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- Schael, S, et al.
(författare)
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Precision electroweak measurements on the Z resonance
- 2006
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Ingår i: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
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Forskningsöversikt (refereegranskat)abstract
- We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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- André, Ingemar, et al.
(författare)
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Streptococcal M protein: Structural studies of the hypervariable region, free and bound to human C4BP
- 2006
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 45:14, s. 4559-4568
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is a Gram-positive bacterium that causes several diseases, including acute tonsillitis and toxic shock syndrome. The surface-localized M protein, which is the most extensively studied virulence factor of S. pyogenes, has an similar to 50-residue N-terminal hypervariable region (HVR) that plays a key role in the escape of the host immunity. Despite the extensive sequence variability in this region, many HVRs specifically bind human C4b-binding protein (C4BP), a plasma protein that inhibits complement activation. Although the more conserved parts of M protein are known to have dimeric coiled-coil structure, it is unclear whether the HVR also is a coiled coil. Here, we use nuclear magnetic resonance (NMR) to study the conformational properties of HVRs from M4 and M22 proteins in isolation and in complex with the M protein binding portion of C4BP. We conclude that the HVRs of M4 and M22 are folded as coiled coils and that the folded nucleus of the M4 HVR has a length of similar to 27 residues. Moreover, we demonstrate that the C4BP binding surface of M4-N is found within a region of four heptad repeats. Using molecular modeling, we propose a model for the structure of the M4 HVR that is consistent with our experimental information from NMR spectroscopy.
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- Chockalingam, Priya, et al.
(författare)
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Not all beta-blockers are equal in the management of Long QT Syndrome types 1 and 2 : higher recurrence of events under metoprolol
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:20, s. 2092-2099
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective.Methods Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented.Results Patients (56% female, 27% symptomatic, heart rate 76 +/- 16 beats/min, QTc 472 +/- 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol.Conclusions Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.(J Am Coll Cardiol 2012;60:2092-9) (C) 2012 by the American College of Cardiology Foundation
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- Hardeland, C, et al.
(författare)
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Description of call handling in emergency medical dispatch centres in Scandinavia: recognition of out-of-hospital cardiac arrests and dispatcher-assisted CPR
- 2021
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Ingår i: Scandinavian journal of trauma, resuscitation and emergency medicine. - : Springer Science and Business Media LLC. - 1757-7241. ; 29:1, s. 88-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe European resuscitation council have highlighted emergency medical dispatch centres as an important key player for early recognition of Out-of-Hospital Cardiac Arrest (OHCA) and in providing dispatcher assisted cardiopulmonary resuscitation (CPR) before arrival of emergency medical services. Early recognition is associated with increased bystander CPR and improved survival rates. The aim of this study is to describe OHCA call handling in emergency medical dispatch centres in Copenhagen (Denmark), Stockholm (Sweden) and Oslo (Norway) with focus on sensitivity of recognition of OHCA, provision of dispatcher-assisted CPR and time intervals when CPR is initiated during the emergency call (NO-CPRprior), and to describe OHCA call handling when CPR is initiated prior to the emergency call (CPRprior).MethodsBaseline data of consecutive OHCA eligible for inclusion starting January 1st 2016 were collected from respective cardiac arrest registries. A template based on the Cardiac Arrest Registry to Enhance Survival definition catalogue was used to extract data from respective cardiac arrest registries and from corresponding audio files from emergency medical dispatch centres. Cases were divided in two groups: NO-CPRpriorand CPRpriorand data collection continued until 200 cases were collected in the NO-CPRprior-group.ResultsNO-CPRpriorOHCA was recognised in 71% of the calls in Copenhagen, 83% in Stockholm, and 96% in Oslo. Abnormal breathing was addressed in 34, 7 and 98% of cases and CPR instructions were started in 50, 60, and 80%, respectively. Median time (mm:ss) to first chest compression was 02:35 (Copenhagen), 03:50 (Stockholm) and 02:58 (Oslo). Assessment of CPR quality was performed in 80, 74, and 74% of the cases. CPRpriorcomprised 71 cases in Copenhagen, 9 in Stockholm, and 38 in Oslo. Dispatchers still started CPR instructions in 41, 22, and 40% of the calls, respectively and provided quality assessment in 71, 100, and 80% in these respective instances.ConclusionsWe observed variations in OHCA recognition in 71–96% and dispatcher assisted-CPR were provided in 50–80% in NO-CPRpriorcalls. In cases where CPR was initiated prior to emergency calls, dispatchers were less likely to start CPR instructions but provided quality assessments during instructions.
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- Mark, Linda, et al.
(författare)
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Localization of functional sites in the viral complement inhibitor KCP
- 2004
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Ingår i: Immunology 2004: Cytokine Network, Regulatory Cells, Signaling, and Apoptosis. ; , s. 243-247
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Konferensbidrag (refereegranskat)abstract
- Kaposi's sarcoma-associated herpes virus (KSHV) encodes a complement inhibitor named KSHV complement control protein (KCP). We have previously shown that KCP inhibits the human complement system by disrupting the C3 convertase of complement. KCP can accelerate the decay of the classical C3 convertase and it can act as a cofactor for factor I (R), which then cleaves and inactivates C4b or C3b (in the classical and alternative convertase, respectively). The aim of this study was to 1) delineate the sites on KCP responsible for complement inhibition 2) study the binding of KCP to heparin and the surface of cells. We constructed a 3D model of the four CCP domains KCP by homology based modeling, which served as basis for site directed mutagenesis. A patch of positively charged amino acids in CCPI, stretching into CCP2 as well as a positive and a negative patch in the region between CCP2-3 were the most functionally important sites. KCP binds to heparin and the surface of cells via a site in CCPI.
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- Mavaddat, N, et al.
(författare)
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Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers
- 2020
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Ingår i: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X. ; 22:1, s. 8-
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk forBRCA1andBRCA2mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly forBRCA2mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.MethodsA multi-centre prospective cohort of 2272BRCA1and 1605BRCA2mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.ResultsThere was no association between RRSO and breast cancer forBRCA1(HR = 1.23; 95% CI 0.94–1.61) orBRCA2(HR = 0.88; 95% CI 0.62–1.24) mutation carriers. ForBRCA2mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR forBRCA2mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.ConclusionWe found no evidence that RRSO reduces breast cancer risk forBRCA1mutation carriers. A potentially beneficial effect forBRCA2mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.
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