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- Rosendahl, J, et al.
(författare)
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Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis
- 2018
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 67:10, s. 1855-1863
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Tidskriftsartikel (refereegranskat)abstract
- Alcohol-related pancreatitis is associated with a disproportionately large number of hospitalisations among GI disorders. Despite its clinical importance, genetic susceptibility to alcoholic chronic pancreatitis (CP) is poorly characterised. To identify risk genes for alcoholic CP and to evaluate their relevance in non-alcoholic CP, we performed a genome-wide association study and functional characterisation of a new pancreatitis locus.Design1959 European alcoholic CP patients and population-based controls from the KORA, LIFE and INCIPE studies (n=4708) as well as chronic alcoholics from the GESGA consortium (n=1332) were screened with Illumina technology. For replication, three European cohorts comprising 1650 patients with non-alcoholic CP and 6695 controls originating from the same countries were used.ResultsWe replicated previously reported risk loci CLDN2-MORC4, CTRC, PRSS1-PRSS2 and SPINK1 in alcoholic CP patients. We identified CTRB1-CTRB2 (chymotrypsin B1 and B2) as a new risk locus with lead single-nucleotide polymorphism (SNP) rs8055167 (OR 1.35, 95% CI 1.23 to 1.6). We found that a 16.6 kb inversion in the CTRB1-CTRB2 locus was in linkage disequilibrium with the CP-associated SNPs and was best tagged by rs8048956. The association was replicated in three independent European non-alcoholic CP cohorts of 1650 patients and 6695 controls (OR 1.62, 95% CI 1.42 to 1.86). The inversion changes the expression ratio of the CTRB1 and CTRB2 isoforms and thereby affects protective trypsinogen degradation and ultimately pancreatitis risk.ConclusionAn inversion in the CTRB1-CTRB2 locus modifies risk for alcoholic and non-alcoholic CP indicating that common pathomechanisms are involved in these inflammatory disorders.
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- Eap, C. B., et al.
(författare)
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Tools for optimising pharmacotherapy in psychiatry (therapeutic drug monitoring, molecular brain imaging and pharmacogenetic tests) : focus on antidepressants
- 2021
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Ingår i: World Journal of Biological Psychiatry. - : Taylor & Francis Group. - 1562-2975 .- 1814-1412. ; 22:8, s. 561-628
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Forskningsöversikt (refereegranskat)abstract
- Objectives: More than 40 drugs are available to treat affective disorders. Individual selection of the optimal drug and dose is required to attain the highest possible efficacy and acceptable tolerability for every patient. Methods: This review, which includes more than 500 articles selected by 30 experts, combines relevant knowledge on studies investigating the pharmacokinetics, pharmacodynamics and pharmacogenetics of 33 antidepressant drugs and of 4 drugs approved for augmentation in cases of insufficient response to antidepressant monotherapy. Such studies typically measure drug concentrations in blood (i.e. therapeutic drug monitoring) and genotype relevant genetic polymorphisms of enzymes, transporters or receptors involved in drug metabolism or mechanism of action. Imaging studies, primarily positron emission tomography that relates drug concentrations in blood and radioligand binding, are considered to quantify target structure occupancy by the antidepressant drugs in vivo. Results: Evidence is given that in vivo imaging, therapeutic drug monitoring and genotyping and/or phenotyping of drug metabolising enzymes should be an integral part in the development of any new antidepressant drug. Conclusions: To guide antidepressant drug therapy in everyday practice, there are multiple indications such as uncertain adherence, polypharmacy, nonresponse and/or adverse reactions under therapeutically recommended doses, where therapeutic drug monitoring and cytochrome P450 genotyping and/or phenotyping should be applied as valid tools of precision medicine.
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- Isakov, S V, et al.
(författare)
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Interplay of quantum and thermal fluctuations in a frustrated magnet
- 2003
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Ingår i: Physical Review B. - : American Physical Society. - 1098-0121. ; 68:10, s. 104409-
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the presence of an extended critical phase in the transverse field Ising magnet on the triangular lattice, in a regime where both thermal and quantum fluctuations are important. We map out a complete phase diagram by means of quantum Monte Carlo simulations, and find that the critical phase is the result of thermal fluctuations destabilising an order established by the quantum fluctuations. It is separated by two Kosterlitz-Thouless transitions from the paramagnet on one hand and the quantum-fluctuation driven three-sublattice ordered phase on the other. Our work provides further evidence that the zero temperature quantum phase transition is in the three-dimensional XY universality class.
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- Isakov, S V, et al.
(författare)
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Magnetization process of spin ice in a [111] magnetic field
- 2004
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Ingår i: Physical Review B. - : American Physical Society. - 1550-235X. ; 70:10, s. 104418-
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Tidskriftsartikel (refereegranskat)abstract
- Spin ice in a magnetic field in the [111] direction displays two magnetization plateaus: one at saturation and an intermediate one with finite entropy. We study the crossovers between the different regimes from a point of view of (entropically) interacting defects. We develop an analytical theory for the nearest-neighbor spin ice model, which covers most of the magnetization curve. We find that the entropy is nonmonotonic, exhibiting a giant spike between the two plateaus. This regime is described by a monomer-dimer model with tunable fugacities. At low fields, we develop an RG treatment for the extended string defects, and we compare our results to extensive Monte Carlo simulations. We address the implications of our results for cooling by adiabatic (de)magnetization.
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