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| 6. |
- Barrett, Jennifer H., et al.
(författare)
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Fine mapping of genetic susceptibility loci for melanoma reveals a mixture of single variant and multiple variant regions
- 2015
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 136:6, s. 1351-1360
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Tidskriftsartikel (refereegranskat)abstract
- At least 17 genomic regions are established as harboring melanoma susceptibility variants, in most instances with genome-wide levels of significance and replication in independent samples. Based on genome-wide single nucleotide polymorphism (SNP) data augmented by imputation to the 1,000 Genomes reference panel, we have fine mapped these regions in over 5,000 individuals with melanoma (mainly from the GenoMEL consortium) and over 7,000 ethnically matched controls. A penalized regression approach was used to discover those SNP markers that most parsimoniously explain the observed association in each genomic region. For the majority of the regions, the signal is best explained by a single SNP, which sometimes, as in the tyrosinase region, is a known functional variant. However in five regions the explanation is more complex. At the CDKN2A locus, for example, there is strong evidence that not only multiple SNPs but also multiple genes are involved. Our results illustrate the variability in the biology underlying genome-wide susceptibility loci and make steps toward accounting for some of the missing heritability. What's new? In genome-wide association studies, researchers identify genetic variants that frequently associate with a particular disease, though the variants identified may not contribute to the molecular cause of the disease. This study took a closer look at 17 regions associated with melanoma, fine mapping the regions both in people with melanoma and in healthy controls. Though single SNPs account for the association in some regions, they found that in a few regions, several SNPs - and possibly multiple genes - contributed to the association signal. These findings illustrate the importance of not overlooking the interaction between multiple genetic markers when conducting such studies.
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| 7. |
- Duffy, DL, et al.
(författare)
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Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 299-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.
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| 8. |
- Egry, I., et al.
(författare)
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Thermophysical properties of gamma-titanium aluminide : The European IMPRESS project
- 2007
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Ingår i: International journal of thermophysics. - : Springer Science and Business Media LLC. - 0195-928X .- 1572-9567. ; 28:3, s. 1026-1036
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of its 6th Framework Programme, the European Union funds the Integrated Project IMPRESS, related to industrial applications of Ti-Al and Ni-Al alloys. One central task of this project is the precise determination of the relevant thermophysical properties of selected alloys for both the solid and liquid phases. The properties to be measured include thermal data such as heat of fusion, specific heat, and thermal conductivity, as well as thermophysical and transport properties such as density, surface tension, and viscosity. In addition to conventional high-temperature equipment, containerless methods are used. This article introduces the IMPRESS project, and discusses the first results obtained to date.
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- Moorkens, E, et al.
(författare)
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The Expiry of Humira® Market Exclusivity and the Entry of Adalimumab Biosimilars in Europe: An Overview of Pricing and National Policy Measures
- 2021
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Ingår i: Frontiers in pharmacology. - : Frontiers Media SA. - 1663-9812. ; 11, s. 591134-
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Tidskriftsartikel (refereegranskat)abstract
- Background: From October 2018, adalimumab biosimilars could enter the European market. However, in some countries, such as Netherlands, high discounts reported for the originator product may have influenced biosimilar entry.Objectives: The aim of this paper is to provide a European overview of (list) prices of originator adalimumab, before and after loss of exclusivity; to report changes in the reimbursement status of adalimumab products; and discuss relevant policy measures.Methods: Experts in European countries received a survey consisting of three parts: 1) general financing/co-payment of medicines, 2) reimbursement status and prices of originator adalimumab, and availability of biosimilars, and 3) policy measures related to the use of adalimumab.Results: In May 2019, adalimumab biosimilars were available in 24 of the 30 countries surveyed. Following introduction of adalimumab biosimilars, a number of countries have made changes in relation to the reimbursement status of adalimumab products. Originator adalimumab list prices varied between countries by a factor of 2.8 before and 4.1 after loss of exclusivity. Overall, list prices of originator adalimumab decreased after loss of exclusivity, although for 13 countries list prices were unchanged. When reported, discounts/rebates on originator adalimumab after loss of exclusivity ranged from 0% to approximately 26% (Romania), 60% (Poland), 80% (Denmark, Italy, Norway), and 80–90% (Netherlands), leading to actual prices per pen or syringe between €412 (Finland) and €50 – €99 (Netherlands). To leverage competition following entry of biosimilar adalimumab, only a few countries adopted measures specifically for adalimumab in addition to general policies regarding biosimilars. In some countries, a strategy was implemented even before loss of exclusivity (Denmark, Scotland), while others did not report specific measures.Conclusion: Even though originator adalimumab is the highest selling product in the world, few countries have implemented specific policies and practices for (biosimilar) adalimumab. Countries with biosimilars on the market seem to have competition lowering list or actual prices. Reported discounts varied widely between countries.
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| 16. |
- Orr, Nick, et al.
(författare)
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Genome-wide association study identifies a common variant in RAD51B associated with male breast cancer risk
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:11, s. 1182-1184
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study of male breast cancer comprising 823 cases and 2,795 controls of European ancestry, with validation in independent sample sets totaling 438 cases and 474 controls. A SNP in RAD51B at 14q24.1 was significantly associated with male breast cancer risk (P = 3.02 x 10(-13); odds ratio (OR) = 1.57). We also refine association at 16q12.1 to a SNP within TOX3 (P = 3.87 x 10(-15); OR = 1.50).
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| 17. |
- Ricci, E., et al.
(författare)
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Thermophysical properties of Cu-based industrial alloys in the liquid phase
- 2009
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Ingår i: High Temperatures-High Pressures. - 0018-1544 .- 1472-3441. ; 38:1, s. 43-61
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Tidskriftsartikel (refereegranskat)abstract
- The thermophysical properties of Cu-based industrial alloys in the liquid phase have been determined in the framework of ThermoLab project. Four commercial copper alloys provided by one member of the industrial user group, Cu-Sn-X (X=P; Ti), Cu-Ni-Si and Cu-Ni-Si-Mg have been investigated by different European laboratories. The results of the ground-based experimental programme concerning classical high-temperature calorimetry, thermal diffusivity, density, surface tension and viscosity measurements were critically compared in order to improve the reliability of data and to identify, when possible, recommended values.
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| 20. |
- Barrett, Jennifer H., et al.
(författare)
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Genome-wide association study identifies three new melanoma susceptibility loci
- 2011
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:11, s. 1108-1113
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study for melanoma that was conducted by the GenoMEL Consortium. Our discovery phase included 2,981 individuals with melanoma and 1,982 study-specific control individuals of European ancestry, as well as an additional 6,426 control subjects from French or British populations, all of whom were genotyped for 317,000 or 610,000 single-nucleotide polymorphisms (SNPs). Our analysis replicated previously known melanoma susceptibility loci. Seven new regions with at least one SNP with P < 10(-5) and further local imputed or genotyped support were selected for replication using two other genome-wide studies (from Australia and Texas, USA). Additional replication came from case-control series from the UK and The Netherlands. Variants at three of the seven loci replicated at P < 10(-3): an SNP in ATM (rs1801516, overall P = 3.4 x 10(-9)), an SNP in MX2 (rs45430, P = 2.9 x 10-9) and an SNP adjacent to CASP8 (rs13016963, P = 8.6 x 10(-10)). A fourth locus near CCND1 remains of potential interest, showing suggestive but inconclusive evidence of replication (rs1485993, overall P = 4.6 x 10(-7) under a fixed-effects model and P = 1.2 x 10(-3) under a random-effects model). These newly associated variants showed no association with nevus or pigmentation phenotypes in a large British case-control series.
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| 21. |
- Bishop, D. Timothy, et al.
(författare)
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Genome-wide association study identifies three loci associated with melanoma risk
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:8, s. 920-925
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study of melanoma conducted by the GenoMEL consortium based on 317K tagging SNPs for 1,650 selected cases and 4,336 controls, with replication in an additional two cohorts (1,149 selected cases and 964 controls from GenoMEL, and a population-based case-control study in Leeds of 1,163 cases and 903 controls). The genome-wide screen identified five loci with genotyped or imputed SNPs reaching P < 5 x 10(-7). Three of these loci were replicated: 16q24 encompassing MC1R (combined P = 2.54 x 10(-27) for rs258322), 11q14-q21 encompassing TYR (P = 2.41 x 10(-14) for rs1393350) and 9p21 adjacent to MTAP and flanking CDKN2A (P = 4.03 x 10(-7) for rs7023329). MC1R and TYR are associated with pigmentation, freckling and cutaneous sun sensitivity, well-recognized melanoma risk factors. Common variants within the 9p21 locus have not previously been associated with melanoma. Despite wide variation in allele frequency, these genetic variants show notable homogeneity of effect across populations of European ancestry living at different latitudes and show independent association to disease risk.
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| 22. |
- Egry, I., et al.
(författare)
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Thermophysical properties of liquid Al-Ni alloys
- 2009
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Ingår i: High Temperatures-High Pressures. - 0018-1544 .- 1472-3441. ; 38:4, s. 343-351
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Tidskriftsartikel (refereegranskat)abstract
- Within the Integrated Project IMPRESS, funded by the EU, thermophysi cal properties of two Al-Ni alloys have been investigated: Raney-nickel (Al-31.5at%Ni) and Al-25at%Ni, corresponding to the intermetallic phase Al3Ni. Transition temperatures, latent heat, heat capacity, density and electrical resistivity were measured in the solid and liquid phases. In addition, surface tension and viscosity of the melts were also determined. All quantities have been obtained as a function of temperature, in some cases also in the undercooled liquid. In this paper, we report on results obtained for the liquid phase using advanced container-based and containerless measurement methods. The obtained data yield a comprehensive characterisation of this technologically relevant class of alloys.
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| 26. |
- Iles, Mark M., et al.
(författare)
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A variant in FTO shows association with melanoma risk not due to BMI
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:4, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- We report the results of an association study of melanoma that is based on the genome-wide imputation of the genotypes of 1,353 cases and 3,566 controls of European origin conducted by the GenoMEL consortium. This revealed an association between several SNPs in intron 8 of the FTO gene, including rs16953002, which replicated using 12,313 cases and 55,667 controls of European ancestry from Europe, the USA and Australia (combined P = 3.6 x 10(-12), per-allele odds ratio for allele A = 1.16). In addition to identifying a new melanomasusceptibility locus, this is to our knowledge the first study to identify and replicate an association with SNPs in FTO not related to body mass index (BMI). These SNPs are not in intron 1 (the BMI-related region) and exhibit no association with BMI. This suggests FTO's function may be broader than the existing paradigm that FTO variants influence multiple traits only through their associations with BMI and obesity.
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| 28. |
- Lepara, O., et al.
(författare)
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Serum levels of non-enzymatic antioxidants in female dementia patients with respect to the degree of cognitive impairment
- 2021
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Ingår i: GLASNIK HEMICARA I TEHNOLOGA BOSNE I HERCEGOVINE. - 0367-4444. ; :56, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the correlation between the severity of cognitive impairment in Alzheimer's disease (AD) and vascular dementia (VD) and the serum antioxidant status of uric acid (UA), albumin (ALB) and bilirubin (BIL) in female patients. The cross-sectional study included 90 subjects, aged >= 65, divided into three groups: 30 patients with AD, 30 patients with VD and 30 control subjects. For cognitive assessment, all participants underwent the Montreal Cognitive Assessment (MoCA). Serum concentrations of ALB, UA and BIL were determined spectrophotometrically. The AD patients had a significant decrease of UA and increase of serum BIL. Upon stratification according to the degree of cognitive impairment, lower UA concentrations were found in patients with severe cognitive impairment, whereas increased BIL was found in patients with moderate cognitive impairment. Patients with VD were characterized by hypoalbuminemia and upon stratification this finding was evident among patients with severe cognitive impairment. The MoCA score correlated positively with BIL in AD patients. The obtained data supports the protective role of serum antioxidants in the pathogenesis of dementia. Further on, we suggest further longitudinal research to confirm the combined use of these parameters as potential biomarkers in AD and VD.
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| 31. |
- Ricci, E., et al.
(författare)
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Density, surface tension, and viscosity of CMSX-((R)) superalloy
- 2007
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Ingår i: International journal of thermophysics. - : Springer Science and Business Media LLC. - 0195-928X .- 1572-9567. ; 28:4, s. 1304-1321
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Tidskriftsartikel (refereegranskat)abstract
- The surface tension, density, and viscosity of the Ni-based superalloy CMSX-4((R)) have been determined in the temperature ranges of 1,650-1,850 K, 1,650-1,950 K, and 1,623-1,800 K, respectively. Each property has been measured in parallel by different techniques at different participating laboratories, and the results are compared with the aim to improve the reliability of data and to identify recommended values. The following relationships have been proposed: density-rho (T) [kg.m(-3)] = 7,876 - 1.23(T - 1,654 K); surface tension-gamma (T) [mN.m(-1)] = 1,773 - 0.56 (T - 1, 654 K); viscosity-eta (T) [mPa.s] = 8.36 - 1.82 x 10(-2)(T - 1,654 K). For a comparison, surface-tension measurements on the Al-88.6 at% Ni liquid alloy with the same Al-content as the CMSX-4((R)) alloy were also performed. In addition, the surface tension and density have been theoretically evaluated by different models, and subsequently compared with new experimental data as well as with those reported in the literature. The surface-tension experimental data for the liquid CMSX-4((R)) alloy were found to be close to that of the A1-88.6 at% Ni alloy which is consistent with results from the compound formation model (CFM).
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| 33. |
- Wacker, A, et al.
(författare)
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Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy
- 2020
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 48:22, s. 12415-12435
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Tidskriftsartikel (refereegranskat)abstract
- The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
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