Diagnoses of uncertain significance: kidney genetics in the 21st century

The increasing availability of sequencing has accelerated the discovery of genetic causes of kidney disease, with clear benefits for patients. However, insufficient or contradictory evidence exists for numerous variants that were previously reported to be pathogenic, calling into question some proposed gene–disease associations. Rigorous re-appraisal of evidence is needed to ensure diagnostic accuracy

Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL

Exact Hybrid Particle/Population Simulation of Rule-Based Models of Biochemical Systems

Detailed modeling and simulation of biochemical systems is complicated by the problem of combinatorial complexity, an explosion in the number of species and reactions due to myriad protein-protein interactions and post-translational modifications. Rule-based modeling overcomes this problem by representing molecules as structured objects and encoding their interactions as pattern-based rules. This greatly simplifies the process of model specification, avoiding the tedious and error prone task of manually enumerating all species and reactions that can potentially exist in a system. From a simulation perspective, rule-based models can be expanded algorithmically into fully-enumerated reaction networks and simulated using a variety of network-based simulation methods, such as ordinary differential equations or Gillespie's algorithm, provided that the network is not exceedingly large. Alternatively, rule-based models can be simulated directly using particle-based kinetic Monte Carlo methods. This "network-free" approach produces exact stochastic trajectories with a computational cost that is independent of network size. However, memory and run time costs increase with the number of particles, limiting the size of system that can be feasibly simulated. Here, we present a hybrid particle/population simulation method that combines the best attributes of both the network-based and network-free approaches. The method takes as input a rule-based model and a user-specified subset of species to treat as population variables rather than as particles. The model is then transformed by a process of "partial network expansion" into a dynamically equivalent form that can be simulated using a population-adapted network-free simulator. The transformation method has been implemented within the open-source rule-based modeling platform BioNetGen, and resulting hybrid models can be simulated using the particle-based simulator NFsim. Performance tests show that significant memory savings can be achieved using the new approach and a monetary cost analysis provides a practical measure of its utility. © 2014 Hogg et al

A Criterion for Brittle Failure of Rocks Using the Theory of Critical Distances

This paper presents a new analytical criterion for brittle failure of rocks and heavily overconsolidated soils. Griffith’s model of a randomly oriented defect under a biaxial stress state is used to keep the criterion simple. The Griffith’s criterion is improved because the maximum tensile strength is not evaluated at the boundary of the defect but at a certain distance from the boundary, known as the critical distance. This fracture criterion is known as the Point Method, and is part of the Theory of Critical Distances, which is utilized in fracture mechanics. The proposed failure criterion has two parameters: the inherent tensile strength, ó0, and the ratio of the half-length of the initial crack/flaw to the critical distance, a/L. These parameters are difficult to measure but they may be correlated with the uniaxial compressive and tensile strengths, óc and ót. The proposed criterion is able to reproduce the common range of strength ratios for rocks and heavily overconsolidated soils (óc/ót=3-50) and the influence of several microstructural rock properties, such as texture and porosity. Good agreement with laboratory tests reported in the literature is found for tensile and low confining stresses.The work presented was initiated during a research project on “Structural integrity assessments of notch-type defects", for the Spanish Ministry of Science and Innovation (Ref.: MAT2010-15721)

Bringing analysis of gender and social–ecological resilience together in small-scale fisheries research: Challenges and opportunities

The demand for gender analysis is now increasingly orthodox in natural resource programming, including that for small-scale fisheries. Whilst the analysis of social–ecological resilience has made valuable contributions to integrating social dimensions into research and policy-making on natural resource management, it has so far demonstrated limited success in effectively integrating considerations of gender equity. This paper reviews the challenges in, and opportunities for, bringing a gender analysis together with social–ecological resilience analysis in the context of small-scale fisheries research in developing countries. We conclude that rather than searching for a single unifying framework for gender and resilience analysis, it will be more effective to pursue a plural solution in which closer engagement is fostered between analysis of gender and social-ecological resilience whilst preserving the strengths of each approach. This approach can make an important contribution to developing a better evidence base for small-scale fisheries management and policy

The Ontology for Biomedical Investigations

The Ontology for Biomedical Investigations (OBI) is an ontology that provides terms with precisely defined meanings to describe all aspects of how investigations in the biological and medical domains are conducted. OBI re-uses ontologies that provide a representation of biomedical knowledge from the Open Biological and Biomedical Ontologies (OBO) project and adds the ability to describe how this knowledge was derived. We here describe the state of OBI and several applications that are using it, such as adding semantic expressivity to existing databases, building data entry forms, and enabling interoperability between knowledge resources. OBI covers all phases of the investigation process, such as planning, execution and reporting. It represents information and material entities that participate in these processes, as well as roles and functions. Prior to OBI, it was not possible to use a single internally consistent resource that could be applied to multiple types of experiments for these applications. OBI has made this possible by creating terms for entities involved in biological and medical investigations and by importing parts of other biomedical ontologies such as GO, Chemical Entities of Biological Interest (ChEBI) and Phenotype Attribute and Trait Ontology (PATO) without altering their meaning. OBI is being used in a wide range of projects covering genomics, multi-omics, immunology, and catalogs of services. OBI has also spawned other ontologies (Information Artifact Ontology) and methods for importing parts of ontologies (Minimum information to reference an external ontology term (MIREOT)). The OBI project is an open cross-disciplinary collaborative effort, encompassing multiple research communities from around the globe. To date, OBI has created 2366 classes and 40 relations along with textual and formal definitions. The OBI Consortium maintains a web resource (http://obi-ontology.org) providing details on the people, policies, and issues being addressed in association with OBI. The current release of OBI is available at http://purl.obolibrary.org/obo/obi.owl

Conversational Flow Promotes Solidarity

<p>Social interaction is fundamental to the development of various aspects of "we-ness''. Previous research has focused on the role the content of interaction plays in establishing feelings of unity, belongingness and shared reality (a cluster of variables referred to as solidarity here). The present paper is less concerned with content, but focuses on the form of social interaction. We propose that the degree to which conversations flow smoothly or not is, of itself, a cue to solidarity. We test this hypothesis in samples of unacquainted and acquainted dyads who communicate via headsets. Conversational flow is disrupted by introducing a delay in the auditory feedback (vs. no delay). Results of three studies show that smoothly coordinated conversations (compared with disrupted conversations and a control condition) increase feelings of belonging and perceptions of group entitativity, independently of conversation content. These effects are driven by the subjective experience of conversational flow. Our data suggest that this process occurs largely beyond individuals' control. We conclude that the form of social interaction is a powerful cue for inferring group solidarity. Implications for the impact of modern communication technology on developing a shared social identity are discussed.</p>