27 research outputs found
Treatment of Aspergillus fumigatus in Patients with Cystic Fibrosis: A Randomized, Placebo-Controlled Pilot Study
Many patients with cystic fibrosis develop persistent airway infection/colonization with Aspergillus fumigatus, however the impact of A. fumigatus on clinical outcomes remains unclear. The objective of this study was to determine whether treatment directed against Aspergillus fumigatus improves pulmonary function and clinical outcomes in patients with cystic fibrosis (CF).We performed a double-blind randomized placebo-controlled pilot clinical trial involving 35 patients with CF whose sputum cultures were chronically positive for A. fumigatus. Participants were centrally randomized to receive either oral itraconazole 5 mg/kg/d (Nâ=â18) or placebo (Nâ=â17) for 24 weeks. The primary outcome was the proportion of patients who experienced a respiratory exacerbation requiring intravenous antibiotics over the 24 week treatment period. Secondary outcomes included changes in FEV(1) and quality of life.Over the 24 week treatment period, 4 of 18 (22%) patients randomized to itraconazole experienced a respiratory exacerbation requiring intravenous antibiotics, compared to 5 of 16 (31%) placebo treated patients, Pâ=â0.70. FEV(1) declined by 4.62% over 24 weeks in the patients randomized to itraconazole, compared to a 0.32% improvement in the placebo group (between group differenceâ=â-4.94%, 95% CI: -15.33 to 5.45, Pâ=â0.34). Quality of life did not differ between the 2 treatment groups throughout the study. Therapeutic itraconazole blood levels were not achieved in 43% of patients randomized to itraconazole.We did not identify clinical benefit from itraconazole treatment for CF patients whose sputum was chronically colonized with A. fumigatus. Limitations of this pilot study were its small sample size, and failure to achieve therapeutic levels of itraconazole in many patients.ClinicalTrials.gov NCT00528190
A many-analysts approach to the relation between religiosity and well-being
The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported ÎČ=0.120). For the second research question, this was the case for 65% of the teams (median reported ÎČ=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates
A Many-analysts Approach to the Relation Between Religiosity and Well-being
The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported ÎČ = 0.120). For the second research question, this was the case for 65% of the teams (median reported ÎČ = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates
The Science Performance of JWST as Characterized in Commissioning
This paper characterizes the actual science performance of the James Webb
Space Telescope (JWST), as determined from the six month commissioning period.
We summarize the performance of the spacecraft, telescope, science instruments,
and ground system, with an emphasis on differences from pre-launch
expectations. Commissioning has made clear that JWST is fully capable of
achieving the discoveries for which it was built. Moreover, almost across the
board, the science performance of JWST is better than expected; in most cases,
JWST will go deeper faster than expected. The telescope and instrument suite
have demonstrated the sensitivity, stability, image quality, and spectral range
that are necessary to transform our understanding of the cosmos through
observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures;
https://iopscience.iop.org/article/10.1088/1538-3873/acb29
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Inflammatory and growth factor response to continuous and intermittent exercise in youth with cystic fibrosis
Background: Children with cystic fibrosis (CF) tend to suffer from chronic systemic inflammation and may have impaired growth associated with muscle catabolism. Therefore, investigating which type of exercise can elicit an anabolic response with minimal inflammation is of clinical value. Methods: Twelve children with CF (mean +/- SD; age: 14.7 +/- 2.3 years, predicted FEV1: 90.0 +/- 21.6%) and biological age-matched controls (age: 13.9 +/- 2.1 years) completed moderate-intensity, continuous exercise (MICE) and high-intensity, intermittent exercise (HIIE) on separate days. During each exercise, blood was drawn at various time points and analyzed for immune cells, inflammatory cytokines, and growth mediators. Results: At rest, children with CF had higher concentrations of neutrophils and IL-6 compared with controls. In children with CF, HUE did not affect immune cell subsets or cytokines: TNF-alpha, IL-6, and tumor necrosis factor-like weak inducer of apoptosis (TWEAK). All immune cell subsets and IL-6 increased significantly with MICE in both groups. Growth hormone (GH) increased with both types of exercise, with a greater change from rest during MICE. Conclusions: HIIE was a sufficient stimulus to increase OH in children with CF, without affecting systemic inflammation. (C) 2011 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved
The Sweat Metabolome of Screen-Positive Cystic Fibrosis Infants: Revealing Mechanisms beyond Impaired Chloride Transport
The sweat chloride test remains the
gold standard for confirmatory
diagnosis of cystic fibrosis (CF) in support of universal newborn
screening programs. However, it provides ambiguous results for intermediate
sweat chloride cases while not reflecting disease progression when
classifying the complex CF disease spectrum given the pleiotropic
effects of gene modifiers and environment. Herein we report the first
characterization of the sweat metabolome from screen-positive CF infants
and identify metabolites associated with disease status that complement
sweat chloride testing. Pilocarpine-stimulated sweat specimens were
collected independently from two CF clinics, including 50 unaffected
infants (e.g., carriers) and 18 confirmed CF cases. Nontargeted metabolite
profiling was performed using multisegment injectionâcapillary
electrophoresisâmass spectrometry as a high throughput platform
for analysis of polar/ionic metabolites in volume-restricted sweat
samples. Amino acids, organic acids, amino acid derivatives, dipeptides,
purine derivatives, and unknown exogenous compounds were identified
in sweat when using high resolution tandem mass spectrometry, including
metabolites associated with affected yet asymptomatic CF infants,
such as asparagine and glutamine. Unexpectedly, a metabolite of pilocarpine,
used to stimulate sweat secretion, pilocarpic acid, and a plasticizer
metabolite from environmental exposure, monoÂ(2-ethylhexyl)Âphthalic
acid, were secreted in the sweat of CF infants at significantly lower
concentrations relative to unaffected CF screen-positive controls.
These results indicated a deficiency in human paraoxonase, an enzyme
unrelated to mutations to the cystic fibrosis transmembrane conductance
regulator (CFTR) and impaired chloride transport, which is a nonspecific
arylesterase/lactonase known to mediate inflammation, bacterial biofilm
formation, and recurrent lung infections in affected CF children later
in life. This work sheds new light into the underlying mechanisms
of CF pathophysiology as required for new advances in precision medicine
of orphan diseases that benefit from early detection and intervention,
including new molecular targets for therapeutic intervention
Sedentary Time and Screen-Based Sedentary Behaviors of Children With a Chronic Disease
The objectives of this study were to (i) assess sedentary time and prevalence of screen-based sedentary behaviors of children with a chronic disease and (ii) compare sedentary time and prevalence of screen-based sedentary behaviors to age- and sex-matched healthy controls. Sixty-five children (aged 6-18 years) with a chronic disease participated: survivors of a brain tumor, hemophilia, type 1 diabetes mellitus, juvenile idiopathic arthritis, cystic fibrosis, and Crohn's disease. Twenty-nine of these participants were compared with age- and sex-matched healthy controls. Sedentary time was measured objectively by an ActiGraph GT1M or GT3x accelerometer worn for 7 consecutive days and defined as less than 100 counts per min. A questionnaire was used to assess screen-based sedentary behaviors. Children with a chronic disease engaged in an average of 10.2 +/- 1.4 hr of sedentary time per day, which comprised 76.5 +/- 7.1% of average daily monitoring time. There were no differences between children with a chronic disease and controls in sedentary time (adjusted for wear time, p = .06) or in the prevalence of TV watching, and computer or video game usage for varying durations (p = .78, p = .39 and, p = .32 respectively). Children with a chronic disease, though relatively healthy, accumulate high levels of sedentary time, similar to those of their healthy peer
Time to First Pulmonary Exacerbation Requiring Oral or Intravenous Antibiotics.
<p>Blue dashed line = placebo-treated patients. Black solid lineâ=âitraconazole-treated patients. The median time to first exacerbation was 77 days for the itraconazole group and 134 days for the placebo group, log-rank Pâ=â0.35. Hash marksâ=âcensored observations.</p