| 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. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- Hirst, Catherine, 1989-
(författare)
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Iron in the Lena River basin, NE Russia : Insights from microscopy, spectroscopy and isotope analysis
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Iron is an important mediator of biotic and abiotic processes on the Earth’s surface, being an electron acceptor in organic matter degradation, a surface for organic matter and trace element adsorption, and a required element for enzymatic processes during primary production. Yet, the role of iron as a mediator of carbon and trace element cycling in high latitude, permafrost-dominated regions remains poorly investigated. The aim of this study was to characterise the chemical reactivity (by size separation, microscopy and spectroscopy) and sources (by isotope composition) of Fe in the Lena River and major tributaries, spanning a wide range in lithology, topography and climate. The Fe transported in the Lena River and major tributaries carries an integrated signal of Fe weathering processes across the permafrost-dominated terrain.A spatial sample set was collected during the post-spring flood period (July 2012, June 2013), from the main channel and tributaries draining contrasting topography and permafrost extent. Across the basin, Fe is mainly transported as chemically reactive ferrihydrite that spans the particulate (> 0.22 µm) and colloidal (0.22 µm – 1 kDa) fractions. The remaining Fe transported as poorly reactive detrital Fe in clays and crystalline oxides. Fe is transported in larger size fractions than the dissolved OM showing that Fe is not a major carrier of DOM. Nano-sized ferrihydrite was attached to OM in the particulate fraction, evidence of a Fe – OM particle association in the Lena River basin.Ferrihydrite shows distinct isotope values in particulate and colloidal fractions, showing that there is a difference in isotopic composition between different size fractions of the same mineral. A conceptual model was developed to understand ferrihydrite formation in the riparian zone of the Lena River and tributaries. Particulate ferrihydrite has isotope values lower than crustal values resulting from redox and organic-ligand promoted mineral dissolution and precipitation of Fe(II)aq to form coatings of ferrihydrite on particles in the riparian zone. Ferrihydrite colloids span a wider range of isotope values, higher than Fe particles, resulting from variations in the size and isotope composition of the Fe(II)aq pool transported in soil groundwaters, and the isotope fractionation factor for Fe oxidation and organic complexation.A temporal sample set was collected in the main channel between September 2012 – March 2013 and every three days during May 2015. The colloidal Fe shows distinct seasonal Fe isotope signatures and Fe fluxes, with isotope values lower than crustal during winter baseflow, overlying crustal values during spring flood and higher than crustal values during summer, attributed to changing sources and thus conditions for isotope fractionation. The combined understanding of Fe reactivity and isotope composition allows us to isolate the dominant sources of Fe entering the Lena River.
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| 6. |
- Andersson, Karin M., 1989-, et al.
(författare)
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Evaluation of two commercial CT metal artifact reduction algorithms for use in proton radiotherapy treatment planning in the head and neck area
- 2018
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Ingår i: Medical physics (Lancaster). - : Wiley-Blackwell Publishing Inc.. - 0094-2405 .- 2473-4209. ; 45:10, s. 4329-4344
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate two commercial CT metal artifact reduction (MAR) algorithms for use in proton treatment planning in the head and neck (H&N) area.METHODS: An anthropomorphic head phantom with removable metallic implants (dental fillings or neck implant) was CT-scanned to evaluate the O-MAR (Philips) and the iMAR (Siemens) algorithms. Reference images were acquired without any metallic implants in place. Water equivalent thickness (WET) was calculated for different path directions and compared between image sets. Images were also evaluated for use in proton treatment planning for parotid, tonsil, tongue base, and neck node targets. The beams were arranged so as to not traverse any metal prior to the target, enabling evaluation of the impact on dose calculation accuracy from artifacts surrounding the metal volume. Plans were compared based on γ analysis (1 mm distance-to-agreement/1% difference in local dose) and dose volume histogram metrics for targets and organs at risk (OARs). Visual grading evaluation of 30 dental implant patient MAR images was performed by three radiation oncologists.RESULTS: In the dental fillings images, ΔWET along a low-density streak was reduced from -17.0 to -4.3 mm with O-MAR and from -16.1 mm to -2.3 mm with iMAR, while for other directions the deviations were increased or approximately unchanged when the MAR algorithms were used. For the neck implant images, ΔWET was generally reduced with MAR but residual deviations remained (of up to -2.3 mm with O-MAR and of up to -1.5 mm with iMAR). The γ analysis comparing proton dose distributions for uncorrected/MAR plans and corresponding reference plans showed passing rates >98% of the voxels for all phantom plans. However, substantial dose differences were seen in areas of most severe artifacts (γ passing rates of down to 89% for some cases). MAR reduced the deviations in some cases, but not for all plans. For a single patient case dosimetrically evaluated, minor dose differences were seen between the uncorrected and MAR plans (γ passing rate approximately 97%). The visual grading of patient images showed that MAR significantly improved image quality (P < 0.001).CONCLUSIONS: O-MAR and iMAR significantly improved image quality in terms of anatomical visualization for target and OAR delineation in dental implant patient images. WET calculations along several directions, all outside the metallic regions, showed that both uncorrected and MAR images contained metal artifacts which could potentially lead to unacceptable errors in proton treatment planning. ΔWET was reduced by MAR in some areas, while increased or unchanged deviations were seen for other path directions. The proton treatment plans created for the phantom images showed overall acceptable dose distributions differences when compared to the reference cases, both for the uncorrected and MAR images. However, substantial dose distribution differences in the areas of most severe artifacts were seen for some plans, which were reduced by MAR in some cases but not all. In conclusion, MAR could be beneficial to use for proton treatment planning; however, case-by-case evaluations of the metal artifact-degraded images are always recommended.
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