| 1. |
|
|
| 2. |
|
|
| 3. |
- Bayley, PJ, et al.
(författare)
-
2013 SYR Accepted Poster Abstracts
- 2013
-
Ingår i: International journal of yoga therapy. - 1531-2054. ; 23:1, s. 32-53
-
Tidskriftsartikel (refereegranskat)
|
|
| 4. |
|
|
| 5. |
- Brennan, D. J., et al.
(författare)
-
The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ER alpha, and is an independent prognostic factor in node-negative breast cancer
- 2012
-
Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 31:30, s. 3483-3494
-
Tidskriftsartikel (refereegranskat)abstract
- Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n = 690; P = 0.002, 0.013). We also show that CART increases the transcriptional activity of ER alpha in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. Oncogene (2012) 31, 3483-3494; doi:10.1038/onc.2011.519; published online 5 December 2011
|
|
| 6. |
- Connolly, Stuart J., et al.
(författare)
-
The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study
- 2013
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:3, s. 237-243
-
Tidskriftsartikel (refereegranskat)abstract
- Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.
|
|
| 7. |
- Amos, Christopher I, et al.
(författare)
-
Genome-wide association study identifies novel loci predisposing to cutaneous melanoma
- 2011
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:24, s. 23-5012
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
|
|
| 8. |
- Ancelle-Park, R., et al.
(författare)
-
Summary of the evidence of breast cancer service screening outcomes in Europe and first estimate of the benefit and harm balance sheet
- 2012
-
Ingår i: Journal of Medical Screening. - : SAGE Publications. - 0969-1413 .- 1475-5793. ; 19, s. 5-13
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives To construct a European 'balance sheet' of key outcomes of population-based mammographic breast cancer screening, to inform policy-makers, stakeholders and invited women. Methods From the studies reviewed, the primary benefit of screening, breast cancer mortality reduction, was compared with the main harms, over-diagnosis and false-positive screening results (FPRs). Results Pooled estimates of breast cancer mortality reduction among invited women were 25% in incidence-based mortality studies and 31% in case-control studies (38% and 48% among women actually screened). Estimates of over-diagnosis ranged from 1% to 10% of the expected incidence in the absence of screening. The combined estimate of over-diagnosis for screened women, from European studies correctly adjusted for lead time and underlying trend, was 6.5%. For women undergoing 10 biennial screening tests, the estimated cumulative risk of a FPR followed by non-invasive assessment was 17%, and 3% having an invasive assessment. For every 1000 women screened biennially from age 50-51 until age 68-69 and followed up to age 79, an estimated seven to nine lives are saved, four cases are over-diagnosed, 170 women have at least one recall followed by non-invasive assessment with a negative result and 30 women have at least one recall followed by invasive procedures yielding a negative result. Conclusions The chance of saving a woman's life by population-based mammographic screening of appropriate quality is greater than that of over-diagnosis. Service screening in Europe achieves a mortality benefit at least as great as the randomized controlled trials. These outcomes should be communicated to women offered service screening in Europe.
|
|
| 9. |
- Barrett, Jennifer H., et al.
(författare)
-
Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
-
Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
|
|
| 10. |
- Byrnes, J. E. K., et al.
(författare)
-
Investigating the relationship between biodiversity and ecosystem multifunctionality: Challenges and solutions
- 2014
-
Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 5:2, s. 111-124
-
Tidskriftsartikel (refereegranskat)abstract
- Summary: Extensive research shows that more species-rich assemblages are generally more productive and efficient in resource use than comparable assemblages with fewer species. But the question of how diversity simultaneously affects the wide variety of ecological functions that ecosystems perform remains relatively understudied. It presents several analytical and empirical challenges that remain unresolved. In particular, researchers have developed several disparate metrics to quantify multifunctionality, each characterizing different aspects of the concept and each with pros and cons. We compare four approaches to characterizing multifunctionality and its dependence on biodiversity, quantifying (i) magnitudes of multiple individual functions separately, (ii) the extent to which different species promote different functions, (iii) the average level of a suite of functions and (iv) the number of functions that simultaneously exceeds a critical threshold. We illustrate each approach using data from the pan-European BIODEPTH experiment and the R multifunc package developed for this purpose, evaluate the strengths and weaknesses of each approach and implement several methodological improvements. We conclude that an extension of the fourth approach that systematically explores all possible threshold values provides the most comprehensive description of multifunctionality to date. We outline this method and recommend its use in future research. © 2013 British Ecological Society.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Hooper, D. U., et al.
(författare)
-
A global synthesis reveals biodiversity loss as a major driver of ecosystem change
- 2012
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 486:7401, s. 105-
-
Tidskriftsartikel (refereegranskat)abstract
- Evidence is mounting that extinctions are altering key processes important to the productivity and sustainability of Earth's ecosystems(1-4). Further species loss will accelerate change in ecosystem processes(5-8), but it is unclear how these effects compare to the direct effects of other forms of environmental change that are both driving diversity loss and altering ecosystem function. Here we use a suite of meta-analyses of published data to show that the effects of species loss on productivity and decomposition-two processes important in all ecosystems-are of comparable magnitude to the effects of many other global environmental changes. In experiments, intermediate levels of species loss (21-40%) reduced plant production by 5-10%, comparable to previously documented effects of ultraviolet radiation and climate warming. Higher levels of extinction (41-60%) had effects rivalling those of ozone, acidification, elevated CO2 and nutrient pollution. At intermediate levels, species loss generally had equal or greater effects on decomposition than did elevated CO2 and nitrogen addition. The identity of species lost also had a large effect on changes in productivity and decomposition, generating a wide range of plausible outcomes for extinction. Despite the need for more studies on interactive effects of diversity loss and environmental changes, our analyses clearly show that the ecosystem consequences of local species loss are as quantitatively significant as the direct effects of several global change stressors that have mobilized major international concern and remediation efforts(9).
|
|
| 14. |
- Kelly, Orla, et al.
(författare)
-
Femtosecond lasers for mass spectrometry : proposed application to catalytic hydrogenation of butadiene.
- 2012
-
Ingår i: The Analyst. - : Royal Society of Chemistry (RSC). - 0003-2654 .- 1364-5528. ; 137:1, s. 64-9
-
Tidskriftsartikel (refereegranskat)abstract
- Mass spectra from the interaction of intense, femtosecond laser pulses with 1,3-butadiene, 1-butene, and n-butane have been obtained. The proportion of the fragment ions produced as a function of intensity, pulse length, and wavelength was investigated. Potential mass spectrometry applications, for example in the analysis of catalytic reaction products, are discussed.
|
|
| 15. |
- MacGregor, Stuart, et al.
(författare)
-
Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1114-1118
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 x 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 x 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.
|
|
| 16. |
- Paci, E., et al.
(författare)
-
European Breast Cancer Service Screening Outcomes : A First Balance Sheet of the Benefits and Harms
- 2014
-
Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 23:7, s. 1159-1163
-
Tidskriftsartikel (refereegranskat)abstract
- A recent comprehensive review has been carried out to quantify the benefits and harms of the European population-based mammographic screening programs. Five literature reviews were conducted on the basis of the observational published studies evaluating breast cancer mortality reduction, breast cancer overdiagnosis, and false-positive results. On the basis of the studies reviewed, the authors present a first estimate of the benefit and harm balance sheet. For every 1,000 women screened biennially from ages 50 to 51 years until ages 68 to 69 years and followed up until age 79 years, an estimated seven to nine breast cancer deaths are avoided, four cases are overdiagnosed, 170 women have at least one recall followed by noninvasive assessment with a negative result, and 30 women have at least one recall followed by invasive procedures yielding a negative result. The chance of a breast cancer death being avoided by population-based mammography screening of appropriate quality is more than that of overdiagnosis by screening. These outcomes should be communicated to women offered service screening in Europe.
|
|
| 17. |
|
|
| 18. |
- Puttabyatappa, M., et al.
(författare)
-
Ovarian Membrane-Type Matrix Metalloproteinases: Induction of MMP14 and MMP16 During the Periovulatory Period in the Rat, Macaque, and Human
- 2014
-
Ingår i: Biology of Reproduction. - : Oxford University Press (OUP). - 0006-3363 .- 1529-7268. ; 91:2
-
Tidskriftsartikel (refereegranskat)abstract
- An intrafollicular increase in proteolytic activity drives ovulatory events. Surprisingly, the periovulatory expression profile of the membrane-type matrix metalloproteinases (MT-MMPs), unique proteases anchored to the cell surface, has not been extensively examined. Expression profiles of the MT-MMPs were investigated in ovarian tissue from well-characterized rat and macaque periovulatory models and naturally cycling women across the periovulatory period. Among the six known MT-MMPs, mRNA expression of Mmp14, Mmp16, and Mmp25 was increased after human chorionic gonadotropin (hCG) administration in rats. In human granulosa cells, mRNA expression of MMP14 and MMP16 increased following hCG treatment. In contrast, mRNA levels of MMP16 and MMP25 in human theca cells were unchanged before ovulation but declined by the postovulatory stage. In macaque granulosa cells, hCG increased mRNA for MMP16 but not MMP14. Immunoblotting showed that protein levels of MMP14 and MMP16 in rats increased, similar to their mRNA expression. In macaque granulosa cells, only the active form of the MMP14 protein increased after hCG, unlike its mRNA or the proprotein. By immunohistochemistry, both MMP14 and MMP16 localized to the different ovarian cell types in rats and humans. Treatment with hCG resulted in intense immunoreactivity of MMP14 and MMP16 proteins in the granulosa and theca cells. The present study shows that MMP14 and MMP16 are increased by hCG administration in the ovulating follicle, demonstrating that these MMPs are conserved among rats, macaques, and humans. These findings suggest that MT-MMPs could have an important role in promoting ovulation and remodeling of the ovulated follicle into the corpus luteum.
|
|
| 19. |
- Ramasamy, Adaikalavan, et al.
(författare)
-
Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
- 2012
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9, s. e44008-
-
Tidskriftsartikel (refereegranskat)abstract
- Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P < 5x10(-8)) and three variants reported as suggestive (P < 5 x 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4x10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
|
|
| 20. |
- Stuart-Smith, Rick D., et al.
(författare)
-
Integrating abundance and functional traits reveals new global hotspots of fish diversity
- 2013
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 539-
-
Tidskriftsartikel (refereegranskat)abstract
- Species richness has dominated our view of global biodiversity patterns for centuries(1,2). The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management(3,4). However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling)(5). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q(6)), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only(7,8). There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness(2,4). Our findings suggest that the contribution of species diversity to a range of ecosystem functions varies over large scales, and imply that in tropical regions, which have higher numbers of species, each species contributes proportionally less to community-level ecological processes on average than species in temperate regions. Metrics of ecological function usefully complement metrics of species diversity in conservation management, including when identifying planning priorities and when tracking changes to biodiversity values.
|
|
