An Explicit Framework for Interaction Nets

Interaction nets are a graphical formalism inspired by Linear Logic proof-nets often used for studying higher order rewriting e.g. \Beta-reduction. Traditional presentations of interaction nets are based on graph theory and rely on elementary properties of graph theory. We give here a more explicit presentation based on notions borrowed from Girard's Geometry of Interaction: interaction nets are presented as partial permutations and a composition of nets, the gluing, is derived from the execution formula. We then define contexts and reduction as the context closure of rules. We prove strong confluence of the reduction within our framework and show how interaction nets can be viewed as the quotient of some generalized proof-nets

Methane Mitigation:Methods to Reduce Emissions, on the Path to the Paris Agreement

The atmospheric methane burden is increasing rapidly, contrary to pathways compatible with the goals of the 2015 United Nations Framework Convention on Climate Change Paris Agreement. Urgent action is required to bring methane back to a pathway more in line with the Paris goals. Emission reduction from “tractable” (easier to mitigate) anthropogenic sources such as the fossil fuel industries and landfills is being much facilitated by technical advances in the past decade, which have radically improved our ability to locate, identify, quantify, and reduce emissions. Measures to reduce emissions from “intractable” (harder to mitigate) anthropogenic sources such as agriculture and biomass burning have received less attention and are also becoming more feasible, including removal from elevated-methane ambient air near to sources. The wider effort to use microbiological and dietary intervention to reduce emissions from cattle (and humans) is not addressed in detail in this essentially geophysical review. Though they cannot replace the need to reach “net-zero” emissions of CO2, significant reductions in the methane burden will ease the timescales needed to reach required CO2 reduction targets for any particular future temperature limit. There is no single magic bullet, but implementation of a wide array of mitigation and emission reduction strategies could substantially cut the global methane burden, at a cost that is relatively low compared to the parallel and necessary measures to reduce CO2, and thereby reduce the atmospheric methane burden back toward pathways consistent with the goals of the Paris Agreement

Clinical evaluation of the role of ceftaroline in the management of community acquired bacterial pneumonia

Ceftaroline fosamil (ceftaroline) was recently approved for the treatment of community- acquired pneumonia (CAP) and complicated skin infections. This newly developed cephalosporin possesses a broad spectrum of activity against gram-positive and gram-negative bacteria. Most importantly, ceftaroline demonstrates potent in vitro antimicrobial activity against multi-drug resistant Streptococcus pneumoniae and methicillin-resistant strains of Staphylococcus aureus. In two Phase III, double-blinded, randomized, prospective trials (FOCUS 1 and FOCUS 2), ceftaroline was shown to be non-inferior to ceftriaxone for the treatment of CAP in hospitalized patients. Ceftaroline exhibits low resistance rates and a safety profile similar to that of other cephalosporins. In this review, we will evaluate the pharmacological characteristics, safety, antimicrobial properties, and efficacy of ceftaroline and its applications in the treatment of CAP

Clinical aspects of usher syndrome and the USH2A gene in a cohort of 433 patients

IMPORTANCE A new statistical approach is needed to describe the clinical differences between type I and type II Usher syndrome and between the 2 most frequent mutations in the USH2A gene. OBJECTIVES To describe the primary phenotypic characteristics and differences between type I and type II Usher syndrome and to establish a phenotype-genotype correlation for the 2 most frequent mutations in the USH2A gene. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study at a genetics department, in which clinical evaluations were performed for 433 patients (297 unrelated families) who were classified as having type I, II, III, atypical, or unclassified Usher syndrome according to their clinical history, pedigree data, results from ophthalmological studies, and audiological, neurophysiological, and vestibular test results. Molecular studies were performed for 304 patients (256 unrelated families). The Mann-Whitney U test or the χ2 test was used for calculating the differences between mean values for the analyzed parameters. MAIN OUTCOMES AND MEASURES Age at diagnosis; age at onset of night blindness, visual field loss, visual acuity loss, and cataracts; and severity and age at diagnosis of hearing loss. RESULTS The comparison between patients with type I Usher syndrome and those with type II Usher syndrome revealed P < .001 for most items analyzed. The most frequent mutations in the USH2A gene were the p.Glu767Serfs*21 and p.Cys759Phe mutations, with an allelic frequency of 23.2%(63 of 272 alleles) and 8.1% (22 of 272 alleles), respectively. The phenotypic analysis for patients carrying p.Cys759Phe showed P < .001 for most items analyzed when compared with patients carrying p.Glu767Serfs*21 and when compared with patients carrying other mutations in the USH2A gene. None of the p.Cys759Phe patients exhibited a severe hearing loss phenotype, and more than 60%had only mild hearing loss. Most patients carrying the p.Glu767Serfs*21 mutation (72.1%) were moderately deaf. CONCLUSIONS AND RELEVANCE Our study presents the clinical differences between type I and type II Usher syndrome and between the 2 most frequent mutations in the USH2A gene. Detailed genotype-phenotype correlations, as presented in our study, allow for a better correlation of clinical signs with a known genotype and can improve the clinical management, genetic counseling, and risk assessment of patients with Usher syndrome because an estimated prognosis of their disease can be madeThis work was supported by grant PI13/00226 (to Servicio de Genética, Instituto de Investigación–Fundación Jiménez Díaz, Madrid, Spain), by grant PI13/00638 (to Unidad de Genética y Diagnóstico Prenatal, Hospital Universitario y Politécnico La Fe, Valencia, Spain), and by grant 06/07/0036 (to Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain) from Fundaluce and Organización Nacional de Ciegos Españole

Helping someone with problem drug use: a delphi consensus study of consumers, carers, and clinicians

<p>Abstract</p> <p>Background</p> <p>Problem use of illicit drugs (i.e. drug abuse or dependence) is associated with considerable health and social harms, highlighting the need for early intervention and engagement with health services. Family members, friends and colleagues play an important role in supporting and assisting individuals with problem drug use to seek professional help, however there are conflicting views about how and when such support should be offered. This paper reports on the development of mental health first aid guidelines for problem drug use in adults, to help inform community members on how to assist someone developing problem drug use or experiencing a drug-related crisis.</p> <p>Methods</p> <p>A systematic review of the scientific and lay literature was conducted to develop a 228-item survey containing potential first-aid strategies to help someone developing a drug problem or experiencing a drug-related crisis. Three panels of experts (29 consumers, 31 carers and 27 clinicians) were recruited from Australia, Canada, New Zealand, the United Kingdom, and the United States. Panel members independently rated the items over three rounds, with strategies reaching consensus on importance written into the guidelines.</p> <p>Results</p> <p>The overall response rate across three rounds was 80% (86% consumers, 81% carers, 74% clinicians). 140 first aid strategies were endorsed as essential or important by 80% or more of panel members. The endorsed strategies provide information and advice on what is problem drug use and its consequences, how to approach a person about their problem drug use, tips for effective communication, what to do if the person is unwilling to change their drug use, what to do if the person does (or does not) want professional help, what are drug-affected states and how to deal with them, how to deal with adverse reactions leading to a medical emergency, and what to do if the person is aggressive.</p> <p>Conclusions</p> <p>The guidelines provide a consensus-based resource for community members who want to help someone with a drug problem. It is hoped that the guidelines will lead to better support and understanding for those with problem drug use and facilitate engagement with professional help.</p

Prediction of peptide and protein propensity for amyloid formation

Understanding which peptides and proteins have the potential to undergo amyloid formation and what driving forces are responsible for amyloid-like fiber formation and stabilization remains limited. This is mainly because proteins that can undergo structural changes, which lead to amyloid formation, are quite diverse and share no obvious sequence or structural homology, despite the structural similarity found in the fibrils. To address these issues, a novel approach based on recursive feature selection and feed-forward neural networks was undertaken to identify key features highly correlated with the self-assembly problem. This approach allowed the identification of seven physicochemical and biochemical properties of the amino acids highly associated with the self-assembly of peptides and proteins into amyloid-like fibrils (normalized frequency of β-sheet, normalized frequency of β-sheet from LG, weights for β-sheet at the window position of 1, isoelectric point, atom-based hydrophobic moment, helix termination parameter at position j+1 and ΔGº values for peptides extrapolated in 0 M urea). Moreover, these features enabled the development of a new predictor (available at http://cran.r-project.org/web/packages/appnn/index.html) capable of accurately and reliably predicting the amyloidogenic propensity from the polypeptide sequence alone with a prediction accuracy of 84.9 % against an external validation dataset of sequences with experimental in vitro, evidence of amyloid formation

Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations

<p>Abstract</p> <p>Background</p> <p>Usher Syndrome type II (USH2) is an autosomal recessive disorder, characterized by moderate to severe hearing impairment and retinitis pigmentosa (RP). Among the three genes implicated, mutations in the <it>USH2A </it>gene account for 74-90% of the USH2 cases.</p> <p>Methods</p> <p>To identify the genetic cause of the disease and determine the frequency of <it>USH2A </it>mutations in a cohort of 88 unrelated USH Spanish patients, we carried out a mutation screening of the 72 coding exons of this gene by direct sequencing. Moreover, we performed functional minigene studies for those changes that were predicted to affect splicing.</p> <p>Results</p> <p>As a result, a total of 144 DNA sequence variants were identified. Based upon previous studies, allele frequencies, segregation analysis, bioinformatics' predictions and <it>in vitro </it>experiments, 37 variants (23 of them novel) were classified as pathogenic mutations.</p> <p>Conclusions</p> <p>This report provide a wide spectrum of <it>USH2A </it>mutations and clinical features, including atypical Usher syndrome phenotypes resembling Usher syndrome type I. Considering only the patients clearly diagnosed with Usher syndrome type II, and results obtained in this and previous studies, we can state that mutations in <it>USH2A </it>are responsible for 76.1% of USH2 disease in patients of Spanish origin.</p

Examining the role of funders in ensuring value and reducing waste in research: An organizational case-study of the Patient-Centered Outcomes Research Institute [version 1; peer review: 2 approved]

International experts have recommended actions that funders can take to improve the value of research investments. They state that self-assessment and public sharing are the basis for accountability and improvement. We examined our policies and practice to determine the extent to which the Patient-Centered Outcomes Research Institute’s (PCORI) policies and practices as a research funder align with international best practice recommendations. A self-audit of current policies and practice against 17 recommendations and 35 sub-recommendations representing five major stages of research production, based on adapted methods used for self-assessment by another funder, was performed.  Fit of existing PCORI policies and practices with 35 sub-recommendations, qualitative assessment of adequacy (area of strength; area of partial strength; area of growth; not applicable) for 17 recommendations for five stages of research production was assessed. Of the 17 recommendations, 15 were applicable to PCORI’s research mission and focus.  PCORI has policies and practices in place for all elements of six recommendations (“area of strength”) and policies that address each element but with some still in active development for three (“area of partial strength”). PCORI is partially addressing six of the 15 relevant recommendations (“area of growth”). Areas for growth include making study protocols publicly available, improving policies on data sharing, and enhancing collaboration with other funders to reduce redundant funding. A voluntary consortium of international funders is underway to encourage further progress, including additional self-assessment and public sharing for accountability. These findings indicate PCORI has undertaken efforts to align its funding practices with international recommendations to ensure the value of public dollars invested in research.  Further efforts will likely require additional coordination and collaboration between funders and stakeholders

Effect of three diets on the gametogenic development and fatty acid profile of Paracentrotus lividus (Lamark, 1816) gonads

Original articleIn this study, the effects of three diets were investigated to enhance Paracentrotus lividus production for commercial purposes. P. lividus were fed ad libitum for 80 days with: diet A—fresh Codium tomentosum Stackhouse, 1797; diet B—formulated using a jellified mix of macroalgae and vegetables, including C. tomentosum (20%), Coralina sp. Linnaeus, 1758 (17%), cabbage Brassica oleracea var. capitata Linnaeus, 1753 (30%), carrot Daucus carota Linnaeus, 1753 (30%) and agar (3%) as a gelling agent. Diet C consisted of maize Zea mays Linnaeus, 1753 (56%) and New Zealand spinach Tetragonia tetragonoides (Pallas, 1781) Kuntze, 1891 (44%). Their effects on the gonadal and somatic growths, gonadosomatic index (GI) and gametogenesis were evaluated, as well as on the total lipid content and fatty acid composition of sea urchin's gonads. Diet A provided high values of eicosapentaenoic acid (EPA). Gonads of sea urchins fed with diet A were found mostly in growth and maturation stages of gametogenesis and showed the lowest lipid content. Sea urchins fed with diet B presented their gonads in the reabsorption stage and had the highest values of omega‐3 polyunsaturated fatty acids (PUFAs). Sea urchins fed with diet C were in the early stages of gametogenesis and had the highest values of lipid content, plus omega‐6 PUFAs. Once as an ingredient in a balanced mix with vegetables, C. tomentosum can be a key factor to the development of new promising high‐quality and low‐cost feed for P. lividus roe enhancementinfo:eu-repo/semantics/publishedVersio