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481.
  • Traylor, Matthew, et al. (författare)
  • A Novel MMP12 Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach.
  • 2014
  • Ingår i: PLoS Genetics. - Public Library of Science. - 1553-7404. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have begun to identify the common genetic component to ischaemic stroke (IS). However, IS has considerable phenotypic heterogeneity. Where clinical covariates explain a large fraction of disease risk, covariate informed designs can increase power to detect associations. As prevalence rates in IS are markedly affected by age, and younger onset cases may have higher genetic predisposition, we investigated whether an age-at-onset informed approach could detect novel associations with IS and its subtypes; cardioembolic (CE), large artery atherosclerosis (LAA) and small vessel disease (SVD) in 6,778 cases of European ancestry and 12,095 ancestry-matched controls. Regression analysis to identify SNP associations was performed on posterior liabilities after conditioning on age-at-onset and affection status. We sought further evidence of an association with LAA in 1,881 cases and 50,817 controls, and examined mRNA expression levels of the nearby genes in atherosclerotic carotid artery plaques. Secondly, we performed permutation analyses to evaluate the extent to which age-at-onset informed analysis improves significance for novel loci. We identified a novel association with an MMP12 locus in LAA (rs660599; p = 2.5×10-7), with independent replication in a second population (p = 0.0048, OR(95% CI) = 1.18(1.05-1.32); meta-analysis p = 2.6×10-8). The nearby gene, MMP12, was significantly overexpressed in carotid plaques compared to atherosclerosis-free control arteries (p = 1.2×10-15; fold change = 335.6). Permutation analyses demonstrated improved significance for associations when accounting for age-at-onset in all four stroke phenotypes (p<0.001). Our results show that a covariate-informed design, by adjusting for age-at-onset of stroke, can detect variants not identified by conventional GWAS.
482.
  • Understanding and Governing Sustainable Tourism Mobility : Psychological and Behavioural Approaches.
  • 2014
  • Samlingsverk (redaktörskap) (övrigt vetenskapligt)abstract
    • Despite a growing contribution to climate change, tourist and traveller behaviour is currently not acknowledged as an important sector within the development of climate policy. Whilst tourists may be increasingly aware of potential impacts on climate change there is evidence that most are unwilling to modify their actual behaviours. Influencing individual behaviour in tourism and informing effective governance is therefore an essential part of climate change mitigation.This significant volume is the first to explore the psychological and social factors that may contribute to and inhibit sustainable change in the context of tourist and traveller behaviour. It draws on a range of disciplines to offer a critical review of the psychological understandings and behavioural aspects of climate change and tourism mobilities, in addition to governance and policies based upon psychological, behavioural and social mechanisms. It therefore provides a more informed understanding of how technology, infrastructure and cost distribution can be developed in order to reach stronger mitigation goals whilst ensuring that resistance from consumers for socio-psychological reasons are minimized.Written by leading academics from a range of disciplinary backgrounds and regions this ground breaking volume is essential reading for all those interested in the effective governance of tourism’s contribution to climate change now and in the future.
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483.
  • Van Bulck, Liesbet, et al. (författare)
  • Patient-reported outcomes of adults with congenital heart disease from eight European countries : scrutinising the association with healthcare system performance
  • 2019
  • Ingår i: European Journal of Cardiovascular Nursing. - Sage Publications. - 1474-5151. ; 18:6, s. 465-473
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Inter-country variation in patient-reported outcomes of adults with congenital heart disease has been observed. Country-specific characteristics may play a role. A previous study found an association between healthcare system performance and patient-reported outcomes. However, it remains unknown which specific components of the countries’ healthcare system performance are of importance for patient-reported outcomes.Aims: The aim of this study was to investigate the relationship between components of healthcare system performance and patient-reported outcomes in a large sample of adults with congenital heart disease.Methods: A total of 1591 adults with congenital heart disease (median age 34 years; 51% men; 32% simple, 48% moderate and 20% complex defects) from eight European countries were included in this cross-sectional study. The following patient-reported outcomes were measured: perceived physical and mental health, psychological distress, health behaviours and quality of life. The Euro Health Consumer Index 2015 and the Euro Heart Index 2016 were used as measures of healthcare system performance. General linear mixed models were conducted, adjusting for patient-specific variables and unmeasured country differences.Results: Health risk behaviours were associated with the Euro Health Consumer Index subdomains about patient rights and information, health outcomes and financing and access to pharmaceuticals. Perceived physical health was associated with the Euro Health Consumer Index subdomain about prevention of chronic diseases. Subscales of the Euro Heart Index were not associated with patient-reported outcomes.Conclusion: Several features of healthcare system performance are associated with perceived physical health and health risk behaviour in adults with congenital heart disease. Before recommendations for policy-makers and clinicians can be conducted, future research ought to investigate the impact of the healthcare system performance on outcomes further.
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484.
  • van Diepen, Sean, et al. (författare)
  • Baseline NT-proBNP and biomarkers of inflammation and necrosis in patients with ST-segment elevation myocardial infarction : insights from the APEX-AMI trial
  • 2012
  • Ingår i: Journal of Thrombosis and Thrombolysis. - 0929-5305 .- 1573-742X. ; 34:1, s. 106-113
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary plaque rupture is associated with a systemic inflammatory response. The relationship between baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), a prognostic marker in patients with acute coronary syndromes, and systemic inflammatory mediators in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) is not well described. Of 5,745 STEMI patients treated with primary PCI in the APEX-AMI trial, we evaluated the relationship between baseline NT-proBNP levels and baseline levels of inflammatory markers and markers of myonecrosis in a subset of 772 who were enrolled in a biomarker substudy. Spearman correlations (r (s)) were calculated between baseline NT-proBNP levels and a panel of ten systemic inflammatory biomarkers. Interleukin (IL)-6, a pro-inflammatory cytokine, was significantly positively correlated with NT-proBNP (r (s) = 0.317, P &lt; 0.001). In a sensitivity analysis excluding all heart failure patients, the correlation between baseline IL-6 and NT-proBNP remained significant (n = 651, r (s) = 0.296, P &lt; 0.001). A positive association was also observed with high sensitivity C-reactive protein (r (s) = 0.377, P &lt; 0.001) and there was a weak negative correlation with the anti-inflammatory cytokine IL-10 (r (s) = -0.109, P = 0.003). No other significant correlations were observed among the other testes inflammatory cytokines and chemokines. In STEMI patients undergoing primary PCI, the pro-inflammatory cytokine IL-6 was modestly correlated with baseline NT-proBNP levels. This relationship remained significant in patients without heart failure. This finding is consistent with pre-clinical and clinical research suggesting that systemic inflammation may influence NT-proBNP expression independently of myocardial stretch.
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485.
  • van Diepen, Sean, et al. (författare)
  • Prognostic relevance of baseline pro- and anti-inflammatory markers in STEMI : An APEX AMI substudy
  • 2013
  • Ingår i: International Journal of Cardiology. - 0167-5273 .- 1874-1754. ; 168:3, s. 2127-2133
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Plaque rupture, acute ischemia, and necrosis in acute coronary syndromes are accompanied by concurrent pro-and anti-inflammatory cascades. Whether STEMI clinical prediction models can be improved with the addition of baseline inflammatory biomarkers remains unknown. Methods: In an APEX-AMI trial substudy, 772 patients had a panel of 9 inflammatory serum biomarkers, high sensitivity C reactive protein (hsCRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measured at baseline after randomization. Baseline biomarkers were incorporated into a clinical prediction model for a composite of 90-day death, shock, or heart failure. Incremental prognostic value was assessed using Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI). Results: Individually, several biomarkers were independent predictors of clinical outcome: hsCRP (hazard ratio [HR] 1.12; 95% confidence interval [CI], 1.03-1.21; p=0.007, per doubling), NT-proBNP (HR 1.14; 95% CI, 1.06-1.23; p&lt;0.001, per doubling), interleukin (IL)-6 (HR 1.26; 95% CI, 1.12-1.41; p&lt;0.001, per doubling), and inducible protein-10 (IP-10) (HR 0.86; 95% CI, 0.76-0.98; p&lt;0.025, per doubling). The addition of baseline NT-proBNP (NRI 8.6%, p=0.028; IDI 0.030, p&lt;0.001) and IL-6 (NRI 8.8%, p=0.012; IDI 0.036, p&lt;0.001) improved the clinical risk prediction model and the addition of hsCRP (NRI 6.5%, p=0.069; IDI 0.018, p=0.004) yielded minimal improvement. After incorporating NT-proBNP into the model, the remaining biomarkers added little additional predictive value. Conclusions: Multiple inflammatory biomarkers independently predicted 90-day death, shock or heart failure; however, they added little value to a clinical prediction model that included NT-proBNP. Future studies of inflammatory biomarkers in STEMI should report incremental value in a prediction model that includes NT-proBNP.
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486.
  • Vollaard, Niels B. J., et al. (författare)
  • Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance
  • 2009
  • Ingår i: Journal of applied physiology. - 8750-7587. ; 106:5, s. 1479-1486
  • Tidskriftsartikel (refereegranskat)abstract
    • Vollaard NB, Constantin-Teodosiu D, Fredriksson K, Rooyackers O, Jansson E, Greenhaff PL, Timmons JA, Sundberg CJ. Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. J Appl Physiol 106: 1479-1486, 2009. First published February 5, 2009; doi:10.1152/japplphysiol.91453.2008.-It has not been established which physiological processes contribute to endurance training-related changes (Delta) in aerobic performance. For example, the relationship between intramuscular metabolic responses at the intensity used during training and improved human functional capacity has not been examined in a longitudinal study. In the present study we hypothesized that improvements in aerobic capacity ((V) over dotO(2max)) and metabolic control would combine equally to explain enhanced aerobic performance. Twenty-four sedentary males (24 +/- 2 yr; 1.81 +/- 0.08 m; 76.6 +/- 11.3 kg) undertook supervised cycling training (45 min at 70% of pretraining (V) over dotO(2max)) 4 times/wk for 6 wk. Performance was determined using a 15-min cycling time trial, and muscle biopsies were taken before and after a 10-min cycle at 70% of pretraining (V) over dotO(2max) to quantify substrate metabolism. Substantial interindividual variability in training-induced adaptations was observed for most parameters, yet ""low responders"" for Delta(V) over dotO(2max) were not consistently low responders for other variables. While (V) over dotO(2max) and time trial performance were related at baseline (r(2) = 0.80, P &lt; 0.001), the change in (V) over dotO(2max) was completely unrelated to the change in aerobic performance. The maximal parameters Delta(V) over dotE(max) and Delta Veq(max) (Delta(V) over dotE/(V) over dotO(2max)) accounted for 64% of the variance in Delta(V) over dotO(2max) (P &lt; 0.001), whereas Delta performance was related to changes in the submaximal parameters Veq(submax) (r(2) = 0.33; P &lt; 0.01), muscle Delta lactate (r(2) = 0.32; P &lt; 0.01), and Delta acetyl-carnitine (r(2) = 0.29; P &lt; 0.05). This study demonstrates that improvements in high-intensity aerobic performance in humans are not related to altered maximal oxygen transport capacity. Altered muscle metabolism may provide the link between training stimulus and improved performance, but metabolic parameters do not change in a manner that relates to aerobic capacity changes.
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487.
  • Waelbroeck, Claire, et al. (författare)
  • Consistently dated Atlantic sediment cores over the last 40 thousand years
  • 2019
  • Ingår i: Scientific Data. - NATURE PUBLISHING GROUP. - 2052-4463. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Rapid changes in ocean circulation and climate have been observed in marine-sediment and ice cores over the last glacial period and deglaciation, highlighting the non-linear character of the climate system and underlining the possibility of rapid climate shifts in response to anthropogenic greenhouse gas forcing. To date, these rapid changes in climate and ocean circulation are still not fully explained. One obstacle hindering progress in our understanding of the interactions between past ocean circulation and climate changes is the difficulty of accurately dating marine cores. Here, we present a set of 92 marine sediment cores from the Atlantic Ocean for which we have established age-depth models that are consistent with the Greenland GICC05 ice core chronology, and computed the associated dating uncertainties, using a new deposition modeling technique. This is the first set of consistently dated marine sediment cores enabling paleoclimate scientists to evaluate leads/lags between circulation and climate changes over vast regions of the Atlantic Ocean. Moreover, this data set is of direct use in paleoclimate modeling studies.
488.
  • Wojno, Jennifer, et al. (författare)
  • Chemical separation of disc components using RAVE
  • 2016
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - Oxford University Press. - 0035-8711. ; 461:4, s. 4246-4255
  • Tidskriftsartikel (refereegranskat)abstract
    • We present evidence from the RAdial Velocity Experiment (RAVE) survey of chemically separated, kinematically distinct disc components in the solar neighbourhood.We apply probabilistic chemical selection criteria to separate our sample into a-low ('thin disc') and a-high ('thick disc') sequences. Using newly derived distances,which will be utilized in the upcoming RAVE DR5, we explore the kinematic trends as a function of metallicity for each of the disc components. For our a-low disc, we find a negative trend in the mean rotational velocity (Vf) as a function of iron abundance ([Fe/H]). We measure a positive gradient ∂Vφ/∂[Fe/H] for the a-high disc, consistent with results from high-resolution surveys.We also find differences between the a-low and a-high discs in all three components of velocity dispersion.We discuss the implications of an a-low, metal-rich population originating from the inner Galaxy, where the orbits of these stars have been significantly altered by radial mixing mechanisms in order to bring them into the solar neighbourhood. The probabilistic separation we propose can be extended to other data sets for which the accuracy in [a/Fe] is not sufficient to disentangle the chemical disc components a priori. For such data sets which will also have significant overlap with Gaia DR1, we can therefore make full use of the improved parallax and proper motion data as it becomes available to investigate kinematic trends in these chemical disc components.
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489.
  • Wojno, Jennifer, et al. (författare)
  • The selection function of the RAVE survey
  • 2017
  • Ingår i: Monthly Notices of the Royal Astronomical Society. - Oxford University Press. - 0035-8711. ; 468:3, s. 3368-3380
  • Tidskriftsartikel (refereegranskat)abstract
    • We characterize the selection function of RAdial Velocity Experiment (RAVE) using 2 Micron All Sky Survey (2MASS) as our underlying population, which we assume represents all stars that could have potentially been observed.We evaluate the completeness fraction as a function of position, magnitude and colour in two ways: first, on a field-by-field basis, and second, in equal-size areas on the sky. Then, we consider the effect of the RAVE stellar parameter pipeline on the final resulting catalogue, which in principle limits the parameter space over which our selection function is valid. Our final selection function is the product of the completeness fraction and the selection function of the pipeline. We then test if the application of the selection function introduces biases in the derived parameters. To do this, we compare a parent mock catalogue generated using GALAXIA with a mock-RAVE catalogue where the selection function of RAVE has been applied. We conclude that for stars brighter than I = 12, between 4000 < Teff < 8000K and 0.5 < log g < 5.0, RAVE is kinematically and chemically unbiased with respect to expectations from GALAXIA.
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490.
  • Women and Gender in Ancient Religions : Interdisciplinary Approaches
  • 2010
  • Samlingsverk (redaktörskap) (övrigt vetenskapligt)abstract
    • Following a scholarly conference given in honor of Adela Yarbro Collins, this collection of essays offers focused studies on the wide range of ways that women and gender contribute to the religious landscape of the ancient world. Experts in Greek and Roman religions, Early Christianity, Ancient Judaism, and Ancient Christianity engage in literary, social, historical, and cultural analysis of various ancient texts, inscriptions, social phenomena, and cultic activity. These studies continue the welcomed trend in scholarship that expands the social location of women in ancient Mediterranean religion to include the public sphere and consciousness. The result is an important and lively book that deepens the understanding of ancient religion as a whole. With contributions by:Patricia D. Ahearne-Kroll, Loveday Alexander, Mary Rose D'Angelo, Stephen J. Davis, Robert Doran, Radcliffe G. Edmonds III, Carin M. C. Green, Fritz Graf, Jan Willem van Henten, Paul A. Holloway, Annette B. Huizenga, Jeremy F. Hultin, Sarah Iles Johnston, James A. Kelhoffer, Judith L. Kovacs, Outi Lehtipuu, Matt Jackson-McCabe, Candida R. Moss, Christopher N. Mount, Susan E. Myers, Clare K. Rothschild, Turid Karlsen Seim.
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