62 research outputs found

    Spatial ecology of marine top predators

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    Electronic version excludes material for which permission has not been granted by the rights holderSpecies distribution maps can provide important information to focus conservation efforts and enable spatial management of human activities. Two sympatric marine predators, grey seals (Halichoerus grypus) and harbour seals (Phoca vitulina), have overlapping ranges but contrasting population dynamics around the UK; whilst grey seals have generally increased, harbour seals have shown significant regional declines. A robust analytical methodology was developed to produce maps of grey and harbour seal usage estimates with corresponding uncertainty, and scales of spatial partitioning between the species were found. Throughout their range, both grey and harbour seals spend the majority of their time within 50 km of the coast. The scalability of the analytical approach was enhanced and environmental information to enable spatial predictions was included. The resultant maps have been applied to inform consent and licensing of marine renewable developments of wind farms and tidal turbines. For harbour seals around Orkney, northern Scotland, distance from haul out, proportion of sand in seabed sediment, and annual mean power were important predictors of space-use. Utilising seal usage maps, a framework was produced to allow shipping noise, an important marine anthropogenic stressor, to be explicitly incorporated into spatial planning. Potentially sensitive areas were identified through quantifying risk of exposure of shipping traffic to marine species. Individual noise exposure was predicted with associated uncertainty in an area with varying rates of co-occurrence. Across the UK, spatial overlap was highest within 50 km of the coast, close to seal haul outs. Areas identified with high risk of exposure included 11 Special Areas of Conservation (from a possible 25). Risk to harbour seal populations was highest, affecting half of all SACs associated with the species. For 20 of 28 animals in the acoustic exposure study, 95% CI for M-weighted cumulative Sound Exposure Levels had upper bounds above levels known to induce Temporary Threshold Shift. Predictions of broadband received sound pressure levels were underestimated on average by 0.7 dB re 1μPa (± 3.3). An analytical methodology was derived to allow ecological maps to be quantitatively compared. The Structural Similarity (SSIM) index was enhanced to incorporate uncertainty from underlying spatial models, and a software algorithm was developed to correct for internal edge effects so that loss of spatial information from the map comparison was limited. The application of the approach was demonstrated using a case study of sperm whales (Physeter macrocephalus, Linneaus 1758) in the Mediterranean Sea to identify areas where local-scale differences in space-use between groups and singleton whales occurred. SSIM is applicable to a broad range of spatial ecological data, providing a novel tool for map comparison

    Fine-scale harbour seal usage for informed marine spatial planning

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    The work was funded through Scottish Government MSQ0174 contract CR/2014/11; CREEM, University of St Andrews; the National Capability fund from the Natural Environment Research Council to the Sea Mammal Research Unit (grant no. SMRU1001); and MASTS pooling initiative, which is funded by the Scottish Funding Council (grant reference HR09011).High-resolution species distribution maps are required for marine spatial planning, consenting, and licensing to assess interactions between anthropogenic activities and ecosystems. This approach can inform conservation measures for protected species and facilitate commercial developments needed for economic growth. A case study centred on Orkney, UK, is an area where concern for a declining harbour seal population has led to constraints being placed on tidal energy generation developments. Telemetry data from 54 animals tagged between 2003 and 2015 were combined with terrestrial counts from 2008 to 2015 to produce density estimation maps. Predictive habitat models using GAM-GEEs provided robust predictions in areas where telemetry data were absent, and were combined with density estimation maps. Harbour seal usage maps with confidence intervals were produced around Orkney and the North coast of Scotland. The selected habitat model showed that distance from haul out, proportion of sand in seabed sediment, and peak flow of tidal current were important predictors of space-use. Fine-scale usage maps can be used in consenting and licensing of anthropogenic developments to determine local abundance. When quantifying anthropogenic impacts through changes to species distributions, usage maps could be spatially explicitly linked to individual-based models to inform predicted movement and behaviour.Publisher PDFPeer reviewe

    Intrinsic and extrinsic drivers of activity budgets in sympatric grey and harbour seals

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    D. J. F. Russell was funded by the UK Department of Energy and Climate Change (DECC) as part of their Offshore Energy Strategic Environmental Assessment programme and by Scottish Government as part of their Marine Mammal Scientific Support Research Programme (MMSS/001/11). The telemetry tags and their deployment were funded by DECC, the Natural Environment Research Council, Scottish Government, Marine Scotland Science and The European Commission.Investigation of activity budgets in relation to seasonal, intrinsic (age, sex) and extrinsic (time of day, spatial) covariates enables an understanding of how such covariates shape behavioural strategies. However, conducting such investigations in the wild is challenging, because of the required large sample size of individuals across the annual cycle, and difficulties in categorising behavioural states and analysing the resulting individual-referenced and serially correlated data. In this study, from telemetry tags deployed on 63 grey seals (Halichoerus grypus) and 126 harbour seals (Phoca vitulina) we used behavioural data, and movement data within a Bayesian state-space model (SSM), to define population-level activity budgets around Britain. Using generalised estimating equations (GEEs) we then examined how time spent in four states (resting on land (hauled out), resting at sea, foraging and travelling) was influenced by seasonal, intrinsic and extrinsic covariates. We present and discuss the following key findings. (1) We found no evidence that regional variation in foraging effort was linked to regional population trajectories in harbour seals. (2) Grey seals demonstrated sex-specific seasonal differences in their activity budgets, independent from those related to reproductive costs. (3) In these sympatric species there was evidence of temporal separation in time hauled out, but not in time foraging. (4) In both species, time spent resting at sea was separated into inshore (associated with tidal haul out availability) and offshore areas. Time spent resting at sea and on land was interchangeable to some extent, suggesting a degree of overlap in their functionality. This may result in a relaxation of the constraints associated with a central place foraging strategy. More generally, we demonstrate how a large dataset, incorporating differing tag parameters, can be analysed to define activity budgets and subsequently address important ecological questions.PostprintPeer reviewe

    Patterns of space use in sympatric marine colonial predators reveals scales of spatial partitioning

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    E.L.J. and D.J.F.R. were funded under Scottish Government grant MMSS001/01. D.J.F.R. was funded by the UK Department of Energy and Climate Change (DECC) as part of their Offshore Energy Strategic Environmental Assessment programme. S.S. was part-funded by the EU MYFISH project.Species distribution maps can provide important information to focus conservation efforts and enable spatial management of human activities. Two sympatric marine predators, grey seals Halichoerus grypus and harbour seals Phoca vitulina have overlapping ranges on land and at sea but contrasting population dynamics around Britain: whilst grey seals have generally increased, harbour seals have shown significant regional declines. We analysed two decades of at-sea movement data and terrestrial count data from these species to produce high resolution, broad-scale maps of distribution and associated uncertainty to inform conservation and management. Our results showed that grey seals use offshore areas connected to their haul-out sites by prominent corridors and harbour seals primarily stay within 50km of the coastline. Both species show fine-scale offshore spatial segregation off the east coast of Britain and broad-scale partitioning off western Scotland. These results illustrate that for broad-scale marine spatial planning, the conservation needs of harbour seals (primarily inshore, the exception being selected offshore usage areas) are different from those of grey seals (up to 100km offshore and corridors connecting these areas to haul-out sites). More generally, our results illustrate the importance of detailed knowledge of marine predator distributions to inform marine spatial planning; for instance, spatial prioritisation is not necessarily the most effective spatial planning strategy even when conserving species with similar taxonomy.Peer reviewe

    Clinical, radiologic, pathologic, and molecular characteristics of long-term survivors of diffuse intrinsic pontine glioma (DIPG): a collaborative report from the International and European Society for Pediatric Oncology DIPG registries

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    Purpose Diffuse intrinsic pontine glioma (DIPG) is a brainstem malignancy with a median survival of < 1 year. The International and European Society for Pediatric Oncology DIPG Registries collaborated to compare clinical, radiologic, and histomolecular characteristics between short-term survivors (STSs) and long-term survivors (LTSs). Materials and Methods Data abstracted from registry databases included patients from North America, Australia, Germany, Austria, Switzerland, the Netherlands, Italy, France, the United Kingdom, and Croatia. Results Among 1,130 pediatric and young adults with radiographically confirmed DIPG, 122 (11%) were excluded. Of the 1,008 remaining patients, 101 (10%) were LTSs (survival ≥ 2 years). Median survival time was 11 months (interquartile range, 7.5 to 16 months), and 1-, 2-, 3-, 4-, and 5-year survival rates were 42.3% (95% CI, 38.1% to 44.1%), 9.6% (95% CI, 7.8% to 11.3%), 4.3% (95% CI, 3.2% to 5.8%), 3.2% (95% CI, 2.4% to 4.6%), and 2.2% (95% CI, 1.4% to 3.4%), respectively. LTSs, compared with STSs, more commonly presented at age < 3 or > 10 years (11% v 3% and 33% v 23%, respectively; P < .001) and with longer symptom duration ( P < .001). STSs, compared with LTSs, more commonly presented with cranial nerve palsy (83% v 73%, respectively; P = .008), ring enhancement (38% v 23%, respectively; P = .007), necrosis (42% v 26%, respectively; P = .009), and extrapontine extension (92% v 86%, respectively; P = .04). LTSs more commonly received systemic therapy at diagnosis (88% v 75% for STSs; P = .005). Biopsies and autopsies were performed in 299 patients (30%) and 77 patients (10%), respectively; 181 tumors (48%) were molecularly characterized. LTSs were more likely to harbor a HIST1H3B mutation (odds ratio, 1.28; 95% CI, 1.1 to 1.5; P = .002). Conclusion We report clinical, radiologic, and molecular factors that correlate with survival in children and young adults with DIPG, which are important for risk stratification in future clinical trials

    Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

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    Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder
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