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"Robinson, Phil"
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Heparin Inhibits SARS-CoV-2 Replication in Human Nasal Epithelial Cells
by
Purcell, Damian F. J.
,
Anderson, Gary P.
,
Subbarao, Kanta
in
Aerosols
,
Anticoagulants
,
antiviral
2022
SARS-CoV-2 is the causative agent of the COVID-19 pandemic. Vaccination, supported by social and public health measures, has proven efficacious for reducing disease severity and virus spread. However, the emergence of highly transmissible viral variants that escape prior immunity highlights the need for additional mitigation approaches. Heparin binds the SARS-CoV-2 spike protein and can inhibit virus entry and replication in susceptible human cell lines and bronchial epithelial cells. Primary infection predominantly occurs via the nasal epithelium, but the nasal cell biology of SARS-CoV-2 is not well studied. We hypothesized that prophylactic intranasal administration of heparin may provide strain-agnostic protection for household contacts or those in high-risk settings against SARS-CoV-2 infection. Therefore, we investigated the ability of heparin to inhibit SARS-CoV-2 infection and replication in differentiated human nasal epithelial cells and showed that prolonged exposure to heparin inhibits virus infection. Furthermore, we establish a method for PCR detection of SARS-CoV-2 viral genomes in heparin-treated samples that can be adapted for the detection of viruses in clinical studies.
Journal Article
Air Trapping on Chest CT Is Associated with Worse Ventilation Distribution in Infants with Cystic Fibrosis Diagnosed following Newborn Screening
2011
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
Glucose Tolerance during Pulmonary Exacerbations in Children with Cystic Fibrosis
2012
Patients with Cystic Fibrosis (CF) are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability.
Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well.
Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77). At the follow up OGTT, 8 of 9 (89%) remained within their respective glucose tolerance status groupings.
The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.
Journal Article
Aeciospore ejection in the rust pathogen Puccinia graminis is driven by moisture ingress
2021
Fungi have evolved an array of spore discharge and dispersal processes. Here, we developed a theoretical model that explains the ejection mechanics of aeciospore liberation in the stem rust pathogen Puccinia graminis. Aeciospores are released from cluster cups formed on its Berberis host, spreading early-season inoculum into neighboring small-grain crops. Our model illustrates that during dew or rainfall, changes in aeciospore turgidity exerts substantial force on neighboring aeciospores in cluster cups whilst gaps between spores become perfused with water. This perfusion coats aeciospores with a lubrication film that facilitates expulsion, with single aeciospores reaching speeds of 0.053 to 0.754 m·s−1. We also used aeciospore source strength estimates to simulate the aeciospore dispersal gradient and incorporated this into a publicly available web interface. This aids farmers and legislators to assess current local risk of dispersal and facilitates development of sophisticated epidemiological models to potentially curtail stem rust epidemics originating on Berberis.Bueno-Sancho et al. use high-speed videography and mathematical modelling to examine aeciospore dispersal mechanics of the stem rust fungus Puccinia graminis. Their model shows that aeciospore ejection is driven by peridium rupture and moisture ingress, with dispersal projections encapsulated in a web interface to help assess risk of disease spread to nearby cereal crops.
Journal Article
Co-curate: Working with Schools and Communities to Add Value to Open Collections
by
Coburn, John
,
Peterson, John
,
Robinson, Phil
in
Academic libraries
,
Archives
,
Archives & records
2016
Co-Curate North East is a cross-discipliry initiative involving Newcastle University and partner organisations, working with schools and community groups in the North East of England. Co-curation builds on the concept of the ‘ecomuseum’ model for heritage based around a virtual territory, social memory and participative input from the wider population. The project also leverages open licencing and facilities to harvest and repurpose collections of photographs, video clips, and other artefacts. Technologies were developed to support co-production and co-curation, including facilities to combine (‘Mashup’) materials from formal collections of museums and archives with Open Access (OA) content from informal community-based resources. The purpose of this paper is to provide an overview of the technologies used and developed during the project, with a particular focus on how Open collections were used, in both formal and informal educatiol contexts.A diverse range of community and school groups participated in the project, including a large-scale pilot with a High School which integrated use of the Website as part of an ‘enquiry-based’ scheme of work over several weeks, culmiting in the students giving an exhibition in a prominent regiol gallery. Levels of knowledge of copyright and licensing varied between groups, but were generally low. Issues around copyright and licenses were a major component of ongoing discussion with groups as part of the co-curation process.Co-Curate is an innovative project using OA materials in a range of educatiol and cultural settings.
Journal Article
Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial
2022
Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance.
We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance.
Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians.
ACTRN12619000564156.
Journal Article
Infection, Inflammation, and Lung Function Decline in Infants with Cystic Fibrosis
by
Williamson, Elizabeth
,
Massie, John
,
Robinson, Phil
in
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
,
Babies
,
Biological and medical sciences
2011
Abstract
Rationale
Better understanding of evolution of lung function in infants with cystic fibrosis (CF) and its association with pulmonary inflammation and infection is crucial in informing both early intervention studies aimed at limiting lung damage and the role of lung function as outcomes in such studies.
Objectives
To describe longitudinal change in lung function in infants with CF and its association with pulmonary infection and inflammation.
Methods
Infants diagnosed after newborn screening or clinical presentation were recruited prospectively. FVC, forced expiratory volume in 0.5 seconds (FEV0.5), and forced expiratory flows at 75% of exhaled vital capacity (FEF75) were measured using the raised-volume technique, and z-scores were calculated from published reference equations. Pulmonary infection and inflammation were measured in bronchoalveolar lavage within 48 hours of lung function testing.
Measurements and Main Results
Thirty-seven infants had at least two successful repeat lung function measurements. Mean (SD) z-scores for FVC were −0.8 (1.0), −0.9 (1.1), and −1.7 (1.2) when measured at the first visit, 1-year visit, or 2-year visit, respectively. Mean (SD) z-scores for FEV0.5 were −1.4 (1.2), −2.4 (1.1), and −4.3 (1.6), respectively. In those infants in whom free neutrophil elastase was detected, FVC z-scores were 0.81 lower (P = 0.003), and FEV0.5 z-scores 0.96 lower (P = 0.001), respectively. Significantly greater decline in FEV0.5 z-scores occurred in those infected with Staphylococcus aureus (P = 0.018) or Pseudomonas aeruginosa (P = 0.021).
Conclusions
In infants with CF, pulmonary inflammation is associated with lower lung function, whereas pulmonary infection is associated with a greater rate of decline in lung function. Strategies targeting pulmonary inflammation and infection are required to prevent early decline in lung function in infants with CF.
Journal Article
Working with Young Homeless People
2008
Young homeless people are ordinary young people trapped in an extraordinary situation. This accessible guide provides information and advice on how to understand the needs of these young people, and how to ensure they are supported effectively.
It combines the latest research and practice to establish what works best when helping young homeless people and provides insights into their world through diary excerpts and interviews. Key issues covered include the relationship between drug and alcohol misuse and youth homelessness, current policies on housing and support for homeless youths and strategies for renewing a young person's familial bonds and friendships after an experience of homelessness.
This book is an invaluable guide for anyone working with young homeless people, including youth workers, counsellors, social workers, residential care staff, teachers, health visitors and managers in the housing, education, health and social welfare sectors.
Anticipate, respond, recover : healthcare leadership and catastrophic events
by
McGlown, K. Joanne
,
Robinson, Phillip D.
in
Disaster Planning -- organization & administration -- United States
,
Emergency medical services -- United States
,
Hospital Administration -- methods -- United States
2011
As disasters continue to increase in frequency and severity, healthcare organizations must be prepared to react quickly and coordinate their efforts with those of other first-responder organizations. This book focuses on disaster preparedness and response from the healthcare leader's perspective. It shares practical strategies derived from the real-world experience of CEOs and administrators. It also includes compelling interviews with healthcare leaders who led their organizations' response to and recovery from catastrophic events including recent hurricanes, floods, and terrorist threats. Creating a solid financial plan and implementing it swiftly following a catastrophe are critical to the long-term stability of the facility. Two chapters of the book are devoted to ensuring fiscal strength before, during, and after a disaster. These chapters and others are illustrated with easy-to-use sample forms and checklists for planning and response. Topics covered include: # Updates of the current status of federal regulations # Definitions of the local, state, and federal roles in catastrophe planning # Descriptions of various planning processes # The most common roadblocks healthcare leaders face in crisis situations # Strategies for recovery and reconstruction following an event # How to minimize the financial impact of disasters
Altered airway ciliary orientation in patients with X-linked retinitis pigmentosa
2019
Previous reports suggested links between respiratory ciliary dysfunction and primary ciliopathies such as X-linked retinitis pigmentosa (XLRP). To investigate if patients with XLRP have abnormal airway ciliary structure or function, we assessed respiratory ciliary beat pattern and ultrastructure, including ciliary orientation, in 12 patients with XLRP without respiratory disease and 10 control subjects. Patients with XLRP had normal ciliary ultrastructure but significantly (p=0.004) increased mean ciliary deviation (33.8°±9.4°) compared with normal subjects (14.8°±5.4°). Altered orientation was associated with impaired ciliary beat pattern in six patients with XLRP. These findings indicate that XLRP mutations, affecting non-motile cilia of the photoreceptors in the retina, can have effects on motile cilia in the respiratory tract. The observation of disrupted ciliary orientation in patients with XLRP is suggestive of a defect in planar cell polarity.
Journal Article