BRITICE Glacial Map, version 2: a map and GIS database of glacial landforms of the last British-Irish Ice Sheet

During the last glaciation, most of the British Isles and the surrounding continental shelf were covered by the British–Irish Ice Sheet (BIIS). An earlier compilation from the existing literature (BRITICE version 1) assembled the relevant glacial geomorphological evidence into a freely available GIS geodatabase and map (Clark et al. 2004: Boreas 33, 359). New high-resolution digital elevation models, of the land and seabed, have become available casting the glacial landform record of the British Isles in a new light and highlighting the shortcomings of the V.1 BRITICE compilation. Here we present a wholesale revision of the evidence, onshore and offshore, to produce BRITICE version 2, which now also includes Ireland. All published geomorphological evidence pertinent to the behaviour of the ice sheet is included, up to the census date of December 2015. The revised GIS database contains over 170 000 geospatially referenced and attributed elements – an eightfold increase in information from the previous version. The compiled data include: drumlins, ribbed moraine, crag-and-tails, mega-scale glacial lineations, glacially streamlined bedrock (grooves, roches moutonnées, whalebacks), glacial erratics, eskers, meltwater channels (subglacial, lateral, proglacial and tunnel valleys), moraines, trimlines, cirques, trough-mouth fans and evidence defining ice-dammed lakes. The increased volume of features necessitates different map/database products with varying levels of data generalization, namely: (i) an unfiltered GIS database containing all mapping; (ii) a filtered GIS database, resolving data conflicts and with edits to improve geo-locational accuracy (available as GIS data and PDF maps); and (iii) a cartographically generalized map to provide an overview of the distribution and types of features at the ice-sheet scale that can be printed at A0 paper size at a 1:1 250 000 scale. All GIS data, the maps (as PDFs) and a bibliography of all published sources are available for download from: https://www.sheffield.ac.uk/geography/staff/clark_chris/britice

Gene-educational attainment interactions in a multi-population genome-wide meta-analysis identify novel lipid loci

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes. Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p &lt; 5 × 10−8) and suggestive (p &lt; 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals). Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue. Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.</p

The influence of prior knowledge structures on website attitudes and behavioral intentions

© 2017 The Persuasion Knowledge Model identifies three knowledge structures (i.e., topic knowledge, persuasion knowledge and agent knowledge) that an individual has prior to exposure to a persuasive attempt. This study extends these knowledge structures by distinguishing between objective and subjective topic knowledge conceptualizations. Specifically, this study examines empirically how an individual's different knowledge structures, held prior to exposure to a web-based intervention, influence subsequent website attitudes and behavioral intentions. The UK's National Health Service (NHS) Live Well website relevant to weight control is used as the web-based intervention in this study. Results suggest that agent (i.e., NHS) knowledge is the most important predictor of website attitudes, while both agent and persuasion knowledge are associated with behavioral intentions to take weight control actions. The results also reveal that the distinction between objective and subjective weight control knowledge is essential given their differential effects on agent and persuasion knowledge. Goal frames, as indicated by the choice between the “healthy eating” and “lose weight” Live Well intervention web pages, are found to moderate the identified Knowledge-Attitude-Behavior links. Theoretical contributions, implications for practice and public policy and future research directions are discussed

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

The Genome of the Model Moss Physcomitrella patens

For more than two decades, the moss Physcomitrella patens has been developed and employed as a model species for comparative studies of plant biology as well as a safe production system for biotechnology. Early on, the generation and dissemination of transcriptomic and genomic resources was an important focal point of Physcomitrella research, which, together with the ease of genetic modification and flexibility of cultivation, over the years has attracted more and more research groups all around the world to use this moss as a model for basic and applied research. The establishment of genomic resources has culminated in the role of the P. patens genome as a reference genome for plant evolution. There are two main parts of this chapter: in the first part we provide an overview and history of the established genomic resources and in the second part we summarize the current biological knowledge about the genome structure, nature of nonprotein- and protein-coding genes including codon usage bias, repeats and transposable elements encoded by the Physcomitrella genome and, where applicable, discuss these attributes in an evolutionary context. Furthermore, we focus on the duplicated parts of the moss genome, like the paralogous genes that were retained after ancestral, large-scale to whole-genome duplication events and can be used to gain insights into the evolutionary history of Physcomitrella. Finally, we conclude this chapter by highlighting a special class of ancient paralogs in the Physcomitrella genome that have been actively retained as redundant copies and might act as pseudoalleles

Mutations of the BRAF gene in human cancer

Cancers arise owing to the accumulation of mutations in critical genes that alter normal programmes of cell proliferation, differentiation and death. As the first stage of a systematic genome-wide screen for these genes, we have prioritized for analysis signalling pathways in which at least one gene is mutated in human cancer. The RAS RAF MEK ERK MAP kinase pathway mediates cellular responses to growth signals. RAS is mutated to an oncogenic form in about 15% of human cancer. The three RAF genes code for cytoplasmic serine/threonine kinases that are regulated by binding RAS. Here we report BRAF somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers. All mutations are within the kinase domain, with a single substitution (V599E) accounting for 80%. Mutated BRAF proteins have elevated kinase activity and are transforming in NIH3T3 cells. Furthermore, RAS function is not required for the growth of cancer cell lines with the V599E mutation. As BRAF is a serine/threonine kinase that is commonly activated by somatic point mutation in human cancer, it may provide new therapeutic opportunities in malignant melanoma