Towards a Simple Model of Compressible Alfvenic Turbulence

A simple model collisionless, dissipative, compressible MHD (Alfvenic) turbulence in a magnetized system is investigated. In contrast to more familiar paradigms of turbulence, dissipation arises from Landau damping, enters via nonlinearity, and is distributed over all scales. The theory predicts that two different regimes or phases of turbulence are possible, depending on the ratio of steepening to damping coefficient (m_1/m_2). For strong damping (|m_1/m_2|<1), a regime of smooth, hydrodynamic turbulence is predicted. For |m_1/m_2|>1, steady state turbulence does not exist in the hydrodynamic limit. Rather, spikey, small scale structure is predicted.Comment: 6 pages, one figure, REVTeX; this version to be published in PRE. For related papers, see http://sdphpd.ucsd.edu/~medvedev/papers.htm

Multi-wavelength interferometry of evolved stars using VLTI and VLBA

We report on our project of coordinated VLTI/VLBA observations of the atmospheres and circumstellar environments of evolved stars. We illustrate in general the potential of interferometric measurements to study stellar atmospheres and envelopes, and demonstrate in particular the advantages of a coordinated multi-wavelength approach including near/mid-infrared as well as radio interferometry. We have so far made use of VLTI observations of the near- and mid-infrared stellar sizes and of concurrent VLBA observations of the SiO maser emission. To date, this project includes studies of the Mira stars S Ori and RR Aql as well as of the supergiant AH Sco. These sources all show strong silicate emission features in their mid-infrared spectra. In addition, they each have relatively strong SiO maser emission. The results from our first epochs of S Ori measurements have recently been published and the main results are reviewed here. The S Ori maser ring is found to lie at a mean distance of about 2 stellar radii, a result that is virtually free of the usual uncertainty inherent in comparing observations of variable stars widely separated in time and stellar phase. We discuss the status of our more recent S Ori, RR Aql, and AH Sco observations, and present an outlook on the continuation of our project.Comment: 9 pages, to appear in the proceedings of the ESO workshop "The Power of Optical/IR Interferometry: Recent Scientific Results and 2nd Generation VLTI Instrumentation", ESO Astrophysics Symposi

Opportunities for evaluating chemical exposures and child health in the United States: the Environmental influences on Child Health Outcomes (ECHO) Program

The Environmental Influences on Child Health Outcomes (ECHO) Program will evaluate environmental factors affecting children’s health (perinatal, neurodevelopmental, obesity, respiratory, and positive health outcomes) by pooling cohorts composed of >50,000 children in the largest US study of its kind. Our objective was to identify opportunities for studying chemicals and child health using existing or future ECHO chemical exposure data. We described chemical-related information collected by ECHO cohorts and reviewed ECHO-relevant literature on exposure routes, sources, and environmental and human monitoring. Fifty-six ECHO cohorts have existing or planned chemical biomonitoring data for mothers or children. Environmental phenols/parabens, phthalates, metals/metalloids, and tobacco biomarkers are each being measured by ≥15 cohorts, predominantly during pregnancy and childhood, indicating ample opportunities to study child health outcomes. Cohorts are collecting questionnaire data on multiple exposure sources and conducting environmental monitoring including air, dust, and water sample collection that could be used for exposure assessment studies. To supplement existing chemical data, we recommend biomonitoring of emerging chemicals, nontargeted analysis to identify novel chemicals, and expanded measurement of chemicals in alternative biological matrices and dust samples. ECHO’s rich data and samples represent an unprecedented opportunity to accelerate environmental chemical research to improve the health of US children

Elevated circulating MMP-9 is linked to increased COPD exacerbation risk in SPIROMICS and COPDGene

BACKGROUND: Matrix metalloprotease 9 (MMP-9) is associated with inflammation and lung remodeling in chronic obstructive pulmonary disease (COPD). We hypothesized that elevated circulating MMP-9 represents a potentially novel biomarker that identifies a subset of individuals with COPD with an inflammatory phenotype who are at increased risk for acute exacerbation (AECOPD). METHODS: We analyzed Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) and Genetic Epidemiology of COPD (COPDGene) cohorts for which baseline and prospective data were available. Elevated MMP-9 was defined based on >95th percentile plasma values from control (non-COPD) sample in SPIROMICS. COPD subjects were classified as having elevated or nonelevated MMP-9. Logistic, Poisson, and Kaplan-Meier analyses were used to identify associations with prospective AECOPD in both cohorts. RESULTS: Elevated MMP-9 was present in 95/1,053 (9%) of SPIROMICS and 41/140 (29%) of COPDGene participants with COPD. COPD subjects with elevated MMP-9 had a 13%-16% increased absolute risk for AECOPD and a higher median (interquartile range; IQR) annual AECOPD rate (0.33 [0-0.74] versus 0 [0-0.80] events/year and 0.9 [0.5-2] versus 0.5 [0-1.4] events/year for SPIROMICS and COPDGene, respectively). In adjusted models within each cohort, elevated MMP-9 was associated with increased odds (odds ratio [OR], 1.71; 95%CI, 1.00-2.90; and OR, 3.03; 95%CI, 1.02-9.01), frequency (incidence rate ratio [IRR], 1.45; 95%CI, 1.23-1.7; and IRR, 1.24; 95%CI, 1.03-1.49), and shorter time-to-first AECOPD (21.7 versus 31.7 months and 14 versus 21 months) in SPIROMICS and COPDGene, respectively. CONCLUSIONS: Elevated MMP-9 was independently associated with AECOPD risk in 2 well-characterized COPD cohorts. These findings provide evidence for MMP-9 as a prognostic biomarker and potential therapeutic target in COPD. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01969344 (SPIROMICS) and NCT00608764 (COPDGene). FUNDING: This work was funded by K08 HL123940 to JMW; R01HL124233 to PJC; Merit Review I01 CX000911 to JLC; R01 (R01HL102371, R01HL126596) and VA Merit (I01BX001756) to AG. SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) is funded by contracts from the NHLBI (HHSN268200900013C, HHSN268200900014C,HHSN268200900015C HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, and HHSN268200900020C) and a grant from the NIH/NHLBI (U01 HL137880), and supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals Inc.; Chiesi Farmaceutici; Forest Research Institute Inc.; GlaxoSmithKline; Grifols Therapeutics Inc.; Ikaria Inc.; Novartis Pharmaceuticals Corporation; Nycomed GmbH; ProterixBio; Regeneron Pharmaceuticals Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; and Theravance Biopharma and Mylan. COPDGene is funded by the NHLBI (R01 HL089897 and R01 HL089856) and by the COPD Foundation through contributions made to an Industry Advisory Board composed of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion

The effects of rare SERPINA1 variants on lung function and emphysema in SPIROMICS

Rationale: The role of PI (protease inhibitor) type Z heterozygotes and additional rare variant genotypes in the gene encoding alpha-1 antitrypsin, SERPINA1 (serpin peptidase inhibitor, clade A,member 1), in determining chronic obstructive pulmonary disease risk and severity is controversial. Objectives: To comprehensively evaluate the effects of rare SERPINA1 variants on lung function and emphysema phenotypes in subjects with significant tobacco smoke exposure using deep gene resequencing and alpha-1 antitrypsin concentrations. Methods: DNA samples from 1,693 non-Hispanic white individuals, 385 African Americans, and 90 Hispanics with >20 pack-years smoking were resequenced for the identification of rare variants (allele frequency,0.05) in 16.9 kB of SERPINA1. Measurements and Main Results: White PI Z heterozygotes confirmed by sequencing (MZ; n = 74) had lower postbronchodilator FEV1 (P = 0.007), FEV1/FVC (P = 0.003), and greater computed tomography-based emphysema (P = 0.02) compared with 1,411 white individuals without PI Z, S, or additional rare variants denoted as VR. PI Z-containing compound heterozygotes (ZS/ZVR; n = 7) had lower FEV1/FVC (P = 0.02) and forced expiratory flow, midexpiratory phase (P = 0.009). Nineteen white heterozygotes for five non-S/Z coding variants associated with lower alpha-1 antitrypsin had greater computed tomography-based emphysema compared with those without rare variants. In African Americans, a 59 untranslated region insertion (rs568223361) was associated with lower alpha-1 antitrypsin and functional small airway disease (P = 0.007). Conclusions: In this integrative deep sequencing study of SERPINA1 with alpha-1 antitrypsin concentrations in a heavy smoker and chronic obstructive pulmonary disease cohort, we confirmed the effects of PI Z heterozygote and compound heterozygote genotypes. We demonstrate the cumulative effects of multiple SERPINA1 variants on alpha-1 antitrypsin deficiency, lung function, and emphysema, thus significantly increasing the frequency of SERPINA1 variation associated with respiratory disease in at-risk smokers

Project TENDR: Targeting environmental neuro-developmental risks. the TENDR consensus statement

Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Phenology of sunflower cultivars. III. Models for prediction in field environments

Models of the daily rate of development for the stages emergence to head visible and head visible to first anthesis were formed for two sunflower cultivars (Helianthus annuus cvv. Sunfola 68-2 and Hysun 30). The models relate rate of development to photoperiod, daily mean temperature and relative cultivar sensitivity to photoperiod. They were derived from controlled-environment and field studies reported in the first two papers of this series. The two cultivars were found not to differ in sensitivity to temperature. The base temperature for development was found to decrease as the life cycle progressed. The models were validated on an independent data set and are applicable to the entire Australian continent, with one possible limitation on the temperature range at long photoperiods (14-18 h). The relationship of these models to the cultivar groups defined in the first paper of this series is discussed and a rapid method of determining relative cultivar sensitivity factors for new cultivars is outlined. The application of the models in planning for avoidance of frost by selecting the time of planting and the cultivar to be planted was demonstrated for three major sunflower-growing districts in Queensland. The possible use of these phenology models in conjunction with growth simulation models for studies of crop adaptation is discussed

Phenology of sunflower cultivars. I. Classification of responses

The phenology of commercial sunflower cultivars available to Queensland growers in 1979 was studied in monthly plantings over a 12-month period at Toowoomba in southern Queensland. By using pattern analysis procedures, the cultivars were classified into three maturity groups, viz. 'Very Quick', 'Quick' and 'Medium', based on the number of days from emergence to the head-visible stage of growth. Most of the cultivars belonged to the Quick and Medium maturity groups. Cultivar differences were most obvious for plantings in the cooler months (March to October). To classify new releases, one or two plantings during this period as well as one planting in summer is recommended. Sunfola 68-2 and Hysun 30 should be included in these plantings as cultivars representative of the two major maturity groups. The study showed that there was very little genetic variability in phenology in the present commercial cultivars and there was little difference in phenology among cultivars in the main summer planting period