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- Lindberg, Anne, et al.
(författare)
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Large underreporting of COPD as cause of death-results from a population-based cohort study
- 2021
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 186
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2019, WHO estimated COPD to be the third leading cause of death in the world. However, COPD is probably underestimated as cause of death due to the well-known under-diagnosis. Aim: To evaluate the proportion of and factors associated with COPD recorded as cause of death in a long-term follow-up of a population-based COPD cohort. Methods: The study population includes all individuals (n = 551) with COPD defined as chronic airway obstruction (post-bronchodilator FEV1/FVC<0.70) + respiratory symptoms identified after re-examinations of four population-based cohorts. Mortality and underlying or contributing cause of death following ICD-10 classification were collected from the Swedish National Board of Health and Welfares register from date of examination in 2002-04 until 2016. Results: The study sample consisted of 32.3% GOLD 1, 55.9% GOLD 2, and 11.8% GOLD 3-4. The mean follow-up time was 10.3 (SD3.77) years and the cumulative mortality 45.0%. COPD (ICD-10 J43-J44) was recorded on 28.2% (n = 70) of the death certificates (11.1%, 25.7% and 57.1% by GOLD stage), whereof n = 35 had COPD recorded as underlying and n = 35 as contributing cause of death. To have COPD recorded as cause of death was independently associated with ex- and current smoking and a self-reported physician diagnosis of COPD, while male sex, overweight/obesity and higher FEV1% of predicted associated with the absence. Conclusions: COPD was largely underreported cause of death. Even among those with severe/very severe disease, COPD was only mentioned on 57.1% of the death certificates.
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- Ameur, Adam, et al.
(författare)
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Comprehensive profiling of the vaginal microbiome in HIV positive women using massive parallel semiconductor sequencing
- 2014
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4, s. 4398-
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Tidskriftsartikel (refereegranskat)abstract
- Infections by HIV increase the risk of acquiring secondary viral and bacterial infections and methods are needed to determine the spectrum of co-infections for proper treatment. We used rolling circle amplification (RCA) and Ion Proton sequencing to investigate the vaginal microbiome of 20 HIV positive women from South Africa. A total of 46 different human papillomavirus (HPV) types were found, many of which are not detected by existing genotyping assays. Moreover, the complete genomes of two novel HPV types were determined. Abundance of HPV infections was highly correlated with real-time PCR estimates, indicating that the RCA-Proton method can be used for quantification of individual pathogens. We also identified a large number of other viral, bacterial and parasitic co-infections and the spectrum of these co-infections varied widely between individuals. Our method provides rapid detection of a broad range of pathogens and the ability to reconstruct complete genomes of novel infectious agents.
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7. |
- Anderson, Henrik, et al.
(författare)
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Quartz crystal microbalance sensor design : I. Experimental study of sensor response and performance
- 2007
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Ingår i: Sensors and actuators. B, Chemical. - : Elsevier BV. - 0925-4005 .- 1873-3077. ; 123:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- This paper investigates a novel quartz crystal microbalance (QCM) biosensor with a small and rectangular flow cell along with a correspondingly shaped crystal electrode. The sensor was evaluated with impedance analysis and compared to standard circular sensor crystals and sensor crystals with small circular electrodes. Comparative QCM measurements on an antibody–antigen interaction system were carried out on the rectangular and standard circular sensor systems. Impedance analysis and subsequent data extraction of the three different sensor crystals showed that the smaller sensors had significantly higher Q-values in air, but that liquid load on the electrodes lowered the Q-values radically for all crystals. Under liquid load, Q-values for the standard circular and the rectangular sensors were similar whereas the Q-value for the small circular sensor was 50% higher. QCM experiments showed that the QCM system with rectangular crystal electrodes was fully functional in a liquid environment. The rectangular system showed higher and more rapid responses for series of antibody injections, albeit at a higher noise level than the standard system. The study elucidates a significant potential for improvement of sensor performance by optimising the sensor electrode size and shape together with the flow cell geometry.
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9. |
- Backman, Helena, et al.
(författare)
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All-cause and cause-specific mortality by spirometric pattern and sex - a population-based cohort study
- 2024
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Ingår i: THERAPEUTIC ADVANCES IN RESPIRATORY DISEASE. - : Sage Publications. - 1753-4658 .- 1753-4666. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Chronic airway obstruction (CAO) and restrictive spirometry pattern (RSP) are associated with mortality, but sex-specific patterns of all-cause and specific causes of death have hardly been evaluated. Objectives: To study the possible sex-dependent differences of all-cause mortality and patterns of cause-specific mortality among men and women with CAO and RSP, respectively, to that of normal lung function (NLF). Design: Population-based prospective cohort study. Methods: Individuals with CAO [FEV1/vital capacity (VC) < 0.70], RSP [FEV1/VC >= 0.70 and forced vital capacity (FVC) < 80% predicted] and NLF (FEV1/VC >= 0.70 and FVC >= 80% predicted) were identified within the Obstructive Lung Disease in Northern Sweden (OLIN) studies in 2002-2004. Mortality data were collected through April 2016, totally covering 19,000 patient-years. Cox regression and Fine-Gray regression accounting for competing risks were utilized to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, body mass index, sex, smoking habits and pack-years. Results: The adjusted hazard for all-cause mortality was higher in CAO and RSP than in NLF (HR, 95% CI; 1.69, 1.31-2.02 and 1.24, 1.06-1.71), and the higher hazards were driven by males. CAO had a higher hazard of respiratory and cardiovascular death than NLF (2.68, 1.05-6.82 and 1.40, 1.04-1.90). The hazard of respiratory death was significant in women (3.41, 1.05-11.07) while the hazard of cardiovascular death was significant in men (1.49, 1.01-2.22). In RSP, the higher hazard for respiratory death remained after adjustment (2.68, 1.05-6.82) but not for cardiovascular death (1.11, 0.74-1.66), with a similar pattern in both sexes. Conclusion: The higher hazard for all-cause mortality in CAO and RSP than in NLF was male driven. CAO was associated with respiratory death in women and cardiovascular death in men, while RSP is associated with respiratory death, similarly in both sexes.
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- Backman, Helena, et al.
(författare)
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Decreased COPD prevalence in Sweden after decades of decrease in smoking
- 2020
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Ingår i: Respiratory Research. - : Springer Nature. - 1465-9921 .- 1465-993X. ; 21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCOPD has increased in prevalence worldwide over several decades until the first decade after the millennium shift. Evidence from a few recent population studies indicate that the prevalence may be levelling or even decreasing in some areas in Europe. Since the 1970s, a substantial and ongoing decrease in smoking prevalence has been observed in several European countries including Sweden. The aim of the current study was to estimate the prevalence, characteristics and risk factors for COPD in the Swedish general population. A further aim was to estimate the prevalence trend of COPD in Northern Sweden from 1994 to 2009.MethodsTwo large random population samples were invited to spirometry with bronchodilator testing and structured interviews in 2009–2012, one in south-western and one in northern Sweden, n = 1839 participants in total. The results from northern Sweden were compared to a study performed 15 years earlier in the same area and age-span. The diagnosis of COPD required both chronic airway obstruction (CAO) and the presence of respiratory symptoms, in line with the GOLD documents since 2017. CAO was defined as post-bronchodilator FEV1/FVC < 0.70, with sensitivity analyses based on the FEV1/FVC < lower limit of normal (LLN) criterion.ResultsBased on the fixed ratio definition, the prevalence of COPD was 7.0% (men 8.3%; women 5.8%) in 2009–2012. The prevalence of moderate to severe (GOLD ≥ 2) COPD was 3.5%. The LLN based results were about 30% lower. Smoking, occupational exposures, and older age were risk factors for COPD, whereof smoking was the most dominating risk factor. In northern Sweden the prevalence of COPD, particularly moderate to severe COPD, decreased significantly from 1994 to 2009, and the decrease followed a decrease in smoking.ConclusionsThe prevalence of COPD has decreased in Sweden, and the prevalence of moderate to severe COPD was particularly low. The decrease follows a major decrease in smoking prevalence over several decades, but smoking remained the dominating risk factor for COPD.
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12. |
- Backman, Helena, et al.
(författare)
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Lung function trajectories and associated mortality among adults with and without airway obstruction
- 2023
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - : American Thoracic Society. - 1073-449X .- 1535-4970. ; 208:10, s. 1063-1074
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Spirometry is essential for diagnosis and assessment of prognosis in COPD.Objectives: To identify FEV1 trajectories and their determinants, based on annual spirometry measurements among individuals with and without airway obstruction. Furthermore, to assess mortality in relation to trajectories.Methods: In 2002-04, individuals with airway obstruction (AO) (FEV1/VC<0.70, n=993) and age- and sex-matched non-obstructive (NO) referents were recruited from population-based cohorts. Annual spirometries until 2014 were utilized in joint-survival Latent Class Mixed Models to identify lung function trajectories. Mortality data were collected during 15 years of follow-up.Results: Three trajectories were identified among the AO-cases and two among the NO referents. Trajectory membership was driven by baseline FEV1%predicted (%pred) in both groups and additionaly, pack-years in AO and current smoking in NO. Longitudinal FEV1%pred level depended on baseline FEV1%pred, pack-years and obesity. The trajectories were distributed: 79.6% T1AO FEV1-high with normal decline, 12.8% T2AO FEV1-high with rapid decline, and 7.7% T3AO FEV1-low with normal decline (mean 27, 72 and 26 mL/year) among AO-individuals, and 96.7% T1NO FEV1-high with normal decline and 3.3% T2NO FEV1-high with rapid decline (mean 34 and 173 mL/year) among referents. Hazard for death was increased for T2AO (HR1.56) and T3AO (HR3.45) vs. T1AO, and for T2NO (HR2.99) vs. T1NO.Conclusions: Three different FEV1 trajectories were identified among those with airway obstruction and two among the referents, with different outcomes in terms of FEV1-decline and mortality. The FEV1 trajectories among airway obstructive and the relationship between low FVC and trajectory outcome are of particular clinical interest.
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13. |
- Baird, John C., et al.
(författare)
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Stimulus Sequence and the Exponent of the Power Function for Loudness
- 1991
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Ingår i: Perceptual and Motor Skills. - : SAGE Publications. - 0031-5125 .- 1558-688X. ; 73:1, s. 3-17
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Tidskriftsartikel (refereegranskat)abstract
- In two experiments, 15 and 13 subjects estimated the loudness of 12 sound-pressure levels (38–104 dB; 6-dB intervals) of a 1000-Hz tone by the method of magnitude estimation with a modulus assigned to the first stimulus presented. The tone duration was 1 sec. and the interstimulus interval was 6 sec. The presentation order was systematically ascending-descending in one experiment and balanced-irregular in the other. The results indicate that (1) loudness is a power function of sound pressure with an exponent of 0.60 for the systematic order and 0.29 for the irregular order. (2) For both the irregular and systematic orders, a large step-size (12 or 18 dB) between the stimulus on Trial n and on Trial n-1 (or n-3) results in a slight assimilation effect. This also occurs for the small step-size (6 dB) in the irregular order. (3) The size of momentary exponents (based on two points, Trials n and n-l or n-3) depends on the sound pressures of successive stimuli, whether the steps are positive or negative, and whether the stimuli have been presented in systematic or irregular order. For positive steps, the momentary exponent is lower for a soft tone (Trial n) than for a loud tone, whereas for negative steps the momentary exponent is lower for a loud tone than for a soft tone. These effects are more pronounced when these stimuli are presented in an irregular order. A relative judgment model is offered for magnitude estimation. It assumes that subjects judge the loudness of a stimulus in terms of three reference markers: the minimum and maximum sound pressures as well as the sound pressure of the previous stimulus.
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14. |
- Baldanzi, Gabriel, et al.
(författare)
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Evening chronotype is associated with elevated biomarkers of cardiometabolic risk in the EpiHealth cohort: a cross-sectional study
- 2022
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Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 45:2
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Tidskriftsartikel (refereegranskat)abstract
- Study objectives: Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population- based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers of cardiometabolic processes. Methods: In 2,471 participants (49.7% men, mean age 61.2±8.4 SD years) from the EpiHealth cohort, circulating proteins were analyzed with a multiplex proximity extension technique. Participants self- reported their chronotype on a five-level scale from extreme morning to extreme evening chronotype. With the intermediate chronotype set as the reference, each protein was added as the dependent variable in a series of linear regression models adjusted for confounders. Next, the chronotype coefficients were jointly tested and the resulting p-values adjusted for multiple testing using false discovery rate (5%). For the associations identified, we then analyzed the marginal effect of each chronotype category. Results: We identified 17 proteins associated with chronotype. Evening chronotype was positively associated with proteins previously linked to insulin resistance and cardiovascular risk, namely retinoic acid receptor protein 2, fatty acid-binding protein adipocyte, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1). Additionally, PAI-1 was inversely associated with the extreme morning chronotype. Conclusions: In this population-based study, proteins previously related with cardiometabolic risk were elevated in the evening chronotypes. These results may guide future research in the relation between chronotype and cardiometabolic disorders.
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15. |
- Baldanzi, Gabriel, et al.
(författare)
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OSA Is Associated With the Human Gut Microbiota Composition and Functional Potential in the Population-Based Swedish CardioPulmonary bioImage Study
- 2023
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Ingår i: Chest. - : Elsevier. - 0012-3692 .- 1931-3543. ; 164:2, s. 503-516
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obstructive sleep apnea (OSA) is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent hypoxia and intermittent airway obstruction, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition and subsequent transplantation of fecal matter to other animals induced changes in blood pressure and glucose metabolism.RESEARCH QUESTION: Does obstructive sleep apnea in adults associate with the composition and metabolic potential of the human gut microbiota?STUDY DESIGN AND METHODS: We used respiratory polygraphy data from up to 3,570 individuals aged 50-64 from the population-based Swedish CardioPulmonary bioImage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, on-site anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register.RESULTS: We found that all three OSA parameters were associated with lower diversity of species in the gut. Further, the OSA-related hypoxia parameters were in multivariable-adjusted analysis associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsela aerofaciens. The latter species was also independently associated with increased systolic blood pressure. Further, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Lastly, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively.INTERPRETATION: OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA.
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17. |
- Berggrund, Malin, et al.
(författare)
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HPV viral load in self-collected vaginal fluid samples as predictor for presence of cervical intraepithelial neoplasia.
- 2019
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Ingår i: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study was performed to evaluate the use of high-risk HPV (hrHPV) viral load in screening tests for cervical cancer to predict persistent infection and presence of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).METHODS: We followed women between 30 and 60 years of age who performed self-sampling of vaginal fluid and subsequently a hrHPV test. Women who were hrHPV positive in their screening test repeated the hrHPV test 3-6 months later and were included in the present study.RESULTS: Our results show that women with a persistent HPV16 infection had higher HPV viral load in their primary screening test than women with transient infections (p = 5.33e-03). This was also true for sum of viral load for all hrHPV types in the primary screening test (p = 3.88e-07). 48% of women with persistent HPV16 infection and CIN2+ had an increase in HPV16 titer in the follow-up test, as compared to only 20% of women with persistent infection but without CIN2+ lesions. For the sum of all hrHPV types, 41% of women with persistent infection and CIN2+ had an increase in titer as compared to 26% of women without CIN2 + .CONCLUSIONS: The results show that hrHPV viral load in the primary screening HPV test is associated with the presence of CIN2+ and could be used in triaging hrHPV positive women for different follow-up strategies or recall times. Serial testing of hrHPV viral load has the potential to distinguish women with CIN2+ lesions from women with persistent infection but without CIN2+ lesions.
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18. |
- Berggrund, Malin, et al.
(författare)
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Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2
- 2020
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Ingår i: Virology Journal. - : Springer Science and Business Media LLC. - 1743-422X. ; 17
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables.MethodsIn total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S™ Metagenomics Kit and Ion 16S™ metagenomics module within the Ion Reporter™ software.ResultsK-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036).ConclusionsThe vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.
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19. |
- Bergström, Göran, 1964, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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20. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
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Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
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Tidskriftsartikel (refereegranskat)abstract
- Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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22. |
- Brännlund, Ulf, et al.
(författare)
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Railway Timetabling Using Lagrangian Relaxation
- 1998
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Ingår i: Transportation Science. - : Institute for Operations Research and the Management Sciences (INFORMS). - 0041-1655 .- 1526-5447. ; 32:4, s. 358-369
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Tidskriftsartikel (refereegranskat)abstract
- We present a novel optimization approach for the timetabling problem of a railway company, i.e., scheduling of a set of trains to obtain a profit maximizing timetable, while not violating track capacity constraints. The scheduling decisions are based on estimates of the value of running different types of service at specified times. We model the problem as a very large integer programming problem. The model is flexible in that if allows for general cost functions. We have used a Lagrangian relaxation solution approach, in which the track capacity constraints are relaxed and assigned prices, so that the problem separates into one dynamic program for each physical train. The number of dual variables is very large. However, it turns out that only a small fraction of these are nonzero, wh ich one may take advantage of in the dual updating schemes. The approach has been, tested on a realistic example suggested by the Swedish National Railway Administration. This example contains 18 passenger trains and 8 freight trains to be scheduled during a day on a stretch of single track, consisting of 17 stations. The computation times are rather modest and the obtained timetables are within a few percent of optimality.
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23. |
- Cervin, Anders, et al.
(författare)
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Cyclic adenosine monophosphate stimulation of mucociliary activity in the upper airways in vivo
- 1995
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Ingår i: Annals of Otology, Rhinology & Laryngology. - 0003-4894. ; 104:5, s. 388-393
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Tidskriftsartikel (refereegranskat)abstract
- Xanthine derivatives are known to accelerate mucociliary transport in the lower airways, probably by preventing degradation of cyclic adenosine monophosphate (cAMP) and thereby increasing its intracellular concentration. The purpose of this study was to investigate the effects of cAMP on mucociliary activity in the upper airways. The effect on the mucociliary activity in the rabbit maxillary sinus of the xanthine derivatives theophylline and enprophylline was compared to that of the cAMP analog dibutyryl cAMP. The compounds were administered into the maxillary artery, and the response was recorded with a photoelectric technique. Infusions of theophylline (1.0 and 10 mg/kg) increased mucociliary activity (22.8% +/- 5.9%, n = 6, and 21.6% +/- 4.9%, n = 7, p < .05, respectively). Infusions of enprophylline (1.0 and 10.0 mg/kg) accelerated mucociliary activity (at the highest dosage tested, 24.3% +/- 4.1%). Infusions of dibutyryl cAMP (0.1 and 1.0 mg/kg) stimulated mucociliary activity, with the maximum increase (20.1% +/- 3.0%, n = 13, p < .05) being observed at a dosage of 0.1 mg/kg. The infused substances increased mucociliary activity within 1 minute after the start of the infusion, the duration of the response being approximately 20 minutes for theophylline, 22 minutes for enprophylline, and 12 minutes for dibutyryl cAMP. The present results support the view that cAMP is involved in regulating mucociliary activity in the upper airways. It remains to be elucidated whether xanthines such as theophylline and enprophylline are beneficial in upper airway disease in which mucociliary function is impaired (eg, chronic sinusitis).
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24. |
- Cervin, Anders, et al.
(författare)
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Effects of halothane on mucociliary activity in vivo
- 1995
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Ingår i: Otolaryngology: Head and Neck Surgery. - 0194-5998. ; 112:6, s. 714-722
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Tidskriftsartikel (refereegranskat)abstract
- The effect of halothane on mucociliary activity in the rabbit maxillary sinus in vivo was recorded photoelectrically. Administration of halothane (1%, 2% or 4%) into the maxillary sinus induced a temporary acceleration of mucociliary activity. The peak increase (39.1% +/- 9.1%, p < 0.05, n = 5) was seen after the 4% concentration. Long-term exposure (60 minutes) of the maxillary sinus to halothane (2%) first induced an increase of 28.4% +/- 4.6% (p < 0.05, n = 6), lasting approximately four minutes, and followed after about 15 minutes by a decrease of mucociliary activity. The maximum decrease during the 60-minute period was 19.6% +/- 2.8% (p < 0.05, n = 6). Mucociliary activity returned to its baseline level approximately 25 minutes after withdrawal of halothane. Halothane delivered to the rabbit through a tracheal cannula at 1.1% for 60 minutes did not impair mucociliary activity in the maxillary sinus. On the contrary, it initially stimulated mucociliary activity, 19.9% +/- 2.7% (p < 0.05, n = 5). There was also an initial increase in respiratory rate from 62 +/- 7.3 to 89 +/- 12.9 breaths per minute (p < 0.05), which was noticeable after approximately 10 seconds and lasted 4 to 5 minutes. The dose-dependent increase in mucociliary activity seen after short-term exposure to halothane is probably due to stimulation of afferent C fibers, because halothane may be considered an airway irritant. The reversible depressant effect seen after 15 minutes of exposure is in accordance with findings in previous studies in vitro. The mechanism by which halothane impairs mucociliary activity is at present not known. However, halothane administered to the lower airways does not impair mucociliary activity in the maxillary sinus, indicating that halothane affects the ciliated epithelium directly and that the state of anesthesia itself has no effect on mucociliary activity.
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25. |
- Cervin, Anders, et al.
(författare)
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Relations between blood flow and mucociliary activity in the rabbit maxillary sinus
- 1988
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Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 1651-2251 .- 0001-6489. ; 105:3-4, s. 350-356
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Tidskriftsartikel (refereegranskat)abstract
- The effects of two sympathomimetic drugs on mucociliary activity and mucosal blood flow in the rabbit maxillary sinus were investigated by using a photo-electric technique (mucociliary activity) and laser Doppler flowmetry (blood flow). The responses produced were compared with effects of ligation of the external carotid artery. The alpha 1-agonist phenylpropanolamine (0.1-100 micrograms/kg) had no effect on the mucociliary activity, whereas the blood flow was reduced by 33.8 +/- 8.9% (mean +/- SE) when the dose was 100 micrograms/kg. The alpha 2-agonist xylometazoline (0.01-10.0 micrograms/kg) reduced mucociliary wave frequency by 21.6 +/- 4.6% (mean +/- SE) (maximum) for the dose 10 micrograms/kg. The blood flow was reduced by xylometazoline in the interval 1.0 to 10.0 micrograms/kg, with a maximum decrease of 65.8 +/- 2.6% (mean +/- SE) for the dose of 10 micrograms/kg. Ligature of the external carotid artery reduced blood flow by 76.0 +/- 4.6% (mean +/- SE), but did not significantly influence the mucociliary wave frequency. It is concluded that the decrease in mucociliary activity induced by alpha 2-adrenoceptor agonists is not due to a reduced blood flow.
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26. |
- Cervin, Anders, et al.
(författare)
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Sympathetic nerve stimulation influences mucociliary activity in the rabbit maxillary sinus
- 1991
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 143:4, s. 405-411
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Tidskriftsartikel (refereegranskat)abstract
- The effect of preganglionic sympathetic nerve stimulation on mucociliary activity in the rabbit maxillary sinus was investigated in vivo. Response to nerve stimulation was recorded photoelectrically and expressed as a percentage of the basal mucociliary activity prior to stimulation. Nerve stimulation (15 V, 5 ms) for 60 s at 2, 10 and 20 Hz stimulated mucociliary activity, the maximum increase being 21.1 +/- 1.3% at 20 Hz, an increase that pretreatment with the cholinergic antagonist atropine reduced to 14.5 +/- 2.4%, suggesting that part of the response involves cholinergic mechanisms. Nerve stimulation (10 Hz) of animals pretreated with the beta-adrenoceptor antagonist propranolol reversed the mucociliary response from an increase to a decrease (-10.6 +/- 1.6%), indicating the involvement of beta-receptors in the nerve-evoked increase. Pretreatment with the alpha-adrenoceptor antagonist phentolamine had no effect on response to nerve stimulation. Rabbits given a combined atropine, propranolol and phentolamine blockade manifested decreased mucociliary activity in response to nerve stimulation (-10.6 +/- 2.1%). Guanethidine pretreatment blocked the effect of nerve stimulation on mucociliary activity, including the observed decrease after combined blockade, indicating the effect to be mediated via sympathetic nerve fibres. The decrease in mucociliary activity in response to nerve stimulation after combined cholinergic-, beta-, and alpha-adrenoceptor blockade suggests the presence of a nonadrenergic, non-cholinergic inhibitory mechanism. It is possible that this effect is mediated by release of neuropeptide Y, as intraarterial injections of neuropeptide Y reduce mucociliary activity in the rabbit maxillary sinus, and as neuropeptide Y is released in the upper airways upon sympathetic nerve stimulation.
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27. |
- Cervin, Anders, et al.
(författare)
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The effect of neuropeptide Y on mucociliary activity in the rabbit maxillary sinus
- 1991
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Ingår i: Acta Oto-Laryngologica. - 1651-2251. ; 111:5, s. 960-966
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Tidskriftsartikel (refereegranskat)abstract
- The effect of neuropeptide Y (NPY) on mucociliary activity in the rabbit maxillary sinus was investigated in vivo by injecting NPY at increasing dosages into the maxillary artery, response being recorded photoelectrically. At dosages of 0.1-5.0 micrograms/kg, NPY reduced mucociliary activity dose-dependently, the maximum decrease being 14.6 +/- 1.8%, at a dosage of 5.0 micrograms/kg. The NPY-induced reduction of the mucociliary activity manifested brief latency, the peak effect occurring within 3 min followed by a slow return to the baseline value 4-9 min after injection. The response of mucociliary activity to NPY remained unaffected by pretreatment with the alpha-adrenergic antagonists yohimbine (alpha 2) at 100.0 micrograms/kg and phentolamine (alpha 1 + alpha 2) at 0.2-1.0 mg/kg, indicating that the effect of NPY is not mediated via alpha-receptors. Pretreatment with the calcium antagonist nifedipine at 100.0 micrograms/kg inhibited the effect of NPY, suggesting that the NPY-induced decrease may be calcium dependent.
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28. |
- Cervin, Anders, et al.
(författare)
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The effect of noradrenaline on mucociliary activity in the rabbit maxillary sinus
- 1993
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Ingår i: Rhinology. - 0300-0729. ; 31:1, s. 17-21
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Tidskriftsartikel (refereegranskat)abstract
- The effect of noradrenaline (NA) on mucociliary activity in the rabbit maxillary sinus was investigated in vivo by injecting it at increasing dosages (10(-11) to 10(-4) mol/kg) into the maxillary artery, the mucociliary response being recorded photoelectrically. NA increased mucociliary activity at a dosage of 10(-5) mol/kg, the maximal increase being 16.1 +/- 2.6%. The NA-induced stimulation of mucociliary activity had a latency of 20 s, and the activity returned to base-line level within 3 min. Pretreatment with the alpha-antagonist phentolamine (0.2 and 1.0 mg/kg) or the cholinergic antagonist atropine (1 mg/kg) did not alter mucociliary response to NA. Blockade with the beta-antagonist propranolol did not significantly reduce the maximal response to NA, which was 16.1 +/- 2.6% before and 11.1 +/- 3.0% after pretreatment with propranolol (n = 7; p = 0.2). In contrast, pretreatment with the prostaglandin-synthesis inhibitor indomethacin reduced the response from 12.9 +/- 2.9% to 6.3 +/- 1.3% (n = 6; p < 0.05), suggesting that at high dosages NA stimulates mucociliary activity via the cyclo-oxygenase pathway.
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29. |
- Chen, Hui, 1992, et al.
(författare)
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MCRB-based Performance Analysis of 6G Localization under Hardware Impairments
- 2022
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Ingår i: 2022 IEEE International Conference on Communications Workshops, ICC Workshops 2022. ; , s. 115-120
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Konferensbidrag (refereegranskat)abstract
- Location information is expected to be the key to meeting the needs of communication and context-aware services in 6G systems. User localization is achieved based on delay and/or angle estimation using uplink or downlink pilot signals. However, hardware impairments (HWIs) distort the signals at both the transmitter and receiver sides and thus affect the localization performance. While this impact can be ignored at lower frequencies where HWIs are less severe, modeling and analysis efforts are needed for 6G to evaluate the localization degradation due to HWIs. In this work, we model various types of impairments and conduct a misspecified Cramér-Rao bound analysis to evaluate the HWI-induced performance loss. Simulation results with different types of HWIs show that each HWI leads to a different level of degradation in angle and delay estimation performance.
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30. |
- Cotgreave, Ian, et al.
(författare)
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Pyriproxifen and microcephaly: an investigation of potential ties to the ongoing "Zika epidemic"
- 2016
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- As part of the Swetox mission to react to emerging concerns in chemical health and environmental safety, a preliminary litterature investigation was undertaken to gather all readily available scientific information on PPF with respect to safety assessment, in order to better understand potential links between chemical exposure and the devopment of microcephaly in affected areas. Therefore the contents of the report do not constitute an attempt at either questioning the use of existing regulatory data in the manner prescribed by international regulatory proceedures, or as a new risk assessment, based on the scientific information and concepts discussed. Here we report our findings, with particular emphasis on exisiting regulatory information, potential for lack of translation of results from regulatory animal testing to humans, lack of human exposure data and suggestions on plausible mode(s) of action of PPF in human neurodevelopmental adversities such as microcephaly.
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31. |
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32. |
- Ek, Anna, et al.
(författare)
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A Parent Treatment Program for Preschoolers With Obesity : A Randomized Controlled Trial
- 2019
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 144:2
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Tidskriftsartikel (refereegranskat)abstract
- Background And Objectives: Early obesity treatment seems to be the most effective, but few treatments exist. In this study, we examine the effectiveness of a parent-only treatment program with and without booster sessions (Booster or No Booster) focusing on parenting practices and standard treatment (ST).Methods: Families of children 4 to 6 years of age with obesity were recruited from 68 child care centers in Stockholm County and randomly assigned to a parent-only program (10 weeks) with or without boosters (9 months) or to ST. Treatment effects on primary outcomes (BMI z score) and secondary outcomes (BMI and waist circumference) during a 12-month period were examined with linear mixed models. The influence of sociodemographic factors was examined by 3-way interactions. The clinically significant change in BMI z score (−0.5) was assessed with risk ratios.Results: A total of 174 children (mean age: 5.3 years [SD = 0.8]; BMI z score: 3.0 [SD = 0.6], 56% girls) and their parents (60% foreign background; 39% university degree) were included in the analysis (Booster, n = 44; No Booster, n = 43; ST, n = 87). After 12 months, children in the parent-only treatment had a greater reduction in their BMI z score (0.30; 95% confidence interval [CI]: −0.45 to −0.15) compared with ST (0.07; 95% CI: −0.19 to 0.05). Comparing all 3 groups, improvements in weight status were only seen for the Booster group (−0.54; 95% CI: −0.77 to −0.30). The Booster group was 4.8 times (95% CI: 2.4 to 9.6) more likely to reach a clinically significant reduction of ≥0.5 of the BMI z score compared with ST.Conclusion: A parent-only treatment with boosters outperformed standard care for obesity in preschoolers.
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33. |
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34. |
- Ekström, Magnus Pär, et al.
(författare)
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The association of body mass index, weight gain and central obesity with activity-related breathlessness : the Swedish Cardiopulmonary Bioimage Study
- 2019
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Ingår i: Thorax. - : BMJ Publishing Group Ltd. - 0040-6376 .- 1468-3296. ; 74:10, s. 958-964
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Breathlessness is common in the population, especially in women and associated with adverse health outcomes. Obesity (body mass index (BMI) >30 kg/m(2)) is rapidly increasing globally and its impact on breathlessness is unclear.Methods: This population-based study aimed primarily to evaluate the association of current BMI and self-reported change in BMI since age 20 with breathlessness (modified Research Council score >= 1) in the middle-aged population. Secondary aims were to evaluate factors that contribute to breathlessness in obesity, including the interaction with spirometric lung volume and sex.Results: We included 13 437 individuals; mean age 57.5 years; 52.5% women; mean BMI 26.8 (SD 4.3); mean BMI increase since age 20 was 5.0 kg/m(2); and 1283 (9.6%) reported breathlessness. Obesity was strongly associated with increased breathlessness, OR 3.54 (95% CI, 3.03 to 4.13) independent of age, sex, smoking, airflow obstruction, exercise level and the presence of comorbidities. The association between BMI and breathlessness was modified by lung volume; the increase in breathlessness prevalence with higher BMI was steeper for individuals with lower forced vital capacity (FVC). The higher breathlessness prevalence in obese women than men (27.4% vs 12.5%; p<0.001) was related to their lower FVC. Irrespective of current BMI and confounders, individuals who had increased in BMI since age 20 had more breathlessness.Conclusion: Breathlessness is independently associated with obesity and with weight gain in adult life, and the association is stronger for individuals with lower lung volumes.
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35. |
- Engström, Gunnar, et al.
(författare)
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Blood biomarkers and measures of pulmonary function-A study from the Swedish twin registry.
- 2012
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 106:9, s. 1250-1257
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is great need of biomarkers for research and clinical purposes in COPD. This study explored the relationships between ten putative plasma biomarkers of COPD and physiological measures of reduced lung function. METHODS: FEV(1), FVC, residual volume/total lung capacity (RV/TLC) and CO diffusion capacity (D(L)CO) were assessed in 357 subjects from the Swedish Twin Registry. The lung function measures were studied in relation to plasma levels of desmosines, C-reactive protein (CRP), plasminogen inhibitor activator (PAI-1) concentration and activity, tissue inhibitor of metalloproteinase (TIMP-1), clara cell protein 16 (CC16), surfactant protein D (SPD), matrix metalloproteinase 9 (MMP-9), hepatocyte growth factor (HGF) and interleukin (IL)-8. RESULTS: After adjustments for age, sex, height, BMI and smoking, FEV(1) was significantly associated with PAI-1 activity and desmosines. RV/TLC was significantly associated with CC16, PAI-1 concentration and PAI-1 activity, and D(L)CO was significantly associated with desmosines, TIMP-1 and CRP. When the multivariate analysis was restricted to subjects with COPD (i.e., FEV(1)/FVC < 0.70), CRP and desmosines were inversely associated with lung function. CONCLUSION: Several biomarkers were associated with lung function in this cross-sectional study. Especially CRP and desmosines could be useful markers to assess disease severity in subjects with COPD.
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36. |
- Engström, Gunnar, et al.
(författare)
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Pulmonary function and atherosclerosis in the general population : causal associations and clinical implications
- 2024
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Ingår i: European Journal of Epidemiology. - : Springer Nature. - 0393-2990 .- 1573-7284. ; 39:1, s. 35-49
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50–64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.
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37. |
- Enroth, Stefan, 1976-, et al.
(författare)
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Data-driven analysis of a validated risk score for ovarian cancer identifies clinically distinct patterns during follow-up and treatment
- 2022
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Ingår i: Communications Medicine. - : Springer Nature. - 2730-664X. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOvarian cancer is the eighth most common cancer among women and due to late detection prognosis is poor with an overall 5-year survival of 30–50%. Novel biomarkers are needed to reduce diagnostic surgery and enable detection of early-stage cancer by population screening. We have previously developed a risk score based on an 11-biomarker plasma protein assay to distinguish benign tumors (cysts) from malignant ovarian cancer in women with adnexal ovarian mass.MethodsProtein concentrations of 11 proteins were characterized in plasma from 1120 clinical samples with a custom version of the proximity extension assay. The performance of the assay was evaluated in terms of prediction accuracy based on receiver operating characteristics (ROC) and multiple hypothesis adjusted Fisher’s Exact tests on achieved sensitivity and specificity.ResultsThe assay’s performance is validated in two independent clinical cohorts with a sensitivity of 0.83/0.91 and specificity of 0.88/0.92. We also show that the risk score follows the clinical development and is reduced upon treatment, and increased with relapse and cancer progression. Data-driven modeling of the risk score patterns during a 2-year follow-up after diagnosis identifies four separate risk score trajectories linked to clinical development and survival. A Cox proportional hazard regression analysis of 5-year survival shows that at time of diagnosis the risk score is the second-strongest predictive variable for survival after tumor stage, whereas MUCIN-16 (CA-125) alone is not significantly predictive.ConclusionThe robust performance of the biomarker assay across clinical cohorts and the correlation with clinical development indicates its usefulness both in the diagnostic work-up of women with adnexal ovarian mass and for predicting their clinical course.
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38. |
- Eriksson, Gunnar, et al.
(författare)
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Allocation of infrastructure cost in the maritime sector
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- This deliverable consists in principle of two parts; one part with a review of the literature around maritime infrastructure cost with a focus on fairways (section 3), pilotage (section 4) and ports (section 5) and another part with an in-depth study on the Baltic icebreaking fleet (section 6). Our main conclusion from the first part is that all these parts of the infrastructure (fairways, pilotage and ports) show significant economies of scale. A long run marginal cost pricing strategy will never recover the cost and a short run pricing strategy (including user costs) will have problems with cost recovery if the capacity utilisation is low. The pricing strategies observed seem to use numerous forms of two part tariffs and "Ramsey" pricing solutions to solve the cost recovery issue of the sector. The consequence of all these (small) deviations from marginal cost pricing should probably be further analysed. The second part deals with icebreaking and notes that icebreaking in open water is not charged for by any EU Member State. Still the case study reported in this paper shows that the operation is characterised by considerable marginal costs. Finally, a relevant question to address is to what extent there are justifications for European or international legislation on maritime charging in the light of economic theory. Obviously, it is useful to address different parts of the maritime infrastructure separately.
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39. |
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40. |
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41. |
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42. |
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43. |
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44. |
- Fornäs, Johan, 1952-, et al.
(författare)
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Tältprojektet : Vi äro tusenden
- 1977
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Ingår i: Tekla: Teori och klasskamp. - Göteborg : Röda Bokförlaget. - 0348-7253. ; :3/4, s. 94-104
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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45. |
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48. |
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49. |
- Forreryd, Andy, et al.
(författare)
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Predicting skin sensitizers with confidence : Using conformal prediction to determine applicability domain of GARD
- 2018
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Ingår i: Toxicology in Vitro. - : Elsevier. - 0887-2333 .- 1879-3177. ; 48, s. 179-187
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Tidskriftsartikel (refereegranskat)abstract
- GARD - Genomic Allergen Rapid Detection is a cell based alternative to animal testing for identification of skin sensitizers. The assay is based on a biomarker signature comprising 200 genes measured in an in vitro model of dendritic cells following chemical stimulations, and consistently reports predictive performances similar to 90% for classification of external test sets. Within the field of in vitro skin sensitization testing, definition of applicability domain is often neglected by test developers, and assays are often considered applicable across the entire chemical space. This study complements previous assessments of model performance with an estimate of confidence in individual classifications, as well as a statistically valid determination of the applicability domain for the GARD assay. Conformal prediction was implemented into current GARD protocols, and a large external test dataset (n = 70) was classified at a confidence level of 85%, to generate a valid model with a balanced accuracy of 88%, with none of the tested chemical reactivity domains identified as outside the applicability domain of the assay. In conclusion, results presented in this study complement previously reported predictive performances of GARD with a statistically valid assessment of uncertainty in each individual prediction, thus allowing for classification of skin sensitizers with confidence.
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50. |
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