladh, Sara, et al.
(author)
-
Exploring Mass-Loss in M-type AGB Stars
- 2015
-
In: WHY GALAXIES CARE ABOUT AGB STARS III. - : ASTRONOMICAL SOC PACIFIC. ; , s. 345-350
-
Conference paper (peer-reviewed)abstract
- Stellar winds observed in asymptotic giant branch (AGB) stars are usually attributed to a combination of stellar pulsations and radiation pressure on dust. Strong candidates for wind-driving dust species in M-type AGB stars are magnesium silicates (Mg2SiO4 and MgSiO3). Such grains can form close to the stellar surface; they consist of abundant materials and, if they grow to sizes comparable to the wavelength of the stellar flux maximum, they experience strong acceleration by photon scattering. Here we present results from an extensive set of time-dependent wind models for M-type AGB stars with a detailed description for the growth of Mg2SiO4 grains. We show that these models reproduce observed mass-loss rates and wind velocities, as well as visual and near-IR photometry. However, the current models do not show the characteristic silicate features at 10 and 18 mu m, due to a rapidly falling temperature of Mg2SiO4 grains in the wind. Including a small amount of Fe in the grains further out in the circumstellar envelope will increase the grain temperature and result in pronounced silicate features, without significantly affecting the photometry in the visual and near-IR.
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41. |
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42. |
- Blomström Lundqvist, Carina, et al.
(author)
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Impact of non-adherence to direct oral anticoagulants amongst Swedish patients with non-valvular atrial fibrillation: results from a real-world cost-utility analysis
- 2022
-
In: Journal of Medical Economics. - : Taylor & Francis. - 1369-6998 .- 1941-837X. ; 25:1, s. 1085-1091
-
Journal article (peer-reviewed)abstract
- Aims: A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers.Methods: A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost–utility ratio.Results: Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81–90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81– 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively.Conclusion: Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system.
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43. |
- Dastani, Zari, et al.
(author)
-
Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
-
In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
-
Journal article (peer-reviewed)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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44. |
- Filipsson, Helena, et al.
(author)
-
A culture-based calibration of benthic foraminiferal paleotemperature proxies : δ18O and Mg/Ca results
- 2010
-
In: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 7:4, s. 1335-1347
-
Journal article (peer-reviewed)abstract
- Benthic foraminifera were cultured for five months at four temperatures (4, 7, 14 and 21 degrees C) to establish the temperature dependence of foraminiferal calcite delta O-18 and Mg/Ca. Two Bulimina species (B. aculeata and B. marginata) were most successful in terms of calcification, adding chambers at all four temperatures and reproducing at 7 and 14 degrees C. Foraminiferal delta O-18 values displayed ontogenetic variations, with lower values in younger individuals. The delta O-18 values of adult specimens decreased with increasing temperature in all but the 4 degrees C treatment, exhibiting a relationship consistent with previous delta O-18 paleotemperature calibration studies. Foraminiferal Mg/Ca values, determined by laser ablation inductively coupled plasma mass spectrometry, were broadly consistent with previous Mg/Ca calibration studies, but extremely high values in the 4 degrees C treatment and higher than predicted values at two of the other three temperatures make it challenging to interpret these results.
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45. |
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46. |
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47. |
- Galon, Jerome, et al.
(author)
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Towards the introduction of the 'Immunoscore' in the classification of malignant tumours
- 2014
-
In: Journal of Pathology. - : Wiley-Blackwell. - 0022-3417 .- 1096-9896. ; 232:2, s. 199-209
-
Research review (peer-reviewed)abstract
- The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).
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48. |
- Gaulton, Kyle J, et al.
(author)
-
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
-
Journal article (peer-reviewed)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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49. |
- Hellmich, Bernhard, et al.
(author)
-
2018 Update of the EULAR recommendations for the management of large vessel vasculitis
- 2020
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 79:1, s. 19-30
-
Journal article (peer-reviewed)abstract
- Background: Since the publication of the European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis (LVV) in 2009, several relevant randomised clinical trials and cohort analyses have been published, which have the potential to change clinical care and therefore supporting the need to update the original recommendations. Methods: Using EULAR standardised operating procedures for EULAR-endorsed recommendations, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 13 countries. We modified existing recommendations and created new recommendations. Results: Three overarching principles and 10 recommendations were formulated. We recommend that a suspected diagnosis of LVV should be confirmed by imaging or histology. High dose glucocorticoid therapy (40-60 mg/day prednisone-equivalent) should be initiated immediately for induction of remission in active giant cell arteritis (GCA) or Takayasu arteritis (TAK). We recommend adjunctive therapy in selected patients with GCA (refractory or relapsing disease, presence of an increased risk for glucocorticoid-related adverse events or complications) using tocilizumab. Methotrexate may be used as an alternative. Non-biological glucocorticoid-sparing agents should be given in combination with glucocorticoids in all patients with TAK and biological agents may be used in refractory or relapsing patients. We no longer recommend the routine use of antiplatelet or anticoagulant therapy for treatment of LVV unless it is indicated for other reasons. Conclusions: We have updated the recommendations for the management of LVV to facilitate the translation of current scientific evidence and expert opinion into better management and improved outcome of patients in clinical practice.
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50. |
- Hellmich, Bernhard, et al.
(author)
-
EULAR recommendations for the management of ANCA-associated vasculitis : 2022 update
- 2024
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 83:1, s. 30-47
-
Journal article (peer-reviewed)abstract
- Background: Since the publication of the EULAR recommendations for the management of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in 2016, several randomised clinical trials have been published that have the potential to change clinical care and support the need for an update. Methods: Using EULAR standardised operating procedures, the EULAR task force undertook a systematic literature review and sought opinion from 20 experts from 16 countries. We modified existing recommendations and created new recommendations. Results: Four overarching principles and 17 recommendations were formulated. We recommend biopsies and ANCA testing to assist in establishing a diagnosis of AAV. For remission induction in life-threatening or organ-threatening AAV, we recommend a combination of high-dose glucocorticoids (GCs) in combination with either rituximab or cyclophosphamide. We recommend tapering of the GC dose to a target of 5 mg prednisolone equivalent/day within 4-5 months. Avacopan may be considered as part of a strategy to reduce exposure to GC in granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). Plasma exchange may be considered in patients with rapidly progressive glomerulonephritis. For remission maintenance of GPA/MPA, we recommend rituximab. In patients with relapsing or refractory eosinophilic GPA, we recommend the use of mepolizumab. Azathioprine and methotrexate are alternatives to biologics for remission maintenance in AAV. Conclusions: In the light of recent advancements, these recommendations provide updated guidance on AAV management. As substantial data gaps still exist, informed decision-making between physicians and patients remains of key relevance.
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