| 1. |
- Hellström, Charlotta, 1973-
(författare)
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Adolescent Gaming and Gambling in Relation to Negative Social Consequences and Health
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aims of the thesis were to study relationships between the effects of online gaming and gambling and negative social consequences and ill health among adolescents and to determine whether gaming and gambling activities occur together.The papers in this thesis used epidemiological methods to obtain self-report information from Swedish adolescents aged 13–18 years. Time spent in online gaming was associated with negative social consequences, and this relationship was explained by online gaming motives. Gaming for fun and social motives was associated with a reduced risk of negative social consequences, whereas gaming to escape problems, gain status, or meet demands from others was associated with an increased risk.Increased online gaming time on weekdays increased the probability of having depressive, musculoskeletal, or psychosomatic symptoms, and was related to online gaming motives. The probability of ill health was low in those who reported gaming for fun or social motives. Adolescents with symptoms of attention deficit hyperactivity disorder (ADHD) were more sensitive to gambling frequency and to developing a gambling problem. However, among those identified as susceptible, adolescents with ADHD were equally affected compared with other susceptible participants in terms of their gambling frequency.Boys had a higher probability than girls of participating in online gambling in association with online gaming. Having at least one parent born outside Scandinavia was associated with a higher probability of online gambling, especially among girls. The effect of alcohol use as a factor contributing to online gambling was greater among boys than among girls.The results of this thesis contribute new knowledge about sex differences in online gaming and gambling behaviours and add to the limited research on online gaming and online gambling behaviours among adolescent girls. Gaming motives may be helpful for identifying online gamers needing support to reduce their unhealthy gaming behaviour. Information about factors related to gaming and gambling problems may be of interest to clinicians in psychiatry, psychology and social work, as well as to policymakers, parents and teachers involved in adolescent health and development. Effect preventive strategies should consider the sex differences in gaming and gambling behaviour in adolescents.
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| 2. |
- Kanders, Sofia H.
(författare)
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The relationship between overweight and depression in view of genes, environment and their joint influence
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Obesity and depression are known to often go hand in hand, but is this due to our genetic heritage, environmental factors or a combination thereof? With a neuroscientific approach, I have investigated the relationship between obesity and depression with the aim of bridging the different levels of research available in order to better understand this complex topic. Using data from a longitudinal cohort with adults, we analysed the genetic contribution to antidepressant response in Study I. The association between antidepressant treatment and changes in body mass index, waist circumference and fat mass was assessed in Study II. In Study III, the importance of bullying victimization for the relationship between obesity and depression was analysed using a longitudinal cohort with adolescents. Lastly, the moderating effect from breastfeeding duration on the relation between a known obesity associated gene and body mass index among adolescents and young adults was examined in Study IV.The bidirectional relationship between obesity and depression is derived from several joint processes and mechanisms such as the stress system and symptomatology overlap with strong environmental influences affecting both disorders, plausibly through epigenetic processes. Even though overweight and obesity were associated with depressive symptoms, one even more important environmental factor for the development of symptoms was bullying victimization – a risk factor that persisted after six years of follow-up. The genetic contribution to these complex disorders from individual variations is small in most cases, but with a credible additive effect and with environmental factors as important moderators of these relationships. One such moderator is breastfeeding duration, which was found to contribute to the relationship between FTO and future BMI with different patterns for the individual variants, which supports the differential susceptibility hypothesis. Finally, when AD treatment is used, the patient should be monitored regularly, both regarding depressive symptoms as well as obesity-related measurements.Overall, it is of high importance to focus on prevention because the frequently chronic course of obesity, as well as depression, has a high burden on individuals, as well as on society.
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| 3. |
- Keijser, Rebecka, 1984-
(författare)
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Depressive Symptoms Among Adolescents and Young Adults : Psychometrics and the Influence of Family Environment, and Candidate Gene–environment Interactions
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aims of this thesis were to evaluate the psychometric properties of a questionnaire designed to evaluate parenting styles, and to study how depressive symptoms among adolescents and young adults may vary depending on the family environment and candidate gene–environment interaction (cG×E).The study sample consisted of participants (born during 1997 or 1999), and their caregivers from the Survey of Adolescent Life in Västmanland Cohort Study. This thesis included data from 2012 when the participants were 13 and 15 years old (Wave I: DNA collection), 2015 at ages 16 and 18 years (Wave II: Parenting styles, parental depression, depressive symptoms, early life stress i.e., ELS) and 2018 at ages 19 and 21 years (Wave III: Depressive symptoms).Paper I: A good model fit was obtained for the Parent as Social Context Questionnaire (PASCQ) parent and adolescent versions through psychometric evaluations. Paper II: Positive and negative parenting styles were associated with fewer or more depressive symptoms among adolescents and young adults, respectively. Parental depression×sex was associated with more depressive symptoms, preponderant among female adolescents. The findings were not significant among young adults. Paper III: A significant cG×E effect between oxytocin receptor single-nucleotide polymorphism (SNP) rs6770632 and negative parenting style on depressive symptoms among young adults was found. Paper IV: Significant cG×E effects were found for the FKBP5 SNPs rs1360780, rs4713916, rs7748266 and rs9394309 moderated by ELS and positive parenting style on depressive symptoms among young adults.These findings suggest that parenting styles may be measured with the PASCQ and that depressive symptoms among adolescents and young adults seem to vary dependent on the family environment and cG×E effects. However, the cG×E effects may be more central for some individuals depending on differences in diathesis- or sensitivity towards the family environment. The variance in depressive symptoms may therefore contain diathesis stress and differential susceptibility effects regarding the cG×E interaction. The insight gained from this thesis provides a foundation for future research and contributes to research areas such as parenting research and the understanding of biological factors behind depressive symptomology among adolescents and young adults.
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| 4. |
- Laurell, Cecilia, 1977-
(författare)
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Microarray Based Gene Expression Analysis in Cancer Research
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Biotechnological inventions during the 20th century have resulted in a wide range of approaches for explorations in the functional genomics field. Microarray technology is one of the recent advances which have provided us with snapshots of which genes are expressed in cells of various tissues and diseases. Methods to obtain reliable microarray data are continuously being developed and improved to meet the demands of biological researchers.In this thesis microarrays have been used to investigate gene expression patterns in cancer research. Four studies in three different areas were carried out covering adrenocortical tumors, p53 target genes and a comparison of RNA amplification methods.Adrenocortical tumours are among the most common tumours with an incidence of 7-9%. Malignancy of these tumors is rare. Distinction between malignant and benign tumours is often difficult to establish which makes an improvement of diagnostic approaches important. To elucidate biological processes in adrenocortical tumour development and to examine if there is a molecular signature associated with malignancy, microarray analysis was performed on 29 adrenocortical tumors and four normal specimens. It was possible to classify malignant and benign samples based on the entire expression profile. A number of potential biomarkers was identified which will be further evaluated.P53 is a gene which is mutated in 50% of all cancers. Functional p53 is a transcription factor which is activated upon cellular stress and DNA damage. Target genes are mainly involved in cell cycle arrest and apoptosis. In solid tumors cells are stressed by hypoxia. To examine which target genes p53 activate under hypoxic conditions a microarray study of the cell lines HCT116p53+/+ and HCT116p53-/- was performed. A set of novel potential p53 target genes was identified while many known target genes were found to be not transcriptionally activated during hypoxia. Follow up which was focused on how p53 affected hypoxia induced apoptosis showed that the death receptor Fas was critical.When small amounts of tissue are available, amplification of the transcript population is necessary for microarray analysis. A new strategy for amplification based on PCR was evaluated and compared to a commercial in vitro transcription protocol. Both protocols produced reliable results. Advantages with the PCR based method are a lower cost and a high flexibility due to compatibility with both sense and antisense strand microarrays.Keywords: adrenocortical tumour, apoptosis, cancer, classification, gene expression, microarray, p53, RNA amplification
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| 5. |
- Lövenhag, Sara, 1981-
(författare)
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Substance Use in Swedish Adolescents : The Importance of Co-occurring Psychiatric Symptoms and Psychosocial Risk
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aims: Study I: Identify substance use disorders (SUDs), psychiatric disorders, and psychosocial risk (PSR) in adolescence, to predict SUD after 5 years in 147 adolescents who sought treatment at a misuse-clinic. Study II: Identify alcohol risk use (ARU) and its association with psychiatric symptoms and PSR in 960 adolescents who sought treatment in general psychiatric care. Study III: Examine the effect of antisocial behavior (ASB) on the association between inattention, hyperactivity, impulsivity, and alcohol use in 3,864 adolescent students. Study IV: Examine the veracity of drug use reports comparing responses in questionnaires, in-depth interview, and hair analysis in 200 adolescent students.Results: Study I: SUDs in adolescence persisted into early adulthood. Predictors for SUD: girls who had mothers with alcohol use disorder, victimization, criminality, SUD, or SUD treatment. Study II: Prevalence of ARU was 20%. ARU increased with the number of psychiatric symptom domains. Probability of psychiatric symptoms increased with ARU. Most ARU was found in: ASB and sexual abuse. Most common in ARU: symptoms of ADHD, depression, and anxiety. Study III: ASB reduced association between inattention, hyperactivity, impulsivity, and alcohol use for boys, and hyperactivity and impulsivity for girls. Girls’ inattention continued to affect alcohol use despite the presence of ASB. Study IV: Twice as many participants reported drug use in interviews compared to questionnaires. Questionnaires and hair-analysis showed low sensitivity and high specificity. Responses from participants in less privileged socioeconomic circumstances were less reliable.Conclusions: Study I: Treatment-as-usual experienced difficulties preventing the persistence of SUD. Participants’ comorbidity and PSR must be attended to. Study II: ARU in general psychiatric care is prevalent and associated with other psychiatric symptoms, and all symptoms must be attended to simultaneously. Study III: ASB should be screened for when symptoms of ADHD are present. Inattention in girls might require special attention to prevent alcohol use. Study IV: Interviews might be an alternative to questionnaires. Hair analysis was less useful in this population, but a physical measure might function as a pipeline procedure. Responses from participants in less privileged circumstances might be interpreted with caution.
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| 6. |
- Nilsson, Anna, 1986-
(författare)
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Characterization of Campylobacter jejuni and Campylobacter coli water isolates
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Campylobacter jejuni and C. coli are together the most common cause of bacterial gastroenteritis in the European Union. Campylobacter can be transmitted to humans via contaminated water, but it is largely unknown how these bacteria survive in water.The aim of this thesis was to better understand the water survival strategies and pathogenic potential of Campylobacter water isolates. For this purpose, C. jejuni and C. coli, originally isolated from incoming water at surface water plants, were characterized using whole genome sequencing, phenotypical assays, water survival experiments and an in vitro infection model.C. jejuni water isolates included both common and uncommon sequence types for human pathogens, whereas C. coli isolates were assigned to clades 2 and 3, associated with environmental sources. For C. jejuni, comparative genomics revealed genes involved in oxidative and aerobic stress response. In C. coli, various carbon metabolism-related sequences were identified in clade 2 isolates and in clade 3 isolates, oxidative stress and putative virulence genes were detected. All water isolates were motile and the majority of C. jejuni isolates, but none of C. coli isolates, were able to form biofilm. C. jejuni survived better than C. coli in untreated well and lake water. Furthermore, in contrast to C. coli, a seasonal difference in survival was observed for C. jejuni with better survival in lake water collected during autumn than in spring. When tested in an in vitro infection model, all water isolates adhered to and induced IL-8 response in HT-29 cells indicating pathogenic potential. However, C. coli clade 3 isolates demonstrated a strong cytotoxic effect on human HT-29 cells leading to rapid cell death. This novel phenomenon was not observed for C. coli clade 2 or C. jejuni isolates.This is, to the best of our knowledge, the first study on Campylobacter water isolates characterized using genomic, phenotypical and in vitro infection analyses. These findings suggest that some Campylobacter isolates might survive better than others in water and water survival patterns shown here help us further understand the seasonality and predominance of water-related C. jejuni infections.
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| 7. |
- Nilsson, Cecilia, 1971-
(författare)
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Characterization of Male Breast Cancer : From Molecule to Clinical Outcome
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this thesis was to investigate different aspects of male breast cancer (MBC), and to compare these with findings in female breast cancer (FBC). In paper I, a population–based study was performed to investigate possible differences in treatment and outcome between MBC and FBC patients. MBC and FBC presented with a similar distribution of stage. Although no differences in primary treatment strategy were demonstrated, MBC patients had significantly poorer overall and relative survival, indicating a more aggressive disease. Paper II aimed to assess the value of clinicopathological factors and molecular subtypes in MBC. One hundred and ninety-seven MBC tumors were characterized using immunohistochemistry (IHC) and the findings were correlated to outcome. Lymph node positivity, larger tumor size and ER-negativity were independent risk factors for breast cancer death. Tumor grade, HER2, Ki 67 or IHC classification into molecular subtypes did not demonstrate any prognostic information. In paper III, the same patient material as in paper II was used for evaluation of proliferation markers. High levels of cyclin A and cyclin B expression and an elevated mitotic count were predictive of breast cancer death. Ki-67 was re-evaluated using different cut-offs, but no prognostic value could be demonstrated. Contrarily, overexpression of cyclin D1 was associated with a lower risk of breast cancer death. In papers IV-V, the molecular background of MBC tumors was investigated. Global GEX analyses were performed and two novel subgroups of MBC tumors were identified; luminal M1 and luminal M2. When comparing the degree of similarity with the “intrinsic” subtypes in FBC tumors, more than half of the MBC tumors remained unclassified. Comparative genomic hybridization was used to investigate DNA aberrations. Two MBC subgroups were identified, of which one did not resemble any of the female subgroups. In both studies on the molecular level, a majority of patients were classified into the subgroup with a more aggressive tumor behavior. In conclusion, MBC seems to be a unique tumor entity. The established molecular subtypes in FBC are not applicable in MBC. Other prognostic profiles, specific for MBC, need to be identified.
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| 8. |
- Nilsson, Cecilia
(författare)
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Flight Behaviour of Passerines on Nocturnal Migration
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Many passerines migrate during the night and at high altitudes, making their migration difficult to observe. By using tracking radars we have been able to make exact observations of the flight behaviour of passerines on nocturnal migration, which has enabled us to test several hypotheses about adaptive values and constraints regarding migratory behaviour in different ecological contexts. We have investigated the birds’ flight speeds and we were able to see that birds consistently fly faster in spring than in autumn. This could be due to optimality reasons, as there might be a higher selection pressure to arrive early at the breeding grounds in spring than at wintering grounds in autumn. We have also investigated the timing of nocturnal migration by exploring how it is affected by midnight sun conditions in the Arctic, and can show that the pattern of nocturnal migration persists even in those conditions. At a site in southernmost Sweden, Falsterbo peninsula, we tested the hypothesis that coastlines affect the flight direction of migrants, and saw no evidence of small scale coastline effects. In Falsterbo we also had the unique opportunity to combine our radar data with data from a radio telemetry system on the peninsula and the longstanding ringing regime in the area. By combining methods we could see that the departure directions and directions during climbing flight differed from the directions of birds in level flight. This suggests that migrating birds adjust their orientation once aloft. We also used our combined methods to investigate what separates birds flying in reverse directions from birds continuing forward on migration. Bird flying in reverse directions flew slower, at lower altitudes and later in the night. They were also leaner and younger than birds continuing forward. All animals that fly must deal with winds, which can have a very large positive or negative effect on the flight conditions. In two comparative studies we show that nocturnally migrating moths and passerines achieve similar ground speeds and flight directions by using contrasting responses to winds.
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| 9. |
- Nilsson, Cecilia, 1973
(författare)
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Perinatal programming and neuroendocrine function
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Perinatal growth and development are dependent on a sufficient metabolic, hormonal and nutritional environment. Suboptimal conditions during specific perinatal developmental windows can lead to permanent programming of physiological systems in the fetus or newborn, with implications for adult health. Epidemiological studies have shown that impaired intrauterine growth and development correlate with an increased risk of developing insulin resistance, hypertension, obesity and cardiovascular disease at adult age. The aim of this study was to examine in a rat model if exposition to endotoxin or hormones perinatally can affect neuroendocrine and metabolic function in the adult offspring. The programming effects of testosterone to newborn female pups were examined. Neonatal testosterone was shown to result in adult female rats with increased insulin resistance. Increased muscle weight and centralization of adipose tissue were seen. Circulating levels of testosterone and progesterone were lower in T-exposed rats. The long-term implications of prenatal exposure to high leptin, a hormone suggested to be involved in fetal growth and development, were explored. Prenatal leptin exposure resulted in reduced skeletal growth, bone formation and adipose tissue in the offspring. Male offspring showed increased response to stress and female offspring had high circulating testosterone levels. The programming effects of exposure to endotoxin (LPS), both prenatally and postnatally were examined. LPS exposure in utero led to male offspring exhibiting obesity, insulin resistance and high levels of estradiol and progesterone. Leptin levels were increased, as were food intake. The HPA-axis response to stress was attenuated and the glucocorticoid receptor was upregulated in hippocampus. Female offspring exposed to LPS in utero had increased corticosterone and testosterone and increased adrenal weight, but showed no effects on body composition and insulin sensitivity. Postnatal LPS exposition left male offspring unaffected whereas female offspring showed increased sensitivity to insulin, had increased muscle weight and decreased intraabdominal fat. Furthermore, they showed increased basal and stress-induced corticosterone levels. Increased basal ACTH levels and adrenal hypertrophy were also seen. LPS exposure is known to stimulate HPA axis with subsequent increased corticosterone secretion in rats. Female pups were exposed to corticosterone postnatally and the programming effects were examined in adulthood. Corticosterone-exposed animals were lean, had reduced food intake and low levels of leptin. Furthermore, as seen after postnatal LPS exposure, corticosterone-exposed animals showed increased sensitivity to insulin. They also had low basal and stress-induced corticosterone levels.To conclude, these results show in a rat model, that perinatal exposition to endotoxin or abnormal levels of hormones, may lead to long-lasting consequences for health in the adult offspring. Body composition, insulin sensitivity and neuroendocrine function are factors that can be programmed perinatally. Depending of timing of exposure and nature of exposure, the long-term outcome varies. A difference in sensitivity between genders also seems to prevail.
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| 10. |
- Nilsson Åhman, Hanna
(författare)
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Powder Bed Fusion – Laser Beam of Mg alloy WE43 : Establishing the process – structure – properties relationship
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Powder bed fusion - laser beam (PBF-LB) of Mg alloy WE43 (Mg-4wt%Y-3wt%RE-Zr) has great potential for the development of future biodegradable metal implants, as well as aerospace lightweight materials. However, the work published thus far has mainly focused on obtaining a fully dense material, and the understanding of the relationship among the PBF-LB process parameters, structure and the resulting material properties remains limited. Thus, the aim of the thesis was to relate the main PBF-LB processing parameters to the formation of key microstructural features in WE43, and their effect on corrosion and tensile test properties. The work was carried out on PBF-LB processing units EOS M100 and EOS M290, and the investigated process parameters included laser power, laser scanning speed, hatch distance and sample wall thickness. Depending on the resulting thermal conditions, two main microstructural regions were observed. For process parameters resulting in warmer processes, such as higher laser powers and shorter scan lengths, mainly equiaxed dendritic grains were observed. The grains measured up to 10 µm in maximum diameter and exhibited a weak texture, with the inter-dendritic regions rich in Mg-RE intermetallic compunds. For process parameters resulting in conductive mode melting, mainly a lamellar structure was observed. The lamellar structure consisted in large grains with basal texture, and an intragranular structure where lines of Mg-RE intermetallic compunds precipitated parallel to the melt pool boundary. The larger grains had a maximum diameter of around 60 µm to 100 µm in the build direction, and up to 250 µm in the transverse direction, with a preferential growth along the melt pool.A larger number of dendritic grains was detrimental to the corrosion properties but resulted in higher tensile strength. The result was ascribed to the higher amount of Mg-RE intermetallics and the smaller grains, strengthening the material, but also causing microgalvanic corrosion. Hot isostatic pressing also resulted in growth of the secondary phases and was thus also detrimental to corrosion properties. While a change in hatch distance (40-60 mm) did not cause any dendritic structure to form, a higher hatch distance resulted in improved corrosion properties, but had minor effect on tensile properties, showing the possibilities of applying hatch distance variations to balance corrosion and tensile properties.In conclusion, the findings presented here show the possibilities of controlling the microstructure and thus the material properties by changing some of the key PBF-LB process parameters, and the major importance of understanding the relationship among process, structure and material properties of PBF-LB processed WE43.
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