Effect modification and interaction between ethnicity and socioeconomic factors in severe COVID-19: analyses of linked national data for Scotland

Objective: Minority ethnic groups disproportionately experienced adverse COVID-19 outcomes, partly a consequence of disproportionate exposure to socioeconomic disadvantage and high-risk occupations. We examined whether minority ethnic groups were also disproportionately vulnerable to the consequences of socioeconomic disadvantage and high-risk occupations in Scotland. Design: We investigated effect modification and interaction between area deprivation, education and occupational risk and ethnicity (assessed as both a binary white vs non-white variable and a multi-category variable) in relation to severe COVID-19 (hospitalisation or death). We used electronic health records linked to the 2011 census and Cox proportional hazards models, adjusting for age, sex and health board. We were principally concerned with additive interactions as a measure of vulnerability, estimated as the relative excess risk due to interaction (RERI). Results: Analyses considered 3 730 837 individuals aged ≥16 years (with narrower age ranges for analyses focused on education and occupation). Severe COVID-19 risk was typically higher for minority ethnic groups and disadvantaged socioeconomic groups, but additive interactions were not consistent. For example, non-white ethnicity and highest deprivation level experienced elevated risk ((HR=2.7, 95% CI: 2.4, 3.2) compared with the white least deprived group. Additive interaction was not present (RERI=−0.1, 95% CI: −0.4, 0.2), this risk being less than the sum of risks of white ethnicity/highest deprivation level (HR=2.4, 95% CI: 2.3, 2.5) and non-white ethnicity/lowest deprivation level (1.4, 95% CI: 1.2, 1.7). Similarly, non-white ethnicity/no degree education (HR=2.5, 95% CI: 2.2, 2.7; RERI=−0.1, 95% CI: −0.4, 0.2) and non-white ethnicity/high-risk occupation (RERI=0.3, 95% CI: −0.2, 0.8) did not experience greater than additive risk. No clear evidence of effect modification was identified when using the multicategory ethnicity variable or on the multiplicative scale either. Conclusion: We found no definitive evidence that minority ethnic groups were more vulnerable to the effect of social disadvantage on the risk of severe COVID-19

Landscape‐Scale Effects of Season and Predation Risk on the Terrestrial Behavior of Chacma Baboons ( Papio ursinus )

Objectives: “Terrestrial” primates are not common nor well defined across the order. In those species that do use the ground, terrestriality is rarely documented outside daylight hours. Predation risk is thought to have shaped conserved behaviors like primates' selection of arboreal sleep sites, but it is less clear—particularly at the landscape scale—how predation risk interacts with other ecological and seasonal variables to drive terrestriality. This camera trapping study investigates patterns in terrestrial behavior both spatially and temporally across neighboring populations of chacma baboons. Materials and Methods: We use camera trap data from two terrestrial grids, one established within and one outside the boundaries of Gorongosa National Park, Mozambique. We model how baboon terrestrial activity varies with woody cover, proximity to water, season, anthropogenic variables, as well as predation risk. We also model how terrestrial activity varies across the diel cycle and use overlap analyses to explore differences in the baboon populations' activity patterns. Results: We find no significant predictors of geospatial variation in the terrestrial activity of baboons across each grid but do find evidence of higher terrestrial activity in the late dry season. We also find significantly different diel patterns of baboon activity detected across each grid. Discussion: Baboons likely use the ground more in the dry season for accessing water and resources when arboreal foods are less abundant. Diel variation between the two populations suggests that baboons might utilize the ground more during “riskier” crepuscular and nocturnal hours where leopards are not present

Electronic structure, reflectivity and X-ray luminescence of MAPbCl 3 crystal in orthorhombic phase

This study provides a comprehensive analysis of the electronic structure, reflectivity, and luminescent spectra of the organic-inorganic, metal-halide MAPbCl3 perovskite, which has considerable potential for various optoelectronic applications. Using density functional theory (DFT) calculations, we investigated the electronic structure of MAPbCl3 and interpreted the key features of its reflectivity spectra across a wide energy range from 3 to 10 eV. The reflectivity spectra reveal prominent excitonic features at 3.22 eV near the absorption edge and additional optical transitions at higher energies, highlighting the material’s intricate electronic structure. Furthermore, we examined the temperature dependence of radiative decay dynamics under high-energy radiation through X-ray luminescence spectra and decay time measurements. We observe emission from free and bound excitons with an exceptionally short decay time (≤ 1 ns) and significant thermal quenching at low temperatures (100 K) in the 385–430 nm range. These findings underline the importance of continued exploration of optoelectronic properties of the material to enhance its performance in practical applications

Power, place, and peoplehood in Chikashshiyaakni': the role of “religion” at Federal Indian Boarding Schools in the Chickasaw Homeland (1799-1837)

This dissertation explores the theoretical limitations of contemporary religious studies by tracing the dynamics of power connected to knowledge production at the first Federal Indian Boarding Schools in the Chickasaw Homeland (1799-1837). In critically analyzing the prevailing ‘substantialist’ and ‘situationalist’ paradigms within religious studies, this dissertation reveals their shortcomings in acknowledging the relationships between Indigenous peoples and their homelands as real. The substantialist perspective perceives a universal phenomenon called “religion,” emphasizing common manifestations across societies while positing an innate inclination towards the sacred. Conversely, situationalist approaches emphasize the role of discourse and intentionality in constructing meaning. Both paradigms fail to adequately address the complex ontic and epistemic relations between Indigenous peoples and their ancestral territories, reducing them to symbolic representations. Drawing on insights from critical Indigenous studies, this dissertation proposes a more nuanced understanding of place that centers Indigenous relationships with land as material, embodied, and interconnected beyond essentialized categories. It critiques contemporary scholarly works on the role of “religion” at Federal Indian Boarding Schools among Southeastern Indians for perpetuating panhuman assumptions and dualistic frameworks that separate spiritual beliefs from material practices, echoing the perspectives of the earliest Protestant missionaries to the Chickasaws in the 1700s. By foregrounding the affective, gendered, and land-based tactics employed by Protestant missionaries operating mission schools in the Chickasaw Homeland, this dissertation challenges prevailing assumptions, calling for a more holistic approach to studying the intersections of peoplehood and place within settler-colonial contexts. Through original archival research, this thesis provides a nuanced and comprehensive analysis of the experiences of Chickasaw children enrolled at the first Federal Indian Boarding Schools in their homeland. Highlighting the strategies employed by Chickasaw pupils to maintain their homeland relations and resist assimilation, it offers valuable insights into the broader dynamics of colonialism and Indigenous resistance during the 18th and 19th centuries

Task-sharing and telemedicine delivery of psychotherapy to treat perinatal depression: a pragmatic, noninferiority randomized trial

Task-sharing and telemedicine can increase access to effective psychotherapies. Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) is pragmatic, multisite, noninferiority, four-arm trial that tested the non-inferiority of provider (non-specialist vs. specialist providers) and modality (telemedicine vs. in-person) in delivering psychotherapy for perinatal depressive symptoms. Across three university-affiliated networks in the United States and Canada, pregnant and postpartum adult participants were randomized 1:1:1:1 to each arm (472 nonspecialist telemedicine, 145 nonspecialist in-person, 469 specialist telemedicine and 144 specialist in-person) and offered weekly behavioral activation treatment sessions. The primary outcome was depressive symptoms (Edinburgh Postnatal Depression Scale (EPDS)) and the secondary outcome was anxiety (Generalized Anxiety Disorder (GAD-7)) symptoms at 3 months post-randomization. Between 8 January 2020 and 4 October 2023, 1,230 participants were recruited. Noninferiority was met for the primary outcome comparing provider (EPDS: nonspecialist 9.27 (95% CI 8.85–9.70) versus specialist 8.91 (95% CI 8.49–9.33)) and modality (EPDS: telemedicine 9.15 (95% CI 8.79–9.50) versus in-person 8.92 (95% CI 8.39–9.45)) for both intention-to-treat and per protocol analyses. Noninferiority was also met for anxiety symptoms in both comparisons. There were no serious or adverse events related to the trial. This trial suggests compelling evidence for task-sharing and telemedicine to improve access to psychotherapies for perinatal depressive and anxiety symptoms. ClinicalTrials.gov NCT0415386

Desire and disinterest in Dusklands

Disinterest is one of the most distrusted of all the terms which pass down to us from post-Kantian aesthetic theory, because it is often taken to imply an ideologically suspect transcendence of the desiring embodied subject. Yet the need to which it points persists, as is evident from Coetzee’s discussion of ‘free play’ in his essay ‘Erasmus: Madness and Rivalry’ (1992), where a certain conception of aesthetic disinterest (a sought-for ‘evasive (non)position inside/outside the play’) is seen as being related to, rather than disavowing, the desire of writer and readers alike. This paper traces the prehistory of these important remarks back to the period of Dusklands, and to Herbert Marcuse’s attempt to conjoin Freudian psychoanalysis with post-Kantian aesthetic theory. I will argue that Marcuse was an influence Coetzee needed both to assimilate and to challenge

Socio-medical factors associated with neurodevelopmental disorders on the Kenyan coast

Neurodevelopmental disorders (NDDs) are a group of conditions with their onset during the early developmental period and include conditions such as autism and intellectual disability. Occurrence of NDDs is thought to be determined by both genetic and environmental factors, but data on the role of environmental factors for NDD in Africa is limited. This study investigates environmental influences on NDDs in children from Kenya. This case-control study compared children with NDDs and typically developing children from two studies on the Kenyan coast. We included 172 study participants from the Kilifi Autism study and 151 from the NeuroDev study who had a diagnosis of at least one NDD and 112 and 73 with no NDD diagnosis from each study, respectively. Potential risk factors were identified using unadjusted univariable analysis and adjusted multivariable logistic regression. Univariable analysis in the Kilifi Autism study sample revealed hypoxic-ischaemic encephalopathy conferred the largest odds ratio (OR) 10.52 [95%CI: 4.04, 27.41] for NDDs, followed by medical complications during pregnancy (gestational hypertension & diabetes, eclampsia, maternal bleeding) (OR=3.17 [95%CI: 1.61, 6.23]). In the NeuroDev study sample, labour and birth complications (OR=7.30 [95%CI 2.17, 24.61]), neonatal jaundice (OR=5.49 [95%CI 1.61,18.72]) and infection during pregnancy (OR= 5.31 [95%CI 1.56, 18.11]) conferred the largest risk associated with NDDs. In the adjusted analysis, seizures before age 3 years in the Kilifi Autism study and labour and birth complications in the NeuroDev study conferred the largest increased risk. Higher parity, the child being older and delivery at home were associated with a reduced risk for NDDs. Recognition of important risk factors such as labour and birth complications could guide preventative interventions, developmental screening of at-risk children and monitoring progress of these children. Further studies examining the aetiology of NDDs in population-based samples, including investigating the interaction between genetic and environmental factors, are needed

The role of the synovial microenvironment in Rheumatoid Arthritis

Rheumatoid Arthritis (RA) remains plagued by poor treatment responses and a lack of curative solutions despite a dense armamentarium. A deeper investigation into the tissue biology of the RA synovium, including its cells but also the remodelled extracellular matrix (ECM) that characterises it, represents a promising new approach in the quest for therapeutic tissue repair and inflammation resolution. Publicly available single cell RNA sequencing datasets were analysed to define the matrisomal gene expression landscape in RA. Distinct fibroblast subsets were found to express distinct matrisomal gene profiles, thereby defining the composition of specific subsynovial microarchitectures. Differential expression analysis identified common and unique matrix gene expression cassettes between fibroblast subsets, between osteoarthritis (OA) and RA, and between active RA and RA in remission. IGF signalling and basement membrane compositional dysregulation were identified as key features of RA pathology and investigated further at the protein level. A multiplexed immunofluorescence dataset was generated to look at the spatial distribution of IGFBP5, IGFBP7, COL4A1, and COL6A1 in human OA and RA synovium. COL6A1 was notably found to correlate positively with remission-associated MerTK+ macrophage abundance in tissue. Its deposition pattern was found to highlight specific areas devoid of collagen VI, termed dark zones, where immune cells localised. Despite the correlation with MerTK+ macrophages in tissue, collagen VI was unable to polarise monocyte derived macrophages towards this remission associated phenotype. Looking more closely into the dark zones however, all immune cell subsets apart from monocytes were tightly locally restricted to collagen VI dark zones. Monocyte ingress into collagen VI-rich regions was found to be associated with active collagen degradation, suggesting potential degradation-dependent migration. Preliminary data point to a direct role for collagen VI in preventing immune cell adhesion and thereby their migration through tissue. Fragments resulting from the cleavage of collagen by migrating monocytes were detectable specifically in human RA synovium. These data point to a novel mechanism of immune migration restriction by synovial stromal cells. Further investigation of this process may hold significant promise in the reestablishment of tissue homeostasis and the curtailing of immune cell infiltration in RA

Sex-specific cardiometabolic multimorbidity, metabolic syndrome and left ventricular function in heart failure with preserved ejection fraction in the UK Biobank

Background: Cardiometabolic disturbances play a central role in the pathogenesis of heart failure with preserved ejection fraction (HFpEF). Due to its complexity, HFpEF is a challenging condition to treat, making phenotype-specific disease management a promising approach. However, HFpEF phenotypes are heterogenous and there is a lack of detailed evidence on the different, sex-specific profiles of cardiometabolic multimorbidity and metabolic syndrome present in HFpEF. Methods: We performed a retrospective, modified cross-sectional study examining a subset of participants in the UK Biobank, an ongoing multi-centre prospective cohort study in the United Kingdom. We defined HFpEF as a record of a heart failure diagnosis using ICD-10 code I50, coupled with a left ventricular ejection fraction (LVEF) ≥ 50% derived from cardiac magnetic resonance (CMR) imaging. We examined sex-specific differences in cardiometabolic comorbidity burden and metabolic syndrome, performed latent class analysis (LCA) to identify distinct clusters of patients based on their cardiometabolic profile, and compared CMR imaging-derived parameters of left ventricular function at rest in the different clusters identified to reflect possible differences in adverse cardiac remodelling. Results: We ascertained HFpEF in 445 participants, of which 299 (67%) were men and 146 (33%) women. The median age was 70 years old (interquartile range: [66.0–74.0]). A combination of hypertension and obesity was the most prevalent cardiometabolic pattern both in men and women with HFpEF. Most men had 2–3 clinical cardiometabolic comorbidities while most women had 1–2, despite a similar metabolic syndrome profile (p = 0.05). LCA revealed three distinct, clinically relevant phenogroups, namely (1) a most male and multimorbid group (n = 117); (2) a group with a high prevalence of severe obesity, abnormal waist circumference and with the highest relative proportion of females (n = 116); and finally (3) a group with an apparently lower comorbidity burden aside from hypertension (n = 212). There were significant differences in clinical measurements and medication across the three phenogroups identified. Cardiac output at rest was significantly higher in group 2 vs. group 3 (males: median 5.6 L/min vs. 5.2 L/min, p < 0.05; females: 5.1 L/min vs. 4.4 L/min, p < 0.01). Absolute global longitudinal strain was significantly lower in women in group 1 vs. group 2 (−17.6% vs. −18.5%, p < 0.05). Conclusion: Women with cardiometabolic HFpEF had a lower comorbidity burden compared to men despite a similar metabolic syndrome profile. Based on patients’ cardiometabolic profile, we identified three distinct subgroups which differed in body shape and mass, lipid biomarker and medication profile, as well as in cardiac output at rest both in men and women. These factors may affect disease trajectory, treatment options and outcomes in those subgroups. Subject to further validation, our findings provide a refined characterisation of the cardiometabolic HFpEF phenotype, contributing towards a better understanding of the condition to enable phenotype-specific disease management

Cost-effectiveness of fenofibrate versus standard care for reducing the progression of diabetic retinopathy: an economic evaluation based on data from the LENS trial

Aims: The LENS trial demonstrated that fenofibrate slowed progression of diabetic retinopathy compared to placebo in participants with early diabetic eye disease. We assessed its cost-effectiveness for reducing progression of diabetic retinopathy versus standard care from a UK National Health Service perspective. Methods: Resource use and outcome data were collected over follow-up for participants enrolled in LENS. Mean costs were compared at two years and per 6-months follow-up (median 4.0 years). Within trial cost-effectiveness was assessed in terms of incremental cost per case of referable disease averted. A microsimulation model, with inputs derived primarily from LENS trial data, was used to assess the incremental cost per quality adjusted life year (QALY). Results: Fenofibrate resulted in a mean (95% confidence interval) reduction in health service costs of -£254 (-1,062 to 624) at two years and -£101 (-243 to 42) per 6-months follow-up. This was accompanied by a 4.4% (1.3% to 8.0%) absolute reduction in any referable diabetic retinopathy or treatment thereof at two years, and a 27% (9%-42%) relative reduction over follow-up. Modelled over ten years, fenofibrate use cost an additional £6 per patient for an expected QALY gain of 0.02, costing £406 per QALY versus standard care under base case assumptions. The probability of cost-effectiveness varied from 70%-79% at a threshold of £20,000 per QALY, depending on the price discount applied to anti-VEGF drugs. Conclusions: Fenofibrate is likely to offer a cost-effective treatment for slowing progression of any diabetic retinopathy in people with early to moderate diabetic retinopathy or maculopathy