648 research outputs found

    Specification for a Program for an Interative Aeroelastic Solution (PIAS)

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    An engineering and software specification which was written for a computer program to calculate aeroelastic structural loads including the effects of nonlinear aerodynamics is presented. The procedure used in the program for an iterative aeroelastic solution (PIAS) is to alternately execute two computer codes: one to calculate aerodynamic loads for a specific wing shape, and another to calculate the deflected shape caused by this loading. A significant advantage to the design of PIAS is that the initial aerodynamic module can be replaced with others. The leading edge vortex (LEV) program is used as the aerodynamic module in PIAS. This provides the capability to calculate aeroelastic loads, including the effects of a separation induced leading edge vortex. The finite element method available in ATLAS Integrated structural analysis and design system is used to determine the deflected wing shape for the applied aerodynamics and inertia loads. The data management capabilities in ATLAS are used by the execution control monitor (ECM) of PIAS to control the solution process

    Association between 24-hour blood pressure variability and chronic kidney disease: a cross-sectional analysis of African Americans participating in the Jackson heart study

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    Background Studies suggest 24-h blood pressure (BP) variability has prognostic value for cardiovascular disease. Several factors associated with high 24-h BP variability are also common among individuals with chronic kidney disease (CKD). We hypothesized 24-h BP variability would be higher for individuals with versus without CKD. Methods We analyzed 1,022 Jackson Heart Study participants who underwent ambulatory blood pressure monitoring (ABPM). Twenty-four hour BP variability was defined by two metrics: day-night standard deviation (SDdn) and average real variability (ARV). CKD was defined as ACR ≥30 mg/g or eGFR <60 mL/min/1.73 m2. Results The mean SDdn of systolic BP (SBP) was 10.2 ± 0.2 and 9.1 ± 0.1 mmHg and the mean ARV of SBP was 9.2 ± 0.2 and 8.6 ± 0.1 mmHg for those with and without CKD, respectively (each p ≤ 0.001). After adjustment for age and sex, SDdn and ARV were 0.98 mmHg (95 % CI 0.59, 1.38) and 0.52 mmHg (95 % CI 0.18, 0.86), respectively, higher among participants with versus without CKD. These differences were not statistically significant after further multivariable adjustment including 24-h mean SBP. Older age, and higher total cholesterol and 24-h mean SBP were associated with higher SDdn and ARV of SBP among participants with CKD. Mean SDdn and ARV of diastolic BP (DBP) were higher for participants with versus without CKD but these associations were not present after multivariable adjustment. Conclusion Data from the current study suggest that CKD is associated with higher 24-h BP variability, but the association is primarily explained by higher mean BP among those with CKD

    Complementary role of cardiac CT in the assessment of aortic valve replacement dysfunction

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    Aortic valve replacement is the second most common cardiothoracic procedure in the UK. With an ageing population, there are an increasing number of patients with prosthetic valves that require follow-up. Imaging of prosthetic valves is challenging with conventional echocardiographic techniques making early detection of valve dysfunction or complications difficult. CT has recently emerged as a complementary approach offering excellent spatial resolution and the ability to identify a range of aortic valve replacement complications including structural valve dysfunction, thrombus development, pannus formation and prosthetic valve infective endocarditis. This review discusses each and how CT might be incorporated into a multimodal cardiovascular imaging pathway for the assessment of aortic valve replacements and in guiding clinical management

    Genetic Variants in Arhgef11 Are Associated With Kidney Injury in the Dahl Salt-Sensitive Rat

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    A previous genetic analysis comparing the Dahl salt-sensitive (S) rat to the spontaneously hypertensive rat (SHR) identified a major locus on chromosome 2 that influences proteinuria in the S rat. In the present study, blood pressure, proteinuria, and renal hemodynamics were evaluated in congenic strains with small segments of the protective SHR genome on the S background. Proteinuria and renal function were significantly improved in the congenic strains compared to the S. The causative locus interval was narrowed to Arhgef11, Pear1, and Sh2d2 were identified as important candidate genes that may be linked to kidney injury in the S rat. In particular, Arhgef11 plays an important role in the activation of the Rho-ROCK signaling pathway. Inhibition of this pathway using fasudil resulted in a significant reduction of proteinuria in treated S rats (compared to untreated S). However, no difference was observed between treated or untreated SHR or congenic strains. The homologous region in humans was found to be associated with estimated glomerular filtration rate (eGFR) in the Candidate Gene Association Resource (CARe) population. In summary, these findings demonstrate that allelic variants in Arhgef11, acting through the Rho-ROCK pathway, could influence kidney injury in the S as well as provide insight into human kidney disease

    Impact of noncardiac findings in patients undergoing CT coronary angiography:a substudy of the Scottish computed tomography of the heart (SCOT-HEART) trial

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    Objectives Noncardiac findings are common on coronary computed tomography angiography (CCTA). We assessed the clinical impact of noncardiac findings, and potential changes to surveillance scans with the application of new lung nodule guidelines. Methods This substudy of the SCOT-HEART randomized controlled trial assessed noncardiac findings identified on CCTA. Clinically significant noncardiac findings were those causing symptoms or requiring further investigation, follow-up or treatment. Lung nodule follow-up was undertaken following the 2005 Fleischner guidelines. The potential impact of the 2015 British Thoracic Society (BTS) and the 2017 Fleischner guidelines was assessed. Results CCTA was performed in 1,778 patients and noncardiac findings were identified in 677 (38%). In 173 patients (10%) the abnormal findings were clinically significant and in 55 patients (3%) the findings were the cause of symptoms. Follow-up imaging was recommended in 136 patients (7.6%) and additional clinic consultations were organized in 46 patients (2.6%). Malignancy was diagnosed in 7 patients (0.4%). Application of the new lung nodule guidelines would have reduced the number of patients undergoing a follow-up CT scan: 68 fewer with the 2015 BTS guidelines and 78 fewer with the 2017 Fleischner guidelines; none of these patients subsequently developed malignancy. Conclusions Clinically significant noncardiac findings are identified in 10% of patients undergoing CCTA. Application of new lung nodule guidelines will reduce the cost of surveillance, without the risk of missing malignancy

    Staphylococcal PknB as the First Prokaryotic Representative of the Proline-Directed Kinases

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    In eukaryotic cell types, virtually all cellular processes are under control of proline-directed kinases and especially MAP kinases. Serine/threonine kinases in general were originally considered as a eukaryote-specific enzyme family. However, recent studies have revealed that orthologues of eukaryotic serine/threonine kinases exist in bacteria. Moreover, various pathogenic species, such as Yersinia and Mycobacterium, require serine/threonine kinases for successful invasion of human host cells. The substrates targeted by bacterial serine/threonine kinases have remained largely unknown. Here we report that the serine/threonine kinase PknB from the important pathogen Staphylococcus aureus is released into the external milieu, which opens up the possibility that PknB does not only phosphorylate bacterial proteins but also proteins of the human host. To identify possible human targets of purified PknB, we studied in vitro phosphorylation of peptide microarrays and detected 68 possible human targets for phosphorylation. These results show that PknB is a proline-directed kinase with MAP kinase-like enzymatic activity. As the potential cellular targets for PknB are involved in apoptosis, immune responses, transport, and metabolism, PknB secretion may help the bacterium to evade intracellular killing and facilitate its growth. In apparent agreement with this notion, phosphorylation of the host-cell response coordinating transcription factor ATF-2 by PknB was confirmed by mass spectrometry. Taken together, our results identify PknB as the first prokaryotic representative of the proline-directed kinase/MAP kinase family of enzymes

    Trait urgency and gambling problems in young people by age: The mediating role of decision-making processes

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    Although the personality trait of urgency has been linked to problem gambling, less is known about psychological mechanisms that mediate the relationship between urgency and problem gambling. One individual variable of potential relevance to impulsivity and addictive disorders is age. The aims of this study were to examine: (i) a theoretical model associating urgency and gambling problems, (ii) the mediating effects of decision-making processes (operationalized as preference for small/immediate rewards and lower levels of deliberative decision-making); and (iii) age differences in these relationships. Participants comprised 986 students (64% male; mean age=19.51 years; SD=2.30) divided into three groups: 16-17 years, 18-21 years, and 22-25 years. All participants completed measures of urgency, problem gambling, and a delay-discounting questionnaire involving choices between a smaller amount of money received immediately and a larger amount of money received later. Participants were also asked to reflect on their decision-making process. Compared to those aged 16-17 years and 22-25 years, participants aged 18-21 years had a higher level of gambling problems and decreased scores on lower levels of deliberative decision-making. Higher levels of urgency were associated with higher levels of gambling problems. The association was mediated by a lower level of deliberative decision-making and preference for an immediate/small reward. A distinct pathway was observed for lower levels of deliberative decision-making. Young people who tend to act rashly in response to extreme moods, had lower levels of deliberative decision-making, that in turn were positively related to gambling problems. This study highlights unique decision-making pathways through which urgency trait may operate, suggesting that those developing prevention and/or treatment strategies may want to consider the model’s variables, including urgency, delay discounting, and deliberative decision-making
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