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Coming dissertations at MedFak

  • Towards an Earlier Detection of Progressive Multiple Sclerosis using Metabolomics and Machine Learning Author: Stephanie Herman Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-416655 Publication date: 2020-08-26 09:11

    Decision-making guided by advanced analytics is becoming increasingly common in many fields. Implementing computationally driven healthcare solutions does, however, pose ethical dilemmas as it involves human health. Therefore, augmenting clinical expertise with advanced analytical insights to support decision-making in healthcare is probably a more feasible strategy.

    Multiple sclerosis is a debilitating neurological disease with two subtypes; relapsing-remitting multiple sclerosis (RRMS) and the typically late-stage progressive subtype (PMS). Progressive multiple sclerosis is a neurodegenerative phenotype, with a vague functional definition, that currently is diagnosed retrospectively. The challenge of diagnosing PMS earlier is a great example where data-driven insights might prove useful.

    This thesis addresses the need for an earlier detection of patients developing the progressive and neurodegenerative subtype of multiple sclerosis, using primarily metabolomics and machine learning approaches. In Paper I, the biochemical differences in cerebrospinal fluid (CSF) from RRMS and PMS patients were characterised, leading to the conclusion that it is possible to distinguish PMS patients based on biochemical alterations. In addition, pathway analysis revealed several metabolic pathways that were affected in the transition to PMS, including tryptophan metabolism and pyrimidine metabolism. In Paper II and III, the possibility of generating a concise PMS signature based on solely low-molecular measurements (III) or in combination with radiological and protein measures (II) was explored. In both cases, it was concluded that it is plausible to generate a condensed set of highly informative markers that can distinguish PMS patients from RRMS patients. In Paper III, the classifier was complemented with conformal prediction that enabled an estimate of confidence in single patient predictions and a personalised evaluation of current disease state. Finally, in Paper IV, the extracted low-molecular marker candidates were characterised in isolation, revealing that several metabolites were distinctively altered in the CSF of PMS patients, including increased levels of 4-acetamidobutanoate, 4-hydroxybenzoate and thymine.

    Overall, the results from this work indicate that it is possible to detect PMS at an earlier stage and that advanced analytical algorithms can support healthcare.

  • Bariatric surgery as treatment of type 2 diabetes – clinical and mechanistic aspects Author: Petros Katsogiannos Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-416646 Publication date: 2020-08-21 10:16

    Bariatric surgery can rapidly improve glycemic control and cardiovascular risk factors in patients with T2D and obesity. These improvements appear to be partly independent of weight loss, however, the underlying mechanisms remain incompletely understood. A randomized controlled trial was designed where 19 patients with obesity and T2D were either operated with a  Roux-en-Y gastric bypass (RYGB) operation or continued with standard-of-care treatment and followed up for 2 years, providing the data for Paper I-III.

    In paper I, we focused on changes in whole-body glucose metabolism in relation to changes in adipose tissue metabolism and morphology. We observed an early adipose tissue remodeling and a reduction in adipocyte size that however, did not correlate to the early improvements in metabolic control.

    In paper II, we analyzed the neuroendocrine changes after RYGB. We observed changes within 4 weeks with signs of enhanced parasympathetic outlow, reduced morning cortisol, and enhanced incretin and glucagon responses to glucose, suggesting that neurohormonal mechanisms can contribute to the rapid improvement of insulin resistance and glycemia following RYGB in T2D.

    In paper III the patients from the RYGB group were interviewed 2 years after surgery to examine the effects of surgery on health-related quality of life (HRQoL). We found that the improved HRQoL after RYGB was not explained specifically by the magnitude of weight loss, but rather by the participants achieving a state of union between body and consciousness.

    In paper IV, we compared changes in circulating cytokine and adipokine levels in obese patients with- and without T2D. We observed that the cytokine profile of these patients is altered when compared to lean healthy control subjects and persist to a large extent after RYGB despite the weight loss and improved metabolic status.

    In conclusion, we observed that in the early post-operative period, neurohormonal changes appear to be more important than adipose tissue changes in improving insulin sensitivity and leading to diabetes remission.

    In the qualitative part of our study, we observed that the improved HRQoL was not solely explained by weight loss

  • Ergonomists’ risk assessments : From guesstimates to strategic approaches Author: Kristina Eliasson Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-411943 Publication date: 2020-08-20 10:40

    Musculoskeletal disorders are among the most prevalent causes of work-related ill-health, consequently risk assessments of hazardous factors related to these disorders are important for prevention. Occupational Health Services (OHS) providers are independent experts, supporting employers regarding work environment issues and rehabilitation. Ergonomists represents one of the professions within OHS, and risk assessment regarding musculoskeletal disorders is within the scope of their work tasks. 

    The overall objective was to explore Swedish ergonomists’ practices and approaches with risk assessments, in order to contribute new knowledge about how ergonomists’ work methods can be further developed to improve prevention of work-related musculoskeletal disorders. 

    Paper I explored the process of risk assessment assignments and the ergonomists’ use of observation-based risk-assessment tools. The result showed a lack of systematic approaches regarding risk assessment assignments and limited use and knowledge of observation-based risk-assessment tools. In Paper II inter-observer and intra-observer reliability of risk assessments, without the use of an explicit observational method were assessed. The results showed a non-acceptable reliability. Paper III explored ergonomists experiences of an e-learning concept for knowledge translation in the OHS context. The e-learning concept was considered as feasible. The knowledge translation inspired increased use of risk-assessment tools, changes in the risk assessment procedures, e.g. selection of tools, and employing a participatory approach. Paper IV described the development of a process model for occupational health surveillance for workers exposed to hand-intensive work (HIW-model), and the studies that will explore the model. Paper V explored company representatives’ experiences of the HIW-model, and factors which facilitated the execution of the model. The model contributed to increased risk awareness and understanding of how individual workers’ musculoskeletal ill-health relates to exposures in work. Facilitating factors were: a joint start-up meeting in which the process was planned, clear communication, and clarity regarding the ownership of the process. 

    In conclusion, the findings showed that ergonomists’ expertise is needed in the entire risk management process and not only in the risk assessment phase. In this process, the ergonomists need to be active and take the expert role (which includes a stocked toolbox) and support the employer through the whole risk management process from initiation to evaluation of risk controlling measures.

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