GEOMETRY OF RECENT RUPTURE ZONE AT СAPE RYTYI BASED ON GROUND PENETRATING RADAR (NORTHWESTERN COAST OF LAKE BAIKAL)

In here, we present the results of the GPR study of the modern rupture zone discovered earlier in the periphery of the Rita River delta flowing into Lake Baikal. The research was aimed at subsurface imaging of dislocation geometry using the Logis-Geotech OKO-2 radar equipped with the ABDL Triton antenna. As a result, the characterizations have been obtained for six 73 to 197 m long profiles across the rupture zone. All disturbances visible on the aerial photography materials are highlighted on the radargrams by the oblique reflection event due to a decrease in the signal amplitude. The rupture zone has two large segments – northeastern and submeridional, – which differ in zone width, number of discontinuities, dip angles, and displacement amounts. The deformation features can be attributed to different amounts of a plastic loamy aggregate of coarse deposits in different parts of the Rita River delta that is indirectly confirmed by weaker signal amplitudes on the northeastern segment. Based on present and previous studies, we proposed that the M=5.2 earthquake occurred on August 13, 1962, in Lake Baikal initiated the gravitational sinking in the Rita river delta edge by subsidence along gently sloped rupture surfaces on one segment and along steeply sloped ones on the other. It is necessary to identify and monitor such phenomena to prevent the development of emergencies associated with the collapse of the coasts of large water reservoirs

СРЕДНЕКЕДРОВАЯ ПАЛЕОСЕЙСМОДИСЛОКАЦИЯ В БАЙКАЛЬСКОМ ХРЕБТЕ: СТРУКТУРА И ОЦЕНКА СМЕЩЕНИЙ ПО ДАННЫМ ГЕОРАДИОЛОКАЦИИ

Our study aimed to clarify the seismic potential of the Severobaikalsk fault and to discover the structural features of active faults on the NW shores of Lake Baikal. Seismogenic faults and large seismogravitational structures were mapped in the area of the Srednekedrovaya paleoseismodislocation, one of the most remarkable seismotectonic structures in the Baikal region. During the field trip, we tested the capacities of an OKO‐2 georadar and an ABDL‐ Triton antenna used to study cross‐sections of the Baikal ridge. Its slopes are steep, covered with Pinus pumila and abundant screes, many of which developed into boulder streams (‘kurumnik’). The first studies of the Sredneked‐ rovaya paleoseismodislocation were conducted by V.P. Solonenko and his team in 1964–1965. To some extent, this zone can be viewed as a reference object that can provide much information and thus deserves an in‐depth investiga‐ tion using new technologies. Our study combined the field observation and the interpretation of high‐resolution satel‐ lite images provided by DigitalGlobe (US) and downloaded by SAS.Planet. The consolidated database was sufficient for constructing a new schematic map showing the seismogenic faults associated with the Srednekedrovaya paleoseis‐ modislocation. The cumulative length of the ruptures observed on the surface amounted to almost 29.5 km. Some ruptures are separate from each other, and the rupture spacing ranges from the first tens of meters to the first kilome‐ ters. The width of the widest rupture zone is 1.9 km. The length of individual ruptures varies from 5.0 m to 2.7 km. Morphologically, the Srednekedrovaya paleoseismodislocation is represented by ledges and ditches that often comprise complex grabens disturbing the bedrock and slope deposits. The fault structure of this zone is a typical set‐ ting of orthogonal and slightly oblique crustal stretching, but its manifestation differs in the zone segments. In general, it is a combination of steeply dipping and listric faults traced to the depth of 13 m. In plan, the faults are observed to form the systems of subparallel ruptures that mainly strike at 30°. A linear relationship is established between the heights of the seismogenic ledges and the throws estimated from the ground‐penetrating radar data. The former are larger by 0.5–2.0 m than the throw measured from the radargrams. Apparently, this reflects the magnitude of expan‐ sion of the ledge upward along the sloping slope. In the zone of the main fault plane coinciding with the main ledge, the maximum and mean arithmetic throws are 8.3 and 4.93 m, respectively. On other fault planes, the throws range from 0.4 to 4.6 m. The paleoearthquake magnitude ranges from 6.8 to 7.6, according to the estimations from the seis‐ mic rock collapse volume, fault length, and the displacements. Our study of the Srednekedrovaya paleoseismodisloca‐ tion confirms that listric normal faulting is widespread along the western side of the North Baikal basin and gives in‐ direct evidence that conditions for accumulation and release of seismic energy are different on the western and east‐ ern shores of Lake Baikal. It should be noted, however, that in the studied near‐surface layer of the crust, the blocks of loose material may move along the flat planes due to gravitational sliding that increases under the impact of cryogenic processes on the steep slopes of the Baikal ridge.Для уточнения сейсмического потенциала Северобайкальского разлома и выявления особенностей строения активных нарушений северо‐западного побережья озера Байкал нами проведено картирование сейсмогенных разрывов и крупных сейсмогравитационных проявлений в районе Среднекедровой палеосейсмодислокации – одной из самых примечательных сейсмотектонических структур в Байкальском регионе. Одновременно мы испытывали возможности применения георадара ОКО‐2 с антенным блоком АБДЛ Тритон для изучения разрезов в условиях крутых склонов Байкальского хребта, покрытых стланиковыми соснами и осыпями, значительная часть которых преобразована в курумники. Впервые изученная в 1964–1965 гг. под руководством В.П. Солоненко Среднекедровая палеосейсмодислокация стала в некоторой степени эталонным объектом, который в силу своей выразительности требует более тщательного изучения в связи с новыми методическими возможностями. В результате выполненных работ нами на основе полевых наблюдений и дешифрирования спутниковых снимков высокого разрешения, предоставляемых американской компанией DigitalGlobe и доступных через программу SAS.Планета, составлена новая схема сейсмогенных нарушений, ассоциированных с палеосейсмодислокацией Среднекедровой. Общая протяженность видимых на поверхности разрывов составила не менее 29.5 км. Некоторые из них отстоят друг от друга на расстоянии от первых десятков метров до первых километров. Наибольшая ширина зоны разрывов составляет 1.9 км. Длина отдельных трещин изменяется от 5 м до 2.7 км. Морфологически Среднекедровая палеосейсмодислокация представлена уступами и рвами, нередко формирующими сложные грабены, которые нарушают коренные породы и склоновые отложения. Разломная структура зоны типична для обстановки ортогонального или чуть косого растяжения, но по‐разному проявляется на отдельных ее сегментах. В целом для нее характерно сочетание крутопадающих и листрических сбросов, прослеженных до глубины 13 м. В плане они образуют системы субпараллельных разрывов с преобладающим простиранием 30°. Полученные высоты сейсмогенных уступов и вертикальные смещения по данным георадиолокации линейно связаны между собой. Значения первых больше величин подвижек, измеренных на радарограммах, на 0.5–2.0 м, что отражает, по‐видимому, величину расширения уступа вверх по осыпному склону. Максимальная и средняя арифметическая вертикальные амплитуды сброса по зоне главного сместителя, совпадающей с главным уступом, имеют значения 8.3 и 4.93 м, соответственно. По отдельным сместителям смещения колеблются от 0.4 до 4.6 м. Оценки магнитуд палеоземлетрясения, рассчитанные по разным зависимостям с использованием объема сейсмообвала, длины разрыва и смещений, колеблются от 6.8 до 7.6. Изучение Среднекедровой палеосейсмодислокации подтвердило, что листрическое сбросообразование широко распространено вдоль западного борта Северобайкальской впадины, что является косвенным свидетельством различных условий накопления и реализации сейсмической энергии на западном и восточном побережье озера Байкал. В то же время в изученном близповерхностном слое земной коры некоторый вклад в движение блоков рыхлого материала по пологим плоскостям может вносить гравитационное скольжение, которое усиливается под воздействием криогенных процессов в условиях крутых склонов Байкальского хребта

Clinico-economic analysis of PD-1 inhibitors and combinations of BRAF and MEK inhibitors for the treatment of metastatic melanoma with a BRAF V600 gene mutation

The high prevalence of BRAF V600 gene mutation in the Russian Federation and the cost of treatment the metastatic melanoma (MM) with immuno-oncology and combined targeted drugs make it relevant to assess the clinical and economic feasibility of their use. Objective. Cost-effectiveness analysis (CEA) and budget impact analysis (BIA) of PD-1 inhibitor pembrolizumab was performed in comparison with nivolumab and combinations of BRAF and MEK inhibitors in the 1st line therapy of MM with BRAF v600 gene mutation. Methodology. CEA and BIA was performed using the results of a network meta-analysis and based on the Markov model, which estimated the number of life years saved (LYS), duration of progression-free survival and direct medical costs (DC). Results. The cost of treatment per year in the 1st line therapy on pembrolizumab was 3.32 million RUB, what is 29 % cheaper than combination of dabrafenib + trametinib (4.67 million RUB), 60 % than vemurafenib + cobimetinib (8.30 million RUB), 1.7 % than nivolumab (3.38 million RUB). Total 3 years DC for the 1st line therapy on pembrolizumab (3.80 million RUB) were 43.9%, 68.2% and 1.8 % lower than the cost of dabrafenib + trametinib (6.76 million RUB), vemurafenib + cobimetinib (11.93 million RUB) and nivolumab (3.86 million RUB). CER per 1 LYS for pembrolizumab was 2.43 million RUB, nivolumab – 2.48 million RUB, dabrafenib + trametinib – 4.24 million RUB and vemurafenib + cobimetinib – 7.49 million RUB increase in the use of pembrolizumab to 50 %, by reducing the share of the use of combinations of BRAF and MEK inhibitors, will result in budget savings up to 1 507,5 million RUB (26.4 %). Conclusion. The use of pembrolizumab in the 1st line of MM therapy with BRAF V600 gene mutation allows to save the budget and is economically feasible

MAGNETOTHERAPY DEVICE

The article describes a new way of forming bipolar current impulses with short fronts and falls in the magnetotherapy device. The method is able to expand the capabilities of the device. The method was realized by including the additional board that consists of a transistor bridge circuit and a driver control board

Cost-effectiveness analysis of pembrolizumab versus targeted therapies in advanced melanoma

Background. The modern therapies of advanced melanoma include targeted medicines for patients with BRAF mutations. Nowadays, a new perspective on immuno-oncologic medicine pembolizumab became available in Russia. Objective. Assessment of the clinical and economic effectiveness of the use of pembolizumab in the treatment of unrespectable and metastatic melanoma in comparison with targeted medicines in the context of Russian public health. Materials and methods. The Markov model was developed, including the states «without progression», «after progression» and «death», the duration of one Markov cycle is 1 month, the modeling time horizon is 5 years. The probabilities of transitions between states were described using mathematical formulas obtained as a result of digitization and approximation of Kaplan-Mayer survival curves, which were derived from randomized clinical trials KEYNOTE-006, COMBI-v and COMBI-d. Direct medical costs (including drug costs, treatment of adverse events, second-line therapy after disease progression, and palliative care) were analyzed. We did not take into account the costs associated with laboratory-diagnostic procedures and visits to the doctor. The sources of information were: weighted average prices of medicines indicated during public procurement for 2016 (the price of the drug pembolizumab provided by the manufacturer), a program of state guarantees for providing free medical care to Russian citizens for 2016, federal coefficients of relative costs for clinical and statistical groups. The effectiveness criterion for cost-effectiveness analysis was the average number of saved months of a patient’s life. Results. The average number of months saved was 30, 23, 24 and 30 months with pembolizumab, vemurafenib, dabrafenib and dabrafenib plus tramethanib, respectively (calculated using the developed model). Thus, pembolizumab has the same effectiveness as a combination of dabrafenib + tramethanib and is more effective than monotherapy with targeted drugs (dabrafenib or vemurafenib). Direct medical costs per patient over 5 years were approximately 4.06, 5.53, 5.91 and 15.72 million rubles when using pembolizumab, dabrafenib, vemurafenib and a combination of dabrafenib + trametinib, respectively. The health budget saving with pembolizumab instead of dabrafenib, vemurafenib and dabrafenib + trametinib combination may be 26%, 31% and 74%, respectively. Conclusion. Pembolizumab is a rational and economically justified choice for the treatment of unresectable and metastatic melanoma since it leads to cost savings when overall survival is increased

ГЕОМЕТРИЯ ЗОНЫ СОВРЕМЕННЫХ РАЗРЫВОВ НА МЫСЕ РЫТОМ ПО ДАННЫМ ГЕОРАДИОЛОКАЦИИ (СЕВЕРО-ЗАПАДНОЕ ПОБЕРЕЖЬЕ ОЗ. БАЙКАЛ)

In here, we present the results of the GPR study of the modern rupture zone discovered earlier in the periphery of the Rita River delta flowing into Lake Baikal. The research was aimed at subsurface imaging of dislocation geometry using the Logis-Geotech OKO-2 radar equipped with the ABDL Triton antenna. As a result, the characterizations have been obtained for six 73 to 197 m long profiles across the rupture zone. All disturbances visible on the aerial photography materials are highlighted on the radargrams by the oblique reflection event due to a decrease in the signal amplitude. The rupture zone has two large segments – northeastern and submeridional, – which differ in zone width, number of discontinuities, dip angles, and displacement amounts. The deformation features can be attributed to different amounts of a plastic loamy aggregate of coarse deposits in different parts of the Rita River delta that is indirectly confirmed by weaker signal amplitudes on the northeastern segment. Based on present and previous studies, we proposed that the M=5.2 earthquake occurred on August 13, 1962, in Lake Baikal initiated the gravitational sinking in the Rita river delta edge by subsidence along gently sloped rupture surfaces on one segment and along steeply sloped ones on the other. It is necessary to identify and monitor such phenomena to prevent the development of emergencies associated with the collapse of the coasts of large water reservoirs.Представлены результаты георадиолокационного изучения современной зоны разрывов, обнаруженной авторами ранее в периферийной части дельты р. Рита, впадающей в оз. Байкал. Работы проведены с целью прослеживания геометрии дислокаций на глубину при помощи георадара ОКО-2 в комплекте с антенным блоком АБДЛ Тритон. В результате вкрест простирания зоны разрывов охарактеризовано шесть профилей протяженностью от 73 до 197 м. Все разрывы, видимые на материалах аэрофотосъемки, выделяются на радарограммах по наклонной оси синфазности, которая образуется за счет понижения амплитуды сигнала. По простиранию зона нарушений разделяется на два крупных сегмента: северо-восточный и субмеридиональный. Первый от второго отличается большей шириной зоны, числом разрывов, более пологими углами их падения и меньшими амплитудами подвижек. Особенности деформирования могут быть обусловлены разным количеством пластичного суглинистого заполнителя грубообломочных отложений в разных частях дельты, что косвенно подтверждается более слабыми амплитудами сигналов на радарограммах северо-восточного сегмента. По результатам этих и предыдущих исследований высказано предположение о том, что землетрясение 13.08.1962 г. с M=5.2 в оз. Байкал могло запустить процесс гравитационного опускания на окраине дельты р. Рита, который на одном сегменте реализуется в основном путем оседания по пологим нарушениям, на другом – по крутым. Необходимо выявление и мониторинг подобных деформаций для предотвращения развития чрезвычайных ситуаций, связанных с обрушением побережий крупных водоемов

PSYCHOLOGICAL FACTORS OF SURVIVAL AND DISEASE COURSE IN WOMEN WITH BREAST CANCER: RESULTS AND PROSPECTS OF THE STUDY

The article presents the results of a study of psychological factors of survival and the course of the disease in women with breast cancer. As a result of a longitudinal study, data were obtained on the relationship of psychological indicators with various variants of the course of the disease, as well as on the dynamics of personal and subjective characteristics with different outcomes of the disease. The authors have outlined further prospects for a longitudinal study on a sample of women with breast cancer with a fiveyear survival rate.В статье приводятся результаты исследования психологических факторов выживаемости и течения болезни у женщин с раком молочной железы. В результате лонгитюдного исследования получены данные о связи психологических показателей с различными вариантами течения болезни, а также о динамике личностных и субъектных характеристик при различных исходах болезни. Авторами обозначены дальнейшие перспективы лонгитюдного исследования на выборке женщин с раком молочной железы при пятилетней выживаемости.Исследование выполнено за счет гранта Российского научного фонда (проект № 19-18-00426)

EMPOWER-lung 1: A randomized, open-label, multi-national, phase III trial of cemiplimab, a human PD-1 monoclonal antibody, versus chemotherapy in first-line treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 50%

Background: Most patients (pts) with NSCLC present with advanced disease at diagnosis. Systemic therapy with platinum-based doublet chemotherapy regimens has been the standard first-line treatment for pts with advanced NSCLC whose tumours do not have EGFR, ALK, or ROS 1 mutations, but there is a need for effective treatments to improve long-term survival. With the recognition that NSCLC tumours express PD-L1, checkpoint inhibitors are being investigated in several clinical trials. There is currently only one PD-1 inhibitor approved as monotherapy in first-line treatment of NSCLC with PD-L1 expression ≥50%. In a phase 1 dose escalation and NSCLC expansion cohort, cemiplimab (REGN2810), a human monoclonal anti-PD-1, has demonstrated antitumour activity with an acceptable safety profile in anti-PD-1 naïve, pre-treated pts with NSCLC. Trial design: This is a randomised (1:1), multicentre, open-label, phase 3 study of cemiplimab versus platinum-based doublet chemotherapy in systemic treatment-naïve pts (≥18 years) with stage IIIB, IIIC or IV squamous or non-squamous NSCLC whose tumours express PD-L1 in ≥ 50% of tumour cells (NCT03088540)

Multijet production in neutral current deep inelastic scattering at HERA and determination of α_{s}

Multijet production rates in neutral current deep inelastic scattering have been measured in the range of exchanged boson virtualities 10 5 GeV and –1 < η_{LAB}^{jet} < 2.5. Next-to-leading-order QCD calculations describe the data well. The value of the strong coupling constant α_{s} (M_{z}), determined from the ratio of the trijet to dijet cross sections, is α_{s} (M_{z}) = 0.1179 ± 0.0013 (stat.)_{-0.0046}^{+0.0028}(exp.)_{-0.0046}^{+0.0028}(th.)