HAE international home therapy consensus document

Hereditary angioedema (C1 inhibitor deficiency, HAE) is associated with intermittent swellings which are disabling and may be fatal. Effective treatments are available and these are most useful when given early in the course of the swelling. The requirement to attend a medical facility for parenteral treatment results in delays. Home therapy offers the possibility of earlier treatment and better symptom control, enabling patients to live more healthy, productive lives. This paper examines the evidence for patient-controlled home treatment of acute attacks ('self or assisted administration') and suggests a framework for patients and physicians interested in participating in home or self-administration programmes. It represents the opinion of the authors who have a wide range of expert experience in the management of HAE

Evolution of genes and repeats in the Nimrod superfamily

The recently identified Nimrod superfamily is characterized by the presence of a special type of EGF repeat, the NIM repeat, located right after a typical CCXGY/W amino acid motif. On the basis of structural features, nimrod genes can be divided into three types. The proteins encoded by Draper-type genes have an EMI domain at the N-terminal part and only one copy of the NIM motif, followed by a variable number of EGF-like repeats. The products of Nimrod B-type and Nimrod C-type genes (including the eater gene) have different kinds of N-terminal domains, and lack EGF-like repeats but contain a variable number of NIM repeats. Draper and Nimrod C-type (but not Nimrod B-type) proteins carry a transmembrane domain. Several members of the superfamily were claimed to function as receptors in phagocytosis and/or binding of bacteria, which indicates an important role in the cellular immunity and the elimination of apoptotic cells. In this paper, the evolution of the Nimrod superfamily is studied with various methods on the level of genes and repeats. A hypothesis is presented in which the NIM repeat, along with the EMI domain, emerged by structural reorganizations at the end of an EGF-like repeat chain, suggesting a mechanism for the formation of novel types of repeats. The analyses revealed diverse evolutionary patterns in the sequences containing multiple NIM repeats. Although in the Nimrod B and Nimrod C proteins show characteristics of independent evolution, many internal NIM repeats in Eater sequences seem to have undergone concerted evolution. An analysis of the nimrod genes has been performed using phylogenetic and other methods and an evolutionary scenario of the origin and diversification of the Nimrod superfamily is proposed. Our study presents an intriguing example how the evolution of multigene families may contribute to the complexity of the innate immune response

dc readout experiment at the Caltech 40m prototype interferometer

The Laser Interferometer Gravitational Wave Observatory (LIGO) operates a 40m prototype interferometer on the Caltech campus. The primary mission of the prototype is to serve as an experimental testbed for upgrades to the LIGO interferometers and for gaining experience with advanced interferometric techniques, including detuned resonant sideband extraction (i.e. signal recycling) and dc readout (optical homodyne detection). The former technique will be employed in Advanced LIGO, and the latter in both Enhanced and Advanced LIGO. Using dc readout for gravitational wave signal extraction has several technical advantages, including reduced laser and oscillator noise couplings as well as reduced shot noise, when compared to the traditional rf readout technique (optical heterodyne detection) currently in use in large-scale ground-based interferometric gravitational wave detectors. The Caltech 40m laboratory is currently prototyping a dc readout system for a fully suspended interferometric gravitational wave detector. The system includes an optical filter cavity at the interferometer's output port, and the associated controls and optics to ensure that the filter cavity is optimally coupled to the interferometer. We present the results of measurements to characterize noise couplings in rf and dc readout using this system

Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions

The clinical, biochemical and genetic features of the conditions known as estrogen-dependent inherited angioedema, estrogen-associated angioedema, hereditary angioedema with normal C-1 inhibitor, type III angioedema, or factor XII angioedema are reviewed. Discussion emphasizes pathogenesis, diagnosis, and management

HAE therapies: past present and future

Advances in understanding the pathophysiology and mechanism of swelling in hereditary angioedema (HAE) has resulted in the development of multiple new drugs for the acute and prophylactic treatment of patients with HAE. This review will recap the past treatment options, review the new current treatment options, and discuss potential future treatment options for patients with HAE

Search for gravitational waves associated with the August 2006 timing glitch of the Vela pulsar

The physical mechanisms responsible for pulsar timing glitches are thought to excite quasinormal mode oscillations in their parent neutron star that couple to gravitational-wave emission. In August 2006, a timing glitch was observed in the radio emission of PSR B0833-45, the Vela pulsar. At the time of the glitch, the two colocated Hanford gravitational-wave detectors of the Laser Interferometer Gravitational wave observatory (LIGO) were operational and taking data as part of the fifth LIGO science run (S5). We present the first direct search for the gravitational-wave emission associated with oscillations of the fundamental quadrupole mode excited by a pulsar timing glitch. No gravitational-wave detection candidate was found. We place Bayesian 90% confidence upper limits of 6.3 x 10^(-21) to 1.4 x 10^(-20) on the peak intrinsic strain amplitude of gravitational-wave ring-down signals, depending on which spherical harmonic mode is excited. The corresponding range of energy upper limits is 5.0 x 10^(-44) to 1.3 x 10^(-45) erg

Hereditary angioedema: beyond international consensus - circa December 2010 - The Canadian Society of Allergy and Clinical Immunology Dr. David McCourtie Lecture

<p>Abstract</p> <p>Background</p> <p>The 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema was published earlier this year in this Journal (Bowen et al. <it>Allergy, Asthma & Clinical Immunology </it>2010, 6:24 - <url>http://www.aacijournal.com/content/6/1/24</url>). Since that publication, there have been multiple phase III clinical trials published on either prophylaxis or therapy of hereditary angioedema and some of these products have changed approval status in various countries. This manuscript was prepared to review and update the management of hereditary angioedema.</p> <p>Objective</p> <p>To review approaches for the diagnosis and management of hereditary angioedema (HAE) circa December 2010 and present thoughts on moving from HAE management from international evidence-based consensus to facilitate more local health unit considerations balancing costs, efficacies of treatments, and risk benefits. Thoughts will reflect Canadian and international experiences.</p> <p>Methods</p> <p>PubMed searches including hereditary angioedema and diagnosis, therapy, management and consensus were reviewed as well as press releases from various pharmaceutical companies to early December 2010.</p> <p>Results</p> <p>The 2010 International Consensus Algorithms for the Diagnosis, Therapy and Management of Hereditary Angioedema is reviewed in light of the newly published phase III Clinical trials for prevention and therapy of HAE. Management approaches and models are discussed.</p> <p>Conclusions</p> <p>Consensus approach and double-blind placebo controlled trials are only interim guides to a complex disorder such as HAE and should be replaced as soon as possible with large phase IV clinical trials, meta analyses, data base registry validation of approaches including quality of life and cost benefit analyses, safety, and head-to-head clinical trials investigating superiority or non-inferiority comparisons of available approaches. Since not all therapeutic products are available in all jurisdictions and since health care delivery approaches and philosophy vary between countries, each health care delivery sector will likely devise their own algorithms based on local practicalities for implementing evidence-based guidelines and standards for HAE disease management. Quality-of-life and cost affordability benefit conclusions will likely vary between countries and health care units. Data base registries for rare disorders like HAE should be used to detect early adverse events for new therapies and to facilitate phase IV clinical trials and encourage superiority and non-inferiority comparisons of HAE management approaches.</p

The BioGRID Interaction Database: 2011 update

The Biological General Repository for Interaction Datasets (BioGRID) is a public database that archives and disseminates genetic and protein interaction data from model organisms and humans (http://www.thebiogrid.org). BioGRID currently holds 347 966 interactions (170 162 genetic, 177 804 protein) curated from both high-throughput data sets and individual focused studies, as derived from over 23 000 publications in the primary literature. Complete coverage of the entire literature is maintained for budding yeast (Saccharomyces cerevisiae), fission yeast (Schizosaccharomyces pombe) and thale cress (Arabidopsis thaliana), and efforts to expand curation across multiple metazoan species are underway. The BioGRID houses 48 831 human protein interactions that have been curated from 10 247 publications. Current curation drives are focused on particular areas of biology to enable insights into conserved networks and pathways that are relevant to human health. The BioGRID 3.0 web interface contains new search and display features that enable rapid queries across multiple data types and sources. An automated Interaction Management System (IMS) is used to prioritize, coordinate and track curation across international sites and projects. BioGRID provides interaction data to several model organism databases, resources such as Entrez-Gene and other interaction meta-databases. The entire BioGRID 3.0 data collection may be downloaded in multiple file formats, including PSI MI XML. Source code for BioGRID 3.0 is freely available without any restrictions