17 research outputs found
Europeanization of sub-arctic environments : perspectives from Norse Greenland's outer fjords
Acknowledgements The authors gratefully acknowledge the financial support of the Leverhulme Trust Footprints on the Edge of Thule Programme Award. ECL acknowledges the support of the Weissman International Internship Program, the Department of Earth and Planetary Sciences and the Department of Anthropology at Harvard. We would also like to thank George McLeod (University of Stirling) for manufacturing soil thin sections.Peer reviewedPostprin
Recommended from our members
The DYMECS project: a statistical approach for the evaluation of convective storms in high-resolution NWP models
A new frontier in weather forecasting is emerging by operational forecast models now being run at convection-permitting resolutions at many national weather services. However, this is not a panacea; significant systematic errors remain in the character of convective storms and rainfall distributions. The DYMECS project (Dynamical and Microphysical Evolution of Convective Storms) is taking a fundamentally new approach to evaluate and improve such models: rather than relying on a limited number of cases, which may not be representative, we have gathered a large database of 3D storm structures on 40 convective days using the Chilbolton radar in southern England. We have related these structures to storm life-cycles derived by tracking features in the rainfall from the UK radar network, and compared them statistically to storm structures in the Met Office model, which we ran at horizontal grid length between 1.5 km and 100 m, including simulations with different subgrid mixing length. We also evaluated the scale and intensity of convective updrafts using a new radar technique. We find that the horizontal size of simulated convective storms and the updrafts within them is much too large at 1.5-km resolution, such that the convective mass flux of individual updrafts can be too large by an order of magnitude. The scale of precipitation cores and updrafts decreases steadily with decreasing grid lengths, as does the typical storm lifetime. The 200-m grid-length simulation with standard mixing length performs best over all diagnostics, although a greater mixing length improves the representation of deep convective storms
Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study
Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation
Geoarchaeological investigations at Sandhavn, South Greenland
First paragraph: This paper presents preliminary results of fieldwork conducted in August 2008 at Sandhavn, south Greenland, within the 'Footprints on the edge of Thule: Landscapes of Norse-Indigenous Interaction' research programme. Sandhavn is located on the south coast of Greenland 3.5km west-north-west of Herjolfsnæs (59°59'N, 44°46'W; Figure 1). Evidence of Norse occupation comprises three ruin groups (Figure 2): Ø221 and Ø221a along the eastern shoreline within a sheltered bay which extends 1.5km north-north-west from the coast; and Ø221b 500m inland next to the river Maakkarneq. Indigenous (Inuit) occupation consists of dwellings and graves. The fieldwork was carried out to characterise the nature and extent of soil and archaeological sediment modification within a landscape where interaction between Norse and Inuit is likely. We anticipated detecting changes in land management, resource exploitation and site formation related to this cultural interaction
Footprints on the Edge of Thule: Landscapes of Norse-Indigenous Interaction : A Major New Research Programme
Broad-scale benthic habitat classification of the South Atlantic
Marine Spatial Planning (MSP) has become a priority for many states wanting to develop national blue economy plans and meet international obligations in response to the increasing cumulative impacts of human activities and climate change. In areas beyond national jurisdiction (ABNJ), MSP is proposed as part of a package of solutions for multi-sectoral management at the ocean basin scale. To facilitate planning, maps showing the spatial distribution of marine biological diversity are required. In areas lacking data, like the South Atlantic, environmental proxies can be used to predict these distributions. We undertook broad-scale benthic habitat classification of the South Atlantic, employing two top-down approaches spanning from national waters to ABNJ. The first was non-hierarchical and clustered groups of environmental variables prior to combination; the second was hierarchical and clustered Principal Components of environmental variables. Areas of agreement between the two approaches were identified and results compared with existing national and global classifications and published biodiversity patterns. We highlight several habitat classes we can be cautiously confident represent variation in biological diversity, such as topographic features, frontal systems and some abyssal basins. We also identify critical gaps in our knowledge of regional biogeography and advocate for collaborative effort to compile benthic species records and promote further exploration of the region to address these gaps. These insights into the distribution of habitats have the potential to support sustainable use and conservation of biodiversity beyond national jurisdiction, enable transboundary and ocean basin scale management, and empower nations to make progress towards achieving Sustainable Development Goals
Impact of the presence of auditory neuropathy spectrum disorder (ANSD) on outcomes of children at three years of age
Europeanization of Sub-Arctic Environments: Perspectives from Norse Greenland’s Outer Fjords
Whole-genome sequencing reveals host factors underlying critical COVID-19
Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease