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No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55926/1/22383_ftp.pd

Thrust reverser design studies for an over-the-wing STOL transport

Aerodynamic and acoustics analytical studies were conducted to evaluate three thrust reverser designs for potential use on commercial over-the-wing STOL transports. The concepts were: (1) integral D nozzle/target reverser, (2) integral D nozzle/top arc cascade reverser, and (3) post exit target reverser integral with wing. Aerodynamic flowpaths and kinematic arrangements for each concept were established to provide a 50% thrust reversal capability. Analytical aircraft stopping distance/noise trade studies conducted concurrently with flow path design showed that these high efficiency reverser concepts are employed at substantially reduced power settings to meet noise goals of 100 PNdB on a 152.4 m sideline and still meet 609.6 m landing runway length requirements. From an overall installation standpoint, only the integral D nozzle/target reverser concept was found to penalize nacelle cruise performance; for this concept a larger nacelle diameter was required to match engine cycle effective area demand in reverse thrust

Therapies for type 2 diabetes: lowering HbA1c and associated cardiovascular risk factors

<p>Abstract</p> <p>Objectives</p> <p>To summarize data supporting the effects of antidiabetes agents on glucose control and cardiovascular risk factors in patients with type 2 diabetes.</p> <p>Methods</p> <p>Studies reporting on the effects of antidiabetes agents on glycemic control, body weight, lipid levels, and blood pressure parameters are reviewed and summarized for the purpose of selecting optimal therapeutic regimens for patients with type 2 diabetes.</p> <p>Results</p> <p>National guidelines recommend the aggressive management of cardiovascular risk factors in patients with type 2 diabetes, including weight loss and achieving lipid and blood pressure treatment goals. All antidiabetes pharmacotherapies lower glucose; however, effects on cardiovascular risk factors vary greatly among agents. While thiazolidinediones, sulfonylureas, and insulin are associated with weight gain, dipeptidyl peptidase-4 inhibitors are considered weight neutral and metformin can be weight neutral or associated with a small weight loss. Glucagon-like peptide-1 receptor agonists and amylinomimetics (e.g. pramlintide) result in weight loss. Additionally, metformin, thiazolidinediones, insulin, and glucagon-like peptide-1 receptor agonists have demonstrated beneficial effects on lipid and blood pressure parameters.</p> <p>Conclusion</p> <p>Management of the cardiovascular risk factors experienced by patients with type 2 diabetes requires a multidisciplinary approach with implementation of treatment strategies to achieve not only glycemic goals but to improve and/or correct the underlying cardiovascular risk factors.</p

Calcific uremic arteriolopathy: Pathophysiology, reactive oxygen species and therapeutic approaches

Calcific uremic arteriolopathy (CUA)/calciphylaxis is an important cause of morbidity and mortality in patients with chronic kidney disease requiring renal replacement. Once thought to be rare, it is being increasingly recognized and reported on a global scale. The uremic milieu predisposes to multiple metabolic toxicities including increased levels of reactive oxygen species and inflammation. Increased oxidative stress and inflammation promote this arteriolopathy by adversely affecting endothelial function resulting in a prothrombotic milieu and significant remodeling effects on vascular smooth muscle cells. These arteriolar pathological effects include intimal hyperplasia, inflammation, endovascular fibrosis and vascular smooth muscle cell apoptosis and differentiation into bone forming osteoblast-like cells resulting in medial calcification. Systemic factors promoting this vascular condition include elevated calcium, parathyroid hormone and hyperphosphatemia with consequent increases in the calcium × phosphate product. The uremic milieu contributes to a marked increased in upstream reactive oxygen species—oxidative stress and subsequent downstream increased inflammation, in part, via activation of the nuclear transcription factor NFκB and associated downstream cytokine pathways. Consitutive anti-calcification proteins such as Fetuin-A and matrix GLA proteins and their signaling pathways may be decreased, which further contributes to medial vascular calcification. The resulting clinical entity is painful, debilitating and contributes to the excess morbidity and mortality associated with chronic kidney disease and end stage renal disease. These same histopathologic conditions also occur in patients without uremia and therefore, the term calcific obliterative arteriolopathy could be utilized in these conditions

Semiparametric Regression for Periodic Longitudinal Hormone Data from Multiple Menstrual Cycles

We consider Semiparametric regression for periodic longitudinal data. Parametric fixed effects are used to model the covariate effects and a periodic nonparametric smooth function is used to model the time effect. The within–subject correlation is modeled using subject-specific random effects and a random stochastic process with a periodic variance function. We use maximum penalized likelihood to estimate the regression coefficients and the periodic nonparametric time function, whose estimator is shown to be a periodic cubic smoothing spline. We use restricted maximum likelihood to simultaneously estimate the smoothing parameter and the variance components. We show that all model parameters can be easily obtained by fitting a linear mixed model. A common problem in the analysis of longitudinal data is to compare the time profiles of two groups, e.g., between treatment and placebo. We develop a scaled chi-squared test for the equality of two nonparametric time functions. The proposed model and the test are illustrated by analyzing hormone data collected during two consecutive menstrual cycles and their performance is evaluated through simulations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65472/1/j.0006-341X.2000.00031.x.pd

The central role of vascular extracellular matrix and basement membrane remodeling in metabolic syndrome and type 2 diabetes: the matrix preloaded

The vascular endothelial basement membrane and extra cellular matrix is a compilation of different macromolecules organized by physical entanglements, opposing ionic charges, chemical covalent bonding, and cross-linking into a biomechanically active polymer. These matrices provide a gel-like form and scaffolding structure with regional tensile strength provided by collagens, elasticity by elastins, adhesiveness by structural glycoproteins, compressibility by proteoglycans – hyaluronans, and communicability by a family of integrins, which exchanges information between cells and between cells and the extracellular matrix of vascular tissues. Each component of the extracellular matrix and specifically the capillary basement membrane possesses unique structural properties and interactions with one another, which determine the separate and combined roles in the multiple diabetic complications or diabetic opathies. Metabolic syndrome, prediabetes, type 2 diabetes mellitus, and their parallel companion (atheroscleropathy) are associated with multiple metabolic toxicities and chronic injurious stimuli. The adaptable quality of a matrix or form genetically preloaded with the necessary information to communicate and respond to an ever-changing environment, which supports the interstitium, capillary and arterial vessel wall is individually examined

Ultrastructure study of the transgenic REN2 rat aorta – part 2: media, external elastic lamina, and adventitia

BackgroundThe renin-angiotensin-aldosterone system (RAAS) plays an important role in the development and progression of vascular stiffness, hypertension and accelerated atherosclerosis, which are associated with the metabolic syndrome (MetS) and type 2 diabetes mellitus. In addition to the intima, RAAS plays an important role in vascular media and adventitial remodeling. Methods Descending thoracic aortas of young male transgenic heterozygous (mRen2) 27 (Ren2) rats were utilized for ultrastructural study. This lean model of hypertension, insulin resistance, and oxidative stress harbors the mouse renin gene and is known to have increased aortic tissue levels of angiotensin II, angiotensin type 1 receptors, and elevated plasma aldosterone levels. ResultsUltrastructural observations substantiate known and novel findings in the tunica media, internal and external elastic lamina, and tunica adventitia, which includes: increased media collagen - proteoglycan matrix expansion, increased secretory and proliferative activity and migration of vascular smooth muscle cells (VSMCs) into a newly developing subendothelial neointima, increased VSMC caveolae, mitochondria degeneration, apoptosis; and lipid retention at the elastin lamellar interface. Openings in the external elastic lamina allow pericyte-to-VSMC contacts. The tunica adventitia exhibits stromal pericyte hyperplasia with actively synthetic phenotype and pericyte-pericyte connections. ConclusionWhile these studies only represent a single snapshot in time, they provide an evaluation of early abnormal ultrastructural vascular remodeling in Ren-2 models of the conduit-elastic thoracic aorta

Cardiac Insulin Resistance and MicroRNA Modulators

Cardiac insulin resistance is a metabolic and functional disorder that is often associated with obesity and/or the cardiorenal metabolic syndrome (CRS), and this disorder may be accentuated by chronic alcohol consumption. In conditions of over-nutrition, increased insulin (INS) and angiotensin II (Ang II) activate mammalian target for rapamycin (mTOR)/p70 S6 kinase (S6K1) signaling, whereas chronic alcohol consumption inhibits mTOR/S6K1 activation in cardiac tissue. Although excessive activation of mTOR/S6K1 induces cardiac INS resistance via serine phosphorylation of INS receptor substrates (IRS-1/2), it also renders cardioprotection via increased Ang II receptor 2 (AT2R) upregulation and adaptive hypertrophy. In the INS-resistant and hyperinsulinemic Zucker obese (ZO) rat, a rodent model for CRS, activation of mTOR/S6K1signaling in cardiac tissue is regulated by protective feed-back mechanisms involving mTOR↔AT2R signaling loop and profile changes of microRNA that target S6K1. Such regulation may play a role in attenuating progressive heart failure. Conversely, alcohol-mediated inhibition of mTOR/S6K1, down-regulation of INS receptor and growth-inhibitory mir-200 family, and upregulation of mir-212 that promotes fetal gene program may exacerbate CRS-related cardiomyopathy

Relation between Childhood Obesity and Adult Cardiovascular Risk

The incidence of overweight and obesity is rising at an alarming pace in the pediatric population, just as in the adult population. The adult comorbidities associated with this risk factor are well-recognized and are being further elucidated continually. Additionally, we are gradually developing a better understanding of the risks of overweight and obesity among children while they are still young. However, there is now a growing body of evidence showing that childhood obesity not only leads all too frequently to adult obesity, but is in itself a risk factor for cardiometabolic syndrome and resultant cardiovascular risk in adulthood. If current trends continue, the problem of pediatric overweight and obesity will become of unmanageable proportions once these individuals reach adulthood. Future research efforts toward understanding this complex problem will need to focus on those overweight and obese children who later went on to change their metabolic course and become normal-weight adults

The Risk for Infant Mortality among Adolescent Childbearing Groups

Objective: To evaluate risk disparities and risk factors for infant mortality among adolescent childbearing age groups. Methods: We combined the 1995 and 1996 comprehensive U.S. birth cohorts provided by the National Center for Heath Statistics. Our analysis included 777,762 singleton, first births to women aged 12-19 years linked to 4631 infant deaths. We used both bivariate comparisons and multivariable logistic regression for our analysis, with infant mortality as our main outcome measure. Results: Rates of infant mortality are substantially higher for ≤15-year-olds (8.1/1000 live births) compared with 16-17-year-olds (6.3/1000 live births) and 18-19-year-olds (5.4/1000 live births). Even after adjusting for risk factors associated with poor outcomes, including alcohol use, tobacco use, and prenatal care use, the risk for infant mortality was 1.6 (95% confidence interval [95% CI] 1.4, 1.7) times greater for infants of mothers ≤15 years old as compared with those mothers 18-19 years old. In the ≤15-year-old group, 62% of fathers were not reported on the child's birth certificate. Not reporting the father was associated with a 24% increased risk for infant mortality after adjusting for maternal and infant risk factors. Conclusions: Childbearing in ≤15-year-olds is associated with a substantial increased risk for infant mortality compared with childbearing in older adolescence. This study suggests that not reporting the father on a birth certificate is a potential risk marker. Risk differences among adolescent age groups may be important to consider when creating tailored intervention and prevention strategies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63403/1/154099902762203722.pd