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| 2. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 3. |
- Johanson, G., et al.
(författare)
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Quantitative relationships of perfluoroalkyl acids in drinking water associated with serum concentrations above background in adults living near contamination hotspots in Sweden
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 219
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Tidskriftsartikel (refereegranskat)abstract
- Contaminated drinking water (DW) is a major source of exposure to per- and polyfluoroalkyl substances (PFAS) at locations around PFAS production/use facilities and military airports. This study aimed to investigate quantitative relationships between concentrations in DW and serum of nine perfluoroalkyl acids (PFAAs) in Swedish adult populations living near contamination hotspots. Short-chained (PFPeA, PFHxA, PFHpA, and PFBS) and long-chained PFAAs (PFOA, PFNA, PFDA, PFHxS and PFOS) were measured in DW and serum. We matched DW and serum concentrations for a total of 398 subjects living or working in areas receiving contaminated DW and in one non-contaminated area. Thereafter, linear regression analysis with and without adjustments for co-variates was conducted. This enabled to derive (i) serum concentrations at background exposure (CB) from sources other than local DW exposure (i.e. food, dust and textiles) at 0 ng/L DW concentration, (ii) population-mean PFAA serum:water ratios (SWR) and (iii) PFAA concentrations in DW causing observable elevated serum PFAA concentrations above background variability. Median concentrations of the sum of nine PFAAs ranged between 2.8 and 1790 ng/L in DW and between 7.6 and 96.9 ng/mL in serum. DW concentration was the strongest predictor, resulting in similar unadjusted and adjusted regression coefficients. Mean CB ranged from <0.1 (PFPeA, PFHpA, PFBS) to 5.1 ng/mL (PFOS). Serum concentrations increased significantly with increasing DW concentrations for all PFAAs except for PFPeA with SWRs ranging from <10 (PFHxA, PFHpA and PFBS) to 111 (PFHxS). Observed elevated serum concentrations above background variability were reached at DW concentrations between 24 (PFOA) and 357 ng/L (PFHxA). The unadjusted linear regression predictions agreed well with serum concentrations previously reported in various populations exposed to low and high DW levels of PFOA, PFHxS and PFOS. The quantitative relationships derived herein should be helpful to translate PFAA concentrations in DW to concentrations in serum at the population level.
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| 4. |
- Lindehammer, Sabina, et al.
(författare)
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Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
- 2008
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-5
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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| 5. |
- Barregård, Lars, 1948, et al.
(författare)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 6. |
- Bjarnason, A., et al.
(författare)
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Incidence, etiology, and outcomes of community-acquired pneumonia: A population-based study
- 2018
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Ingår i: Open Forum Infectious Diseases. - : Oxford University Press (OUP). - 2328-8957. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- Background. The microbial etiology of community-acquired pneumonia (CAP) is often unclear in clinical practice, and previous studies have produced variable results. Population-based studies examining etiology and incidence are lacking. This study examined the incidence and etiology of CAP requiring hospitalization in a population-based cohort as well as risk factors and outcomes for specific etiologies. Methods. Consecutive admissions due to CAP in Reykjavik, Iceland were studied. Etiologic testing was performed with cultures, urine-antigen detection, and polymerase chain reaction analysis of airway samples. Outcomes were length of stay, intensive care unit admission, assisted ventilation, and mortality. Results. The inclusion rate was 95%. The incidence of CAP requiring hospitalization was 20.6 cases per 10 000 adults/year. A potential pathogen was detected in 52% (164 of 310) of admissions and in 74% (43 of 58) with complete sample sets. Streptococcus pneumoniae was the most common pathogen (61 of 310, 20%; incidence: 4.1/10 000). Viruses were identified in 15% (47 of 310; incidence: 3.1/10 000), Mycoplasma pneumoniae were identified in 12% (36 of 310; incidence: 2.4/10 000), and multiple pathogens were identified in 10% (30 of 310; incidence: 2.0/10 000). Recent antimicrobial therapy was associated with increased detection of M pneumoniae (P ≤ .001), whereas a lack of recent antimicrobial therapy was associated with increased detection of S pneumoniae (P = .02). Symptoms and outcomes were similar irrespective of microbial etiology. Conclusions. Pneumococci, M pneumoniae, and viruses are the most common pathogens associated with CAP requiring hospital admission, and they all have a similar incidence that increases with age. Symptoms do not correlate with specific agents, and outcomes are similar irrespective of pathogens identified. © The Author(s) 2018.
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| 7. |
- Caporale, N., et al.
(författare)
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From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures
- 2022
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 375:6582
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Tidskriftsartikel (refereegranskat)abstract
- Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio, as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay. © 2022 American Association for the Advancement of Science. All rights reserved.
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| 8. |
- Elfving, Kristina, et al.
(författare)
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Pathogen Clearance and New Respiratory Tract Infections Among Febrile Children in Zanzibar Investigated With Multitargeting Real-Time Polymerase Chain Reaction on Paired Nasopharyngeal Swab Samples
- 2018
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Ingår i: Pediatric Infectious Disease Journal. - : Ovid Technologies (Wolters Kluwer Health). - 0891-3668. ; 37:7, s. 643-648
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Tidskriftsartikel (refereegranskat)abstract
- Background: New molecular methods have revealed frequent and often polymicrobial respiratory infections in children in low-income settings. It is not known whether presence of multiple pathogens is due to prolonged infections or to frequent exposure. The aim of this study was to analyze short-term pathogen clearance from nasopharynx and the rate of new respiratory tract infections in febrile preschool children. Methods: Children (n = 207) with uncomplicated acute febrile illness 2-59 months of age presenting to a health center in Zanzibar, Tanzania, April-July 2011, were included. Paired nasopharyngeal swab samples, collected at enrolment and after 14 days, were analyzed by multiple real-time polymerase chain reaction for Adenovirus, bocavirus, Bordetella pertussis, Chlamydophila pneumoniae, Coronaviruses, Enterovirus, influenza A and B virus, metapneumovirus, measles virus, Mycoplasma pneumoniae, parainfluenza virus, Parechovirus, respiratory syncytial virus and Rhinovirus. An age-matched and geographically matched healthy control group (n = 166) underwent nasopharyngeal sampling on 1 occasion. Results: At baseline, 157/207 (76%) patients had at least 1 pathogen detected, in total 199 infections. At follow-up (day 14), 162/199 (81%) of these infections were not detected, including >95% of the previously detected infections with Enterovirus, influenza A virus, influenza B virus, metapneumovirus or parainfluenza virus. Still 115 (56%) children were positive for at least 1 pathogen at follow-up, of which 95/115 (83%) were not found at baseline. Detection of influenza B on day 14 was significantly associated with fever during follow-up. Conclusion: The results suggest that children with acute febrile illness in Zanzibar rapidly clear respiratory tract infections but frequently acquire new infections within 14 days.
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| 9. |
- Gullberg, Joanna, et al.
(författare)
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The challenge of applying digital image processing software on intraoral radiographs for osteoporosis risk assessment
- 2022
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Ingår i: Dentomaxillofacial Radiology. - : British Institute of Radiology. - 0250-832X .- 1476-542X. ; 51:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to evaluate rater agreement and the accuracy of a semi-automated software and its fully automated tool for osteoporosis risk assessment in intraoral radiographs. Methods: A total of 567 intraoral radiographs was selected retrospectively from women aged 75-80 years participating in a large population based study (SUPERB) based in Gothenburg, Sweden. Five raters assessed participants' risk of osteoporosis in the intraoral radiographs using a semi-automated software. Assessments were repeated after 4 weeks on 121 radiographs (20%) randomly selected from the original 567. Radiographs were also assessed by the soft wares' fully automated tool for analysis. Results: Overall interrater agreement for the five raters was 0.37 (95% CI 0.32-0.41), and for the five raters with the fully automated tool included as 'sixth rater' the overall Kappa was 0.34 (0.30-0.38). Intrarater agreement varied from moderate to substantial according to the Landis and Koch interpretation scale. Diagnostic accuracy was calculated in relation to reference standard for osteoporosis diagnosis which is T score values for spine, total hip and femoral neck and presented in form of sensitivities, specificities, predictive values, likelihood ratios and odds ratios. All raters' mean sensitivity, including the fully automated tool, was 40,4% (range 14,3%-57,6%). Corresponding values for specificity was 69,5% (range 59,7%-90,4%). The diagnostic odds ratios ranged between 1 and 2.7. Conclusion: The low diagnostic odds ratio and agreement between raters in osteoporosis risk assessment using the software for analysis of the trabecular pattern in intraoral radiographs shows that more work needs to be done to optimise the automation of trabecular pattern analysis in intraoral radiographs.
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| 10. |
- Haglund, A., et al.
(författare)
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Interpersonal violence and the prediction of short-term risk of repeat suicide attempt
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- In this multi-center cohort study, suicide attempters presenting to hospital (N = 355, 63% women) were interviewed using the Karolinska Interpersonal Violence Scale (KIVS) and followed-up by medical record review. Main outcome was non-fatal or fatal repeat suicide attempt within six months. Also, repeat attempt using a violent method was used as an additional outcome in separate analyses. Data were analyzed for the total group and for men and women separately. Repeat attempts were observed within six months in 78 persons (22%) and 21 (6%) of these used a violent method. KIVS total score of 6 or more was associated with repeat suicide attempt within six months (OR = 1.81, CI 1.08-3.02) and predicted new attempts with a sensitivity of 62% and a specificity of 53%. A three-fold increase in odds ratio was observed for repeat attempt using a violent method (OR = 3.40, CI 1.22-9.49). An association between exposure to violence in adulthood and violent reattempt was seen in women (OR = 1.38, CI 1.06-1.82). The overall conclusions are that information about interpersonal violence may help predict short-term risk for repeat suicide attempt, and that structured assessment of interpersonal violence may be of value in risk assessment after attempted suicide.
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