Hypervirulent Clostridium difficile Strains in Hospitalized Patients, Canada1

To determine the incidence rate of infections with North American pulsed-field types 7 and 8 (NAP7/NAP8) strains of Clostrodium difficile, ribotype 078, and toxinotype V strains, we examined data collected for the Canadian Nosocomial Infections Surveillance Program (CNISP) CDI surveillance project during 2004–2008. Incidence of human infections increased from 0.5% in 2004/2005 to 1.6% in 2008

"Looking all lost towards a Cook's guide for beauty”: the art of literature and the lessons of the guidebook in modernist writing

This article explores the impact of the guidebook, especially the Baedeker series, on modernist literary culture. It argues that the guidebook is a literary phenomenon in its own right and that, as such, it attracts special attention from those engaged in defending and/or extending the category of literature as part of a modernist agenda. In particular, modernist writers are concerned as to whether the guidebook counts as a form of literature and, if so, what this means for the more familiar forms seen in their own essays, fiction and travelogues. What might the invention of the star system to rank scenes and monuments mean for the future of art criticism? How might the guidebook help or hinder the traveller in his/her pursuit of the beautiful or the picturesque? What does recourse to the guidebook reveal about the taste and education of the traveller? And, more pointedly still, what kind and quality of writing is the guidebook itself? This article surveys the extent of modernism's interest in the guidebook, both as a noteworthy new form and as a form modernist writers adapted for use in their own books, before turning in detail to commentary on the guidebook by E.M. Forster, Ernest Hemingway, H.D. and Virginia Woolf. In conclusion, it finds that the guidebook in modernism is very rarely just that. Instead, the guidebook finds unexpected affinities with modernism in its attempt to “modernise” literature – to make it more rational, more totalising and, in the eyes of its critics, less able to discriminate.This is an Accepted Manuscript of an article published by Taylor & Francis in Studies in Travel Writing on 4th March 2015, available online: http://wwww.tandfonline.com/10.1080/13645145.2014.994924

Future-proofing and maximizing the utility of metadata: The PHA4GE SARS-CoV-2 contextual data specification package

Background The Public Health Alliance for Genomic Epidemiology (PHA4GE) (https://pha4ge.org) is a global coalition that is actively working to establish consensus standards, document and share best practices, improve the availability of critical bioinformatics tools and resources, and advocate for greater openness, interoperability, accessibility, and reproducibility in public health microbial bioinformatics. In the face of the current pandemic, PHA4GE has identified a need for a fit-for-purpose, open-source SARS-CoV-2 contextual data standard. Results As such, we have developed a SARS-CoV-2 contextual data specification package based on harmonizable, publicly available community standards. The specification can be implemented via a collection template, as well as an array of protocols and tools to support both the harmonization and submission of sequence data and contextual information to public biorepositories. Conclusions Well-structured, rich contextual data add value, promote reuse, and enable aggregation and integration of disparate datasets. Adoption of the proposed standard and practices will better enable interoperability between datasets and systems, improve the consistency and utility of generated data, and ultimately facilitate novel insights and discoveries in SARS-CoV-2 and COVID-19. The package is now supported by the NCBI’s BioSample database

Lessons Learned from Multi-scale Modeling of the Failing Heart

[EN] Heart failure constitutes a major public health problem worldwide. Affected patients experience a number of changes in the electrical function of the heart that predispose to potentially lethal cardiac arrhythmias. Due to the multitude of electrophysiological changes that may occur during heart failure, the scientific literature is complex and sometimes ambiguous, perhaps because these findings are highly dependent on the etiology, the stage of heart failure, and the experimental model used to study these changes. Nevertheless, a number of common features of failing hearts have been documented. Prolongation of the action potential (AP) involving ion channel remodeling and alterations in calcium handling have been established as the hallmark characteristics of myocytes isolated from failing hearts. Intercellular uncoupling and fibrosis are identified as major arrhythmogenic factors. Multi-scale computational simulations are a powerful tool that complements experimental and clinical research. The development of biophysically detailed computer models of single myocytes and cardiac tissues has contributed greatly to our understanding of processes underlying excitation and repolarization in the heart. The electrical, structural, and metabolic remodeling that arises in cardiac tissues during heart failure has been addressed from different computational perspectives to further understand the arrhythmogenic substrate. This review summarizes the contributions from computational modeling and simulation to predict the underlying mechanisms of heart failure phenotypes and their implications for arrhythmogenesis, ranging from the cellular level to whole-heart simulations. The main aspects of heart failure are presented in several related sections. An overview of the main electrophysiological and structural changes that have been observed experimentally in failing hearts is followed by the description and discussion of the simulation work in this field at the cellular level, and then in 2D and 3D cardiac structures. The implications for arrhythmogenesis in heart failure are also discussed including therapeutic measures, such as drug effects and cardiac resynchronization therapy. Finally, the future challenges in heart failure modeling and simulation will be discussed.This work was partially supported by (i) the "VI Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica" from the Ministerio de Economia y Competitividad of Spain and the European Commission (European Regional Development Funds ERDF-FEDER) (grant number TIN2012-37546-C03-01), and by (ii) Programa Prometeo de la Conselleria d'Educacio Formacio I Ocupacio, Generalitat Valenciana (grant number PROMETEO/2012/030).Gómez García, JF.; Cardona-Urrego, KE.; Trénor Gomis, BA. (2015). Lessons Learned from Multi-scale Modeling of the Failing Heart. Journal of Molecular and Cellular Cardiology. 89:146-159. https://doi.org/10.1016/j.yjmcc.2015.10.016S1461598

Mathematical modeling of electronic interactions between human ventricular myoctyes and cardiac fibroblasts

Bibliography: p. 143-152Some pages are in colour

K(+) Currents Activated by Depolarization in Cardiac Fibroblasts

K(+) currents expressed in freshly dispersed rat ventricular fibroblasts have been studied using whole-cell patch-clamp recordings. Depolarizing voltage steps from a holding potential of −90 mV activated time- and voltage-dependent outward currents at membrane potentials positive to ∼−30 mV. The relatively slow activation kinetics exhibited strong dependence on the membrane potential. Selected changes in extracellular K(+) concentration ([K(+)](o)) revealed that the reversal potentials of the tail currents changed as expected for a K(+) equilibrium potential. The activation and inactivation kinetics of this K(+) current, as well as its recovery from inactivation, were well-fitted by single exponential functions. The steady-state inactivation was well described by a Boltzmann function with a half-maximal inactivation potential (V(0.5)) of −24 mV. Increasing [K(+)](o) (from 5 to 100 mM) shifted this V(0.5) in the hyperpolarizing direction by −11 mV. Inactivation was slowed by increasing [K(+)](o) to 100 mM, and the rate of recovery from inactivation was decreased after increasing [K(+)](o). Block of this K(+) current by extracellular tetraethylammonium also slowed inactivation. These [K(+)](o)-induced changes and tetraethylammonium effects suggest an important role for a C-type inactivation mechanism. This K(+) current was sensitive to dendrotoxin-I (100 nM) and rTityustoxin Kα (50 nM)

A mathematical model of electrotonic interactions between ventricular myocytes and fibroblasts

Functional intercellular coupling has been demonstrated among networks of cardiac fibroblasts, as well as between fibroblasts and atrial or ventricular myocytes. In this study, the consequences of these interactions were examined by implementing the ten Tusscher model of the human ventricular action potential, and coupling it to our electrophysiological models for mammalian ventricular fibroblasts. Our simulations reveal significant electrophysiological consequences of coupling between 1 and 4 fibroblasts to a single ventricular myocyte. These include alterations in plateau height and/or action potential duration (APD) and changes in underlying ionic currents. Two series of simulations were carried out. First, fibroblasts were modeled as a spherical cell with a capacitance of 6.3 pF and an ohmic membrane resistance of 10.7 GΩ. When these “passive” fibroblasts were coupled to a myocyte, they caused slight prolongation of APD with no changes in the plateau, threshold for firing, or rate of initial depolarization. In contrast, when the same myocyte-fibroblast complexes were modeled after addition of the time- and voltage-gated K+ currents that are expressed in fibroblasts, much more pronounced effects were observed: the plateau height of the action potential was reduced and the APD shortened significantly. In addition, each fibroblast exhibited significant electrotonic depolarizations in response to each myocyte action potential and the resting potential of the fibroblasts closely approximated the resting potential of the coupled ventricular myocyte