Optimal intensity of oral anticoagulant therapy after myocardial infarction

AbstractObjectives.This study attempted to determine the optimal intensity of anticoagulant therapy in patients after myocardial infarction.Background.Treatment with oral anticoagulant therapy entails a delicate balance between over- (risk of bleeding) and under-anticoagulant (risk of thromboemboli). The optimal intensity required to prevent the occurrence of either event (bleeding or thromboembolic) is not known.Methods.A method was used to determine the optimal intensity of anticoagulant therapy by calculating incidence rates for either event associated with a specific international normalized ratio. The numerator included events occurring at given international normalized ratios, and the denominator comprised the total observation time.Results.The study population included 3,404 myocardial infarction patients enrolled in the ASPECT (anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis) trial. Total treatment was 6,918 patient-years. Major bleeding occurred in 57 patients (0.8/100 patient-years), and thromboembolic complications in 397 (5.7/100 patient-years). The incidence of the combined outcome (bleeding or thromboembolic complications) with international normalized ratio < 2 was 8.0/100 patient-years (283 events in 3,559 patient-years), with international normalized ratios between 2 and 3, 3.9/100 patient-years (33 events in 838 patient-years); 3.2/100 patient-years (57 events in 1,775 patient-years) for international normalized ratios between 3 and 4; 6.6/100 patient-years (37 events in 564 patient-years) for international normalized ratios between 4 and 5; and 7.7/100 patient-years (14 events in 182 patient-years) for international normalized ratios >5. After adjustment for achieved international normalized ratio levels, significant predictors were higher levels of systolic blood pressure and age.Conclusions.If equal weight is given to hemorrhagic and thromboembolic complications, these results suggest that the optimal intensity of long-term anticoagulant therapy for myocardial infarction patients lies between 2.0 and 4.0 international normalized ratio, with a trend to suggest an optimal intensity of 3.0 to 4.0

Searching for low radio-frequency gravitational wave counterparts in wide-field LOFAR data

High Energy Astrophysic

Ultrasonic evidence of an uncorrelated cluster formation temperature in manganites with first-order magnetic transition at T_C

Ultrasonic attenuation and phase velocity measurements have been carried out in the ferromagnetic perovskites La_{2/3}Ca_{1/3}MnO_3 and La_{2/3}Sr_{1/3}MnO_3. Data show that the transition at the Curie temperature, T_C, changes from first- to second-order as Sr replaces Ca in the perovskite. The compound with first-order transition shows also another transition at a temperature T* > T_C. We interpret the temperature window T_C < T < T* as a region of coexistence of a phase separated regime of metallic and insulating regions, in the line of recent theoretical proposals.Comment: 4 pages, 2 figure

New methods to constrain the radio transient rate: results from a survey of four fields with LOFAR

We report on the results of a search for radio transients between 115 and 190 MHz with the LOw-Frequency ARray (LOFAR). Four fields have been monitored with cadences between 15 minutes and several months. A total of 151 images were obtained, giving a total survey area of 2275 deg2. We analysed our data using standard LOFAR tools and searched for radio transients using the LOFAR Transients Pipeline (TraP). No credible radio transient candidate has been detected; however, we are able to set upper limits on the surface density of radio transient sources at low radio frequencies. We also show that low-frequency radio surveys are more sensitive to steep-spectrum coherent transient sources than GHz radio surveys. We used two new statistical methods to determine the upper limits on the transient surface density. One is free of assumptions on the flux distribution of the sources, while the other assumes a power-law distribution in flux and sets more stringent constraints on the transient surface density. Both of these methods provide better constraints than the approach used in previous works. The best value for the upper limit we can set for the transient surface density, using the method assuming a power-law flux distribution, is 1.3 · 10-3 deg-2 for transients brighter than 0.3 Jy with a time-scale of 15 min, at a frequency of 150 MHz. We also calculated for the first time upper limits for the transient surface density for transients of different time-scales. We find that the results can differ by orders of magnitude from previously reported, simplified estimates

Impaired Intestinal Farnesoid X Receptor Signaling in Cystic Fibrosis Mice

Background & Aims: The bile acid (BA)-activated farnesoid X receptor (FXR) controls hepatic BA synthesis and cell proliferation via the intestinal hormone fibroblast growth factor 19. Because cystic fibrosis (CF) is associated with intestinal dysbiosis, anomalous BA handling, and biliary cirrhosis, we investigated FXR signaling in CF. Methods: Intestinal and hepatic expression of FXR target genes and inflammation markers was assessed in Cftr null mice and controls. Localization of the apical sodium-dependent BA transporter was assessed, and BAs in gastrointestinal tissues were analyzed. The CF microbiota was characterized and FXR signaling was investigated in intestinal tissue and organoids. Results: Ileal murine fibroblast growth factor 19 ortholog (Fgf15) expression was strongly reduced in CF mice, compared with controls. Luminal BA levels and localization of apical sodium-dependent BA transporter was not affected, and BAs induced Fgf15 up to normal levels in CF ileum, ex vivo, and CF organoids. CF mice showed a dysbiosis that was associated with a marked up-regulation of genes involved in host–microbe interactions, including those involved in mucin glycosylation, antimicrobial defense, and Toll-like receptor signaling. Antibiotic treatment reversed the up-regulation of inflammatory markers and restored intestinal FXR signaling in CF mice. Conversely, FXR-dependent gene induction in ileal tissue and organoids was repressed by bacterial lipopolysaccharide and proinflammatory cytokines, respectively. Loss of intestinal FXR activity was associated with a markedly blunted hepatic trophic response to oral BA supplementation, and with impaired repression of Cyp7a1, the gene encoding the rate-limiting enzyme in BA synthesis. Conclusions: In CF mice, the gut microbiota represses intestinal FXR activity, and, consequently, FXR-dependent hepatic cell proliferation and feedback control of BA synthesis