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

Uranium and thorium behavior in groundwater of the natural spa area "Choygan mineral water" (East Tuva)

The natural spa area "Choygan mineral waters", a unique deposit of natural carbon dioxide mineral waters in Siberia, is located in the Eastern Sayan Mountains. There are 33 spring discharges in this area. Spring waters are mainly of HCO[3]-Na-Ca type. TDS varies from 300 mg/L to 2600 mg/L, the temperature ranges from 7 °С (in spring 33) to 39 °С (in spring 12), pH varies from 5.9 to 8.3, and the value of the oxidation-reduction potential is from -170 mV to 236 mV. All studied waters were divided into two groups according to their temperature and geochemical conditions: cold fresh water in oxidizing environment and warm slightly brackish water in reducing environment. The uranium concentration varies from 0.7 to 14 [mu]g/l and the thorium concentration varies from 0.001 to 0.33 [mu]g/l in the studied waters. The predominant uranium complexes are (UO[2](CO[3])[3]){4-}, (UO[2](CO[3])[2]){2-}, UO[2]CO[3], (UO[2](PO[4])[2]){4-} in the waters in oxidizing and reducing environments. It was found that acid-alkaline and oxidizing-reducing conditions were the determining factors for uranium behavior and speciation in the studied waters. The pH conditions are determining factors for thorium behavior and speciation in the studied waters. In slightly acidic water the predominant thorium species is negatively charge complex (ThCO[3](OH)[3])- (more than 95 %)

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

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

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

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

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

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

Возрастание уровня стресса среди выпускников школы

Данная статья исследует проблему возрастания уровня стрессовых ситуаций среди учеников старшей школы, причиной которого является образовательная деятельность по подготовке школьников к единому государственному экзамену (ЕГЭ). Высокий уровень стресса оказывает деструктивное влияние на все сферы человеческой жизни. В статье также изучаются другие факторы, влияющие на психическое здоровье учащихся, и приводятся способы борьбы со стрессовыми факторами и снижения их влияния на жизнь ребенка.This report examines the problem of increasing stress levels among high school students, the cause of which is educational activity, namely, the preparation of schoolchildren for the unified state exam (USE). A high level of stress has a destructive effect on all spheres of human life. The article also studies other factors affecting the mental health of students, and provides ways to combat stress factors and reduce their impact on the child's life