Administrative Reforms in Post-Soviet Russia: Principal Problems and Results

The article is devoted to the analyses of main problems and results of administrative reforms in Russia during the transition period (since 1985) from the Soviet administrative system to the actual administrative structure. The basis for it is the model developed by German researches H. Wollmann and S. Kuhlmann and included by them into the textbook «Administra tion and administrative reforms in Europe» one part of which in Russian translation is published in the 11th and 12th issues of this journal. The core of the book builds the administrative reforms analysis approach consisting of three stages (institutions, processes, final effects) and based on the actual new institutionalism theories. The author of the article sees such approach as a possibility for in depth analyses of the reforming process in Russia and development of a further reconfiguration conceptions for the Russian administrative system with the goal to rationalize its structure, optimize main processes, to get positive final effects. As one of the main difficulties during the reform the author together with other researchers sees in the rational bureaucracy experience absence in Russia connected also with a lack of appropriate normative and administrative culture. The influence of these factors is stressed in the conceptions of the historical and sociological institutionalism. The same negative factors put obstacles in the way of new managerial instruments usage seen as the most efficient and effective modernization stimulus for a rational administration by the new public management model in a frame of the institutionalism based on the rational choice theory. The actual administrative reform results are evaluated by the author in a whole as insufficient and requiring further correction

Russia and China: Prospects for the Development of Urban Agglomerations

This research is aimed at studying the development of cities and agglomerations, which is an urgent problem equally for the People’s Republic of China and the Russian Federation. The level of urbanization increases with the development of territories, which makes it necessary to comprehend the processes taking place in urbanized regions and make management decisions to improve the quality of life and equalize it throughout the territory. Within the framework of these processes, the role of core cities remains, which are the centres of preferential development for the entire urban system as a whole.Aim. Comparative analysis of development trends in urbanized regions of China and Russia.Tasks. To analyse the main parameters of the quality of life in large cities of Russia and China. To consider the main trends in the development of urban agglomerations in the direction of its alignment. To determine the development and possibilities of mutual use of the experience of both countries in this process.Methods. The study uses a systematic approach with elements of a structural and functional approach and a comparative research method.Results and conclusion. As the main trends in the development of urbanized regions of Russia and China, the following are highlighted: the growth of the scale of territories and the concentration of a significant population on them, the associated aggravation of a number of problems, such as increasing competition in the integrated labour market, standardization and unification of the p rovision of basic services, increasing burden on local budgets and often limiting the autonomy of municipalities, the need to improve transport systems to increase the mobility of the population throughout the territory of the agglomeration

Mobility as a Life Quality Domain

The land areas covered by cities are growing rapidly in size in the 21st century, and huge urban agglomerations and megalopolises are becoming highly interconnected. Their functioning is impossible without rapid transportation modes providing the possibility to populations to move easily in the daily rhythms of life and commuting. This mobility has become an established “way of life,” growing hand in hand with increasing urbanism in the 20th century. As a consequence, mobility is now one of the most important subjects of research in a number of scientific disciplines.This article analyzes different approaches to the theoretical research of mobility systems and assesses their practical effectiveness and efficiency. The approaches are evaluated as possible development ideas for the very unstable and underdeveloped mobility system in St.Petersburg, the second-largest city in Russia. Among other data, use is made of analytical reports and documents from Russian research centers and the municipal authorities of St.Petersburg.The main research approach employs an analysis of comparative mobility systems, and it evaluates mobility as a crucial city life domain based on a mobility model developed by the author. The research results illustrate the character of the global mobility problem and the full inclusion of Russian cities into the modern context. They also provide a detailed picture of aspects of the problem which are relevant for St.Petersburg. The conclusion presents multiple ideas about the development rationality of city mobility systems: rail and computer controlled electric cars as possible solutions

Problems and Contradictions in the Process of Formation of Local Self-Government in the Post-Soviet Space (on the Example of Central Asian Countries)

The formation of local self-government in the post-Soviet space takes place in difficult economic and political conditions under the influence of various, often directed in the opposite way, factors. For Russia, the experience of forming a new institution for all post-Soviet states is of significant practical importance since it faces many difficulties in its course. Within the framework of the invariant of the transition from centralized management to decentralization, the variant of this process in the Central Asian countries is more relevant for our country since it is carried out under conditions largely similar to those in Russia. In this regard, the purpose of this article is to highlight the key historical, economic and political factors of local self-government formation in the Central Asian states in order to deepen the understanding of the ways and possibilities of creating a sufficiently autonomous local level of public power in systems that have long operated within the framework of strict centralization and seek to form a new organizational structure and use new management mechanisms and tools to improve the efficiency of the process and achieve the main systemic goal of the modern state – improving the quality of life in the country. The relevance of the study of these processes is beyond doubt due to the need to understand the role and place of self-government in the structure of public power in accordance with the amendments made in 2020 to the Constitution of the Russian Federation. The study of options for local-level opportunities in a comparative perspective when analyzing public authorities in Central Asian countries also opens the way to new solutions to Russian problems

Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells

Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p<0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p<0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p<0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology

Development of an Orthotopic Human Pancreatic Cancer Xenograft Model Using Ultrasound Guided Injection of Cells

Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. In particular, orthotopic tumor xenograft mouse models are emerging as the preference for cancer research due to increased clinical relevance over subcutaneous mouse models. In the current study, we developed orthotopic pancreatic cancer xenograft models in mice by a minimally invasive method, ultrasound guided injection (USGI) comparable to highly invasive surgical orthotopic injection (SOI) methods. This optimized method prevented injection complications such as recoil of cells through the injection canal or leakage of cells out of the pancreas into the peritoneal cavity. Tumor growth was monitored in vivo and quantified by ultrasound imaging weekly, tumors were also detected by in vivo fluorescence imaging using a tumor targeted molecular probe. The mean tumor volumes for the USGI and SOI models after 2 weeks of tumor growth were 205 mm3 and 178 mm3 respectively. By USGI of human pancreatic cancer cell lines, human orthotopic pancreatic cancer xenografts were established. Based on ultrasound imaging, the orthotopic human pancreatic cancer xenograft take rate was 100% for both human pancreatic cancer cell lines used, MiaPaCa-2 and Su86.86, with mean tumor volumes of 28 mm3and 30 mm3. We demonstrated that this USGI method is feasible, reproducible, facile, minimally invasive and improved compared to the highly-invasive SOI method for establishing orthotopic pancreatic tumor xenograft models suitable for molecular imaging

Development of an Orthotopic Human Pancreatic Cancer Xenograft Model Using Ultrasound Guided Injection of Cells

Mice have been employed as models of cancer for over a century, providing significant advances in our understanding of this multifaceted family of diseases. In particular, orthotopic tumor xenograft mouse models are emerging as the preference for cancer research due to increased clinical relevance over subcutaneous mouse models. In the current study, we developed orthotopic pancreatic cancer xenograft models in mice by a minimally invasive method, ultrasound guided injection (USGI) comparable to highly invasive surgical orthotopic injection (SOI) methods. This optimized method prevented injection complications such as recoil of cells through the injection canal or leakage of cells out of the pancreas into the peritoneal cavity. Tumor growth was monitored in vivo and quantified by ultrasound imaging weekly, tumors were also detected by in vivo fluorescence imaging using a tumor targeted molecular probe. The mean tumor volumes for the USGI and SOI models after 2 weeks of tumor growth were 205 mm3 and 178 mm3 respectively. By USGI of human pancreatic cancer cell lines, human orthotopic pancreatic cancer xenografts were established. Based on ultrasound imaging, the orthotopic human pancreatic cancer xenograft take rate was 100% for both human pancreatic cancer cell lines used, MiaPaCa-2 and Su86.86, with mean tumor volumes of 28 mm3and 30 mm3. We demonstrated that this USGI method is feasible, reproducible, facile, minimally invasive and improved compared to the highly-invasive SOI method for establishing orthotopic pancreatic tumor xenograft models suitable for molecular imaging