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| 4. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 6. |
- Gorlova, Olga, et al.
(författare)
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Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
- 2011
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:7
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (IcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and autoantibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
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| 7. |
- Khatri, B., et al.
(författare)
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Genome-wide association study identifies Sjogren's risk loci with functional implications in immune and glandular cells
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Sjogren's disease is a complex autoimmune disease with twelve established susceptibility loci. This genome-wide association study (GWAS) identifies ten novel genome-wide significant (GWS) regions in Sjogren's cases of European ancestry: CD247, NAB1, PTTG1-MIR146A, PRDM1-ATG5, TNFAIP3, XKR6, MAPT-CRHR1, RPTOR-CHMP6-BAIAP6, TYK2, SYNGR1. Polygenic risk scores yield predictability (AUROC = 0.71) and relative risk of 12.08. Interrogation of bioinformatics databases refine the associations, define local regulatory networks of GWS SNPs from the 95% credible set, and expand the implicated gene list to >40. Many GWS SNPs are eQTLs for genes within topologically associated domains in immune cells and/or eQTLs in the main target tissue, salivary glands. The genetic architecture underlying Sjogren's syndrome is not fully understood. Here, the authors perform a genome-wide association study to identify 10 new genetic risk regions, implicating genes involved in immune and salivary gland function.
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| 8. |
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| 9. |
- Cenit, MC, et al.
(författare)
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Influence of the IL6 gene in susceptibility to systemic sclerosis
- 2012
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Ingår i: The Journal of rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 39:12, s. 2294-2302
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Tidskriftsartikel (refereegranskat)abstract
- Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and phenotype expression of SSc.Methods.We performed a large metaanalysis including a total of 2749 cases and 3189 controls from 6 white populations (Germany, The Netherlands, Norway, Spain, Sweden, and United Kingdom). Three IL6 single-nucleotide polymorphisms (SNP; rs2069827, rs1800795, and rs2069840) were selected by SNP tagging and genotyped using TaqMan® allele discrimination technology.Results.Individual SNP metaanalysis showed no evidence of association of the 3 IL6 genetic variants with the global disease. Phenotype analyses revealed a significant association between the minor allele of rs2069840 and the limited cutaneous SSc clinical form (Bonferroni p = 0.036, OR 1.14, 95% CI 1.04–1.25). A trend of association between the minor allele of the rs1800795 and the diffuse cutaneous SSc clinical form was also evident (Bonferroni p = 0.072, OR 0.86, 95% CI 0.77–0.96). In the IL6 allelic combination analyses, the GGC allelic combination rs2069827-rs1800795-rs2069840 showed an association with overall SSc (Bonferroni p = 0.016, OR 1.13, 95% CI 1.04–1.23).Conclusion.Our results suggest that the IL6 gene may influence the development of SSc and its progression.
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| 10. |
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| 11. |
- Rannikmäe, K., et al.
(författare)
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Reliability of intracerebral hemorrhage classification systems: A systematic review
- 2016
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 11:6, s. 626-636
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Tidskriftsartikel (refereegranskat)abstract
- Background: Accurately distinguishing non-traumatic intracerebral hemorrhage (ICH) subtypes is important since they may have different risk factors, causal pathways, management, and prognosis. We systematically assessed the inter- and intra-rater reliability of ICH classification systems. Methods: We sought all available reliability assessments of anatomical and mechanistic ICH classification systems from electronic databases and personal contacts until October 2014. We assessed included studies’ characteristics, reporting quality and potential for bias; summarized reliability with kappa value forest plots; and performed meta-analyses of the proportion of cases classified into each subtype. Summary of review: We included 8 of 2152 studies identified. Inter- and intra-rater reliabilities were substantial to perfect for anatomical and mechanistic systems (inter-rater kappa values: anatomical 0.78–0.97 [six studies, 518 cases], mechanistic 0.89–0.93 [three studies, 510 cases]; intra-rater kappas: anatomical 0.80–1 [three studies, 137 cases], mechanistic 0.92–0.93 [two studies, 368 cases]). Reporting quality varied but no study fulfilled all criteria and none was free from potential bias. All reliability studies were performed with experienced raters in specialist centers. Proportions of ICH subtypes were largely consistent with previous reports suggesting that included studies are appropriately representative. Conclusions: Reliability of existing classification systems appears excellent but is unknown outside specialist centers with experienced raters. Future reliability comparisons should be facilitated by studies following recently published reporting guidelines. © 2016, © 2016 World Stroke Organization.
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| 12. |
- Sorelius, Karl, et al.
(författare)
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The Microbiology of Infective Native Aortic Aneurysms in a Population-Based Setting
- 2022
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Ingår i: Annals of Vascular Surgery. - : Elsevier. - 0890-5096 .- 1615-5947. ; 78, s. 112-122
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs). Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures. Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P =.051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year. Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings.
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| 13. |
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| 14. |
- Bossini-Castillo, Lara, et al.
(författare)
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A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations
- 2012
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:4, s. 926-933
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Tidskriftsartikel (refereegranskat)abstract
- A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P-MH = 1.92 x 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P-MH = 4.84 x 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P-chi 2 = 2.82 x 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P-MH = 2.82 x 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.
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| 15. |
- Bossini-Castillo, Lara, et al.
(författare)
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A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort
- 2011
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:4, s. 638-641
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. Methods A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers. Results A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively). Conclusions The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.
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| 16. |
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| 17. |
- de Laat, A. T. J., et al.
(författare)
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Validation of five years (2003-2007) of SCIAMACHY CO total column measurements using ground-based spectrometer observations
- 2010
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 3:5, s. 1457-1471
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a validation study of SCanning Imaging Absorption spectroMeter for Atmospheric CHartographY (SCIAMACHY) carbon monoxide (CO) total column measurements from the Iterative Maximum Likelihood Method (IMLM) algorithm using ground-based spectrometer observations from twenty surface stations for the five year time period of 2003-2007. Overall we find a good agreement between SCIAMACHY and ground-based observations for both mean values as well as seasonal variations. For high-latitude Northern Hemisphere stations absolute differences between SCIAMACHY and ground-based measurements are close to or fall within the SCIAMACHY CO 2 sigma precision of 0.2 x 10(18) molecules/cm(2) (similar to 10%) indicating that SCIAMACHY can observe CO accurately at high Northern Hemisphere latitudes. For Northern Hemisphere mid-latitude stations the validation is complicated due to the vicinity of emission sources for almost all stations, leading to higher ground-based measurements compared to SCIAMACHY CO within its typical sampling area of 8 degrees x 8 degrees. Comparisons with Northern Hemisphere mountain stations are hampered by elevation effects. After accounting for these effects, the validation provides satisfactory results. At Southern Hemisphere mid-to high latitudes SCIAMACHY is systematically lower than the ground-based measurements for 2003 and 2004, but for 2005 and later years the differences between SCIAMACHY and ground-based measurements fall within the SCIAMACHY precision. The 2003-2004 bias is consistent with previously reported results although its origin remains under investigation. No other systematic spatial or temporal biases could be identified based on the validation presented in this paper. Validation results are robust with regard to the choices of the instrument-noise error filter, sampling area, and time averaging required for the validation of SCIAMACHY CO total column measurements. Finally, our results show that the spatial coverage of the ground-based measurements available for the validation of the 2003-2007 SCIAMACHY CO columns is sub-optimal for validation purposes, and that the recent and ongoing expansion of the ground-based network by carefully selecting new locations may be very beneficial for SCIAMACHY CO and other satellite trace gas measurements validation efforts.
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| 18. |
- Eshmvminov, D., et al.
(författare)
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FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review
- 2023
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Ingår i: Annals of Surgical Oncology. - 1068-9265. ; 30:7, s. 4417-4428
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Forskningsöversikt (refereegranskat)abstract
- BackgroundPancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.MethodsWe performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.ResultsA total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.ConclusionsIn patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
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| 19. |
- Hansson, Lars, et al.
(författare)
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Annie, a Tool for Integrating Ergonomics in the Design of Car Interiors
- 1999
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- An example of a result from a long-term cooperation with Lund University (together with professor Roland Axelsson at the Department for Work Environment) there some of the authors. (Engström) gained extensive grants (Wallenberg Stifelsen regarding equipment as well as other founding from e.g. the Swedish Work Environment Found).
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| 20. |
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| 21. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 22. |
- Segesten, K, et al.
(författare)
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Kommentarer
- 2004
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Ingår i: Närståendes behov. - Stockholm : Svensk sjuksköterskeförening. ; , s. 112-5
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 23. |
- Vigouroux, C., et al.
(författare)
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Trends of ozone total columns and vertical distribution from FTIR observations at eight NDACC stations around the globe
- 2015
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 15:6, s. 2915-2933
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Tidskriftsartikel (refereegranskat)abstract
- Ground-based Fourier transform infrared (FTIR) measurements of solar absorption spectra can provide ozone total columns with a precision of 2% but also independent partial column amounts in about four vertical layers, one in the troposphere and three in the stratosphere up to about 45 km, with a precision of 5-6 %. We use eight of the Network for the Detection of Atmospheric Composition Change (NDACC) stations having a long-term time series of FTIR ozone measurements to study the total and vertical ozone trends and variability, namely, Ny-Alesund (79 degrees N), Thule (77 degrees N), Kiruna (68 degrees N), Harestua (60 degrees N), Jungfraujoch (47 degrees N), Izana (28 degrees N), Wollongong (34 degrees S) and Lauder (45 degrees S). The length of the FTIR time series varies by station but is typically from about 1995 to present. We applied to the monthly means of the ozone total and four partial columns a stepwise multiple regression model including the following proxies: solar cycle, quasi-biennial oscillation (QBO), El Nino-Southern Oscillation (ENSO), Arctic and Antarctic Oscillation (AO/AAO), tropopause pressure (TP), equivalent latitude (EL), Eliassen-Palm flux (EPF), and volume of polar stratospheric clouds (VPSC). At the Arctic stations, the trends are found mostly negative in the troposphere and lower stratosphere, very mixed in the middle stratosphere, positive in the upper stratosphere due to a large increase in the 1995-2003 period, and non-significant when considering the total columns. The trends for mid-latitude and subtropical stations are all non-significant, except at Lauder in the troposphere and upper stratosphere and at Wollongong for the total columns and the lower and middle stratospheric columns where they are found positive. At Jungfraujoch, the upper stratospheric trend is close to significance (+0.9 +/- 1.0% decade(-1)). Therefore, some signs of the onset of ozone mid-latitude recovery are observed only in the Southern Hemisphere, while a few more years seem to be needed to observe it at the northern mid-latitude station.
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| 24. |
- Ali, Rashid, et al.
(författare)
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Study of flow boiling characteristics of a microchannel using high speed visualization
- 2013
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Ingår i: Journal of heat transfer. - : ASME International. - 0022-1481 .- 1528-8943. ; 135:8, s. 081501-
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the visualization results obtained for an experimental study of R134a during flow boiling in a horizontal microchannel. The microchannel used was a fused silica tube having an internal diameter of 781 lm, a heated length of 191mm, and was coated with a thin, transparent, and electrically conductive layer of indium-tin-oxide (ITO) on the outer surface. The operating parameters during the experiments were: mass flux 100-400 kg/m2 s, heat flux 5-45 kW/m2, saturation temperatures 25 and 30 °C, corresponding to saturation pressures of 6.65 bar and 7.70 bar and reduced pressures of 0.163 and 0.189, respectively. A high speed camera with a close up lens was used to capture the flow patterns that evolved along the channel. Flow pattern maps are presented in terms of the superficial gas and liquid velocity and in terms of the Reynolds number and vapor quality plots. The results are compared with some flow pattern maps for conventional and micro scale channels available in the literature. Rigorous boiling and increased coalescence rates were observed with an increase in the heat flux.
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| 25. |
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| 26. |
- Berthelsen, A., et al.
(författare)
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Recording marine airgun shots at offsets between 300 and 700 km
- 1991
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Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 18:4, s. 645-648
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Tidskriftsartikel (refereegranskat)abstract
- This paper demonstrates that - under favorable conditions - by using multichannel recording and subsequent stacking of adjacent records marine airgun shots have been detected at offset distances up to 700 km, the maximum offset at which the authors attempted to record data.^Besides a powerful airgun array, a low noise environment at the recording site and the elimination of static shifts are the prerequisites to obtain refracted and reflected arrivals from the crust and upper mantle at such large offsets.^Primary arrivals detected at offsets between 400 and 700 km image the upper mantle from 70 to about 120 km depth.^Stacking of neighboring shots and/or receivers successfully increases the signal-to-noise ratio, if the traces have been corrected for offset differences, which requires knowledge of the apparent phase velocities.^The data presented here were collected in autumn 1989 during the BABEL Project on the Baltic Shield.
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| 27. |
- Björkelund, Cecilia, 1948, et al.
(författare)
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Long-term effects of a primary health care intervention program for women: lower blood pressure and stable weight
- 2000
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Ingår i: Family Medicine. ; 32, s. 246-251
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Tidskriftsartikel (refereegranskat)abstract
- Department of Primary Health Care, Sahlgrenska Hospital, Göteborg University, Sweden. cecilia.bjorkelund@allmed.gu.se BACKGROUND: In Strömstad, with 10,000 inhabitants, a cardiovascular prevention program was launched during 1985-1987 because of high rates of cardiovascular disease. To study long-term effects in women, an 8-year follow-up was conducted. METHODS: Participants (n = 114) and nonparticipants (n = 269) in the lifestyle intervention program in 1985-1987 (both groups with cardiovascular risk factors) were compared regarding risk factor levels after 8 years. Effects were also compared to another community not exposed to intervention. RESULTS: After 8 years, intervention participants showed significant reduction of mean systolic blood pressure compared to the control group and had higher intake of dietary fibers and more-positive attitudes to and better knowledge of healthy diets. There was no increase of mean body weight or serum triglyceride levels whatsoever in the intervention group. Compared with another female population not exposed to intervention, body weight and systolic blood pressure changed in a significantly more favorable way. CONCLUSIONS: Results from the prevention program could be discerned after 8 years. Advantages in risk factor changes could also be found when comparing with another female population. Given the high level of stroke in women within the community, the blood pressure advantage in the intervention group is particularly encouraging. PMID: 10782370 [PubMed - indexed for MEDLINE]
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| 28. |
- Blumenstock, T., et al.
(författare)
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Characterization and potential for reducing optical resonances in Fourier transform infrared spectrometers of the Network for the Detection of Atmospheric Composition Change (NDACC)
- 2021
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 14:2, s. 1239-1252
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Tidskriftsartikel (refereegranskat)abstract
- Although optical components in Fourier transform infrared (FTIR) spectrometers are preferably wedged, in practice, infrared spectra typically suffer from the effects of optical resonances ("channeling") affecting the retrieval of weakly absorbing gases. This study investigates the level of channeling of each FTIR spectrometer within the Network for the Detection of Atmospheric Composition Change (NDACC). Dedicated spectra were recorded by more than 20 NDACC FTIR spectrometers using a laboratory mid-infrared source and two detectors. In the indium antimonide (InSb) detector domain (1900-5000 cm-1), we found that the amplitude of the most pronounced channeling frequency amounts to 0.1 ‰ to 2.0 ‰ of the spectral background level, with a mean of (0:68±0:48) ‰ and a median of 0.60 ‰. In the mercury cadmium telluride (HgCdTe) detector domain (700-1300 cm-1), we find even stronger effects, with the largest amplitude ranging from 0.3 ‰ to 21 ‰ with a mean of (2:45±4:50) ‰ and a median of 1.2 ‰. For both detectors, the leading channeling frequencies are 0.9 and 0.11 or 0.23 cm-1 in most spectrometers. The observed spectral frequencies of 0.11 and 0.23 cm-1 correspond to the optical thickness of the beam splitter substrate. The 0.9 cm-1 channeling is caused by the air gap in between the beam splitter and compensator plate. Since the air gap is a significant source of channeling and the corresponding amplitude differs strongly between spectrometers, we propose new beam splitters with the wedge of the air gap increased to at least 0.8. We tested the insertion of spacers in a beam splitter's air gap to demonstrate that increasing the wedge of the air gap decreases the 0.9 cm-1 channeling amplitude significantly. A wedge of the air gap of 0.8 reduces the channeling amplitude by about 50 %, while a wedge of about 2 removes the 0.9 cm-1 channeling completely. This study shows the potential for reducing channeling in the FTIR spectrometers operated by the NDACC, thereby increasing the quality of recorded spectra across the network.
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| 29. |
- Boswell, M. T., et al.
(författare)
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Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS
- 2022
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Ingår i: Virus Evolution. - : Oxford University Press (OUP). - 2057-1577. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
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| 30. |
- Bäck, Tom, 1964, et al.
(författare)
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211At radioimmunotherapy of subcutaneous human ovarian cancer xenografts: evaluation of relative biologic effectiveness of an alpha-emitter in vivo
- 2005
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Ingår i: J Nucl Med. - 0161-5505. ; 46:12, s. 2061-7
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Tidskriftsartikel (refereegranskat)abstract
- The use of alpha-particle emitters in radioimmunotherapy (RIT) appears to be promising. We previously obtained convincing results in the treatment of microscopic intraperitoneal ovarian cancer in nude mice by using the alpha-emitter 211At. This study was performed to evaluate the relative biological effectiveness (RBE) of 211At compared with that of 60Co gamma-irradiation in an RIT model. Our endpoint was growth inhibition (GI) of subcutaneous xenografts. METHODS: GI after irradiation was studied with subcutaneous xenografts of the human ovarian cancer cell line NIH:OVCAR-3 implanted in nude mice. The animals received an intravenous injection of 211At-labeled monoclonal antibody MX35 F(ab')2 at different levels of radioactivity (0.33, 0.65, and 0.90 MBq). Control mice received unlabeled MX35 F(ab')2 only. To calculate the mean absorbed dose to tumor, a separate biodistribution study established the uptake of 211At in tumors and organs at different times after injection. External irradiation of the tumors was performed with 60Co. Tumor growth was monitored, and the normalized tumor volume (NTV) was calculated for each tumor. GI was defined by dividing the NTV values by the fitted NTV curve obtained from the corresponding control mice. To compare the biologic effects of the 2 radiation qualities, the mean value for GI (from day 8 to day 23) was plotted for each tumor as a function of its corresponding absorbed dose. From exponential fits of these curves, the doses required for a GI of 0.37 (D37) were derived, and the RBE of 211At was calculated. RESULTS: The biodistribution study showed the uptake of the immunoconjugate by the tumor (amount of injected radioactivity per gram) to be 14% after 7 h. At 40 h, the ratio of uptake in tumors to uptake in blood reached a maximum value of 6.2. The administered activities of 211At corresponded to doses absorbed by tumors of 1.35, 2.65, and 3.70 Gy. The value (mean+/-SEM) for D37 was 1.59+/-0.08 Gy. Tumor growth after 60Co external irradiation showed a value for D37 of 7.65+/-1.0 Gy. The corresponding RBE of 211At irradiation was 4.8+/-0.7. CONCLUSION: Using a tumor GI model in nude mice, we were able to derive an RBE of alpha-particle RIT with 211At. The RBE was found to be 4.8+/-0.7.
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| 31. |
- Chio, Iok In Christine, et al.
(författare)
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NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 166:4, s. 936-976
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic cancer is a deadly malignancy that lacks effective therapeutics. We previously reported that oncogenic Kras induced the redox master regulator Nfe2l2/Nrf2 to stimulate pancreatic and lung cancer initiation. Here, we show that NRF2 is necessary to maintain pancreatic cancer proliferation by regulating mRNA translation. Specifically, loss of NRF2 led to defects in autocrine epidermal growth factor receptor (EGFR) signaling and oxidation of specific translational regulatory proteins, resulting in impaired cap-dependent and cap-independent mRNA translation in pancreatic cancer cells. Combined targeting of the EGFR effector AKT and the glutathione antioxidant pathway mimicked Nrf2 ablation to potently inhibit pancreatic cancer ex vivo and in vivo, representing a promising synthetic lethal strategy for treating the disease.
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| 32. |
- Davids, Mariska, et al.
(författare)
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Simultaneous determination of asymmetric and symmetric dimethylarginine, L-monomethylarginine, L-arginine, and L-homoarginine in biological samples using stable isotope dilution liquid chromatography tandem mass spectrometry
- 2012
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Ingår i: Journal of chromatography. B. - : Elsevier BV. - 1570-0232 .- 1873-376X. ; 900, s. 38-47
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Tidskriftsartikel (refereegranskat)abstract
- Production of the endogenous vasodilator nitric oxide (NO) from L-arginine by NO synthase is modulated by L-homoarginine, L-monomethylargine (MMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). Here we report on a stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of these metabolites in plasma, cells and tissues. After addition of the internal standards (D-7-ADMA, D-4-L-homoarginine and C-13(6)-Larginine), analytes were extracted from the samples using Waters Oasis MCX solid phase extraction cartridges. Butylated analytes were separated isocratically on a Waters XTerra MS C18 column (3.5 mu m. 3.9 mm x 100 mm) using 600 mg/L ammonium formate in water - acetonitrile (95.5:4.5, v/v) containing 0.1 vol% formic acid, and subsequently measured on an AB Sciex API 3000 triple quadrupole mass spectrometer. Multiple reaction monitoring in positive mode was used for analyte quantification. Validation was performed in plasma. Calibration lines were linear (r(2) >= 0.9979) and lower limits of quantification in plasma were 0.4 nM for ADMA and SDMA and 0.8 nM for the other analytes. Accuracy (% bias) was <3% except for MMA (<7%), intra-assay precision (expressed as CV) was <3.5%, inter-assay precision <9.6%, and recovery 92.9-103.2% for all analytes. The method showed good correlation (r(2) >= 0.9125) with our previously validated HPLC-fluorescence method for measurement in plasma, and was implemented with good performance for measurement of tissue samples. Application of the method revealed the remarkably fast (i.e. within 60 min) appearance in plasma of stable isotope-labeled ADMA, SDMA, and MMA during infusion of D-3-methyl-1-C-13-methionine in healthy volunteers.
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| 33. |
- Dekempeneer, Y., et al.
(författare)
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Labeling of Anti-HER2 Nanobodies with Astatine-211: Optimization and the Effect of Different Coupling Reagents on Their in Vivo Behavior
- 2019
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 16:8, s. 3524-3533
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Tidskriftsartikel (refereegranskat)abstract
- The use of nanobodies (Nbs) as vehicles in targeted alpha therapy (TAT) has gained great interest because of their excellent properties. They combine high in vivo affinity and specificity of binding with fast kinetics. This research investigates a novel targeted therapy that combines the alpha-particle emitter astatine-211 (At-211) and the anti-HER2 Nb 2Rs15d to selectively target HER2+ cancer cells. Two distinctive radiochemical methodologies are investigated using three different coupling reagents. The first method uses the coupling reagents, N-succinimidyl 4-(1,2-bis-tert-butoxycarbonyl)guanidinomethyl-3-(trimethylstannyl)benzo ate (Boc(2)-SGMTB) and N-succinimidyl-3-(trimethylstannyl)-benzoate (m-MeATE), which are both directed to amino groups on the Nb, resulting in random conjugation. The second method aims at obtaining a homogeneous tracer population, via a site-specific conjugation of the N-[2-(maleimido)ethyl]-3-(trimethylstannyl)benzamide (MSB) reagent onto the carboxyl-terminal cysteine of the Nb. The resulting radioconjugates are evaluated in vitro and in vivo. 2Rs15d is labeled with At-211 using Boc(2)-SGMTB, m-MeATE, and MSB. After astatination and purification, the binding specificity of the radioconjugates is validated on HER2+ cells, followed by an in vivo biodistribution assessment in SKOV-3 xenografted mice. alpha-camera imaging is performed to determine uptake and activity distribution in kidneys/tumors. 2Rs15d astatination resulted in a high radiochemical purity >95% for all radioconjugates. The biodistribution studies of all radioconjugates revealed comparable tumor uptake (higher than 8% ID/g at 1 h). [At-211]SAGMB-2Rs15d showed minor uptake in normal tissues. Only in the kidneys, a higher uptake was measured after 1 h, but decreased rapidly after 3 h. Astatinated Nbs consisting of m-MeATE or MSB reagents revealed elevated uptake in lungs and stomach, indicating the presence of released At-211. alpha-Camera imaging of tumors revealed a homogeneous activity distribution. The radioactivity in the kidneys was initially concentrated in the renal cortex, while after 3 h most radioactivity was measured in the medulla, confirming the fast washout into urine. Changing the reagents for Nb astatination resulted in different in vivo biodistribution profiles, while keeping the targeting moiety identical. Boc(2)-SGMTB is the preferred reagent for Nb astatination because of its high tumor uptake, its low background signals, and its fast renal excretion. We envision [At-211]SAGMB-2Rs15d to be a promising therapeutic agent for TAT and aim toward efficacy evaluation.
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| 34. |
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| 35. |
- Dyberg, C., et al.
(författare)
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Rho-associated kinase is a therapeutic target in neuroblastoma
- 2017
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 114:32
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Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is a peripheral neural system tumor that originates from the neural crest and is the most common and deadly tumor of infancy. Here we show that neuroblastoma harbors frequent mutations of genes controlling the Rac/Rho signaling cascade important for proper migration and differentiation of neural crest cells during neuritogenesis. RhoA is activated in tumors from neuroblastoma patients, and elevated expression of Rho-associated kinase (ROCK) 2 is associated with poor patient survival. Pharmacological or genetic inhibition of ROCK1 and 2, key molecules in Rho signaling, resulted in neuroblastoma cell differentiation and inhibition of neuroblastoma cell growth, migration, and invasion. Molecularly, ROCK inhibition induced glycogen synthase kinase 3 beta-dependent phosphorylation and degradation of MYCN protein. Small-molecule inhibition of ROCK suppressed MYCN-driven neuroblastoma growth in TH-MYCN homozygous transgenic mice and MYCN gene-amplified neuroblastoma xenograft growth in nude mice. Interference with Rho/Rac signaling might offer therapeutic perspectives for high-risk neuroblastoma.
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| 36. |
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| 37. |
- Edsbacker, E, et al.
(författare)
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STAT3 is activated in multicellular spheroids of colon carcinoma cells and mediates expression of IRF9 and interferon stimulated genes
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 536-
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Tidskriftsartikel (refereegranskat)abstract
- Three-dimensional cell cultures, such as multicellular spheroids (MCS), reflect the in vivo architecture of solid tumours and multicellular drug resistance. We previously identified interferon regulatory factor 9 (IRF9) to be responsible for the up-regulation of a subset of interferon (IFN)-stimulated genes (ISGs) in MCS of colon carcinoma cells. This set of ISGs closely resembled a previously identified IFN-related DNA-damage resistance signature (IRDS) that was correlated to resistance to chemo- and radiotherapy. In this study we found that transcription factor STAT3 is activated upstream of IRF9 and binds to the IRF9 promoter in MCS of HCT116 colorectal carcinoma cells. Transferring conditioned media (CM) from high cell density conditions to non-confluent cells resulted in STAT3 activation and increased expression of IRF9 and a panel of IRDS genes, also observed in MCS, suggesting the involvement of a soluble factor. Furthermore, we identified gp130/JAK signalling to be responsible for STAT3 activation, IRF9, and IRDS gene expression in MCS and by CM. Our data suggests a novel mechanism where STAT3 is activated in high cell density conditions resulting in increased expression of IRF9 and, in turn, IRDS genes, underlining a mechanism by which drug resistance is regulated.
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| 38. |
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| 39. |
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| 40. |
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| 41. |
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| 42. |
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| 43. |
- Goroshchuk, O, et al.
(författare)
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Polo-like kinases and acute leukemia
- 2019
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 38:1, s. 1-16
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Tidskriftsartikel (refereegranskat)
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| 44. |
- Goroshchuk, O, et al.
(författare)
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Targeting Plk1 with siRNNs in primary cells from pediatric B-cell acute lymphoblastic leukemia patients
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 2688-
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Tidskriftsartikel (refereegranskat)abstract
- B-cell acute lymphoblastic leukemia (B-ALL) accounts for nearly one fifth of all childhood cancers and current challenges in B-ALL treatment include resistance, relapse and late-onset side effects due to the chemotherapy. To overcome these hurdles, novel therapies need to be investigated. One promising target is Polo-like kinase 1 (Plk1), a key regulator of the cell cycle. In this study, the Plk family expression is investigated in primary peripheral blood and bone marrow mononuclear cells from ten pediatric B-ALL patients. For the first time, short interfering RiboNucleic Neutrals (siRNNs) that enter cells without a transfection reagent are used to target Plk1 mRNA in primary cells from pediatric B-ALL patients. Our results show that the expression of Plk1 and Plk4 is significantly higher in pediatric B-ALL patients compared to healthy donors. Moreover, treatment of primary peripheral blood and bone marrow mononuclear cells from pediatric B-ALL patients, cultured ex vivo, with Plk1-targeting siRNNs results in cleavage of Plk1 mRNA. Importantly, the Plk1 knockdown is specific and does not affect other Plk members in contrast to many small molecule Plk1 inhibitors. Thus, Plk1 is a potential therapeutic target in pediatric B-ALL and selective targeting of Plk1 can be achieved by the use of siRNNs.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
- Hansell, Peter, et al.
(författare)
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Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension
- 2013
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Ingår i: Clinical and experimental pharmacology & physiology. - : Blackwell Publishing. - 0305-1870 .- 1440-1681. ; 40:2, s. 123-137
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Forskningsöversikt (refereegranskat)abstract
- The high renal oxygen (O2) demand is associated primarily with tubular O2 consumption (Qo2) necessary for solute reabsorption. Increasing O2 delivery relative to demand via increased blood flow results in augmented tubular electrolyte load following elevated glomerular filtration, which, in turn, increases metabolic demand. Consequently, elevated kidney metabolism results in decreased tissue oxygen tension. The metabolic efficiency for solute transport (Qo2/TNa) varies not only between different nephron sites, but also under different conditions of fluid homeostasis and disease. Contributing mechanisms include the presence of different Na+ transporters, different levels of oxidative stress and segmental tubular dysfunction. Sustained hyperglycaemia results in increased kidney Qo2, partly due to mitochondrial dysfunction and reduced electrolyte transport efficiency. This results in intrarenal tissue hypoxia because the increased Qo2 is not matched by a similar increase in O2 delivery. Hypertension leads to renal hypoxia, mediated by increased angiotensin receptor tonus and oxidative stress. Reduced uptake in the proximal tubule increases load to the thick ascending limb. There, the increased load is reabsorbed, but at greater O2 cost. The combination of hypertension, angiotensin II and oxidative stress initiates events leading to renal damage and reduced function. Tissue hypoxia is now recognized as a unifying pathway to chronic kidney disease. We have gained good knowledge about major changes in O2 metabolism occurring in diabetic and hypertensive kidneys. However, further efforts are needed to elucidate how these alterations can be prevented or reversed before translation into clinical practice.
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| 49. |
- Hanson, Lars, et al.
(författare)
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ANNIE, a Tool for Integrating Ergonomics in the Design of Car Interiors
- 2000
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Ingår i: SAE Transactions – Journal of Materials and Manufacturing. Technical Paper 1999-01-3372. Reprinted From: Proceedings of the 1999 SAE Southern Automotive Manufacturing.. ; , s. 1-11
-
Konferensbidrag (refereegranskat)abstract
- An example of a result from a long-term cooperation with Lund University (together with professor Roland Akselsson at the Department for Work Environment) there some of the authors (Engström) gained extensive grants (Wallenberg Stifelsen regarding equipment as well as other founding from e.g. the Swedish Work Environment Found). In this case the just mentioned EU-financing.
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| 50. |
- Henry, Carole, et al.
(författare)
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Monoclonal Antibody Responses after Recombinant Hemagglutinin Vaccine versus Subunit Inactivated Influenza Virus Vaccine : a Comparative Study
- 2019
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Ingår i: Journal of Virology. - : AMER SOC MICROBIOLOGY. - 0022-538X .- 1098-5514. ; 93:21
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Tidskriftsartikel (refereegranskat)abstract
- Vaccination is the best measure of protection against influenza virus infection. Vaccine-induced antibody responses target mainly the hemagglutinin (HA) surface glycoprotein, composed of the head and the stalk domains. Recently two novel vaccine platforms have been developed for seasonal influenza vaccination: a recombinant HA vaccine produced in insect cells (Flublok) and Flucelvax, prepared from virions produced in mammalian cells. In order to compare the fine specificity of the antibodies induced by these two novel vaccine platforms, we characterized 42 Flublok-induced monoclonal antibodies (MAbs) and 38 Flucelvax-induced MAbs for avidity, cross-reactivity, and any selectivity toward the head versus the stalk domain. These studies revealed that Flublok induced a greater proportion of MAbs targeting epitopes near the receptor-binding domain on HA head (hemagglutinin inhibition-positive MAbs) than Flucelvax, while the two vaccines induced similar low frequencies of stalk-reactive MAbs. Finally, mice immunized with Flublok and Flucelvax also induced similar frequencies of stalk-reactive antibody-secreting cells, showing that HA head immunodominance is independent of immune memory bias. Collectively, our results suggest that these vaccine formulations are similarly immunogenic but differ in the preferences of the elicited antibodies toward the receptor-binding domain on the HA head.IMPORTANCE: There are ongoing efforts to increase the efficacy of influenza vaccines and to promote production strategies that can rapidly respond to newly emerging viruses. It is important to understand if current alternative seasonal vaccines, such as Flublok and Flucelvax, that use alternate production strategies can induce protective influenza-specific antibodies and to evaluate what type of epitopes are targeted by distinct vaccine formulations.
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