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Mass community testing is a critical means for monitoring the spread of the COVID-19 pandemic. Polymerase chain reaction (PCR) is the gold standard for detecting the causative coronavirus 2 (SARS-CoV-2) but the test is invasive, test centers may not be readily available, and the wait for laboratory results can take several days. Various machine learning based alternatives to PCR screening for SARS-CoV-2 have been proposed, including cough sound analysis. Cough classification models appear to be a robust means to predict infective status, but collecting reliable PCR confirmed data for their development is challenging and recent work using unverified crowdsourced data is seen as a viable alternative. In this study, we report experiments that assess cough classification models trained (i) using data from PCR-confirmed COVID subjects and (ii) using data of individuals self-reporting their infective status. We compare performance using PCR-confirmed data. Models trained on PCR-confirmed data perform better than those trained on patient-reported data. Models using PCR-confirmed data also exploit more stable predictive features and converge faster. Crowd-sourced cough data is less reliable than PCR-confirmed data for developing predictive models for COVID-19, and raises concerns about the utility of patient reported outcome data in developing other clinical predictive models when better gold-standard data are available. [ABSTRACT FROM AUTHOR]

We first introduce the class of bipartite absolute retracts with respect to tree obstructions with at most k leaves. Then, using the theory of homomorphism duality, we show that this class of absolute retracts coincides exactly with the bipartite graphs which admit a (k + 1) -ary near-unanimity polymorphism. This result mirrors the case for reflexive graphs and generalizes a known result for bipartite graphs which admit a 3-ary near-unanimity polymorphism. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We combine survey and administrative data for about 13,000 New Zealand firms from 2005 to 2013 to study intangible investment and firm performance. We find that firm size and moderate competition is associated with higher intangible investment, while firm age is associated with lower intangible investment. Examining firm performance, we find that higher investment is associated with higher labour and capital input, higher revenue, and higher firm-reported employee and customer satisfaction, but not with higher productivity or profitability. The evidence suggests that intangible investment is associated with growth and ‘soft’ performance objectives, but not with productivity or profitability. [ABSTRACT FROM AUTHOR]

Children with asthma have a high prevalence of anxiety disorders, however, very little is known about the mechanisms that confer vulnerability for anxiety in this population. This study investigated whether children with asthma and anxiety disorders display attentional biases towards threatening stimuli, similar to what has been seen in children with anxiety disorders more generally. We also examined the relationships between attentional biases and anxiety symptomatology and asthma control for children with asthma. Ninety-three children, aged 8-13, took part in the study and were recruited into one of four conditions (asthma/anxiety, asthma, anxiety, control). Asthma was medically confirmed and anxiety was assessed through clinical interview. We used self- and parent-report questionnaires to measure child asthma (ATAQ) and anxiety (SCAS, CASI) variables. Participants completed a visual dot-probe task designed to measure attentional bias towards two types of stimuli: asthma related words and general threat words, as well as tasks to assess reading ability and attentional control. Results showed that attentional biases did not differ between the groups, although children with anxiety disorders displayed poorer attentional control. A significant correlation was found between poor asthma control and an attentional bias of asthma stimuli. While we found no evidence that anxiety disorders in children with asthma were associated with threat- or asthma-related attentional biases, preliminary evidence suggested that children with poor asthma control displayed biases towards asthma-specific stimuli. Future research is needed to explore whether these attentional biases are adaptive. [ABSTRACT FROM AUTHOR]

Background: Defects in bacterial host defenses in the cystic fibrosis (CF) airways have been extensively investigated, but the role of the intestinal innate immune system in CF is unknown. Human β-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces and upregulated by inflammation. Its expression in the CF intestine is unknown.Aim: To determine whether HBD-2 was present in the feces of patients with CF, and to compare fecal HBD-2 levels between CF and healthy controls (HC). To compare fecal HBD-2 levels in inflamed and noninflamed states, as measured by fecal calprotectin, as a secondary aim.Methods: Feces from children with CF and HC were collected for analysis.Results: Thirty-three CF patients and 33 HC were recruited. All CF patients had detectable fecal HBD-2. There was no difference between fecal HBD-2 in CF and HC (median (IQR) 49.1 (19.7-77.2) versus 43.4 (26.5-71.9) ng/g; P = 0.7). Fecal calprotectin was significantly higher in the CF cohort than in HC (median (IQR) 61.3 (43.8-143.8) versus 19.5 (19.5-35.1) mg/kg; P < 0.0001). There was no difference in fecal HBD-2 levels between CF subjects with fecal calprotectin ≥50 mg/kg and <50 mg/kg (50.5 (19.6-80.2) versus 43.0 (19.0-70.4); P = 0.7). There was no correlation between fecal HBD-2 and calprotectin in CF (r = 0.14; P = 0.4).Conclusion: Fecal HBD-2 levels were not increased in children with CF, in inflamed or noninflamed states. The lack of HBD-2 induction and upregulation under inflammatory conditions may suggest a diminished intestinal innate immune response in CF. [ABSTRACT FROM AUTHOR]

Nat. Biotechnol. 36, 31–39 (2018); published online 10 January 2018; corrected after print 13 March 2018 In the version of this article initially published, the acknowledgment "M.D. and J.M. were supported by the intramural research program of the National Library of Medicine, National Institutes ofHealth" was omitted. [ABSTRACT FROM AUTHOR]

Background: In children with cystic fibrosis (CF) sleep, eating/mealtime, physiotherapy adherence and internalising problems are common. Caregivers also often report elevated depression, anxiety and stress symptoms. Purpose: To identify, through principal components analysis (PCA), coping strategies used by Australian caregivers of children with CF and to assess the relationship between the derived coping components, caregiver mental health symptoms and child treatment related and non-treatment related problem behaviours. Method: One hundred and two caregivers of children aged 3 to 8 years from three CF clinic sites in Australia, completed self-report questionnaires about their coping and mental health and reported on their child's sleep, eating/mealtime, treatment adherence and internalising and externalising behaviours. Results: Two caregiver coping components were derived from the PCA: labelled 'proactive' and 'avoidant' coping. 'Avoidant' coping correlated moderately with caregiver depression (0.52), anxiety (0.57) and stress (0.55). For each unit increase in caregiver use of avoidant coping strategies, the odds of frequent child eating/mealtime behaviour problems increased by 1.3 (adjusted 95 % CI 1.0 to 1.6, p = .03) as did the odds of children experiencing borderline/clinical internalising behaviour problems (adjusted 95 % CI 1.1 to 1.7, p = .01). Proactive coping strategies were not associated with reduced odds of any child problem behaviours. Conclusions: Avoidant coping strategies correlated with caregiver mental health and child problem behaviours. Intervening with caregiver coping may be a way to improve both caregiver mental health and child problem behaviours in pre-school and early school age children with CF. [ABSTRACT FROM AUTHOR]

Asthma is a prevalent health condition in children, with economic implications for the individual and their family, as well as for societies with nationalized healthcare. Pharmaceutical cost is the main driver of healthcare expenditure in asthma. Existent explicit guidelines are meant to guide asthma management across all age groups, but they are failing. Pharmacologic management of asthma consists of a stepwise treatment approach to achieve symptom control. Various studies suggest a significant number of medical practitioners are prescribing inhaled corticosteroids (ICS) and ICS/long-acting beta agonist (LABA) combination inhalers inappropriately, including prescribing high doses of ICS without specialist consultation. ICS/LABA combination inhalers should only be used in persistent asthmatics, which account for approximately 5% of all children with asthma. Despite this, there is an increase in prescribing rates of ICS/LABA combination inhalers in the context of a decrease in the prevalence of asthma. Furthermore, there is inappropriate prescribing of ICS/LABA combination inhalers in children under 5 years of age, and initiation of relatively more expensive ICS/LABA combination inhalers in patients who have not previously been prescribed ICS. There is evidence to suggest that cost is a significant barrier to asthma management, especially for the more expensive ICS/LABA combination inhalers. Hence, prescribing cost-effective asthma medications appropriately is one of the most important strategies in reducing the morbidity and mortality associated with asthma. It is incumbent on every medical practitioner to not prescribe expensive medications if not indicated, both for the sake of the patient and for society. [ABSTRACT FROM AUTHOR]

Developing the “Science of Science Policy” will require data collection and analysis related to the processes of innovation and technological change, and the effects of government policy on those processes. There has been much work on these topics in the last three decades, but there remain difficult problems of finding proxies for subtle concepts, endogeneity, distinguishing private and social returns, untangling cumulative effects, measuring the impact of government programs in a true “but for” sense, and sorting out national and global effects. I offer observations on how to think about these issues. [ABSTRACT FROM AUTHOR]

The macrolide antibiotics are a family of related 14- or 15-membered lactone ring antibiotics. There has been recent interest in the beneficial effects of these drugs as immune modulators in respiratory conditions in children. Cystic fibrosis (CF) and asthma, both of which occur in childhood, have an underlying inflammatory component and are associated with significant morbidity. The pathogenesis of both conditions is poorly understood but several molecular mechanisms have been suggested. In CF, these mechanisms broadly involve altered chloride transport and alteration of the airway surface liquid with disordered neutrophilic inflammation. There is much evidence for a proinflammatory propensity in CF immune effector and epithelial cells and many studies indicate that macrolides modulate these inflammatory processes. Recent studies have confirmed a clinical improvement in CF following treatment with macrolides, but the exact mechanisms by which they work are unknown. Asthma is likely to represent several different phenotypes but in all of these, airway obstruction, bronchial hyperresponsiveness, and inflammation are central processes. Results from trials using macrolides have suggested an improvement in clinical outcome. The putative mechanisms of macrolide immunomodulatory action include improvement of the primary defense mechanisms, inhibition of the bacteria-epithelial cell interaction, modulation of the signaling pathway and chemokine release, and direct neutrophil effects. Putative mechanisms of phenotypic modulation have also been proposed involving interactions with nitric oxide, endothelin-1, and bronchoconstriction, endothelial growth factors and airway remodeling, and bioactive phospholipids in both CF and asthma. Further characterization of these effects and development of targeted designer drugs will further expand our therapeutic repertoire and lead to improved quality and quantity of life for patients with CF and asthma. [ABSTRACT FROM AUTHOR]

Discusses the relationship between technological change and environmental policy. Approaches for measuring technological change; Frameworks for investigating the economics of such change; Issues related to the empirical analysis of technology innovation and diffusion.

Government policies like the Advanced Technology Program (“ATP”) are intended, at least in part, to remedy the “market failure” inherent in the fact that a significant portion of the social benefits of new knowledge and technology are not captured by a firm that invests in R&D. ATP’s project selection, and its evaluation of the impact of its program, can be made more effective by explicitly incorporating the analysis of such “spillovers.” For project selection, this means identifying technological, organizational and economic factors that tend to oint to a large “spillover gap,” or deviation between the social and private rates of return to a proposed project. For program evaluation and assessment, it means adapting existing study methods that measure social returns to innovation in ways that explicitly capture spillover effects. [ABSTRACT FROM AUTHOR]

Intestinal dysbiosis has been observed in children with cystic fibrosis (CF), yet the functional consequences are poorly understood. We investigated the functional capacity of intestinal microbiota and inflammation in children with CF. Stool samples were collected from 27 children with CF and 27 age and gender matched healthy controls (HC) (aged 0.8–18 years). Microbial communities were investigated by iTag sequencing of 16S rRNA genes and functional profiles predicted using Tax4Fun. Inflammation was measured by faecal calprotectin and M2-pyruvate kinase. Paediatric CF gastrointestinal microbiota demonstrated lower richness and diversity compared to HC. CF samples exhibited a marked taxonomic and inferred functional dysbiosis when compared to HC. In children with CF, we predicted an enrichment of genes involved in short-chain fatty acid (SCFA), antioxidant and nutrient metabolism (relevant for growth and nutrition) in CF. The notion of pro-inflammatory GI microbiota in children with CF is supported by positive correlations between intestinal inflammatory markers and both genera and functional pathways. We also observed an association between intestinal genera and both growth z-scores and FEV1%. These taxonomic and functional changes provide insights into gastrointestinal disease in children with CF and future gastrointestinal therapeutics for CF should explore the aforementioned pathways and microbial changes. [ABSTRACT FROM AUTHOR]

Chronic pneumonitis of infancy (CPI) is a very rare entity. We report the chest radiography and high-resolution CT (HRCT) findings in an infant with histopathologically confirmed CPI. The child was admitted for intensive care 18 h after birth and died at 39 days of age. On HRCT there was diffuse ground-glass change, interlobular septal thickening and discrete centrilobular nodules. An accurate diagnosis is crucial for correct management; however, several entities with the same HRCT findings are recognized. [ABSTRACT FROM AUTHOR]

Nat. Biotechnol. 36, 31–39 (2018); published online 10 January 2018; corrected after print 13 March 2018 In the version of this article initially published, the acknowledgment "M.D. and J.M. were supported by the intramural research program of the National Library of Medicine, National Institutes ofHealth" was omitted. [ABSTRACT FROM AUTHOR]