Introduction: Obsessive-compulsive disorder (OCD) is a complex disorder that is associated with significantly impaired functioning. The current prevailing model of OCD implicates dysfunction of the serotonergic neurotransmitter system and fronto-striatal neural networks, but challenges in replicating findings within OCD samples are often attributed to clinical heterogeneity. OCD symptoms that develop or worsen within the perinatal period appears to reflect a distinct subtype of the disorder, but the genetic and neurobiological factors that contributes to its presentation in women is poorly understood. In this dissertation, we aimed to review the literature on the genetic architecture of OCD, identify potential gene candidates for perinatal OCD and analyze one serotonin system gene according to OCD and possible subtypes using meta-analytic techniques. Based on these findings, we then tested the association of serotonergic candidate gene polymorphisms with the presence of infant-related obsessive-compulsive symptoms (OCS). Lastly, we investigated the cortical morphological features associated with perinatal OCD and OCS symptom severity in postpartum mothers. Results: From prior reports in the literature and our own meta-analytic investigation, polymorphic variants in genes coding for the serotonergic transporter and serotonin 2A receptor subtype (SLC6A4 and HTR2A, respectively) appear to be candidates for perinatal OCD due to their association in female samples. However, upon investigation in our perinatal sample (n=107), we found no evidence to support the association of the 5-HTTLPR polymorphism of SLC6A4 with perinatal-related OCS, but larger samples are needed to confirm this finding. Due to technical challenges, the HTR2A polymorphism remains to be tested. Our novel whole-brain explorations revealed distinct cortical morphology associated with symptom worsening across the perinatal period, irrespective of diagnosis. Cortical parameters were not able to differentiate mothers with and without OCD; however, OCD mothers displayed positive correlations between cortical surface area and symptom severity in widespread regions, including the frontal, parietal, temporal and occipital cortex. Conclusions: Overall, this body of work aimed to fill the gap in the literature by exploring the possible genetic and cortical correlates of perinatal-related OCS and OCD. While 5-HTTLPR or HTR2A are candidates for perinatal OCD, it is not yet clear whether they increase susceptibility for the development of infant-related OCS in the perinatal period. Distinct cortical alterations in surface area appeared alongside OCS exacerbation in the postpartum period in regions that extend beyond the frontoparietal network. This suggests that additional neural networks may be contributing to symptom severity and that the cortical plasticity that occurs across the perinatal period may predispose women for risk of OCD. Future studies should continue to use a multiple perspective approach, that utilizes genetic and neurobiological techniques, in order to provide greater insight into the etiology of perinatal OCD. / Dissertation / Doctor of Philosophy (PhD) / Women are at greater risk for the development of mental illness in the time surrounding pregnancy and postpartum, known as the perinatal period. In the case of perinatal obsessive-compulsive disorder (OCD), mothers may experience unique worries in regard to their parenting or fears that their baby may be harmed. While these worries are common, they can become disruptive when persistent and impact the mother’s mood and ability to bond with the infant. Our current understanding of OCD includes the influence of genetic factors and brain changes, but little is understood about what factors may increase risk for OCD in the perinatal period. In this thesis, we aimed to review whether certain alterations within DNA segments, known as gene variants, may be linked to the development of OCD in females and if these gene changes, as well as differences in brain structures in postpartum mothers, are associated with OCD symptoms during the perinatal period. The genes we examined are important for regulating a chemical signaling substance in the brain known as serotonin. Based on our results, we did not find a relationship between serotonin gene variants and OCD symptoms in perinatal women. We also found no differences when comparing the cortical brain structures between mothers with OCD and healthy mothers; however, we observed that measures of surface area across several cortical brain regions were related to symptom worsening from pregnancy to postpartum, and also with symptom severity in postpartum mothers with OCD. These results suggest that there are widespread brain changes during the postpartum period that may increase a mother’s risk for developing OCD. Overall, the work in this thesis provides the first glimpse into potential risk factors for perinatal OCD.

Transportsektorns utsläpp av växthusgaser står för ungefär en tredjedel av de totala utsläppen i Sverige. Till 2030 ska dessa minska med 70% jämfört med 2010 års nivåer. Utöver växthusgaser ger biltransporter upphov till trängsel och utsläpp av partiklar och gaser som påverkar hälsa och miljö negativt, särskilt i tät i stadsmiljö. På global, såväl som nationell nivå finns mål som strävar efter att förbättra miljön och inte sällan lyfts kollektivtrafik, gång och cykel fram som hållbara transportslag för stadsmiljö.  Studien Södertälje, cykel, city har sitt ursprung i Södertälje kommuns ambition att bli en bättre stad för cyklister. Idag konstateras att andelen resor som sker med cykel är låg trots stadens goda förutsättningar för cyklism. Ett mål i den kommunala cykelplanen är att understödja fler cykelresor med hjälp av förbättrad cykelinfrastruktur. Cykelinfrastrukturen innefattar flera delar och den här studien fokuserar på cykelparkering då brist på säker cykelparkering är en vanlig orsak till att södertäljebor avstår från att cykla. Med kartläggning av nuvarande cykelparkeringssituationen syftar denna studie till att producera kunskap till hjälp i planeringen av stadens framtida cykelparkering.  Med hjälp av litteratur på området, insamlad empirisk data och GIS-teknik visualiseras och analyseras hur stadskärnans cyklister parkerar och utformningen av stadskärnans cykelparkeringar. Av studiens resultat framgår att ungefär hälften av cyklarna inom undersökningsområdet parkeras utanför anordnad parkering och att det generellt sett inte råder någon kapacitetsbrist på cykelparkeringarna. Av de cyklar som parkerats utanför ställ återfinns 65% längre bort än 25 meter ifrån anordnade parkering. En av studiens slutsatser är att närhet till cykelparkering inom undersökningsområdet är bristfällig och att andra typer av cykelinfrastruktur är mer adekvat för att nå uppsatta mål om fler resor på cykel. / The transport sector's emissions of greenhouse gases account for about a third of the total emissions in Sweden, by the year 2030 these shall decrease by 70% compared to 2010 levels. In addition to greenhouse gases, car transport contributes to congestion and emissions of particles and gases that negatively affect health and the environment, especially in dense urban environments. At global, national and local levels there are goals in order to improve the environment which often highlight public transport, walking and cycling as sustainable modes of transport in the urban environment. The study Södertälje, cycle, city has its origins in the municipality of Södertälje’s ambition to become a better city for cyclists. Today, the municipality considers the proportion of trips made by bicycle is low even though the city has good conditions to incubate cycling. A designated tool in the municipal cycle plan is to support more cycle journeys with the use of an improved bicycling infrastructure. Organised bicycle parking is part of the bicycle infrastructure that can provide users a number of benefits. At the same time there is an inherent advantage of the bicycle which is its flexibility in terms of parking. Due to that, this study maps and analyses the bicycle parking situation in a central Södertälje. This in order to create greater knowledge and understanding of cyclists' needs but also to support the planning of the city's future bicycle parking. With the help of literature in the field, collected empirical data and GIS technology, how the city centre cyclists park and the design of the city centre bicycle parking is visualized and analysed. The results of the study show that approximately half of the bicycles in the study area are parked outside organized parking and that there is no generall lack of capacity in the organised bicycle parking. Of the bicycles parked outside racks, 90% are found far further than 25 meters from an organized car park. One of the study's conclusions is that proximity to bicycle parking within the study area is deficient and that other types of bicycle infrastructure are more adequate to achieve set goals for more trips by bicycle.

Inom stadsutvecklingen har bilen länge haft en dominerade ställning, med tiden har den dock kommit att bli allt mer ifrågasatt. Flera alternativa planeringsmodeller har tagits fram för att minska bilberoendet varav Morenos 15-minuterstad är en som fått stort genomslag. Dock har mycket få studier gjorts i en nordisk kontext där befolkningstätheten är låg. Syftet har därför varit att undersöka åsikter om 15-minuterstadens centrala pelare och möjligheten till förändrade resvanor i en medelstor svensk stad. Syftet besvarades med en enkät samtidigt som en dokumentanalys genomfördes över stadens översiktsplan med tillhörande trafikstrategi (2010). Resultatet från studien visade att både kommunen och invånare är generellt positivt inställda till 15-minuterstaden men det finns ett visst motstånd till en fullständig implementation. Social practice theory har använts i analysen för att förstå människors svårföränderliga vanor, vilka kan brytas ner till material, kompentens och mening. Materialaspekten har förändrats genom ny infrastruktur vilket kommunen motiverar med ny kompetens om hållbarhet. Invånarna tillskriver 15-minuterstaden en positiv mening genom bemärkelser som rörelse, omväxling, tillgänglighet, bekvämlighet, trygghet och flexibilitet. / Within urban development, the car has long had a dominant position, but over time it has come to be increasingly questioned. Several alternative planning models have been proposed to reduce car dependence, of which Moreno's 15-minute city is one that has become very popular. However, very few studies have been conducted in a Nordic context where the population density is low. The purpose has therefore been to examine opinions about the central pillars of the 15-minute city and the possibility of changing travel habits in a medium-sized Swedish city. The purpose was answered with a survey at the same time as a document analysis was carried out on the city's general plan with associated traffic strategy (2010). The results of the study showed that both the municipality and residents are generally positive about the 15-minute city, but there is some resistance to a full implementation. Social practice theory has been used in the analysis to understand people's hard-to-change habits, which can be broken down into material, competence and meaning. The material aspect has changed through new infrastructure, which the municipality justifies with new competence in sustainability. The residents attribute a positive meaning to the 15-minute city through meanings such as movement, change, accessibility, convenience, safety, and flexibility.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13558号 / 論医博第2287号 / 新制||医||1067(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 岩田 想, 教授 中川 一路, 教授 妹尾 浩 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

Das Mikromilieu solider Tumor (tumor mircoenvironment, TME) weist verschiedene Besonderheiten auf, von denen bekannt ist, dass sie zu Chemotherapieresistenz und Tumorprogression beitragen können. Neben der Extrazellulären Matrix (ECM), den cancer associated cells (CAC) und diversen Entzündungszellen tragen auch chemische und physikalische Besonderheiten (Hypoxie, Azidose, erhöhter Gewebedruck, oxidativer Stress und Nährstoffmangel) zu Tumorprogression und Chemotherapieresistenz bei. Zudem wissen wir, dass Hitzeschock-Proteine (HSPs), Toll-like Rezeptoren (TLRs) und ABC-Transporter mit erhöhter Chemotherapieresistenz und Tumorprogression im Pankreas- und Kolonkarzinom einhergehen. Hier wurde untersucht, ob ein in vitro induzierter Nährstoffmangel im HT29 Kolonkarzinom, im Panc-1 Pankreaskarzinom und im MIA PaCa-2 Pankreaskarzinom zu einer gesteigerten Expression von HSP70, HSP90, MDR1, ABCB5 und TLR1 bis TLR10 auf mRNA und Proteinebene führt. Zudem wurde unter allen Versuchsbedingungen die Stoffwechselaktivität über einen MTS-Test gemessen. Der Nährstoffmangel wurde über die Kultivierung in einem Hybridomamedium, welches als proteinfreies Medium gilt und über die Kultivierung in einem serumfreien Medium induziert. Es zeigte sich, dass insbesondere die entdifferenzierte Panc-1 Pankreaskarzinomzelllinie eine erhöhte Resistenz gegenüber dem induzierten Nährstoffmangel aufwies. Auf mRNA-Ebene zeigten sich bei allen drei Tumorzelllinien deutliche Expressionssteigerungen. Diese waren insbesondere im Hybridomamedium nachweisbar und traten beim HT29-Kolonkarzinom nach 48h und im Panc-1 Pankreaskarzinom bereits nach 24h auf. Besonders intensive Expressionssteigerungen konnten im HT29 Kolonkarzinom bei ABCB5, TLR7 und TLR9 nachgewiesen werden. Die Expression von MDR1 war insbesondere im MIA PaCa-2 Pankreaskarzinom gesteigert. Auf Proteinebene konnte im HT29 Kolonkarzinom eine Expressionssteigerung bei HSP90 und TLR6 nachgewiesen werden. Die Ergebnisse lassen zwei Interpretationen zu. Zum einen könnte über den Nährstoffmangel eine aggressivere Subpopulation selektioniert worden sein. In diesem Zusammenhang konnten die Expressionsdaten des Tumorstammzellmarkers CD133 leider nicht ausgewertet werden. Alternativ kann angenommen werden, dass die untersuchten Tumorzelllinien ihren aggressiven Phänotyp erst unter Nährstoffmangelbedingungen, wie wir sie regelmäßig in soliden Tumoren finden, zur Expression bringen. / The tumor microenvironment (TME) in solid tumors is low on nutrients and favors tumor progression and resistance to chemotherapies in different ways. In this study we cultured HT29 colorectal carcinoma cells, Panc-1 pancreatic carcinoma cells and MIA PaCa-2 pancreatic carcinoma cells in nutrient deprived conditions (NDC) and performed rtPCR expression analysis, SDS-PAGE and immunohistochemical staining after 24, 48 and 72 hours. Gene expression of ABC transporters (ABCB5, MDR1), heat-shock proteins (HSP70, HSP90) and Toll-like receptors (TLR1 – TLR10) in the NDC compared to normal condition was analyzed. We performed MTS tetrazolium assays to monitor the activity of the respiratory chain in any condition. We showed that the examined cell lines, and in particular Panc-1 pancreatic carcinoma, are very resistant to the NDC. The gens of interest showed increase expression after 48 hours (HT29) and 24 hours (Panc-1). The results suggest that culturing in NDC either selects a very aggressive and resistant subpopulation or NDC induces gene expression changes and shows us how cancer cells really perform in the nutrient deprived tumor environment. Unfortunately, we were not able to use the gene expression analysis of the stem cell marker CD133.

Exercise has been considered a cornerstone of diabetes prevention and treatment for decades, but the benefits of resistance training are less clear. Nineteen non-diabetic subjects (10 metabolic syndrome, 9 sedentary controls) underwent 8 weeks of supervised resistance training. After training, strength and V̇ O2max increased by 10% in both groups. Percent body fat decreased in subjects with the metabolic syndrome. Additionally, lean body mass increased in both groups (p<0.05). Expression of glucose transporter protein-4 (GLUT4), the principle insulin-responsive glucose transporter, increased significantly in both groups. 5-adenosine monophosphateactivated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) expression increased in both groups, indicating increased protein synthesis and mitochondrial biogenesis. Markers of insulin resistance measured by a euglycemic hyperinsulinemic clamp did not improve in subjects with the metabolic syndrome but increased significantly in control subjects (13%). Resistance training upregulates intracellular signaling pathways that may be beneficial for ameliorating the metabolic syndrome.

Bakgrund: Prognoser för den framtida konjunkturutvecklingen är av värde för såväl allmänheten som beslutsfattare i många led. De förlitar sig på olika former av ekonomiska prognoser för att justera sina förväntningar på efterfrågan och prissättning därefter.Forskningen kring transportsektorn som en konjunkturindikator har visat olika resultat beroende på flera faktorer men Tyskland som har en liknande transportsektor som Sverige introducerade nyligen ett nytt konjunktursmått som var baserat på tunga transporter. Syfte: Uppsatsen syftar till att med statistiska metoder undersöka om det finns eventuella samband mellan efterfrågan på transport genom tunga fordon och hela eller delar av den ekonomiska utvecklingen i Sverige som är av sådant slag att olika variabler kopplat till godstransport kan användas för att prognostisera ekonomisk upp- och nedgång. Genomförande: För att uppfylla studiens syfte har sekundärdata samlats in från OECD samt SCB &amp; Trafa. Variablerna som hämtats är BNP, IPI, transportarbete &amp; nyregistreringar. För att klargöra huruvida variablerna samspelar på kort &amp; lång sikt så testar vi för kointegration och Granger-Kausalitet. Slutsats: Vi finner inga bevis på att transportarbete eller nyregistreringar innehåller värdefull information för att prognosticera framtida konjunkturvärden. Vi finner samband mellan BNP &amp; IPI och nyregistreringar både på kort och lång sikt men tvärtom från vad studien syftade till visar vi att BNP och IPI föregår nyregistreringar i testet för Granger-kausalitet. / Background: Predicting economic growth is valuable for both the general public and decision makers in different parts of society. They rely on different kinds of econometric predictions to adjust their expectations related to price and demand. Studies based around the ability of transportation to predict future values of economic growth has shown differing results depending on various factors but Germany, who has a relatively similar transportation sector as Sweden, has recently implemented a new economic growth measure based on road freight. Aim: Through econometrical methods we aimed to study the relationship between the transportation sector, more specifically the road freight part, and economic growth and study road freights ability to predict future economic growth in Sweden. Completion: To fulfill the aim of the study we collected secondary data from SCB and OECD &amp; Trafa. Our data collection consisted of four variables which was GDP and IPI as economic growth proxies and new registrations for road freight vehicles and road freight per kilometer were chosen as variables for the road freight sector. To understand how road freight could predict future economic growth for both short- and long term we tested for Granger-causality and cointegration. Conclusion: Our study shows no evidence for road freight being a valuable indicator for predicting future economic growth. Relationships were found between GDP &amp; IPI and new registrations on short- and long term but in contradiction to our studies purpose the relationship was found to be from GDP &amp; IPI to new registrations and not the other way around.

The synthetic cathinones, 3,4- methylenedioxypyrovalerone (MDPV), 4-methylmethcathinone (mephedrone), and 3,4- methylenedioxymethcathinone (methylone), gained worldwide notoriety as the psychoactive components of ‘bath salts;’ a marketing term used to circumvent federal drug laws and permit their legal sale. Previous studies have shown that these drugs share pharmacological characteristics with cocaine and the amphetamines, however, descriptions of their neurotoxic properties are limited. Moreover, while forensic analysis has revealed that the most frequently abused bath salts ‘brands’ contain binary and ternary mixtures of MDPV, mephedrone, and methylone, the majority of preclinical research has focused on explicating the individual effects of these drugs. Therefore, the present dissertation aimed to address this limitation and characterize the acute and chronic effects of combined synthetic cathinone exposure on dopaminergic tone in mesolimbic and nigrostriatal brain regions. To accomplish this, male Swiss-Webster mice were administered MDPV, mephedrone, and methylone, individually or concomitantly, 1 time or 7 times over the course of two weeks and the corresponding effects of each treatment on mesolimbic and nigrostriatal brain tissue levels of dopamine (DA) and DA metabolites were analyzed using a high performance liquid chromatography – electrochemical detection (HPLC-ECD) assay. Additionally, motor-stimulant activity was evaluated after both dosing regimens using locomotor activity assays, while immunoblot and immunostaining techniques were used to evaluate the chronic effects of co-synthetic cathinone exposure on tissue levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), monoamine oxidase B (MAO-B), catechol-O-methyltransferase (COMT), and glial fibrillary acidic protein (GFAP). Results from these studies provide evidence of a significant pharmacological interaction among major bath salt constituents, MDPV, mephedrone, and methylone. This was observed acutely as enhanced DA responses and chronically as functional toxicity at the DA synapse. Furthermore, such interactions may contribute to the deleterious effects reported by bath salt users. Together, these findings have shown that the composition of bath salts preparations can significantly influence their psychostimulant and toxic effects, substantiating the importance of modeling bath salts as drug mixtures.

The Swedish government has stated an ambition that traveling by bicycle should increase. Therefore, Swedish municipalities are obliged to form strategies to promote bicycling. The aim for this paper was to examine strategies for promoting bicycling in Swedish municipalities and reveal its core content. Method: documents from 18 municipalities was identified and examined by using an established qualitative method. The examination took part in February and March of 2021. Result: Nine categories emerged which was sorted into five domains (continuous maintenance, promotion/influence, new construction, overall ambitions and follow-up) which constitute the main result. Conclusion: The content of the strategies tends to be of a quite general and overall nature with the potential to cover most aspects of the phenomenon bicycling. There is a lack of focus on behavioral changing measures and focus on specific tools or methods for evaluation can also improve / <p>Betyg i Ladok 220617.</p>

No description available.