RATIONAL SOLUTIONS OF NONLINEAR PARTIAL DIFFERENTIAL EQUATIONS

The work in this thesis considers rational solutions of nonlinear partial differential equations formed from polynomials. The main work will be on the Boussinesq equation and the Kadomtsev-Petviashvili-I (KP-I) equation, the nonlinear Schroedinger equation will also be included for completeness. Rational solutions of the Boussinesq equation model rogue wave behaviour. These solutions are shown to be highly structured which, it is hypothesised, is due to the inherent structure and form of integrable differential equations. Rogue wave solutions have been observed in equations such as the nonlinear Schr\"odinger equation, KP equation and the Boussinesq equation, to name but a few. By examining the form of these solutions and considering the behaviour of the roots, the aim is to establish the behaviour of this family of solutions. All solutions are bounded and real. Additionally, since a generating function for the KP equation solutions already exists, a characterisation of the solutions will be made along with an attempt at understanding the current generating function in order to improve its adaptability. Links between solutions of the three equations will be shown as well as a function that can solve all three equations subject to certain criteria on the parameters

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Student Success Evaluation Framework: Determining causality in activities to improve attendance and attainment

This paper provides an overview of the Student Success Evaluation Framework as a mechanism to assess and identify the outcomes and areas of impact of Student Success interventions on students’ attainment and engagement. Delivered across academic schools, these interventions are examined in the context of the Student Success Programme, an institutional research and practice initiative to address attainment and continuation differentials at the University of Kent. The paper provides insights into the rationale behind the Student Success Programme, the institutional factors that have influenced the requirement for an evaluation framework of its implementation and delivery, the challenges faced, and journey undertaken so far to develop, pilot and embed this evaluation framework in the mainstreaming of Student Success across the University of Kent academic divisions. To this end, this paper contributes to the higher education endeavours to assess outcomes and impact of initiatives to reduce and address awarding and continuation gaps, by providing a case study and a model of evaluation that combines process and impact evaluation through the application of Theory of Change, mathematical testing and Contribution Analysis as the main pillars of an innovative evaluation model

Approaches to addressing continuation and attainment gaps for Black Asian and Minority Ethnic (BAME) students at the University of Kent

We evaluated the pilot of the University of Kent’s “Diversity Mark” initiative, a collaboration between the Student Success Team, students, and library services designed to include more BAME perspectives in the formal curriculum, making it more culturally sensitive. The Diversity Mark initiative involves a student-led reading list audit, student focus groups, and debriefs with module convenors. The intervention lead interviewed module convenors following an initial audit and student debrief. If module convenors discussed detailed plans for diversifying reading lists, those modules were deemed reformed. If module convenors did not express commitment to substantial further diversification, those modules were deemed comparators. Core, first year (level 4) modules in the School of Social Policy, Sociology and Social Research (SSPSSR) were studied. For the implementation and process evaluation (IPE), we compared two reformed modules with two comparison modules. In 2020-21, we also re-audited the reading lists of all 21 of the originally audited modules. The IPE focal modules and the impact evaluation (IE) modules were drawn from this larger pool. We researched one iteration of each focal module, taught in the same term in 2020-21. Each module was a core (required) module in its degree programme at level 4 worth 15 credits, running over 12 weeks. All had a typical teaching pattern combining lectures and small group seminars, longer reading lists with a variety of sources, and a typical assessment pattern of two to three short, take home written assignments (1000-2500 words) that students completed individually. We also analysed the core reading lists in Moodle of all 21 modules in 2020-21. We used a mixed-methods, quasi-experimental design to compare the reformed modules with the comparator modules, with a particular focus on BAME students’ experiences. To understand whether the intervention was implemented as planned, we undertook content analyses of curricular materials for the four focal modules. We analysed the authorship of core readings as well as representation of racially minoritised individuals in lecture images, and the cultural sensitivity of assessments. To understand implementation from the students’ perspectives, we conducted focus groups with a subset of BAME students enrolled on the four modules. We surveyed focal module students on their perceptions of the cultural sensitivity of the curriculum. To test the theory of change, we also surveyed students about their interest in the subject, interactions with teachers, and perceptions of their teachers, which we theorised would mediate between perceptions of cultural sensitivity of the curriculum and attainment. We report on key findings and conclusions and contextualise the findings from the external evaluators' impact evaluation that analysed the impact of diversification of curricula on racial attainment gaps