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Sökning: WFRF:(Isakov S V)

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  • Isakov, V., et al. (författare)
  • Sofosbuvir/velpatasvir for the treatment of HCV: excellent results from a phase-3, open-label study in Russia and Sweden
  • 2019
  • Ingår i: Infectious Diseases. - 2374-4235. ; 51:2, s. 131-139
  • 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.
  • Brownstein, Catherine A., et al. (författare)
  • An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
  • 2014
  • Ingår i: Genome Biology. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
  • Rönkä, N., et al. (författare)
  • Panmixia at a distribution-wide scale but indications of genetic differentiation in isolated populations of the Terek Sandpiper (Xenus cinereus)
  • 2016
  • Ingår i: International Wader Study Group Conference 2016, 9-12 September 2016, Trabolgan, Cork, Ireland.
  • Konferensbidrag (övrigt vetenskapligt)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.
  • Isakov, S V, et al. (författare)
  • Magnetization process of spin ice in a [111] magnetic field
  • 2004
  • Ingår i: Physical Review B. - : American Physical Society. - 1550-235X. ; 70:10, s. 104418-
  • 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.
  • Ronka, N., et al. (författare)
  • Near panmixia at the distribution-wide scale but evidence of genetic differentiation in a geographically isolated population of the Terek Sandpiper Xenus cinereus
  • 2019
  • Ingår i: Ibis. - 0019-1019. ; 161:3, s. 632-647
  • 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.
  • Isakov, S V, et al. (författare)
  • Interplay of quantum and thermal fluctuations in a frustrated magnet
  • 2003
  • Ingår i: Physical Review B. - : American Physical Society. - 1098-0121. ; 68:10, s. 104409-
  • 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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