Unstable air : How COVID-19 remade knowing air quality in school classrooms

Air quality is neither a stable material phenomenon, nor form of knowledge. This was made clear upon the arrival of COVID-19 in school classrooms when humans emerged as the primary source of poor indoor air quality (IAQ), and a host of new devices were placed into schools to monitor and clean IAQ. In this paper we examine this instability as it had consequences within a research-business project attempting to measure IAQ and assess the effectiveness of an air cleaning device in school classrooms pre- and post- the emergence of COVID-19. Using a ‘near’ Actor-Network Theory analytical framework we focus on how a network of ‘science in action’ became re-assembled to COVID-19. Drawing on IAQ data that we collected, government and industry statements and reports, and the direct involvement of the lead author using both reflexive and relational ethnographic approaches, we show how our IAQ measurements, combined with other material inscriptions, were powerful actants that changed the relationship between the air indoors and outdoors. We bring Maria Puig de la Bellacasa’s concept of ‘matters of care’ into conversation with the project detailing how changing socio-material circumstances led to a more active role to reconfigure classroom IAQ, and how we might better care for IAQ in the future. We also relate our project to the wider – and ongoing – process of reassembling IAQ, asking how this might relate to questions of inequalities and responsibilities

Indoor-Outdoor Air Pollution & Environmental Justice

Environmental Justice research has focused on demonstrating the extent to which air pollution is equally—or unequally— distributed across particular defined social groups. A socioeconomic group of particular importance are children, as they are especially susceptible to air pollution because of their high inhalation rates relative to body mass, high activity concentrations, narrower lung airways, and immature immune systems (Lipsett, 1989; Pope, 1989;; Wiley et. al., 1991). More than just exhibiting negative health consequences, exposure to air pollution has also been associated with poor academic performance among schoolaged children (Mohai et al., 2011).Research has focused on outdoor air pollution, however, the conclusions drawn have a methodological myopia: the research assumes that outdoor air pollution is an accurate indicator of personal exposure. Yet, on average, people spend more than 90% of their time indoors (Klepeis et al. 2001), where levels can be 2-5 times more polluted than outdoors (Hulin, Simoni, Viegi, & AnnesiMaesano, 2012).  The combination of both the length of time spent inside, and the potential for higher concentrations means that personal exposure is greater indoors rather than outdoors (Vardoulakis, 2009). However, to understand indoor air quality (IAQ), one must rely on the principle that the indoor atmosphere is an extension of the outdoor atmosphere. To understand environmental justice, one must have a holistic understanding of air pollution, indoors and outdoors. The aim of the research is to develop new understandings of patterns of exposure to poor air quality for school children. This will involve simultaneously monitoring multiple pollutants inside and outside using the NAQTS V1000 in a range of different places and indoor environments (schools and school buses) and with a fine temporal resolution. This will permit a holistic and more complex understanding of patterns of exposure for school children to be developed, including in terms of its implications for vulnerability and distributive justice

(Re)assembling air quality science : Exploring air quality knowledge production

In this thesis I critically examine the production of knowledge about air quality. I do so to explore how air quality knowledge is produced, and critically engage with how we can reconfigure our relations with the air to begin to address air inequalities. I draw upon my direct involvement in three different forms of doing air quality science. I analyse these involvements across three papers that make up the thesis along with Introduction, Literature Review, Methodology, and Conclusion chapters. In Paper 1, using an autoethnographic analysis of PhD fieldwork, I contrast the difference between ‘ready made science’ and ‘science in the making’ through challenging my own conventional account of a school air quality monitoring project. In Paper 2, I show how a research-business project in UK schools that measured indoor air quality to assess the effectiveness of an air cleaning device became re-assembled following the emergence of COVID-19. In Paper 3, I reflect on a citizen science air quality monitoring project: drawing on interviews with citizen scientists I illuminate tensions in the dynamics of knowledge production, including air quality research design and reporting. Moreover, drawing upon science and technology studies, critical physical geography, and environmental justice literatures, I propose a new Critical Air Quality Science framework. This thesis contributes to ‘hybrid’ ways of thinking about the air that pays attention to its materiality, but also its cultural, social, economic, and political relations: in particular for indoor air quality. Additionally, through drawing upon Actor-Network Theory and other ‘more-than-human’ approaches, I contribute to research characterising the mediating role of scientists in the production of the air. Moreover, through focusing on my own mediating role in the doing of air quality science, I contribute to emerging strands of environmental justice, namely epistemic justice

A Critical Air Quality Science Perspective on Citizen Science in Action

Air pollution is a hybrid phenomenon, understood and produced through social practices and material environmental processes. This hybridity leads us to engage critically with how air quality science is carried out. In dialogue with the critical physical geography subdiscipline, we propose a critical air quality science (CAQS) framework to study air pollution’s sociomateriality. We use CAQS to illuminate four tensions in the dynamics of knowledge production during a citizen science air quality monitoring project: making undone science matter, blurring “insiderness”/“outsiderness”, traffic as both life and death, and changing behaviours versus changing systems. Drawing on interviews with citizen scientists, we outline the implications of these tensions for air quality research design and reporting. The CAQS framework provokes critical thought about the consequences of how air quality science understands, creates and communicates knowledge, and how we can reconfigure our relations with the air to minimise air inequalities

Characterization of lysosomal proteins Progranulin and Prosaposin and their interactions in Alzheimer\u27s disease and aged brains: increased levels correlate with neuropathology.

Progranulin (PGRN) is a protein encoded by the GRN gene with multiple identified functions including as a neurotrophic factor, tumorigenic growth factor, anti-inflammatory cytokine and regulator of lysosomal function. A single mutation in the human GRN gene resulting in reduced PGRN expression causes types of frontotemporal lobar degeneration resulting in frontotemporal dementia. Prosaposin (PSAP) is also a multifunctional neuroprotective secreted protein and regulator of lysosomal function. Interactions of PGRN and PSAP affect their functional properties. Their roles in Alzheimer\u27s disease (AD), the leading cause of dementia, have not been defined. In this report, we examined in detail the cellular expression of PGRN in middle temporal gyrus samples of a series of human brain cases (n = 45) staged for increasing plaque pathology. Immunohistochemistry showed PGRN expression in cortical neurons, microglia, cerebral vessels and amyloid beta (Aβ) plaques, while PSAP expression was mainly detected in neurons and Aβ plaques, and to a limited extent in astrocytes. We showed that there were increased levels of PGRN protein in AD cases and corresponding increased levels of PSAP. Levels of PGRN and PSAP protein positively correlated with amyloid beta (Aβ), with PGRN levels correlating with phosphorylated tau (serine 205) levels in these samples. Although PGRN colocalized with lysosomal-associated membrane protein-1 in neurons, most PGRN associated with Aβ plaques did not. Aβ plaques with PGRN and PSAP deposits were identified in the low plaque non-demented cases suggesting this was an early event in plaque formation. We did not observe PGRN-positive neurofibrillary tangles. Co-immunoprecipitation studies of PGRN from brain samples identified only PSAP associated with PGRN, not sortilin or other known PGRN-binding proteins, under conditions used. Most PGRN associated with Aβ plaques were immunoreactive for PSAP showing a high degree of colocalization of these proteins that did not change between disease groups. As PGRN supplementation has been considered as a therapeutic approach for AD, the possible involvement of PGRN and PSAP interactions in AD pathology needs to be further considered

Randomized double-blind trial of pregabalin versus placebo in conjunction with palliative radiotherapy for cancer-induced bone pain

Purpose Cancer-induced bone pain (CIBP) affects one third of patients with cancer. Radiotherapy remains the gold-standard treatment; however, laboratory and clinical work suggest that pregabalin may be useful in treating CIBP. The aim of this study was to examine pregabalin in patients with CIBP receiving radiotherapy. Patients and Methods A multicenter, double-blind randomized trial of pregabalin versus placebo was conducted. Eligible patients were age ≥ 18 years, had radiologically proven bone metastases, were scheduled to receive radiotherapy, and had pain scores ≥ 4 of 10 (on 0-to-10 numeric rating scale). Before radiotherapy, baseline assessments were completed, followed by random assignment. Doses of pregabalin and placebo were increased over 4 weeks. The primary end point was treatment response, defined as a reduction of ≥ 2 points in worst pain by week 4, accompanied by a stable or reduced opioid dose, compared with baseline. Secondary end points assessed average pain, interference of pain with activity, breakthrough pain, mood, quality of life, and adverse events. Results A total of 233 patients were randomly assigned: 117 to placebo and 116 to pregabalin. The most common cancers were prostate (n = 88; 38%), breast (n = 77; 33%), and lung (n = 42; 18%). In the pregabalin arm, 45 patients (38.8%) achieved the primary end point, compared with 47 (40.2%) in the placebo arm (adjusted odds ratio, 1.07; 95% CI, 0.63 to 1.81; P = .816). There were no statistically significant differences in average pain, pain interference, or quality of life between arms. There were differences in mood (P = .031) and breakthrough pain duration (P = .037) between arms. Outcomes were compared at 4 weeks. Conclusion Our findings do not support the role of pregabalin in patients with CIBP receiving radiotherapy. The role of pregabalin in CIBP with a clinical neuropathic pain component is unknown

Epigenome-wide association study of global cortical volumes in Generation Scotland:Scottish Family Health Study

Funding This work was supported by the Wellcome Trust [104036/Z/14/Z]. Acknowledgements Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, University of Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z). MCB is supported by a Guarantors of Brain Non-clinical Post-Doctoral Fellowship. AMM is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). KLE is supported by the NARSAD Independent Investigator Award (Grant ID: 21956). JMW is supported by UK Dementia Research Institute which is funded by the MRC, Alzheimer’s Research UK and Alzheimer’s Society, by the Fondation Leducq (16 CVD 05), and the Row Fogo Centre for Research Into Ageing and the Brain (BRO- D.FID3668413). This work is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 847776.Peer reviewedPublisher PD

Novel fluorinated derivative of curcumin negatively regulates thioredoxin-interacting protein expression in retinal pigment epithelial and macrophage cells.

Thioredoxin-interacting protein (TXNIP) has multiple disease-associated functions including inducing oxidative stress by inhibiting the anti-oxidant and thiol reducing activity of thioredoxin (TRX), reducing cellular glucose transport, and is a component of the activated inflammasome complex. Increased expression of TXNIP is encountered in diabetic conditions of high glucose. Curcumin and chemical derivatives have multiple therapeutic properties as anti-inflammatories, anti-oxidants, amyloid aggregation inhibitors and modulate a number of cellular signaling pathways. Using a fluorinated-derivative of curcumin (designated Shiga-Y6), we showed significant inhibition of TXNIP mRNA and protein expression, and induction of TRX mRNA and protein in ARPE-19 retinal pigment epithelial cells and THP-1-derived macrophages, while the non-fluorinated structural equivalent (Shiga-Y52) and native curcumin did not show these same effects. Shiga-Y6 was effective in reducing high glucose, endoplasmic reticulum stress-induced TXNIP in ARPE-19 cells, and reducing lipopolysaccharide and endoplasmic stress-induced proinflammatory gene expression in THP-1 macrophages. Moreover, TXNIP-knockdown experiments showed that the anti-inflammatory effect of Shiga-Y6 in LPS-stimulated THP-1 macrophages was TXNIP-independent

Effects of FTMT Expression by Retinal Pigment Epithelial Cells on Features of Angiogenesis.

Aberrant angiogenesis is a pathological feature of a number of diseases and arises from the uncoordinated expression of angiogenic factors as response to different cellular stresses. Age-related macular degeneration (AMD), a leading cause of vision loss, can result from pathological angiogenesis. As a mutation in the mitochondrial ferritin (FTMT) gene has been associated with AMD, its possible role in modulating angiogenic factors and angiogenesis was investigated. FTMT is an iron-sequestering protein primarily expressed in metabolically active cells and tissues with high oxygen demand, including retina. In this study, we utilized the human retinal pigment epithelial cell line ARPE-19, both as undifferentiated and differentiated cells. The effects of proinflammatory cytokines, FTMT knockdown, and transient and stable overexpression of FTMT were investigated on expression of pro-angiogenic vascular endothelial growth factor (VEGF) and anti-angiogenic pigment epithelial-derived factor (PEDF). Proinflammatory cytokines induced FTMT and VEGF expression, while NF-κB inhibition significantly reduced FTMT expression. VEGF protein and mRNA expression were significantly increased in FTMT-silenced ARPE-19 cells. Using an in vitro angiogenesis assay with endothelial cells, we showed that conditioned media from FTMT-overexpressing cells had significant antiangiogenic effects. Collectively, our findings indicate that increased levels of FTMT inhibit angiogenesis, possibly by reducing levels of VEGF and increasing PEDF expression. The cellular models developed can be used to investigate if increased FTMT may be protective in angiogenic diseases, such as AMD