| 1. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 2. |
- Anderson, Christopher D., et al.
(författare)
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Genetic variants in CETP increase risk of intracerebral hemorrhage
- 2016
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 80:5, s. 730-740
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: In observational epidemiologic studies, higher plasma high-density lipoprotein cholesterol (HDL-C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL-C; as such, medicines that inhibit CETP and raise HDL-C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL-C also increase risk for ICH.METHODS: We performed 2 candidate-gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL-C as well as ICH risk.RESULTS: Twelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10(-4) ) with no heterogeneity across studies (I(2) = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL-C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10(-6) ).INTERPRETATION: Genetic variants in CETP associated with increased HDL-C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL-raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730-740.
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| 3. |
- Ben Abdesslem, Fehmi, et al.
(författare)
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Understanding usage and activity in cellular networks by investigating HTTP requests
- 2015. - 11
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Ingår i: 2015 12th Annual IEEE Consumer Communications and Networking Conference (CCNC). - 9781479963904 ; , s. 570-575
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Konferensbidrag (refereegranskat)abstract
- The number of mobile devices is estimated to now exceed the world’s population, using more and more cloud services, and hence generating more and more traffic. Smartphones generate 95% of the total global handset traffic, and while approximately half of this traffic is sent to cellular networks, other handsets such as tablets are also using increasingly the cellular networks. This paper provides a closer look at the traffic generated on cellular networks by exploring billions of HTTP requests sent by millions of users to a nation-wide cellular network during 41 days. We confirm that - as in many other contexts - 20% of the users are responsible for more than 80% of the requests and provide a deeper analysis of the cellular network usage. Furthermore, we characterise the activity of users on their mobile device and which cloud services they use. For instance, almost 30% of the users use the cellular network frequently, mainly using search services and social networks, but 20% of their requests are sent to advertisement and tracking systems.
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| 4. |
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Electronic Government : 18th IFIP WG 8.5 International Conference, EGOV 2019, San Benedetto Del Tronto, Italy, September 2–4, 2019, Proceedings
- 2019
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Proceedings (redaktörskap) (refereegranskat)abstract
- This book constitutes the proceedings of the 18th IFIP WG 8.5 International Conference on Electronic Government, EGOV 2019, held in San Benedetto del Tronto, Italy, in September 2019, in conjunction with the IFIP WG 8.5 IFIP International Conference on Electronic Participation (ePart 2019) and the International Conference for E-Democracy and Open Government Conference (CeDEM 2019).The 27 revised full papers presented were carefully reviewed and selected from 64 submissions. The papers are clustered under the following topical sections: E-Government Foundations; E-Government Services and Open Government; Open Data: Social and Technical Aspects; AI, Data Analytics and Automated Decision Making; and Smart Cities.
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| 5. |
- Green, Henrik, et al.
(författare)
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Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities
- 2016
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 22:2, s. 366-373
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/ carboplatin chemotherapy. (C)2015 AACR.
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| 6. |
- Gulyas, Miklos, et al.
(författare)
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COX-2 expression and effects of celecoxib in addition to standard chemotherapy in advanced non-small cell lung cancer.
- 2018
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 244-250
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Inhibition of cyclooxygenase-2 (COX-2) is proposed as a treatment option in several cancer types. However, in non-small cell lung cancer (NSCLC), phase III trials have failed to demonstrate a benefit of adding COX-2 inhibitors to standard chemotherapy. The aim of this study was to analyze COX-2 expression in tumor and stromal cells as predictive biomarker for COX-2 inhibition.Methods: In a multicenter phase III trial, 316 patients with advanced NSCLC were randomized to receive celecoxib (400 mg b.i.d.) or placebo up to one year in addition to a two-drug platinum-based chemotherapy combination. In a subset of 122 patients, archived tumor tissue was available for immunohistochemical analysis of COX-2 expression in tumor and stromal cells. For each compartment, COX-2 expression was graded as high or low, based on a product score of extension and intensity of positively stained cells.Results: An updated analysis of all 316 patients included in the original trial, and of the 122 patients with available tumor tissue, showed no survival differences between the celecoxib and placebo arms (HR 1.01; 95% CI 0.81–1.27 and HR 1.12; 95% CI 0.78–1.61, respectively). High COX-2 scores in tumor (n = 71) or stromal cells (n = 55) was not associated with a superior survival outcome with celecoxib vs. placebo (HR =0.96, 95% CI 0.60–1.54; and HR =1.51; 95% CI 0.86–2.66), and no significant interaction effect between COX-2 score in tumor or stromal cells and celecoxib effect on survival was detected (p = .48 and .25, respectively).Conclusions: In this subgroup analysis of patients with advanced NSCLC treated within the context of a randomized trial, we could not detect any interaction effect of COX-2 expression in tumor or stromal cells and the outcome of celecoxib treatment in addition to standard chemotherapy.
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| 7. |
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| 8. |
- Jansson, Johan, 1973-, et al.
(författare)
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Adoption of alternative fuel vehicles : Influence from neighbors, family and coworkers
- 2017
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Ingår i: Transportation Research Part D. - : Elsevier BV. - 1361-9209 .- 1879-2340. ; 54, s. 61-73
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Tidskriftsartikel (refereegranskat)abstract
- During the last years, many governments have set targets for increasing the share of biofuels in the transportation sector. Understanding consumer behavior is essential in designing policies that efficiently increase the uptake of cleaner technologies. In this paper we analyze adopters and non-adopters of alternative fuel vehicles (AFVs). We use diffusion of innovation theory and the established notion that the social system and interpersonal influence play important roles in adoption. Based on a nationwide database of car owners we analyze interpersonal influence on adoption from three social domains: neighbors, family and coworkers. The results point primarily at a neighbor effect in that AFV adoption is more likely if neighbors also have adopted. The results also point at significant effects of interpersonal influence from coworkers and family members but these effects weaken or disappear when income, education level, marriage, age, gender and green party votes are controlled for. The results extend the diffusion of innovation and AFV literature with empirical support for interpersonal influence based on objective data where response bias is not a factor. Implications for further research, environmental and transport policy, and practitioners are discussed.
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| 9. |
- Knowles, Joshua W., et al.
(författare)
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Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene
- 2015
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Ingår i: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 125:4, s. 1739-1751
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Tidskriftsartikel (refereegranskat)abstract
- Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.
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| 10. |
- Lindgren, Ola, et al.
(författare)
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Incretin Effect after Oral Amino Acid Ingestion in Humans.
- 2015
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:3, s. 1172-1176
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Tidskriftsartikel (refereegranskat)abstract
- Context: The incretin effect is the augmented insulin secretion by oral versus intravenous glucose at matching glucose levels. We previously demonstrated an augmented insulin secretion when fat is given orally rather than intravenously, suggesting an incretin effect also after fat. However, whether there is an incretin effect is also present after amino acid ingestion is not known. Objective: To explore insulin secretion and islet hormones after oral and intravenous amino acid administration at matched total amino acid concentrations in healthy subjects. Design: Amino acid mixture (Vaminolac(R)) was administered orally or intravenously at a rate resulting in matching total amino acid concentrations to twelve male volunteers with age 22.5±1.4 yr and BMI 22.4±1.4 kg/m(2), who had no history of diabetes. Main outcome measures: Area under the 120 min curve (AUC) for insulin, C-peptide, glucagon, intact and total glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and insulin secretory rate and insulin clearance. Results: Insulin, C-peptide and glucagon levels increased after both oral and intravenous administration, but insulin secretion was 25% higher after oral than after intravenous amino acid challenges (P=0.006), whereas there was no significant difference in the glucagon response. Intact and total GIP rose after oral but not after intravenous amino acid administration, whereas intact and total GLP-1 levels did not change significantly in either test. Conclusion: Oral amino acid mixture ingestion elicits a stronger insulin secretory response than intravenous amino acid at matching amino acid levels and that this is associated with increased GIP level, suggesting that an incretin effect exists also after oral amino acids, possibly mediated by GIP.
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| 11. |
- Mannberg, Andrea, et al.
(författare)
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Påverkar skatteundantag hushållens benägenhet att köpa miljöbilar? En studie av Stockholms trängselskatt
- 2015
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Ingår i: Ekonomisk Debatt. - 0345-2646. ; 43:1, s. 32-39
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Tidskriftsartikel (refereegranskat)abstract
- Sedan januari 2006 är in- och ut-passage genom tullarna i Stockholm belagt med en avgift för bilister. Som ett led i riksdagens mål att helt eliminera utsläppen av växthusgaser 2050 och ha en bilpark oberoende av fossila bränslen 2030 (Regeringens proposition 2008/09:162) undantogs sk miljöbilar från trängselskatten mellan 2006 och 2009. I denna studie har vi undersökt om undantaget av miljöbilar från trängselskatten i Stockholm påverkade sannolikheten att köpa etanolbil (E85). Våra resultat visar att undantaget för etanolbilar i trängselskatten hade en signifikant effekt på etanolbilsförsäljningeni Stockholm.
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| 12. |
- Mark, Davis, et al.
(författare)
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Understanding media publics and the antimicrobial resistance crisis
- 2018
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Ingår i: Global Public Health. - : Informa UK Limited. - 1744-1692 .- 1744-1706. ; 13:9, s. 1158-1168
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) imperils health for people across the world. This enormous challenge is being met with the rationalisation of prescription, dispensing and consumption of antimicrobials in clinical settings and in the everyday lives of members of the general population. Individuals need to be reached outside clinical settings to prepare them for the necessary changes to the pharmaceutical management of infections; efforts that depend on media and communications and, therefore, how the AMR message is mediated, received and applied. In 2016, the UK Review on Antimicrobial Resistance called on governments to support intense, worldwide media activity to promote public awareness and to further efforts to rationalise the use of antimicrobial pharmaceuticals. In this article, we consider this communications challenge in light of contemporary currents of thought on media publics, including: the tendency of health communications to cast experts and lay individuals in opposition; the blaming of individuals who appear to ‘resist’ expert advice; the challenges presented by negative stories of AMR and their circulation in public life, and; the problems of public trust tied to the construction and mediation of expert knowledge on the effective management of AMR.
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| 13. |
- Tuisku, Jouni, et al.
(författare)
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Effects of age, BMI and sex on the glial cell marker TSPO : a multicentre [11C]PBR28 HRRT PET study
- 2019
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 46:11, s. 2329-2338
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C-11]PBR28. Methods [C-11]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V-T) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts. Results There were significant positive correlations between age and V-T in the frontal and temporal cortex. BMI showed a significant negative correlation with V-T in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V-T. A subgroup analysis revealed a positive correlation between V-T and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects. Conclusion These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.
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| 14. |
- Valerio, Lorenzo, et al.
(författare)
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Offloading Cellular Traffic with Opportunistic Networks : A Feasibility Study
- 2015. - 17
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Ingår i: 2015 14th Annual Mediterranean Ad Hoc Networking Workshop (MED-HOC-NET). - 9781467373067
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Konferensbidrag (refereegranskat)abstract
- The widespread diffusion of powerful mobile devices with diverse networking and multimedia capabilities, and the associated blossoming of content-centric multimedia services is contributing to the exponential increase of data traffic in cellular networks. Mobile data offloading is a promising technique to cope with these problems, which allows to deliver data originally targeted for cellular networks to complementary networking technologies. Among the various forms of mobile data offloading in this study we focus on offloading through opportunistic networks. Differently from previous studies in this field we evaluate the efficiency of opportunistic offloading schemes by using a real cellular traffic dataset collected in a large metropolitan area over a period of one month. We focus our analysis on video requests for popular video providers, and we evaluate the potential benefits of using an opportunistic data dissemination scheme to request this videos from local users instead of using the cellular network. As a benchmark, we compare the performance of such system with a simple caching mechanism. We show that a simple opportunistic offloading scheme can improve the performance of the caching system even if only 10% of the users participate in the opportunistic dissemination. This means that operators could offload their network efficiently without needing to deploy additional caching infrastructure.
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| 15. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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