Experimental Measurement of the Size of Gaps Required to Compromise Fit of an N95 Respirator.

OBJECTIVES: The effectiveness of filtering facepiece respirators such as N95 respirators is heavily dependent on the fit. However, there have been limited efforts to discover the size of the gaps in the seal required to compromise filtering facepiece respirator performance, with prior studies estimating this size based on in vitro models. In this study, we measure the size of leak necessary to compromise the fit of N95 respirators. METHODS: Two methods were used to create a gap of specific dimensions. A set of 3D-printed resin spacers and hollow steel rods were used to generate gaps in N95 respirators while worn on two participants. Occupational Safety and Health Administration (OSHA) quantitative fit testing methods were used to quantify mask performance with gaps between 0.4 and 2.9mm diameters. RESULTS: Gap size was regressed against fit factor, showing that overall the minimum gap size to compromise N95 performance was between 1.5mm2 and 3mm2. CONCLUSIONS: These findings suggest the fit of a N95 respirator is compromised by gaps that may be difficult to visually detect. The study also adds to the body of evidence supporting the routine use of quantitative fit testing to ensure that masks are well-fitting.

Nicotine exposure decreases likelihood of SARS-CoV-2 RNA expression and neuropathology in the hACE2 mouse brain but not moribundity.

Individuals infected by SARS-CoV-2 are at risk of developing neurological-related post-acute disorders. Disputed epidemiological data indicated nicotine may reduce the severity of infection. Here we find exposure to nicotine in drinking water does not alter the moribundity of hACE2 mice. However, pre-exposure to nicotine decreased the likelihood of SARS-CoV-2 RNA expression and pathology in the brain. These results suggest mechanisms involving targets of nicotine could be leveraged to prevent the neurovirulence of SARS-CoV-2.

Australian First Nations response to the pandemic: A dramatic reversal of the 'gap'.

Until the recent death in Dubbo of an Aboriginal man, there have been no deaths from Covid 19 in Australia. The extraordinary success of Aboriginal and Torres Strait Islander populations in controlling the effects of this pandemic has been a global role model. Until early 2021, in spite of their high risk status, dispersed population and fear of health services due to racism, Indigenous outcomes were better than those for non-Indigenous. Aboriginal health leaders at every level brought in worlds best practices and applied them in all urban, rural and remote locations. Instead of the many hundreds of cases, hospitalisation and deaths expected, there were only 150 cases nationwide with15% hospitalised but no one in ICU and no deaths. This result is a complete reversal of the gap and was due to the outstanding Indigenous leadership, that governments at all levels listened to Aboriginal wisdom and that control was handed to those who knew what to do. This result is not only evidence for why a Voice enshrined in the Constitution would work, it heralds a new way of working with Aboriginal people in Australia. This viewpoint makes the case for a different model to engage and empower First Nations to really close the gap - themselves.

Risk of severe illness from COVID-19 among Aboriginal and Torres Strait Islander adults: the construct of 'vulnerable populations' obscures the root causes of health inequities.

OBJECTIVE: To quantify the prevalence of known health-related risk factors for severe COVID-19 illness among Aboriginal and Torres Strait Islander adults, and their relationship with social determinants. METHODS: Weighted cross-sectional analysis of the 2018-19 National Aboriginal and Torres Strait Islander Health Survey; Odds Ratios for cumulative risk count category (0, 1, or ≥2 health-related risk factors) by social factors calculated using ordered logistic regression. RESULTS: Of the adult population, 42.9%(95%CI:40.6,45.2) had none of the examined health-related risk factors; 38.9%(36.6,41.1) had 1, and 18.2%(16.7,19.7) had ≥2. Adults experiencing relative advantage across social indicators had significantly lower cumulative risk counts, with 30-70% lower odds of being in a higher risk category. CONCLUSIONS: Aboriginal and Torres Strait Islander peoples must continue to be recognised as a priority population in all stages of pandemic preparedness and response as they have disproportionate exposure to social factors associated with risk of severe COVID-19 illness. Indigeneity itself is not a 'risk' factor and must be viewed in the wider context of inequities that impact health Implications for public health: Multi-sectoral responses are required to improve health during and after the COVID-19 pandemic that: enable self-determination; improve incomes, safety, food security and culturally-safe healthcare; and address discrimination and trauma.

A decentralised point-of-care testing model to address inequities in the COVID-19 response.

The COVID-19 pandemic is growing rapidly, with over 37 million cases and more than 1 million deaths reported by mid-October, 2020, with true numbers likely to be much higher in the many countries with low testing rates. Many communities are highly vulnerable to the devastating effects of COVID-19 because of overcrowding in domestic settings, high burden of comorbidities, and scarce access to health care. Access to testing is crucial to globally recommended control strategies, but many communities do not have adequate access to timely laboratory services. Geographic dispersion of small populations across islands and other rural and remote settings presents a key barrier to testing access. In this Personal View, we describe a model for the implementation of decentralised COVID-19 point-of-care testing in remote locations by use of the GeneXpert platform, which has been successfully scaled up in remote Aboriginal and Torres Strait Islander communities across Australia. Implementation of the decentralised point-of-care testing model should be considered for communities in need, especially those that are undertested and socially vulnerable. The decentralised testing model should be part of the core global response towards suppressing COVID-19.

Differential Activity and Utilization of Glucocorticoid Receptor Binding Sites Yields Transcriptional Heterogeneity

Synthetic glucocorticoids such as Dexamethasone (Dex) are widely prescribed drugs used to treat a variety of human diseases including auto-immune disorders, asthma, cancer, and COVID-19. The transcriptional response to glucocorticoids is elicited by the Glucocorticoid Receptor (GR), which enters the nucleus upon Dex treatment and interacts with thousands of enhancer elements throughout the genome. We recently demonstrated that the Dex response in human breast cancer cells is highly heterogeneous and that individual cells have unique transcriptional responses to Dex. To examine whether this heterogeneity arises from differential utilization of distinct GR-bound enhancers, we focused on the Dex response at the DNA Damage Inducible Transcript 4 (DDIT4) gene. Using a variety of genomic techniques, we identified four GR binding sites (GBSs) 18-30kb upstream of the DDIT4 TSS with differential patterns of chromatin accessibility, histone acetylation, SWI/SNF recruitment, and enhancer RNA (eRNA) transcription. To determine whether these GBSs had unique requirements for DDIT4 transcription, we used CRISPR-CAS9 to generate homozygous deletions of each site. Using ChIP-seq, 4C-seq, single molecule fluorescent in situ hybridization (smFISH), and RT-PCR, we demonstrated GR binding to these GBSs was independent and each GBS deletion had unique effects on DDIT4 and eRNA transcription, local histone acetylation, and chromatin looping. Deletion of any of the first three GBSs resulted in delayed and/or decreased induction of DDIT4 transcription whereas deletion of the fourth GBS resulted in significant upregulation of both DDIT4 and eRNA transcription. Thus, three of the GBSs acted as enhancers of DDIT4 expression while the fourth functioned as a suppressor. Strikingly, smFISH also revealed that these enhancers contributed to cellular heterogeneity, as deleting the GBSs altered the frequency and amplitude of DDIT4 transcription across cell populations. Taken together, these results demonstrate that individual GBSs uniquely contribute to cell-to-cell heterogeneity within the transcriptional response of DDIT4 to Dex. Furthermore, they underscore the possibility that targeted modification of individual GBSs could be utilized to tailor custom, patient-specific strategies for the treatment of human diseases.

Comparing the fit of N95, KN95, surgical, and cloth face masks and assessing the accuracy of fit checking.

INTRODUCTION: The COVID-19 pandemic has made well-fitting face masks a critical piece of protective equipment for healthcare workers and civilians. While the importance of wearing face masks has been acknowledged, there remains a lack of understanding about the role of good fit in rendering protective equipment useful. In addition, supply chain constraints have caused some organizations to abandon traditional quantitative or/and qualitative fit testing, and instead, have implemented subjective fit checking. Our study seeks to quantitatively evaluate the level of fit offered by various types of masks, and most importantly, assess the accuracy of implementing fit checks by comparing fit check results to quantitative fit testing results. METHODS: Seven participants first evaluated N95 and KN95 respirators by performing a fit check. Participants then underwent quantitative fit testing wearing five N95 respirators, a KN95 respirator, a surgical mask, and fabric masks. RESULTS: N95 respirators offered higher degrees of protection than the other categories of masks tested; however, it should be noted that most N95 respirators failed to fit the participants adequately. Fit check responses had poor correlation with quantitative fit factor scores. KN95, surgical, and fabric masks achieved low fit factor scores, with little protective difference recorded between respiratory protection options. In addition, small facial differences were observed to have a significant impact on quantitative fit. CONCLUSION: Fit is critical to the level of protection offered by respirators. For an N95 respirator to provide the promised protection, it must fit the participant. Performing a fit check via NHS self-assessment guidelines was an unreliable way of determining fit.

Roadmap to recovery: Reporting on a research taskforce supporting Indigenous responses to COVID-19 in Australia.

In April 2020 a Group of Eight Taskforce was convened, consisting of over 100 researchers, to provide independent, research-based recommendations to the Commonwealth Government on a "Roadmap to Recovery" from COVID-19. The report covered issues ranging from pandemic control and relaxation of social distancing measures, to well-being and special considerations for vulnerable populations. Our work focused on the critical needs of Aboriginal and Torres Strait Islander communities; this paper presents an overview of our recommendations to the Roadmap report. In addressing the global challenges posed by pandemics for citizens around the world, Indigenous people are recognised as highly vulnerable. At the time of writing Australia's First Nations Peoples have been largely spared from COVID-19 in comparison to other Indigenous populations globally. Our recommendations emphasise self-determination and equitable needs-based funding to support Indigenous communities to recover from COVID-19, addressing persistent overcrowded housing, and a focus on workforce, especially for regional and remote communities. These latter two issues have been highlighted as major issues of risk for Indigenous communities in Australia It remains to be seen how governments across Australia take up these recommendations to support Indigenous peoples' health and healing journey through yet another, potentially catastrophic, health crisis.

Ability of fabric face mask materials to filter ultrafine particles at coughing velocity.

OBJECTIVE: We examined the ability of fabrics which might be used to create home-made face masks to filter out ultrafine (0.02-0.1 µm) particles at the velocity of adult human coughing. METHODS: Twenty commonly available fabrics and materials were evaluated for their ability to reduce air concentrations of ultrafine particles at coughing face velocities. Further assessment was made on the filtration ability of selected fabrics while damp and of fabric combinations which might be used to construct home-made masks. RESULTS: Single fabric layers blocked a range of ultrafine particles. When fabrics were layered, a higher percentage of ultrafine particles were filtered. The average filtration efficiency of single layer fabrics and of layered combination was found to be 35% and 45%, respectively. Non-woven fusible interfacing, when combined with other fabrics, could add up to 11% additional filtration efficiency. However, fabric and fabric combinations were more difficult to breathe through than N95 masks. CONCLUSIONS: The current coronavirus pandemic has left many communities without access to N95 face masks. Our findings suggest that face masks made from layered common fabric can help filter ultrafine particles and provide some protection for the wearer when commercial face masks are unavailable.

Performing Qualitative Mask Fit Testing Without a Commercial Kit: Fit Testing Which Can Be Performed at Home and at Work.

OBJECTIVE: Qualitative fit testing is a popular method of ensuring the fit of sealing face masks such as N95 and FFP3 masks. Increased demand due to the coronavirus disease 2019 (COVID-19) pandemic has led to shortages in testing equipment and has forced many institutions to abandon fit testing. Three key materials are required for qualitative fit testing: the test solution, nebulizer, and testing hood. Accessible alternatives to the testing solution have been studied. This exploratory qualitative study evaluates alternatives to the nebulizer and hoods for performing qualitative fit testing. METHODS: Four devices were trialed to replace the test kit nebulizer. Two enclosures were tested for their ability to replace the test hood. Three researchers evaluated promising replacements under multiple mask fit conditions to assess functionality and accuracy. RESULTS: The aroma diffuser and smaller enclosures allowed participants to perform qualitative fit tests quickly and with high accuracy. CONCLUSIONS: Aroma diffusers show significant promise in their ability to allow individuals to quickly, easily, and inexpensively perform qualitative fit testing. Our findings indicate that aroma diffusers and homemade testing hoods may allow for qualitative fit testing when conventional apparatus is unavailable. Additional research is needed to evaluate the safety and reliability of these devices.