| 1. |
- Månsson, Kristoffer N. T.
(författare)
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Restructuring the socially anxious brain : Using magnetic resonance imaging to advance our understanding of effective cognitive behaviour therapy for social anxiety disorder
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Social anxiety disorder (SAD) is a common psychiatric disorder associated with considerable suffering. Cognitive behaviour therapy (CBT) has been shown to be effective but a significant proportion does not respond or relapses, stressing the need of augmenting treatment. Using neuroimaging could elucidate the psychological and neurobiological interaction and may help to improve current therapeutics. To address this issue, functional and structural magnetic resonance imaging (MRI) were repeatedly conducted on individuals with SAD randomised to receive CBT or an active control condition. MRI was performed pre-, and post-treatment, as well as at one-year follow-up. Matched healthy controls were also scanned to be able to evaluate disorder-specific neural responsivity and structural morphology. This thesis aimed at answering three major questions. I) Does the brain’s fear circuitry (e.g., the amygdala) change, with regard to neural response and structural morphology, immediately after CBT? II) Are the immediate changes in the brain still present at long-term follow-up? III) Can neural responsivity in the fear circuitry predict long-term treatment outcome at the level of the individual? Thus, different analytic methods were performed. Firstly, multimodal neuroimaging addressed questions on concomitant changes in neural response and grey matter volume. Secondly, two different experimental functional MRI tasks captured both neural response to emotional faces and self-referential criticism. Thirdly, support vector machine learning (SVM) was used to evaluate neural predictors at the level of the individual.Amygdala responsivity to self-referential criticism was found to be elevated in individuals with SAD, as compared to matched healthy controls, and the neural response was attenuated after effective CBT. In individuals with SAD, amygdala grey matter volume was positively correlated with symptoms of anticipatory speech anxiety, and CBT-induced symptom reduction was associated with decreased grey matter volume of the amygdala. Also, CBT-induced reduction of amygdala grey matter volume was evident both at short- and long-term follow-up. In contrast, the amygdala neural response was weakened immediately after treatment, but not at one-year follow-up. In extension to treatment effects on the brain, pre-treatment connectivity between the amygdala and the dorsal anterior cingulate cortex (dACC) was stronger in long-term CBT non-responders, as compared to long-term CBT responders. Importantly, by use of an SVM algorithm, pre-treatment neural response to self-referential criticism in the dACC accurately predicted (>90%) the clinical response to CBT.In conclusion, modifying the amygdala is a likely mechanism of action in CBT, underlying the anxiolytic effects of this treatment, and the brain’s neural activity during self-referential criticism may be an accurate and clinically relevant predictor of the long-term response to CBT. Along these lines, neuroimaging is a vital tool in clinical psychiatry that could potentially improve clinical decision-making based on an individual’s neural characteristics.
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| 2. |
- Eriksson, Therese, 1979-
(författare)
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Organelle movement in melanophores: Effects of Panax ginseng, ginsenosides and quercetin
- 2009
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Panax ginseng is a traditional herb that has been used for over 2000 years to promote health and longevity. Active components of ginseng include ginsenosides, polysaccharides, flavonoids, polyacetylenes, peptides, vitamins, phenols and enzymes, of which the ginsenosides are considered to be the major bioactive constituents. Although widely used, the exact mechanisms of ginseng and its compounds remain unclear. In this thesis we use melanophores from Xenopus laevis to investigate the effects of Panax ginseng extract G115 and its constituents on organelle transport and signalling. Due to coordinated bidirectional movement of their pigmented granules (melanosomes), in response to defined chemical signals, melanophores are capable of fast colour changes and provide a great model for the study of intracellular transport. The movement is regulated by alterations in cyclic adenosine 3’:5’-monophosphate (cAMP) concentration, where a high or low level induce anterograde (dispersion) or retrograde (aggregation) transport respectively, resulting in a dark or light cell. Here we demonstrate that Panax ginseng and its constituents ginsenoside Rc and Rd and flavonoid quercetin induce a concentration-dependent anterograde transport of melanosomes. The effect of ginseng is shown to be independent of cAMP changes and protein kinase A activation. Upon incubation of melanophores with a combination of Rc or Rd and quercetin, a synergistic increase in anterograde movement was seen, indicating cooperation between the ginsenoside and flavonoid parts of ginseng. Protein kinase C (PKC) inhibitor Myristoylated EGF-R Fragment 651-658 decreased the anterograde movement stimulated by ginseng and ginsenoside Rc and Rd. Moreover, ginseng, but not ginsenosides or quercetin, stimulated an activation of 44/42-mitogen activated protein kinase (MAPK), previously shown to be involved in both aggregation and dispersion of melanosomes. PKC-inhibition did not affect the MAPK-activation, suggesting a role for PKC in the ginseng- and ginsenoside-induced dispersion but not as an upstream activator of MAPK.
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| 3. |
- Gdaniec, Sandra, 1988-
(författare)
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231Pa, 230Th and 232Th as tracers of deep water circulation and particle transport : Insights from the Mediterranean Sea and the Arctic Ocean
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The naturally occurring U and Th-series radionuclides have shown to have a considerable importance for the understanding of biogeochemical processes on Earth and in the ocean. In this thesis, the isotopes 230-thorium (230Th), 232-thorium (232Th) and 231-protactinium (231Pa) are used as tracers of the transport and scavenging of marine particles and water circulation. Pa and Th are particle reactive elements, which makes the production, transport and distribution of Pa and Th key factors for our understanding of the origin, fate and distribution of marine particles in the oceans. This thesis explores the distribution of 231Pa, 230Th and 232Th in two different ocean continental margin environments. In particular, the relative influence of water circulation and particles on the 231Pa, 230Th and 232Th distributions in the Arctic Ocean and Mediterranean Sea was investigated. 231Pa, 230Th and 232Th were analyzed in particles and seawater collected in the Mediterranean Sea during the MedSeA-GA04-S cruise along the GEOTRACES section GA04S and in the Arctic Ocean during the PS94 GN04 ARK-XXIX/3 along the GEOTRACES section GN04.One of the important findings of this thesis was the low fractionation between 231Pa and 230Th in the Mediterranean Sea, contrasting what is observed in the open ocean. Additionally, the observed depth profiles of Pa-Th allowed the identification of deep water convection and ventilation in the Western and Eastern Basins, respectively. Moreover, the particle settling speed was reevaluated to ~500 – 1000 m/y.In the Arctic Ocean, scavenging onto particles derived from hydrothermal activity was producing relatively low F-factors (FTh/Pa ~ 10), while higher values were observed in deep waters (FTh/Pa ~ 20). Additionally, the hydrothermal particles in the Nansen interior produce lower FTh/Pa values compared to FTh/Pa observed at the Nansen continental margin. Application of a boundary scavenging model revealed the importance of 230Th scavenging at the continental margin along the Nansen Basin, hereafter the Nansen margin, and advocate for the advection of 231Pa into the Atlantic Ocean. As the ocean margin was included in this model, a particle settling speed of 600 m/y was obtained at the Nansen margin.Moreover, this thesis includes an inter-comparison of dissolved and particulate 231Pa, 230Th and 232Th measurements between four laboratories of the GEOTRACES community. This comparison was conducted to provide detailed descriptions of various chemical procedures used for Pa-Th analysis and to provide a measure of consistency between the laboratories. Results demonstrated that participating labs can determine concentrations of dissolved 230Th and 231Pa in deep water (below 500 m depth) that are internally consistent within 4 % of the mean values. Analysis of particulate 231Pa, 230Th and 232Th allowed the highlighting of an incomplete Pa dissolution problem with our initial leaching procedure, a problem solved by measuring aliquots of particulate samples at two labs. However, in the present work, consistent particulate 231Pa concentrations as low as ~ 0.002 fg/kg were obtained. Overall, it suggests an improvement of the results consistency compared to the previous GEOTRACES intercalibration exercise.
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| 4. |
- Halling Linder, Cecilia, 1975-
(författare)
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Biochemical and functional properties of mammalian bone alkaline phosphatase isoforms during osteogenesis
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human skeleton is a living and dynamic tissue that constantly is being renewed in a process called bone remodeling. Old bone is resorbed by osteoclasts and new bone is formed by osteoblasts. Bone is a composite material made up by mineral crystals in the form of hydroxyapatite (calcium and phosphate) that provides the hardness of bone, and collagen fibrils that provides elasticity and flexibility. Alkaline phosphatase (ALP) is a family of enzymes that is present in most species and catalyzes the hydrolysis of various phosphomonoesters at alkaline pH. Despite the generalized use of ALP as a biochemical marker of bone formation, the precise function of bone ALP (BALP) is only now becoming clear. Three circulating human BALP isoforms (B1, B2, and B/I) can be distinguished in healthy individuals and a fourth isoform (B1x) has been discovered in patients with chronic kidney disease and in bone tissue.Paper I. Three endogenous phosphocompounds, (i.e., inorganic pyrophosphate (PPi), pyridoxal 5′-phosphate (PLP) and phosphoethanolamine (PEA)), have been suggested to serve as physiological substrates for BALP. The BALP isoforms display different catalytic properties towards PPi and PLP, which is attributed to their distinct N-linked glycosylation patterns. The catalytic activity, using PEA as substrate, was barely detectable for all BALP isoforms indicating that PEA is not a physiological substrate for BALP.Paper II. Mouse serum ALP is frequently measured and interpreted in mammalian bone research. However, little is known about the circulating ALPs in mice and their relation to human ALP. We characterized the circulating and tissue-derived mouse ALP isozymes and isoforms from mixed strains of wild-type and knockout mice. All four BALP isoforms (B/I, B1x, B1, and B2) were identified in mouse serum and bone tissues, in good correspondence with those found in human bones. All mouse tissues, except liver, contained significant ALP activities. This is a notable difference as human liver contains vast amounts of ALP.Paper III. The objective of this study was to investigate the binding properties of human collagen type I to human BALP, including the two BALP isoforms B1 and B2, together with ALP from human liver, human placenta and E. coli. A surface plasmon resonance-based analysis showed that BALP binds stronger to collagen type I in comparison with ALPs expressed in non-mineralizing tissues. The B2 isoform binds significantly stronger to collagen type I in comparison with the B1 isoform, indicating that glycosylation differences in human ALPs are of crucial importance for protein–protein interactions with collagen type I.Paper IV. Tartrate-resistant acid phosphatase (TRAP) is highly expressed in osteoclasts and frequently used as a marker of bone resorption. Intriguingly, recent studies show that TRAP is also expressed in osteoblasts and osteocytes. TRAP displays enzymatic activity towards the endogenous substrates for BALP, i.e., PPi and PLP. Both TRAP and BALP can alleviate the inhibitory effect of osteopontin on mineralization by dephosphorylation, which suggests a novel role for TRAP in skeletal mineralization.
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| 5. |
- Hansson, Per-Olof
(författare)
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New ways of learning : Participatory action research and Kenyan runners’ appropriation of smartphones to improve their daily lives and participation in m-learning
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In Kenya, mobile technology is widely used, with more and more people gaining access to the Internet. Mobile technology has the potential to support learning and improve lives, particular those of impoverished people. In this study, 30 Kenyan runners from poor backgrounds and with limited formal education participated. They were provided with a basic smartphone and Internet data bundles for one year so that they could participate in m-learning. The participatory action research approach was used. Sources of data included interviews, observations, fieldnotes, web inquiries, and mobile log files. A sociocultural perspective was used to analyze how the participants learned informally using the smartphones.Findings indicate that the Kenyan runners’ rapid appropriation and mastery of the smartphones was based on their curiosity and interest in sports. The runners’ skills and knowledge increased over time, showing how digital resources improved their training, increased their social interactions, developed entrepreneurial skills, created awareness in and with the rest of society, and improved participation in m-learning. Sociocultural analysis showed that feedback from peers and the tool itself were both significant for learning. The participants themselves influenced the research process. From their interest emerged an online course (MOOC) about human rights. Key challenges in the process were power consumption, lack of electricity, and the availability and cost of Internet access. A lack of critical attitude about content on the Internet was also discernible. The main findings highlight how mobile technology can not only improve daily lives, but also develop new ways for people to participate in mlearning.
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| 6. |
- Johansson, Robert
(författare)
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Treating depression and its comorbidity : From individualized Internet-delivered cognitive behavior therapy to affect-focused psychodynamic psychotherapy
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overarching goal of this thesis has been to enhance Internet-delivered psychological treatments for depression and its comorbidity. To this end, three randomized controlled trials (Study II, III and IV) with a total of 313 participants were conducted. A prevalence study (Study I) was also conducted to provide an up-to-date estimate of the prevalence of depression, anxiety disorders, and their comorbidity in the Swedish general population.Study I showed that more than every sixth individual in Sweden suffers from symptoms of depression and/or anxiety. Comorbidity between depression and anxiety was substantial and associated with higher symptom burden and lower health-related quality of life. Study II showed that a tailored Internet-based CBT protocol (ICBT) was effective in reducing symptoms of depression when compared to a control group. Among individuals with more severe depression and comorbidities, the tailored ICBT treatment worked better than standardized ICBT. Study III showed that a psychodynamic Internet-based psychotherapy was highly effective in the treatment of depression, when compared to a group who received psychoeducation and online support. In Study IV, an Internet-delivered affect-focused psychodynamic psychotherapy proved to have a large effect on depression and a moderately large effect on anxiety disorders.In conclusion, this thesis shows that in the context of treating depression and its comorbidity, Internet-delivered psychological treatments can be potentially enhanced by psychodynamic psychotherapy and by individualization.
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| 7. |
- Kutscher, Liselott, 1976-
(författare)
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Export and sources of organic carbon in the Lena River basin, Northeastern Siberia
- 2016
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Permafrost areas are considered to be one of the largest terrestrial storages of carbon. In a warming climate these areas are expected to experience changes in carbon transport to rivers and the oceans due to permafrost thawing, which could enhance erosion, change water flow pathways and increase greenhouse gas emissions. Large amounts of the carbon transported from the terrestrial environment to rivers are in the form of natural organic matter (NOM). The Lena River basin in northeastern Siberia, which is mainly underlain by continuous permafrost, is the largest contributor of NOM to the Arctic Ocean. In this study we present a spatial data set of NOM, including concentrations and stable carbon isotope values (δ13C) of dissolved (DOC) and particulate organic carbon (POC) as well as carbon and nitrogen ratios (C/N) from 77 sample stations in the Lena River and its tributaries. The samples were collected during two field seasons in July 2012 and June 2013.The results from this study showed large spatial variations in concentrations, annual export and fluxes of organic carbon. These variations were primarily due to variations in discharge and topography. The δ13C and C/N indicated that terrestrial sources such as plants and soil organic matter (SOM), were the main sources of the dissolved organic matter (DOM), while particulate organic matter (POM) was mainly derived from aquatic produced material or SOM. There were clear differences in δ13C and C/N of DOM between sampling years, indicating more surficial flow pathways in samples collected earlier in the summer compared to samples collected later in the summer. The δ13C of POM was correlated with water temperatures and topography, showing that tributaries with origin in mountainous areas in general had soil derived POM and lower water temperatures, while tributaries from lowland areas had higher water temperatures and more influence of aquatic sources. We suggest that this pattern is probably due to differences in water flow pathways. Shifts in export of NOM from drainage areas underlain by permafrost will likely be dependent of spatial changes in hydroclimate and the depth of the active layer in a warming climate.
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| 8. |
- Nussipova, Gulnar, 1978-
(författare)
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Unpacking the Value of Emerging Technologies : Experimentation, Communication and Knowledge Brokering
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- While many emerging technologies are making significant strides in the marketplace, others are developing at a slower pace. Historical experience has shown that their success can vary widely, from outright failure to becoming indispensable to daily life. The creation of value associated with emerging technologies has become a focal point for CEOs, business leaders, policymakers, and global forums such as the World Economic Forum. They actively explore opportunities for value creation using these technologies. Yet, the value of emerging technologies often remains uncertain since their adoption in new contexts and usage may deviate significantly from providers' intended use cases. The commercialization of emerging technologies presents a profound challenge due to the uncertain value and complex landscape of innovation.This thesis aims to investigate the processes that help unpack the value of emerging technologies to customers in a B2B context, with a focus on processes that recognize the evolving, dynamic nature of value. The thesis contends that co - creation processes help customers in unpacking the value of emerging technologies. Given the constantly evolving nature of emerging technologies, it is important to adopt a comprehensive perspective in order to fully comprehend their complex nature. In order to address the challenges presented by the uncertain value of emerging technologies in B2B settings, this thesis proposes a framework that focuses on three co-creation processes - experimentation, communication, and knowledge brokering - that may assist customers in unpacking the value of emerging technologies for their businesses. Finally, the thesis concludes with a discussion of its contributions, both theoretical and practical implications, and recommendations for further research.
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| 9. |
- Alim, Abdul, 1983-
(författare)
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Mechanisms in Tendon Healing : Pain, Biomarkers and the Role of Mast Cells
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tendon injuries and tendinopathy are common disorders, but the underlying mechanisms are not well understood. The overall aim of this thesis was to better understand the mechanisms underlying tendon healing, pain, and inflammation.The aim of the first study was to assess biomarkers of tendon healing, including procollagen type I (PINP) and type III (PIIINP) in relation to patient outcome in 65 patients with Achilles tendon rupture (ATR). At two weeks post-ATR, PINP and PIIINP-levels were quantified using microdialysis followed by ELISA. At one-year post-ATR patient outcome was assessed using the validated Achilles tendon Total Rupture Score. We found that higher ratio of PINP and PIIINP to total protein were significantly associated with less pain but more fatigue in the affected limb.In the second study, we applied Intermittent Pneumatic Compression (IPC) therapy for two weeks to stimulate tendon healing. The patients received either adjuvant IPC treatment or treatment-as-usual in a plaster cast without IPC. We observed that IPC therapy significantly increased PINP levels in the injured tendon, suggesting enhanced healing response.In our third study, we investigated healing response and the role of mast cells (MCs) in-vivo using an ATR rat model. Three weeks postoperatively, we demonstrated an increased number of MCs and a higher proportion of degranulated MCs in the injured tendon compared to the control. We further established that MCs in the injured tendon were positive for the glutamate receptor NMDAR1.In our final study, we assessed the effect of glutamate stimulation on in-vitro-derived mouse bone marrow MCs. Mast cell degranulation was quantified through β-hexosaminidase release, immunofluorescence was used to quantify NMDARs at the protein level, and RT-qPCR/microarray was used to study the expression of NMDARs and associated genes. Glutamate induced a robust upregulation of glutamate receptors of both ionotropic and metabotropic type, both at the mRNA and at protein level. NMDAR1 co-localized with glutamate in the membrane of MCs, thereby confirming an interaction between glutamate and its receptor. Glutamate also induced expression of pro-inflammatory compounds such as IL-6 and CCL2 and transcription factors such as Egr2, Egr3 and FosB. Moreover, the NMDA-channel blocker MK-801 completely abrogated the response of MCs to glutamate, supporting a functional glutamate–glutamate receptor axis in MCs.Together, findings presented in this dissertation reveal possible mechanisms of tendon healing in relation to pain and function, and establish a novel principle for how immune cells can communicate with nerve cells after ATR.
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| 10. |
- Andersson, Henrik
(författare)
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Immigration and the Neighborhood : Essays on the Causes and Consequences of International Migration
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Essay 1 (with Kristoffer Jutvik): This paper uses quasi-experimental evidence to understand how changes in migration policy affect the number of asylum seekers. We look specifically at a sudden, regulatory change in the Swedish reception of Syrian asylum seekers. The change took place in September 2013, and implied that all Syrian asylum seekers would be granted permanent, instead of temporary residence permits. Using high frequency data and an interrupted time series set-up, we study the extent to which this change caused more Syrian citizens to apply for asylum in Sweden, and how the change affected the distribution of asylum seekers in Europe. Results show that the change in policy almost doubled the number of asylum seekers from Syria within 2013, with a significant jump in numbers already within the first week after the implementation of the policy. While this also decreased the share of asylum seekers to other large recipient countries (Germany), the effects were highly temporary.Essay 2: In this paper I estimate the causal effect of ethnic enclaves on the probability of self-employment. To account for neighborhood selection I make use of a refugee dispersal program. Results indicate that larger ethnic enclaves, measured as the share of self-employed coethnics in the municipality immigrants first arrive into, affect the probability of self-employment positively, while the share of all other coethnics has a negative effect. Results however also indicate that there is a long term economic penalty to being placed with a larger share of self-employed coethnics, an effect which is partly mediated through the choice of self-employment.Essay 3 (with Heléne Berg and Matz Dahlberg): In this paper we investigate the migration behavior of the native population following foreign (refugee) immigration, with a particular focus on examining whether there is any support for an ethnically based migration response. If ethnicity is the mechanism driving the change in natives' migration behavior, our maintained hypothesis is that native-born individuals who are more ethnically similar to arriving refugees should not change their migration behavior to the same extent as native-born individuals with native-born parents (who are ethnically quite different from refugees). Using rich geo-coded register data from Sweden, spanning over 20 consecutive years, we account for possible endogeneity problems with an improved so-called ``shift-share" instrumental variable approach; in particular, our strategy combines policy-induced initial immigrant settlements with exogenous contemporaneous immigration as captured by refugee shocks. We find no evidence of neither native flight nor native avoidance when studying the full population. We do, however, find native flight among individuals who are expected to be more mobile, and within this group, we find that all natives, irrespective of their parents' foreign background, react similarly to increased immigration. Our results therefore indicate that preferences for ethnically homogeneous neighborhoods may not be the dominant channel inducing flight. Instead our estimates indicate that immigration leads to more socio-economically segregated neighborhoods. This conclusion can have important implications for the ethnically based tipping point literature.Essay 4 (with Matz Dahlberg): In this paper we examine the short-run housing market effects of refugee immigration to Sweden. Given that Sweden is a major refugee receiving country, it constitutes an interesting and important case to study. To deal with the endogeneity resulting from the refugees' location choices, we use an econometric specification that includes neighborhood fixed effects and an instrumental variable that is based on a historical settlement pattern mainly determined by a refugee placement policy. We find that refugee immigration to small neighborhoods has no average effect on changes in housing prices in that neighborhood. We find a positive effect on increased housing supply, measured as the number of objects on sale. The zero effect of immigration on housing prices stands in contrast to the negative results found in earlier studies. We hypothesize that the reason is due to different preferences for homogeneity in Sweden, and/or to institutional features in the Swedish rental sector.
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