The Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial: Rationale and Design

Background: Although 40% to 50% of patients with chronic heart failure (HF) have relatively preserved systolic function (PSF), few trials have been conducted in this population and treatment guidelines do not include evidence-based recommendations. Methods and Results: The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) is enrolling 4100 subjects with HF-PSF to evaluate whether 300 mg irbesartan is superior to placebo in reducing mortality and prespecified categories of cardiovascular hospitalizations. The principal inclusion criteria are age ≥60 years, heart failure symptoms, an ejection fraction ≥45%, and either hospitalization for heart failure within 6 months or corroborative evidence of heart failure or the substrate for diastolic heart failure. Additional secondary end points include cardiovascular mortality, cause-specific mortality and morbidity, change in New York Heart Association functional class, quality of life, and N-terminal pro-BNP measurements. Follow-up will continue until 1440 patients experience a primary end point. Substudies will evaluate changes in echocardiographic measurements and serum collagen markers. Conclusion: I-PRESERVE is the largest trial in this understudied area and will provide crucial information on the characteristics and course of the syndrome, as well as the efficacy of the angiotensin receptor blocker irbesartan

The Irbesartan in Heart Failure With Preserved Systolic Function (I-PRESERVE) Trial: Rationale and Design

Background: Although 40% to 50% of patients with chronic heart failure (HF) have relatively preserved systolic function (PSF), few trials have been conducted in this population and treatment guidelines do not include evidence-based recommendations. Methods and Results: The Irbesartan in Heart Failure with Preserved Systolic Function (I-PRESERVE) is enrolling 4100 subjects with HF-PSF to evaluate whether 300 mg irbesartan is superior to placebo in reducing mortality and prespecified categories of cardiovascular hospitalizations. The principal inclusion criteria are age ≥60 years, heart failure symptoms, an ejection fraction ≥45%, and either hospitalization for heart failure within 6 months or corroborative evidence of heart failure or the substrate for diastolic heart failure. Additional secondary end points include cardiovascular mortality, cause-specific mortality and morbidity, change in New York Heart Association functional class, quality of life, and N-terminal pro-BNP measurements. Follow-up will continue until 1440 patients experience a primary end point. Substudies will evaluate changes in echocardiographic measurements and serum collagen markers. Conclusion: I-PRESERVE is the largest trial in this understudied area and will provide crucial information on the characteristics and course of the syndrome, as well as the efficacy of the angiotensin receptor blocker irbesartan

Existence and Stability of Standing Pulses in Neural Networks : I Existence

We consider the existence of standing pulse solutions of a neural network integro-differential equation. These pulses are bistable with the zero state and may be an analogue for short term memory in the brain. The network consists of a single-layer of neurons synaptically connected by lateral inhibition. Our work extends the classic Amari result by considering a non-saturating gain function. We consider a specific connectivity function where the existence conditions for single-pulses can be reduced to the solution of an algebraic system. In addition to the two localized pulse solutions found by Amari, we find that three or more pulses can coexist. We also show the existence of nonconvex ``dimpled'' pulses and double pulses. We map out the pulse shapes and maximum firing rates for different connection weights and gain functions.Comment: 31 pages, 29 figures, submitted to SIAM Journal on Applied Dynamical System

Caracterización bioquímica preliminar de clonas de Babesia bovis irradiadas con cobalto 60

Con objeto de caracterizar parcialmente los cambios inducidos por la irradiación gamma en el crecimiento in vitro y bioquímicamente, dos clonas de Babesia bovis fueron expuestas a dosis de 81, 135 Y 189 Greys (Gy) de irradiación usando una fuente de 60 C

Local Compression in Automated Breast Ultrasound in the Mammographic Geometry

Background, Motivation and Objective: Automated ultrasound scanning (AUS) of the breast has developed more slowly than anticipated. The main limitation, beyond achieving adequate acoustic coupling to the breast, has been excessive shadow artifacts, as reflecting structures at acute angles to the ultrasound beam are not flattened by the transducer as well as in manual scanning. We believe that imaging of the breast in near mammographic compression provides much of the needed flattening. The question under initial study in this effort is, whether in breast AUS under very light mammographic compression, local compression by the transducer might flatten the acutely oriented structures further and reduce the acoustic path length to key structures in the breast. We suspect these improvements will be possible without distorting the breast so dramatically that the lesion registration advantages of scanning the breast in the same system as mammography or digital breast tomosynthesis (DBT) are not realized. Preliminary tests are reported here, as well as design of a system for a more refined human study. Statement of Contribution/Methods: Initial imaging tests were performed in our combined AUS/DBT system. A fiber mesh, loosened slightly in its frame, replaced the standard plastic mammography compression paddle. The transducer, in contact with the mesh and the breast, was translated by motors. The compression force of the linear array transducer on its vertical was manually controlled. Breast phantoms and the breasts of three women were scanned with usual compression by the mesh paddle and then with less global, but added local, compression. Results: Examples of flattened structures were observed more brightly in the locally compressed breasts, and acoustic paths longer than 35 mm were reduced, by _10 mm. In many areas image penetration was 3 cm greater. In one case, image volumes w/wo local compression were spatially aligned by nonlinear image registration software. - - Discussion and Conclusions: Visual indicators of image features expected to provide improved ultrasonic imaging were observed with local compression and lateral movement of tissues appeared acceptable. These results motivated design and construction of an apparatus to make local compression practical and safe. It utilizes joystick control of the vertical compression force during scanning, realized by pneumatic actuators attached to the transducer. The air pressure applied to these actuators is also applied to actuators in the joystick for force feedback to the operator. Two miniature vibrators attached to the joystick provide vibrotactile feedback of the reaction torques computed from the measurements of 6 force sensors on the transducer holder. The fail-safe system design insures no pneumatic compression force application to the breast in case of power loss or emergency shutdown.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87269/4/Saitou50.pd

Sonographic Evaluation of Early‐Stage Breast Cancers That Undergo Neoadjuvant Chemotherapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135555/1/jum2005247885.pd

Automated Ultrasound Scanning on a Dual‐Modality Breast Imaging System

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135219/1/jum2007265645.pd

Methods for the Drug Effectiveness Review Project

Abstract The Drug Effectiveness Review Project was initiated in 2003 in response to dramatic increases in the cost of pharmaceuticals, which lessened the purchasing power of state Medicaid budgets. A collaborative group of state Medicaid agencies and other organizations formed to commission high-quality comparative effectiveness reviews to inform evidence-based decisions about drugs that would be available to Medicaid recipients. The Project is coordinated by the Center for Evidence-based Policy (CEbP) at Oregon Health & Science University (OHSU), and the systematic reviews are undertaken by the Evidence-based Practice Centers (EPCs) at OHSU and at the University of North Carolina. The reviews adhere to high standards for comparative effectiveness reviews. Because the investigators have direct, regular communication with policy-makers, the reports have direct impact on policy and decision-making, unlike many systematic reviews. The Project was an innovator of methods to involve stakeholders and continues to develop its methods in conducting reviews that are highly relevant to policy-makers. The methods used for selecting topics, developing key questions, searching, determining eligibility of studies, assessing study quality, conducting qualitative and quantitative syntheses, rating the strength of evidence, and summarizing findings are described. In addition, our on-going interactions with the policy-makers that use the reports are described

Citrobacter rodentium Subverts ATP Flux and Cholesterol Homeostasis in Intestinal Epithelial Cells In Vivo.

The intestinal epithelial cells (IECs) that line the gut form a robust line of defense against ingested pathogens. We investigated the impact of infection with the enteric pathogen Citrobacter rodentium on mouse IEC metabolism using global proteomic and targeted metabolomics and lipidomics. The major signatures of the infection were upregulation of the sugar transporter Sglt4, aerobic glycolysis, and production of phosphocreatine, which mobilizes cytosolic energy. In contrast, biogenesis of mitochondrial cardiolipins, essential for ATP production, was inhibited, which coincided with increased levels of mucosal O2 and a reduction in colon-associated anaerobic commensals. In addition, IECs responded to infection by activating Srebp2 and the cholesterol biosynthetic pathway. Unexpectedly, infected IECs also upregulated the cholesterol efflux proteins AbcA1, AbcG8, and ApoA1, resulting in higher levels of fecal cholesterol and a bloom of Proteobacteria. These results suggest that C. rodentium manipulates host metabolism to evade innate immune responses and establish a favorable gut ecosystem