“I’VE KNOWN RIVERS:” REPRESENTATIONS OF THE MISSISSIPPI RIVER IN AFRICAN AMERICAN LITERATURE AND CULTURE

My dissertation, titled “I’ve Known Rivers”: Representations of the Mississippi River in African American Literature and Culture, uncovers the impact of the Mississippi River as a powerful, recurring geographical feature in twentieth-century African American literature that conveys the consequences of capitalist expansion on the individual and communal lives of Black Americans. Recent scholarship on the Mississippi River theorizes the relationship between capitalism, geography, and slavery. Walter Johnson’s River of Dark Dreams: Slavery and Empire in the Cotton Kingdom, Sven Beckert’s Empire of Cotton: A Global History, and Edward Baptist’s The Half Has Never Been Told: Slavery and the Making of American Capitalism examine how enslaved black labor contributed to the expansion of capitalism in the nineteenth century, but little is known about artistic representations of the Mississippi in the twentieth century. While scholars point primarily to the Mississippi River’s impact on slavery in the nineteenth century, I’ve Known Rivers reveals how black writers and artists capture the relationship between slavery, capitalism, and the Mississippi River. I consider a wide variety of texts in this study, from Richard Wright’s Uncle Tom’s Children and early 20th century Blues music, to late 20th century novels such as Toni Morrison’s Sula. This broad array of interdisciplinary texts illustrates a literary tradition in which the Mississippi’s representation in twentieth-century African American literature serves as both a reflection of the continuously changing economic landscape and a haunting reminder of slavery’s aftermath through the cotton empire. Furthermore, I’ve Known Rivers demonstrates how traumatic sites of slavery along the river are often reclaimed by black artists as source of empowerment, thereby contributing a long overdue analysis of the Mississippi River in African American literature as a potent symbol of racial progress

Novel variants in KAT6B spectrum of disorders expand our knowledge of clinical manifestations and molecular mechanisms

The phenotypic variability associated with pathogenic variants in Lysine Acetyltransferase 6B (KAT6B, a.k.a. MORF, MYST4) results in several interrelated syndromes including Say-Barber-Biesecker-Young-Simpson Syndrome and Genitopatellar Syndrome. Here we present 20 new cases representing 10 novel KAT6B variants. These patients exhibit a range of clinical phenotypes including intellectual disability, mobility and language difficulties, craniofacial dysmorphology, and skeletal anomalies. Given the range of features previously described for KAT6B-related syndromes, we have identified additional phenotypes including concern for keratoconus, sensitivity to light or noise, recurring infections, and fractures in greater numbers than previously reported. We surveyed clinicians to qualitatively assess the ways families engage with genetic counselors upon diagnosis. We found that 56% (10/18) of individuals receive diagnoses before the age of 2 years (median age = 1.96 years), making it challenging to address future complications with limited accessible information and vast phenotypic severity. We used CRISPR to introduce truncating variants into the KAT6B gene in model cell lines and performed chromatin accessibility and transcriptome sequencing to identify key dysregulated pathways. This study expands the clinical spectrum and addresses the challenges to management and genetic counseling for patients with KAT6B-related disorders

Being cut off from social identity resources has shaped loneliness during the coronavirus pandemic: A longitudinal interview study with medically vulnerable older adults from the United Kingdom

Loneliness is a pernicious problem in older adulthood, associated with physical decline and isolation from valued social groups. However, the long‐term evolving experiences of ageing, identity and loneliness have yet to be elucidated. We use a Qualitative Longitudinal Research interview approach with nine vulnerable older adults (Agemean = 79.4 years), in which five participants were interviewed twice between 2019 and 2020, and four participants were interviewed at three‐time points from 2019 to 2021. This study aims to understand the unfolding experiences of ageing, social identity and loneliness during a prolonged period of social isolation during the Coronavirus pandemic. A theoretically guided thematic analysis highlights that participants initially experience ‘Categorisation as Vulnerable and Loss of Agency’ and ‘Shrinking Social Worlds’, leading to ‘Undermining of Reciprocal Support’ and ‘Fears of Persistent Loneliness’. Findings suggest that interventions to ameliorate loneliness among older adults would benefit from addressing age‐based stereotypes and emphasising the value of reciprocal contributions that older adults can make to their networks, as well as scaffolding and enhancing social identification with new groups. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement

Digital Intervention in Loneliness in Older Adults: Qualitative Analysis of User Studies

Background: Loneliness is a significant well-being issue that affects older adults. Existing, commonly used social connection platforms do not contain facilities to break the cognitive cycle of loneliness, and loneliness interventions implemented without due processes could have detrimental effects on well-being. There is also a lack of digital technology designed with older adults.Objective:We aimed to iteratively design a user-centered smartphone app that can address loneliness in older adults. The aim of this study was to investigate the loneliness-related psychological processes that our conceptual smartphone app promotes. We also identified the emergent needs and concerns that older adults raised regarding the potential benefits and detriments of the app.Methods: We used technology probes to elicit older adults' reflections on the concept of using the app in 2 studies as follows: concept focus groups (n=33) and concept interviews (n=10). We then conducted a prototype trial with 1 week of use and follow-up interviews (n=12).Results: Thematic analysis explored the experiences and emergent challenges of our app through the design process. This led to the development of 4 themes as follows occurring in all 3 qualitative data sets: reflection on a digital social map is reassuring; app features encourage socializing; the risk of compounding loneliness; and individuals feel more control with mutual, socially beneficial activities.Conclusions: Smartphone apps have the potential to increase older adults' awareness of the richness of their social connections, which may support loneliness reduction. Our qualitative approach to app design enabled the inclusion of older adults' experiences in technology design. Thus, we conclude that the older adults in our study most desired functionalities that can support mutual activities and maintain or find new connections rather than enable them to share an emotional state. They were wary of the app replacing their preferred in-person social interaction. Participants also raised concerns about making the user aware of the lack of support in their social network and wanted specific means of addressing their needs. Further user-centered design work could identify how the app can support mutual activities and socializing

Influenza A virus challenge models in cynomolgus macaques using the authentic inhaled aerosol and intra-nasal routes of infection

Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis) are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units). This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation) and low to moderate doses (103 to 106 plaque forming units) of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units) did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common) influenza infections

Cause for concern in the use of non-steroidal anti-inflammatory medications in the community -a population-based study

Background: Non-steroidal anti-inflammatory (NSAID) medications are a common cause of reported adverse drug side-effects. This study describes the prevalence of non-steroidal anti-inflammatory (NSAID) use (other than low-dose aspirin) and the presence of co-existing relative contraindications to NSAID use and chronic conditions in a representative population sample. Methods: Data were analysed from 3,206 adults attending first follow-up of the North West Adelaide Health Study (NWAHS) in 2004 - 2006, a longitudinal representative population study. Medications were brought into study clinic visits by participants. Clinical assessment included measured blood pressure, kidney function, serum cholesterol, blood glucose. Questionnaires assessed demographics, lifestyle risk factors, physician-diagnosed chronic conditions. Data were weighted to census measures by region, age group, gender, and probability of selection in the household, to provide population representative estimates. Pearson's Chi-square tests determined significant differences in proportions. Multiple logistic regression was used to examine associations of socio-demographic characteristics with use of NSAIDs. Results: Of 3,175 participants, 357 (11.2%), and 16% of those aged > 55 years, reported using either non-specific NSAIDs or COX-2 inhibitors, other than low-dose aspirin. Among people using NSAIDs, 60.8% had hypertension, 30.8% had Stage 3 or higher chronic kidney disease, 17.2% had a history of cardiovascular disease (CVD) and 20.7% had a > 15% 10-year CVD risk. The prevalence of NSAID use among people with hypertension was 16%, with kidney disease 15.9%, and a history of CVD 20.0%. Among people taking diuretics, 24.1% were also taking NSAIDs, and of those taking medications for gastro-esophageal reflux, 24.7% were on NSAIDs. Prescription-only COX-2 inhibitors, but not other NSAIDs, were used more by people > 75 years than by 35-54 year olds (OR 3.7, 95% CI 2.0, 6.7), and also were more commonly used by people with hypertension, cardiac and kidney disease. Conclusions: There is a high prevalence of current NSAID use among groups at-risk for significant drug-related adverse events or who have major chronic conditions that are relative contraindications to NSAID use. Assessment of absolute risks regarding cardiovascular and kidney disease need to take into account use of medications such as NSAIDs. The potential to make a substantial impact on chronic disease burden via improved use of NSAIDs is considerable.Robert J Adams, Sarah L Appleton, Tiffany K Gill, Anne W Taylor, David H Wilson and Catherine L Hil