| 1. |
- 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. - : American Heart Association. - 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- Engström, Gunnar, et al.
(författare)
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The Swedish CArdioPulmonary BioImage Study : objectives and design
- 2015
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
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Tidskriftsartikel (refereegranskat)abstract
- Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.
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| 5. |
- Karady, Julia, et al.
(författare)
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Coronary plaque in people with HIV vs non-HIV asymptomatic community and symptomatic higher-risk populations
- 2024
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Ingår i: JACC: Advances. - : Elsevier. - 2772-963X. ; 3:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: People with HIV (PWH) have a high burden of coronary plaques; however, the comparison to people without known HIV (PwoH) needs clarification.Objectives: The purpose of this study was to determine coronary plaque burden/phenotype in PWH vs PwoH.Methods: Nonstatin using participants from 3 contemporary populations without known coronary plaques with coronary CT were compared: the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) studying PWH without cardiovascular symptoms at low-to-moderate risk (n = 755); the SCAPIS (Swedish Cardiopulmonary Bioimage Study) of asymptomatic community PwoH at low-to-intermediate cardiovascular risk (n = 23,558); and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) of stable chest pain PwoH (n = 2,291). The coronary plaque prevalence on coronary CT was compared, and comparisons were stratified by 10-year atherosclerotic cardiovascular disease (ASCVD) risk, age, and coronary artery calcium (CAC) presence.Results: Compared to SCAPIS and PROMISE PwoH, REPRIEVE PWH were younger (50.8 ± 5.8 vs 57.3 ± 4.3 and 60.0 ± 8.0 years; P < 0.001) and had lower ASCVD risk (5.0% ± 3.2% vs 6.0% ± 5.3% and 13.5% ± 11.0%; P < 0.001). More PWH had plaque compared to the asymptomatic cohort (48.5% vs 40.3%; P < 0.001). When stratified by ASCVD risk, PWH had more plaque compared to SCAPIS and a similar prevalence of plaque compared to PROMISE. CAC = 0 was more prevalent in PWH (REPRIEVE 65.2%; SCAPIS 61.6%; PROMISE 49.6%); among CAC = 0, plaque was more prevalent in PWH compared to the PwoH cohorts (REPRIEVE 20.8%; SCAPIS 5.4%; PROMISE 12.3%, P < 0.001).Conclusions: Asymptomatic PWH in REPRIEVE had more plaque than asymptomatic PwoH in SCAPIS but had similar prevalence to a higher-risk stable chest pain cohort in PROMISE. In PWH, CAC = 0 does not reliably exclude plaque.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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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. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.522.7) and 16.5 cm (13.319.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 12. |
- Bentham, James, et al.
(författare)
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A century of trends in adult human height
- 2016
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3– 19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8– 144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.
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| 13. |
- Bergström, Göran, 1964, et al.
(författare)
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Body weight at age 20 and in midlife is more important than weight gain for coronary atherosclerosis: Results from SCAPIS.
- 2023
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 373, s. 46-54
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Tidskriftsartikel (refereegranskat)abstract
- Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change.We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS).The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p<0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women.Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis.
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| 14. |
- Blomberg, Anders, et al.
(författare)
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Chronic Airflow Limitation, Emphysema and Impaired Diffusing Capacity in Relation to Smoking Habits in a Swedish Middle-Aged Population.
- 2024
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Ingår i: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621.
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE: Chronic obstructive pulmonary disease (COPD) includes respiratory symptoms and chronic airflow limitation (CAL). In some cases, emphysema and impaired diffusing capacity for carbon monoxide (DLCO) are present, but characteristics and symptoms vary with smoking exposure.OBJECTIVES: To study the prevalence of CAL, emphysema and impaired DLCO in relation to smoking and respiratory symptoms in a middle-aged population.METHODS: We investigated 28,746 randomly invited individuals (52% women) aged 50-64 years across six Swedish sites. We performed spirometry, DLCO, high-resolution computed tomography (HRCT) and asked for smoking habits and respiratory symptoms. CAL was defined as post-bronchodilator forced expiratory volume in 1 second divided by forced expiratory volume (FEV1/FVC)<0.7.RESULTS: The overall prevalence was for CAL 8.8%, for impaired DLCO (DLCOCONCLUSIONS: In this large population-based study of middle-aged people, CAL and impaired DLCO were associated with common respiratory symptoms. Self-reported asthma was not associated with CAL in never-smokers. Our findings suggest that CAL in never-smokers signifies a separate clinical phenotype that may be monitored and, possibly, treated differently from smoking-related COPD. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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| 15. |
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| 16. |
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| 17. |
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| 18. |
- 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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| 19. |
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| 20. |
- 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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| 21. |
- 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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| 22. |
- 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
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Ingår i: The EPMA journal. - : Springer Science and Business Media LLC. - 1878-5085 .- 1878-5077. ; 3:7
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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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| 23. |
- Dahl, Markus, et al.
(författare)
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Fine-Tuning of Smad Protein Function by Poly(ADP-Ribose) Polymerases and Poly(ADP-Ribose) Glycohydrolase during Transforming Growth Factor β Signaling
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e103651-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Initiation, amplitude, duration and termination of transforming growth factor β (TGFβ) signaling via Smad proteins is regulated by post-translational modifications, including phosphorylation, ubiquitination and acetylation. We previously reported that ADP-ribosylation of Smads by poly(ADP-ribose) polymerase 1 (PARP-1) negatively influences Smad-mediated transcription. PARP-1 is known to functionally interact with PARP-2 in the nucleus and the enzyme poly(ADP-ribose) glycohydrolase (PARG) can remove poly(ADP-ribose) chains from target proteins. Here we aimed at analyzing possible cooperation between PARP-1, PARP-2 and PARG in regulation of TGFβ signaling.METHODS:A robust cell model of TGFβ signaling, i.e. human HaCaT keratinocytes, was used. Endogenous Smad3 ADP-ribosylation and protein complexes between Smads and PARPs were studied using proximity ligation assays and co-immunoprecipitation assays, which were complemented by in vitro ADP-ribosylation assays using recombinant proteins. Real-time RT-PCR analysis of mRNA levels and promoter-reporter assays provided quantitative analysis of gene expression in response to TGFβ stimulation and after genetic perturbations of PARP-1/-2 and PARG based on RNA interference.RESULTS:TGFβ signaling rapidly induces nuclear ADP-ribosylation of Smad3 that coincides with a relative enhancement of nuclear complexes of Smads with PARP-1 and PARP-2. Inversely, PARG interacts with Smads and can de-ADP-ribosylate Smad3 in vitro. PARP-1 and PARP-2 also form complexes with each other, and Smads interact and activate auto-ADP-ribosylation of both PARP-1 and PARP-2. PARP-2, similar to PARP-1, negatively regulates specific TGFβ target genes (fibronectin, Smad7) and Smad transcriptional responses, and PARG positively regulates these genes. Accordingly, inhibition of TGFβ-mediated transcription caused by silencing endogenous PARG expression could be relieved after simultaneous depletion of PARP-1.CONCLUSION:Nuclear Smad function is negatively regulated by PARP-1 that is assisted by PARP-2 and positively regulated by PARG during the course of TGFβ signaling.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- 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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| 28. |
- Elmsjö, Albert, et al.
(författare)
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Postmortem Metabolomics Reveal Acylcarnitines as Potential Biomarkers for Fatal Oxycodone-Related Intoxication
- 2022
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Ingår i: Metabolites. - : MDPI. - 2218-1989. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Postmortem metabolomics has recently been suggested as a potential tool for discovering new biological markers able to assist in death investigations. Interpretation of oxycodone concentrations in postmortem cases is complicated, as oxycodone tolerance leads to overlapping concentrations for oxycodone intoxications versus non-intoxications. The primary aim of this study was to use postmortem metabolomics to identify potential endogenous biomarkers that discriminate between oxycodone-related intoxications and non-intoxications. Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry data from 934 postmortem femoral blood samples, including oxycodone intoxications and controls positive and negative for oxycodone, were used in this study. Data were processed and evaluated with XCMS and SIMCA. A clear trend in group separation was observed between intoxications and controls, with a model sensitivity and specificity of 80% and 76%. Approximately halved levels of short-, medium-, and long-chain acylcarnitines were observed for oxycodone intoxications in comparison with controls (p < 0.001). These biochemical changes seem to relate to the toxicological effects of oxycodone and potentially acylcarnitines constituting a biologically relevant biomarker for opioid poisonings. More studies are needed in order to elucidate the potential of acylcarnitines as biomarker for oxycodone toxicity and their relation to CNS-depressant effects.
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| 29. |
- 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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| 30. |
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| 31. |
- Johansson, Rolf, et al.
(författare)
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Functional Safety and Evolvable Architectures for Autonomy
- 2016
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Ingår i: Automated Driving. - Cham : Springer. - 9783319318936 ; , s. 547-560, s. 547-560
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The presented paper presents the ongoing Swedish national research project FUSE (FUnctional Safety and Evolvable architectures for autonomy). Some of the research questions addressed in this project are summarized. The research questions are related both to functional safety and the E/E architecture of vehicles aimed for higher degrees of automation, including fully autonomous ones.
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| 32. |
- Koos, Björn, et al.
(författare)
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Analysis of protein interactions in situ by proximity ligation assays
- 2014
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Ingår i: High-Dimensional Single Cell Analysis. - Berlin, Heidelberg : Springer. ; , s. 111-26
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Bokkapitel (refereegranskat)abstract
- The fate of the cell is governed by interactions among proteins, nucleic acids, and other biomolecules. It is vital to look at these interactions in a cellular environment if we want to increase our understanding of cellular processes. Herein we will describe how the in situ proximity ligation assay (in situ PLA) can be used to visualize protein interactions in fixed cells and tissues. In situ PLA is a novel technique that uses DNA, together with DNA modifying processes such as ligation, cleavage, and polymerization, as tools to create surrogate markers for protein interactions of interest. Different in situ PLA designs make it possible not only to detect protein-protein interactions but also post-translational modifications and interactions of proteins with nucleic acids. Flexibility in DNA probe design and the multitude of different DNA modifying enzymes provide the basis for modifications of the method to make it suitable to use in many applications. Furthermore, examples of how in situ PLA can be combined with other methods for a comprehensive view of the cellular activity status are discussed.
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| 33. |
- Koos, Björn, et al.
(författare)
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Proximity Depended Initiation of Hybridization Chain Reaction
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: Sensitive detection of protein interactions and post-translational modifications of native proteins is a challenge for research and diagnostic purposes. A method for this, which could be used in point of care devices should be cheap and robust.Results: Building on hybridization chain reaction, we designed a four hairpin system which is metastable in solution at 37°C for several hours and undergoes rapid signal amplification upon introduction of an initiator oligonucleotide. When the proximity hairpins are conjugated to antibodies these proximity probes in combination with the HCR hairpins and the initiator oligonucleotide provide a specific, enzyme free method to detect HIF-1α/HIF-1β and potentially other protein interactions and PTMs in situ. Furthermore it was possible to detect single proteins in the different compartments of the cell, further proving the specificity of this technique.Conclusion: In this study we present proximity dependent HCR, which is a cheap and robust method to detect protein interactions and post-translational modifications. Because of its independence from enzymes the technique has only low demands on storage and handling which makes it interesting for point of care devices.
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| 34. |
- Koos, Björn, et al.
(författare)
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Proximity-dependent initiation of hybridization chain reaction
- 2015
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
-
Tidskriftsartikel (refereegranskat)abstract
- Sensitive detection of protein interactions and post-translational modifications of native proteins is a challenge for research and diagnostic purposes. A method for this, which could be used in point-of-care devices and high-throughput screening, should be reliable, cost effective and robust. To achieve this, here we design a method (proxHCR) that combines the need for proximal binding with hybridization chain reaction (HCR) for signal amplification. When two oligonucleotide hairpins conjugated to antibodies bind in close proximity, they can be activated to reveal an initiator sequence. This starts a chain reaction of hybridization events between a pair of fluorophore-labelled oligonucleotide hairpins, generating a fluorescent product. In conclusion, we show the applicability of the proxHCR method for the detection of protein interactions and posttranslational modifications in microscopy and flow cytometry. As no enzymes are needed, proxHCR may be an inexpensive and robust alternative to proximity ligation assays.
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| 35. |
- Leuchowius, Karl-Johan, et al.
(författare)
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Parallel Visualization of Multiple Protein Complexes in Individual Cells in Tumor Tissue
- 2013
-
Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 12:6, s. 1563-1571
-
Tidskriftsartikel (refereegranskat)abstract
- Cellular functions are regulated and executed by complex protein interaction networks. Accordingly, it is essential to understand the interplay between proteins in determining the activity status of signaling cascades. New methods are therefore required to provide information on different protein interaction events at the single cell level in heterogeneous cell populations such as in tissue sections. Here, we describe a multiplex proximity ligation assay for simultaneous visualization of multiple protein complexes in situ. The assay is an enhancement of the original proximity ligation assay, and it is based on using proximity probes labeled with unique tag sequences that can be used to read out which probes, from a pool of probes, have bound a certain protein complex. Using this approach, it is possible to gain information on the constituents of different protein complexes, the subcellular location of the complexes, and how the balance between different complex constituents can change between normal and malignant cells, for example. As a proof of concept, we used the assay to simultaneously visualize multiple protein complexes involving EGFR, HER2, and HER3 homo- and heterodimers on a single-cell level in breast cancer tissue sections. The ability to study several protein complex formations concurrently at single cell resolution could be of great potential for a systems understanding, paving the way for improved disease diagnostics and possibilities for drug development.
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| 36. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten : 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
- 2022
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Ingår i: Aftonbladet. - : Aftonbladet. ; :2022-12-07
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Vi, 1 620 forskare samt lärare vid universitet och högskolor, är eniga med de unga bakom Auroramålet: De drabbas och riskerar att drabbas allvarligt av klimatkrisen under sin livstid. De klimatåtgärder vi vidtar i närtid avgör deras framtid. Sverige måste ta ansvar och göra sin rättvisa andel av det globala klimatarbetet. I strid med Parisavtalet ökar utsläppen av växthusgaser i en takt som gör att 1,5-gradersmålet kan överskridas om några år. De globala effekterna blir allt mer synliga med ständiga temperaturrekord, smältande isar, havshöjning och extremväder som torka, förödande bränder och skyfall med enorma översvämningar, som i Pakistan nyligen. Försörjningen av befolkningen utsätts för allvarliga hot i många länder.Minskningen av den biologiska mångfalden är extrem. Klimatkrisen är enligt WHO det största hotet mot människors hälsa i hela världen och barn utgör en särskilt sårbar grupp. Med Sveriges nordliga läge sker uppvärmningen här dubbelt så fort som det globala genomsnittet. Det förskjuter utbredningsområden för växtlighet och sjukdomsbärande insekter och ökar förekomsten av extremväder såsom värmeböljor, skogsbränder och översvämningar samt av många olika sorters infektioner och allergier. När extremväder ökar, ökar även stressen och risken för mental ohälsa. Värmeböljor ökar risken för sjukdom och död hos sårbara grupper som äldre, små barn och personer med kroniska sjukdomar. De negativa effekterna på hälsan kommer att öka i takt med klimatkrisen och barn riskerar att drabbas av ackumulerade negativa hälsoeffekter under hela sina liv. Redan i dag är mer än hälften av unga mellan 12 och 18 år i Sverige ganska eller mycket oroliga för klimat och miljö. Detta är förståeligt när våra beslutsfattare inte gör vad som krävs.Den juridiska och moraliska grunden för arbetet mot klimatförändringarna är att varje land måste göra sin rättvisa andel av det globala klimatarbetet. Centralt i det internationella klimatramverket är att rika länder med höga historiska utsläpp, däribland Sverige, måste gå före resten av världen. Dessa länder måste också bidra till att finansiera klimatomställningen i länderna i det Globala Syd, som är minst ansvariga för klimatkrisen men drabbas hårdast. Denna rättviseprincip är tydlig i Parisavtalet och var en het diskussionsfråga under COP27 i Sharm el-Sheikh, men lyser med sin frånvaro i det svenska klimatarbetet. Sverige har satt mål för att minska sina utsläpp. Men de är helt otillräckliga: minskningstakten är för låg och målen tillåter samtidigt att åtgärder skjuts på framtiden. Dessutom exkluderas merparten av Sveriges utsläpp från de svenska nationella utsläppsmålen; bland annat utelämnas utsläpp som svensk konsumtion orsakar utanför Sveriges gränser, utsläpp från utrikes transporter och utsläpp från markanvändning och skogsbruk, exempelvis utsläpp från förbränning av biobränslen eller utsläpp från dikade våtmarker (Prop. 2016/17:146 s.25-28).Sverige saknar dessutom ett eget mål för att öka upptaget av växthusgaser genom utökat skydd och restaurering av ekosystem, något som krävs för att begränsa de värsta konsekvenserna av klimatkrisen (IPCC s.32). Trots dessa låga ambitioner misslyckas Sverige med att nå sina utsläppsmål, konstaterar både Klimatpolitiska rådet och Naturvårdsverket. En klimatpolitik i linje med Parisavtalet kräver både att alla typer av växthusgasutsläpp minskar samtidigt som – inte i stället för – upptaget av växthusgaser maximeras: i dag misslyckas Sverige på bägge fronter.Slutsatsen är tydlig. Sverige vidtar inte de åtgärder som krävs för att skydda barns och ungdomars rättigheter enligt Europakonventionen till skydd för de mänskliga rättigheterna. Detta medför allvarliga risker för liv och hälsa för unga generationer, människor i andra länder och särskilt utsatta grupper. Detta kan inte fortsätta. Därför ställer vi oss bakom Auroras krav att Sverige börjar göra sin rättvisa andel och omedelbart sätter igång ett omfattande och långtgående klimatarbete som vilar på vetenskaplig grund och sätter rättvisa i centrum.
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| 37. |
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| 38. |
- Raja, Erna, et al.
(författare)
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The protein kinase LKB1 negatively regulates bone morphogenetic protein receptor signaling
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:2, s. 1120-1143
-
Tidskriftsartikel (refereegranskat)abstract
- The protein kinase LKB1 regulates cell metabolism and growth and is implicated in intestinal and lung cancer. Bone morphogenetic protein (BMP) signaling regulates cell differentiation during development and tissue homeostasis. We demonstrate that LKB1 physically interacts with BMP type I receptors and requires Smad7 to promote downregulation of the receptor. Accordingly, LKB1 suppresses BMP-induced osteoblast differentiation and affects BMP signaling in Drosophila wing longitudinal vein morphogenesis. LKB1 protein expression and Smad1 phosphorylation analysis in a cohort of non-small cell lung cancer patients demonstrated a negative correlation predominantly in a subset enriched in adenocarcinomas. Lung cancer patient data analysis indicated strong correlation between LKB1 loss-of-function mutations and high BMP2 expression, and these two events further correlated with expression of a gene subset functionally linked to apoptosis and migration. This new mechanism of BMP receptor regulation by LKB1 has ramifications in physiological organogenesis and disease.
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| 39. |
- Sadeghi Tabar, Roham, 1989, et al.
(författare)
-
Selective disassembly planning considering process capability and component quality utilizing reinforcement learning
- 2024
-
Ingår i: Procedia CIRP. - 2212-8271. ; 121, s. 1-6
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Konferensbidrag (refereegranskat)abstract
- Disassembly is a crucial process for achieving circular products, enabling function recovery, material reuse, and recycling. Disassembly planning is complex due to epistemic uncertainty associated with each unique product’s conditions, i.e., quality and aleatoric uncertainty about the capabilities of available resources and processes, and the cost benefits of associated operations impede planning. Therefore, the disassembly is intended to result in keeping the maximum value for the disassembled units of the product. In selective disassembly, the specification of the units of the product to be disassembled is acquired, leaving the rest of the product intact. The benefit of selective disassembly is to minimize waste during dismantling and maximize the reuse of the disassembled components for economic and ecological sustainability. The challenges in disassembly sequence planning include product complexity, operational and technological process capabilities, and the lack of information regarding the product architecture. For this complex planning task, limited studies have been performed on incorporating process capabilities with respect to the operations resources for selective disassembly planning. In this paper, an approach for optimal sequence planning of the selective disassembly process is put forward, taking into account multiple constraints, i.e., quality, time, and process capability. The intelligent planning approach takes advantage of a reinforcement learning model to handle the complexity of the planning problem. The approach has been implemented and tested on an industrial reference assembly. The result shows that the complex task of selective disassembly planning can be efficiently performed utilizing the proposed approach.
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| 40. |
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| 41. |
- Sundqvist, Anders, et al.
(författare)
-
Specific interactions between Smad proteins and AP-1 components determine TGFβ-induced breast cancer cell invasion
- 2013
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 32:31, s. 3606-3615
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Tidskriftsartikel (refereegranskat)abstract
- Deregulation of the transforming growth factor β (TGFβ) signal transduction cascade is functionally linked to cancer. In early phases, TGFβ acts as a tumor suppressor by inhibiting tumor cell proliferation, whereas in late phases, it can act as a tumor promoter by stimulating tumor cell invasion and metastasis. Smad transcriptional effectors mediate TGFβ responses, but relatively little is known about the Smad-containing complexes that are important for epithelial-mesenchymal transition and invasion. In this study, we have tested the hypothesis that specific members of the AP-1 transcription factor family determine TGFβ signaling specificity in breast cancer cell invasion. Using a 3D model of collagen-embedded spheroids of MCF10A-MII premalignant human breast cancer cells, we identified the AP-1 transcription factor components c-Jun, JunB, c-Fos and Fra1 as essential factors for TGFβ-induced invasion and found that various mesenchymal and invasion-associated TGFβ-induced genes are co-regulated by these proteins. In situ proximity ligation assays showed that TGFβ signaling not only induces complexes between Smad3 and Smad4 in the nucleus but also complexes between Smad2/3 and Fra1, whereas complexes between Smad3, c-Jun and JunB could already be detected before TGFβ stimulation. Finally, chromatin immunoprecipitations showed that c-Jun, JunB and Fra1, but not c-Fos, are required for TGFβ-induced binding of Smad2/3 to the mmp-10 and pai-1 promoters. Together these results suggest that in particular formation of Smad2/3-Fra1 complexes may reflect activation of the Smad/AP-1-dependent TGFβ-induced invasion program.
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| 42. |
- Sundström, Johan, Professor, 1971-, et al.
(författare)
-
Weight gain and blood pressure
- 2020
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 38:3, s. 387-394
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Although the causality of the obesity—hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure.METHODS: We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol.RESULTS: On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years.CONCLUSION: In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.
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| 43. |
- Swahn, Eva, et al.
(författare)
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Sex differences in prevalence and characteristics of imaging detected atherosclerosis - a population-based study.
- 2024
-
Ingår i: European heart journal. Cardiovascular Imaging. - 2047-2412.
-
Tidskriftsartikel (refereegranskat)abstract
- Men are more likely to suffer a myocardial infarction than women, but population-based studies on sex differences in imaging detected atherosclerosis are lacking. The aims were to assess sex differences in prevalence of imaging detected coronary and carotid atherosclerosis, as well as multivariable adjusted associations between sex and atherosclerosis.Participants aged 50-65, recruited from the general population to the Swedish Cardiopulmonary bioImage Study (SCAPIS), were included in this population-based cross-sectional study. Comprehensive diagnostics, including coronary computed tomography angiography and carotid ultrasound, were performed. The image findings were any coronary atherosclerosis, coronary stenosis ≥50%, segment involvement score (SIS) ≥4, coronary artery calcium score (CACS) ≥100, and any ultrasound-detected carotid plaque.In 25,580 participants (50% women), men had more hypertension (20.3% vs 17.0%), hyperlipidaemia (9.0% vs 5.5%), and diabetes (8.5% vs 4.7%). The prevalence was 56.2% vs 29.5% for any coronary atherosclerosis (p<0.01), 9.0% vs 2.3% for coronary stenosis ≥50% (p<0.01), 20.2% vs 5.3% for SIS≥4 (p<0.01), 18.2% vs 5.6% for CACS≥100 (p<0.01), and 60.9% vs 48.7% for carotid plaque (p<0.01), in men vs women, respectively. Multivariable adjustment only marginally changed these associations: odds ratios [OR] (95% confidence interval [CI]): 2.75 (2.53-2.99) for coronary atherosclerosis, 2.88 (2.40-3.45) for coronary stenosis ≥50%, 3.99 (3.50-4.55) for SIS≥4, 3.29 (2.88-3.75), for CACS≥100, and 1.57 (1.45-1.70) for carotid plaque.Men had higher prevalence of imaging detected carotid and coronary atherosclerosis with prevalence in women aged 65 corresponding to men 10-14 years younger. The associations remained after extensive multivariable adjustment.
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| 44. |
- Söderberg, Carl, et al.
(författare)
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Antipsychotics - Postmortem fatal and non-fatal reference concentrations
- 2016
-
Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 266, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Making the diagnosis fatal intoxication is a challenging task for the forensic pathologist and toxicologist, particularly when the cases involve substances where reference information is scarce or not at all available. This study presents postmortem femoral blood concentrations for 24 antipsychotic substances, based on samples collected and analyzed from 4949 autopsy cases in Sweden during 1992-2010. In addition our study provides information about the prevalence of different antipsychotics in accidental, suicidal, homicidal and uncertain deaths.The data have been selected and evaluated according to strict inclusion and exclusion criteria as well as a manual, multi-reviewer, case-by-case evaluation. The reference information is subdivided into intoxications by one specific substance only (group A, n = 259), multi-substance intoxications (group B, n = 614) and postmortem controls, consisting of deaths not involving incapacitation by substances (group C, n = 507). Moreover, the results are compared with data based on therapeutic drug monitoring, and data collected from driving under the influence cases.Median concentrations in group A were significantly higher than in group C for all substances evaluated. For 17 of 24 substances, the median concentrations in group B were significantly higher than in group C. In general, the therapeutic drug monitoring and driving under the influence concentrations were similar to, or lower than, the concentrations in group C.
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| 45. |
- Söderberg, Carl
(författare)
-
Evaluation of postmortem toxicological results
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Postmortem diagnosis of fatal intoxications is complicated. Autopsy findings indicative of an intoxication related death are scarce and mostly unspecific. Instead, the diagnosis is more dependent on the circumstances surrounding death, and on the toxicological results. In order to correctly evaluate the toxicological results, the forensic investigator needs to know the concentrations of various substances that can be considered “normal” and which concentrations that may be “lethal”. While a wealth of scientific data exist concerning concentrations and effects in experimental animals and in living human subjects, these data cannot simply be translated into postmortem concentrations. Due to various changes occurring already in the early phase after death, the blood postmortem concentration of a substance postmortem often does not mirror the concentration antemortem. In order to correctly evaluate postmortem toxicological results there is a need for postmortem reference values, allowing for the separation between the lethal and non-lethal concentrations. Toxicological data based on the analysis of whole blood from the femoral vein collected at autopsies conducted between 1992 and 2010 were used to establish multiple categories of reference concentrations; Group A (intoxications with a single substance only), Group B (mixed intoxications) and Group C (controls). A well-defined automated selection process followed by a standardized multi-reviewer process and a case-by-case evaluation were applied to generate reference values for each group. Paper I-IV present postmortem reference concentrations of 48 substances. In most cases there are separate reference concentrations for different types of intoxications (group A and group B) as well as controls (group C). In general, there is a substantial overlap in concentrations between the two intoxication groups, whereas the controls often show much lower levels. In addition to the establishment of postmortem reference concentrations the different studies included in this thesis provide some additional information. Paper I presents a fatal toxicity index of sedative and hypnotic drugs; Paper II presents the occurrence of antipsychotics among different manners of death; and in Paper III an attempt is made to assess differences in concentrations between acute, acute-on-chronic and chronic intoxications. Further, Paper IV presents the impact of sample size on the precision, power and risk for type 1 error of postmortem reference concentrations. Using the method presented in paper I-IV, >5 cases in each group are needed to reduce the risk of type 1 error (<5%) and >10 cases in each group is needed to have a high power (>0.95). It is suggested that a target number of between 20-30 cases in each group provides a reasonable stability of the reference concentration.
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| 46. |
- Söderberg, Carl, et al.
(författare)
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Postmortem reference concentrations of 68 elements in blood and urine
- 2023
-
Ingår i: International journal of legal medicine. - : Springer Science and Business Media Deutschland GmbH. - 0937-9827 .- 1437-1596. ; 137, s. 655-669
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fatal intoxications, both accidental and intentional, are a global issue. In the Western world, intoxications with pharmaceuticals dominate, but in other parts of the world, other substances are more common. In a forensic setting, elemental intoxications are of great importance when investigating both accidental, suicidal, and homicidal deaths. The current study presents normal postmortem reference concentrations of 68 elements in femoral blood and urine. In addition, possible sources of error such as contamination from sample tubes, preservative potassium fluoride (KF) solution, and storage time are evaluated.Methods: Paired femoral blood and urine samples from 120 cases of death by suicidal hanging in Sweden were collected. Additionally, multiple batches of sample tubes and multiple batches of KF solution were also analyzed. Concentrations of elements were determined by double focusing sector field ICP-MS.Results: Key descriptive statistics for 68 elements are provided in blood and urine. Contamination from sample tubes was minor compared to the overall mean elemental concentrations in both blood and urine. KF solution contained a large assortment of elements, but the overall contribution is relatively minor for most elements given the small amounts of solution added to samples. There were significant differences for 22 elements in blood and 17 elements in urine between samples with short and long storage time.Conclusion: The present study provides an important tool when evaluating postmortem elemental concentrations. It fills a needed gap between large antemortem population studies and postmortem case reports or small case series of elemental intoxications.
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| 47. |
- Söderberg, Emma, et al.
(författare)
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Association of clinicopathologic variables and patient preference with the choice of surgical treatment for early-stage breast cancer : A registry-based study
- 2024
-
Ingår i: Breast. - : Elsevier. - 0960-9776 .- 1532-3080. ; 73
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Observational studies suggest that breast conserving surgery (BCS) and radiotherapy (RT) offers superior survival compared to mastectomy. The aim was to compare patient and tumour characteristics in women with invasive breast cancer <= 30 mm treated with either BCS or mastectomy, and to explore the underlying reason for choosing mastectomy.Methods: Women registered with breast cancer <= 30 mm and <= 4 positive axillary lymph nodes in the Swedish National Breast Cancer Register 2013-2016 were included. Logistic regression analyses were performed to assess the association of tumour and patient characteristics with receiving a mastectomy vs. BCS.Results: Of 1860 breast cancers in 1825 women, 1346 were treated by BCS and 514 by mastectomy. Adjuvant RT was given to 1309 women (97.1 %) after BCS and 146 (27.6 %) after mastectomy. Variables associated with receiving a mastectomy vs. BCS included clinical detection (Odds Ratio (OR) 4.15 (95 % Confidence Interval (CI) 3.35-5.14)) and clinical stage (T2 vs. T1 (OR 3.68 (95 % CI 2.90-4.68)), N1 vs. N0 (OR 2.02 (95 % CI 1.38-2.96)). Women receiving mastectomy more often had oestrogen receptor negative, HER2 positive tumours of higher histological grade. The most common reported reason for mastectomy was large or multifocal tumours (53.5 %), followed by patient preference (34.5 %).Conclusion: Choice of surgery is strongly associated with key prognostic factors among women undergoing BCS with RT compared to mastectomy. Failure to control for all relevant confounders may bias results in outcome studies in favour of BCS.
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| 48. |
- Söderberg, Elisabeth, et al.
(författare)
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Subjective well-being in patients with chronic tension-type headache: effect of acupuncture, physical training, and relaxation training.
- 2011
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Ingår i: The Clinical journal of pain. - 1536-5409. ; 27:5, s. 448-56
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Forskningsöversikt (refereegranskat)abstract
- Episodic tension-type headache is a common problem affecting approximately 2 of 3 of the population. The origin of tension-type headache is multifactorial, but the pathogenesis is still unclear. In some individuals episodic tension-type headache transforms into chronic tension-type headache (CTTH). Subjective symptoms related to the central nervous system might affect patients subjective well-being and quality of life.
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| 49. |
- Söderberg, Lina, et al.
(författare)
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Transformation. En del av en skulpturstig i Österbybruk : Modell av en pendel
- 2019
-
Ingår i: Som en utställning I galleri Sadelmakarlängan I Österbybruk, Uppland. Detta drivs av Katarina Persson som också är projektledare..
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Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
- Katarina Persson har initierat projektet med konstnärsgruppen Transformation som hon tidigare har samarbetat och gjort utställningar med. Jag, Lina Söderberg är medlem i Transformation, och deltagare i detta projekt. Projektet startade i somras med att gruppen träffades i Österbybruk och hade studiebesök och föreläsningar på orten i en vecka. Detta utmynnade i en skissutställning under hösten.
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| 50. |
- Söderberg, Per G, et al.
(författare)
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Evaluation of response variables in computer simulated virtual reality cataract surgery
- 2006
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Ingår i: Proceedings of SPIE, the International Society for Optical Engineering. - San José, CA : SPIE. - 0277-786X .- 1996-756X. ; 6138, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- We have developed a virtual reality (VR) simulator for phacoemulsification (phaco) surgery. The current work aimed atevaluating the precision in the estimation of response variables identified for measurement of the performance of VRphaco surgery. We identified 31 response variables measuring; the overall procedure, the foot pedal technique, thephacoemulsification technique, erroneous manipulation, and damage to ocular structures. Totally, 8 medical oroptometry students with a good knowledge of ocular anatomy and physiology but naive to cataract surgery performedthree sessions each of VR Phaco surgery. For measurement, the surgical procedure was divided into a sculpting phaseand an evacuation phase. The 31 response variables were measured for each phase in all three sessions. The variancecomponents for individuals and iterations of sessions within individuals were estimated with an analysis of varianceassuming a hierarchal model. The consequences of estimated variabilities for sample size requirements weredetermined. It was found that generally there was more variability for iterated sessions within individuals formeasurements of the sculpting phase than for measurements of the evacuation phase. This resulted in larger requiredsample sizes for detection of difference between independent groups or change within group, for the sculpting phase ascompared to for the evacuation phase. It is concluded that several of the identified response variables can be measuredwith sufficient precision for evaluation of VR phaco surgery.
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