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2.
  • Dumanski, Jan P., et al. (författare)
  • Mosaic Loss of Chromosome Y in Blood Is Associated with Alzheimer Disease
  • 2016
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 98:6, s. 1208-1219
  • Tidskriftsartikel (refereegranskat)abstract
    • Men have a shorter life expectancy compared with women but the underlying factor(s) are not clear. Late-onset, sporadic Alzheimer disease (AD) is a common and lethal neurodegenerative disorder and many germline inherited variants have been found to influence the risk of developing AD. Our previous results show that a fundamentally different genetic variant, i.e., lifetime-acquired loss of chromosome Y (LOY) in blood cells, is associated with all-cause mortality and an increased risk of non-hematological tumors and that LOY could be induced by tobacco smoking. We tested here a hypothesis that men with LOY are more susceptible to AD and show that LOY is associated with AD in three independent studies of different types. In a case-control study, males with AD diagnosis had higher degree of LOY mosaicism (adjusted odds ratio = 2.80, p = 0.0184, AD events = 606). Furthermore, in two prospective studies, men with LOY at blood sampling had greater risk for incident AD diagnosis during follow-up time (hazard ratio [HR] = 6.80, 95% confidence interval [95% CI] = 2.16-21.43, AD events = 140, p = 0.0011). Thus, LOY in blood is associated with risks of both AD and cancer, suggesting a role of LOY in blood cells on disease processes in other tissues, possibly via defective immunosurveillance. As a male-specific risk factor, LOY might explain why males on average live shorter lives than females.
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4.
  • Dumanski, Jan P., et al. (författare)
  • Smoking is associated with mosaic loss of chromosome Y
  • 2015
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6217, s. 81-83
  • Tidskriftsartikel (refereegranskat)abstract
    • Tobacco smoking is a risk factor for numerous disorders, including cancers affecting organs outside the respiratory tract. Epidemiological data suggest that smoking is a greater risk factor for these cancers in males compared to females. This observation, together with the fact that males have a higher incidence of and mortality from most non-sex-specific cancers, remains unexplained. Loss of chromosome Y (LOY) in blood cells is associated with increased risk of nonhematological tumors. We demonstrate here that smoking is associated with LOY in blood cells in three independent cohorts [TwinGene: odds ratio (OR) = 4.3, 95% CI = 2.8-6.7; ULSAM: OR = 2.4, 95% CI = 1.6-3.6; and PIVUS: OR = 3.5, 95% CI = 1.4-8.4] encompassing a total of 6014 men. The data also suggest that smoking has a transient and dose-dependent mutagenic effect on LOY status. The finding that smoking induces LOY thus links a preventable risk factor with the most common acquired human mutation.
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5.
  • Forsberg, Anna, et al. (författare)
  • Once-only colonoscopy or two rounds of faecal immunochemical testing 2 years apart for colorectal cancer screening (SCREESCO): preliminary report of a randomised controlled trial
  • 2022
  • Ingår i: The Lancet Gastroenterology & Hepatology. - : ELSEVIER INC. - 2468-1253. ; 7:6, s. 513-521
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Screening for colorectal cancer is done with lower gastrointestinal endoscopy or stool-based tests. There is little evidence from randomised trials to show primary colonoscopy reduces mortality in colorectal cancer We aimed to investigate the effect of screening with once-only colonoscopy or two rounds of faecal immunochemical test screening on colorectal cancer mortality and incidence. Methods We did a randomised controlled trial in Sweden (SCREESCO). Residents in 18 of 21 regions who were age 60 years in the year of randomisation were identified from a population register maintained by the Swedish Tax Agency. A statistician with no further involvement in the trial used a randomised block method to assign individuals to once-only colonoscopy, two rounds of faecal immunochemical testing (OC-Sensor; 2 years apart), or a control group (no intervention; standard diagnostic pathways), in a ratio of 1:6 for colonoscopy versus control and 1:2 for faecal immunochemical testing versus control. Masking was not possible due to the nature of the trial. The primary endpoints of the trial are colorectal cancer mortality and colorectal cancer incidence. Here, we report preliminary participation rates, baseline findings, and adverse events from March, 2014, to December, 2020, in the two intervention groups after completion of recruitment and screening, up to the completion of the second faecal immunochemical testing round. Analyses were done in the intention-to-screen population, defined as all individuals who were randomly assigned to the respective study group. This study is registered with Clinical Trials.gov, NCT02078804. Findings Between March 1, 2014, and Dec 31, 2020, 278 280 people were induded in the study; 31 140 were assigned to the colonoscopy group, 60 300 to the faecal immunochemical test group, and 186 840 to the control group. 10 679 (35.1%) of 30 400 people who received an invitation for colonoscopy participated. 33 383 (55.5%) of 60 137 people who received a postal faecal immunochemical test participated. In the intention-to-screen analysis, colorectal cancer was detected in 49 (0.16%) of 31140 people in the colonoscopy group versus 121 (0. 20%) of 60 300 in the faecal immunochemical test group (relative risk [RR] 0.78, 95% CI 0.56-1.09). Advanced adenomas were detected in 637 (2.05%) people in the colonoscopy group and 968 (1.61%) in the faecal immunochemical test group (RR 1.27, 95% CI 1.15-1.41). Colonoscopy detected more right-sided advanced adenomas than faecal immunochemical testing. There were two perforations and 15 major bleeds in 16 555 colonoscopies. No intervention-related deaths occurred. Interpretation The diagnostic yield and the low number of adverse events indicate that the design from this trial, both for once-only colonoscopy and faecal immunochemical test screening, could be transferred to a population-based screening service if a benefit in disease-specific mortality is subsequently shown. Copyright (C) 2022 Elsevier Ltd. All rights reserved.
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6.
  • Forsberg, Lars A., 1974-, et al. (författare)
  • Mosaic loss of chromosome Y in leukocytes matters
  • 2019
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:1, s. 4-7
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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7.
  • Forsberg, Lars A., et al. (författare)
  • Mosaic loss of chromosome Y in peripheral blood is associated with shorter survival and higher risk of cancer
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:6, s. 624-628
  • Tidskriftsartikel (refereegranskat)abstract
    • Incidence and mortality for sex-unspecific cancers are higher among men, a fact that is largely unexplained(1,2). Furthermore, age-related loss of chromosome Y (LOY) is frequent in normal hematopoietic cells(3,4), but the phenotypic consequences of LOY have been elusive(5-10). From analysis of 1,153 elderly men, we report that LOY in peripheral blood was associated with risks of all-cause mortality (hazards ratio (HR) = 1.91, 95% confidence interval (CI) = 1.17-3.13; 637 events) and non-hematological cancer mortality (HR = 3.62, 95% CI = 1.56-8.41; 132 events). LOY affected at least 8.2% of the subjects in this cohort, and median survival times among men with LOY were 5.5 years shorter. Association of LOY with risk of all-cause mortality was validated in an independent cohort (HR = 3.66) in which 20.5% of subjects showed LOY. These results illustrate the impact of post-zygotic mosaicism on disease risk, could explain why males are more frequently affected by cancer and suggest that chromosome Y is important in processes beyond sex determination. LOY in blood could become a predictive biomarker of male carcinogenesis.
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8.
  • Hugerth, Luisa W., et al. (författare)
  • No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population
  • 2020
  • Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69:6, s. 1076-1084
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective The ethiopathogenesis of irritable bowel syndrome (IBS) is unknown. While a link to the gut microbiome is postulated, the heterogeneity of the healthy gut makes it difficult to draw definitive conclusions. We aimed to describe the faecal and mucosa-associated microbiome (MAM) and health correlates on a community cohort of healthy and IBS individuals with no colonoscopic findings.Design The PopCol study recruited a random sample of 3556 adults; 745 underwent colonoscopy. IBS was defined by Rome IV criteria and organic disease excluded. 16S rRNA gene sequencing was conducted on sigmoid biopsy samples from 376 representative individuals (63 IBS cases) and faecal samples from 185 individuals (32 IBS cases).Results While sigmoid MAM was dominated by Lachnospiraceae, faeces presented a higher relative abundance of Ruminococcaceae. Microbial richness in MAM was linearly correlated to that in faeces from the same individual (R-2=0.255, p<3E-11) as was diversity (R-2=0.06, p=0.0022). MAM diversity decreased with increasing body mass index (BMI; Pearson's r=-0.1, p=0.08) and poorer self-rated health (r=-0.15, p=0.007), but no other health correlates. Faecal microbiome diversity was correlated to stool consistency (r=-0.16, p=0.043). Several taxonomic groups were correlated to age, BMI, depression and self-reported health, including Coprococcus catus associated with lower levels of depression (r=-0.003, p=0.00017). The degree of heterogeneity observed between IBS patients is higher than that observed between healthy individuals.Conclusions No distinct microbial signature was observed in IBS. Individuals presenting with low self-rated health or high BMI have lower gut microbiome richness.
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9.
  • Mattsson, Patrik, et al. (författare)
  • β-Amyloid binding in elderly subjects with declining or stable episodic memory function measured with PET and [11C]AZD2184
  • 2015
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 42:10, s. 1507-1511
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Cognitive decline has been suggested as an early marker for later onset of Alzheimer's disease. We therefore explored the relationship between decline in episodic memory and β-amyloid using positron emission tomography (PET) and [11C]AZD2184, a radioligand with potential to detect low levels of amyloid deposits.Methods: Healthy elderly subjects with declining (n = 10) or stable (n = 10) episodic memory over 15 years were recruited from the population-based Betula study and examined with PET. Brain radioactivity was measured after intravenous administration of [11C]AZD2184 The binding potential BP ND was calculated using linear graphical analysis with the cerebellum as reference region.Results: The binding of [11C]AZD2184 in total grey matter was generally low in the declining group, whereas some binding could be observed in the stable group. Mean BP ND was significantly higher in the stable group compared to the declining group (p = 0.019). An observation was that the three subjects with the highest BPND were ApoE ε4 allele carriers.Conclusions: We conclude that cognitive decline in the general population does not seem to stand by itself as an early predictor for amyloid deposits.
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10.
  • Agreus, Lars, et al. (författare)
  • Towards a healthy stomach? : Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community
  • 2016
  • Ingår i: United European Gastroenterology journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 4:5, s. 686-696
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden.Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22-80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n=145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status.Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11-0.59, p=0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p=0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6-15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8-5.5); all cases were 57 years old.Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.
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11.
  • Alexandersson, Bjarki T., et al. (författare)
  • Diverticulosis is not associated with altered gut microbiota nor is it predictive of future diverticulitis : a population-based colonoscopy study
  • 2023
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 58:10, s. 1131-1138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The etiopathogenesis of diverticular disease is unknown.Objective: To compare the fecal and mucosa-associated microbiota between participants with and without diverticulosis and participants who later developed diverticulitis versus those that did not from a population-based study.Methods: The PopCol study, conducted in Stockholm, Sweden, invited a random sample of 3556 adults to participate, of which 745 underwent colonoscopy. Overall, 130 participants (17.5%) had diverticulosis. 16S rRNA gene sequencing was conducted on available sigmoid biopsy samples from 529 and fecal samples from 251 individuals. We identified individuals who subsequently developed acute diverticulitis up to 13 years after sample collection. In a case-control design matching for gender, age (+/−5 years), smoking and antibiotic exposure, we compared taxonomic composition, richness and diversity of the microbiota between participants with or without diverticulosis, and between participants who later developed acute diverticulitis versus those who did not.Results: No differences in microbiota richness or diversity were observed between participants with or without diverticulosis, nor for those who developed diverticulitis compared with those who did not. No bacterial taxa were significantly different between participants with diverticulosis compared with those without diverticulosis. Individuals who later developed acute diverticulitis (2.8%) had a higher abundance of genus Comamonas than those who did not (p = .027).Conclusions: In a population-based cohort study the only significant difference was that those who later develop diverticulitis had more abundance of genus Comamonas. The significance of Comamonas is unclear, suggesting a limited role for the gut microbiota in the etiopathogenesis of diverticular disease.
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12.
  • Andreasson, Anna, et al. (författare)
  • An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years : A Prospective Population-Based Study in Sweden
  • 2021
  • Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 116:1, s. 210-213
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing.METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21–79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22–80 years, rr = 87%), 1995 (n = 1,139, 20–85 years, rr = 76%), and 2011 (n = 1,175, 20–93 years, rr = 63%).RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60–4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42–1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50–2.73).DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.
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13.
  • Annika, Hagenbjörk-Gustafsson, et al. (författare)
  • Spatial variation of ground level ozone and the relation between ozone and NO2/NOx in two Swedish cities
  • 2013
  • Konferensbidrag (refereegranskat)abstract
    • Background Ozone is a pollutant known to cause adverse effects on human health. It is formed by reactions between nitrogen oxides (NOx) and hydrocarbons under the influence of sunlight. In urban areas ozone is consumed oxidating nitrogen oxide (NO) to nitrogen dioxide (NO2). Despite the potential to cause adverse health effects, the local spatial distribution of ozone and the relationship between ozone, NO2 and NOx in different environments is poorly studied.Aims Our aim was to study the concentrations and spatial distribution of ozone in two cities, Malmö in the south of Sweden and Umeå in the north of Sweden, since the contribution of ozone from other parts of Europe decreases with higher latitude. We also wanted to investigate differences in the ozone/NO2 and the ozone/NOx ratios between the cities and between different environments.Methods Ozone, NO2 and NOx concentrations were measured with Ogawa diffusive samplers during three one-week campaigns in April, May/June and in August 2012. Measurements were conducted simultaneously at 20 sites in each city outside preschools, distributed at traffic sites, urban background sites and regional background (rural) sites. Results The average concentration of ozone in Malmö and Umeå were 67,5 µg/m3 and 50,6 µg/m3, respectively. The mean ozone/NOx ratio was of equal magnitude in Malmö and in Umeå, and in both cities the ratio was highest at rural sites and lowest at traffic sites. In Umeå there was a clear trend with highest ozone concentrations at rural sites and lowest concentrations at traffic sites, a trend that was not as obvious in Malmö. In Umeå the ozone/NO2 ratio at rural sites was about three times larger compared to Malmö.Conclusions There is a clear local variation of ozone, with stronger gradients in northern (Umeå) Sweden in comparison to southern Sweden (Malmö). This can partly be explained by less long-range transport of ozone and larger impact of local NO emissions that reduce ozone in northern Sweden.
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14.
  • Benckert, Lars, et al. (författare)
  • Fresnel diffraction of a Gaussian laser beam by polished metal cylinders
  • 1990
  • Ingår i: Applied Optics. - 1559-128X .- 2155-3165. ; 29:3, s. 416-421
  • Tidskriftsartikel (refereegranskat)abstract
    • A laser beam touching the periphery of a polished cylinder is subjected to both diffraction and reflection. Inthe area where diffracted light and reflected light interact the resulting intensity distribution differs from thepattern predicted by diffraction theory for a sharp edge. The difference increases with cylinder radius. Inthis paper it is shown that a good description of the resulting intensity pattern is obtained by adding thereflected light amplitude to the diffracted amplitude as predicted by the Fresnel-Kirchhoff theory for a sharpedge.
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15.
  • Bränström, Robert, et al. (författare)
  • Electrical short-circuit in β-cells from a patient with non-insulinoma pancreatogenous hypoglycemic syndrome (NIPHS) : a case report
  • 2010
  • Ingår i: Journal of Medical Case Reports. - : Springer Science and Business Media LLC. - 1752-1947. ; 4:1, s. 315-
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Non-insulinoma pancreatogenous hypoglycemic syndrome is a rare disorder among adults, and, to our knowledge, only about 40 cases have been reported in the literature. CASE PRESENTATION: The patient is a previously healthy 35-year-old Caucasian man. His symptoms began four years ago when he suddenly felt weakness in his legs and started sweating for unknown reasons. The symptoms worsened, and laboratory tests revealed hypoglycemia and hyperinsulinemia at the time of the symptoms. All diagnostics attempts using magnetic resonance imaging, computed tomography, and endoscopic ultrasound did not reveal any abnormalities. At this stage, surgical intervention was planned, and a distal 80% pancreatectomy was performed. The histopathologic and immunohistochemical investigations of the pancreas showed an increased number of islets of different sizes, more or less evenly distributed in the gland, but no insulinoma. Patch-clamp recordings from isolated pancreatic β-cells showed that, even at a low glucose concentration (3 mmol/L), the β-cell membrane was depolarized, and action potentials were seen. Surprisingly, in patch-clamp experiments, the addition of diazoxide had a marked effect on K-ATP channel activity and membrane potential, but no effect on insulin levels in vivo before surgery. CONCLUSION: This case report adds new information on the pathogenesis of non-insulinoma pancreatogenous hypoglycemic syndrome, as we performed an electrophysiologic characterization of isolated islet cells. We show, for the first time, that β-cells isolated from a non-insulinoma pancreatogenous hypoglycemic syndrome patient are constantly depolarized, even at low glucose levels, but display normal K-ATP channel physiology.
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16.
  • Cap, Fabienne, et al. (författare)
  • SWORD : Towards Cutting-Edge Swedish Word Processing
  • 2016
  • Ingår i: Proceedings of SLTC 2016.
  • Konferensbidrag (refereegranskat)abstract
    • Despite many years of research on Swedish language technology, there is still no well-documented standard for Swedish word processing covering the whole spectrum from low-level tokenization to morphological analysis and disambiguation. SWORD is a new initiative within the SWE-CLARIN consortium aiming to develop documented standards for Swedish word processing. In this paper, we report on a pilot study of Swedish tokenization, where we compare the output of six different tokenizers on four different text types. For one text type (Wikipedia articles), we also compare to the tokenization produced by six manual annotators.
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18.
  • Carlbring, Per, et al. (författare)
  • Behavioral Activation vs. Physical Exercise in the Treatment of Mild to Moderate Depression
  • 2015
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Despite their potential as low-threshold, low-cost and high-flexibility treatments of depression, behavioral activation and physical exercise have not yet been directly compared. This study has examined the effects of these interventions, administered via the Internet. In this randomized controlled trial a total of 312 participants meeting the diagnostic criteria for mild to moderate major depression, recruited in multiple cycles and randomized to either a waiting list control group with delayed treatment, or one of the four active treatment groups: (1) physical exercise without a clear psychological treatment rationale; (2) physical exercise with a psychological treatment rationale; (3) behavioral activation a la Lewinsohn; or (4) behavioral activation a la Martel. A total of 72% were women and the average age of the participants were M=42.3 years (SD=13,5). More than half (53,9%) had a history of previous psychological treatment. Primary outcome measure was the 9-item Patient Health Questionnaire. Assessments were made on a weekly basis for the full duration of the acute treatment which was 12 weeks. The preliminary results are in line with previous online studies showing that all active treatment groups were superior to the waitlist (large effect sizes) and that only minor differences could be identified between the four active groups (large within effect sizes). At the time of the conference 6-month follow-up data will be available in addition to the already collected post-assessment data (analyzed according to the intention-to-treat principle).
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19.
  • Carlbring, Per, et al. (författare)
  • The effects on depression of Internet-administered behavioural activation and physical exercise with treatment rationale and relapse prevention : study protocol for a randomised controlled trial
  • 2013
  • Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14, s. 35-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Despite their potential as low-threshold, low-cost and high-flexibility treatments of depression, behavioural activation and physical exercise have not yet been directly compared. This study will examine the effects of these interventions, administered via the Internet. The added effect of providing a treatment rationale will also be studied, as well as a relapse prevention program featuring cognitive behavioural therapy components.Methods/Design: This randomised controlled trial will include 500 participants meeting the diagnostic criteria for major depression, recruited in multiple cycles and randomised to either a waiting list control group with delayed treatment, or one of the four treatment groups: (1) physical exercise without a clear treatment rationale; (2) physical exercise with treatment rationale; (3) behavioural activation with treatment rationale; or (4) behavioural activation without a clear treatment rationale. Post treatment, half of the participants will be offered a relapse prevention program. Primary outcome measure will be the Patient Health Questionnaire 9-item. Secondary measures include diagnostic criteria for depression, as well as self-reported anxiety, physical activity and quality of life. Measurements - done via telephone and the Internet - will be collected pre-treatment, weekly during treatment period, immediately post treatment and then monthly during a 24-month follow-up period.Discussion: The results of this study will constitute an important contribution to the body of knowledge of the respective interventions. Limitations are discussed.
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20.
  • Chase, A., et al. (författare)
  • Profound parental bias associated with chromosome 14 acquired uniparental disomy indicates targeting of an imprinted locus
  • 2015
  • Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 29:10, s. 2069-2074
  • Tidskriftsartikel (refereegranskat)abstract
    • Acquired uniparental disomy (aUPD) is a common finding in myeloid malignancies and typically acts to convert a somatically acquired heterozygous mutation to homozygosity. We sought to identify the target of chromosome 14 aUPD (aUPD14), a recurrent abnormality in myeloid neoplasms and population cohorts of elderly individuals. We identified 29 cases with aUPD14q that defined a minimal affected region (MAR) of 11.2 Mb running from 14q32.12 to the telomere. Exome sequencing (n = 7) did not identify recurrently mutated genes, but methylation-specific PCR at the imprinted MEG3-DLK1 locus located within the MAR demonstrated loss of maternal chromosome 14 and gain of paternal chromosome 14 (P < 0.0001), with the degree of methylation imbalance correlating with the level of aUPD (r = 0.76; P = 0.0001). The absence of driver gene mutations in the exomes of three individuals with aUPD14q but no known haematological disorder suggests that aUPD14q may be sufficient to drive clonal haemopoiesis. Analysis of cases with both aUPD14q and JAK2 V617F (n = 11) indicated that aUPD14q may be an early event in some cases but a late event in others. We conclude that aUPD14q is a recurrent abnormality that targets an imprinted locus and may promote clonal haemopoiesis either as an initiating event or as a secondary change.
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21.
  • Danielsson, Marcus, et al. (författare)
  • Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals
  • 2020
  • Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 28:3, s. 349-357
  • Tidskriftsartikel (refereegranskat)abstract
    • Mosaic loss of chromosome Y (LOY) is the most common somatic genetic aberration and is associated with increased risk for all-cause mortality, various forms of cancer and Alzheimer's disease, as well as other common human diseases. By tracking LOY frequencies in subjects from which blood samples have been serially collected up to five times during up to 22 years, we observed a pronounced intra-individual variation of changes in the frequency of LOY within individual men over time. We observed that in some individuals the frequency of LOY in blood clearly progressed over time and that in other men, the frequency was constant or showed other types of longitudinal development. The predominant method used for estimating LOY is calculation of the median Log R Ratio of probes located in the male specific part of chromosome Y (mLRRY) from intensity data generated by SNP-arrays, which is difficult to interpret due to its logarithmic and inversed scale. We present here a formula to transform mLRRY-values to percentage of LOY that is a more comprehensible unit. The formula was derived using measurements of LOY from matched samples analysed using SNP-array, whole genome sequencing and a new AMELX/AMELY-based assay for droplet digital PCR. The methods described could be applied for analyses of the vast amount of SNP-array data already generated in the scientific community, allowing further discoveries of LOY associated diseases and outcomes.
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22.
  • Dumanski, Jan P., et al. (författare)
  • A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
  • 2017
  • Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:8, s. 427-443
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.
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23.
  • Forsberg, Anna, et al. (författare)
  • Colonoscopy findings in high-risk individuals compared to an average-risk control population
  • 2015
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 50:7, s. 866-874
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. Methods: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. Results: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. Conclusions: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.
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24.
  • Forsberg, Anna M., et al. (författare)
  • Prevalence of colonic neoplasia and advanced lesions in the normal population : a prospective population-based colonoscopy study
  • 2012
  • Ingår i: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 47:2, s. 184-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. There are few prospective studies of the prevalence of colonic neoplasia in the normal population. In order to properly evaluate screening-protocols for colorectal cancer in risk groups (e.g., older subjects or those with a family history), it is essential to know the prevalence of adenomas and cancer in the normal population. Methods. A prospective population-based colonoscopy study on 745 individuals born in Sweden aged 19-70 years was conducted (mean age 51.1 years). All polyps seen were retrieved and examined. Results. Out of the 745 individuals 27% had polyps, regardless of kind. Adenomas were found in 10% of the individuals and finding of adenomas was positively correlated to higher age. Men had adenomas in 15% and women in 6% of the cases. Women had a right-sided dominance of adenomas. Hyperplastic polyps were seen in 21% of the individuals. The presence of hyperplastic polyps was significantly positively correlated to the presence of adenomas. Advanced adenomas were seen in 2.8% of the study participants, but no cancers were detected. Conclusion. One in 10 healthy subjects had an adenoma but advanced adenomas were uncommon. Men and women have a different adenoma prevalence and localization. The results provide baseline European data for evaluating colonoscopy screening-protocols for colorectal cancer risk groups, and the findings may have implications for colon cancer screening in the normal, otherwise-healthy population.
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25.
  • Forsberg, Lars A., et al. (författare)
  • Age-related somatic structural changes in the nuclear genome of human blood cells
  • 2012
  • Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 90:2, s. 217-228
  • Tidskriftsartikel (refereegranskat)abstract
    • Structural variations are among the most frequent interindividual genetic differences in the human genome. The frequency and distribution of de novo somatic structural variants in normal cells is, however, poorly explored. Using age-stratified cohorts of 318 monozygotic (MZ) twins and 296 single-born subjects, we describe age-related accumulation of copy-number variation in the nuclear genomes in vivo and frequency changes for both megabase- and kilobase-range variants. Megabase-range aberrations were found in 3.4% (9 of 264) of subjects ≥60 years old; these subjects included 78 MZ twin pairs and 108 single-born individuals. No such findings were observed in 81 MZ pairs or 180 single-born subjects who were ≤55 years old. Recurrent region- and gene-specific mutations, mostly deletions, were observed. Longitudinal analyses of 43 subjects whose data were collected 7-19 years apart suggest considerable variation in the rate of accumulation of clones carrying structural changes. Furthermore, the longitudinal analysis of individuals with structural aberrations suggests that there is a natural self-removal of aberrant cell clones from peripheral blood. In three healthy subjects, we detected somatic aberrations characteristic of patients with myelodysplastic syndrome. The recurrent rearrangements uncovered here are candidates for common age-related defects in human blood cells. We anticipate that extension of these results will allow determination of the genetic age of different somatic-cell lineages and estimation of possible individual differences between genetic and chronological age. Our work might also help to explain the cause of an age-related reduction in the number of cell clones in the blood; such a reduction is one of the hallmarks of immunosenescence.
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26.
  • Forsberg, Lisa, et al. (författare)
  • Clinician acquisition and retention of motivational interviewing skills : a two-and-a-half-year exploratory study
  • 2010
  • Ingår i: Substance Abuse Treatment, Prevention, and Policy. - Stockholm : Karolinska Institutet, Dept of Public Health Sciences. - 1747-597X.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Motivational interviewing (MI) is a collaborative, client-centred counselling style aimed at eliciting and strengthening clients' intrinsic motivation to change. There is strong research evidence supporting the efficacy of MI, notably in its application among alcohol and drug abuse populations. MI interventions in smoking cessation may yield modest but significant increases in quitting. The present study sought to assess the acquisition and retention of MI skills in counsellors at the Swedish National Tobacco Quitline. Methods: Three audio-recorded sessions from each of three counsellors were assessed using the Motivational Interviewing Treatment Integrity (MITI) Code Version 3.0 over 11 assessment periods at fixed intervals in a two-and-a-half year period during which counsellors received ongoing supervision. Results: The mean skill for all counsellors improved throughout the study period in most MITI variables. However, great variations in MI skill between counsellors were observed, as well as fluctuations in performance in counsellors over time. Conclusion: The present exploratory study covers a longer time period than most evaluations of MI training, and has several advantages with regard to study design. It may provide a basis for (larger sample) replication to test MI skill (as measured by the MITI) in relation to behaviour change in clients, to evaluate MI training, and to assess the acquisition and retention of MI skill over time. Difficulties in acquiring and retaining MI skill may raise the issue of a selection policy for MI training. Moreover, fluctuations in MI skill over time emphasise the greater importance of continuous feedback and supervision over initial MI training, and the need for the use of validated treatment integrity assessment instruments in ordinary clinical implementations of MI.
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27.
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28.
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29.
  • Jonsson, Lars, et al. (författare)
  • Targeting Academic Engagement in Open Innovation: Tools, Effects and Challenges for University Management
  • 2015
  • Ingår i: Journal of the Knowledge Economy. - : Springer Science and Business Media LLC. - 1868-7865 .- 1868-7873. ; 6:3, s. 522-550
  • Tidskriftsartikel (refereegranskat)abstract
    • Besides commercialization, university knowledge is commonly transferred through different interactions constituting the so called academic engagement. Very little attention has been paid to professionalizing these various interactions compared to the linear commercialization funnel. In this paper, we conducted a qualitative case study of the innovation support organization at Uppsala University, Sweden, analysing the following: Which mechanisms and tools the university management does apply in order to create targeted open innovation interactions and which effects and challenges emerge when applying these tools? We found that staff with experience of both academia and industry is important for enabling open innovation interactions to evolve and that tools can be used to concretize specific and deeper interactions. However, six challenges was also identified: (1) the intermittent nature of university-industry interactions; (2) lack of codified ways to trace effects; (3) extensive and time consuming preparatory work; (4) the extra resources and low conversion rates in engaging academically unrelated small and medium-sized enterprises (SMEs); (5) high costs of recruiting staff with double competence and running the studied tools; and (6) the interdependencies which makes the system sensitive. Our results indicate that the tools used help the university to follow a mode 3 of knowledge creation. The study addressed the research gap regarding organizational support in academic engagement by indicating which tools can be used by the university management to target and focus industryacademia interactions, their effects and associated challenges. A lot of the effects still need to be codified, and more research is needed to understand their impact over time.
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30.
  • Lu, Ming, et al. (författare)
  • Expression and association of TRPC subtypes with Orai1 and STIM1 in human parathyroid
  • 2010
  • Ingår i: Journal of Molecular Endocrinology. - 0952-5041 .- 1479-6813. ; 44:5, s. 285-294
  • Tidskriftsartikel (refereegranskat)abstract
    • The mechanism behind Ca2+ entry into the parathyroid cells has been widely debated, and the molecular identities of the responsible ion channels have not been established yet. In this study, we show that the parathyroid cells lack voltage-operated Ca2+ channels. Passive store depletion by thapsigargin, on the other hand, induces a large non-voltage-activated non-selective cation current. The increase in intracellular Ca2+ caused by thapsigargin is attenuated by 2-aminoethoxydiphenyl borate, a blocker of store-operated Ca2+ entry (SOCE). Candidate molecules for non-voltage-operated Ca2+ signaling were investigated. These included members of the transient receptor potential canonical (TRPC) ion channel family, as well as Ca2+ release-activated Ca2+ modulator 1 (Orai1) and stromal interaction molecule 1 (STIM1) that are key proteins in the SOCE pathway. Using RT-PCR screening, quantitative real-time PCR, and western blot, we showed expression of TRPC1, TRPC4, and TRPC6; Orai1; and STIM1 genes and proteins in normal and adenomatous human parathyroid tissues. Furthermore, co-immunoprecipitation experiments demonstrated a ternary complex of TRPC1-Orai1-STIM1, supporting a physical interaction between these molecules in human parathyroid.
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31.
  • Malmqvist, Ebba, et al. (författare)
  • Assessing ozone exposure for epidemiological studies in Malmo and Umea, Sweden
  • 2014
  • Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 94, s. 241-248
  • Tidskriftsartikel (refereegranskat)abstract
    • Ground level ozone [ozone] is considered a harmful air pollutant but there is a knowledge gap regarding its long term health effects. The main aim of this study is to develop local Land Use Regression [LUR] models that can be used to study long term health effects of ozone. The specific aim is to develop spatial LUR models for two Swedish cities, Umea and Malmo, as well as a temporal model for Malmo in order to assess ozone exposure for long term epidemiological studies. For the spatial model we measured ozone, using Ogawa passive samplers, as weekly averages at 40 sites in each study area, during three seasons. This data was then inserted in the LUR-model with data on traffic, land use, population density and altitude to develop explanatory models of ozone variation. To develop the temporal model for Malmo, hourly ozone data was aggregated into daily means for two measurement stations in Malmo and one in a rural area outside Malmo. Using regression analyses we inserted meteorological variables into different temporal models and the one that performed best for all three stations was chosen. For Malmo the LUR-model had an adjusted model R-2 of 0.40 and cross validation R-2 of 0.17. For Umea the model had an adjusted model R-2 of 0.67 and cross validation adjusted R-2 of 0.48. When restricting the model to only including measuring sites from urban areas, the Malmo model had adjusted model R-2 of 0.51 (cross validation adjusted R-2 0.33) and the Umea model had adjusted model R-2 of 0.81 (validation adjusted R-2 of 0.73). The temporal model had adjusted model R-2 0.54 and 0.61 for the two Malmo sites, the cross validation adjusted R-2 was 0.42. In conclusion, we can with moderate accuracy, at least for Umea, predict the spatial variability, and in Malmo the temporal variability in ozone variation. (C) 2014 The Authors. Published by Elsevier Ltd.
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32.
  • Mattsson, Patrik, et al. (författare)
  • High Contrast PET Imaging of Subcortical and Allocortical Amyloid-β in Early Alzheimer's Disease Using [11C]AZD2184
  • 2024
  • Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 98:4, s. 1391-1401
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Deposits of amyloid-β (Aβ) appear early in Alzheimer's disease (AD).OBJECTIVE: The aim of the present study was to compare the presence of cortical and subcortical Aβ in early AD using positron emission tomography (PET).METHODS: Eight cognitively unimpaired (CU) subjects, 8 with mild cognitive impairment (MCI) and 8 with mild AD were examined with PET and [11C]AZD2184. A data driven cut-point for Aβ positivity was defined by Gaussian mixture model of isocortex binding potential (BPND) values.RESULTS: Sixteen subjects (3 CU, 5 MCI and 8 AD) were Aβ-positive. BPND was lower in subcortical and allocortical regions compared to isocortex. Fifteen of the 16 Aβ-positive subjects displayed Aβ binding in striatum, 14 in thalamus and 10 in allocortical regions.CONCLUSIONS: Aβ deposits appear to be widespread in early AD. It cannot be excluded that deposits appear simultaneously throughout the whole brain which has implications for improved diagnostics and disease monitoring.
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33.
  • Modig, Lars, 1976- (författare)
  • Asthma, rhinitis, and asthma-related symptoms in relation to vehicle exhaust using different exposure metrics
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Air pollution is a well known public health problem that involves both long-term and acute effects. An outcome associated with traffic-related air pollution is respiratory illness. Many studies have described the relationship between asthmatic symptoms and traffic-related air pollution; however, few have investigated the potential of air pollution to cause asthma itself, especially among adults. The overall aim of this thesis was to study the relationship between vehicle exhaust levels at home and the prevalence of self-reported annoyance and asthmatic symptoms, and the incidence of asthma and rhinitis. These relationships were evaluated using different indicators of exposure with a high spatial resolution. Three different data sets were used for the four papers included in this thesis. The first paper (paper I) is based on a questionnaire that was sent to a random selection of the adult population within three Swedish cities (Gothenburg, Uppsala, and Umeå) as part of the Swedish Environmental Protection Agency’s health-related environmental monitoring. The aim was to study the degree of self-reported annoyance and the prevalence of asthmatic symptoms in relation to the levels of vehicle exhaust outside the home. The level of exposure was described using modeled levels of nitrogen dioxide (NO2) as the exposure indicator. The second paper (paper II) is based on new asthma cases identified within the Obstructive Lung disease In Northern Sweden (OLIN) study, each with a matched referent. The aim of this study was to analyze if new cases of asthma had higher levels of vehicle exhaust outside the home compared to the population controls. Exposure was assessed using both measured levels of NO2 outside each home, and by summarizing the amount of traffic within a 200 metre buffer surrounding each participant’s home. Papers III and IV were based on the Respiratory Health in Northern Europe (RHINE) Cohort, a prospective cohort of adults included in 1990 and followed up with in 1999. The proportion of new cases of asthma (papers III and IV) and rhinitis (paper IV) were identified based on the answers from the initial and follow-up questionnaires. In paper III, exposure was assessed by using meteorological dispersion models to calculate the levels of NO2 outside each home as an indicator of the levels of vehicle exhaust. As an alternative indicator, the distance from each participant’s home to the nearest major road was calculated using geographical information system (GIS) tools. The exposure assessment in paper IV was also based on meteorological dispersion models, but expressed the levels of vehicle exhaust as particle mass concentration. The results show that the levels of vehicle exhaust outside the home are significantly correlated with the degree of self-reported annoyance and the prevalence of asthmatic symptoms, and also with the risk of developing asthma, but not rhinitis, among adults. The odds ratio (OR) for high annoyance to vehicle exhaust and reporting asthmatic symptoms was 1.14 (95% Confidence Interval, CI 1.11-1.18) and 1.04 (95% CI 1.01-1.07) per 1 µg/m3 increase in the NO2 level outside the home, respectively. Paper II showed there was a non-significant tendency for increased risk of developing asthma among those living with high levels of vehicle exhaust outside their home. This finding was then supported by papers III and IV, showing a significant relationship between the onset of asthma and the mean (winter) levels of NO2 outside the home (OR=1.46, 95% CI 1.07-1.99 per 10 µg/m3) and the levels of vehicle exhaust particles outside the home. In paper III, living close to a major road was significantly related to the risk of developing asthma. No significant results were shown between vehicle exhaust and rhinitis. In conclusion, vehicle exhaust outside the home is associated with the prevalence of annoyance and asthmatic symptoms, and with the risk of developing asthma, but not rhinitis, among adults.
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34.
  • Nayeri, Fariba, 1958-, et al. (författare)
  • Hepatocyte Growth Factor Levels in Cerebrospinal Fluid : A Comparison between Acute Bacterial and Nonbacterial Meningitis
  • 2000
  • Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 181:6, s. 2092-2094
  • Tidskriftsartikel (refereegranskat)abstract
    • The organotrophic functions of the hepatocyte growth factor (HGF) have been the subject of several studies. In the more recent studies, this function has been reported in the brain. In the present study, we have measured the levels of HGF in cerebrospinal fluid (CSF) and sera from 78 patients divided into 6 different groups according to central nervous system (CNS) infection and control. Quantitative measurements of HGF in the CSF and serum were performed by an enzyme-linked immunosorbent assay. Elevated values of CSF HGF were found in the patients with acute bacterial/probable bacterial meningitis (P < .001), compared with nonbacterial CNS infections and facial palsy, as well as with a control group without signs of CNS involvement. The values of CSF HGF were not correlated to blood-brain-barrier disruption in the groups. These observations might indicate an intrathecal production of HGF in acute bacterial/probable bacterial meningitis.
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35.
  • Nilsson, Madeleine, et al. (författare)
  • The perceived threat of the risk for graft rejection and health-related quality of life among organ transplant recipients
  • 2011
  • Ingår i: Journal of Clinical Nursing. - : Wiley. - 0962-1067 .- 1365-2702. ; 20:1-2, s. 274-282
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. This study was primarily aimed for developing and testing a valid and reliable instrument that measures perceived threat of the risk for graft rejection after organ transplantation. A second aim was to report descriptive data regarding graft rejection and Health-Related Quality of Life. Background. The most serious risk connected with transplantations besides infection is graft rejection. Design. Non experimental, descriptive involving instrument development and psychometric assessment. Method. Questionnaires about perceived threat of the risk for graft rejection and Health-Related Quality of Life were mailed to 229 OTRs between 19-65 years old. The items were formed from a previous interview study. Patients were transplanted with a kidney, a liver or a heart and/or a lung. All patients with follow-up time of one year +/- three months and three years +/- three months were included. Results. With an 81% response rate, the study comprised of 185 OTRs, who had received either a kidney (n = 117), a liver (n = 39) or heart or lung (n = 29). Three homogenous factors of perceived threat for graft rejection were revealed, labelled 'intrusive anxiety', 'graft-related threat' and 'lack of control'. Tests of internal consistency showed good item-scale convergent and discriminatory validity. A majority of the OTRs scored low levels for 'intrusive anxiety'. The kidney transplant recipients experienced more 'graft-related threat' by acute graft rejection than those transplanted with a liver, heart or lung. Conclusion. In conclusion, this study suggests that it is possible to measure the perceived threat of the risk for graft rejection in three homogenous factors. Relevance to clinical practice. The instrument perceived threat of the risk for graft rejection, might be usable to measure the impact of fear of graft rejection, to predict needs of pedagogical intervention strategies to reduce fear and to improve Health-Related Quality of Life related to graft rejection.
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36.
  • Oudin, Anna, et al. (författare)
  • Traffic-Related Air Pollution and Dementia Incidence in Northern Sweden : A Longitudinal Study
  • 2016
  • Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 124:3, s. 306-312
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Exposure to ambient air pollution is suspected to cause cognitive effects, but a prospective cohort is needed to study exposure to air pollution at the home address and the incidence of dementia.OBJECTIVES: We aimed to assess the association between long-term exposure to traffic-related air pollution and dementia incidence in a major city in northern Sweden.METHODS: Data on dementia incidence over a 15-year period were obtained from the longitudinal Betula study. Traffic air pollution exposure was assessed with a Land Use Regression Model with a spatial resolution of 50 m x 50 m. Annual mean nitrogen oxide levels at the residential address of the participants at baseline (the start of follow-up) was used as a marker for long-term exposure to air pollution.RESULTS: Out of 1806 participants at baseline, 191 were diagnosed with Alzheimer's disease during follow-up, and 111 were diagnosed with vascular dementia. Participants in the highest exposure group were more likely to be diagnosed with dementia (Alzheimer's disease or vascular dementia), with a Hazard Ratio (HR) of 1.43 (95% Confidence Interval (CI): 0.998, 2.05 for the highest versus lowest quartile). The estimates were similar for Alzheimer's disease (HR 1.38) and vascular dementia (HR 1.47). The HR for dementia associated for the third quartile versus the lowest quartile was 1.48 (95% CI: 1.03, 2.11). A sub-analysis that excluded a younger sample that had been re-tested after only 5 years of follow-up suggested stronger associations with exposure than in the full cohort (HR = 1.71; 95% CI: 1.08, 2.73 for the highest versus lowest quartile).CONCLUSIONS: If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer's disease.
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37.
  • Pedersen, Bolette, et al. (författare)
  • Nordic and Baltic wordnets aligned and compared through “WordTies”
  • 2013
  • Ingår i: Proceedings of the 19th Nordic Conference of Computational Linguistics (NODALIDA 2013), May 22–24, 2013, Oslo University, Norway. NEALT Proceedings Series 16. - 1650-3686 .- 1650-3740. ; :16, s. 147-162
  • Konferensbidrag (refereegranskat)abstract
    • During the last few years, extensive wordnets have been built locally for the Nordic and Baltic languages applying very different compilation strategies. The aim of the present investigation is to consolidate and examine these wordnets through an alignment via Princeton Core WordNet and thereby compare them along the measures of taxonomical structure, synonym structure, and assigned relations to approximate to a best practice. A common web interface and visualizer “WordTies” is developed to facilitate this purpose. Four bilingual wordnets are automatically processed and evaluated exposing interesting differences between the wordnets. Even if the alignments are judged to be of a good quality, the precision of the translations vary due to considerable differences in hyponymy depth and interpretation of the synset. All seven monolingual and four bilingual wordnets as well as WordTies have been made available via META-SHARE through the META-NORD project.
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38.
  • Stockfelt, Leo, 1981, et al. (författare)
  • Long-Term Exposure to Particulate Air Pollution, Black Carbon, and Their Source Components in Relation to Ischemic Heart Disease and Stroke
  • 2019
  • Ingår i: Journal of Environmental Health Perspectives. - Durham : National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 127:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Long-term exposure to particulate matter (PM) in ambient air has been associated with cardiovascular mortality, but few studies have considered incident disease in relation to PM from different sources.OBJECTIVES: We aimed to study associations between long-term exposure to different types of PM and sources, and incident ischemic heart disease (IHD) and stroke in three Swedish cities.METHODS: ), and black carbon (BC) from road wear, traffic exhaust, residential heating, and other sources in Gothenburg, Stockholm, and Umeå. Registry data for participants from four cohorts were used to obtain incidence of IHD and stroke for first hospitalization or death. We constructed time windows of exposure for same-year, 1- to 5-y, and 6- to 10-y averages preceding incidence from annual averages at residential addresses. Risk estimates were based on random effects meta-analyses of cohort-specific Cox proportional hazard models.RESULTS: exposure from residential heating.DISCUSSION: Few consistent associations were observed between different particulate components and IHD or stroke. However, long-term residential exposure to locally emitted BC from traffic exhaust was associated with stroke incidence. The comparatively low exposure levels may have contributed to the paucity of associations.
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39.
  • Strömberg, Ulf, 1964, et al. (författare)
  • Colorectal cancer screening with fecal immunochemical testing or primary colonoscopy: An analysis of health equity based on a randomised trial
  • 2022
  • Ingår i: eClinicalMedicine. - : Elsevier BV. - 2589-5370. ; 47
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: We have addressed health equity attained by fecal immunochemical testing (FIT) and primary colonoscopy (PCOL), respectively, in the randomised controlled screening trial SCREESCO conducted in Sweden. Methods: We analysed data on the individuals recruited between March 2014, and March 2020, within the study registered with ClinicalTrials.gov, NCT02078804. Swedish population registry data on educational level, household income, country of birth, and marital status were linked to each 60-year-old man and woman who had been randomised to two rounds of FIT 2 years apart (n = 60,123) or once-only PCOL (n = 30,390). Furthermore, we geo-coded each study individual to his/her residential area and assessed neighbourhood-level data on deprivation, proportion of non-Western immigrants, population density, and average distance to healthcare center for colonoscopy. We estimated adjusted associations of each covariate with the colonoscopy attendance proportion out of all invited to respective arms; ie, the preferred outcome for addressing health equity. In the FIT arm, the test uptake and the colonoscopy uptake among the test positives were considered as the secondary outcomes. Findings: We found a marked socioeconomic gradient in the colonoscopy attendance proportion in the PCOL arm (adjusted odds ratio [95% credibility interval] between the groups categorised in the highest vs. lowest national quartile for household income: 2·20 [2·01–2·42]) in parallel with the gradient in the test uptake of the FIT × 2 screening (2·08 [1·96–2·20]). The corresponding gradient in the colonoscopy attendance proportion out of all invited to FIT was less pronounced (1·29 [1·16–1·42]), due to higher proportions of FIT positives in socioeconomically disadvantaged groups. Interpretation: The unintended risk of exacerbating inequalities in health by organised colorectal cancer screening may be higher with a PCOL strategy than a FIT strategy, despite parallel socioeconomic gradients in uptake. Funding: This work was supported by the Swedish Cancer Society under Grant 20 0719. CB and US provided economic support from the Swedish Research Council for Health, Working life, and Welfare under Grant 2020–00962.
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40.
  • Sundström, Johan, Professor, 1971-, et al. (författare)
  • Risk factors for subarachnoid haemorrhage : a nationwide cohort of 950 000 adults
  • 2019
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press. - 0300-5771 .- 1464-3685. ; 48:6, s. 2018-2025
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Subarachnoid haemorrhage (SAH) is a devastating disease, with high mortality rate and substantial disability among survivors. Its causes are poorly understood. We aimed to investigate risk factors for SAH using a novel nationwide cohort consortium.METHODS: We obtained individual participant data of 949 683 persons (330 334 women) between 25 and 90 years old, with no history of SAH at baseline, from 21 population-based cohorts. Outcomes were obtained from the Swedish Patient and Causes of Death Registries.RESULTS: During 13 704 959 person-years of follow-up, 2659 cases of first-ever fatal or non-fatal SAH occurred, with an age-standardized incidence rate of 9.0 [95% confidence interval (CI) (7.4-10.6)/100 000 person-years] in men and 13.8 [(11.4-16.2)/100 000 person-years] in women. The incidence rate increased exponentially with higher age. In multivariable-adjusted Poisson models, marked sex interactions for current smoking and body mass index (BMI) were observed. Current smoking conferred a rate ratio (RR) of 2.24 (95% CI 1.95-2.57) in women and 1.62 (1.47-1.79) in men. One standard deviation higher BMI was associated with an RR of 0.86 (0.81-0.92) in women and 1.02 (0.96-1.08) in men. Higher blood pressure and lower education level were also associated with higher risk of SAH.CONCLUSIONS: The risk of SAH is 45% higher in women than in men, with substantial sex differences in risk factor strengths. In particular, a markedly stronger adverse effect of smoking in women may motivate targeted public health initiatives.
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41.
  • Sundström, Lars, 1967- (författare)
  • Det hotade kollektivet : Neolitiseringsprocessen ur ett östmellansvenskt perspektiv
  • 2003
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This dissertation questions the established view on the social process in connection with Neolithisation. Therefore it has been necessary to discuss more general principles, on how to understand this process of change, when iterant hunter-gatherers became settled farmers. The dissertation begins with a theoretical discussion on the foundations for the interpretation and most important a discussion on differences between the interpretations presented and the treatment of the empirical material on which they are based. A necessary point of departure for understanding the implications an incorporation of domesticates in prehistoric society, i.e. emergence of Funnel Beaker Culture in Sweden, is a principal discussion, social mechanisms of hunters-gatherers on one hand and peoples reactions to changes threatening the social ideology, on the other. Four case studies are used to discuss people’s reaction to change. They clearly indicate that the reaction involved the lifting up of blurred and semiconscious structures to a conscious, ideological level. Inherent in this awareness process has been an active use of material culture, both in the production of symbols and in communication. The most important reason for stating that the Neolithisation must have meant a clear break with the earlier existence is the abandonment of itinerant way of life, both geographically and socially. This abandonment resulted in reactionary process involving material culture. Thus the material culture of the Funnel-Beaker period can be perceived as instruments of reproduction of a historically well-anchored egalitarian ideology. In the dispersed settlement system of autonomous individual farmsteads the collective aggregation sites are given a focal role of the discussion on social reproduction. The social mechanisms of the Early Neolithic society of Eastern Central Sweden are investigated on a local settlement level by an analysis of the production of locally available raw material. This study involve a petrological investigation showed a system of local management in relation to raw material extraction, production and consumption. This system is considered as one way of upholding the social ideology historically situated in the life style of hunters and gatherers.
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42.
  • Talley, Nicholas J., et al. (författare)
  • Role of smoking in functional dyspepsia and irritable bowel syndrome : three random population-based studies
  • 2021
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : John Wiley & Sons. - 0269-2813 .- 1365-2036. ; 54:1, s. 32-42
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: It is uncertain if functional dyspepsia (FD) or irritable bowel syndrome (IBS) are linked to smoking, and smoking cessation is not part of the routine advice provided to these patients.Aim: To assess if smoking is an independent risk factor for FD and IBS.Methods: Three population-based endoscopy studies in Sweden with 2560 community individuals in total (mean age 51.5 years, 46% male). IBS (14.9%), FD (33.5%), and associated symptoms were assessed using the validated abdominal symptom questionnaire, and smoking (17.9%) was obtained from standardised questions during a clinic visit. The effect of smoking on symptom status was analysed in an individual person data meta-analysis using mixed effect logistic regression, adjusted for snuffing, age and sex.Results: Individuals smoking cigarettes reported significantly higher odds of postprandial distress syndrome (FD-PDS) (OR 10-19 cig/day = 1.42, 95% CI 1.04-1.98 P = 0.027, OR ≥20 cig/day = 2.16, 95% CI 1.38-3.38, P = 0.001) but not epigastric pain. Individuals smoking 20 or more cigarettes per day reported significantly higher odds of IBS-diarrhoea (OR = 2.40, 95% CI 1.12-5.16, P = 0.025), diarrhoea (OR = 2.01, 95%CI 1.28-3.16, P = 0.003), urgency (OR = 2.21, 95%CI 1.41-3.47, P = 0.001) and flatus (OR = 1.77, 95%CI 1.14-2.76, P = 0.012) than non-smokers. Smoking was not associated with IBS-constipation or IBS-mixed.Conclusion: Smoking is an important environmental risk factor for postprandial distress syndrome, the most common FD subgroup, with over a twofold increased odds of PDS in heavy smokers. The role of smoking in IBS-diarrhoea, but not constipation, is also likely important.
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43.
  • Varrone, Andrea, et al. (författare)
  • 5-HT1B receptor imaging and cognition : A positron emission tomography study in control subjects and parkinson's disease patients
  • 2015
  • Ingår i: Synapse. - : Wiley. - 0887-4476 .- 1098-2396. ; 69:7, s. 365-374
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionThe serotonin 5-HT1B receptor subtype is involved in the modulation of serotonin release and is a target of interest for neuroreceptor imaging. Previous studies have shown that the serotonin system is affected in Parkinson's disease (PD). Cognitive function, frequently impaired in PD, has been linked to the serotonin system. The aim of this study was to examine whether 5-HT1B receptor availability in the brain of healthy subjects and PD patients is associated with measures of cognitive function. MethodsTwelve control subjects and ten PD patients with normal mini-mental state examination scores were included in this study. Cognitive function was evaluated by assessment of semantic, episodic, and working memory, as well as fluency and visual attention. Creative ability, a measure of divergent thinking, was examined with the alternative uses of objects task. PET measurements were performed with the 5-HT1B receptor-radioligand [C-11]AZ10419369 using the HRRT system. ResultsPD patients showed statistically significant lower measures of semantic and episodic memory, as well as creative ability, compared with control subjects. Statistically significant positive correlations were found in control subjects between creative ability and average 5-HT1B receptor availability in grey matter, and in PD patients between scores of Beck Depression Inventory-II and creative ability. ConclusionThough creativity has been conventionally linked to dopamine function, our findings in control subjects suggest a link between 5-HT1B receptor availability and creative ability. In PD patients, creative ability was significantly associated with depressive symptoms but not with 5-HT1B receptor availability. This finding deserves further investigation in future studies.
  •  
44.
  • Varrone, Andrea, et al. (författare)
  • Positron emission tomography imaging of 5-hydroxytryptamine(1B) receptors in Parkinson's disease
  • 2014
  • Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 35:4, s. 867-875
  • Tidskriftsartikel (refereegranskat)abstract
    • Impairment of the central serotonin system in Parkinson's disease (PD) has been shown postmortem and in vivo with positron emission tomography (PET). The aim of this PET study was to examine and compare the availability of the 5-hydroxytryptamine (5-HT)(1B)-receptor subtype in patients with PD and age-matched control subjects. Twelve control subjects and 12 PD patients were examined with PET using the 5-HT1B-radioligand [C-11]AZ10419369. In PD patients, 5-HT1B-receptor availability in the right orbitofrontal cortex was lower than in control subjects. A statistically significant negative correlation between 5-HT1B-receptor availability and age was obtained for the right temporal cortex in control subjects and for the right midbrain and left parahippocampal gyrus in PD patients. The lower regional 5-HT1B-receptor availability is in line with previous studies showing a decrease of serotonin imaging markers in PD and corroborates a role of the serotonin system in the pathophysiology of PD. The demonstrated age effect on 5-HT1B receptors suggest a physiologic and PD-related decline of serotonin function, indicating the importance of controlling for age in clinical studies.
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45.
  •  
46.
  • Abednazari, Hossein, 1959-, et al. (författare)
  • Hepatocyte growth factor is a better indicator of therapeutic response than C-reactive protein within the first day of treatment in pneumonia
  • 2006
  • Ingår i: Chemotherapy. - : S. Karger AG. - 0009-3157 .- 1421-9794. ; 52:5, s. 260-263
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute bacterial infectious diseases are mostly treated empirically at admission before the culture results are available. According to the risk for serious complications in the case of therapeutic failure, it is important to evaluate the therapy results and change to a more appropriate antibiotic regime as soon as possible. In the present study, 40 patients with X-ray-verified community-acquired pneumonia were examined and blood specimens were collected before and within 24 h of treatment. Body temperature, C-reactive protein (CRP) and hepatocyte growth factor (HGF) were investigated. Thirty-two patients received an appropriate initial antibiotic therapy regarding clinical outcome, but in 8 patients the treatment was changed because of therapy failure. Changes of HGF levels after 18–24 h of treatment could predict the therapeutic results accurately in 38 of 40 cases (sensitivity 100%, specificity 94%, positive likelihood ratio 16.0). HGF was significantly better to predict therapy outcome than CRP (p < 0.0001).
  •  
47.
  • Abrahamsson, Niclas, et al. (författare)
  • Föremålet för inlärning [kap. 3]
  • 2014
  • Ingår i: avancerad andraspråksanvändning. - Göteborg : Makadam Förlag. - 9789170616624 ; , s. 20-46
  • Bokkapitel (refereegranskat)
  •  
48.
  • Adamsson, Marie, 1966, et al. (författare)
  • Toxicity Identification Evaluation of ammonia, nitrite and heavy metals at the Stensund Wastewater Aquaculture plant, Sweden.
  • 1998
  • Ingår i: Water Science and Technology. - 0273-1223. ; 38:3, s. 151-157
  • Tidskriftsartikel (refereegranskat)abstract
    • The Stensund Wastewater Aquaculture plant was built in 1989. The plant is contained in a greenhouse because of its northern location with a temperate climate; The plant receives wastewater from 40 persons and has a residence time of 30 days. The purification concept is to use a constructed aquatic food chain (algae, zooplankton and fish) combined with hydroponic culture of higher plants to further deplete the nutrients in the wastewater. However, the production of algae and zooplankton has not been working as expected from pilot studies. The purpose of this investigation was to study if toxic chemicals were limiting the production of zooplankton (Daphnia magna) in the aquaculture treatment system. Grab samples were taken at six sites and tested for acute toxicity to Daphnia magna and analyzed for BOD, COD, ammonium-, nitrite-, nitrate- and total nitrogen, total phosphorus and heavy metals (Cd, Ci, Cu, Ni, Pb, Zn). Toxicity to D. magna was also determined after addition of EDTA, sodium thiosulphate and pH adjustment of the,water to 6, 7 and 8, in order to assess if heavy metals and/or pH-dependent toxicants were present Potential toxicants, with concentrations high enough to intoxicate Daphnia magna, were Cu, ammonia and nitrite. Subsequent improvement of nitrification reduced the ammonia and nitrite concentrations as well as the toxicity. Furthermore, the improved production of algae and Daphnia at the Stensund Wastewater Aquaculture plant verified that the primary cause of toxicity was ammonia. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.
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49.
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50.
  • Adesam, Yvonne, 1975, et al. (författare)
  • Språkteknologi för svenska språket genom tiderna
  • 2016
  • Ingår i: Kungliga Skytteanska Samfundets Handlingar. - Umeå : Institutionen för språkstudier, Umeå universitet & Kungl. Skytteanska Samfundet. - 0560-2416. ; 76:Studier i svensk språkhistoria 13, s. 65-87, s. 65-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Språkbanken, the Swedish Language Bank, is a language technology research unit at the Department of Swedish, University of Gothenburg. We develop language resources – such as corpora, lexical resources, and analytical tools – for all variants of Swedish, from Old Swedish laws to present-day social media. Historical texts offer exciting theoretical and methodological challenges for language technology because they often defy the assumption inherent in most automatic analysis tools that the texts contain a standardized written language. In this article, we describe our ongoing work on the development of annotated historical corpora, as well as our efforts on linking various resources (both corpora and lexical resources). This research advances the state of the art of language technology as well as enables new research for scholars in other disciplines.
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