The role of small airway dysfunction in asthma control and exacerbations:a longitudinal, observational analysis using data from the ATLANTIS study

Background Although small airway disease is a feature of asthma, its association with relevant asthma outcomes remains unclear. The ATLANTIS study was designed to identify the combination of physiological and imaging variables that best measure the presence and extent of small airway disease in asthma, both cross-sectionally and longitudinally. In this longitudinal analysis, we evaluated which small airway parameters studied were most strongly associated with asthma control, exacerbations, and quality of life.Methods In this observational cohort study, participants with mild, moderate, or severe stable asthma were recruited between June 30, 2014, and March 3, 2017, via medical databases and advertisements in nine countries worldwide. Eligible participants were aged 18-65 years with a clinical asthma diagnosis for at least 6 months. Participants were followed up for 1 year, with visits at baseline, 6 months, and 12 months. Physiological tests included spirometry, lung volumes, impulse oscillometry, multiple breath nitrogen washout (MBNW), and percentage decrease in forced vital capacity during methacholine challenge. CT densitometry was performed to evaluate small airway disease. We examined the associations between these measurements and asthma exacerbations, asthma control, and quality of life using univariate and multivariate analyses. A composite ordinal score comprising percent predicted R5-20 (resistance of small-to-mid-sized airways), AX (area of reactance), and X5 (reactance of more central, conducting small airways at 5 Hz) was constructed.Findings 773 participants (median age 46 years [IQR 34-54]; 450 [58%] female) were included in this longitudinal study. Univariate analyses showed that components of impulse oscillometry, lung volumes, MBNW, and forced expiratory flow at 25-75% of FVC were significantly correlated with asthma control and exacerbations (Spearman correlations 0.20-0.25, p<0.0001 after Bonferroni correction). As a composite of impulse oscillometry, the ordinal score independently predicted asthma control and exacerbations in a multivariate analysis with known exacerbation predictors. CT parameters were not significantly correlated with asthma control, exacerbation, or quality of life.Interpretation Small airway disease, as measured by physiological tests, is longitudinally associated with clinically important asthma outcomes, such as asthma control and exacerbations. Copyright (C) 2022 Elsevier Ltd. All rights reserved

Simulating Emulating

(Statement of Responsibility) by Brian Hallmark(Thesis) Thesis (B.A.) -- New College of Florida, 2001(Supplements) Accompanying materials: CD-ROM included(Electronic Access) RESTRICTED TO NCF STUDENTS, STAFF, FACULTY, AND ON-CAMPUS USE(Bibliography) Includes bibliographical references.(Source of Description) This bibliographic record is available under the Creative Commons CC0 public domain dedication. The New College of Florida, as creator of this bibliographic record, has waived all rights to it worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law.(Local) Faculty Sponsor: McDonald, Patric

Association between Dietary Fatty Acid Intake and Liver Steatosis and Fibrosis in a Sample of Mexican-Origin Hispanic Adults with Overweight or Obesity

Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population

Association between Dietary Fatty Acid Intake and Liver Steatosis and Fibrosis in a Sample of Mexican-Origin Hispanic Adults with Overweight or Obesity

Rates of non-alcoholic fatty liver disease (NAFLD) vary dramatically among Hispanic subpopulations, with Mexican-origin (MO) Hispanics experiencing a disproportionate burden. This study examined dietary fatty acid (FA) intake among overweight and obese MO Hispanic adults in the United States (US) and evaluated its association with liver steatosis and fibrosis. Participants (N = 285, MO Hispanic adults) completed 24-h dietary recalls to assess dietary FA exposure. Liver steatosis and fibrosis were estimated using transient elastography (FibroScan®). Multiple regression analysis tested relationships between FA intakes and liver steatosis or fibrosis, adjusting for age, sex, body mass index (BMI) and total energy. A total of 51% (n = 145) of participants were suspected to have NAFLD and 20% self-reported a type 2 diabetes diagnosis. No significant association was observed between Linoleic Acid and α-Linolenic Acid (LA:ALA) ratio, or omega-6 to omega-3 (n-6:n-3) ratio and liver steatosis. However, a one-point increase in the LA:ALA ratio resulted in a 1.01% increase in the liver fibrosis scores (95% CI: [1.00, 1.03]; p = 0.03), and a one-point increase in the n-6:n-3 ratio resulted in a 1.02% increase in liver fibrosis score (95% CI: [1.01, 1.03]; p = 0.01). Further research is needed to determine if modulation of FA intake could reduce NAFLD risk in this high-risk population

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1 Historical relationships among languages are used as a proxy for social history in many non-linguistic settings, including the fields of cultural and molecular anthropology. Linguists have traditionally assembled this information using the standard comparative method. While providing extremely nuanced linguistic information, this approach is time consuming and labor intensive. Conversely, computational approaches are appreciably quicker, but can potentially introduce significant error. Furthermore, current methods often use cognate sets that were themselves coded by historical linguists, thus reducing the benefit of computational approaches. Here we develop a method, based on the ALINE distance, to extract feature-sensitive relationships from paired glosses, datasets that require minimal contribution from trained linguists beyond transcription from primary sources. We validate our results by comparison with data generated independently via the comparative method, and quantify error rates using consistency indices. To showcase our method’s utility and to demonstrate its robustness at local and regional scales, we apply it to two language datasets from eastern Indonesia. As linguistic datasets proliferate, scalable computational methods that mimic historical linguistic reconstruction will become increasingly necessary

Geomicrobiological Changes in Two Ephemeral Desert Playa Lakes in the Western United States

The geochemistry and microbiology of two ephemeral playa lakes in the Western United States, Surprise Valley Alkali Lake (SVAL) and Eldorado Playa (EP), were examined over one wetting cycle, revealing dramatic temporal changes in suspended mineralogy, aqueous chemistry, and bacterial populations. In SVAL the predominant suspended mineral changed from smectite to vermiculite and clinoptilolite, which led to a depletion of soluble Mg2+. Nitrate became depleted in both playas as a result of biological nitrogen demand imparted by unusually dense microbial communities reaching 1 × 108 cultivable heterotrophs per ml of water. One hundred eighty eight bacterial isolates were obtained, representing sixty phylotypes and four phyla: Actinobacteria, Bacteroidetes, Proteobacteria, and Firmicutes. Phylogenetic analyses suggested that the microbial communities reflected different phases of succession, with SVAL changing from a diverse community with abundant Yonghaparkia to a less diverse late summer community with abundant Bacteroidetes and Proteobacteria such as Loktanella, Rhodobaca, Saccharospirillum, Flexibacter, and phylogenetically novel members of the Flexibacteriaceae. In EP, a diverse assemblage of bacteria often associated with soils was replaced very quickly by a much less even community dominated by Yonghaparkia, Sandarakinorhabdus, and relatives of Belliella baltica. Strikingly, the early summer microbial community from SVAL was not significantly different from the EP community that developed within one week of flooding, even though these playas are almost 1000 km apart, whereas sympatric communities in different phases of succession were different. To our knowledge, this is one of the first geomicrobiological studies of a recharge playa, the dominant playa type worldwide

Exome Sequencing Provides Evidence of Polygenic Adaptation to a Fat-Rich Animal Diet in Indigenous Siberian Populations

Siberia is one of the coldest environments on Earth and has great seasonal temperature variation. Long-term settlement in northern Siberia undoubtedly required biological adaptation to severe cold stress, dramatic variation in photoperiod, and limited food resources. In addition, recent archeological studies show that humans first occupied Siberia at least 45,000 years ago; yet our understanding of the demographic history of modern indigenous Siberians remains incomplete. In this study, we use whole-exome sequencing data from the Nganasans and Yakuts to infer the evolutionary history of these two indigenous Siberian populations. Recognizing the complexity of the adaptive process, we designed a model-based test to systematically search for signatures of polygenic selection. Our approach accounts for stochasticity in the demographic process and the hitchhiking effect of classic selective sweeps, as well as potential biases resulting from recombination rate and mutation rate heterogeneity. Our demographic inference shows that the Nganasans and Yakuts diverged similar to 12,000-13,000 years ago from East-Asian ancestors in a process involving continuous gene flow. Our polygenic selection scan identifies seven candidate gene sets with Siberian-specific signals. Three of these gene sets are related to diet, especially to fat metabolism, consistent with the hypothesis of adaptation to a fat-rich animal diet. Additional testing rejects the effect of hitchhiking and favors a model in which selection yields small allele frequency changes at multiple unlinked genes.National Science Foundation [PLR-1203874, DEB-1146074]; State Research Project [0324-2016-0002]12 month embargo; published online: 12 September 2017This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

FADS genetic and metabolomic analyses identify the ∆5 desaturase (FADS1) step as a critical control point in the formation of biologically important lipids

Humans have undergone intense evolutionary selection to optimize their capacity to generate necessary quantities of long chain (LC-) polyunsaturated fatty acid (PUFA)-containing lipids. To better understand the impact of genetic variation within a locus of three FADS genes (FADS1, FADS2, and FADS3) on a diverse family of lipids, we examined the associations of 247 lipid metabolites (including four major classes of LC-PUFA-containing molecules and signaling molecules) with common and low-frequency genetic variants located within the FADS locus. Genetic variation in the FADS locus was strongly associated (p < 1.2 × 10-8) with 52 LC-PUFA-containing lipids and signaling molecules, including free fatty acids, phospholipids, lyso-phospholipids, and an endocannabinoid. Notably, the majority (80%) of FADS-associated lipids were not significantly associated with genetic variants outside of this FADS locus. These findings highlight the central role genetic variation at the FADS locus plays in regulating levels of physiologically critical LC-PUFA-containing lipids that participate in innate immunity, energy homeostasis, and brain development/function.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]