<p>Soft tissue sarcomas (STSs) are a heterogeneous group of mesenchymal tumors comprised of >70 subtypes. An important question is how the cell of origin and the pathways to tumor development shape the broad array of STS subtypes. By forcing identical tumor-promoting mutations to different cell types in Genetically Engineered Mouse Models (GEMMs) of STS, I have a unique model system to investigate this question. In the process of performing these experiments I observed that genetic mutations are necessary, but not sufficient for rapid sarcoma formation. However, tissue injury dramatically accelerates sarcoma formation in our GEMM of STS. For my thesis, I have worked to understand how cell of origin affects sarcoma subtype and how the microenvironment in our models promotes transformation. I have observed that cell of origin plays an important, but not the only, role in defining STS subtype. Additionally, I have concluded that the microenvironment, and specifically the HGF/c-MET signaling pathway play a crucial role in promoting sarcoma development after acute tissue injury.</p> / Dissertation

Outdoor workers are often subjected to thermal conditions beyond the comfort zone, but to what degree do such conditions affect the health and safety of those workers is still a matter requiring further investigation. The purpose of this study is to examine the relationship between thermal conditions and (1) heat-related disorders and (2) acute injuries using injury and illness data collected during the BP Deepwater Horizon clean-up operations. Over an eleven month period, 5,485 cases were identified as either heat-related or an acute injury (incident type) and further divided by severity. Daily weather data were used to estimate the wet bulb globe temperature (WBGT) based on the time of day. Heat Stress Levels intervals were defined using the estimated WBGT. Labor-hours by month were estimated by the prevailing shift length in the month and the number of workers. The incidents were assigned a Heat Stress Level and the number of labor-hours by heat stress level were determined. The next step was to calculate the incident rate ratio by Heat Stress Level against the baseline of thermal comfort. The results indicated that the rate ratios for heat-related disorders and acute injury increased for thermal conditions from 24⁰C-WBGT to 30⁰C-WBGT. There was a further significant increase in rate ratio for heat-related injury above 33 °C-WBGT. It was notable that the incident rates for both heat-related disorders and acute injuries increased at thermal conditions generally considered to be below the occupational exposure limit (OEL) at 30 ⁰C-WBGT. The rate of heat-related disorders increased substantially above the occupational exposure limit.

Physical activity is an essential component of a healthy life, e.g. to prevent obesity, cardiovascular disease and premature death, of which sports can be an important part. Unfortunately, sports activities increase the risk of both overuse and acute injuries. Severe acute injuries may also lead to a permanent medical impairment (PMI), which may influence the ability to be physically active throughout life. However, sports injuries may be prevented, but a profound understanding of the injuries and how to prevent them is needed. This doctoral thesis examine acute sports injuries reported by licensed athletes of all ages and level of sports nationwide in Sweden, by using national insurance data. Approximately 80% of all the Sports Federations (SF) had their mandatory accident insurance in the insurance company Folksam, and since there is no national sports injury surveillance system in Sweden, this is a unique database, able to be used in epidemiological studies on acute injuries occurring in organized sports in Sweden. The main aim of this thesis was to identify high-risk sports for acute injuries, the most common and the most severe injuries, especially in large sports with numerous licensed athletes, many injuries and injuries resulting in PMI. Based on the results, there will be recommendations regarding sports and body locations where injury prevention efforts should be focused to gain the greatest prevention effect at a national level in Sweden. Another aim was to evaluate the effectiveness of a neuromuscular knee control training program (KCP) that has been implemented nationwide to reduce knee and cruciate ligament injuries, among football players in Sweden. After evaluating the validity and reliability of the information within the database based on international guidelines, acute injury data were examined and the results presented in four papers. These results showed that there is a need of injury prevention especially in motorcycle sports, team ball sports, and ice hockey. Particularly, knee injuries need to be prevented since they were both the most common injuries and leading to PMI. The severe head- and upper limb injuries also need attention. Sixty-nine percent of the PMI injured athletes, were younger than 25 years. The injury prevention training program, KCP can be considered partially implemented nationwide, since 21 out of 24 district SFs provided KCP educations. The incidence of knee and cruciate ligament injuries has decreased among football players in Sweden. A concerning aspect is that there is no national official policy regarding sports injury and injury prevention in Sweden, nor an official authority that has the explicit responsibility for these issues.