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| 3. |
- 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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| 4. |
- 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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| 10. |
- Andersson, Sandra, et al.
(författare)
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Insufficient antibody validation challenges oestrogen receptor beta research
- 2017
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of oestrogen receptor beta (ER beta/ESR2) was a landmark discovery. Its reported expression and homology with breast cancer pharmacological target ER alpha (ESR1) raised hopes for improved endocrine therapies. After 20 years of intense research, this has not materialized. We here perform a rigorous validation of 13 anti-ER beta antibodies, using well-characterized controls and a panel of validation methods. We conclude that only one antibody, the rarely used monoclonal PPZ0506, specifically targets ER beta in immunohistochemistry. Applying this antibody for protein expression profiling in 44 normal and 21 malignant human tissues, we detect ER beta protein in testis, ovary, lymphoid cells, granulosa cell tumours, and a subset of malignant melanoma and thyroid cancers. We do not find evidence of expression in normal or cancerous human breast. This expression pattern aligns well with RNA-seq data, but contradicts a multitude of studies. Our study highlights how inadequately validated antibodies can lead an exciting field astray.
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| 11. |
- Barath, Stefan, et al.
(författare)
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Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions
- 2010
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Ingår i: Particle and Fibre Toxicology. - : BioMed Central. - 1743-8977. ; 7:1, s. 19-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.
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| 12. |
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| 13. |
- Berg, Staffan, et al.
(författare)
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Evaluation in pig of an intestinal administration device for oral peptide delivery
- 2023
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 353, s. 792-801
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Tidskriftsartikel (refereegranskat)abstract
- The bioavailability of peptides co-delivered with permeation enhancers following oral administration remains low and highly variable. Two factors that may contribute to this are the dilution of the permeation enhancer in the intestinal fluid, as well as spreading of the released permeation enhancer and peptide in the lumen by intestinal motility. In this work we evaluated an Intestinal Administration Device (IAD) designed to reduce the luminal dilution of drug and permeation enhancer, and to minimize movement of the dosage form in the intestinal lumen. To achieve this, the IAD utilizes an expanding design that holds immediate release mini tablets and places these in contact with the intestinal epithelium, where unidirectional drug release can occur. The expanding conformation limits movement of the IAD in the intestinal tract, thereby enabling drug release at a single focal point in the intestine. A pig model was selected to study the ability of the IAD to promote intestinal absorption of the peptide MEDI7219 formulated together with the permeation enhancer sodium caprate. We compared the IAD to intestinally administered enteric coated capsules and an intestinally administered solution. The IAD restricted movement of the immediate release tablets in the small intestine and histological evaluation of the mucosa indicated that high concentrations of sodium caprate were achieved. Despite significant effect of the permeation enhancer on the integrity of the intestinal epithelium, the bioavailability of MEDI7219 was of the same order of magnitude as that achieved with the solution and enteric coated capsule formulations (2.5–3.8%). The variability in plasma concentrations of MEDI7219 were however lower when delivered using the IAD as compared to the solution and enteric coated capsule formulations. This suggests that dosage forms that can limit intestinal dilution and control the position of drug release can be a way to reduce the absorptive variability of peptides delivered with permeation enhancers but do not offer significant benefits in terms of increasing bioavailability.
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| 14. |
- Berg, Staffan, et al.
(författare)
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Impact of Intestinal Concentration and Colloidal Structure on the Permeation-Enhancing Efficiency of Sodium Caprate in the Rat
- 2022
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 19:1, s. 200-212
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Tidskriftsartikel (refereegranskat)abstract
- In this work, we set out to better understand how the permeation enhancer sodium caprate (C10) influences the intestinal absorption of macromolecules. FITC-dextran 4000 (FD4) was selected as a model compound and formulated with 50-300 mM C10. Absorption was studied after bolus instillation of liquid formulation to the duodenum of anesthetized rats and intravenously as a reference, whereafter plasma samples were taken and analyzed for FD4 content. It was found that the AUC and C-max of FD4 increased with increasing C10 concentration. Higher C10 concentrations were associated with an increased and extended absorption but also increased epithelial damage. Depending on the C10 concentration, the intestinal epithelium showed significant recovery already at 60-120 min after administration. At the highest studied C10 concentrations (100 and 300 mM), the absorption of FD4 was not affected by the colloidal structures of C10, with similar absorption obtained when C10 was administered as micelles (pH 8.5) and as vesicles (pH 6.5). In contrast, the FD4 absorption was lower when C10 was administered at 50 mM formulated as micelles as compared to vesicles. Intestinal dilution of C10 and FD4 revealed a trend of decreasing FD4 absorption with increasing intestinal dilution. However, the effect was smaller than that of altering the total administered C10 dose. Absorption was similar when the formulations were prepared in simulated intestinal fluids containing mixed micelles of bile salts and phospholipids and in simple buffer solution. The findings in this study suggest that in order to optimally enhance the absorption of macromolecules, high (>= 100 mM) initial intestinal C10 concentrations are likely needed and that both the concentration and total dose of C10 are important parameters.
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| 15. |
- 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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| 16. |
- 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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| 17. |
- Bergström, Göran, et al.
(författare)
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Self-report tool for identification of individuals with coronary atherosclerosis : the Swedish cardiopulmonary bioimage study
- 2024
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 13:14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis.METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly.CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.
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| 18. |
- Berner, Karin, et al.
(författare)
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Dose optimisation of double-contrast barium enema examinations.
- 2010
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 139:1-3, s. 388-392
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present work was to optimise the filtration and dose setting for double-contrast barium enema examinations using a Philips MultiDiagnost Eleva FD system. A phantom study was performed prior to a patient study. A CDRAD phantom was used in a study where copper and aluminium filtration, different detector doses and tube potentials were examined. The image quality was evaluated using the software CDRAD Analyser and the phantom dose was determined using the Monte Carlo-based software PCXMC. The original setting [100 % detector dose (660 nGy air kerma) and a total filtration of 3.5 mm Al, at 81 kVp] and two other settings identified by the phantom study (100 % detector dose and additional filtration of 1 mm Al and 0.2 mm Cu as well as 80 % detector dose and added filtration of 1 mm Al and 0.2 mm Cu) were included in the patient study. The patient study included 60 patients and up to 8 images from each patient. Six radiologists performed a visual grading characteristics study to evaluate the image quality. A four-step scale was used to judge the fulfillment of three image quality criteria. No overall statistical significant difference in image quality was found between the three settings (P > 0.05). The decrease in the effective dose for the settings in the patient study was 15 % when filtration was added and 34 % when both filtrations was added and detector dose was reduced. The study indicates that additional filtration of 1 mm Al and 0.2 mm Cu and a decrease in detector dose by 20 % from the original setting can be used in colon examinations with Philips MultiDiagnost Eleva FD to reduce the patient dose by 30 % without significantly affecting the image quality. For 20 exposures, this corresponds to a decrease in the effective dose from 1.6 to 1.1 mSv.
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| 20. |
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| 21. |
- Bonev, Petyo, et al.
(författare)
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Implicit yardstick competition between heating monopolies in urban areas : Theory and evidence from Sweden
- 2022
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Ingår i: Energy Economics. - Amsterdam : Elsevier. - 0140-9883 .- 1873-6181. ; 109
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Tidskriftsartikel (refereegranskat)abstract
- This article examines a novel regulatory mechanism in a setting with multiple local monopolists. The mechanism rests upon the behavioral assumption that customers form opinions about prices by comparing them with prices set by nearby monopolies and that this comparison influences their behavior. In this way, an “implicit yardstick competition” emerges among monopolists although they do not operate in the same markets. We test this mechanism using a unique dataset of unregulated district heating monopolists in Sweden. We find a large effect of neighbors’ prices, which indicates that the implicit yardstick competition has a considerable disciplining effect on monopolies’ pricing behavior. © 2022 The Author(s)
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| 22. |
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| 23. |
- Camuz, Soner, 1988, et al.
(författare)
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Contact Variation Optimization for Surface-to-Surface Contacts
- 2017
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Ingår i: Proceedings of International Mechanical Engineering Congress & Exposition. ; 2
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Konferensbidrag (refereegranskat)abstract
- Locating schemes, used to position parts during manufacturing, are usually designed in such a way that the response from the system is minimized. This implies that the position of the fasteners and/or welds are known in an assembly. Today there exist numerous of methods aiming to find an optimal set of locating points to increase the stability of an assembly, for both rigid and compliant parts. However, various industrial applications use surface-to-surface contacts to constrain certain degrees of freedom. This can lead to designs sensitive to geometric and load variations. As the complexity of the surfaces increases, difficulties of allocating geometric tolerances arise. An approach to control this is to keep the contact locations statistically stable. In this paper a methodology is presented where the First-Order reliability Method (FORM) is applied for numerical data, retrieved through Finite Element Analysis (FEA), to ensure that statistically stable contact location are achieved for two bodies with surface-to-suface contact. The FEA data represents how much of the total stress that lies within a given area, sW. The data is continuous and therefore it is assumed that the gradient can be calculated numerically with small steps. The objective function is to maximize sW for n variables. The data set is simulated through Finite Element Analysis using the commercial software Ansys and the results is illustrated on a case study from the machining industry.
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| 24. |
- Camuz, Soner, 1988, et al.
(författare)
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Reliability based design optimization of surface-to-surface contact for cutting tool interface designs
- 2019
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Ingår i: Journal of manufacturing science and engineering. - ASME : ASME International. - 1087-1357 .- 1528-8935.
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Tidskriftsartikel (refereegranskat)abstract
- In recent year, cutting tool manufacturers are moving towards improving the robustness of the positioning of an insert in the tool body interface. Increasing the robustness of the interface involves designs with both chamfered and serrated surfaces. These designs have a tendency to over-determine the positioning and cause instabilities in the interface. Cutting forces generated from the machining process will also plastically deform the interface, consequently, altering the positioning of the insert. Current methodologies within positioning and variation simulation use point-based contacts and assume linear material behaviour. In this article, a first order reliability-based design optimization framework that allows robust positioning of surface-to-surface-based contacts is presented. Results show that the contact variation over the interface can be limited to pre-defined contact zones, consequently allowing successful positioning of inserts in early design phases of cutting tool designs.
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| 25. |
- Carlander, A, et al.
(författare)
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Clinical evaluation of a dual-side readout technique computed radiography system in chest radiography of premature neonates.
- 2008
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 49:4, s. 468-74
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recently, the dual-side readout technique has been introduced in computed radiography, leading to an increase in detective quantum efficiency (DQE) compared with the single-side readout technique. PURPOSE: To evaluate if the increase in DQE with the dual-side readout technique results in a higher clinical image quality in chest radiography of premature neonates at no increase in radiation dose. MATERIAL AND METHODS: Twenty-four chest radiographs of premature neonates were collected from both a single-side readout technique system and a double-side readout technique system. The images were processed in the same image-processing station in order for the comparison to be only dependent on the difference in readout technique. Five radiologists rated the fulfillment of four image quality criteria, which were based on important anatomical landmarks. The given ratings were analyzed using visual grading characteristics (VGC) analysis. RESULTS: The VGC analysis showed that the reproduction of the carina with the main bronchi and the thoracic vertebrae behind the heart was better with the dual-side readout technique, whereas no significant difference for the reproduction of the central vessels or the peripheral vessels could be observed. CONCLUSIONS: The results indicate that the higher DQE of the dual-side readout technique leads to higher clinical image quality in chest radiography of premature neonates at no increase in radiation dose.
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| 26. |
- Carlander, Anna, et al.
(författare)
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The effect of radiation dose reduction on clinical image quality in chest radiography of premature neonates using a dual-side readout technique computed radiography system
- 2010
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Ingår i: Radiation protection dosimetry. - : Oxford University Press (OUP). - 1742-3406 .- 0144-8420. ; 139:1-3, s. 275-280
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate if the exposure could be reduced from the clinical setting (resulting in an effective dose of 8 microSv for a neonate of weight 0.7 kg and height 25 cm at a tube voltage of 90 kV) without negatively influencing the image quality for a dual-side readout technique computed radiography (CR) system in chest radiography of premature neonates. Chest radiographs of premature neonates were acquired with the double-side readout technique CR system. The images underwent simulated dose reduction in steps of 20 % to represent five different radiation dose levels. Four image quality criteria, related to the visibility of important anatomical structures, were used in a visual grading study where five experienced radiologists rated how well the criteria were fulfilled for all images. When reducing the radiation dose, a decrease in image quality could be observed already at the 80 % dose level for all the structures. The results indicate that a decrease in exposure from the clinically used setting affects the image quality negatively for the CR system.
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| 27. |
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| 30. |
- Chadalavada, Sucharitha, et al.
(författare)
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Diabetes and heart failure associations in women and men : Results from the MORGAM consortium
- 2023
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Ingår i: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diabetes and its cardiovascular complications are a growing concern worldwide. Recently, some studies have demonstrated that relative risk of heart failure (HF) is higher in women with type 1 diabetes (T1DM) than in men. This study aims to validate these findings in cohorts representing five countries across Europe.Methods: This study includes 88,559 (51.8% women) participants, 3,281 (46.3% women) of whom had diabetes at baseline. Survival analysis was performed with the outcomes of interest being death and HF with a follow-up time of 12 years. Sub-group analysis according to sex and type of diabetes was also performed for the HF outcome.Results: 6,460 deaths were recorded, of which 567 were amongst those with diabetes. Additionally, HF was diagnosed in 2,772 individuals (446 with diabetes). A multivariable Cox proportional hazard analysis showed that there was an increased risk of death and HF (hazard ratio (HR) of 1.73 [1.58–1.89] and 2.12 [1.91–2.36], respectively) when comparing those with diabetes and those without. The HR for HF was 6.72 [2.75–16.41] for women with T1DM vs. 5.80 [2.72–12.37] for men with T1DM, but the interaction term for sex differences was insignificant (p for interaction 0.45). There was no significant difference in the relative risk of HF between men and women when both types of diabetes were combined (HR 2.22 [1.93–2.54] vs. 1.99 [1.67–2.38] respectively, p for interaction 0.80).Conclusion: Diabetes is associated with increased risks of death and heart failure, and there was no difference in relative risk according to sex.
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| 31. |
- Clausson, Carl-Magnus, 1985-, et al.
(författare)
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Compaction of rolling circle amplification products increases signal integrity and signal–to–noise ratio
- 2015
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 12317:1-10
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Tidskriftsartikel (refereegranskat)abstract
- Rolling circle amplification (RCA) for generation of distinct fluorescent signals in situ relies upon the self-collapsing properties of single-stranded DNA in commonly used RCA-based methods. By introducing a cross-hybridizing DNA oligonucleotide during rolling circle amplification, we demonstrate that the fluorophore-labeled RCA products (RCPs) become smaller. The reduced size of RCPs increases the local concentration of fluorophores and as a result, the signal intensity increases together with the signal-to-noise ratio. Furthermore, we have found that RCPs sometimes tend to disintegrate and may be recorded as several RCPs, a trait that is prevented with our cross-hybridizing DNA oligonucleotide. These effects generated by compaction of RCPs improve accuracy of visual as well as automated in situ analysis for RCA based methods, such as proximity ligation assays (PLA) and padlock probes.
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| 32. |
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| 33. |
- Clausson, Carl-Magnus, et al.
(författare)
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Increasing the dynamic range of in situ PLA
- 2011
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 8:11, s. 892-893
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Tidskriftsartikel (refereegranskat)
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| 34. |
- Clausson, Carl-Magnus, 1985-
(författare)
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Making Visible the Proximity Between Proteins
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Genomic DNA is the template of life - the entity which is characterized by a self-sustaining anatomical development, regulated signaling processes, the ability to reproduce and to respond to stimuli. Through what is classically known as the central dogma, the genome is transcribed into mRNA, which in turn is translated into proteins. The proteins take part in most, if not all, cellular processes, and it is by unraveling these processes that we can begin to understand life and disease-causing mechanisms.In vitro and in vivo assays are two levels at which protein communication may be studied, and which permit manipulation and control over the proteins under investigation. But in order to retrieve a representation of the processes as close to reality as possible, in situ analysis may instead be applied as a complement to the other two levels of study. In situ PLA offers the ability to survey protein activity in tissue samples and primary cell lines, at a single cell level, detecting single targets in their natural unperturbed environment. In this thesis new developments of the in situ PLA are described, along with a new technique offering in situ enzyme-free detection of proximity between biomolecules.The dynamic range of in situ PLA has now been increased by several orders of magnitude to cover analogous ranges of protein expression; the output signals have been modified to offer a greater signal-to-noise ratio and to limit false-positive-rates while also extending the dynamic range further; simultaneous detection of multiple protein complexes is now possible; proximity-HCR is presented as a robust and inexpensive enzyme-free assay for protein complex detection.The thesis also covers descriptions on how the techniques may be simultaneously applied, also together with other techniques, for the multiple data-point acquisition required by the emerging realm of systems biology. A future perspective is presented for how much more information may be simultaneously acquired from tissue samples to describe biomolecular interactions in a new manner. This will allow new types of biomarkers and drugs to be discovered, and a new holistic understanding of life.
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| 35. |
- Clausson, Carl-Magnus, et al.
(författare)
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Methods for analysis of the cancer microenvironment and their potential for disease prediction, monitoring and personalized treatments
- 2012
-
Ingår i: The EPMA journal. - : Springer Science and Business Media LLC. - 1878-5085 .- 1878-5077. ; 3:7
-
Forskningsöversikt (refereegranskat)abstract
- A tumor does not consist of a homogenous population of cancer cells. Therefore, to understand cancer, the tumor microenvironment and the interplay between the different cell types present in the tumor has to be taken into account, and how this regulates the growth and survival of the cancer cells. To achieve a full picture of this complex interplay, analysis of tumor tissue should ideally be performed with cellular resolution, providing activity status of individual cells in this heterogeneous population of different cell-types. In addition, in situ analysis provides information on the architecture of the tissue wherein the cancer cells thrive, providing information of the identity of neighboring cells that can be used to understand cell-cell communication. Herein we describe how padlock probes and in situ PLA can be used for visualization of nucleic acids and protein activity, respectively, directly in tissue sections, and their potential future role in personalized medicine.
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| 36. |
- Cohen, F., et al.
(författare)
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Consumer myopia, imperfect competition and the energy efficiency gap: Evidence from the UK refrigerator market
- 2017
-
Ingår i: European Economic Review. - : Elsevier BV. - 0014-2921. ; 93, s. 1-23
-
Tidskriftsartikel (refereegranskat)abstract
- The empirical literature on the energy efficiency gap concentrates on demand inefficiencies in the energy-using durables markets and finds evidence that consumers underestimate future energy costs when purchasing a new appliance. We take a broader view and also consider the impact of imperfect competition. Using data on the UK refrigerator market (2002-2007), we find that the average energy consumption of appliances sold during this period was only 7.2% higher than what would have been observed under a scenario with a perfectly competitive market and non-myopic consumers. One reason for this small gap is that market power actually reduces energy use. (C) 2017 Elsevier B.V. All rights reserved.
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| 37. |
- Cohen, F., et al.
(författare)
-
The impact of energy prices on product innovation: Evidence from the UK refrigerator market
- 2017
-
Ingår i: Energy Economics. - : Elsevier BV. - 0140-9883. ; 68:S1, s. 81-88
-
Tidskriftsartikel (refereegranskat)abstract
- This paper uses product-level data from the UK refrigerator market to evaluate the impact of electricity prices on product innovation. Our best estimate is that a 10% increase in the electricity price reduces the average energy consumption of commercialized refrigerator models by 2%. A large share of this reduction is explained by a reduction of freezing space. We also show that the exit of energy-inefficient products contributes more to energy reduction than the launch of new energy-efficient models. These findings suggest that innovation - the development of better technologies embodied in new products - does not respond strongly to energy price variations. (C) 2017 Published by Elsevier B.V.
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| 38. |
- Coppo, Rosanna, et al.
(författare)
-
Risk factors for progression in children and young adults with IgA nephropathy : an analysis of 261 cases from the VALIGA European cohort
- 2017
-
Ingår i: Pediatric nephrology (Berlin, West). - : Springer Science and Business Media LLC. - 0931-041X .- 1432-198X. ; 32:1, s. 139-150
-
Tidskriftsartikel (refereegranskat)abstract
- There is a need for early identification of children with immunoglobulin A nephropathy (IgAN) at risk of progression of kidney disease. Data on 261 young patients [age < 23 years; mean follow-up of 4.9 (range 2.5-8.1) years] enrolled in VALIGA, a study designed to validate the Oxford Classification of IgAN, were assessed. Renal biopsies were scored for the presence of mesangial hypercellularity (M1), endocapillary hypercellularity (E1), segmental glomerulosclerosis (S1), tubular atrophy/interstitial fibrosis (T1-2) (MEST score) and crescents (C1). Progression was assessed as end stage renal disease and/or a 50 % loss of estimated glomerular filtration rate (eGFR) (combined endpoint) as well as the rate of renal function decline (slope of eGFR). Cox regression and tree classification binary models were used and compared. In this cohort of 261 subjects aged < 23 years, Cox analysis validated the MEST M, S and T scores for predicting survival to the combined endpoint but failed to prove that these scores had predictive value in the sub-group of 174 children aged < 18 years. The regression tree classification indicated that patients with M1 were at risk of developing higher time-averaged proteinuria (p < 0.0001) and the combined endpoint (p < 0.001). An initial proteinuria of ae0.4 g/day/1.73 m(2) and an eGFR of < 90 ml/min/1.73 m(2) were determined to be risk factors in subjects with M0. Children aged < 16 years with M0 and well-preserved eGFR (> 90 ml/min/1.73 m(2)) at presentation had a significantly high probability of proteinuria remission during follow-up and a higher remission rate following treatment with corticosteroid and/or immunosuppressive therapy. This new statistical approach has identified clinical and histological risk factors associated with outcome in children and young adults with IgAN.
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| 39. |
- Dalin, Frida, 1984-, et al.
(författare)
-
Clinical and immunological characteristics of Autoimmune Addison's disease : a nationwide Swedish multicenter study
- 2017
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:2, s. 379-389
-
Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Studies on clinical and immunological features of Autoimmune Addison's disease (AAD) are needed to understand the disease burden and increased mortality.OBJECTIVE: To provide upgraded data on autoimmune comorbidities, replacement therapy, autoantibody profiles and cardiovascular risk factors.DESIGN, SETTING AND PARTICIPANTS: Cross sectional, population-based study. 660 AAD patients were included utilizing the Swedish Addison Registry (SAR) 2008-2014. When analyzing cardiovascular risk factors, 3,594 individuals from the population-based survey in Northern Sweden, MONICA (MONItoring of Trends and Determinants of CArdiovascular Disease), served as controls.MAIN OUTCOME MEASURE: Prevalence of autoimmune comorbidities and cardiovascular risk factors. Autoantibodies against 13 autoantigens were determined.RESULTS: Sixty percent of the SAR cohort consisted of females. Mean age at diagnosis was significantly higher for females than for males (36.8 vs. 31.1 years). The proportion of 21-hydroxylase autoantibody positive patients was 83% and 62% of patients had one or more associated autoimmune diseases, more frequently coexisting in females (p<0.0001). AAD patients had lower BMI (p<0.0001) and prevalence of hypertension (p=0.027) compared with controls. Conventional hydrocortisone tablets were used by 89% of patients; with the mean dose 28.1±8.5 mg/day. The mean hydrocortisone equivalent dose normalized to body surface was 14.8±4.4 mg/m(2)/day. Higher hydrocortisone equivalent dose was associated with higher incidence of hypertension (p=0.046).CONCLUSIONS: Careful monitoring of AAD patients is warranted to detect associated autoimmune diseases. Contemporary Swedish AAD patients do not have increased prevalence of overweight, hypertension, T2DM or hyperlipidemia. However, high glucocorticoid replacement doses may be a risk factor for hypertension.
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| 40. |
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| 41. |
- Ek, Claes, 1983, et al.
(författare)
-
Does teaching school children about recycling reduce household waste?
- 2020
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Reduced waste generation is a prioritized environmental policy objective in the EU as well as worldwide. We perform a randomized controlled trial in Sweden with school children aged 10-16 to evaluate an intervention designed to reduce household waste, Environmental Education Programs (EEP). Crucially, we are able to examine the causal e ect of a wastethemed EEP on the actual waste generated in households where a child was treated. This is done by coupling the addresses of participating students with high-resolution address-level panel data on collected waste amounts, supplied by municipal waste authorities. Our design allows identi cation of the di erential e ect of the EEP on waste generation in treated versus control households. We nd no signi cant evidence that the intervention had any e ect on waste generation. There is also no indication that this null result is due to interference between treated and control students.
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| 42. |
- Ek, Claes, 1983, et al.
(författare)
-
Norm-based feedback on household waste: Large-scale field experiments in two Swedish municipalities
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We conduct separate randomized controlled trials of norm-based feedback nudges on household waste in two municipalities in western Sweden. Our main treatment presents recipients with accurate, household-speci c feedback highly similar to the standard Home Energy Report design, but with residual (unsorted) waste as the object of comparison. We also test a novel `dynamic' norm design informed by psychological research. Post-experimental reductions are on the order of 7-12% in both municipalities, substantially larger than in most previous studies. We estimate that the reduction corresponds to a 30-60% increase in unit-based waste fees. E ect di erences between our main treatment and the dynamicnorm treatment are not signi cant. We nd that feedback nudges are highly cost-e ective compared to alternative means for reducing household residual waste. However, net social bene ts depend on whether existing waste fees internalize the marginal social cost of residual waste. Our results have implications for the usefulness of feedback interventions as well as for unit-based pricing of waste, on which our feedback materials rely.
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| 43. |
- Erlandsson, Helen, et al.
(författare)
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Scoring of medial arterial calcification predicts cardiovascular events and mortality after kidney transplantation
- 2022
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 291:6, s. 813-823
-
Tidskriftsartikel (refereegranskat)abstract
- Background Progression of vascular calcification causes cardiovascular disease, which is the most common cause of death in chronic kidney failure and after kidney transplantation (KT). The prognostic impact of the extent of medial vascular calcification at KT is unknown. Methods In this prospective cohort study, we investigated the impact of medial calcification compared to a mix of intimal and medial calcification represented by coronary artery calcification (CAC score) and aortic valve calcification in 342 patients starting on kidney failure replacement therapy. The primary outcomes were cardiovascular events (CVE) and death. The median follow-up time was 6.4 years (interquartile range 3.7-9.6 years). Exposure was CAC score and arteria epigastrica medial calcification scored as none, mild, moderate, or severe by a pathologist at time of KT (n = 200). We divided the patients according to kidney failure replacement therapy during follow-up, that is, living donor KT, deceased donor KT, or dialysis. Results Moderate to severe medial calcification in the arteria epigastrica was associated with higher mortality (p = 0.001), and the hazard ratio for CVE was 3.1 (95% confidence interval [CI] 1.12-9.02, p < 0.05) compared to no or mild medial calcification. The hazard ratio for 10-year mortality in the dialysis group was 33.6 (95% CI, 10.0-113.0, p < 0.001) compared to living donor recipients, independent of Framingham risk score and prevalent CAC. Conclusion Scoring of medial calcification in the arteria epigastrica identified living donor recipients as having 3.1 times higher risk of CVE, independent of traditional risk factors. The medial calcification score could be a reliable method to identify patients with high and low risk of CVE and mortality following KT.
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| 44. |
- Fahlgren, Siv, et al.
(författare)
-
Having Your Cake and Eating It? : The “Painful Cake” Incident of 2012 Examined
- 2015
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Ingår i: Konsthistorisk Tidskrift. - : Routledge. - 0023-3609 .- 1651-2294. ; 84:1, s. 55-70
-
Tidskriftsartikel (refereegranskat)abstract
- On the 15th of April, 2012, The Modern Museum (Modernamuseet) in Stockholm celebrated the World Art Day by having a reception with the Swedish cultural minister present, at which an artwork in the form of a cake made in the likeness of the body of a caricatured black woman was served, cut up and eaten, while the artist, masked as the cakes head, screamed. This conceptual, relational, and contextualizing artwork, which leads to a much heated debate in Sweden and which was also internationally picked up on, was made by the explicitly anti-racist artist Makode Linde. In this article, we explore the problem of this event in terms of its sociocultural significance. How did we react upon the drama that we were following from a distance? What did it make us see? What questions did the incident raise about the Swedish society of today? These are examples of the questions we as gender researchers working in Sweden will discuss in the form of a triptych. We use the triptych metaphor as a tool for opening dialogue. By opening its panels it becomes possible to decommodify the single image of the artwork and make relations between agents traceable, visible, and readable.
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| 45. |
- Flachenecker, Florian, et al.
(författare)
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The causal impact of economic growth on material use in Europe
- 2017
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Ingår i: Journal of Environmental Economics and Policy. - : Informa UK Limited. - 2160-6544 .- 2160-6552. ; 6:4, s. 415-432
-
Tidskriftsartikel (refereegranskat)abstract
- Several scholars and policy makers have claimed that Europe, and Western Europe in particular, has managed to ‘decouple’ economic growth from material use. We identify and address one major limitation in the existing literature – failure to take the endogeneity of economic growth into account. Based on a panel data set of 32 European countries from 2000 to 2014, we estimate the causal impact of gross domestic product (GDP) on domestic material consumption (DMC) applying an instrumental variable approach. We use the number of storm occurrences as an instrument for GDP, which we show is both relevant and valid. Our results provide new evidence that increasing the GDP growth rate causes the DMC growth rate to increase for Western Europe, whereas the effect is insignificant for the Eastern European economies and Europe as a whole. As our results partly question current wisdom on the achievements of ‘decoupling’, especially among European policy makers, we offer two explanations that are consistent with these results.
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| 46. |
- Forsgren Johansson, Gunilla, et al.
(författare)
-
Samordnad kustfiskövervakning i Östersjön – övervakningsstrategi
- 2005
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Kustfiskprojektet är ett specialprojekt inom den nationella miljöövervakningen och har finansierats av Naturvårdsverket, Fiskeriverket samt länsstyrelserna. Deltagare i projektet sedan starten 2002 har varit länsstyrelserna i Norrbottens, Västerbottens, Västernorrlands, Gävleborgs, Uppsala, Stockholms och Södermanlands län, Fiskeriverkets Kustlaboratorium i Öregrund, Fiskeriverkets Utredningskontor i Luleå och Härnösand samt Umeå Marina Forskningscentrum. Föreliggande rapport tillsammans med undersökningstyp i Naturvårdsverkets Handbok för Miljöövervakning och områdesvisa resultatblad tillgängliga på Fiskeriverkets hemsida utgör slutredovisning av projektet.SMHI:s indelning i kustvattentyper (Håkansson och Hansson 2003) har legat till grund för ett förslag till dimensionering av ett samordnat övervakningsprogram av kustfisk. För att möjliggöra uppföljning av förändringar på havsbassängnivå har projektet dimensionerat ett övervakningsprogram med minst ett referensområde per kustvattentyp av inre- och mellantyp, alternativt minst två områden per havsbassäng, vilket ger elva referensområden i Östersjön. I den föreslagna dimensioneringen har inte ett eventuellt behov av regional förtätning av provfiskeområden i Egentliga Östersjöns kustvatten (söder om Södermanlands läns kustvatten) beaktats. Referensområdena är utvalda enligt de kriterier som tagits fram inom projektet. Så långt möjligt har urvalet av nya områden gjorts så att både inneslutna kustmiljöer och mer exponerade kuststräckor är representerade.Den reviderade provtagningsstrategi och metodik, Djupstratifierat provfiske med Nordiska kustöversiktsnät, som har testats inom kustfiskprojektet har visats bättre kunna skatta kustfiskbestånden i ett provfiskeområde samt bättre kunna följa förändringar i biologisk mångfald och rekryteringsframgång än tidigare provtagningsmetodik. Provfiskemetodiken är inriktad mot varmvattenarter så som abborre, gers, gös, gädda och de flesta karpfiskar som mört, braxen etc. Abborre fungerar som modellart, vilket innebär att programmet är fördjupat för den arten med beskrivning av köns- och åldersfördelning. Projektet rekommenderar att den färdigställda undersökningstypen tillämpas vid provfiske i kustvatten där syftet är att följa förändringar i fisksamhället.Projektet lämnar förslag till indikatorer för uppföljning av förändringar i kustfisksamhället. Indikatorer har valts inom olika indikatorgrupper; Fisksamhällets diversitet, fisksamhällets kvantitet och struktur, fisksamhällets funktion samt individdata för abborre.Förekomst av rekryteringsområden i provfiskeområdets närhet är ett av de kriterier som ligger till grund för val av referensområden för kustfiskövervakning. Inom projektet har potentiellt intressanta områden för fiskrekrytering i kustmiljö identifierats för samtliga provfiskeområden i det samordnade programmet. Projektet förordar att vattentemperatur ska följas i en representativ grund miljö i området samt att fysisk påverkan bör kartläggas och följas upp regelbundet i provfiskeområdets närhet.Projektet föreslår en organisation och ansvarsfördelning som ska säkerställa driften av det samordnade programmet på lång sikt. Kustlaboratoriet i Öregrund ansvarar för samordningen av det nationella/regionala programmet för kustfiskövervakning i Östersjön. Det regionala och nationella nätverk som har byggts upp under projektets gång skapar förutsättningar för bättre samordning av den regionala och nationella marina miljöövervakningen. De Marina Forskningscentra bör vara naturliga intressenter i den kustsamverkan som utvecklas i Östersjön.Det är kustfiskprojektets förhoppning att erfarenheter och strategier som tagits fram inom projektet ska kunna användas som modell för nationell/regional samverkan avseende övervakning av kustfisk i andra kustområden i Östersjön och för annan typ av övervakning i marina ekosystem än kustfisk. Samordning av resurser, metoder och strategier mellan nationell och regional tidsserieövervakning är en förutsättning för att på lång sikt kunna upprätthålla en hög kvalitet på kustfiskövervakning i Östersjön.
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| 47. |
- Golembiewska, Edyta, et al.
(författare)
-
Copeptin is independently associated with vascular calcification in chronic kidney disease stage 5
- 2020
-
Ingår i: BMC Nephrology. - Stockholm : Karolinska Institutet, Dept of Clinical Science, Intervention and Technology. - 1471-2369.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Vascular calcification (VC) is an independent predictor of cardiovascular disease (CVD) present in 30– 70% of patients with chronic kidney disease (CKD). Copeptin is a sensitive surrogate marker of arginine vasopressin (AVP), which is involved in many pathophysiologic processes in CKD. The aim of the present study was to explore the association of copeptin with VC in CKD stage 5. Methods: Copeptin was investigated in conjunction with living donor kidney transplantation in 149 clinically stable CKD stage 5 patients (CKD5), including 53 non-dialyzed (CKD5-ND) and 96 dialysis patients treated by peritoneal dialysis (PD) (n = 43) or hemodialysis (HD) (n = 53). We analyzed the association of copeptin with presence and extent of VC ascertained both histologically in biopsies from the inferior epigastric artery (n = 137) and by coronary artery calcification (CAC) score measured by computed tomography. Results: Patients with higher copeptin were older, had higher systolic blood pressure, higher prevalence of CVD and their preceding time on chronic dialysis was longer. In Spearman’s rank correlations (Rho), copeptin concentrations were significantly associated with CAC score (Rho = 0.27; p = 0.003) and presence of medial VC (Rho = 0.21; p = 0.016). Multivariate logistic regression analysis showed that 1-SD higher age, male gender, diabetes and 1-SD higher copeptin were significantly associated with the presence of moderate-extensive VC. Conclusions: High circulating levels of copeptin in CKD5 patients are independently associated with the degree of medial calcification ascertained by histology of arterial biopsies. Thus, plasma copeptin may serve as a marker of the uremic calcification process.
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| 48. |
- Gyllenhammar, Magnus, 1992-, et al.
(författare)
-
Towards an Operational Design Domain That Supports the Safety Argumentation of an Automated Driving System
- 2020
-
Ingår i: Proceeding of the 10th European Congress on Embedded Real Time Software and Systems. - Toulouse.
-
Konferensbidrag (refereegranskat)abstract
- One of the biggest challenges for self-driving road vehicles is how to argue that their safety cases are complete. The operational design domain (ODD) of the automated driving system (ADS) can be used to restrict where the ADS is valid and thus confine the scope of the safety case as well as the verification. To complete the safety case there is a need to ensure that the ADS will not exit its ODD. We present four generic strategies to ensure this. Use cases (UCs) provide a convenient way providing such a strategy for a collection of operating conditions (OCs) and further ensures that the ODD allows for operation within the real world. A framework to categorise the OCs of a UC is presented and it is suggested that the ODD is written with this structure in mind to facilitate mapping towards potential UCs. The ODD defines the functional boundary of the system and modelling it with this structure makes it modular and generalisable across different potential UCs. Further, using the ODD to connect the ADS to the UC enables the continuous delivery of the ADS feature. Two examples of dimensions of the ODD are given and a strategy to avoid an ODD exit is proposed in the respective case.
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| 49. |
- Hansson, Göran, 1936-
(författare)
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Såld spannmål av kyrkotionden : Priser i Östergötland under Sveriges stormaktstid
- 2006
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The thesis presents annual price series for rye and barley in Östergötland during the period 1592-1735. Prices of wheat, oats, animal products, building materials, iron, nails, horse shoes and horse shoe nails from about the mid-17th century up to 1735 are also presented and analysed. New data has been excerpted from four hospitals and about fifty parishes in Östergötland. Prices from other provinces have also been excerpted for the study. This nes data is compared to already published prices from Sweden´s capital and from several provinces in central parts of the western national region of Sweden of that time. This area constituted Sweden´s core region. By linking the studies results to previous research, a description is made of the price developments for rye, butter and tallow up to 1775, that is, during Sweden´s period of great power and age of freedom. A principal result for the roughly 150 years primarily covered by the thesis is that it was chiefly the prices of rye and barley, the most important food at the time, that fluctuated in twelve cycles. Periodically there were large fluctuatons. The price cycles for corn (half rye, half barley) had an average amplitude of somewhat more than 100 % and a duration of 11 years on average. The prices were on average higher further north in the country. The causes of the price fluctuations are complex. During the major part of the period studied, Sweden was at war or in armistice period, which occupied a large part of the male population. Politically, increasingly great power was gradually concentrated to the king and autocracy was introduced, culminating at the end of Charles XII´s regency. The peasantry was burdened by high taxes and other onuses. After the middle of the 17th century the country was no longer self-subsistent but largely dependent on corn import. The production of foddstuffs decreased, partly through a smaller part of the country´s resources beeing used for production, and partly due to bad harvests. Recurrent epidemics reduced the population even up to the early 18th century.
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| 50. |
- Hellqvist, Eva, 1978-, et al.
(författare)
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Myelin protein zero is naturally processed in IgM MGUS B cells : Aberrant triggering of patient T cells
- 2010
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Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 95:4, s. 627-636
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Monoclonal gammopathy of undetermined significance (MGUS) of IgM isotype is a condition with clonally expanded B cells, recently suggested having an infectious origin. MGUS is frequently associated with polyneuropathy and antibodies against myelin protein zero (P0), whereas the role of the T cells remains largely unknown. Here we have analyzed P0-specific B cells, as antigen-presenting cells, and their capacity to activate T helper cells. Design and Methods: We used a well-characterized MGUS-derived B cell line, TJ2, expressing anti-P0 IgM. The ability of TJ2 cells to bind, endocytose, process, and present P0 was investigated by receptor-clustering and immunofluorescence. The activation of P0-specific autologous T cells was studied by measuring IL2 and IFNγ with flow cytometry, immunobeads, and ELISPOT. Results: Surface-receptor clustering and endocytosis of receptor-ligand (IgM/P0) complexes were pronounced after P0 exposure. Naturally processed or synthetic P0 peptide (194-208)-pulsed TJ2 cells significantly induced IL2 secretion from autologous T cells compared to control antigen pulsed cells (p<0 .001). The numbers of IFNγ producing T helper cells, including CD4+/CD8+ cells, were also significantly increased (p=0.0152). Affinity-isolated naturally processed myelin peptides were potent IFNγ stimulators for autologous PBMCs, but not for control PBMCs. Interpretation and conclusions: We show for the first time that myelin P0 is naturally processed in IgM MGUS B cells, acting as aberrant antigen-presenting cells in activation of patients T helper cells. Our findings cast new light on the important role of autoreactive P0-specific B cells in he induction of the pathogenic T cell responses found in nerve lesions of MGUS patients with peripheral neuropathy.
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