QUADRATIC MODEL TO ESTIMATE THE DOSES CAUSING THE HIGHEST CHOLESTEROL CONCENTRATION AND THE SAME CHOLESTEROL CONCENTRATION AS CONTROL GROUP

High plasma cholesterol (particularly high LDL-cholesterol) is a high risk factor for coronary heart disease (CHD), which causes a high CHD morbidity and mortality. Besides clinical drugs, more and more interest is focused on finding natural components in the diet that may have hypocholesterolemic effects. Plant sterols are natural components in human diets and found to have cholesterol-lowering effects in humans. Sheanut oil has a relatively high amolmt of plant sterols. Therefore, the two experiments were designed to investigate the hypocholesterolemic effect of sheanut oil in hamsters. The response was not monotonic. Low doses increased plasma cholesterol, but high doses decreased plasma cholesterol. Because there was partial dose repetition between the two experiments, the two were combined together to estimate the dose leading to the highest cholesterol concentration and the dose leading to the same cholesterol concentration as the control group. A quadratic model was selected to fit the combined data after appropriate transformation of exploratory and response variable. Nonparametric smoothing method was used to justify the quadratic model. The results of point estimation and confidence interval were compared by Delta, Fieller\u27s and bootstrapping methods

Defective peroxisomal proliferators activated receptor gamma activity due to dominant-negative mutation synergizes with hypertension to accelerate cardiac fibrosis in mice

Aims Humans with inactivating mutations in peroxisomal proliferators activated receptor gamma (PPARγ) typically develop a complex metabolic syndrome characterized by insulin resistance, diabetes, lipodystrophy, hypertension, and dyslipidaemia which is likely to increase their cardiovascular risk. Despite evidence that the activation of PPARγ may prevent cardiac fibrosis and hypertrophy, recent evidence has suggested that pharmacological activation of PPARγ causes increased cardiovascular mortality. In this study, we investigated the effects of defective PPARγ function on the development of cardiac fibrosis and hypertrophy in a murine model carrying a human dominant‐negative mutation in PPARγ. Methods and results Mice with a dominant‐negative point mutation in PPARγ (P465L) and their wild‐type (WT) littermates were treated with either subcutaneous angiotensin II (AngII) infusion or saline for 2 weeks. Heterozygous P465L and WT mice developed a similar increase in systolic blood pressure, but the mutant mice developed significantly more severe cardiac fibrosis to AngII that correlated with increased expression of profibrotic genes. Both groups similarly increased the heart weight to body weight ratio compared with saline‐treated controls. There were no differences in fibrosis between saline‐treated WT and P465L mice. Conclusion These results show synergistic pathogenic effects between the presence of defective PPARγ and AngII‐induced hypertension and suggest that patients with PPARγ mutation and hypertension may need more aggressive therapeutic measures to reduce the risk of accelerated cardiac fibrosis

The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report

The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument

The Habitable Exoplanet Observatory (HabEx) Mission Concept Study Final Report

The Habitable Exoplanet Observatory, or HabEx, has been designed to be the Great Observatory of the 2030s. For the first time in human history, technologies have matured sufficiently to enable an affordable space-based telescope mission capable of discovering and characterizing Earthlike planets orbiting nearby bright sunlike stars in order to search for signs of habitability and biosignatures. Such a mission can also be equipped with instrumentation that will enable broad and exciting general astrophysics and planetary science not possible from current or planned facilities. HabEx is a space telescope with unique imaging and multi-object spectroscopic capabilities at wavelengths ranging from ultraviolet (UV) to near-IR. These capabilities allow for a broad suite of compelling science that cuts across the entire NASA astrophysics portfolio. HabEx has three primary science goals: (1) Seek out nearby worlds and explore their habitability; (2) Map out nearby planetary systems and understand the diversity of the worlds they contain; (3) Enable new explorations of astrophysical systems from our own solar system to external galaxies by extending our reach in the UV through near-IR. This Great Observatory science will be selected through a competed GO program, and will account for about 50% of the HabEx primary mission. The preferred HabEx architecture is a 4m, monolithic, off-axis telescope that is diffraction-limited at 0.4 microns and is in an L2 orbit. HabEx employs two starlight suppression systems: a coronagraph and a starshade, each with their own dedicated instrument.Comment: Full report: 498 pages. Executive Summary: 14 pages. More information about HabEx can be found here: https://www.jpl.nasa.gov/habex

IVUS Image Interpretation and Measurements

Intravascular ultrasound (IVUS) is a valuable adjunct to angiography, providing new insights in the diagnosis and therapy of coronary disease. Angiography depicts only a 2D silhouette of the lumen, whereas IVUS allows tomographic assessment of lumen area, plaque size, distribution, and composition. The safety of IVUS is well documented, and the assessment of luminal dimensions represents an important application of this modality. Comparative studies show the greatest disparities between angiography and ultrasound after mechanical interventions. In young subjects, normal intimal thickness is typically ≈0.15 mm. With IVUS, lipid-laden lesions appear hypoechoic, fibromuscular lesions generate low-intensity echoes, and fibrous or calcified tissues are echogenic. Calcium reflects ultrasound effectively and obscures the underlying peripheral wall (acoustic shadowing). The extent and severity of disease by angiography and ultrasound are frequently discrepant. Arterial remodeling refers to changes in vascular dimensions during the development of atherosclerosis. At diseased sites, the external elastic membrane may actually shrink in size, contributing to luminal stenosis.  This is referred to as negative remodeling. The interpretation of IVUS relies on simple visual inspection of acoustic reflections to determine plaque composition. However, different tissue components may look similar, and artifacts may adversely affect ultrasound images. IVUS commonly detects occult disease in angiographically “normal” sites. In ambiguous lesions, ultrasound permits lesion quantification, particularly for left main coronary disease. IVUS has emerged as the optimal method for the detection of transplant vasculopathy. An important potential application of ultrasound is the identification of atheromas at risk of rupture. The mechanisms of action of interventional devices have been elucidated using IVUS. Ultrasound imaging is used by some operators to select the most suitable interventional device. IVUS-derived residual plaque burden is the most useful predictor of clinical outcome. In restenosis after balloon angioplasty, neo-intimal growth and negative remodeling are major mechanisms of late lumen loss. Although IVUS is not routinely used for stent optimization, the understanding of how to improve stent deployment based on IVUS insights, have dramatically altered interventional cardiology. New and emerging applications for IVUS are continuing to evolve, particularly in atherosclerosis regression-progression trials.   Volume II  (1:13:02)  MPG4  3.4 Gb  (1996

IVUS Image Interpretation and Measurements

Intravascular ultrasound (IVUS) is a valuable adjunct to angiography, providing new insights in the diagnosis and therapy of coronary disease. Angiography depicts only a 2D silhouette of the lumen, whereas IVUS allows tomographic assessment of lumen area, plaque size, distribution, and composition. The safety of IVUS is well documented, and the assessment of luminal dimensions represents an important application of this modality. Comparative studies show the greatest disparities between angiography and ultrasound after mechanical interventions. In young subjects, normal intimal thickness is typically ≈0.15 mm. With IVUS, lipid-laden lesions appear hypoechoic, fibromuscular lesions generate low-intensity echoes, and fibrous or calcified tissues are echogenic. Calcium reflects ultrasound effectively and obscures the underlying peripheral wall (acoustic shadowing). The extent and severity of disease by angiography and ultrasound are frequently discrepant. Arterial remodeling refers to changes in vascular dimensions during the development of atherosclerosis. At diseased sites, the external elastic membrane may actually shrink in size, contributing to luminal stenosis.  This is referred to as negative remodeling. The interpretation of IVUS relies on simple visual inspection of acoustic reflections to determine plaque composition. However, different tissue components may look similar, and artifacts may adversely affect ultrasound images. IVUS commonly detects occult disease in angiographically “normal” sites. In ambiguous lesions, ultrasound permits lesion quantification, particularly for left main coronary disease. IVUS has emerged as the optimal method for the detection of transplant vasculopathy. An important potential application of ultrasound is the identification of atheromas at risk of rupture. The mechanisms of action of interventional devices have been elucidated using IVUS. Ultrasound imaging is used by some operators to select the most suitable interventional device. IVUS-derived residual plaque burden is the most useful predictor of clinical outcome. In restenosis after balloon angioplasty, neo-intimal growth and negative remodeling are major mechanisms of late lumen loss. Although IVUS is not routinely used for stent optimization, the understanding of how to improve stent deployment based on IVUS insights, have dramatically altered interventional cardiology. New and emerging applications for IVUS are continuing to evolve, particularly in atherosclerosis regression-progression trials.   Volume II  (1:13:02)  MPG4  3.4 Gb  (1996

Multi-Device Applications of IVUS

The management of intermediate coronary lesions, defined by an angiographic diameter stenosis of 40% to 70%, continues to be a therapeutic dilemma for cardiologists. The 2-dimensional representation of the arterial lesion provided by angiography is limited in distinguishing intermediate lesions that require stenting from those that simply need appropriate medical therapy. In the era of drug-eluting stents, some might propose that stenting all intermediate coronary lesions is an appropriate solution. However, the possibility of procedural complications such as coronary dissection, no reflow phenomenon, in-stent restenosis, and stent thrombosis requires accurate stratification of patients with intermediate coronary lesions to appropriate therapy. Intravascular ultrasound (IVUS) and fractional flow reserve index (FFR) provide anatomic and functional information that can be used in the catheterization laboratory to designate patients to the most appropriate therapy. The purpose of this video is to discuss the critical information obtained from IVUS and FFR in guiding treatment of patients with intermediate coronary lesions. In addition, the importance of IVUS and FFR in the management of patients with serial stenoses, bifurcation lesions, left main disease, saphenous vein graft disease, and acute coronary syndrome are discussed.Volume III  (1:22:38)  MPG4  3.82 Gb  (1996