| 1. |
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| 2. |
- Uhlén, Mathias, et al.
(författare)
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A human protein atlas for normal and cancer tissues based on antibody proteomics
- 2005
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Ingår i: Molecular & Cellular Proteomics. - 1535-9476 .- 1535-9484. ; 4:12, s. 1920-1932
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Tidskriftsartikel (refereegranskat)abstract
- Antibody-based proteomics provides a powerful approach for the functional study of the human proteome involving the systematic generation of protein-specific affinity reagents. We used this strategy to construct a comprehensive, antibody-based protein atlas for expression and localization profiles in 48 normal human tissues and 20 different cancers. Here we report a new publicly available database containing, in the first version, similar to 400,000 high resolution images corresponding to more than 700 antibodies toward human proteins. Each image has been annotated by a certified pathologist to provide a knowledge base for functional studies and to allow queries about protein profiles in normal and disease tissues. Our results suggest it should be possible to extend this analysis to the majority of all human proteins thus providing a valuable tool for medical and biological research.
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| 3. |
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| 4. |
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| 5. |
- Berglund, Emelie, et al.
(författare)
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Automation of Spatial Transcriptomics library preparation to enable rapid and robust insights into spatial organization of tissues
- 2020
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Ingår i: BMC Genomics. - : Springer Nature. - 1471-2164. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Interest in studying the spatial distribution of gene expression in tissues is rapidly increasing. Spatial Transcriptomics is a novel sequencing-based technology that generates high-throughput information on the distribution, heterogeneity and co-expression of cells in tissues. Unfortunately, manual preparation of high-quality sequencing libraries is time-consuming and subject to technical variability due to human error during manual pipetting, which results in sample swapping and the accidental introduction of batch effects. All these factors complicate the production and interpretation of biological datasets.Results: We have integrated an Agilent Bravo Automated Liquid Handling Platform into the Spatial Transcriptomics workflow. Compared to the previously reported Magnatrix 8000+ automated protocol, this approach increases the number of samples processed per run, reduces sample preparation time by 35%, and minimizes batch effects between samples. The new approach is also shown to be highly accurate and almost completely free from technical variability between prepared samples.Conclusions: The new automated Spatial Transcriptomics protocol using the Agilent Bravo Automated Liquid Handling Platform rapidly generates high-quality Spatial Transcriptomics libraries. Given the wide use of the Agilent Bravo Automated Liquid Handling Platform in research laboratories and facilities, this will allow many researchers to quickly create robust Spatial Transcriptomics libraries.
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| 6. |
- Berglund, Emelie
(författare)
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Molecular and Spatial Profiling of Prostate Tumors
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Every cancer tumor is unique, with characteristics that change over time. The evolution of a full-blown malignancy from a single cell that gives rise to a heterogeneous population of cancer cells is a complex process. The use of spatial information makes a big contribution to understanding the progression of tumors and how patients respond to treatment. Currently, the scientific community is taking a step further in order to understand gene expression heterogeneity in the context of tissue spatial organization to shed light on cell- to-cell interactions. Technological advances in recent years have increased the resolution at which heterogeneity can be observed. Spatial transcriptomics (ST) is an in situ capturing technique that uses a glass slide containing oligonucleotides to capture mRNAs while maintaining the spatial information of histological tissue sections. It combines histology and Illumina sequencing to detect and visualize the whole transcriptome information of tissue sections. In Paper I, an AI method was developed to create a computerized tissue anatomy. The rich source of information enables the AI method to identify genetic patterns that cannot be seen by the naked eye. This study also provided insights into gene expression in the environment surrounding the tumor, the tumor microenvironment, which interacts with tumor cells for cancer growth and progression. In Paper II, we investigate the cellular response of treatment. It is well known that virtually all patients with hormone naïve prostate cancer treated with GnRH agonists will relapse over time and that the cancer will transform into a castration-resistant form denoted castration-resistant prostate cancer. This study shows that by characterizing the non-responding cell populations, it may be possible to find an alternative way to target them in the early stages and thereby decrease the risk of relapse. In Paper III, we deal with scalability limitations, which in the ST method are represented by time- consuming workflow in the library preparation. This study introduces an automated library preparation protocol on the Agilent Bravo Automated Liquid Handling Platform to enable rapid and robust preparation of ST libraries. Finally, Paper IV expands on the first work and illustrates the utility of the ST technology by constructing, for the first time, a molecular view of a cross-section of a prostate organ.
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| 7. |
- Berglund, Emelie, et al.
(författare)
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Spatial maps of prostate cancer transcriptomes reveal an unexplored landscape of heterogeneity
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Intra-tumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.
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| 8. |
- Berglund, Fanny, et al.
(författare)
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An updated phylogeny of the metallo-β-lactamases.
- 2021
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Ingår i: The Journal of antimicrobial chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 76:1, s. 117-123
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Tidskriftsartikel (refereegranskat)abstract
- Metallo-β-lactamases (MBLs) are enzymes that use zinc-dependent hydrolysis to confer resistance to almost all available β-lactam antibiotics. They are hypothesized to originate from commensal and environmental bacteria, from where some have mobilized and transferred horizontally to pathogens. The current phylogeny of MBLs, however, is biased as it is founded largely on genes encountered in pathogenic bacteria. This incompleteness is emphasized by recent findings of environmental MBLs with new forms of zinc binding sites and atypical functional profiles.To expand the phylogeny of MBLs to provide a more accurate view of their evolutionary history.We searched more than 16 terabases of genomic and metagenomic data for MBLs of the three subclasses B1, B2 and B3 using the validated fARGene method. Predicted genes, together with the previously known ones, were used to infer phylogenetic trees.We identified 2290 unique MBL genes forming 817 gene families, of which 741 were previously uncharacterized. MBLs from subclasses B1 and B3 separated into distinct monophyletic groups, in agreement with their taxonomic and functional properties. We present evidence that clinically associated MBLs were mobilized from Proteobacteria. Additionally, we identified three new variants of the zinc binding sites, indicating that the functional repertoire is broader than previously reported.Based on our results, we recommend that the nomenclature of MBLs is refined into the phylogenetic groups B1.1-B1.5 and B3.1-B3.4 that more accurately describe their molecular and functional characteristics. Our results will also facilitate the annotation of novel MBLs, reflecting their taxonomic organization and evolutionary origin.
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| 9. |
- Berglund, Fanny, et al.
(författare)
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Comprehensive screening of genomic and metagenomic data reveals a large diversity of tetracycline resistance genes
- 2020
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Ingår i: Microbial genomics. - : Microbiology Society. - 2057-5858. ; 6:11
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Tidskriftsartikel (refereegranskat)abstract
- Tetracyclines are broad-spectrum antibiotics used to prevent or treat a variety of bacterial infections. Resistance is often mediated through mobile resistance genes, which encode one of the three main mechanisms: active efflux, ribosomal target protection or enzymatic degradation. In the last few decades, a large number of new tetracycline-resistance genes have been discovered in clinical settings. These genes are hypothesized to originate from environmental and commensal bacteria, but the diversity of tetracycline-resistance determinants that have not yet been mobilized into pathogens is unknown. In this study, we aimed to characterize the potential tetracycline resistome by screening genomic and metagenomic data for novel resistance genes. By using probabilistic models, we predicted 1254 unique putative tetracycline resistance genes, representing 195 gene families (<70% amino acid sequence identity), whereof 164 families had not been described previously. Out of 17 predicted genes selected for experimental verification, 7 induced a resistance phenotype in an Escherichia coli host. Several of the predicted genes were located on mobile genetic elements or in regions that indicated mobility, suggesting that they easily can be shared between bacteria. Furthermore, phylogenetic analysis indicated several events of horizontal gene transfer between bacterial phyla. Our results also suggested that acquired efflux pumps originate from proteobacterial species, while ribosomal protection genes have been mobilized from Firmicutes and Actinobacteria. This study significantly expands the knowledge of known and putatively novel tetracycline resistance genes, their mobility and evolutionary history. The study also provides insights into the unknown resistome and genes that may be encountered in clinical settings in the future.
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| 10. |
- Berglund, Fanny, et al.
(författare)
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Evidence for wastewaters as environments where mobile antibiotic resistance genes emerge
- 2023
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The emergence and spread of mobile antibiotic resistance genes (ARGs) in pathogens have become a serious threat to global health. Still little is known about where ARGs gain mobility in the first place. Here, we aimed to collect evidence indicating where suchinitial mobilizationevents of clinically relevant ARGs may have occurred. We found that the majority of previously identified origin species did not carry the mobilizing elements that likely enabled intracellular mobility of the ARGs, suggesting a necessary interplay between different bacteria. Analyses of a broad range of metagenomes revealed that wastewaters and wastewater-impacted environments had by far the highest abundance of both origin species and corresponding mobilizing elements. Most origin species were only occasionally detected in other environments. Co-occurrence of origin species and corresponding mobilizing elements were rare in human microbiota. Our results identify wastewaters and wastewater-impacted environments as plausible arenas for the initial mobilization of resistance genes.
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| 11. |
- Berglund, Fanny, 1988, et al.
(författare)
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Identification and reconstruction of novel antibiotic resistance genes from metagenomes
- 2019
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundEnvironmental and commensal bacteria maintain a diverse and largely unknown collection of antibiotic resistance genes (ARGs) that, over time, may be mobilized and transferred to pathogens. Metagenomics enables cultivation-independent characterization of bacterial communities but the resulting data is noisy and highly fragmented, severely hampering the identification of previously undescribed ARGs. We have therefore developed fARGene, a method for identification and reconstruction of ARGs directly from shotgun metagenomic data.ResultsfARGene uses optimized gene models and can therefore with high accuracy identify previously uncharacterized resistance genes, even if their sequence similarity to known ARGs is low. By performing the analysis directly on the metagenomic fragments, fARGene also circumvents the need for a high-quality assembly. To demonstrate the applicability of fARGene, we reconstructed -lactamases from five billion metagenomic reads, resulting in 221 ARGs, of which 58 were previously not reported. Based on 38 ARGs reconstructed by fARGene, experimental verification showed that 81% provided a resistance phenotype in Escherichia coli. Compared to other methods for detecting ARGs in metagenomic data, fARGene has superior sensitivity and the ability to reconstruct previously unknown genes directly from the sequence reads.ConclusionsWe conclude that fARGene provides an efficient and reliable way to explore the unknown resistome in bacterial communities. The method is applicable to any type of ARGs and is freely available via GitHub under the MIT license.
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| 12. |
- Berglund, Fanny, 1988, et al.
(författare)
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Identification of 76 novel B1 metallo-beta-lactamases through large-scale screening of genomic and metagenomic data
- 2017
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 5:1, s. 134-134
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metallo-beta-lactamases are bacterial enzymes that provide resistance to carbapenems, the most potent class of antibiotics. These enzymes are commonly encoded on mobile genetic elements, which, together with their broad substrate spectrum and lack of clinically useful inhibitors, make them a particularly problematic class of antibiotic resistance determinants. We hypothesized that there is a large and unexplored reservoir of unknown metallo-beta-lactamases, some of which may spread to pathogens, thereby threatening public health. The aim of this study was to identify novel metallo-beta-lactamases of class B1, the most clinically important subclass of these enzymes. Results: Based on a new computational method using an optimized hidden Markov model, we analyzed over 10,000 bacterial genomes and plasmids together with more than 5 terabases of metagenomic data to identify novel metallo-beta-lactamase genes. In total, 76 novel genes were predicted, forming 59 previously undescribed metallo-beta-lactamase gene families. The ability to hydrolyze imipenem in an Escherichia coli host was experimentally confirmed for 18 of the 21 tested genes. Two of the novel B1 metallo-beta-lactamase genes contained atypical zinc-binding motifs in their active sites, which were previously undescribed for metallo-beta-lactamases. Phylogenetic analysis showed that B1 metallo-beta-lactamases could be divided into five major groups based on their evolutionary origin. Our results also show that, except for one, all of the previously characterized mobile B1 beta-lactamases are likely to have originated from chromosomal genes present in Shewanella spp. and other Proteobacterial species. Conclusions: This study more than doubles the number of known B1 metallo-beta-lactamases. The findings have further elucidated the diversity and evolutionary history of this important class of antibiotic resistance genes and prepare us for some of the challenges that may be faced in clinics in the future.
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| 13. |
- Berglund, Fanny, et al.
(författare)
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The resistome and microbiome of wastewater treatment plant workers - The AWARE study.
- 2023
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Ingår i: Environment international. - 0160-4120 .- 1873-6750. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Urban wastewater treatment plants harbor a large collection of antibiotic resistant enteric bacteria. It is therefore reasonable to hypothesize that workers at such plants would possess a more diverse set of resistant enteric bacteria, compared to the general population. To address this hypothesis, we have compared the fecal microbiome and resistome of 87 workers at wastewater treatment plants (WWTPs) from Romania and the Netherlands to those of 87 control individuals, using shotgun metagenomics. Controlling for potential confounders, neither the total antibiotic resistance gene (ARG) abundance, nor the overall bacterial composition were significantly different between the two groups. If anything, the ARG richness was slightly lower in WWTP workers, and in a stratified analysis the total ARG abundance was significantly lower in Dutch workers compared to Dutch control participants. We identified country of residence, together with recent antibiotic intake in the Dutch population, as the largest contributing factors to the total abundance of ARGs. A striking side-finding was that sex was associated with carriage of disinfectant resistance genes, with women in both Romania and the Netherlands having significantly higher abundance compared to men. A follow up investigation including an additional 313 publicly available samples from healthy individuals from three additional countries showed that the difference was significant for three genes conferring resistance to chemicals commonly used in cosmetics and cleaning products. We therefore hypothesize that the use of cosmetics and, possibly, cleaning products leads to higher abundance of disinfectant resistance genes in the microbiome of the users. Altogether, this study shows that working at a WWTP does not lead to a higher abundance or diversity of ARGs and no large shifts in the overall gut microbial composition in comparison to participants not working at a WWTP. Instead, other factors such as country of residence, recent antibiotic intake and sex seem to play a larger role.
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| 14. |
- Berglund, Henrik, 1973, et al.
(författare)
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CBIs studie om innovationsledning
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- CBI har under andra halvåret 2010 och första halvåret 2011 genomfört en studie av innovationsledning hos 38 utvalda svenska företag inom tillverkning, IT och Telekom. Syftet var att undersöka hur företagen leder och organiserar innovation samt vilka utmaningar de står inför. Frågorna har besvarats av antingen VD eller en medlem i ledningsgruppen med insyn i företagets hantering av innovation.Resultatet visar att -de flesta företagen inte skiljer på radikal och inkrementell innovation-i många företag används ordet innovation för all produkt- och tjänsteutveckling-de flesta företag ser en ökning av innovationstakten inom sin respektive bransch-de flesta företag uttrycker att innovation är viktigt, samtidigt som få företag har innovationsfrågor bland sina tre största utmaningar-hälften av företagen använder någon form av rutin för att stärka sin förmåga att skapa nya produkter och tjänster, men endast ett fåtal använder flera olika rutiner-förstainnovationsföretagen (mindre, relativt nystartade företag) skiljer sig från de övriga i det att de är starkt innovationscentrerade-många företag välkomnar stöd från akademin, men endast ett fåtal önskar stöd att öka sin innovationsförmågaCBIs samtliga seniora forskare har genomfört intervjuerna.
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| 15. |
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| 16. |
- Berglund, Leo, 1986-
(författare)
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Kritiskt tänkande som utbildningsmål : Från modernistisk filosofi till policy för högre utbildning
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The goal of critical thinking in higher education is paradoxical, since it implies a form of education that both directs the student towards a pre-defined goal, and commands the student to be autonomous. This paradox is studied in four contexts, as to investigate what pedagogical contradictions the goal of critical thinking generates, and how they transform pedagogical thinking. 1) In the 1930s, European logical positivists cooperated with American pragmatists to "unify science". For Dewey, the realisation of this ideal depended on individuals adopting a "scientific attitude", which could be cultivated in schools and universities. Dewey’s position influenced a pedagogical discourse of critical thinking as the spirit of rational and democratic citizenship. 2) In the 1980s, the Critical Thinking Movement (CTM) addressed the issue on how to make logical thinking applicable in everyday life. Understanding critical thinking as individuals’ problem-solving skills, the CTM essentially inverted the collectivist political orientation of Dewey and the neo-positivists. 3) In the Swedish 1968 governmental investigation of higher education (U 68), a sociologically informed conception of critical thinking, that involved the student in the project of social planning, was promoted. However, educational experts perceived critical thinking as a vague goal, which could not be operationalised. In the 1990s, critical thinking reappeared as part of the doctrine of learning, but only as a generic term used to signify advanced cognitive operations in relation to different subject matters. 4) In contemporary courses in critical thinking held at Swedish universities, radically diverse conceptions are being taught. An analysis of three courses identified three subjectivities "called" by the arrangements and bodies of literature in the courses: the critical thinker as reason, intellect, and moral consciousness. Each of the subjectivities, however, comprises inconsistencies and contradictions, since they are all to be both produced by and autonomous from the orders that the educational institution represents. The dissertation is concluded by a discussion on critical thinking as both a goal and a by-product of education.
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| 17. |
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| 18. |
- Berglund, Sten, et al.
(författare)
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Cleavages and Political Transformations
- 2010
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Ingår i: Handbook of European Societies. - Berlin : Springer. - 9780387881980 ; , s. 91-109
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 19. |
- Berglund, Sten, 1947-, et al.
(författare)
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Cleavages and political transformations
- 2010
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Ingår i: Handbook of European societies. - Berlin : Springer. - 9780387881980 ; , s. 91-109
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 20. |
- Berglund, Sten, 1947-, et al.
(författare)
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Concluding remarks
- 2013. - 3
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Ingår i: The handbook of political change in Eastern Europe. - Cheltenham, UK : Edward Elgar Publishing. - 978 0 85793 537 3 - 978 1 78254 588 0 - 0857935372 ; , s. 823-830, s. 239-248
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Bokkapitel (refereegranskat)
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| 21. |
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| 22. |
- Berglund, Sten, 1947-, et al.
(författare)
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The challenge of history in Central and Eastern Europe
- 2004. - 2
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Ingår i: The handbook of political change in Eastern Europe. - Cheltenham : Edward Elgar. - 1840648546 ; , s. 13-56
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 23. |
- Berglund, Sten, 1947-, et al.
(författare)
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The current state of political science in Sweden
- 2007
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Ingår i: The state of political science in Western Europe. - Opladen : Barbara Budrich. - 9783866490451 ; , s. 342-360
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 24. |
- Berglund, Sten, 1947-, et al.
(författare)
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The diversity of political regimes
- 2013. - 3
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Ingår i: The handbook of political change in Eastern Europe. - Cheltenham, UK : Edward Elgar Publishing. - 9780857935373 - 9781782545880 - 0857935372 ; , s. 1-13
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Bokkapitel (refereegranskat)
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| 25. |
- Berglund, Sten, 1947-, et al.
(författare)
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The diversity of post-communist Europe
- 2004. - 2
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Ingår i: The handbook of political change in Eastern Europe. - Cheltenham : Edward Elgar. - 1840648546 ; , s. 1-12
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 26. |
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| 27. |
- Berglund, Sten, 1947-, et al.
(författare)
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The resilience of history
- 2013. - 3
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Ingår i: The handbook of political change in Eastern Europe. - Cheltenham, UK : Edward Elgar Publishing. - 978 0 85793 537 3 - 978 1 78254 588 0 - 0857935372 ; , s. 15-34
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Bokkapitel (refereegranskat)
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| 28. |
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| 29. |
- 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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| 30. |
- Bergström, Göran, et al.
(författare)
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Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
- 2021
-
Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
-
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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| 31. |
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| 32. |
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| 33. |
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| 34. |
- Boulund, Fredrik, 1985, et al.
(författare)
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Computational discovery and functional validation of novel fluoroquinolone resistance genes in public metagenomic data sets
- 2017
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 18:1, s. Art 682-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Fluoroquinolones are broad-spectrum antibiotics used to prevent and treat a wide range of bacterial infections. Plasmid-mediated qnr genes provide resistance to fluoroquinolones in many bacterial species and are increasingly encountered in clinical settings. Over the last decade, several families of qnr genes have been discovered and characterized, but their true prevalence and diversity still remain unclear. In particular, environmental and host-associated bacterial communities have been hypothesized to maintain a large and unknown collection of qnr genes that could be mobilized into pathogens. Results: In this study we used computational methods to screen genomes and metagenomes for novel qnr genes. In contrast to previous studies, we analyzed an almost 20-fold larger dataset comprising almost 13 terabases of sequence data. In total, 362,843 potential qnr gene fragments were identified, from which 611 putative qnr genes were reconstructed. These gene sequences included all previously described plasmid-mediated qnr gene families. Fifty-two of the 611 identified qnr genes were reconstructed from metagenomes, and 20 of these were previously undescribed. All of the novel qnr genes were assembled from metagenomes associated with aquatic environments. Nine of the novel genes were selected for validation, and six of the tested genes conferred consistently decreased susceptibility to ciprofloxacin when expressed in Escherichia coli. Conclusions: The results presented in this study provide additional evidence for the ubiquitous presence of qnr genes in environmental microbial communities, expand the number of known qnr gene variants and further elucidate the diversity of this class of resistance genes. This study also strengthens the hypothesis that environmental bacterial communities act as sources of previously uncharacterized qnr genes.
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| 35. |
- Böling, Susanna, et al.
(författare)
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No ordinary consultation : a qualitative inquiry of hospital palliative care consultation services
- 2020
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Ingår i: Journal of Health Organization and Management. - : Emerald Group Publishing Limited. - 1477-7266. ; 34:6, s. 621-638
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Tidskriftsartikel (refereegranskat)abstract
- Purpose – Considering the great need for palliative care in hospitals, it is essential for hospital staff to havepalliative care knowledge. Palliative consultations have been shown to have positive effects on in-hospital care.However, barriers to contact with and uptake of palliative consultation advice are reported, posing a need forfurther knowledge about the process of palliative consultations. The purpose of this study therefore was toexamine how palliative consultations in hospitals are practised, as perceived by consultants and health careprofessionals on receiving wards.Design/methodology/approach – Focus groups with palliative care consultation services, health carepersonnel from receiving wards and managers of consultation services. Interpretive description and constantcomparative method guided the analysis.No ordinaryconsultationThe authors would like to thank participating colleagues for sharing their knowledge and experiencesabout palliative consultations.Ethics approval and consent to participate: The project received ethical approval from the SwedishEthical Review Authority, No. 809–16. Informed consent preceded participation for all of the participants.Consent for publication: Not applicable.Availability of data and material: The datasets generated and analysed during the current study are notpublicly available due to the inclusion of potentially sensitive individual data about health status. Theethical approval includes a statement that the data will be kept in a private repository but are availablefromthe corresponding author on reasonable request.Funding: Sahlgrenska Academy at the University of Gothenburg.Authors' contributions: JO, HB and JB planned the study. All authors conducted focus group €interviews. Analysis and interpretation of focus group data was performed by SB with support from JO, €HB and JB. SB wrote the first draft of the manuscript, JO, HB and JB commented on the manuscript and €contributed to the final version. The final manuscript was read and approved by all authors.Competing interests: The authors declare that they have no competing interests.The current issue and full text archive of this journal is available on Emerald Insight at:https://www.emerald.com/insight/1477-7266.htmReceived 14 April 2020Revised 24 June 2020Accepted 2 July 2020Journal of Health Organization andManagement© Emerald Publishing Limited1477-7266DOI 10.1108/JHOM-04-2020-0130Findings – Variations were seen in several aspects of practice, including approach to practice and representedprofessions. The palliative consultants were perceived to contribute by creating space for palliative care,adding palliative knowledge and approach, enhancing cooperation and creating opportunity to amelioratetransition. Based on a perception of carrying valuable perspectives and knowledge, a number of consultationservices utilised proactive practices that took the initiative in relation to the receiving wards.Originality/value – A lack of policy and divergent views on how to conceptualise palliative care appeared tobe associated with variations in consultation practices, tentative approaches and a bottom-up drivendevelopment. This study adds knowledge, implying theoretical transferability as to how palliative careconsultations can be practised, which is useful when designing and starting new consultation services.
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| 36. |
- Böling, Susanna, et al.
(författare)
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Rethinking Consultation - Investigating the Perceived Work Models of a Palliative Consultation Team
- 2018
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Ingår i: Palliative Medicine : A Multiprofessional Journal. Vol. 32, Suppl. 1. Abstract PO38. - : SAGE Publications. - 0269-2163 .- 1477-030X.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: Previous research has shown that palliative consultation in hospital contexts sometimes face multifaceted challenges. Possibly creat- ing barriers between the consulting team and patients in need of palliative care. Hence, there is a need to consider how we implement and perform palliative consultation to inform future initiatives. This study is part of an ongoing project with the aim to analyse the discourse around implement- ing palliative care in a hospital context. Aim: The aim of this study was to identify and analyse various work models applied in a hospital context by a palliative consultation team. Method: Repeated focus group discussions with a palliative consultation team and its managers. A total of six focus group discussions were held from April 2016 to June 2017. The focus groups were audio recorded and transcribed verbatim. The data was read and analysed; identifying and categorising different work models. Result: According to what was expressed in the focus groups there were variations in how the consultation team operated in different hospital units and wards. Consulting as a team, consisting of a nurse, social worker and physician, was emphasised. One of the significant features was that they visited several wards on a weekly basis without receiving formal referrals beforehand. Although varying in form, the visits shared the function of being a forum for the wards to raise questions regarding palliative care relating to specific patients with palliative needs. Furthermore, during the introduction of consultation in some of the wards, the consultation team chose to designate time where a nurse from the team were present in the ward and among other things; identified patients with palliative care needs together with the ward staff and paved the way for the weekly palliative consultation.
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| 37. |
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| 38. |
- Duvold, Kjetil, et al.
(författare)
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Political Culture in the Baltic States : Between National and European Integration
- 2020. - First
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Bok (refereegranskat)abstract
- Offers a comparative case study of the Baltic states of Estonia, Latvia and LithuaniaRevolves around the Baltic Barometers from 1993 and onwards and presents new data from 2014 and 2015 for the first timeAnalyzes one of the geographical hotspots in the current conflict between Russia and the West
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| 39. |
- Ebmeyer, Stefan, 1990, et al.
(författare)
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GEnView: a gene-centric, phylogeny-based comparative genomics pipeline for bacterial genomes and plasmids
- 2022
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 38:6, s. 1727-1728
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Tidskriftsartikel (refereegranskat)abstract
- Comparing genomic loci of a given bacterial gene across strains and species can provide insights into their evolution, including information on e.g. acquired mobility, the degree of conservation between different taxa or indications of horizontal gene transfer events. While thousands of bacterial genomes are available to date, there is no software that facilitates comparisons of individual gene loci for a large number of genomes. GEnView (Genetic Environment View) is a Python-based pipeline for the comparative analysis of gene-loci in a large number of bacterial genomes, providing users with automated, taxon-selective access to the >800.000 genomes and plasmids currently available in the NCBI Assembly and RefSeq databases, and is able to process local genomes that are not deposited at NCBI, enabling searches for genomic sequences and to analyze their genetic environments through the interactive visualization and extensive metadata files created by GEnView.
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| 40. |
- Einarsdottir, Berglind Osk, 1979, et al.
(författare)
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A patient-derived xenograft pre-clinical trial reveals treatment responses and a resistance mechanism to karonudib in metastatic melanoma
- 2018
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Ingår i: Cell Death & Disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Karonudib (TH1579) is a novel compound that exerts anti-tumor activities and has recently entered phase I clinical testing. The aim of this study was to conduct a pre-clinical trial in patient-derived xenografts to identify the possible biomarkers of response or resistance that could guide inclusion of patients suffering from metastatic melanoma in phase II clinical trials. Patient-derived xenografts from 31 melanoma patients with metastatic disease were treated with karonudib or a vehicle for 18 days. Treatment responses were followed by measuring tumor sizes, and the models were categorized in the response groups. Tumors were harvested and processed for RNA sequencing and protein analysis. To investigate the effect of karonudib on T-cell-mediated anti-tumor activities, tumor-infiltrating T cells were injected in mice carrying autologous tumors and the mice treated with karonudib. We show that karonudib has heterogeneous anti-tumor effect on metastatic melanoma. Thus, based on the treatment responses, we could divide the 31 patient-derived xenografts in three treatment groups: progression group (32%), suppression group (42%), and regression group (26%). Furthermore, we show that karonudib has anti-tumor effect, irrespective of major melanoma driver mutations. Also, we identify high expression of ABCB1, which codes for p-gp pumps as a resistance biomarker. Finally, we show that karonudib treatment does not hamper T-cell-mediated anti-tumor responses. These findings can be used to guide future use of karonudib in clinical use with a potential approach as precision medicine.
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| 41. |
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| 42. |
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| 43. |
- Ekman, Joakim, 1970-, et al.
(författare)
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Multi-country Social-Political Survey 2016 : (Public opinion data: representative samples of the adult population in Hungary, Poland, Czech Republic, Slovakia, Slovenia, Bulgaria, Romania and Croatia)
- 2023
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Annan publikationabstract
- Public opinion data. Surveys were carried out in representative samples of inhabitants between 15 and 74 in the following countries: Bulgaria, Croatia, Czech Republic, Hungary, Poland, Romania, Slovakia, Slovenia. Questions include trust in political institutions, support for democracy, attitudes to immigrants and refugees, attitudes to socioeconomic conditions.
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| 44. |
- Ekman, Joakim
(författare)
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National identity in divided and unified Germany : continuity and change
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation deals with the construction, maintenance and change of national identities in divided and unified Germany. Following World War II, Germany was divided in two parts. For a period of more than 40 years, two German states developed in separation from each other, and because of the horrors of the recent past, both states badly needed to develop new national self-images. Using a four-fold model of ‘national identity’, this study starts out by outlining these different processes of identity formation and nation-building. In the German Democratic Republic (GDR), the communist regime desperately tried to foster a distinct socialist GDR identity among the East Germans. In the Federal Republic of Germany (FRG), the successful economic and political development led to the emergence of a new, post-war national identity. The Berlin Wall was opened on November 9, 1989, and Germany was formally reunified not even a year later, on October 3, 1990. The past decade has shown, however, that Germany has had difficulties in becoming ‘informally’ unified. Drawing on large scale public opinion surveys, this dissertation examines if differences between East Germans and West Germans today are primarily ascribable to the different historical experiences, or rather an outcome of the uneasy unification process. The findings of this study indicate that the East German nation-building project essentially was a failure, since it did not create support for the GDR as a political system. At the same time, the unique experience of living in the GDR shaped a certain ‘East German identity’ and political culture, different from the kind of German identity and political culture that emerged in the FRG. But the findings of this study also suggest that an East German identity in unified Germany should not be reduced to a lingering ‘legacy of the past’. It is, at the same time, an outcome of the unification process itself. A new East German self-awareness has developed as a result of the hardships and challenges posed by the uneasy transformation from a state socialist political system to a liberal democratic system. Consequently, when it comes to the German national identity issue, ‘inner unification’ remains to be seen.
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| 45. |
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| 46. |
- Ekman, Joakim, 1970-, et al.
(författare)
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Post-Crimea Barometer : (Public opinion data: representative samples of the adult population in Hungary, Bulgaria and Latvia, including the Russian-speaking minority)
- 2023
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Annan publikationabstract
- Opinion data from Hungary, Bulgaria and Latvia (including the Russian-speaking minority).This survey focuses on relations with and attitudes towards Russia in three East European countries with a record of close ties with Russia – Latvia, Hungary, and Bulgaria. The survey was carried out against the backdrop of Russia´s annexation of Crimea and Eastern Ukraine. It may be the very first survey to tap East European reactions to Russia’s drastic attempt to redraw the map of post-war Eastern Europe. The 2015 Post-Crimea Survey asks many of the key questions in the Baltic Barometer questions about identity, democracy, and the European Union (Baltic Barometer 2014).
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| 47. |
- Erickson, A, et al.
(författare)
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Spatially resolved clonal copy number alterations in benign and malignant tissue
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 608:7922, s. 360-
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Tidskriftsartikel (refereegranskat)abstract
- Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer1. Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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| 48. |
- Erickson, Andrew, et al.
(författare)
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The spatial landscape of clonal somatic mutations in benign and malignant tissue
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Defining the transition from benign to malignant tissue is fundamental to improve early diagnosis of cancer. Here, we provide an unsupervised approach to study spatial genome integrity in situ to gain molecular insight into clonal relationships. We employed spatially resolved transcriptomics to infer spatial copy number variations in >120 000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of an unsupervised approach to capture the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy.
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| 49. |
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| 50. |
- Frögren, Joakim, et al.
(författare)
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Designing a model app for older persons with cognitive impairment : insights from a usability perspective
- 2018
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Ingår i: Gerontechnology. - : International Society for Gerontechnology. - 1569-1101 .- 1569-111X. ; 17, s. 80-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Research indicates that health-oriented applications on mobile units such as smartphones and PDAs, so called mHealth applications, can be useful to support older persons with cognitive impairment and their informal caregivers1. However, several studies suggest that a prerequisite for older persons to start using computer-based technology is that it offers individual customization according to personal preference 2,3,4. In the ongoing Horizon 2020 project SMART4MD (Support, Monitoring And Reminder Technology for older persons with Mild Dementia), an health-oriented model app has been developed through a user-centered process involving stakeholders in six European countries and with an emphasis on customization to allow for the various needs of older persons with cognitive impairment and their informal caregivers. The aim of this study is to gain insights about the specific needs of the target group and success factors related to the user-centered design process. Method Within the frames of the SMART4MD project, an initial Feasibility study was conducted in two countries (Spain and Sweden) simultaneously, in which in total nineteen persons with cognitive impairment aged 66-93, and their respective informal caregivers, performed a taskbased usability test of the SMART4MD model app individually in a clinical setting, followed by a four-week testing of the app in their home environment. Finally, a usability evaluation was done through individual structured interviews. Results & Discussion The result indicates that less exposure to similar technology affects both ability and self-esteem when confronted with the model app, and that evaluating usability with the target group using standard forms within usability testing requires pre-cautions. © 2018 International Society for Gerontechnology.
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