Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS. Conclusion: Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug

Комплементарная модель самодетерминации личности

Introduction. The relevance of studying the phenomenon of self-determination is substantiatedby the compliance of this research problem with two actively developing areas of personalitypsychology – the psychology of a change and the psychology of a possible. The variety ofmanifestations of personality self-determination, the complexity and uniqueness of this phenomenonnecessitate the generalization of existing theoretical developments, ideas and concepts, as wellas accumulated empirical material. Modern Russian authors formulate theoretical prerequisitesfor the study of self-determination in the framework of the subject-activity approach, however,providing empirical research, they are often based on the methodology of foreign colleagues.The originality of the present work consists in the search for new methodological foundations forthe study of personality self-determination. Theoretical justification. The complexity and ambiguityof the phenomenon of self-determination enhance the differentiation of theoretical approachesto its description. The researchers focus on different levels of manifestations of self-determination:the nature-conditioned ability to self-organization and the innate need for autonomy of theindividuum, the processes of self-regulation of behavior and activity by the Subject, the mechanismsof the formation of subjectity and the development of the Self, as well as personality’s ways torealize a freedom and an intentionality. Along with a wide variety of theories and concepts,there is a deficiency of systemic and complex models. Results. The authors of the article firstproposed the complementary model of self-determination, which allows to integrate existingtheoretical approaches to research through a level-by-level consideration of individ’s, subject’sand personality characteristics. The basic level of spontaneous (functional) self-determinationcorresponds to the principles of self-organization of complex open non-equilibrium systems witha naturally conditioned ability to self-deterministic behavior. The second level of purposeful or“activity-based” self-determination demonstrates the role of conscious planning, volitional effortand conscious choice as a tool for achieving goals and self-regulation of the Subject. Finally, thethird, highest level of meaningful self-determination describes the value and moral self-regulationassociated with the implementation of meaningful choices. Discussion. The research presents anew look at the scientific problem of personality self-determination. The complementary modelreflects a complex multilevel system of self-determination, the evolution of its mechanisms in the process of ontogenesis from the basic psychological needs of the individuum to the complexprocesses of meaningful self-determination of the personality.Введение. Актуальность изучения феномена самодетерминации определяется соответствием данной исследовательской проблематики сразу двум активно развивающимся направлениям психологии личности – психологии изменений и психологии возможного. Многообразие проявлений самодетерминации личности, сложность и уникальность этого феномена обуславливают необходимость обобщения имеющихся теоретических разработок, идей и концепций, а также накопленного эмпирического материала. Современные отечественные авторы формулируют теоретические предпосылки изучения самодетерминации в русле субъектно-деятельностного подхода, но при этом часто заимствуют методологию исследования у зарубежных коллег. Оригинальность данной работы заключается в поиске новых методологических оснований исследования самодетерминации личности. Теоретическое обоснование. Сложность и неоднозначность феномена самодетерминации усиливает дифференциацию теоретических подходов к его описанию. В фокусе внимания исследователей оказываются разноуровневые проявления самодетерминации: природообусловленная способность к самоорганизации и врожденная потребность индивида в автономии, процессы саморегуляции субъектом поведения и деятельности, механизмы становления субъектности и развития Я, а также способы реализации свободы и интенциональности личности. Наряду с широким разнообразием теорий и концепций отмечается дефицит системных и комплексных моделей. Результаты. Авторами впервые предложена комплементарная модель самодетерминации, позволяющая интегрировать имеющиеся теоретические подходы к исследованию за счет уровневого рассмотрения индивидных, субъектных и личностных характеристик. Базовый уровень спонтанной (функциональной), самодетерминации соответствует принципам самоорганизации сложных открытых неравновесных систем, обладающих природообусловленной способностью к самодетерминированному поведению. Второй уровень целенаправленной или «деятельностной» самодетерминации показывает роль сознательного планирования, волевого усилия и осознанного выбора как инструмента достижения цели и саморегуляции субъекта. Наконец, третий, наивысший уровень смысловой самодетерминации описывает ценностную и нравственную саморегуляцию, связанную с осуществлением смысловых выборов. Обсуждение результатов. Данное исследование представляет новый взгляд на научную проблему самодетерминации личности. Комплементарная модель отражает сложную многоуровневую систему самодетерминации, эволюцию ее механизмов в процессе онтогенеза от базовых психологических потребностей индивида до сложных процессов смыслового самоопределения личности

Sputnik V Effectiveness against Hospitalization with COVID-19 during Omicron Dominance

Mass vaccination campaigns against COVID-19 affected more than 90% of the population in most developed countries. The new epidemiologic wave of COVID-19 has been ongoing since the end of 2021. It is caused by a virus variant B.1.1.529, also known as &ldquo;Omicron&rdquo; and its descendants. The effectiveness of major vaccines against Omicron is not known. The purpose of this study is to evaluate the efficacy of the Sputnik V vaccine. The main goal is to assess its protection against hospitalization in the period of Omicron dominance. We conducted our study based on a large clinical center in Moscow (Russia) where 1112 patients were included. We used the case-population method to perform the calculations. The data we obtained indicate that the Omicron variant causes at least 90% of infections in the studied cohort. The effectiveness of protection against hospitalization with COVID-19 in our study was 85.9% (95% CI 83.0&ndash;88.0%) for those who received more than one dose. It was 87.6% (95% CI 85.4&ndash;89.5%) and 97.0% (95% CI 95.9&ndash;97.8%) for those who received more than two or three doses. The effectiveness in cases of more severe forms was higher than for less severe ones. Thus, present study indicates the high protective efficacy of vaccination against hospitalization with COVID-19 in case of Omicron lineage

DataSheet_1_Estimation of anti-orthopoxvirus immunity in Moscow residents and potential risks of spreading Monkeypox virus.docx

WHO has declared the outbreak of monkeypox as a public health emergency of international concern. In less than three months, monkeypox was detected in more than 30 000 people and spread to more than 80 countries around the world. It is believed that the immunity formed to smallpox vaccine can protect from monkeypox infection with high efficiency. The widespread use of Vaccinia virus has not been carried out since the 1980s, which raises the question of the level of residual immunity among the population and the identification of groups requiring priority vaccination. We conducted a cross-sectional serological study of remaining immunity among Moscow residents. To do this, a collection of blood serum samples of age group over 30 years old was formed, an in-house ELISA test system was developed, and a virus neutralization protocol was set up. Serum samples were examined for the presence of IgG antibodies against Vaccinia virus (n=2908), as well as for the ability to neutralize plaque formation with a Vaccinia virus MNIIVP-10 strain (n=299). The results indicate the presence of neutralizing antibody titer of 1/20 or more in 33.3 to 53.2% of people older than 45 years. Among people 30-45 years old who probably have not been vaccinated, the proportion with virus neutralizing antibodies ranged from 3.2 to 6.7%. Despite the higher level of antibodies in age group older than 66 years, the proportion of positive samples in this group was slightly lower than in people aged 46-65 years. The results indicate the priority of vaccination in groups younger than 45, and possibly older than 66 years to ensure the protection of the population in case of spread of monkeypox among Moscow residents. The herd immunity level needed to stop the circulation of the virus should be at least 50.25 – 65.28%.</p