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Background: University Hospital Hairmyres is a small District General Hospital in Lanarkshire Scotland. We have an active Care of the Elderly Department with a well established Acute Care of the Elderly (ACE) team of Advanced Nurse Practitioners, supported by Consultants. This team delivers Comprehensive Geriatric Assessment (CGA) to frail older people in acute medical receiving as well as offering liaison to medical, surgical and orthopaedic wards. Local problem and intervention: Our patients were not always being managed by the correct professionals in a timely manner, leading to delays especially in the Emergency Department (ED). We set up a Frailty at the Front Door (FAFD) service to address this, commencing July 2018. Supported by additional consultant sessions, we re-focused the ACE team on assessing and managing frail patients in the ED. The aim was to get the right patient to the right place at the right time and to manage acutely ill people at home where this was safe. Where admission was required we aimed to admit directly to a specialty bed, bypassing acute receiving wards. Methods: We routinely collect important data including number of frail patients, %patients receiving CGA within 24 hours, number of discharges. To assess the impact of our change we analysed the data by plotting on run charts and statistical process control charts. In addition we assessed the effect on referrals from medical specialties and the number of direct-to-specialty admissions. Results: After the 22 July 2018 we noticed a significant increase in patients screened for frailty, and a significant increase in discharges. We were able to reliably sustain over 95% of frail patients getting CGA within 24 hrs. There was an increased use of hospital at home. There was a reduction in referrals from medical wards (median = 10/week before, 5/week after intervention). Between August 2018 and May 2019 we were able to admit 163 patients directly to specialty beds. There was no change in re-admission rate. Conclusions: We successfully changed our service to have consultant delivered Frailty at the Front Door, assessing more frail patients. Most importantly, we have an improved patient pathway, both managing more people at home but also reducing ward moves by achieving direct to specialty admissions. CGA can be safely delivered in the ED. [ABSTRACT FROM AUTHOR]

Abstract Background Bronchiectasis unrelated to cystic fibrosis (CF) is being increasingly recognized in children and adults globally, both in resource-poor and in affluent countries. However, high-quality evidence to inform management is scarce. Oral amoxycillin-clavulanate is often the first antibiotic chosen for non-severe respiratory exacerbations, because of the antibiotic-susceptibility patterns detected in the respiratory pathogens commonly associated with bronchiectasis. Azithromycin has a prolonged half-life, and with its unique anti-bacterial, immunomodulatory, and anti-inflammatory properties, presents an attractive alternative. Our proposed study will test the hypothesis that oral azithromycin is non-inferior (within a 20% margin) to amoxycillin-clavulanate at achieving resolution of non-severe respiratory exacerbations by day 21 of treatment in children with non-CF bronchiectasis. Methods This will be a multicenter, randomized, double-blind, double-dummy, placebo-controlled, parallel group trial involving six Australian and New Zealand centers. In total, 170 eligible children will be stratified by site and bronchiectasis etiology, and randomized (allocation concealed) to receive: 1) azithromycin (5 mg/kg daily) with placebo amoxycillin-clavulanate or 2) amoxycillin-clavulanate (22.5 mg/kg twice daily) with placebo azithromycin for 21 days as treatment for non-severe respiratory exacerbations. Clinical data and a parent-proxy cough-specific quality of life (PC-QOL) score will be obtained at baseline, at the start and resolution of exacerbations, and on day 21. In most children, blood and deep-nasal swabs will also be collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 21. The main secondary outcome is the PC-QOL score. Other outcomes are: time to next exacerbation; requirement for hospitalization; duration of exacerbation, and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood inflammatory markers will be reported where available. Discussion Currently, there are no published randomized controlled trials (RCT) to underpin effective, evidence-based management of acute respiratory exacerbations in children with non-CF bronchiectasis. To help address this information gap, we are conducting two RCTs. The first (bronchiectasis exacerbation study; BEST-1) evaluates the efficacy of azithromycin and amoxycillin-clavulanate compared with placebo, and the second RCT (BEST-2), described here, is designed to determine if azithromycin is non-inferior to amoxycillin-clavulanate in achieving symptom resolution by day 21 of treatment in children with acute respiratory exacerbations. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number http://ACTRN12612000010897. http://www.anzctr.org.au/trial_view.aspx?id=347879

Abstract Background The prevalence of chronic suppurative lung disease (CSLD) and bronchiectasis unrelated to cystic fibrosis (CF) among Indigenous children in Australia, New Zealand and Alaska is very high. Antibiotics are a major component of treatment and are used both on a short or long-term basis. One aim of long-term or maintenance antibiotics is to reduce the frequency of acute pulmonary exacerbations and symptoms. However, there are few studies investigating the efficacy of long-term antibiotic use for CSLD and non-CF bronchiectasis among children. This study tests the hypothesis that azithromycin administered once a week as maintenance antibiotic treatment will reduce the rate of pulmonary exacerbations in Indigenous children with bronchiectasis. Methods/design We are conducting a multicentre, randomised, double-blind, placebo controlled clinical trial in Australia and New Zealand. Inclusion criteria are: Aboriginal, Torres Strait Islander, Maori or Pacific Island children aged 1 to 8 years, diagnosed with bronchiectasis (or probable bronchiectasis) with no underlying disease identified (such as CF or primary immunodeficiency), and having had at least one episode of pulmonary exacerbation in the last 12 months. After informed consent, children are randomised to receive either azithromycin (30 mg/kg once a week) or placebo (once a week) for 12–24 months from study entry. Primary outcomes are the rate of pulmonary exacerbations and time to pulmonary exacerbation determined by review of patient medical records. Secondary outcomes include length and severity of pulmonary exacerbation episodes, changes in growth, school loss, respiratory symptoms, forced expiratory volume in 1-second (FEV1; for children ≥6 years), and sputum characteristics. Safety endpoints include serious adverse events. Antibiotic resistance in respiratory bacterial pathogens colonising the nasopharynx is monitored. Data derived from medical records and clinical assessments every 3 to 4 months for up to 24 months from study entry are recorded on standardised forms. Discussion Should this trial demonstrate that azithromycin is efficacious in reducing the number of pulmonary exacerbations, it will provide a much-needed rationale for the use of long-term antibiotics in the medical management of bronchiectasis in Indigenous children. Trial registration Australian New Zealand Clinical Trials Registry: ACTRN12610000383066

Abstract Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.

Abstract Background Acute lower respiratory infections are the commonest cause of morbidity and potentially preventable mortality in Indigenous infants. Infancy is also a critical time for post-natal lung growth and development. Severe or repeated lower airway injury in very young children likely increases the likelihood of chronic pulmonary disorders later in life. Globally, bronchiolitis is the most common form of acute lower respiratory infections during infancy. Compared with non-Indigenous Australian infants, Indigenous infants have greater bacterial density in their upper airways and more severe bronchiolitis episodes. Our study tests the hypothesis that the anti-microbial and anti-inflammatory properties of azithromycin, improve the clinical outcomes of Indigenous Australian infants hospitalised with bronchiolitis. Methods We are conducting a dual centre, randomised, double-blind, placebo-controlled, parallel group trial in northern Australia. Indigenous infants (aged ≤ 24-months, expected number = 200) admitted to one of two regional hospitals (Darwin, Northern Territory and Townsville, Queensland) with a clinical diagnosis of bronchiolitis and fulfilling inclusion criteria are randomised (allocation concealed) to either azithromycin (30 mg/kg/dose) or placebo administered once weekly for three doses. Clinical data are recorded twice daily and nasopharyngeal swab are collected at enrolment and at the time of discharge from hospital. Primary outcomes are 'length of oxygen requirement' and 'duration of stay,' the latter based upon being judged as 'ready for respiratory discharge'. The main secondary outcome is readmission for a respiratory illness within 6-months of leaving hospital. Descriptive virological and bacteriological (including development of antibiotic resistance) data from nasopharyngeal samples will also be reported. Discussion Two published studies, both involving different patient populations and settings, as well as different macrolide antibiotics and treatment duration, have produced conflicting results. Our randomised, placebo-controlled trial of azithromycin in Indigenous infants hospitalised with bronchiolitis is designed to determine whether it can reduce short-term (and potentially long-term) morbidity from respiratory illness in Australian Indigenous infants who are at high risk of developing chronic respiratory illness. If azithromycin is efficacious in reducing the morbidly of Indigenous infants hospitalised with bronchiolitis, the intervention would lead to improved short term (and possibly long term) health benefits. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000326099

Abstract Background In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV) given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months of age. This study presents carriage serotypes following this schedule. Methods We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs) in 2003 and 2005. Nasal secretions were collected and processed according to published methods. Results 902 children (mean age 25 months) living in 29 communities in 2003 and 818 children (mean age 35 months) in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order) 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL) strains (15% overall) was detected in serotypes (descending order) 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL) strains (5% overall), was detected in serotypes (descending order) 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C. Conclusion Pneumococcal carriage remains high (~80%) in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined years were 16F, 19A, 11A, 6C and 23B. Antimicrobial non-susceptibility was detected in these and 17 additional serotypes. Shifts in serotype-specific carriage suggest a need more research to clarify the association between pneumococcal vaccination and carriage at the serotype level.

Abstract Background Tumour hypoxia is known to be a poor prognostic indicator, predictive of increased risk of metastatic disease and reduced survival. Genomic instability has been proposed as one of the potential mechanisms for hypoxic tumour progression. Both of these features are commonly found in many cancer types, but their relationship and association with tumour progression has not been examined in the same model. Methods To address this issue, we determined the effects of 6 week in vivo acute hypoxic exposure on the levels of mutagenic lipid peroxidation product, malondialdehyde, and 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA (8-oxo-dG) lesions in the transgenic polyomavirus middle T (PyMT) breast cancer mouse model. Results We observed significantly increased plasma lipid peroxidation and 8-oxo-dG lesion levels in the hypoxia-exposed mice. Consumption of malondialdehyde also induced a significant increase in the PyMT tumour DNA lesion levels, however, these increases did not translate into enhanced tumour progression. We further showed that the in vivo exposure to acute hypoxia induced accumulation of F4/80 positive tumour-associated macrophages (TAMs), demonstrating a relationship between hypoxia and macrophages in an experimental model. Conclusion These data suggest that although exposure to acute hypoxia causes an increase in 8-oxo-dG lesions and TAMs in the PyMT tumours, these increases do not translate into significant changes in tumour progression at the primary or metastatic levels in this strong viral oncogene-driven breast cancer model.

Among large cetaceans in the Southern Hemisphere, fin whales were the most heavily exploited in terms of numbers taken during the period of intense industrial whaling. Recent studies suggest that, whilst some humpback whale populations in the Southern Hemisphere appears to have almost completely recovered to their estimated pre-whaling abundance, much less is known about the status of Southern Hemisphere fin whales. Circumpolar estimates in the 1990s suggest an abundance of about 5500 animals south of 60° S, while the IDCR/SOWER-2000 survey for the Scotia Sea and Antarctic Peninsula areas estimated 4670 fin whales within this region in the year 2000. More recent studies in smaller regions indicate higher densities, suggesting that previous estimates are overly conservative and/or that fin whales are undergoing a substantial increase. Here we report findings from a recent multi-vessel single-platform sightings survey carried out as part of the 2019 Area 48 Survey for Antarctic krill. While fin whales were encountered throughout the entire survey area, which covered the majority of CCAMLR Management Area 48, they were particularly abundant around the South Orkney Islands and the eastern Bransfield Strait. Large feeding aggregations were also encountered within the central Scotia Sea between South Orkney Islands and South Georgia. Distance sampling analyses suggest an average fin whale density throughout the Scotia Sea of 0.0256 ( CV = 0.149 ) whales per km 2 , which agrees well with recent density estimates reported from smaller sub-regions within the Scotia Sea. Design-based distance sampling analyses resulted in an estimated total fin whale abundance of 53,873 (CV = 0.15, 95% CI 40,233-72,138), while a density surface model resulted in a slightly lower estimate of 50,837 (CV: 0.136, 95% CI 38,966-66,324). These estimates are at least an order of magnitude greater than the previous estimate from the same region based on the IDCR/SOWER-2000 data, suggesting that fin whales are undergoing a substantial abundance increase in the South Atlantic. This may have important implications for the assessment of cetacean population trends, but also for CCAMLRs spatial overlap analysis process and efforts to implement a Feedback Management system for Antarctic krill. Our abundance estimate suggests an annual summer krill consumption by fin whales in the Antarctic Peninsula and Scotia Sea area of 7.97 (95% CI 4.94-11.91) million tonnes, which would represent around 20 times the total krill catch taken by the commercial fishery in Area 48 in the same season, or about 12.7% of the 2019 summer krill standing stock estimated from data collected during the same survey. This highlights the crucial importance of including cetacean krill predators in assessment and management efforts for living marine resources in the Southern Ocean, and particularly stresses the urgent need for a re-appraisal of abundance, distribution and ecological role of Southern Hemisphere fin whales., (© 2024. The Author(s).)

Objectives: To assess the prevalence of bronchiectasis among Aboriginal and Torres Strait Islander (Indigenous) adults in the Top End of the Northern Territory, and mortality among Indigenous adults with bronchiectasis., Study Design: Retrospective cohort study., Setting, Participants: Aboriginal and Torres Strait Islander adults (18 years or older) living in the Top End Health Service region of the NT in whom bronchiectasis was confirmed by chest computed tomography (CT) during 1 January 2011 - 31 December 2020., Main Outcome Measures: Prevalence of bronchiectasis, and all-cause mortality among Indigenous adults with CT-confirmed bronchiectasis - overall, by sex, and by health district - based on 2011 population numbers (census data)., Results: A total of 23 722 Indigenous adults lived in the Top End Health Service region in 2011; during 2011-2020, 459 people received chest CT-confirmed diagnoses of bronchiectasis. Their median age was 47.5 years (interquartile range [IQR], 39.9-56.8 years), 254 were women (55.3%), and 425 lived in areas classified as remote (93.0%). The estimated prevalence of bronchiectasis was 19.4 per 1000 residents (20.6 per 1000 women; 18.0 per 1000 men). The age-adjusted prevalence of bronchiectasis was 5.0 (95% CI, 1.4-8.5) cases per 1000 people in the Darwin Urban health area, and 18-36 cases per 1000 people in the three non-urban health areas. By 30 April 2023, 195 people with bronchiectasis had died (42.5%), at a median age of 60.3 years (IQR, 50.3-68.9 years)., Conclusion: The prevalence of bronchiectasis burden among Indigenous adults in the Top End of the NT is high, but differed by health district, as is all-cause mortality among adults with bronchiectasis. The socio-demographic and other factors that contribute to the high prevalence of bronchiectasis among Indigenous Australians should be investigated so that interventions for reducing its burden can be developed., (© 2024 The Authors. Medical Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of AMPCo Pty Ltd.)

Directed evolution provides a powerful route for in vitro enzyme engineering. State-of-the-art techniques functionally screen up to millions of enzyme variants using high throughput microfluidic sorters, whose operation remains technically challenging. Alternatively, in vitro self-selection methods, analogous to in vivo complementation strategies, open the way to even higher throughputs, but have been demonstrated only for a few specific activities. Here, we leverage synthetic molecular networks to generalize in vitro compartmentalized self-selection processes. We introduce a programmable circuit architecture that can link an arbitrary target enzymatic activity to the replication of its encoding gene. Microencapsulation of a bacterial expression library with this autonomous selection circuit results in the single-step and screening-free enrichment of genetic sequences coding for programmed enzymatic phenotypes. We demonstrate the potential of this approach for the nicking enzyme Nt.BstNBI (NBI). We applied autonomous selection conditions to enrich for thermostability or catalytic efficiency, manipulating up to 10 7 microcompartments and 5 × 10 5 variants at once. Full gene reads of the libraries using nanopore sequencing revealed detailed mutational activity landscapes, suggesting a key role of electrostatic interactions with DNA in the enzyme's turnover. The most beneficial mutations, identified after a single round of self-selection, provided variants with, respectively, 20 times and 3 °C increased activity and thermostability. Based on a modular molecular programming architecture, this approach does not require complex instrumentation and can be repurposed for other enzymes, including those that are not related to DNA chemistry.

Biogeography is the study of species distribution and diversity within an ecosystem and is at the core of how we understand ecosystem dynamics and interactions at the macroscale. In gut microbial communities, a historical reliance on bulk sequencing to probe community composition and dynamics has overlooked critical processes whereby microscale interactions affect systems-level microbiota function and the relationship with the host. In recent years, higher-resolution sequencing and novel single-cell level data have uncovered an incredible heterogeneity in microbial composition and have enabled a more nuanced spatial understanding of the gut microbiota. In an era when spatial transcriptomics and single-cell imaging and analysis have become key tools in mammalian cell and tissue biology, many of these techniques are now being applied to the microbiota. This fresh approach to intestinal biogeography has given important insights that span temporal and spatial scales, from the discovery of mucus encapsulation of the microbiota to the quantification of bacterial species throughout the gut. In this Review, we highlight emerging knowledge surrounding gut biogeography enabled by the observation and quantification of heterogeneity across multiple scales., (© 2023. Springer Nature Limited.)

Background: Bronchiectasis is a chronic pulmonary disorder which is prevalent among Australian First Nations people in the Northern Territory (NT). Current guidelines recommend physiotherapy as part of multi-disciplinary management of children with bronchiectasis, however in our setting, involvement of physiotherapy remains unknown. We thus undertook a retrospective chart audit to examine physiotherapy management of First Nations children (<18 years) from remote First Nations communities in the Top End of the NT at the index bronchiectasis diagnosis and 12 months following diagnosis., Methods: Participants were identified from a larger prospective study of children investigated for bronchiectasis at Royal Darwin Hospital, NT (2007-2016). Children were included if they were First Nations, aged <18 years, had a radiological diagnosis of bronchiectasis on high resolution computed tomography scan and lived in a remote community serviced by NT Government health clinics. The medical records from NT Government hospitals, health clinics and where possible other medical service attendance were reviewed for physiotherapy referral and management at the time of bronchiectasis diagnosis and in the following 12 months in the community., Results: Of 143 children included, the mean age was 3.1 (standard deviation 2.4) years and 84 (58.7%) were males. At the index diagnosis, 76/122 (62.3%) children were reviewed by a physiotherapist, consisting of airway clearance techniques (83.8%), physical activity/exercise (81.7%) and caregiver education (83.3%), with only 7/127 (5.5%) having evidence of referral for community-based physiotherapy. In the following 12 months, only 11/143 (7.7%) children were reviewed by a physiotherapist, consisting of airway clearance techniques (54.5%), physical activity/exercise (45.5%) and caregiver education (36.4%)., Conclusion: This study demonstrates a significant gap in the provision of physiotherapy services in our setting and the need to develop a standardized pathway, to support the best practice management of children with bronchiectasis in remote Top End communities of the NT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Welford, McCallum, Hodson and Johnston.)

Importance: Multiple SARS-CoV-2 variants have emerged over the COVID-19 pandemic. The implications for COVID-19 severity in children worldwide are unclear., Objective: To determine whether the dominant circulating SARS-CoV-2 variants of concern (VOCs) were associated with differences in COVID-19 severity among hospitalized children., Design, Setting, and Participants: Clinical data from hospitalized children and adolescents (younger than 18 years) who were SARS-CoV-2 positive were obtained from 9 countries (Australia, Brazil, Italy, Portugal, South Africa, Switzerland, Thailand, UK, and the US) during 3 different time frames. Time frames 1 (T1), 2 (T2), and 3 (T3) were defined to represent periods of dominance by the ancestral virus, pre-Omicron VOCs, and Omicron, respectively. Age groups for analysis were younger than 6 months, 6 months to younger than 5 years, and 5 to younger than 18 years. Children with an incidental positive test result for SARS-CoV-2 were excluded., Exposures: SARS-CoV-2 hospitalization during the stipulated time frame., Main Outcomes and Measures: The severity of disease was assessed by admission to intensive care unit (ICU), the need for ventilatory support, or oxygen therapy., Results: Among 31 785 hospitalized children and adolescents, the median age was 4 (IQR 1-12) years and 16 639 were male (52.3%). In children younger than 5 years, across successive SARS-CoV-2 waves, there was a reduction in ICU admission (T3 vs T1: risk ratio [RR], 0.56; 95% CI, 0.42-0.75 [younger than 6 months]; RR, 0.61, 95% CI; 0.47-0.79 [6 months to younger than 5 years]), but not ventilatory support or oxygen therapy. In contrast, ICU admission (T3 vs T1: RR, 0.39, 95% CI, 0.32-0.48), ventilatory support (T3 vs T1: RR, 0.37; 95% CI, 0.27-0.51), and oxygen therapy (T3 vs T1: RR, 0.47; 95% CI, 0.32-0.70) decreased across SARS-CoV-2 waves in children 5 years to younger than 18 years old. The results were consistent when data were restricted to unvaccinated children., Conclusions and Relevance: This study provides valuable insights into the impact of SARS-CoV-2 VOCs on the severity of COVID-19 in hospitalized children across different age groups and countries, suggesting that while ICU admissions decreased across the pandemic in all age groups, ventilatory and oxygen support generally did not decrease over time in children aged younger than 5 years. These findings highlight the importance of considering different pediatric age groups when assessing disease severity in COVID-19.

Prions are self-propagating protein aggregates formed by specific proteins that can adopt alternative folds. Prions were discovered as the cause of the fatal transmissible spongiform encephalopathies in mammals, but prions can also constitute nontoxic protein-based elements of inheritance in fungi and other species. Prion propagation has recently been shown to occur in bacteria for more than a hundred cell divisions, yet a fraction of cells in these lineages lost the prion through an unknown mechanism. Here, we investigate prion propagation in single bacterial cells as they divide using microfluidics and fluorescence microscopy. We show that the propagation occurs in two distinct modes. In a fraction of the population, cells had multiple small visible aggregates and lost the prion through random partitioning of aggregates to one of the two daughter cells at division. In the other subpopulation, cells had a stable large aggregate localized to the pole; upon division the mother cell retained this polar aggregate and a daughter cell was generated that contained small aggregates. Extending our findings to prion domains from two orthologous proteins, we observe similar propagation and loss properties. Our findings also provide support for the suggestion that bacterial prions can form more than one self-propagating state. We implement a stochastic version of the molecular model of prion propagation from yeast and mammals that recapitulates all the observed single-cell properties. This model highlights challenges for prion propagation that are unique to prokaryotes and illustrates the conservation of fundamental characteristics of prion propagation.

Bronchiectasis in children can progress to a severe lung condition if not diagnosed and treated early. The radiological diagnostic criteria for the diagnosis of bronchiectasis is an increased broncho-arterial (BA) ratio. From high-resolution computed tomography (HRCT) scans, the BA pairs must be detected first to derive the BA ratio. This study aims to identify potential BA pairs from HRCT scans of children undertaken to evaluate suppurative lung disease through an automated approach. After segmenting the lung regions, the HRCT scans are cleaned using a histogram analysis-based approach followed by a potential arteries identification process comprising four conditions based on imaging features. Potential arteries and their connected components are extracted, and potential bronchi are identified. Finally, the coordinates of potential arteries and potential bronchi are matched as the last step of BA pairs extraction. A total of 8-50 BA pairs are detected for each patient. Additionally, the area and several diameters of the bronchi and arteries are measured, and BA ratios based on these are calculated. Through this approach, the BA pairs of a CT scan datasets are detected and utilizing a deep learning model, a high classification test accuracy of 98.53% is achieved, validating the robustness of the proposed BA detection approach. The results show that visible BA pairs can be identified and segmented automatically, and the BA ratio calculated may help diagnose bronchiectasis with less effort and time.

Background: We aimed to assess the direct protective effect of 13 valent pneumococcal conjugate vaccine (13vPCV) against invasive pneumococcal pneumonia (IPP; including pneumonia and empyema) in children using a nation-wide case-control study across 11 paediatric tertiary hospitals in Australia., Methods: Children < 18 years old admitted with pneumonia were eligible for enrolment. IPP was defined as Streptococcus pneumoniae (SP) cultured or detected by polymerase chain reaction (PCR) from blood or pleural fluid. Causative SP serotype (ST) was determined from blood or pleural fluid SP isolates by molecular methods in PCR positive specimens or else inferred from nasopharyngeal isolates. For each IPP case, 20 population controls matched by age and socio-economic status were sampled from the Australian Immunisation Register. Conditional logistic regression was used to estimate the adjusted odds ratio (aOR) of being fully vaccinated with 13vPCV (≥3 doses versus < 3 doses) among IPP cases compared to controls, adjusted for sex and Indigenous status., Results: From February 2015 to September 2018, we enrolled 1,168 children with pneumonia; 779 were 13vPCV-eligible and were individually matched to 15,580 controls. SP was confirmed in 195 IPP cases, 181 of whom had empyema. ST3 and ST19A were identified in 52% (102/195) and 11% (21/195) of IPP cases respectively. The aOR of being fully vaccinated with 13vPCV was 0.8 (95% CI 0.6-1.0) among IPP cases compared to matched controls., Conclusion: We failed to identify a strong direct protective effect of 13vPCV against IPP among Australian children, where disease was largely driven by ST3., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)