Oral cysteamine as an adjunct treatment in cystic fibrosis pulmonary exacerbations: An exploratory randomized clinical trial

Background Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? Methods and findings Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire–Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. Conclusion In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. Clinical trial registration NCT03000348; www.clinicaltrials.gov

Numerical Weather Prediction (NWP) and hybrid ARMA/ANN model to predict global radiation

We propose in this paper an original technique to predict global radiation using a hybrid ARMA/ANN model and data issued from a numerical weather prediction model (ALADIN). We particularly look at the Multi-Layer Perceptron. After optimizing our architecture with ALADIN and endogenous data previously made stationary and using an innovative pre-input layer selection method, we combined it to an ARMA model from a rule based on the analysis of hourly data series. This model has been used to forecast the hourly global radiation for five places in Mediterranean area. Our technique outperforms classical models for all the places. The nRMSE for our hybrid model ANN/ARMA is 14.9% compared to 26.2% for the na\"ive persistence predictor. Note that in the stand alone ANN case the nRMSE is 18.4%. Finally, in order to discuss the reliability of the forecaster outputs, a complementary study concerning the confidence interval of each prediction is proposedComment: Energy (2012)

Visual impairment and the useful field of vision

The aim of this study was to measure the useful field of vision (UFoV) in people with visual impairment and to compare results with clinical measures of vision. UFoV, visual acuity, contrast sensitivity and visual fields were measured in 36 participants with low vision and 22 age-matched controls in two age groups. For both the low vision and control groups the presence of distractors (cluttered field) increased the error rates on our UFoV measure but there was no significant effect of the presence of a central task (divided attention). Participants with low vision made more errors on UFoV than did controls, but this difference disappeared once their visual field defects were accounted for. By multiple regression analysis, age, visual fields and contrast sensitivity were shown to predict the different UFoV scores. As for observers with normal vision, standard clinical visual field tests may not fully describe the difficulties that may be encountered by people with visual impairment undertaking tasks in the cluttered environments and multiple demands of everday life