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Sökning: WFRF:(Mannucci E)

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  • Kann, D. A., et al. (författare)
  • THE AFTERGLOWS OF SWIFT-ERA GAMMA-RAY BURSTS. I. COMPARING PRE-SWIFT AND SWIFT-ERA LONG/SOFT (TYPE II) GRB OPTICAL AFTERGLOWS
  • 2010
  • Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 720:2, s. 1513-1558
  • Tidskriftsartikel (refereegranskat)abstract
    • We have gathered optical photometry data from the literature on a large sample of Swift-era gamma-ray burst (GRB) afterglows including GRBs up to 2009 September, for a total of 76 GRBs, and present an additional three pre-Swift GRBs not included in an earlier sample. Furthermore, we publish 840 additional new photometry data points on a total of 42 GRB afterglows, including large data sets for GRBs 050319, 050408, 050802, 050820A, 050922C, 060418, 080413A, and 080810. We analyzed the light curves of all GRBs in the sample and derived spectral energy distributions for the sample with the best data quality, allowing us to estimate the host-galaxy extinction. We transformed the afterglow light curves into an extinction-corrected z = 1 system and compared their luminosities with a sample of pre-Swift afterglows. The results of a former study, which showed that GRB afterglows clustered and exhibited a bimodal distribution in luminosity space, are weakened by the larger sample. We found that the luminosity distribution of the two afterglow samples (Swift-era and pre-Swift) is very similar, and that a subsample for which we were not able to estimate the extinction, which is fainter than the main sample, can be explained by assuming a moderate amount of line-of-sight host extinction. We derived bolometric isotropic energies for all GRBs in our sample, and found only a tentative correlation between the prompt energy release and the optical afterglow luminosity at 1 day after the GRB in the z = 1 system. A comparative study of the optical luminosities of GRB afterglows with echelle spectra (which show a high number of foreground absorbing systems) and those without, reveals no indication that the former are statistically significantly more luminous. Furthermore, we propose the existence of an upper ceiling on afterglow luminosities and study the luminosity distribution at early times, which was not accessible before the advent of the Swift satellite. Most GRBs feature afterglows that are dominated by the forward shock from early times on. Finally, we present the first indications of a class of long GRBs, which form a bridge between the typical high-luminosity, high-redshift events and nearby low-luminosity events (which are also associated with spectroscopic supernovae) in terms of energetics and observed redshift distribution, indicating a continuous distribution overall.
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  • Castro-Tirado, A. J., et al. (författare)
  • GRB 030227 : The first multiwavelength afterglow of an INTEGRAL GRB
  • 2003
  • Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 411:1, s. 315-319
  • Tidskriftsartikel (refereegranskat)abstract
    • We present multiwavelength observations of a gamma-ray burst detected byINTEGRAL (GRB 030227) between 5.3 hours and ~ 1.7days after the event. Here we report the discovery of a dim opticalafterglow (OA) that would not have been detected by many previoussearches due to its faintess (R ~ 23). This OA was seen to declinefollowing a power law decay with index alpha R = -0.95 +/-0.16. The spectral index beta_ opt/NIR yielded -1.25 +/- 0.14. Thesevalues may be explained by a relativistic expansion of a fireball (withp = 2.0) in the cooling regime. We also find evidence for inverseCompton scattering in X-rays.Based on observations with INTEGRAL, an ESA project with instruments andscience data centre funded by ESA member states (especially the PIcountries: Denmark, France, Germany, Italy, Switzerland, Spain), CzechRepublic and Poland, and with the participation of Russia and the USA.Also partially based on observations collected by the Gamma-Ray BurstCollaboration at ESO (GRACE) at the European Southern Observatory, Chile(ESO Large Programme 165.H-0464).
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  • Astier, P., et al. (författare)
  • Extending the supernova Hubble diagram to z similar to 1.5 with the Euclid space mission
  • 2014
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 572, s. A80-
  • Tidskriftsartikel (refereegranskat)abstract
    • We forecast dark energy constraints that could be obtained from a new large sample of Type Ia supernovae where those at high redshift are acquired with the Euclid space mission. We simulate a three-prong SN survey: a z < 0.35 nearby sample (8000 SNe), a 0.2 < z < 0.95 intermediate sample (8800 SNe), and a 0.75 < z < 1.55 high-z sample (1700 SNe). The nearby and intermediate surveys are assumed to be conducted from the ground, while the high-z is a joint ground-and space-based survey. This latter survey, the Dark Energy Supernova Infra-Red Experiment (DESIRE), is designed to fit within 6 months of Euclid observing time, with a dedicated observing programme. We simulate the SN events as they would be observed in rolling-search mode by the various instruments, and derive the quality of expected cosmological constraints. We account for known systematic uncertainties, in particular calibration uncertainties including their contribution through the training of the supernova model used to fit the supernovae light curves. Using conservative assumptions and a 1D geometric Planck prior, we find that the ensemble of surveys would yield competitive constraints: a constant equation of state parameter can be constrained to sigma(omega) = 0.022, and a Dark Energy Task Force figure of merit of 203 is found for a two-parameter equation of state. Our simulations thus indicate that Euclid can bring a significant contribution to a purely geometrical cosmology constraint by extending a high-quality SN Ia Hubble diagram to z similar to 1.5. We also present other science topics enabled by the DESIRE Euclid observations.
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  • Corona, G, et al. (författare)
  • Thyroid hormones and male sexual function.
  • 2012
  • Ingår i: International Journal of Andrology. - : Wiley. - 1365-2605 .- 0105-6263. ; 35:5, s. 668-679
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of thyroid hormones in the control of erectile functioning has been only superficially investigated. The aim of the present study was to investigate the association between thyroid and erectile function in two different cohorts of subjects. The first one derives from the European Male Ageing Study (EMAS study), a multicentre survey performed on a sample of 3369 community-dwelling men aged 40-79 years (mean 60 ± 11 years). The second cohort is a consecutive series of 3203 heterosexual male patients (mean age 51.8 ± 13.0 years) attending our Andrology and Sexual Medicine Outpatient Clinic for sexual dysfunction at the University of Florence (UNIFI study). In the EMAS study all subjects were tested for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Similarly, TSH levels were checked in all patients in the UNIFI study, while FT4 only when TSH resulted outside the reference range. Overt primary hyperthyroidism (reduced TSH and elevated FT4, according to the reference range) was found in 0.3 and 0.2% of EMAS and UNIFI study respectively. In both study cohorts, suppressed TSH levels were associated with erectile dysfunction (ED). Overt hyperthyroidism was associated with an increased risk of severe erectile dysfunction (ED, hazard ratio = 14 and 16 in the EMAS and UNIFI study, respectively; both p < 0.05), after adjusting for confounding factors. These associations were confirmed in nested case-control analyses, comparing subjects with overt hyperthyroidism to age, BMI, smoking status and testosterone-matched controls. Conversely, no association between primary hypothyroidism and ED was observed. In conclusion, erectile function should be evaluated in all individuals with hyperthyroidism. Conversely, assessment of thyroid function cannot be recommended as routine practice in all ED patients.
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  • Peake, I R, et al. (författare)
  • Haemophilia : strategies for carrier detection and prenatal diagnosis
  • 1993
  • Ingår i: Bulletin of the World Health Organization. - 0042-9686. ; 71:3-4, s. 58-429
  • Tidskriftsartikel (refereegranskat)abstract
    • In 1977 WHO published in the Bulletin a Memorandum on Methods for the Detection of Haemophilia Carriers. This was produced following a WHO/WFH (World Federation of Haemophilia) Meeting of Investigators in Geneva in November 1976, and has served as a valuable reference article on the genetics of haemophilia. The analyses discussed were based on phenotypic assessment, which, at that time, was the only procedure available. The molecular biology revolution in genetics during the 1980s made enormous contributions to our understanding of the molecular basis of the haemophilias and now permits precise carrier detection and prenatal diagnosis. WHO and WFH held a joint meeting on this subject in February 1992 in Geneva. This article is the result of these discussions.
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  • Berntorp, E., et al. (författare)
  • Fifth Åland Island conference on von Willebrand disease
  • 2018
  • Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 2424 Suppl 4, s. 5-19
  • Tidskriftsartikel (refereegranskat)abstract
    • The fifth Åland Island meeting on von Willebrand disease (VWD) was held on the Åland Islands, Finland, from 22 to 24 September 2016—90 years after the first case of VWD was diagnosed in a patient from the Åland Islands in 1926. This meeting brought together experts in the field of VWD to share knowledge and expertise on current trends and challenges in VWD. Topics included the storage and release of von Willebrand factor (VWF), epidemiology and diagnostics in VWD, treatment of VWD, angiogenesis and VWF inhibitors.
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  • Furberg, Helena, et al. (författare)
  • Genome-wide meta-analyses identify multiple loci associated with smoking behavior
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 134-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Consistent but indirect evidence has implicated genetic factors in smoking behavior1,2. We report meta-analyses of several smoking phenotypes within cohorts of the Tobacco and Genetics Consortium (n = 74,053). We also partnered with the European Network of Genetic and Genomic Epidemiology (ENGAGE) and Oxford-GlaxoSmithKline (Ox-GSK) consortia to follow up the 15 most significant regions (n > 140,000). We identified three loci associated with number of cigarettes smoked per day. The strongest association was a synonymous 15q25 SNP in the nicotinic receptor gene CHRNA3 (rs1051730[A], b = 1.03, standard error (s.e.) = 0.053, beta = 2.8 x 10(-73)). Two 10q25 SNPs (rs1329650[G], b = 0.367, s. e. = 0.059, beta = 5.7 x 10(-10); and rs1028936[A], b = 0.446, s. e. = 0.074, beta = 1.3 x 10(-9)) and one 9q13 SNP in EGLN2 (rs3733829[G], b = 0.333, s. e. = 0.058, P = 1.0 x 10(-8)) also exceeded genome-wide significance for cigarettes per day. For smoking initiation, eight SNPs exceeded genome-wide significance, with the strongest association at a nonsynonymous SNP in BDNF on chromosome 11 (rs6265[C], odds ratio (OR) = 1.06, 95% confidence interval (Cl) 1.04-1.08, P = 1.8 x 10(-8)). One SNP located near DBH on chromosome 9 (rs3025343[G], OR = 1.12, 95% Cl 1.08-1.18, P = 3.6 x 10(-8)) was significantly associated with smoking cessation.
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  • Graham, J B, et al. (författare)
  • Carrier detection in hemophilia A : a cooperative international study. I. The carrier phenotype
  • 1986
  • Ingår i: Blood. - 0006-4971. ; 67:6, s. 9-1554
  • Tidskriftsartikel (refereegranskat)abstract
    • Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non-O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.
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  • Green, P P, et al. (författare)
  • Carrier detection in hemophilia A : a cooperative international study. II. The efficacy of a universal discriminant
  • 1986
  • Ingår i: Blood. - 0006-4971. ; 67:6, s. 7-1560
  • Tidskriftsartikel (refereegranskat)abstract
    • Factor VIII (F.VIII) and von Willebrand factor (VWF):Ag data collected by eight laboratories on a total of 336 obligatory carriers of hemophilia A and 137 normal women were used to answer several questions concerning the construction of linear discriminants for carrier detection. It was found: that a "universal" linear discriminant can be constructed which is suitable for use in all laboratories and is nearly as effective as laboratory-specific discriminants; that inclusion of age and ABO blood type data improved the efficacy of these discriminants; that substitution of alternative assays for F.VIII and VWF:Ag did not generally improve the efficacy of the discriminants over that obtained using the bioassay for F.VIII:C and Laurell's immunoassay for VWF:Ag; that linear discriminants were far more effective than discriminants based on the F.VIII:C/VWF:Ag ratio. A step-wise procedure is given which any laboratory may follow in using the universal discriminant for carrier detection.
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  • Sadler, J. E., et al. (författare)
  • Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor
  • 2006
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 4:10, s. 2103-2114
  • Forskningsöversikt (refereegranskat)abstract
    • von Willebrand disease (VWD) is a bleeding disorder caused by inherited defects in the concentration, structure, or function of von Willebrand factor (VWF). VWD is classified into three primary categories. Type 1 includes partial quantitative deficiency, type 2 includes qualitative defects, and type 3 includes virtually complete deficiency of VWF. VWD type 2 is divided into four secondary categories. Type 2A includes variants with decreased platelet adhesion caused by selective deficiency of high-molecular-weight VWF multimers. Type 2B includes variants with increased affinity for platelet glycoprotein Ib. Type 2M includes variants with markedly defective platelet adhesion despite a relatively normal size distribution of VWF multimers. Type 2N includes variants with markedly decreased affinity for factor VIII. These six categories of VWD correlate with important clinical features and therapeutic requirements. Some VWF gene mutations, alone or in combination, have complex effects and give rise to mixed VWD phenotypes. Certain VWD types, especially type 1 and type 2A, encompass several pathophysiologic mechanisms that sometimes can be distinguished by appropriate laboratory studies. The clinical significance of this heterogeneity is under investigation, which may support further subdivision of VWD type 1 or type 2A in the future.
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  • Voight, Benjamin F, et al. (författare)
  • Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
  • 2012
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
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24.
  • Abshire, T. C., et al. (författare)
  • Prophylaxis in severe forms of von Willebrand's disease: results from the von Willebrand Disease Prophylaxis Network (VWD PN)
  • 2013
  • Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 19:1, s. 76-81
  • Tidskriftsartikel (refereegranskat)abstract
    • The bleeding patterns of severe von Willebrand's disease (VWD) adversely affect quality of life, and may be life threatening. There is a presumed role for prophylaxis with VWF-containing concentrates, but data are scarce. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is not responsive to other treatment(s). Using a retrospective design, the effect of prophylaxis was studied. Availability of records to document, or reliably assess, the type and frequency of bleeding episodes prior to, and after, the initiation of prophylaxis was required. Annualized bleeding rates were calculated for the period prior to prophylaxis, during prophylaxis and by primary bleeding indication defined as the site accounting for more than half of all bleeding symptoms. The Wilcoxon signed-rank test of differences in the medians was used. Sixty-one subjects from 20 centres in 10 countries were enrolled. Data for 59 were used in the analysis. The median age at onset of prophylaxis was 22.4 years. Type 3 VWD accounted for the largest number (N = 34, 57.6%). Differences in bleeding rates within individuals during compared with before prophylaxis were significant for the total group (P < 0.0001), and for those with primary bleeding indications of epistaxis (P = 0.0005), joint bleeding (P = 0.002) and GI bleeding (P = 0.001). The effect of prophylaxis was similar among those age < 18 years and those >= 18. One person developed an inhibitor during treatment. We conclude that prophylactic treatment of VWD is efficacious.
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25.
  • Astermark, J., et al. (författare)
  • Symposium in memory of Professor Inga Marie Nilsson
  • 2001
  • Ingår i: Haemophilia. - : Wiley. - 1351-8216. ; 7:4, s. 401-410
  • Konferensbidrag (refereegranskat)abstract
    • Professor Inga Marie Nilsson (1923-99) was a pioneer in the field of bleeding and thrombo-embolic disorders and made several major scientific contributions during her career. To honour her memory, colleagues from all over the world were invited to cover several aspects of haemostasis by giving state-of-the-art lectures at an international symposium in Malmö on September 22-23, 2000, chaired by Professors Lou Aledort and Erik Berntorp. Colleagues of Professor Nilsson in Malmö gave a short introduction to each topic. A short review of the meeting will be presented.
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26.
  • Cicone, C., et al. (författare)
  • SUPER VI. A giant molecular halo around a z similar to 2 quasar
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the discovery of copious molecular gas in the halo of cid_346, a z=2.2 quasar studied as part of the SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER). New Atacama Compact Array (ACA) CO(3-2) observations detect a much higher flux (by a factor of 14 +/- 5) than measured on kiloparsec scales (r less than or similar to 8 kpc) using previous snapshot Atacama Large Millimeter/submillimeter Array data. Such additional CO(3-2) emission traces a structure that extends out to r similar to 200 kpc in projected size, as inferred through direct imaging and confirmed by an analysis of the uv visibilities. This is the most extended molecular circumgalactic medium (CGM) reservoir that has ever been mapped. It shows complex kinematics, with an overall broad line profile (FWHM=1000 km s(-1)) that is skewed towards redshifted velocities up to at least v similar to 1000 km s(-1). Using the optically thin assumption, we estimate a strict lower limit for the total molecular CGM mass observed by ACA of M-mol(CGM) > 10(10) M-circle dot. There is however room for up to M-mol(CGM) similar to 1.7 x 10(12) M-circle dot, once optically thick CO emission with alpha(CO) = 3.6 M-circle dot (K km s(-1) pc(2))(-1) and LCO(3- 2)'/LCO(1-0)' = 0.5 are assumed. Since cid_346 hosts quasar-driven ionised outflows and since there is no evidence of merging companions or an overdensity, we suggest that outflows may have played a crucial rule in seeding metal-enriched, dense gas on halo scales. However, the origin of such an extended molecular CGM remains unclear.
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27.
  • d'Alessandro, Elisa, et al. (författare)
  • Thrombo-Inflammation in Cardiovascular Disease : An Expert Consensus Document from the Third Maastricht Consensus Conference on Thrombosis
  • 2020
  • Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 120:4, s. 538-564
  • Tidskriftsartikel (refereegranskat)abstract
    • Thrombo-inflammation describes the complex interplay between blood coagulation and inflammation that plays a critical role in cardiovascular diseases. The third Maastricht Consensus Conference on Thrombosis assembled basic, translational, and clinical scientists to discuss the origin and potential consequences of thrombo-inflammation in the etiology, diagnostics, and management of patients with cardiovascular disease, including myocardial infarction, stroke, and peripheral artery disease. This article presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following topics: (1) challenges of the endothelial cell barrier; (2) circulating cells and thrombo-inflammation, focused on platelets, neutrophils, and neutrophil extracellular traps; (3) procoagulant mechanisms; (4) arterial vascular changes in atherogenesis; attenuating atherosclerosis and ischemia/reperfusion injury; (5) management of patients with arterial vascular disease; and (6) pathogenesis of venous thrombosis and late consequences of venous thromboembolism.
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28.
  • Deacon, C F, et al. (författare)
  • Glycaemic efficacy of glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors as add-on therapy to metformin in subjects with type 2 diabetes-a review and meta analysis.
  • 2012
  • Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 14:8, s. 762-767
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: During recent years, two strategies of incretin-based therapy [glucagon-like peptide-1 (GLP-1) receptor agonism and dipeptidyl peptidase-4 (DPP-4) inhibition] have entered the market for pharmacological management of type 2 diabetes. A main indication for this therapy is as add-on to on-going metformin therapy in subjects with type 2 diabetes who have insufficient glycaemic control with metformin alone. The aim of this study was to compare improvements in glycaemic control and changes in body weight, as well as adverse events, in comparable studies with incretin-based therapy as add-on to metformin. Methods: Studies having a duration of 16-30 weeks were identified from PubMed. Results: A total of 27 study groups in 21 studies fulfilled the criteria of examining incretin-based therapy as add-on to metformin at clinically recommended doses in patients with type 2 diabetes for 16-30 weeks; 7 of these used a short-acting GLP-1 receptor agonist (exenatide BID), 7 used longer acting GLP-1 receptor agonists (liraglutide or exenatide LAR), whereas 14 studies examined DPP-4 inhibitors. In all studies, incretin-based therapy reduced HbA1c concentrations. The reduction in HbA1c was significantly greater in study groups with long-acting GLP-1 receptor agonists than with the other two groups (both p < 0.001), whereas there were no differences between exenatide BID and DPP-4 inhibitors. Across all study groups, there was a negative linear correlation between baseline HbA1c and change in HbA1c (r = -0.70; p < 0.001). Fasting glucose also fell significantly more in study groups given liraglutide or exenatide LAR than in those given exenatide BID or DPP-4 inhibitors (both p < 0.001). Furthermore, body weight was reduced by a similar extent in the two groups with GLP-1 receptor agonists and was not significantly altered in the groups with DPP-4 inhibitors. Lipids, blood pressure and heart rate were not reported consistently, which did not allow general conclusions. Adverse events were rare, apart from increased incidence of nausea and vomiting with GLP-1 receptor agonists. Conclusion: Incretin-based therapy efficiently improves glycaemia when added to metformin in patients with type 2 diabetes, and within 16-30 weeks there is a more pronounced reduction in HbA1c with long-acting GLP-1 receptor agonists (liraglutide and exenatide LAR) than with exenatide BID and DPP-4 inhibitors, although the magnitude of the effect is dependent on the baseline values. Both strategies appear to be associated with a very low risk of adverse events, including hypoglycaemia. Finally, the injectable GLP-1 receptor agonists also reduce body weight (whereas the DPP-4 inhibitors are weight neutral) but are also associated with a greater incidence of gastrointestinal side effects and a tendency to increase heart rate.
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31.
  • Kakkad, D., et al. (författare)
  • SUPER: II. Spatially resolved ionised gas kinematics and scaling relations in z 2 ∼ AGN host galaxies
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER) aims to trace and characterise ionised gas outflows and their impact on star formation in a statistical sample of X-ray selected active galactic nuclei (AGN) at z ∼ 2. We present the first SINFONI results for a sample of 21 Type 1 AGN spanning a wide range in bolometric luminosity (log Lbol = 45.4-47.9 erg s-1). The main aims of this paper are to determine the extension of the ionised gas, characterise the occurrence of AGN-driven outflows, and link the properties of such outflows with those of the AGN. Methods. We used adaptive optics-assisted SINFONI observations to trace ionised gas in the extended narrow line region using the [O» III] λ5007 line. We classified a target as hosting an outflow if its non-parametric velocity of the [O» III] line, w80, was larger than 600 km s-1. We studied the presence of extended emission using dedicated point-spread function (PSF) observations, after modelling the PSF from the Balmer lines originating from the broad line region. Results. We detect outflows in all the Type 1 AGN sample based on the w80 value from the integrated spectrum, which is in the range ∼650-2700 km s-1. There is a clear positive correlation between w80 and the AGN bolometric luminosity (> 99% correlation probability), and the black hole mass (98% correlation probability). A comparison of the PSF and the [O» III] radial profile shows that the [O» III] emission is spatially resolved for ∼35% of the Type 1 sample and the outflows show an extension up to ∼6 kpc. The relation between maximum velocity and the bolometric luminosity is consistent with model predictions for shocks from an AGN-driven outflow. The escape fraction of the outflowing gas increases with the AGN luminosity, although for most galaxies, this fraction is less than 10%.
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32.
  • Lamperti, I., et al. (författare)
  • SUPER: V. ALMA continuum observations of z ∼2 AGN and the elusive evidence of outflows influencing star formation
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
  • Tidskriftsartikel (refereegranskat)abstract
    • We study the impact of active galactic nuclei (AGN) ionised outflows on star formation in high-redshift AGN host galaxies, by combining near-infrared integral field spectroscopic (IFS) observations, mapping the H emission and [O iii]5007 outflows, with matched-resolution observations of the rest-frame far-infrared (FIR) emission.We present high-resolution ALMA Band 7 observations of eight X-ray selected AGN (L2-10 keV = 1043:81045:2 erg s1) at z 2 from the SUPER (SINFONI Survey for Unveiling the Physics and Eect of Radiative feedback) sample, targeting the observed-frame 870 m (rest-frame 260 m) continuum at 2 kpc (0.200) spatial resolution. The targets were selected among the SUPER AGN with an [O iii] detection in the IFS maps and with a detection in the FIR photometry. We detected six out of eight targets with signal-to-noise ratio S=N & 10 in the ALMA maps, from which we measured continuum flux densities in the range 0:272:58 mJy and FIR half-light radii (Re) in the range 0:8-2:1 kpc. The other two targets were detected with S/N of 3.6 and 5.9, which are insucient for spatially resolved analysis. The FIR Re of our sample are comparable to other AGN and star-forming galaxies at a similar redshift from the literature. However, combining our sample with the literature samples, we find that the mean FIR size in X-ray AGN (Re = 1:16 0:11 kpc) is slightly smaller than in non-AGN (Re = 1:69 0:13 kpc). From spectral energy distribution fitting, we find that the main contribution to the 260 m flux density is dust heated by star formation, with 4% contribution from AGN-heated dust and 1% from synchrotron emission. The majority of our sample show dierent morphologies for the FIR (mostly due to reprocessed stellar emission) and the ionised gas emission (H and [O iii], mostly due to AGN emission). This could be due to the dierent locations of dust and ionised gas, the dierent sources of the emission (stars and AGN), or the eect of dust obscuration.We are unable to identify any residual H emission, above that dominated by AGN, that could be attributed to star formation. Under the assumption that the FIR emission is a reliable tracer of obscured star formation, we find that the obscured star formation activity in these AGN host galaxies is not clearly aected by the ionised outflows. However, we cannot rule out that star formation suppression is happening on smaller spatial scales than the ones we probe with our observations (<2 kpc) or on dierent timescales.
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33.
  • Monami, M., et al. (författare)
  • Dipeptidyl peptidase-4 inhibitors and cardiovascular risk: a meta-analysis of randomized clinical trials
  • 2013
  • Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 15:2, s. 112-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Preliminary data from randomized trials with metabolic outcomes have shown that treatment with dipeptidyl peptidase-4 inhibitors (DPP4i) could be associated with a reduced incidence of major cardiovascular events (MACE). The present meta-analysis is aimed at verifying this protective effect, collecting all available data from randomized trials. Methods A comprehensive search for published and unpublished trials with a duration =24 weeks comparing DPP4i with placebo or other drugs was performed, retrieving all MACE reported as serious adverse events together with death from any cause. MantelHaenzel odds ratio (MHOR) was calculated with random effect models for MACE, myocardial infarction, stroke and mortality. When available, effects on glycated haemoglobin, lipid profile and blood pressure were also assessed and used for the estimation of the modification of risk for myocardial infarction using the UKPDS risk engine. Results A total of 70 trials, enrolling 41?959 patients with a mean follow-up of 44.1 weeks, was collected and included in the analysis. The MHOR (95% Confidence Interval) was 0.71[0.59;0.86], 0.64[0.44;0.94], 0.77[0.48;1.24] and 0.60[0.41;0.88] for MACE, myocardial infarction, stroke and mortality, respectively. Conclusions Treatment with DPP4i reduces the risk of cardiovascular events (particularly myocardial infarction) and all-cause mortality in patients with type 2 diabetes. The reduction in the incidence of myocardial infarction is greater than what predicted on the basis of conventional risk factors, suggesting a role for other mechanisms.
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34.
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35.
  • Schunkert, Heribert, et al. (författare)
  • Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
  • Tidskriftsartikel (refereegranskat)abstract
    • We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
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36.
  • Vietri, G., et al. (författare)
  • SUPER - III. Broad line region properties of AGNs at z ∼ 2
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. The SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER) was designed to conduct a blind search for AGN-driven outflows on X-ray-selected AGNs at redshift z similar to 2 with high (similar to 2 kpc) spatial resolution, and to correlate them with the properties of their host galaxy and central black hole. The main aims of this paper are: (a) to derive reliable estimates for the masses of the black holes and accretion rates for the Type-1 AGNs in this survey; and (b) to characterise the properties of the AGN-driven winds in the broad line region (BLR).Methods. We analysed rest-frame optical and UV spectra of 21 Type-1 AGNs. We used H alpha, H beta, and MgII line profiles to estimate the masses of the black holes. We used the blueshift of the CIV line profile to trace the presence of winds in the BLR.Results. We find that the H alpha and H beta line widths are strongly correlated, as is the line continuum luminosity at 5100 angstrom with H alpha line luminosity, resulting in a well-defined correlation between black hole masses estimated from H alpha and H beta. Using these lines, we estimate that the black hole masses for our objects are in the range Log (M-BH/M-circle dot) = 8.4-10.8 and are accreting at lambda (Edd) = 0.04-1.3. Furthermore, we confirm the well-known finding that the CIV line width does not correlate with the Balmer lines and the peak of the line profile is blueshifted with respect to the [OIII]-based systemic redshift. These findings support the idea that the CIV line is tracing outflowing gas in the BLR for which we estimated velocities up to similar to 4700 km s(-1). We confirm the strong dependence of the BLR wind velocity on the UV-to-X-ray continuum slope, the bolometric luminosity, and Eddington ratio. We infer BLR mass outflow rates in the range 0.005-3 M-circle dot yr(-1), revealing a correlation with the bolometric luminosity consistent with that observed for ionised winds in the narrow line region (NLR), and X-ray winds detected in local AGNs, and kinetic power similar to 10(-7)-10(-4)xL(Bol). The coupling efficiencies predicted by AGN-feedback models are much higher than the values reported for the BLR winds in the SUPER sample; although it should be noted that only a fraction of the energy injected by the AGN into the surrounding medium is expected to become kinetic power in the outflow. Finally, we find an anti-correlation between the equivalent width of the [OIII] line and the CIV velocity shift, and a positive correlation between this latter parameter and [OIII] outflow velocity. These findings, for the first time in an unbiased sample of AGNs at z similar to 2, support a scenario where BLR winds are connected to galaxy-scale detected outflows, and are therefore capable of affecting the gas in the NLR located at kiloparsec scale distances.
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