An experimental investigation on the theoretical development of conditioned inhibition

The Hullian Intervening variables, reactive Inhibition (IR) and conditioned inhibition (SIR) have, like many other Hullian intervening variables, generated large amounts of research as reported in the psychological literature. These views of Hull are presented systematically in two of a proposed three-book system

Performance and loads data from a hover test of a full-scale XV-15 rotor

A hover test of a full-scale XV-15 rotor was conducted at the Outdoor Aerodynamic Research Facility at Ames Research Center. The primary objective of the test was to obtain accurate measurements of the hover performance of the original, metal-blade XV-15 rotor system. Data were acquired for rotor tip Mach numbers ranging from 0.60 to 0.73. This report presents data on rotor performance, rotor wake downwash velocities, and rotor loads

Performance and loads data from a hover test of a 0.658-scale V-22 rotor and wing

A hover test of a 0.658-scale model of a V-22 rotor and wing was conducted at the Outdoor Aerodynamic Research Facility at Ames Research Center. The primary objectives of the test were to obtain accurate measurements of the hover performance of the rotor system, and to measure the aerodynamic interactions between the rotor and wing. Data were acquired for rotor tip Mach numbers ranging from 0.1 to 0.73. This report presents data on rotor performance, rotor-wake downwash velocities, rotor system loads, wing forces and moments, and wing surface pressures

Improved cache performance in Monte Carlo transport calculations using energy banding

We present an energy banding algorithm for Monte Carlo (MC) neutral particle transport simulations which depend on large cross section lookup tables. In MC codes, read-only cross section data tables are accessed frequently, exhibit poor locality, and are typically too much large to fit in fast memory. Thus, performance is often limited by long latencies to RAM, or by off-node communication latencies when the data footprint is very large and must be decomposed on a distributed memory machine. The proposed energy banding algorithm allows maximal temporal reuse of data in band sizes that can flexibly accommodate different architectural features. The energy banding algorithm is general and has a number of benefits compared to the traditional approach. In the present analysis we explore its potential to achieve improvements in time-to-solution on modern cache-based architectures.United States. Department of Energy. Office of Science (Contract DE-AC02-06CH11357

Combined coronary and late-enhanced multidetector-computed tomography for delineation of the etiology of left ventricular dysfunction: comparison with coronary angiography and contrast-enhanced cardiac magnetic resonance imaging

AIMS: To evaluate whether comprehensive evaluation of coronary anatomy and delayed enhancement (DE) by multidetector-computed tomography (MDCT) would allow determination of etiology of left ventricular dysfunction (LVD) as compared with coronary angiography (CA) and DE-magnetic resonance (CMR). METHODS AND RESULTS: Seventy-one consecutive patients (50 males, 59 +/- 16 years) with LVD (ejection fraction: 26 +/- 11%) of unknown etiology underwent MDCT, LGE (late Gd-DTPA-enhanced)-CMR and CA. Patients were classified into four groups according to coronary artery disease (CAD) by CA and LGE-CMR patterns. Patients (n = 24) with CAD and transmural or sub-endocardial DE by CMR were considered having definite ischaemic LVD (group 1). Patients (n = 36) without CAD by CA and with no/atypical LGE-CMR were considered non-ischaemic LVD (group 2). Further we identified four patients with transmural DE but no CAD (group 3) and seven patients with CAD but no DE (group 4). On per-patient basis, combined coronary and DE-MDCT had excellent agreement (kappa = 0.89; P < 0.001) with CA/LGE-CMR to classify patients into the same four groups. Sensitivity, specificity and accuracy of MDCT were 97, 92 and 94%, respectively for detecting patients with definite (group 1) or likely (groups 3 and 4) ischaemic LVD. CONCLUSION: Combined coronary and DE-MDCT can accurately differentiate ischaemic vs. non-ischaemic etiology of LVD

Acute treatment with omecamtiv mecarbil to increase contractility in acute heart failure

Background: Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that increases myocardial function in healthy volunteers and in patients with chronic heart failure. Objectives: This study evaluated the pharmacokinetics, pharmacodynamics, tolerability, safety, and efficacy of OM in patients with acute heart failure (AHF). Methods: Patients admitted for AHF with left ventricular ejection fraction ≤40%, dyspnea, and elevated plasma concentrations of natriuretic peptides were randomized to receive a double-blind, 48-h intravenous infusion of placebo or OM in 3 sequential, escalating-dose cohorts. Results: In 606 patients, OM did not improve the primary endpoint of dyspnea relief (3 OM dose groups and pooled placebo: placebo, 41%; OM cohort 1, 42%; cohort 2, 47%; cohort 3, 51%; p = 0.33) or any of the secondary outcomes studied. In supplemental, pre-specified analyses, OM resulted in greater dyspnea relief at 48 h (placebo, 37% vs. OM, 51%; p = 0.034) and through 5 days (p = 0.038) in the high-dose cohort. OM exerted plasma concentration-related increases in left ventricular systolic ejection time (p &lt; 0.0001) and decreases in end-systolic dimension (p &lt; 0.05). The adverse event profile and tolerability of OM were similar to those of placebo, without increases in ventricular or supraventricular tachyarrhythmias. Plasma troponin concentrations were higher in OM-treated patients compared with placebo (median difference at 48 h, 0.004 ng/ml), but with no obvious relationship with OM concentration (p = 0.95). Conclusions: In patients with AHF, intravenous OM did not meet the primary endpoint of dyspnea improvement, but it was generally well tolerated, it increased systolic ejection time, and it may have improved dyspnea in the high-dose group. (Acute Treatment with Omecamtiv Mecarbil to Increase Contractility in Acute Heart Failure [ATOMIC-AHF]; NCT01300013)

Tailoring a two-dimensional electron gas at the LaAlO3/SrTiO3 (001) interface by epitaxial strain

Recently a metallic state was discovered at the interface between insulating oxides, most notably LaAlO3 and SrTiO3. Properties of this two-dimensional electron gas (2DEG) have attracted significant interest due to its potential applications in nanoelectronics. Control over this carrier density and mobility of the 2DEG is essential for applications of these novel systems, and may be achieved by epitaxial strain. However, despite the rich nature of strain effects on oxide materials properties, such as ferroelectricity, magnetism, and superconductivity, the relationship between the strain and electrical properties of the 2DEG at the LaAlO3/SrTiO3 heterointerface remains largely unexplored. Here, we use different lattice constant single crystal substrates to produce LaAlO3/SrTiO3 interfaces with controlled levels of biaxial epitaxial strain. We have found that tensile strained SrTiO3 destroys the conducting 2DEG, while compressively strained SrTiO3 retains the 2DEG, but with a carrier concentration reduced in comparison to the unstrained LaAlO3/SrTiO3 interface. We have also found that the critical LaAlO3 overlayer thickness for 2DEG formation increases with SrTiO3 compressive strain. Our first-principles calculations suggest that a strain-induced electric polarization in the SrTiO3 layer is responsible for this behavior. It is directed away from the interface and hence creates a negative polarization charge opposing that of the polar LaAlO3 layer. This both increases the critical thickness of the LaAlO3 layer, and reduces carrier concentration above the critical thickness, in agreement with our experimental results. Our findings suggest that epitaxial strain can be used to tailor 2DEGs properties of the LaAlO3/SrTiO3 heterointerface

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)