Publications by authors named "I R Bradbury"

149 Publications

Genomic stability through time despite decades of exploitation in cod on both sides of the Atlantic.

Proc Natl Acad Sci U S A 2021 Apr;118(15)

Centre for Ecological and Evolutionary Synthesis, Department of Biosciences, University of Oslo, Blindern, NO-0316 Oslo, Norway;

The mode and extent of rapid evolution and genomic change in response to human harvesting are key conservation issues. Although experiments and models have shown a high potential for both genetic and phenotypic change in response to fishing, empirical examples of genetic responses in wild populations are rare. Here, we compare whole-genome sequence data of Atlantic cod () that were collected before (early 20th century) and after (early 21st century) periods of intensive exploitation and rapid decline in the age of maturation from two geographically distinct populations in Newfoundland, Canada, and the northeast Arctic, Norway. Our temporal, genome-wide analyses of 346,290 loci show no substantial loss of genetic diversity and high effective population sizes. Moreover, we do not find distinct signals of strong selective sweeps anywhere in the genome, although we cannot rule out the possibility of highly polygenic evolution. Our observations suggest that phenotypic change in these populations is not constrained by irreversible loss of genomic variation and thus imply that former traits could be reestablished with demographic recovery.
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http://dx.doi.org/10.1073/pnas.2025453118DOI Listing
April 2021

Chromosome level reference of Atlantic halibut Hippoglossus hippoglossus provides insight into the evolution of sexual determination systems.

Mol Ecol Resour 2021 Mar 2. Epub 2021 Mar 2.

Biology Department, Dalhousie University, Halifax, NS, Canada.

Changes in the genetic mechanisms that control sexual determination have occurred independently across the tree of life, and with exceptional frequency in teleost fishes. To investigate the genomic changes underlying the evolution of sexual determination, we sequenced a chromosome-level genome, multitissue transcriptomes, and reduced representation population data for the Atlantic halibut (Hippoglossus hippoglossus), which has an XY/XX sex determination mechanism and has recently diverged (0.9-3.8 Ma) from the Pacific halibut (Hippoglossus stenolepis), which has a ZZ/ZW system. We used frequency and coverage-based population approaches to identify a putative sex-determining factor, GSDF. We characterized regions with elevated heterozygosity and linkage disequilibrium indicating suppression of recombination across a nascent sex chromosome. We detected testis-specific expression of GSDF, the sequence of which is highly conserved across flatfishes. Based on evidence from genome-wide association, coverage, linkage disequilibrium, testis and brain transcriptomes, and sequence conservation with other flatfishes, we propose a mechanism for the recent evolution of an XY sex-determination mechanism in Atlantic halibut. Changes to the ancestral sex-determining gene DMRT1 in regulating the downstream gene GSDF probably coincided with GSDF, or a proximal regulatory element of it, becoming the primary sex-determining factor. Our results suggest changes to a small number of elements can have drastic repercussions for the genomic substrate available to sex-specific evolutionary forces, providing insight into how certain elements repeatedly evolve to control sex across taxa. Our chromosome-level assembly, multitissue transcriptomes, and population genomic data provide a valuable resource and understanding of the evolution of sexual systems in fishes.
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http://dx.doi.org/10.1111/1755-0998.13369DOI Listing
March 2021

Meta-analyses of visceral versus non-visceral metastatic hormone receptor-positive breast cancer treated by endocrine monotherapies.

NPJ Breast Cancer 2021 Feb 12;7(1):11. Epub 2021 Feb 12.

Biostatistics, Frontier Science, Kincraig, Scotland, UK.

Endocrine therapy (ET) is recommended as first-line therapy for the majority of patients with hormone receptor-positive (HR+), human epidermal growth factor 2-negative advanced breast cancer (ABC); however, the efficacy of ET in patients with visceral metastases (VM) versus patients whose disease is limited to non-visceral metastases (non-VM) is debated. Meta-analyses including available data from randomised controlled trials of first- and second-line endocrine monotherapies for patients with HR+ ABC were performed to address this question. In one and two-stage meta-analyses, progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and duration of clinical benefit (DoCB) outcomes were analysed. In the first-line meta-analysis (seven trials; n = 1988) tamoxifen and fulvestrant significantly improved PFS, OS and CBR for patients with non-VM versus those whose disease included VM. The most substantial hazard ratios were observed for fulvestrant 500 mg; 0.56 (95% confidence interval [CI] 0.45-0.70) and 0.55 (95% CI 0.42-0.72) for PFS and OS, respectively. In the second-line meta-analysis (seven trials; n = 2324), all ET combined was more effective (in terms of PFS, OS and DoCB) for non-VM versus VM. In both meta-analyses, patients with non-liver VM had better clinical outcomes than patients with liver VM for all types of ET. Patients whose disease included non-VM sites had better clinical outcomes with endocrine monotherapy compared with patients whose disease included VM. These findings may facilitate better informed treatment decision-making.
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http://dx.doi.org/10.1038/s41523-021-00222-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881093PMC
February 2021

Meta-analyses of phase 3 randomised controlled trials of third generation aromatase inhibitors versus tamoxifen as first-line endocrine therapy in postmenopausal women with hormone receptor-positive advanced breast cancer.

Eur J Cancer 2021 Mar 7;145:19-28. Epub 2021 Jan 7.

Biostatistics, Frontier Science, Kincraig, Scotland, UK.

Background: Four randomised controlled trials (RCTs) in postmenopausal women with advanced breast cancer (ABC) comparing aromatase inhibitors (AIs) versus the selective estrogen receptor modulator tamoxifen, each individually reported significantly longer progression-free survival (PFS) but none showed a significant difference in overall survival (OS). In these trials between 6.8% and 55% of tumours were hormone receptor (HR) status unknown or negative. This meta-analysis restricted the comparison to HR-positive (HR+) tumours.

Methods: Anonymised individual patient data were obtained from three RCTs, EORTC (exemestane versus tamoxifen), Study 0027 and Study 0030 (both anastrozole versus tamoxifen). For the remaining RCT (Femara Study PO25; letrozole versus tamoxifen), odds ratio (OR) or hazard ratio (HzR), with confidence intervals were obtained from the clinical study report, for patients with HR+ tumours, in addition to published data. In total, data were obtained from 2296 patients; 1560 (68%) had HR+ ABC.

Findings: The OR for clinical benefit rate was 1.56, in favour of AIs (p < 0.001). The duration of clinical benefit was not significantly increased by AIs (HzR 0·88; p = 0.08). For PFS the HzR (0.82) was in favour of AIs (p = 0·007). However, for OS the HzR (1.05) was not significantly different between AIs and tamoxifen (p = 0.42).

Interpretation: Although third generation AIs put significantly more patients into 'clinical benefit', their tumours were not controlled for significantly longer. Overall, while this resulted in a significantly greater PFS in favour of the AIs, this did not translate into improvement in OS.
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http://dx.doi.org/10.1016/j.ejca.2020.11.038DOI Listing
March 2021

Limited genetic parallelism underlies recent, repeated incipient speciation in geographically proximate populations of an Arctic fish (Salvelinus alpinus).

Mol Ecol 2020 11 3;29(22):4280-4294. Epub 2020 Oct 3.

Department of Biology, Dalhousie University, Halifax, NS, Canada.

The genetic underpinnings of incipient speciation, including the genomic mechanisms which contribute to morphological and ecological differentiation and reproductive isolation, remain poorly understood. The repeated evolution of consistently, phenotypically distinct morphs of Arctic Charr (Salvelinus alpinus) within the Quaternary period offer an ideal model to study the repeatability of evolution at the genomic level. Sympatric morphs of Arctic Charr are found across this species' circumpolar distribution. However, the specific genetic mechanisms driving this morph differentiation are largely unknown despite the cultural and economic importance of the anadromous morph. We used a newly designed 87k SNP chip to investigate the character and consistency of the genomic differences among sympatric morphs within three recently deglaciated and geographically proximate lakes in Labrador, Canada. We found genetically distinct small and large morph Arctic Charr in all three lakes consistent with resident and anadromous morphs, respectively. A degree of reproductive isolation among sympatric morphs is likely given genome-wide distributions of outlier SNPs and high genome-wide F s. Across all lakes, outlier SNPs were largely nonoverlapping suggesting a lack of genetic parallelism driving morph differentiation. Alternatively, several genes and paralogous copies of the same gene consistently differentiated morphs across multiple lakes suggesting their importance to the manifestation of morphs. Our results confirm the utility of Arctic Charr as a model for investigating the predictability of evolution and support the importance of both genetic parallelism and nonparallelism to the incipient speciation of Arctic Charr morphs.
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http://dx.doi.org/10.1111/mec.15634DOI Listing
November 2020

Divergent and linked selection shape patterns of genomic differentiation between European and North American Atlantic salmon (Salmo salar).

Mol Ecol 2020 06 21;29(12):2160-2175. Epub 2020 Jun 21.

Fisheries and Oceans Canada, Northwest Atlantic Fisheries Centre, St. John's, NL, Canada.

As populations diverge many processes can shape genomic patterns of differentiation. Regions of high differentiation can arise due to divergent selection acting on selected loci, genetic hitchhiking of nearby loci, or through repeated selection against deleterious alleles (linked background selection); this divergence may then be further elevated in regions of reduced recombination. Atlantic salmon (Salmo salar) from Europe and North America diverged >600,000 years ago and despite some evidence of secondary contact, the majority of genetic data indicate substantial divergence between lineages. This deep divergence with potential gene flow provides an opportunity to investigate the role of different mechanisms that shape the genomic landscape during early speciation. Here, using 184,295 single nucleotide polymorphisms (SNPs) and 80 populations, we investigate the genomic landscape of differentiation across the Atlantic Ocean with a focus on highly differentiated regions and the processes shaping them. We found evidence of high (mean F  = 0.26) and heterogeneous genomic differentiation between continents. Genomic regions associated with high trans-Atlantic differentiation ranged in size from single loci (SNPs) within important genes to large regions (1-3 Mbp) on four chromosomes (Ssa06, Ssa13, Ssa16 and Ssa19). These regions showed signatures consistent with selection, including high linkage disequilibrium, despite no significant reduction in recombination. Genes and functional enrichment of processes associated with differentiated regions may highlight continental differences in ocean navigation and parasite resistance. Our results provide insight into potential mechanisms underlying differences between continents, and evidence of near-fixed and potentially adaptive trans-Atlantic differences concurrent with a background of high genome-wide differentiation supports subspecies designation in Atlantic salmon.
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http://dx.doi.org/10.1111/mec.15480DOI Listing
June 2020

Multiple decades of stocking has resulted in limited hatchery introgression in wild brook trout () populations of Nova Scotia.

Evol Appl 2020 May 20;13(5):1069-1089. Epub 2020 Feb 20.

Marine Gene Probe Lab Biology Department Dalhousie University Halifax NS Canada.

Many populations of freshwater fishes are threatened with losses, and increasingly, the release of hatchery individuals is one strategy being implemented to support wild populations. However, stocking of hatchery individuals may pose long-term threats to wild populations, particularly if genetic interactions occur between wild and hatchery individuals. One highly prized sport fish that has been heavily stocked throughout its range is the brook trout (). In Nova Scotia, Canada, hatchery brook trout have been stocked since the early 1900s, and despite continued stocking efforts, populations have suffered declines in recent decades. Before this study, the genetic structure of brook trout populations in the province was unknown; however, given the potential negative consequences associated with hatchery stocking, it is possible that hatchery programs have adversely affected the genetic integrity of wild populations. To assess the influence of hatchery supplementation on wild populations, we genotyped wild brook trout from 12 river systems and hatchery brook trout from two major hatcheries using 100 microsatellite loci. Genetic analyses of wild trout revealed extensive population genetic structure among and within river systems and significant isolation-by-distance. Hatchery stocks were genetically distinct from wild populations, and most populations showed limited to no evidence of hatchery introgression (<5% hatchery ancestry). Only a single location had a substantial number of hatchery-derived trout and was located in the only river where a local strain is used for supplementation. The amount of hatchery stocking within a watershed did not influence the level of hatchery introgression. Neutral genetic structure of wild populations was influenced by geography with some influence of climate and stocking indices. Overall, our study suggests that long-term stocking has not significantly affected the genetic integrity of wild trout populations, highlighting the variable outcomes of stocking and the need to evaluate the consequences on a case-by-case basis.
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http://dx.doi.org/10.1111/eva.12923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232767PMC
May 2020

Resolving fine-scale population structure and fishery exploitation using sequenced microsatellites in a northern fish.

Evol Appl 2020 May 20;13(5):1055-1068. Epub 2020 Feb 20.

Department of Ocean Sciences Memorial University of Newfoundland St. John's NL Canada.

The resiliency of populations and species to environmental change is dependent on the maintenance of genetic diversity, and as such, quantifying diversity is central to combating ongoing widespread reductions in biodiversity. With the advent of next-generation sequencing, several methods now exist for resolving fine-scale population structure, but the comparative performance of these methods for genetic assignment has rarely been tested. Here, we evaluate the performance of sequenced microsatellites and a single nucleotide polymorphism (SNP) array to resolve fine-scale population structure in a critically important salmonid in north eastern Canada, Arctic Charr (). We also assess the utility of sequenced microsatellites for fisheries applications by quantifying the spatial scales of movement and exploitation through genetic assignment of fishery samples to rivers of origin and comparing these results with a 29-year tagging dataset. Self-assignment and simulation-based analyses of 111 genome-wide microsatellite loci and 500 informative SNPs from 28 populations of Arctic Charr in north-eastern Canada identified largely river-specific genetic structure. Despite large differences (~4X) in the number of loci surveyed between panels, mean self-assignment accuracy was similar with the microsatellite loci and the SNP panel (>90%). Subsequent analysis of 996 fishery-collected samples using the microsatellite panel revealed that larger rivers contribute greater numbers of individuals to the fishery and that coastal fisheries largely exploit individuals originating from nearby rivers, corroborating results from traditional tagging experiments. Our results demonstrate the efficacy of sequence-based microsatellite genotyping to advance understanding of fine-scale population structure and harvest composition in northern and understudied species.
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http://dx.doi.org/10.1111/eva.12922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232759PMC
May 2020

Modular chromosome rearrangements reveal parallel and nonparallel adaptation in a marine fish.

Ecol Evol 2020 Jan 11;10(2):638-653. Epub 2020 Jan 11.

Fisheries and Oceans Canada Northwest Atlantic Fisheries Centre St. John's NL Canada.

Genomic architecture and standing variation can play a key role in ecological adaptation and contribute to the predictability of evolution. In Atlantic cod (), four large chromosomal rearrangements have been associated with ecological gradients and migratory behavior in regional analyses. However, the degree of parallelism, the extent of independent inheritance, and functional distinctiveness of these rearrangements remain poorly understood. Here, we use a 12K single nucleotide polymorphism (SNP) array to demonstrate extensive individual variation in rearrangement genotype within populations across the species range, suggesting that local adaptation to fine-scale ecological variation is enabled by rearrangements with independent inheritance. Our results demonstrate significant association of rearrangements with migration phenotype and environmental gradients across the species range. Individual rearrangements exhibit functional modularity, but also contain loci showing multiple environmental associations. Clustering in genetic distance trees and reduced differentiation within rearrangements across the species range are consistent with shared variation as a source of contemporary adaptive diversity in Atlantic cod. Conversely, we also find that haplotypes in the LG12 and LG1 rearranged region have diverged across the Atlantic, despite consistent environmental associations. Exchange of these structurally variable genomic regions, as well as local selective pressures, has likely facilitated individual diversity within Atlantic cod stocks. Our results highlight the importance of genomic architecture and standing variation in enabling fine-scale adaptation in marine species.
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http://dx.doi.org/10.1002/ece3.5828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988541PMC
January 2020

Assisted standing for Duchenne muscular dystrophy.

Cochrane Database Syst Rev 2019 Oct 13;10:CD011550. Epub 2019 Oct 13.

Centre for Health and Rehabilitation Technologies (CHaRT), Institute of Nursing and Health Research, Ulster University, Room 1F110, Shore Road, Newtownabbey, County Antrim, UK, BT37 OQB.

Background: Duchenne muscular dystrophy (DMD) is the most common X-linked neuromuscular disorder. When boys with DMD reach the second decade of life, they lose their ability to walk and become wheelchair dependent. Standing devices and orthoses are considered to be an essential component in the therapy management of DMD. Clinical opinion and research from other neurological conditions highlight the proposed benefits of standing device use, however, its effect within this population is currently unknown. A review of the evidence for the use of standing devices and orthoses is necessary to inform all stakeholders, including people with DMD, clinicians, decision makers and funders, and to guide future research.

Objectives: To assess the effects of standing devices and orthoses on musculoskeletal impairments (such as pain, contracture, scoliosis development and bone density) in boys and men with DMD, and secondarily to determine their effect on quality of life, participation in activities, and patient experience (satisfaction). We also considered any adverse events associated with their use.

Search Methods: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, AMED, PsycINFO, CINAHL Plus, PEDro, and ProQuest Dissertations & Theses Global up to 5 September 2019. We checked references in identified trials, handsearched journal abstracts, and searched trials registries.

Selection Criteria: We planned to include randomised controlled trials (RCTs) and quasi-RCTs of any model of standing device for use in DMD. The control interventions would have been any other comparison group, including no standing device, a different model of standing device, usual care, or an alternative form of assistive weight bearing.

Data Collection And Analysis: We used standard Cochrane methodological procedures.

Main Results: Although we identified 13 potentially relevant studies, none met the inclusion criteria for this review.

Authors' Conclusions: Since there were no RCTs or quasi-RCTs available to evaluate the effectiveness of standing devices in people with DMD, studies are needed to investigate the effectiveness of standing devices in this population.
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http://dx.doi.org/10.1002/14651858.CD011550.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6790222PMC
October 2019

Genomic signatures and correlates of widespread population declines in salmon.

Nat Commun 2019 07 5;10(1):2996. Epub 2019 Jul 5.

Fisheries and Oceans Canada, Northwest Atlantic Fisheries Centre, 80 E White Hills Rd, St. John's, Newfoundland, A1C 5X1, Canada.

Global losses of biodiversity are occurring at an unprecedented rate, but causes are often unidentified. Genomic data provide an opportunity to isolate drivers of change and even predict future vulnerabilities. Atlantic salmon (Salmo salar) populations have declined range-wide, but factors responsible are poorly understood. Here, we reconstruct changes in effective population size (N) in recent decades for 172 range-wide populations using a linkage-based method. Across the North Atlantic, N has significantly declined in >60% of populations and declines are consistently temperature-associated. We identify significant polygenic associations with decline, involving genomic regions related to metabolic, developmental, and physiological processes. These regions exhibit changes in presumably adaptive diversity in declining populations consistent with contemporary shifts in body size and phenology. Genomic signatures of widespread population decline and associated risk scores allow direct and potentially predictive links between population fitness and genotype, highlighting the power of genomic resources to assess population vulnerability.
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http://dx.doi.org/10.1038/s41467-019-10972-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611788PMC
July 2019

A migration-associated supergene reveals loss of biocomplexity in Atlantic cod.

Sci Adv 2019 06 26;5(6):eaav2461. Epub 2019 Jun 26.

Fisheries and Oceans Canada, Northwest Atlantic Fisheries Centre, St. John's, Newfoundland, Canada.

Chromosome structural variation may underpin ecologically important intraspecific diversity by reducing recombination within supergenes containing linked, coadapted alleles. Here, we confirm that an ancient chromosomal rearrangement is strongly associated with migratory phenotype and individual genetic structure in Atlantic cod () across the Northwest Atlantic. We reconstruct trends in effective population size over the last century and reveal declines in effective population size matching onset of industrialized harvest (after 1950). We find different demographic trajectories between individuals homozygous for the chromosomal rearrangement relative to heterozygous or homozygous individuals for the noninverted haplotype, suggesting different selective histories across the past 150 years. These results illustrate how chromosomal structural diversity can mediate fine-scale genetic, phenotypic, and demographic variation in a highly connected marine species and show how overfishing may have led to loss of biocomplexity within Northern cod stock.
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http://dx.doi.org/10.1126/sciadv.aav2461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594766PMC
June 2019

Are we assuming too much with our statistical assumptions? Lessons learned from the ALTTO trial.

Ann Oncol 2019 09;30(9):1507-1513

Department of Data Sciences, Dana-Farber Cancer Institute, Harvard Medical School, Harvard T.H. Chan School of Public Health, Frontier Science and Technology Research Foundation, Boston, USA. Electronic address:

Background: Design, conduct, and analysis of randomized clinical trials (RCTs) with time to event end points rely on a variety of assumptions regarding event rates (hazard rates), proportionality of treatment effects (proportional hazards), and differences in intensity and type of events over time and between subgroups.

Design And Methods: In this article, we use the experience of the recently reported Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) RCT, which enrolled 8381 patients with human epidermal growth factor 2-positive early breast cancer between June 2007 and July 2011, to highlight how routinely applied statistical assumptions can impact RCT result reporting.

Results And Conclusions: We conclude that (i) futility stopping rules are important to protect patient safety, but stopping early for efficacy can be misleading as short-term results may not imply long-term efficacy, (ii) biologically important differences between subgroups may drive clinically different treatment effects and should be taken into account, e.g. by pre-specifying primary subgroup analyses and restricting end points to events which are known to be affected by the targeted therapies, (iii) the usual focus on the Cox model may be misleading if we do not carefully consider non-proportionality of the hazards. The results of the accelerated failure time model illustrate that giving more weight to later events (as in the log rank test) can affect conclusions, (iv) the assumption that accruing additional events will always ensure gain in power needs to be challenged. Changes in hazard rates and hazard ratios over time should be considered, and (v) required family-wise control of type 1 error ≤ 5% in clinical trials with multiple experimental arms discourages investigations designed to answer more than one question.

Trial Registration: clinicaltrials.gov Identifier NCT00490139.
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http://dx.doi.org/10.1093/annonc/mdz195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931237PMC
September 2019

A meta-analysis of clinical benefit rates for fulvestrant 500 mg vs. alternative endocrine therapies for hormone receptor-positive advanced breast cancer.

Breast Cancer 2019 Nov 11;26(6):703-711. Epub 2019 May 11.

Frontier Science, Grampian View, Kincraig, Kingussie, PH21 1NA, UK.

Background: Fulvestrant, a selective estrogen receptor degrader, is approved for first- and second-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer (ABC).

Methods: Meta-analysis of randomized controlled trials (RCTs) evaluating fulvestrant 500 mg in postmenopausal hormone receptor-positive ABC, to evaluate differences in clinical benefit rate (CBR; proportion of patients experiencing best overall response of complete response, partial response, or stable disease for ≥ 24 weeks) between fulvestrant 500 mg and comparator endocrine therapies. Odds ratios (OR) and 95% confidence intervals (CI) for CBR were calculated; fixed effects (FE) models were constructed (first- and second-line data, alone and combined).

Results: Six RCTs were included. Four studies evaluated fulvestrant 500 mg vs. fulvestrant 250 mg; two evaluated fulvestrant 500 mg vs. anastrozole 1 mg. In total, 1054 and 534 patients were included (first- and second-line treatment, respectively). Analysis of OR and 95% CI of CBR by therapy line favored fulvestrant 500 mg vs. comparator therapy. Assessing all results combined in the FE model indicated significant improvement in CBR with fulvestrant 500 mg vs. comparator treatments (OR 1.33; 95% CI 1.13-1.57; p = 0.001). Restricting the FE model to therapy line demonstrated significant improvement in CBR vs. comparator treatments (OR 1.33; 95% CI 1.02-1.73; p = 0.035) for first-line, and a trend to improvement vs. comparator treatments (OR 1.27; 95% CI 0.90-1.79; p = 0.174) for second-line.

Conclusions: In postmenopausal patients with hormone receptor-positive ABC, fulvestrant 500 mg first-line was associated with significantly greater CBR (more patients benefiting from treatment) vs. comparator endocrine therapy.
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http://dx.doi.org/10.1007/s12282-019-00973-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821663PMC
November 2019

Estimating the relative fitness of escaped farmed salmon offspring in the wild and modelling the consequences of invasion for wild populations.

Evol Appl 2019 Apr 28;12(4):705-717. Epub 2019 Jan 28.

Science Branch, Fisheries and Oceans Canada St. John's Newfoundland and Labrador Canada.

Throughout their native range, wild Atlantic salmon populations are threatened by hybridization and introgression with escapees from net-pen salmon aquaculture. Although domestic-wild hybrid offspring have shown reduced fitness in laboratory and field experiments, consequential impacts on population abundance and genetic integrity remain difficult to predict in the field, in part because the strength of selection against domestic offspring is often unknown and context-dependent. Here, we follow a single large escape event of farmed Atlantic salmon in southern Newfoundland and monitor changes in the in-river proportions of hybrids and feral individuals over time using genetically based hybrid identification. Over a three-year period following the escape, the overall proportion of wild parr increased consistently (total wild proportion of 71.6%, 75.1% and 87.5% each year, respectively), with subsequent declines in feral (genetically pure farmed individuals originating from escaped, farmed adults) and hybrid parr. We quantify the strength of selection against parr of aquaculture ancestry and explore the genetic and demographic consequences for populations in the region. Within-cohort changes in the relative proportions of feral and F1 parr suggest reduced relative survival compared to wild individuals over the first (0.15 and 0.81 for feral and F1, respectively) and second years of life (0.26, 0.83). These relative survivorship estimates were used to inform an individual-based salmon eco-genetic model to project changes in adult abundance and overall allele frequency across three invasion scenarios ranging from short-term to long-term invasion and three relative survival scenarios. Modelling results indicate that total population abundance and time to recovery were greatly affected by relative survivorship and predict significant declines in wild population abundance under continued large escape events and calculated survivorship. Overall, this work demonstrates the importance of estimating the strength of selection against domestic offspring in the wild to predict the long-term impact of farmed salmon escape events on wild populations.
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http://dx.doi.org/10.1111/eva.12746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6439497PMC
April 2019

Chromosome polymorphisms track trans-Atlantic divergence and secondary contact in Atlantic salmon.

Mol Ecol 2019 04 29;28(8):2074-2087. Epub 2019 Apr 29.

Fisheries and Oceans Canada, Northwest Atlantic Fisheries Centre, St. John's, Newfoundland, Canada.

Pleistocene glaciations drove repeated range contractions and expansions shaping contemporary intraspecific diversity. Atlantic salmon (Salmo salar) in the western and eastern Atlantic diverged >600,000 years before present, with the two lineages isolated in different southern refugia during glacial maxima, driving trans-Atlantic genomic and karyotypic divergence. Here, we investigate the genomic consequences of glacial isolation and trans-Atlantic secondary contact using 108,870 single nucleotide polymorphisms genotyped in 80 North American and European populations. Throughout North America, we identified extensive interindividual variation and discrete linkage blocks within and between chromosomes with known trans-Atlantic differences in rearrangements: Ssa01/Ssa23 translocation and Ssa08/Ssa29 fusion. Spatial genetic analyses suggest independence of rearrangements, with Ssa01/Ssa23 showing high European introgression (>50%) in northern populations indicative of post-glacial trans-Atlantic secondary contact, contrasting with low European ancestry genome-wide (3%). Ssa08/Ssa29 showed greater intrapopulation diversity, suggesting a derived chromosome fusion polymorphism that evolved within North America. Evidence of potential selection on both genomic regions suggests that the adaptive role of rearrangements warrants further investigation in Atlantic salmon. Our study highlights how Pleistocene glaciations can influence large-scale intraspecific variation in genomic architecture of northern species.
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http://dx.doi.org/10.1111/mec.15065DOI Listing
April 2019

Disentangling structural genomic and behavioural barriers in a sea of connectivity.

Mol Ecol 2019 03 15;28(6):1394-1411. Epub 2019 Mar 15.

Centre for Ecological and Evolutionary Synthesis (CEES), Department of Biosciences, University of Oslo, Oslo, Norway.

Genetic divergence among populations arises through natural selection or drift and is counteracted by connectivity and gene flow. In sympatric populations, isolating mechanisms are thus needed to limit the homogenizing effects of gene flow to allow for adaptation and speciation. Chromosomal inversions act as an important mechanism maintaining isolating barriers, yet their role in sympatric populations and divergence with gene flow is not entirely understood. Here, we revisit the question of whether inversions play a role in the divergence of connected populations of the marine fish Atlantic cod (Gadus morhua), by exploring a unique data set combining whole-genome sequencing data and behavioural data obtained with acoustic telemetry. Within a confined fjord environment, we find three genetically differentiated Atlantic cod types belonging to the oceanic North Sea population, the western Baltic population and a local fjord-type cod. Continuous behavioural tracking over 4 year revealed temporally stable sympatry of these types within the fjord. Despite overall weak genetic differentiation consistent with high levels of gene flow, we detected significant frequency shifts of three previously identified inversions, indicating an adaptive barrier to gene flow. In addition, behavioural data indicated that North Sea cod and individuals homozygous for the LG12 inversion had lower fitness in the fjord environment. However, North Sea and fjord-type cod also occupy different depths, possibly contributing to prezygotic reproductive isolation and representing a behavioural barrier to gene flow. Our results provide the first insights into a complex interplay of genomic and behavioural isolating barriers in Atlantic cod and establish a new model system towards an understanding of the role of genomic structural variants in adaptation and diversification.
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http://dx.doi.org/10.1111/mec.15010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518941PMC
March 2019

Range-wide genomic data synthesis reveals transatlantic vicariance and secondary contact in Atlantic cod.

Ecol Evol 2018 Dec 16;8(23):12140-12152. Epub 2018 Nov 16.

School of Biological Sciences Bangor University Bangor UK.

Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic cod (), existing range-wide examinations suggest significant transatlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transatlantic phylogeography in Atlantic cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transatlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transatlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.
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http://dx.doi.org/10.1002/ece3.4672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303715PMC
December 2018

Demographic and genetic description of Greenland's only indigenous Atlantic salmon Salmo salar population.

J Fish Biol 2019 Jan 7;94(1):154-164. Epub 2019 Jan 7.

Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway.

A survey of the Kapisillit River system was conducted in 2005 and 2012 to study the only indigenous Atlantic salmon Salmo salar population in Greenland. Little is known about its characteristics or its relationship with other S. salar populations across the species range. Juvenile S. salar were captured in all stations surveyed within the lower river with the highest densities lower in the river and decreasing densities with increasing distance from the river mouth. Captured juveniles ranged from 0+ to 7+ years old and the predominant smolt age was between 4 and 6 years. Median length of 0+ and 1+ juveniles in August-September was 38.8 and 70.4 mm, respectively. The proportion of mature male parr increased from 4% for 1+ year old fish to 95% for fish greater than 2 years old. Genetic analysis using 96 single nucleotide polymorphisms (SNP) revealed a high degree of genetic similarity between collections, extremely low genetic diversity and low estimates of effective population size (N = 28.7; 95% CI = 19.7-42.4). Genetic comparison to range-wide S. salar populations demonstrated that the Kapisillit River S. salar is an outgroup of the eastern Atlantic stock complex, which is consistent with the hypothesised colonisation from the east. River morphology and the absence of glacier runoff are hypothesised to be the main reasons for the relatively high river temperatures supporting this self-sustaining population of S. salar. Given its uniqueness and persistence, this population represents an important part of range-wide biodiversity of S. salar.
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http://dx.doi.org/10.1111/jfb.13887DOI Listing
January 2019

Quality control for multiple breath washout tests in multicentre bronchiectasis studies: Experiences from the BRONCH-UK clinimetrics study.

Respir Med 2018 12 1;145:206-211. Epub 2018 Nov 1.

The Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, UK.

Introduction: Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or "over-reading" is resource intensive and the impact is unclear.

Objectives: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading.

Methods: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared.

Results: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity.

Conclusion: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW.
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http://dx.doi.org/10.1016/j.rmed.2018.10.030DOI Listing
December 2018

Temporal dynamics of genetic clines of invasive European green crab () in eastern North America.

Evol Appl 2018 Oct 28;11(9):1656-1670. Epub 2018 Jun 28.

Northwest Atlantic Fisheries Centre Fisheries and Oceans Canada St. John's Newfoundland Canada.

Two genetically distinct lineages of European green crabs () were independently introduced to eastern North America, the first in the early 19th century and the second in the late 20th century. These lineages first came into secondary contact in southeastern Nova Scotia, Canada (NS), where they hybridized, producing latitudinal genetic clines. Previous studies have documented a persistent southward shift in the clines of different marker types, consistent with existing dispersal and recruitment pathways. We evaluated current clinal structure by quantifying the distribution of lineages and fine-scale hybridization patterns across the eastern North American range (25 locations, ~39 to 49°N) using informative single nucleotide polymorphisms (SNPs;  = 96). In addition, temporal changes in the genetic clines were evaluated using mitochondrial DNA and microsatellite loci ( = 9-11) over a 15-year period (2000-2015). Clinal structure was consistent with prior work demonstrating the existence of both northern and southern lineages with a hybrid zone occurring between southern New Brunswick (NB) and southern NS. Extensive later generation hybrids were detected in this region and in southeastern Newfoundland. Temporal genetic analysis confirmed the southward progression of clines over time; however, the rate of this progression was slower than predicted by forecasting models, and current clines for all marker types deviated significantly from these predictions. Our results suggest that neutral and selective processes contribute to cline dynamics, and ultimately, highlight how selection, hybridization, and dispersal can collectively influence invasion success.
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http://dx.doi.org/10.1111/eva.12657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6183463PMC
October 2018

GPs and spiritual care: signed up or souled out? A quantitative analysis of GP trainers' understanding and application of the concept of spirituality.

Educ Prim Care 2018 11 19;29(6):367-375. Epub 2018 Oct 19.

d Centre for Rural Health, Institute for Applied Health Sciences , University of Aberdeen , Aberdeen , Scotland.

GPs have a wide range of attitudes to spirituality which contribute to variations in reported spiritual care. Study aims were: to assess concepts of spirituality and their application in a sample of GP trainers; explore statistically the relationship between personal spiritual affiliation, attitudes to, and reported practice of, spiritual care and; to examine whether GP trainers consider training in spiritual care to be adequate. Questionnaire involving 87 GP trainers using Likert scale responses and multinomial trend tests to analyse the relationships between 'concept of spirituality' and attitude to, or practice of, spiritual care. Cluster and latent class analysis to investigate whether groups of GPs are categorically different. Results were GPs largely considered spirituality to be a meaningful, useful, but unclear concept. 8% did not wish involvement in spiritual care, 27.6% had reservations, 46% were pragmatically willing and 12.6% expressed keenness. 35.6% reported they tend not to discuss spiritual matters. Latent class analysis suggests two groups exist: two thirds being pragmatic supporters of spiritual care and one third are tentative sceptics. GPs vary widely in their attitude to, and practice of spiritual care. Only 10.3% reported receiving adequate training in spiritual care.
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http://dx.doi.org/10.1080/14739879.2018.1531271DOI Listing
November 2018

RADProc: A computationally efficient de novo locus assembler for population studies using RADseq data.

Mol Ecol Resour 2019 Jan 21;19(1):272-282. Epub 2018 Dec 21.

Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.

Restriction site-associated DNA sequencing (RADseq) is a powerful tool for genotyping of individuals, but the identification of loci and assignment of sequence reads is a crucial and often challenging step. The optimal parameter settings for a given de novo RADseq assembly vary between data sets and can be difficult and computationally expensive to determine. Here, we introduce RADProc, a software package that uses a graph data structure to represent all sequence reads and their similarity relationships. Storing sequence-comparison results in a graph eliminates unnecessary and redundant sequence similarity calculations. De novo locus formation for a given parameter set can be performed on the precomputed graph, making parameter sweeps far more efficient. RADProc also uses a clustering approach for faster nucleotide-distance calculation. The performance of RADProc compares favourably with that of the widely used Stacks software. The run-time comparisons between RADProc and Stacks for 32 different parameter settings using 20 green-crab (Carcinus maenas) samples showed that RADProc took as little as 2 hr 40 min compared to 78 hr by Stacks, while 16 brown trout (Salmo trutta L.) samples were processed by RADProc and Stacks in 23 and 263 hr, respectively. Comparisons of the de novo loci formed, and catalog built using both the methods demonstrate that the improvement in processing speeds achieved by RADProc does not affect much the actual loci formed and the results of downstream analyses based on those loci.
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http://dx.doi.org/10.1111/1755-0998.12954DOI Listing
January 2019

Extensive hybridization following a large escape of domesticated Atlantic salmon in the Northwest Atlantic.

Commun Biol 2018 9;1:108. Epub 2018 Aug 9.

Science Branch, Fisheries and Oceans Canada, 80 East White Hills Road, St. John's, Newfoundland, A1C 5X1, Canada.

Domestication is rife with episodes of interbreeding between cultured and wild populations, potentially challenging adaptive variation in the wild. In Atlantic salmon, , the number of domesticated individuals far exceeds wild individuals, and escape events occur regularly, yet evidence of the magnitude and geographic scale of interbreeding resulting from individual escape events is lacking. We screened juvenile Atlantic salmon using 95 single nucleotide polymorphisms following a single, large aquaculture escape in the Northwest Atlantic and report the landscape-scale detection of hybrid and feral salmon (27.1%, 17/18 rivers). Hybrids were reproductively viable, and observed at higher frequency in smaller wild populations. Repeated annual sampling of this cohort revealed decreases in the presence of hybrid and feral offspring over time. These results link previous observations of escaped salmon in rivers with reports of population genetic change, and demonstrate the potential negative consequences of escapes from net-pen aquaculture on wild populations.
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http://dx.doi.org/10.1038/s42003-018-0112-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6123692PMC
August 2018

Clinician-Facilitated Physical Activity Intervention Versus Pulmonary Rehabilitation for Improving Physical Activity in COPD: A Feasibility Study.

COPD 2018 06 5;15(3):254-264. Epub 2018 Sep 5.

i Centre for Experimental Medicine, School of Medicine, Dentistry & Biomedical Sciences , Queens University Belfast , Belfast , UK.

Pulmonary rehabilitation (PR) may not suit all individuals with chronic obstructive pulmonary disease (COPD) and may not result in increased physical activity. Higher levels of physical activity are associated with reduced mortality and morbidity. The aim of this study was to assess the feasibility of conducting a trial to investigate the effectiveness of a clinician-facilitated physical activity intervention (PAI) versus PR in improving physical activity in patients with COPD referred to PR. In this randomised controlled mixed methods feasibility study, all patients referred to PR who were eligible and willing were assessed at baseline and then randomised to the PAI or to PR. The assessments were repeated post-intervention and at 3-month follow-up. The main outcome was step count measured by Actigraph. Semi-structured interviews were conducted post-intervention. The N = 50 patients; mean (SD) age, 64.1(8.6) years, 24M were recruited and randomised; N = 23 (PAI) and n = 26 (PR): one patient was excluded from the analysis as that person did not meet the GOLD diagnostic criteria. Key feasibility criteria were met; recruitment was 11%, dropouts in PAI were 26% (n = 6) and 50% (n = 13/26) PR. Participants in both groups experienced a range of health benefits from their respective programmes. The PAI appears to be effective in increasing step counts in people with COPD: mean change (standard deviation) [confidence interval] for the PAI group was 972.0(3230.3)[-1080.3 to 3024.4], n = 12 and 4.3(662.7)[-440.9 to 449.5], n = 11 for the PR group. The PAI met all domains of fidelity. This study provides key information to inform a future-randomised controlled trial in physical activity.
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http://dx.doi.org/10.1080/15412555.2018.1486396DOI Listing
June 2018

Environmental extremes drive population structure at the northern range limit of Atlantic salmon in North America.

Mol Ecol 2018 10 17;27(20):4026-4040. Epub 2018 Sep 17.

Science Branch, Department of Fisheries and Oceans Canada, St. John's, NL, Canada.

Conservation of exploited species requires an understanding of both genetic diversity and the dominant structuring forces, particularly near range limits, where climatic variation can drive rapid expansions or contractions of geographic range. Here, we examine population structure and landscape associations in Atlantic salmon (Salmo salar) across a heterogeneous landscape near the northern range limit in Labrador, Canada. Analysis of two amplicon-based data sets containing 101 microsatellites and 376 single nucleotide polymorphisms (SNPs) from 35 locations revealed clear differentiation between populations spawning in rivers flowing into a large marine embayment (Lake Melville) compared to coastal populations. The mechanisms influencing the differentiation of embayment populations were investigated using both multivariate and machine-learning landscape genetic approaches. We identified temperature as the strongest correlate with genetic structure, particularly warm temperature extremes and wider annual temperature ranges. The genomic basis of this divergence was further explored using a subset of locations (n = 17) and a 220K SNP array. SNPs associated with spatial structuring and temperature mapped to a diverse set of genes and molecular pathways, including regulation of gene expression, immune response, and cell development and differentiation. The results spanning molecular marker types and both novel and established methods clearly show climate-associated, fine-scale population structure across an environmental gradient in Atlantic salmon near its range limit in North America, highlighting valuable approaches for predicting population responses to climate change and managing species sustainability.
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http://dx.doi.org/10.1111/mec.14849DOI Listing
October 2018

PMERGE: Computational filtering of paralogous sequences from RAD-seq data.

Ecol Evol 2018 Jul 11;8(14):7002-7013. Epub 2018 Jun 11.

Faculty of Computer Science Dalhousie University Halifax NS Canada.

Restriction-site associated DNA sequencing (RAD-seq) can identify and score thousands of genetic markers from a group of samples for population-genetics studies. One challenge of de novo RAD-seq analysis is to distinguish paralogous sequence variants (PSVs) from true single-nucleotide polymorphisms (SNPs) associated with orthologous loci. In the absence of a reference genome, it is difficult to differentiate true SNPs from PSVs, and their impact on downstream analysis remains unclear. Here, we introduce a network-based approach, PMERGE that connects fragments based on their DNA sequence similarity to identify probable PSVs. Applying our method to de novo RAD-seq data from 150 Atlantic salmon () samples collected from 15 locations across the Southern Newfoundland coast allowed the identification of 87% of total PSVs identified through alignment to the Atlantic salmon genome. Removal of these paralogs altered the inferred population structure, highlighting the potential impact of filtering in RAD-seq analysis. PMERGE is also applied to a green crab () data set consisting of 242 samples from 11 different locations and was successfully able to identify and remove the majority of paralogous loci (62%). The PMERGE software can be run as part of the widely used Stacks analysis package.
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http://dx.doi.org/10.1002/ece3.4219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065343PMC
July 2018

Genotyping-by-sequencing of genome-wide microsatellite loci reveals fine-scale harvest composition in a coastal Atlantic salmon fishery.

Evol Appl 2018 Jul 11;11(6):918-930. Epub 2018 Mar 11.

Department of Biology Dalhousie University Halifax NS Canada.

Individual assignment and genetic mixture analysis are commonly utilized in contemporary wildlife and fisheries management. Although microsatellite loci provide unparalleled numbers of alleles per locus, their use in assignment applications is increasingly limited. However, next-generation sequencing, in conjunction with novel bioinformatic tools, allows large numbers of microsatellite loci to be simultaneously genotyped, presenting new opportunities for individual assignment and genetic mixture analysis. Here, we scanned the published Atlantic salmon genome to identify 706 microsatellite loci, from which we developed a final panel of 101 microsatellites distributed across the genome (average 3.4 loci per chromosome). Using samples from 35 Atlantic salmon populations ( = 1,485 individuals) from coastal Labrador, Canada, a region characterized by low levels of differentiation in this species, this panel identified 844 alleles (average of 8.4 alleles per locus). Simulation-based evaluations of assignment and mixture identification accuracy revealed unprecedented resolution, clearly identifying 26 rivers or groups of rivers spanning 500 km of coastline. This baseline was used to examine the stock composition of 696 individuals harvested in the Labrador Atlantic salmon fishery and revealed that coastal fisheries largely targeted regional groups (<300 km). This work suggests that the development and application of large sequenced microsatellite panels presents great potential for stock resolution in Atlantic salmon and more broadly in other exploited anadromous and marine species.
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http://dx.doi.org/10.1111/eva.12606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999200PMC
July 2018

Genomewide evidence of environmentally mediated secondary contact of European green crab () lineages in eastern North America.

Evol Appl 2018 Jul 23;11(6):869-882. Epub 2018 Feb 23.

Fisheries and Oceans Canada Bedford Institute of Oceanography Dartmouth NS Canada.

Genetic-environment associations are increasingly revealed through population genomic data and can occur through a number of processes, including secondary contact, divergent natural selection, or isolation by distance. Here, we investigate the influence of the environment, including seasonal temperature and salinity, on the population structure of the invasive European green crab () in eastern North America. Green crab populations in eastern North America are associated with two independent invasions, previously shown to consist of distinct northern and southern ecotypes, with a contact zone in southern Nova Scotia, Canada. Using a RAD-seq panel of 9,137 genomewide SNPs, we detected 41 SNPs (0.49%) whose allele frequencies were highly correlated with environmental data. A principal components analysis of 25 environmental variables differentiated populations into northern, southern, and admixed sites in concordance with the observed genomic spatial structure. Furthermore, a spatial principal components analysis conducted on genomic and geographic data revealed a high degree of global structure ( < .0001) partitioning a northern and southern ecotype. Redundancy and partial redundancy analyses revealed that among the environmental variables tested, winter sea surface temperature had the strongest association with spatial structuring, suggesting that it is an important factor defining range and expansion limits of each ecotype. Understanding environmental thresholds associated with intraspecific diversity will facilitate the ability to manage current and predict future distributions of this aquatic invasive species.
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http://dx.doi.org/10.1111/eva.12601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999199PMC
July 2018

Education of healthcare professionals for preventing pressure ulcers.

Cochrane Database Syst Rev 2018 05 25;5:CD011620. Epub 2018 May 25.

School of Health Sciences, University of Ulster, Shore Road, Newtownabbey, Belfast, Co Antrim, UK, BT37 0QB.

Background: Pressure ulcers, also known as bed sores or pressure sores, are localised areas of tissue damage arising due to excess pressure and shearing forces. Education of healthcare staff has been recognised as an integral component of pressure ulcer prevention. These educational programmes are directed towards influencing behaviour change on the part of the healthcare professional, to encourage preventative practices with the aim of reducing the incidence of pressure ulcer development.

Objectives: To assess the effects of educational interventions for healthcare professionals on pressure ulcer prevention.

Search Methods: In June 2017 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting.

Selection Criteria: We included randomised controlled trials (RCTs) and cluster-RCTs, that evaluated the effect of any educational intervention delivered to healthcare staff in any setting to prevent pressure ulceration.

Data Collection And Analysis: Two review authors independently assessed titles and abstracts of the studies identified by the search strategy for eligibility. We obtained full versions of potentially relevant studies and two authors independently screened these against the inclusion criteria.

Main Results: We identified five studies that met the inclusion criteria for this review: four RCTs and one cluster-RCT. The study characteristics differed in terms of healthcare settings, the nature of the interventions studied and outcome measures reported. The cluster-RCT, and two of the RCTs, explored the effectiveness of education delivered to healthcare staff within residential or nursing home settings, or nursing home and hospital wards, compared to no intervention, or usual practices. Educational intervention in one of these studies was embedded within a broader, quality improvement bundle. The other two individually randomised controlled trials explored the effectiveness of educational intervention, delivered in two formats, to nursing staff cohorts.Due to the heterogeneity of the studies identified, pooling was not appropriate and we have presented a narrative overview. We explored a number of comparisons (1) education versus no education (2) components of educational intervention in a number of combinations and (3) education delivered in different formats. There were three primary outcomes: change in healthcare professionals' knowledge, change in healthcare professionals' clinical behaviour and incidence of new pressure ulcers.We are uncertain whether there is a difference in health professionals' knowledge depending on whether they receive education or no education on pressure ulcer prevention (hospital group: mean difference (MD) 0.30, 95% confidence interval (CI) -1.00 to 1.60; 10 participants; nursing home group: MD 0.30, 95% CI -0.77 to 1.37; 10 participants). This was based on very low-certainty evidence from one study, which we downgraded for serious study limitations, indirectness and imprecision.We are uncertain whether there is a difference in pressure ulcer incidence with the following comparisons: training, monitoring and observation, versus monitoring and observation (risk ratio (RR) 0.63, 95% CI 0.37 to 1.05; 345 participants); training, monitoring and observation, versus observation alone (RR 1.21, 95% CI 0.60 to 2.43; 325 participants) or, monitoring and observation versus observation alone (RR 1.93, 95% CI 0.96 to 3.88; 232 participants). This was based on very low-certainty evidence from one study, which we downgraded for very serious study limitations and imprecision. We are uncertain whether multilevel intervention versus attention control makes any difference to pressure ulcer incidence. The report presented insufficient data to enable further interrogation of this outcome.We are uncertain whether education delivered in different formats such as didactic education versus video-based education (MD 4.60, 95% CI 3.08 to 6.12; 102 participants) or e-learning versus classroom education (RR 0.92, 95% CI 0.80 to 1.07; 18 participants), makes any difference to health professionals' knowledge of pressure ulcer prevention. This was based on very low-certainty evidence from two studies, which we downgraded for serious study limitations and study imprecision.None of the included studies explored our other primary outcome: change in health professionals' clinical behaviour. Only one study explored the secondary outcomes of interest, namely, pressure ulcer severity and patient and carer reported outcomes (self-assessed quality of life and functional dependency level respectively). However, this study provided insufficient information to enable our independent assessment of these outcomes within the review.

Authors' Conclusions: We are uncertain whether educating healthcare professionals about pressure ulcer prevention makes any difference to pressure ulcer incidence, or to nurses' knowledge of pressure ulcer prevention. This is because the included studies provided very low-certainty evidence. Therefore, further information is required to clarify the impact of education of healthcare professionals on the prevention of pressure ulcers.
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http://dx.doi.org/10.1002/14651858.CD011620.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494581PMC
May 2018