A novel light source with tuneable uniformity of light distribution for artificial daylight photodynamic therapy

This project was supported by the University of St. Andrews through the Science and Technology Facilities Council (STFC) Impact Accelerator Award (IAA) and by the Laser Research and Therapy Fund (registered charity SC030850). P O’M is funded by Medi-lase (registered charity SC 037390) and the Alfred Stewart Trust.Objectives: Implementation of daylight photodynamic therapy (dPDT) is somewhat limited by variable weather conditions. Light sources have been employed to provide artificial dPDT indoors, with low irradiances and longer treatment times. Uniform light distribution across the target area is key to ensuring effective treatment, particularly for large areas. A novel light source is developed with tuneable direction of light emission in order to meet this challenge. Methods: Wavelength composition of the novel light source is controlled such that the protoporphyrin-IX (PpIX) weighed spectra of both the light source and daylight match. The uniformity of the light source is characterised on a flat surface, a model head and a model leg. For context, a typical conventional PDT light source is also characterised. Additionally, the wavelength uniformity across the treatment site is characterised. Results: The PpIX-weighted spectrum of the novel light source matches with PpIX-weighted daylight spectrum, with irradiance values within the bounds for effective dPDT. By tuning the direction of light emission, improvements are seen in the uniformity across large anatomical surfaces. Wavelength uniformity is discussed. Conclusions: We have developed a light source that addresses the challenges in uniform, multiwavelength light distribution for large area artificial dPDT across curved anatomical surfaces.PostprintPeer reviewe

X-Ray Luminous Supernovae: Threats to Terrestrial Biospheres

The spectacular outbursts of energy associated with supernovae (SNe) have long motivated research into their potentially hazardous effects on Earth and analogous environments. Much of this research has focused primarily on the atmospheric damage associated with the prompt arrival of ionizing photons within days or months of the initial outburst, and the high-energy cosmic rays that arrive thousands of years after the explosion. In this study, we turn the focus to persistent X-ray emission, arising in certain SNe that have interactions with a dense circumstellar medium, and observed months and/or years after the initial outburst. The sustained high X-ray luminosity leads to large doses of ionizing radiation out to formidable distances. We provide an assessment of the threat posed by these X-ray luminous SNe by analyzing the collective X-ray observations from Chandra, Swift-XRT, XMM-Newton, NuSTAR, and others. We find that this threat is particularly acute for SNe showing evidence of strong circumstellar interaction, such as Type IIn explosions, which have significantly larger ranges of influence than previously expected, and lethal consequences up to $\sim$ 50 pc away. Furthermore, X-ray bright SNe could pose a substantial and distinct threat to terrestrial biospheres, and tighten the Galactic habitable zone. We urge follow-up X-ray observations of interacting SNe for months and years after the explosion to shed light on the physical nature of the emission and its full time evolution, and to clarify the danger that these events pose for life in our Galaxy and other star-forming regions.Comment: 24 pages, 6 figures. Now includes a more detailed analysis of X-ray effectiveness for ozone destruction; conclusions unchanged. Matches version to appear in Ap

Exploring the origins of perpendicular magnetic anisotropy in amorphous Tb-Co via changes in medium-range ordering

Amorphous thin films of Tb$_{17}$Co$_{83}$ (a-Tb-Co) grown by magnetron co-sputtering exhibit changes in magnetic anisotropy with varying growth and annealing temperatures. The magnetic anisotropy constant increases with increasing growth temperature, which is reduced or vanishes upon annealing at temperatures above the growth temperature. The proposed explanation for this growth-induced anisotropy in high orbital moment Tb-based transition metal alloys such as a-Tb-Co is an amorphous phase texturing with preferential in-plane and out-of-plane local bonding configurations for the rare-earth and transition metal atoms. Scanning nanodiffraction performed in a transmission electron microscope (TEM) is applied to a-Tb$_{17}$Co$_{83}$ films deposited over a range of temperatures to measure relative changes in medium-range ordering (MRO). These measurements reveal an increase in MRO with higher growth temperatures and a decrease in MRO with higher annealing temperatures. The trend in MRO indicates a relationship between the magnetic anisotropy and local atomic ordering. Tilting select films between 0$^{\circ}$ and 40$^{\circ}$ in the TEM measures variations in the local atomic structure a function of orientation within the films. The findings support claims that preferential ordering along the growth direction results from temperature-mediated adatom configurations during deposition, and that oriented MRO correlates with the larger anisotropy constants.Comment: 13 pages, 9 figure

Development of a predictive Monte Carlo radiative transfer model for ablative fractional skin lasers

L.M. would like to acknowledge the funding from EPSRC grant code: EP/K503162/1. P.O'M. is funded by Medi‐Lase (registered charity SC 037390) and the Alfred Stewart Trust'.It is possible to enhance topical drug delivery by pretreatment of the skin with ablative fractional lasers (AFLs). However, the parameters to use for a given AFL to achieve the desired depth of ablation or the desired therapeutic or cosmetic outcome are hard to predict. This leaves open the real possibility of overapplication or underapplication of laser energy to the skin. In this study, we developed a numerical model consisting of a Monte Carlo radiative transfer (MCRT) code coupled to a heat transfer and tissue damage algorithm. The simulation is designed to predict the depth effects of AFL on the skin, verified with in vitro experiments in porcine skin via optical coherence tomography (OCT) imaging. Ex vivo porcine skin is irradiated with increasing energies (50–400 mJ/pixel) from a CO2 AFL. The depth of microscopic treatment zones is measured and compared with our numerical model. The data from the OCT images and MCRT model complement each other well. Nonablative thermal effects on surrounding tissue are also discussed. This model, therefore, provides an initial step toward a predictive determination of the effects of AFL on the skin.Publisher PDFPeer reviewe

Shared Antigen-specific CD8⁺ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants

We report here on antigens from the SARS-CoV-2 virus spike protein, that when presented by Class I MHC, can lead to cytotoxic CD8⁺ T cell anti-viral responses in COVID-19 patients. We present a method in which the SARS-CoV-2 spike protein is converted into a library of peptide antigen-Major Histocompatibility Complexes (pMHCs) as single chain trimers that contain the peptide antigen, the MHC HLA allele, and the β-2 microglobulin sub-unit. That library is used to detect the evolution of virus-specific T cell populations from two COVID-19 patients, at two time points over the course of infection. Both patients exhibit similar virus-specific T cell populations, but very different time-trajectories of those populations. These results can be used to track those virus-specific T cell populations over the course of an infection, thus providing deep insight into the variations in immune system trajectories observed in different COVID-19 patients

The prevalence and long-term health effects of Long Covid among hospitalised and non-hospitalised populations: A systematic review and meta-analysis

BACKGROUND: The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population. METHODS: A systematic literature search was conducted using multiple electronic databases (MEDLINE and The Cochrane Library, Scopus, CINAHL, and medRxiv) until January 2022. Studies with at least 100 people with confirmed or self-reported COVID-19 symptoms at ≥28 days following infection onset were included. Patient-reported outcome measures and clinical investigations were both assessed. Results were analysed descriptively, and meta-analyses were conducted to derive prevalence estimates. This study was pre-registered (PROSPERO-ID: CRD42021238247). FINDINGS: 194 studies totalling 735,006 participants were included, with five studies conducted in those <18 years of age. Most studies were conducted in Europe (n = 106) or Asia (n = 49), and the time to follow-up ranged from ≥28 days to 387 days. 122 studies reported data on hospitalised patients, 18 on non-hospitalised, and 54 on hospitalised and non-hospitalised combined (mixed). On average, at least 45% of COVID-19 survivors, regardless of hospitalisation status, went on to experience at least one unresolved symptom (mean follow-up 126 days). Fatigue was frequently reported across hospitalised (28.4%; 95% CI 24.7%-32.5%), non-hospitalised (34.8%; 95% CI 17.6%-57.2%), and mixed (25.2%; 95% CI 17.7%-34.6%) cohorts. Amongst the hospitalised cohort, abnormal CT patterns/x-rays were frequently reported (45.3%; 95% CI 35.3%-55.7%), alongside ground glass opacification (41.1%; 95% CI 25.7%-58.5%), and impaired diffusion capacity for carbon monoxide (31.7%; 95% CI 25.8%-3.2%). INTERPRETATION: Our work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at ∼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies. FUNDING: No funding

From Interactions to Institutions: Microprocesses of Framing and Mechanisms for the Structuring of Institutional Fields

Despite the centrality of meaning to institutionalization, little attention has been paid to how meanings evolve and amplify to become institutionalized cultural conventions. We develop an interactional framing perspective to explain the microprocesses and mechanisms by which this occurs. We identify three amplification processes and three ways frames stack up or laminate that become the building blocks for diffusion and institutionalization of meanings within organizations and fields. Although we focus on “bottom-up” dynamics, we argue that framing occurs in a politicized social context and is inherently bidirectional, in line with structuration, because microlevel interactions instantiate macrostructures. We consider how our approach complements other theories of meaning making, its utility for informing related theoretical streams, and its implications for organizing at the meso and macro levels