Publications by authors named "N W Marshall"

839 Publications

Optimal shutdown strategies for COVID-19 with economic and mortality costs: British Columbia as a case study.

R Soc Open Sci 2021 Sep 8;8(9):202255. Epub 2021 Sep 8.

CMPS Department, University of British Columbia Okanagan, 1177 Research Road, Kelowna, British Columbia, Canada V1V 1V7.

Decision makers with the responsibility of managing policy for the COVID-19 epidemic have faced difficult choices in balancing the competing claims of saving lives and the high economic cost of shutdowns. In this paper, we formulate a model with both epidemiological and economic content to assist this decision-making process. We consider two ways to handle the balance between economic costs and deaths. First, we use the statistical value of life, which in Canada is about C$7 million, to optimize over a single variable, which is the sum of the economic cost and the value of lives lost. Our second method is to calculate the Pareto optimal front when we look at the two variables-deaths and economic costs. In both cases we find that, for most parameter values, the optimal policy is to adopt an initial shutdown level which reduces the reproduction number of the epidemic to close to 1. This level is then reduced once a vaccination programme is underway. Our model also indicates that an oscillating policy of strict and mild shutdowns is less effective than a policy which maintains a moderate shutdown level.
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http://dx.doi.org/10.1098/rsos.202255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424295PMC
September 2021

Dermal exposure to the immunomodulatory antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice.

Toxicol Sci 2021 Sep 13. Epub 2021 Sep 13.

Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV.

Triclosan is an antimicrobial chemical used in healthcare settings that can be absorbed through the skin. Exposure to triclosan has been positively associated with food and aeroallergy and asthma exacerbation in humans and, although not directly sensitizing, has been demonstrated to augment the allergic response in a mouse model of asthma. The skin barrier and microbiome are thought to play important roles in regulating inflammation and allergy and disruptions may contribute to development of allergic disease. To investigate potential connections of the skin barrier and microbiome with immune responses to triclosan, SKH1 mice were exposed dermally to triclosan (0.5-2%) or vehicle for up to 7 consecutive days. Exposure to 2% triclosan for 5-7 days on the skin was shown to increase trans-epidermal water loss levels. Seven days of dermal exposure to triclosan decreased filaggrin 2 and keratin 10 expression, but increased filaggrin and keratin 14 protein along with the danger signal S100a8 and interleukin-4. Dermal exposure to triclosan for 7 days also altered the alpha and beta diversity of the skin and gut microbiome. Specifically, dermal triclosan exposure increased the relative abundance of the Firmicutes family, Lachnospiraceae on the skin but decreased the abundance of Firmicutes family, Ruminococcaceae in the gut. Collectively, these results demonstrate that repeated dermal exposure to the antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice, suggesting that these changes may contribute to the increase in allergic immune responses following dermal exposure to triclosan.
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http://dx.doi.org/10.1093/toxsci/kfab111DOI Listing
September 2021

Deep immune profiling of the maternal-fetal interface with mild SARS-CoV-2 infection.

bioRxiv 2021 Aug 23. Epub 2021 Aug 23.

Pregnant women are an at-risk group for severe COVID-19, though the majority experience mild/asymptomatic disease. Although severe COVID-19 has been shown to be associated with immune activation at the maternal-fetal interface even in the absence of active viral replication, the immune response to asymptomatic/mild COVID-19 remains unknown. Here, we assessed immunological adaptations in both blood and term decidua from 9 SARS-exposed pregnant women with asymptomatic/mild disease and 15 pregnant SARS-naive women. In addition to selective loss of tissue-resident decidual macrophages, we report attenuation of antigen presentation and type I IFN signaling but upregulation of inflammatory cytokines and chemokines in blood monocyte derived decidual macrophages. On the other hand, infection was associated with remodeling of the T cell compartment with increased frequencies of activated CD69+ tissue-resident T cells and decreased abundance of Tregs. Interestingly, frequencies of cytotoxic CD4 and CD8 T cells increased only in the blood, while CD8 effector memory T cells were expanded in the decidua. In contrast to decidual macrophages, signatures of type I IFN signaling were increased in decidual T cells. Finally, T cell receptor diversity was significantly reduced with infection in both compartments, albeit to a much greater extent in the blood. The resulting aberrant immune activation in the placenta, even with asymptomatic disease may alter the exquisitely sensitive developing fetal immune system, leading to long-term adverse outcomes for offspring.
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http://dx.doi.org/10.1101/2021.08.23.457408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404883PMC
August 2021

The monocyte-to-lymphocyte ratio: Sex-specific differences in the tuberculosis disease spectrum, diagnostic indices and defining normal ranges.

PLoS One 2021 30;16(8):e0247745. Epub 2021 Aug 30.

Department of Respiratory Medicine, Homerton University Hospital, London, United Kingdom.

Background: The monocyte-to-lymphocyte ratio (MLR) has been advocated as a biomarker in tuberculosis. Our objective was to evaluate its clinical value and associations.

Methods: Blood counts, inflammatory markers and clinical parameters were measured in patients with and those screened for tuberculosis. Complete blood counts (CBCs) from a multi-ethnic population aged 16 to 65 years were evaluated; a sub-group with normal hematological indices was used to define the range of MLRs.

Results: Multivariate analysis in proven tuberculosis (n = 264) indicated MLR associated with low serum albumin, high white cell counts and a positive culture; values were higher in sputum smear-positive pulmonary tuberculosis (S+PTB). Analysis in S+PTB (n = 296) showed higher MLRs in males and those with high neutrophil counts, low serum albumin and high C-reactive protein. The diagnostic value of MLRs was assessed by comparing notified patients with TB (n = 264) with denotified cases (n = 50), active case-finding in non-contacts (TB n = 111 and LTBI n = 373) and contacts of S+PTB (n = 149) with S+PTB found at screening (n = 75). Sensitivities and specificities ranged from 58.0-62.5% and 50.0-70.0% respectively for optimal cut-off values, defined by ROC curves. In CBCs obtained over one month, ratios correlated with neutrophil counts (ρ = 0.48, P<0.00001, n = 14,573; MLR = 0.45 at 8-8.9 x 109/L) and were higher in males than females (P<0.0001). The MLR range (mean ± 2SD) in those with normal hematological indices (n = 3921: females 0.122-0.474; males 0.136-0.505) paralleled LTBI MLRs. Ratios did not predict death (n = 29) nor response to treatment (n = 178 S+PTB with follow-up CBCs). Ratios were higher in males than female in the 16-45 years age group, where immune differences due to sex hormones are likely greatest.

Conclusions: Severe tuberculosis and male sex associated with high MLRs; the same variables likely affect the performance of other biomarkers. The ratio performed poorly as a clinical aid.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247745PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405018PMC
August 2021

Thresholds of polarization vision in octopuses.

J Exp Biol 2021 04 15;224(7). Epub 2021 Apr 15.

Ecology of Vision Group, School of Biological Sciences, University of Bristol, Bristol BS8 1TQ, UK.

Polarization vision is widespread in nature, mainly among invertebrates, and is used for a range of tasks including navigation, habitat localization and communication. In marine environments, some species such as those from the Crustacea and Cephalopoda that are principally monochromatic, have evolved to use this adaptation to discriminate objects across the whole visual field, an ability similar to our own use of colour vision. The performance of these polarization vision systems varies, and the few cephalopod species tested so far have notably acute thresholds of discrimination. However, most studies to date have used artificial sources of polarized light that produce levels of polarization much higher than found in nature. In this study, the ability of octopuses to detect polarization contrasts varying in angle of polarization (AoP) was investigated over a range of different degrees of linear polarization (DoLP) to better judge their visual ability in more ecologically relevant conditions. The 'just-noticeable-differences' (JND) of AoP contrasts varied consistently with DoLP. These JND thresholds could be largely explained by their 'polarization distance', a neurophysical model that effectively calculates the level of activity in opposing horizontally and vertically oriented polarization channels in the cephalopod visual system. Imaging polarimetry from the animals' natural environment was then used to illustrate the functional advantage that these polarization thresholds may confer in behaviourally relevant contexts.
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http://dx.doi.org/10.1242/jeb.240812DOI Listing
April 2021
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