| 1. |
- Webb, Thomas R., et al.
(författare)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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| 2. |
- Borch, Kurt, 1944-, et al.
(författare)
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Changing pattern of histological type, location, stage and outcome of surgical treatment of gastric carcinoma
- 2000
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 87:5, s. 618-626
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are indications that some features of gastric carcinoma are changing, with a possible impact on prognosis. The aim of this study was to examine any changes in type, location, stage, resection rate, postoperative mortality rate or prognosis for patients with gastric carcinoma in a well defined population. Methods: During 1974-1991, 1161 new cases of gastric adenocarcinoma were diagnosed in Ostergotland County, Sweden. Tumour location, Lauren histological type, tumour node metastasis (TNM) stage, radicality of tumour resection and postoperative complications were recorded after histological re-evaluation of tissue specimens and examination of all patient records. Dates of death were obtained from the Swedish Central Bureau of Statistics. Time trends were studied by comparing the intervals 1974-1982 (period 1) and 1983-1991 (period 2). Results: The proportion of diffuse type of adenocarcinoma increased (from 27 to 35 per cent), while that of mixed type decreased (from 16 to 9 per cent) and that of intestinal type was unchanged. The proportion of tumours located in the proximal two-thirds of the stomach increased (from 32 to 42 per cent) and the proportion of patients with tumours in TNM stage IV decreased (from 32 to 25 per cent). Overall tumour resection rates were unchanged, although the proportion of radical total gastrectomies increased (from 36 to 50 per cent). Excluding tumours of the cardia or gastric remnant after previous ulcer surgery, the 5-year relative survival rate after radical resection increased from 25 to 36 per cent and the postoperative mortality rate decreased for both radical (from 11 to 4 per cent) and palliative (from 18 to 6 per cent) resection. Conclusion: The patterns of tumour histology, location and stage of gastric carcinoma have changed in the authors' region. These changes were paralleled by a significant improvement in survival and postoperative mortality rates.
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| 3. |
- Söderqvist, Tore, et al.
(författare)
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Cost–benefit analysis of beach-cast harvest : Closing land-marine nutrient loops in the Baltic Sea region
- 2022
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Ingår i: Ambio. - : Springer Nature. - 0044-7447 .- 1654-7209. ; 51:5, s. 1302-1313
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Tidskriftsartikel (refereegranskat)abstract
- Harvesting beach-cast can help mitigate marine eutrophication by closing land-marine nutrient loops and provide a blue biomass raw material for the bioeconomy. Cost–benefit analysis was applied to harvest activities during 2009–2018 on the island of Gotland in the Baltic Sea, highlighting benefits such as nutrient removal from the marine system and improved recreational opportunities as well as costs of using inputs necessary for harvest. The results indicate that the activities entailed a net gain to society, lending substance to continued funding for harvests on Gotland and assessments of upscaling of harvest activities to other areas in Sweden and elsewhere. The lessons learnt from the considerable harvest experience on Gotland should be utilized for developing concrete guidelines for carrying out sustainable harvest practice, paying due attention to local conditions but also to what can be generalized to a wider national and international context.
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| 4. |
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| 5. |
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| 6. |
- Bohlin, Jan
(författare)
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Enzymes and electron transport in microbial chlorate respiration
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Microbial chlorate respiration plays an important role in the turnover of oxochlorates in nature and industrial waste management. This thesis deals with the characterization of the molecular components of chlorate respiration in Ideonella dechloratans. Chlorate respiration utilizes two soluble periplasmic enzymes, chlorate reductase and chlorite dismutase, to convert chlorate to chloride and oxygen. The genes encoding the enzymes participating in the chlorate degradation have been sequenced, and are found in close proximity, forming a gene cluster for chlorate metabolism. This work also includes the successful recombinant expression of three genes from Ideonella dechloratans. Two of the gene products, chlorite dismutase and the C subunit of chlorate reductase, participate in the chlorate respiration. The third gene, which is found close to the gene cluster for chlorate metabolism, encodes a soluble c-type cytochrome. The localization of the gene suggests the corresponding protein as a candidate for a role as electron donor to chlorate reductase. Also, the role of soluble periplasmic c cytochromes of Ideonella dechloratans in chlorate respiration was studied. At least one of the soluble c cytochromes was found capable of serving as electron donor for chlorate reduction. This c cytochrome, and several others, can also donate electrons to a terminal oxidase for subsequent reduction of oxygen, as required for the branched electron flow during chlorate respiration.
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| 7. |
- Fallows, Richard A., et al.
(författare)
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A LOFAR observation of ionospheric scintillation from two simultaneous travelling ionospheric disturbances
- 2020
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Ingår i: Journal of Space Weather and Space Climate. - : EDP Sciences. - 2115-7251. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the results from one of the first observations of ionospheric scintillation taken using the Low-Frequency Array (LOFAR). The observation was of the strong natural radio source Cassiopeia A, taken overnight on 18-19 August 2013, and exhibited moderately strong scattering effects in dynamic spectra of intensity received across an observing bandwidth of 10-80 MHz. Delay-Doppler spectra (the 2-D FFT of the dynamic spectrum) from the first hour of observation showed two discrete parabolic arcs, one with a steep curvature and the other shallow, which can be used to provide estimates of the distance to, and velocity of, the scattering plasma. A cross-correlation analysis of data received by the dense array of stations in the LOFAR "core" reveals two different velocities in the scintillation pattern: a primary velocity of similar to 20-40 ms(-1) with a north-west to south-east direction, associated with the steep parabolic arc and a scattering altitude in the F-region or higher, and a secondary velocity of similar to 110 ms(-1) with a north-east to south-west direction, associated with the shallow arc and a scattering altitude in the D-region. Geomagnetic activity was low in the mid-latitudes at the time, but a weak sub-storm at high latitudes reached its peak at the start of the observation. An analysis of Global Navigation Satellite Systems (GNSS) and ionosonde data from the time reveals a larger-scale travelling ionospheric disturbance (TID), possibly the result of the high-latitude activity, travelling in the north-west to south-east direction, and, simultaneously, a smaller-scale TID travelling in a north-east to south-west direction, which could be associated with atmospheric gravity wave activity. The LOFAR observation shows scattering from both TIDs, at different altitudes and propagating in different directions. To the best of our knowledge this is the first time that such a phenomenon has been reported.
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| 8. |
- Forsgren, Malin, et al.
(författare)
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A Novel Approach to Railway Planning
- 2009. - 14
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Konferensbidrag (refereegranskat)abstract
- Today, detailed railway timetables in Sweden are published up to a year in advance, despite being based on volatile facts. We describe a new railway planning concept for Banverket, the Swedish Rail Administration, that aims to reduce the workload and increase the timetable quality, thus making railway traffic more cost-effective and attractive. The concept distinguishes between deliverables and production plans. The former are settled early and involve a selection of arrival and departure times that Banverket promises to deliver to the operators. The latter are fixed later, and only when sufficient information is available.
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| 9. |
- Franzen, Bo, et al.
(författare)
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A fine-needle aspiration-based protein signature discriminates benign from malignant breast lesions
- 2018
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 12:9, s. 1415-1428
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Tidskriftsartikel (refereegranskat)abstract
- There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and to follow-up personalized cancer therapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissues; however, the minute sample amounts require sensitive multiplex molecular analysis to achieve clinical utility. We have applied proximity extension assays (PEA) and NanoString (NS) technology for analyses of proteins and of RNA, respectively, in FNA samples. Using samples from patients with breast cancer (BC, n=25) or benign lesions (n=33), we demonstrate that these FNA-based molecular analyses (a) can offer high sensitivity and reproducibility, (b) may provide correct diagnosis in shorter time and at a lower cost than current practice, (c) correlate with results from routine analysis (i.e., benchmarking against immunohistochemistry tests for ER, PR, HER2, and Ki67), and (d) may also help identify new markers related to immunotherapy. A specific 11-protein signature, including FGF binding protein 1, decorin, and furin, distinguished all cancer patient samples from all benign lesions in our main cohort and in smaller replication cohort. Due to the minimally traumatic sampling and rich molecular information, this combined proteomics and transcriptomic methodology is promising for diagnostics and evaluation of treatment efficacy in BC.
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| 10. |
- Franzen, Bo, et al.
(författare)
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Protein profiling of fine-needle aspirates reveals subtype-associated immune signatures and involvement of chemokines in breast cancer
- 2019
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Ingår i: Molecular Oncology. - : WILEY. - 1574-7891 .- 1878-0261. ; 13:2, s. 376-391
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Tidskriftsartikel (refereegranskat)abstract
- There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and for follow-up of personalized cancer therapy, including immunotherapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissue samples; however, the minute amounts of sample require sensitive multiplex molecular analysis to be of clinical biomarker utility. We have applied proximity extension assays (PEA) to analyze 167 proteins in FNA samples from patients with breast cancer (BC; n = 25) and benign lesions (n = 32). We demonstrate that the FNA BC samples could be divided into two main clusters, characterized by differences in expression levels of the estrogen receptor (ER) and the proliferation marker Ki67. This clustering corresponded to some extent to established BC subtypes. Our analysis also revealed several proteins whose expression levels differed between BC and benign lesions (e.g., CA9, GZMB, IL-6, VEGFA, CXCL11, PDL1, and PCD1), as well as several chemokines correlating with ER and Ki67 status (e.g., CCL4, CCL8, CCL20, CXCL8, CXCL9, and CXCL17). Finally, we also identified three signatures that could predict Ki67 status, ER status, and tumor grade, respectively, based on a small subset of proteins, which was dominated by chemokines. To our knowledge, expression profiles of CCL13 in benign lesions and BC have not previously been described but were shown herein to correlate with proliferation (P = 0.00095), suggesting a role in advanced BC. Given the broad functional range of the proteins analyzed, immune-related proteins were overrepresented among the observed alterations. Our pilot study supports the emerging role of chemokines in BC progression. Due to the minimally traumatic sampling and clinically important molecular information for therapeutic decisions, this methodology is promising for future immunoscoring and monitoring of treatment efficacy in BC.
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