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Sökning: WFRF:(Johansson Marcus)

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1.
  • Johansson, Lovisa, et al. (författare)
  • Genetic variance in the adiponutrin gene family and childhood obesity.
  • 2009
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:4
  • Tidskriftsartikel (refereegranskat)abstract
    • AIM: The adiponutrin gene family consists of five genes (PNPLA1-5) coding for proteins with both lipolytic and lipogenic properties. PNPLA3 has previously been associated with adult obesity. Here we investigated the possible association between genetic variants in these genes and childhood and adolescent obesity. METHODS/RESULTS: Polymorphisms in the five genes of the adiponutrin gene family were selected and genotyped using the Sequenom platform in a childhood and adolescent obesity case-control study. Six variants in PNPLA1 showed association with obesity (rs9380559, rs12212459, rs1467912, rs4713951, rs10947600, and rs12199580, p<0.05 after adjustment for age and gender). Three variants in PNPLA3 showed association with obesity before, but not after, adjustment for age and gender (rs139051, rs12483959, and rs2072907, p>0.05). When analyzing these SNPs in relation to phenotypes, two SNPs in the PNPLA3 gene showed association with insulin sensitivity (rs12483959: beta = -0.053, p = 0.016, and rs2072907: beta = -0.049, p = 0.024). No associations were seen for PNPLA2, PNPLA4, and PNPLA5. CONCLUSIONS: Genetic variation in the adiponutrin gene family does not seem to contribute strongly to obesity in children and adolescents. PNPLA1 exhibited a modest effect on obesity and PNPLA3 on insulin sensitivity. These data, however, require confirmation in other cohorts and ethnic groups.
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2.
  • van de Vegte, Yordi, et al. (författare)
  • Genetic insights into resting heart rate and its role in cardiovascular disease
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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3.
  • Carreras-Torres, Robert, et al. (författare)
  • Obesity, metabolic factors and risk of different histological types of lung cancer : a Mendelian randomization study
  • 2017
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 12:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings: We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01-1.43] and for small cell lung cancer (OR [95% CI] = 1.52 [1.15-2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m(2)]), but not for adenocarcinoma (OR [95% CI] = 0.93 [0.79-1.08]) (P-heterogeneity = 4.3x10(-3)). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10(-3)), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95% CI] = 0.90 [0.84-0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95% CI] = 1.63 [1.25-2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions: Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior.
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4.
  • Chursa, Urszula, et al. (författare)
  • Overexpression of protein kinase STK25 in mice exacerbates ectopic lipid accumulation, mitochondrial dysfunction and insulin resistance in skeletal muscle.
  • 2017
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 60:3, s. 553-567
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding the molecular networks controlling ectopic lipid deposition and insulin responsiveness in skeletal muscle is essential for developing new strategies to treat type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of liver steatosis, hepatic lipid metabolism and whole body glucose and insulin homeostasis. Here, we assessed the role of STK25 in control of ectopic fat storage and insulin responsiveness in skeletal muscle.Skeletal muscle morphology was studied by histological examination, exercise performance and insulin sensitivity were assessed by treadmill running and euglycaemic-hyperinsulinaemic clamp, respectively, and muscle lipid metabolism was analysed by ex vivo assays in Stk25 transgenic and wild-type mice fed a high-fat diet. Lipid accumulation and mitochondrial function were also studied in rodent myoblasts overexpressing STK25. Global quantitative phosphoproteomics was performed in skeletal muscle of Stk25 transgenic and wild-type mice fed a high-fat diet to identify potential downstream mediators of STK25 action.We found that overexpression of STK25 in transgenic mice fed a high-fat diet increases intramyocellular lipid accumulation, impairs skeletal muscle mitochondrial function and sarcomeric ultrastructure, and induces perimysial and endomysial fibrosis, thereby reducing endurance exercise capacity and muscle insulin sensitivity. Furthermore, we observed enhanced lipid accumulation and impaired mitochondrial function in rodent myoblasts overexpressing STK25, demonstrating an autonomous action for STK25 within cells. Global phosphoproteomic analysis revealed alterations in the total abundance and phosphorylation status of different target proteins located predominantly to mitochondria and sarcomeric contractile elements in Stk25 transgenic vs wild-type muscle, respectively, providing a possible molecular mechanism for the observed phenotype.STK25 emerges as a new regulator of the complex interplay between lipid storage, mitochondrial energetics and insulin action in skeletal muscle, highlighting the potential of STK25 antagonists for type 2 diabetes treatment.
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5.
  • Dolinska, Monika, et al. (författare)
  • Characterization of the bone marrow niche in patients with chronic myeloid leukemia identifies CXCL14 as a new therapeutic option
  • 2023
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 142:1, s. 73-89
  • Tidskriftsartikel (refereegranskat)abstract
    • Although tyrosine kinase inhibitors (TKIs) are effective in treating chronic myeloid leukemia (CML), they often fail to eradicate the leukemia-initiating stem cells (LSCs), causing disease persistence and relapse. Evidence indicates that LSC persistence may be because of bone marrow (BM) niche protection; however, little is known about the underlying mechanisms. Herein, we molecularly and functionally characterize BM niches in patients with CML at diagnosis and reveal the altered niche composition and function in these patients. Long -term culture initiating cell assay showed that the mesenchymal stem cells from patients with CML displayed an enhanced supporting capacity for normal and CML BM CD34+CD38- cells. Molecularly, RNA sequencing detected dysregulated cytokine and growth factor expression in the BM cellular niches of patients with CML. Among them, CXCL14 was lost in the BM cellular niches in contrast to its expression in healthy BM. Restoring CXCL14 significantly inhibited CML LSC maintenance and enhanced their response to imatinib in vitro, and CML engraftment in vivo in NSG-SGM3 mice. Importantly, CXCL14 treatment dramatically inhibited CML engraftment in patient-derived xenografted NSG-SGM3 mice, even to a greater degree than imatinib, and this inhibition persisted in patients with suboptimal TKI response. Mechanistically, CXCL14 upregulated inflammatory cytokine signaling but downregulated mTOR signaling and oxidative phosphorylation in CML LSCs. Together, we have discovered a suppressive role of CXCL14 in CML LSC growth. CXCL14 might offer a treatment option targeting CML LSCs.
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6.
  • Furukawa, Toshi A., et al. (författare)
  • Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
  • 2021
  • Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
  • Forskningsöversikt (refereegranskat)abstract
    • Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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7.
  • Gaines, Hans, et al. (författare)
  • Six-week follow-up after HIV-1 exposure: a position statement from the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy
  • 2016
  • Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 48:2, s. 93-98
  • Forskningsöversikt (refereegranskat)abstract
    • In 2014 the Public Health Agency of Sweden and the Swedish Reference Group for Antiviral Therapy (RAV) conducted a review and analysis of the state of knowledge on the duration of follow-up after exposure to human immunodeficiency virus (HIV). Up until then a follow-up of 12 weeks after exposure had been recommended, but improved tests and new information on early diagnosis motivated a re-evaluation of the national recommendations by experts representing infectious diseases and microbiology, county medical officers, the RAV, the Public Health Agency, and other national authorities. Based on the current state of knowledge the Public Health Agency of Sweden and the RAV recommend, starting in April 2015, a follow-up period of 6 weeks after possible HIV-1 exposure, if HIV testing is performed using laboratory-based combination tests detecting both HIV antibody and antigen. If point-of-care rapid HIV tests are used, a follow-up period of 8 weeks is recommended, because currently available rapid tests have insufficient sensitivity for detection of HIV-1 antigen. A follow-up period of 12 weeks is recommended after a possible exposure for HIV-2, since presently used assays do not include HIV-2 antigens and only limited information is available on the development of HIV antibodies during early HIV-2 infection. If pre- or post-exposure prophylaxis is administered, the follow-up period is recommended to begin after completion of prophylaxis. Even if infection cannot be reliably excluded before the end of the recommended follow-up period, HIV testing should be performed at first contact for persons who seek such testing.
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8.
  • Galván, Ignacio Fdez., et al. (författare)
  • OpenMolcas : From Source Code to Insight
  • 2019
  • Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 15:11, s. 5925-5964
  • Tidskriftsartikel (refereegranskat)abstract
    • In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.
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9.
  • Ji, Xuemei, et al. (författare)
  • Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk
  • 2018
  • Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
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10.
  • Ji, Xuemei, et al. (författare)
  • Protein-altering germline mutations implicate novel genes related to lung cancer development
  • 2020
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
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12.
  • Johansson, Cecilia, et al. (författare)
  • Alcohol consumption and risk of incident atrial fibrillation : a population-based cohort study
  • 2020
  • Ingår i: European journal of internal medicine. - : Elsevier. - 0953-6205 .- 1879-0828. ; 76, s. 50-57
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: Atrial fibrillation (AF) is a common tachyarrhythmia. High alcohol consumption is associated with increased AF risk. It remains unclear whether lower levels of alcohol consumption are also associated with AF risk, and whether the association differs between men and women. In this study, we investigated the association between low to moderate levels of alcohol consumption and AF risk in men and women.METHODS: We performed a population-based cohort study of 109,230 health examination participants in northern Sweden. Data regarding alcohol intake were obtained using a questionnaire administered at the health examination. Incident AF cases were identified from the Swedish National Patient Registry.RESULTS: AF was diagnosed in 5,230 individuals during a total follow-up of 1,484,547 person-years. Among men, AF risk increased over quartiles of weekly alcohol consumption (P for trend 0.001). Men with alcohol consumption in the highest quartile (≥4.83 standard drinks [each drink containing 12 gs of ethanol] per week; SDW) had a HR of 1.21 (95% CI 1.09-1.34) for AF compared to men in the lowest quartile (<0.90 SDW). In men, problem drinking was also associated with an increased AF risk (HR: 1.24; 95% CI: 1.10-1.39). Among women, AF risk was not significantly associated with alcohol consumption (P for trend 0.09 for decreasing risk of AF over quartiles of weekly alcohol consumption) or problem drinking (HR: 1.00; 95% CI 0.70-1.42).CONCLUSION: Self-reported alcohol consumption and problem drinking were associated with an increased risk of AF among men, but not in women.
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13.
  • Johansson, Cecilia, et al. (författare)
  • Diabetes, prediabetes, and atrial fibrillation : a population-based cohort study based on national and regional registers
  • 2023
  • Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:5, s. 605-615
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF.Objective: To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF.Methods: We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference.Results: The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF.Conclusions/interpretation: The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.
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14.
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15.
  • Johansson, Cecilia, 1988- (författare)
  • Risk markers and incidence of atrial fibrillation in northern Sweden
  • 2023
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Atrial fibrillation (AF) is the most common clinically significant arrythmia with a prevalence of approximately 3% in the general population. Less is known about the incidence of AF. In order to reduce the incidence of AF, it is of essence to identify modifiable risk factors for the disease.Aims: The aims of this thesis were (1) to estimate the incidence of AF and to assess the prevalence of provoking factors and risk factors for stroke and systemic embolism at the time of AF diagnosis, (2) to study the association between alcohol consumption and risk of AF, (3) to study the association between weight, height, weight change, and risk of AF, and (4) to study the association between normal or high normal blood pressure (BP), compared to optimal BP, and risk of AF.Methods: To determine the incidence of AF and the prevalence of provoking factors and risk factors for stroke and systemic embolism at AF diagnosis, an observational study was performed between January 1, 2011, and December 31, 2012, in the municipalities of Skellefteå and Norsjö, Västerbotten, Sweden. Diagnosis registries were searched for cases of incident AF. All AF diagnoses were verified by electrocardiogram. Data regarding provoking factors, type of AF and presence of risk factors for stroke and systemic embolism (as assessed by the CHA2DS2-VASc score) was obtained from medical records. Incidence was calculated by dividing the number of incident AF cases by the time at risk for the population.The association between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF was investigated in a population-based cohort study of participants of the Västerbotten Intervention Programme (VIP). Residents of Västerbotten County aged 30, 40, 50 and 60 years who had participated in the VIP health examinations between January 1, 1988, and September 5, 2014, were included. Individuals who had been diagnosed with AF before participating in the VIP were excluded. Study participants were followed until a diagnosis of AF, death, migration from the study area, or the end of the study on September 5, 2014. Incident AF cases were identified using the Swedish National Patient Registry. The health examinations included measurements of height and weight, systolic BP, diastolic BP, fasting glucose, oral glucose tolerance, and cholesterol. Participants also answered a questionnaire addressing any history of diabetes and myocardial infarction, alcohol use, education level, smoking habits, medications, and physical activity. Optimal BP was defined as BP < 120/80 mm Hg. Normal BP was defined as BP 120–129/80–84 mm Hg. High normal BP was defined as BP 130–139/85–89 mm Hg. Hypertension was defined as BP ≥ 140/90 mm Hg. Cox proportional hazards regression analysis was used to assess the associations between alcohol consumption, weight, height, weight change, normal BP, high normal BP, and risk of AF. These were performed with crude, age-adjusted, and multivariable models adjusted for other cardiovascular risk factors (age, sex, body mass index, hypertension, cholesterol, previous myocardial infarction, diabetes, problem drinking, smoking, education level, and leisure-time physical activity).Results: The incidence of AF was 4.0 cases of AF per 1000 person-years. In approximately one fifth of participants, a provoking factor was present at the first episode of AF. The CHA2DS2-VASc score was 2 or higher in 81% of participants. Permanent AF was the most common type of AF and was seen in about one third of the participants.When studying the association between alcohol consumption and risk of AF, 109,230 health examination participants were included in the study cohort and were followed for 1,484,547 person-years. During the study period, 5230 participants developed incident AF. Men with alcohol consumption in the highest quartile (≥ 4.83 standard drinks weekly) had a hazard ratio (HR) of 1.21 (95% confidence interval [CI] 1.09-1.34) for AF in a multivariable model when compared to men with an alcohol consumption in the lowest quartile (< 0.90 standard drinks weekly). In men, problem drinking was also associated with an increased risk of AF (HR 1.24, 95% CI 1.10–1.39 in a multivariable model). Among women, no significant association between alcohol consumption, problem drinking, and risk of AF was identified.In a fully adjusted model, height, weight, body mass index, and body surface area were positively associated with risk of incident AF. Among participants who underwent two health examinations 10 years apart, 1142 persons developed AF. The mean weight change from baseline was a weight gain of 4.8%. There was no significant association between either weight gain or weight loss and risk of AF.In the study of the association between normal BP, high normal BP, and risk of AF, 109,697 persons with a total of 162,982 health examinations were included. Incident AF was diagnosed in 5260 participants. There was an increased risk of incident AF in persons with normal BP (HR 1.11, 95% CI 1.01–1.27) and in persons with high normal BP (HR 1.23, 95% CI 1.10–1.38) compared to optimal BP in a multivariable model. Systolic BP and diastolic BP were associated with risk of incident AF, with HRs of 1.11 (95% CI 1.10–1.13) and 1.13 (95% CI 1.09–1.16) per 10 mmHg, respectively, in multivariable models. A restricted cubic spline analysis indicated a gradually increasing risk of AF with increasing systolic BP and diastolic BP.Conclusions: AF has an incidence of 4.0 per 1000 person-years. Alcohol consumption and problem drinking were associated with higher risk of AF in men, but not in women. Weight, height, body mass index, and body surface area were associated with increased risk of incident AF. Normal BP and high normal BP, when compared to optimal BP, were associated with increased risk of incident AF.
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16.
  • Johansson, Cecilia, et al. (författare)
  • Weight, height, weight change, and risk of incident atrial fibrillation in middle-aged men and women
  • 2020
  • Ingår i: Journal of Arrhythmia. - : John Wiley & Sons. - 1880-4276 .- 1883-2148. ; 36:6, s. 974-981
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Anthropometric factors are reported to be risk factors for atrial fibrillation (AF), but it is unclear whether weight change in mid‐life is associated with AF. We aimed to study the possible associations of weight, height, and weight change with the risk of incident AF in men and women.Methods: Our study cohort included 108 417 persons (51% women) who participated in a population‐based health examination in northern Sweden at 30, 40, 50, or 60 years of age. The health examination included weight and height measurement and collection of data regarding cardiovascular risk factors. Within this cohort, 40 275 participants underwent two health examinations with a 10‐year interval. We identified cases with a first‐ever diagnosis of AF through the Swedish National Patient Registry.Results: During a total follow‐up of 1 469 820 person‐years, 5154 participants developed incident AF. The mean age at inclusion was 46.3 years, and mean age at AF diagnosis was 66.6 years. After adjustment for potential confounders, height, weight, body mass index (BMI), and body surface area (BSA) were positively associated with risk of incident AF in both men and women. Among participants who underwent two health examinations 10 years apart, 1142 persons developed AF. The mean weight change from baseline was a gain of 4.8%. Weight gain or weight loss was not significantly associated with risk of incident AF.Conclusions: Height, weight, BMI, and BSA showed positive associations with risk of incident AF in both men and women. Midlife weight change was not significantly associated with AF risk.
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17.
  • Johansson, Kristina, 1986- (författare)
  • Biomarkers and risk of intracerebral hemorrhage : population-based studies in northern Sweden
  • 2021
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • BackgroundIntracerebral hemorrhage (ICH) is a disease associated with a high morbidity and mortality and treatment options for the condition are limited. Even though an ICH event usually comes as a surprise to the affected individual, pathogenetic processes often have occurred before the sudden ICH event and may have preceded disease onset by years. It is possible that individuals at increased risk of ICH could be identified using biomarkers, for example markers of hemostasis and fibrinolysis. Even if these biomarkers are not part of the causal chain, they could be used as risk indicators to better define high-risk groups. Another approach could be to measure already established risk markers for ICH, such as self-reported alcohol consumption, using a blood biomarker. That could increase measurement reliability and consequently the accuracy of the estimates of ICH risk.AimsThe aim of this thesis was to investigate potential biomarkers and risk of ICH. Specific aims were to evaluate the associations between factor XII, D-dimer, von Willebrand factor (VWF), ABO blood groups with focus on blood group O, phosphatidylethanol (PEth), and risk of ICH.MethodsIn our first study, aiming to investigate the association between factor XII and risk of hemorrhagic stroke, we followed participants of the health examination northern Sweden MONItoring trends and determinants in CArdiovascular disease (MONICA) performed in 1994 as a cohort until 2011. Factor XII concentrations were measured in blood samples drawn at the baseline health examination where the participants also answered a questionnaire regarding lifestyle factors and medical history. Diagnosis codes from the National Patient Register and the Swedish Cause of Death Register were used to find cases of hemorrhagic stroke, defined as ICH or subarachnoid hemorrhage.  In the subsequent studies, the associations between biomarkers (factor XII, D-dimer, VWF, ABO blood groups, and PEth) and risk of ICH were investigated using a matched, nested case-referent design including individuals that had participated in the Västerbotten Intervention Programme, the MONICA and the Mammography Screening Project in 1985–2007. The participants donated blood samples at baseline for future research which were stored at -80 degrees C until biomarker analyses. The majority of the participants also underwent a baseline health examination including a questionnaire. First-ever ICH diagnoses during the study period 1985–2007 were validated using medical records and autopsy reports. To each case, two referents were matched for age, sex, geographical region, health examination date and health examination setting.  ResultsIn the cohort study of the association between factor XII concentrations and risk of hemorrhagic stroke, 1,852 participants were included among which 30 experienced a hemorrhagic stroke event. There was an association between high factor XII and risk of hemorrhagic stroke in a multivariable model (hazard ratio 1.51; 95% confidence interval [CI] 1.03–2.21 per standard deviation [SD] of factor XII). In the case-referent study of the association between factor XII and risk of ICH, 70 cases with ICH and 137 matched referents were included. We found no association between factor XII and risk of ICH in a multivariable model (odds ratio [OR] 1.06; 95% CI 0.57–1.97 per SD of factor XII). The study of the association between D-dimer and risk of ICH included 141 cases and 255 matched referents. We found an association between D-dimer and risk of ICH in a multivariable model (OR 1.36; 95% CI 1.05–1.77 per SD of D-dimer). When stratifying the analysis for time between blood sampling and ICH event in tertiles, the association remained significant in the cases with the shortest time between blood sampling and ICH event in a multivariable model (OR 1.78; 95% CI 1.05–3.05 per SD of D-dimer). The study investigating the association between VWF and risk of ICH included 139 cases and 276 referents. We found no association between VWF and risk of ICH in a multivariable model (OR 0.85; 95% CI 0.54–1.34 per SD of VWF). In the analysis investigating the associations between ABO blood groups and risk of ICH, 162 cases and 317 referents were included. We found no association between blood group O compared to non-O blood groups and risk of ICH (OR 0.96; 95% CI 0.65–1.42). In the study of the association between PEth concentrations and risk of ICH, 97 cases and 180 referents were included. There was an association between PEth concentrations > 0.30 µmol/L compared to < 0.01 µmol/L and risk of ICH in a multivariable model (OR 4.64; 95% CI 1.49–14.40).ConclusionsHigh concentrations of D-dimer and PEth are associated with an increased risk of ICH. Our conclusion of the two studies investigating the association between factor XII and risk of hemorrhagic stroke and ICH respectively is that there is no association between factor XII and risk of ICH. We found no association between VWF or blood group O and risk of ICH.
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18.
  • Johansson, Kristina, et al. (författare)
  • D-Dimer is associated with first-ever intracerebral hemorrhage : a nested case-control study
  • 2018
  • Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 49:9, s. 2034-2039
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose - Hypertension is the most important risk factor for intracerebral hemorrhage (ICH), but further characterization is needed for groups at high risk of ICH. One way to predict the risk of developing a disease is with plasma biomarkers. This study aimed to investigate the association between the biomarker, D-dimer, and ICH risk.Methods - This population-based, nested case-control study was conducted using data from 2 population-based surveys; the Vasterbotten Intervention Programme and MONICA Northern Sweden (Monitoring Trends and Determinants in Cardiovascular Disease). All participants underwent a health examination and blood sampling at baseline before the event. Cases (n=141) were diagnosed with a first-ever ICH between 1985 and March 2007. One or 2 controls (n=255) were matched to each case.Results - The median age was 60 years; 39% of participants were women; and the median time from blood sampling to ICH was 5.2 years. When D-dimer was evaluated as a continuous variable, it was significantly associated with ICH. After multivariable adjustment (for hypertension, body mass index, cholesterol levels, diabetes mellitus, and smoking), the odds ratio was 1.36 per SD of D-dimcr (95% CI, 1.05-1.77). When participants were stratified in 3 groups according to time from blood sampling at health examination to ICH, we found that the association between D-dimer levels and ICH was most pronounced in individuals with the shortest time from blood sampling to ICH event (<3.5 years; odds ratio, 1.78; 95% CI, 1.05-3.05).Conclusions - High plasma concentrations of D-dimer were associated with increased risk of a future ICH, after adjusting for cardiovascular risk factors. This association was predominantly driven by the cases with the shortest time from blood sampling to ICH event.
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19.
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20.
  • Johansson, Kristina, et al. (författare)
  • Factor XII as a Risk Marker for Hemorrhagic Stroke : A Prospective Cohort Study
  • 2017
  • Ingår i: Cerebrovascular diseases extra. - : S. Karger. - 1664-5456. ; 7:1, s. 84-94
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Coagulation factor XII (FXII) is involved in pathological thrombus formation and is a suggested target of anticoagulants. It is unclear whether FXII levels are correlated with cardiovascular risk factors and whether they are associated with myocardial infarction or ischemic or hemorrhagic stroke. The aim of this study was to investigate the correlation between FXII and cardiovascular risk factors in the general population. We also aimed to study the associations between FXII levels and future myocardial infarction and ischemic and hemorrhagic stroke.METHODS: This prospective cohort study measured FXII levels in 1,852 randomly selected participants in a health survey performed in northern Sweden in 1994. Participants were followed until myocardial infarction, stroke, death, or until December 31, 2011.RESULTS: During the median follow-up of 17.9 years, 165 individuals were diagnosed with myocardial infarction, 108 with ischemic stroke, and 30 with hemorrhagic stroke. There were weak correlations between FXII and body mass index, cholesterol, and hypertension. There was no association between FXII and myocardial infarction or ischemic stroke, neither in univariable Cox regression analysis nor after adjustment for age, sex, smoking, body mass index, cholesterol, hypertension, and diabetes. In univariable Cox regression analysis, the hazard ratio for the association between FXII levels and hemorrhagic stroke was 1.42 per SD (95% confidence interval: 0.99-2.05). In the multivariable model, higher levels of FXII were associated with increased risk of hemorrhagic stroke (hazard ratio 1.51 per SD; 95% confidence interval: 1.03-2.21).CONCLUSION: We found an independent association between FXII levels and the risk of hemorrhagic stroke, but not between FXII levels and ischemic stroke or myocardial infarction.
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21.
  • Johansson, Kristina, et al. (författare)
  • Factor XII Concentrations and Risk of Intracerebral Haemorrhage : A Prospective Case-Referent Study
  • 2021
  • Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier. - 1052-3057 .- 1532-8511. ; 30:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: In a previous pilot study, we found an association between high factorXII levels and risk of haemorrhagic stroke suggesting that factor XII is a risk markerfor intracerebral haemorrhage (ICH). The aim of this study was to further investigate the association between factor XII and risk of ICH in a larger population.Materials and Methods:This study was conducted as a prospective nested case-referent study. All participants underwent a health examination and blood sampling for factor XII analysis at baseline. Cases were defined as participants who were diagnosed with a first-ever ICH between 1985 and 2000. Two referents were matched to eachcase.Results:We identified 70 individuals withfirst-ever ICH and 137 matchedreferents who had undergone a health examination and donated blood samples Factor XII Concentrations and Risk of Intracerebral Haemorrhage. A Prospective Case-Referent Studybefore the ICH event. The mean age was 54 years, and 33% were women. The median time-to-event was 3.5 years (range 0.04 to 10.2 years). Conditional logistic regression showed no association between factor XII and risk of ICH, (odds ratio1.06 per SD; [95% confidence interval: 0.57–1.97] in a multivariable model).Conclusions: A previous finding of an association between high concentration of factor XII and risk of ICH could not be replicated in this larger study
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22.
  • Johansson, Kristina, et al. (författare)
  • Phosphatidylethanol Levels, As a Marker of Alcohol Consumption, Are Associated With Risk of Intracerebral Hemorrhage
  • 2020
  • Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 51:7, s. 2148-2152
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: Previous observational studies have shown a moderately increased risk of intracerebral hemorrhage (ICH) with high self-reported alcohol consumption. However, self-reported data tend to underestimate alcohol consumption. Phosphatidylethanol is a specific biomarker reflecting alcohol intake during the last month and correlates with the amount of alcohol consumed. The present study aimed to investigate the association between phosphatidylethanol levels and the risk of future ICH.Methods: This population-based nested case-referent study was conducted within the Northern Sweden Health and Disease Cohort. At baseline, all participants underwent a health examination, including a questionnaire with questions about alcohol consumption. A blood sample was collected and stored at −80°C, and phosphatidylethanol 16:0/18:1 levels were measured in packed erythrocytes. Cases (n=97) were diagnosed with a first-ever ICH between 1985 and 2007. Two referents (n=180) were matched to each case.Results: The mean age at baseline was 55 years, 39% of participants were women, and the mean time from blood sampling to ICH was 7.3 years. Only phosphatidylethanol and hypertension remained independently associated with ICH in a multivariable model. Participants with phosphatidylethanol >0.30 μmol/L had an increased risk of ICH compared with those with phosphatidylethanol <0.01 μmol/L (odds ratio, 4.64 [95% CI, 1.49–14.40]).Conclusions: High blood concentrations of phosphatidylethanol were associated with an increased risk of future ICH. This association was independent of hypertension and other risk factors for ICH. Our findings suggest that phosphatidylethanol, as a marker of alcohol consumption, may be used as a risk marker of future ICH.
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23.
  • Johansson, Kristina, et al. (författare)
  • Von Willebrand factor, ABO blood group, and risk of first-ever intracerebral hemorrhage : A prospective nested case-control study
  • 2020
  • Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 195, s. 77-80
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and purpose: Low levels of von Willebrand factor (VWF) were associated with intracerebral hemorrhage (ICH) in a previous study. Persons with blood group O have lower VWF levels than other ABO blood groups. This study aimed to investigate the association between VWF and the risk of ICH in adults, as well as the association between ABO blood group and risk of ICH.Methods: This population-based, nested case-control study was conducted using data and blood samples from health examinations between 1985 and 2007. All participants were followed, and cases with first-ever ICH were identified and validated. One or two controls were matched to each case.Results: During a median follow-up time from blood sampling to ICH of 5.6 years, 176 cases with ICH were identified. The mean age at health examination was 57 years; 50% of participants were women. There was an association between hypertension and risk of ICH, but there was no association between VWF level and risk of ICH. There was no association between blood group O and risk of ICH.Conclusions: To our knowledge this is the largest prospective study investigating the association between VWF, ABO blood group and ICH. We found no association between VWF or blood group O and risk of future ICH.
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24.
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25.
  • Johansson, Marcus, 1992, et al. (författare)
  • A TEST IMPLEMENTATION OF THE CORE MANUFACTURING SIMULATION DATA SPECIFICATION
  • 2007
  • Ingår i: Proceedings of the 2007 Winter Simulation Conference in Washington D.C. USA, December 9-12 2007. ; , s. 1673-1681
  • Konferensbidrag (refereegranskat)abstract
    • This paper describes an effort of testing the Core Manufacturing Simulation Data (CMSD) information model as a neutral data interface for a discrete event simulation model developed using Enterprise Dynamics. The implementation is based upon a model of a paint shop at a Volvo Car Corporation plant in Sweden. The model is built for a Swedish research project (FACTS), which focuses on the work procedure of developing new and modified production systems. FACTS has found standardized simulation data structures to be of high interest to achieve efficient data collection in conceptual stages of production development programs. For the CMSD-development team, implementations serve as an approach to validate the structures in CMSD and to gather requirements for future enhancements. CMSD was originally developed to support job shops, but the results of this implementation indicate a good possibility to extend CMSD to also support flow shops.
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26.
  • Johansson, Magdalena, et al. (författare)
  • Alcohol Consumption and Risk of First-Time Venous Thromboembolism in Men and Women
  • 2019
  • Ingår i: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 119:6, s. 962-970
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The relationship between alcohol intake and risk of venous thromboembolism (VTE) is unclear. Men and women differ in their drinking habits, which may affect a possible association.OBJECTIVE: This article investigates the association between alcohol consumption, alcohol dependence and VTE in the total population as well as in men and women separately.METHODS: We performed a prospective, population-based cohort study in northern Sweden. Study participants were 108,025 (51% women) persons aged 30 to 60 years who underwent a health examination between 1985 and 2014. We assessed alcohol consumption and defined alcohol dependence using a questionnaire. The outcome was a validated first-time VTE.RESULTS: The mean follow-up time was 13.9 years, and 2,054 participants had a first-time VTE. The mean alcohol consumption was 3.5 standard drinks weekly in men and 1.5 in women. Alcohol dependence was found in 10% of men and 3% of women. There was an association between alcohol consumption (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.00-1.03 per standard drink weekly) as well as alcohol dependence (HR, 1.27; 95% CI, 1.06-1.52) and VTE after adjustments. In men, the risk of VTE increased over quartiles of weekly alcohol consumption (p for trend 0.02), with a HR of 1.22 (95% CI, 1.01-1.47) for the highest quartile. Alcohol dependence was associated with VTE in men (HR, 1.30; 95% CI, 1.07-1.59). In women, there were no significant associations.CONCLUSION: High alcohol consumption and alcohol dependence were associated with increased risk of first-time VTE in men, but not in women.
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27.
  • Johansson, Magdalena, 1984- (författare)
  • Epidemiology of venous thromboembolism with focus on risk markers
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: Venous thromboembolism (VTE) is a vascular disease with an incidence of approximately 140 cases per 100,000 person-years in adults. The incidence of VTE has increased over the last decades, and more than 20% of affected individuals die in the first year after diagnosis. To reduce the incidence of VTE, it is important to identify modifiable risk factors for the condition.Aims: The aims of this thesis were a) To study the incidence of first-time VTE and the prevalence of risk markers for VTE at the time of VTE diagnosis, b) To determine the validity of diagnoses of deep vein thrombosis and pulmonary embolism in administrative registries, and c) To study the association between glucose levels, diabetes, alcohol consumption, physical activity and risk of first-time VTE.Methods: To determine the incidence of first-time VTE and the prevalence of risk markers for VTE at the time of VTE diagnosis, a retrospective, population-based cohort study was conducted. The study included all adult residents of Västerbotten County during the year 2006. All other aims were addressed in the prospective, population-based Venous thromboEmbolism In Northern Sweden (VEINS) cohort study. The VEINS cohort included 108,025 residents of Västerbotten County aged 30 to 60 years without previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination within the Västerbotten Intervention Programme where weight, height, blood pressure and glucose levels were measured, and answered a questionnaire regarding smoking, education level, medication use, history of diabetes, alcohol intake and physical activity. VTE diagnoses were validated by review of medical records and radiology reports. To study the validity of diagnoses of deep vein thrombosis and pulmonary embolism in administrative registries, a registry search for International Classification of Diseases diagnosis codes indicating pulmonary embolism and/or deep vein thrombosis events was made in the Swedish National Patient Registry and the Cause of Death Registry. An additional search using an extended set of International Classification of Diseases diagnosis codes was performed in order to identify misclassified events.Results: The incidence of first-time VTE was 137 (95% confidence interval [CI] 122–154) per 100,000 adults per year. The most common risk markers for VTE were recent hospitalization and concurrent malignancy. The positive predictive value for a diagnosis of pulmonary embolism was 80.7% (95% CI 78.4–82.9), and that of deep vein thrombosis 59.2% (95% CI 56.7–61.7). Misclassification occurred in 1.1% (95% CI 0.4–1.7) of pulmonary embolism events and in 16.4% (95% CI 14.2–18.7) of deep vein thrombosis events. In the VEINS cohort, a total of 2,054 participants experienced an objectively verified first-time VTE event during approximately 1.5 million person-years of follow-up. In univariable analysis, there were associations between fasting plasma glucose, oral glucose tolerance test two-hour post-load plasma glucose, diabetes and increased risk of first-time VTE. These associations were attenuated after adjustment for potential confounders, and were no longer significant. There was an association between alcohol consumption and risk of first-time VTE in men (P for trend 0.02 after adjustments for increased risk of first-time VTE over quartiles of weekly alcohol consumption). Alcohol dependence was associated with risk of first-time VTE in men (hazard ratio [HR] 1.30; 95% CI 1.07–1.59 after adjustments). In women, there were no significant associations between alcohol consumption and risk of first-time VTE. Women who performed leisure time physical activity at least once a week had a lower risk of first-time VTE (HR 0.83; 95% CI 0.71–0.98 after adjustments) compared to women with less or no physical activity. Women with high occupational physical activity also had a lower risk of first-time VTE (HR 0.85; 95% CI 0.74–0.98 after adjustments). In men, there were no consistent association between either measure of physical activity and risk of first-time VTE. Conclusions: VTE is a common vascular disease. Registry data on diagnoses of pulmonary embolism, but not deep vein thrombosis, is of acceptable quality and can be considered for use in registry-based studies. Glucose levels and diabetes are not associated with risk of first-time VTE. Alcohol intake and alcohol dependence are associated with an increased risk of first-time VTE in men, whereas high leisure time physical activity and occupational physical activity are associated with a decreased risk of first-time VTE in women.
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28.
  • Johansson, Magdalena, et al. (författare)
  • Fasting plasma glucose, oral glucose tolerance test, and the risk of first-time venous thromboembolism. A report from the VEINS cohort study
  • 2018
  • Ingår i: Thrombosis Research. - : Elsevier. - 0049-3848 .- 1879-2472. ; 165, s. 86-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: It remains unclear whether high plasma glucose levels are associated with venous thromboembolism (VTE). This study investigated the association between fasting plasma glucose (FPG), oral glucose tolerance test (two-hour post-load plasma glucose (2HPG)), diabetes, and VTE. Materials and methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 residents of Vasterbotten County in northern Sweden. The participants were aged 30 to 60 years and had no previous VTE events. They were included from 1985 onwards and were followed until a VTE event, death, emigration, or the study end on September 5, 2014. All underwent a health examination that measured weight, height, FPG, and 2HPG and included a questionnaire regarding smoking, education level, and history of diabetes. Potential VTE events were identified by an extensive diagnosis registry search and were validated by reviewing medical records and radiology reports. Results: An objectively verified first-time VTE event was experienced by 2054 participants during 1,496,669 person-years of follow-up. In univariable analysis, there were associations between FPG, 2HPG, diabetes, and the risk of VTE. These associations disappeared after adjustment for potential confounders (age, sex, body mass index, cancer at inclusion, education level, smoking, and hypertension). The adjusted hazard ratios were 1.01 (95% confidence interval 0.83-1.23) for diabetes, 1.01 for each standard deviation of FPG (95% confidence interval 0.97-1.05), and 0.96 for each standard deviation of 2HPG (95% confidence interval 0.91-1.00). Conclusions: There were no independent associations between FPG, 2HPG, diabetes, and future risk of VTE.
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29.
  • Johansson, Magdalena, et al. (författare)
  • Incidence of venous thromboembolism in northern Sweden (VEINS) : a population-based study
  • 2014
  • Ingår i: Thrombosis Journal. - : BioMed Central (BMC). - 1477-9560. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The reported incidence of venous thromboembolism (VTE) varies considerably among studies. The primary aim of this study was to describe the incidence of VTE in relation to age and sex. The secondary aim was to describe the risk factor pattern at the time of diagnosis.METHODS: This retrospective, population-based cohort study included all adult residents in the County of Västerbotten in northern Sweden during the year 2006 (n = 204,836). All potential VTE events were manually validated and classified according to location. The presence of risk factors for VTE at the time of diagnosis was recorded.RESULTS: We identified 517 adult individuals with potential VTE. Among these, 343 individuals (158 men and 185 women) had a verified VTE event in 2006. The mean incidence was 167 individuals per 100,000 person years; 155 for men and 180 for women. The mean age at diagnosis was 67.6 years in men and 72.5 years in women. The incidence of VTE increased with age. The incidence was highest in women aged 85 years or more. Pulmonary embolism with or without concurrent deep vein thrombosis was diagnosed in 161 individuals (46.9%); lower extremity deep vein thrombosis without concurrent pulmonary embolism was diagnosed in 157 individuals (45.8%); and VTE in another location was diagnosed in 25 individuals (7.3%). The most common risk factors for VTE were recent hospitalization and concurrent malignancy.CONCLUSION: The incidence of VTE was 167 per 100,000 person years and increased with age. The incidence was highest among older women. Pulmonary embolism was the most common form of VTE; it affected 47% of individuals with VTE. Malignancy and hospitalization were the most prevalent risk factors for VTE.
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30.
  • Johansson, Magdalena, 1984-, et al. (författare)
  • Physical activity and risk of first-time venous thromboembolism
  • 2019
  • Ingår i: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 26:11, s. 1181-1187
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Physical activity may have a protective effect against venous thromboembolism (VTE). The aim of this study was to investigate the association between leisure time physical activity, occupational physical activity, and the risk of VTE in men and women separately.Methods: The population-based, prospective Venous thromboEmbolism In Northern Sweden (VEINS) cohort study included 108,025 participants of health examinations between 1985 and 2014. Physical activity data were collected by questionnaire. Participants were followed from health examination to first-time VTE event, death, emigration or the end of the study. All VTE events were validated by reviewing medical records and radiology reports.Results: During 1,496,669 person-years, 2054 participants experienced VTE. Women who performed leisure time physical activity at least once a week had a lower risk of first-time VTE (hazard ratio (HR) 0.83; 95% confidence interval (CI) 0.71–0.98 after adjustments) compared with women with less or no physical activity. Furthermore, women with high occupational physical activity also had a lower risk of VTE (HR 0.85; 95% CI 0.74–0.98). In men, there was no consistent association between either measure of physical activity and the risk of VTE.Conclusion: We found an association between increased physical activity and a lower risk of first-time VTE in women.
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31.
  • Johansson, Roger, et al. (författare)
  • Eye-movement replay supports episodic remembering
  • 2022
  • Ingår i: Proceedings of the Royal Society B: Biological Sciences. - : The Royal Society. - 1471-2954 .- 0962-8452. ; 289:1977
  • Tidskriftsartikel (refereegranskat)abstract
    • When we bring to mind something we have seen before, our eyes spontaneously unfold in a sequential pattern strikingly similar to that made during the original encounter, even in the absence of supporting visual input. Oculomotor movements of the eye may then serve the opposite purpose of acquiring new visual information; they may serve as self-generated cues, pointing to stored memories. Over 50 years ago Donald Hebb, the forefather of cognitive neuroscience, posited that such a sequential replay of eye movements supports our ability to mentally recreate visuospatial relations during episodic remembering. However, direct evidence for this influential claim is lacking. Here we isolate the sequential properties of spontaneous eye movements during encoding and retrieval in a pure recall memory task and capture their encoding-retrieval overlap. Critically, we show that the fidelity with which a series of consecutive eye movements from initial encoding is sequentially retained during subsequent retrieval predicts the quality of the recalled memory. Our findings provide direct evidence that such scanpaths are replayed to assemble and reconstruct spatio-temporal relations as we remember and further suggest that distinct scanpath properties differentially contribute depending on the nature of the goal-relevant memory.
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32.
  • Johansson, Roger, et al. (författare)
  • Scanpath components reveal how eye movement reinstatements differentially contribute to episodic remembering
  • 2019
  • Konferensbidrag (refereegranskat)abstract
    • An extensive body of research has shown that episodic remembering involves spontaneous eye movements that largely reproduce the gaze patterns that were present during encoding (e.g., Brandt & Stark, 1997; Johansson et al., 2012). Recent work has further shown that fixation locations that overlap between encoding and recall promote cortical episodic reconstruction (Bone et al., 2018; Johansson et al., 2018) and successful remembering (Johansson & Johansson, 2014). While such findings indicate that gaze location plays an active role during episodic reconstruction, the unfolding scanpaths also encompass more complex information over and above simple gaze locations, such as order, direction, shape, length and duration. Virtually nothing is known about how such spatio-temporal components contribute to episodic reconstruction. The present study investigated the encoding-retrieval overlap in scanpaths for 60 participants who encoded and recalled 36 visuospatial stimuli of two types: scenes and object arrangements. Results replicate and extend previous findings, by analyzing scanpath reinstatement over a multitude of spatio-temporal components. Critically, by combining subjective ratings of memory quality with a surprise test of forced-choice recognition, we demonstrate how such components contribute to successful remembering to different extents, and in different ways depending on the stimulus type. Results indicate that scanpath shape contributes to reconstructing the global scene structure whereas scanpath position, order and direction contribute to reconstructing the arrangement of individual objects in a spatial context. To our knowledge, this is the first systematic demonstration of how eye movement reinstatements contribute to episodic remembering in a multifaceted way.
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33.
  • Johansson, Sara, 1984- (författare)
  • Mellan orten och kalifatet : En studie om utresandefenomenet
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Starting 2011, many travelled from other countries to support different parties of the Syrian revolution. Many came from Sweden, and many joined the Islamic State. Swedish “Syria travellers” often came from areas labelled as [especially] vulnerable. The purpose of the thesis is to examine and analyse different understandings of the phenomenon of individuals travelling from Sweden to the conflict areas in Syria and Iraq, based on narratives collected from actors with local anchoring. The empirical material consists of 54 interviews with public and local actors, and Syria travellers. The results show a territorial stigmatization and a moral differentiation where the residents of the [especially] vulnerable area is understood as “failed” or "tolerated" citizens, something that informants link to the study object. There is a gap between those who seek background explanations in religion and those who seek them in social structures. Furthermore, the results indicate that there are several possible representations of Syria travellers, ranging from terrorists and nihilists to moralists. The work against “radicalization” is described as poorly anchored among practitioners and an extended supply of knowledge is requested. The interviewed Syria travellers describe them-selves as moral actors, and often highly religiously motivated. The thesis also show how guilt by association is a lived reality for Muslims in a time where negative representations of Islam dominate. The thesis should be regarded as a contribution to the expansion of the important field of research on professionals' social representations of why some individuals make violent interpretations of Islam and are attracted to movements such as the Islamic State. The thesis is also a call to further explore Syria travellers' own representations and arguments. Both local actors and Syria travellers represent groups that professionals may en-counter in their work. Knowledge of such social groups, and about the representations articulated within them, is valuable for the practice of Social Work, but also for other professions such as teachers, leisure workers, police, and decision makers at different levels in society.
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34.
  • Kachuri, Linda, et al. (författare)
  • Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci
  • 2016
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 37:1, s. 96-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000x) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73x10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64x10(-6)), rs112290073 (OR = 1.85, P = 1.27x10(-5)), rs138895564 (OR = 2.16, P = 2.06x10(-5); among young cases, OR = 3.77, P = 8.41x10(-4)). In addition, we found that rs139852726 (P = 1.44x10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84x10(-7)) and lung cancer (P = 2.37x10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
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35.
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36.
  • Leong, Swee, et al. (författare)
  • A real world pilot implementation of the Core Manufacturing Simulation Data model
  • 2008
  • Ingår i: ; , s. 334-341
  • Konferensbidrag (refereegranskat)abstract
    • While software for discrete event simulation (DES) has emerged into sophisticated tools for decision support in a wide range of contexts, the need to integrate DES tools with other applications is increasing. In the industrial engineering context, simulation engineers strive to use real world data, e.g., logs of machine breakdown, to make behavior of DES models imitate reality. However, the format used for describing simulation data is often specialized to the current situation. The Core Manufacturing Simulation Data (CMSD) is a collaborative effort with academia and industry to standardize the format used for simulation data, to facilitate data exchange among simulation and manufacturing applications. This paper describes the results from a pilot implementation study at Volvo Trucks, where CMSD was utilized as the data exchange format between two data systems and two DES models. The DES tools used were commercial software packages Unigraphics Plant Simulation and InControl Enterprise Dynamics. Generic and reusable interfaces for CMSD-file communication were developed for each of these tools. The CMSD interfaces were successfully connected to a model in each simulation tool describing the same manufacturing process. A stand alone application was developed to collect and analyze raw data and to create the CMSD file being used as input data for both models. The result is a system including raw data analysis, data reformatting, CMSD interfacing, and model execution. Based on the result, a generic methodology for CMSD interface development in DES tools has evolved. The most important conclusion is that CMSD data can be interpretable by both Plant Simulation and Enterprise Dynamics, and that it saves engineering development time during the model building phase.
  •  
37.
  • Li, Bo, et al. (författare)
  • Quantitative detection of hydrogen peroxide in an HCCI engine using photofragmentation laser-induced fluorescence
  • 2013
  • Ingår i: Proceedings of the Combustion Institute. - : Elsevier BV. - 1540-7489. ; 34, s. 3573-3581
  • Tidskriftsartikel (refereegranskat)abstract
    • A photofragmentation laser-induced fluorescence (PF-LIF) technique was applied to an HCCI engine for hydrogen peroxide (H2O2) measurements. A pump-probe strategy was adopted with the pump laser (266 nm) photolyzing H2O2, and with the probe laser (283 nm) detecting the generated OH photofragments. An on-line calibration process was performed by introducing a known amount of vaporized H2O2/water solution into the engine cylinder. Crank-angle resolved mass fractions of H2O2 were obtained, and for the first time, single-shot imaging of H2O2 was realized in the HCCI engine. It has also been verified that the PF-LIF signal originates mainly from H2O2 with a smaller interference from HO2. The crank-angle resolved experimental data were compared to mass fractions calculated with the software package Digital Analysis of Reaction Systems (DARS). The calculated H2O2 profile agrees well with the experimental results regarding mass fraction level, while the shapes of the profiles deviate slightly. Calculated mass fractions of HO2 indicate that interfering signal contributions from HO2 is the major reason for the deviation. (C) 2012 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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38.
  • Li, Yafang, et al. (författare)
  • Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development
  • 2019
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 10:19, s. 1760-1774
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
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39.
  • Li, Yafang, et al. (författare)
  • Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population
  • 2018
  • Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 39:3, s. 336-346
  • Tidskriftsartikel (refereegranskat)abstract
    • Non-small cell lung cancer is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between single nucleotide polymorphisms (SNPs) and smoking status (never- versus ever-smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13 336 non-small cell lung cancer cases. Candidate SNPs with P-value <0.001 were further analyzed using a standard case-control interaction analysis including 13 970 controls. The significant SNPs with P-value <3.5 × 10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 non-small cell lung cancer cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis P-value for these two SNPs were 1.24 with 6.96 × 10-7 and 1.37 with 3.49 × 10-7, respectively. In addition, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and P-value of 8.12 × 10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
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40.
  • Lind, Marcus, et al. (författare)
  • Incidence and risk factors of venous thromboembolism in men and women
  • 2022
  • Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 214, s. 82-86
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Studies have indicated that men have a higher overall risk of VTE than women. In previous studies, we have noted that risk factors for VTE, such as alcohol consumption and physical activity, can differ between sexes.The aim of the present study was to estimate the incidence of first-ever VTE and the association of traditional cardiovascular risk factors with VTE risk in men and women separately.Materials and methods: Inhabitants of Västerbotten County in northern Sweden, who had participated in a health examination between 1985 and 2014 were included. The mean age at inclusion was 46.3 years (range 26–65 years). All first-ever VTE events experienced by the participants from the health examination to September 5, 2014 were identified and validated.Results: A total of 1110 men and 944 women had an objectively verified first-ever VTE event. The incidence of VTE was 1.54 (95% CI 1.45–1.63) per 1000 years of follow-up for men and 1.22 (95% CI 1.14–1.30) for women. Higher age, weight and body mass index were associated with increased risk of VTE in both sexes. Men with hypertension had a lower risk of VTE, HR 0.75 (95% CI 0.65–0.87) and men with more than secondary school education had a higher risk of VTE. Taller women had an increased risk of VTE.Conclusions: In the studied age group, we found that men had a higher incidence of first-ever VTE than women. Notably, we also found that hypertension was associated with lower risk of VTE in men but not in women.
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41.
  • Lundgren, Marcus, et al. (författare)
  • Optical study on combustion transition from HCCI to PPC with gasoline compression ignition in a HD engine
  • 2016. - April
  • Ingår i: SAE 2016 World Congress and Exhibition. - 400 Commonwealth Drive, Warrendale, PA, United States : SAE International. ; 2016-April
  • Konferensbidrag (refereegranskat)abstract
    • The partially premixed combustion (PPC) concept has shown high efficiency with low soot emissions. However, the in-cylinder phenomena are still to be explained and evaluated for further progress in the research. This work studies the start of combustion process during a transition from homogenous charge compression ignition (HCCI) to PPC. The process is visualized using a heavy-duty, non-swirling engine modified for optical access. High speed video was used to capture the natural luminosity of the combustion. The fuel used was PRF87. Single and double injection strategies were used at a load kept to the moderate level of 7.5 bar IMEPg. Single injections were swept from early HCCI to retarded PPC conditions whilst running a cycle to cycle temperature sweep, to capture the effect of injection timing and temperature differences simultaneously. Results show that retarded injections show less cycle-to-cycle variation due to temperature variations. Advanced in-bowl injections show a stochastic behavior in the location of the first combustion, due to large variations in local fuel rich zones. For the double injection case the main injection cools the bulk temperature and hence delays the start of combustion before igniting in the fuel rich zones.
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42.
  • McKay, James D., et al. (författare)
  • Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes
  • 2017
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 49:7, s. 1126-1132
  • Tidskriftsartikel (refereegranskat)abstract
    • Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
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43.
  • Nylund, Otto, et al. (författare)
  • The association between self-rated health, health-related quality of life, and risk of venous thromboembolism
  • 2023
  • Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 36
  • Tidskriftsartikel (refereegranskat)abstract
    • Poor self-rated health (SRH) is associated with various adverse health outcomes, including cardiovascular disease. Little is known about SRH and health-related quality of life (HRQoL) as predictors of first-time venous thromboembolism (VTE). Our aim was to investigate the association between SRH, HRQoL, and risk of VTE in a whole cohort, as well as in women and men separately. A total of 108,025 middle-aged inhabitants (51 % women) of Västerbotten, Sweden, participated in a health examination between 1985 and 2014. Data on SRH, HRQoL, and potential confounders were collected by questionnaire. Participants were followed as a cohort and validated first-time VTE events were registered. The mean follow-up time was 13.9 years, during which 2054 participants experienced a first-time VTE. Overall, 27 % of participants reported their health as very good, 46 % as good, 20 % as average, 5 % as somewhat bad, and 1 % as bad. In a multivariable analysis, compared with participants who self-rated as having very good SRH, hazard ratios (95 % confidence intervals) for VTE were 1.17 (1.02–1.33) with good SRH, 1.27 (1.09–1.47) with average SRH, and 1.48 (1.00–2.18) with bad SRH. The risk of VTE increased with lower SRH for both men (p for trend 0.02) and women (p for trend 0.04). In a fully adjusted model, we also found significant associations between four aspects of HRQoL (general health, bodily pain, vitality, emotional well-being) and VTE risk. In conclusion, lower perceived health is associated with an increased risk of VTE in both men and women.
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44.
  • Rosqvist, Fredrik, 1985-, et al. (författare)
  • Overeating saturated fat promotes fatty liver and ceramides compared to polyunsaturated fat : a randomized trial
  • 2019
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 104:12, s. 6207-6219
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Saturated fat (SFA) versus polyunsaturated fat (PUFA) may promote non-alcoholic fatty liver disease (NAFLD) by yet unclear mechanisms.OBJECTIVE: To investigate if overeating SFA- and PUFA-enriched diets lead to differential liver fat accumulation in overweight and obese humans.DESIGN: Double-blind randomized trial (LIPOGAIN-2). Overfeeding SFA vs PUFA for 8 weeks, followed by 4 weeks of caloric restriction.SETTING: General community.Participants: n=61 overweight or obese men and women.INTERVENTION: Muffins high in either palm (SFA)- or sunflower oil (PUFA) were added to the habitual diet.MAIN OUTCOME MEASURE: Lean tissue mass (not reported here). Secondary and exploratory outcomes included liver and ectopic fat depots.RESULTS: By design, body weight gain was similar in SFA (2.31±1.38 kg) and PUFA (2.01±1.90 kg) groups, P=0.50. SFA markedly induced liver fat content (50% relative increase) along with liver enzymes and atherogenic serum lipids. In contrast, despite similar weight gain, PUFA did not increase liver fat or liver enzymes or cause any adverse effects on blood lipids. SFA had no differential effect on the accumulation of visceral fat, pancreas fat or total body fat compared with PUFA. SFA consistently increased, while PUFA reduced circulating ceramides; changes that were moderately associated with liver fat changes and proposed markers of hepatic lipogenesis. The adverse metabolic effects of SFA were reversed by calorie restriction.CONCLUSIONS: Saturated fat markedly induces liver fat and serum ceramides whereas dietary polyunsaturated fat prevent liver fat accumulation, reduce ceramides and hyperlipidemia during excess energy intake and weight gain in overweight individuals.
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45.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
  •  
46.
  • Svahn, Sara L, et al. (författare)
  • Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis
  • 2016
  • Ingår i: Infection and Immunity. - : American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 84:4, s. 1205-1213
  • Tidskriftsartikel (refereegranskat)abstract
    • Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics, S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus. Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.
  •  
47.
  • Zhu, Ying, et al. (författare)
  • Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer : A Mendelian Randomization Analysis
  • 2019
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:5, s. 935-942
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall nonsmall cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15-2.27; P = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.
  •  
48.
  • Öhman, Ludvig, et al. (författare)
  • Positive predictive value and misclassification of diagnosis of pulmonary embolism and deep vein thrombosis in Swedish patient registries
  • 2018
  • Ingår i: Clinical Epidemiology. - : Dove Medical Press. - 1179-1349. ; 10, s. 1215-1221
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To validate diagnoses of pulmonary embolism (PE) and deep vein thrombosis (DVT) in administrative registries. We also estimated the frequency of misclassified PE and DVT events.Patients and methods: A registry search for ICD codes representing PE and DVT was performed between 1985 and 2014 in a large population-based cohort in northern Sweden. An additional search using an extended set of ICD codes was performed to identify misclassified events. Diagnoses were validated manually by reviewing medical records and radiology reports.Results: Searching ICD codes in the National Patient Registry and Cause of Death Registry identified 2,450 participants with a first-time diagnosis of PE or DVT. The positive predictive value (PPV) for a diagnosis of PE or DVT was 80.7% and 59.2%, respectively. For the period of 2009 to 2014, the PPV was higher for PE (85.8%) but lower for DVT (54.1%). Misclassification occurred in 16.4% of DVT events and 1.1% of PE events.Conclusion: Registry-based data on PE, especially in recent years, are of acceptable quality and can be considered for use in registry-based studies. For DVT, we found that data were of low quality in regards to both PPV and misclassification and should not be used without validation.
  •  
49.
  • Abad, Alberto, 1972, et al. (författare)
  • The use of iron oxide as oxygen carrier in a chemical-looping reactor
  • 2007
  • Ingår i: Fuel. - : Elsevier BV. - 0016-2361. ; 86:7-8, s. 1021-1035
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemical-looping combustion (CLC) is a method for the combustion of fuel gas with inherent separation of carbon dioxide. This technique involves the use of two interconnected reactors, an air reactor and a fuel reactor. The oxygen demanded in the fuel combustion is supplied by a solid oxygen carrier, which circulates between both reactors. Fuel gas and air are never mixed and pure CO2 can be obtained from the flue gas exit. This paper presents the results from the use of an iron-based oxygen-carrier in a continuously operating laboratory CLC unit, consisting of two interconnected fluidized beds. Natural gas or syngas was used as fuel, and the thermal power was between 100 and 300 W. Tests were performed at four temperatures: 1073, 1123, 1173 and 1223 K. The prototype was successfully operated for all tests and stable conditions were maintained during the combustion. The same particles were used during 60 h of hot fluidization conditions, whereof 40 h with combustion. The combustion efficiency of syngas was high, about 99% for all experimental conditions. However, in the combustion tests with natural gas, there was unconverted methane in the exit flue gases. Higher temperature and lower fuel flows increase the combustion efficiency, which ranged between 70% and 94% at 1123 K. No signs of agglomeration or mass loss were detected, and the crushing strength of the oxygen carrier particles did not change significantly. Complementary experiments in a batch fluidized bed were made to compare the reactivity of the oxygen carrier particles before and after the 40 h of operation, but the reactivity of the particles was not affected significantly.
  •  
50.
  • Adman, Per, et al. (författare)
  • 171 forskare: ”Vi vuxna bör också klimatprotestera”
  • 2019
  • Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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