52 research outputs found
Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice
Background. Due to the significant increase in life expectancy and the quality of life in patients with chronic myeloid leukemia (CML) as well as the growing need for expensive tyrosine kinase inhibitors (TKI), the analysis of cost-effectiveness and lifelong monitoring of patients is especially important.
Aim. We present the results of a multicenter observational study âThe Russian Registry of Chronic Myeloid Leukemia in routine clinical practice (2011â2016)â.
Materials & Methods. The study included Russian patients with CML, confirmed by the detection of a Ph-chromosome or a BCR-ABL transcript. The statistical analysis (July 1, 2016) included 7609 patients from 80 regions of the Russian Federation (covering 95 % of the population). The annual increase in the number of patients with newly diagnosed CML was 600â650 patients. At the time of the statistical analysis, 6995 (92 %) patients remained under observation, 473 (6 %) died and 141 (2 %) were withdrawn. The registry included 44 % of men and 56 % of women, the median age was 49 years (range 2â94 years). The peak incidence (46.3 %) occurred at the age of 40â60 years. The median disease duration by the time of the analysis was 6 years (range 0.1â30 years).
Results. The disease was diagnosed in the chronic phase (CP), acceleration phase, and blast crisis in 6560 (93.8 %), 380 (5.5 %) and 47 (0.7 %) patients, respectively. The proportion of risk groups according to Sokal for low, intermediate and high risk in CP was 49 %, 30 %, and 21 %, respectively. TKI were administered to 6473 (92.5 %) patients. Imatinib and the second generation TKI (TKI2) were administered to 5570 (86 %) and 903 (14 %) patients, respectively. The total of 30.4 % of patients received the increased imatinib dose of 600â800 mg. In the TKI2 group, 558 (61.7 %) patients received nilotinib and 345 (38.2 %) patients received dasatinib. The proportion of patients with completed molecular genetic studies (MGS) in 2014, 2015 and the first 6 months of 2016 amounted to 61 %, 58 % and 23 %, respectively. The proportion of patients with cytogenetic studies (CS) for the same period was 28 %, 26 % and 7 %, respectively. No CS or MGS data were presented for 34 %, 35 % and 63 % of patients during this period. Optimal molecular response and major molecular response (MMR) for TKI therapy were observed in 23 % and 58 % of patients treated 12 months, respectively. When nilotinib was used in the second line, MMR was obtained in 42 % of patients, and a deep molecular response was obtained in 25 % of patients (BCR-ABL < 0.01 %).
Conclusion. The high efficacy of TKI therapy was observed in the majority of patients with the possibility of achieving a minimal residual disease. The problems concerning untimely monitoring and suboptimal administration of second line treatment were identified. In general, the CML patient registry allowed the data integration of data and information management of population with CML in Russia
The Evolution of Compact Binary Star Systems
We review the formation and evolution of compact binary stars consisting of
white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and
BHs are thought to be the primary astrophysical sources of gravitational waves
(GWs) within the frequency band of ground-based detectors, while compact
binaries of WDs are important sources of GWs at lower frequencies to be covered
by space interferometers (LISA). Major uncertainties in the current
understanding of properties of NSs and BHs most relevant to the GW studies are
discussed, including the treatment of the natal kicks which compact stellar
remnants acquire during the core collapse of massive stars and the common
envelope phase of binary evolution. We discuss the coalescence rates of binary
NSs and BHs and prospects for their detections, the formation and evolution of
binary WDs and their observational manifestations. Special attention is given
to AM CVn-stars -- compact binaries in which the Roche lobe is filled by
another WD or a low-mass partially degenerate helium-star, as these stars are
thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure
The Impact of Long-Term Exposure to Space Environment on Adult Mammalian Organisms: A Study on Mouse Thyroid and Testis
Hormonal changes in humans during spaceflight have been demonstrated but the underlying mechanisms are still unknown. To clarify this point thyroid and testis/epididymis, both regulated by anterior pituitary gland, have been analyzed on long-term space-exposed male C57BL/10 mice, either wild type or pleiotrophin transgenic, overexpressing osteoblast stimulating factor-1. Glands were submitted to morphological and functional analysis
Genome-wide evolutionary and functional analysis of the Equine Repetitive Element 1: an insertion in the myostatin promoter affects gene expression
BACKGROUND: In mammals, an important source of genomic variation is insertion polymorphism of retrotransposons. These may acquire a functional role when inserted inside genes or in their proximity. The aim of this work was to carry out a genome wide analysis of ERE1 retrotransposons in the horse and to analyze insertion polymorphism in relation to evolution and function. The effect of an ERE1 insertion in the promoter of the myostatin gene, which is involved in muscle development, was also investigated. RESULTS: In the horse population, the fraction of ERE1 polymorphic loci is related to the degree of similarity to their consensus sequence. Through the analysis of ERE1 conservation in seven equid species, we established that the level of identity to their consensus is indicative of evolutionary age of insertion. The position of ERE1s relative to genes suggests that some elements have acquired a functional role. Reporter gene assays showed that the ERE1 insertion within the horse myostatin promoter affects gene expression. The frequency of this variant promoter correlates with sport aptitude and racing performance. CONCLUSIONS: Sequence conservation and insertion polymorphism of ERE1 elements are related to the time of their appearance in the horse lineage, therefore, ERE1s are a useful tool for evolutionary and population studies. Our results suggest that the ERE1 insertion at the myostatin locus has been unwittingly selected by breeders to obtain horses with specific racing abilities. Although a complex combination of environmental and genetic factors contributes to athletic performance, breeding schemes may take into account ERE1 insertion polymorphism at the myostatin promoter. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12863-015-0281-1) contains supplementary material, which is available to authorized users
Regional dynamics of social partnership:: political, legal and value characteristic
The subject of this work is the study of the level of development, key problems and directions for
the development of social partnership via expert surveys conducted in 13 regions of the Russian
Federation. As a result, the development of regions, the provision of positive social dynamics in the
development of the latter is associated with the formation and stimulation of social partnership. In
conclusion, the model of joint development of the key actors of the political and socio-economic
processes is the most adequate in comparison with the liberal-democratic forms and practices, to
solve many regional problems, conflicts and contradictions.El tema de este trabajo es el estudio del nivel de desarrollo, problemas clave y direcciones para el
desarrollo de la asociación social a través de encuestas de expertos realizadas en 13 regiones de la
FederaciĂłn Rusa. Como resultado, el desarrollo de las regiones, la provisiĂłn de dinĂĄmicas sociales
positivas en el desarrollo de estas Ășltimas se asocia con la formaciĂłn y el estĂmulo de la sociedad
social. En conclusiĂłn, el modelo de desarrollo conjunto de los actores clave de los procesos
polĂticos y socioeconĂłmicos es el mĂĄs adecuado en comparaciĂłn con las formas y prĂĄcticas liberaldemocrĂĄticas, para resolver muchos problemas, conflictos y contradicciones regionales
Recommended from our members
Strategically placed landscape fuel treatments decrease fire severity and promote recovery in the northern Sierra Nevada
Strategically placed landscape area treatments (SPLATs) are landscape fuel reduction treatments designed to reduce fire severity across an entire landscape with only a fraction of the landscape treated. Though SPLATs have gained attention in scientific and policy arenas, they have rarely been empirically tested. This study takes advantage of a strategically placed landscape fuel treatment network that was implemented and monitored before being burned by a wildfire. We evaluated treatment efficacy in terms of resistance, defined here as the capacity to withstand disturbance, and recovery, defined here as regeneration following disturbance. We found that the treated landscape experienced lower fire severity than an adjacent control landscape: in the untreated control landscape, 26% of land area was burned with >90% basal area mortality, according to the remote-sensing-derived relative differenced Normalized Burn Ratio (RdNBR), while in the treated landscape only 11% burned at the same severity. This difference was despite greater pre-treatment fire risk in the treatment landscape, as indicated by FARSITE fire behavior modeling. At a more local scale, monitoring plots within the treatments themselves saw greater regeneration of conifer seedlings two years following the fire than plots outside the treatments. Mean seedling densities for all conifer species were 7.8 seedlings m â2 in treated plots and only 1.4 seedlings m â2 in control plots. These results indicate that SPLATs achieved their objective of increasing forest resistance and recovery
Recommended from our members
Strategically placed landscape fuel treatments decrease fire severity and promote recovery in the northern Sierra Nevada
Strategically placed landscape area treatments (SPLATs) are landscape fuel reduction treatments designed to reduce fire severity across an entire landscape with only a fraction of the landscape treated. Though SPLATs have gained attention in scientific and policy arenas, they have rarely been empirically tested. This study takes advantage of a strategically placed landscape fuel treatment network that was implemented and monitored before being burned by a wildfire. We evaluated treatment efficacy in terms of resistance, defined here as the capacity to withstand disturbance, and recovery, defined here as regeneration following disturbance. We found that the treated landscape experienced lower fire severity than an adjacent control landscape: in the untreated control landscape, 26% of land area was burned with >90% basal area mortality, according to the remote-sensing-derived relative differenced Normalized Burn Ratio (RdNBR), while in the treated landscape only 11% burned at the same severity. This difference was despite greater pre-treatment fire risk in the treatment landscape, as indicated by FARSITE fire behavior modeling. At a more local scale, monitoring plots within the treatments themselves saw greater regeneration of conifer seedlings two years following the fire than plots outside the treatments. Mean seedling densities for all conifer species were 7.8 seedlings m in treated plots and only 1.4 seedlings m in control plots. These results indicate that SPLATs achieved their objective of increasing forest resistance and recovery. â2 â
- âŠ