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  • Peden, John F., et al. (författare)
  • A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
  • 2011
  • Ingår i: Nature Genetics. - 1061-4036. ; 43:4, s. 339-344
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
  • Angelstam, Per, et al. (författare)
  • Evidence-Based Knowledge Versus Negotiated Indicators for Assessment of Ecological Sustainability:
  • 2013
  • Ingår i: Ambio. - 0044-7447. ; 42:2, s. 229-240
  • Tidskriftsartikel (refereegranskat)abstract
    • Assessing ecological sustainability involves monitoring of indicators and comparison of their states with performance targets that are deemed sustainable. First, a normative model was developed centered on evidence-based knowledge about (a) forest composition, structure, and function at multiple scales, and (b) performance targets derived by quantifying the habitat amount in naturally dynamic forests, and as required for presence of populations of specialized focal species. Second, we compared the Forest Stewardship Council (FSC) certification standards' ecological indicators from 1998 and 2010 in Sweden to the normative model using a Specific, Measurable, Accurate, Realistic, and Timebound (SMART) indicator approach. Indicator variables and targets for riparian and aquatic ecosystems were clearly under-represented compared to terrestrial ones. FSC's ecological indicators expanded over time from composition and structure towards function, and from finer to coarser spatial scales. However, SMART indicators were few. Moreover, they poorly reflected quantitative evidence-based knowledge, a consequence of the fact that forest certification mirrors the outcome of a complex social negotiation process.
  • Evans, Susan, et al. (författare)
  • Targeting Free Prostate-Specific Antigen for In Vivo Imaging of Prostate Cancer Using a Monoclonal Antibody Specific for Unique Epitopes Accessible on Free Prostate-Specific Antigen Alone.
  • 2012
  • Ingår i: Cancer biotherapy & radiopharmaceuticals. - Mary Ann Liebert. - 1557-8852. ; 27:4, s. 243-251
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected (125)I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting (125)I-labeled PSA30. Tissue uptake of (125)I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, (18)F-fluoro-deoxy-glucose ((18)F-FDG) or (18)F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high (125)I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either (18)F-FDG or (18)F-choline. Biodistribution of (125)I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24-48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.
  • Axelsson, Petter, et al. (författare)
  • Leaf litter from insect-resistant transgenic trees causes changes in aquatic insect community composition
  • 2011
  • Ingår i: Journal of Applied Ecology. - Malden : Wiley-Blackwell. - 0021-8901. ; 48:6, s. 1472-1479
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. Recent research has addressed how transgenic residues fromarable crops may influence adjacent waterways, aquatic consumers and important ecosystem processes such as litter breakdown rates. With future applications of transgenic plants in forestry, such concerns may apply to forest stream ecosystems. Before any large-scale release of genetically modified (GM) trees, it is therefore imperative to evaluate the effects of genetic modifications in trees on such ecosystems. 2. We conducted decomposition experiments under natural stream conditions using leaf litter from greenhouse grown GM trees (Populus tremula x Populus tremuloides) that express Bacillus thuringiensis (Bt) toxins (cry3Aa; targeting coleopteran leaf-feeding beetles) to examine the hypothesis that GM trees would affect litter decomposition rates and/or the aquatic arthropod community that colonizes and feeds on leaf litter in streams. 3. We show that two independent transformations of isogenic Populus trees to express Bt toxins caused similar changes to the composition of aquatic insects colonizing the leaf litter, ultimately manifested in a 25% and 33% increases in average insect abundance. 4. Measurements of 24 phenolic compounds as well as nitrogen (N) and carbon (C) in the litter did not significantly differ among modified and wild-type trees and were thus not sufficient to explain these differences in the insect assemblage. 5. Decomposition rates were comparable among litter treatments suggesting that the normal suite of leaf traits influencing decomposition was similar among litter treatments and that the shredding functions of the community were maintained despite the changes in insect community composition. 6. Synthesis and applications. We report that leaf litter from GM trees affected the composition of aquatic insect communities that colonized litter under natural stream conditions. This suggests that forest management using GM trees may affect adjacent waterways in unanticipated ways, which should be considered in future commercial applications of GM trees. We also argue that studies at different scales (e.g. species, communities and ecosystems) will be needed for a full understanding of the environmental effects of Bt plants.
  • Axelsson, Petter, et al. (författare)
  • Leaf ontogeny interacts with Bt modification to affect innate resistance in GM aspens
  • 2011
  • Ingår i: Chemoecology. - 0937-7409. ; 21:3, s. 161-169
  • Tidskriftsartikel (refereegranskat)abstract
    • Bioassays with a non-target slug (Deroceras spp.) and chemical analyses were conducted using leaf tissue from already existing genetically modified insect-resistant aspen trees to examine whether genetic modifications to produce Bacillus thuringiensis (Bt) toxins could affect plant phytochemistry, which in turn might influence plant-herbivore interactions. Three major patterns emerged. First, two independent modifications for Bt resistance affected the phytochemical profiles of leaves such that both were different from the isogenic wild-type (Wt) control leaves, but also different from each other. Among the contributors to these differences are substances with a presumed involvement in resistance, such as salicortin and soluble condensed tannins. Second, bioassays with one Bt line suggest that the modification somehow affected innate resistance ("Innate" is used here in opposition to the "acquired" Bt resistance) in ways such that slugs preferred Bt over Wt leaves. Third, the preference test suggests that the innate resistance in Bt relative to Wt plants may not be uniformly expressed throughout the whole plant and that leaf ontogeny interacts with the modification to affect resistance. This was manifested through an ontogenetic determined increase in leaf consumption that was more than four times higher in Bt compared to Wt leaves. Our result are of principal importance, as these indicate that genetic modifications can affect innate resistance and thus non-target herbivores in ways that may have commercial and/or environmental consequences. The finding of a modification-ontogeny interaction effect on innate resistance may be especially important in assessments of GM plants with a long lifespan such as trees.
  • Bill-Axelson, A, et al. (författare)
  • Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
  • 2008
  • Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 100:16, s. 1144-54
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up. METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided. RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001). CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
  • Dahlgren, Anders, et al. (författare)
  • Planning Rescue Services with Non-Stationary Rescue Units
  • 2009
  • Ingår i: Fire Technology. - Springer Netherlands. - 0015-2684. ; 45:3, s. 239-255
  • Tidskriftsartikel (refereegranskat)abstract
    • Geographical accessibility is fundamental when planning rescue services. At present there are several programs for computing the accessibility of stationary rescue units. This study suggests a method for evaluating geographic accessibility in scenarios containing also non-stationary units. The method supports the planning process by matching the risk of an incident occurring with the rescue units’ capabilities and accessibility. The method is implemented in the computer program Rescue Unit Planner. The result of the analysis is presented in thematic maps and graphs as level of coverage, mean response time and concentration. The method and the computer program have been evaluated in two case studies: one urban area in southern Sweden and one rural area in northern Sweden. The case studies show that that this method can be useful in the rescue service planning process.
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