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Small datasets are common in many fields due to factors such as limited data collection opportunities or privacy concerns. These datasets often contain high-dimensional features, yet present significant challenges of dimensionality, wherein the sparsity of data in high-dimensional spaces makes it difficult to extract meaningful information and less accurate predictive models are produced. In this regard, feature extraction algorithms are important in addressing these challenges by reducing dimensionality while retaining essential information. These algorithms can be classified into supervised, unsupervised, and semi-supervised methods and categorized as linear or nonlinear. To overview this critical issue, this review focuses on unsupervised feature extraction algorithms (UFEAs) due to their ability to handle high-dimensional data without relying on labelled information. From this review, eight representative UFEAs were selected: principal component analysis, classical multidimensional scaling, Kernel PCA, isometric mapping, locally linear embedding, Laplacian Eigenmaps, independent component analysis and Autoencoders. The theoretical background of these algorithms has been presented, discussing their conceptual viewpoints, such as whether they are linear or nonlinear, manifold-based, probabilistic density function-based, or neural network-based. After classifying these algorithms using these taxonomies, we thoroughly and systematically reviewed each algorithm from the perspective of their working mechanisms, providing a detailed algorithmic explanation for each UFEA. We also explored how these mechanisms contribute to an effective reduction in dimensionality, particularly in small datasets with high dimensionality. Furthermore, we compared these algorithms in terms of transformation approach, goals, parameters, and computational complexity. Finally, we evaluated each algorithm against state-of-the-art research using various datasets to assess their accuracy, highlighting which algorithm is most appropriate for specific scenarios. Overall, this review provides insights into the strengths and weaknesses of various UFEAs, offering guidance on selecting appropriate algorithms for small high-dimensional datasets.

Bronchiectasis is conventionally defined as irreversible dilatation of the bronchial tree. Bronchiectasis unrelated to cystic fibrosis is an increasingly appreciated cause of chronic respiratory-related morbidity worldwide. Few randomised controlled trials provide high-level evidence for management strategies to treat the children affected by bronchiectasis. However, both decades-old and more recent studies using technological advances support the notion that prompt diagnosis and optimal management of paediatric bronchiectasis is particularly important in early childhood. Although considered to be of a non-reversible nature, mild bronchiectasis determined by radiography might be reversible at any age if treated early, and the lung function decline associated with disease progression could then be halted. Although some management strategies are extrapolated from cystic fibrosis or adult-based studies, or both, non-cystic fibrosis paediatric-specific data to help diagnose and manage these children still need to be generated. We present current knowledge and an updated definition of bronchiectasis, and review controversies relating to the management of children with bronchiectasis, including applying the concept of so-called treatable traits.

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.

In Australian remote communities, First Nations children with otitis media (OM)-related hearing loss are disproportionately at risk of developmental delay and poor school performance, compared to those with normal hearing. Our objective was to compare OM-related hearing loss in children randomised to one of 2 pneumococcal conjugate vaccine (PCV) formulations. In 2 sequential parallel, open-label, randomised controlled trials (the PREVIX trials), eligible infants were first allocated 1:1:1 at age 28 to 38 days to standard or mixed PCV schedules, then at age 12 months to PCV13 (13-valent pneumococcal conjugate vaccine, +P) or PHiD-CV10 (10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine, +S) (1:1). Here, we report prevalence and level of hearing loss outcomes in the +P and +S groups at 6-monthly scheduled assessments from age 12 to 36 months. From March 2013 to September 2018, 261 infants were enrolled and 461 hearing assessments were performed. Prevalence of hearing loss was 78% (25/32) in the +P group and 71% (20/28) in the +S group at baseline, declining to 52% (28/54) in the +P groups and 56% (33/59) in the +S group at age 36 months. At primary endpoint age 18 months, prevalence of moderate (disabling) hearing loss was 21% (9/42) in the +P group and 41% (20/49) in the +S group (difference -19%; (95% confidence interval (CI) [-38, -1], p = 0.07) and prevalence of no hearing loss was 36% (15/42) in the +P group and 16% (8/49) in the +S group (difference 19%; (95% CI [2, 37], p = 0.05). At subsequent time points, prevalence of moderate hearing loss remained lower in the +P group: differences -3%; (95% CI [-23, 18], p = 1.00 at age 24 months), -12%; (95% CI [-30, 6], p = 0.29 at age 30 months), and -9%; (95% CI [-23, 5], p = 0.25 at age 36 months). A major limitation was the small sample size, hence low power to reach statistical significance, thereby reducing confidence in the effect size. In this study, we observed a high prevalence and persistence of moderate (disabling) hearing loss throughout early childhood. We found a lower prevalence of moderate hearing loss and correspondingly higher prevalence of no hearing loss in the +P group, which may have substantial benefits for high-risk children, their families, and society, but warrant further investigation. ClinicalTrials.gov NCT01735084 and NCT01174849.

In microbiome fields of study, meta-analyses have proven to be a valuable tool for identifying the technical drivers of variation among studies and results of investigations in several diseases, such as those of the gut and sinuses. Meta-analyses also represent a powerful and efficient approach to leverage existing scientific data to both reaffirm existing findings and generate new hypotheses within the field. However, there are currently limited data in other fields, such as the paediatric respiratory tract, where extension of original data becomes even more critical due to samples often being difficult to obtain and process for a range of both technical and ethical reasons. Performing such analyses in an evolving field comes with challenges related to data accessibility and heterogeneity. This is particularly the case in paediatric respiratory microbiomics — a field in which best microbiome-related practices are not yet firmly established, clinical heterogeneity abounds and ethical challenges can complicate sharing of patient data. Having recently conducted a large-scale, individual participant data meta-analysis of the paediatric respiratory microbiota ( n = 2624 children from 20 studies), we discuss here some of the unique barriers facing these studies and open and invite a dialogue towards future opportunities. 2j7-xL3uMZN3KE5gLUMq2Z Video Abstract

Chronic suppurative lung disease (CSLD) is characterized by the presence of a chronic wet or productive cough and recurrent lower respiratory infections. The aim of this study was to identify features of innate, cell-mediated and humoral immunity that may increase susceptibility to respiratory infections in children with CSLD. Because non-typeable Haemophilus influenzae (NTHi) is commonly isolated from the airways in CSLD, we examined immune responses to this organism in 80 age-stratified children with CSLD and compared their responses with 51 healthy control children. Cytokines involved in the generation and control of inflammation (IFN-γ, IL-13, IL-5, IL-10 at 72 hours and TNFα, IL-6, IL-10 at 24 hours) were measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. We also measured circulating IgG subclass antibodies (IgG1 and IgG4) to two H. influenzae outer membrane proteins, P4 and P6. The most notable finding was that PBMC from children with CSLD produced significantly less IFN-γ in response to NTHi than healthy control children whereas mitogen-induced IFN-γ production was similar in both groups. Overall there were minor differences in innate and humoral immune responses between CSLD and control children. This study demonstrates that children with chronic suppurative lung disease have an altered systemic cell-mediated immune response to NTHi in vitro. This deficient IFN-γ response may contribute to increased susceptibility to NTHi infections and the pathogenesis of CSLD in children.

Background Bronchiectasis is a major contributor to respiratory morbidity and healthcare utilization in children. Children with bronchiectasis exhibit low levels of physical activity (PA) and poor fundamental movement skills (FMS) may be a contributing factor. However, there are no data on FMS’s in this population. The current study assessed FMS proficiency in children with bronchiectasis and examined associations with objectively measured PA. Methods Forty-six children with bronchiectasis (mean age 7.5 ± 2.6 year, 63% Male) were recruited from the Queensland Children’s Hospital, Brisbane. PA was measured using the ActiGraph GT3X + accelerometer. Raw accelerometer data were processed into daily time spent in sedentary activities, light-intensity activities and games, walking, running, and moderate-to-vigorous activities and games using a random forest (RF) PA classification algorithm specifically developed for children. Daily MVPA was calculated by summing time spent in walking, running, and moderate-to-vigorous activities and games. FMS were assessed using the Test of Gross Motor Development 2nd Edition (TGMD-2). Results Fewer than 5% of children demonstrated mastery in the run, gallop, hop, and leap; while fewer than 10% demonstrated mastery for the two-handed strike, overarm throw, and underarm throw. Only eight of the 46 children (17.4%) achieved their age equivalency for locomotor skills, while just four (8.7%) achieved their age equivalency for object control skills. One-way ANCOVA revealed that children achieving their age equivalency for FMS had significantly higher levels of MVPA than children not achieving their age equivalency (51.7 vs 36.7 min/day). When examined by the five activity classes predicted by the RF algorithm, children achieving their age equivalency exhibited significantly greater participation moderate-to-vigorous intensity activities and games (22.1 vs 10.7 min/day). No significant differences were observed for sedentary activities, light-intensity activities and games, walking, and running. Conclusion Children with bronchiectasis exhibit significant delays in their FMS development. However, those who meet their age equivalency for FMS proficiency participate in significantly more daily MVPA than children who do not meet their age-equivalency. Therapeutic exercise programs designed to improve FMS proficiency are thus likely to be beneficial in this population.

To evaluate the use of an adult-based algorithmic approach to chronic cough in a cohort of children with a history of > 3 weeks of cough and to describe the etiology of chronic cough in this cohort. A prospective cohort study of children referred to a tertiary hospital with a history of > 3 weeks of cough between June 2002 and June 2004. All included children followed a pathway of investigation (including flexible bronchoscopy and evaluation of airway cytology via BAL) until diagnosis was made and/or their cough resolved. In our cohort of 108 young children (median age 2.6 years), the majority had wet cough (n = 96; 89%), and BAL fluid samples obtained during bronchoscopy led to a diagnosis in 45.4% (n = 49). The most common final diagnosis was protracted bacterial bronchitis (n = 43; 39.8%). These patients had neutrophil levels on BAL samples that were significantly higher than those in other diagnostic groups (p < 0.0001). Asthma, gastroesophageal reflux disease (GERD), and upper airway cough syndrome (UACS), which are common causes of chronic cough in adults, were found in < 10% of the cohort (n = 10). The adult-based anatomic pathway, which involves the investigation and treatment of patients with asthma, GERD, and UACS first is largely unsuitable for use in the management of chronic cough in young children as the common etiologies of chronic cough in children are different from those in adults.

Background Bronchiectasis in children is an important, but under-researched, chronic pulmonary disorder that has negative impacts on health-related quality of life. Despite this, it does not receive the same attention as other chronic pulmonary conditions in children such as cystic fibrosis. We measured health resource use and health-related quality of life over a 12-month period in children with bronchiectasis. Methods We undertook a prospective cohort study of 85 children aged < 18-years with high-resolution chest computed-tomography confirmed bronchiectasis undergoing management in three pediatric respiratory medical clinics in Darwin and Brisbane, Australia and Auckland, New Zealand. Children with cystic fibrosis or receiving cancer treatment were excluded. Data collected included the frequency of healthcare attendances (general practice, specialists, hospital and/or emergency departments, and other), medication use, work and school/childcare absences for parents/carers and children respectively, and both parent/carer and child reported quality of life and cough severity. Results Overall, 951 child-months of observation were completed for 85 children (median age 8.7-years, interquartile range 5.4–11.3). The mean (standard deviation) number of exacerbations was 3.3 (2.2) per child-year. Thirty of 264 (11.4%) exacerbation episodes required hospitalization. Healthcare attendance and antibiotic use rates were high (30 and 50 per 100 child-months of observation respectively). A carer took leave from work for 53/236 (22.5%) routine clinic visits. Absences from school/childcare due to bronchiectasis were 24.9 children per 100 child-months. Quality of life scores for both the parent/carer and child were highly-correlated with one another, remained stable over time and were negatively associated with cough severity. Conclusions Health resource use in this cohort of children is high, reflecting their severe disease burden. Studies are now needed to quantify the direct and societal costs of disease and to evaluate interventions that may reduce disease burden, particularly hospitalizations.

Non-typeable Haemophilus influenzae (NTHi) is commonly associated with chronic suppurative lung disease in children. We have previously shown that children with chronic suppurative lung disease have a reduced capacity to produce IFN-γ in response to NTHi compared with healthy control children. The aim of this study was to determine if deficient NTHi-specific IFN-γ production is associated with heightened systemic or airway inflammation. We measured a panel of cytokines (IFN-γ, IL-1β, IL-6, IL-8, IL-12 p70), antimicrobial proteins (LL-37, IP-10) as well as cellular and clinical factors associated with airway and systemic inflammation in 70 children with chronic suppurative lung disease. IFN-γ was measured in peripheral blood mononuclear cells challenged in vitro with live NTHi. Regression analysis was used to assess the association between the systemic and airway inflammation and the capacity to produce IFN-γ. On multivariate regression, NTHi-specific IFN-γ production was significantly negatively associated with the BAL concentrations of the inflammatory cytokines IL-6 (β=-0.316; 95%CI -0.49, -0.14; p=0.001) and IL-1β (β=-0.023; 95%CI -0.04, -0.01; p=0.001). This association was independent of bacterial or viral infection, BAL cellularity and the severity of bronchiectasis (using modified Bhalla score on chest CT scans). We found limited evidence of systemic inflammation in children with chronic suppurative lung disease. In summary, increased local airway inflammation is associated with a poorer systemic cell-mediated immune response to NTHi in children with chronic suppurative lung disease. These data support the emerging body of evidence that impaired cell-mediated immune responses and dysregulated airway inflammation may be linked and contribute to the pathobiology of chronic suppurative lung disease.