Early dyspnoea relief in acute heart failure: prevalence, association with mortality, and effect of rolofylline in the PROTECT Study

AIMS: Dyspnoea and pulmonary and/or peripheral congestion are the most frequent manifestations of acute heart failure (AHF) and are important targets for therapy. We have assessed changes in dyspnoea, their relationship with mortality, and the effects of the adenosine A1 receptor antagonist rolofylline on these endpoints in patients enrolled in the PROTECT trial. METHODS AND RESULTS: PROTECT was a prospective, double-blind, placebo-controlled study assessing the effect of rolofylline in patients hospitalized for AHF with dyspnoea, fluid overload, increased plasma natriuretic peptides, and mild-to-moderate renal dysfunction. Early dyspnoea relief, prospectively defined as moderately or markedly better dyspnoea at both 24 and 48 h after the start of study drug administration, occurred in 49.8% of the patients. Early dyspnoea relief was associated with greater weight loss and with reduced mortality at Days 14 and 30 [hazard ratio (HR) 0.28, 95% confidence interval (CI): 0.15, 0.50; and 0.35, 95% CI: 0.22, 0.55, respectively]. Rolofylline administration was associated with an increase in the proportion of patients showing early dyspnoea relief (HR 1.30; 95% CI: 1.08, 1.57) and with a numerically lower mortality at 14 and 30 days, largely driven by the mortality due to HF [at 30 days, HR (95% CI, P-value): 0.65 (0.38-1.10, P= 0.107)]. Rolofylline did not reduce episodes of in-hospital worsening HF or post-discharge re-admissions, nor did it improve survival at 60 or 180 days. CONCLUSION: The present analysis from PROTECT demonstrated that more weight loss was associated with early dyspnoea relief and reduced short-term mortality

Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV)

BACKGROUND: The OAV questionnaire has been developed to integrate research on altered states of consciousness (ASC). It measures three primary and one secondary dimensions of ASC that are hypothesized to be invariant across ASC induction methods. The OAV rating scale has been in use for more than 20 years and applied internationally in a broad range of research fields, yet its factorial structure has never been tested by structural equation modeling techniques and its psychometric properties have never been examined in large samples of experimentally induced ASC. METHODOLOGY/PRINCIPAL FINDINGS: The present study conducted a psychometric evaluation of the OAV in a sample of psilocybin (n = 327), ketamine (n = 162), and MDMA (n = 102) induced ASC that was obtained by pooling data from 43 experimental studies. The factorial structure was examined by confirmatory factor analysis, exploratory structural equation modeling, hierarchical item clustering (ICLUST), and multiple indicators multiple causes (MIMIC) modeling. The originally proposed model did not fit the data well even if zero-constraints on non-target factor loadings and residual correlations were relaxed. Furthermore, ICLUST suggested that the "oceanic boundlessness" and "visionary restructuralization" factors could be combined on a high level of the construct hierarchy. However, because these factors were multidimensional, we extracted and examined 11 new lower order factors. MIMIC modeling indicated that these factors were highly measurement invariant across drugs, settings, questionnaire versions, and sexes. The new factors were also demonstrated to have improved homogeneities, satisfactory reliabilities, discriminant and convergent validities, and to differentiate well among the three drug groups. CONCLUSIONS/SIGNIFICANCE: The original scales of the OAV were shown to be multidimensional constructs. Eleven new lower order scales were constructed and demonstrated to have desirable psychometric properties. The new lower order scales are most likely better suited to assess drug induced ASC

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Introduction to the functional RG and applications to gauge theories

These lectures contain an introduction to modern renormalization group (RG) methods as well as functional RG approaches to gauge theories. In the first lecture, the functional renormalization group is introduced with a focus on the flow equation for the effective average action. The second lecture is devoted to a discussion of flow equations and symmetries in general, and flow equations and gauge symmetries in particular. The third lecture deals with the flow equation in the background formalism which is particularly convenient for analytical computations of truncated flows. The fourth lecture concentrates on the transition from microscopic to macroscopic degrees of freedom; even though this is discussed here in the language and the context of QCD, the developed formalism is much more general and will be useful also for other systems.Comment: 60 pages, 14 figures, Lectures held at the 2006 ECT* School "Renormalization Group and Effective Field Theory Approaches to Many-Body Systems", Trento, Ital

Development time and new product sales: A contingency analysis of product innovativeness and price

Opposing theories and conflicting empirical results with regard to the effect of development time on new product sales suggest the need for a contingency analysis into factors affecting this relationship. This study uses a unique combination of accounting and perceptual data from 129 product development projects to test the combined contingency effect of product innovativeness and new product price on the relationship between development time and new product sales. The results show that for radically new products with short development times, price has no effect on new product sales. When the development time is long, price has a negative effect on the sales of radical new products. The findings additionally show that price has no effect on sales for incremental new products with short development times and a negative effect for incremental new products with long development times. Together, these findings shed new light on the relationship between development time and new product sales

Larvicidal activity of metabolites from the endophytic Podospora sp. against the malaria vector Anopheles gambiae

In a screening for natural products with mosquito larvicidal activities, the endophytic fungus Podospora sp. isolated from the plant Laggera alata (Asteraceae) was conspicuous. Two xanthones, sterigmatocystin (1) and secosterigmatocystin (2), and an anthraquinone derivative (3) 13-hydroxyversicolorin B were isolated after fermentation on M2 medium. These compounds were characterised using spectroscopic and X-ray analysis and examined against third instar larvae of Anopheles gambiae. The results demonstrated that compound 1 was the most potent one with LC50 and LC90 values of 13.3 and 73.5 ppm, respectively. Over 95% mortality was observed at a concentration 100 ppm after 24 h. These results compared farvourably with the commercial larvicide pylarvex® that showed 100% mortality at the same concentration. Compound 3 was less potent and had an LC50 of 294.5 ppm and over 95% mortality was achieved at a concentration of 1,000 ppm. Secosterigmatocystin (2) revealed relatively weak activity and therefore LC values were not determined

Effects of Genetic Variants in ADCY5, GIPR, GCKR and VPS13C on Early Impairment of Glucose and Insulin Metabolism in Children

OBJECTIVE: Recent genome-wide association studies identified novel candidate genes for fasting and 2 h blood glucose and insulin levels in adults. We investigated the role of four of these loci (ADCY5, GIPR, GCKR and VPS13C) in early impairment of glucose and insulin metabolism in children. RESEARCH DESIGN AND METHODS: We genotyped four variants (rs2877716; rs1260326; rs10423928; rs17271305) in 638 Caucasian children with detailed metabolic testing including an oGTT and assessed associations with measures of glucose and insulin metabolism (including fasting blood glucose, insulin levels and insulin sensitivity/secretion indices) by linear regression analyses adjusted for age, sex, BMI-SDS and pubertal stage. RESULTS: The major allele (C) of rs2877716 (ADCY5) was nominally associated with decreased fasting plasma insulin (P = 0.008), peak insulin (P = 0.009) and increased QUICKI (P = 0.016) and Matsuda insulin sensitivity index (P = 0.013). rs17271305 (VPS13C) was nominally associated with 2 h blood glucose (P = 0.009), but not with any of the insulin or insulin sensitivity parameters. We found no association of the GIPR and GCKR variants with parameters of glucose and insulin metabolism. None of the variants correlated with anthropometric traits such as height, WHR or BMI-SDS, which excluded potential underlying associations with obesity. CONCLUSIONS: Our data on obese children indicate effects of genetic variation within ADCY5 in early impairment of insulin metabolism and VPS13C in early impairment of blood glucose homeostasis

Signature Movements Lead to Efficient Search for Threatening Actions

The ability to find and evade fighting persons in a crowd is potentially life-saving. To investigate how the visual system processes threatening actions, we employed a visual search paradigm with threatening boxer targets among emotionally-neutral walker distractors, and vice versa. We found that a boxer popped out for both intact and scrambled actions, whereas walkers did not. A reverse correlation analysis revealed that observers' responses clustered around the time of the “punch", a signature movement of boxing actions, but not around specific movements of the walker. These findings support the existence of a detector for signature movements in action perception. This detector helps in rapidly detecting aggressive behavior in a crowd, potentially through an expedited (sub)cortical threat-detection mechanism

Experts see it all: configural effects in action observation

Biological motion perception is influenced by observers’ familiarity with the observed action. Here we used classical dance as a means to investigate how visual and motor experience modulates perceptual mechanism for configural processing of actions. While some ballet moves are performed by only one gender, male and female dancers train together and acquire visual knowledge of all ballet moves. 24 expert ballet dancers (12 female) and matched non-expert participants viewed pairs of upright and inverted point light female and common dance movements. Visual discrimination between different exemplars of the same movement presented upright was significantly better in experts than controls, while no differences were found when the same stimuli were presented upside down. These results suggest expertise influences configural action processing. Within the expert group, effects were stronger for female participants than for males, while no differences were found between movement types. This observer gender effect could suggest an additional role for motor familiarity in action perception, over and above visual experience. Our results are consistent with a specific motor contribution to configural processing of action