Contribution of tumour and immune cells to PD-L1 expression as a predictive biomarker in metastatic triple-negative breast cancer: exploratory analysis from KEYNOTE-119

Pembrolizumab; Triple‐negative breast cancerPembrolizumab; Cáncer de mama triple negativoPembrolizumab; Càncer de mama triple negatiuThe efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD-L1) expression, as quantified by combined positive score (CPS; PD-L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple-negative breast cancer (mTNBC) in the phase 3 KEYNOTE-119 study. This exploratory analysis was conducted to determine whether the expression of PD-L1 on tumour cells contributes to the predictive value of PD-L1 CPS in mTNBC. PD-L1 expression in tumour samples was assessed using PD-L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD-L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58–0.80) for CPS, 0.55 (95% CI = 0.46–0.64) for TPS, and 0.67 (95% CI = 0.56–0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression-free survival, and overall survival. Data from this exploratory analysis suggest that, although PD-L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD-L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD-L1 expression) may improve prediction. PD-L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types

The MetNet vehicle : a lander to deploy environmental stations for local and global investigations of Mars

Investigations of global and related local phenomena on Mars such as atmospheric circulation patterns, boundary layer phenomena, water, dust and climatological cycles and investigations of the planetary interior would benefit from simultaneous, distributed in situ measurements. Practically, such an observation network would require low-mass landers, with a high packing density, so a large number of landers could be delivered to Mars with the minimum number of launchers. The Mars Network Lander (MetNet Lander; MNL), a small semi-hard lander/penetrator design with a payload mass fraction of approximately 17 %, has been developed, tested and prototyped. The MNL features an innovative Entry, Descent and Landing System (EDLS) that is based on inflatable structures. The EDLS is capable of decelerating the lander from interplanetary transfer trajectories down to a surface impact speed of 50-70 ms(-1) with a deceleration of <500 g for <20 ms. The total mass of the prototype design is approximate to 24 kg, with approximate to 4 kg of mass available for the payload. The EDLS is designed to orient the penetrator for a vertical impact. As the payload bay will be embedded in the surface materials, the bay's temperature excursions will be much less than if it were fully exposed on the Martian surface, allowing a reduction in the amount of thermal insulation and savings on mass. The MNL is well suited for delivering meteorological and atmospheric instruments to the Martian surface. The payload concept also enables the use of other environmental instruments. The small size and low mass of a MNL makes it ideally suited for piggy-backing on larger spacecraft. MNLs are designed primarily for use as surface networks but could also be used as pathfinders for high-value landed missions.Peer reviewe

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 9th edition

Dear Colleagues! We are glad to present the 9th Edition (revised) of Standards of Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation. The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), American Diabetes Association (ADA, 2018, 2019), American Association of Clinical Endocrinologists (AACE, 2019), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2014, 2018) and Russian Association of Endocrinologists (RAE, 2011, 2012, 2015). Current edition of the &ldquo;Standards&rdquo; also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals. Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 463 million patients by the end of 2019. According to the current estimation by the International Diabetes Federation, 578 million patients will be suffering from diabetes mellitus by by 2030 and 700 million by 2045. Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 584 575 patients with DM in this country by the end of 2018 (3,1% of population) with 92% (4 238 503) &ndash; Type 2 DM, 6% (256 202) &ndash; Type 1 DM and 2% (89 870) &ndash; other types of DM, including 8 006 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) con- firmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 9 million patients (about 6% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don&rsquo;t receive any treatment ant have high risk of vascular complications. Severe consequences of the global pandemics of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral, coronary and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death. In сurrent edition of the &ldquo;Standards&rdquo;: New goals of glycemic control for the elderly, based on the presence of functional dependence, as well as for pregnant women, children and adolescents, are given. Added a snippet that describes the continuous glucose monitoring. Only low-density lipoprotein cholesterol level is used as a target for lipid metabolism. Proposes more stringent target levels of blood pressure. It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes: the excess of the initial level of HbA1c over the target level was used as a criterion. In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages. Recommendations for psychosocial support are added. The position of metabolic surgery as a method of treatment of DM with morbid obesity is updated. Recommendations for diagnostic and treatment of hypogonadism syndrome in men with DM are added. For the first time, evidence levels of confidence and credibility levels of recommendations for diagnostic, therapeutic, rehabilitative and preventive interventions based on a systematic review of the literature are given in accordance with the recommendations of the Center for Healthcare Quality Assessment and Control of the Ministry of Health of the Russian Federation. This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discus- sions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians and other medical professionals involved in the treatment of DM. On behalf of the Working Grou

Standards of specialized diabetes care. Edited by Dedov I.I., Shestakova M.V., Mayorov A.Yu. 10th edition

Dear Colleagues!We are glad to present the 10th Edition (revised) of the Standards of Specialized Diabetes Care. These evidence-based guidelines were designed to standardize and facilitate diabetes care in all regions of the Russian Federation.The Standards are updated on the regular basis to incorporate new data and relevant recommendations from national and international clinical societies, including World Health Organization Guidelines (WHO, 2011, 2013), International Diabetes Federation (IDF, 2011, 2012, 2013), European Association for the Study of Diabetes (EASD 2018, 2019), American Diabetes Association (ADA, 2018, 2019, 2021), American Association of Clinical Endocrinologists (AACE, 2020, 2021), International Society for Pediatric and Adolescent Diabetes (ISPAD, 2018) and Russian Association of Endocrinologists (RAE, 2019). Current edition of the “Standards” also integrates results of completed randomized clinical trials (ADVANCE, ACCORD, VADT, UKPDS, SAVOR, TECOS, LEADER, EXAMINE, ELIXA, SUSTAIN, DEVOTE, EMPA-REG OUTCOME, CANVAS, DECLARE, CARMELINA, REWIND, CREDENCE, CAROLINA, DAPA-CKD, DAPA-HF, EMPEROR-Reduced trial, VERIFY, VERTIS CV, PIONEER, etc.), as well as findings from the national studies of diabetes mellitus (DM), conducted in close partnership with a number of Russian hospitals.Latest data indicates that prevalence of DM in the world increased during the last decade more than two-fold, reaching some 537 million patients by the end of 2021. According to the current estimation by the International Diabetes Federation, 643 million patients will be suffering from DM by 2030 and 784 million by 2045.Like many other countries, Russian Federation experiences a sharp rise in the prevalence of DM. According to Russian Federal Diabetes Register, there are at least 4 871 863 patients with DM in this country on 01.01.2021 (3,34% of population) with 92,3% (4 498 826)–Type 2 DM, 5,6% (271 468)–Type 1 DM and 2,1% (101 569)–other types of DM, including 9 729 women with gestational DM. However, these results underestimates real quantity of patients, because they consider only registered cases. Results of Russian epidemiological study (NATION) confirmed that only 54% of Type 2 DM are diagnosed. So real number of patients with DM in Russia is 10 million patients (about 7% of population). This is a great long-term problem, because a lot of patients are not diagnosed, so they don’t receive any treatment and have high risk of vascular complications.Severe consequences of the global pandemic of DM include its vascular complications: nephropathy, retinopathy, coronary, cerebral and peripheral vascular disease. These conditions are responsible for the majority of cases of diabetes-related disability and death.In сurrent edition of the “Standards”:New goals of glycemic control for continuous glucose monitoring (time in range, below range and above range, glucose variability) are given.It also features updated guidelines on stratification of treatment in newly diagnosed Type 2 diabetes.In the recommendations for the personalization of the choice of antidiabetic agents, it is taken into account that in certain clinical situations (the presence of atherosclerotic cardiovascular diseases and their risk factors, chronic heart failure, chronic kidney disease, obesity, the risk of hypoglycemia) certain classes of hypoglycemic agents (or individual drugs) have proven advantages.Indications for the use of antidiabetic agents in chronic kidney disease are expanded.Information about insulin pump therapy is added.Recommendations on vaccination are added.An algorithm for replacing some insulin preparations with others is given.This text represents a consensus by the absolute majority of national experts, achieved through a number of fruitful discussions held at national meetings and forums. These guidelines are intended for endocrinologists, primary care physicians, pediatricians and other medical professionals involved in the treatment of DM.Compared with previous edition of the Standards of Specialized Diabetes Care edited by Dedov I.I., Shestakova M.V., ­Mayorov A.Yu., 10th edition, Moscow, 2021 (signed for printing on 10.09.2021) a number of changes have been made.On behalf of the Working Grou

An Efficient Supply Chain Management Model: The Analysis of Domestic and International Practices

Abstract— The study discusses the challenge of providing an effective supply chain management model that would meet modern requirements. The purpose of the study is to analyze the theoretical and practical aspects of developing business processes of supply chain management, as well as to substantiate an efficient business logistics management model. The survey revealed that supply chain management is carried out in a highly competitive environment while business owners are in very difficult conditions: on the one hand, customer requirements are being expanded and diversified, and on the other hand, global logistics market entry requires better service and price cuts. It has been concluded that it is feasible to outsource IT logistics processes due to the global tendency to complicate supply chain management, the introduction of information technologies, increasing customer requirements, and major business processes within the supply chain. This is reflected through an increase in investment / demand in the IT industry, an increase in the number of providers, an increase in equipment, a shortage of specialists, etc. The trend observed in our country is consistent with the ones of developed economies. An algorithm for the implementation of the supply chain formation mechanism has been developed

ЗАХИСТ СИСТЕМ СУПУТНИКОВОГО ЗВ’ЯЗКУ ВІД РАДІОЕЛЕКТРОННОГО ПРИДУШЕННЯ

The results of analysis of methods of the special satellite lines from the radio electronic suppression are presented in the article. It is considered some perspective directions of antijamming of the satellite communication systems for example of three systems, such as: the system antijamming with spatial indemnification of hindrances; the system antijamming with carrying “receiving” and “transmitter” companions-repeaters (СR); the system monitoring and analysis of radiations of companions-repeaters.The use of spatial indemnification of hindrances allows to reduce their influence on 20…30 dB in a centimeter and decimeter ranges of waves, in the relative (to 50%) stripe of frequencies. Setting about companions-repeaters allows to hide from an opponent position of receiving СR and to prevent influence on him intentional hindrances. The use of automated systems of radio monitoring allows to carry out the analysis of radiations of СR, educe the location of source of hindrances and remove their influence.В статье представлены результаты анализа методов повышения помехозащищенности специальных линий спутниковой связи и рассмотрены некоторые перспективные направления помехозащиты систем спутниковой связи.У статті надані результати аналізу методів підвищення завадозахищеності спеціальних ліній супутникового зв’язку та розглянуті деякі перспективні напрями завадозахисту систем супутникового зв’язку

Fast-Processable Non-Flammable Phthalonitrile-Modified Novolac/Carbon and Glass Fiber Composites

Phthalonitrile resins (PN) are known for their incredible heat resistance and at the same time poor processability. Common curing cycle of the PN includes dozens hours of heating at temperatures up to 375 &deg;C. This work was aimed at reducing processing time of phthalonitrile resin, and with this purpose, a novolac oligomer with hydroxyl groups fully substituted by phthalonitrile moieties was synthesized with a quantitative yield. Formation of the reaction byproducts was investigated depending on the synthesis conditions. The product was characterized by 1H NMR and FT-IR. Curing of the resins with the addition of different amounts of novolac phenolic as curing agent (25, 50 and 75 wt.%) was studied by rheological and DSC experiments. Based on these data, a curing program was developed for the further thermosets&rsquo; investigation: hot-pressing at 220 &deg;C and 1.7 MPa for 20 min. TGA showed the highest thermal stability of the resin with 25 wt.% of novolac (T5% = 430 &deg;C). The post-curing program was developed by the use of DMA with different heating rates and holding for various times at 280 or 300 &deg;C (heating rate 0.5 &deg;C/min). Carbon and glass fiber plastic laminates were fabricated via hot-pressing of prepregs with Tg&rsquo;s above 300 &deg;C. Microcracks were formed in the CFRP, but void-free GFRP were fabricated and demonstrated superior mechanical properties (ILSS up to 86 MPa; compressive strength up to 620 MPa; flexural strength up to 946 MPa). Finally, flammability tests showed that the composite was extinguished in less than 5 s after the flame source was removed, so the material can be classified as V-0 according to the UL94 ratings. For the first time, fast-curing phthalonitrile prepregs were presented. The hot-pressing cycle of 20 min with 150 min free-standing post-curing yielded composites with the unique properties. The combination of mechanical properties, scale-up suitable fast-processing and inflammability makes the presented materials prospective for applications in the electric vehicle industries, fast train construction and the aerospace industry

Random Laser Based on Ytterbium-Doped Fiber with a Bragg Grating Array as the Source of Continuous-Wave 976 nm Wavelength Radiation

A random narrow-linewidth lasing at a wavelength of 976 nm was obtained in an ytterbium-doped germanophosphosilicate fiber with an array of weakly reflecting fiber Bragg gratings (FBGs). A random laser cavity was formed by implementing the standard phase mask method of FBG inscription directly during the fiber drawing process. The UV radiation pulses of a KrF excimer laser (248 nm wavelength) synchronized with the fiber drawing speed were used to fabricate the in-fiber array of hundreds of similar FBGs. The developed laser’s slope efficiency in the backward-pumping scheme was measured as high as 33%. The stable continuous-wave operation mode of the laser was detected. The magnitude of the laser power fluctuations depends linearly on the cavity length. The random laser cavity modified with a single highlyreflected (90%) FBG demonstrates significantly better power stability and higher slope efficiency than the same one without an FBG

Random Laser Based on Ytterbium-Doped Fiber with a Bragg Grating Array as the Source of Continuous-Wave 976 nm Wavelength Radiation

A random narrow-linewidth lasing at a wavelength of 976 nm was obtained in an ytterbium-doped germanophosphosilicate fiber with an array of weakly reflecting fiber Bragg gratings (FBGs). A random laser cavity was formed by implementing the standard phase mask method of FBG inscription directly during the fiber drawing process. The UV radiation pulses of a KrF excimer laser (248 nm wavelength) synchronized with the fiber drawing speed were used to fabricate the in-fiber array of hundreds of similar FBGs. The developed laser&rsquo;s slope efficiency in the backward-pumping scheme was measured as high as 33%. The stable continuous-wave operation mode of the laser was detected. The magnitude of the laser power fluctuations depends linearly on the cavity length. The random laser cavity modified with a single highlyreflected (90%) FBG demonstrates significantly better power stability and higher slope efficiency than the same one without an FBG