Mapping Lung Hematopoietic Progenitors: Developmental Kinetics and Response to Influenza A Infection.

The bone marrow is a specialised niche responsible for the maintenance of hematopoietic stem and progenitor cells during homeostasis and inflammation. Recent studies however have extended this essential role to the extramedullary and extravascular lung microenvironment. Here, we provide further evidence for a reservoir of hematopoietic stem and progenitor cells within the lung from embryonic day 18.5 until adulthood. These lung progenitors display distinct microenvironment-specific developmental kinetics compared to their bone marrow counterparts, exemplified by a rapid shift from a common myeloid to megakaryocyte-erythrocyte progenitor dominated niche with increasing age. In adult mice, Influenza A viral infection results in a transient reduction in multipotent progenitors within the lungs, with a parallel increase in downstream granulocyte-macrophage progenitors and dendritic cell populations associated with acute viral infections. Our findings suggest lung hematopoietic progenitors play a role in re-establishing immunological homeostasis in the respiratory mucosa, which may have significant clinical implications for maintaining pulmonary health following inflammatory perturbation.

MIRRORS: a prospective cohort study assessing the feasibility of robotic interval debulking surgery for advanced-stage ovarian cancer.

OBJECTIVE: To establish the feasibility and safety of robotic interval debulking surgery following the MIRRORS protocol (robot-assisted laparoscopic assessment prior to robotic or open surgery) in women with advanced-stage ovarian cancer. MIRRORS is the first of three planned trials: MIRRORS, MIRRORS-RCT (pilot), and MIRRORS-RCT. METHODS: The participants were patients with stage IIIc-IVb epithelial ovarian cancer undergoing neo-adjuvant chemotherapy, suitable for interval debulking surgery with a pelvic mass ≤8 cm. The intervention was robot-assisted laparoscopic assessment prior to robotic or open interval debulking surgery (MIRRORS protocol). The primary outcome was feasibility of recruitment, and the secondary outcomes were quality of life (EORTC QLQC30/OV28, HADS questionnaires), pain, surgical complications, complete cytoreduction rate (%), conversion to open surgery (%), and overall and progression-free survival at 1 year. RESULTS: Overall, 95.8% (23/24) of patients who were eligible were recruited. Median age was 68 years (range 53-83). All patients had high grade serous histology and were BRCA negative. In total, 56.5% were stage IV, 43.5% were stage III, 87.0% had a partial response, while 13.0% had stable disease by RECIST 1.1. Median peritoneal cancer index was 24 (range 6-38). Following MIRRORS protocol, 87.0% (20/23) underwent robotic interval debulking surgery, and 13.0% (3/23) had open surgery. All patients achieved R<1 (robotic R0=47.4%, open R0=0%). No patients had conversion to open. Median estimated blood loss was 50 mL for robotic (range 20-500 mL), 2026 mL for open (range 2000-2800 mL) (p=0.001). Median intensive care length of stay was 0 days for robotic (range 0-8) and 3 days (range 3-13) for MIRRORS Open (p=0.012). The median length of stay was 1.5 days for robotic (range 1-17), 6 days for open (range 5-41) (p=0.012). The time to chemotherapy was as follows 18.5 days for robotic (range 13-28), 25 days for open (range 22-28) (p=0.139). CONCLUSIONS: Robotic interval debulking surgery appears safe and feasible for experienced robotic surgeons in patients with a pelvic mass ≤8 cm. A randomized controlled trial (MIRRORS-RCT) will determine whether MIRRORS protocol has non-inferior survival (overall and progression-free) compared with open interval debulking surgery.

Penetration performance of protective materials from crossbow attack: a preliminary study.

Crossbow-related injuries resulting in serious and mortal consequences have increased in recent years, and although significant research exists for both injury and fatality on the human body, limited data exists on the lethality of the bolt and the failure modes of protective materials. This paper concerns itself with the experimental validation of four differing crossbow bolt geometries, their effects on material failure and potentially lethality. During this study, four different types of crossbow bolt geometries were tested against two protection mechanisms that differed in mechanical properties, geometry, mass and size. The results show that at 67 ms-1, ogive, field and combo tips do not provide lethal effect at 10-m range, whilst a broadhead tip will perforate both the para-aramid and a reinforced area of polycarbonate material consisting of two 3-mm plates at 63-66 ms-1. Although perforation was apparent with a more honed tip geometry, the chain mail layering within the para-aramid protection and friction caused by polycarbonate petalling on the arrow body reduced the velocity enough to demonstrate the materials under test are effective at withstanding crossbow attack. Subsequent calculation of the maximum velocity that arrows could achieve if fired from the crossbow within this study shows results close to the overmatch value of each material and therefore a requirement to advance the knowledge in this field to influence the development of more effective armour protection mechanisms.

Sustainable and economical alternatives to fragment capture materials in explosive and ballistic trials.

Strawboard has been utilised as a fragmentation capture material since the 1960s, mainly employed to capture fragments from explosives and explosive devices from arena trials of munitions. As this material has historically been calibrated to a known standard, it has a proven record of allowing research establishments to ascertain the velocity of a fragment based on the depth of penetration of the strawboard. During the time of calibration, strawboard was used as a common building material which was both widely available and relatively affordable; however, due to the recent economic crisis and geopolitical supply issues, this is no longer the case. Building on initial testing, this paper investigates alternatives to strawboard to determine if a cheaper, more readily available material can be used instead. The alternatives are compared and judged based on the NATO ARSP-03 guideline for capture material which includes metrics such as price and attainability, as well as assessing environmental impact and its ability to be used as a viable alternative to strawboard in an explosive environment. Based on these NATO guidelines, explosive fragmentation and ballistic experiments were conducted, and ten materials were tested based on the following criteria: Handling, Density, Flammability, Calibration, Cost and Availability. Medium Density Fibreboard (MDF) was found to be a suitable alternative to strawboard. The data demonstrates that it provides the same capture performance as strawboard at approximately a quarter of the cost and is far more readily available. Other materials also showed potential and further testing should be undertaken to validate these materials as alternatives to MDF.

Quantification of fragmentation capture materials and an assessment of the viability of economical alternatives: a preliminary study.

High pressure, high-temperature events need to be quantified experimentally. Where fragmentation occurs, i.e. against personal protective equipment, there is a requirement for both a reliable and repeatable measurement of numerous experimental metrics. Typically, the most critical is calculating the energy absorbed by the target material, to characterize target performance. This is achieved by detonating a device and capturing a proportion of the fragmentation in a suitable material that can achieve successful recovery of all fragmentation produced. Therefore, allowing the estimation of the target's response using the depth of penetration within the capture material which allows the calculation of energy absorption. The current standardized fragmentation capture material used within the UK is known as strawboard. Although effective, this material is both expensive and limited in its availability. This study explores the classification of strawboard to provide a suitable baseline to compare against medium density fibreboard (MDF) and flooring underlay, which represent two more economically friendly alternatives on the openmarket. It was found that the uniformity of response for the MDF material was better than that of strawboard, due to its reproducibility between batches and velocity ranges. To further explore this phenomena, high explosive trials were conducted, further demonstrating MDF to be a viable, reliable and cheaper alternative. This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 2)'.

Protection against severe infant lower respiratory tract infections by immune training: Mechanistic studies.

BACKGROUND: Results from recent clinical studies suggest potential efficacy of immune training (IT)-based approaches for protection against severe lower respiratory tract infections in infants, but underlying mechanisms are unclear. OBJECTIVE: We used systems-level analyses to elucidate IT mechanisms in infants in a clinical trial setting. METHODS: Pre- and posttreatment peripheral blood mononuclear cells from a placebo-controlled trial in which winter treatment with the IT agent OM85 reduced infant respiratory infection frequency and/or duration were stimulated for 24 hours with the virus/bacteria mimics polyinosinic:polycytidylic acid/lipopolysaccharide. Transcriptomic profiling via RNA sequencing, pathway and upstream regulator analyses, and systems-level gene coexpression network analyses were used sequentially to elucidate and compare responses in treatment and placebo groups. RESULTS: In contrast to subtle changes in antivirus-associated polyinosinic:polycytidylic acid response profiles, the bacterial lipopolysaccharide-triggered gene coexpression network responses exhibited OM85 treatment-associated upregulation of IFN signaling. This was accompanied by network rewiring resulting in increased coordination of TLR4 expression with IFN pathway-associated genes (especially master regulator IRF7); segregation of TNF and IFN-γ (which potentially synergize to exaggerate inflammatory sequelae) into separate expression modules; and reduced size/complexity of the main proinflammatory network module (containing, eg, IL-1,IL-6, and CCL3). Finally, we observed a reduced capacity for lipopolysaccharide-induced inflammatory cytokine (eg, IL-6 and TNF) production in the OM85 group. CONCLUSION: These changes are consistent with treatment-induced enhancement of bacterial pathogen detection/clearance capabilities concomitant with enhanced capacity to regulate ensuing inflammatory response intensity and duration. We posit that IT agents exemplified by OM85 potentially protect against severe lower respiratory tract infections in infants principally by effects on innate immune responses targeting the bacterial components of the mixed respiratory viral/bacterial infections that are characteristic of this age group.

Newtonian Equivalence Principles.

The equivalence principle has constituted one of the cornerstones of discussions in the foundations of spacetime theories over the past century. However, up to this point the principle has been considered overwhelmingly only within the context of relativistic physics. In this article, we demonstrate that the principle has much broader, super-theoretic significance: to do so, we present a unified framework for understanding the principle in its various guises, applicable to both relativistic and Newtonian contexts. We thereby deepen significantly our understanding of the role played by the equivalence principle in a broad class of spacetime theories.

Multi-Excitation Raman Spectroscopy for Label-Free, Strain-Level Characterization of Bacterial Pathogens in Artificial Sputum Media.

The current methods for diagnosis of acute and chronic infections are complex and skill-intensive. For complex clinical biofilm infections, it can take days from collecting and processing a patient's sample to achieving a result. These aspects place a significant burden on healthcare providers, delay treatment, and can lead to adverse patient outcomes. We report the development and application of a novel multi-excitation Raman spectroscopy-based methodology for the label-free and non-invasive detection of microbial pathogens that can be used with unprocessed clinical samples directly and provide rapid data to inform diagnosis by a medical professional. The method relies on the differential excitation of non-resonant and resonant molecular components in bacterial cells to enhance the molecular finger-printing capability to obtain strain-level distinction in bacterial species. Here, we use this strategy to detect and characterize the respiratory pathogens Pseudomonas aeruginosa and Staphylococcus aureus as typical infectious agents associated with cystic fibrosis. Planktonic specimens were analyzed both in isolation and in artificial sputum media. The resonance Raman components, excited at different wavelengths, were characterized as carotenoids and porphyrins. By combining the more informative multi-excitation Raman spectra with multivariate analysis (support vector machine) the accuracy was found to be 99.75% for both species (across all strains), including 100% accuracy for drug-sensitive and drug-resistant S. aureus. The results demonstrate that our methodology based on multi-excitation Raman spectroscopy can underpin the development of a powerful platform for the rapid and reagentless detection of clinical pathogens to support diagnosis by a medical expert, in this case relevant to cystic fibrosis. Such a platform could provide translatable diagnostic solutions in a variety of disease areas and also be utilized for the rapid detection of anti-microbial resistance.

Predators attacking virtual prey reveal the costs and benefits of leadership.

A long-standing assumption in social behavior is that leadership incurs costs as well as benefits, and this tradeoff can result in diversified social roles in groups. The major cost of leadership in moving animal groups is assumed to be predation, with individuals leading from the front of groups being targeted more often by predators. Nevertheless, empirical evidence for this is limited, and experimental tests are entirely lacking. To avoid confounding effects associated with observational studies, we presented a simulation of virtual prey to real fish predators to directly assess the predation cost of leadership. Prey leading others are at greater risk than those in the middle of groups, confirming that any benefits of leading may be offset by predation costs. Importantly, however, followers confer a net safety benefit to leaders, as prey leading others were less likely to be attacked compared with solitary prey. We also find that the predators preferentially attacked when solitary individuals were more frequent, but this effect was relatively weak compared with the preference for attacking solitary prey during an attack. Using virtual prey, where the appearance and behavior of the prey can be manipulated and controlled exactly, we reveal a hierarchy of risk from solitary to leading to following social strategies. Our results suggest that goal-orientated individuals (i.e., potential leaders) are under selective pressure to maintain group cohesion, favoring effective leadership rather than group fragmentation. Our results have significant implications for understanding the evolution and maintenance of different social roles in groups.

Fish Avoid Visually Noisy Environments Where Prey Targeting Is Reduced.

AbstractThe environment contains different forms of ecological noise that can reduce the ability of animals to detect information. Here, we ask whether animals adapt their behavior to either exploit or avoid areas of their environment with increased dynamic visual noise. Three-spined sticklebacks (Gasterosteus aculeatus) were immersed in environments with a simulated form of naturally occurring visual noise-moving light bands that form on underwater substrates caused by the refraction of light through surface waves. We tested whether this form of visual noise affected fish's habitat selection, movements, and prey-targeting behavior. Fish avoided areas of the environment with increased visual noise and achieved this by increasing their activity as a function of the locally perceived noise level. Fish were less likely to respond to virtual prey in environments with increased visual noise, highlighting a potential impact that visual noise has on their perceptual abilities. Fish did not increase or decrease their refuge use in environments with increased visual noise, providing no evidence that visual noise increased either exploratory or risk-aversive behavior. Our results indicate that animals can use simple behavioral strategies to avoid visually noisy environments, thereby mitigating the impacts that these environments appear to have on their perceptual abilities.

Selective Imaging of Microplastic and Organic Particles in Flow by Multimodal Coherent Anti-Stokes Raman Scattering and Two-Photon Excited Autofluorescence Analysis.

Microplastic pollution is an urgent global issue. While spectroscopic techniques have been widely used for the identification of plastics collected from aquatic environments, these techniques are often labor-intensive and time-consuming due to sample collection, preparation, and long measurement times. In this study, a method for the two-dimensional detection and classification of flowing microplastic and organic biotic particles with high spatial and temporal resolutions has been proposed based on the simultaneous detection of coherent anti-Stokes Raman scattering (CARS) and two-photon excited autofluorescence (TPEAF) signals. Poly(methyl methacrylate) (PMMA), polystyrene (PS), and low-density polyethylene (LDPE) particles with sizes ranging from several tens to hundreds of micrometers were selectively detected in flow with an average velocity of 4.17 mm/s by CARS line scanning. With the same flow velocity, flowing PMMA and alga particles were measured using a multimodal system of CARS and TPEAF signals. The average intensities of both PMMA and alga particles in the CARS signals at a frequency of 2940 cm-1 were higher than the background level, while only algae emitted TPEAF signals. This allowed the classification of PMMA and alga particles to be successfully performed in flow by the simultaneous detection of CARS and TPEAF signals. With the proposed method, the monitoring of microplastics in a continuous water flow without collection or extraction is possible, which is game-changing for the current sampling-based microplastic analysis.

The measure of spatial position within groups that best predicts predation risk depends on group movement.

Both empirical and theoretical studies show that an individual's spatial position within a group can impact the risk of being targeted by predators. Spatial positions can be quantified in numerous ways, but there are no direct comparisons of different spatial measures in predicting the risk of being targeted by real predators. Here, we assess these spatial measures in groups of stationary and moving virtual prey being attacked by three-spined sticklebacks (Gasterosteus aculeatus). In stationary groups, the limited domain of danger best predicted the likelihood of attack. In moving groups, the number of near neighbours was the best predictor but only over a limited range of distances within which other prey were counted. Otherwise, measures of proximity to the group's edge outperformed measures of local crowding in moving groups. There was no evidence that predators preferentially attacked the front or back of the moving groups. Domains of danger without any limit, as originally used in the selfish herd model, were also a poor predictor of risk. These findings reveal that the collective properties of prey can influence how spatial position affects predation risk, via effects on predators' targeting. Selection may therefore act differently on prey positioning behaviour depending on group movement.

Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing.

Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7hi versus IRF7lo molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes. For IRF7lo children, symptom duration prior to hospital presentation was more than twice as long from initial symptoms (p = 0.011) and nearly three times as long for cough (p < 0.001), the odds ratio of admission to hospital was increased more than 4-fold (p = 0.018), and time to recurrence was shorter (p = 0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7hi versus IRF7lo phenotypes with associated differences in clinical phenotypes.

Contrasting stripes are a widespread feature of group living in birds, mammals and fishes.

Grouping is a widespread form of predator defence, with individuals in groups often performing evasive collective movements in response to attack by predators. Individuals in these groups use behavioural rules to coordinate their movements, with visual cues about neighbours' positions and orientations often informing movement decisions. Although the exact visual cues individuals use to coordinate their movements with neighbours have not yet been decoded, some studies have suggested that stripes, lines, or other body patterns may act as conspicuous conveyors of movement information that could promote coordinated group movement, or promote dazzle camouflage, thereby confusing predators. We used phylogenetic logistic regressions to test whether the contrasting achromatic stripes present in four different taxa vulnerable to predation, including species within two orders of birds (Anseriformes and Charadriiformes), a suborder of Artiodactyla (the ruminants), and several orders of marine fishes (predominantly Perciformes) were associated with group living. Contrasting patterns were significantly more prevalent in social species, and tended to be absent in solitary species or species less vulnerable to predation. We suggest that stripes taking the form of light-coloured lines on dark backgrounds, or vice versa, provide a widespread mechanism across taxa that either serves to inform conspecifics of neighbours' movements, or to confuse predators, when moving in groups. Because detection and processing of patterns and of motion in the visual channel is essentially colour-blind, diverse animal taxa with widely different vision systems (including mono-, di-, tri-, and tetrachromats) appear to have converged on a similar use of achromatic patterns, as would be expected given signal-detection theory. This hypothesis would explain the convergent evolution of conspicuous achromatic patterns as an antipredator mechanism in numerous vertebrate species.

In infants with sufficient vitamin D status at birth, vitamin D supplementation does not impact immune development.

BACKGROUND: Low vitamin D levels have been associated with allergic diseases. Vitamin D has potent immunomodulatory properties, but the mechanisms remain unclear. We have investigated the effect of oral vitamin D supplementation on circulating immune cell phenotypes in infants. METHOD: A double-blinded randomised controlled trial was conducted to investigate the effect of oral vitamin D supplementation (400 IU/d) on eczema and immune development. A subset of 78 infants was included in this analysis. Phenotypic analysis of immune cell subsets was performed using flow cytometry. RESULTS: Vitamin D supplementation resulted in median 25(OH)D levels of 80.5 vs 59.5 nmol/L in the placebo group at 3 months of age (P = .002) and 87.5 vs 77 nmol/L at 6 months of age (P = .08). We observed significant changes in immune cell composition from birth (cord blood) to 6 months of age. Vitamin D supplementation did not impact these changes, nor did immune cell composition correlate with plasma 25(OH)D levels. Through exploratory analysis, we identified possible associations with eczema development and increased abundance of naïve CD4- T cells at birth, as well as associations with basophils, iNKT and central memory CD4+ T cells, and altered expression patterns of IgE receptor (FcεR1) on monocytes and dendritic cells with eczema at 6 months. CONCLUSIONS: Vitamin D supplementation in infants who were vitamin D sufficient at birth did not affect developmental changes in immune cells during the first 6 months of life. However, immune cell profiles at birth and at 6 months of age were associated with early life eczema.

Personalized Transcriptomics Reveals Heterogeneous Immunophenotypes in Children with Viral Bronchiolitis.

Rationale: A subset of infants are hypersusceptible to severe/acute viral bronchiolitis (AVB), for reasons incompletely understood. Objectives: To characterize the cellular/molecular mechanisms underlying infant AVB in circulating cells/local airway tissues. Methods: Peripheral blood mononuclear cells and nasal scrapings were obtained from infants (<18 mo) and children (≥18 mo to 5 yr) during AVB and after convalescence. Immune response patterns were profiled by multiplex analysis of plasma cytokines, flow cytometry, and transcriptomics (RNA-Seq). Molecular profiling of group-level data used a combination of upstream regulator and coexpression network analysis, followed by individual subject-level data analysis using personalized N-of-1-pathways methodology. Measurements and Main Results: Group-level analyses demonstrated that infant peripheral blood mononuclear cell responses were dominated by monocyte-associated hyperupregulated type 1 IFN signaling/proinflammatory pathways (drivers: TNF [tumor necrosis factor], IL-6, TREM1 [triggering receptor expressed on myeloid cells 1], and IL-1B), versus a combination of inflammation (PTGER2 [prostaglandin E receptor 2] and IL-6) plus growth/repair/remodeling pathways (ERBB2 [erbb-b2 receptor tyrosine kinase 2], TGFB1 [transforming growth factor-ß1], AREG [amphiregulin], and HGF [hepatocyte growth factor]) coupled with T-helper cell type 2 and natural killer cell signaling in children. Age-related differences were not attributable to differential steroid usage or variations in underlying viral pathogens. Nasal mucosal responses were comparable qualitatively in infants/children, dominated by IFN types 1-3, but the magnitude of upregulation was higher in infants (range, 6- to 48-fold) than children (5- to 17-fold). N-of-1-pathways analysis confirmed differential upregulation of innate immunity in infants and natural killer cell networks in children, and additionally demonstrated covert AVB response subphenotypes that were independent of chronologic age. Conclusions: Dysregulated expression of IFN-dependent pathways after respiratory viral infections is a defining immunophenotypic feature of AVB-susceptible infants and a subset of children. Susceptible subjects seem to represent a discrete subgroup who cluster based on (slow) kinetics of postnatal maturation of innate immune competence.

Challenges to well-being for general practice trainee doctors: a qualitative study of their experiences and coping strategies.

PURPOSES OF THE STUDY: To identify the challenges to well-being experienced by general practice postgraduate trainees and to explore how the trainees respond to those challenges. STUDY DESIGN: Qualitative focus group study with doctors in their final year of general practice training (n=16). The participants in the study were recruited from one training scheme in South West England. Data were thematically analysed. RESULTS: Participants reported challenges to well-being relating to dysfunctional relationships with colleagues and patients, their workload, a perceived lack of support at work and also physical environmental challenges. They identified response strategies focused on cognitive processing, physical self-care, focusing on their professional purpose, building supportive relationships and adapting their working environment where possible. Additionally, there were factors that could support trainee well-being, including personal factors such as adaptability and self-awareness, but also external and organisational factors, such as culture, supportive colleagues and organisational adaptability in relation to workload management. The importance to trainees of the idea of being a 'good doctor' arose repeatedly in the data, as did the importance of the organisational environment. Participants reported finding their training placements in secondary care environments particularly challenging. CONCLUSION: This research highlights the strategies that general practice trainees use in response to challenges, but also that the responsibility for maintaining well-being cannot be borne by individuals alone. This study identifies that supportive approaches by healthcare organisations and educators are vitally important to general practitioner trainees' well-being.

Decoding Susceptibility to Respiratory Viral Infections and Asthma Inception in Children.

Human Respiratory Syncytial Virus and Human Rhinovirus are the most frequent cause of respiratory tract infections in infants and children and are major triggers of acute viral bronchiolitis, wheezing and asthma exacerbations. Here, we will discuss the application of the powerful tools of systems biology to decode the molecular mechanisms that determine risk for infection and subsequent asthma. An important conceptual advance is the understanding that the innate immune system is governed by a Bow-tie architecture, where diverse input signals converge onto a few core pathways (e.g., IRF7), which in turn generate diverse outputs that orchestrate effector and regulatory functions. Molecular profiling studies in children with severe exacerbations of asthma/wheeze have identified two major immunological phenotypes. The IRF7hi phenotype is characterised by robust upregulation of antiviral response networks, and the IRF7lo phenotype is characterised by upregulation of markers of TGFß signalling and type 2 inflammation. Similar phenotypes have been identified in infants and children with severe viral bronchiolitis. Notably, genome-wide association studies supported by experimental validation have identified key pathways that increase susceptibility to HRV infection (ORMDL3 and CHDR3) and modulate TGFß signalling (GSDMB, TGFBR1, and SMAD3). Moreover, functional deficiencies in the activation of type I and III interferon responses are already evident at birth in children at risk of developing febrile lower respiratory tract infections and persistent asthma/wheeze, suggesting that the trajectory to asthma begins at birth or in utero. Finally, exposure to microbes and their products reprograms innate immunity and provides protection from the development of allergies and asthma in children, and therefore microbial products are logical candidates for the primary prevention of asthma.

Fine-scale behavioural adjustments of prey on a continuum of risk.

In the wild, prey species often live in the vicinity of predators, rendering the ability to assess risk on a moment-to-moment basis crucial to survival. Visual cues are important as they allow prey to assess predator species, size, proximity and behaviour. However, few studies have explicitly examined prey's ability to assess risk based on predator behaviour and orientation. Using mosquitofish, Gambusia holbrooki, and their predator, jade perch, Scortum barcoo, under controlled conditions, we provide some of the first fine-scale characterization of how prey adapt their behaviour according to their continuous assessment of risk based on both predator behaviour and angular distance to the predator's mouth. When these predators were inactive and posed less of an immediate threat, prey within the attack cone of the predator showed reductions in speed and acceleration characteristic of predator-inspection behaviour. However, when predators became active, prey swam faster with greater acceleration and were closer together within the attack cone of predators. Most importantly, this study provides evidence that prey do not adopt a uniform response to the presence of a predator. Instead, we demonstrate that prey are capable of rapidly and dynamically updating their assessment of risk and showing fine-scale adjustments to their behaviour.

Progressive increase of FcεRI expression across several PBMC subsets is associated with atopy and atopic asthma within school-aged children.

BACKGROUND: Antigen-specific IgE binds the Fcε receptor I (FcεRI) expressed on several types of immune cells, including dendritic cells (DCs). Activation of FcεRI on DCs in atopics has been shown to modulate immune responses that potentially contribute to asthma development. However, the extent to which DC subsets differ in FcεRI expression between atopic children with or without asthma is currently not clear. This study aimed to analyse the expression of FcεRI on peripheral blood mononuclear cells (PBMCs) from atopic children with and without asthma, and non-atopic/non-asthmatic age-matched healthy controls. METHODS: We performed multiparameter flow cytometry on PBMC from 391 children across three community cohorts and one clinical cohort based in Western Australia. RESULTS: We confirmed expression of FcεRI on basophils, monocytes, plasmacytoid and conventional DCs, with higher proportions of all cell populations expressing FcεRI in atopic compared to non-atopic children. Further, we observed that levels of FcεRI expression were elevated across plasmacytoid and conventional DC as well as basophils in atopic asthmatic compared to atopic non-asthmatic children also after adjusting for serum IgE levels. CONCLUSION: Our data suggest that the expression pattern of FcεRI on DC and basophils differentiates asthmatic from non-asthmatic atopic children. Given the significant immune modulatory effects observed as a consequence of FcεRI expression, this altered expression pattern is likely to contribute to asthma pathology in children.