| 43561. |
- Lang Kuhs, Krystle A, et al.
(författare)
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Human Papillomavirus 16 E6 Antibodies in Individuals without Diagnosed Cancer : A Pooled Analysis
- 2015
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 24:4, s. 683-689
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The increasing incidence of oropharyngeal cancer in many developed countries has been attributed to human papillomavirus type 16 (HPV16) infections. Recently, HPV16 E6 serology has been identified as a promising early marker for oropharyngeal cancer. Therefore, characterization of HPV16 E6 seropositivity among individuals without cancer is warranted.METHODS: A total of 4,666 controls were pooled from several studies of cancer and HPV seropositivity, all tested within the same laboratory. HPV16 E6 seropositive controls were classified as having (i) moderate [mean fluorescent intensity (MFI) ≥ 484 and <1,000] or (ii) high seroreactivity (MFI ≥ 1,000). Associations of moderate and high HPV16 E6 seroreactivity with (i) demographic risk factors; and seropositivity for (ii) other HPV16 proteins (E1, E2, E4, E7, and L1), and (iii) E6 proteins from non-HPV16 types (HPV6, 11, 18, 31, 33, 45, and 52) were evaluated.RESULTS: Thirty-two (0.7%) HPV16 E6 seropositive controls were identified; 17 (0.4%) with moderate and 15 (0.3%) with high seroreactivity. High HPV16 E6 seroreactivity was associated with former smoking [odds ratio (OR), 5.5; 95% confidence interval (CI), 1.2-51.8], and seropositivity against HPV16 L1 (OR, 4.8; 95% CI, 1.3-15.4); E2 (OR, 7.7; 95% CI, 1.4-29.1); multiple HPV16 proteins (OR, 25.3; 95% CI, 2.6-119.6 for three HPV16 proteins beside E6) and HPV33 E6 (OR, 17.7; 95% CI, 1.9-81.8). No associations were observed with moderate HPV16 E6 seroreactivity.CONCLUSIONS: High HPV16 E6 seroreactivity is rare among individuals without diagnosed cancer and was not explained by demographic factors.IMPACT: Some HPV16 E6 seropositive individuals without diagnosed HPV-driven cancer, especially those with seropositivity against other HPV16 proteins, may harbor a biologically relevant HPV16 infection.
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| 43562. |
- Lang, Lisa, et al.
(författare)
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SOD1 aggregation in ALS mice shows simplistic test tube behavior
- 2015
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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. ; 112:32, s. 9878-9883
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Tidskriftsartikel (refereegranskat)abstract
- A longstanding challenge in studies of neurodegenerative disease has been that the pathologic protein aggregates in live tissue are not amenable to structural and kinetic analysis by conventional methods. The situation is put in focus by the current progress in demarcating protein aggregation in vitro, exposing new mechanistic details that are now calling for quantitative in vivo comparison. In this study, we bridge this gap by presenting a direct comparison of the aggregation kinetics of the ALS-associated protein superoxide dismutase 1 (SOD1) in vitro and in transgenic mice. The results based on tissue sampling by quantitative antibody assays show that the SOD1 fibrillation kinetics in vitro mirror with remarkable accuracy the spinal cord aggregate buildup and disease progression in transgenic mice. This similarity between in vitro and in vivo data suggests that, despite the complexity of live tissue, SOD1 aggregation follows robust and simplistic rules, providing new mechanistic insights into the ALS pathology and organism-level manifestation of protein aggregation phenomena in general.
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| 43563. |
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| 43564. |
- Lange, Bettina, et al.
(författare)
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New forms of European Union governance in the education sector? : A preliminary analysis of the Open Method of Coordination
- 2007
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Ingår i: European Educational Research Journal. - Oxford, United Kingdom : Symposium Journals Ltd. - 1474-9041. ; 6:4, s. 321-335
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Tidskriftsartikel (refereegranskat)abstract
- This article critically explores how a new form of European Union (EU) governance - the open method of coordination (OMC) - impinges on education policies. The first part discusses three key characteristics of the OMC, in particular its flexibility, reflexivity and reliance on the techniques of new public management. It also outlines briefly why the OMC is being applied to EU education policy. The second and main part of the article develops a critical analysis of the OMC in education by questioning to what extent it can be considered as a new form of EU governance and with what vision of Social Europe it is associated. Most importantly, the second part argues that there may be significant potential for the politicization of mutual policy learning in the context of OMC education measures.
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| 43565. |
- Lange, Bettina, et al.
(författare)
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Policy learning and governance of education policy in the EU
- 2010
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Ingår i: Journal of education policy. - : Taylor & Francis Group. - 0268-0939 .- 1464-5106. ; 25:4, s. 443-463
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Tidskriftsartikel (refereegranskat)abstract
- Open methods for coordinating (OMC) education policies in the EU rely on a number of techniques, one of which is policy learning. This article examines how policy learning and governance transform each other. More specifically, policy‐learning in the education OMC becomes differentiated into four distinct learning styles: mutual, competitive, surface and imperialistic learning. While they overlap with some forms of policy learning discussed in the literature, they are also different by focusing upon interactions and political dynamics between the European Commission and the member states. In seeking to understand how governing through learning occurs, we argue that any 'impact' of EU‐level policy‐learning is co‐constructed by both the European Commission and the member states. The analysis of this article is grounded in a discourse analytical and institutionalist perspective. It draws on qualitative data derived from semi‐structured interviews with officials from the Directorate General for Education and Culture in the European Commission and on EU documents generated during policy‐learning activities.
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| 43566. |
- Lange, Dale J., et al.
(författare)
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Pyrimethamine decreases levels of SOD1 in leukocytes and cerebrospinal fluid of ALS patients : A phase I pilot study
- 2013
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Ingår i: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. - London : Informa Healthcare. - 2167-8421 .- 2167-9223. ; 14:3, s. 199-204
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Tidskriftsartikel (refereegranskat)abstract
- The mutated SOD1 protein appears to have a gene dose-dependent effect on the severity and progression of ALS. Lowering of SOD1 protein levels might reduce severity and progression of the disease. The antimalarial drug pyrimethamine (PYR) was identified to cause a dose-dependent reduction in SOD1 protein levels in human cells in vitro. To determine if there was a similar effect in humans, we performed a phase I pilot study in 16 ALS patients with SOD1 mutations, 18 weeks in duration. Blood samples were obtained during all visits. The actin normalized leukocyte SOD1 levels were analyzed using Western blot. SOD1 content in the cerebrospinal fluid (CSF) was determined by ELISA and the SOD1 enzymic activity by spectrophotometric analysis using KO2. Clinical assessment of disease severity was assessed using Appel ALS scale and ALSFRS-R. The leukocyte SOD1 levels showed a significant reduction (p < 0.0001) by the third study visit and this reduction was sustained throughout the remainder of the study. CSF also showed a decrease in SOD1 protein content and enzymic activity in the two patients so tested. Thus, PYR use may be associated with a reduction in SOD1 in ALS patients. The significance is uncertain and further detailed study is required.
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| 43567. |
- Lange, Dale J., et al.
(författare)
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Pyrimethamine Significantly Lowers Cerebrospinal Fluid Cu/Zn Superoxide Dismutase in Amyotrophic Lateral Sclerosis Patients with SOD1 Mutations
- 2017
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Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 81:6, s. 837-848
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). Methods: A multicenter (5 sites), open-label, 9-month-duration, dose-ranging study was undertaken to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1. All participants underwent 3 lumbar punctures, blood draw, clinical assessment of strength, motor function, quality of life, and adverse effect assessments. SOD1 levels were measured in erythrocytes and CSF. Pyrimethamine was measured in plasma and CSF. Appel ALS score, ALS Functional Rating Scale-Revised, and McGill Quality of Life Single-Item Scale were measured at screening, visit 6, and visit 9. Results: We enrolled 32 patients; 24 completed 6 visits (18 weeks), and 21 completed all study visits. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit 6 (p<0.001) with a mean reduction of 13.5% (95% confidence interval [CI] 58.4-18.5) and at visit 9 (p<0.001) with a mean reduction of 10.5% (95% CI55.2-15.8). Interpretation: Pyrimethamine is safe and well tolerated in ALS. Pyrimethamine is capable of producing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by different SOD1 mutations. Further long-term studies are warranted to assess clinical efficacy.
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| 43568. |
- Lange, Katharina, et al.
(författare)
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Light, nutrients and grazing interact to determine stream diatom community composition and functional group structure
- 2011
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070 .- 1365-2427. ; 56:2, s. 264-278
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Tidskriftsartikel (refereegranskat)abstract
- P>1. Benthic algal communities are shaped by the availability of nutrients and light and by herbivore consumption. Many studies have examined how one of these factors affects algal communities, but studies simultaneously addressing all three are rare. 2. We investigated the effects of nutrients, light and a herbivore (the snail Potamopyrgus antipodarum) on benthic stream algae in a fully factorial experiment in 128 circular streamside channels. Four nutrient levels (none added to highly enriched), four snail grazing pressures (no snails to 777 individuals m-2) and two light levels (ambient and 65% reduced) were applied. Colonising algae were dominated by diatoms (Bacillariophyta), which were determined to species using acid-cleaned samples and assigned to functional groups according to their physiognomic growth form. 3. Diatom community structure changed considerably in response to our manipulations. Light had the strongest influence (as indicated by manova effect size), whereas nutrients had an intermediate effect and grazing was fairly weak. Relative abundances of six common diatom taxa decreased under reduced light, whereas five others became more prevalent. Eight taxa benefitted from nutrient enrichment, while three became rarer. Grazing affected the relative density of only one common taxon, which increased at higher grazing pressure. 4. Diatom functional groups also responded strongly. 'Low profile' taxa dominated at low resource levels (nutrients and especially light), whereas 'high profile' and 'motile' taxa became markedly more prevalent at higher resource levels. 5. Two-way interactions between experimental factors were quite common. For example, Planothidium lanceolatum and Rossithidium petersenii responded more strongly to nutrient enrichment at reduced than at ambient light, whereas Cocconeis placentula responded more strongly at ambient light. For diatom functional groups, the benefit of nutrient enrichment for 'motile' diatoms was greater at ambient than at reduced light. 6. Our results imply that multifactor experiments are required to determine the main forces driving the composition of benthic algal communities. Further, our findings highlight the considerable potential of using functional algal groups as indicators of changing environmental conditions to complement the traditional taxonomic approach.
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| 43569. |
- Lange, Martin, et al.
(författare)
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The Barents Sea impact study (BASIS) : methodology and first results
- 2003
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Ingår i: Contintental Shelf Research. - : Elsevier. - 0278-4343. ; 23:17-19, s. 1673-1694
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Tidskriftsartikel (refereegranskat)abstract
- Global and climate changes are subject to scientific, societal and political debates. Recent observational evidence and results of global climate models have identified the circumpolar North as a region particularly susceptible to future climate change. To understand and assess the consequences of these changes for environmental and societal components of the European Arctic, the Barents Sea Impact Study (BASIS), an EU-funded integrated regional impact study (IRIS) has been carried out (ENV4-CT-97-0637). In common with global integrated assessments (IAs), IRISs also take a holistic view on climate change and its impact. Contrary to IAs, however, IRISs adopt a regional to sub-regional spatial scale. BASIS was carried out by an interdisciplinary team of specialists from 13 institutions in 6 countries. Major results pertain to impacts of possible climate change on marine and terrestrial ecosystems, freshwater hydrology, marine trace gas budgets, forestry and fishery. However, in this paper we focus on the major methodological aspects of an IRIS in general and on methods applied in BASIS in particular.
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| 43570. |
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