Genetic variation in genes regulating skeletal muscle regeneration and tissue remodelling associated with weight loss in chronic obstructive pulmonary disease

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach. METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m2). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein–protein interaction (PPI) data. RESULTS: At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3–5.6, P = 3.2 × 10−8) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling. CONCLUSIONS: The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling

Women’s responses to changes in U.S. preventive task force’s mammography screening guidelines: results of focus groups with ethnically diverse women

Background: The 2009 U.S. Preventive Services Task Force (USPSTF) changed mammography guidelines to recommend routine biennial screening starting at age 50. This study describes women’s awareness of, attitudes toward, and intention to comply with these new guidelines. Methods: Women ages 40–50 years old were recruited from the Boston area to participate in focus groups (k = 8; n = 77). Groups were segmented by race/ethnicity (Caucasian = 39%; African American = 35%; Latina = 26%), audio-taped, and transcribed. Thematic content analysis was used. Results: Participants were largely unaware of the revised guidelines and suspicious that it was a cost-savings measure by insurers and/or providers. Most did not intend to comply with the change, viewing screening as obligatory. Few felt prepared to participate in shared decision-making or advocate for their preferences with respect to screening. Conclusions: Communication about the rationale for mammography guideline changes has left many women unconvinced about potential disadvantages or limitations of screening. Since further guideline changes are likely to occur with advances in technology and science, it is important to help women become informed consumers of health information and active participants in shared decision-making with providers. Additional research is needed to determine the impact of the USPSTF change on women’s screening behaviors and on breast cancer outcomes

Extreme enrichment of Se, Te, PGE and Au in Cu sulfide microdroplets: evidence from LA-ICP-MS analysis of sulfides in the Skaergaard Intrusion, east Greenland

The Platinova Reef, in the Skaergaard Intrusion, east Greenland, is an example of a magmatic Cu–PGE–Au sulfide deposit formed in the latter stages of magmatic differentiation. As is characteristic with such deposits, it contains a low volume of sulfide, displays peak metal offsets and is Cu rich but Ni poor. However, even for such deposits, the Platinova Reef contains extremely low volumes of sulfide and the highest Pd and Au tenor sulfides of any magmatic ore deposit. Here, we present the first LA-ICP-MS analyses of sulfide microdroplets from the Platinova Reef, which show that they have the highest Se concentrations (up to 1200 ppm) and lowest S/Se ratios (190–700) of any known magmatic sulfide deposit and have significant Te enrichment. In addition, where sulfide volume increases, there is a change from high Pd-tenor microdroplets trapped in situ to larger, low tenor sulfides. The transition between these two sulfide regimes is marked by sharp peaks in Au, and then Te concentration, followed by a wider peak in Se, which gradually decreases with height. Mineralogical evidence implies that there is no significant post-magmatic hydrothermal S loss and that the metal profiles are essentially a function of magmatic processes. We propose that to generate these extreme precious and semimetal contents, the sulfides must have formed from an anomalously metal-rich package of magma, possibly formed via the dissolution of a previously PGE-enriched sulfide. Other processes such as kinetic diffusion may have also occurred alongside this to produce the ultra-high tenors. The characteristic metal offset pattern observed is largely controlled by partitioning effects, producing offset peaks in the order Pt+Pd>Au>Te>Se>Cu that are entirely consistent with published D values. This study confirms that extreme enrichment in sulfide droplets can occur in closed-system layered intrusions in situ, but this will characteristically form ore deposits that are so low in sulfide that they do not conform to conventional deposit models for Cu–Ni–PGE sulfides which require very high R factors, and settling of sulfide liquids

Baryon content of massive galaxy clusters at 0.57

© 2015 The Authors. We study the stellar, brightest cluster galaxy (BCG) and intracluster medium (ICM) masses of 14 South Pole Telescope (SPT) selected galaxy clusters with median redshift z = 0.9 and mass M500 = 6 × 1014M⊙. We estimate stellar masses for each cluster and BCG using six photometric bands, the ICM mass using X-ray observations and the virial masses using the SPT Sunyaev-Zel'dovich effect signature. At z = 0.9, the BCG mass M*BCG constitutes 0.12 ± 0.01 per cent of the halo mass for a 6 × 1014M⊙ cluster, and this fraction falls as M 500-0.58±0.07. The cluster stellar mass function has a characteristic mass M0 = 1011.0 ± 0.1M⊙, and the number of galaxies per unit mass in clusters is larger than in the field by a factor of 1.65 ± 0.20. We combine our SPT sample with previously published samples at low redshift and correct to a common initial mass function and for systematic virial mass differences. We then explore mass and redshift trends in the stellar fraction f*, the ICM fraction fICM, the collapsed baryon fraction fc and the baryon fraction fb. At a pivot mass of 6 × 1014M⊙ and redshift z = 0.9, the characteristic values are f* = 1.1 ± 0.1 per cent, fICM = 9.6 ± 0.5 per cent, fc = 10.7 ± 1.1 per cent and fb = 10.7 ± 0.6 per cent. These fractions all vary with cluster mass at high significance, with higher mass clusters having lower f* and fc and higher fICM and fb. When accounting for a 15 per cent systematic virial mass uncertainty, there is no statistically significant redshift trend at fixed mass. Our results support the scenario where clusters grow through accretion from subclusters (higher f*, lower fICM) and the field (lower f*, higher fICM), balancing to keep f* and fICM approximately constant since z ~ 0.9

Galaxy populations in the most distant SPT-SZ clusters: I. Environmental quenching in massive clusters at 1.4 ≲ z ≲ 1.7

© 2019 ESO. We present the first results from a galaxy population study in the highest redshift galaxy clusters identified in the 2500 deg 2 South Pole Telescope Sunyaev Zel'dovich effect (SPT-SZ) survey, which is sensitive to M 500 ≳ 3 × 10 14 M · clusters from z ∼ 0.2 out to the highest redshifts where such massive structures exist. The cluster selection is to first order independent of galaxy properties, making the SPT-SZ sample particularly well suited for cluster galaxy population studies. We carried out a four-band imaging campaign with the Hubble and Spitzer Space Telescopes of the five z≳ 1.4, S/N SZE > 5 clusters, that are among the rarest most massive clusters known at this redshift. All five clusters show clear overdensities of red galaxies whose colors agree with the initial cluster redshift estimates, although one (SPT-CLJ0607-4448) shows a galaxy concentration much less prominent than the others. The highest redshift cluster in this sample, SPT-CLJ0459-4947 at z ∼ 1.72, is the most distant M 500 > 10 14 M · cluster discovered thus far through its intracluster medium, and is one of only three known clusters in this mass range at z≳ 1.7, regardless of selection. Based on UVJ-like photometric classification of quiescent and star-forming galaxies, we find that the quiescent fraction in the cluster central regions (r/r 500 10.85. We have explored the impact of emission from star formation on the selection of this sample, concluding that all five clusters studied here would still have been detected with S/N SZE > 5, even if they had the same quiescent fraction as measured in the field. Our results thus point towards an efficient suppression of star formation in the central regions of the most massive clusters, occurring already earlier than z ∼ 1.5

Spectroscopic Confirmation of Five Galaxy Clusters at z > 1.25 in the 2500 deg(2) SPT-SZ Survey

We present spectroscopic confirmation of five galaxy clusters at 1.25 1.25 from three to eight, further demonstrating the efficacy of SZ selection for the highest redshift massive clusters and enabling detailed study of these systems