| 41. |
- Ahl, Ing-Marie, 1974-
(author)
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Protein Engineering of Extracellular Superoxide Dismutase : Characterization of Binding to Heparin and Cellular Surfaces
- 2010
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Doctoral thesis (other academic/artistic)abstract
- Accumulating evidence indicates that oxygen free radicals are involved in many diseases and pathological conditions, such as aging, inflammation, reperfusion damage of ischemic tissue and various cardiovascular diseases. Extracellular superoxide dismutase (ECSOD) thus plays a major role in the maintenance of cells by providing protection against these toxic substances in the extracellular space. Various animal studies have shown that ECSOD has the ability to protect against many of these disorders, and interest has therefore evolved in the potential therapeutic use of the enzyme.However, despite strenuous efforts, large-scale production of the enzyme has not been achieved. To overcome this problem, a mimic of the enzyme, PseudoECSOD, has previouslybeen constructed. This chimera is easy to produce in large amounts and has all the structural, enzymatic and heparin-binding characteristics of ECSOD, making it a potential substitute for ECSOD in therapeutic situations. However, the copper content of PseudoECSOD has been shown to be rather low, and since the copper ion is very important for the catalytic function of the enzyme, a production system that utilizes a copper chaperone for proper insertion of copper into the active site of the enzyme was constructed. The results show that the copper content of PseudoECSOD produced by this system is close to 100 %.In order to use PseudoECSOD therapeutically, further investigations of its binding capability and protective properties are needed. Therefore, the binding of ECSOD and PseudoECSOD to heparin was investigated using isothermal titration calorimetry. The results show that although some purely ionic interactions are important for the binding between ECSOD and heparin, there is also a substantial contribution from non-ionic interactions. The investigation also showed that the C-terminal domain is the only part of ECSOD that contributes to productive binding, and that the binding of PseudoECSOD and ECSOD to heparin is similar.In addition, analysis of mutant proteins strongly indicated that the amino acids R210, K211 and R214 are important for optimal binding of ECSOD to heparin, accounting for about 30 % of the total binding energy. The structural placement of these amino acids in an α-helix also confirms the hypothesis postulated by Margalit et al., that a common structural motif for heparin-binding proteins may be two positively charged amino acids at a distance of approximately 20 Å in the 3D-structure, facing opposite directions of a α-helix. The importance of these residues was also confirmed by analysis of a phage display library of the C-terminal domain of ECSOD.The binding of PseudoECSOD to heparan sulfate on cell surfaces of two different cell types, HepG2 and endothelial cells, was also investigated. The results clearly show that PseudoECSOD binds to these cells in a very similar manner to ECSOD. To investigate the protective properties of PseudoECSOD against ischemia-reperfusion injuries, an isolated rabbit heart model was used. The results indicate that the enzyme has a protective effect. However, more experiments using the rabbit heart and other animal models are needed to identify the optimal dose for protective purposes. The protective properties of PseudoECSOD in human tissue should also be thoroughly investigated.In summary, the findings in these studies, together with earlier results showing the close resemblance of PseudoECSOD to ECSOD in structural, enzymatic and heparin-binding properties, further support the proposition that PseudoECSOD may be a good substitute for ECSOD to use in therapeutic interventions.
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| 42. |
- Ahlander, Britt-Marie, 1954-
(author)
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Magnetic Resonance Imaging of the Heart : Image quality, measurement accuracy and patient experience
- 2016
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Doctoral thesis (other academic/artistic)abstract
- Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.
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| 43. |
- Ahlbeck, Lars, 1964-
(author)
-
Intralymphatic Immunotherapy : A Novel Route to Ameliorate Allergic Rhinitis Due to Pollen
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Allergy to pollen and animal dander is a major public health problem. Close to 30% of the population have symptoms from the upper and/or lower respiratory tract when they meet fur animals or pollen. Whereas symptom-relieving medications have a good to sufficient effect on about 80% of those affected, a large group of 10–20% have severe symptoms, despite medication, with an impact on well-being and ability to work. In Sweden, the annual cost of allergy was calculated at €1.3 billion in 2014.Immunotherapy is effective in treating and preventing pollen allergy and allergic asthma, but is expensive, complicated, requiring 40 injections, and takes more than three years to complete if subcutaneous injections are used. Tablets placed under the tongue are another method, with one tablet taken every day for three years. Only 1.5‰ receive such treatment, yet just over 3% would need it.With intralymphatic immunotherapy, a small dose of allergen is given in a lymph node in the groin on 3 occasions, one month apart. As this method takes only eight weeks, it is a much faster and less costly treatment. However, although several studies have shown that the treatment is safe, its efficacy remains the subject of doubt.Our pilot study in 2012, with a 3-year follow-up to 2015, showed encouraging results, and was followed by a double-blind randomised study with 72 participants from 2014 to 2018. The research subjects then received treatment with birch and grass pollen extract or one extract and a placebo. Regardless of treatment, symptoms, quality of life and medication consumption improved during the birch and grass pollen seasons in the 3 years after treatment. Increased frequencies of T-regulatory lymphocytes may explain the non-specific effects.In 2017 to 2018, we conducted a double-blind study with 38 participants, half of whom received placebo and half, active treatment. In this study, we saw no difference between the treatment groups in the first year after treatment. However, after discontinuation and unblinding in 2019, i.e., two years after treatment, the actively treated group improved in terms of symptoms, and quality of life was improved compared with the placebo group despite less need for medication. T-regulatory lymphocytes increased one year after treatment only in the actively treated group.A long-term follow-up of the research subjects from our two larger studies in 2022, i.e., five to eight years after treatment, showed in the double-blind study without a pure placebo that the scores for symptoms, medication use, and quality of life remained as low as after the first three years. In the placebo-controlled study, a statistically significant improvement in symptoms remained during the grass pollen season. Analysing the two studies together, symptom improvement was significant even during the birch pollen season. Thus, although the effect does not seem to diminish, those who did not receive birch, but only grass, needed to use more medication during the birch pollen season in 2022, seven to eight years after treatment. Moreover, those who did not receive grass but only birch needed more medication during the grass pollen season. This may suggest that the non-specific effect begins to wane after seven to eight years.Allergy to pollen is a major problem for individuals and society, where symptom-relieving treatment with drugs is not enough for many. They can be helped with immunotherapy, which takes at least three years, is expensive and fraught with side effects. In contrast, intralymphatic immunotherapy involves three injections over eight weeks. Our three studies show that the treatment is safe and indicate that it has a clinical effect up to eight years after treatment. T-regulatory cells appear to be important to the immunological mechanism, leading to tolerance to pollen.
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| 44. |
- Ahlberg, Mona, 1966-
(author)
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Being cared for in an Intensive Care Unit – family functioning and support
- 2022
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Doctoral thesis (other academic/artistic)abstract
- When COVID-19 came as an uninvited guest into our everyday lives, nursing in intensive care was affected and thus the studies contain data from both before and during the COVID-19 pandemic.Before the pandemic, most intensive care units, which care for patients with critical illness in a technical setting, allowed family members to visit the patient 24 hours a day. The intensive care unit is a stressful and frightening environment for both the patient and their family. They can be affected both mentally and physically, showing symptoms such as difficulty sleeping, stress and depression. The intensive cared patient often does not remember anything from the time they were cared for in the intensive care unit, and the family needs to explain and recount this unconscious time. During the pandemic, this changed, with restrictions and limited opportunities to visit the hospital and patient due to virus outbreaks. Family members received information about the patient's medical condition by phone from a physician. The overall aim of this thesis was to explore and conceptualise the family functioning of families with a family member treated in the intensive care unit. There was also an intention to describe and evaluate how an intervention affects the family and individual family members in families where a family member received intensive care.In these studies, qualitative, quantitative, as well as mixed methods were utilised. Participants were adult intensive cared patients from seven intensive care clinics, and their families. The results examined between families are based on the patient and family characteristics. The results from study I show that families who have experienced COVID-19 and with a family member who was cared for in an intensive care unit, have existential thoughts. Study II shows no major impact on family function between families, but the answers differ within the families who experienced intensive care. In study III, concerning families experiencing intensive care and attending family health conversations, there was an awareness of family function. The conversations brought the family closer together, through improved understanding of each other. In study IV family functioning, hope and sense of coherence were com-pared among the participants in two intervention groups: Family health conversations and support group conversations. Family functioning and hope were higher in the group that participated in the family health conversations and comprehensibility, meaningfulness and vitality were higher among the participants in the support group conversation. By exploring how family function affects the individual family member and the family as a unit during critical illness and intensive care, new ways of working can be strengthened in the care of patients and their families.
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| 45. |
- Ahle, Margareta, 1966-
(author)
-
Necrotising Enterocolitis : epidemiology and imaging
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- Necrotising enterocolitis (NEC) is a potentially devastating intestinal inflammation of multifactorial aetiology in premature or otherwise vulnerable neonates. Because of the broad spectrum of presentations, diagnosis and timing of surgical intervention may be challenging, and imaging needs to be an integrated part of management.The first four studies included in this thesis used routinely collected, nationwide register data to describe the incidence of NEC in Sweden 1987‒2009, its variation with time, seasonality, space-time clustering, and associations with maternal, gestational, and perinatal factors, and the risk of intestinal failure in the aftermath of the disease.Early infant survival increased dramatically during the study period. The incidence rate of NEC was 0.34 per 1,000 live births, rising from 0.26 per 1,000 live births in the first six years of the study period to 0.57 in the last five. The incidence rates in the lowest birth weights were 100‒160 times those of the entire birth cohort. Seasonal variation was found, as well as space-time clustering in association with delivery hospitals but not with maternal residential municipalities.Comparing NEC cases with matched controls, some factors, positively associated with NEC, were isoimmunisation, fetal distress, caesarean section, persistent ductus arteriosus, cardiac and gastrointestinal malformations, and chromosomal abnormalities. Negative associations included maternal pre-eclampsia, maternal urinary infection, and premature rupture of the membranes. Intestinal failure occurred in 6% of NEC cases and 0.4% of controls, with the highest incidence towards the end of the study period.The last study investigated current practices and perceptions of imaging in the management of NEC, as reported by involved specialists. There was great consensus on most issues. Areas in need of further study seem mainly related to imaging routines, the use of ultrasound, and indications for surgery.Developing alongside the progress of neonatal care, NEC is a complex, multifactorial disease, with shifting patterns of predisposing and precipitating causes, and potentially serious long-term complications. The findings of seasonal variation, spacetime clustering, and negative associations with antenatal exposure to infectious agents, fit into the growing understanding of the central role of bacteria and immunological processes in normal maturation of the intestinal canal as well as in the pathogenesis of NEC. Imaging in the management of NEC may be developed through future studies combining multiple diagnostic parameters in relation to clinical outcome.
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| 46. |
- Ahlgren, Ewa, 1959-
(author)
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Cerebral complications after cardiac surgery
- 2002
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Doctoral thesis (other academic/artistic)abstract
- Cerebral injuty remains a major cause of morbidity and mortality after cardiac surgery. Previous studies have mainly focused on preoperative risk factors and intraoperative events but cerebral complications may also occur in the postoperative period. Cognitive impairment is common after cardiac surgery but the consequences of this complication for activities of daily life are less known. Safe driving involves a complex set of skills requiring preserved cognitive function. A substantial number of patients with heart disease are active drivers. The impact of postoperative cognitive dysfunction on driving performance, however, has not previously been investigated in this large patient group.In this thesis pre-, intra- and postoperative risk factors for focal cerebral complications were determined and the onset time of cerebral symptoms were evaluated in two cohorts of cardiac surgical patients, comprising 2480 and 3282 patients respectively. Data analysed were drafted from a clinical register and the surgical database of Linköping University Hospital Heart Center. Cerebral complication was delayed, i.e occurred after a free interval, in about one third of patients suggesting causes other than intraoperative events. Different risk factors were found for early and delayed cerebral complications suggesting different mechanisms of cerebral injury. Advanced age, preoperative hypertension, aortic surgery, prolonged cardiopulmonary bypass (CPB) time, intraoperative hypotension after completion of CPB, and arrhytlunia in the early postoperative period increased the risk for early cerebral complication. Female gender, diabetes, previous cerebrovascular disease, combined coronary artery bypass grafting (CABG) and valve surgery and arrhythmia on the thoracic ward increased the risk for delayed cerebral complication. Cognitive function and driving performance were evaluated in 27 patients before and 4-6 weeks after CABG. The patients underwent neuropsychological testing, an on-road driving test and a test in an advanced driving simulator. Twenty patients scheduled for percutaneous coronary intervention (PCI) served as controls. Complete data were obtained in 23 and 19 patients respectively. Furthermore cognitive function and driving performance in on-road driving of the 44 patients with complete tests before intervention were compared with controls of similar age without heart symptoms. Cognitive function and driving performance were already impaired in patients with coronary artery disease before intervention when compared with controls. After surgery 48% of the patients showed cognjtive decline compared to 10% after PCI. These patients also scored less in the on-road driving test to a greater extent than did patients without postoperative cognitive decline.
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| 47. |
- Ahmad, Awais, 1987-
(author)
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Autoantibodies in healthy blood donors, rheumatic and autoimmune liver diseases
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Autoimmunity is a common phenomenon where the immune system recognises the body's own tissues. Autoimmunity can lead to disease if tissue damage occurs. Autoimmune diseases affect 5–10% of the global population and in many of these autoantibodies can be detected. The autoantibodies can be detected with several different methods. In this thesis, line immunoassays and fluorescence enzyme immunoassay were used to investigate the presence of autoantibodies in blood donors and various disease groups. Line immunoassays use strips while fluorescence enzyme immunoassay uses wells. The strips and wells are coated with proteins that are allowed to react with serum samples from the patient. In the presence of autoantibodies, either a color change (line immunoassay) or a light reaction (fluorescence enzyme immunoassay) occurs.Study I and II: With the EuroLine -Autoimmune Liver Diseases- (IgG) line immunoassay, the presence of autoantibodies associated with autoimmune liver diseases was analysed in blood donors, patients with autoimmune liver diseases and patients with SLE. Autoantibodies could be detected in several blood donors. A very rare autoantibody, anti-LC- 1, was more common in blood donors than in patients with autoimmune liver diseases. Despite the presence of the autoantibodies, no association was seen with abnormal liver values in blood donors or patients with SLE. By raising the cut-off, the number of "false positive" results decreased. However, this could not correct the problem with anti-LC-1, which seems to indicate that there is a problem with the LC-1 antigen so that non-specific reactions are detected. The risk of developing autoimmune liver disease was considered to be low in the SLE patients, as none of these patients developed autoimmune liver disease despite several years of follow-up. Most of the positive findings with the EuroLine immunoassay could not be confirmed with other methods, indicating that this method is very sensitive.Study III: With the EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) line immunoassay, the rare autoantibodies anti-Th/To and anti-NOR90 could be detected as frequently in blood donors as in patients with systemic sclerosis. Most of the other autoantibodies were more common in patients with systemic sclerosis compared to blood donors and other disease groups. Some of these autoantibodies were associated with specific clinical manifestations, including renal involvement in patients with SLE. These findings need to be verified.Study IV: Autoantibodies that bind the U1-RNP protein (anti-U1-RNP) can be detected in patients with SLE. Patients with anti-U1-RNP can be further analysed for the presence of autoantibodies against the protein RNP 70kDa (anti-RNP70). However, the clinical value of further analysis of anti-RNP70 is uncertain. In this study, fluorescence enzyme immunoassay was used to analyse anti-U1-RNP positive samples for anti-RNP70 to evaluate whether it added anything of clinical value in SLE patients. Presence of anti-U1-RNP was associated with low white blood cell counts and less organ damage. However, analysis of anti-RNP70 in patients with SLE did not add any additional clinical information.Conclusion: Euroline -Autoimmune Liver Diseases- (IgG) and EuroLine Systemic Sclerosis (Nucleoli) Profile (IgG) are tools that are of value in the diagnosis of autoimmune liver diseases and systemic sclerosis, but the methods have high sensitivity which can lead to false positive results. By raising the cut-off, the risk of this can be reduced. Some rare antibodies were found more frequently in blood donors than in patients with the different disease groups, suggesting potential problems with the antigen source. Subtyping of anti-RNP70 in SLE patients with anti-U1-RNP did not add anything of clinical value.
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| 48. |
- Ahmadi, Ahmad, 1964-
(author)
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Genetic predisposition and risk factors for neurodegenerative diseases with special emphasis on Parkinson's disease and solvent-induced chronic toxic encephalopathy
- 2004
-
Doctoral thesis (other academic/artistic)abstract
- The inter-individual variability in biotransformation, may lead to differences in activation and detoxification of both endogenous and exogenous compounds. Polymorphism studies in such genes were applied for Parkinson's disease (PD) and Chronic toxic encephalopathy (CTE), two diseases influenced by both genetic and enviromnental factors.An elevated median age for the onset of PD was found among GS1M1 gene carriers compared to PD patients being GS1M1 null genotypes (68 years versus 57 years). No similar difference was found for GSTT1. mEPHX (113HH) isoform, which has been suggested as a low activity variant, is over represented in PD patients (OR=3.8, CI 95%, 1.2-11.8).Monoamine oxidases (MAO-A and -B) are important in the dopamine metabolism and in the detoxification of neurotoxins and genetic variants in these genes have earlier been assigned to PD. However, no difference was revealed between any of the polymorphisms studied in the MAO-A and -B genes and PD. Smoking displayed an enviromnental exposure with a strong decreased risk for PD in this study (OR=0.40 for men and OR=0.48 for women) but no obvious interaction with the MAO genotypes could be observed.Mitochondrial dysfunction and oxidative stress have been hypothesized to contribute to the pathogenesis of PD. The superoxide dismutases (SOD) potentially play an important role in PD by detoxifying superoxide radicals in mitochondria. Polymorphisms neither in superoxide dismutase 2 (SOD2) nor mitochondrial complex I subunit, NDUFV2, were associated with PD.An increased risk ratio for CTE was found in smokers with the GSTM1 null genotype (RR=2.5, Cl 95%, 1.4-4.2) or the GSTT1 null genotype (RR=1.4, Ci 95%, 1.02-2.0). In non-smokers GS1M1 null genotype did not confer any risk for CTE. Polymorphisms in mEPHX were not associated with an increased risk for CTE.Thus, various genetic and enviromnental factors most likely influence both PD and solvent-induced CTE. Detoxification pathways may represent important protective mechanisms against reactive intermediates, thus genetic predisposition in these pathways could modify the susceptibility and onset of PD and solvent-induced CTE.
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| 49. |
- Ahnström Waltersson, Marie, 1976-
(author)
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Cell cycle alterations and 11q13 amplification in breast cancer : prediction of adjuvant treatment response
- 2009
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Doctoral thesis (other academic/artistic)abstract
- The growth and development of the breast is to a large extent regulated by oestrogens through the oestrogen receptor (ER). Activation of the ERα triggers transcription of genes that are important for cell proliferation and stimulates entry into the G1 phase of the cell cycle. In breast cancer the ERα is often upregulated and is therefore a suitable target for adjuvant therapies such as tamoxifen. Although tamoxifen is an effective treatment in most cases, tumours sometimes acquire resistance to the drug. The aim of this thesis was to investigate the impact of G1 phase proteins and 11q13 amplification on prognosis and treatment response in breast cancer. The material used was from a clinical trial in which postmenopausal breast cancer patients were randomised to chemotherapy or radiotherapy and tamoxifen or no adjuvant treatment. We studied the expression of cyclin D1, cyclin E and Rb with immunohisochemistry and amplification of CCND1 and PAK1 with real time PCR. We found that among patients with high tumour expression of cyclin D1, overexpression of ErbB2 was associated with reduced recurrence-free survival. Both cyclin D1 and cyclin E overexpression were associated with reduced tamoxifen response. High expression of cyclin D1 has been found to induce ligand independent activation of ERα in breast cancer cells and might also switch tamoxifen from acting as an antagonist to an agonist. Overexpression of cyclin E has been shown to be associated with expression of low molecular weight isoforms of the protein that possess an increased kinase activity and are insensitive to p21 and p27 inhibition. Furthermore, amplification of 11q13, and in particular the gene PAK1, was a strong predictor of tamoxifen resistance. The pak1 protein is involved in phosphorylation and ligand independent activation of the ERα. We also found that lost expression of either p53 or Rb reduced the patients benefit from radiotherapy compared with patients with normal expression of both proteins. Normally, ionizing radiation upregulates p53 resulting in G1 arrest or apoptosis. If either functional p53 or Rb is missing the cells can proceed from G1 to the S phase despite damaged DNA. The expression of the microRNA, miR-206, was analysed with real time PCR, and the results showed that high expression of miR-206 correlated to low expression of ERα and 11q13 amplification. In vitro studies have shown that miR-206 negatively regulates the expression of ERα. Taken together the G1 regulators and amplification of 11q13 seem to have an important role in predicting the patient’s response to adjuvant therapy.
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| 50. |
- Aho, Nikolas, 1970-
(author)
-
Victimization, Prevalence, Health and Peritraumatic Reactions in Swedish Adolescents
- 2016
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Doctoral thesis (other academic/artistic)abstract
- The aim of this thesis was to expand the knowledge of victimization in children and youth in Sweden. Victimization, prevalence, health and peritraumatic reactions were explored in a cross sectional, representative sample of 5,960 second grade high school students in Sweden. A computerized survey was developed and administered in class room setting.Lifetime victimization was found in 84.1% of the sample (m=83.0%, f=85.2%), and, in relation to the five domains, 66.4% had experienced conventional crime, 24% child maltreatment, 54.4% peer and sibling victimization, 21.8% sexual victimization, and 54% had experienced witness victimization. Females experienced significantly more child maltreatment, peer and sibling victimization, sexual victimization, and witnessed victimization, males more conventional crime (p<0.001). Using logistic regression risk factors for victimization were confirmed by a significant increase OR regarding gender, environment and lack of both parents.Symptoms (TSCC), were clearly associated with both victimizations per se and the number of victimizations. The results indicated a relatively linear increase in symptoms with an increase in number of events experienced. Mental health of the polyvictimized group was significantly worse than that of the non-polyvictimized group, with significantly elevated TSCC scores (t<0.001). Hierarchical regression analysis resulted in beta value reduction when polyvictimization was introduced supporting the independent effect on symptoms. Social anxiety was found in 10.2 % (n = 605) of the total group (n = 5,960). A significant gender difference emerged, with more females than males reporting social anxiety. Elevated PTSS was found in 14.8 % (n=883). Binary logistic regression revealed the highest OR for having had contact with child and adolescent psychiatry was found for the combined group with social anxiety and elevated PTSS (OR = 4.88, 95 % CI = 3.53–6.73, p<001). Significant associations were also found between use of child and adolescent psychiatry and female gender (OR = 2.05, 95 % CI = 1.70–2.45), Swedish birth origin (OR = 1.68, 95 % CI = 1.16–2.42) and living in a small municipality (OR = 1.33, 95 % CI = 1.02–1.73).Mediation models used peritraumatic reactions (PT): total, physiological arousal (PA), peritraumatic dissociation (PD), and intervention thoughts (IT) and JVQ and TSCC. Of the n=5,332 cases, a total of n=4,483 (84.1%) reported at least one victimizing event (m = 83.0%, f = 85.2%). Of these, 74.9% (n=3,360) also experienced a PT reaction of some kind. The effect mediated by PT tot was b= 0.479, BCa CI [0.342 – 0.640], representing a relatively small effect of 7.6%, κ2=0.076, 95% BCa CI [0.054- 0.101]. The mediating effect of JVQ on TSCC was mediated by PD more for males (b=0.394 BCa CI [0.170-0.636]) than for females (b=0.247, BCa CI [0.021-0.469]). The indirect effect of the JVQ on the TSCC tot mediated by the different PT reactions was significant for PD (b=0.355, BCa CI [0.199- 0.523]. In males a mediating effect of PD could be seen in the different models, while females had a more mixed result. IT did not show any indirect effect in males, but had a mixed effect for females.The empirical findings in this thesis lead to the conclusion that victimization is highly prevalent in children and youth and is related to health issues. The association of victimization on symptoms was mediated by peritraumatic reactions. Using a comprehensive instrument such as the JVQ provides the researcher or clinician the opportunity to acquire more complete measurement and also makes it possible to identify polyvictimization, a high-level category of events with severe impact on health.
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