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| 2. |
- Munk, P., et al.
(författare)
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Genomic analysis of sewage from 101 countries reveals global landscape of antimicrobial resistance
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) is a major threat to global health. Understanding the emergence, evolution, and transmission of individual antibiotic resistance genes (ARGs) is essential to develop sustainable strategies combatting this threat. Here, we use metagenomic sequencing to analyse ARGs in 757 sewage samples from 243 cities in 101 countries, collected from 2016 to 2019. We find regional patterns in resistomes, and these differ between subsets corresponding to drug classes and are partly driven by taxonomic variation. The genetic environments of 49 common ARGs are highly diverse, with most common ARGs carried by multiple distinct genomic contexts globally and sometimes on plasmids. Analysis of flanking sequence revealed ARG-specific patterns of dispersal limitation and global transmission. Our data furthermore suggest certain geographies are more prone to transmission events and should receive additional attention.
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| 4. |
- Grunddal, K. V., et al.
(författare)
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Neurotensin Is Coexpressed, Coreleased, and Acts Together With GLP-1 and PYY in Enteroendocrine Control of Metabolism
- 2016
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 157:1, s. 176-194
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Tidskriftsartikel (refereegranskat)abstract
- The 2 gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are well known to be coexpressed, costored, and released together to coact in the control of key metabolic target organs. However, recently, it became clear that several other gut hormones can be coexpressed in the intestinal-specific lineage of enteroendocrine cells. Here, we focus on the anatomical and functional consequences of the coexpression of neurotensin with GLP-1 and PYY in the distal small intestine. Fluorescence-activated cell sorting analysis, laser capture, and triple staining demonstrated that GLP-1 cells in the crypts become increasingly multihormonal, ie, coexpressing PYY and neurotensin as they move up the villus. Proglucagon promoter and pertussis toxin receptor-driven cell ablation and reappearance studies indicated that although all the cells die, the GLP-1 cells reappear more quickly than PYY- and neurotensin-positive cells. High-resolution confocal fluorescence microscopy demonstrated that neurotensin is stored in secretory granules distinct from GLP-1 and PYY storing granules. Nevertheless, the 3 peptides were cosecreted from both perfused small intestines and colonic crypt cultures in response to a series of metabolite, neuropeptide, and hormonal stimuli. Importantly, neurotensin acts synergistically, ie, more than additively together with GLP-1 and PYY to decrease palatable food intake and inhibit gastric emptying, but affects glucose homeostasis in a more complex manner. Thus, neurotensin is a major gut hormone deeply integrated with GLP-1 and PYY, which should be taken into account when exploiting the enteroendocrine regulation of metabolism pharmacologically.
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| 5. |
- 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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| 6. |
- Abrahamsen, R., et al.
(författare)
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Association of respiratory symptoms and asthma with occupational exposures: findings from a population-based cross-sectional survey in Telemark, Norway
- 2017
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to estimate the prevalence of respiratory symptoms and physiciandiagnosed asthma and assess the impact of current occupational exposure. Design: Cross-sectional analyses of the prevalence of self-reported respiratory health and association with current occupational exposure in a random sample of the general population in Telemark County, Norway. Settings: In 2013, a self-administered questionnaire was mailed to a random sample of the general population, aged 16-50, in Telemark, Norway. The overall response rate was 33%, comprising 16 099 responders. Outcome measures: The prevalence for respiratory symptoms and asthma, and OR of respiratory symptoms and asthma for occupational groups and exposures were calculated. Occupational exposures were assessed using self-reported exposure and an asthma-specific job-exposure matrix (JEM). Results: The prevalence of physician-diagnosed asthma was 11.5%. For the occupational groups, the category with agriculture/fishery workers and craft/related trade workers was associated with wheezing and asthma attack in the past 12 months, showing OR 1.3 (1.1 to 1.6) and 1.9 (1.2 to 2.8), respectively. The group including technicians and associated professionals was also associated with wheezing OR 1.2 (1.0 to 1.3) and asthma attack OR 1.4 (1.1 to 1.9). The JEM data show that exposure to flour was associated with wheezing OR 3.2 (1.4 to 7.3) and woken with dyspnoea OR 3.5 (1.3 to 9.5), whereas exposures to diisocyanates, welding/soldering fumes and exposure to vehicle/motor exhaust were associated with dyspnoea OR 2.9 (1.5 to 5.7), 3.2 (1.6 to 6.4) and 1.4 (1.0 to 1.8), respectively. Conclusions: The observed prevalence of physiciandiagnosed asthma was 11.5%. The 'manual' occupations were associated with respiratory symptoms. Occupational exposure to flour, diisocyanates, welding/soldering fumes and vehicle/motor exhaust was associated with respiratory symptoms in the past 12 months and use of asthma medication. However, prospective data are needed to confirm the observed associations.
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| 7. |
- Abrahamsen, R., et al.
(författare)
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Non-response in a cross-sectional study of respiratory health in Norway
- 2016
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Declining participation in epidemiological studies has been reported in recent decades and may lead to biased prevalence estimates and selection bias. The aim of the study was to identify possible causes and effects of non-response in a population-based study of respiratory health in Norway. Design: The Telemark study is a longitudinal study that began with a cross-sectional survey in 2013. Setting: In 2013, a random sample of 50 000 inhabitants aged 16-50 years, living in Telemark county, received a validated postal questionnaire. The response rate was 33%. In this study, a random sample of 700 non-responders was contacted first by telephone and then by mail. Outcome measures: Response rates, prevalence and OR of asthma and respiratory symptoms based on exposure to vapours, gas, dust or fumes (VGDF) and smoking. Causes of non-response. Results: A total of 260 non-responders (37%) participated. Non-response was associated with younger age, male sex, living in a rural area and past smoking. The prevalence was similar for responders and non-responders for physician-diagnosed asthma and several respiratory symptoms. The prevalence of chronic cough and use of asthma medication was overestimated in the Telemark study, and adjusted prevalence estimates were 17.4% and 5%, respectively. Current smoking was identified as a risk factor for respiratory symptoms among responders and non-responders, while occupational VGDF exposure was a risk factor only among responders. The Breslow-Day test detected heterogeneity between productive cough and occupational VGDF exposure among responders. Conclusions: The Telemark study provided valid estimates for physician-diagnosed asthma and several respiratory symptoms, while it was necessary to adjust prevalence estimates for chronic cough and use of asthma medication. Reminder letters had little effect on risk factor associations. Selection bias should be considered in future investigations of the relationship between respiratory outcomes and exposures.
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| 8. |
- Artigas, J., et al.
(författare)
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Towards a renewed research agenda in ecotoxicology
- 2012
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Ingår i: Environmental Pollution. - : Elsevier BV. - 0269-7491. ; 160, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- New concerns about biodiversity, ecosystem services and human health triggered several new regulations increasing the need for sound ecotoxicological risk assessment. The PEER network aims to share its view on the research issues that this challenges. PEER scientists call for an improved biologically relevant exposure assessment. They promote comprehensive effect assessment at several biological levels. Biological traits should be used for Environmental risk assessment (ERA) as promising tools to better understand relationships between structure and functioning of ecosystems. The use of modern high throughput methods could also enhance the amount of data for a better risk assessment. Improved models coping with multiple stressors or biological levels are necessary to answer for a more scientifically based risk assessment. Those methods must be embedded within life cycle analysis or economical models for efficient regulations. Joint research programmes involving humanities with ecological sciences should be developed for a sound risk management. (C) 2011 Elsevier Ltd. All rights reserved.
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| 9. |
- Christiansen, Morten K, et al.
(författare)
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Incidence, Predictors, and Success of Ventricular Tachycardia Catheter Ablation in Arrhythmogenic Right Ventricular Cardiomyopathy (from the Nordic ARVC Registry).
- 2020
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Ingår i: The American journal of cardiology. - : Elsevier BV. - 1879-1913 .- 0002-9149. ; 125:5, s. 803-811
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Tidskriftsartikel (refereegranskat)abstract
- Catheter ablation may reduce ventricular tachycardia (VT) burden in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, little is known about factors predicting need for ablation. Therefore, we sought to investigate predictors and use of VT ablation and to evaluate the postprocedural outcome in ARVC patients. We studied 435 patients from the Nordic ARVC registry including 220 probands with definite ARVC according to the 2010 task force criteria and 215 mutation-carrying relatives identified through cascade screening. Patients were followed until first-time VT ablation, death, heart transplantation, or January 1st 2018. Additionally, patients undergoing VT ablation were further followed from the time of ablation for recurrent ventricular arrhythmias. The cumulative use of VT ablation was 4% (95% confidence interval [CI] 3% to 6%) and 11% (95% CI 8% to 15%) after 1 and 10 years. All procedures were performed in probands in whom cumulative use was 8% (95% CI 5% to 12%) and 20% (95% CI 15% to 26%). In adjusted analyses among probands, only young age predicted ablation. In patients undergoing ablation, risk of recurrent arrhythmias was 59% (95% CI 44% to 71%) and 74% (95% CI 59% to 84%) 1 and 5 years after the procedure. Despite high recurrence rates, the burden of ventricular arrhythmias was reduced after ablation (p=0.0042). Young age, use of several antiarrhythmic drugs and inducibility to VT after ablation were associated with an unfavorable outcome. In conclusion, twenty percent of ARVC probands developed a clinical indication for VT ablation within 10 years whereas mutation-carrying relatives were without such need. Although the burden of ventricular arrhythmias decreased after ablation, risk of recurrence was substantial.
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| 10. |
- Clarhed, Ulrika, et al.
(författare)
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Occupational exposure and the risk of new-onset chronic rhinosinusitis - a prospective study 2013-2018.
- 2020
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Ingår i: Rhinology. - 0300-0729. ; 58:6, s. 597-604
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Tidskriftsartikel (refereegranskat)abstract
- The aetiology behind chronic rhinosinusitis (CRS) is still poorly understood. The aim of this study was to investigate the association between the onset of CRS and several common occupational exposures over time.An adult random population from Telemark, Norway, comprising 7,952 subjects, who answered a comprehensive respiratory questionnaire including questions on CRS and occupational exposure first in 2013 and again in 2018.New-onset CRS during the five-year follow-up was independently associated with occupational exposure to hair-care products, cleaning agents among women, super glue, strong acids, cooking fumes and wood dust.In this random population cohort from Norway, exposure to several common occupational agents, such as hair-care products, super glue and wood dust, was associated with the onset of CRS. It is important that physicians who see patients with CRS inquire about workplace exposure.
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