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- Abe, O, et al.
(author)
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Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
- 2005
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In: The Lancet. - 1474-547X. ; 365:9472, s. 1687-1717
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Journal article (peer-reviewed)abstract
- Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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- Jiang, X., et al.
(author)
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Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7x10(-9) at rs8018720 in SEC23A, and P = 1.9x10(-14) at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
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- Bergersen, L H, et al.
(author)
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Immunogold detection of L-glutamate and D-serine in small synaptic-like microvesicles in adult hippocampal astrocytes.
- 2012
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In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 22:7, s. 1690-1697
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Journal article (peer-reviewed)abstract
- Glutamate and the N-methyl-D-aspartate receptor ligand D-serine are putative gliotransmitters. Here, we show by immunogold cytochemistry of the adult hippocampus that glutamate and D-serine accumulate in synaptic-like microvesicles (SLMVs) in the perisynaptic processes of astrocytes. The estimated concentration of fixed glutamate in the astrocytic SLMVs is comparable to that in synaptic vesicles of excitatory nerve terminals (≈ 45 and ≈ 55 mM, respectively), whereas the D-serine level is about 6 mM. The vesicles are organized in small spaced clusters located near the astrocytic plasma membrane. Endoplasmic reticulum is regularly found in close vicinity to SLMVs, suggesting that astrocytes contain functional nanodomains, where a local Ca(2+) increase can trigger release of glutamate and/or D-serine.
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- Hultborn, Ragnar, 1946, et al.
(author)
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Efficacy of pamidronate in breast cancer with bone metastases: a randomized, double-blind placebo-controlled multicenter study
- 1999
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In: Anticancer Res. - 0250-7005. ; 19:4C, s. 3383-92
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Journal article (peer-reviewed)abstract
- PURPOSE: To evaluate the efficacy of pamidronate 60 mg i.v. q 4 weeks in women with advanced breast cancer with skeletal metastases. PATIENTS AND METHODS: 404 woman with skeletal metastases from breast cancer in Sweden and Norway were included in a randomized, placebo-controlled, multicenter study. Except for the study medication, other palliative treatment was chosen at the discretion of the physician. Skeletal related events, i.e. increased pain, treatment of hypercalcemia, pathologic fractures of long bones or pelvis, paralyses due to vertebral compression, palliative radiotherapy for skeletal metastases, surgery on bone and change of antitumor therapy were recorded every third month as well as a self-estimated pain-score using visual Analog Scales and analgesic consumption. RESULTS: There was a significantly increased time to progression of pain (p < 0.01), to hypercalcemic events (p < 0.05) as well as for the cumulative number of skeletal related events (p < 0.01) in favor for the pamidronate group. No statistically significant reduction of pathologic fractures of long bones or pelvis, or pareses due to vertebral compression occurred. No statistically significant differences were found for the need of radiotherapy and surgery on bone. The pamidronate group faired better regarding performance status (p < 0.05). There was a statistically not significant lower consumption of opioid analgesics in the pamidronate group (p = 0.14). CONCLUSION: Pamidronate 60 mg i.v. q 4 weeks reduces skeletal events and improves the quality of life in women with bone metastases from breast cancer.
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- Krause-Jensen, D, et al.
(author)
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Nordic Blue Carbon Ecosystems: Status and Outlook
- 2022
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
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Research review (peer-reviewed)abstract
- Vegetated coastal and marine habitats in the Nordic region include salt marshes, eelgrass meadows and, in particular, brown macroalgae (kelp forests and rockweed beds). Such habitats contribute to storage of organic carbon (Blue Carbon – BC) and support coastal protection, biodiversity and water quality. Protection and restoration of these habitats therefore have the potential to deliver climate change mitigation and co-benefits. Here we present the existing knowledge on Nordic BC habitats in terms of habitat area, C-stocks and sequestration rates, co-benefits, policies and management status to inspire a coherent Nordic BC roadmap. The area extent of BC habitats in the region is incompletely assessed, but available information sums up to 1,440 km2 salt marshes, 1,861 (potentially 2,735) km2 seagrass meadows, and 16,532 km2 (potentially 130,735 km2, including coarse Greenland estimates) brown macroalgae, yielding a total of 19,833 (potentially 134,910) km2. Saltmarshes and seagrass meadows have experienced major declines over the past century, while macroalgal trends are more diverse. Based on limited salt marsh data, sediment C-stocks average 3,311 g Corg m-2 (top 40-100 cm) and sequestration rates average 142 g Corg m-2 yr-1. Eelgrass C-stocks average 2,414 g Corg m-2 (top 25 cm) and initial data for sequestration rates range 5-33 g Corg m-2, quantified for one Greenland site and one short term restoration. For Nordic brown macroalgae, peer-reviewed estimates of sediment C-stock and sequestration are lacking. Overall, the review reveals substantial Nordic BC-stocks, but highlights that evidence is still insufficient to provide a robust estimate of all Nordic BC-stocks and sequestration rates. Needed are better quantification of habitat area, C-stocks and fluxes, particularly for macroalgae, as well as identification of target areas for BC management. The review also points to directives and regulations protecting Nordic marine vegetation, and local restoration initiatives with potential to increase C-sequestration but underlines that increased coordination at national and Nordic scales and across sectors is needed. We propose a Nordic BC roadmap for science and management to maximize the potential of BC habitats to mitigate climate change and support coastal protection, biodiversity and additional ecosystem functions.
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- Kvile, KØ, et al.
(author)
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Kelp Forest Distribution in the Nordic Region.
- 2022
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In: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
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Journal article (peer-reviewed)abstract
- Kelp forests are productive coastal ecosystems that provide a range of ecosystem services. Mapping the distribution and area occupied by kelp forests is a critical step to identify their ecosystem functions and services, including their role in the carbon cycle, and to detect changes in their distribution. We compiled quantitative data of the dominant genera Laminaria and Saccharina across the Nordic region, allowing us to separate kelp forests (areas with dense or moderately dense kelp coverage) from occurrences of single or few individuals. By fitting boosted regression trees to the compiled data, we modelled and predicted the distribution of kelp forests across the Nordic region. Despite the large scale of the analyses, the models captured well the kelps’ environmental affinities and predicted the presence of kelp forests with high accuracy. Dense kelp forests are found along the rocky shores of all the Nordic countries, except in the brackish Baltic Sea, with largest areas in Norway, Greenland and Iceland. The results of this study set the scene for future studies on the importance of kelp forests in the Nordic region, including their contribution to the marine carbon budget.
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- Luo, Y. -W, et al.
(author)
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Database of diazotrophs in global ocean : abundance, biomass and nitrogen fixation rates
- 2012
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In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 4:1, s. 47-73
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Journal article (peer-reviewed)abstract
- Marine N-2 fixing microorganisms, termed di-azotrophs, are a key functional group in marine pelagic ecosystems. The biological fixation of dinitrogen ( N-2) to bioavailable nitrogen provides an important new source of nitrogen for pelagic marine ecosystems and influences primary productivity and organic matter export to the deep ocean. As one of a series of efforts to collect biomass and rates specific to different phytoplankton functional groups, we have constructed a database on diazotrophic organisms in the global pelagic upper ocean by compiling about 12 000 direct field measurements of cyanobacterial diazotroph abundances (based on microscopic cell counts or qPCR assays targeting the nifH genes) and N-2 fixation rates. Biomass conversion factors are estimated based on cell sizes to convert abundance data to diazotrophic biomass. The database is limited spatially, lacking large regions of the ocean especially in the Indian Ocean. The data are approximately log-normal distributed, and large variances exist in most sub-databases with non-zero values differing 5 to 8 orders of magnitude. Reporting the geometric mean and the range of one geometric standard error below and above the geometric mean, the pelagic N-2 fixation rate in the global ocean is estimated to be 62 (52-73) Tg Nyr(-1) and the pelagic diazotrophic biomass in the global ocean is estimated to be 2.1 (1.4-3.1) Tg C from cell counts and to 89 (43-150) Tg C from nifH- based abundances. Reporting the arithmetic mean and one standard error instead, these three global estimates are 140 +/- 9.2 Tg Nyr(-1), 18 +/- 1.8 Tg C and 590 +/- 70 Tg C, respectively. Uncertainties related to biomass conversion factors can change the estimate of geometric mean pelagic diazotrophic biomass in the global ocean by about +/- 70 %. It was recently established that the most commonly applied method used to measure N-2 fixation has underestimated the true rates. As a result, one can expect that future rate measurements will shift the mean N-2 fixation rate upward and may result in significantly higher estimates for the global N-2 fixation. The evolving database can nevertheless be used to study spatial and temporal distributions and variations of marine N-2 fixation, to validate geochemical estimates and to parameterize and validate biogeochemical models, keeping in mind that future rate measurements may rise in the future.
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- Ramirez-Llodra, E., et al.
(author)
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A snap shot of the short-term response of crustaceans to macrophyte detritus in the deep Oslofjord
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- A test deployment of a time-lapse camera lander in the deep Oslofjord (431 m) was used to obtain initial information on the response of benthic fauna to macroalgal debris. Three macroalgal species were used on the lander baited plate: Fucus serratus, Saccharina latissima and Laminaria hyperborea and observed during 41.5 hours. The deep-water shrimp Pandalus borealis were attracted to the macroalgae rapidly (3 min after the lander reached the seafloor), followed by amphipods. Shrimp abundances were significantly higher in areas covered by macroalgae compared to the adjacent seafloor and the number of shrimp visiting the macroalgae increased with time. Amphipods arrived 13 hours later and were observed mainly on decaying L. hyperborea. The abundance of amphipods on L. hyperborea increased rapidly, reaching a peak at 31 h after deployment. These initial observations suggest that debris from kelp forests and other macroalgal beds may play an important role in fuelling deep benthic communities in the outer Oslofjord and, potentially, enhance secondary production of commercial species such as P. borealis.
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- Aamodt, A., et al.
(author)
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Case-based reasoning for assessment and diagnosis of depression in palliative care
- 2010
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In: Proceedings - IEEE Symposium on Computer-Based Medical Systems. ; , s. 480-485
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Conference paper (peer-reviewed)abstract
- The goal of the research presented is to create a computational framework and system architecture for clinical decision support in palliative care. The application focused is the classification of depression. The method under investigation is case-based reasoning, motivated by the complexity of the domain and a lack of generalized principles of sufficient coverage and strength for diagnosis and treatment. A system architecture is described and exemplified through an implemented prototype. The outcome of the research so far is a system that captures the properties intended, and for which a clinical test set-up has been defined. © 2010 IEEE.
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- Espen Yttri, Karl, et al.
(author)
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Trends, composition, and sources of carbonaceous aerosol at the Birkenes Observatory, northern Europe, 2001-2018
- 2021
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 21:9, s. 7149-7170
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Journal article (peer-reviewed)abstract
- We present 18 years (2001-2018) of aerosol measurements, including organic and elemental carbon (OC and EC), organic tracers (levoglucosan, arabitol, mannitol, trehalose, glucose, and 2-methyltetrols), trace elements, and ions, at the Birkenes Observatory (southern Norway) - a site representative of the northern European region. The OC=EC (2001-2018) and the levoglucosan (2008-2018) time series are the longest in Europe, with OC=EC available for the PM10, PM2:5 (fine), and PM10-2:5 (coarse) size fractions, providing the opportunity for a nearly 2-decade-long assessment. Using positive matrix factorization (PMF), we identify seven carbonaceous aerosol sources at Birkenes: mineraldust- dominated aerosol (MIN), traffic/industry-like aerosol (TRA/IND), short-range-transported biogenic secondary organic aerosol (BSOASRT), primary biological aerosol particles (PBAP), biomass burning aerosol (BB), ammoniumnitrate- dominated aerosol (NH4NO3), and (one low carbon fraction) sea salt aerosol (SS). We observed significant (p < 0:05), large decreases in EC in PM10 (-3:9%yr-1) and PM2:5 (-4:2%yr-1) and a smaller decline in levoglucosan (-2:8%yr-1), suggesting that OC=EC from traffic and industry is decreasing, whereas the abatement of OC=EC from biomass burning has been slightly less successful. EC abatement with respect to anthropogenic sources is further supported by decreasing EC fractions in PM2:5 (-3:9%yr-1) and PM10 (-4:5%yr-1). PMF apportioned 72% of EC to fossil fuel sources; this was further supported by PMF applied to absorption photometer data, which yielded a two-factor solution with a low aerosol ngstr m exponent (AAED0.93) fraction, assumed to be equivalent black carbon from fossil fuel combustion (eBCFF), contributing 78% to eBC mass. The higher AAE fraction (AAED2.04) is likely eBC from BB (eBCBB). Source-receptor model calculations (FLEXPART) showed that continental Europe and western Russia were the main source regions of both elevated eBCBB and eBCFF. Dominating biogenic sources explain why there was no downward trend for OC. A relative increase in the OC fraction in PM2:5 (C3:2%yr-1) and PM10 (C2:4%yr-1) underscores the importance of biogenic sources at Birkenes (BSOA and PBAP), which were higher in the vegetative season and dominated both fine (53 %) and coarse (78 %) OC. Furthermore, 77 %-91% of OC in PM2:5, PM10-2:5, and PM10 was attributed to biogenic sources in summer vs. 22 %- 37% in winter. The coarse fraction had the highest share of biogenic sources regardless of season and was dominated by PBAP, except in winter. Our results show a shift in the aerosol composition at Birkenes and, thus, also in the relative source contributions. The need for diverse offline and online carbonaceous aerosol speciation to understand carbonaceous aerosol sources, including their seasonal, annual, and long-term variability, has been demonstrated.
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- Gundersen, OH, et al.
(author)
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Evaluation of the alcohol use disorders identification test and the drug use disorders identification test among patients at a Norwegian psychiatric emergency ward
- 2013
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In: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 19:5, s. 252-260
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Journal article (peer-reviewed)abstract
- High rates of substance use disorders (SUD) among psychiatric patients are well documented. This study explores the usefulness of the Alcohol Use Disorders Identification Test (AUDIT) and the Drug Use Disorders Identification Test (DUDIT) in identifying SUD in emergency psychiatric patients. Of 287 patients admitted consecutively, 256 participants (89%) were included, and 61-64% completed the questionnaires and the Mini-International Neuropsychiatric Interview (MINI), used as the reference standard. Both AUDIT and DUDIT were valid (area under the curve above 0.92) and reliable (Cronbach's alpha above 0.89) in psychotic and nonpsychotic men and women. The suitable cutoff scores for AUDIT were higher among the psychotic than nonpsychotic patients, with 12 versus 10 in men and 8 versus 5 in women. The suitable cutoff scores for DUDIT were 1 in both psychotic and nonpsychotic women, and 5 versus 1 in psychotic and nonpsychotic men, respectively. This study shows that AUDIT and DUDIT may provide precise information about emergency psychiatric patients' problematic alcohol and drug use.
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- Lokke, H, et al.
(author)
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Critical Loads
- 2000
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In: Arbejdsrapport fra DMU No. 121. ; , s. 1-48
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Conference paper (other academic/artistic)
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