Publications by authors named "M L Sutton"

1,294 Publications

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Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles.

ACS Nano 2021 Nov 29. Epub 2021 Nov 29.

Department of Physics, McGill University, 3600 University, Montreal Quebec, Canada H3A2T8.

Nanoparticles are a promising solution for delivery of a wide range of medicines and vaccines. Optimizing their design depends on being able to resolve, understand, and predict biophysical and therapeutic properties, as a function of design parameters. While existing tools have made great progress, gaps in understanding remain because of the inability to make detailed measurements of multiple correlated properties. Typically, an average measurement is made across a heterogeneous population, obscuring potentially important information. In this work, we develop and apply a method for characterizing nanoparticles with single-particle resolution. We use convex lens-induced confinement (CLiC) microscopy to isolate and quantify the diffusive trajectories and fluorescent intensities of individual nanoparticles trapped in microwells for long times. First, we benchmark detailed measurements of fluorescent polystyrene nanoparticles against prior data to validate our approach. Second, we apply our method to investigate the size and loading properties of lipid nanoparticle (LNP) vehicles containing silencing RNA (siRNA), as a function of lipid formulation, solution pH, and drug-loading. By taking a comprehensive look at the correlation between the intensity and size measurements, we gain insights into LNP structure and how the siRNA is distributed in the LNP. Beyond introducing an analytic for size and loading, this work allows for future studies of dynamics with single-particle resolution, such as LNP fusion and drug-release kinetics. The prime contribution of this work is to better understand the connections between microscopic and macroscopic properties of drug-delivery vehicles, enabling and accelerating their discovery and development.
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http://dx.doi.org/10.1021/acsnano.1c04862DOI Listing
November 2021

Assessment of the Toronto Psoriatic Arthritis Screen 2 as a Screening Tool for Psoriasis.

J Cutan Med Surg 2021 Nov 29:12034754211061085. Epub 2021 Nov 29.

26625 Division of Dermatology, Department of Medicine, Toronto Western Hospital, ON, Canada.

Background: Psoriasis is a chronic inflammatory disease affecting multiple organ systems and resulting in reduced quality of life for many patients. A screening tool would be useful, particularly in underserviced or research settings with limited access to dermatologists. The Toronto Psoriatic Arthritis Screen, version 2 (ToPAS 2) is a validated screening tool for psoriatic arthritis containing questions specific for psoriasis.

Objectives: To evaluate the performance of skin-specific questions from ToPAS 2 for the diagnosis of psoriasis.

Methods: Participants aged >18 were recruited from Dermatology and Family Medicine clinics and completed the ToPAS 2 questionnaire prior to being examined by a dermatologist for psoriasis. Two scoring indexes were derived from the ToPAS 2 skin-related questions using backward selection regression models. Statistical analysis was performed using receiver operating characteristic (ROC) curves to measure their performances.

Results: Two hundred and fifty eight participants were recruited. 32 (12%) were diagnosed with psoriasis by dermatologist assessment. Index 1 includes all 5 skin-related questions from ToPAS 2, while Index 2 includes three of the five questions. Both indexes demonstrate high specificity (82% to 92%), sensitivity (69% to 84%), and excellent negative predictive value (NPV) (>95%) for a diagnosis of psoriasis. The overall discriminatory power of these models is 0.823 (Index 1) and 0.875 (Index 2).

Conclusions: Skin-related questions from ToPAS 2 have discriminatory value in detecting psoriasis, specifically questions relating to a family history, a prior physician diagnosis of psoriasis or a rash consistent with images of plaque psoriasis. This study is a valuable step in developing a screening tool for psoriasis.
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http://dx.doi.org/10.1177/12034754211061085DOI Listing
November 2021

Estimating the late-life effects of social and emotional skills in childhood using midlife mediators.

Soc Sci Med 2021 Nov 1:114522. Epub 2021 Nov 1.

Health Organisation, Policy and Economics (HOPE), Centre for Primary Care & Health Services Research, School of Health Sciences, The University of Manchester, Manchester, UK; Melbourne Institute: Applied Economic and Social Research, University of Melbourne, Australia. Electronic address:

Social and emotional skills are known to affect health and non-health outcomes, but there is limited evidence on whether these skills in childhood affect late life outcomes because of a shortage of long-running datasets containing this information. We develop a three-stage procedure and use it to estimate the effect of childhood social and emotional skills on health and labour market outcomes in late-life. This procedure makes use of mediators in midlife which are shown to be predicted by childhood skills in one dataset and to predict late-life outcomes in another dataset. We use this method to combine estimates from the National Child Development Survey and the British Household Panel Survey. We find that childhood skills predict marital status, education, home ownership, income and health at age 46 years and these midlife variables predict levels of quality-adjusted life years and labour income accumulated by age 63 years. The combined estimates suggest a standard deviation increase in average Bristol Social Adjustment Guide total score at ages 7 and 11 is associated with 4.2% (standard error = 0.6%) additional quality-adjusted life years and more than 9.9% (£14,539, standard error = £2072) additional accumulated pre-tax earnings by age 63 years. Therefore, childhood interventions to increase social and emotional skills would be expected to reduce future healthcare costs and increase wealth. Our three-stage methodology can be used to predict the life-course effects of investments in childhood skills by combining results from datasets across population cohorts.
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http://dx.doi.org/10.1016/j.socscimed.2021.114522DOI Listing
November 2021

Abating ammonia is more cost-effective than nitrogen oxides for mitigating PM air pollution.

Science 2021 11 4;374(6568):758-762. Epub 2021 Nov 4.

UK Centre for Ecology & Hydrology, Edinburgh Research Station, Bush Estate, Penicuik, Midlothian EH26 0QB, UK.

[Figure: see text].
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http://dx.doi.org/10.1126/science.abf8623DOI Listing
November 2021

Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance - COVID-NET, 14 States, January-August 2021.

MMWR Morb Mortal Wkly Rep 2021 Oct 29;70(43):1513-1519. Epub 2021 Oct 29.

In mid-June 2021, B.1.671.2 (Delta) became the predominant variant of SARS-CoV-2, the virus that causes COVID-19, circulating in the United States. As of July 2021, the Delta variant was responsible for nearly all new SARS-CoV-2 infections in the United States.* The Delta variant is more transmissible than previously circulating SARS-CoV-2 variants (1); however, whether it causes more severe disease in adults has been uncertain. Data from the CDC COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system for COVID-19-associated hospitalizations, were used to examine trends in severe outcomes in adults aged ≥18 years hospitalized with laboratory-confirmed COVID-19 during periods before (January-June 2021) and during (July-August 2021) Delta variant predominance. COVID-19-associated hospitalization rates among all adults declined during January-June 2021 (pre-Delta period), before increasing during July-August 2021 (Delta period). Among sampled nonpregnant hospitalized COVID-19 patients with completed medical record abstraction and a discharge disposition during the pre-Delta period, the proportion of patients who were admitted to an intensive care unit (ICU), received invasive mechanical ventilation (IMV), or died while hospitalized did not significantly change from the pre-Delta period to the Delta period. The proportion of hospitalized COVID-19 patients who were aged 18-49 years significantly increased, from 24.7% (95% confidence interval [CI] = 23.2%-26.3%) of all hospitalizations in the pre-Delta period, to 35.8% (95% CI = 32.1%-39.5%, p<0.01) during the Delta period. When examined by vaccination status, 71.8% of COVID-19-associated hospitalizations in the Delta period were in unvaccinated adults. Adults aged 18-49 years accounted for 43.6% (95% CI = 39.1%-48.2%) of all hospitalizations among unvaccinated adults during the Delta period. No difference was observed in ICU admission, receipt of IMV, or in-hospital death among nonpregnant hospitalized adults between the pre-Delta and Delta periods. However, the proportion of unvaccinated adults aged 18-49 years hospitalized with COVID-19 has increased as the Delta variant has become more predominant. Lower vaccination coverage in this age group likely contributed to the increase in hospitalized patients during the Delta period. COVID-19 vaccination is critical for all eligible adults, including those aged <50 years who have relatively low vaccination rates compared with older adults.
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http://dx.doi.org/10.15585/mmwr.mm7043e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553023PMC
October 2021
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