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- Aleksic, J., et al.
(författare)
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Measurement of the Crab Nebula spectrum over three decades in energy with the MAGIC telescopes
- 2015
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Ingår i: Journal of High Energy Astrophysics. - : Elsevier BV. - 2214-4048 .- 2214-4056. ; 5-6, s. 30-38
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Tidskriftsartikel (refereegranskat)abstract
- The MAGIC stereoscopic system collected 69 hours of Crab Nebula data between October 2009 and April 2011. Analysis of this data sample using the latest improvements in the MAGIC stereoscopic software provided an unprecedented precision of spectral and night-by-night light curve determination at gamma rays. We derived a differential spectrum with a single instrument from 50 GeV up to almost 30 TeV with 5 bins per energy decade. At low energies, MAGIC results, combined with Fermi-LAT data, show a flat and broad Inverse Compton peak. The overall fit to the data between 1 GeV and 30 TeV is not well described by a log-parabola function. We find that a modified log-parabola function with an exponent of 2.5 instead of 2 provides a good description of the data (chi(2)(red) = 35/26). Using systematic uncertainties of the MAGIC and Fermi-LAT measurements we determine the position of the Inverse Compton peak to be at (53 +/- 3(stat)+ 31(syst)-13(syst)) GeV, which is the most precise estimation up to date and is dominated by the systematic effects. There is no hint of the integral flux variability on daily scales at energies above 300 GeV when systematic uncertainties are included in the flux measurement. We consider three state-of-the-art theoretical models to describe the overall spectral energy distribution of the Crab Nebula. The constant B-field model cannot satisfactorily reproduce the VHE spectral measurements presented in this work, having particular difficulty reproducing the broadness of the observed IC peak. Most probably this implies that the assumption of the homogeneity of the magnetic field inside the nebula is incorrect. On the other hand, the time-dependent 1D spectral model provides a good fit of the new VHE results when considering a 80 mu G magnetic field. However, it fails to match the data when including the morphology of the nebula at lower wavelengths.
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| 5. |
- Wu, J. H. Y., et al.
(författare)
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Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis
- 2016
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Ingår i: Lancet Diabetes & Endocrinology. - : Elsevier BV. - 2213-8587. ; 4:5, s. 411-419
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Tidskriftsartikel (refereegranskat)abstract
- Background In patients with type 2 diabetes, sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to reduce glucose concentrations, blood pressure, and weight, but to increase LDL cholesterol and the incidence of urogenital infections. Protection against cardiovascular events has also been reported, as have possible increased risks of adverse outcomes such as ketoacidosis and bone fracture. We aimed to establish the effects of SGLT2 inhibitors on cardiovascular events, death, and safety outcomes in adults with type 2 diabetes, both overall and separately for individual drugs. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and websites of US, European, and Japanese regulatory authorities from Jan 1, 1950, to Sept 30, 2015, for data from prospective randomised controlled trials assessing the effects of SGLT2 treatment compared with controls. We excluded duplicate reports, trials of compound drugs, trials that lasted 7 days or fewer, trials that did not report on outcomes of interest, and articles that presented pooled trial data for which the individual trials could not be identified. We extracted data in duplicate using a standardised approach. The primary outcome was major adverse cardiovascular events. Secondary outcomes were cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, admission to hospital for unstable angina, heart failure, and all-cause mortality. We estimated summary relative risks with fixed-effects meta-analysis, with the I-2 statistic used to estimate heterogeneity of results beyond chance. Findings The analyses included data from six regulatory submissions (37 525 participants) and 57 published trials (33 385 participants), which provided data for seven different SGLT2 inhibitors. SGLT2 inhibitors protected against the risk of major adverse cardiovascular events (relative risk 0.84 [95% CI 0.75-0.95]; p=0.006), cardiovascular death (0.63 [0.51-0.77]; p<0.0001), heart failure (0.65 [0.50-0.85]; p=0.002), and death from any cause (0.71 [0.61-0.83]; p<0.0001). No clear effect was apparent for non-fatal myocardial infarction (0.88 [0.72-1.07]; p=0.18) or angina (0.95 [0.73-1.23]; p=0.70), but we noted an adverse effect for non-fatal stroke (1.30 [1.00-1.68]; p=0.049). We noted no clear evidence that the individual drugs had different effects on cardiovascular outcomes or death (all I I-2 < 43%). Safety analyses showed consistent increased risks of genital infections (regulatory submissions 4.75 [4.00-5.63]; scientific reports 2.88 [2.48-3.34]), but findings for some safety outcomes varied depending on whether anlayses were based on data extracted from regulatory submissions or trials reported in the scientific literature. Interpretation These data suggest net protection of SGLT2 inhibitors against cardiovascular outcomes and death. The efficacy results were driven by findings for empagliflozin (the only SGLT2 inhibitor for which data from a dedicated long-term cardiovascular safety trial have been reported), although results for the other drugs in the class were not clearly different. Adverse events were more difficult to quantify than was efficacy, with the effects of individual drugs in the class seeming to differ for some safety outcomes. Results from ongoing studies will be crucial to substantiate these findings across the drug class, but the available data provide a strong rationale to expect benefit from use of SGLT2 inhibitors in patients with type 2 diabetes at high risk of cardiovascular events.
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