The clinical utility of lung clearance index in early cystic fibrosis lung disease is not impacted by the number of multiple-breath washout trials

© ERS 2018. The lung clearance index (LCI) from the multiple-breath washout (MBW) test is a promising surveillance tool for pre-school children with cystic fibrosis (CF). Current guidelines for MBW testing recommend that three acceptable trials are required. However, success rates to achieve these criteria are low in children aged < 7 years and feasibility may improve with modified pre-school criteria that accepts tests with two acceptable trials. This study aimed to determine if relationships between LCI and clinical outcomes of CF lung disease differ when only two acceptable MBW trials are assessed. Healthy children and children with CF aged 3–6 years were recruited for MBW testing. Children with CF also underwent bronchoalveolar lavage fluid collection and a chest computed tomography scan. MBW feasibility increased from 46% to 75% when tests with two trials were deemed acceptable compared with tests where three acceptable trials were required. Relationships between MBW outcomes and markers of pulmonary inflammation, infection and structural lung disease were not different between tests with three acceptable trials compared with tests with two acceptable trials. This study indicates that pre-school MBW data from two acceptable trials may provide sufficient information on ventilation distribution if three acceptable trials are not possible

Natural history of HFE simple heterozygosity for C282Y and H63D: A prospective 12-year study

Background and Aim - The risk of hemochromatosis-related morbidity for HFE simple heterozygosity for either the C282Y or H63D substitutions in the HFE protein was assessed using a prospective community-based cohort study. Methods - HFE genotypes were measured for 31 192 persons of northern European descent, aged between 40 and 69 years when recruited to the Melbourne Collaborative Cohort Study, and subjects were followed for an average of 12 years. For a random sample of 1438 participants stratified according to HFE genotype, two sets of biochemical iron indices performed 12 years apart and, at follow-up only, the presence/absence of six disease features associated with hereditary hemochromatosis were obtained. Summary data for 257 (139 female) C282Y simple heterozygotes and 123 (74 female) H63D simple heterozygotes were compared with 330 (181 female) controls with neither HFE mutation. Results - At baseline, mean transferrin saturation (TS) (95% confidence interval) and prevalence of TS > 55% were 35.14% (33.25, 37.04) and 3/112 (3%), 33.03% (29.9, 36.15) and 0/39 (0%), and 29.67% (27.93, 31.4) and 3/135 (2%) for C282Y, H63D and wild-type male participants, respectively. At follow-up, mean TS levels remained similar to baseline levels for both men and women irrespective of simple heterozygosity for either mutation. No HFE C282Y or H63D simple heterozygotes had documented iron overload (based on hepatic iron measures or serum ferritin greater than 1000 mg/L at baseline with documented therapeutic venesection). Conclusion - No documented iron overload was observed for HFE simple heterozygotes for either C282Y or H63D, and morbidity for both HFE simple heterozygote groups was similar to that of HFE wild-type participants

Rose Bengal sensitized bilayered photoanode of nano-crystalline TiO–CeO for dye-sensitized solar cell application

There are two traditional ways to read Kant’s claim that every event necessarily has a cause: the weaker every-event some-cause (WCP) and the stronger same-cause same-effect (SCP) causal principles. The debate on whether and where he subscribes to the SCP has focused on the Analogies in the Critique of Pure Reason (Guyer, Allison, and Watkins) and on the Metaphysical Foundations of Natural Science (Friedman). By analysing the arguments and conclusions of both the Analogies and the Postulates, as well as the two Latin principles non datur casus and non datur fatum that summarise their results, I will argue that the SCP is actually demonstrated in the Postulates section of the First Critique

Consensus statement for stability assessment and reporting for perovskite photovoltaics based on ISOS procedures

Funder: 2017 SGR 329 Severo Ochoa program from Spanish MINECO (Grant No. SEV-2017-0706)Funder: This article is based upon work from COST Action StableNextSol MP1307 supported by COST (European Cooperation in Science and Technology). M. V. K., E. A. K., V. B., and A. Osherov thank the financial support of the United States – Israel Binational Science Foundation (grant no. 2015757). E. A. K., A. A., and I. V.-F. acknowledge a partial support from the SNaPSHoTs project in the framework of the German-Israeli bilateral R&D cooperation in the field of applied nanotechnology. M. S. L. thanks the financial support of NSF (ECCS, award #1610833). S. C., M. Manceau and M. Matheron thank the financial support of European Union’s Horizon 2020 research and innovation programme under grant agreement No 763989 (APOLO project). F. De R. and T. M. W. would like to acknowledge the support from the Engineering and Physical Sciences Research Council (EPSRC) through the SPECIFIC Innovation and Knowledge Centre (EP/N020863/1) and express their gratitude to the Welsh Government for their support of the Ser Solar programme. P. A. T. acknowledges financial support from Russian Science Foundation (project No. 19-73-30020). J.K. acknowledges the support by the Solar Photovoltaic Academic Research Consortium II (SPARC II) project, gratefully funded by WEFO. M.K.N. acknowledges financial support from Innosuisse project 25590.1 PFNM-NM, Solaronix, Aubonne, Switzerland. C.-Q. M. would like to acknowledge The Bureau of International Cooperation of Chinese Academy of Sciences for the support of ISOS11 and the Ministry of Science and Technology of China for the financial support (No 2016YFA0200700). N.G.P. acknowledges financial support from the National Research Foundation of Korea (NRF) grants funded by the Ministry of Science, ICT Future Planning (MSIP) of Korea under contracts NRF-2012M3A6A7054861 and NRF-2014M3A6A7060583 (Global Frontier R&D Program on Center for Multiscale Energy System). CSIRO’s contribution to this work was conducted with funding support from the Australian Renewable Energy Agency (ARENA) through its Advancing Renewables Program. A. F. N gratefully acknowledges support from FAPESP (Grant 2017/11986-5) and Shell and the strategic importance of the support given by ANP (Brazil’s National Oil, Natural Gas and Biofuels Agency) through the R&D levy regulation. Y.-L.L. and Q.B. acknowledge support from the National Science Foundation Division of Civil, Mechanical and Manufacturing Innovation under award #1824674. S.D.S. acknowledges the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (HYPERION, grant agreement No. 756962), and the Royal Society and Tata Group (UF150033). The work at the National Renewable Energy Laboratory was supported by the U.S. Department of Energy (DOE) under contract DE-AC36-08GO28308 with Alliance for Sustainable Energy LLC, the manager and operator of the National Renewable Energy Laboratory. The authors (J.J.B, J.M.L., M.O.R, K.Z.) acknowledge support from the De-risking halide perovskite solar cells program of the National Center for Photovoltaics, funded by the U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy, Solar Energy Technology Office. The views expressed in the article do not necessarily represent the views of the DOE or the U.S. Government. The U.S. Government retains and the publisher, by accepting the article for publication, acknowledges that the U.S. Government retains a nonexclusive, paid-up, irrevocable, worldwide license to publish or reproduce the published form of this work, or allow others to do so, for U.S. Government purposes. H.J.S. acknowledges the support of EPSRC UK, Engineering and Physical Sciences Research Council. V.T. and M. Madsen acknowledges ‘Villum Foundation’ for funding of the project CompliantPV, under project number 13365. M. Madsen acknowledges Danmarks Frie Forskningsfond, DFF FTP for funding of the project React-PV, No. 8022-00389B. M.G. and S.M.Z. thank the King Abdulaziz City for Science and technology (KACST) for financial support. S.V. acknowledges TKI-UE/Ministry of Economic Affairs for financial support of the TKI-UE toeslag project POP-ART (No. 1621103). M.L.C. and H.X. acknowledges the support from Spanish MINECO for the grant GraPErOs (ENE2016-79282-C5-2-R), the OrgEnergy Excellence Network CTQ2016-81911- REDT, the Agència de Gestiód'Ajuts Universitaris i de Recerca (AGAUR) for the support to the consolidated Catalonia research group 2017 SGR 329 and the Xarxa de Referència en Materials Avançats per a l'Energia (Xarmae). ICN2 is supported by the Severo Ochoa program from Spanish MINECO (Grant No. SEV-2017-0706) and is funded by the CERCA Programme / Generalitat de Catalunya.Abstract: Improving the long-term stability of perovskite solar cells is critical to the deployment of this technology. Despite the great emphasis laid on stability-related investigations, publications lack consistency in experimental procedures and parameters reported. It is therefore challenging to reproduce and compare results and thereby develop a deep understanding of degradation mechanisms. Here, we report a consensus between researchers in the field on procedures for testing perovskite solar cell stability, which are based on the International Summit on Organic Photovoltaic Stability (ISOS) protocols. We propose additional procedures to account for properties specific to PSCs such as ion redistribution under electric fields, reversible degradation and to distinguish ambient-induced degradation from other stress factors. These protocols are not intended as a replacement of the existing qualification standards, but rather they aim to unify the stability assessment and to understand failure modes. Finally, we identify key procedural information which we suggest reporting in publications to improve reproducibility and enable large data set analysis

Lung function trajectories throughout childhood in survivors of very preterm birth: a longitudinal cohort study

© 2018 Elsevier Ltd. Background: Data on longitudinal respiratory follow-up after preterm birth in the surfactant era are scarce and of increasing importance, with concerns that preterm survivors are destined for early onset chronic obstructive airway disease. We aimed to comprehensively assess lung function longitudinally from early childhood to mid-childhood in very preterm children (=32 weeks gestation), and to explore factors negatively impacting on lung function trajectories. Methods: Preterm children (with and without bronchopulmonary dysplasia) and healthy term children as controls were studied. All preterm participants were born at 32 weeks' gestation or earlier at King Edward Memorial Hospital, Perth, WA, Australia, between 1997 and 2003. Bronchopulmonary dysplasia was defined as at least 28 days of supplemental oxygen requirement as assessed at 36 weeks' post-menstrual age. Spirometry, oscillatory mechanics, gas exchange, lung volumes, and respiratory symptoms were assessed at three visits, two in early childhood (4–8 years) and one in mid-childhood (9–12 years). CT of the chest was done in preterm children in mid-childhood. Respiratory symptoms were documented via questionnaire at each visit. Data were analysed longitudinally using linear mixed models. Findings: 200 very preterm children (126 with bronchopulmonary dysplasia and 74 without bronchopulmonary dysplasia) and 67 healthy term control children attended 458 visits between age 4 and 12 years. Chest CT was done on 133 preterm children at a mean age of 10·9 (SD 0·6) years. Preterm children, with and without bronchopulmonary dysplasia, had declines in spirometry z-scores over time compared with controls: forced expiratory volume in 1 s (FEV 1 ), forced expiratory flow at 25–75% of the pulmonary volume, and FEV 1 /forced vital capacity all declined by at least 0·1 z-score per year in children with bronchopulmonary dysplasia (all p < 0·001). Respiratory mechanics and gas exchange also deteriorated over time in children with bronchopulmonary dysplasia (relative to term controls, respiratory system reactance at 8 Hz decreased by -0·05 z-score per year [95% CI -0·08 to -0·01; p=0·006] and diffusing capacity of the lungs for carbon monoxide decreased by -0·03 z-score per year [95% CI -0·06 to -0·01; p=0·048] ). Preterm children with bronchial wall thickening on chest CT (suggestive of inflammation) had bigger decreases in spirometry outcomes through childhood. For example, children with bronchial wall thickening on chest CT had an FEV 1 z-score decline of -0·61 (95% CI -1·03 to–0·19; p=0·005) more than those without. Similarly, children exposed to tobacco smoke, those with earlier gestation, or those requiring more neonatal supplemental oxygen declined at a faster rate. Interpretation: Lung function trajectories are impaired in survivors of very preterm birth. Survivors with bronchopulmonary dysplasia, ongoing respiratory symptoms, or CT changes reflecting inflammation have the poorest trajectories and might be at increased risk of lung disease in later life. Close targeted pulmonary follow-up of these individuals is necessary

Lung clearance index and structural lung disease on computed tomography in early cystic fibrosis

Rationale: The lung clearance index is a measure of ventilation distribution derived from the multiple-breath washout technique. It has been suggested as a surrogate for chest computed tomography to detect structural lung abnormalities in individuals with cystic fibrosis (CF); however, the associations between lung clearance index and early structural lung disease are unclear. Objectives: We assessed the ability of the lung clearance index to reflect structural lung disease on the basis of chest computed tomography across the entire pediatric age range. Methods: Lung clearance index was assessed in 42 infants (ages 0–2 yr), 39 preschool children (ages 3–6 yr), and 38 school-age children (7–16 yr) with CF before chest computed tomography and in 72 healthy control subjects. Scans were evaluated for CF-related structural lung disease using the Perth-Rotterdam Annotated Grid Morphometric Analysis for Cystic Fibrosis quantitative outcome measure. Measurements and Main Results: In infants with CF, lung clearance index is insensitive to structural disease (κ = −0.03 [95% confidence interval, −0.05 to 0.16]). In preschool children with CF, lung clearance index correlates with total disease extent. In school-age children, lung clearance index correlates with extent of total disease, bronchiectasis, and air trapping. In preschool and school-age children, lung clearance index has a good positive predictive value (83–86%) but a poor negative predictive value (50–55%) to detect the presence of bronchiectasis. Conclusions: These data suggest that lung clearance index may be a useful surveillance tool to monitor structural lung disease in preschool and school-age children with CF. However, lung clearance index cannot replace chest computed tomography to screen for bronchiectasis in this population