Coming theses from other universities
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Climate services for malaria and cholera control in Mozambique : developing climate-dependent models for early warning systems and projections of climate change impacts on disease burden
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-231754
Background: The transmission of malaria and cholera depends on a great deal on climatic and environmental conditions, which are modulated by socioeconomic conditions, so understanding the influence of lagged climatic factors while adjusting for socioeconomic factors affecting malaria and cholera risk can aid in the timely implementation of interventions to reduce disease burden and adapt to changing climate. The aim of this thesis was to identify climatic and socio–demographic factors that influence malaria and cholera incidence in Mozambique, to develop and evaluate a climate-driven spatio–temporal malaria prediction model that could potentially be used in an early warning system, and to project future malaria incidence in Mozambique based on climate and socioeconomic projection scenarios.
Methods: Bayesian spatio–temporal models with integrated nested Laplace approximation (INLA) in combination with distributed lag nonlinear models (DLNMs) were used to assess the delayed and non-linear relationship between climatic and land use factors, on one hand, and malaria and cholera risk, on the other, while adjusting for socioeconomic conditions, spatio–temporal covariance, and seasonality. In addition, a spatio–temporal malaria prediction model was developed using lagged climatic covariates. The model’s ability to distinguish between high and low malaria seasons was evaluated using receiver operating characteristic (ROC) analysis. Future projection of malaria incidence to the end of twenty-first century in Mozambique was conducted based on a spatio–temporal Bayesian model, considering an ensemble of climate models in a multi-scenario approach.
Results: In papers I and IV, we identified the delayed and non-linear influence of climatic and land use factors on malaria and cholera risk. We found that malaria risk significantly increased at temperatures between 20 and 26°C and then dropped afterwards with a delay of more than four months. However, we found no significant influence of temperature on cholera risk. We observed that precipitation below 100 mm elevated malaria risk with a longer delay of up to five months, while malaria risk decreased with higher precipitation above 400 mm with a delay of just one month. For cholera, risk increased with precipitation above 200 mm with a delay of zero to two months. We found the highest malaria risk was associated with relative humidity (RH) of 55%, while RH above 70% decreased the risk. At RH values of 50–60%, malaria risk was elevated for shorter lags below two months. Similarly, RH of 54–67% increased cholera risk with a lag of three to five months. We found diverging influences of the Normalized Difference Vegetation Index (NDVI) on malaria and cholera risk. NDVI values above 0.2 were associated with high malaria risk with a delay of three months, while NDVI values below 0.2 were associated with elevated cholera risk with a delay of two to four months. We show that a high proportion of asset ownership (e.g., radios and mobile phones), a proxy for high social economic status, was associated with low malaria and cholera risk. We also show that toilet sharing increases cholera risk.
In Paper II, the selected spatio–temporal malaria prediction model included the non-linear functions of climate and NDVI variables with different lag combinations after adjusting for space and season, providing a lead time of up to four months. The model displayed high predictive accuracy with an R2 of 0.8 between observed and predicted cases. The model’s ability to classify high and low malaria months was also high with an overall area under the curve (AUC) of 0.83.
In the third paper, we projected 21 million malaria cases, about a threefold (over 170%) increase by 2080, based on the SSP370 economic and emission scenario, relative to the baseline of 2018, when 7.7 million malaria cases were recorded. In the same period, mean temperatures in Mozambique are projected to increase by 3.6°C according to the SSP370 scenario.
Conclusion: In this thesis we employed advanced spatio–temporal Bayesian models to show that, when controlling for socioeconomic conditions, the lagged climate and land use factors impact malaria and cholera risk, following the biological mechanism of exposure before risk with some delay. We used the derived lag patterns to develop a spatio-temporal malaria prediction model with high skill, providing sufficient lead times up to four months, which could potentially be integrated into a malaria early warning system in Mozambique. Additionally, based on the developed prediction model, we show that climate change will triple the malaria burden in Mozambique in the future, so adequate actions to limit emissions should be taken. We show that combining climate services, disease surveillance, and advanced modelling can aid in adaptation to climate change.
The thesis contributes to key components of an early warning system, specifically on risk assessment and the use of surveillance data for predictive modeling, offering valuable guidance for malaria control initiatives in Mozambique and serving as a reference for low-resource settings.
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Promoting epistemic justice through kindness and reflective practice : towards recovery-oriented practice in general emergency care for people with mental ill-health
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-231976
Background: Negative experiences and inadequate treatment can impact the well-being and mental health recovery of people with mental ill-health seeking general emergency care. In addition to people with mental ill-health reporting that their physical and mental health needs are not being met in this context, nursing staff in general emergency departments (EDs) describe a lack of knowledge and training regarding mental ill-health. While person-centred, recovery-oriented practices are advocated for in mental health care, their practical application in general emergency care remains unexplored, highlighting the need for research in this area.
Aim: The overarching aim of this thesis is to generate knowledge on how nursing staff in general emergency care can support mental health recovery, with a focus on recovery-oriented practices.
Methods: Studies I and II employed a qualitative design aimed at describing the experiences of people with mental ill-health in general emergency care (I) and the nursing staff caring for them in general EDs (II). In both studies, individual semi-structured interviews were conducted and analysed using qualitative content analysis. The participants included 11 people with experiences of mental ill-health (I) and 14 nursing staff working in general EDs (II). Study III employed a modified Delphi technique to systematically gather explicit and implicit knowledge from a 24-member expert panel, with the goal of reaching group consensus on key aspects of recovery-oriented practices in general ED care. The expert panel included people with lived experience of mental ill-health, registered nurses (RNs) working in emergency care, RNs specialized in psychiatric and mental health nursing and mental health recovery researchers.
Findings: The findings from these studies (I, II, III) suggest three values as central to guiding nursing staff in supporting mental health recovery through recovery-oriented practices in general emergency care. First, the recognition of patients’ experiences and self-knowledge is vital. For ED nursing staff, this recognition involves actively listening to and acknowledging patients with mental ill-health as capable persons with valuable insights and perspectives regarding their own health issues and situations. It also requires ED nursing staff to reflect on their own biases, knowledge gaps, and attitudes towards mental ill-health, as these factors may affect their engagement with patients. Second, kindness, manifested through small caring actions, can influence the interactions between ED nursing staff and patients with mental ill-health, making a difference in both the short and long term. For ED nursing staff, such kindness involves recognising and reflecting on the importance of seemingly ‘simple’ personal interactions alongside technical care, where these interactions can often be perceived as challenging and are underestimated. Third, knowledge-sharing which emphasises the recognition and integration of the ED nursing staff’s experience-based and practical knowledge, alongside the opportunities to learn from patient encounters. Such knowledge-sharing requires a culture of collaboration and support within the ED, with dedicated time and resources for sharing experiences and insights through reflection.
Conclusion: By prioritizing recognition, kindness, and knowledge-sharing, ED nursing staff can support the mental health recovery of people with mental ill-health through recovery-oriented practices. Such practices can not only promote epistemic justice but also highlight the importance of a deeper understanding of kindness, manifested through small caring actions, and underscore the need for reflective practice. In conclusion, this thesis demonstrates that discussing mental health recovery is meaningful within the context of general emergency care.
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Translational Aspects of Brain-Specific Drug Delivery by Targeting Active Uptake at Brain Barriers
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-540918
Challenges in central nervous system (CNS) drug development often arise from difficulties in achieving safe and effective brain drug delivery. Key to addressing this issue is ensuring sufficient drug concentrations at the CNS target site. This requires efficient drug transport across brain barriers and reliable translation of preclinical findings to clinical settings. The proton-coupled organic cation (H+/OC) antiporter, associated with blood-brain barrier (BBB) uptake of several marketed CNS drugs, has emerged as a promising target in this regard. However, several critical questions are unresolved for fully leveraging this system in drug development. The studies in this thesis investigated key translational pharmacokinetic questions of the CNS delivery of antiporter substrates. This included characterization of the uptake across several CNS barriers, potential sex and species differences, the impact of inflammation, in vitro-in vivo correlations, and regional CNS distribution. Oxycodone served as the primary model substrate across in vitro and in vivo studies, including microdialysis, the Combinatory Mapping Approach for Regions of Interest, and in vitro BBB cell models. Active uptake was confirmed at the BBB and revealed at the blood-cerebrospinal fluid barrier (BCSFB) and blood-spinal cord barrier in rats. Novel evidence of active uptake at the pig BBB and BCSFB was presented, suggesting potential translatability to humans. Cerebrospinal fluid, often used as a proxy for brain concentrations in the clinic, underestimated antiporter substrate exposure, necessitating caution in its use as a surrogate for brain interstitial fluid. Importantly, no sex-related differences were observed in BBB uptake, supporting the antiporter as a viable target in CNS drug development. Lipopolysaccharide-induced inflammation significantly reduced the uptake. Although the active uptake was reduced, net uptake was still present during inflammation. In vitro BBB models of various origins (mouse, rat, pig, human) reflected in vivo findings, supporting the utility of these models for verification of active uptake. A consistent net uptake, with minor regional differences, was observed in the CNS delivery of antiporter substrates. These findings contribute to advancing CNS drug development by highlighting the significance of active uptake transporters and the necessity for comprehensive neuropharmacokinetic evaluations both in vitro and in vivo.