A stitch in time: Efficient computation of genomic DNA melting bubbles

Background: It is of biological interest to make genome-wide predictions of the locations of DNA melting bubbles using statistical mechanics models. Computationally, this poses the challenge that a generic search through all combinations of bubble starts and ends is quadratic. Results: An efficient algorithm is described, which shows that the time complexity of the task is O(NlogN) rather than quadratic. The algorithm exploits that bubble lengths may be limited, but without a prior assumption of a maximal bubble length. No approximations, such as windowing, have been introduced to reduce the time complexity. More than just finding the bubbles, the algorithm produces a stitch profile, which is a probabilistic graphical model of bubbles and helical regions. The algorithm applies a probability peak finding method based on a hierarchical analysis of the energy barriers in the Poland-Scheraga model. Conclusions: Exact and fast computation of genomic stitch profiles is thus feasible. Sequences of several megabases have been computed, only limited by computer memory. Possible applications are the genome-wide comparisons of bubbles with promotors, TSS, viral integration sites, and other melting-related regions.Comment: 16 pages, 10 figure

CompaGB: An open framework for genome browsers comparison

<p>Abstract</p> <p>Background</p> <p>Tools to visualize and explore genomes hold a central place in genomics and the diversity of genome browsers has increased dramatically over the last few years. It often turns out to be a daunting task to compare and choose a well-adapted genome browser, as multidisciplinary knowledge is required to carry out this task and the number of tools, functionalities and features are overwhelming.</p> <p>Findings</p> <p>To assist in this task, we propose a community-based framework based on two cornerstones: (i) the implementation of industry promoted software qualification method (QSOS) adapted for genome browser evaluations, and (ii) a web resource providing numerous facilities either for visualizing comparisons or performing new evaluations. We formulated 60 criteria specifically for genome browsers, and incorporated another 65 directly from QSOS's generic section. Those criteria aim to answer versatile needs, ranging from a biologist whose interest primarily lies into user-friendly and informative functionalities, a bioinformatician who wants to integrate the genome browser into a wider framework, or a computer scientist who might choose a software according to more technical features. We developed a dedicated web application to enrich the existing QSOS functionalities (weighting of criteria, user profile) with features of interest to a community-based framework: easy management of evolving data, user comments...</p> <p>Conclusions</p> <p>The framework is available at <url>http://genome.jouy.inra.fr/CompaGB</url>. It is open to anyone who wishes to participate in the evaluations. It helps the scientific community to (1) choose a genome browser that would better fit their particular project, (2) visualize features comparatively with easily accessible formats, such as tables or radar plots and (3) perform their own evaluation against the defined criteria. To illustrate the CompaGB functionalities, we have evaluated seven genome browsers according to the implemented methodology. A summary of the features of the compared genome browsers is presented and discussed.</p

Cost-effectiveness of HBV and HCV screening strategies:a systematic review of existing modelling techniques

Introduction: Studies evaluating the cost-effectiveness of screening for Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) are generally heterogeneous in terms of risk groups, settings, screening intervention, outcomes and the economic modelling framework. It is therefore difficult to compare cost-effectiveness results between studies. This systematic review aims to summarise and critically assess existing economic models for HBV and HCV in order to identify the main methodological differences in modelling approaches. Methods: A structured search strategy was developed and a systematic review carried out. A critical assessment of the decision-analytic models was carried out according to the guidelines and framework developed for assessment of decision-analytic models in Health Technology Assessment of health care interventions. Results: The overall approach to analysing the cost-effectiveness of screening strategies was found to be broadly consistent for HBV and HCV. However, modelling parameters and related structure differed between models, producing different results. More recent publications performed better against a performance matrix, evaluating model components and methodology. Conclusion: When assessing screening strategies for HBV and HCV infection, the focus should be on more recent studies, which applied the latest treatment regimes, test methods and had better and more complete data on which to base their models. In addition to parameter selection and associated assumptions, careful consideration of dynamic versus static modelling is recommended. Future research may want to focus on these methodological issues. In addition, the ability to evaluate screening strategies for multiple infectious diseases, (HCV and HIV at the same time) might prove important for decision makers

Engaging communication experts in a Delphi process to identify patient behaviors that could enhance communication in medical encounters

<p>Abstract</p> <p>Background</p> <p>The communication literature currently focuses primarily on improving physicians' verbal and non-verbal behaviors during the medical interview. The Four Habits Model is a teaching and research framework for physician communication that is based on evidence linking specific communication behaviors with processes and outcomes of care. The Model conceptualizes basic communication tasks as "Habits" and describes the sequence of physician communication behaviors during the clinical encounter associated with improved outcomes. Using the Four Habits Model as a starting point, we asked communication experts to identify the verbal communication behaviors of patients that are important in outpatient encounters.</p> <p>Methods</p> <p>We conducted a 4-round Delphi process with 17 international experts in communication research, medical education, and health care delivery. All rounds were conducted via the internet. In round 1, experts reviewed a list of proposed patient verbal communication behaviors within the Four Habits Model framework. The proposed patient verbal communication behaviors were identified based on a review of the communication literature. The experts could: approve the proposed list; add new behaviors; or modify behaviors. In rounds 2, 3, and 4, they rated each behavior for its fit (agree or disagree) with a particular habit. After each round, we calculated the percent agreement for each behavior and provided these data in the next round. Behaviors receiving more than 70% of experts' votes (either agree or disagree) were considered as achieving consensus.</p> <p>Results</p> <p>Of the 14 originally-proposed patient verbal communication behaviors, the experts modified all but 2, and they added 20 behaviors to the Model in round 1. In round 2, they were presented with 59 behaviors and 14 options to remove specific behaviors for rating. After 3 rounds of rating, the experts retained 22 behaviors. This set included behaviors such as asking questions, expressing preferences, and summarizing information.</p> <p>Conclusion</p> <p>The process identified communication tasks and verbal communication behaviors for patients similar to those outlined for physicians in the Four Habits Model. This represents an important step in building a single model that can be applied to teaching patients and physicians the communication skills associated with improved satisfaction and positive outcomes of care.</p

Emergent Properties of Tumor Microenvironment in a Real-life Model of Multicell Tumor Spheroids

Multicellular tumor spheroids are an important {\it in vitro} model of the pre-vascular phase of solid tumors, for sizes well below the diagnostic limit: therefore a biophysical model of spheroids has the ability to shed light on the internal workings and organization of tumors at a critical phase of their development. To this end, we have developed a computer program that integrates the behavior of individual cells and their interactions with other cells and the surrounding environment. It is based on a quantitative description of metabolism, growth, proliferation and death of single tumor cells, and on equations that model biochemical and mechanical cell-cell and cell-environment interactions. The program reproduces existing experimental data on spheroids, and yields unique views of their microenvironment. Simulations show complex internal flows and motions of nutrients, metabolites and cells, that are otherwise unobservable with current experimental techniques, and give novel clues on tumor development and strong hints for future therapies.Comment: 20 pages, 10 figures. Accepted for publication in PLOS One. The published version contains links to a supplementary text and three video file

International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies. In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders

International Veterinary Epilepsy Task Force recommendations for systematic sampling and processing of brains from epileptic dogs and cats

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals. The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures. Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements. The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations

Enriching Peptide Libraries for Binding Affinity and Specificity Through Computationally Directed Library Design

Peptide reagents with high affinity or specificity for their target protein interaction partner are of utility for many important applications. Optimization of peptide binding by screening large libraries is a proven and powerful approach. Libraries designed to be enriched in peptide sequences that are predicted to have desired affinity or specificity characteristics are more likely to yield success than random mutagenesis. We present a library optimization method in which the choice of amino acids to encode at each peptide position can be guided by available experimental data or structure-based predictions. We discuss how to use analysis of predicted library performance to inform rounds of library design. Finally, we include protocols for more complex library design procedures that consider the chemical diversity of the amino acids at each peptide position and optimize a library score based on a user-specified input model.National Institute of General Medical Sciences (U.S.) (Award R01 GM110048

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed