Hepatitis C Viral Dynamics Using a Combination Therapy of Interferon, Ribavirin, and Telaprevir: Mathematical Modeling and Model Validation

Groundbreaking new drugs called direct acting antivirals have been introduced recently for the treatment of chronic Hepatitis C virus infection. We introduce a mathematical model for Hepatitis C dynamics treated with the direct acting antiviral drug, telaprevir, alongside traditional interferon and ribavirin treatments to understand how this combination therapy affects the viral load of patients exhibiting different types of response. We use sensitivity and identifiability techniques to determine which model parameters can be best estimated from viral load data. Parameter estimation with these best estimable parameters is then performed to give patient-specific fits of the model to partial virologic response, sustained virologic response and breakthrough patients

Multi-Class ECG Feature Importance Rankings: Cardiologists vs. Algorithms

Cardiologists have been using electrocardiogram features to diagnose a wide variety of heart conditions for many decades. There are also numerous algorithms that rank feature importance for a particular classification task. However, different algorithms often give quite different feature rankings. Therefore, we compared the feature importance rankings obtained by various algorithms with the features that cardiologists use for diagnosis

PTB-XL+, a comprehensive electrocardiographic feature dataset

Machine learning (ML) methods for the analysis of electrocardiography (ECG) data are gaining importance, substantially supported by the release of large public datasets. However, these current datasets miss important derived descriptors such as ECG features that have been devised in the past hundred years and still form the basis of most automatic ECG analysis algorithms and are critical for cardiologists’ decision processes. ECG features are available from sophisticated commercial software but are not accessible to the general public. To alleviate this issue, we add ECG features from two leading commercial algorithms and an open-source implementation supplemented by a set of automatic diagnostic statements from a commercial ECG analysis software in preprocessed format. This allows the comparison of ML models trained on clinically versus automatically generated label sets. We provide an extensive technical validation of features and diagnostic statements for ML applications. We believe this release crucially enhances the usability of the PTB-XL dataset as a reference dataset for ML methods in the context of ECG data

Hybrid Meson Decay Phenomenology

The phenomenology of a newly developed model of hybrid meson decay is developed. The decay mechanism is based on the heavy quark expansion of QCD and the strong coupling flux tube picture of nonperturbative glue. A comprehensive list of partial decay widths of a wide variety of light, $s\bar s$, $c\bar c$, and $b \bar b$ hybrid mesons is presented. Results which appear approximately universal are highlighted along with those which distinguish different hybrid decay models. Finally, we examine several interesting hybrid candidates in detail.Comment: 37 pages, 2 figures, 6 tables, Revte

Mycobacteria counteract a TLR-mediated nitrosative defense mechanism in a zebrafish infection model.

Pulmonary tuberculosis (TB), caused by the intracellular bacterial pathogen Mycobacterium tuberculosis (Mtb), is a major world health problem. The production of reactive nitrogen species (RNS) is a potent cytostatic and cytotoxic defense mechanism against intracellular pathogens. Nevertheless, the protective role of RNS during Mtb infection remains controversial. Here we use an anti-nitrotyrosine antibody as a readout to study nitration output by the zebrafish host during early mycobacterial pathogenesis. We found that recognition of Mycobacterium marinum, a close relative of Mtb, was sufficient to induce a nitrosative defense mechanism in a manner dependent on MyD88, the central adaptor protein in Toll like receptor (TLR) mediated pathogen recognition. However, this host response was attenuated by mycobacteria via a virulence mechanism independent of the well-characterized RD1 virulence locus. Our results indicate a mechanism of pathogenic mycobacteria to circumvent host defense in vivo. Shifting the balance of host-pathogen interactions in favor of the host by targeting this virulence mechanism may help to alleviate the problem of infection with Mtb strains that are resistant to multiple drug treatments