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[...]the CF STORM trial (ISRCTN14081521), embedded within the UK CF Registry, will use a randomised controlled open-label design to explore the reduction of nebulised mucoactive therapies after commencement of elexacaftor–tezacaftor–ivacaftor. [...]the results of such trials can provide guidance, the large burden of chronic CF treatments will remain for many. [...]not all people with CF will qualify for potent modulator therapy, experience similar benefits or indeed tolerate therapy. [...]the need to address adherence to treatment will remain an important issue in CF. [...]the study highlights the importance of a well-informed, comprehensive approach to overcoming barriers to adherence.

Human metabolism involves thousands of reactions and metabolites. To interpret this complexity, computational modeling becomes an essential experimental tool. One of the most popular techniques to study human metabolism as a whole is genome scale modeling. A key challenge to applying genome scale modeling is identifying critical metabolic reactions across diverse human tissues. Here we introduce a novel algorithm called Cost Optimization Reaction Dependency Assessment (CORDA) to build genome scale models in a tissue-specific manner. CORDA performs more efficiently computationally, shows better agreement to experimental data, and displays better model functionality and capacity when compared to previous algorithms. CORDA also returns reaction associations that can greatly assist in any manual curation to be performed following the automated reconstruction process. Using CORDA, we developed a library of 76 healthy and 20 cancer tissue-specific reconstructions. These reconstructions identified which metabolic pathways are shared across diverse human tissues. Moreover, we identified changes in reactions and pathways that are differentially included and present different capacity profiles in cancer compared to healthy tissues, including up-regulation of folate metabolism, the down-regulation of thiamine metabolism, and tight regulation of oxidative phosphorylation.

Surfactant, which was first identified in the 1920s, is pivotal to lower the surface tension in alveoli of the lungs and helps to lower the work of breathing and prevents atelectasis. Surfactant proteins, such as surfactant protein B and surfactant protein C, contribute to function and stability of surfactant film. Additionally, adenosine triphosphate binding cassette 3 and thyroid transcription factor-1 are also integral for the normal structure and functioning of pulmonary surfactant. Through the study and improved understanding of surfactant over the decades, there is increasing interest into the study of childhood interstitial lung diseases (chILD) in the context of surfactant protein disorders. Surfactant protein deficiency syndrome (SPDS) is a group of rare diseases within the chILD group that is caused by genetic mutations of SFTPB, SFTPC, ABCA3 and TTF1 genes.Conclusion: This review article seeks to provide an overview of surfactant protein disorders in the context of chILD. What is Known:• Surfactant protein disorders are an extremely rare group of disorders caused by genetic mutations of SFTPB, SPTPC, ABCA3 and TTF1 genes.• Given its rarity, research is only beginning to unmask the pathophysiology, inheritance, spectrum of disease and its manifestations.What is New:• Diagnostic and treatment options continue to be explored and evolve in these conditions.• It is, therefore, imperative that we as paediatricians are abreast with current development in this field.

Modulation of airway surface liquid (ASL) pH has been proposed as a therapy for cystic fibrosis (CF). However, evidence that ASL pH is reduced in CF is limited and conflicting. The technical challenges associated with measuring ASL pH in vivo have precluded accurate measurements in humans. In order to address this deficiency, ASL pH was measured in vivo in children using a novel luminescent technology integrated with fibre-optic probes. Here we show that ASL pH in children with CF is similar to that of children without CF. Findings were supported by highly controlled direct pH measurements in primary human airway epithelial cell culture models, which also suggest that the potential ASL pH gradient produced by defective apical ion transport is balanced out by paracellular shunting of acid/base. Thus, reduced baseline ASL pH is unlikely to be an important pathobiological factor in early CF lung disease. Modulation of airway surface liquid pH has been proposed as a therapy for cystic fibrosis, but whether pH is indeed altered in cystic fibrosis is controversial. Here, the authors develop a novel fibre-optic based pH measurement technology, and show that pH is not altered in children with cystic fibrosis.

The purpose of this paper is to highlight a perspective for decolonizing research with Australian First Nations and provide a framework for successful and sustained knowledge translation by drawing on the recent work conducted by a research group, in five remote communities in North-Western Australia. The perspective is discussed in light of national and international calls for meaningful and dedicated engagement with First Nations people in research, policy and practice, to help close the health gap between First Nations and other Australians.

[...]the risk of serious azithromycin-related side effects appears to be low even when azithromycin is used for extended periods. [...]despite the widespread use of regular upper airway sampling for microbial surveillance in young children with CF, there is no obvious reason why the presence of P. aeruginosa in the upper airway should affect the occurrence of pulmonary exacerbations. [...]although the evidence in favor of long-term azithromycin use in children with CF is accumulating, concerns remain.

The continued faster rates of improvement in lung function and nutritional outcomes in the United States compared with Canada were thought to be partly attributable to newborn screening, which was implemented earlier in some American states, and also partly to major U.S. CFF-driven clinical care quality improvement programs that included leadership development, identification of best CF care practices, and working with individuals with CF and their families on the quality improvement process (4, 5).The more modest gains seen in older individuals should be a motivation to improve healthcare access for all individuals with CF, irrespective of age.Because of the nature of registry data, Goss and colleagues could not compare treatments between the CFFR and the CFFPR.Platform trials offer the potential to test multiple therapies simultaneously and hold the promise of delivering answers and improving survival in CF in a timely way (10).[...]future improvements in CF survival are likely to rely on ensuring equitable access to healthcare for everyone and ongoing quality improvement across health systems.

BackgroundHigh-flow nasal oxygen (HFNO) is frequently used in hospitals, producing droplets and aerosols that could transmit SARS-CoV-2.AimTo determine if a headbox could reduce droplet and aerosol transmission from patients requiring HFNO.MethodsThe size and dispersion of propylene glycol (model for patient-derived infectious particles) was measured using a spectrometer and an infant mannequin receiving 10–50 L/min of HFNO using (1) no headbox, (2) open headbox, (3) headbox-blanket or (4) headbox with a high-efficiency particulate (HEP) filter covering the neck opening.ResultsAll headbox set-ups reduced the dispersal of droplets and aerosols compared with no headbox. The headbox-blanket system increased aerosol dispersal compared with the open headbox. The fraction of aerosols retained in the headbox for HFNO of 10 and 50 L/min was, respectively, as follows: (1) open headbox: 82.4% and 42.2%; (2) headbox-blanket: 56.8% and 39.5%; (3) headbox-HEP filter: 99.9% and 99.9%.ConclusionA HEP-filter modified headbox may serve as an effective droplet and aerosol barrier adjunct for the protection of staff caring for children receiving HFNO.

In economics, the local knowledge advantage is arguably one of the key arguments in favor of decentralizing the public sector. However, empirical investigations of this particular effect have been scarce. This paper tests the existence of the local knowledge advantage in a real-world setting. Specifically, it looks at the variation in local knowledge across regions based on the origins and careers of regional politicians, assuming that politicians who have spent more time in a particular region possess more and better knowledge of that region than outsiders. To avoid the reverse causality problem, the paper investigates how local origins affected the performances of politicians in a 'natural experimental' environment, studying the responses of regional governors in Russia to disastrous forest fires in 2010. We confirm that local knowledge improves gubernatorial performance. In a highly centralized federation such as Russia, though, the effect is dependent on access to federal resources obtainable through close ties to the federal center. We also discuss alternative interpretations of the local origins of politicians and test whether the effects found are indeed more plausibly explained by local knowledge.

Background Childhood interstitial lung disease (chILD) represents a rare heterogeneous group of respiratory disorders. In the absence of randomized controlled clinical trials, global collaborations have utilized case series with an aim to standardising approaches to diagnosis and management. Australasian data are lacking. The aim of this study was to calculate prevalence and report the experience of chILD in Australasia over a decade. Methods Paediatric pulmonologists in Australia and New Zealand involved in the care of patients aged 0–18 years with chILD completed a questionnaire on demographics, clinical features and outcomes, over a 10 year period. These data, together with data from the 2 reference genetics laboratories, were used to calculate prevalence. Results One hundred fifteen cases were identified equating to a period prevalence (range) of 1.5 (0.8–2.1) cases/million for children aged 0–18years. Clinical data were provided on 106 patients: the <2 year group comprised 66 children, median age (range) 0.50 years (0.01–1.92); the ≥2 year group comprised 40 children, median age 8.2 years (2.0–18.0). Management approach was heterogeneous. Overall, 79% of patients had a good clinical outcome. Mortality rate was 7% in the study population. Conclusion chILD is rare in Australasia. This study demonstrates variation in the investigations and management of chILD cases across Australasia, however the general outcome is favorable. Further international collaboration will help finesse the understanding of these disorders.