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AbstractThe primary purpose of understanding disease etiology is to explain how a specific phenotype is determined by genotype. In pursue of this aim, exploring the diversity in DNA sequence variants that affect biomedical traits, especially those related to the onset and progression of genetically determined human disease. The human leukocyte antigens (HLA) are highly polymorphic cell surface pro
Importance: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein-1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. Objective: To explore whether circulating levels of MCP-1 are associated with risk of inc
Background: 27-Hydroxycholesterol (27HC) stimulates estrogen receptor-positive (ER+) breast cancer (BC) progression. Inhibiting the sterol 27-hydroxylase (CYP27A1) abrogates these growth-promoting effects of 27HC in mice. However, the significance of CYP27A1 expression on BC biology and prognosis is unclear. Methods: Intratumoral CYP27A1 expression in invasive BC was measured by immunohistochemist
Background Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder occurring predominantly in young women. POTS is characterized by an excessive heart rate increase when assuming upright posture accompanied by symptoms of orthostatic intolerance. The pathophysiology of POTS has not been fully established and is believed to be multifactorial. Purpose We a
Importance: Adjuvant imatinib is associated with improved recurrence-free survival (RFS) when administered after surgery to patients with operable gastrointestinal stromal tumor (GIST), but its influence on overall survival (OS) has remained uncertain. Objective: To evaluate the effect of adjuvant imatinib on OS of patients who have a high estimated risk for GIST recurrence after macroscopically c
Aims/hypothesis: Genetic studies show coupling of genes affecting beta cell function to type 1 diabetes, but hitherto no studies on whether beta cell dysfunction could precede insulitis and clinical onset of type 1 diabetes are available. Methods: We used 40-day-old BioBreeding (BB) DRLyp/Lyp rats (a model of spontaneous autoimmune type 1 diabetes) and diabetes-resistant DRLyp/+ and DR+/+ litterma
Background: Regimens based on ibrutinib alone and lenalidomide and rituximab in combination show high activity in patients with relapsed or refractory mantle cell lymphoma. We hypothesised that the combination of all three drugs would improve efficacy compared with previously published data on either regimen alone. Methods: In this multicentre, open-label, single-arm, phase 2 trial, we enrolled pa
Background: The purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer. Methods: We applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the curren
Jordens plattektoniska rörelser leder till tektoniska skeenden vid plattgränserna, bland annat bergskedjebildning, då berggrunden utsätts för förändringar i tryck och temperatur. Vid ändrat tryck och ändrad temperatur förändras också bergarter: de ursprungliga mineralen konsumeras i kemiska reaktioner och i stället bildas nya mineral som är stabila vid de nya fysikaliska förhållandena - en processDating of metamorphic events is crucial for the understanding and reconstruction of large-scale geological processes such as orogenesis. Zircon is one of the most commonly used minerals for dating of igneous and metamorphic events. Zircon incorporates uranium and excludes lead during crystallization, and with time the uranium decays to lead. The diffusion rates of both elements are slow, making zi
Although recent clinical trials targeting amyloid-β in Alzheimer's disease have shown promising results, there is increasing evidence suggesting that understanding alternative disease pathways that interact with amyloid-β metabolism and amyloid pathology might be important to halt the clinical deterioration. In particular, there is evidence supporting a critical role of astroglial activation and a
AIMS: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability.METHODS AND RESULTS: Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage assoc
Att planera lokal och regional kollektivtrafik i så kallade ’starka stråk’ – det vill säga att koncentrera infrastruktur och resurser till ett antal färre, men attraktivare stråk i en stad eller en region – är ett standardförfarande i samtida kollektivtrafikplanering. Så har inte alltid varit fallet dock. Denna avhandling visar hur organiseringen av beslutsfattande, planeringspraktiker och den rumPlanning local and regional public transport in so-called ’transit corridors’ – i.e., to concentrate infrastructure and resources to few, but more attractive corridors in a city or a region – is commonplace in contemporary public transport planning. This has not always been the case, however. In this thesis I analyze how transit corridors have come to dominate the policies and planning practices o
Post partum depression är ett omfattande folkhälsoproblem som utlandsfödda mödrar löper ökad risk att drabbas av. Rutinmässig screening av alla nyblivna mödrar för post partum depression har implementerats i många länder för att öka identifikationen, men tidigare forskning indikerar att hälso- och sjukvårdspersonal upplever screening av utlandsfödda mödrar som en svår arbetsuppgift. Det övergripanPostpartum depression is a major public health problem, which immigrant mothers are at particular risk of being affected by. Routine screening is implemented by many countries to increase identification, but research suggests that health care professionals experience screening of immigrant mothers as challenging. The overall aim of this thesis was therefore to develop an evidence-based educational
Trots likadana tekniska förutsättningar visade den aktuella avhandlingen på att energianvändningen varierade stort mellan hushåll – vilket även tidigare forskning pekat på. Det skiljde en faktor två till tre mellan högsta och lägsta energianvändningen för de grupper av likadana hus som studerades. Skillnaden i vattenanvändning var ännu större, nämnare bestämt en faktor sex. De boendes val och vardTo achieve global energy goals, energy use in residential buildings must decrease. The implementation of technical measures is crucial but alone it is not sufficient; residents need to change their behaviour as well. However, households are not a homogeneous group in terms of their energy use and behaviour; rather, the use varies between households and over time. To promote energy savings in build
Background Immunotherapy targeting the amyloid beta (A beta) peptide is a potential strategy to slow the progression of Alzheimer's disease. We aimed to assess the safety and tolerability of CAD106, a novel active A beta immunotherapy for patients with Alzheimer's disease, designed to induce N-terminal A beta-specific antibodies without an A beta-specific T-cell response. Methods We did a phase 1,
The aim of this work was to develop a model suited for detailed studies of aerosol dynamics, gas and particle phase chemistry within urban plumes, from local scale (1x1 km(2)) to regional scale. This article describes and evaluates the trajectory model for Aerosol Dynamics, gas and particle phase CHEMistry and radiative transfer (AD-CHEM). The model treats both vertical and horizontal dispersion p
Purpose -- The overall purpose of this study is to enhance the understanding of customer perceived service quality within grocery retailing in a North European context. We do this by comparing customer perceived service quality evaluations of the traditional supermarket store with evaluations of the discount store. Design/methodology/approach -- This study is based on empirical data from four stor
