Celli et al discuss the need to revise the definition and nomenclature of chronic obstructive pulmonary disease. The definition and the diagnostic criteria (terms often mixed or confused) of a ...disease represent different constructs. A definition must describe its essential attributes while avoiding circularity, it must also not consist of terms that are synonymous with it. It should not be too wide or too narrow (not miss or include anything to which the term should not be applied). It should also be clear, understandable, and positive, attempting to avoid concepts derived by exclusions.
A critical determination of a phase diagram of the Zn-Fe binary system was carried out by EPMA analysis for skillfully prepared and equilibrated two-phase alloys for solid phases and by EDS areal ...analysis for the Fe solubility in the heterogeneously solidified liquid phase instead of the conventional diffusion couple method. It was newly confirmed that equilibrium compositions of intermetallic compounds tend to shift toward the Fe side compared to the previous phase diagram on the whole and that the solubility ranges of the Γ-Fe3Zn10 and Γ1-Fe11Zn40 phases are much narrower than those in the literature. The critical composition of the second-order order-disorder transition between δ1k-FeZn7 and δ1p-FeZn10 at high temperature was estimated by Vickers hardness measurement. Furthermore, the phase separation, i.e., the first-order transition, between the δ1k and δ1p phases in the low temperature region was directly found out and its equilibrium compositions were confirmed by EPMA analysis for the two-phase microstructures. The width of the δ1k + δ1p two-phase region at 500 °C is only 0.5 at.% and the δ1p decomposes into the δ1k and ζ-FeZn13 phases via a eutectoid reaction at a temperature between 455 °C and 445 °C. While being mostly coincident with those in the previous literature at temperatures between 1000 °C and 600 °C, the solubility of Fe in the liquid (L) Zn phase is about twenty times larger than the assessed value in the literature at temperatures below 500 °C. A eutectic reaction, L → ζ + (ηZn), was confirmed to occur by precise EPMA analysis and DSC measurement.
•A phase diagram of the Zn-Fe binary system was determined by two-phase alloys.•Solubility ranges of IMC phases were confirmed to shift to Fe-rich side.•A first-order order (δ1k) + disorder (δ1p) miscibility gap was found out.•Solubility of Fe in the liquid Zn at 450 °C was over twenty times larger than that in the literature.•An invariant reaction consisting of the liquid, ζ and (ηZn) phases is confirmed to be eutectic.
In this study, the investigators found a strong association, in two cohorts, between future exacerbations of COPD and the ratio of the diameter of the pulmonary artery to the diameter of the aorta ...(with both diameters measured from a baseline CT scan) that is greater than 1.
Acute exacerbations of chronic obstructive pulmonary disease (COPD) are critical events in the natural history of the disease and are associated with accelerated loss of lung function and poor quality of life.
1
,
2
Hospitalizations for exacerbations account for $18 billion in direct costs annually in the United States and are associated with 1-year mortality of 21% and 5-year mortality of 55%.
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Identification of patients at risk for these events is therefore of major importance.
Acute exacerbations of COPD are defined as an increase in dyspnea, cough, or sputum production warranting a change in therapy. These acute exacerbations often result from . . .
To test the hypothesis-given the increasing emphasis on quantitative computed tomographic (CT) phenotypes of chronic obstructive pulmonary disease (COPD)-that a relationship exists between COPD ...exacerbation frequency and quantitative CT measures of emphysema and airway disease.
This research protocol was approved by the institutional review board of each participating institution, and all participants provided written informed consent. One thousand two subjects who were enrolled in the COPDGene Study and met the GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria for COPD with quantitative CT analysis were included. Total lung emphysema percentage was measured by using the attenuation mask technique with a -950-HU threshold. An automated program measured the mean wall thickness and mean wall area percentage in six segmental bronchi. The frequency of COPD exacerbation in the prior year was determined by using a questionnaire. Statistical analysis was performed to examine the relationship of exacerbation frequency with lung function and quantitative CT measurements.
In a multivariate analysis adjusted for lung function, bronchial wall thickness and total lung emphysema percentage were associated with COPD exacerbation frequency. Each 1-mm increase in bronchial wall thickness was associated with a 1.84-fold increase in annual exacerbation rate (P = .004). For patients with 35% or greater total emphysema, each 5% increase in emphysema was associated with a 1.18-fold increase in this rate (P = .047).
Greater lung emphysema and airway wall thickness were associated with COPD exacerbations, independent of the severity of airflow obstruction. Quantitative CT can help identify subgroups of patients with COPD who experience exacerbations for targeted research and therapy development for individual phenotypes.
Chronic obstructive pulmonary disease diagnosis rests on chronic pulmonary symptoms and airflow obstruction. This study showed that people may have chronic COPD symptoms but no airflow obstruction. ...Such patients have more COPD exacerbations than those without chronic symptoms.
Among the criteria that are needed to make a diagnosis of chronic obstructive pulmonary disease (COPD) are deficits in the rate at which one can forcefully exhale. Most experts consider a low ratio (<0.70) of the forced expiratory volume in 1 second (FEV
1
) to the forced vital capacity (FVC) after bronchodilator use to be a key diagnostic criterion.
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Once the diagnosis of COPD has been established, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) nomenclature grades severity according to the degree to which the measured FEV
1
is lower than the patient’s predicted value. GOLD stage 1, . . .
We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease ...(COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD.
SPIROMICS was a multicentre, observational study in patients aged 40-80 years recruited from six clinical sites and additional subsites in the USA. In this analysis, MUC5AC and MUC5B were quantitated by stable isotope-labelled mass spectrometry in induced sputum samples from healthy never-smokers, ever-smokers at risk for COPD, and ever-smokers with COPD. Participants were extensively characterised using results from questionnaires, such as the COPD assessment test (CAT) and St George's Respiratory Questionnaire; quantitative CT, such as residual volume/total lung capacity ratio (RV/TLC) and parametric response mapping-functional small airway disease (PRM-fSAD); and pulmonary function tests, such as FEV
, forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF
). Absolute concentrations of both MUC5AC and MUC5B were related to cross-sectional (baseline, initial visit) and 3-year follow-up longitudinal data, including lung function, small airways obstruction, prospective acute exacerbations, and smoking status as primary outcomes. This study is registered with ClinicalTrials.gov (NCT01969344).
This analysis included 331 participants (mean age 63 years SEM 9·40), of whom 40 were healthy never-smokers, 90 were at-risk ever-smokers, and 201 were ever-smokers with COPD. Increased MUC5AC concentrations were more reliably associated with manifestations of COPD than were MUC5B concentrations, including decreased FEV
and FEF
, and increased prospective exacerbation frequency, RV/TLC, PRM-fSAD, and COPD assessment scores. MUC5AC concentrations were more reactive to cigarette smoke exposure than were MUC5B concentrations. Longitudinal data from 3-year follow-up visits generated a multivariate-adjusted odds ratio for two or more exacerbations of 1·24 (95% CI 1·04-1·47, p=0·015) for individuals with high baseline MUC5AC concentration. Increased MUC5AC, but not MUC5B, concentration at baseline was a significant predictor of FEV
, FEV
/FVC, FEF
, and CAT score decline during the 3-year follow-up. Moreover, current smokers in the at-risk group showed raised MUC5AC concentrations at initial visits and decreased lung function over 3 years. By contrast, former smokers in the at-risk group showed normal MUC5AC concentrations at the initial visit and preserved lung function over 3 years.
These data indicate that increased MUC5AC concentration in the airways might contribute to COPD initiation, progression, exacerbation risk, and overall pathogenesis. Compared with MUC5B, greater relative changes in MUC5AC concentrations were observed as a function of COPD severity, and MUC5AC concentration seems to be an objective biomarker to detect disease in at-risk and pre-COPD individuals. These data suggest that MUC5AC-producing pathways could be potential targets for future therapeutic strategies. Thus, MUC5AC could be a novel biomarker for COPD prognosis and for testing the efficacy of therapeutic agents.
National Institutes of Health; National Heart, Lung, and Blood Institute.
High-harmonic generation (HHG) of laser radiation has led to attosecond pulse formation which offers unprecedented temporal resolution in observing and controlling electron and nuclear dynamics. But ...the energy of attosecond pulses remains quite small, especially for photon energies exceeding 100 eV, which limits their practical applications. We propose a method for amplification of attosecond pulses in the active medium of a plasma-based x-ray laser dressed by a replica of the laser field used for HHG. The experimental implementation is suggested in hydrogenlike C5+ x-ray laser at 3.4 nm wavelength in the "water window" range.
Speech emotion recognition predicts the emotional state of a speaker based on the person's speech. It brings an additional element for creating more natural human-computer interactions. Earlier ...studies on emotional recognition have been primarily based on handcrafted features and manual labels. With the advent of deep learning, there have been some efforts in applying the deep-network-based approach to the problem of emotion recognition. As deep learning automatically extracts salient features correlated to speaker emotion, it brings certain advantages over the handcrafted-feature-based methods. There are, however, some challenges in applying them to the emotion recognition problem, because data required for properly training deep networks are often lacking. Therefore, there is a need for a new deep-learning-based approach which can exploit available information from given speech signals to the maximum extent possible. Our proposed method, called "Fusion-ConvBERT", is a parallel fusion model consisting of bidirectional encoder representations from transformers and convolutional neural networks. Extensive experiments were conducted on the proposed model using the EMO-DB and Interactive Emotional Dyadic Motion Capture Database emotion corpus, and it was shown that the proposed method outperformed state-of-the-art techniques in most of the test configurations.
We investigated whether oral health, represented by missing teeth, was associated with an increased risk of cardiovascular disease, including myocardial infarction (MI), heart failure (HF), stroke, ...and all-cause mortality. Subjects who underwent routine dental examinations and health checkups provided by the Korean National Health Insurance from 2007 to 2008 (n = 4,440,970) were followed up for incident MI, HF, stroke, and death until 2016. During follow-up of 7.56 y, 68,063 (1.5%) subjects died, and 31,868 (0.7%) were admitted for MI, 22,637 (0.5%) for HF, and 30,941 (0.7%) for stroke. Cardiovascular events and mortality increased in proportion to tooth loss. Tooth loss was an independent risk factor for cardiovascular events after multivariable analysis adjusted for cardiovascular risk, behavioral, and income factors. Each missing tooth was associated with an approximately 1% increase in MI (HR, 1.010; 95% CI, 1.007 to 1.014), 1.5% increase in HF (HR, 1.016; 95% CI, 1.013 to 1.019) and stroke (HR, 1.015; 95% CI, 1.012 to 1.018), and 2% increase in mortality (HR, 1.022; 95% CI, 1.020 to 1.023). Having ≥5 missing teeth substantially increased risk for cardiovascular outcomes, and even a small number of missing teeth (1 to 4) was associated with an increased risk for MI, stroke, and death. This association was consistent in subgroup analyses and especially strong among the younger subjects (age <65 y) and those with periodontitis. In this large Korean nationwide cohort study, we found that tooth loss showed a dose-dependent association with incident MI, HF, ischemic stroke, and all-cause death and was a good predictor of cardiovascular outcome. In clinical practice, the number of missing teeth can aid physicians in discriminating patients with a higher cardiovascular risk.
Hyper-secretion and/or hyper-concentration of mucus is a defining feature of multiple obstructive lung diseases, including chronic obstructive pulmonary disease (COPD). Mucus itself is composed of a ...mixture of water, ions, salt and proteins, of which the gel-forming mucins, MUC5AC and MUC5B, are the most abundant. Recent studies have linked the concentrations of these proteins in sputum to COPD phenotypes, including chronic bronchitis (CB) and acute exacerbations (AE). We sought to determine whether common genetic variants influence sputum mucin concentrations and whether these variants are also associated with COPD phenotypes, specifically CB and AE. We performed a GWAS to identify quantitative trait loci for sputum mucin protein concentration (pQTL) in the Sub-Populations and InteRmediate Outcome Measures in COPD Study (SPIROMICS, n = 708 for total mucin, n = 215 for MUC5AC, MUC5B). Subsequently, we tested for associations of mucin pQTL with CB and AE using regression modeling (n = 822-1300). Replication analysis was conducted using data from COPDGene (n = 5740) and by examining results from the UK Biobank. We identified one genome-wide significant pQTL for MUC5AC (rs75401036) and two for MUC5B (rs140324259, rs10001928). The strongest association for MUC5B, with rs140324259 on chromosome 11, explained 14% of variation in sputum MUC5B. Despite being associated with lower MUC5B, the C allele of rs140324259 conferred increased risk of CB (odds ratio (OR) = 1.42; 95% confidence interval (CI): 1.10-1.80) as well as AE ascertained over three years of follow up (OR = 1.41; 95% CI: 1.02-1.94). Associations between rs140324259 and CB or AE did not replicate in COPDGene. However, in the UK Biobank, rs140324259 was associated with phenotypes that define CB, namely chronic mucus production and cough, again with the C allele conferring increased risk. We conclude that sputum MUC5AC and MUC5B concentrations are associated with common genetic variants, and the top locus for MUC5B may influence COPD phenotypes, in particular CB.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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