Coming dissertations at Uppsala university
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Skein-valued Gromov-Witten theory and Hofer geometry in contact manifolds
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540446
The thesis consists of an introduction and five research articles in the fields of Hofer contact Geometry and skein-valued open Gromov-Witten theory.
In Paper I, we refine Murphy's h-principle for loose Legendrians by obtaining upper bounds on the Shelukhin-Chekanov-Hofer distance of loose Legendrians, generalizing an earlier result of Dimitroglou Rizell and Sullivan. In Paper II, we give first examples of closed Legendrian submanifolds with vanishing Shelukhin-Chekanov-Hofer metric, thereby providing counterexamples to a conjecture of Rosen and Zhang. In Paper III, we introduce a pseudo-metric on the contactomorphism group and on isotopy classes of Legendrian submanifolds whose topology agrees with the interval topology of Chernov and Nemirovski. We prove a dichotomy for its non-degeneracy which resolves a question of Chernov and Nemirovski.
In Paper IV, we introduce a family of partition functions in the skein of a disjoint union of solid tori, one for each compact, oriented surface with boundary, which reduce to the BPS partition functions in the case without boundary. We prove gluing formulas and a version of the unknot skein relation for all partition functions and a crossing formula in case of disks which generalizes the pentagon relation for disk partition functions. In Paper V, we conjecture in joint work with T. Ekholm and P. Longhi the existence of a skein-valued D-module for links in the three-sphere and exemplify this general conjecture in the case of the Hopf link. We use this to obtain quiver-like expressions for different fillings of the Hopf link unit conormal covering the augmentation variety.
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Effects of psychosocial stimulation on children’s development and growth using an unconditional cash transfer programme for lactating mothers of a deprived urban setting in Bangladesh
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540088
An estimated 249 million children under the age of five in low-and-middle-income countries (LMICs) are at risk of not reaching their developmental potential, with the majority of them living in South Asia. Despite this, there is limited evidence of early childhood development (ECD) programs focused on parenting for 0-3 years children in urban areas of LMICs. This study aimed to deliver a parenting programme in combination with a social safety-net (unconditional cash transfer-UCT) initiative to enhance child development and mother’s well-being.
A cluster randomized controlled trial (cRCT) was implemented with 599 mother-child dyads (children aged 6-16 months) in the deprived urban settings of Rangpur City Corporation, Bangladesh, from 2018 to 2020. The parenting intervention was integrated into the Bangladesh Government’s UCT programme for a period of one year. The cRCT consisted of two arms: i) Parenting and nutrition education combined with UCT (n=299, clusters=10) and ii) UCT only (n=300, clusters=10). Intention-to-treat analysis was performed to assess the effects and the cost effectiveness of the intervention in the trial.
Baseline information from the cRCT in children (n=599) indicated that factors such as age, sex, stunting, and quality of home stimulation environment were common determinants of child development. Attrition rate was only 6.2% (n=37) after one year of intervention. Adjusted multiple linear regression analysis (n=562) controlling for clusters showed that the intervention improved children’s cognitive, language and motor development. However, there was no improvement in physical growth. The intervention also improved fathers’ engagement in child development activities and reduced household violence against mothers. Mothers’ knowledge of childcare and home stimulation environment were the positive mediators for child development. The study also found that the intervention reduced maternal depressive symptoms and improved quality of life (n=547). The incremental cost effectiveness analysis within trial arms confirmed that the intervention was cost-effective for children’s development. An additional US$100 expenditure for parenting intervention was estimated to improve 0.42 SD in cognition, 0.38 SD in language and 0.17 SD in motor development.
Parenting intervention using UCT platform can improve child development outcomes for disadvantaged children and enhance mother’s well-being. These interventions have the potential to be scaled up in similar urban settings within LMICs.
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Pharmacometric Modeling to Support Tuberculosis Drug Development and Treatment Optimization
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540295
Tuberculosis (TB) remains a global health challenge and has been around since ancient times. Even though standard treatment for drug-susceptible and drug-resistant TB is available, the development of novel anti-TB drugs and regimens is still needed as resistance to the currently available drugs is rising. However, development of a new drug is often costly and lengthy. Pharmacometric modeling has been shown to aid different stages of TB drug development, making it more efficient. Furthermore, optimizing the usage of drugs in the current standard treatment is also essential to improve the treatment outcome. The aim of this thesis was to apply pharmacometrics modeling to support different phases of TB drug development and optimize the current treatment.
The pharmacometric modeling applied in this thesis to aid drug development focused on translating preclinical to clinical studies of drug combinations as well as evaluating the impact of different formulations on the PK of a new anti-TB drug candidate. A translational approach to predict the early bactericidal activity of drug combination in humans based on an in vitro time-kill study was developed using rifampicin and isoniazid as an example. The framework allowed for the evaluation of pharmacodynamic interactions and informed the dosing of drug combinations. A population pharmacokinetics (PK) model describing the PK of macozinone (MCZ) and the active metabolites in healthy volunteers was developed. The impact of the formulation on MCZ PK was investigated.
In this thesis, the application of pharmacometric modeling to optimize the current treatment is focused on rifampicin. A comparison of PK exposure between flat dosing and weight-band dosing was performed for rifampicin to evaluate the utility of dosing based on the patient’s body weight. Furthermore, a novel dosing strategy for the high dose of rifampicin was investigated using staggered dosing to maximize the efficacy and reduce the tolerability problem.
In conclusion, pharmacometrics modeling was applied to support TB drug development and to optimize the current standard treatment.