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"Simpson, Phil, (L. Phil)"
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Genomic Evidence of In-Flight Transmission of SARS-CoV-2 Despite Predeparture Testing
Since the first wave of coronavirus disease in March 2020, citizens and permanent residents returning to New Zealand have been required to undergo managed isolation and quarantine (MIQ) for 14 days and mandatory testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of October 20, 2020, of 62,698 arrivals, testing of persons in MIQ had identified 215 cases of SARS-CoV-2 infection. Among 86 passengers on a flight from Dubai, United Arab Emirates, that arrived in New Zealand on September 29, test results were positive for 7 persons in MIQ. These passengers originated from 5 different countries before a layover in Dubai; 5 had negative predeparture SARS-CoV-2 test results. To assess possible points of infection, we analyzed information about their journeys, disease progression, and virus genomic data. All 7 SARS-CoV-2 genomes were genetically identical, except for a single mutation in 1 sample. Despite predeparture testing, multiple instances of in-flight SARS-CoV-2 transmission are likely.
Journal Article
Impact of sewer biofilms on fate of SARS-CoV-2 RNA and wastewater surveillance
With wastewater surveillance being implemented worldwide to aid in managing coronavirus disease 2019 (COVID-19), there is a need to understand the fate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in sewer systems. Here we employed a sewer reactor to investigate sorption, decay and persistence of SARS-CoV-2 RNA in sewers. RNA concentrations were positively correlated between wastewater liquid and suspended solids, and between wastewater mixture and sewer biofilms. We identified two roles of biofilms in mediating the fate of SARS-CoV-2 RNA. Firstly, biofilms could affect RNA in-sewer stability. This impact could be limited in typical sewer systems with high COVID-19 prevalence, as estimated RNA loss was relatively small. However, in low-case settings, in-sewer RNA decay could affect detectability and precision of analysis, particularly over long hydraulic retention times before sample collection. The second role of biofilms is a reservoir for accumulating, retaining and distributing SARS-CoV-2 RNA under hydraulic changes, which could lead to prolonged virus presence and affect wastewater surveillance interpretation.Understanding the fate of the severe acute respiratory syndrome coronavirus 2 RNA in sewage is essential to develop reliable wastewater surveillance. Research employing a sewer reactor shows that biofilms affect the RNA stability and can act as reservoirs for accumulating, retaining and distributing severe acute respiratory syndrome coronavirus 2 RNA under hydraulic changes.
Journal Article
A population-level framework to estimate unequal exposure to indoor heat and air pollution
As people in the UK spend 95% of their time indoors, buildings are an important modifier of exposure to both non-optimal temperatures and air pollution. High ambient temperature and high PM2.5 (particulate matter) concentrations often occur together in urban areas. Residential building types prone to overheating (e.g. purpose-built flats) are often also more common in urban areas. Together, this may lead to spatial and demographic inequalities in indoor exposure to heat and PM2.5 from outdoor sources. By combining building simulations (EnergyPlus), a spatially distributed description of the residential building stock—from publicly available Energy Performance Certificate (EPC) data, ambient temperature, PM2.5 data and area-level (40–250 households) socio-demographic data—we estimated these inequalities in exposure for the population of England and Wales. Maximum indoor temperature was higher in areas with larger ethnic minority and infant populations, and lower in areas with a higher proportion of people aged ≥ 65 years. Indoor concentrations of outdoor-source PM2.5 were higher in areas with larger ethnic minority and low-income populations. With rising inequality in England and Wales, housing and environmental conditions play an important role in contributing to health inequalities from social disadvantage. Policy relevance Differences in environmental exposures may partly explain inequalities in health outcomes. These differences are mediated by dwelling type and quality. Identifying the driving factors for differences in environmental exposures may allow for the development of interventions to address health inequalities more effectively. This study finds differences in indoor exposure across socio-demographic groups due to both location and housing. This could be of interest to national, regional and local authorities responsible for targeting building retrofit interventions across the housing stock.
Journal Article
Air Trapping on Chest CT Is Associated with Worse Ventilation Distribution in Infants with Cystic Fibrosis Diagnosed following Newborn Screening
In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.
Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M(1)/M(0) and M(2)/M(0), respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping.
Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M(2)/M(0) but not LCI or M(1)/M(0). There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes.
These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.
Journal Article
The Preterm Clinical Network (PCN) Database: a web-based systematic method of collecting data on the care of women at risk of preterm birth
Background
Despite much research effort, there is a paucity of conclusive evidence in the field of preterm birth prediction and prevention. The methods of monitoring and prevention strategies offered to women at risk vary considerably around the UK and depend on local maternity care provision. It is becoming increasingly recognised that this experience and knowledge, if captured on a larger scale, could be a utilized as a valuable source of evidence for others. The UK Preterm Clinical Network (UKPCN) was established with the aim of improving care and outcomes for women at risk of preterm birth through the sharing of a wealth of experience and knowledge, as well as the building of clinical and research collaboration. The design and development of a bespoke internet-based database was fundamental to achieving this aim.
Method
Following consultation with UKPCN members and agreement on a minimal dataset, the Preterm Clinical Network (PCN) Database was constructed to collect data from women at risk of preterm birth and their children. Information Governance and research ethics committee approval was given for the storage of historical as well as prospectively collected data. Collaborating centres have instant access to their own records, while use of pooled data is governed by the PCN Database Access Committee. Applications are welcomed from UKPCN members and other established research groups. The results of investigations using the data are expected to provide insights into the effectiveness of current surveillance practices and preterm birth interventions on a national and international scale, as well as the generation of ideas for innovation and research. To date, 31 sites are registered as Data Collection Centres, four of which are outside the UK.
Conclusion
This paper outlines the aims of the PCN Database along with the development process undertaken from the initial idea to live launch.
Journal Article
Expression of a Truncated Brca1 Protein Delays Lactational Mammary Development in Transgenic Mice
To address the hypothesis that certain disease-associated mutants of the breast-ovarian cancer susceptibility gene BRCA1 have biological activity in vivo, we have expressed a truncated Brca1 protein (trBrca1) in cell-lines and in the mammary gland of transgenic mice. Immunofluorescent analysis of transfected cell-lines indicates that trBRCA1 is a stable protein and that it is localized in the cell cytoplasm. Functional analysis of these cell-lines indicates that expression of trBRCA1 confers an increased radiosensitivity phenotype on mammary epithelial cells, consistent with abrogation of the BRCA1 pathway. MMTV-trBrca1 transgenic mice from two independent lines displayed a delay in lactational mammary gland development, as demonstrated by altered histological profiles of lobuloalveolar structures. Cellular and molecular analyses indicate that this phenotype results from a defect in differentiation, rather than altered rates of proliferation or apoptosis. The results presented in this paper are consistent with trBrca1 possessing dominant-negative activity and playing an important role in regulating normal mammary development. They may also have implications for germline carriers of BRCA1 mutations.
Journal Article