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)

The Wow Factor? A Comparative Study of the Development of Student Music Teachers' Talents in Scotland and Australia

For some time there has been debate about differing perspectives on musical gift and musical intelligence. One view is that musical gift is innate: that it is present in certain individuals from birth and that the task of the teacher is to develop the potential which is there. A second view is that musical gift is a complex concept which includes responses from individuals to different environments and communities (Howe and Sloboda, 1997). This then raises the possibility that musical excellence can be taught. We have already explored this idea with practising musicians (Stollery and McPhee, 2002). Our research has now expanded to include music teachers in formation, and, in this paper, we look at the influences in their musical development which have either 'crystallised' or 'paralysed' the musical talent which they possess. Our research has a comparative dimension, being carried out in Scotland and in Australia. We conclude that there are several key influences in the musical development of the individual, including home and community support, school opportunities and teaching styles and that there may be education and culture-specific elements to these influences

Post-thaw development of in vitro produced buffalo embryos cryopreserved by cytoskeletal stabilization and vitrification

The present study was conducted to examine post-thaw in vitro developmental competence of buffalo embryos cryopreserved by cytoskeletal stabilization and vitrification. In vitro produced embryos were incubated with a medium containing cytochalasin-b (cyto-b) in a CO2 incubator for 40 min for microfilament stabilization and were cryopreserved by a two-step vitrification method at 24℃ in the presence of cyto-b. Initially, the embryos were exposed to 10% ethylene glycol (EG) and 10% dimethylsulfoxide (DMSO) in a base medium for 4 min. After the initial exposure, the embryos were transferred to a 7 µl drop of 25% EG and 25% DMSO in base medium and 0.3 M sucrose for 45 sec. After warming, the embryos were cultured in vitro for 72 h. The post-thaw in vitro developmental competence of the cyto-b-treated embryos did not differ significantly from those vitrified without cyto-b treatment. The hatching rates of morulae vitrified without cyto-b treatment was significantly lower than the non-vitrified control. However, the hatching rate of cyto-b-treated vitrified morulae did not differ significantly from the non-vitrified control. This study demonstrates that freezing of buffalo embryos by cytoskeletal stabilization and vitrification is a reliable method for long-term preservation

Do adults with high functioning autism or Asperger Syndrome differ in empathy and emotion recognition?

The present study examined whether adults with high functioning autism (HFA) showed greater difficulties in (i) their self-reported ability to empathise with others and/or (ii) their ability to read mental states in others’ eyes than adults with Asperger syndrome (AS). The Empathy Quotient (EQ) and ‘Reading the Mind in the Eyes’ Test (Eyes Test) were compared in 43 adults with AS and 43 adults with HFA. No significant difference was observed on EQ score between groups, while adults with AS performed significantly better on the Eyes Test than those with HFA. This suggests that adults with HFA may need more support, particularly in mentalizing and complex emotion recognition, and raises questions about the existence of subgroups within autism spectrum conditions

Bond graph modelling of chemoelectrical energy transduction

Energy-based bond graph modelling of biomolecular systems is extended to include chemoelectrical transduction thus enabling integrated thermodynamically-compliant modelling of chemoelectrical systems in general and excitable membranes in particular. Our general approach is illustrated by recreating a well-known model of an excitable membrane. This model is used to investigate the energy consumed during a membrane action potential thus contributing to the current debate on the trade-off between the speed of an action potential event and energy consumption. The influx of Na+ is often taken as a proxy for energy consumption; in contrast, this paper presents an energy based model of action potentials. As the energy based approach avoids the assumptions underlying the proxy approach it can be directly used to compute energy consumption in both healthy and diseased neurons. These results are illustrated by comparing the energy consumption of healthy and degenerative retinal ganglion cells using both simulated and in vitro data

SPEAR: The Next Generation GFDL Modeling System for Seasonal to Multidecadal Prediction and Projection

We document the development and simulation characteristics of the next generation modeling system for seasonal to decadal prediction and projection at the Geophysical Fluid Dynamics Laboratory (GFDL). SPEAR (Seamless System for Prediction and EArth System Research) is built from component models recently developed at GFDL—the AM4 atmosphere model, MOM6 ocean code, LM4 land model, and SIS2 sea ice model. The SPEAR models are specifically designed with attributes needed for a prediction model for seasonal to decadal time scales, including the ability to run large ensembles of simulations with available computational resources. For computational speed SPEAR uses a coarse ocean resolution of approximately 1.0° (with tropical refinement). SPEAR can use differing atmospheric horizontal resolutions ranging from 1° to 0.25°. The higher atmospheric resolution facilitates improved simulation of regional climate and extremes. SPEAR is built from the same components as the GFDL CM4 and ESM4 models but with design choices geared toward seasonal to multidecadal physical climate prediction and projection. We document simulation characteristics for the time mean climate, aspects of internal variability, and the response to both idealized and realistic radiative forcing change. We describe in greater detail one focus of the model development process that was motivated by the importance of the Southern Ocean to the global climate system. We present sensitivity tests that document the influence of the Antarctic surface heat budget on Southern Ocean ventilation and deep global ocean circulation. These findings were also useful in the development processes for the GFDL CM4 and ESM4 models

Composition, production and procurement of glass at San Vincenzo: an early medieval monastic complex in southern Italy

136 glasses from the ninth-century monastery of San Vincenzo and its workshops have been analysed by electron microprobe in order to situate the assemblage within the first millennium CE glass making tradition. The majority of the glass compositions can be paralleled by Roman glass from the first to third centuries, with very few samples consistent with later compositional groups. Colours for trailed decoration on vessels, for vessel bodies and for sheet glass for windows were largely produced by melting the glass tesserae from old Roman mosaics. Some weakly-coloured transparent glass was obtained by re-melting Roman window glass, while some was produced by melting and mixing of tesserae, excluding the strongly coloured cobalt blues. Our data suggest that to feed the needs of the glass workshop, the bulk of the glass was removed as tesserae and windows from a large Roman building. This is consistent with a historical account according to which the granite columns of the monastic church were spolia from a Roman temple in the region. The purported shortage of natron from Egypt does not appear to explain the dependency of San Vincenzo on old Roman glass. Rather, the absence of contemporary primary glass may reflect the downturn in long-distance trade in the later first millennium C.E., and the role of patronage in the “ritual economy” founded upon donations and gift-giving of the time

Management and Tillage Infl uence Barley Forage Productivity and Water Use in Dryland Cropping Systems

Annual cereal forages are resilient in water use (WU), water use efficiency (WUE), and weed control compared with grain crops in dryland systems. The combined influence of tillage and management systems on annual cereal forage productivity and WU is not well documented. We conducted a field study for the effects of tillage (no-till and tilled) and management (ecological and conventional) systems on WU and performance of forage barley (Hordeum vulgare L.) and weed biomass in two crop rotations (wheat [Triticum aestivum L.]–forage barley–pea [Pisum sativum L.] and wheat–forage barley–corn [Zea mays L.] –pea) from 2004 to 2010 in eastern Montana. Conventional management included recommended seeding rates, broadcast N fertilization, and short stubble height of wheat. Ecological management included 33% greater seeding rates, banded N fertilization at planting, and taller wheat stubble. Forage barley in ecological management had 28 more plants m–2, 2 cm greater height, 65 more tillers m–2, 606 kg ha–1 greater crop biomass, 3.5 kg ha–1 mm–1greater WUE, and 47% reduction in weed biomass at harvest than in conventional management. Pre-plant and post-harvest soil water contents were similar among tillage and management systems, but barley WU was 13 mm greater in 4-yr than 3-yr rotation. Tillage had little effect on barley performance and WU. Dryland forage barley with higher seeding rate and banded N fertilization in more diversified rotation produced more yield and used water more efficiently than that with conventional seeding rate, broadcast N fertilization, and less diversified rotation in the semiarid northern Great Plains

Executive summary: heart disease and stroke statistics--2013 update: a report from the American Heart Association.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update*The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on heart disease, stroke, and other cardiovascular disease-related morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document*Indeed, since 1999, the Statistical Update has been cited \u3e10 500 times in the literature, based on citations of all annual versions*In 2011 alone, the various Statistical Updates were cited ≈1500 times (data from ISI Web of Science)*In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled*For this year\u27s edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year*This year\u27s edition also implements a new chapter organization to reflect the spectrum of cardiovascular health behaviors and health factors and risks, as well as subsequent complicating conditions, disease states, and outcomes*Also, the 2013 Statistical Update contains new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA\u27s 2020 Impact Goals*Below are a few highlights from this year\u27s Update . © 2013 American Heart Association, Inc

The severity of pandemic H1N1 influenza in the United States, from April to July 2009: A Bayesian analysis

Background: Accurate measures of the severity of pandemic (H1N1) 2009 influenza (pH1N1) are needed to assess the likely impact of an anticipated resurgence in the autumn in the Northern Hemisphere. Severity has been difficult to measure because jurisdictions with large numbers of deaths and other severe outcomes have had too many cases to assess the total number with confidence. Also, detection of severe cases may be more likely, resulting in overestimation of the severity of an average case. We sought to estimate the probabilities that symptomatic infection would lead to hospitalization, ICU admission, and death by combining data from multiple sources. Methods and Findings: We used complementary data from two US cities: Milwaukee attempted to identify cases of medically attended infection whether or not they required hospitalization, while New York City focused on the identification of hospitalizations, intensive care admission or mechanical ventilation (hereafter, ICU), and deaths. New York data were used to estimate numerators for ICU and death, and two sources of data - medically attended cases in Milwaukee or self-reported influenza-like illness (ILI) in New York - were used to estimate ratios of symptomatic cases to hospitalizations. Combining these data with estimates of the fraction detected for each level of severity, we estimated the proportion of symptomatic patients who died (symptomatic case-fatality ratio, sCFR), required ICU (sCIR), and required hospitalization (sCHR), overall and by age category. Evidence, prior information, and associated uncertainty were analyzed in a Bayesian evidence synthesis framework. Using medically attended cases and estimates of the proportion of symptomatic cases medically attended, we estimated an sCFR of 0.048% (95% credible interval [CI] 0.026%-0.096%), sCIR of 0.239% (0.134%-0.458%), and sCHR of 1.44% (0.83%-2.64%). Using self-reported ILI, we obtained estimates approximately 7-96lower. sCFR and sCIR appear to be highest in persons aged 18 y and older, and lowest in children aged 5-17 y. sCHR appears to be lowest in persons aged 5-17; our data were too sparse to allow us to determine the group in which it was the highest. Conclusions: These estimates suggest that an autumn-winter pandemic wave of pH1N1 with comparable severity per case could lead to a number of deaths in the range from considerably below that associated with seasonal influenza to slightly higher, but with the greatest impact in children aged 0-4 and adults 18-64. These estimates of impact depend on assumptions about total incidence of infection and would be larger if incidence of symptomatic infection were higher or shifted toward adults, if viral virulence increased, or if suboptimal treatment resulted from stress on the health care system; numbers would decrease if the total proportion of the population symptomatically infected were lower than assumed.published_or_final_versio