| 21. |
- Teerlink, Craig C., et al.
(författare)
-
Association analysis of 9,560 prostate cancer cases from the International Consortium of Prostate Cancer Genetics confirms the role of reported prostate cancer associated SNPs for familial disease
- 2014
-
Ingår i: Human Genetics. - : Springer. - 0340-6717 .- 1432-1203. ; 133:3, s. 347-356
-
Tidskriftsartikel (refereegranskat)abstract
- Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction (p a parts per thousand currency sign 1E (-3)) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease.
|
|
| 22. |
- van Kuilenburg, André B P, et al.
(författare)
-
Intragenic deletions and a deep intronic mutation affecting pre-mRNA splicing in the dihydropyrimidine dehydrogenase gene as novel mechanisms causing 5-fluorouracil toxicity
- 2010
-
Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 128:5, s. 529-538
-
Tidskriftsartikel (refereegranskat)abstract
- Dihydropyrimidine dehydrogenase (DPD) is the initial enzyme acting in the catabolism of the widely used antineoplastic agent 5-fluorouracil (5FU). DPD deficiency is known to cause a potentially lethal toxicity following administration of 5FU. Here, we report novel genetic mechanisms underlying DPD deficiency in patients presenting with grade III/IV 5FU-associated toxicity. In one patient a genomic DPYD deletion of exons 21-23 was observed. In five patients a deep intronic mutation c.1129-5923C>G was identified creating a cryptic splice donor site. As a consequence, a 44 bp fragment corresponding to nucleotides c.1129-5967 to c.1129-5924 of intron 10 was inserted in the mature DPD mRNA. The deleterious c.1129-5923C>G mutation proved to be in cis with three intronic polymorphisms (c.483 + 18G>A, c.959-51T>G, c.680 + 139G>A) and the synonymous mutation c.1236G>A of a previously identified haplotype. Retrospective analysis of 203 cancer patients showed that the c.1129-5923C>G mutation was significantly enriched in patients with severe 5FU-associated toxicity (9.1%) compared to patients without toxicity (2.2%). In addition, a high prevalence was observed for the c.1129-5923C>G mutation in the normal Dutch (2.6%) and German (3.3%) population. Our study demonstrates that a genomic deletion affecting DPYD and a deep intronic mutation affecting pre-mRNA splicing can cause severe 5FU-associated toxicity. We conclude that screening for DPD deficiency should include a search for genomic rearrangements and aberrant splicing.
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Abul-Kasim, Kasim, et al.
(författare)
-
Radiological and clinical outcome of screw placement in adolescent idiopathic scoliosis: evaluation with low-dose computed tomography.
- 2010
-
Ingår i: European Spine Journal. - : Springer Science and Business Media LLC. - 0940-6719 .- 1432-0932. ; 19:1, s. 96-104
-
Tidskriftsartikel (refereegranskat)abstract
- Posterior corrective surgery using "all pedicle screw construct" carries risk of neurovascular complications. The study aims were to assess the screw placement in patients with adolescent idiopathic scoliosis using CT with low-radiation dose, and to evaluate the clinical outcome in patients with misplaced pedicle screws. CTs of 49 consecutive patients (873 screws, 79% thoracic) were retrospectively evaluated by two independent radiologists. A new grading system was developed to distinguish between lateral, medial and anterior cortical perforations, endplate perforation and foraminal perforation. The grading system is based on whether the cortical violation is partial or total rather than on mm-basis. The overall rate of screw misplacement was 17% (n = 149): 8% were laterally placed and 6.1% were medially placed. The rates of anterior cortical, endplate and foraminal perforation were 1.5, 0.9, and 0.5%, respectively. Lateral cortical perforation was more frequent in the thoracic spine (P = 0.005), whereas other types of misplacement including medial cortical perforation were more frequent on the left and the concave side of scoliotic curves (P = 0.002 and 0.003). No neurovascular complications were reported. The association between the occurrence of screw misplacement and the Cobb angle was statistically significant (P = 0.037). Misplacements exceeding half screw diameter should be classified as unacceptable. Low-dose CT implies exposing these young individuals to a significantly lower radiation dose than do other protocols used in daily clinical practice. We recommend using low-dose CT and the grading system proposed here in the postoperative assessment of screw placement.
|
|
| 26. |
- Fuchs, Jürgen, 1957-, et al.
(författare)
-
Bicategories for boundary conditions and for surface defects in 3-d TFT
- 2013
-
Ingår i: Communications in Mathematical Physics. - Berlin : Springer. - 0010-3616 .- 1432-0916. ; 321:2, s. 543-575
-
Tidskriftsartikel (refereegranskat)abstract
- We analyze topological boundary conditions and topological surface defects in three-dimensional topological field theories of Reshetikhin-Turaev type based on arbitrary modular tensor categories. Boundary conditions are described by central functors that lift to trivializations in the Witt group of modular tensor categories. The bicategory of boundary conditions can be described through the bicategory of module categories over any such trivialization. A similar description is obtained for topological surface defects. Using string diagrams for bicategories we also establish a precise relation between special symmetric Frobenius algebras and Wilson lines involving special defects. We compare our results with previous work of Kapustin-Saulina and of Kitaev-Kong on boundary conditions and surface defects in abelian Chern-Simons theories and in Turaev-Viro type TFTs, respectively
|
|
| 27. |
- Kozlov, Vladimir
(författare)
-
Domain dependence of eigenvalues of elliptic type operators
- 2013
-
Ingår i: Mathematische Annalen. - : Springer Verlag (Germany). - 0025-5831 .- 1432-1807. ; 357:4, s. 1509-1539
-
Tidskriftsartikel (refereegranskat)abstract
- The dependence on the domain for the Dirichlet eigenvalues of elliptic operators considered in bounded domains is studied. The proximity of domains is measured by a norm of the difference of two orthogonal projectors corresponding to the reference domain and the perturbed one; this allows to compare eigenvalues corresponding to domains that have non-smooth boundaries and different topology. The main result is an asymptotic formula in which the remainder is evaluated in terms of this quantity. Applications of this result are given. The results are new for the Laplace operator.
|
|
| 28. |
- Fuchs, Jürgen, et al.
(författare)
-
A geometric approach to boundaries and surface defects in Dijkgraaf-Witten theories
- 2014
-
Ingår i: Communications in Mathematical Physics. - : Springer Science and Business Media LLC. - 0010-3616 .- 1432-0916. ; 332, s. 981-1015
-
Tidskriftsartikel (refereegranskat)abstract
- Dijkgraaf-Witten theories are extended three-dimensional topological field theories of Turaev-Viro type. They can be constructed geometrically from categories of bundles via linearization. Boundaries and surface defects or interfaces in quantum field theories are of interest in various applications and provide structural insight. We perform a geometric study of boundary conditions and surface defects in Dijkgraaf-Witten theories. A crucial tool is the linearization of categories of relative bundles. We present the categories of generalized Wilson lines produced by such a linearization procedure. We establish that they agree with the Wilson line categories that are predicted by the general formalism for boundary conditions and surface defects in three-dimensional topological field theories that has been developed in arXive:1203.4568.
|
|
