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- Albert, A., et al.
(författare)
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SEARCHING FOR DARK MATTER ANNIHILATION IN RECENTLY DISCOVERED MILKY WAY SATELLITES WITH FERMI-LAT
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 834:2
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Tidskriftsartikel (refereegranskat)abstract
- We search for excess gamma-ray emission coincident with the positions of confirmed and candidate Milky Way satellite galaxies using six years of data from the Fermi Large Area Telescope (LAT). Our sample of 45 stellar systems includes 28 kinematically confirmed dark-matter-dominated dwarf spheroidal galaxies (dSphs) and 17 recently discovered systems that have photometric characteristics consistent with the population of known dSphs. For each of these targets, the relative predicted gamma-ray flux due to dark matter annihilation is taken from kinematic analysis if available, and estimated from a distance-based scaling relation otherwise, assuming that the stellar systems are DM-dominated dSphs. LAT data coincident with four of the newly discovered targets show a slight preference (each similar to 2 sigma local) for gamma-ray emission in excess of the background. However, the ensemble of derived gamma-ray flux upper limits for individual targets is consistent with the expectation from analyzing random blank-sky regions, and a combined analysis of the population of stellar systems yields no globally significant excess (global significance < 1 sigma). Our analysis has increased sensitivity compared to the analysis of 15 confirmed dSphs by Ackermann et al. The observed constraints on the DM annihilation cross section are statistically consistent with the background expectation, improving by a factor of similar to 2 for large DM masses (m(DM, b<(b)over bar>) greater than or similar to 1 TeV and m(DM, tau+tau-) greater than or similar to 70 GeV) and weakening by a factor of similar to 1.5 at lower masses relative to previously observed limits.
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- Bohm, M., et al.
(författare)
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Twenty-four-hour heart rate lowering with ivabradine in chronic heart failure: insights from the SHIFT Holter substudy
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:5, s. 518-26
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Analysis of 24-h Holter recordings was a pre-specified substudy of SHIFT (Systolic Heart Failure Treatment with the If Inhibitor Ivabradine Trial) for exploring the heart rhythm safety of ivabradine and to determine effects of ivabradine on 24-h, daytime, and night-time heart rate (HR) compared with resting office HR. METHODS AND RESULTS: The 24-h Holter monitoring was performed at baseline and 8 months after randomization to ivabradine (n = 298) or matching placebo (n = 304) titrated maximally to 7.5 mg b.i.d. in patients with baseline HR >/=70 b.p.m. Patients received guideline-based optimized heart failure therapy including ACE inhibitors and/or ARBs in 93% and beta-blockers at maximally tolerated doses in 93%. After 8 months, HR over 24 h decreased by 9.5 +/- 10.0 b.p.m. with ivabradine, from 75.4 +/- 10.3 b.p.m. (P < 0.0001), and by 1.2 +/- 8.9 b.p.m. with placebo, from 74.8 +/- 9.7 b.p.m. (P < 0.0001 for difference vs. ivabradine). HR reduction with ivabradine was similar in resting office and in 24-h, awake, and asleep recordings, with beneficial effects on HR variability and no meaningful increases in supraventricular or ventricular arrhythmias. At 8 months, 21.3% on ivabradine vs. 8.5% on placebo had >/=1 episode of HR <40 b.p.m. (P < 0.0001). No episode of HR <30 b.p.m. was recorded; 3 (1.2%) patients had RR intervals >2.5 s on ivabradine vs. 4 (1.6%) patients on placebo. No RR intervals >3 s were identified in patients taking ivabradine. CONCLUSION: Ivabradine safely and significantly lowers HR and improves HR variability in patients with systolic heart failure, without inducing significant bradycardia, ventricular arrhythmias, or supraventricular arrhythmias.
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- Reil, J. C., et al.
(författare)
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Selective heart rate reduction with ivabradine unloads the left ventricle in heart failure patients
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 62:21, s. 1977-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The study aimed to determine whether isolated heart rate (HR) reduction with ivabradine reduces afterload of patients with systolic heart failure. BACKGROUND: The effective arterial elastance (Ea) represents resistive and pulsatile afterload of the heart derived from the pressure volume relation. HR modulates Ea, and, therefore, afterload burden. METHODS: Among the patients with systolic heart failure (ejection fraction
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- Reil, J. C., et al.
(författare)
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Heart rate reduction in cardiovascular disease and therapy
- 2011
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Ingår i: Clinical research in cardiology. - : Springer Science and Business Media LLC. - 1861-0692 .- 1861-0684. ; 100:1, s. 11-19
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Tidskriftsartikel (refereegranskat)abstract
- Heart rate influences myocardial oxygen demand, coronary blood flow, and myocardial function. Clinical and experimental studies support an association between elevated resting heart rate and a broad range of maladaptive effects on the function and structure of the cardiovascular system. Heart rate has been shown to be an important predictor of mortality in cardiovascular disorders such as coronary artery disease, myocardial infarction, and chronic heart failure. This review summarizes the specific influence of heart rate on vascular morphology and function as well as on myocardial lesions leading from early impact on vascular homeostasis to myocardial hemodynamics in chronic heart failure. Heart rate can be easily determined during physical examination of the patient and therefore allows a simple hint on prognosis and efficiency of therapy.
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- Reil, J. C., et al.
(författare)
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Impact of left bundle branch block on heart rate and its relationship to treatment with ivabradine in chronic heart failure
- 2013
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 15:9, s. 1044-1052
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Left bundle branch block (LBBB) increases morbidity and mortality in heart failure (HF). Heart rate reduction with ivabradine improves outcomes in patients with systolic HF. Therefore, we aimed to analyse the impact of LBBB on outcomes in patients with systolic HF as a function of heart rate, and the relationship between LBBB and the effect of treatment with ivabradine. METHODS AND RESULTS: Patients from the SHIFT (n = 6505) were divided into groups with (n = 912) or without (n = 5593) LBBB at baseline, and according to tertiles of heart rate (70-73, 74-80, and >/=81 b.p.m.). The effect of LBBB, heart rate, and ivabradine on the primary endpoint (cardiovascular death or HF hospitalization) and other endpoints was analysed. LBBB was associated with increases in the primary endpoint by 65%, cardiovascular mortality by 49%, HF hospitalization by 86%, and all-cause mortality by 49% (all P < 0.001). No interaction appeared between the impact of heart rate on outcomes and presence of LBBB (P = 0.83 for the primary endpoint); thus LBBB increases risk for all heart rates. No interaction was apparent in the effect of ivabradine with LBBB or without LBBB. Ivabradine did not increase the prevalence of bradycardia in patients with LBBB. CONCLUSION: LBBB increases risk in HF patients with heart rates >/=70 b.p.m. in sinus rhythm, unmodulated by heart rate. Ivabradine was safe in LBBB. Its effect was directionally similar to that in patients without LBBB, but did not reach statistical significance, possibly due to lack of power to test this effect because of the small number of LBBB patients.
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- Flesch, BK, et al.
(författare)
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Multicenter Study on Differential Human Neutrophil Antigen 2 Expression and Underlying Molecular Mechanisms
- 2020
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Ingår i: Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. - : S. Karger AG. - 1660-3796. ; 47:5, s. 385-395
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> The human neutrophil antigen 2 (HNA-2), which is expressed on CD177, is undetectable in 3–5% of the normal population. Exposure of these HNA-2<sub>null</sub> individuals to HNA-2-positive cells can cause immunization and production of HNA-2 antibodies, which can induce immune neutropenia and transfusion-related acute lung injury. In HNA-2-positive individuals, neutrophils are divided into a CD177<sup>pos.</sup> and a CD177<sup>neg.</sup> subpopulation. The molecular background of HNA-2 deficiency and the bimodal expression pattern, however, are not completely decoded. <b><i>Study Design:</i></b> An international collaboration was conducted on the genetic analysis of HNA-2-phenotyped blood samples, including HNA-2-deficient individuals, mothers, and the respective children with neonatal immune neutropenia and regular blood donors. <b><i>Results:</i></b> From a total of 54 HNA-2<sub>null</sub> individuals, 43 were homozygous for the <i>CD177</i>*<i>787A>T</i> substitution. Six carried the <i>CD177</i>*<i>c.1291G>A</i> single nucleotide polymorphism. All HNA-2-positive samples with >40% CD177<sup>pos.</sup> neutrophils carried the *<i>787A</i> wild-type allele, whereas a lower rate of CD177<sup>pos.</sup> neutrophils was preferentially associated with *<i>c.787AT</i> heterozygosity. Interestingly, only the *<i>c.787A</i> allele sequence was detected in complementary DNA (cDNA) sequence analysis carried out on all *<i>c.787AT</i> heterozygous individuals. However, cDNA analysis after sorting of CD177<sup>pos.</sup> and CD177<sup>neg.</sup> neutrophil subsets from HNA-2-positive individuals showed identical sequences, which makes regulatory elements within the promoter unlikely to affect <i>CD177</i> gene transcription in different CD177 neutrophil subsets. <b><i>Conclusion:</i></b> This comprehensive study clearly demonstrates the impact of single nucleotide polymorphisms on the expression of HNA-2 on the neutrophil surface but challenges the hypothesis of regulatory epigenetic effects being implicated in the bimodal CD177 expression pattern.
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