| 1. |
- Norlén, Olov
(författare)
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Small Intestinal Neuroendocrine Tumor : A Rare Malignancy with Favorable Outcome
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Small intestinal neuroendocrine tumor (SI-NET) is the most common small bowel tumor in Europe and USA, with an annual incidence of around 0.3-1.3/100000 persons. SI-NETs are the most common type of gastroenteropancreatic NETs (GEP-NETs), and they are known for their ability to produce hormones such as tachykinins and serotonin, as well as for their favorable long-term prognosis in comparison to gastrointestinal adenocarcinoma. The overall aim of the thesis was to investigate unknown or unclear aspects of SI-NET disease, in connection with prognosis, treatment and follow-up. Paper I confirmed several known negative prognostic factors and also showed, for the first time, that para-aortal lymph node metastases and peritoneal carcinomatosis were associated with worse survival by multivariable analyses. Locoregional surgery was associated with a low post-operative mortality, and a prolonged long-term survival by multivariable analysis. In Paper II we continued to investigate peritoneal carcinomatosis and found it be a risk factor not only for death, but also for emergency re-surgery. Furthermore, genetic analyses of samples from primary tumors in patients with and without peritoneal carcinomatosis showed a difference in the DNA between these two groups. In Paper III the outcome after liver surgery and/or radiofrequency ablation of liver metastases was investigated. To summarize, no difference in survival was seen in patients treated with surgery/radiofrequency ablation in comparison with matched controls. However, a superior radiological response of liver metasases and lower U-5-HIAA values were seen in patients subjected to liver surgery and/or radiofrequency ablation compared to matched controls. Paper IV compared ultrasonography, computed tomography and 11C-5HTP-PET in the follow-up after radiofrequency ablation of NET liver metastases. The study concluded that 11C-5HTP-PET depicted all residual tumors after RFA and that it, if used, should be combined with computed tomography for easier interpretation, as RFA areas are not clearly distinguishable with 11C-5HTP-PET alone. Paper V studied gallstone complications after somatostatin analog treatment in SI-NET patients, and concluded that there was a rather high risk to be subjected to a cholecystectomy due to biliary colic, cholecystitis, cholangitis or pancreatitis after primary surgery in somatostatin analog treated patients.
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| 2. |
- Cantillana, Tatiana, 1969-
(författare)
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Toxicologically important DDT metabolites : Synthesis, enantioselective analysis and kinetics
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- DDT was extensively and globally used as a pesticide in agriculture and for malaria vector control from the 1940’s until the 1970’s. Due to its heavy use, DDT became ubiquitously distributed throughout the environment. DDT and several DDT metabolites are persistent organic pollutants. Two DDT metabolites, 3-MeSO2-DDE and o,p’-DDD have been proved to be tissue specific toxicants in the adrenal cortex. They are bioactivated to reactive intermediates which bind covalently to the adrenal cortex causing cell death. Due to its tissue specific toxicity o,p’-DDD has been used as a chemotherapy drug for adrenal cancer in humans. The efficacy and potency is however low and o,p’-DDD treatment is associated with serious side effects. 3-MeSO2-DDE has been suggested as a potential alternative therapeutic agent. A key aim of this thesis has been to improve the understanding of the kinetics of the two adrenocorticolytic compounds o,p’-DDD, its two enantiomers and 3-MeSO2-DDE. To meet this objective chemical synthesis and enantioselective analysis were required. Furthermore, in vitro toxicity of o,p’-DDD enantiomers and diastereomers were performed. An 11 step synthesis of 3-SH-DDE has been developed to promote both labelled and unlabelled synthesis of 3-alkylsulfonyl-DDE. Toxicokinetic studies showed that 3-MeSO2-DDE and o,p’-DDD were accumulated in tissues and retained in adipose tissue in minipigs. 3-MeSO2-DDE however had a twice as long biological t1/2 and a considerably lower Vd compared to o,p’-DDD. Suckling offspring were more exposed to 3-MeSO2-DDE than their mothers who were given 3-MeSO2-DDE orally. Interindividual differences in enantiomer kinetics in minipigs were observed suggesting polymorphism among the minipigs. Preparative isolation of the o,p’-DDD enantiomers is presented allowing determination of the absolute structures of the o,p’-DDD enantiomers by X-ray. The pure enantiomer of o,p’-DDD showed significant differences in toxicity in human adrenocortical cells.
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| 3. |
- Eskilsson, Anna, 1977-
(författare)
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På plats i historien : Studier av hembygsföreningar på 2000-talet
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Local heritage societies were established in Sweden for about a hundred years ago. The societies responded to the large changes of industrialisation, emigration and urbanisation during that time. Today there are about 2 000 societies with almost half a million members altogether. Why do people turn to local heritage societies today? The image of them, associated with folklore costumes and quaint old cottages, is not consistent with the extensive activity in the 21st century. That raises questions that have not been clarified in previous research. The aim of this thesis is to find out what today's local heritage societies do, as well as to investigate what their meanings are for people and the local society. Thereby the intention is to contribute to an understanding of their present extent and endurance over time.The activities of three local heritage societies in and around the city of Linköping are mapped out in this thesis. The survey shows extensive and very broad activities that are well adjusted to present time. The traditional image has become rigid, but in parts it is accurate since the activities are still dominated by local use of history., which also contributes to their extent and continuity. Place and history as common ground is something universal: The need for people to be oriented in time and space contributes to the persistence of the local heritage societies. At the same time there seems to be something strong in society today which contributes to their extent.The thesis shows that the societies can have knowledge-generating, ideological, existential and social meaning. Through the local heritage society people can learn about, evaluate and gain feelings for the place. The society also contributes to strengthening the power of togetherness in the local community as a part of the civilian society. The multifaceted meaning of the activities makes it possible for the societies to keep or even strengthen their attraction, especially among the large group of retired people.
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| 4. |
- Hiswåls, Anne-Sofie
(författare)
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Employment Status and Inequalities in Health Outcomes : Population-based Studies from Gävleborg County
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and objectives: From a public health perspective, it is important not only to improve and maintain health, but also to promote equality in health. Epidemiological research has showed the importance of work and unemployment in the development of socio-economic health inequalities, and peoples life chances are suggested to be conditioned by participation or exclusion from the labour market. The most recent economic recession has brought further changes to the labour market that might have aggravated the already multifaceted image of inequalities in health. Gävleborg County was one of the hardest hit counties in Sweden, which experienced a myriad of changes in the labour market that went beyond those of the Swedish national average, in terms of increase in flexible forms of employment, factory closures, and lay-offs. The overall objective of this thesis was to investigate the relationship between employment status and health-related inequalities in Gävleborg County, Sweden. In addition, the Specific objectives for the thesis were to: assess the relationship between employment status and self-reported health in Gävleborg (Study I); to estimate the relationship between employment status and suicidal ideation during the economic recession in Gävleborg (Study II); to estimate the prevalence of anxiety and depression among economically active people living in the Municipality of Gävle (Study III) and to assess experiences and perceptions of well-being after involuntary job loss in Gävle (Study IV).Methods: Study I and II in this thesis used data from the 2010 Health in Equal Terms survey, a cross-sectional survey carried out in Gävleborg County in Sweden. A total of 4,245 individuals, aged 16–65 years were included in the analyses. Study III was performed in Wave 1 (baseline survey) of the Gävle Household, Labour Market Dynamics and Health Outcomes survey (GHOLDH), a panel survey with household as the follow-up unit. A total of 241 persons completed a self-administered postal questionnaire which collected information on the employment status and psychological health (anxiety and depression) among persons aged 18–65 years. The thesis used descriptive analyses and logistic regression models to describe and explore the relationship between employment status, self-reported health and suicidal ideation in Gävleborg County (Studies I and II). Descriptive analysis of means and a multiple regression analysis for adjusted means of HADS, were used in order to estimate the prevalence of anxiety and depression among economically active persons residing in the Gävle Municipality (Study III). Study IV used a qualitative approach to gain a deeper understanding of how involuntarily unemployed persons in Gävlexperceive their well-being. Sixteen unemployed men and women aged 28–62 were interviewed face-to-face. A purposeful sampling strategy was used in order to suit the research question and to increase the variation among informants. The interview texts in Study IV were analysed using thematic analysis.Results: In Study I, the prevalence of poor self-reported health (SRH) was twice as high in the group of people who were not employed (42%) compared to the employed group (21.6%). Individuals outside the labour market had odds of poor health of 2.64 (Cl 2.28–3.05) compared to their employed counterparts. Controlling for other covariates reduced the risk slightly to 2.10 (1.69–2.60), but remained statistically significant. Moreover, other variables such as long-standing illness, age, income and lack of social support were associated with self-reported poor health. In Study II, among those not employed, 11.2% had been in a situation where they had seriously considered taking their life (at some time during the past 12 months). The corresponding figure for those employed was 2.9%. Unadjusted results of the logistic regression analysis revealed that people who were not employed had about a four times higher risk of suicidal ideation, with an OR of 4.21 (CI: 3.14–5.64) compared to their employed counterparts. Controlling for other covariates, reduced the risk from 4.21(CI 3.14–5.64) in model I, to 1.73 (CI 1.16–2.57) in model IV, but remained statistically significant. In addition, other variables were associated with suicidal ideation. In Study III, the prevalence and risk of anxiety and depression were high among people who were out of work. In the multiple regression analysis, compared to employed people, those who were not employed had a risk of anxiety of 7.76 (5.97–9.75) and 4.67 (3.60–5.74) for depression. Study IV revealed six different themes from the interviews: Work was perceived as the basis for belonging; loss of work affected people’s social life and consumption patterns due to changes in their financial situation. Feelings of isolation, loss of self-esteem, and feelings of hopelessness were reported, affecting the respondents’ physical well-being. Longer duration of unemployment increased the respondents’ negative emotions. Activities, structure, and affiliation in other contexts were reported as part of their strategy for coping with poor mental health.Conclusion: This thesis found a statistically significant relationship between being outside the labour market and poor SRH, a high risk of suicidal ideation, anxiety, and depression during the recent economic recession. The relationship between employment status and SRH was partially explained by socioeconomic, demographic and lifestyle variables. In addition, the relationship between employment status and suicidal ideation was, for the most part, explained by demographic, socio-economic and self-reported psychological variables. Atxithe municipal level, the prevalence of anxiety and depression was higher among those who were out of the labour market as compared to those who were employed and the odds of anxiety and depression were higher among people out of the labour market, but this was less prominent for depression than for anxiety. Job loss created feelings of loss of dignity and belonging as a human being. The participants experienced feelings of worry, insecurity, and stress due to their changed financial situation, which in turn led to isolation and loss of self-esteem. Social support and having activities other than work gave structure and meaning to everyday life. The results of this thesis indicate a need for early detection and potential treatment of people out of the labour force and for being aware of the increased risk of poor health symptoms and disorders among unemployed individuals. The findings also indicate a need for primary prevention strategies, implying that policy-makers must pay attention to the health status of those who are out of work, especially during times of combined economic hardship and labour market fluctuations. However, longitudinal studies are warranted to shed further light on the mechanisms through which employment status and conditions impact physical and psychological health outcomes.
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| 5. |
- Selegård, Peter, 1972-
(författare)
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Tillväxtbilder, regionala intentioner samt entreprenörers orsaksförklaringar av tillväxt : en penroseisk syn på regional tillväxt
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Regional utveckling har fått större betydelse de senaste årtiondena. En mer liberal frihandelsstruktur antas ha bidragit till en ökad globalisering, vilket lett fram till en ökad konkurrensutsatthet. Nationers begränsade förmåga att snabbt fatta beslut har lett fram till att regionerna har fått ökat ansvar avseende sin egen utveckling och tillväxt. I Sverige visades sig ansvaret genom att regionförbund började bildas där ansvaret för regionala näringslivsfrågor hamnade. Under 2003 ombads Sveriges regioner att utveckla regionala tillväxtprogram (RTP) där man inom regionen skulle komma överens om vilka åtgärder och områden som var viktigast för att nå tillväxt i länet. I Södermanlands län ansvarade Länsstyrelsen för att utarbeta ett RTP i ett brett partnerskap med olika aktörer från akademi, politik samt näringsliv. Regionförbundet Sörmland, vilka bildades 2004, blev samordningsanvariga för genomförandet av programmet mellan åren 2004 tom 2007. Hösten 2004 inleddes ett forskningsprojekt vars syfte var att erhålla lärdomar om det regionala tillväxtprogrammet. Interaktiv kunskapsutveckling inom ramen för det regionala tillväxtprogrammen var ett projekt där både Södermanland samt Västmanlands län har varit delaktiga tillsammans med Mälardalens högskola. Två doktorander anställdes vilka skulle följa ett regionalt tillväxtprogram utifrån geografisk utgångspunkt. Föreliggande studie har haft Södermanlands läns RTP i fokus. Avhandlingens syfte erhölls efter intervjuer med tolv praktiker berörda av RTP i sitt eget arbete (här regionala samordningsansvariga, offentliga samt privata regionala näringslivsorganisationer, kommunalråd, kommunala näringslivstjänstemän). Samtidigt närvarade författaren på ett otal möten årligen vilka var knutna till RTP:s genomförandeprocess. I intervjumaterialet söktes kärnkategorier, vilka indikerade uppkomsten av liknande svarsbilder. Ett svar som bidrog till studiens intresse var svaret om hur olika aktörer såg på näringslivsmedverkan inom ramen för RTP:s genomförandeprocess. Generellt svarade de regionala offentliga näringslivsorganisationerna att det inte var självklart med en näringslivsmedverkan inom ramen för det partnerskap som skulle arbeta med regional tillväxt, medan kommunalråd samt kommunala näringslivtjänstemän tenderade att svara att det var en svaghet att inte låta näringslivet vara mer involverat i RTP. Svaren bidrog till att det fanns ett intresse att undersöka vilken typ av näringslivsmedverkan som fanns inom ramen för RTP. En genomgång av olika arenor med anknytning till RTP studerades och resultatet indikerade att det saknades praktiska näringslivkopplingar i RTP:s genomförandeprocess, i vart fall på partnerskapsnivå. Ett antagande växte sig starkare om det var möjligt att en inkongruens mellan ett regionalt tillväxtprograms innehåll samt ett lokalt näringslivs (entreprenörer från en solo-, mikro- samt småföretagskontext i Södermanlands län) upplevda tillväxtbilder samt orsaksförklaringar av tillväxt uppstått till följd av bristen av näringslivsmedverkan. En frågeställning formulerades. Hur en regional offentlig bild av tillväxt via ett RTP skiljer sig mot den bild av tillväxt som förmedlas av entreprenörer från en solo-, mikro- samt småföretagarkontext? Tillväxtbilder undersöktes, men även regionala intentioner ställt i relation till entreprenörernas orsaksförklaringar. Processen som följde efter frågeställningens tillkomst var intervjuer med elva entreprenörer från en solo-, mikro samt småföretagarkontext. Intervjuerna transkriberades och bearbetades ner till berättelser där kategorisering av nyckelmeningar ringades in. Tillväxt definierades huvudsakligen som ökning av omsättning samt vinst även fast inslag av företagets interna process även gick att åskådliggöra (t.ex. utvecklande arbetsuppgifter). Entreprenörers tillväxtdefinition kan betecknas vara situationsberoende där typ av verksamhet och situation kan förklara begreppet tillväxt. Resultatet av entreprenörernas orsaksförklaringar till sin historiska tillväxt indikerade interna (företagsförmåga eller personrelaterade förklaringar) samt externa (nätverk (stödjande omgivning) eller konjunktur) orsaksförklaringar. De interna orsaksförklaringarna tenderade dock att vara i majoritet. Edith Penrose (1959) teori om företagstillväxt (The Theory of the Growth of the Firm) med fokus på företags interna tillväxtprocess förenades med det induktivt framväxta resultatet från intervjuerna med entreprenörerna. I studien växte en teoretisk analysmodell fram (penroseisk analysmodell) vilken lyfte fram entreprenörskaps- samt managementförmågors betydelse för möjligheten att nå intern företagstillväxt. Den regionala bilden av tillväxt och intentioner utgick främst från RTP:s utkast och handlingsprogram (2003) samt revideringarna under programperioden (2004-2007). Textanalys av materialet resulterade i att tillväxt som begrepp inte entydigt definierades. Definition av regional tillväxt blev funnen i RTP:s målsättningar. Regionala intentioner för att nå regional tillväxt kan kategoriseras i dels interna regionala strategier (insatser riktade inåt regionen) dels i externa regionala strategier (insatser riktade från regionen). Huvuddelen av strategierna ansågs ha ett internt perspektiv med fokus på att utnyttja och utveckla regionens inneboende resurser. Teorier, vilka riktade sin uppmärksamhet mot regional utveckling samt tillväxt växte fram och skapade en regional analysmodell, vilken innehöll dels olika ekonomiska skolbildningar, dels skilda teorier om samverkan. Resultat En jämförelse mellan tillväxtbilder indikerar både likheter och skillnader. Ideologiskt finns en skiljelinje som delvis står i direkt kontrast till varandra. Exempel på detta är tillväxt via ökad arbetskraft i ett regionalt perspektiv, medan arbetskraftsökningar inte alltid ses som en del av det regionala näringslivets tillväxtdefinition. Likheter finns där RTP diskuterar förädlingsvärdet som ett mått på tillväxt och där näringlivet diskuterar vinst. Ett heterogent näringsliv indikerar även andra värden än ekonomiska och framställer personligt utvecklande samt kreativa uppdrag som tillväxt, bilder av tillväxt vilka saknas i RTP. Resultatet av entreprenörers orsaksförklaring av tillväxt och RTP:s intentioner indikerar likheter i synen på att nätverk och relationer, företagsförmåga samt konjunkturläget är av betydelse för tillväxten. En skillnad är att tillväxten orsakas eller hämmas av interna orsaksförklaringar och speciellt personrelaterade faktorer enligt entreprenörer. En annan skillnad är att regionala intentioner framhärdar att fler individer i arbete leder till regional tillväxt, vilket inte självklart orsakar tillväxt i en företagskontext. I relation till en penroseisk analysmodell har entreprenörerna brister i framförallt managementförmåga. Entreprenörskapsförmåga verkar lättare att uppnå för intervjuade entreprenörer. Den penroseiska analysmodellen indikerar att det är komplicerat att utläsa om regionala intentioner utifrån RTP kan svara mot en företagsteoretiskt tillväxt. En hög abstraktionsgrad i RTP bidrar till att RTP delvis kan ses som en resurs i jämförelse med en företagskontext utifrån penroseisk analys. Den finns ett behov av att beskriva intentionerna i ett RTP tydligare för att klargöra effekterna och innebörden för entreprenören av en intention. Ett resultat är också att intentioner, vilka RTP lyfter fram, vänder sig bort ifrån företagskontexten och riktar sig inåt dvs. mot de regionala näringslivsaktörerna. Däremot finns regionala intentioner vilka är relativt tydliga och med fokus på näringslivet, men som ur ett penroseiskt perspektiv mer fokuserar på resultatet av en tillväxtprocess snarare än på själva tillväxtprocessen inom ett företag. Den regionala analysmodellen indikerar överlappningar mellan olika ekonomiska teoribildningar (neoklassisk, neoösterrikisk, keyniansk) inom RTP. Det pekar på en region med mer pragmatisk inställning till ekonomisk teoribildning. Enligt Helliwell och Putnam (1995) kännetecknas en positiv regional utveckling av just en mer pragmatisk inställning av regionala beslutsfattare. Andra resultat från studien, vilka fokuserar på ökad näringslivsmedverkan i regionala tillväxtprocesser, indikerar att samverkan i partnerskap kan underlättas i lokala [kommunala] partnerskap. En diskussion fokuserar på att regionala näringslivsaktörer bör ha tillgång till entreprenörers berättelser för att ha möjlighet att göra gemensamma tolkningar och därmed undvika näringslivsorganisationers särintressen. Studien introducerar low-bottom-up-begreppet som ett tydligare tänk om ett målgruppsanpassat partnerskap, men också som ett tänk att närma sig entreprenörer via dess berättelser. Ett low-bottom-up-perspektiv kan se olika ut beroende på om partnerskapet söker radikala eller inkrementella lösningar.
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| 6. |
- Silins, Isabella, 1983-
(författare)
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Improved adrenocortical PET imaging
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Adrenal tumours can either be benign or malignant, hormone secreting or not, and they can be discovered through clinical examination of the patient or by pure chance. Increased knowledge in the area, plus the widespread use of imaging techniques, have resulted in a rising number of patients with adrenal tumours that subsequently need to be diagnosed. Improved imaging is needed for primary aldosteronism (PA) and adrenocortical carcinoma (ACC) but the positron emission tomography (PET) tracer currently in use, [11C]metomidate (MTO), has many important limitations. This thesis aims to improve adrenocortical PET imaging.Methods: Paper 1 investigated the pre-clinical properties of Para-Chloro-2-[18F]fluoroethyl-etomidate (CETO), by autoradiography, binding studies, ex vivo biodistribution on rats and in vivo imaging using mice and one non-human primate (NHP). Paper II investigated the clinical properties of [18F]CETO and included patients with various kinds of adrenocortical tumours, and healthy volunteers. Metabolic and kinetic analyses were performed and three out of five healthy volunteers also underwent [15O]water PET/CT to measure adrenal blood flow. Test-retest was performed on all healthy volunteers. Paper III assessed the in vivo and in-human radiation dosimetry of [18F]CETO. Ex vivo uptake data from rats and in vivo PET/CT from NHP and humans were used to calculate residence times. Paper IV evaluated the use of the block-sequential regularized expectation maximization (BSREM) reconstruction algorithm (Q.Clear, GE Healthcare, Milwaukee, USA) for [11C]MTO PET/CT in patients with PA.Results: Papers I and II demonstrated that [18F]CETO is highly specific to the adrenal cortex both in vitro and in vivo. The non-specific binding of [18F]CETO in the liver was significantly lower than that of [11C]MTO. [18F]CETO metabolizes rapidly and the single tissue irreversible (1T1k) kinetic model provided the best fit. [15O]water PET/CT results indicated that the adrenal [18F]CETO uptake was flow limited. Several retest values, including adrenal blood flow, were lower than the test values. Paper III found that the effective dose based on human data was 18.2 μSv/MBq and that the adrenal glands were the limiting organ regardless of species used. Paper IV showed that the BSREM reconstruction algorithm improves image quality, without compromising SUVmax quantification, and a β-value between 70 and 130 was found optimal.Conclusion: [18F]CETO PET/CT is a promising method for adrenocortical imaging and is safe for clinical imaging in terms of radiation dose. [18F]CETO PET/CT should be further investigated in patients with PA or ACC, preferably in conjunction with BSREM reconstruction.
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