| 1. |
- Isakov, V., et al.
(författare)
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Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden
- 2019
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Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 51:2, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- Background: In both Russia and Sweden, the dominant hepatitis C virus (HCV) is genotype 1, but around one-third of patients have genotype 3 infection. For such countries, HCV genotype testing is recommended prior to therapy. An effective pangenotypic therapy may potentially eliminate the need for genotyping. In this study, we evaluated the efficacy and safety of sofosbuvir/velpatasvir for 12 weeks in patients from Russia and Sweden. Methods: In an open-label, single-arm phase-3 study, patients could have HCV genotype 1-6 infection and were treatment-naive or interferon treatment-experienced. All patients received sofosbuvir/velpatasvir, once daily for 12 weeks. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). Results: Of 122 patients screened, 119 were enrolled and treated. Overall, half (50%) were male, 18% had cirrhosis, and 24% had failed prior interferon-based therapy. In total, 66% of patients were infected with HCV genotype 1 (59% 1b and 7% 1a), 6% with genotype 2, and 29% with genotype 3. The overall SVR12 rate was 99% (118/119, 95% confidence interval 95-100%). One treatment-experienced patient infected with HCV genotype 3 experienced virologic relapse after completing treatment. The most common adverse events were headache (16%) and fatigue (7%). Serious adverse events were observed in four patients, but none were related to treatment. No patients discontinued treatment due to adverse events. Conclusion: Sofosbuvir/velpatasvir as a pangenotypic treatment for 12 weeks was highly effective in patients from Russia and Sweden infected with HCV genotypes 1, 2, or 3. Sofosbuvir/velpatasvir was safe and well-tolerated.
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| 2. |
- Rönkä, N., et al.
(författare)
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Panmixia at a distribution-wide scale but indications of genetic differentiation in isolated populations of the Terek Sandpiper (Xenus cinereus)
- 2016
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Ingår i: International Wader Study Group Conference 2016, 9-12 September 2016, Trabolgan, Cork, Ireland.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Populations at different parts of the species range may vary in their population dynamics and in their genetic structure and variation. Geographically separated populations or those located at the edge of the range may differ from the populations located at the core, or even be independent of them. The peripheral populations may hold genetic variation that is important for the adaptive potential of the species and therefore be of special conservation value. We studied the distribution-wide population genetic structure of the Terek Sandpiper (Xenus cinereus) using 13 microsatellite loci and two mitochondrial DNA markers: the control region and cytochrome oxidase I (COI). We evaluated the difference in genetic variation between the peripheral and core populations. Specifically, we sought signs of changes in population sizes and evaluated the management need of the populations. Distribution-wide differentiation was negligible, but geographically isolated populations in Finland and Dnieper River basin in Eastern Europe were differentiated from the main range. Edge populations had lower genetic variation than populations at the core when estimated with microsatellites and the COI, supporting the hypotheses where the core area of the distribution preserves the most variation. However, no such trend was observed with the control region data, which follows the model of no change throughout the distribution. The differences between the markers may reflect their different mutation rates, or be linked to the species’ dispersal behaviour. Our results revealed low overall nucleotide diversity and signs of past population contractions followed by expansion. Although the estimated current effective population size is large and therefore global conservation measures are not needed, the Finnish and Dnieper River basin populations nevertheless warrant management actions – not only because they may possess variation not present anywhere else, but also due to their smallness and large distances to the main range.
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| 3. |
- Ronka, N., et al.
(författare)
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Near panmixia at the distribution-wide scale but evidence of genetic differentiation in a geographically isolated population of the Terek Sandpiper Xenus cinereus
- 2019
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Ingår i: Ibis. - : Wiley. - 0019-1019. ; 161:3, s. 632-647
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Tidskriftsartikel (refereegranskat)abstract
- Populations from different parts of a species range may vary in their genetic structure, variation and dynamics. Geographically isolated populations or those located at the periphery of the range may differ from those located in the core of the range. Such peripheral populations may harbour genetic variation important for the adaptive potential of the species. We studied the distribution-wide population genetic structure of the Terek Sandpiper Xenus cinereus using 13 microsatellite loci and the mitochondrial DNA (mtDNA) control region. In addition, we estimated whether genetic variation changes from the core towards the edge of the breeding range. We used the results to evaluate the management needs of the sampled populations. Distribution-wide genetic structure was negligible; the only population that showed significant genetic differentiation was the geographically isolated Dnieper River basin population in Eastern Europe. The genetic variation of microsatellites decreased towards the edge of the distribution, supporting the abundant-centre hypotheses in which the core area of the distribution preserves the most genetic variation; however, no such trend could be seen with mtDNA. Overall genetic variation was low and there were signs of past population contractions followed by expansion; this pattern is found in most northern waders. The current effective population size (N-e) is large, and therefore global conservation measures are not necessary. However, the marginal Dnieper River population needs to be considered its own management unit. In addition, the Finnish population warrants conservation actions due to its extremely small size and degree of isolation from the main range, which makes it vulnerable to genetic depletion.
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| 4. |
- Bordería, Antonio V, et al.
(författare)
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Group Selection and Contribution of Minority Variants during Virus Adaptation Determines Virus Fitness and Phenotype.
- 2015
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Understanding how a pathogen colonizes and adapts to a new host environment is a primary aim in studying emerging infectious diseases. Adaptive mutations arise among the thousands of variants generated during RNA virus infection, and identifying these variants will shed light onto how changes in tropism and species jumps can occur. Here, we adapted Coxsackie virus B3 to a highly permissive and less permissive environment. Using deep sequencing and bioinformatics, we identified a multi-step adaptive process to adaptation involving residues in the receptor footprints that correlated with receptor availability and with increase in virus fitness in an environment-specific manner. We show that adaptation occurs by selection of a dominant mutation followed by group selection of minority variants that together, confer the fitness increase observed in the population, rather than selection of a single dominant genotype.
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| 5. |
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| 6. |
- Fogelberg, Birger, et al.
(författare)
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Neutron separation energies at N=83 and the isomer position in 136I
- 2007
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Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 75:5, s. 054308-
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Tidskriftsartikel (refereegranskat)abstract
- New experimental total β-decay energies of 135,136Te and of the two isomers of 136I have been obtained, giving much improved accuracy for the nuclear masses of these nuclides. The neutron separation energies at N=83 were deduced and are compared to recent theoretical and systematic predictions. The new results resolve the problem with the excitation energy of the isomeric state of 136I. Theoretical calculations of the isomer splitting of 136I are in good agreement with the new data.
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| 7. |
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Isakov, V.I., et al.
(författare)
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Isomeric and two-quasiparticle states in the neutron-excess odd-odd nucleus 134Sb
- 2007
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Ingår i: Physics of Atomic Nuclei. - 1063-7788 .- 1562-692X. ; 70:5, s. 818-826
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Tidskriftsartikel (refereegranskat)abstract
- Detailed theoretical calculations of the properties of the neutron-excess odd–odd nucleus134 Sb are performed by using different theoretical approaches. A comprehensive comparison with the recentexperimental data is performed; this comparison suggests the presence of isomeric states among the low-lying levels of this nucleus. These states are the twins of the corresponding levels of the odd–odd nucleus210 Bi that is situated near the stability line. The obtained results manifest the similarity of nuclear structurein the region of the “remote” doubly magic nucleus 132 Sn and in the region of the classical stable doublymagic nucleus 208 Pb.
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