| 1. |
- Kiemeney, Lambertus A, et al.
(författare)
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A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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| 2. |
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| 3. |
- Nilsson, Anders, et al.
(författare)
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Environmental Conditions and Intraspecific Interference: Unexpected Effects of Turbidity on Pike (Esox lucius) Foraging
- 2009
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Ingår i: Ethology. - : Wiley. - 1439-0310 .- 0179-1613. ; 115:1, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- Interference among predators decreases per capita foraging rates and has implications for both community dynamics and top-down trophic processes. Interference originates from behavioural interactions among foragers, and these behaviours could be affected by environmental conditions. In experiments on pike foraging alone or among conspecifics in different levels of water turbidity, we expected high turbidity to decrease the perceived risk of intraspecific interactions among pike, and thereby decrease the strength of interference, as turbidity would decrease the visual contact between individuals and act as a refuge from behavioural interactions. The results show that this is not the case, but suggest that interference is induced instead of reduced in high turbidity. Per capita foraging rates do not differ between pike foraging alone or in groups in our clear and moderately turbid treatments, indicating no effect of interference. As high turbidity enhances prey consumption for pike individuals foraging alone, but does not have this effect for pike in groups, high turbidity induces the relative interference effect. We suggest that future evaluations of the stabilizing effects of interference on community dynamics and its reduction of predation impact on top-down trophic cascades should consider potential unexpected effects of environmental conditions.
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| 4. |
- Rafnar, Thorunn, et al.
(författare)
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European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
- 2011
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 20:21, s. 4268-81
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Tidskriftsartikel (refereegranskat)abstract
- Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
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| 5. |
- Risum, Malene, et al.
(författare)
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Introduction of a Comprehensive Diagnostic and Interdisciplinary Management Approach in Haematological Patients with Mucormycosis : A Pre and Post-Intervention Analysis
- 2020
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Ingår i: JOURNAL OF FUNGI. - : MDPI. - 2309-608X. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016-2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012-2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012-2015 and 2016-2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; p = 0.039). Initial systemic AFT was liposomal amphotericin B (n = 12) or posaconazole (n = 1) given as monotherapy (n = 4) or in combination with isavuconazole/posaconazole (n = 3/6) and terbinafine (n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (n = 13). Mucormycosis related six month mortality was 3/5 in 2012-2015 and 0/7 patients in 2016-2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.
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| 6. |
- Rothman, Nathaniel, et al.
(författare)
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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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| 7. |
- Schmidt, Rüdiger, et al.
(författare)
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Sputter Yield Amplification of reactively sputtered TiO2
- 2011
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Konferensbidrag (refereegranskat)abstract
- TiO2 is a material with attractive properties which have led to various applications such as anti-reflective coatings [1] or self cleaning surfaces [2]. One of the most applied deposition techniques used for TiO2 is reactive magnetron sputtering. Unfortunately TiO2 suffers from a comparatively low deposition rate when reactively sputtered. To increase the deposition rate, Sputter Yield Amplification (SYA) can be used through recoil of the sputtering species at implanted heavy dopants below the target surface [3,4]. Here we present experimental results showing a large increase of the TiO2 deposition rate when doped with Tungsten. Although SYA has been proposed earlier [5], the production of doped targets was complicated. We have built a designated sputter deposition tool which enables systematic studies of SYA. In this study the rate increase by SYA is investigated for two different dopants, namely Tungsten and Bismuth. Bismuth was chosen since it is the heaviest non-radioactive material available. Our experiments show that the rate increase of TiO2 by Bismuth is surprisingly low. Tungsten on the other hand results in a large rate increase of 160% in DC and 220% in HiPIMS mode. A number of additional experiments have been carried out to verify and explain this observation. Finally TRIDYN [6] simulations have been performed which reproduce the experimental results.
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