Varijacija i norma u hrvatskom crkvenoslavenskom

On the basis of A. Issatschenko\u27s definition of "literary language" and P. Rehder\u27s recent explication of that definition with the reference to medieval Croatia, the author concludes that Croatian Chruch Slavonic (CCS), neither by itself nor as part of a functional unity including also the čakavian dialect, texts composed in that dialect, and mixed čakavian-CCS text, could be characterized as a literary language. Medieval Croatian literacy was based on the coexistence of two independent sociolinguistic systems. One was the "Latinic complex", based on Latin-Čakavian bilingualism. Its most visible characteristics were the Latinic script and Latin liturgy. The second was the "Glagolitic complex", based on CCS-čakavian diglossia. The most visible features of this complex were the Glagolitic script and Slavonic liturgy. Croatian diglossia was probably of the type which the High and Low variants represent not only a functional, but also a linguistic unity. In the absence of explicit codification (grammatical-orthographical manuals and/or polemics concerning the linguistic norm), the norm was established and maintained through the example of the most authoritative texts. In such a situation, one genre (or group of genres) had to be set apart as an exemplary genre, in which infiltration of non-normative elements was not allowed. Stylistically motivated deviation from the norm in other genres would be conditioned by the establishment and documentation of the norm in the exemplary genre. The author suggests as a working hypothesis that the exemplary genre of CCS consisted of the biblical lections (i. e. lectionary) of the missal.Varijacija i norma u hrvatskom crkvenoslavenskom Na temelju Isačenkove definicije književnog jezika i Rehderova nedavna objašnjenja definicije u odnosu na srednjovjekovnu Hrvatsku, autor zaključuje da hrvatski crkvenoslavenski (HC), ni samostalno ni kao dio funkcionalnog jedinstva koje uključuje i čakavski dijalekt, ne može biti određen kao književni jezik. Srednjovjekovna hrvatska književnost temeljila se na supostojanju dvaju neovisnih sociolingvističkih sustava. Jedan je bio "latinski kompleks", koji se temeljio na latinsko-čakavskoj dvojezičnosti (bilingvizmu). Njegovo najočitije svojstvo bila je latinica i latinska liturgija. Drugi je "glagoljski kompleks", koji se temelji na HC-čakavskoj diglosiji. Najočitija svojstva toga kompleksa bila su glagoljica i slavenska liturgija. Hrvatska diglosija vjerojatno je takva u kojoj visoka i niska varijanta pokazuju ne samo funkcionalno već i lingvističko jedinstvo. U nedostatku eksplicitne kodifikacije (gramatičko-ortografski priručnik i/ili polemike o lingvističkoj normi) norma je uspostavljena i održavana na primjeru najautoritativnijih tekstova. U tom slučaju, jedan žanr (ili skupina žanrova) morao se istaknuti kao primjerni žanr u kojem infiltracija nenormativnih elemenata nije dopuštena. Stilistički motivirano odstupanje od norme u drugim žanrovima bilo bi uvjetovano uspostavom dokumentacije norme u primjernom žanru. Autor predlaže radnu hipotezu da se primjerni žanr HC sastojao od biblijskih lekcija (tj. lekcionara) iz misala

Flat fiber: the flexible format for distributed lab-on-a-chip

Integrated optical devices offer dense, multifunctional capability in a single robust package but are rarely considered compatible with the fields of remote or distributed sensing or long-haul 'one-dimensional' fibers. Here we aim to change that by introducing a 'flat-fiber' process that combines the advantages of existing low-cost fiber drawing with the functionality of planar lightwave circuits in a novel hybrid format. By taking this approach, we hope to extend beyond the limitations of traditional planar and fiber substrates - allowing exotic material compositions, device layouts, and local sensing functions to be distributed over extended distances with no coupling or compatibility concerns in highly functional distributed lab-on-a-chip devices

Gene3D: merging structure and function for a Thousand genomes

Over the last 2 years the Gene3D resource has been significantly improved, and is now more accurate and with a much richer interactive display via the Gene3D website (http://gene3d.biochem.ucl.ac.uk/). Gene3D provides accurate structural domain family assignments for over 1100 genomes and nearly 10 000 000 proteins. A hidden Markov model library, constructed from the manually curated CATH structural domain hierarchy, is used to search UniProt, RefSeq and Ensembl protein sequences. The resulting matches are refined into simple multi-domain architectures using a recently developed in-house algorithm, DomainFinder 3 (available at: ftp://ftp.biochem.ucl.ac.uk/pub/gene3d_data/DomainFinder3/). The domain assignments are integrated with multiple external protein function descriptions (e.g. Gene Ontology and KEGG), structural annotations (e.g. coiled coils, disordered regions and sequence polymorphisms) and family resources (e.g. Pfam and eggNog) and displayed on the Gene3D website. The website allows users to view descriptions for both single proteins and genes and large protein sets, such as superfamilies or genomes. Subsets can then be selected for detailed investigation or associated functions and interactions can be used to expand explorations to new proteins. Gene3D also provides a set of services, including an interactive genome coverage graph visualizer, DAS annotation resources, sequence search facilities and SOAP services

Metrics of salbutamol use as predictors of future adverse outcomes in asthma

Background Beta-agonist overuse is associated with adverse outcomes in asthma, however, the relationships between different metrics of salbutamol use and future risk are uncertain. Objective To investigate the relationship between metrics of salbutamol use and adverse outcome. Methods In a 24-week randomized controlled trial of 303 asthma patients at risk of severe exacerbations which compared the efficacy and safety of combination budesonide/formoterol inhaler according to a single inhaler regimen (SMART) with a fixed-dose regimen with salbutamol as reliever (‘Standard’), actual medication use was measured by electronic monitoring (Australian New Zealand Clinical Trials Registry Number ACTRN12610000515099). A nested cohort study explored the relationship between metrics of baseline salbutamol use over 2 weeks and future severe asthma exacerbations, poor asthma control (ACQ-5 ≥ 1.5) or ‘extreme’ salbutamol overuse (> 32 salbutamol actuations/24-h period). Results Higher mean daily salbutamol use (per two actuations/day) [Odds ratio (OR) (95% CI) 1.24 (1.06–1.46)], higher days of salbutamol use (per 2 days in 2 weeks) [OR 1.15 (1.00–1.31)] and higher maximal 24-h use (per two actuations/day) [OR 1.09 (1.02–1.16)] were associated with future severe exacerbations. Higher mean daily salbutamol use was associated with future poor asthma control [OR 1.13 (1.02–1.26)]. Higher mean daily salbutamol use [OR 2.73 (1.84–4.07)], number of days of use [OR 1.46 (1.24–1.71)], and maximal daily use [OR 1.57 (1.31–1.89)] were associated with an increased risk of future extreme salbutamol overuse. Conclusion and Clinical Relevance Electronically recorded frequency of current salbutamol use is a strong predictor of risk of future adverse outcomes in asthma, with average daily use performing the best. These findings provide new information for clinicians considering metrics of salbutamol as predictors of future adverse outcomes in asthma

Assignment of epidemiological lineages in an emerging pandemic using the pangolin tool.

Funder: Oxford Martin School, University of OxfordThe response of the global virus genomics community to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been unprecedented, with significant advances made towards the 'real-time' generation and sharing of SARS-CoV-2 genomic data. The rapid growth in virus genome data production has necessitated the development of new analytical methods that can deal with orders of magnitude of more genomes than previously available. Here, we present and describe Phylogenetic Assignment of Named Global Outbreak Lineages (pangolin), a computational tool that has been developed to assign the most likely lineage to a given SARS-CoV-2 genome sequence according to the Pango dynamic lineage nomenclature scheme. To date, nearly two million virus genomes have been submitted to the web-application implementation of pangolin, which has facilitated the SARS-CoV-2 genomic epidemiology and provided researchers with access to actionable information about the pandemic's transmission lineages

A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch.

As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones

Randomised controlled trial of topical kanuka honey for the treatment of rosacea

OBJECTIVE: To investigate the efficacy of topical 90% medical-grade kanuka honey and 10% glycerine (Honevo) as a treatment for rosacea. DESIGN: Randomised controlled trial with blinded assessment of primary outcome variable. SETTING: Outpatient primary healthcare population from 5 New Zealand sites. PARTICIPANTS: 138 adults aged ≥16, with a diagnosis of rosacea, and a baseline blinded Investigator Global Assessment of Rosacea Severity Score (IGA-RSS) of ≥2. 69 participants were randomised to each treatment arm. 1 participant was excluded from the Honevo group, and 7 and 15 participants withdrew from the Honevo and control groups, respectively. INTERVENTIONS: Participants were randomly allocated 1:1 to Honevo or control cream (Cetomacrogol), applied twice daily for 8 weeks. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of participants who had a ≥2 improvement in the 7-point IGA-RSS at week 8 compared to baseline. Secondary outcomes included change in IGA-RSS and subject-rated visual analogue score of change in severity (VAS-CS) on a 100 mm scale (0 mm 'much worse', 100 mm 'much improved') at weeks 2 and 8. RESULTS: 24/68 (34.3%) in the Honevo group and 12/69 (17.4%) in the control group had a ≥2 improvement in IGA-RSS at week 8 compared to baseline (relative risk 2.03; 95% CI 1.11 to 3.72, p=0.020). The change in IGA-RSS for Honevo compared to control at week 2 minus baseline was -1 (Hodges-Lehman estimate, 95% CI -1 to 0, p=0.03), and at week 8 minus baseline was -1 (Hodges-Lehman estimate, 95% CI -1 to 0, p=0.005). The VAS-CS at week 2 was 9.1 (95% CI 3.5 to 14.7), p=0.002, and at week 8 was 12.3 (95% CI 5.7 to 18.9)¸ p<0.001 for Honevo compared to control. CONCLUSIONS: Honevo is an effective treatment for rosacea. TRIAL REGISTRATION NUMBER: This trial was registered in the Australian and New Zealand Clinical Trials Registry ACTRN12614000004662

An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D

Background The phenotypic effects of sequence variations in protein-coding regions come about primarily via their effects on the resulting structures, for example by disrupting active sites or affecting structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms of their structural manifestation. Although many mutations occur within domains whose structure has been solved, many more occur within genes whose protein products have not been structurally characterized.&lt;p&gt;&lt;/p&gt; Results Here we present 3DSim (3D Structural Implication of Mutations), a database and web application facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein structures even where the structure of the protein of interest is unknown. The server displays information on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with domains predicted to belong to structural families in the CATH database. Mappings between domain sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 three-dimensional structures corresponding to CATH structural domains are currently included in 3DSim; these domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the distribution of mutations in structural space.&lt;p&gt;&lt;/p&gt; Conclusion The server is publicly available at http://3DSim.bioinfo.cnio.es/ webcite. In addition, the database containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the functionality is available through programmatic web service access.&lt;p&gt;&lt;/p&gt

A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch.

As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones

Globetrotting strangles: the unbridled national and international transmission of Streptococcus equi between horses.

The equine disease strangles, which is characterized by the formation of abscesses in the lymph nodes of the head and neck, is one of the most frequently diagnosed infectious diseases of horses around the world. The causal agent, Streptococcus equi subspecies equi, establishes a persistent infection in approximately 10 % of animals that recover from the acute disease. Such 'carrier' animals appear healthy and are rarely identified during routine veterinary examinations pre-purchase or transit, but can transmit S. equi to naïve animals initiating new episodes of disease. Here, we report the analysis and visualization of phylogenomic and epidemiological data for 670 isolates of S. equi recovered from 19 different countries using a new core-genome multilocus sequence typing (cgMLST) web bioresource. Genetic relationships among all 670 S. equi isolates were determined at high resolution, revealing national and international transmission events that drive this endemic disease in horse populations throughout the world. Our data argue for the recognition of the international importance of strangles by the Office International des Épizooties to highlight the health, welfare and economic cost of this disease. The Pathogenwatch cgMLST web bioresource described herein is available for tailored genomic analysis of populations of S. equi and its close relative S. equi subspecies zooepidemicus that are recovered from horses and other animals, including humans, throughout the world. This article contains data hosted by Microreact