214 research outputs found

    Memory management in the Smalltalk-80 system

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    This work presents an examination of the memory management area of the Smalltalk-80 system. Two implementations of this system were completed. The first system used virtual memory managed in an object oriented manner, the performance and related factors of this system is examined in detail. The second system implemented was based wholly in RAM and was used to examine in detail the factors that affected the performance of the system. Two areas of the RAM based system are examined in detail. The first of these is the logical manner in which the memory of the system is structured and its effects on the performance of the system. The second field is the way in which object reference counts are decremented. This second field has potentially the large effect on the system's running speed

    Effect of eplerenone on extracellular cardiac matrix biomarkers in patients with acute ST-elevation myocardial infarction without heart failure: insights from the randomized double-blind REMINDER Study

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    Objective: Aldosterone stimulates cardiac collagen synthesis. Circulating biomarkers of collagen turnover provide a useful tool for the assessment of cardiac remodeling in patients with an acute myocardial infarction (MI).  Methods: The REMINDER trial assessed the effect of eplerenone in patients with an acute ST-elevation Myocardial Infarction (STEMI) without known heart failure (HF), when initiated within 24 h of symptom onset. The primary outcome was almost totally (>90%) driven by natriuretic peptide (NP) thresholds after 1-month post-MI (it also included a composite of cardiovascular death or re-hospitalization or new onset HF or sustained ventricular tachycardia or fibrillation or LVEF ≤40% after 1-month post-MI). This secondary analysis aims to assess the extracellular matrix marker (ECMM) levels with regards to: (1) patients` characteristics; (2) determinants; (3) and eplerenone effect.  Results: Serum levels of ECMM were measured in 526 (52%) of the 1012 patients enrolled in the REMINDER trial. Patients with procollagen type III N-terminal propeptide (PIIINP) above the median were older and had worse renal function (p < 0.05). Worse renal function was associated with increased levels of PIIINP (standardized β ≈ 0.20, p < 0.05). Eplerenone reduced PIIINP when the levels of this biomarker were above the median of 3.9 ng/mL (0.13 ± 1.48 vs. -0.37 ± 1.56 ng/mL, p = 0.008). Higher levels of PIIINP were independently associated with higher proportion of NP above the prespecified thresholds (HR = 1.95, 95% CI 1.16-3.29, p = 0.012).  Conclusions: Eplerenone effectively reduces PIIINP levels when baseline values were above the median. Eplerenone may limit ECMM formation in post-MI without HF

    Effect of cellular and extracellular pathology assessed by T1 mapping on regional contractile function in hypertrophic cardiomyopathy

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    Background Regional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction. Methods We prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient. Results Individually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P < 0.001 for all) but not ECV. LGE (Beta 2.603, P = 0.024) had a significant association with circumferential strain measured by tissue tagging. In a second multivariable model (segment thickness, LGE and native T1) all strain parameters were associated with both segment thickness (P < 0.001 for all) and native T1 (P < 0.001 for all) but not LGE. Conclusion Impairment of contractile function in HCM is predominantly associated with the degree of hypertrophy and native T1 but not markers of extracellular fibrosis (ECV or LGE). These findings suggest that impairment of contractility in HCM is mediated by mechanisms other than extracellular expansion that include cellular changes in structure and function. The cellular mechanisms leading to increased native T1 and its prognostic significance remain to be established

    A retrospective review of great ape cardiovascular disease epidemiology and pathology

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    Cardiovascular disease is associated with significant mortality in zoo‐housed great apes, yet little is known about its epidemiology and aetiopathogenesis, and therefore its diagnosis, treatment and prevention. In this retrospective study, the frequency and patterns of cardiovascular disease‐associated mortality in zoo‐housed great apes is explored. Data relating to 71 great apes [Bonobos Pan paniscus (n = 13), Chimpanzees Pan troglodytes (n = 37), Western lowland gorillas Gorilla gorilla gorilla (n = 15), and Bornean orangutans Pongo pygmaeus and Sumatran orangutans Pongo abelii (n = 6)], which died between 2004 and 2014, were studied and key information relating to their signalment (taxa, age, sex), and manner and cause of death analysed. Male sex and increasing age were found to be associated with an increased risk of cardiovascular disease‐associated death. Relative to the other taxa, orangutans appeared to be less at risk of heart disease‐associated mortality. Deaths were often found to be sudden and unexpected. Cardiomyopathies were the most frequently diagnosed cardiovascular disorder. Of these, a group of cardiomyopathies characterized by the presence of myocardial fibrosis were most common, although there were inconsistencies with regards the reporting of other histopathological features. The study identified potential risk factors involved in great ape cardiovascular disease aetiopathogenesis which warrant further exploration. The findings also suggest a need for proactive screening to identify those affected earlier in the disease course. Finally, the study highlights a critical need for improvements to be made to the current approach to post‐mortem investigation of great ape heart disease and the subsequent reporting of cardiovascular lesions

    Mutation Testing Advances: An Analysis and Survey

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