| 1. |
- Block, Tomas, 1976-
(författare)
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Acute Occlusion of the Superior Mesenteric Artery : Diagnosis and treatment
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Acute occlusion of the superior mesenteric artery (SMA) is a condition associated with high mortality and morbidity. The aim of this thesis is to evaluate diagnostic and therapeutic approaches for acute SMA occlusion. In a prospective study of patients with suspected intestinal ischemia, no biomarker was sufficiently accurate to detect this condition. In a second retrospective study, pancreatic amylase and troponin-I were elevated in a substantial proportion of patients with verified SMA occlusion. In an experimental animal model of acute SMA occlusion, microarray studies of ischemic small bowel wall were used to characterize the mRNA response to ischemia. Thrombospondin, Monocyte Chemoattractant Protein 1 and Gap Junction Alpha 1 were consistently up-regulated in all pigs with intestinal ischemia. Genes encoding previously proposed biomarkers for intestinal ischemia were either up-regulated, such as lactate dehydrogenase and creatine kinase, or down-regulated, such as intestinal fatty acid binding protein and glutathione S-transferase. In a study of the role of computed tomography in the diagnosis of SMA occlusion, it was shown that computed tomography with intravenous contrast was associated with improved survival. A retrospective analysis of all acute SMA revascularizations in Sweden 1999-2006 revealed that D-dimer was elevated in all 35 measured cases. Endovascular surgery was associated with better outcome than open surgery, both in short and in long term. The presence of postoperative short bowel syndrome was a strong independent risk-factor for decreased long-term survival. Conclusions: Data affirm that D-dimer may serve as an exclusion test for acute SMA occlusion, whereas elevated troponin-I and pancreatic amylase are potential diagnostic pitfalls. Contrast-enhanced computed tomography of the visceral arteries seems to be the best diagnostic method. Endovascular surgery is an option to open surgery in selected cases, and was associated with favourable outcome.
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| 2. |
- Muder, Daniel
(författare)
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Finger Joint Reconstruction with Rib Perichondrium
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Difficulties in repairing and reconstructing articular cartilage damaged by trauma or disease remain unsolved and are one of the major challenges confronting orthopedic and hand surgeons in their clinical work. Relevant research has not adequately described the long-term clinical results, nor has it made a direct comparison to implant surgery after finger joint reconstruction with rib perichondrium. The role of the transplanted perichondrium and the resulting tissue's quality after transplantation have not been detailed with methods investigating gene and protein expression. Therefore, the overall aim of this thesis was to investigate the role and suitability of perichondrium transplants for finger joint reconstruction of cartilage defects and its potential for the field of tissue engineering.Study I is a longitudinal cohort study to evaluate the long-term clinical outcome of finger joint reconstruction with perichondrium transplants. The study cohort included all 11 traceable and alive patients after a median follow-up of 37 (range 34-41) years. The clinical results regarding range of motion, grip strength, pain and scores on the disability of the arm, shoulder, and hand (DASH) were good to excellent without any donor site morbidity. Study II is a retrospective cohort study evaluating 163 joints in 124 patients, divided into 138 surface replacement (SR) implants in 102 patients and 25 perichondrium transplants in 22 patients. The median follow-up was 6 years for the SR group and 26 years for the transplant group. Revision rates and 10-year survival favored patients treated with perichondrium transplants, but below the threshold of statistical significance. Study III is an in vitro study to develop highly sensitive and specific protocols for immunohistochemistry, immunofluorescence, and in situ hybridization on bone tissue. The protocol modifications in this study represent critical steps that can empower highly sensitive and specific mRNA and protein localization in formalin-fixed and decalcified skeletal tissues needed for study IV. In Study IV, an experimental animal study, perichondrium transplants from enhanced green fluorescent protein (EGFP) positive rats were transplanted to wild type recipients. The reconstructed cartilage's cellular contribution and quality were assessed by immunohistochemistry, immunofluorescence, confocal microscopy and in situ hybridization at different times after surgery. The study showed that perichondrium transplants differentiated into a cartilage structure that filled out the defects with chondrocytes expressing elevated levels of Col2a1 and producing a matrix rich in proteoglycans. Study V is a case series of four patients with a mean age of 40 (range 37-47) years with osteoarthritis in the distal radioulnar joint. Our retrospective clinical follow-up is presented and discussed in relation to more traditional techniques. Pain, range of motion, strength, and patient-rated outcome measures improved and were stable at the mid-term follow-up 7.5 years after surgery.In conclusion, perichondrium seems to be a suitable tissue for joint reconstruction and tissue engineering.
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| 3. |
- Sivertsson, Fredrik, 1984-
(författare)
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Criminal Careers in the Long Run : Patterns and Predictions of Criminal Convictions across Age, Time, and Gender
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Why is it that a small proportion of the population accounts for the majority of crime? This question has stimulated a great deal of theoretical and methodological controversy in criminology. In essence, the debate is rooted in different theoretical underpinnings of continuity and change in crime, and the extent to which it is possible to foresee a life of crime by zeroing in on at-risk juvenile offenders. The current thesis explores four contentious empirical issues that may move this debate forward: the long-term predictability of persistent offending in adulthood on the basis of childhood risk factors (Study I); the magnitude of adult-onset offending (Study II); the predictive value of gender for criminal recidivism (Study III); and the association between birth cohort membership and criminal career parameters (Study IV). All four studies employ longitudinal Swedish administrative data, based on cohorts of individuals born between the early 1940s and the mid-1980s, and followed on the basis of detailed conviction data. The thesis also utilizes qualitative life-history narratives with former at-risk juvenile delinquents. The results suggest that theories aiming to explain crime beyond the transition to adulthood should incorporate factors presumed to cause within-individual change, even among high-risk juvenile offenders. Although childhood cumulative risk, including a wide range of individual, family, school, and peer measures, were clearly associated with adult crime, they had limited value for predicting those persistent offenders who eventually ended up in the tail of the crime distribution. Furthermore, although gender is generally one of the main demographic predictors of criminal convictions, the results indicate that it is important to include females for the purpose of understanding continuity and change in adulthood. This is in part because adult-onset offending is more prevalent within the female offending population than within the male offending population and in part because the risk for criminal recidivism among female offenders becomes increasingly similar to that found among male offenders as convictions accumulate over the life span. Finally, the results suggest that the typical criminal career has undergone significant changes both within and across gender groups during the period since the mid-1970s, a period which has witnessed a historical decline in the aggregate conviction rate in Sweden. Taking this into consideration, the employment and extensive analysis of longitudinal multiple cohort data ought to provide a basis for furthering our knowledge on the inherent complexity of crime trends, while at the same time also locating the study of criminal careers in its historical context.
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| 4. |
- Farkas, Sanja, 1983-
(författare)
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DNA methylation in the placenta and in cancerwith special reference to folate transporting genes
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- DNA methylation is an epigenetic mechanism that regulates the gene transcription. Folate is used in cellular synthesis of methyl groups, nucleic acids and amino acids. In complex diseases like cancer and neural tube defects (NTD), various genetic and epigenetic alterations can be found that disrupt the normal cell function. The main goals of this thesis were to analyze whether the genes responsible for the folate transport (FOLR1, PCFT, and RFC1) could be regulated by DNA methylation in placenta, blood leukocytes and colorectal cancer. We also addressed the genome-wide DNA methylation changes in colorectal cancer andcervical cancer.We found that changes in the methylated fraction of the RFC1 gene were dependent on the RFC1 80G>A polymorphism in placental specimens with NTDs and blood leukocytes from subjects with high homocysteine (Paper I). In colorectal cancer, the greatest difference in DNA methylation was observed in the RFC1 gene and was related to a lower protein expression (Paper II).In Paper III and IV we studied the DNA methylated fraction using a high-density array. Paper III was focused on genes in the DNA repair pathway and frequently mutated in colorectal cancer. We found that aberrant methylation in the DNA mismatch repair genes was not a frequent event in colorectal cancer and we identified five candidate biomarker genes in colorectal cancer, among them the GPC6 and DCLRE1C genes. In Paper IV, we found hypomethylation of genes involved in the immune system in cervical cancer specimens compared to healthy cervical scrapes and we identified twenty four candidate genes for further evaluation ofclinical value.In conclusion, the work of this thesis filled a relevant knowledge gap regarding the role of differential methylation of the folate transport genes in NTD and colorectal cancer. This thesis work also provided insights into the functional role of DNA methylation in cancer specific pathways and identified potential novel biomarker genes.
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| 5. |
- Hall, Bo G, 1938-
(författare)
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Perspektiv på Patron : Bruksägaren och statsministern Christian Lundeberg (1842–1911)
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The dissertation is a biography of the industrialist and statesman Christian Lundeberg, a leading and stongly pronounced conservative actor in Swedish political life during the decades around1900, but nowadays almost forgotten. The purpose is to identify the main forces – convictions as well as external factors – behind his actions. He was very influential within a range of important sectors, i.a. compulsory national service, repeated interventions to keep the iron ore of Norrland under Swedish ownership, establishment of a regular conservative party and the decision on the vote to right (for men) in 1907. His most well-known action was as Swedish Prime Minister and head architect behind the peaceful dissolution in 1905 of the union with Norway.However for a long time biographies have not been regarded as ”real” scientific work within the concerned academic Swedish circles. For this reason the introductory chapter analyses these discussions and concludes that time now is ready for the genre to come in from the cold , enumerating six criteria regarded to be of paramount importance. These are being observed in the consecutive parts of the study.The following chapter studies the concept of paternalism as defined within Swedish professional circles, forming a background to the remaining parts of the dissertation. In their turn these present thorough reviews both of Lundeberg’s activities as a paternalistic foundry proprietor in the local family owned community of Forsbacka and of his contributions on the central political level.The final chapter summarizes the driving forces behind Lundeberg’s activities in stating that he was not an ultraconservative person, a priori opposing all progress. Instead as the years passed he developed a clear readiness for compromise solutions. Three key concepts are said to be central to the understanding of his person: “Fatherland”, ”Responsibility” and “Duty”. Throughout all his life he adhered to many of the paternalistic principles and values he learnt at an early age in Forsbacka. His present anonymity is explained by the fact that he in a retrospective very often is considered as being defeated in a number of political convictions now regarded as important.
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| 6. |
- Hellström, John
(författare)
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Den svenska sporthjälten : Kontinuitet och förändring i medieberättelsen om den svenska sporthjälten från 1920-talet till idag
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis examines the media construction of five Swedish sports heroes, active from the 1920’s to the beginning of the 2000’s. The analyses are based on the assumption that sports heroes are social products that reflect the dominating ideals and values of a society or culture, and that the media plays an important role in this process. Firstly, the media provide the attention necessary for successful athletes to become publically known and, secondly, they create the stories in which some athletes are represented as heroes while others are represented as villains. The use of narrative theory in this thesis builds on the idea that a story is not merely a way of presenting information, but a way of creating meaning. A person becomes a hero when he or she is described as a hero in a heroic tale. To analyze the media construction of sports heroes is thus to analyze the media stories of them as heroes.In order to examine and compare the construction of sports heroes in the media, articles from daily press and magazines as well as broadcasts in radio and television have been analyzed. The results show that although each of the five heroes were valued and represented according to ideals and values specific of his or her time, there are similarities in the media representation of them that suggest that there is some degree of stability in the narrative of the Swedish sports hero over time. In many ways, the story of the Swedish sports hero is still intact since the 1920’s. However, this story is an ideal story and the process of constructing athletes as heroes has proved to be filled with compromise and contradictions. It can be argued that the media is more concerned with fitting the athletes into an already existing narrative of the Swedish sports hero than with representing them as individuals.Seen in a wider historical context, sports heroes represent an example of how national identity is constructed in the media. National identity is, as many theorists have shown, a dynamic and relational process. What is considered typically Swedish thus changes over time and in different contexts. In this process the social status of sports heroes helps to stabilize as well as legitimize dominating ideas of Swedish national identity.
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| 7. |
- Isaksson, Helena, 1978-
(författare)
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Clinical studies of RNA as a prognostic and diagnostic marker for disease
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Technologies for RNA detection are evolving rapidly and gives an op-portunity for discovery of new markers for early detection of complex diseases. Today in clinical work we rely on signs and symptoms in com-bination with the measurement of protein levels for diagnosis. The quick turnaround time of mRNA synthesis may provide an earlier diagnostic signal than protein-based biomarkers assays, in acute dramatic condi-tions such as acute mesenteric ischemia (AMI), for early detection of cancer, as prognostic tool in cancer treatment and as an aid in difficult diagnosis of unknown origin.The main goals of this thesis was to apply a whole genome approach to study different complex diseases to evaluate the applicability of RNA as a diagnostic or prognostic marker for disease, preferably from an easily accessible source such as peripheral blood. This was investigated in an animal model with induced AMI, a cohort of ovarian cancer patients and in a single-patient study of a girl with a severe inflammatory syn-drome.Through this thesis we have gained insight into how gene expression is regulated in ischemic intestinal tissue.We found that a peripheral blood test can distinguish between ovarian cancer patients with or without residual tumour mass after surgery with the help of expression analysis of six genes. We also found that gene expressions of three genes can predict overall survival in peripheral whole blood from ovarian cancer patients. And that gene expression profiles indeed can significantly distinguish between two groups of high and low risk ovarian cancer. In the single-patient study, we tried but failed to device a successful treatment before it was too late. Neverthe-less, the things we learned and the case studies that were published may serve as a diagnostic tool for clinicians facing similar syndromes.
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| 8. |
- Lindqvist, Breezy Malakkaran, 1978-
(författare)
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Biological signature of HER2-positive breast cancer
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human epidermal growth factor receptor 2 (HER2) overexpressing breast cancers (HER2+ breast cancer) are associated with an aggressive disease course. This thesis is focused on improving the understanding of the biological signature of HER2+ breast cancer.In Paper I, we identified a common deletion spanning the SLC25A43 gene which codes for a mitochondrial transport protein. Loss of heterozygosity in this gene was confirmed in an extended cohort of HER2+ breast cancer and in other types of cancers. Protein expression analysis of SLC25A43using immunohistochemistry (IHC) in HER2+ breast cancers showed that tumours with negative or low expression of SLC25A43 had lower S-phase fraction compared to tumours with medium or high expression, indicating its possible role in cell proliferation. Absence of mutations in this gene in HER2+ breast cancers led to Paper II where DNA methylation in the SLC25A43 gene was interrogated using Pyrosequencing. HER2+ breast cancer with no deletion in the SLC25A43 gene showed higher methylation in the CpG island (CGI), suggesting methylation in the CGI as an alternate mechanism for SLC25A43 gene inactivation. Methylation in the CGI and in the adjacent shores of the SLC25A43 gene was associated with negative oestrogen receptor status and positive lymph node status. In Paper III, genome-wide DNA methylation analysis of HER2+ breast cancer and normal breast tissue revealed hypermethylation in HER2+ breast cancer affecting particularly the homeobox gene family when compared to normal. We identified a total of 73 candidate genes showing differential methylation in HER2+ breast cancer and external validation of gene expression in a selected group of these genes revealed lowered mean expression in HER2+ breast cancer, warranting future clinical studies of these candidate genes. In Paper IV, we investigated expression and localisation of phosphorylated (p) Akt and FOXO3a and FOXG1 in HER2+ breast cancer using IHC. Cytoplasmic expression of pFOXO3a was associated with sentinel node metastasis while cytoplasmic expression of FOXG1 was correlated to negative progesterone receptor status. This indicates the biological and prognostic value of these proteins in HER2+ breast cancer.Thus, this thesis identified changes at the genetic, epigenetic and protein levels which add new information and improve our understanding of HER2+ breast cancer.
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| 9. |
- Magnusson, Anders, 1957-
(författare)
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Evaluation of surgically assisted rapid maxillary expansion and orthodontic treatment : Effects on dental, skeletal and nasal structures and rhinological findings
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Surgically Assisted Rapid Maxillary Expansion (SARME) is frequently used to treat skeletal maxillary transverse deficiency (MTD) in skeletally mature and non-growing individuals. Despite previous research in the field, questions remain with respect to the long-term stability of SARME and its effects on hard and soft tissue.The overall aim of the present doctoral work was to achieve a greater understanding of SARME, using modern image technology and a multidisciplinary approach, with special reference to effects on the hard and soft tissues and respiration. A more specific aim was to evaluate the long-term stability in a retrospective sample of patients treated with SARME and orthodontic treatment and to compare the results with a matched, untreated control group. The studies in this doctoral project are thus based on two different samples and study designs.The first sample, Study I (Paper I), is a retrospective, consecutive, long-term follow-up material of study models from 31 patients (17 males and 14 females) treated with SARME and orthodontic treatment between 1991 and 2000. The mean pre-treatment age was 25.9 years (SD 9.6) with a mean follow-up time of 6.4 years (SD 3.3). Direct measurements on study models were made with a digital sliding caliper at reference points on molars and canines. To evaluate treatment outcome and long-term stability, the results were compared with study models from an untreated control group, matched for age, gender and follow-up time.The second sample, Study II (Papers II-IV), is a prospective consecutive, longitudinal material of 40 patients scheduled to undergo SARME and orthodontic treatment between 2006 and 2009.In Paper II, one patient was excluded because of a planned adenoidectomy. The final sample comprised 39 patients (16 males and 23 females). The mean age at treatment start was 19.9 years (range 15.9 – 43.9). Acoustic rhinometry, rhinomanometry and a questionnaire were used to assess the degree of nasal obstruction at three time-points; pre-treatment, three months after expansion and after completed treatment (mean 18 months).In Papers III–IV, three patients declined to participate and two had to be excluded because their CT-records were incomplete. The final sample comprised 35 patients (14 males and 21 females). The mean age at treatment start was 19.7 years (range 16.1 – 43.9). Helical CT-images were taken pre-treatment and eighteen months’ post-expansion. 3D models were registered and superimposed at the anterior cranial base. The automated voxel-based image registration method allows precise, accurate measurements in all areas of the maxilla. In Papers II–IV, the treatment groups constituted their own control groups.The main findings in the retrospective, long-term follow-up study were that SARME and orthodontic treatment normalized the transverse discrepancy and was stable for a mean of 6 years post-treatment. Pterygoid detachment did not entirely eliminate the side effect of buccal tipping of the posterior molars. Relapse is time-related and is most pronounced during the first 3 years after treatment. Thus the retention period should be extended and should be considered for this period. The main rhinological findings in the prospective longitudinal study were that SARME had a shortterm, favourable effect on nasal respiration, but the effect did not persist in the long-term. However, subjects with pre-treatment nasal obstruction reported a lasting sensation of improved nasal function.SARME and orthodontic treatment had a significant but non-uniform skeletal treatment effect, with significantly greater expansion posteriorly than anteriorly. The expansion was parallel anteriorly but not posteriorly. The lateral tipping of the posterior segment was significant, despite careful surgical separation. No correlation was found between tipping and the patient's age. Furthermore, SARME and orthodontic treatment significantly affected all dimensions of the external features of the nose. The most obvious changes were at the most lateral alar-bases. The difference in lateral displacement profoundly influenced the perception of a more rounded nose. There were no predictive correlations between the changes. Patients with narrow and constrained nostrils can benefit from these changes with respect to the subjective experience of nasal obstruction. It is questionable whether an alar-cinch suture will prevent widening at the alar-base.The 3D superimposition applied in Study II is a reliable method, circumventing projection and measurement errors. In conclusion, SARME and orthodontic treatment normalize the transverse deficiency, with long-term stability. SARME has a favourable effect on the subjective perception of nasal respiration. SARME significantly affects dental, skeletal and nasal structures.
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| 10. |
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