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Coming theses from other universities

  • Quantification of population exposure and health impacts associated with air pollution Author: David Segersson Link: Publication date: 2021-12-21 08:00

    There is substantial evidence that air pollution, in particular particulate matter (PM), affects our health. The overall objective of this thesis is to understand and quantify population exposure to ambient air pollution and related health impacts. In four included papers, atmospheric dispersion modelling is used to estimate source-specific contributions to pollution levels. Results from the dispersion modelling are evaluated by comparison with available concentration measurements and used to estimate the related health impact. New approaches for health impact assessment are proposed and new methods for exposure assessment are developed. Assessment of health impacts related to different sources of air pollution can be used to identify the most cost-effective abatement strategies. The proposed methods for health impact assessment are applied to evaluate three viable abatement strategies for Stockholm and Gothenburg, the two largest cities in Sweden.

    The first two papers in the thesis more specifically investigate the importance of using source-specific associations between exposure and premature mortality. One of the main conclusions is that different health risk functions should be applied for near-source and long-range exposure to fine PM. The praxis of today, to use the same linear risk function regardless of source and composition of the PM, most likely underestimates the importance of local sources and may thereby discourage cities from acting to reduce emissions. It is also concluded that a more specific risk function for exposure to coarse PM from road wear would allow for better prioritizations between different abatement measures, especially for countries where studded winter tires are used.

    Near-source exposure in the urban environment is characterized by strong gradients, requiring a relatively high spatial resolution to capture variations within the population. A new method that allow estimating source-specific exposure with sufficient spatial resolution over large areas and long time periods is presented and applied to create a uniquely detailed NOx exposure assessment for Sweden over three decades.

    Emissions from road traffic and residential wood combustion (RWC) are found to be the most important contributors to near-source exposure to PM. When three abatement strategies for road traffic are evaluated for Stockholm and Gothenburg, it is shown that a strategy resulting in overall traffic reduction, such as introduction of congestion charges, is a good choice. Reduced use of studded tires is also evaluated, but this measure mainly affects the emissions of coarse PM from road wear, for which health impacts are more uncertain. The on-going electrification of light vehicles also has more uncertain health benefits, at least when studded tires are used, given that the heavier electric vehicles lead to increased emissions of coarse PM from road wear.

    Improving the description of exposure to PM from RWC is identified as first priority to increase the accuracy in estimates of near-source exposure in Sweden. A comparative study of how this exposure is estimated in the Nordic countries is presented. It is concluded that a more extensive reference dataset with descriptions of emissions and concentration measurements for RWC would be highly valuable for model evaluation and further improvement of model parametrizations.

  • Mosaic loss of chromosome Y : methods for detection and consequences for affected leukocytes and men Author: Marcus Danielsson Link: Publication date: 2021-12-17 13:34

    It has been known for centuries that men live shorter lives than women, but until recently, the biological mechanisms driving this sex bias has been poorly understood. Mosaic loss of chromosome Y (mLOY) refers to chromosome Y aneuploidy, a male specific and the most common somatic mutation in human blood cells. Known risk factors include age, smoking and genetic predisposition. Men with mLOY carry a fraction of blood cells without the Y chromosome, due to its loss from hematopoietic progenitor cells during life. Hence, in a single cell LOY is a binary event causing the absence of almost 2% of the male haploid nuclear genome. When measured in bulk samples, it is present as a continuous mosaicism affecting a fraction of cells. A paper published in 1963 demonstrated that mLOY is frequent in cells of the hematopoietic system in aging men, but it was long viewed as a neutral event. In contrast, recent discoveries demonstrate that mLOY in blood is associated with various forms of cancer, autoimmune conditions, Alzheimer’s disease, cardiovascular events, diabetes as well as age-related macular degeneration. Studies support the hypothesis that mLOY in leukocytes may exacerbate disease processes in other organs. Thus, given the associations with several common diseases, mLOY in blood cells could help explain reduced male longevity.

    A main aim and a long term goal of the work presented in this thesis is the development of novel methods for improved mLOY detection. Focus here is exploration of analytes such as DNA, RNA and proteins, including studies of bulk samples as well as single cell approaches. Among the evaluated methods are SNP-arrays, ddPCR, WGS, RNA-seq and CITE-seq. Furthermore, a novel method called SPARC was developed for co-detection of the transcriptome and a panel of 92 proteins in single cells. Future methods with clinical utility for mLOY should, in addition to robust detection, be able to simultaneously discriminate mLOY in different types of immune cells. The latter builds on recent results showing cell type specificity with regard to disease associations. To meet these needs, single cell analyses using mLOY associated cell surface proteins have been pursued and proof-of-concept established. Implementation of mLOY screening in general populations has the potential to identify men with increased risk for various disease. It could be envisioned that further medical examination of men affected with mLOY would enable earlier diagnoses of ongoing disease processes as well as serving to guide targeted interventions.

  • Musculoskeletal disorders in Swedish military aircrew : screening and clinical examination of the cervico-thoracic region Author: Matthias Tegern Link: Publication date: 2021-12-17 06:00

    Musculoskeletal disorders (MSD) are a common and growing occupational problem in military aircrew. Intervention studies attempting to reduce such issues have only showed limited preventive effects. Furthermore, in-depth knowledge of the clinical presentation of aircrew members with painful episodes is lacking. This thesis was conducted to add evidence to the ongoing work of the Swedish Armed Forces (SAF) for the prevention of MSD. The overall aim of this thesis was to estimate the occurrence of MSD in general and specifically cervico-thoracic pain and its associated factors among SAF aircrew and to evaluate clinically relevant tests, prior to the adaptation of a musculoskeletal screening protocol (MSP) for use in the SAF medical health care system. 

    All participants included in the four studies of this thesis were employed in the SAF. Two cross-sectional studies (Study I; n=351, Study III; n=73) aimed to establish the occurrence of MSD in aircrew compared with army deployed soldiers (Study I) and between fighter pilots, helicopter pilots and rear crew (Study I), as well as identify associated factors of cervical, thoracic and shoulder region pain (Study I) and cervico-thoracic pain (Study III). Study II had a test-retest design and aimed to examine inter-rater (n=37) and test-retest (n=45) reliability of movement control tests. In study III, test performance was compared between fighter pilots, helicopter pilots and rear crew. Study IV had a cross-sectional (n=18) and a prospective observational cohort (n=47) design and aimed to explore physical symptoms and functional limitations in aircrew with cervico-thoracic pain, establish 12-month cumulative incidence and to identify risk factors for cervico-thoracic pain.

    The main findings of this thesis were that when compared to deployed soldiers, military aircrew reported higher prevalence of MSD in the cervical, thoracic, shoulder, and lumbar regions (80% reported at least one painful area during the previous year). Working as aircrew, and a lower rating of one’s physical health, were significantly associated with pain in the cervical, thoracic and shoulder regions (Study I). Two physical therapists could reliably rate movement patterns for the majority of movement control tests in the affected areas. Lower reliability was however seen for test-retest conditions (Study II). Movement control and measures of cervical range of motion (ROM), but not cervical strength and endurance, were associated with cervico-thoracic pain among military aircrew. Specifically, less control of both neck and lumbar flexion movements, and lesser cervical flexion ROM were associated with cervico-thoracic pain. Differences were found between fighter pilots, helicopter pilots and rear crew for lumbar flexion movement control and cervical lateral flexion ROM (Study III). Physical symptoms and functional impairments of aircrew with high (pain) intensity, flight-elicited and work-affecting cervico-thoracic pain showed an individual presentation. Previous pain episodes, lesser cervical flexion ROM, and lesser cervical flexor muscle endurance were identified as risk factors for future cervico-thoracic pain, which had a 12-month cumulative incidence of 23% (Study IV).

    Findings from this thesis strongly indicate that MSD in SAF aircrew is an occupational problem that need to be solved. The cervico-thoracic region was especially common in SAF aircrew. Movement control can reliably be assessed, but with less stability for repeated measures. While pain history and physical performance can to some degree be used to identify aircrew at risk for further cervico-thoracic pain, the clinical presentation of their physical symptoms showed individual presentation. The effects of implementing the MSP in the SAF as a primary and secondary preventive intervention, as well as rehabilitative strategies, need be systematically evaluated.