Improving Human Diets and Welfare through Using Herbivore-Based Foods: 1. Human and Animal Perspectives.

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.

Rapid antigen testing for SARS-CoV-2 by lateral flow assay: A field evaluation of self- and professional testing at UK community testing sites.

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.

The Application of High-Resolution, Embedded Fibre Optic (FO) Sensing for Large-Diameter Composite Steel/Plastic Pipeline Performance under Dynamic Transport Loads.

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.

Swab pooling enables rapid expansion of high-throughput capacity for SARS-CoV-2 community testing.

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.

Resilience as an Independent Predictor of Bowel Related Quality of Life After Spinal Cord Injury.

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.

Long-Term outcomes of cecostomy tube insertion for patients with bowel dysfunction: A retrospective review.

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.

CCS-GAN: COVID-19 CT Scan Generation and Classification with Very Few Positive Training Images.

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.

Model analysis of multiple breath nitrogen washout data: robustness to variations in breathing pattern.

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 Scond, Sacin 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 (FRCM), dead space volume (VD), the coefficient of variation of regional specific ventilation ([Formula: see text]), and the model equivalent of Sacin (Sacin-M). Intra-participant coefficients of variation for the model parameters for both health and asthma were FRCM < 5.2%, VD < 5.4%, [Formula: see text] < 9.0%, and Sacin-M < 45.6% for controlled breathing, and FRCM < 4.6%, VD < 5.3%, [Formula: see text] < 13.2%, and Sacin-M < 103.2% for free breathing. The coefficients of variation limits for conventional parameters were FRC < 6.1%, with Scond < 73.6% and Sacin < 49.2% for controlled breathing and Scond < 35.0% and Sacin < 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 Scond.

Pulmonary function testing during SARS-CoV-2: An ANZSRS/TSANZ position statement.

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.

The effect of oxygen and carbon dioxide cross-sensitivity sensor error in the Eco Medics Exhalyzer D device on measures of conductive and acinar airway function.

Introduction: The multiple breath nitrogen washout (MBNW) test provides important clinical information in obstructive airways diseases. Recently, a significant cross-sensitivity error in the O2 and CO2 sensors of a widely used commercial MBNW device (Exhalyzer D, Eco Medics AG, Duernten, Switzerland) was detected, which leads to overestimation of N2 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 O2 and CO2 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.

Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants.

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.).

Normal limits for oscillometric bronchodilator responses and relationships with clinical factors.

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 rs6 ) and reactance (X rs6 ) 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 rs6 and 95th percentile increase in X rs6 in a healthy subgroup. RESULTS: Of 1318 participants, 1145 (570 female) were analysed. The lower threshold for ΔR rs6 was -1.38 cmH2O·s·L-1 (-30.0% or -1.42 Z-scores) and upper threshold for ΔX rs6 was 0.57 cmH2O·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, ΔX rs6 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.

Ethnic and regional differences in the temporal trends of prostate cancer incidence and mortality in New Zealand.

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, Maori and Asian men had significantly lower Pca incidence. Mortality rates demonstrated a steady decline, which was more prominent until 2010. Maori and Pacific men had higher mortality rates when compared to European men. In most recent years, the difference in mortality is decreasing for Maori 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 Maori and Pacific men.

Presence of defective viral genes in H1N1 live attenuated influenza vaccine strains is not associated with reduced human cell fitness or vaccine effectiveness.

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.

Daily testing for contacts of individuals with SARS-CoV-2 infection and attendance and SARS-CoV-2 transmission in English secondary schools and colleges: an open-label, cluster-randomised trial.

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.

Maternal Particulate Matter Exposure Impairs Lung Health and Is Associated with Mitochondrial Damage.

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 PM2.5 (PM2.5, 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. PM2.5 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 PM2.5 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 PM2.5 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 PM2.5 exerted transgenerational impairment on lung health.