237 research outputs found
Damage Identification for Prestressed Adjacent Box-Beam Bridges
Structural health monitoring (SHM) has gained considerable attention as a tool for monitoring the health of civil infrastructure. For bridge infrastructure, previous methods have focused on the detection of localized damage through modal parameters extracted from the longitudinal direction of the structure. This paper investigates a new damage detection method based on the change in the first vertical mode extracted from the transverse direction of the bridge. The mode is determined through application of modal curve fitting to frequency response functions (FRFs) that are formed using vertical response data obtained in the direction perpendicular to the bridgeâs longitudinal axis. Using this method, both local damage and global damage in the bridge reveal themselves as having a localized effect on the bridge response. Furthermore, damage is revealed in such a way that it enables differentiation of the damage types. To demonstrate the effectiveness of the method, modal parameters were extracted from acceleration data obtained from a finite element model of a full bridge. Analysis of the modal parameters showed that the proposed approach could not only detect both local and global bridge damage, but could also differentiate between damage types using only one mode shape. The proposed method was compared to a previously developed SHM method
Insulin-stimulated phosphorylation of endothelial nitric oxide synthase at serine-615 contributes to nitric oxide synthesis
Insulin stimulates endothelial NO (nitric oxide) synthesis via PKB (protein kinase B)/Akt-mediated phosphorylation and activation of eNOS (endothelial NO synthase) at Ser-1177. In previous studies, we have demonstrated that stimulation of eNOS phosphorylation at Ser-1177 may be required, yet is not sufficient for insulin-stimulated NO synthesis. We therefore investigated the role of phosphorylation of eNOS at alternative sites to Ser-1177 as candidate parallel mechanisms contributing to insulin-stimulated NO synthesis. Stimulation of human aortic endothelial cells with insulin rapidly stimulated phosphorylation of both Ser-615 and Ser-1177 on eNOS, whereas phosphorylation of Ser-114, Thr-495 and Ser-633 was unaffected. Insulin-stimulated Ser-615 phosphorylation was abrogated by incubation with the PI3K (phosphoinositide 3-kinase) inhibitor wortmannin, infection with adenoviruses expressing a dominant-negative mutant PKB/Akt or pre-incubation with TNFα (tumour necrosis factor α), but was unaffected by high culture glucose concentrations. Mutation of Ser-615 to alanine reduced insulin-stimulated NO synthesis, whereas mutation of Ser-615 to aspartic acid increased NO production by NOS in which Ser-1177 had been mutated to an aspartic acid residue. We propose that the rapid PKB-mediated stimulation of phosphorylation of Ser-615 contributes to insulin-stimulated NO synthesis
Use and Outcomes Associated With Bridging During Anticoagulation Interruptions in Patients With Atrial Fibrillation: Findings From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF)
BACKGROUND: Temporary interruption of oral anticoagulation for procedures is often required, and some propose using bridging anticoagulation. However, the use and outcomes of bridging during oral anticoagulation interruptions in clinical practice are unknown. METHODS AND RESULTS: The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) registry is a prospective, observational registry study of US outpatients with atrial fibrillation. We recorded incident temporary interruptions of oral anticoagulation for a procedure, including the use and type of bridging therapy. Outcomes included multivariable-adjusted rates of myocardial infarction, stroke or systemic embolism, major bleeding, cause-specific hospitalization, and death within 30 days. Of 7372 patients treated with oral anticoagulation, 2803 overall interruption events occurred in 2200 patients (30%) at a median follow-up of 2 years. Bridging anticoagulants were used in 24% (n=665), predominantly low-molecular-weight heparin (73%, n=487) and unfractionated heparin (15%, n=97). Bridged patients were more likely to have had prior cerebrovascular events (22% versus 15%; P=0.0003) and mechanical valve replacements (9.6% versus 2.4%; P/=2 in 94% versus 95%; P=0.5). Bleeding events were more common in bridged than nonbridged patients (5.0% versus 1.3%; adjusted odds ratio, 3.84;
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Early Adoption of Dabigatran and Its Dosing in US Patients With Atrial Fibrillation: Results From the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation
Background: Dabigatran is a novel oral anticoagulant approved for thromboprophylaxis in atrial fibrillation. Adoption patterns of this new agent in community practice are unknown. Methods and Results: We studied patterns of dabigatran use among patients enrolled in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBITâAF) Registry between June 2010 and August 2011 and followed for 12 months. Among 9974 atrial fibrillation patients included, 1217 (12%) were treated with dabigatran during the study. Overall, patients receiving dabigatran were younger (median age 72 versus 75 years, P<0.0001), more likely to be white (92% versus 89%, P=0.005), more likely to have private insurance (33% versus 25%, P<0.0001), and less likely to have prior cardiovascular disease (4% versus 33%, P<0.0001). They had more newâonset atrial fibrillation (8.8% versus 4.1%, P<0.0001), lower CHADS2 scores (estimated risk based on the presence of congestive heart failure, hypertension, aged â„75 years, diabetes mellitus, and prior stroke or transient ischemic attack; mean 2.0 versus 2.3, P<0.0001), and lower Anticoagulation and Risk Factors in Atrial Fibrillation scores (mean 2.4 versus 2.8, P<0.0001). More than half (n=14/25, 56%) of patients with severe kidney disease were not prescribed reduced dosing, whereas 10% (n=91/920) with preserved renal function received lower dosing. Among patients not on dabigatran at baseline, 8% had dabigatran initiated during followâup. Patient education was significantly associated with switching from warfarin to dabigatran (adjusted odds ratio for postgraduate 1.73, P=0.007), whereas antiarrhythmic drug use significantly correlated with de novo adoption of dabigatran (adjusted odds ratio 2.4, P<0.0001). Conclusions: Patients receiving dabigatran were younger and at a lower risk of stroke and bleeding. Patients appeared to drive switching from warfarin, whereas clinical characteristics influenced de novo start of dabigatran. These data suggest cautious early uptake of dabigatran, and more careful attention to dosing adjustments is warranted. Clinical Trial Registration URL: Clinicaltrials.gov. Unique identifier: NCT01165710
Initial Independent Outcomes from Focal Impulse and Rotor Modulation Ablation for Atrial Fibrillation: Multicenter FIRM Registry
Introduction
The success of pulmonary vein isolation (PVI) for atrial fibrillation (AF) may be improved if stable AF sources identified by Focal Impulse and Rotor Mapping (FIRM) are also eliminated. The long-term results of this approach are unclear outside the centers where FIRM was developed; thus, we assessed outcomes of FIRM-guided AF ablation in the first cases at 10 experienced centers.
Methods
We prospectively enrolled n = 78 consecutive patients (61 ± 10 years) undergoing FIRM guided ablation for persistent (n = 48), longstanding persistent (n = 7), or paroxysmal (n = 23) AF. AF recordings from both atria with a 64-pole basket catheter were analyzed using a novel mapping system (Rhythm Viewâą; Topera Inc., CA, USA). Identified rotors/focal sources were ablated, followed by PVI.
Results
Each institution recruited a median of 6 patients, each of whom showed 2.3 ± 0.9 AF rotors/focal sources in diverse locations. 25.3% of all sources were right atrial (RA), and 50.0% of patients had â„1 RA source. Ablation of all sources required a total of 16.6 ± 11.7 minutes, followed by PVI. On >1 year follow-up with a 3-month blanking period, 1 patient lost to follow-up (median time to 1st recurrence: 245 days, IQR 145â354), single-procedure freedom from AF was 87.5% (patients without prior ablation; 35/40) and 80.5% (all patients; 62/77) and similar for persistent and paroxysmal AF (P = 0.89).
Conclusions
Elimination of patient-specific AF rotors/focal sources produced freedom-from-AF of â80% at 1 year at centers new to FIRM. FIRM-guided ablation has a rapid learning curve, yielding similar results to original FIRM reports in each centerâs first cases
Puberty Predicts Approach But Not Avoidance on the Iowa Gambling Task in a Multinational Sample
According to the dual systems model of adolescent risk taking, sensation seeking and impulse control follow different developmental trajectories across adolescence and are governed by two different brain systems. The authors tested whether different underlying processes also drive age differences in reward approach and cost avoidance. Using a modified Iowa Gambling Task in a multinational, crossâsectional sample of 3,234 adolescents (ages 9â17; M = 12.87, SD = 2.36), pubertal maturation, but not age, predicted reward approach, mediated through higher sensation seeking. In contrast, age, but not pubertal maturation, predicted increased cost avoidance, mediated through greater impulse control. These findings add to evidence that adolescent behavior is best understood as the product of two interacting, but independently developing, brain systems
Long-term Psychological and Occupational Effects of Providing Hospital Healthcare during SARS Outbreak
TOC Summary Line: Healthcare workers in hospitals affected by SARS experience increased psychological stress 1â2 years after the outbreak
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Higher risk of death and stroke in patients with persistent vs. paroxysmal atrial fibrillation: results from the ROCKET-AF Trial
Aim Anticoagulation prophylaxis for stroke is recommended for at-risk patients with either persistent or paroxysmal atrial fibrillation (AF). We compared outcomes in patients with persistent vs. paroxysmal AF receiving oral anticoagulation. Methods and results Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). Of 14 062 patients, 11 548 (82%) had persistent AF and 2514 (18%) had paroxysmal AF. Patients with persistent AF were marginally older (73 vs. 72, P = 0.03), less likely female (39 vs. 45%, P < 0.0001), and more likely to have previously used vitamin K antagonists (64 vs. 56%, P < 0.0001) compared with patients with paroxysmal AF. In patients randomized to warfarin, time in therapeutic range was similar (58 vs. 57%, P = 0.94). Patients with persistent AF had higher adjusted rates of stroke or systemic embolism (2.18 vs. 1.73 events per 100-patient-years, P = 0.048) and all-cause mortality (4.78 vs. 3.52, P = 0.006). Rates of major bleeding were similar (3.55 vs. 3.31, P = 0.77). Rates of stroke or systemic embolism in both types of AF did not differ by treatment assignment (rivaroxaban vs. warfarin, Pinteraction = 0.6). Conclusion: In patients with AF at moderate-to-high risk of stroke receiving anticoagulation, those with persistent AF have a higher risk of thrombo-embolic events and worse survival compared with paroxysmal AF
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Genome-wide Association Analysis Identifies 14 New Risk Loci for Schizophrenia
Schizophrenia is a heritable disorder with substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases, 6,243 controls) followed by meta-analysis with prior schizophrenia GWAS (8,832 cases, 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls, and 581 trios). In total, 22 regions met genome-wide significance (14 novel and one previously implicated in bipolar disorder). The results strongly implicate calcium signaling in the etiology of schizophrenia, and include genome-wide significant results for CACNA1C and CACNB2 whose protein products interact. We estimate that âŒ8,300 independent and predominantly common SNPs contribute to risk for schizophrenia and that these collectively account for most of its heritability. Common genetic variation plays an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this devastating disorder
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