Lung infections with Mycobacterium abscessus, a species of multidrug resistant nontuberculous mycobacteria, are emerging as an important global threat to individuals with cystic fibrosis (CF) where they accelerate inflammatory lung damage leading to increased morbidity and mortality. Previously, M. abscessus was thought to be independently acquired by susceptible individuals from the environment. However, using whole genome analysis of a global collection of clinical isolates, we show that the majority of M. abscessus infections are acquired through transmission, potentially via fomites and aerosols, of recently emerged dominant circulating clones that have spread globally. We demonstrate that these clones are associated with worse clinical outcomes, show increased virulence in cell-based and mouse infection models, and thus represent an urgent international infection challenge.Nontuberculous mycobacteria (NTM; referring to mycobacterial species other than M. tuberculosis complex and M. leprae) are ubiquitous environmental organisms that can cause chronic pulmonary infections in susceptible individuals [1,2], particularly those with preexisting inflammatory lung diseases such as cystic fibrosis (CF) [3]. The major NTM infecting CF individuals around the world is Mycobacterium abscessus; a rapidly growing, intrinsically multidrug-resistant species, which can be impossible to treat despite prolonged combination antibiotic therapy [1,[3][4][5], leads to accelerated decline in lung function [6,7], and remains a contraindication to lung transplantation in many centers [3,8,9].Until recently, NTM infections were thought to be independently acquired by individuals through exposure to soil or water [10][11][12]. As expected, previous analyses from the 1990s and 2000s [13][14][15][16] showed that CF patients were infected with unique, genetically diverse strains of M. abscessus, presumably from environmental sources. We used whole genome sequencing at a single UK CF center and identified two clusters of patients (11 individuals in total) infected with identical or near-identical M. abscessus isolates, which social network analysis suggested were acquired within hospital via indirect transmission between patients Phylogenetic analysis of these sequences (using one isolate per patient), supplemented by published genomes from US, France, Brazil, Malaysia, China, and South Korea (Table S1), was performed and analysed in the context of the geographical provenance of isolates ( Figure 1; Figure S1). Within each subspecies, we found multiple examples of deep branches (indicating large genetic differences) between isolates from different individuals, consistent with independent acquisition of unrelated environmental bacteria. However, we also identified multiple clades of near-identical isolates from geographically diverse locations (Figure 1), suggesting widespread transmission of circulating clones within the global CF patient community.To investigate further the relatedness of isolates from different individuals, we a...

Background and Aims: The measurement of airway resistance using the interrupter technique (R int ) is feasible in preschool children and other subjects unable to undertake spirometry. This makes it potentially useful for the measurement of lung function in these groups. Commercial devices use different algorithms to measure pressure and flow from which R int is derived. This study provides normative values for British children using devices from a single manufacturer. Methods: R int was measured in 236 healthy children of three ethnic groups (Afro-Caribbean and black African, Bangladeshi, and white British) aged 2-10 years using Micro Medical devices. Software in the devices calculated R int from pressure measured by the two point, back extrapolation method from the pressure transient during valve closure, with flow measured just before valve closure. Results: R int is related to both age and height, but when age is allowed for there is not a significant relation with height. Neither gender nor any of the ethnicities studied was significantly related to R int . Discussion: These measurements in healthy children using this technique may be used as reference data for similar populations.

Background: To be able to interpret any measurement, its repeatability should be known. This study reports the repeatability of airway resistance measurements using the interrupter technique (Rint) in children with and without respiratory symptoms. Methods: Children aged 2-10 years who were healthy, had persistent isolated cough, or who had previous wheeze were studied. On the same occasion, three Rint measurements were made 15 minutes apart, before and after placebo and salbutamol given in random order. Results from those given placebo first were analysed for within-occasion repeatability. Between-occasion repeatability measurements were made 2-20 weeks apart (median 3 weeks). Results: For 85 pairs of measurements before and after placebo the limits of agreement were 20% expected resistance and were unaffected by age or health status. The change in resistance following bronchodilator in one of 18 healthy children, 12 of 28 with cough, and 22 of 39 with wheeze exceeded this threshold. For between-occasion measurements the limits of agreement were 32% in 72 healthy subjects, 49% in 57 with cough, and 53% in 95 with previous wheeze. Conclusion: The measurement of airways resistance by the interrupter technique is clinically meaningful when change following an intervention such as the administration of bronchodilator is greater than its within-occasion repeatability. Between-occasion repeatability is too poor to judge change confidently.

Plexitonic nanoparticles offer variable optical properties through tunable excitations, in addition to electric field enhancements that far exceed molecular resonators. This study demonstrates a way to design an ultrabright surface-enhanced Raman spectroscopy (SERS) signal while simultaneously quenching the fluorescence background through silica encapsulation of the semiconductor-metal composite nanoparticles. Using a multistep approach, a J-aggregate-forming organic dye is assembled on the surface of gold nanoparticles using a cationic linker. Excitonic resonance of the J-aggregate-metal system shows an enhanced SERS signal at an appropriate excitation wavelength. Further encapsulation of the decorated particles in silica shows a significant reduction in the fluorescence signal of the Raman spectra (5× reduction) and an increase in Raman scattering (7× enhancement) when compared to phospholipid encapsulation. This reduction in fluorescence is important for maximizing the useful SERS enhancement from the particle, which shows a signal increase on the order of 10 times greater than J-aggregated dye in solution and 24 times greater than Oxonica S421 SERS tag. The silica layer also serves to promote colloidal stability. The combination of reduced fluorescence background, enhanced SERS intensity, and temporal stability makes these particles highly distinguishable with potential to enable high-throughput applications such as SERS flow cytometry.

Background: Diagnosing childhood asthma is dependent upon parental symptom reporting but there are problems in the use of words and terms. The purpose of this study was to describe and compare understandings of childhood 'asthma' by mothers from three different ethnic backgrounds who have no personal experience of diagnosing asthma. A better understanding of parents' perceptions of an illness by clinicians should improve communication and management of the illness.