Composition mechanisms for retrenchment

Retrenchment is a flexible model evolution formalism that arose as a reaction to the limitations imposed by refinement, and for which the proof obligations feature additional predicates for accommodating design data. Composition mechanisms for retrenchment are studied. Vertical, horizontal, dataflow, parallel and fusion compositions are described. Of particular note are the means by which the additional predicates compose. It is argued that all of the compositions introduced are associative, and that they are mutually coherent. Composition of retrenchment with refinement, so important for the smooth interworking of the two techniques, is discussed. Decomposition, allowing finer grained retrenchments to be extracted from a single large grained retrenchment, is also investigated

Association between telomere length and complete blood count in US adults

Introduction: Telomere length (TL) is related to age-related health outcomes, but little is known about the relationship between TL and complete blood count (CBC) parameters. We aimed to determine the relationship between TL and CBC in a sample of healthy US adults. Material and methods: Participants in the National Health and Nutrition Examination Survey (NHANES) recruited between 1999 and 2002 who had essential data on total CBC and TL were studied. We computed age- and race-adjusted mean values for total CBC using analysis of covariance (ANCOVA). All statistical analyses accounted for the survey design and sample weights by using SPSS Complex Samples v22.0 (IBM Corp, Armonk, NY). Results: Of the 8892 eligible participants, 47.8% (n = 4123) were men. The mean age was 41.8 years overall, 41.0 years in men and 42.6 in women (p = 0.238). The sex-stratified ANCOVA showed no significant difference in the total CBC across TL quartiles (all p > 0.05) in both sexes. In the adjusted model, there was a significant negative relationship with monocyte count ( = –0.051, 95% CI: –0.422; –0.142), mean cell hemoglobin ( = –0.051, 95% CI: –0.038; –0.011) and red cell distribution width ( = –0.031, 95% CI: –0.054; –0.003), while there was a significant positive relationship with basophil ratio ( = 0.046, 95% CI: 0.049–0.171). Conclusions: These results support the possibility that telomere attrition may be a marker for reduced proliferative reserve in hematopoietic progenitor cells

LDL-C: Lower is Better for Longer - Even at Low Risk

Background: Low-density lipoprotein cholesterol (LDL-C) causes atherosclerotic disease, as demonstrated in experimental and epidemiological cohorts, randomised controlled trials, and Mendelian randomisation studies. Main text: There is considerable inconsistency between existing guidelines as to how to effectively manage patients at low overall risk of cardiovascular disease (CVD) who have persistently elevated levels of LDL-C. We propose a step-by-step practical approach for the management of cardiovascular risks in individuals with low ( 140 mg/dL, 3.6 mmol/L) LDL-C. The strategy proposed is based on the level of adherence to lifestyle interventions (LSI), and in case of non-adherence, stepwise practical management, including lipid-lowering therapy, is recommended to achieve a target LDL-C levels (< 115 mg/dL, 3.0 mmol/L). Conclusions: Further studies are necessary to answer the questions on the long-term efficacy, safety, and cost-effectiveness of the suggested approach. This is critical, considering the ever-increasing numbers of such low-risk patients seen in clinical practice

Evaluating bempedoic acid for the treatment of hyperlipidaemia

Introduction: Despite the effectiveness of statins in the treatment of lipid disorders, residual risk still exists, and hitherto studies where additional drugs were added to statin therapy have been mainly negative or the outcomes were very modest. Therefore there is still a need for new and effective oral agents in the combination therapy of lipid disorders. Areas Covered: The review covers the current state of knowledge on the mechanism of action of bempedoic acid (ETC-1002) and results from recent clinical studies. Expert Opinion: ETC-1002 is a novel oral lipid-lowering therapy. The reduction of both low-density lipoprotein cholesterol (LDL-C) and high sensitivity C-reactive protein (hsCRP) demonstrated by ETC-1002 in clinical trials suggests that agent may have the potential for CV risk reduction. Adverse effects of current lipid-lowering agents can be dose-limiting, and combination approaches to lipid-lowering may often be utilized for optimal CV risk reduction. Because of this, new lipid-modulating drugs are urgently required. ETC-1002 has a unique mechanism of action (adenosine triphosphate-citrate lyase inhibition). It has been shown to be safe in combination with statins as well as ezetimibe, and appears to effectively lower LDL-C and has the potential to reduce the risk of muscle-related adverse events, which can limit the utilization and effectiveness of statin therapy

Quantum Stability of (2+1)-Spacetimes with Non-Trivial Topology

Quantum fields are investigated in the (2+1)-open-universes with non-trivial topologies by the method of images. The universes are locally de Sitter spacetime and anti-de Sitter spacetime. In the present article we study spacetimes whose spatial topologies are a torus with a cusp and a sphere with three cusps as a step toward the more general case. A quantum energy momentum tensor is obtained by the point stripping method. Though the cusps are no singularities, the latter cusps cause the divergence of the quantum field. This suggests that only the latter cusps are quantum mechanically unstable. Of course at the singularity of the background spacetime the quantum field diverges. Also the possibility of the divergence of topological effect by a negative spatial curvature is discussed. Since the volume of the negatively curved space is larger than that of the flat space, one see so many images of a single source by the non-trivial topology. It is confirmed that this divergence does not appear in our models of topologies. The results will be applicable to the case of three dimensional multi black hole\cite{BR}.Comment: 17 pages, revtex, 3 uuencoded figures containe

D-003 (Saccharum officinarum): The forgotten lipid-lowering agent.

Reduction of elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is essential in primary and secondary prevention of cardiovascular disease (CVD). Therefore there is still a large need for new effective drugs, which would be able to essentially reduce LDL-C and in the consequence CV residual risk. D-003 is a mixture of high aliphatic primary acids purified from sugarcane (Saccharum officinarum) wax. It showed promising hypocholesterolemic effects in both animal and human studies; it significantly lowers both serum total cholesterol (TC) and LDL-C, and increases high-density lipoprotein cholesterol (HDL-C). In addition, it showed a favorable safety profile. In this review, we evaluated the profile of D-003 as a lipid-lowering agent based on data from available preclinical and clinical studies

The Role of Nutraceuticals In The Prevention of Cardiovascular Disease

Cardiovascular disease (CVD) ranks among the most common health-related and economic issues worldwide. Dietary factors are important contributors to cardiovascular risk, either directly, or through their effects on other cardiovascular risk factors including hypertension, dyslipidemia and diabetes mellitus. Nutraceuticals are natural nutritional compounds, which have been shown to be efficacious in preventative medicine or in the treatment of disease. Several foods and dietary supplements have been shown to protect against the development of cardiovascular disease. The aim of this review is to present an update on the most recent evidence relating to the use of nutraceuticals in the context of the prevention and treatment of cardiovascular disease