Carvedilol alone or in combination with digoxin for the management of atrial fibrillation in patients with heart failure?

AbstractObjectivesThis study examined the relative merits of digoxin, carvedilol, and their combination for the management of patients with atrial fibrillation (AF) and heart failure (HF).BackgroundIn patients with AF and HF, both digoxin and beta-blockers reduce the ventricular rate, and both may improve symptoms, but only beta-blockers have been shown to improve prognosis. If combined therapy is not superior to beta-blockers alone, treatment of patients with HF and AF could be simplified by stopping digoxin.MethodsWe enrolled 47 patients (29 males; mean age 68 years) with persistent AF and HF (mean left ventricular ejection fraction [LVEF] 24%) in a randomized, double-blinded, placebo-controlled study. In the first phase of the study, digoxin was compared with the combination of digoxin and carvedilol (four months). In the second phase, digoxin was withdrawn in a double-blinded manner in the carvedilol-treated arm, thus allowing a comparison between digoxin and carvedilol (six months). Investigations were undertaken at baseline and at the end of each phase.ResultsCompared with digoxin alone, combination therapy lowered the ventricular rate on 24-h ambulatory electrocardiographic monitoring (p < 0.0001) and during submaximal exercise (p < 0.05), whereas LVEF (p < 0.05) and symptom score (p < 0.05) improved. In phase 2, there was no significant difference between digoxin alone and carvedilol alone in any variable. The mean ventricular rate rose and LVEF fell when patients switched from combination therapy to carvedilol alone. Six-minute walk distance was not significantly influenced by any therapy.ConclusionsThe combination of carvedilol and digoxin appears generally superior to either carvedilol or digoxin alone in the management of AF in patients with HF

Sharing and visualizing environmental data using Virtual Globes

Virtual globe technology holds many exciting possibilities for environmental science. These easy-to-use, intuitive systems provide means for simultaneously visualizing four-dimensional environmental data from many different sources, enabling the generation of new hypotheses and driving greater understanding of the Earth system. Through the use of simple markup languages, scientists can publish and consume data in interoperable formats without the need for technical assistance. In this paper we give, with examples from our own work, a number of scientific uses for virtual globes, demonstrating their particular advantages. We explain how we have used Web Services to connect virtual globes with diverse data sources and enable more sophisticated usage such as data analysis and collaborative visualization. We also discuss the current limitations of the technology, with particular regard to the visualization of subsurface data and vertical sections

GazeLens: Guiding Attention to Improve Gaze Interpretation in Hub-Satellite Collaboration

In hub-satellite collaboration using video, interpreting gaze direction is critical for communication between hub coworkers sitting around a table and their remote satellite colleague. However, 2D video distorts images and makes this interpretation inaccurate. We present GazeLens, a video conferencing system that improves hub coworkers’ ability to interpret the satellite worker’s gaze. A 360∘ camera captures the hub coworkers and a ceiling camera captures artifacts on the hub table. The system combines these two video feeds in an interface. Lens widgets strategically guide the satellite worker’s attention toward specific areas of her/his screen allow hub coworkers to clearly interpret her/his gaze direction. Our evaluation shows that GazeLens (1) increases hub coworkers’ overall gaze interpretation accuracy by 25.8% in comparison to a conventional video conferencing system, (2) especially for physical artifacts on the hub table, and (3) improves hub coworkers’ ability to distinguish between gazes toward people and artifacts. We discuss how screen space can be leveraged to improve gaze interpretation

Macrophage Subset Sensitivity to Endotoxin Tolerisation by Porphyromonas gingivalis

Macrophages (MΦs) determine oral mucosal responses; mediating tolerance to commensal microbes and food whilst maintaining the capacity to activate immune defences to pathogens. MΦ responses are determined by both differentiation and activation stimuli, giving rise to two distinct subsets; pro-inflammatory M1- and anti-inflammatory/regulatory M2- MΦs. M2-like subsets predominate tolerance induction whereas M1 MΦs predominate in inflammatory pathologies, mediating destructive inflammatory mechanisms, such as those in chronic P.gingivalis (PG) periodontal infection. MΦ responses can be suppressed to benefit either the host or the pathogen. Chronic stimulation by bacterial pathogen associated molecular patterns (PAMPs), such as LPS, is well established to induce tolerance. The aim of this study was to investigate the susceptibility of MΦ subsets to suppression by P. gingivalis. CD14hi and CD14lo M1- and M2-like MΦs were generated in vitro from the THP-1 monocyte cell line by differentiation with PMA and vitamin D3, respectively. MΦ subsets were pre-treated with heat-killed PG (HKPG) and PG-LPS prior to stimulation by bacterial PAMPs. Modulation of inflammation was measured by TNFα, IL-1β, IL-6, IL-10 ELISA and NFκB activation by reporter gene assay. HKPG and PG-LPS differentially suppress PAMP-induced TNFα, IL-6 and IL-10 but fail to suppress IL-1β expression in M1 and M2 MΦs. In addition, P.gingivalis suppressed NFκB activation in CD14lo and CD14hi M2 regulatory MΦs and CD14lo M1 MΦs whereas CD14hi M1 pro-inflammatory MΦs were refractory to suppression. In conclusion, P.gingivalis selectively tolerises regulatory M2 MΦs with little effect on pro-inflammatory CD14hi M1 MΦs; differential suppression facilitating immunopathology at the expense of immunity

Genetic Biocontrol for Invasive Species

Invasive species are increasingly affecting agriculture, food, fisheries, and forestry resources throughout the world. As a result of global trade, invasive species are often introduced into new environments where they become established and cause harm to human health, agriculture, and the environment. Prevention of new introductions is a high priority for addressing the harm caused by invasive species, but unfortunately efforts to prevent new introductions do not address the economic harm that is presently manifested where invasive species have already become established. Genetic biocontrol can be defined as the release of organisms with genetic methods designed to disrupt the reproduction of invasive populations. While these methods offer the potential to control or even eradicate invasive species, there is a need to ensure that genetic biocontrol methods can be deployed in a way that minimizes potential harm to the environment. This review provides an overview of the state of genetic biocontrol, focusing on several approaches that were the subject of presentations at the Genetic Biocontrol for Invasive Species Workshop in Tarragona, Spain, March 31st, 2019, a workshop sponsored by the OECD’s Co-operative Research Program on Biological Resource Management for Sustainable Agricultural Systems. The review considers four different approaches to genetic biocontrol for invasive species; sterile-release, YY Males, Trojan Female Technique, and gene drive. The different approaches will be compared with respect to the efficiency each affords as a genetic biocontrol tool, the practical utility and cost/benefits associated with implementation of the approach, and the regulatory considerations that will need to be addressed for each. The opinions expressed and arguments employed in this publication are the sole responsibility of the authors and do not necessarily reflect those of the OECD or of the governments of its Member countries

Building genomic infrastructure: Sequencing platinum-standard reference-quality genomes of all cetacean species.

International audienc

Geochemical Sourcing of New Zealand Obsidians by Portable X-Ray Fluorescence from 2011 to 2018

This dataset includes 4,582 obsidian artefacts matched to their natural geological source from 45 archaeological sites in New Zealand (Aotearoa). It is a compilation of a number of independent projects conducted in the laboratories of the University of Auckland and University of Otago from 2011 to 2018 [1–13]. It combines previously published studies [3, 5–13], an MA thesis [1], a BA(Hons) dissertation [2], a site report [4], and other previously unpublished primary data. The dataset has high reuse potential for future non-destructive studies of artefacts and social network analyses.   Funding statement: This database began as part of a project funded by Royal Society of New Zealand Marsden Grant (UOA1619) and the support of Te Pūnaha Matatini

Resistance to natural and synthetic gene drive systems

Scientists are rapidly developing synthetic gene drive elements intended for release into natural populations. These are intended to control or eradicate disease vectors and pests, or to spread useful traits through wild populations for disease control or conservation purposes. However, a crucial problem for gene drives is the evolution of resistance against them, preventing their spread. Understanding the mechanisms by which populations might evolve resistance is essential for engineering effective gene drive systems. This review summarizes our current knowledge of drive resistance in both natural and synthetic gene drives. We explore how insights from naturally occurring and synthetic drive systems can be integrated to improve the design of gene drives, better predict the outcome of releases and understand genomic conflict in general