The Exile’s Epic Path to Healing: Authorial Intrusion in Purgatorio and Omeros

This paper explores why two seemingly dissimilar poets, Dante Alighieri and Derek Walcott, writing from different time periods and places, both utilized authorial intrusion and became secondary characters in their respective epic poems, the Purgatorio and Omeros. I propose that by inserting themselves into their stories as minor characters, they were able to address their keen sense of exile. Exile granted these poets a freedom not only in what they could write, but also in how they could write, by allowing them to merge the personal and the political. As minor characters in the larger dramas they created on the page, Dante and Walcott used their character personae to reclaim both their lost homeland and history; as secondary characters they were better able to challenge the sins and injustices of larger institutions and establishments of the time, namely the crisis of Church and State in Christendom for Dante, and colonialism and its lingering aftereffects for Walcott.

Barriers to Pediatric Blood Lead Screening

Background: The pernicious effects of lead on the health of children are well-documented. The severity of many of these effects directly correlates with increasing blood lead levels (BLLs). The current recommendation from the Centers for Disease Control and Prevention (CDC) and the American Academy of Pediatrics (AAP) is that BLLs 10 g/dL are dangerous. However, new evidence demonstrates that there is no safe BLL and that children with BLLs /dL exhibit neurological and social deficits. The Vermont Department of Health (VDH) currently recommends universal blood lead screening for 12 and 24 month-old children. In 2006, 79% of 12 month-old children and 41% of 24 month-old children were screened in Vermont.https://scholarworks.uvm.edu/comphp_gallery/1003/thumbnail.jp

Molecular correlates of vaccine-induced protection against typhoid fever

BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have been developed based on the surface Vi-capsular polysaccharide of S. Typhi; these include a plain-polysaccharide-based vaccine, ViPS, and a glycoconjugate vaccine, ViTT. To understand immune responses to these vaccines and their vaccine-induced immunological protection, molecular signatures were analyzed using bioinformatic approaches.METHODSBulk RNA-Seq data were generated from blood samples obtained from adult human volunteers enrolled in a vaccine trial, who were then challenged with S. Typhi in a controlled human infection model (CHIM). These data were used to conduct differential gene expression analyses, gene set and modular analyses, B cell repertoire analyses, and time-course analyses at various post-vaccination and post-challenge time points between participants receiving ViTT, ViPS, or a control meningococcal vaccine.RESULTSTranscriptomic responses revealed strong differential molecular signatures between the 2 typhoid vaccines, mostly driven by the upregulation in humoral immune signatures, including selective usage of immunoglobulin heavy chain variable region (IGHV) genes and more polarized clonal expansions. We describe several molecular correlates of protection against S. Typhi infection, including clusters of B cell receptor (BCR) clonotypes associated with protection, with known binders of Vi-polysaccharide among these.CONCLUSIONThe study reports a series of contemporary analyses that reveal the transcriptomic signatures after vaccination and infectious challenge, while identifying molecular correlates of protection that may inform future vaccine design and assessment.TRIAL REGISTRATIONClinicalTrials.gov NCT02324751

Developing clinical skills in paediatric dysphagia management using human patient simulation (HPS)

Purpose: The use of simulated learning environments to develop clinical skills is gaining momentum in speech-language pathology training programs. The aim of the current study was to examine the benefits of adding Human Patient Simulation (HPS) into the university curriculum in the area of paediatric dysphagia. Method: University students enrolled in a mandatory dysphagia course (n = 29) completed two, 2-hour HPS scenarios: (a) performing a clinical feeding assessment with a medically complex infant; and (b) conducting a clinical swallow examination (CSE) with a child with a tracheostomy. Scenarios covered technical and non-technical skills in paediatric dysphagia management. Surveys relating to students' perceived knowledge, skills, confidence and levels of anxiety were conducted: (a) pre-lectures; (b) post-lectures, but pre-HPS; and (c) post-HPS. A fourth survey was completed following clinical placements with real clients. Result: Results demonstrate significant additive value in knowledge, skills and confidence obtained through HPS. Anxiety about working clinically reduced following HPS. Students rated simulation as very useful in preparing for clinical practice. Post-clinic, students indicated that HPS was an important component in their preparation to work as a clinician. Conclusion: This trial supports the benefits of incorporating HPS as part of clinical preparation for paediatric dysphagia management

Mitochondrial calcium exchange links metabolism with the epigenome to control cellular differentiation.

Fibroblast to myofibroblast differentiation is crucial for the initial healing response but excessive myofibroblast activation leads to pathological fibrosis. Therefore, it is imperative to understand the mechanisms underlying myofibroblast formation. Here we report that mitochondrial calcium (mCa2+) signaling is a regulatory mechanism in myofibroblast differentiation and fibrosis. We demonstrate that fibrotic signaling alters gating of the mitochondrial calcium uniporter (mtCU) in a MICU1-dependent fashion to reduce mCa2+ uptake and induce coordinated changes in metabolism, i.e., increased glycolysis feeding anabolic pathways and glutaminolysis yielding increased α-ketoglutarate (αKG) bioavailability. mCa2+-dependent metabolic reprogramming leads to the activation of αKG-dependent histone demethylases, enhancing chromatin accessibility in loci specific to the myofibroblast gene program, resulting in differentiation. Our results uncover an important role for the mtCU beyond metabolic regulation and cell death and demonstrate that mCa2+ signaling regulates the epigenome to influence cellular differentiation

Starting school:A large-scale start of school assessment within the ‘Born in Bradford’ longitudinal cohort

The Born in Bradford (BiB) cohort of 13,776 children born between 2007-2011 and their parents provides a rich data resource for researchers exploring protective and risk factors influencing long-term developmental and health outcomes. Educational attainment is a critical factor related to later health. Literacy and communication, fine motor skills and social and emotional health are key ‘early’ predictors of educational attainment and can be used to identify children in need of additional support. We describe our BiB ‘Starting School’ data collection protocol which assessed literacy and communication, fine motor skills and social and emotional health on 3,444 BiB children aged 4-5 years old. These measures supplement the existing dataset, and complement the routine educational, health and social care data available for the cohor

Immune responses to typhoid conjugate vaccine in a two dose schedule among Nepalese children <2 years of age

Background Previously, the Vi-typhoid conjugate vaccine (Vi-TT) was found to be highly efficacious in Nepalese children under 16 years of age. We assessed the immunogenicity of Vi-TT at 9 and 12 months of age and response to a booster dose at 15 months of age. Methods Infants were recruited at Patan Hospital, Kathmandu and received an initial dose of Vi-TT at 9 or 12 months of age with a booster dose at 15 months of age. Blood was taken at four timepoints, and antibody titres were measured using a commercial ELISA kit. The primary study outcome was seroconversion (4-fold rise in antibody titre) of IgG one month after both the doses. Findings Fifty children were recruited to each study group.Some visits were disrupted by the COVID19 pandemic and occurred out of protocol windows. Both the study groups attained 100 % IgG seroconversion after the initial dose. IgG seroconversion in the 9-month group was significantly higher than in the 12-month group (68.42 % vs 25.8 %, p < 0.001). Among individuals who attended visits per protocol, IgG seroconversion after the first dose occurred in 100 % of individuals (n = 27/27 in 9-month and n = 32/32 in 12-month group). However, seroconversion rates after the second dose were 80 % in the 9-month and 0 % in the shorter dose-interval 12-month group (p < 0.001) (n = 16/20 and n = 0/8, respectively). Interpretation Vi-TT is highly immunogenic at both 9 and 12 months of age. Stronger response to a booster in the 9-month group is likely due to the longer interval between doses

(Re)theorising laddish masculinities in higher education

In the context of renewed debates and interest in this area, this paper reframes the theoretical agenda around laddish masculinities in UK higher education, and similar masculinities overseas. These can be contextualised within consumerist neoliberal rationalities, the neoconservative backlash against feminism and other social justice movements, and the postfeminist belief that women are winning the ‘battle of the sexes’. Contemporary discussions of ‘lad culture’ have rightly centred sexism and men¹s violence against women: however, we need a more intersectional analysis. In the UK a key intersecting category is social class, and there is evidence that while working class articulations of laddism proceed from being dominated within alienating education systems, middle class and elite versions are a reaction to feeling dominated due to a loss of gender, class and race privilege. These are important differences, and we need to know more about the conditions which shape and produce particular performances of laddism, in interaction with masculinities articulated by other social groups. It is perhaps unhelpful, therefore, to collapse these social positions and identities under the banner of ‘lad culture’, as has been done in the past

The Role of Dynamin and Its Binding Partners in Coated Pit Invagination and Scission

Plasma membrane clathrin-coated vesicles form after the directed assembly of clathrin and the adaptor complex, AP2, from the cytosol onto the membrane. In addition to these structural components, several other proteins have been implicated in clathrin-coated vesicle formation. These include the large molecular weight GTPase, dynamin, and several Src homology 3 (SH3) domain–containing proteins which bind to dynamin via interactions with its COOH-terminal proline/arginine-rich domain (PRD). To understand the mechanism of coated vesicle formation, it is essential to determine the hierarchy by which individual components are targeted to and act in coated pit assembly, invagination, and scission

Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines