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Background/objectives: We investigated if performing two lateral flow device (LFD) tests, LFD2 immediately after LFD1, could improve diagnostic sensitivity or specificity for detecting severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) antigen., Study Design: Individuals aged ≥16 years attending UK community testing sites (February-May 2021) performed two successive LFD tests and provided a nose-and-throat sample for a polymerase chain reaction (PCR) test. Using the PCR result as the reference diagnosis, we assessed whether improvements could be achieved in sensitivity (by counting a positive result in either LFD as a positive overall test result) or specificity (by using LFD2 as confirmatory test)., Results: Overall, 2231 participants were included with 159 (7 %) having a positive PCR test. Of 2223 participants who completed both LFD tests, LFD results were highly concordant both with each other and with PCR tests (>97 %). The proportion of discord LFD results decreased significantly over the study period. Combined LFD usage achieved a sensitivity of 68.6 %, versus 67.1 % for either LFD individually. The specificity increased from 99.5 % to 99.8 % when using LFD2 as confirmatory test. Observed increases in sensitivity and specificity were not statistically significant. Void results were recorded for 31 (1.4 %) LFD1s, 19 (0.9 %) LFD2s and 6 (0.3 %) combined LFD tests., Conclusions: LFD tests were highly reproducible even when they were performed by untrained users following only written instructions and without supervision. While performing two LFD tests of the same type in quick succession marginally increased sensitivity or specificity, statistically significant improvements were not detected in our study., 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., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Background: Many individuals with chronic obstructive pulmonary disease (COPD) experience frequent hospitalization and readmissions, which is burdensome on the health system. This study aims to investigate factors associated with unplanned readmissions and mortality following a COPD-related hospitalization over a 12-month period in Australia, focusing on mental disorders and accounting for the acute phase of the COVID-19 pandemic., Methods: A retrospective cohort study using linked hospitalization and mortality records identified individuals aged ≥40 years who had at least one hospital admission with a principal diagnosis of COPD between 2014 and 2020 in New South Wales, Australia. A semi-competing risk analysis was conducted to examine factors associated with unplanned readmission and mortality., Results: Adults with a mental disorder diagnosis, specifically anxiety, had a higher risk of 12-month unplanned readmission. Individuals with anxiety and dementia also had a higher risk of mortality pre- and post-unplanned readmission. Individuals who were admitted during the acute phase of the COVID-19 pandemic period had lower risk of unplanned readmission, but higher risk of mortality without unplanned readmission., Conclusion: Interventions aimed at reducing admissions should consider adults living with mental disorders such as anxiety or dementia to improve healthcare delivery and health outcomes for individuals living with COPD., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health.)

Purpose: In April 2020, the UK Government implemented NHS Test and Trace to provide SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (qRT-PCR) testing for the public, with nose-and-throat swabbing for samples performed by trained staff. Self-swabbing (SS) would allow rapid scale-up of testing capacity and access. Six studies were undertaken to determine whether SS was as effective for detecting SARS-CoV-2 as swabbing performed by trained staff., Methods: Six prospective studies were conducted between April-October 2020, using six swab/media combinations. Differences between assisted swabbing (AS) and SS were evaluated for concordance, positivity, sensitivity, cycle threshold (Ct) values and void rates. Statistical analysis was performed using 95% confidence intervals (CIs), paired t-tests and model-based methods., Results: Overall, 3,253 individuals were recruited (median age 37 years, 49% female), with 2,933 having valid paired qRT-PCR results. Pooled concordance rate was 98% (95% CI: 96%, 99%). Positivity rate differences for SS (8.1%) and AS (8.4%) and differences in pooled sensitivities between SS (86%; 95% CI: 78%, 92%) and AS (91%; 95% CI: 78%, 96%) were nonsignificant. Both types of swabbing led to pooled void rates below 2% and strongly correlated Ct values. Age, sex and previous swabbing experience did not have a significant impact on concordance or sensitivity., Conclusion: The UK adopted a policy to promote self-testing for SARS-CoV-2 based on data demonstrating equivalence of SS versus AS. Positive outcomes with SS are likely generalisable to testing for other respiratory pathogens, and we consider self-sampling and self-testing essential for future pandemic preparedness., (© 2024. Crown.)

Animal-sourced foods are important for human nutrition and health, but they can have a negative impact on the environment. These impacts can result in land use tensions associated with population growth and the loss of native forests and wetlands during agricultural expansion. Increased greenhouse gas emissions, and high water use but poor water quality outcomes can also be associated. Life cycle analysis from cradle-to-distribution has shown that novel plant-based meat alternatives can have an environmental footprint lower than that of beef finished in feedlots, but higher than for beef raised on well-managed grazed pastures. However, several technologies and practices can be used to mitigate impacts. These include ensuring that grazing occurs when feed quality is high, the use of dietary additives, breeding of animals with higher growth rates and increased fecundity, rumen microbial manipulations through the use of vaccines, soil management to reduce nitrous oxide emission, management systems to improve carbon sequestration, improved nutrient use efficacy throughout the food chain, incorporating maize silage along with grasslands, use of cover crops, low-emission composting barns, covered manure storages, and direct injection of animal slurry into soil. The technologies and systems that help mitigate or actually provide solutions to the environmental impact are under constant refinement to enable ever-more efficient production systems to allow for the provision of animal-sourced foods to an ever-increasing population.

Human health and diet are closely linked. The diversity of diets consumed by humans is remarkable, and most often incorporates both animal and plant-based foods. However, there has been a recent call for a reduced intake of animal-based foods due to concerns associated with human health in developed countries and perceived impacts on the environment. Yet, evidence for the superior nutritional quality of animal-sourced food such as meat, milk, and eggs, compared with plant-based foods, indicates that consumption of animal-sourced food should and will continue. This being the case, the aim here is to examine issues associated with animal-sourced foods in terms of both the quantification and mitigation of unintended consequences associated with environment, animal health, and herd management. Therefore, we examined the role of animal proteins in human societies with reference to the UN-FAO issues associated with animal-sourced foods. The emphasis is on dominant grazed pastoral-based systems, as used in New Zealand and Ireland, both with temperate moist climates and a similar reliance on global markets for generating net wealth from pastoral agricultural products. In conclusion, animal-sourced foods are shown to be an important part of the human diet. Production systems can result in unintended consequences associated with environment, animal health, and herd management, and there are technologies and systems to provide solutions to these that are available or under refinement.

Background: The advent of lateral flow devices (LFDs) for SARS-CoV-2 detection enabled widespread use of rapid self-tests during the pandemic. While self-testing using LFDs is now common, whether self-testing provides comparable performance to professional testing was a key question that remained important for pandemic planning., Methods: Three prospective multi-centre studies were conducted to compare the performance of self- and professional testing using LFDs. Participants tested themselves or were tested by trained (professional) testers at community testing sites in the UK. Corresponding qRT-PCR test results served as reference standard. The performance of Innova, Orient Gene and SureScreen LFDs by users (self) and professional testers was assessed in terms of sensitivity, specificity, and kit failure (void) rates. Impact of age, sex and symptom status was analysed using logistic regression modelling., Results: 16,617 participants provided paired tests, of which 15,418 were included in the analysis. Self-testing with Innova, Orient Gene or SureScreen LFDs achieved sensitivities of 50 %, 53 % or 72 %, respectively, compared to qRT-PCR. Self and professional LFD testing showed no statistically different sensitivity with respect to corresponding qRT-PCR testing. Specificity was consistently equal to or higher than 99 %. Sex and age had no or only marginal impact on LFD performance while sensitivity was significantly higher for symptomatic individuals. Sensitivity of LFDs increased strongly to up to 90 % with higher levels of viral RNA measured by qRT-PCR., Conclusions: Our results support SARS-CoV-2 self-testing with LFDs, especially for the detection of individuals whose qRT-PCR tests showed high viral concentrations., 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 © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Distributed optical fibre sensing (DOFS)-based strain measurement systems are now routinely deployed across infrastructure health monitoring applications. However, there are still practical performance and measurement issues associated with the fibre's attachment method, particularly with thermoplastic pipeline materials (e.g., high-density polyethylene, HDPE) and adhesive affixment methods. In this paper, we introduce a new optical fibre installation method that utilises a hot-weld encapsulation approach that fully embeds the fibre onto the pipeline's plastic surface. We describe the development, application and benefits of the new embedment approach (as compared to adhesive methods) and illustrate its practical performance via a full-scale, real-world, dynamic loading trial undertaken on a 1.8 m diameter, 6.4 m long stormwater pipeline structure constructed from composite spiral-wound, steel-reinforced, HDPE pipe. The optical frequency domain reflectometry (OFDR)-based strain results show how the new method improves strain transference and dynamic measurement performance and how the data can be easily interpreted, in a practical context, without the need for complex strain transfer functions. Through the different performance tests, based on UK rail-road network transport loading conditions, we also show how centimetre- to metre-scale strain variations can be clearly resolved at the frequencies and levels consistent with transport- and construction-based, buried infrastructure loading scenarios.

Bowel dysfunction remains a prominent priority in the rehabilitation of patients with spinal cord injuries (SCIs). However, our understanding of the factors that influence bowel-related quality of life (QoL) in this population remains limited. This study aimed to investigate the potential role of resilience, defined as an individual's capacity to cope with and adapt to adversity, as a predictor of bowel-related QoL among the patients with SCI. A cohort of adult patients with SCI who received bowel and bladder care at an outpatient clinic within a large rehabilitation hospital was identified through a prospectively collected database. Resilience was measured using the Spinal Cord Injury-Quality of Life (SCI-QOL) Resilience Short Form, whereas bowel QoL was assessed using the Irritable Bowel Syndrome-Quality of Life (IBS-QoL) questionnaire. Univariate and multivariate regression analyses were employed to identify predictors of bowel-related QoL. The examined variables included age, gender, level and completeness of injury, time since injury, hand function, resilience, and the severity of bowel dysfunction as measured using the Neurogenic Bowel Dysfunction Score (NBDS). A total of 73 patients participated in this study, with a mean age of 44.01 ± 13.43 years and comprising mostly men ( n  = 57, 78%). The results revealed a significant correlation between resilience scores and the total score of IBS-QoL ( ρ  = -0.47, p  < 0.0001). The multivariate analysis demonstrated that both resilience and the severity of bowel dysfunction were significant independent predictors of bowel-related QoL, with resilience demonstrating a stronger association. Overall, this study elucidates the importance of resilience in shaping patients' perceptions of their bowel health within the SCI population. In addition to the more expected determinants of bowel-related QoL, such as the severity of bowel dysfunction, resilience emerged as a notable factor. Accordingly, integrating interventions that enhance resilience within bowel rehabilitation programs may yield improvements in patients' perceived bowel health beyond the benefits achievable through bowel function enhancement alone.

Background: The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement., Objective: This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline., Methods: Two cohorts of 10 (Pool10: 1,030 participants and 103 pools) and 6 (Pool6: 1,284 participants and 214 pools) samples per pool were tested for concordance, sensitivity, specificity, and Ct value differences with individual testing as reference., Results: Swab pooling allowed unmodified application of an existing high-throughput SARS-Cov-2 testing pipeline with only marginal loss of accuracy. For Pool10, concordance was 98.1% (95% Confidence interval: 93.3-99.8%), sensitivity was 95.7% (85.5-99.5%), and specificity was 100.0% (93.6-100.0%). For Pool6, concordance was 97.2% (94.0-99.0%), sensitivity was 97.5% (93.7-99.3%), and specificity was 96.4% (87.7-99.6%). Differences of outcomes measure between pool size were not significant. Most positive individual samples, which were not detected in pools, had very low viral concentration. If only individual samples with a viral concentration > 400 copies/ml (i.e. Ct value < 30) were considered positive, the overall sensitivity of pooling increased to 99.5%., Conclusion: The study demonstrated high sensitivity and specificity by swab pooling and the immediate capability of high-throughput laboratories to implement this method making it an option in planning of rapid upscaling of laboratory capacity for future pandemics., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Constipation is common in the pediatric population and in severe forms it can lead to debilitating fecal incontinence which has a significant impact on quality of life. Cecostomy tube insertion is a procedural option for cases refractory to medical management, however there is limited data investigating the long-term success and complication rate., Methods: A retrospective review was performed evaluating patients at our centre undergoing cecostomy tube (CT) insertion between 2002 and 2018. The primary outcomes of the study were the rate of fecal continence at 1-year, and the incidence of unplanned exchanges prior to annual scheduled exchange. Secondary outcomes include the frequency of anaesthetic requirements and length of hospital stay. Descriptive statistics, t-test, and chi-square analysis was performed where appropriate using SPSS v25., Results: Of 41 patients, the average age at the time of initial insertion was 9.9 years with the average length of stay in hospital being 3.47 days. The most common etiology of bowel dysfunction was spina bifida, which was present in 48.8% (n = 20) of patients. Fecal continence was achieved in 90% (n = 37) of patients at 1 year and the average rate of cecostomy tube exchange was 1.3/year with an average of 3.6 general anaesthetics being required by patients and the average age of no longer requiring one being 14.9 years., Discussion: Analysis of patients undergoing cecostomy tube insertion at our centre has further supported the use of cecostomy tubes as a safe and effective option for management of fecal incontinence refractory to medical management. However, a number of limitations exist in this study including its retrospective design and failure to investigate changes in quality of life using validated questionnaires. Additionally, while our research provides greater insight to practitioners and patients what degree of care and types of complications or issues they may encounter with an indwelling tube over the long-term, our single-cohort design limits any conclusions that could be made regarding optimal management strategies for overflow fecal incontinence through direct comparison with other management strategies., Conclusions: CT insertion is a safe and effective method for managing fecal incontinence due to constipation in the pediatric population, however, unplanned exchange of tube due to malfunction, mechanical breakage, or dislodgment occurs frequently and may impact quality of life and independence., Level of Evidence: IV., (Copyright © 2023. Published by Elsevier Ltd.)

We present a novel algorithm that is able to generate deep synthetic COVID-19 pneumonia CT scan slices using a very small sample of positive training images in tandem with a larger number of normal images. This generative algorithm produces images of sufficient accuracy to enable a DNN classifier to achieve high classification accuracy using as few as 10 positive training slices (from 10 positive cases), which to the best of our knowledge is one order of magnitude fewer than the next closest published work at the time of writing. Deep learning with extremely small positive training volumes is a very difficult problem and has been an important topic during the COVID-19 pandemic, because for quite some time it was difficult to obtain large volumes of COVID-19-positive images for training. Algorithms that can learn to screen for diseases using few examples are an important area of research. Furthermore, algorithms to produce deep synthetic images with smaller data volumes have the added benefit of reducing the barriers of data sharing between healthcare institutions. We present the cycle-consistent segmentation-generative adversarial network (CCS-GAN). CCS-GAN combines style transfer with pulmonary segmentation and relevant transfer learning from negative images in order to create a larger volume of synthetic positive images for the purposes of improving diagnostic classification performance. The performance of a VGG-19 classifier plus CCS-GAN was trained using a small sample of positive image slices ranging from at most 50 down to as few as 10 COVID-19-positive CT scan images. CCS-GAN achieves high accuracy with few positive images and thereby greatly reduces the barrier of acquiring large training volumes in order to train a diagnostic classifier for COVID-19., (© 2023. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

We recently developed a model-based method for analyzing multiple breath nitrogen washout data that does not require identification of Phase-III. In the present study, we assessed the effect of irregular breathing patterns on the intra-subject variabilities of the model parameters. Nitrogen fraction at the mouth was measured in 18 healthy and 20 asthmatic subjects during triplicate performances of multiple breath nitrogen washout, during controlled (target tidal volume 1 L at 8-12 breaths per minute) and free (unrestricted) breathing. The parameters S cond , S acin and functional residual capacity (FRC) were obtained by conventional analysis of the slope of Phase-III. Fitting the model to the washout data provided functional residual capacity (FRC M ), dead space volume (V D ), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of S acin (S acin-M ). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRC M  < 5.2%, V D  < 5.4%, [Formula: see text] < 9.0%, and S acin-M  < 45.6% for controlled breathing, and FRC M  < 4.6%, V D  < 5.3%, [Formula: see text] < 13.2%, and S acin-M  < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with S cond  < 73.6% and S acin  < 49.2% for controlled breathing and S cond  < 35.0% and S acin  < 74.4% for free breathing. The model-fitting approach to multiple breath nitrogen washout analysis provides a measure of regional ventilation heterogeneity in [Formula: see text] that is less affected by irregularities in the breathing pattern than its corresponding Phase-III slope analysis parameter S cond ., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The Thoracic Society of Australia and New Zealand (TSANZ) and the Australian and New Zealand Society of Respiratory Science (ANZSRS) commissioned a joint position paper on pulmonary function testing during coronavirus disease 2019 (COVID-19) in July 2021. A working group was formed via an expression of interest to members of both organizations and commenced work in September 2021. A rapid review of the literature was undertaken, with a 'best evidence synthesis' approach taken to answer the research questions formed. This allowed the working group to accept findings of prior relevant reviews or societal document where appropriate. The advice provided is for providers of pulmonary function tests across all settings. The advice is intended to supplement local infection prevention and state, territory or national directives. The working group's key messages reflect a precautionary approach to protect the safety of both healthcare workers (HCWs) and patients in a rapidly changing environment. The decision on strategies employed may vary depending on local transmission and practice environment. The advice is likely to require review as evidence grows and the COVID-19 pandemic evolves. While this position statement was contextualized specifically to the COVID-19 pandemic, the working group strongly advocates that any changes to clinical/laboratory practice, made in the interest of optimizing the safety and well-being of HCWs and patients involved in pulmonary function testing, are carefully considered in light of their potential for ongoing use to reduce transmission of other droplet and/or aerosol borne diseases., (© 2022 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Introduction: The multiple breath nitrogen washout (MBNW) test provides important clinical information in obstructive airways diseases. Recently, a significant cross-sensitivity error in the O 2 and CO 2 sensors of a widely used commercial MBNW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) was detected, which leads to overestimation of N 2 concentrations. Significant errors in functional residual capacity (FRC) and lung clearance index (LCI) have been reported in infants and children. This study investigated the impact in adults, and on additional important indices reflecting conductive ( S cond ) and acinar ( S acin ) ventilation heterogeneity, in health and disease., Methods: Existing MBNW measurements of 27 healthy volunteers, 20 participants with asthma and 16 smokers were reanalysed using SPIROWARE V 3.3.1, which incorporates an error correction algorithm. Uncorrected and corrected indices were compared using paired t-tests and Bland-Altman plots., Results: Correction of the sensor error significantly lowered FRC (mean difference 9%) and LCI (8-10%) across all three groups. S cond was higher following correction (11%, 14% and 36% in health, asthma and smokers, respectively) with significant proportional bias. S acin was significantly lower following correction in the asthma and smoker groups, but the effect was small (2-5%) and with no proportional bias., Discussion: The O 2 and CO 2 cross-sensitivity sensor error significantly overestimated FRC and LCI in adults, consistent with data in infants and children. There was a high degree of underestimation of S cond but minimal impact on S acin . The presence of significant proportional bias indicates that previous studies will require reanalysis to confirm previous findings and to allow comparability with future studies., Competing Interests: Conflict of interest: No conflicts of interest, financial or otherwise, relating to this study are declared by the authors., (Copyright ©The authors 2022.)

Background: Before the emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination reduced transmission of SARS-CoV-2 from vaccinated persons who became infected, potentially by reducing viral loads. Although vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated persons who are infected with the delta variant call into question the degree to which vaccination prevents transmission., Methods: We used contact-testing data from England to perform a retrospective observational cohort study involving adult contacts of SARS-CoV-2-infected adult index patients. We used multivariable Poisson regression to investigate associations between transmission and the vaccination status of index patients and contacts and to determine how these associations varied with the B.1.1.7 (alpha) and delta variants and time since the second vaccination., Results: Among 146,243 tested contacts of 108,498 index patients, 54,667 (37%) had positive SARS-CoV-2 polymerase-chain-reaction (PCR) tests. In index patients who became infected with the alpha variant, two vaccinations with either BNT162b2 or ChAdOx1 nCoV-19 (also known as AZD1222), as compared with no vaccination, were independently associated with reduced PCR positivity in contacts (adjusted rate ratio with BNT162b2, 0.32; 95% confidence interval [CI], 0.21 to 0.48; and with ChAdOx1 nCoV-19, 0.48; 95% CI, 0.30 to 0.78). Vaccine-associated reductions in transmission of the delta variant were smaller than those with the alpha variant, and reductions in transmission of the delta variant after two BNT162b2 vaccinations were greater (adjusted rate ratio for the comparison with no vaccination, 0.50; 95% CI, 0.39 to 0.65) than after two ChAdOx1 nCoV-19 vaccinations (adjusted rate ratio, 0.76; 95% CI, 0.70 to 0.82). Variation in cycle-threshold (Ct) values (indicative of viral load) in index patients explained 7 to 23% of vaccine-associated reductions in transmission of the two variants. The reductions in transmission of the delta variant declined over time after the second vaccination, reaching levels that were similar to those in unvaccinated persons by 12 weeks in index patients who had received ChAdOx1 nCoV-19 and attenuating substantially in those who had received BNT162b2. Protection in contacts also declined in the 3-month period after the second vaccination., Conclusions: Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission. (Funded by the U.K. Government Department of Health and Social Care and others.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Prostate cancer (Pca) is the most frequently diagnosed cancer in New Zealand (NZ) men and the third leading cause of cancer deaths. Temporal changes in Pca incidence and mortality have not been reported despite changes in the Pca landscape. This study aims to analyse the temporal trends in Pca with focus on ethnic and regional variations., Methods: The study cohort was identified from the NZ Cancer Registry and the mortality collection databases. Men who were diagnosed with Pca between 2000 and 2018 were included in the incidence analysis. Men who died from Pca between 2000 and 2015 were included in the mortality analysis. Other data collected were ethnicity and geographical information. Pca incidence and mortality were calculated as age-standardized rates using the 2001 World Health Organization population., Results: A total of 58 966 men were diagnosed (incidence: 105.2 per 100 000) and 14 749 men died (mortality: 49.3 per 100 000) from Pca. When compared to European men, Māori and Asian men had significantly lower Pca incidence. Mortality rates demonstrated a steady decline, which was more prominent until 2010. Māori and Pacific men had higher mortality rates when compared to European men. In most recent years, the difference in mortality is decreasing for Māori but increasing for Pacific men. There were no regional differences in mortality., Conclusion: Pca incidence in NZ has fluctuated over the last 20 years, while mortality rates have shown to steadily decline. Pca mortality was shown to disproportionately affect Māori and Pacific men., (© 2021 Royal Australasian College of Surgeons.)

Introduction: We aimed to determine normal thresholds for positive bronchodilator responses for oscillometry in an Australian general population sample aged ≥40 years, to guide clinical interpretation. We also examined relationships between bronchodilator responses and respiratory symptoms, asthma diagnosis, smoking and baseline lung function., Methods: Subjects recruited from Sydney, Melbourne and Busselton, Australia, underwent measurements of spirometry, resistance ( R rs 6 ) and reactance ( X rs 6 ) at 6 Hz, before and after inhalation of salbutamol 200 μg. Respiratory symptoms and/or medication use, asthma diagnosis, and smoking were recorded. Threshold bronchodilator responses were defined as the fifth percentile of decrease in R rs 6 and 95th percentile increase in X rs 6 in a healthy subgroup., Results: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for Δ R rs 6 was -1.38 cmH 2 O·s·L -1 (-30.0% or -1.42 Z-scores) and upper threshold for Δ X rs 6 was 0.57 cmH 2 O·s·L -1 (1.36 Z-scores). Respiratory symptoms and/or medication use, asthma diagnosis, and smoking all predicted bronchodilator response, as did baseline oscillometry and spirometry. When categorised into clinically relevant groups according to those predictors, Δ X rs 6 was more sensitive than spirometry in smokers without current asthma or chronic obstructive pulmonary disease (COPD), ∼20% having a positive response. Using absolute or Z-score change provided similar prevalences of responsiveness, except in COPD, in which responsiveness measured by absolute change was twice that for Z-score., Discussion: This study describes normative thresholds for bronchodilator responses in oscillometry parameters, including intra-breath parameters, as determined by absolute, relative and Z-score changes. Positive bronchodilator response by oscillometry correlated with clinical factors and baseline function, which may inform the clinical interpretation of oscillometry., Competing Interests: Conflict of interest: K. Jetmalani is a part-time employee of GlaxoSmithKline. Conflict of interest: N.J. Brown has nothing to disclose. Conflict of interest: C. Boustany has nothing to disclose. Conflict of interest: B.G. Toelle has nothing to disclose. Conflict of interest: G.B. Marks has nothing to disclose. Conflict of interest: M.J. Abramson reports an investigator-initiated grant to conduct the BOLD study in Australia from the National Health and Medical Research Council during the conduct of the study; and investigator-initiated grants for unrelated research from Pfizer and Boehringer Ingelheim, personal fees for unrelated consultancies and assistance with congress attendance from Sanofi, and a speaker's fee from GlaxoSmithKline, outside the submitted work. Conflict of interest: D.P. Johns has nothing to disclose. Conflict of interest: A.L. James has nothing to disclose. Conflict of interest: M. Hunter has nothing to disclose. Conflict of interest: A.W. Musk has nothing to disclose. Conflict of interest: N. Berend is a part-time employee of GlaxoSmithKline. Conflict of interest: C.S. Farah has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: C. Thamrin has a patent WO 2006130922 A1 issued, which is broadly relevant to the work. In addition, she has intellectual property arrangements with Thorasys, Thoracic Medical Systems and Restech srl relating to research collaborations, but does not have any financial relationships with either company. Conflict of interest: G.G. King reports intellectual property arrangements covering research collaborations and provision of FOT devices for research from Restech during the conduct of the study; fees for consultancy services (which include lectures and advisory board services), conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants and fellowships from the National Health and Medical Research Council, the Asthma Foundation and philanthropic donations via Sydney University, outside the submitted work., (Copyright ©The authors 2021.)

In the 2013-2014 and 2015-2016 seasons, quadrivalent live attenuated influenza vaccine (LAIV) showed reduced pandemic 2009 H1N1 (A/H1N1pdm09) vaccine effectiveness (VE) in the U.S. Impaired fitness of A/H1N1pdm09 LAIV strains in primary human nasal epithelial cells (hNEC) was subsequently shown to be associated with reduced VE. As defective viral genes (DVG) have been detected in QLAIV, it was hypothesised that these might play a role in reduced A/H1N1pdm09 fitness. By applying RT-PCR based approaches, DVG for PB2, PB1 and PA segments were detected in all influenza A LAIV strains tested. Absolute quantification of PA vRNA as a biomarker, using a novel digital RT-PCR assay (RT-dPCR), showed that DVG were a minority population (between 10.2 and 27.8 % of PA vRNA) in LAIV, irrespective of subtype or VE. Importantly, no difference was observed between the fitter pre-2009 H1N1 A/New Caledonia/20/1999 (A/NC99) and less fit A/H1N1pdm09 A/Bolivia/509/2013 (A/BOL13), containing medians of 16.0 % and 10.2 % PA DVG, respectively. Manipulating propagation conditions and minimising A/BOL13 PA DVG to 5.2 % failed to improve viral replication in hNEC, suggesting DVG were not limiting A/BOL13 fitness. Conversely, DVG were able to reduce A/NC99 replication in hNEC to A/BOL13-like levels, but only by enrichment of PA DVG to 66.5 % of vRNA. Notably, this required LAIV propagation under conditions markedly different to those used for vaccine production. We conclude from these data that abundance of DVG in QLAIV is not associated with variations in influenza A VE and that the reduced fitness of A/BOL13 previously described was not driven by the presence of DVG., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: At the time of data generation for this publication, Sameer Ayaz, David Chapman and Oliver Dibben, were employees and shareholders of AstraZeneca plc. AstraZeneca plc are the manufacturers of Fluenz® Tetra/FluMist® Quadrivalent intranasal influenza live virus vaccine., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: We aimed to evaluate the size reduction and complications after transcatheter embolization of renal angiomyolipomas (AMLs)., Methods: Cases from a single tertiary center were analyzed retrospectively. A blinded radiologist provided measurements of AMLs using a combination of ultrasound (US), computed tomography (CT), and magnetic resonance imaging (MRI). Electronic clinical notes, radiographic imaging, and laboratory data were reviewed., Results: Twenty-one embolization procedures from 2002-2019 were analyzed. Four cases were emergency, the remainder elective. The average followup time after intervention was 42 months. Techniques included ethanol, polyvinyl alcohol (PVA), Gelfoam, Embospheres ® , Histacryl ® , and coils. The median diameter size of AMLs was 8.6 cm pre-procedure and 6.0 cm post-procedure. The median volume of AMLs was 200 cc pre-procedure and 67 cc post-procedure, with a median reduction in volume of 55%. One case (4.8%) had a re-embolization and three cases (14.3%) proceeded with surgical management of the AML. No cases re-presented with bleeding. Post-embolization syndrome is common. Renal arterial dissection and renal abscess are infrequent complications (9% and 4.5%, respectively). There was no treatment-based mortality., Conclusions: Embolization for renal AMLs is an established, safe, and effective method of treatment and our series further supports that. Determining when to intervene and how long to follow up patients is an issue that has not been well-described; more research needs to be done in this area.

Background: School-based COVID-19 contacts in England have been asked to self-isolate at home, missing key educational opportunities. We trialled daily testing of contacts as an alternative to assess whether this resulted in similar control of transmission, while allowing more school attendance., Methods: We did an open-label, cluster-randomised, controlled trial in secondary schools and further education colleges in England. Schools were randomly assigned (1:1) to self-isolation of school-based COVID-19 contacts for 10 days (control) or to voluntary daily lateral flow device (LFD) testing for 7 days with LFD-negative contacts remaining at school (intervention). Randomisation was stratified according to school type and size, presence of a sixth form, presence of residential students, and proportion of students eligible for free school meals. Group assignment was not masked during procedures or analysis. Coprimary outcomes in all students and staff were COVID-19-related school absence and symptomatic PCR-confirmed COVID-19, adjusted for community case rates, to estimate within-school transmission (non-inferiority margin <50% relative increase). Analyses were done on an intention-to-treat basis using quasi-Poisson regression, also estimating complier average causal effects (CACE). This trial is registered with the ISRCTN registry, ISRCTN18100261., Findings: Between March 18 and May 4, 2021, 204 schools were taken through the consent process, during which three decided not to participate further. 201 schools were randomly assigned (control group n=99, intervention group n=102) in the 10-week study (April 19-May 10, 2021), which continued until the pre-appointed stop date (June 27, 2021). 76 control group schools and 86 intervention group schools actively participated; additional national data allowed most non-participating schools to be included in analysis of coprimary outcomes. 2432 (42·4%) of 5763 intervention group contacts participated in daily contact testing. There were 657 symptomatic PCR-confirmed infections during 7 782 537 days-at-risk (59·1 per 100 000 per week) in the control group and 740 during 8 379 749 days-at-risk (61·8 per 100 000 per week) in the intervention group (intention-to-treat adjusted incidence rate ratio [aIRR] 0·96 [95% CI 0·75-1·22]; p=0·72; CACE aIRR 0·86 [0·55-1·34]). Among students and staff, there were 59 422 (1·62%) COVID-19-related absences during 3 659 017 person-school-days in the control group and 51 541 (1·34%) during 3 845 208 person-school-days in the intervention group (intention-to-treat aIRR 0·80 [95% CI 0·54-1·19]; p=0·27; CACE aIRR 0·61 [0·30-1·23])., Interpretation: Daily contact testing of school-based contacts was non-inferior to self-isolation for control of COVID-19 transmission, with similar rates of symptomatic infections among students and staff with both approaches. Infection rates in school-based contacts were low, with very few school contacts testing positive. Daily contact testing should be considered for implementation as a safe alternative to home isolation following school-based exposures., Funding: UK Government Department of Health and Social Care., Competing Interests: Declaration of interests DWE reports lecture fees from Gilead outside the submitted work. VB, RO, and DC are consultants employed by Department of Health and Social Care as part of Deloitte's broader project work supporting the delivery of NHS Test and Trace. TF reports honoraria from Qatar National Research Fund outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Interprofessional care provided in a free community-based clinic that focuses on chronic health conditions and health promotion provides an innovative solution to improve societal health. Many existing clinics provide a range of professions, but few include allied health services such as occupational and physical therapy. This paper provides a description of the development and implementation of an expanded faculty-guided student-led community-based primary care clinic that includes occupational and physical therapists as part of an interprofessional collaborative practice model. A detailed description and explanation of the partners involved, the institutional missions that drive this work, the logistics completed that enabled the 'doors to open,' faculty and student roles, and initial outcomes will be provided. A review of the service delivery model, lessons learned, and future directions for the clinic will also be offered.

Purpose: An ill-defined proportion of patients undergoing urethroplasty fail to experience improvement in lower urinary tract symptoms (LUTS) despite being stricture-free. We aim to identify the incidence, associations and causes of "LUTS failure" after urethroplasty., Materials and Methods: Patients undergoing urethroplasty over a 6-year period were offered enrollment in a prospective study examining urinary function after urethroplasty. Patients were assessed preoperatively and 6 months postoperatively using the International Prostate Symptom Score (IPSS) and cystoscopy. "LUTS failure" was defined as ≤3-point improvement in IPSS despite an anatomically successful urethroplasty. Multivariable logistic regression was utilized to evaluate the association between patient factors and "LUTS failure.", Results: Of 365 patients meeting inclusion criteria, mean postoperative IPSS (20.3 vs. 5.4, p <0.0001) and median urinary quality of life (UQOL; 5 vs. 1; p <0.0001) were significantly improved. Despite being stricture-free, 7.7% of patients reported "LUTS failure" and 10.1% reported UQOL nonresponse. On multivariable logistic regression, increasing age (OR 1.04, 95% CI 1.01-1.06; p=0.006) and hypospadias (OR 18.2, 95% CI 2.1-156.0; p=0.008) were associated with "LUTS failure," while stricture location (p=0.76), length (p=0.14), previous urethroplasty (p=0.96), failed endoscopic treatment (p=0.17), type of urethroplasty (p=0.93) and other etiologies were not. Qualitatively, the most likely causes of "LUTS failure" were detrusor underactivity (39.3%), overactivity (21.4%), pelvic floor dysfunction (21.4%) or benign prostatic hyperplasia (14.3%). Only increasing age was associated with UQOL nonresponse (OR 1.03, 95% CI 1.01-1.07; p=0.02)., Conclusions: While many patients experience improved voiding function after urethroplasty, 7.7% experience "LUTS failure" and 10.1% report UQOL nonresponse. Both occurrences are independently associated with increasing patient age and most commonly related to detrusor underactivity.

Asthma is characterized by heterogeneous ventilation as measured by three-dimensional ventilation imaging. Combination inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA) treatment response is variable in asthma, and effects on regional ventilation are unknown. Our aims were to determine whether regional ventilation defects decrease after ICS/LABA treatment and whether small airways dysfunction predicts response in uncontrolled asthma. Twenty-two symptomatic participants with asthma underwent single-photon emission computed tomography (SPECT)/CT imaging with Technegas, before and after 8-wk fluticasone/formoterol (1,000/40 µg/day) treatment. Lung regions that were nonventilated, low ventilated, or well ventilated were calculated using an adaptive threshold method and were expressed as a percentage of total lung volume. Multiple-breath nitrogen washout (MBNW) was used to measure diffusion-dependent and convection-dependent small airways function (Sacin and Scond, respectively). Forced oscillation technique (FOT) was used to measure respiratory system resistance and reactance. At baseline and posttreatment, Scond z -score was related to percentage of nonventilated lung, whereas Sacin z -score was related to percentage of low-ventilated lung. Although symptoms, spirometry, FOT, and MBNW improved following treatment, there was no mean change in ventilation measured by SPECT. There was, however, a wide range of changes in SPECT ventilation such that greater percentage of nonventilated lung, older age, and higher Scond predicted a reduction in nonventilated lung after treatment. SPECT ventilation defects are overall unresponsive to ICS/LABA, but the response is variable, with improvement occurring when small airways dysfunction and ventilation defects are more severe. Persistent ventilation defects that correlate with Scond suggest that mechanisms such as non-ICS responsive inflammation or remodeling underlie these defects. NEW & NOTEWORTHY This study provides insights into the mechanisms of high-dose ICS treatment in uncontrolled asthma. Ventilation defects as measured by SPECT/CT imaging respond heterogeneously to increased ICS/LABA treatment, with improvement occurring when ventilation defects and impairment of convection-dependent small airways function are more severe. Persistent correlations between ventilation defects and measures of small airways function suggest the potential presence of ICS nonresponsive inflammation and/or remodeling.

Relatively little is known about the transgenerational effects of chronic maternal exposure to low-level traffic-related air pollution (TRAP) on the offspring lung health, nor are the effects of removing such exposure before pregnancy. Female BALB/c mice were exposed to PM 2.5 (PM 2.5, 5 µg/day) for 6 weeks before mating and during gestation and lactation; in a subgroup, PM was removed when mating started to model mothers moving to cleaner areas during pregnancy to protect their unborn child (Pre-exposure). Lung pathology was characterised in both dams and offspring. A subcohort of female offspring was also exposed to ovalbumin to model allergic airways disease. PM 2.5 and Pre-exposure dams exhibited airways hyper-responsiveness (AHR) with mucus hypersecretion, increased mitochondrial reactive oxygen species (ROS) and mitochondrial dysfunction in the lungs. Female offspring from PM 2.5 and Pre-exposure dams displayed AHR with increased lung inflammation and mitochondrial ROS production, while males only displayed increased lung inflammation. After the ovalbumin challenge, AHR was increased in female offspring from PM 2.5 dams compared with those from control dams. Using an in vitro model, the mitochondria-targeted antioxidant MitoQ reversed mitochondrial dysfunction by PM stimulation, suggesting that the lung pathology in offspring is driven by dysfunctional mitochondria. In conclusion, chronic exposure to low doses of PM 2.5 exerted transgenerational impairment on lung health.

We present a hybrid algorithm to estimate lung nodule malignancy that combines imaging biomarkers from Radiologist's annotation with image classification of CT scans. Our algorithm employs a 3D Convolutional Neural Network (CNN) as well as a Random Forest in order to combine CT imagery with biomarker annotation and volumetric radiomic features. We analyze and compare the performance of the algorithm using only imagery, only biomarkers, combined imagery + biomarkers, combined imagery + volumetric radiomic features, and finally the combination of imagery + biomarkers + volumetric features in order to classify the suspicion level of nodule malignancy. The National Cancer Institute (NCI) Lung Image Database Consortium (LIDC) IDRI dataset is used to train and evaluate the classification task. We show that the incorporation of semi-supervised learning by means of K-Nearest-Neighbors (KNN) can increase the available training sample size of the LIDC-IDRI, thereby further improving the accuracy of malignancy estimation of most of the models tested although there is no significant improvement with the use of KNN semi-supervised learning if image classification with CNNs and volumetric features is combined with descriptive biomarkers. Unexpectedly, we also show that a model using image biomarkers alone is more accurate than one that combines biomarkers with volumetric radiomics, 3D CNNs, and semi-supervised learning. We discuss the possibility that this result may be influenced by cognitive bias in LIDC-IDRI because malignancy estimates were recorded by the same radiologist panel as biomarkers, as well as future work to incorporate pathology information over a subset of study participants., (© 2021. The Author(s).)

Airway smooth muscle cells from severe asthma patients with FAO respond to β 2 -agonists and corticosteroids in vitro , and at a level similar to mild asthmatics. Intrinsic dysfunction of these signalling pathways is unlikely to contribute to FAO. https://bit.ly/3muvNsW., Competing Interests: Conflict of interest: S. Rutting has nothing to disclose. Conflict of interest: D. Xenaki has nothing to disclose. Conflict of interest: K.D. Reddy has nothing to disclose. Conflict of interest: M. Baraket has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: G.G. King reports grants, personal fees and nonfinancial support from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, MundiPharma and Novartis; and unrestricted research grants from the NHMRC, Boehringer Ingelheim, CycloPharma, GlaxoSmithKline, Menarini, MundiPharma, philanthropic individuals and societies; and nonfinancial and other support from Restech, Italy, during the conduct of the study. Conflict of interest: B.G. Oliver has nothing to disclose. Conflict of interest: K.O. Tonga reports a Lung Foundation Australia Ludwig Engel grant-in-aid during the conduct of the study., (Copyright ©The authors 2021.)

Higher body mass index (BMI) is associated with less severe airway obstruction in older asthma patients with fixed airflow obstruction. This is potentially mediated through BMI-related mechanisms that increase lung stiffness ( i.e. reduce lung compliance). https://bit.ly/3jBwCNy., Competing Interests: Conflict of interest: S. Rutting has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: T. Badal has nothing to disclose. Conflict of interest: F. Sanai has nothing to disclose. Conflict of interest: S.C. Zimmermann reports nonfinancial support for travel and accommodation for educational respiratory symposia attendance from GlaxoSmithKline, Boehringer Ingelheim, Menarini, AstraZeneca and Novartis, outside the submitted work. Conflict of interest: C. Thamrin has nothing to disclose. Conflict of interest: G.G. King reports unrestricted research grants to support research projects, fees for consultancy services (which include lectures and advisory board services) and conference attendance support from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants from the National Health & Medical Research Council, professional societies, The University of Sydney, and philanthropic individuals and societies, outside the submitted work. Conflict of interest: K.O. Tonga has nothing to disclose., (Copyright ©ERS 2021.)

Multiple breath nitrogen washout (MBNW) quantifies ventilation heterogeneity. Two distinct protocols are currently used for MBNW testing: "controlled breathing", with targeted tidal volume ( V T ) and respiratory rate (RR); and "free breathing", with no constraints on breathing pattern. Indices derived from the two protocols (functional residual capacity (FRC), lung clearance index (LCI), S cond , S acin ) have not been directly compared in adults. We aimed to determine whether MBNW indices are comparable between protocols, to identify factors underlying any between-protocol differences and to determine the between-session variabilities of each protocol. We performed MBNW testing by both protocols in 27 healthy adult volunteers, applying the currently proposed correction for V T to S cond and S acin derived from free breathing. To establish between-session variability, we repeated testing in 15 volunteers within 3 months. While FRC was comparable between controlled versus free breathing (3.17 (0.98) versus 3.18 (0.94) L, p=0.88), indices of ventilation heterogeneity derived from the two protocols were not, with poor correlation for S cond (r=0.18, p=0.36) and significant bias for S acin (0.057 (0.021) L -1 versus 0.085 (0.038) L -1 , p=0.0004). Between-protocol differences in S acin were related to differences in the breathing pattern, i.e. V T (p=0.004) and RR (p=0.01), rather than FRC. FRC and LCI showed good between-session repeatability, but S cond and S acin from free breathing showed poor repeatability with wide limits of agreement. These findings have implications for the ongoing clinical implementation of MBNW, as they demonstrate that S cond and S acin from free breathing, despite V T correction, are not equivalent to the controlled breathing protocol. The poor between-session repeatability of S cond during free breathing may limit its clinical utility., Competing Interests: Conflict of interest: B.M. Handley has nothing to disclose. Conflict of interest: E. Jeagal has nothing to disclose. Conflict of interest: R.E. Schoeffel has nothing to disclose. Conflict of interest: T. Badal has nothing to disclose. Conflict of interest: D.G. Chapman has nothing to disclose. Conflict of interest: C.E. Farrow has nothing to disclose. Conflict of interest: G.G. King reports fees for consultancy services (which include lectures and advisory board services), conference attendance support and unrestricted research grants from AstraZeneca, Boehringer Ingelheim, CycloPharm, GlaxoSmithKline, Novartis, Menarini and MundiPharma, and research grants and fellowships from the National Health & Medical Research Council and the Asthma Foundation, outside the submitted work. Conflict of interest: P.D. Robinson has nothing to disclose. Conflict of interest: S. Milne reports personal fees from Novartis and Boehringer Ingelheim outside the submitted work, and is supported by the MITACS Accelerate programme. Conflict of interest: C. Thamrin has nothing to disclose., (Copyright ©ERS 2021.)

Background: Laparoscopic sleeve gastrectomy (LSG) is the most common bariatric surgical procedure worldwide. Educational videos of LSGs are available from online sources with YouTube® being the most popular online video repository. However, due to the unrestricted and uncontrolled nature of YouTube®, anyone can upload videos without peer review or standardization. The LAP-VEGaS guidelines were formed to guide the production of high-quality surgical videos. The aim of this study is to use the LAP-VEGaS guidelines to determine if videos of LSGs available on Youtube® are of an acceptable standard for surgical educational purposes., Methods: A YouTube® search was performed using the term laparoscopic sleeve gastrectomy. Appropriate videos were analysed by two individuals using the sixteen LAP-VEGaS guidelines., Results: A total of 575 videos were found, of which 202 videos were included and analysed using the LAP-VEGaS guidelines. The median video guideline score was 6/16 with 89% of videos meeting less than half of all guidelines. There was no correlation between the LAP-VEGaS score and view count., Conclusions: There is an abundance of laparoscopic sleeve gastrectomy educational videos available on YouTube®; however, when analysed using the LAP-VEGaS guidelines, the majority do not meet acceptable educational standards for surgical training purposes.

Objective: To characterise the working arrangements of medical research scientists and support staff in Australia during the COVID-19 pandemic, and to evaluate factors (in particular: wearing pyjamas) that influence the self-assessed productivity and mental health of medical institute staff working from home., Design: Prospective cohort survey study, 30 April - 18 May 2020., Setting, Participants: Staff (scientists and non-scientists) and students at five medical research institutes in Sydney, New South Wales., Main Outcome Measures: Self-assessed overall and task-specific productivity, and mental health., Results: The proportions of non-scientists and scientists who wore pyjamas during the day were similar (3% v 11%; P = 0.31). Wearing pyjamas was not associated with differences in self-evaluated productivity, but was significantly associated with more frequent reporting of poorer mental health than non-pyjama wearers while working from home (59% v 26%; P < 0.001). Having children in the home were significantly associated with changes in productivity. Larger proportions of people with toddlers reported reduced overall productivity (63% v 32%; P = 0.008), and reduced productivity in writing manuscripts (50% v 17%; P = 0.023) and data analysis (63% v 23%; P = 0.002). People with primary school children more frequently reported reduced productivity in writing manuscripts (42% v 16%; P = 0.026) and generating new ideas (43% v 19%; P = 0.030). On a positive note, the presence of children in the home was not associated with changes in mental health during the pandemic. In contrast to established researchers, early career researchers frequently reported reduced productivity while working at home., Conclusions: Our findings are probably applicable to scientists in other countries. They may help improve work-from-home policies by removing the stigma associated with pyjama wearing during work and by providing support for working parents and early career researchers., (© 2020 AMPCo Pty Ltd.)

African swine fever virus (ASFV) causes a lethal hemorrhagic disease of domestic pigs, against which no vaccine is available. ASFV has a large, double-stranded DNA genome that encodes over 150 proteins. Replication takes place predominantly in the cytoplasm of the cell and involves complex interactions with host cellular components, including small noncoding RNAs (sncRNAs). A number of DNA viruses are known to manipulate sncRNA either by encoding their own or disrupting host sncRNA. To investigate the interplay between ASFV and sncRNAs, a study of host and viral small RNAs extracted from ASFV-infected primary porcine macrophages (PAMs) was undertaken. We discovered that ASFV infection had only a modest effect on host miRNAs, with only 6 miRNAs differentially expressed during infection. The data also revealed 3 potential novel small RNAs encoded by ASFV, ASFVsRNA1-3. Further investigation of ASFVsRNA2 detected it in lymphoid tissue from pigs with ASF. Overexpression of ASFVsRNA2 led to an up to 1-log reduction in ASFV growth, indicating that ASFV utilizes a virus-encoded small RNA to disrupt its own replication. IMPORTANCE African swine fever (ASF) poses a major threat to pig populations and food security worldwide. The disease is endemic to Africa and Eastern Europe and is rapidly emerging into Asia, where it has led to the deaths of millions of pigs in the last 12 months. The development of safe and effective vaccines to protect pigs against ASF has been hindered by lack of understanding of the complex interactions between ASFV and the host cell. We focused our work on characterizing the interactions between ASFV and sncRNAs. Although comparatively modest changes to host sncRNA abundances were observed upon ASFV infection, we discovered and characterized a novel functional ASFV-encoded sncRNA. The results from this study add important insights into ASFV host-pathogen interactions. This knowledge may be exploited to develop more effective ASFV vaccines that take advantage of the sncRNA system., (Copyright © 2020 Dunn et al.)

Many mouse models of allergic asthma exhibit eosinophil-predominant cellularity rather than the mixed-granulocytic cytology in steroid-unresponsive severe disease. Therefore, we sought to implement a novel mouse model of antigen-driven, mixed-granulocytic, severe allergic asthma to determine biomarkers of the disease process and potential therapeutic targets. C57BL/6J wild-type, interleukin-6 knockout (IL-6-/-), and IL-6 receptor knockout (IL-6R-/-), mice were injected with an emulsion of complete Freund's adjuvant and house dust mite antigen (CFA/HDM) on day 1 . Dexamethasone, a lymphocyte-depleting biological, or anti-IL-17A was administered during the intranasal HDM challenge on days 19-22 . On day 23 , the CFA/HDM model elicited mixed bronchoalveolar lavage (BAL) cellularity (typically 80% neutrophils and 10% eosinophils), airway hyperresponsiveness (AHR) to methacholine, diffusion impairment, lung damage, body weight loss, corticosteroid resistance, and elevated levels of serum amyloid A (SAA), pro-inflammatory cytokines, and T helper type 1/ T helper type 17 (Th1/Th17) cytokines compared with eosinophilic models of HDM-driven allergic airway disease. BAL cells in IL-6- or IL-6R-deficient mice were predominantly eosinophilic and associated with elevated T helper type 2 (Th2) and reduced Th1/Th17 cytokine production, along with an absence of SAA. Nevertheless, AHR remained in IL-6-deficient mice even when dexamethasone was administered. However, combined administration of anti-IL-17A and systemic corticosteroid significantly attenuated both overall and neutrophilic airway inflammation and also reduced AHR and body weight loss. Inhibition of IL-17A combined with systemic corticosteroid treatment during antigen-driven exacerbations may provide a novel therapeutic approach to prevent the pathological pulmonary and constitutional changes that greatly impact patients with the mixed-granulocytic endotype of severe asthma.

The TSANZ develops position statements where insufficient data exist to write formal clinical guidelines. In 2018, the TSANZ addressed the question of potential benefits and health impacts of electronic cigarettes (EC). The working party included groups focused on health impacts, smoking cessation, youth issues and priority populations. The 2018 report on the Public Health Consequences of E-Cigarettes from the United States NASEM was accepted as reflective of evidence to mid-2017. A search for papers subsequently published in peer-reviewed journals was conducted in August 2018. A small number of robust and important papers published until March 2019 were also identified and included. Groups identified studies that extended, modified or contradicted the NASEM report. A total of 3793 papers were identified and reviewed, with summaries and draft position statements developed and presented to TSANZ membership in April 2019. After feedback from members and external reviewers, a collection of position statements was finalized in December 2019. EC have adverse lung effects and harmful effects of long-term use are unknown. EC are unsuitable consumer products for recreational use, part-substitution for smoking or long-term exclusive use by former smokers. Smokers who require support to quit smoking should be directed towards approved medication in conjunction with behavioural support as having the strongest evidence for efficacy and safety. No specific EC product can be recommended as effective and safe for smoking cessation. Smoking cessation claims in relation to EC should be assessed by established regulators., (© 2020 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Introduction: Penectomy as the traditional surgical treatment of penile cancer has substantial adverse functional and psychological impact. Glansectomy with split-thickness skin graft (STSG) reconstruction aims to provide curative resection while maximizing functional outcomes and minimizing psychological harm. We describe our outcomes of glansectomy with STSG reconstruction for penile cancer in a Canadian setting., Methods: We identified patients undergoing glansectomy with STSG genital reconstruction for squamous cell carcinoma of the penis from July 2006 to July 2019 at a single center. Patients undergoing glansectomy for reasons other than penile cancer were excluded. We collected clinical and pathological data, including patient demographics, 90-day complications, positive margin rate, local recurrence rate, disease-specific survival, and functional outcomes. Descriptive statistics were used to characterize our cohort and to examine outcomes., Results: Twelve men met study criteria with a median age of 62 years. Seven patients had failed prior treatment. The 90-day complication rate (Clavien >2) was 0% and graft take was excellent in all cases. The positive margins rate was 16.7% (n=2). Local recurrence occurred in two patients (16.7%), one of whom underwent a repeat organ-sparing surgery for salvage, while the other underwent radical penectomy for high-risk pathological features. Disease-free survival at a median followup of 14 months was 91.7% (11/12). Standing voiding and erectile function, as well as satisfactory cosmesis, were preserved in all patients., Conclusions: Glansectomy with STSG reconstruction is a safe and effective treatment for men with localized penile cancer with simultaneous preservation of cosmesis, as well as urinary and sexual function.

Asthma and COPD make up the majority of obstructive airways diseases (OADs), which affects ∼11 % of the population. The main drugs used to treat OADs have not changed in the past five decades, with advancements mainly comprising variations on existing treatments. The recent biologics are beneficial to only specific subsets of patients. Part of this may lie in our inability to adequately characterise the tremendous heterogeneity in every aspect of OAD. The field is currently moving towards the concept of personalised medicine, based on a focus on treatable traits that are objective, measurable and modifiable. We propose extending this concept via the use of emerging clinical tools for comprehensive physiological phenotyping. We describe, based on published data, the evidence for the use of functional imaging, gas washout techniques and oscillometry, as well as potential future applications, to more comprehensively assess and predict treatment response in OADs. In this way, we hope to demonstrate how physiological phenotyping tools will improve the way in which drugs are prescribed, but most importantly, will facilitate development of new drugs for OADs., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Trauma arising from landmines and improvised explosive devices promotes heterotopic ossification, the formation of extra-skeletal bone in non-osseous tissue. To date, experimental platforms that can replicate the loading parameter space relevant to improvised explosive device and landmine blast wave exposure have not been available to study the effects of such non-physiological mechanical loading on cells. Here, we present the design and calibration of three distinct in vitro experimental loading platforms that allow us to replicate the spectrum of loading conditions recorded in near-field blast wave exposure. We subjected cells in suspension or in a three-dimensional hydrogel to strain rates up to 6000 s -1 and pressure levels up to 45 MPa. Our results highlight that cellular activation is regulated in a non-linear fashion-not by a single mechanical parameter, it is the combined action of the applied mechanical pressure, rate of loading and loading impulse, along with the extracellular environment used to convey the pressure waves. Finally, our research indicates that PO MSCs are finely tuned to respond to mechanical stimuli that fall within defined ranges of loading.

Background and Objective: Abnormal peripheral airway function is an important feature of asthma and relates to asthma symptoms and poor asthma control. We aimed to determine whether peripheral airway function, as measured by forced oscillatory impedance and multiple-breath nitrogen washout (MBNW), relates to symptom improvement in asthmatic participants with uncontrolled asthma, after stepping up to high-dose ICS/LABA treatment., Methods: A total of 19 subjects (14 females, mean age: 29.9 ± 13.6 years) with uncontrolled asthma, as defined by an ACQ5 > 1.5, taking 500 μg/day fluticasone equivalent or less, underwent spirometry, plethysmography, fractional exhaled FeNO, forced oscillatory resistance (Rrs 5Hz ) and reactance (Xrs 5Hz ), and indices of MBNW ventilation heterogeneity (lung clearance index (LCI), diffusion-convection-dependent (Sacin) and convection-dependent (Scond)). Measurements were made before and after 8 weeks of treatment with fluticasone/formoterol combination inhaler 250/10 μg, 2 puffs twice daily., Results: Treatment improved ACQ5 (P = 0.0002), FEV 1 (P = 0.02), FVC (P = 0.04), FeNO (P = 0.0008), Xrs 5Hz (P = 0.01), LCI (P = 0.0002), Sacin (P = 0.006) and Scond (P = 0.01). At baseline, ACQ5 correlated with Xrs 5Hz (r s = 0.52, P = 0.03) and Rrs 5Hz (r s = 0.55, P = 0.02). The improvement in ACQ5 was predicted by more abnormal baseline LCI (P = 0.03), Scond (P = 0.02) and Rrs 5Hz (P = 0.006). Baseline Scond was the best predictor of a clinically meaningful improvement in asthma control (ΔACQ > 0.5, ROC-AUC = 0.91, P = 0.007)., Conclusion: Step-up to high-dose combination treatment in uncontrolled asthma is associated with improved peripheral airway function as measured by Xrs 5Hz and MBNW. Baseline MBNW and FOT parameters correlated with the improvement in symptoms and may predict a positive response to up-titration in uncontrolled asthmatic patients., (© 2020 Asian Pacific Society of Respirology.)

This article will discuss in detail the pathophysiology of asthma from the point of view of lung mechanics. In particular, we will explain how asthma is more than just airflow limitation resulting from airway narrowing but in fact involves multiple consequences of airway narrowing, including ventilation heterogeneity, airway closure, and airway hyperresponsiveness. In addition, the relationship between the airway and surrounding lung parenchyma is thought to be critically important in asthma, especially as related to the response to deep inspiration. Furthermore, dynamic changes in lung mechanics over time may yield important information about asthma stability, as well as potentially provide a window into future disease control. All of these features of mechanical properties of the lung in asthma will be explained by providing evidence from multiple investigative methods, including not only traditional pulmonary function testing but also more sophisticated techniques such as forced oscillation, multiple breath nitrogen washout, and different imaging modalities. Throughout the article, we will link the lung mechanical features of asthma to clinical manifestations of asthma symptoms, severity, and control. © 2020 American Physiological Society. Compr Physiol 10:975-1007, 2020., (Copyright © 2020 American Physiological Society. All rights reserved.)

Background and Objective: Fixed airflow obstruction (FAO) in asthma occurs despite optimal inhaled treatment and no smoking history, and remains a significant problem, particularly with increasing age and duration of asthma. Increased lung compliance and loss of lung elastic recoil has been observed in older people with asthma, but their link to FAO has not been established. We determined the relationship between abnormal lung elasticity and airflow obstruction in asthma., Methods: Non-smoking asthmatic subjects aged >40 years, treated with 2 months of high-dose inhaled corticosteroid/long-acting beta-agonist (ICS/LABA), had FAO measured by spirometry, and respiratory system resistance at 5 Hz (Rrs 5 ) and respiratory system reactance at 5 Hz (Xrs 5 ) measured by forced oscillation technique. Lung compliance (K) and elastic recoil (B/A) were calculated from pressure-volume curves measured by an oesophageal balloon. Linear correlations between K and B/A, and forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC), Rrs 5 and Xrs 5 were assessed., Results: Eighteen subjects (11 males; mean ± SD age: 64 ± 8 years, asthma duration: 39 ± 22 years) had moderate FAO measured by spirometry ((mean ± SD z-score) post-bronchodilator FEV 1 : -2.2 ± 0.5, FVC: -0.7 ± 1.0, FEV 1 /FVC: -2.6 ± 0.7) and by increased Rrs 5 (median (IQR) z-score) 2.7 (1.9 to 3.2) and decreased Xrs 5 : -4.1(-2.4 to -7.3). Lung compliance (K) was increased in 9 of 18 subjects and lung elastic recoil (B/A) reduced in 5 of 18 subjects. FEV 1 /FVC correlated negatively with K (r s = -0.60, P = 0.008) and Rrs 5 correlated negatively with B/A (r s = -0.52, P = 0.026), independent of age. Xrs 5 did not correlate with lung elasticity indices., Conclusion: Increased lung compliance and loss of elastic recoil relate to airflow obstruction in older non-smoking asthmatic subjects, independent of ageing. Thus, structural lung tissue changes may contribute to persistent, steroid-resistant airflow obstruction., Clinical Trial Registration: ACTRN126150000985583 at anzctr.org.au (UTN: U1111-1156-2795)., (© 2019 Asian Pacific Society of Respirology.)