Regional differences in APD restitution can initiate wavebreak and re-entry in cardiac tissue: A computational study

Background Regional differences in action potential duration (APD) restitution in the heart favour arrhythmias, but the mechanism is not well understood. Methods We simulated a 150 × 150 mm 2D sheet of cardiac ventricular tissue using a simplified computational model. We investigated wavebreak and re-entry initiated by an S1S2S3 stimulus protocol in tissue sheets with two regions, each with different APD restitution. The two regions had a different APD at short diastolic interval (DI), but similar APD at long DI. Simulations were performed twice; once with both regions having steep (slope > 1), and once with both regions having flat (slope < 1) APD restitution. Results Wavebreak and re-entry were readily initiated using the S1S2S3 protocol in tissue sheets with two regions having different APD restitution properties. Initiation occurred irrespective of whether the APD restitution slopes were steep or flat. With steep APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms with S1S2 of 250 ms, to 75 ms (S1S2 180 ms). With flat APD restitution, the range of S2S3 intervals resulting in wavebreak increased from 1 ms (S1S2 250 ms), to 21 ms (S1S2 340 ms) and then 11 ms (S1S2 400 ms). Conclusion Regional differences in APD restitution are an arrhythmogenic substrate that can be concealed at normal heart rates. A premature stimulus produces regional differences in repolarisation, and a further premature stimulus can then result in wavebreak and initiate re-entry. This mechanism for initiating re-entry is independent of the steepness of the APD restitution curve

Measuring new product and service portfolio advantage

The current study introduces the concept of new product and service portfolio (NPSP) advantage by creating and validating a three-dimensional measurement method that reflects novelty, meaningfulness and superiority – the three characteristics of NPSP advantage. Based on industry-wide homogeneous generalizable quantitative data from 108 manufacturing companies, the results indicate that these three characteristics of NPSP – novelty, meaningfulness and superiority – are distinct characteristics that together constitute NPSP advantage. This paper contributes to the literature on new product development, as its findings suggest that when measuring the concept of NPSP advantage, the three-dimensional construct that includes the three aforementioned characteristics has a better fit to the data than the unidimensional structure. Because it considers both new products and services, the current study offers an integrated approach to measure the desired innovation process outcome (NPSP advantage). In this way, this paper bridges the research on new product development with that on new service development.fi=vertaisarvioitu|en=peerReviewed

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Supporting new product commercialization through managerial social ties and market knowledge development in an emerging economy

University of Tasmania, Australi

Drucker\u27s Insights on Market Orientation and Innovation: Implications for Emerging Areas in High-Technology Marketing

In 1954, Drucker boldly declared that organizations have only two basic functions, marketing and innovation. While true for any organization, this insight is particularly pertinent for technology-based businesses. The complicated environment surrounding high-tech companies creates a great need for sophisticated marketing, yet these companies continue to have under-developed competencies in marketing and in understanding customer needs. In its first two sections, this essay explores Drucker’s insights with respect to two particularly salient issues for high-tech companies: developing and implementing a market orientation, and sustained break-through innovations. We review Drucker’s insights and synthesize them with the scholarly research on these issues. In the third section, we discuss three emerging areas in high-tech marketing where academics and managers could build on Drucker’s insight to guide future research and practice: market-driving, customer co-creation, and corporate social responsibility. The illustrative examples provided by these emerging areas highlight that even today, Drucker’s writings continue to offer remarkable guidance to scholars and managers who are willing to take the time to reflect, understand, and incorporate these insights in the unique context of high-tech industries

Measurement of cosmic-ray muon spallation products in a xenon-loaded liquid scintillator with KamLAND

Cosmic-ray muons produce various radioisotopes when passing through material. These spallation products can be backgrounds for rare event searches such as in solar neutrino, double-beta decay, and dark matter search experiments. The KamLAND-Zen experiment searches for neutrinoless double-beta decay in 745kg of xenon dissolved in liquid scintillator. The experiment includes dead-time-free electronics with a high efficiency for detecting muon-induced neutrons. The production yields of different radioisotopes are measured with a combination of delayed coincidence techniques, newly developed muon reconstruction and xenon spallation identification methods. The observed xenon spallation products are consistent with results from the FLUKA and Geant4 simulation codes

KamLAND's search for correlated low-energy electron antineutrinos with astrophysical neutrinos from IceCube

We report the results of a search for MeV-scale astrophysical neutrinos in KamLAND presented as an excess in the number of coincident neutrino interactions associated with the publicly available high-energy neutrino datasets from the IceCube Neutrino Observatory. We find no statistically significant excess in the number of observed low-energy electron antineutrinos in KamLAND, given a coincidence time window of $\pm$500s, $\pm$1,000s, $\pm$3,600s, and $\pm$10,000s around each of the IceCube neutrinos. We use this observation to present limits from 1.8 MeV to 100 MeV on the electron antineutrino fluence, assuming a mono-energetic flux. We then compare the results to several astrophysical measurements performed by IceCube and place a limit at the 90% confidence level on the electron antineutrino isotropic thermal luminosity from the TXS 0506+056 blazar.Comment: 12 pages, 5 figure

Search for solar flare neutrinos with the KamLAND detector

We report the result of a search for neutrinos in coincidence with solar flares from the GOES flare database. The search was performed on a 10.8 kton-year exposure of KamLAND collected from 2002 to 2019. This large exposure allows us to explore previously unconstrained parameter space for solar flare neutrinos. We found no statistical excess of neutrinos and established 90% confidence level upper limits of 8.4 × 10^7 cm^−2 (3.0 × 10^9 cm^−2) on the electron antineutrino (electron neutrino) fluence at 20 MeV normalized to the X12 flare, assuming that the neutrino fluence is proportional to the X-ray intensity.https://arxiv.org/abs/2105.0245

First measurement of the strange axial coupling constant using neutral-current quasi-elastic interactions of atmospheric neutrinos at KamLAND

We report a measurement of the strange axial coupling constant $g_A^s$ using atmospheric neutrino data at KamLAND. This constant is a component of the axial form factor of the neutral current quasi-elastic (NCQE) interaction. The value of $g_A^s$ significantly changes the ratio of proton and neutron NCQE cross sections. KamLAND is suitable for measuring NCQE interactions as it can detect nucleon recoils with low energy thresholds and measure neutron multiplicity with high efficiency. KamLAND data, including the information on neutron multiplicity associated with the NCQE interactions, makes it possible to measure $g_A^s$ with a suppressed dependence on the axial mass $M_A$, which has not yet been determined. For a comprehensive prediction of the neutron emission associated with neutrino interactions, we establish a simulation of particle emission via nuclear de-excitation of $^{12}$C, a process not considered in existing neutrino Monte Carlo event generators. Energy spectrum fitting for each neutron multiplicity gives $g_A^s =-0.14^{+0.25}_{-0.26}$, which is the most stringent limit obtained using NCQE interactions without $M_A$ constraints