Ventricular Geometry From Non-contrast Non-ECG-gated CT Scans:An Imaging Marker of Cardiopulmonary Disease in Smokers

Cardiovascular disease is a major cause of morbidity in smokers, and as much as 50% of the estimated 24 million patients in the United States with chronic obstructive pulmonary disease (COPD) die of cardiovascular causes (1,2). Although echocardiography and cardiac magnetic resonance imaging (MRI) are often used to study cardiac structure and function in COPD (3), these are not routinely deployed in all smokers. Computed tomographic (CT) imaging of the chest is broadly used in clinical care and is increasingly used for lung cancer screening in high-risk smokers (4). Assessment of cardiac structure on those CT scans may help identify patients with COPD at greater risk of developing cardiac dysfunction. Rapid, noninvasive assessments of cardiac morphology and a better understanding of the functional interdependence of heart and lung may improve healthcare outcomes through early detection and initiation of treatment

A planet within the debris disk around the pre-main-sequence star AU Microscopii

AU Microscopii (AU Mic) is the second closest pre main sequence star, at a distance of 9.79 parsecs and with an age of 22 million years. AU Mic possesses a relatively rare and spatially resolved3 edge-on debris disk extending from about 35 to 210 astronomical units from the star, and with clumps exhibiting non-Keplerian motion. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic activity on the star. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3 sigma confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution.Comment: Nature, published June 24th [author spelling name fix

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

BackgroundChronic 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.MethodsParticipants 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.ResultsAt 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 à  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.ConclusionsThe 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.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/171220/1/jcsm12782_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/171220/2/jcsm12782.pd

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

BackgroundChronic 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.MethodsParticipants with COPD (N&nbsp;=&nbsp;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&nbsp;&gt;&nbsp;5% in the past year or low BMI (BMI&nbsp;&lt;&nbsp;20&nbsp;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.ResultsAt the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio&nbsp;=&nbsp;3.6, 95% confidence interval&nbsp;=&nbsp;2.3-5.6, P&nbsp;=&nbsp;3.2&nbsp;×&nbsp;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&nbsp;=&nbsp;0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P&nbsp;=&nbsp;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&nbsp;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.ConclusionsThe 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

A planet within the debris disk around the pre-main-sequence star AU Microscopii

AU Microscopii (AU Mic) is the second closest pre-main-sequence star, at a distance of 9.79 parsecs and with an age of 22 million years. AU Mic possesses a relatively rare and spatially resolved edge-on debris disk extending from about 35 to 210 astronomical units from the star, and with clumps exhibiting non-Keplerian motion. Detection of newly formed planets around such a star is challenged by the presence of spots, plage, flares and other manifestations of magnetic ‘activity’ on the star. Here we report observations of a planet transiting AU Mic. The transiting planet, AU Mic b, has an orbital period of 8.46 days, an orbital distance of 0.07 astronomical units, a radius of 0.4 Jupiter radii, and a mass of less than 0.18 Jupiter masses at 3σ confidence. Our observations of a planet co-existing with a debris disk offer the opportunity to test the predictions of current models of planet formation and evolution

Publisher Correction: A planet within the debris disk around the pre-main-sequence star AU Microscopii

Correction to: Nature https://www.nature.com/articles/s41586-020-2400-zPublished online 24 June 2020In Fig. 3 of this Article, the subscript ‘Sun’ symbols on both axis labels (R☉ and M☉) should have been subscript ‘Earth’ symbols (R⊕ and M⊕), as appears correctly in the legend. This error has been corrected online