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Coming dissertations at MedFak

  • Patient Positioning in Radiotherapy Using Body Surface Scanning Author: Kenneth Wikström Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-427519 Publication date: 2021-01-28 09:26

    External radiotherapy uses ionising radiation to damage the DNA of the tumour cells and thereby inhibit their uncontrolled proliferation. The technical development regarding imaging and visualisation for radiotherapy has increased considerably during the last decades. By a submillimetre accuracy, a body surface laser scanning (BSLS) system maps the patient body contour in the treatment position by scanning a transversal laser line and detecting its reflection. A treatment plan is created for each patient to find a treatment that delivers a high dose to the tumour whilst keeping the dose to the surrounding normal tissue as low as possible. The setup done for treatment planning must be reproduced in the treatment room. Commonly patient skin-marks are aligned to room lasers to setup the patient in the treatment position. The setup is then verified by the BSLS and a cone-beam CT (CBCT) system. For left-sided-breast cancer patients, the dose to radiosensitive parts of the heart can be decreased by letting the patient take a deep breath and hold it in deep inspiration breath-hold (DIBH) position during treatment. The BSLS system can guide the patient to this position via visual and audial instructions to the patient. The breathing trace of a lung cancer patient can be monitored by the BSLS system to estimate the quality of the images used for treatment planning and also to support the treatment target definition process. The number of application of the BSLS system has increased over the years. Together with its increased accuracy and robustness, surface scanning has now reached a level where it can be used as a primary setup system, replacing skin-marks (paper I), guiding left-sided breast cancer patient to a reproducible DIBH position (paper II) and lung tumour motion can be determined more accurately (paper III and IV).

  • The publics’ perspective on cardiovascular risk information : Implications for practice Author: Åsa Grauman Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-427327 Publication date: 2021-01-27 13:26

    Lay people struggle to understand the implications of cardiovascular risk information. With new advanced testing techniques and the digitalization of personal health information, the communication of cardiovascular risk becomes a challenge. 

    The overall aim of the thesis was to investigate the publics’ perspective of cardiovascular risk information through a multi-method approach, including how individuals perceive risk, factors affecting an underestimation of risk, how cardiovascular risk communication affects individuals’ psychosocial health, and their preferences for risk communication. 

    In study I, research participants’ perceptions about risk information were explored in five focus group interviews. The participants’ (n=31) perceptions about cardiovascular risk were complex, where multifactorial aspects were disregarded. The communication of cardiovascular risk information did not meet the participants’ need for understanding, support, and guidance regarding what to do with this information. 

    Study II was a before-after investigation regarding the impact of cardiovascular risk information on research participants’ health-related quality of life and mental distress. Increased worry and anxiety were observed in individuals referred to hospital because of coronary artery stenosis. 

    Study III was a cross-sectional study, which found that individuals with a very good or excellent self-perceived general health and individuals without a family history of CVD were more likely to underestimate their cardiovascular risk compared to participants with poor or fairly good general health and without a family history. 

    Study IV was a cross-sectional study, investigating the preferences of the Swedish population for communication of cardiovascular risk information from a health checkup using a Discrete Choice Experiment. Besides cost, consultation time was the most important aspect when communicating cardiovascular risk. 

    The findings suggest that cardiovascular risk communication does not reach its fullest potential when it comes to recipients’ perspective of the benefits of CV risk communication. Improvements should aim at increasing the recipients’ personal control and health literacy and furthermore, acknowledge the fact that self-perceived risk is influenced by how a person feels in general and experiences of family history. 

  • Multi-omics analysis of relapsed acute myeloid leukemia Author: Svea Stratmann Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-425965 Publication date: 2021-01-22 07:12

    The prognosis for patients suffering from acute myeloid leukemia (AML) remains unsatisfactory and survival is often measured in months. Although the majority of patients achieve complete remission after aggressive treatment, most of them relapse within a few years. Those patients that relapse frequently show accelerated disease progression and therapy resistance and represent the major clinical challenge in AML oncology. The advent of massive parallel sequencing launched the detailed understanding of the molecular basis of AML leukemogenesis, however, studies focused on relapse and primary resistant (R/PR) AML remain sparse.

    This thesis explores the spectrum of molecular alterations present in R/PR AML, using a multi-omics analysis approach on sequential primary patient specimens from 48 adult and 25 pediatric R/PR AML patients. In Paper I we applied genome wide next generation sequencing to investigate genomic alterations in adult and pediatric R/PR AML. We identified recurrent alterations affecting MGA, ARID1A and H3F3A, specific for adult R/PR AML cases. In addition, we reported previously unappreciated internal tandem duplications in UBTF, solely found in pediatric cases. In Paper II we showed an association between a pro-inflammatory signature and AML relapse, utilizing transcriptome wide RNA sequencing. Further, through a novel machine learning based analysis we were able to depict gene interactive networks and predictive features in AML relapse. In Paper III we performed DNA methylation analysis to further understand transcriptional changes during disease progression that could not be explained by genomic alterations. We identified hypermethylation of promoter associated sites of RNF180 and DSC3 at relapse and in treatment resistant AML samples, respectively, as well as concordant downregulated transcription of these genes. In Paper IV we were able to confirm some of the above mentioned alterations at the proteomic level by exploiting high resolution mass spectrometry data. In addition, we showed higher levels of mitochondrial related proteins at AML relapse.

    In summary, molecular associations identified in this thesis, together with AML-specific neoantigens discovered via a proteogenomic approach in Paper IV, predict novel therapeutic targets and/or help to further optimize current treatment schemes. We envision that knowledge gathered through our studies will shed further light on the molecular characteristics underlying disease progression, thus contributing to prolong AML patient survival.

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