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Abstract Blood transcriptional biomarkers of acute viral infections typically reflect type 1 interferon (IFN) signalling, but it is not known whether there are biological differences in their regulation that can be leveraged for distinct translational applications. We use high frequency sampling in the SARS-CoV-2 human challenge model to show induction of IFN-stimulated gene (ISG) expression with different temporal and cellular profiles. MX1 gene expression correlates with a rapid and transient wave of ISG expression across all cell types, which may precede PCR detection of replicative infection. Another ISG, IFI27, shows a delayed but sustained response restricted to myeloid cells, attributable to gene and cell-specific epigenetic regulation. These findings are reproducible in experimental and naturally acquired infections with influenza, respiratory syncytial virus and rhinovirus. Blood MX1 expression is superior to IFI27 expression for diagnosis of early infection, as a correlate of viral load and for discrimination of virus culture positivity. Therefore, MX1 expression offers potential to stratify patients for antiviral therapy or infection control interventions. Blood IFI27 expression is superior to MX1 expression for diagnostic accuracy across the time course of symptomatic infection and thereby, offers higher diagnostic yield for respiratory virus infections that incur a delay between transmission and testing.

For undergraduate students, excessive screen time is associated with poorer mental health and greater perceived stress. Objective: The purpose of the present investigation was to determine the potential moderating influence of physical activity and sleep on the relationship between screen time and stress. Participants & Methods: A cross-sectional sample of 513 undergraduate students between Fall 2017 & Spring 2020 were given a questionnaire to assess perceived stress level, physical activity engagement, screen time, and sleep. Results: Stepwise hierarchical regression analyses identified that screen time, sleep, and the three-way interaction between screen time, sleep, and physical activity were associated with stress. Post-hoc decomposition revealed that higher levels of physical activity and sleep both mitigated the relationship between screen time and stress. Conclusions: Findings suggest that modifiable health behaviors such as physical activity and sleep may be important factors for managing the negative effects of screen time on stress in college-aged adults.

Although children learn more when teachers gesture, it is not clear "how" gesture supports learning. Here, we sought to investigate the nature of the memory processes that underlie the observed benefits of gesture on lasting learning. We hypothesized that instruction with gesture might create memory representations that are particularly resistant to interference. We investigated this possibility in a classroom study with 402 second- and third-grade children. Participants received classroom-level instruction in mathematical equivalence using videos with or without accompanying gesture. After instruction, children solved problems that were either visually similar to the problems that were taught, and consistent with an operational interpretation of the equal sign (interference), or visually distinct from equivalence problems and without an equal sign (control) in order to assess the role of gesture in resisting interference after learning. Gesture facilitated learning, but the effects of gesture and interference varied depending on type of problem being solved and the strategies that children used to solve problems prior to instruction. Some children benefitted from gesture, while others did not. These findings have implications for understanding the mechanisms underlying the beneficial effect of gesture on mathematical learning, revealing that gesture does not work via a general mechanism like enhancing attention or engagement that would apply to children with all forms of prior knowledge.

Abstract A 10‐year‐old male neutered crossbreed dog and an 8‐year‐old female neutered greyhound presented after peracute onset of cerebellar dysfunction. The crossbreed dog had anisocoria with the left pupil being mydriatic, spontaneous conjugate rotatory nystagmus with fast phase to the left and delayed postural reactions on the left side. The greyhound had anisocoria with the left pupil being mydriatic, right positional ventral strabismus, absent menace response in the left eye and postural reaction deficits on the left side. For both dogs, the neuroanatomical localization was left cerebellum with paradoxical vestibular syndrome. Magnetic resonance imaging identified a left cerebellar ischemic territorial infarct of the rostral cerebellar artery, involving the region of the left interposital nucleus. Both dogs were given supportive care and at 2‐week follow‐up the anisocoria had resolved. Anisocoria with mydriasis can be a clinical sign in dogs with naturally‐occurring cerebellar ischemic infarcts in the region of the ipsilateral interposital nucleus.

The western North Atlantic Ocean is strongly influenced by continental outflow, making it an ideal region to study the atmospheric transition from a polluted coastline to the marine environment. Utilizing eight transit flights between the NASA Langley Research Center (LaRC) in Hampton, Virginia, and the remote island of Bermuda from NASA's Aerosol Cloud meTeorology Interactions oVer the western ATlantic Experiment (ACTIVATE), we examine the evolution of trace gas and aerosol properties off the US East Coast. The first pair of flights flew along the wind trajectory of continental outflow, while the other flights captured a mix of marine and continental air mass sources. For measurements within the boundary layer (BL), there was an offshore decline in particle N, N>100 nm, CH4, CO, and CO2 concentrations, all leveling off around ∼900 km offshore from the LaRC. These trends are strongest for the first pair of flights. In the BL, offshore declines in organic mass fraction and increases in sulfate mass fraction coincide with increasing hygroscopicity based on f(RH) measurements. Free troposphere measurements show a decline in N, but other measured parameters are more variable when compared to the prominent offshore gradients seen in the BL. Pollution layers exist in the free troposphere, such as smoke plumes, that can potentially entrain into the BL. This work provides detailed case studies with a broad set of high-resolution measurements to further our understanding of the transition between continental and marine environments.

Abstract The outer membrane is a formidable barrier that protects Gram-negative bacteria against environmental threats. Its integrity requires the correct folding and insertion of outer membrane proteins (OMPs) by the membrane-embedded β-barrel assembly machinery (BAM). Unfolded OMPs are delivered to BAM by the periplasmic chaperone SurA, but how SurA and BAM work together to ensure successful OMP delivery and folding remains unclear. Here, guided by AlphaFold2 models, we use disulphide bond engineering in an attempt to trap SurA in the act of OMP delivery to BAM, and solve cryoEM structures of a series of complexes. The results suggest that SurA binds BAM at its soluble POTRA-1 domain, which may trigger conformational changes in both BAM and SurA that enable transfer of the unfolded OMP to the BAM lateral gate for insertion into the outer membrane. Mutations that disrupt the interaction between BAM and SurA result in outer membrane assembly defects, supporting the key role of SurA in outer membrane biogenesis.

Remote marine regions comprise a high fraction of Earth's surface, but in situ vertically resolved measurements over these locations remain scarce. Here we use airborne data during 15 vertical spiral soundings (0.15–8.5 km) over Bermuda during the NASA Aerosol Cloud meTeorology Interactions over the western ATlantic Experiment (ACTIVATE) to investigate the impact of different source regions on the vertical structure of trace gases, aerosol particles, and meteorological variables over 1000 km offshore of the US East Coast. Results reveal significant differences in vertical profiles of variables between three different air mass source categories (North America, Ocean, Caribbean/North Africa) identified using the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) model: (i) the strongest pollution signature is from air masses from the North America category, while the weakest one is from the Ocean category; (ii) North America air has the highest levels of CO, CH4, submicron particle number concentration, aerosol mass spectrometer (AMS) mass, and organic mass fraction along with smoke layers in the free troposphere (FT); (iii) Ocean air has the highest relative amount of nitrate, non-sea-salt sulfate, and oxalate, which are key acidic species participating in chloride depletion; (iv) air masses from the Caribbean/North Africa showed a pronounced coarse aerosol signature in the FT and reduced aerosol hygroscopicity, which is associated with dust transport; and (v) there is considerable vertical heterogeneity for almost all variables examined, including higher O3 and submicron particle concentrations with altitude, suggesting that the FT is a potential contributor of both constituents in the marine boundary layer. This study highlights the importance of considering air mass source origin and vertical resolution to capture aerosol and trace gas properties over remote marine areas.

Background: Plasma-derived Extracellular Vesicles (EVs) have been suggested as novel biomarkers in melanoma, due to their ability to reflect the cell of origin and ease of collection. This study aimed to identify novel EV biomarkers that can discriminate between disease stages. This was achieved by characterising the plasma-derived EVs of patients with melanoma, and comparing their proteomic and metabolomic profile to those from healthy controls. Methods: EVs were isolated from the plasma of 36 patients with melanoma and 13 healthy controls using Size Exclusion Chromatography. Proteomic and Metabolomic Analyses were performed, and machine learning algorithms were used to identify potential proteins and metabolites to differentiate the plasma-derived EVs from melanoma patients of different disease stages. Results: The concentration and size of the EV population isolated was similar between groups. Proteins (APOC4, PRG4, PLG, TNC, VWF and SERPIND1) and metabolites (lyso PC a C18:2, PC ae C44:3) previously associated with melanoma pathogenesis were identified as relevant in differentiating between disease stages. Conclusion: The results further support the continued investigation of circulating plasma-derived EVs as biomarkers in melanoma. Furthermore, the potential of combined proteo-metabolomic signatures for differentiation between disease stages may provide valuable insights into early detection, prognosis, and personalised treatment strategies.

Abstract Menopause is associated with reduced endothelial‐dependent vasodilation and increased cardiovascular disease (CVD) risk. Dietary nitrate, a non‐pharmacological approach, may increase vasodilatory capacity consequentially reducing CVD risk. We investigated macro‐ and microvascular function after acute nitrate supplementation in postmenopausal females (PMF). Vascular function was studied with flow‐mediated vasodilation (FMD) and near‐infrared post occlusive reactive hyperemia (PORH). Incremental handgrip exercise was performed to investigate blood flow and tissue oxygenation. We hypothesized acute dietary nitrate would not impact resting endothelial measures but would increase post ischemic vasodilation and incremental exercise blood flow. Late‐phase PMF (n = 12) participated in a randomized crossover design with 140 mL of nitrate‐rich (NR) beetroot juice or nitrate‐poor black currant juice. Testing included a 5‐min FMD, a 3‐min ischemic exercise FMD, and incremental exercise at 10%, 15%, and 20% maximal voluntary contraction to measure blood flow and pressure responses. A p ≤ 0.05 was considered significant. One‐way ANOVA indicated lower resting pressures, but no change to FMD, or PORH in either protocol. Two‐way repeated measures ANOVA indicated NR supplementation significantly reduced mean arterial pressure at rest and during incremental exercise at all intensities without changes to blood flow. Acute nitrate is effective for resting and exercising blood pressure management in PMF.

IntroductionWith the goal of patient engagement, an initiative was formulated to equip each patient in the general wards with a tablet whereby they can access their health information and patient education materials and communicate with their healthcare team. This paper presented the methodology of the implementation efforts as well as an evaluation of the preliminary outcomes.MethodsThe process of hospital-wide implementation was shared using the implementation research logic model. The bedside tablets were rolled out hospital-wide in a step-wedge manner over 12 months. Barriers and facilitators to this implementation were discussed together with strategies to optimize the situation. Preliminary outcomes of the implementation were evaluated using the RE-AIM framework.ResultsThe initial adoption rate for the bedside tablet was low. Additional strategies, such as survey audits and provision of feedback, development of education materials for patients, facilitation, and purposefully re-examining the implementation strategies, were used to improve adoption. The trend of adoption increased over the course of 2 years from the start of implementation.DiscussionThe initial lower adoption rates may reflect Singapore's paternalistic healthcare culture. While this implementation was driven by the need to move away from paternalism and toward patient engagement, more time is required for significant cultural change.

Young adulthood is an important developmental milestone during which individuals could greatly benefit from health promotion tools. Civic engagement has been linked with positive mental health and well-being; however, little is known about civic behavior among young adults who do not attend college. We investigated the relationship between civic engagement and well-being among non-college-bound young adults (NCYAs). Investigators conducted semi-structured focus groups and interviews with 14 young adults (aged 18–25 years old) who were not enrolled in college. Using qualitative thematic analysis procedures, coders defined five key themes within the data pertaining to the intersection of civic engagement and mental health: (1) experiencing, witnessing, and believing in the fruits of civic engagement labor; (2) managing emotions and conflict; (3) balancing individual needs with those of the collective; (4) garnering social connectedness and support; and (5) acting in alignment with values. Participants described complex, bidirectional relationships between civic engagement and well-being. Participants experiencing empowerment and political efficacy resulting from their civic engagement experiences reported greater well-being. Some participants used civic engagement as a strategy to cope with distressing emotions, while others were civically disengaged to avoid conflict and negative affect. Participants described the need to attend to personal needs first before engaging in actions to help the collective. Connecting with others was a notable promoter of well-being among those who were civically active, although negative peer influence was also a notable detractor. Finally, participants described strong value systems and identities related to civic engagement. Civic engagement can elicit both positive and negative emotional, psychological, and social well-being. The results underscore potential mechanisms that mediate the civic engagement to well-being pathway, which can be used to inform efforts to engage and retain NCYAs in civic engagement. Interventionists should cultivate strong coping and conflict management skills among engagers to manage difficult emotions that arise before, during, and after civic activity if health outcomes are to be achieved.

Ocean surface wind speed (i.e., wind speed 10 m above sea level) is a critical parameter used by atmospheric models to estimate the state of the marine atmospheric boundary layer (MABL). Accurate surface wind speed measurements in diverse locations are required to improve characterization of MABL dynamics and assess how models simulate large-scale phenomena related to climate change and global weather patterns. To provide these measurements, this study introduces and evaluates a new surface wind speed data product from the NASA Langley Research Center nadir-viewing High Spectral Resolution Lidar – generation 2 (HSRL-2) using data collected as part of the NASA Aerosol Cloud meTeorology Interactions oVer the western ATlantic Experiment (ACTIVATE) mission. The HSRL-2 can directly measure vertically resolved aerosol backscatter and extinction profiles without additional constraints or assumptions, enabling the instrument to accurately derive atmospheric attenuation and directly determine surface reflectance (i.e., surface backscatter). Also, the high horizontal spatial resolution of the HSRL-2 retrievals (0.5 s or ∼ 75 m along track) allows the instrument to probe the fine-scale spatial variability in surface wind speeds over time along the flight track and over breaks in broken cloud fields. A rigorous evaluation of these retrievals is performed by comparing coincident HSRL-2 and National Center for Atmospheric Research (NCAR) Airborne Vertical Atmosphere Profiling System (AVAPS) dropsonde data, owing to the joint deployment of these two instruments on the ACTIVATE King Air aircraft. These comparisons show correlations of 0.89, slopes of 1.04 and 1.17, and y intercepts of −0.13 and −1.05 m s−1 for linear and bisector regressions, respectively, and the overall accuracy is calculated to be 0.15 ± 1.80 m s−1. It is also shown that the dropsonde surface wind speed data most closely follow the HSRL-2 distribution of wave slope variance using the distribution proposed by Hu et al. (2008) rather than the ones proposed by Cox and Munk (1954) and Wu (1990) for surface wind speeds below 7 m s−1, with this category comprising most of the ACTIVATE data set. The retrievals are then evaluated separately for surface wind speeds below 7 m s−1 and between 7 and 13.3 m s−1 and show that the HSRL-2 retrieves surface wind speeds with a bias of ∼ 0.5 m s−1 and an error of ∼ 1.5 m s−1, a finding not apparent in the cumulative comparisons. Also, it is shown that the HSRL-2 retrievals are more accurate in the summer (−0.18 ± 1.52 m s−1) than in the winter (0.63 ± 2.07 m s−1), but the HSRL-2 is still able to make numerous (N=236) accurate retrievals in the winter. Overall, this study highlights the abilities and assesses the performance of the HSRL-2 surface wind speed retrievals, and it is hoped that further evaluation of these retrievals will be performed using other airborne and satellite data sets.

Aerosol optical depth was retrieved from two airborne remote sensing instruments, the Research Scanning Polarimeter (RSP) and Second Generation High Spectral Resolution Lidar (HSRL-2), during the National Aeronautics and Space Administration (NASA) Aerosol Cloud meTeorology Interactions oVer the western ATlantic Experiment (ACTIVATE). The field campaign offers a unique opportunity to evaluate an extensive 3-year dataset under a wide range of meteorological conditions from two instruments on the same platform. However, a long-standing issue in atmospheric field studies is that there is a lack of reference datasets for properly validating field measurements and estimating their uncertainties. Here we address this issue by using the triple collocation method, in which a third collocated satellite dataset from the Moderate Resolution Imaging Spectroradiometer (MODIS) is introduced for comparison. HSRL-2 is found to provide a more accurate retrieval than RSP over the study region. The error standard deviation of HSRL-2 with respect to the ground truth is 0.027. Moreover, this approach enables us to develop a simple, yet efficient, quality control criterion for RSP data. The physical reasons for the differences in two retrievals are determined to be cloud contamination, aerosols near the surface, multiple aerosol layers, absorbing aerosols, non-spherical aerosols, and simplified retrieval assumptions. These results demonstrate the pathway for optimal aerosol retrievals by combining information from both lidars and polarimeters for future airborne and satellite missions.

Background: Type 2 diabetes mellitus can significantly affect oral health, potentially leading to morphological changes in the dental pulp. Aim: The study aims to assess and compare the coronal pulpal height of the maxillary canine and mandibular first molar between type 2 diabetics and nondiabetics by utilizing panoramic radiographs. The coronal pulpal height of the maxillary canine and mandibular first molar between individuals with type 2 diabetes and those without diabetes using panoramic radiographs. Settings and Design: The study was conducted as a retrospective cross-sectional study in the Department of Oral Medicine and Radiology. Materials and Methods: Coronal pulp heights of the maxillary canine and mandibular first molar were measured in 100 orthopantomograms (OPGs) from the diabetic and nondiabetic groups, along with the corresponding same-day random blood glucose levels in the diabetic group. Statistical Analysis: A t-test was used to compare blood glucose and coronal pulpal height between the two groups and Pearson correlation coefficients to assess relationships between blood sugar level and coronal pulpal height. Results: In the maxillary canine, the diabetic group had a coronal pulpal height of 3.50 mm, while the nondiabetic group had 2.55 mm, with P = 0.002 and 0.047, respectively. Positive correlations between blood glucose levels and the maxillary canine’s coronal pulpal height (1.000), with a weaker correlation with the mandibular first molar’s height (0.116), were also observed. A negative correlation (−0.256) was observed between the coronal pulpal heights of the maxillary canine and mandibular first molar. Conclusions: The diabetic group showed increased coronal pulpal height in the maxillary canine compared to the nondiabetic group. There was a positive correlation between blood glucose levels and the pulpal height of the maxillary canine, with a weaker correlation for the mandibular first molar. Clinical Significance: This study highlights the critical role of early oral health monitoring for individuals with type 2 diabetes, enabling dental professionals to detect potential signs of undiagnosed diabetes through radiographic assessments.

Abstract Identifying factors linked to autism traits in the general population may improve our understanding of the mechanisms underlying divergent neurodevelopment. In this study we assess whether factors increasing the likelihood of childhood autism are related to early autistic trait emergence, or if other exposures are more important. We used data from 536 toddlers from London (UK), collected at birth (gestational age at birth, sex, maternal body mass index, age, parental education, parental language, parental history of neurodevelopmental conditions) and at 18 months (parents cohabiting, measures of socio-economic deprivation, measures of maternal parenting style, and a measure of maternal depression). Autism traits were assessed using the Quantitative Checklist for Autism in Toddlers (Q-CHAT) at 18 months. A multivariable model explained 20% of Q-CHAT variance, with four individually significant variables (two measures of parenting style and two measures of socio-economic deprivation). In order to address variable collinearity we used principal component analysis, finding that a component which was positively correlated with Q-CHAT was also correlated to measures of parenting style and socio-economic deprivation. Our results show that parenting style and socio-economic deprivation correlate with the emergence of autism traits at age 18 months as measured with the Q-CHAT in a community sample.

Introduction: Diagnosing Tuberculosis (TB) in children is difficult as they do not expectorate sputum on their own, and the sample is usually paucibacillary. Hence, alternative sampling methods like Gastric juice Aspiration (GA), which is the widely accepted method, and Induced Sputum (IS) collection, a more novel approach, are used. The IS method has several advantages, such as being less invasive, not requiring inpatient admission, causing less discomfort, and not necessitating overnight fasting, compared to the GA method. Aim: To evaluate IS against GA for diagnosing TB using XpertMTB/RIF assay, as well as mycobacterial culture, in children aged between 2 and 15 years. Materials and Methods: This cross-sectional study was conducted in the Department of Paediatrics at Christian Medical College and Hospital, Vellore, Tamil Nadu, India from June 2019 to March 2020, involving 138 children aged between 2 and 15 years who were being evaluated for TB. GA samples were collected after an overnight fast, and on the same day, atleast two hours later, IS samples were collected by trained staff. Both samples underwent mycobacterial smear and culture using the Mycobacteria Growth Indicator Tube (MGIT) method and Xpert MTB/RIF assay. Confirmation of pulmonary TB was based on atleast one of these tests being positive. The ‘Wong-Baker’ Visual Analogue Scale (VAS) was individually administered to each patient to compare the discomfort associated with GA and IS procedures. The differences in yield between IS and GA were tested for significance using the Two-sample test of proportions with a significance level set at 5%. McNemar's χ2 test was employed to compare matched observations. The Mann-Whitney test was used for comparing continuous variables, and the Chi-Square test for categorical variables. Cohen’s Kappa (κ) was used to assess interobserver agreement between the sampling methods using the different tests. Results: Out of the 138 cases recruited with suspected pulmonary TB, the diagnosis was microbiologically confirmed in 13 cases (9.4%). The overall diagnostic yield was 12/138 (8.7%) for GA and 10/138 (7.2%) for IS. In children under 10 years, GA outperformed IS with all three cases being positive by GA and none by IS. For those aged 10 years and above, 10 children (100%) tested positive with IS, while nine children (90%) were positive with GA. According to the Wong-Baker VAS measuring discomfort during the procedure, IS was favoured over GA (p-value

Risk of death from undernutrition is thought to be higher in younger than in older children, but evidence is mixed. Research also demonstrates sex differences whereby boys have a higher prevalence of undernutrition than girls. This analysis described mortality risk associated with anthropometric deficits (wasting, underweight and stunting) in children 6-59 months by age and sex. We categorised children into younger (6-23 months) and older (24-59 months) age groups. Age and sex variations in near-term (within 6 months) mortality risk, associated with individual anthropometric deficits were assessed in a secondary analysis of multi-country cohort data. A random effects meta-analysis was performed. Data from seven low-or-middle-income-countries collected between 1977 and 2013 were analysed. One thousand twenty deaths were recorded for children with anthropometric deficits. Pooled meta-analysis estimates showed no differences by age in absolute mortality risk for wasting (RR 1.08, p = 0.826 for MUAC

Students benefit from instruction with hand gestures when learning to solve mathematical equivalence problems. However, the mechanism by which gestures support student’s learning is unknown. One way that gestures may support student learning is by influencing students’ visual attention. To investigate this, we taught children how to solve mathematical equivalence problems using video instruction with or without gestures and used eye-tracking to observe how gestures influenced visual attention when solving problems after instruction. When compared to children taught without gestures, children taught using instruction with gestures had increased attention to the answer blank, but not to the numbers in the problem. Children’s visual attention to the blank also varied by problem features and whether children learned from the instruction. Attention to the answer blank may be an important characteristic of children’s equivalence problem solving, and observing gestures can influence children’s visual attention beyond the moment in which gestures are perceived.

Wildland–urban interfaces (WUIs), the juxtaposition of highly and minimally developed lands, are an increasingly prominent feature on Earth. WUIs are hotspots of environmental and ecological change that are often priority areas for planning and management. A better understanding of WUI dynamics and their role in the coupling between cities and surrounding wildlands is needed to reduce the risk of environmental hazards, ensure the continued provisioning of ecosystem services, and conserve threatened biodiversity. To fill this need, we propose an expanded framework for WUIs that not only conceptualizes these interfaces as emergent and functional components of socioecological processes but also extends them vertically from the bedrock to the top of the vegetation and horizontally across heterogeneous landscapes. This framework encourages management that reconciles pervasive trade-offs between development and resulting multiple environmental impacts. Focusing on southern California as a case study, we use the framework to facilitate integration across disciplines and between scientists and managers.

Abstract Mucin protein glycosylation is important in determining biological properties of mucus gels, which form protective barriers at mucosal surfaces of the body such as the intestine. Ecological factors including: age, sex, and diet can change mucus barrier properties by modulating mucin glycosylation. However, as our understanding stems from controlled laboratory studies in house mice, the combined influence of ecological factors on mucin glycosylation in real-world contexts remains limited. In this study, we used histological staining with ‘Alcian Blue, Periodic Acid, Schiff’s’ and ‘High-Iron diamine’ to assess the acidic nature of mucins stored within goblet cells of the intestine, in a wild mouse population (Mus musculus). Using statistical models, we identified sex as among the most influential ecological factors determining the acidity of intestinal mucin glycans in wild mice. Our data from wild mice and experiments using laboratory mice suggest estrogen signalling associates with an increase in the relative abundance of sialylated mucins. Thus, estrogen signalling may underpin sex differences observed in the colonic mucus of wild and laboratory mice. These findings highlight the significant influence of ecological parameters on mucosal barrier sites and the complementary role of wild populations in augmenting standard laboratory studies in the advancement of mucus biology.

Abstract Background Exhaled volatile organic compounds (VOCs), particularly hydrocarbons from oxidative stress-induced lipid peroxidation, are associated with hyperoxia exposure. However, important heterogeneity amongst identified VOCs and concerns about their precise pathophysiological origins warrant translational studies assessing their validity as a marker of hyperoxia-induced oxidative stress. Therefore, this study sought to examine changes in VOCs previously associated with the oxidative stress response in hyperoxia-exposed lung epithelial cells. Methods A549 alveolar epithelial cells were exposed to hyperoxia for 24 h, or to room air as normoxia controls, or hydrogen peroxide as oxidative-stress positive controls. VOCs were sampled from the headspace, analysed by gas chromatography coupled with mass spectrometry and compared by targeted and untargeted analyses. A secondary analysis of breath samples from a large cohort of critically ill adult patients assessed the association of identified VOCs with clinical oxygen exposure. Results Following cellular hyperoxia exposure, none of the targeted VOCs, previously proposed as breath markers of oxidative stress, were increased, and decane was significantly decreased. Untargeted analysis did not reveal novel identifiable hyperoxia-associated VOCs. Within the clinical cohort, three previously proposed breath markers of oxidative stress, hexane, octane, and decane had no real diagnostic value in discriminating patients exposed to hyperoxia. Conclusions Hyperoxia exposure of alveolar epithelial cells did not result in an increase in identifiable VOCs, whilst VOCs previously linked to oxidative stress were not associated with oxygen exposure in a cohort of critically ill patients. These findings suggest that the pathophysiological origin of previously proposed breath markers of oxidative stress is more complex than just oxidative stress from hyperoxia at the lung epithelial cellular level.

Abstract Brain dynamic functional connectivity characterises transient connections between brain regions. Features of brain dynamics have been linked to emotion and cognition in adult individuals, and atypical patterns have been associated with neurodevelopmental conditions such as autism. Although reliable functional brain networks have been consistently identified in neonates, little is known about the early development of dynamic functional connectivity. In this study we characterise dynamic functional connectivity with functional magnetic resonance imaging (fMRI) in the first few weeks of postnatal life in term-born (n = 324) and preterm-born (n = 66) individuals. We show that a dynamic landscape of brain connectivity is already established by the time of birth in the human brain, characterised by six transient states of neonatal functional connectivity with changing dynamics through the neonatal period. The pattern of dynamic connectivity is atypical in preterm-born infants, and associated with atypical social, sensory, and repetitive behaviours measured by the Quantitative Checklist for Autism in Toddlers (Q-CHAT) scores at 18 months of age.

Abstract Cells of the innate immune system retain memory of prior exposures through a process known as innate immune training. β-glucan, a Dectin-1 ligand purified from the Candida albicans cell wall, has been one of the most widely utilized ligands for inducing innate immune training. However, many Dectin-1 ligands exist, and it is not known whether these all produce the same phenotype. Using a well-established in vitro model of innate immune training, we compared two commercially available Dectin-1 agonists, zymosan and depleted zymosan, with the gold standard β-glucan in the literature. We found that depleted zymosan, a β-glucan purified from Saccharomyces cerevisiae cell wall through alkali treatment, produced near identical effects as C. albicans β-glucan. However, untreated zymosan produced a distinct training effect from β-glucans at both the transcript and cytokine level. Training with zymosan diminished, rather than potentiated, induction of cytokines such as TNF and IL-6. Zymosan activated NFκB and AP-1 transcription factors more strongly than β-glucans. The addition of the toll-like receptor (TLR) ligand Pam3CSK4 was sufficient to convert the training effect of β-glucans to a phenotype resembling zymosan. We conclude that differential activation of TLR signaling pathways determines the phenotype of innate immune training induced by Dectin-1 ligands.

Abstract Pituitary‐dependent hypersomatotropism is rarely diagnosed in dogs and surgical treatment is not reported. A 6‐year‐10‐month male neutered Patterdale Terrier presented with polyuria, polydipsia, progressive pharyngeal stertor, excessive hair growth and widened facial features and paws. Serum insulin‐like growth factor‐1 concentration via radioimmunoassay was consistent with hypersomatotropism (1783 ng/mL). A pituitary mass was identified on magnetic resonance and computed tomography imaging. Six weeks later, glucosuria, starved hyperglycemia and serum fructosamine above the reference range (467.6 μmol/L, RI 177‐314) were documented, consistent with diabetes mellitus. Transsphenoidal hypophysectomy was performed under general anesthesia without complications. Pituitary histopathology identified an acidophil neoplasm, with positive immunostaining for growth hormone. Postoperatively, there was rapid resolution of clinical, biochemical and morphologic changes of hypersomatotropism with persistence of diabetes mellitus. This case demonstrates successful resolution of hypersomatotropism with ongoing diabetes mellitus in a dog after surgical treatment by transsphenoidal hypophysectomy.

The current study evaluated the success of implementing a blended + flipped structure in a Calculus for Life and Management Sciences course. By reimagining two of the three weekly instructional hours as online asynchronous lessons, we redesigned a 200-person section into 30-person sections, with minimal additional instructor resources. Findings indicated that students viewed the course positively, with perceptions positively correlating with course outcomes. Further, students reported more positive beliefs relating to their ability to accomplish course learning outcomes, comfort with math, and perceptions of in-class readiness compared to those in the traditional course format. Significant differences in grade distributions were also observed.

Background: The risk of hospital insulin prescription errors in the UK has remained unchanged despite the adoption of several national initiatives. This audit was conducted to evaluate whether the prescription errors were related to the information source used. Aims: To determine what sources of information are used at the time of hospital admission of patients with diabetes to obtain details of their insulin regimen and how different sources relate to prescription errors. Method: We examined the clinical notes of 85 patients with diabetes and confirmed the insulin doses with the patient or the carer administering insulin. Results: Only 44 out of 85 (52%) patients or carers administering insulin recalled being asked about insulin; prescription errors were slightly lower in these patients but overall insulin prescription error remains at one in four. Conclusion: The persisting inpatient insulin error rate calls for a review of how the information on insulin regimen is collected and used by the healthcare services.

Laboratory model organisms have provided a window into how the immune system functions. An increasing body of evidence, however, suggests that the immune responses of naive laboratory animals may differ substantially to those of their wild counterparts. Past exposure, environmental challenges and physiological condition may all impact on immune responsiveness. Chronic infections of soil-transmitted helminths, which we define as establishment of adult, fecund worms, impose significant health burdens on humans, livestock and wildlife, with limited treatment success. In laboratory mice, Th1 versus Th2 immune polarisation is the major determinant of helminth infection outcome. Here we compared antigen-specific immune responses to the soil-transmitted whipworm Trichuris muris between controlled laboratory and wild free-ranging populations of house mice (Mus musculus domesticus). Wild mice harbouring chronic, low-level infections produced lower levels of cytokines in response to Trichuris antigen than laboratory-housed C57BL/6 mice. Wild mouse effector/memory CD4+ T cell phenotype reflected the antigen-specific cytokine response across the Th1/Th2 spectrum. Increasing egg shedding was associated with body condition loss. However, local Trichuris-specific Th1/Th2 balance was positively associated with worm burden only in older wild mice. Thus, although the fundamental relationships between the CD4+ T helper cell response and resistance to T. muris infection are similar in both laboratory and wild M. m. domesticus, there are quantitative differences and age-specific effects that are analogous to human immune responses. These context-dependent immune responses demonstrate the fundamental importance of understanding the differences between model and natural systems for translating mechanistic models to 'real world' immune function.