A view on the problems of Quantum Gravity

The existing approaches to quantization of gravity aim at giving quantum description of 3-geometry following to the ideas of the Wheeler -- DeWitt geometrodynamics. In this description the role of gauge gravitational degrees of freedom is missed. A probable alternative is to consider gravitational dynamics in extended phase space, taking into account the distinctions between General Relativity and other field theories. The formulation in extended phase space leads to some consequences at classical and quantum levels. At the classical level, it ensures that Hamiltonian dynamics is fully equivalent to Lagrangian dynamics, and the algebra of Poisson brackets is invariant under reparametrizations in a wide enough class including reparametrizations of gauge variables, meantime in the canonical Dirac approach the constraints' algebra is not invariant that creates problems with quantization. At the quantum level, the approach come to the description in which the observer can see various but complementary quantum gravitational phenomena in different reference frames that answers the spirit of General Relativity and Quantum Theory. Though until now the approach was applied to General Relativity in its original formulations, its implementation in different trends, including Quantum Loop Gravity or some other representations of gravitational variables, would also be of interest.Comment: 6 pages, talk presented at the International Conference on Quantum Gravity "Loops 11", Madrid, May 201

Impact of the "New normal" concept on China's economic development

Understanding the current «New Normal» of China’s economy in the context of market economy does not only refers to the state of economic development, but also to the transformation of China’s economic development state. China’s economy could not return to the «old normal of a planned economy» before reform and opening up, instead, China’s economy should turn to a new development state in which the operation mechanism depends more on the laws of the market itself, the economic growth rate and economic structure adapt to the objective requirements of industrialization entering the middle and later development stage. Its core lies in the formation of new market economic rules, operation, mechanism and new market structure and models

Effects of GLP-1RAs on cardiovascular outcomes in patients with type 2 diabetes mellitus: review of real-world data on target populations from diabetes registry in Russian Federation

RATIONALE. Over the past 20 years the prevalence of type 2 diabetes in Russia has more than doubled and reached 4.43 million people in 2020, while the growth rate keeps increasing. Most patients with T2DM are at a higher risk of developing major adverse cardiovascular events (MACE) associated with significant mortality. There is a strong evidence base that the drugs belonging to GLP-1RA class contribute to reducing the risk of cardiovascular events and renal outcomes. At the same time, the current prescribing rates of these treatments in Russia are quite low - only about 0.1% of patients are prescribed GLP-1RAs, according to Diabetes Registry data.AIM. Review the results of several randomized clinical trials (RCTs) concerning effects of GLP-1RA treatments on prevention of primary and secondary cardiovascular events and estimate the number of diabetic target population.MATERIALS AND METHODS. We examined the data from clinical trials on GLP-1RA treatments registered in Russia and used in routine clinical practice (ELIXA, EXSCEL, LEADER, SUSTAIN-6 and REWIND) and data from two meta-analyzes published as of December 1, 2020. The task was to evaluate the inclusion criteria, patient profile, and the clinical efficacy and safety profiles of  the studied therapies. Also, the analysis of clinical information from the Diabetes Registry (DR) was performed to estimate the number of target T2DM patients meeting RCTs inclusion criteria that could benefit from prescribing of GLP-1RAs.RESULTS. The reviewed clinical trials demonstrated a statistically significant reduction (p <0.05) in the risk of serious cardiovascular events in patients treated with Liraglutide [RR 0.87 (95% CI, 0.78-0.97)], Semagltuide [OP 0.74 (95% CI 0.58-0.95)] and Dulaglutide [RR 0.88 (95% CI 0.79-0.99)]. Meta-analyzes utilizing data from 6 RCTs with the total number of 56,004 T2DM patients, also, confirmed a statistically significant reduction in the risk of developing MACE (by 12%) in the studied population, and a 17% reduction in the risk of combined renal outcomes [RR 0.83 (95% CI 0.78-0.89), p <0.0001]. The DR patient population that met the RCTs inclusion criteria amounted to 538.6 thous. subjects in case of REWIND and 432.4 thous. in case of LEADER and SUSTAIN-6. The key differences between FDR patients and patients engaged in RCTs included gender and age characteristics. The DR patients were generally older and the bulk of them were women, which has to do with overall Russian demographic trends. The proportion of DR patients with established CVD was 26%, which closely matched the profile of patients from REWIND study (31.5%). According to DR data, the number of patients in whom the treatment was intensified following prescription of basal insulin was 7612 per year, which is close to a potential cohort eligible for alternative treatment with GLP-1RAs.CONCLUSION. All the drugs belonging to GLP-1RA class are clinically effective in reducing the risk of cardiovascular and renal outcomes, while demonstrating a favorable safety profile including with respect to lower risk of developing hypoglycemia. The decreased risk of complications was recorded both in patients with existing cardiovascular risks and patients with established CVD. Of all GLP-1RA treatments available in Russia at this point, the greatest clinical effectiveness is achieved by Liraglutide, Semaglutide and Dulaglutide. The estimated patient population from DR, meeting RCTs inclusion criteria and matching RCTs patient profile was over 500, 000 people with the largest number of patients meeting the REWIND criteria. The target population of patients with T2DM who may potentially benefit from the administration of GLP-1RAs is over 500, 000 people. Out of that number at least 7.5 thousand are patients, whose treatment is intensified following prescription of basal insulin (with an aim of improving glycemic control, but without consideration of cardiovascular risks).Currently, if we take the real world clinical setting in Russia, the number of patients receiving GLP-1RA treatments is substantially lower than the estimated figures (less than 1%), which requires reconsideration of the approach toward their prescribing as is recommended by state-of-the-art clinical guidelines prioritizing prevention of cardiovascular risks

The role of renin-angiotensin system and angiotensin-converting enzyme 2 (ACE2) in the development and course of viral infection COVID-19 in patients with diabetes mellitus

The role of renin-angiotensin system (RAS) in general and angiotensin-converting enzyme 2 (ACE2) in particular in the  pathogenesis and course of viral infection caused by SARS-CoV-2 (COVID-19) is of particular interest. This is due not only to the fact that ACE2 is a receptor for the virus the target cells. RAS hyperactivation in patients with arterial hypertension, cardiovascular disease and diabetes mellitus, is considered one of the most important factors for a more severe infection in persons with concomitant pathology. In addition, the effects of PAS blockage with angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (ARBs) remains one of the most discussed topics in the literature on COVID-19. This review presents the data on the interaction between the virus and the main components of RAS and the factors influencing their expression level, the impact of ACE ­inhibitors and ARBs therapy on the disease outcome, and presents the perspectives of the treatment with recombinant ACE 2

Resource use associated with type 2 diabetes in Africa, the Middle East, South Asia, Eurasia and Turkey: results from the International Diabetes Management Practice Study (IDMPS)

Objective: Type 2 diabetes (T2D) and its complications form a global healthcare burden but the exact impact in some geographical regions is still not well documented. We describe the healthcare resource usage (HRU) associated with T2D in Africa, the Middle East, South Asia, Eurasia and Turkey. Research design and methods: In the fifth wave of the International Diabetes Management Practices Study (IDMPS; 2011-2012), we collected self-reported and physician-reported cross-sectional data from 8156 patients from 18 countries across 5 regions, including different types of HRU in the previous 3-6 months. Negative binomial regression was used to identify parameters associated with HRU, using incidence rate ratios (IRRs) to express associations. Results: Patients in Africa (n=2220), the Middle East (n=2065), Eurasia (n=1843), South Asia (n=1195) and Turkey (n=842) experienced an annual hospitalization rate (mean±SD) of 0.6±1.9, 0.3±1.2, 1.7±4.1, 0.4±1.5 and 1.3±2.7, respectively. The annual number of diabetes-related inpatient days (mean±SD) was 4.7 ±22.7, 1.1±6.1, 16.0±30.0, 1.5±6.8 and 10.8±34.3, respectively. Despite some inter-regional heterogeneity, macrovascular complications (IRRs varying between 1.4 and 8.9), microvascular complications (IRRs varying between 3.4 and 4.3) and, to a large extent, inadequate glycemic control (IRRs varying between 1.89 and 10.1), were independent parameters associated with hospitalization in these respective regions. Conclusions: In non-Western countries, macrovascular/microvascular complications and inadequate glycemic control were common and important parameters associated with increased HRU.Centro de Endocrinología Experimental y Aplicad

Resource use associated with type 2 diabetes in Africa, the Middle East, South Asia, Eurasia and Turkey: results from the International Diabetes Management Practice Study (IDMPS)

Objective: Type 2 diabetes (T2D) and its complications form a global healthcare burden but the exact impact in some geographical regions is still not well documented. We describe the healthcare resource usage (HRU) associated with T2D in Africa, the Middle East, South Asia, Eurasia and Turkey. Research design and methods: In the fifth wave of the International Diabetes Management Practices Study (IDMPS; 2011-2012), we collected self-reported and physician-reported cross-sectional data from 8156 patients from 18 countries across 5 regions, including different types of HRU in the previous 3-6 months. Negative binomial regression was used to identify parameters associated with HRU, using incidence rate ratios (IRRs) to express associations. Results: Patients in Africa (n=2220), the Middle East (n=2065), Eurasia (n=1843), South Asia (n=1195) and Turkey (n=842) experienced an annual hospitalization rate (mean±SD) of 0.6±1.9, 0.3±1.2, 1.7±4.1, 0.4±1.5 and 1.3±2.7, respectively. The annual number of diabetes-related inpatient days (mean±SD) was 4.7 ±22.7, 1.1±6.1, 16.0±30.0, 1.5±6.8 and 10.8±34.3, respectively. Despite some inter-regional heterogeneity, macrovascular complications (IRRs varying between 1.4 and 8.9), microvascular complications (IRRs varying between 3.4 and 4.3) and, to a large extent, inadequate glycemic control (IRRs varying between 1.89 and 10.1), were independent parameters associated with hospitalization in these respective regions. Conclusions: In non-Western countries, macrovascular/microvascular complications and inadequate glycemic control were common and important parameters associated with increased HRU.Centro de Endocrinología Experimental y Aplicad

Epidemiological characteristics of diabetes mellitus in the Russian Federation: clinical and statistical analysis according to the Federal diabetes register data of 01.01.2021

BACKGROUND. One of the priority directions in the development of the health care system is to reduce the medical and social damage caused by the increase in the prevalence of diabetes mellitus (DM). From this point of view, the development of a diabetes register is very important as the main information and analytical platform for clinical and epidemiological monitoring of diabetes in the Russian Federation (RF).AIMS. The aim of our study was to analyze a dynamic (2016–2020) of the epidemiological characteristics of diabetes mellitus in the Russian Federation (prevalence, morbidity, mortality), the prevalence of complications, the level of HbA1c and the dynamics of the structure of glucose-lowering therapy (GLT) according to the Federal Diabetes Register (FDR).MATERIALS AND METHODs. The database of FRD (http://diaregistry.ru) 84 regions of the RF. The data are presented in dynamics 2016→2020.RESULTS. The total number of DM patients in the RF as of 01.01.2021 was 4,799,552 (3.23% of the population), including: Type 1 (T1) — 5.5% (265.4 ths) , T2 — 92.5% (4.43 million), other DM types — 2.0% (99.3 ths). The dynamics of prevalence was 168.7→180.9/100 ths people with T1, and 2709 → 3022/100 ths people with T2; morbidity in T1 10.5→7.7/100 ths population, in T2 219.6→154.2/100 ths population. Age and sex characteristics: the proportion of men in T1 — 54%, in T2 — 30%; the max proportion of patients with T1 at the age of 30–39 years, T2 65–69 years. Mortality: T1 3.0 → 2.7/100 ths population, T2 87.7→93.9/100 ths of the population, the main cause of death was cardiovascular: in T1 38,1% cases, in T2 — 52,0%. Life expectancy (average age of death of patients): T1 was 53.2years, the dynamics in males 50.7 → 50.5years, ­females 58.7→55.2years; in T2 — 73.5 years, males 70.2→70.1years, females 75.7→75.4 years. The dynamic of DM duration until the death: in T1 17.4→19.0 years; in T2 11→11.4 years. The incidence of diabetic complications in T1 and T2 patients: neuropathy 43.3% and 24.4%, nephropathy (CKD) 25.9% and 18.4%, retinopathy 31.7% and 13.5%, respectively. The ­proportion of ­patients with HbA1c <7%: in T1 32.3%→36.9%, in T2 51.9%→52.1%, with HbA1c ≥ 9.0% in T1 23.1%→18.7% , in T2 8.9%→8.0%. The structure GLT in T2 patients: glucose lowering medications (GLM) — 76.2% (monotherapy — 44.1%; ­combination of  2 GLM — 28.9%, 3 GLM — 3.2%), insulin therapy in 18,8%, without drug therapy in 4.9%.CONCLUSIONS. The performed analysis demonstrates the importance of dynamic assessment of epidemiological characteristics and monitoring of clinical data on patients with diabetes through a registry for assessing the quality of diabetes care and the prospects for its development

Diabetes mellitus in Russian Federation: prevalence, morbidity, mortality, parameters of glycaemic control and structure of glucose lowering therapy according to the Federal Diabetes Register, status 2017

BACKGROUND: The enormous social lesion caused by high prevalence of diabetes mellitus (DM) determines the state importance of clinical and epidemiological monitoring organization. AIMS: To analyze epidemiological characteristics (prevalence, mortality, morbidity), the level of HbA1c, evaluate the therapy in Russian Federation in 2013–2017. METHODS: We have used the database of the Russian Federal Diabetes register – 81 regions included in the online register system. RESULTS: The total number of patients with DM was 4,498m. (3.06% RF population), including: Type 1 (T1) 5,7% (0,26 m), T2 92,1% (4,15m), other DM types 1,9% (83,8 ths). Distribution male/female: T1 53.5%/46.5%, T2 29%/71%, other DM types 24%/76%. The proportion of men decreases with aging. Number of patients >65 years was 2.293.520, including T1 21.97ths (3.6%), T2 2m271.5ths (54.7%). The prevalence 2013→2017 per 100,000 population was as follows: T1 159,8→169,6; T2 2455.3→2775.6; other DM types 51,2→65,8. Morbidity: T1 9,8→7,0; T2 226,7→185,2; other DM types 7,8→12,4. The structure of causes of death 2013→2017: T1: diabetic coma 2,0→1,5%, myocardial infarction 4,0→4,4%, cerebral circulation disorders 8,2→7,6%, cardiovascular insufficiency 18,5→16,4%, chronic renal failure 6,1→ 6,0%; T2 0,2→0,2%, 4,5→4,5%, 12,7→12,2%, 29,0→28,6%, 1,2→1,8%, respectively. Mortality: T1 2.3; T2 68.4, other DM types 0,8. Life expectancy (average age of death of patients): T1 male 50.3→50.2, female 60.2→ 57.2; T2 69.8→70.3, 75.1→75.9 respectively. The number of patients with target HbA1c level <7%: T1 22.3→34.0%, T2 38.0→52.4%; HbA1c≥9.0%: T1 29.2→21.1%, T2 12.6→8.8%. The most commonly prescribed classes of glucose lowering medications (GLM) in 2017: in monotherapy Metformin (57.3%), Sulfonilurea (SU) (41,1%); in combination of 2 GLM: Metformin+SU 92,58% Metformin+iDPP-4 5.63%; 3 or more GLM: Metformin+SU+iDPP-4 83,9%, Metformin+SU+iSGLT-2 8.98%. The proportion of patients on aGPP-1 therapy is 0.01%. CONCLUSIONS: We observed the growth of prevalence of DM in Russian Federation and decrease in registered morbidity rate; an increase in life expectancy in T2; decrease in mortality due to diabetic coms and stable mortality rate from cardiovascular events (heart attack, stroke, cv deficiency), gangrene, chronic renal failure in both types of DM; a steady improvement in glycemic control. In the structure of T2 therapy the oral GLMs are dominated, especially Metformin and SU. In the dynamics the prescription of Metformin, insulin, iDPP-4, iSGLT-2 has increased, the proportion of SU has decreased

General Relativity as Classical Limit of Evolutionary Quantum Gravity

We analyze the dynamics of the gravitational field when the covariance is restricted to a synchronous gauge. In the spirit of the Noether theorem, we determine the conservation law associated to the Lagrangian invariance and we outline that a non-vanishing behavior of the Hamiltonian comes out. We then interpret such resulting non-zero ``energy'' of the gravitational field in terms of a dust fluid. This new matter contribution is co-moving to the slicing and it accounts for the ``materialization'' of a synchronous reference from the corresponding gauge condition. Further, we analyze the quantum dynamics of a generic inhomogeneous Universe as described by this evolutionary scheme, asymptotically to the singularity. We show how the phenomenology of such a model overlaps the corresponding Wheeler-DeWitt picture. Finally, we study the possibility of a Schr\"odinger dynamics of the gravitational field as a consequence of the correspondence inferred between the ensemble dynamics of stochastic systems and the WKB limit of their quantum evolution. We demonstrate that the time dependence of the ensemble distribution is associated with the first order correction in $\hbar$ to the WKB expansion of the energy spectrum.Comment: 23 pages, to appear on Class. Quant. Gra

Covariance and Time Regained in Canonical General Relativity

Canonical vacuum gravity is expressed in generally-covariant form in order that spacetime diffeomorphisms be represented within its equal-time phase space. In accordance with the principle of general covariance, the time mapping {\T}: {\yman} \to {\rman} and the space mapping {\X}: {\yman} \to {\xman} that define the Dirac-ADM foliation are incorporated into the framework of the Hilbert variational principle. The resulting canonical action encompasses all individual Dirac-ADM actions, corresponding to different choices of foliating vacuum spacetimes by spacelike hypersurfaces. In this framework, spacetime observables, namely, dynamical variables that are invariant under spacetime diffeomorphisms, are not necessarily invariant under the deformations of the mappings \T and \X, nor are they constants of the motion. Dirac observables form only a subset of spacetime observables that are invariant under the transformations of \T and \X and do not evolve in time. The conventional interpretation of the canonical theory, due to Bergmann and Dirac, can be recovered only by postulating that the transformations of the reference system ({\T},{\X}) have no measurable consequences. If this postulate is not deemed necessary, covariant canonical gravity admits no classical problem of time.Comment: 41 pages, no figure