Coev-web: a web platform designed to simulate and evaluate coevolving positions along a phylogenetic tree.

BACKGROUND: Available methods to simulate nucleotide or amino acid data typically use Markov models to simulate each position independently. These approaches are not appropriate to assess the performance of combinatorial and probabilistic methods that look for coevolving positions in nucleotide or amino acid sequences. RESULTS: We have developed a web-based platform that gives a user-friendly access to two phylogenetic-based methods implementing the Coev model: the evaluation of coevolving scores and the simulation of coevolving positions. We have also extended the capabilities of the Coev model to allow for the generalization of the alphabet used in the Markov model, which can now analyse both nucleotide and amino acid data sets. The simulation of coevolving positions is novel and builds upon the developments of the Coev model. It allows user to simulate pairs of dependent nucleotide or amino acid positions. CONCLUSIONS: The main focus of our paper is the new simulation method we present for coevolving positions. The implementation of this method is embedded within the web platform Coev-web that is freely accessible at http://coev.vital-it.ch/, and was tested in most modern web browsers.

Prototype of a web-based participative decision support platform in natural hazards and risk management

This paper presents the current state and development of a prototype web-GIS (Geographic Information System) decision support platform intended for application in natural hazards and risk management, mainly for floods and landslides. This web platform uses open-source geospatial software and technologies, particularly the Boundless (formerly OpenGeo) framework and its client side software development kit (SDK). The main purpose of the platform is to assist the experts and stakeholders in the decision-making process for evaluation and selection of different risk management strategies through an interactive participation approach, integrating web-GIS interface with decision support tool based on a compromise programming approach. The access rights and functionality of the platform are varied depending on the roles and responsibilities of stakeholders in managing the risk. The application of the prototype platform is demonstrated based on an example case study site: Malborghetto Valbruna municipality of North-Eastern Italy where flash floods and landslides are frequent with major events having occurred in 2003. The preliminary feedback collected from the stakeholders in the region is discussed to understand the perspectives of stakeholders on the proposed prototype platform.

The International LAM Registry: a component of an innovative web-based clinician, researcher, and patient-driven rare disease research platform.

BACKGROUND: A relative inability to capture a sufficiently large patient population in any one geographic location has traditionally limited research into rare diseases. METHODS AND RESULTS: Clinicians interested in the rare disease lymphangioleiomyomatosis (LAM) have worked with the LAM Treatment Alliance, the MIT Media Lab, and Clozure Associates to cooperate in the design of a state-of-the-art data coordination platform that can be used for clinical trials and other research focused on the global LAM patient population. This platform is a component of a set of web-based resources, including a patient self-report data portal, aimed at accelerating research in rare diseases in a rigorous fashion. CONCLUSIONS: Collaboration between clinicians, researchers, advocacy groups, and patients can create essential community resource infrastructure to accelerate rare disease research. The International LAM Registry is an example of such an effort. 82.

EORTC Radiation Oncology Group quality assurance platform: establishment of a digital central review facility.

OBJECTIVE: Quality assurance (QA) in clinical trials is essential to ensure treatment is safely and effectively delivered. As QA requirements have increased in complexity in parallel with evolution of radiation therapy (RT) delivery, a need to facilitate digital data exchange emerged. Our objective is to present the platform developed for the integration and standardization of QART activities across all EORTC trials involving RT. METHODS: The following essential requirements were identified: secure and easy access without on-site software installation; integration within the existing EORTC clinical remote data capture system; and the ability to both customize the platform to specific studies and adapt to future needs. After retrospective testing within several clinical trials, the platform was introduced in phases to participating sites and QART study reviewers. RESULTS: The resulting QA platform, integrating RT analysis software installed at EORTC Headquarters, permits timely, secure, and fully digital central DICOM-RT based data review. Participating sites submit data through a standard secure upload webpage. Supplemental information is submitted in parallel through web-based forms. An internal quality check by the QART office verifies data consistency, formatting, and anonymization. QART reviewers have remote access through a terminal server. Reviewers evaluate submissions for protocol compliance through an online evaluation matrix. Comments are collected by the coordinating centre and institutions are informed of the results. CONCLUSIONS: This web-based central review platform facilitates rapid, extensive, and prospective QART review. This reduces the risk that trial outcomes are compromised through inadequate radiotherapy and facilitates correlation of results with clinical outcomes.

The inflammasome: an integrated view.

An inflammasome is a multiprotein complex that serves as a platform for caspase-1 activation and caspase-1-dependent proteolytic maturation and secretion of interleukin-1β (IL-1β). Though a number of inflammasomes have been described, the NLRP3 inflammasome is the most extensively studied but also the most elusive. It is unique in that it responds to numerous physically and chemically diverse stimuli. The potent proinflammatory and pyrogenic activities of IL-1β necessitate that inflammasome activity is tightly controlled. To this end, a priming step is first required to induce the expression of both NLRP3 and proIL-1β. This event renders the cell competent for NLRP3 inflammasome activation and IL-1β secretion, and it is highly regulated by negative feedback loops. Despite the wide array of NLRP3 activators, the actual triggering of NLRP3 is controlled by integration a comparatively small number of signals that are common to nearly all activators. Minimally, these include potassium efflux, elevated levels of reactive oxygen species (ROS), and, for certain activators, lysosomal destabilization. Further investigation of how these and potentially other as yet uncharacterized signals are integrated by the NLRP3 inflammasome and the relevance of these biochemical events in vivo should provide new insight into the mechanisms of host defense and autoinflammatory conditions.

Update of the FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation.

The international Functional Annotation Of the Mammalian Genomes 4 (FANTOM4) research collaboration set out to better understand the transcriptional network that regulates macrophage differentiation and to uncover novel components of the transcriptome employing a series of high-throughput experiments. The primary and unique technique is cap analysis of gene expression (CAGE), sequencing mRNA 5'-ends with a second-generation sequencer to quantify promoter activities even in the absence of gene annotation. Additional genome-wide experiments complement the setup including short RNA sequencing, microarray gene expression profiling on large-scale perturbation experiments and ChIP-chip for epigenetic marks and transcription factors. All the experiments are performed in a differentiation time course of the THP-1 human leukemic cell line. Furthermore, we performed a large-scale mammalian two-hybrid (M2H) assay between transcription factors and monitored their expression profile across human and mouse tissues with qRT-PCR to address combinatorial effects of regulation by transcription factors. These interdependent data have been analyzed individually and in combination with each other and are published in related but distinct papers. We provide all data together with systematic annotation in an integrated view as resource for the scientific community (http://fantom.gsc.riken.jp/4/). Additionally, we assembled a rich set of derived analysis results including published predicted and validated regulatory interactions. Here we introduce the resource and its update after the initial release.

An interactive web-GIS tool for risk analysis: a case study in the Fella River basin, Italy

This paper presents a prototype of an interactive web-GIS tool for risk analysis of natural hazards, in particular for floods and landslides, based on open-source geospatial software and technologies. The aim of the presented tool is to assist the experts (risk managers) in analysing the impacts and consequences of a certain hazard event in a considered region, providing an essential input to the decision-making process in the selection of risk management strategies by responsible authorities and decision makers. This tool is based on the Boundless (OpenGeo Suite) framework and its client-side environment for prototype development, and it is one of the main modules of a web-based collaborative decision support platform in risk management. Within this platform, the users can import necessary maps and information to analyse areas at risk. Based on provided information and parameters, loss scenarios (amount of damages and number of fatalities) of a hazard event are generated on the fly and visualized interactively within the web-GIS interface of the platform. The annualized risk is calculated based on the combination of resultant loss scenarios with different return periods of the hazard event. The application of this developed prototype is demonstrated using a regional data set from one of the case study sites, Fella River of northeastern Italy, of the Marie Curie ITN CHANGES project.

A follow-up study on the quality of alcohol dependence-related information on the web.

ABSTRACT: In order to evaluate the one-year evolution of web-based information on alcohol dependence, we re-assessed alcohol-related sites in July 2007 with the same evaluating tool that had been used to assess these sites in June 2006. Websites were assessed with a standardized form designed to rate sites on the basis of accountability, presentation, interactivity, readability, and content quality. The DISCERN scale was also used, which aimed to assist persons without content expertise in assessing the quality of written health publications. Scores were highly stable for all components of the form one year later (r = .77 to .95, p < .01). Analysis of variance for repeated measures showed no time effect, no interaction between time and scale, no interaction between time and group (affiliation categories), and no interaction between time, group, and scale. The study highlights lack of change of alcohol-dependence-related web pages across one year.

Malaria vaccine development using synthetic peptides as a technical platform.

The review covers the development of synthetic peptides as vaccine candidates for Plasmodium falciparum- and Plasmodium vivax-induced malaria from its beginning up to date and the concomitant progress of solid phase peptide synthesis (SPPS) that enables the production of long peptides in a routine fashion. The review also stresses the development of other complementary tools and actions in order to achieve the long sought goal of an efficacious malaria vaccine.

Integrated care organizations in Switzerland.

INTRODUCTION: The Swiss health care system is characterized by its decentralized structure and high degree of local autonomy. Ambulatory care is provided by physicians working mainly independently in individual private practices. However, a growing part of primary care is provided by networks of physicians and health maintenance organizations (HMOs) acting on the principles of gatekeeping. TOWARDS INTEGRATED CARE IN SWITZERLAND: The share of insured choosing an alternative (managed care) type of basic health insurance and therefore restrict their choice of doctors in return for lower premiums increased continuously since 1990. To date, an average of one out of eight insured person in Switzerland, and one out of three in the regions in north-eastern Switzerland, opted for the provision of care by general practitioners in one of the 86 physician networks or HMOs. About 50% of all general practitioners and more than 400 other specialists have joined a physician networks. Seventy-three of the 86 networks (84%) have contracts with the healthcare insurance companies in which they agree to assume budgetary co-responsibility, i.e., to adhere to set cost targets for particular groups of patients. Within and outside the physician networks, at regional and/or cantonal levels, several initiatives targeting chronic diseases have been developed, such as clinical pathways for heart failure and breast cancer patients or chronic disease management programs for patients with diabetes. CONCLUSION AND IMPLICATIONS: Swiss physician networks and HMOs were all established solely by initiatives of physicians and health insurance companies on the sole basis of a healthcare legislation (Swiss Health Insurance Law, KVG) which allows for such initiatives and developments. The relevance of these developments towards more integration of healthcare as well as their implications for the future are discussed.

Quality of web-based information on bipolar disorder

Rapport de synthèse : Introduction : Internet est une source importante d'information sur la santé mentale. Le trouble bipolaire est communément associé à un handicap, des comorbidités, un faible taux d'introspection et une mauvaise compliance au traitement. Le fardeau de la maladie, de par les épisodes dépressifs et maniaques, peut conduire les personnes (dont le diagnostic de trouble bipolaire a été déjà posé ou non), ainsi que leur famille à rechercher des informations sur Internet. De ce fait, il est important que les sites Web traitant du sujet contiennent de l'information de haute qualité, basée sur les évidences scientifiques. Objectif.: évaluer la qualité des informations consultables sur Internat au sujet du trouble bipolaire et identifier des indicateurs de qualité. Méthode: deux mots-clés : « bipolar disorder » et « manic depressive illness » ont été introduits dans les moteurs de recherche les plus souvent utilisés sur Internet. Les sites Internet ont été évalués avec un formulaire standard conçu pour noter les sites sur la base de l'auteur (privé, université, entreprise,...), la présentation, l'interactivité, la lisibilité et la qualité du contenu. Le label de qualité « Health On the Net» (HON), et l'outil DISCERN ont été utilisés pour vérifier leur efficacité comme indicateurs de la qualité. Résultats: sur les 80 sites identifiés, 34 ont été inclus. Sur la base de la mesure des résultats, la qualité du contenu des sites s'est avérée être bonne. La qualité du contenu des sites Web qui traitent du trouble bipolaire est expliquée de manière significative par la lisibilité, la responsabilité et l'interactivité aussi bien que par un score global. Conclusions: dans l'ensemble, la qualité du contenu de l'étude des sites Web traitant du trouble bipolaire est de bonne qualité.

Complementary function and integrated wiring of the evolutionarily distinct Drosophila olfactory subsystems.

To sense myriad environmental odors, animals have evolved multiple, large families of divergent olfactory receptors. How and why distinct receptor repertoires and their associated circuits are functionally and anatomically integrated is essentially unknown. We have addressed these questions through comprehensive comparative analysis of the Drosophila olfactory subsystems that express the ionotropic receptors (IRs) and odorant receptors (ORs). We identify ligands for most IR neuron classes, revealing their specificity for select amines and acids, which complements the broader tuning of ORs for esters and alcohols. IR and OR sensory neurons exhibit glomerular convergence in segregated, although interconnected, zones of the primary olfactory center, but these circuits are extensively interdigitated in higher brain regions. Consistently, behavioral responses to odors arise from an interplay between IR- and OR-dependent pathways. We integrate knowledge on the different phylogenetic and developmental properties of these receptors and circuits to propose models for the functional contributions and evolution of these distinct olfactory subsystems.

Combining food web and species distribution models for improved community projections

The ability to model biodiversity patterns is of prime importance in this era of severe environmental crisis. Species assemblage along environmental gradient is subject to the interplay of biotic interactions in complement to abiotic environmental filtering. Accounting for complex biotic interactions for a wide array of species remains so far challenging. Here, we propose to use food web models that can infer the potential interaction links between species as a constraint in species distribution models. Using a plant-herbivore (butterfly) interaction dataset, we demonstrate that this combined approach is able to improve both species distribution and community forecasts. Most importantly, this combined approach is very useful in rendering models of more generalist species that have multiple potential interaction links, where gap in the literature may be recurrent. Our combined approach points a promising direction forward to model the spatial variation of entire species interaction networks. Our work has implications for studies of range shifting species and invasive species biology where it may be unknown how a given biota might interact with a potential invader or in future climate.