The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.
We hypothesized a novel computed tomography (CT) ...biomarker of small airway disease predicts FEV1 decline.
We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRM(emph)) and functional small airways disease (PRM(fSAD)), a measure of nonemphysematous air trapping.
Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P < 0.001). In multivariable linear regression, for participants without airflow obstruction, PRM(fSAD) but not PRM(emph) was associated with FEV1 decline (P < 0.001). In GOLD 1-4 participants, both PRM(fSAD) and PRM(emph) were associated with FEV1 decline (P < 0.001 and P = 0.001, respectively). Based on the model, the proportional contribution of the two CT metrics to FEV1 decline, relative to each other, was 87% versus 13% and 68% versus 32% for PRM(fSAD) and PRM(emph) in GOLD 1/2 and 3/4, respectively.
CT-assessed functional small airway disease and emphysema are associated with FEV1 decline, but the association with functional small airway disease has greatest importance in mild-to-moderate stage chronic obstructive pulmonary disease where the rate of FEV1 decline is the greatest. Clinical trial registered with www.clinicaltrials.gov (NCT 00608764).
We present direct evidence for complex p-wave order parameter symmetry and the presence of dynamical chiral order parameter domains of the form px +/- ipy in the ruthenate superconductor Sr2RuO4. The ...domain structure creates differences in the magnetic field modulation of the critical current of Josephson junctions fabricated on orthogonal faces of Sr2RuO4 single crystals. Transitions between the chiral states of a domain or the motion of domain walls separating them generates telegraph noise in the critical current as a function of magnetic field or time and is responsible for hysteresis observed in field sweeps of the critical current. The presence of such domains confirms the p-wave triplet spin and complex (broken time-reversal symmetry) nature of the superconducting pairing state in Sr2RuO4.
Order parameter symmetry is one of the basic characteristics of a superconductor. The heavy fermion compound UPt3 provides a rich system for studying the competition between superconductivity and ...other forms of electronic order and exhibits two distinct superconducting phases that are characterized by different symmetries. We fabricated a series of Josephson tunnel junctions on the as-grown surfaces of UPt3 single crystals spanning the a-b plane. By measuring their critical current, we mapped out the magnitude of the superconducting order parameter as a function of the momentum-space direction and temperature. In the high-temperature phase, we observed a sharp node in the superconducting gap at 45 degrees with respect to the a axis; an out-of-phase component appeared in the low-temperature phase, creating a complex order parameter.
Abstract
Atlantic salmon is an economically and culturally important species. The species encounters several natural and man-made threats during its migration between fresh water and the ocean, which ...in combination may explain its ongoing decline. With the aim to better understand whether post-smolt behaviour is influenced by physical oceanographic conditions, the migratory behaviour of 173 post-smolts in a high-latitude Norwegian fjord was investigated, combining acoustic telemetry with site- and time-specific environmental variables from an oceanographic model. Most post-smolts (94%) performed a unidirectional migration out the fjord. Progression rates were relatively high (0.42–2.41 km h−1; 0.84–3.78 BL s−1) and increased with distance from the river. While post-smolts had an affinity for lower salinities in the inner fjord, statistical models failed to detect any significant relationship between the small-scale (within arrays) migratory behaviour and salinity, temperature, or coastal surface currents within the fjord. In the outer part, the post-smolts predominantly exited the fjord system through the strait with the highest surface salinities and lowest temperatures, independently of the current direction. Our findings indicate that the macro-habitat selection of the Atlantic salmon post-smolts was influenced by environmental factors: the post-smolts directed their migration towards “ocean cues.” However, this was not confirmed on the micro-habitat level.
► Identifying genetic markers for yield requires rapid quantification of crop traits. ► Proximal sensing offers promise for field-based phenotyping (FBP). ► Efficient data integration and ...modeling-assisted analysis are key for FBP. ► FBP scaled to thousands of field plots is a feasible, attainable goal. ► FBP systems require new, integrative collaborations that cross disciplines.
A major challenge for crop research in the 21st century is how to predict crop performance as a function of genetic architecture. Advances in “next generation” DNA sequencing have greatly improved genotyping efficiency and reduced genotyping costs. Methods for characterizing plant traits (phenotypes), however, have much progressed more slowly over the past 30 years, and constraints in phenotyping capability limit our ability to dissect the genetics of quantitative traits, especially those related to harvestable yield and stress tolerance. As a case in point, mapping populations for major crops may consist of 20 or more families, each represented by as many as 200 lines, necessitating field trials with over 20,000 plots at a single location. Investing in the resources and labor needed to quantify even a few agronomic traits for linkage with genetic markers in such massive populations is currently impractical for most breeding programs. Herein, we define key criteria, experimental approaches, equipment and data analysis tools required for robust, high-throughput field-based phenotyping (FBP). The focus is on simultaneous proximal sensing for spectral reflectance, canopy temperature, and plant architecture where a vehicle carrying replicated sets of sensors records data on multiple plots, with the potential to record data throughout the crop life cycle. The potential to assess traits, such as adaptations to water deficits or acute heat stress, several times during a single diurnal cycle is especially valuable for quantifying stress recovery. Simulation modeling and related tools can help estimate physiological traits such as canopy conductance and rooting capacity. Many of the underlying techniques and requisite instruments are available and in use for precision crop management. Further innovations are required to better integrate the functions of multiple instruments and to ensure efficient, robust analysis of the large volumes of data that are anticipated. A complement to the core proximal sensing is high-throughput phenotyping of specific traits such as nutrient status, seed composition, and other biochemical characteristics, as well as underground root architecture. The ability to “ground truth” results with conventional measurements is also necessary. The development of new sensors and imaging systems undoubtedly will continue to improve our ability to phenotype very large experiments or breeding nurseries, with the core FBP abilities achievable through strong interdisciplinary efforts that assemble and adapt existing technologies in novel ways.
Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on ...outcomes of the type, number, and duration of drugs used to treat MDR-TB.
Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio aOR: 2.5 95% CI 1.1-6.0), ofloxacin (aOR: 2.5 1.6-3.9), ethionamide or prothionamide (aOR: 1.7 1.3-2.3), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 1.3-3.9), and three or more likely effective drugs in the continuation phase (aOR: 2.7 1.7-4.1). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 1.7-4.3), ofloxacin (aOR: 2.3 1.3-3.8), ethionamide or prothionamide (aOR: 1.7 1.4-2.1), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 1.9-3.9), and three or more likely effective drugs in the continuation phase (aOR: 4.5 3.4-6.0).
In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study compared the severity of intimate partner violence (IPV) and the relationship between risk factors for IPV and overall risk judgments of future IPV in urban, rural, and remote areas. IPV ...risk assessments conducted by the Swedish police between 2010 and 2014 in urban (n = 564), rural (n = 456), and remote (n = 196) areas were examined. Rurality was associated with the severity of IPV reported, as well as the presence of risk factors and their relationship to overall risk judgments. Cases in remote areas included more severe IPV as well as more risk factors.
BACKGROUND The usual interstitial pneumonia (UIP) pattern of lung injury may occur in the setting of connective tissue disease (CTD), but it is most commonly found in the absence of a known cause, in ...the clinical context of idiopathic pulmonary fibrosis (IPF). Our objective was to observe and compare longitudinal changes in pulmonary function and survival between patients with biopsy-proven UIP found in the clinical context of either CTD or IPF. METHODS We used longitudinal data analytic models to compare groups (IPF n = 321 and CTD-UIP n = 56) on % predicted FVC (FVC %) or % predicted diffusing capacity of the lung for carbon monoxide (Dlco%), and we used both unadjusted and multivariable techniques to compare survival between these groups. RESULTS There were no significant differences between groups in longitudinal changes in FVC % or Dlco% up to diagnosis, or from diagnosis to 10 years beyond (over which time, the mean decrease in FVC % per year 95% CI was 4.1 3.4, 4.9 for IPF and 3.5 1.8, 5.1 for CTD-UIP, P = .49 for difference; and the mean decrease in Dlco% per year was 4.7 4.0, 5.3 for IPF and 4.3 3.0, 5.6 for CTD-UIP, P = .60 for difference). Despite the lack of differences in pulmonary function, subjects with IPF had worse survival in unadjusted (log-rank P = .003) and certain multivariable analyses. CONCLUSIONS Despite no significant differences in changes in pulmonary function over time, patients with CTD-UIP (at least those with certain classifiable CTDs) live longer than patients with IPF—an observation that we suspect is due to an increased rate of mortal acute exacerbations in patients with IPF.
Activation of the steroidogenic enzyme CYP11A1 was shown to be necessary for the development of peanut-induced intestinal anaphylaxis and IL-13 production in allergic mice. We determined if levels of ...CYP11A1 in peripheral blood T cells from peanut-allergic (PA) children compared to non-allergic controls were increased and if levels correlated to IL-13 production and oral challenge outcomes to peanut. CYP11A1 mRNA and protein levels were significantly increased in activated CD4.sup.+ T cells from PA patients. In parallel, IL-13 production was significantly increased; IFNgamma levels were not different between groups. There were significant correlations between expression levels of CYP11A1 mRNA and levels of IL13 mRNA and protein, levels of serum IgE anti-Ara h 2 and to outcomes of peanut challenge. The importance of CYP11A1 on cytokine production was tested using a CYP11A1 CRISPR/Cas9 KO plasmid or an inhibitor of enzymatic CYP11A1 activity. Inhibition of CYP11A1 activation in patient cells treated with the inhibitor, aminoglutethimide, or CD4.sup.+ T cell line transfected with the CYP11A1 KO plasmid resulted in reduced IL-13 production. These data suggest that the CYP11A1-CD4.sup.+ Tcell-IL-13 axis in activated CD4.sup.+ T cells from PA children is associated with development of PA reactions. CYP11A1 may represent a novel target for therapeutic intervention in PA children.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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