| 1. |
- Dalin, Frida, 1984-
(författare)
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Model diseases for studies of autoimmunity.
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The events triggering autoimmune diseases are to large extent unknown and model diseases are an important tool in studies aiming to elucidate molecular mechanisms in autoimmunity. Autoimmune Addison’s disease (AAD) is a rare disease characterized by autoimmune destruction of adrenal glands and most patients with AAD have autoantibodies against the enzyme 21‑hydroxylase in the adrenal cortex. The autoimmune destruction in AAD is however suspected to be initiated by T cells. One of the most important investigations in this thesis was to characterize the T cell response in AAD. It could be concluded the T cells in AAD patients respond to three immunodominant epitopes on the 21-hydroxylase.In addition, this thesis aims to gain updated data on comorbidities, replacement therapy, autoantibody profiles, and metabolic factors in AAD. A cohort of 660 AAD patients was studied and it was found that AAD patients are prone to develop other autoimmune conditions. AAD is one of three main disease components Autoimmune Polyendocrine Syndrome type 1 (APS-1), a rare disorder caused by mutations in the AutoImmune REgulator gene (AIRE) that can be potentially fatal without timely diagnosis. Screening for autoantibodies against interferon-ω, interferon-α4, and interleukin-22 revealed four new APS-1 patients among the AAD cohort, confirmed by the presence of disease causing mutations in the AIRE gene.Cancer Associated Retinopathy (CAR) is a paraneoplastic phenomenon arising as a consequence to an autoimmune response triggered by a malignant neoplasm present in the body. This disease is devastating and it is valuable to identify new biomarkers associated with CAR, not least from a tumor diagnostic perspective. In this thesis, a patient with osteosarcoma and CAR was studied and by screening of a proteom array, and the novel CAR autoantigen Aryl hydrocarbon receptor interacting protein-like 1 (AIPL1) was identified.In conclusion, this thesis covers studies on T cell and B cell responses in AAD. Moreover, it includes an update on clinical and immunological characterisation of AAD patients. Finally, a novel autoantigen in CAR was identified and proposed as a diagnostic marker for the paraneoplastic syndrome.
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| 2. |
- Hermann, Veronica, 1972-
(författare)
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”Det är liksom en stor grej som händer just nu i våra liv” : Psykisk hälsa och stigma bland ungdomar
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Adolescents’ mental health is a current public health issue. However, research, on adolescents’ views on different aspects of mental health, and the prevalence of mental well-being, mental illness and related stigma, among adolescents is limited in Sweden. The overall aim of this thesis was to explore perceptions and status of mental health and stigma related to mental health problems among adolescents in a Swedish context. Study I and II were based on qualitative interviews with 32 adolescents on the Swedish island Gotland. Study I indicated that the adolescents had a complex understanding of various mental health concepts but labelled mental well-being as ‘feeling good’ and mental illness as ‘feeling bad’. In Study II, the adolescents described mental health problems as common due to current living conditions, e.g. stress related to school performance and social media and an increased openness about mental health problems. Stigmatisation of people with mental health problems was perceived as problematic, caused by lack of experience and knowledge, but also as related to rumour spreading and stereotypical gender norms. Study III and IV were based on the Life and Health Youth survey, conducted in secondary schools located on Gotland. In study III, the results according to the dual-factor model of mental health showed that most adolescents had vulnerable mental health status (47.5%), while 36.2% had complete mental health. A smaller proportion had troubled (13,9%) or symptomatic but content (2,5%) mental health status. Associations were observed between mental health status and gender, grades, truancy, stress level, resilience, and subjective social status in school. In study IV, the factor structure and internal consistency was acceptable for the modified Attitudes About Mental Illness and its Treatment scale, but the adolescents perceived it as difficult to answer. Further, negative attitudes towards people with mental health problems were present, and more common among boys and foreign-born adolescents. The findings of this thesis suggests the two-factor model of mental health and the three-part description of stigma, including stereotypes, prejudice and discrimination, to be applicable among adolescents. Further, the findings suggest a need for promotion of mental well-being and prevention of mental health problems such as interventions to reduce school-related stress, increase resilience and promote societal knowledge about mental health, stigma and gender stereotypes among adolescents. The findings also motivate support to adolescents with low mental wellbeing and minor mental health problems as well as to adolescents who have friends with mental health problems.
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| 3. |
- Höglund, Berit, 1955-
(författare)
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Pregnancy, Childbirth and Midwifery Care among Women with Intellectual Disability in Sweden : Epidemiological and Descriptive Studies
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of this thesis was to investigate pregnancy and childbirth in women with intellectual disability (ID), in Sweden, the health of their newborns and midwifery care for these women. Two register studies and two descriptive studies are included. Pregnancy and birth outcomes as well as data on the newborns’ health were examined by linking data from the National Patient Register and the Medical Birth Register (I-II). The women’s experience of pregnancy and delivery was investigated with repeated interviews (III). Midwives’ knowledge of, experience of and attitudes towards pregnancy and childbirth in women with ID were evaluated with questionnaires (IV). Mothers with ID were more often teenagers, smoked more during pregnancy and had more Caesarean Sections. Their children had a higher proportion of pre-term births, were small-for-gestational-age, stillborn or died in the perinatal period. The women with ID struggled to attain motherhood and feared to lose custody of the child. The pregnancy was seen as a happy event, even though relatives did not always approve. Parent education was considered important, but not adequately adapted to their needs. The birth process was overwhelming and difficult to understand, but the child was welcomed with warm feelings, and breastfeeding was natural. Midwives stated it was different to care for women with ID and requested additional knowledge. The majority of midwives affirmed that women with ID could not manage the mother role satisfactorily, and one-third expressed that women with ID should refrain from having children. A majority of the midwives considered that the children should grow up with the parents with support from family and society, but one out of five stated that the children should grow up in foster care.Conclusion: Women with ID and their children should be considered as risk groups in pregnancy and childbirth. Professionals in maternity services need to elucidate their knowledge and skills for counselling and supporting this particular group of pregnant women in pre-, intra- and post-partum care.
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| 4. |
- Johansson, Jonas, 1970-
(författare)
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Comparative Treatment Planning in Radiotherapy and Clinical Impact of Proton Relative Biological Effectiveness
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The development of new irradiation techniques is presently a very active field of research with increased availability of more sophisticated modalities such as intensity modulated photons (IMRT), protons and light ions. The primary aim of this work is to evaluate if the dose-distributions using IMRT and protons contribute to clinical advantages. A secondary aim is to investigate the potential clinical implication of the increased relative biological effect (RBE) for protons at the end of the Bragg peak. The potential benefits are evaluated using physical dose measures and dose-response models for normal tissue complication probability (NTCP) and tumour control probability (TCP). Comparative treatment planning was performed using three locally advanced tumour types, left-sided node positive breast cancer, hypopharyngeal cancer, and rectal cancer. All studies showed that both IMRT and protons could improve the dose distributions compared to 3D-CRT, and significantly improve treatment results with lower NTCPs and, concerning hypopharyngeal cancer, higher TCP. Protons always resulted in smaller volumes receiving intermediate and low radiation doses.Using protons or IMRT for left-sided node-positive breast cancer, the advantage is a significantly decreased risk for cardiac mortality (from 6.7% to 1%) and radiation induced pneumonitis (from 28.2% to less than 3%) compared to 3D-CRT. For hypopharyngeal cancer, protons and IMRT provide more selective treatment plans, higher TCP since a simultaneous boost technique is feasible, and better parotid gland sparing for several patients. For locally advanced rectal cancer, the NTCP for small bowel is potentially reduced by approximately 50% using IMRT or protons; protons have an even greater potential if the structure of the small bowel is parallel.A variable RBE correction is developed and applied to a clinical proton treatment plan. A significant difference is obtained compared to the commonly accepted RBE correction of 1.1. This indicates that a variable RBE may be of importance in future proton treatment planning.This thesis provides support for increased use both IMRT and proton radiotherapy, although stronger for protons. Therefore, investments in proton facilities with capacity for large clinical trials can be supported.
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| 5. |
- Nayeb, Laleh
(författare)
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Lika men ändå olika : Språkscreening av enspråkiga och flerspråkiga barn vid 2,5-3 år på BVC
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Children who do not develop their language as expected are at risk of difficulties in school and with peer relations. The Swedish Child Health Services (CHS) offer preventive health surveillance, including language screening, at 2.5-3 years. However, the screening has only been validated for monolingual children. The aims of the thesis were to explore CHS nurses’ experiences of language screening of bilingual children, to evaluate the 3-year screening for language disorder for use at 2.5 years, and to assess the stability of the children’s diagnoses and the classification accuracy of the screening after 6 months. In Study I, 863 nurses answered a web-based survey. Half of the nurses simplified the screening processes for bilingual children, and 74% postponed referrals to speech and language services. About 80% believed that language development was slower in bilingual children which was the strongest predictor of simplified screening practices. In Studies II and III, 105 monolingual and 111 bilingual children were screened and clinically assessed at age 2.5. The screening classification accuracy for monolinguals vs bilinguals screened in both their languages was: sensitivity 91% vs 88%, specificity 91% vs 82%, PPV 56% vs 67%, and NPV 99% vs 94%, respectively. Study IV reassessed 141 children (48 mono- and 93 bilinguals) at age 3, i.e. all children with a positive outcome at age 2.5 from studies II and III, and matched children from the same studies with negative outcomes. The number of new cases with language disorder (n=4) was about the same as the number who had recovered (n=5) at age 3. These few changes were statistically significant, but not considered to be of clinical relevance since the classification accuracy of the screening was still within 95 CI after 6 months. The screening classification accuracy for monolinguals vs bilinguals was: sensitivity 71% vs 81%, specificity 93% vs 82%, PPV 39% vs 67%, and NPV 98% vs 90%. In conclusion, the modified language screening can be recommended for use at age 2.5. Bilingual children who don’t pass the screening in Swedish, should be screened in their mother tongue using a standard procedure. The wait-and-see strategy reported by the nurses in Study I was not supported as screening results remained stable between 2.5 and 3 years. There is a need to implement new evidence-based routines in child health services to equitably screen both monolingual and bilingual children for language disorder.
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| 6. |
- Wallby, Thomas, 1956-
(författare)
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Lika för alla? : Social position och etnicitet som determinanter för amning, föräldrars rökvanor och kontakter med BVC
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Child Health Services (CHS) in Sweden are offered free of charge to all Swedish parents with children 0-5 years of age. The regular service schedule includes home visits, health examinations, vaccinations and participation in parenting groups. The CHS should pay extra attention to disadvantaged families. The aim of this thesis was to investigate to what extent the CHS reaches groups of families with special needs, e.g. immigrant families, low income families, young and single mothers, with universal or selective measures, as well as to investigate the variation of two determinants of child health, second hand smoke and breastfeeding, in these groups of families. The thesis also aimed at investigating validity of data in the county CHS quality database (Basta). The thesis is based on data from Basta together with several national registers. The CHS equally reached all families with infants with the universal program except for participation in parenting group. Foreign born, young, single and low-income mothers had lower participation rates. Smoking rates were lower in foreign-born than in Swedish-born mothers and higher for foreign-born than in Swedish-born fathers. Smoking was more common among single and low income parents and young mothers. Young and single mothers had lower breastfeeding rates at 6 months. At 12 months the breastfeeding rates were higher among foreign-born mothers. The validity test of data in the Basta database showed sensitivity values for immunizations, breastfeeding and smoking at 90-100 % and for any home visit, participation in parenting group at any time, a minimum number of 6 visits at the Child Health Centre (CHC) and a minimum number of 11 visits at the CHC at 88 - 96 %. The sensitivity value for the exact match of number of CHC visits (+/- 3 visits) was 88 %. Conclusions: The universal programme was equally distributed in different immigrant and socio-demographic populations. However, the results did not indicate equality according to the assumption that some families need more input than others in order to achieve equity of outcome. Individual data routinely collected from CHS records to a quality database provides data of good quality that can be used for both quality surveillance and research.
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