412 research outputs found

    Geometrical and structural properties of an Aeroelastic Research Wing (ARW-2)

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    Transonic steady and unsteady pressure tests were conducted on a large elastic wing known as the DAST ARW-2 wing. The wing has a supercritical airfoil, an aspect ratio of 10.3, a leading edge sweepback angle of 28.8 deg and is equipped with two inboard and one outboard trailing edge control surfaces. The geometrical and structural characteristics are presented of this elastic wing, using a combination of measured and calculated data, to permit future analyst to compare the experimental surface pressure data with theoretical predictions

    Applying the logic of sample surveys to qualitative case studies: The case cluster method

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    This is the publisher's version, also available electronically from "http://www.jstor.org"

    The use of percutaneous coronary intervention in black and white veterans with acute myocardial infarction

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    BACKGROUND: It is uncertain whether black white differences in the use of percutaneous coronary intervention (PCI) persist in the era of drug eluting stents. The purpose of this study is to determine if black veterans with acute myocardial infarction (AMI) are less likely to receive PCI than their white counterparts. METHODS: This study included 680 black and 3529 white veterans who were admitted to Veterans Health Administration (VHA) medical centers between July 2003 and August 2004. Information for this study was collected as part of the VHA External Peer Review Program for quality monitoring and improvement for a variety of medical conditions and procedures, including AMI. In addition, Department of Veterans Affairs workload files were used to determine PCI utilization after hospital discharge. Standard statistical methods including the Chi-square, 2 sample t-test, and logistic regression with a cluster correction for medical center were used to assess the association between race and the use of PCI ≤ 30 days from admission. RESULTS: Black patients were younger, more often had diabetes mellitus, renal disease, or dementia and less often had lipid disorders, previous coronary artery bypass surgery, or chronic obstructive pulmonary disease than their white counterparts. Equal proportions of blacks and whites underwent cardiac catheterization ≤ 30 days after admission, but the former were less likely to undergo PCI (32% vs. 40%, p < 0.0001). This difference persisted after multivariate adjustment, although measures of the extent of coronary artery disease were not available. CONCLUSION: Given the equivalent use of cardiac catheterization, it is possible that less extensive or minimal coronary artery disease in black patients could account for the observed difference

    Changes in the use of coronary artery revascularization procedures in the Department of Veterans Affairs, the National Hospital Discharge Survey, and the Nationwide Inpatient Sample, 1991–1999

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    BACKGROUND: There have been dramatic increases in the number of coronary artery bypass surgeries (CABS) and percutaneous coronary interventions (PCI) performed during the last decade. Whether this finding is true for revascularization procedures performed in Department of Veterans Affairs (VA) medical centers is the subject of this paper. METHODS: This study compared the number of revascularization procedures and rates of use in the VA, the National Hospital Discharge Survey, and the Nationwide Inpatient Sample. Included were men who underwent isolated CABS and/or PCI, including stenting, between 1991 and 1999, although data for the Nationwide Inpatient Sample were available only between 1993 and 1997. Age adjusted use rates were calculated with the direct method of standardization. RESULTS: The percent of users of VA healthcare 75 years and older increased from 10% in 1991 to 20% in 1999. In the VA, the number of isolated CABS declined from 6227 in 1991 to 6147 in 1999, whereas age adjusted rates declined from 167.6 per 100,000 in 1991 to 107.9 per 100,000 in 1999. In the 2 national surveys, both the estimated numbers of procedures and use rates increased over time. In all 3 settings, there were increases in both numbers and rate of PCI from 1993, although in the VA, use rates decreased from 191.2 per 100,000 in 1996 to 139.7 per 100,000 in 1999. VA use rates for both CABS and PCI were lower than those in the 2 national surveys. CONCLUSION: Age adjusted rates of CABS and PCI were lower in the VA than in 2 national surveys. Since 1996, there has been a decrease in the rate of use of revascularization procedures in the VA

    Regulation of heparanase expression in coronary artery disease in diabetic, hyperlipidemic swine

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    Objective Enzymatic degradation of the extracellular matrix is known to be powerful regulator of atherosclerosis. However, little is known about the enzymatic regulation of heparan sulfate proteoglycans (HSPGs) during the formation and progression of atherosclerotic plaques. Methods and results Swine were rendered diabetic through streptozotocin injection and hyperlipidemic through a high fat diet. Arterial remodeling and local endothelial shear stress (ESS) were assessed using intravascular ultrasound, coronary angiography and computational fluid dynamics at weeks 23 and 30. Coronary arteries were harvested and 142 arterial subsegments were analyzed using histomorphologic staining, immunostaining and real time PCR. Heparanase staining and activity was increased in arterial segments with low ESS, in lesions with thin cap fibroatheroma (TCFA) morphology and in lesions with severely degraded internal elastic laminae. In addition, heparanase staining co-localized with staining for CD45 and MMP-2 within atherosclerotic plaques. Dual staining with gelatinase zymography and heparanase immunohistochemical staining demonstrated co-localization of matrix metalloprotease activity with heparanase staining. A heparanase enzymatic activity assay demonstrated increased activity in TCFA lesions, subsegments with low ESS and in macrophages treated with oxidized LDL or angiotensin II. Conclusions Taken together, our results support a critical role for heparanase in the development of vulnerable plaques and suggest a novel therapeutic target for the treatment of atherosclerosis.Novartis (Firm)Boston Scientific CorporationNational Institutes of Health (U.S.) (Grant R01 GM49039

    Thin-Capped Atheromata With Reduced Collagen Content in Pigs Develop in Coronary Arterial Regions Exposed to Persistently Low Endothelial Shear Stress

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    Objective—The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques. Approach and Results—Coronary angiography and 3-vessel intravascular ultrasound were serially performed at 5 consecutive time points in vivo in 5 diabetic, hypercholesterolemic pigs. ESS was calculated along the course of each artery with computational fluid dynamics at all 5 time points. At follow-up, 184 arterial segments with previously identified in vivo ESS underwent histopathologic analysis. Compared with other plaque types, eccentric thin-capped atheromata developed more in segments that experienced lower ESS during their evolution. Compared with lesions with higher preceding ESS, segments persistently exposed to low ESS (<1.2 Pa) exhibited reduced intimal smooth muscle cell content; marked intimal smooth muscle cell phenotypic modulation; attenuated procollagen-I gene expression; increased gene and protein expression of the interstitial collagenases matrix-metalloproteinase-1, -8, -13, and -14; increased collagenolytic activity; reduced collagen content; and marked thinning of the fibrous cap. Conclusions—Eccentric thin-capped atheromata, lesions particularly prone to rupture, form more frequently in coronary regions exposed to low ESS throughout their evolution. By promoting an imbalance of attenuated synthesis and augmented collagen breakdown, low ESS favors the focal evolution of early lesions toward plaques with reduced collagen content and thin fibrous caps—2 critical determinants of coronary plaque vulnerability.Novartis (Firm)Boston Scientific CorporationBehrakis Foundation (Research Fellowship)Hellenic Heart FoundationHellenic Atherosclerosis SocietyNational Institutes of Health (U.S.) (Grant RO1 GM49039

    Augmented Expression and Activity of Extracellular Matrix-Degrading Enzymes in Regions of Low Endothelial Shear Stress Colocalize With Coronary Atheromata With Thin Fibrous Caps in Pigs

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    Background—The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata. : Methods and Results—Intravascular ultrasound–based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet. Local endothelial shear stress was calculated in plaque-free subsegments of interest (n=142) with computational fluid dynamics. At week 30, the coronary arteries (n=31) were harvested and the same subsegments were identified. The messenger RNA and protein expression and elastolytic activity of selected elastases and their endogenous inhibitors were assessed. Subsegments with low preceding endothelial shear stress at week 23 showed reduced endothelial coverage, enhanced lipid accumulation, and intense infiltration of activated inflammatory cells at week 30. These lesions showed increased expression of messenger RNAs encoding matrix metalloproteinase-2, -9, and -12, and cathepsins K and S relative to their endogenous inhibitors and increased elastolytic activity. Expression of these enzymes correlated positively with the severity of internal elastic lamina fragmentation. Thin-capped atheromata developed in regions with lower preceding endothelial shear stress and had reduced endothelial coverage, intense lipid and inflammatory cell accumulation, enhanced messenger RNA expression and elastolytic activity of MMPs and cathepsins, and severe internal elastic lamina fragmentation. : Conclusions—Low endothelial shear stress induces endothelial discontinuity and accumulation of activated inflammatory cells, thereby augmenting the expression and activity of elastases in the intima and shifting the balance with their inhibitors toward matrix breakdown. Our results provide new insight into the mechanisms of regional formation of plaques with thin fibrous caps.Novartis Pharmaceuticals CorporationBoston Scientific CorporationHellenic Heart FoundationHellenic Atherosclerosis SocietyAlexander S. Onassis Public Benefit FoundationPropondis FoundationHellenic Harvard FoundationA.G. Leventis FoundationPhilip Morris International. External Research ProgramAmerican Heart Association (Scientist Development Grant)National Institutes of Health (U.S.) (Grant NIHR01 GM49039

    Declining mortality following acute myocardial infarction in the Department of Veterans Affairs Health Care System

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    <p>Abstract</p> <p>Background</p> <p>Mortality from acute myocardial infarction (AMI) is declining worldwide. We sought to determine if mortality in the Veterans Health Administration (VHA) has also been declining.</p> <p>Methods</p> <p>We calculated 30-day mortality rates between 2004 and 2006 using data from the VHA External Peer Review Program (EPRP), which entails detailed abstraction of records of all patients with AMI. To compare trends within VHA with other systems of care, we estimated relative mortality rates between 2000 and 2005 for all males 65 years and older with a primary diagnosis of AMI using administrative data from the VHA Patient Treatment File and the Medicare Provider Analysis and Review (MedPAR) files.</p> <p>Results</p> <p>Using EPRP data on 11,609 patients, we observed a statistically significant decline in adjusted 30-day mortality following AMI in VHA from 16.3% in 2004 to 13.9% in 2006, a relative decrease of 15% and a decrease in the odds of dying of 10% per year (p = .011). Similar declines were found for in-hospital and 90-day mortality.</p> <p>Based on administrative data on 27,494 VHA patients age 65 years and older and 789,400 Medicare patients, 30-day mortality following AMI declined from 16.0% during 2000-2001 to 15.7% during 2004-June 2005 in VHA and from 16.7% to 15.5% in private sector hospitals. After adjusting for patient characteristics and hospital effects, the overall relative odds of death were similar for VHA and Medicare (odds ratio 1.02, 95% C.I. 0.96-1.08).</p> <p>Conclusion</p> <p>Mortality following AMI within VHA has declined significantly since 2003 at a rate that parallels that in Medicare-funded hospitals.</p

    General practitioner workforce planning: assessment of four policy directions

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    <p>Abstract</p> <p>Background</p> <p>Estimating the supply of GPs into the future is important in forecasting shortages. The lengthy training process for medicine means that adjusting supply to meet demand in a timely fashion is problematic. This study uses Ireland as a case study to determine the future demand and supply of GPs and to assess the potential impact of several possible interventions to address future shortages.</p> <p>Methods</p> <p>Demand was estimated by applying GP visit rates by age and sex to national population projections. Supply was modelled using a range of parameters derived from two national surveys of GPs. A stochastic modelling approach was adopted to determine the probable future supply of GPs. Four policy interventions were tested: increasing vocational training places; recruiting GPs from abroad; incentivising later retirement; increasing nurse substitution to enable practice nurses to deliver more services.</p> <p>Results</p> <p>Relative to most other European countries, Ireland has few GPs per capita. Ireland has an ageing population and demand is estimated to increase by 19% by 2021. Without intervention, the supply of GPs will be 5.7% less than required in 2021. Increasing training places will enable supply to meet demand but only after 2019. Recruiting GPs from overseas will enable supply to meet demand continuously if the number recruited is approximately 0.8 per cent of the current workforce per annum. Later retirement has only a short-term impact. Nurse substitution can enable supply to meet demand but only if large numbers of practice nurses are recruited and allowed to deliver a wide range of GP services.</p> <p>Conclusions</p> <p>A significant shortfall in GP supply is predicted for Ireland unless recruitment is increased. The shortfall will have numerous knock-on effects including price increases, longer waiting lists and an increased burden on hospitals. Increasing training places will not provide an adequate response to future shortages. Foreign recruitment has ethical considerations but may provide a rapid and effective response. Increased nurse substitution appears to offer the best long-term prospects of addressing GP shortages and presents the opportunity to reshape general practice to meet the demands of the future.</p

    Calculating Evolutionary Dynamics in Structured Populations

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    Evolution is shaping the world around us. At the core of every evolutionary process is a population of reproducing individuals. The outcome of an evolutionary process depends on population structure. Here we provide a general formula for calculating evolutionary dynamics in a wide class of structured populations. This class includes the recently introduced “games in phenotype space” and “evolutionary set theory.” There can be local interactions for determining the relative fitness of individuals, but we require global updating, which means all individuals compete uniformly for reproduction. We study the competition of two strategies in the context of an evolutionary game and determine which strategy is favored in the limit of weak selection. We derive an intuitive formula for the structure coefficient, σ, and provide a method for efficient numerical calculation
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