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 (N = 18) or placebo (N = 17) 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, P = 0.70. 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 difference = -4.94%, 95% CI: -15.33 to 5.45, P = 0.34). 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 β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=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 β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 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 $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ 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

AbstractBackgroundChildren 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.MethodsTwelve children with CF (mean±SD; age: 14.7±2.3years, predicted FEV1: 90.0±21.6%) and biological age-matched controls (age: 13.9±2.1years) 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.ResultsAt rest, children with CF had higher concentrations of neutrophils and IL-6 compared with controls. In children with CF, HIIE did not affect immune cell subsets or cytokines: TNF-α, 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.ConclusionsHIIE was a sufficient stimulus to increase GH in children with CF, without affecting systemic inflammation

Percussion Palm Cup: Safety and Usability of Newly Designed Products in Infants and Children with Cystic Fibrosis

Background: Manual percussion is used during airway clearance sessions for children with cystic fibrosis. Use of percussor cups can assist manual chest physiotherapy percussion when the treatment is too taxing, or the adult hand is too large. The Canadian distribution for the usual commercial percussor was recently discontinued. The McMaster Manufacturing Research Institute (MMRI) was approached to produce two percussor cup prototypes as potential alternatives. The objective of this study was to evaluate the useability, satisfaction, preference, and safety of the MMRI percussor cups compared to the Smiths Palm Cup® Percussor. Methods: Participants were allocated to two groups based on age. Order of percussor cup use was randomized; caregivers used each percussor cup for 2 consecutive days. Data collection included: demographics, the Quebec User Evaluation of Satisfaction with assistive Technology 2.0, the Pictorial Single-Item Usability Scale, adverse effect report, overall satisfaction ratings and top percussor cup ranking. Results: Twenty-five caregivers and their children enrolled in and completed the study. The MMRI narrow handle percussor prototype, regardless of cup size, was comparable in usability, safety and effectiveness. This can be a locally sourced, innovative solution in Canada for a pediatric percussor cup. Conclusions: All percussor types were favourably reported across metrics examining usability, safety, and effectiveness, apart from the MMRI small cup, wide handle prototype. Overall, the MMRI wide handle prototype was the least preferred, regardless of cup size, while the MMRI narrow handle prototype was comparable to the Smiths Palm Cup® Percussor across all metrics, regardless of cup size.</jats:p

Reduced fat oxidation rates during submaximal exercise in boys with cystic fibrosis

AbstractBackgroundExercise is a viable form of therapy for children with cystic fibrosis (CF). Understanding the energy sources used during exercise would aid CF patients in obtaining proper nutrition in order to sustain an active lifestyle.MethodsSix boys with CF (mean age±SD: 14.8±2.3yrs, FEV1: 99±18% predicted) and six matched controls (14.0±2.2yrs) completed a session of two 30min bouts of cycling at an intensity set at 50% peak mechanical power. Rates of total fat and carbohydrate (CHO) oxidation were calculated from expired gases. Plasma insulin, glucose and free fatty acid (FFA) were determined before, during and at the end of the exercise.ResultsRates of fat oxidation (expressed in mean mg×kg body weight−1×min−1±SD) were significantly lower in children with CF (5.7±1.6) compared to controls (8.6±1.8, p<0.05). Children with CF also had lower values than controls in amount of fat oxidized (CF: 17.3±5.0g, controls: 26.1±5.9g, p<0.05) and percent of total energy expenditure from fat (CF: 32±6%, controls: 43±7%, p<.0.05), but a higher contribution from CHO (CF: 68±6%, controls: 57±7% p<.0.05). Plasma FFA was significantly lower in children with CF compared to controls during (CF: 252.5±117.9μM, controls: 602.2±295.6) and at the end of exercise (CF: 430.9±180.6, controls: 1147.5±473.5). There were no differences in the rates of CHO oxidation, insulin or glucose between groups.ConclusionFat metabolism during exercise is impaired in boys with CF and may be attributed to an inability to mobilize FFA