The Stellar Metallicity Distribution Function of the Galactic Halo from SDSS Photometry

We explore the stellar metallicity distribution function of the Galactic halo based on SDSS ugriz photometry. A set of stellar isochrones is calibrated using observations of several star clusters and validated by comparisons with medium-resolution spectroscopic values over a wide range of metal abundance. We estimate distances and metallicities for individual main-sequence stars in the multiply scanned SDSS Stripe 82, at heliocentric distances in the range 5 - 8 kpc and |b| > 35 deg, and find that the in situ photometric metallicity distribution has a shape that matches that of the kinematically-selected local halo stars from Ryan & Norris. We also examine independent kinematic information from proper-motion measurements for high Galactic latitude stars in our sample. We find that stars with retrograde rotation in the rest frame of the Galaxy are generally more metal poor than those exhibiting prograde rotation, which is consistent with earlier arguments by Carollo et al. that the halo system comprises at least two spatially overlapping components with differing metallicity, kinematics, and spatial distributions. The observed photometric metallicity distribution and that of Ryan & Norris can be described by a simple chemical evolution model by Hartwick (or by a single Gaussian distribution); however, the suggestive metallicity-kinematic correlation contradicts the basic assumption in this model that the Milky Way halo consists primarily of a single stellar population. When the observed metallicity distribution is deconvolved using two Gaussian components with peaks at [Fe/H] ~ -1.7 and -2.3, the metal-poor component accounts for ~20% - 35% of the entire halo population in this distance range.Comment: Accepted for publication in Ap

PAR4 (Protease-Activated Receptor 4) Antagonism with BMS-986120 Inhibits Human Ex Vivo Thrombus Formation

Objective-BMS-986120 is a novel first-in-class oral PAR4 (protease-Activated receptor 4) antagonist with potent and selective antiplatelet effects. We sought to determine for the first time, the effect of BMS-986120 on human ex vivo thrombus formation. Approach and Results-Forty healthy volunteers completed a phase 1 parallel-group PROBE trial (Prospective Randomized Open-Label Blinded End Point). Ex vivo platelet activation, platelet aggregation, and thrombus formation were measured at 0, 2, and 24 hours after (1) oral BMS-986120 (60 mg) or (2) oral aspirin (600 mg) followed at 18 hours with oral aspirin (600 mg) and oral clopidogrel (600 mg). BMS-986120 demonstrated highly selective and reversible inhibition of PAR4 agonist peptide (100 μM)-stimulated P-selectin expression, platelet-monocyte aggregates, and platelet aggregation (P<0.001 for all). Compared with pretreatment, total thrombus area (μm2/mm) at high shear was reduced by 29.2% (95% confidence interval, 18.3%-38.7%; P<0.001) at 2 hours and by 21.4% (9.3%-32.0%; P=0.002) at 24 hours. Reductions in thrombus formation were driven by a decrease in platelet-rich thrombus deposition: 34.8% (19.3%-47.3%; P<0.001) at 2 hours and 23.3% (5.1%-38.0%; P=0.016) at 24 hours. In contrast to aspirin alone, or in combination with clopidogrel, BMS-986120 had no effect on thrombus formation at low shear (P=nonsignificant). BMS-986120 administration was not associated with an increase in coagulation times or serious adverse events. Conclusions-BMS-986120 is a highly selective and reversible oral PAR4 antagonist that substantially reduces platelet-rich thrombus formation under conditions of high shear stress. Our results suggest PAR4 antagonism has major potential as a therapeutic antiplatelet strategy. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439190

More than sense of place? Exploring the emotional dimension of rural tourism experiences

It is widely suggested that participation in rural tourism is underpinned by a sense of rural place or “rurality”. However, although nature and the countryside have long been recognised as a source of spiritual or emotional fulfilment, few have explored the extent to which tourism, itself often claimed to be a sacred experience, offers an emotional/spiritual dimension in the rural context. This paper addresses that literature gap. Using in-depth interviews with rural tourists in the English Lake District, it explores the extent to which, within respondents’ individual understanding of spirituality, a relationship exists between sense of place and deeper, emotional experiences and, especially, whether participation in rural tourism may induce spiritual or emotional responses. The research revealed that all respondents felt a strong attachment to the Lake District; similarly, and irrespective of their openness to spirituality, engaging in rural tourism activities resulted in highly emotive experiences for all respondents, the description/interpretation of such experiences being determined by individual “beliefs”. However, sense of place was not a prerequisite to emotional or spiritual experiences. Being in and engaging with the landscape � effectively becoming part of it � especially through physical activity is fundamental to emotional responses

Left ventricular remodeling and hypertrophy in patients with aortic stenosis:insights from cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Cardiovascular magnetic resonance (CMR) is the gold standard non-invasive method for determining left ventricular (LV) mass and volume but has not been used previously to characterise the LV remodeling response in aortic stenosis. We sought to investigate the degree and patterns of hypertrophy in aortic stenosis using CMR.</p> <p>Methods</p> <p>Patients with moderate or severe aortic stenosis, normal coronary arteries and no other significant valve lesions or cardiomyopathy were scanned by CMR with valve severity assessed by planimetry and velocity mapping. The extent and patterns of hypertrophy were investigated using measurements of the LV mass index, indexed LV volumes and the LV mass/volume ratio. Asymmetric forms of remodeling and hypertrophy were defined by a regional wall thickening <b>≥</b>13 mm and >1.5-fold the thickness of the opposing myocardial segment.</p> <p>Results</p> <p>Ninety-one patients (61±21 years; 57 male) with aortic stenosis (aortic valve area 0.93±0.32cm2) were recruited. The severity of aortic stenosis was unrelated to the degree (r²=0.012, P=0.43) and pattern (P=0.22) of hypertrophy. By univariate analysis, only male sex demonstrated an association with LV mass index (P=0.02). Six patterns of LV adaption were observed: normal ventricular geometry (n=11), concentric remodeling (n=11), asymmetric remodeling (n=11), concentric hypertrophy (n=34), asymmetric hypertrophy (n=14) and LV decompensation (n=10). Asymmetric patterns displayed considerable overlap in appearances (wall thickness 17±2mm) with hypertrophic cardiomyopathy.</p> <p>Conclusions</p> <p>We have demonstrated that in patients with moderate and severe aortic stenosis, the pattern of LV adaption and degree of hypertrophy do not closely correlate with the severity of valve narrowing and that asymmetric patterns of wall thickening are common.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Reference Number: NCT00930735</p

The Metallicity Distribution Functions of SEGUE G and K dwarfs: Constraints for Disk Chemical Evolution and Formation

We present the metallicity distribution function (MDF) for 24,270 G and 16,847 K dwarfs at distances from 0.2 to 2.3 kpc from the Galactic plane, based on spectroscopy from the Sloan Extension for Galactic Understanding and Exploration (SEGUE) survey. This stellar sample is significantly larger in both number and volume than previous spectroscopic analyses, which were limited to the solar vicinity, making it ideal for comparison with local volume-limited samples and Galactic models. For the first time, we have corrected the MDF for the various observational biases introduced by the SEGUE target selection strategy. The SEGUE sample is particularly notable for K dwarfs, which are too faint to examine spectroscopically far from the solar neighborhood. The MDF of both spectral types becomes more metal-poor with increasing |Z|, which reflects the transition from a sample with small [alpha/Fe] values at small heights to one with enhanced [alpha/Fe] above 1 kpc. Comparison of our SEGUE distributions to those of two different Milky Way models reveals that both are more metal-rich than our observed distributions at all heights above the plane. Our unbiased observations of G and K dwarfs provide valuable constraints over the |Z|-height range of the Milky Way disk for chemical and dynamical Galaxy evolution models, previously only calibrated to the solar neighborhood, with particular utility for thin- and thick-disk formation models.Comment: 70 pages, 25 figures, 7 tables. Accepted by The Astrophysical Journa

Serum Lipoprotein(a) and Bioprosthetic Aortic Valve Degeneration

AIMS: Bioprosthetic aortic valve degeneration demonstrates pathological similarities to aortic stenosis. Lipoprotein(a) [Lp(a)] is a well-recognized risk factor for incident aortic stenosis and disease progression. The aim of this study is to investigate whether serum Lp(a) concentrations are associated with bioprosthetic aortic valve degeneration. METHODS AND RESULTS: In a post hoc analysis of a prospective multimodality imaging study (NCT02304276), serum Lp(a) concentrations, echocardiography, contrast-enhanced computed tomography (CT) angiography, and 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) were assessed in patients with bioprosthetic aortic valves. Patients were also followed up for 2 years with serial echocardiography. Serum Lp(a) concentrations [median 19.9 (8.4-76.4) mg/dL] were available in 97 participants (mean age 75 ± 7 years, 54% men). There were no baseline differences across the tertiles of serum Lp(a) concentrations for disease severity assessed by echocardiography [median peak aortic valve velocity: highest tertile 2.5 (2.3-2.9) m/s vs. lower tertiles 2.7 (2.4-3.0) m/s, P = 0.204], or valve degeneration on CT angiography (highest tertile n = 8 vs. lower tertiles n = 12, P = 0.552) and 18F-NaF PET (median tissue-to-background ratio: highest tertile 1.13 (1.05-1.41) vs. lower tertiles 1.17 (1.06-1.53), P = 0.889]. After 2 years of follow-up, there were no differences in annualized change in bioprosthetic hemodynamic progression [change in peak aortic valve velocity: highest tertile [0.0 (-0.1-0.2) m/s/year vs. lower tertiles 0.1 (0.0-0.2) m/s/year, P = 0.528] or the development of structural valve degeneration. CONCLUSION: Serum lipoprotein(a) concentrations do not appear to be a major determinant or mediator of bioprosthetic aortic valve degeneration

Midwall Fibrosis Is an Independent Predictor of Mortality in Patients With Aortic Stenosis

ObjectivesThe goal of this study was to assess the prognostic significance of midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic stenosis.BackgroundMyocardial fibrosis occurs in aortic stenosis as part of the hypertrophic response. It can be detected by LGE, which is associated with an adverse prognosis in a range of other cardiac conditions.MethodsBetween January 2003 and October 2008, consecutive patients with moderate or severe aortic stenosis undergoing cardiovascular magnetic resonance with administration of gadolinium contrast were enrolled into a registry. Patients were categorized into absent, midwall, or infarct patterns of LGE by blinded independent observers. Patient follow-up was completed using patient questionnaires, source record data, and the National Strategic Tracing Service.ResultsA total of 143 patients (age 68 ± 14 years; 97 male) were followed up for 2.0 ± 1.4 years. Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in all-cause mortality despite similar aortic stenosis severity and coronary artery disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase. Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p = 0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to 0.99; p = 0.01) were independent predictors of all-cause mortality by multivariate analysis.ConclusionsMidwall fibrosis was an independent predictor of mortality in patients with moderate and severe aortic stenosis. It has incremental prognostic value to ejection fraction and may provide a useful method of risk stratification. (The Prognostic Significance of Fibrosis Detection in Cardiomyopathy; NCT00930735