RationaleSystemic levels of C reactive protein (CRP), surfactant protein D (SPD), fibrinogen, soluble receptor of activated glycogen end-product (sRAGE) and club cell protein 16 (CC-16) have been ...associated with chronic obstructive pulmonary disease (COPD) outcomes. However, they require validation in different cohorts.ObjectivesRelate systemic levels of those proteins to forced expiratory volume in 1 s (FEV1) decline, exacerbations, hospitalisations and mortality in COPD patients (FEV1 of ≥50 and ≤70% predicted) and heightened cardiovascular risk in a substudy of the Study to Understand Mortality and MorbidITy trial.MethodsParticipants were randomised to daily inhalations of placebo, vilanterol 25 µg (VI), fluticasone furoate 100 µg (FF) or their combination (VI 25/FF 100) and followed quarterly until 1000 deaths in the overall 16 485 participants occurred. Biomarker blood samples were available from 1673 patients. The FEV1 decline (mL/year), COPD exacerbations, hospitalisations and death were determined. Associations between biomarker levels and outcomes were adjusted by age and gender.ResultsSystemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen did not relate to baseline FEV1, FEV1 decline, exacerbations or hospitalisations. Fibrinogen and CRP were related to mortality over a median follow-up of 2.3 years. Only the CC-16 changed with study therapy (VI, FF and FF/VI, p<0.01) at 3 months.ConclusionsIn COPD, systemic levels of CC-16, CRP, sRAGE, SPD and fibrinogen were not associated with FEV1 decline, exacerbations or hospitalisations. These results cast doubts about the clinical usefulness of the systemic levels of these proteins as surrogate markers of these COPD outcomes. The study confirms that CRP and fibrinogen are associated with increased risk of death in patients with COPD.Trial registration numberNCT01313676.
Optimal analyses of many signals in the cosmic microwave background (CMB) require map-level extraction of individual components in the microwave sky, rather than measurements at the power spectrum ...level alone. To date, nearly all map-level component separation in CMB analyses has been performed exclusively using satellite data. In this paper, we implement a component separation method based on the internal linear combination (ILC) approach which we have designed to optimally account for the anisotropic noise (in the 2D Fourier domain) often found in ground-based CMB experiments. Using this method, we combine multi-frequency data from the Planck satellite and the Atacama Cosmology Telescope Polarimeter (ACTPol) to construct the first wide-area, arcminute-resolution component-separated maps (≈ 2100 sq. deg.) of the CMB temperature anisotropy and the thermal Sunyaev-Zel'dovich (tSZ) effect sourced by the inverse-Compton scattering of CMB photons off hot, ionized gas. Our ILC pipeline allows for explicit deprojection of various contaminating signals, including a modified blackbody approximation of the cosmic infrared background (CIB) spectral energy distribution. The cleaned CMB maps will be a useful resource for CMB lensing reconstruction, kinematic SZ cross-correlations, and primordial non-Gaussianity studies. Here, the tSZ maps will be used to study the pressure profiles of galaxies, groups, and clusters through cross-correlations with halo catalogs, with dust contamination controlled via CIB deprojection. The data products described in this paper are available on LAMBDA.
Species endemic to coldwater springs in the southeastern United States are some of the rarest and most imperiled in this region, yet little is known about their genetic composition and conservation ...needs. Here, microsatellite based levels of genetic diversity and estimates of effective population size (
N
e
) were compared between a narrow spring endemic fish,
Etheostoma nuchale
, and its widespread stream-dwelling relative,
E. swaini
. We applied several analytical methods to assess how demographic history is reflected in contemporary levels of genetic diversity for populations of
E. nuchale
. Phylogenetic analyses based on mitochondrial and nuclear DNA sequence data revealed a complex history among
E. nuchale
and
E. swaini
, but suggested ancient divergence and historic periods of isolation since colonization of spring habitats by
E. nuchale
. Populations of
E. nuchale
have levels of genetic diversity approximately one-half that of
E. swaini
, a result most likely due to founder effects and recent bottlenecks. Statistically significant
F
st
values (0.05−0.27) and STRUCTURE analyses implied high levels of differentiation among
E. nuchale
populations. Estimates of current
N
e
suggest relatively consistent levels across populations of
E. nuchale
, but one population may suffer from habitat degradation. We suggest that high levels of population structure and low levels of genetic diversity may be typical in other spring endemics inhabiting this region. Therefore, effective management planning for these unique species will require a detailed knowledge of the genetic and demographic history of each population.
Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, with a 5-y survival rate of ∼65%. Therefore, the identification of modifiable health ...factors to improve CRC survival is crucial.
Objective: We investigated the association of 4 prediagnostic a priori diet quality indexes with CRC-specific and all-cause mortality in the Multiethnic Cohort (MEC).
Methods: The MEC included >215,000 African-American, Native Hawaiian, Japanese-American, Latino, and white adults living in Hawaii and California who completed a validated quantitative food-frequency questionnaire in 1993–1996. CRC cases and deaths were identified through linkages to cancer registries and to state and national vital registries. Sex-specific HRs and 95% CIs were estimated for the Healthy Eating Index (HEI) 2010, the Alternative HEI (AHEI) 2010, the alternate Mediterranean Diet (aMED) score, and the Dietary Approaches to Stop Hypertension (DASH) index with CRC-specific and overall mortality as the primary outcomes. Ethnicity-specific analyses were the secondary outcomes.
Results: Among 4204 MEC participants diagnosed with invasive CRC through 2010, 1976 all-cause and 1095 CRC-specific deaths were identified. A higher aMED score was associated with lower CRC-specific mortality in women HR continuous pattern score divided by its respective SD (HR1SD): 0.86; 95% CI: 0.77, 0.96 but not in men (HR1SD: 1.01; 95% CI: 0.92, 1.11). A higher aMED score was also associated with lower all-cause mortality in women (HR1SD: 0.88; 95% CI: 0.81, 0.96) but not in men (HR1SD: 1.00; 95% CI: 0.93, 1.07). The HEI-2010, AHEI-2010, and DASH index were not significantly associated with CRC-specific or with all-cause mortality. The inverse relation for the aMED score was limited to African Americans and to colon (compared with rectal) cancer.
Conclusions: The aMED score was related to lower mortality only in African-American women (1 of 5 ethnic groups studied). The results should be interpreted with caution due to the small numbers of cases within ethnic groups and the issue of multiple testing.
This paper presents a maximum-likelihood algorithm for combining sky maps with disparate sky coverage, angular resolution and spatially varying anisotropic noise into a single map of the sky. We use ...this to merge hundreds of individual maps covering the 2008–2018 ACT observing seasons, resulting in by far the deepest ACT maps released so far. We also combine the maps with the full Planck maps, resulting in maps that have the best features of both Planck and ACT: Planck’s nearly white noise on intermediate and large angular scales and ACT’s high-resolution and sensitivity on small angular scales. The maps cover over 18 000 square degrees, nearly half the full sky, at 100, 150 and 220 GHz. Furthermore, they reveal 4 000 optically-confirmed clusters through the Sunyaev Zel’dovich effect (SZ) and 18 500 point source candidates at > 5σ, the largest single collection of SZ clusters and millimeter wave sources to date. The multi-frequency maps provide millimeter images of nearby galaxies and individual Milky Way nebulae, and even clear detections of several nearby stars. Other anticipated uses of these maps include, for example, thermal SZ and kinematic SZ cluster stacking, CMB cluster lensing and galactic dust science. The method itself has negligible bias. However, due to the preliminary nature of some of the component data sets, we caution that these maps should not be used for precision cosmological analysis. The maps are part of ACT DR5, and will be made available on LAMBDA no later than three months after the journal publication of this article, along with an interactive sky atlas.
Purpose: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Impaired lung function is associated with heightened risk for death, cardiovascular events, and ...COPD exacerbations. However, it is unclear if forced expiratory volume in one second (FEV.sub.1) and forced vital capacity (FVC) differ in predictive value. Patients and Methods: Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed. Patients were grouped into quintiles for each lung function parameter (FEV.sub.1 %predicted, FVC %predicted, FEV.sub.1/FVC). The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations. Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score. Results: Compared to Q1 (<53.5% FEV.sub.1 predicted), increasing FEV.sub.1 quintiles (Q2 53.5-157.5% predicted, Q3 57.5-161.6% predicted, Q4 61.6-165.8% predicted, and Q5 greater than or equal to65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-10%), 23% (7-36%), and 30% (15-12%) risk reduction, respectively). In contrast, a significant risk reduction (21% (1-35%)) was seen only between Q1 and Q5 quintiles of FVC. Neither FEV.sub.1 nor FVC was associated with cardiovascular risk. Increased FEV.sub.1 and FEV.sub.1/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase). Conclusion: Our results suggest that FEV.sub.1 is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks. Keywords: airflow limitation, cardiovascular risk, exacerbation, lung function, lung volumes, death rate
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Impaired lung function is associated with heightened risk for death, cardiovascular events, and COPD ...exacerbations. However, it is unclear if forced expiratory volume in one second (FEV
) and forced vital capacity (FVC) differ in predictive value.
Data from 16,485 participants in the Study to Understand Mortality and Morbidity (SUMMIT) in COPD were analyzed. Patients were grouped into quintiles for each lung function parameter (FEV
%predicted, FVC %predicted, FEV
/FVC). The four highest quintiles (Q2-Q5) were compared to the lowest (Q1) to assess their relationship with all-cause mortality, cardiovascular events, and moderate-to-severe and severe exacerbations. Cox-regression was used, adjusted for age, sex, ethnicity, body-mass index, smoking status, previous exacerbations, cardiovascular disease, treatment, and modified Medical Research Council dyspnea score.
Compared to Q1 (<53.5% FEV
predicted), increasing FEV
quintiles (Q2 53.5-457.5% predicted, Q3 57.5-461.6% predicted, Q4 61.6-465.8% predicted, and Q5 ≥65.8%) were all associated with significantly decreased all-cause mortality (20% (4-34%), 28% (13-40%), 23% (7-36%), and 30% (15-42%) risk reduction, respectively). In contrast, a significant risk reduction (21% (4-35%)) was seen only between Q1 and Q5 quintiles of FVC. Neither FEV
nor FVC was associated with cardiovascular risk. Increased FEV
and FEV
/FVC quintiles were also associated with the reduction of moderate-to-severe and severe exacerbations while, surprisingly, the highest FVC quintile was related to the heightened exacerbation risk (28% (8-52%) risk increase).
Our results suggest that FEV
is a stronger predictor for all-cause mortality than FVC in moderate COPD patients with heightened cardiovascular risk and that subjects with moderate COPD have very different risks.
Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of ...the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning
stoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO).
The phenotype of a cell and its underlying molecular state is strongly influenced by extracellular signals, including growth factors, hormones, and extracellular matrix proteins. While these signals ...are normally tightly controlled, their dysregulation leads to phenotypic and molecular states associated with diverse diseases. To develop a detailed understanding of the linkage between molecular and phenotypic changes, we generated a comprehensive dataset that catalogs the transcriptional, proteomic, epigenomic and phenotypic responses of MCF10A mammary epithelial cells after exposure to the ligands EGF, HGF, OSM, IFNG, TGFB and BMP2. Systematic assessment of the molecular and cellular phenotypes induced by these ligands comprise the LINCS Microenvironment (ME) perturbation dataset, which has been curated and made publicly available for community-wide analysis and development of novel computational methods ( synapse.org/LINCS_MCF10A ). In illustrative analyses, we demonstrate how this dataset can be used to discover functionally related molecular features linked to specific cellular phenotypes. Beyond these analyses, this dataset will serve as a resource for the broader scientific community to mine for biological insights, to compare signals carried across distinct molecular modalities, and to develop new computational methods for integrative data analysis.
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