The Benefit of Enhanced Contractility in the Infarct Borderzone: A Virtual Experiment

Objectives: Contractile function in the normally perfused infarct borderzone (BZ) is depressed. However, the impact of reduced BZ contractility on left ventricular (LV) pump function is unknown. As a consequence, there have been no therapies specifically designed to improve BZ contractility. We tested the hypothesis that an improvement in borderzone contractility will improve LV pump function. Methods: From a previously reported study, magnetic resonance imaging (MRI) images with non-invasive tags were used to calculate 3D myocardial strain in five sheep 16 weeks after anteroapical myocardial infarction. Animal-specific finite element (FE) models were created using MRI data and LV pressure obtained at early diastolic filling. Analysis of borderzone function using those FE models has been previously reported. Chamber stiffness, pump function (Starling’s law) and stress in the fiber, cross fiber, and circumferential directions were calculated. Animal-specific FE models were performed for three cases: (a) impaired BZ contractility (INJURED); (b) BZ-contractility fully restored (100% BZ IMPROVEMENT); or (c) BZ-contractility partially restored (50% BZ IMPROVEMENT). Results: 100% BZ IMPROVEMENT and 50% BZ IMPROVEMENT both caused an upward shift in the Starling relationship, resulting in a large (36 and 26%) increase in stroke volume at LVPED = 20 mmHg (8.0 ml, p < 0.001). Moreover, there were a leftward shift in the end-systolic pressure volume relationship, resulting in a 7 and 5% increase in LVPES at 110 mmHg (7.7 ml, p < 0.005). It showed that even 50% BZ IMPROVEMENT was sufficient to drive much of the calculated increase in function. Conclusion: Improved borderzone contractility has a beneficial effect on LV pump function. Partial improvement of borderzone contractility was sufficient to drive much of the calculated increase in function. Therapies specifically designed to improve borderzone contractility should be developed

Equilibrium of Global Amphibian Species Distributions with Climate

A common assumption in bioclimatic envelope modeling is that species distributions are in equilibrium with contemporary climate. A number of studies have measured departures from equilibrium in species distributions in particular regions, but such investigations were never carried out for a complete lineage across its entire distribution. We measure departures of equilibrium with contemporary climate for the distributions of the world amphibian species. Specifically, we fitted bioclimatic envelopes for 5544 species using three presence-only models. We then measured the proportion of the modeled envelope that is currently occupied by the species, as a metric of equilibrium of species distributions with climate. The assumption was that the greater the difference between modeled bioclimatic envelope and the occupied distribution, the greater the likelihood that species distribution would not be at equilibrium with contemporary climate. On average, amphibians occupied 30% to 57% of their potential distributions. Although patterns differed across regions, there were no significant differences among lineages. Species in the Neotropic, Afrotropics, Indo-Malay, and Palaearctic occupied a smaller proportion of their potential distributions than species in the Nearctic, Madagascar, and Australasia. We acknowledge that our models underestimate non equilibrium, and discuss potential reasons for the observed patterns. From a modeling perspective our results support the view that at global scale bioclimatic envelope models might perform similarly across lineages but differently across regions

Probe-Based Confocal Laser Endomicroscopy to Guide Real-Time Endoscopic Therapy in Barrett's Esophagus with Dysplasia

Probe-based confocal laser endomicroscopy (pCLE) is a novel imaging technique which utilizes a low-power laser light passed through a fiber-optic bundle, within a miniprobe that is advanced into the working channel, to obtain microscopic images of the mucosa. This allows the endoscopist to evaluate the microarchitecture of the gastrointestinal epithelium in real time. At this time pCLE cannot replace histopathology, but it can provide diagnostic information as well as guide therapeutic management in patients with Barrett's esophagus (BE) with high-grade dysplasia (HGD). We describe a retrospective case series in which four patients with BE and biopsy-proven HGD underwent endoscopy with pCLE to direct real-time endoscopic ablation therapy and/or endoscopic mucosal resection (EMR), which was performed in conjunction with pCLE. All four patients had pCLE showing features of HGD. After either EMR or radiofrequency ablation (RFA), pCLE was again used to evaluate the margins after therapy to assure accuracy. In one case, pCLE had features of dysplasia at the margin and further repeat EMR was immediately performed. Another case had a normal-appearing esophagus, but pCLE found features of BE in discrete areas and targeted biopsies were performed, which confirmed BE. This patient subsequently underwent RFA therapy of the residual areas of BE. In conclusion, in patients with BE and dysplasia, pCLE is an effective tool used to target biopsies, guide endoscopic therapy and assess the accuracy of EMR or RFA

A genetically encoded reporter of synaptic activity in vivo

To image synaptic activity within neural circuits, we tethered the genetically encoded calcium indicator (GECI) GCaMP2 to synaptic vesicles by fusion to synaptophysin. The resulting reporter, SyGCaMP2, detected the electrical activity of neurons with two advantages over existing cytoplasmic GECIs: it identified the locations of synapses and had a linear response over a wider range of spike frequencies. Simulations and experimental measurements indicated that linearity arises because SyGCaMP2 samples the brief calcium transient passing through the presynaptic compartment close to voltage-sensitive calcium channels rather than changes in bulk calcium concentration. In vivo imaging in zebrafish demonstrated that SyGCaMP2 can assess electrical activity in conventional synapses of spiking neurons in the optic tectum and graded voltage signals transmitted by ribbon synapses of retinal bipolar cells. Localizing a GECI to synaptic terminals provides a strategy for monitoring activity across large groups of neurons at the level of individual synapses

Not all coping strategies are created equal: a mixed methods study exploring physicians' self reported coping strategies

<p>Abstract</p> <p>Background</p> <p>Physicians experience workplace stress and draw on different coping strategies. The primary goal of this paper is to use interview data to explore physicians' self reported coping strategies. In addition, questionnaire data is utilized to explore the degree to which the coping strategies are used and are associated with feelings of emotional exhaustion, a key symptom of burnout.</p> <p>Methods</p> <p>This mixed methods study explores factors related to physician wellness within a large health region in Western Canada. This paper focuses on the coping strategies that physicians use in response to work-related stress. The qualitative component explores physicians' self reported coping strategies through open ended interviews of 42 physicians representing diverse medical specialties and settings (91% response rate). The major themes extracted from the qualitative interviews were used to construct 12 survey items that were included in the comprehensive quantitative questionnaire. Questionnaires were sent to all eligible physicians in the health region with 1178 completed surveys (40% response rate.) Questionnaire items were used to measure how often physicians draw on the various coping strategies. Feelings of burnout were also measured in the survey by 5 items from the Emotional Exhaustion subscale of the revised Maslach Burnout Inventory.</p> <p>Results</p> <p>Major themes identified from the interviews include coping strategies used at work (e.g., working through stress, talking with co-workers, taking a time out, using humor) and after work (e.g., exercise, quiet time, spending time with family). Analysis of the questionnaire data showed three often used workplace coping strategies were positively correlated with feeling emotionally exhausted (i.e., keeping stress to oneself (r = .23), concentrating on what to do next (r = .16), and going on as if nothing happened (r = .07)). Some less often used workplace coping strategies (e.g., taking a time out) and all those used after work were negatively correlated with frequency of emotional exhaustion.</p> <p>Conclusions</p> <p>Physicians' self reported coping strategies are not all created equal in terms of frequency of use and correlation with feeling emotionally exhausted from one's work. This knowledge may be integrated into practical physician stress reduction interventions.</p

A reverse engineering approach to the suppression of citation biases reveals universal properties of citation distributions

The large amount of information contained in bibliographic databases has recently boosted the use of citations, and other indicators based on citation numbers, as tools for the quantitative assessment of scientific research. Citations counts are often interpreted as proxies for the scientific influence of papers, journals, scholars, and institutions. However, a rigorous and scientifically grounded methodology for a correct use of citation counts is still missing. In particular, cross-disciplinary comparisons in terms of raw citation counts systematically favors scientific disciplines with higher citation and publication rates. Here we perform an exhaustive study of the citation patterns of millions of papers, and derive a simple transformation of citation counts able to suppress the disproportionate citation counts among scientific domains. We find that the transformation is well described by a power-law function, and that the parameter values of the transformation are typical features of each scientific discipline. Universal properties of citation patterns descend therefore from the fact that citation distributions for papers in a specific field are all part of the same family of univariate distributions.Comment: 9 pages, 6 figures. Supporting information files available at http://filrad.homelinux.or

Heritage branding orientation: The case of Ach. Brito and the dynamics between corporate and product heritage brands

The notion of heritage branding orientation is introduced and explicated. Heritage branding orientation is designated as embracing both product and corporate brands and differs from corporate heritage brand orientation which has an explicit corporate focus. Empirical insights are drawn from an in-depth and longitudinal case study of Ach. Brito, a celebrated Portuguese manufacturer of soaps and toiletries. This study shows how, by the pursuance of a strategy derived from a heritage branding orientation Ach. Brito – after a prolonged period of decline – achieved a dramatic strategic turnaround. The findings reveal how institutional heritage can be a strategic resource via its adoption and activation at both the product and corporate levels. Moreover, the study showed how the bi-lateral interplay between product and corporate brand levels can be mutually reinforcing. In instrumental terms, the study shows how heritage can be activated and articulated in different ways. For instance, it can re-position both product and/or corporate brands; it can be meaningfully informed by product brand heritage and shape corporate heritage; and can be of strategic importance to both medium-sized and small enterprises

Riparian ecotones and spatial variation of fish assemblages in Portuguese lowland streams

The first results of a long-term study on the role of riparian ecotones on the population and community dynamics of Iberian stream fish are presented and discussed . Riparian and macrophyte cover, bank slope and depth were among the most important variables affecting fish distribution . In general small fish favoured shallow areas with high macrophyte cover, whereas large fish dominated in deep areas with a high riparian cover . Slight spatial changes in terrestrial prey use were found suggesting a minor role for this resource during autumn . Finally, no significant spatial differences were found for linear growth, although some differences were obtained for the condition facto