Isles of Boshen : Edward Lear's literary nonsense in context

This thesis investigates three major areas in the background of Edward Lear's literary nonsense: the parodic relationship with text and genre of early children's literature, the trends behind Lear's innovative illustration style, and the "nonsense" child construct manifest within the genre, which I claim is, in many ways, an expression of the Romantic conception of the child. The first chapter explores the parodic basis of nonsense. Most literary nonsense is referential; it often begins by inhabiting a genre or individual work, but what it does to the original is debatable. Some critics see nonsense as parody, while others claim that nonsense precludes parody in its intentional purposelessness. In this chapter I explore the critical debate surrounding parody in nonsense, and parody in general. I then examine the works of Lear, and some Carroll, looking first at their genuine, clear parodies. Next, I look at the many borderline cases of parody which use nonsense as a device but are not overshadowed by it. Finally, I discuss the more "pure" literary nonsense which, I argue, goes beyond parody to establish a new genre. The next chapter looks at the background of Lear's nonsense illustration. His style of illustration was a widely original combination of devices which are best seen in the context of the children's book illustrations of his day. With Bewick's innovations in woodcuts, the quality of children's illustrations had drastically improved. Diverging from this trend, Lear's illustrations hearken back to the rough chapbooks which he probably read as a child. His child-like style, coupled with an expert draughtsman's eye, began a rival tradition of children's book illustration. His illustrations are in way caricatures of chapbooks. His text and illustrations, like those of Blake and Hood, are integral, and their self-reflexiveness with the verses places them in an altogether different class of illustration

Pathways into STEM Among Low-Income, Urban Immigrant Emergent Bilingual/Multilingual Young Adults: Opportunity, Access, and Persistence

This project builds upon the author's multi-year critical ethnographic study of urban immigrant students and their trajectories into STEM (science, technology, engineering, or mathematics) from high school through their transition to college. At its core, this study investigates the paths of over three dozen newcomer immigrant English language learner students in high-poverty urban neighborhoods who are not generally considered “legitimate contenders” for Bachelor’s degrees in STEM fields on the basis of such characteristics as test scores, high school and prior preparation, and age. The students are followed through their high school experiences, their transition to college, and through their current progress in college, with explicit attention paid to key mediating experiences and relationships in and especially outside of the classroom that were associated with their toward persistence and success. Thick description and analysis of the students and their experiences, among those who persisted as well as the minority who switched out of STEM majors, helps to demonstrate a proof-of-concept of these students’ ability to succeed while painting a comprehensive picture of their march forward to degrees in STEM fields against a backdrop of economic, linguistic, and other barriers to entry and success. Using a framework of social and capital and resilience theories, this work has uncovered a number of themes and factors that will help educators to better understand the evolution of these traditionally marginalized students' STEM-related interests, skills, and career plans. The findings center around students’ exposure to research internships and other STEM enrichment and outreach experiences, long-term mentoring and other key relationships, and integration of STEM and college access efforts in setting them up for a successful transition to college, as well as an emphasis on the importance of students’ calling upon their own resilience and other strengths and prior experiences. The results provide novel insights and recommendations for improving access and persistence in STEM among students in areas of concentrated poverty who are also struggling with mastering a new language and a host of other challenges

Long COVID (post-COVID-19 condition) in children: a modified Delphi process

OBJECTIVE: The aim of this study was to derive a research definition for 'Long COVID (post-COVID-19 condition)' in children and young people (CYP) to allow comparisons between research studies. DESIGN: A three-phase online Delphi process was used, followed by a consensus meeting. Participants were presented with 49 statements in each phase and scored them from 1 to 9 based on how important they were for inclusion in the research definition of Long COVID in CYP. The consensus meeting was held to achieve representation across the stakeholder groups. Statements agreed at the consensus meeting were reviewed by participants in the Patient and Public Involvement (PPI) Research Advisory Group. SETTING: The study was conducted remotely using online surveys and a virtual consensus meeting. PARTICIPANTS: 120 people with relevant expertise were divided into three panels according to their area of expertise: Service Delivery, Research (or combination of research and service delivery) and Lived Experience. The PPI Research Advisory group consisted of CYP aged 11-17 years. MAIN OUTCOME MEASURES: Consensus was defined using existing guidelines. If consensus was achieved in two or more panels or was on the border between one and two panels, those statements were discussed and voted on at the consensus meeting. RESULTS: Ten statements were taken forward for discussion in the consensus meeting and five statements met threshold to be included in the research definition of Long COVID among CYP. The research definition, aligned to the clinical case definition of the WHO, is proposed as follows: Post-COVID-19 condition occurs in young people with a history of confirmed SARS-CoV-2 infection, with at least one persisting physical symptom for a minimum duration of 12 weeks after initial testing that cannot be explained by an alternative diagnosis. The symptoms have an impact on everyday functioning, may continue or develop after COVID infection, and may fluctuate or relapse over time. The positive COVID-19 test referred to in this definition can be a lateral flow antigen test, a PCR test or an antibody test. CONCLUSIONS: This is the first research definition of Long COVID (post-COVID-19 condition) in CYP and complements the clinical case definition in adults proposed by the WHO

Balanced forced‐diuresis as a renal protective approach in cardiac surgery: Secondary outcomes of electrolyte changes

© 2021 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1111/jocs.15925Objectives Forced-diuresis during cardiopulmonary bypass (CPB) can be associated with significant electrolyte shifts. This study reports on the serum electrolyte changes during balanced forced-diuresis with the RenalGuard® system (RG) during CPB. Methods Patients at risk of acute kidney injury (AKI)—(history of diabetes &/or anaemia, e-GFR 20–60 ml/min/1.73 m2, anticipated CPB time >120 min, Log EuroScore >5)—were randomized to either RG (study group) or managed as per current practice (control group). Results The use of RG reduced AKI rate (10% for RG and 20.9% in control, p = .03). Mean urine output was significantly higher in the RG group during surgery (2366 ± 877 ml vs. 765 ± 549 ml, p < .001). The serum potassium levels were maintained between 3.96 and 4.97 mmol/L for the RG group and 4.02 and 5.23 mmol/L for the controls. Median potassium supplemental dose was 60 (0–220) mmol (RG group) as compared to 30 (0–190) mmol for control group over first 24 h (p < .001). On Day 1 post-op, there were no significant differences in the serum sodium, potassium, calcium, magnesium, phosphate, and chloride levels between the two groups. Otherwise, postoperative clinical recovery was also similar. Conclusions Balanced forced-diuresis with the RG reduced AKI rates after on-pump cardiac surgery compared to controls. Although the RG group required higher doses of IV potassium replacement in the postoperative period, normal serum levels of potassium were maintained by appropriate intravenous potassium supplementation and the clinical outcomes between groups were similar.This work was supported by a research grant from RenalGuard Solutions and by the National Institute of Healthcare Research (NIHR), Clinical Research Network, UK (Ref: NIHR CRN No 32769)Published onlin

Balanced forced-diuresis compared to control as a reno-protective approach in cardiac surgery: secondary outcome of a randomized controlled trial, assessment of neutrophil gelatinase-associated lipocalin levels

© 2021 The Authors. Published by Springer Nature. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1186/s13019-021-01620-wBackground: Neutrophil gelatinase-associated lipocalin (NGAL) is a recognised biomarker for acute kidney injury (AKI).This study investigated the impact of balanced forced-diuresis using RenalGuard® system (RG), in reducing acute kidney injury (AKI) rates and the associated NGAL levels (6-h post-CPB plasma level) post adult cardiac surgery with cardiopulmonary bypass (CPB). Methods: Patients included in the study were at high-risk for AKI post cardiac surgery, namely history of diabetes and/or anaemia, e-GFR 20–60 ml/min/1.73 m2, Logistic EuroScore > 5, anticipated CPB time > 120 min. Patients were randomized to either RG (n = 110) or managed as per current practice (control = 110). RIFLE-defined AKI rate (based on serum creatinine level increase) within first 3 days of surgery and 6-h post CPB NGAL levels were the primary and secondary end-points. Results: Pre and intra-operative characteristics between the two groups were similar (p > 0.05) including the pre-op NGAL levels, the oxygen delivery (ecDO2i) and the carbon dioxide production (ecVCO2i) during CPB. Patients in the RG group had a significantly lower post-operative RIFLE-defined AKI rate compared to control (10% (11/110) v/s 20.9% (23/110), p = 0.03). Overall, median 6-h post CPB NGAL levels in patients with AKI were significantly higher than those who did not develop AKI (211 vs 150 ng/ml, p < 0.001). Patients managed by balanced forced-diuresis had lower post-operative NGAL levels (146 vs 178 ng/ml, p = 0.09). Using previously reported NGAL cut-off level for AKI (142 ng/ml), binary logistic regression analysis confirmed a beneficial effect of the RG system, with an increased risk of AKI of 2.2 times in the control group (OR 2.2, 95% CI 1.14–4.27, p = 0.02). Conclusions: Overall, the 6-h post-CPB plasma NGAL levels were significantly higher in patients who developed AKI. Patients managed with the novel approach of balanced forced-diuresis, provided by the RenalGuard® system, had a lower AKI rate and lower NGAL levels indicating a lesser degree of renal tissue injury. Trial registration ClinicalTrials.gov website, NCT02974946, https://clinicaltrials.gov/ct2/show/NCT02974946.This work was supported by a research grant from RenalGuard Solutions and by the National Institute of Healthcare Research (NIHR), Clinical Research Network, UK [Ref: NIHR CRN No. 32769].Accepted versio

Reduction in acute kidney injury post cardiac surgery using balanced forced diuresis: a randomized, controlled trial

© 2020 The Authors. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/ejcts/ezaa395OBJECTIVES Our goal was to investigate the efficacy of balanced forced diuresis in reducing the rate of acute kidney injury (AKI) in cardiac surgical patients requiring cardiopulmonary bypass (CPB), using the RenalGuard® (RG) system. METHODS Patients at risk of developing AKI (history of diabetes and/or anaemia; estimated glomerular filtration rate 20–60 ml/min/1.73 m2; anticipated CPB time >120 min; log EuroSCORE > 5) were randomized to the RG system group (n = 110) or managed according to current practice (control = 110). The primary end point was the development of AKI within the first 3 postoperative days as defined by the RIFLE (Risk, Injury, Failure, Loss of kidney function, End-stage renal disease) criteria. RESULTS There were no significant differences in preoperative and intraoperative characteristics between the 2 groups. Postoperative AKI rates were significantly lower in the RG system group compared to the control group [10% (11/110) vs 20.9% (23/110); P = 0.025]. This effect persisted even after controlling for a number of potential confounders (odds ratio 2.82, 95% confidence interval 1.20–6.60; P = 0.017) when assessed by binary logistic regression analysis. The mean volumes of urine produced during surgery and within the first 24 h postoperatively were significantly higher in the RG system group (P < 0.001). There were no significant differences in the incidence of blood transfusions, atrial fibrillation and infections and in the median duration of intensive care unit stays between the groups. The number needed to treat with the RG system to prevent AKI was 9 patients (95% confidence interval 6.0–19.2). CONCLUSIONS In patients at risk for AKI who had cardiac surgery with CPB, the RS RG system significantly reduced the incidence of AKI and can be used safely and reproducibly. Larger studies are required to confirm cost benefits.This work was supported by RenalGuard Solutions; and National Institute of Healthcare Research (NIHR), Clinical Research Network, UK [Ref: NIHR CRN No 32769].Published onlin

Imported Melioidosis, Israel, 2008

In 2008, melioidosis was diagnosed in an agricultural worker from Thailand in the southern Jordan Valley in Israel. He had newly diagnosed diabetes mellitus, fever, multiple abscesses, and osteomyelitis. Burkholderia pseudomallei was isolated from urine and blood. Four of 10 laboratory staff members exposed to the organism received chemoprophylaxis, 3 of whom had adverse events

Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer

Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells.National Science Foundation (U.S.) (Grant T32GM007287

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes

Publisher Copyright: © 2022 Ferrata Storti Foundation Published under a CC BY-NC license.Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1, 464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1, 166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1, 464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.Peer reviewe

Asparaginase-Associated Pancreatitis in Acute Lymphoblastic Leukemia : Results From the NOPHO ALL2008 Treatment of Patients 1-45 Years of Age

PURPOSE Asparaginase-associated pancreatitis (AAP) is common in patients with acute lymphoblastic leukemia (ALL), but risk differences across age groups both in relation to first-time AAP and after asparaginase re-exposure have not been explored. PATIENTS AND METHODS We prospectively registered AAP (n = 168) during treatment of 2,448 consecutive ALL patients aged 1.0-45.9 years diagnosed from July 2008 to October 2018 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol. RESULTS Compared with patients aged 1.0-9.9 years, adjusted AAP hazard ratios (HRa) were associated with higher age with almost identical HRa (1.6; 95% CI, 1.1 to 2.3; P = .02) for adolescents (10.0-17.9 years) and adults (18.0-45.9 years). The day 280 cumulative incidences of AAP were 7.0% for children (1.0-9.9 years: 95% CI, 5.4 to 8.6), 10.1% for adolescents (10.0 to 17.9 years: 95% CI, 7.0 to 13.3), and 11.0% for adults (18.0-45.9 years: 95% CI, 7.1 to 14.9; P = .03). Adolescents had increased odds of both acute (odds ratio [OR], 5.2; 95% CI, 2.1 to 13.2; P = .0005) and persisting complications (OR, 6.7; 95% CI, 2.4 to 18.4; P = .0002) compared with children (1.0-9.9 years), whereas adults had increased odds of only persisting complications (OR, 4.1; 95% CI, 1.4 to 11.8; P = .01). Fifteen of 34 asparaginase-rechallenged patients developed a second AAP. Asparaginase was truncated in 17/21 patients with AAP who subsequently developed leukemic relapse, but neither AAP nor the asparaginase truncation was associated with increased risk of relapse. CONCLUSION Older children and adults had similar AAP risk, whereas morbidity was most pronounced among adolescents. Asparaginase re-exposure should be considered only for patients with an anticipated high risk of leukemic relapse, because multiple studies strongly indicate that reduction of asparaginase treatment intensity increases the risk of relapse. (C) 2019 by American Society of Clinical OncologyPeer reviewe