Self-preservation behavior as a component of demographic municipal policy

В статье дается определение молодежи как социальной общности, раскрывается вопрос о важности решения социальных и демографических проблем молодежи и о необходимости изменения социальной политики в отношении данной социально незащищенной категории населения. Показано, что существует несколько этапов влияния на потребность молодежи в самосохранительном поведении. Определена значимость самосохранительного поведения в демографической и муниципальной политике.This paper provides a definition of youth as a social community, revealed the importance of resolving social and demographic problems of youth and the need for changes in social policy in relation to this, socially vulnerable categories of society. It is shown that there are several stages of influence on young people and the need. The importance of self-preservation behavior in population and municipal politics

IMscin001 Part 2: a randomised phase III, open-label, multicentre study examining the pharmacokinetics, efficacy, immunogenicity, and safety of atezolizumab subcutaneous versus intravenous administration in previously treated locally advanced or metastatic non-small-cell lung cancer and pharmacokinetics comparison with other approved indications

Non-small-cell lung cancer; Pharmacokinetics; SubcutaneousCàncer de pulmó de cèl·lules no petites; Farmacocinètica; SubcutaniCáncer de pulmón de células no pequeñas; Farmacocinética; SubcutáneoBackground Atezolizumab intravenous (IV) is approved for the treatment of various solid tumours. To improve treatment convenience and health care efficiencies, a coformulation of atezolizumab and recombinant human hyaluronidase PH20 was developed for subcutaneous (SC) use. Part 2 of IMscin001 (NCT03735121) was a randomised phase III, open-label, multicentre, noninferiority study comparing the drug exposure of atezolizumab SC with atezolizumab IV. Patients and methods Eligible patients with locally advanced/metastatic non-small-cell lung cancer were randomised 2 : 1 to receive atezolizumab SC (1875 mg; n = 247) or IV (1200 mg; n = 124) every 3 weeks. The co-primary endpoints were cycle 1 observed trough serum concentration (Ctrough) and model-predicted area under the curve from days 0 to 21 (AUC0-21 d). The secondary endpoints were steady-state exposure, efficacy, safety, and immunogenicity. Exposure following atezolizumab SC was then compared with historical atezolizumab IV values across approved indications. Results The study met both of its co-primary endpoints: cycle 1 observed Ctrough {SC: 89 μg/ml [coefficient of variation (CV): 43%] versus IV: 85 μg/ml (CV: 33%); geometric mean ratio (GMR), 1.05 [90% confidence interval (CI) 0.88-1.24]} and model-predicted AUC0-21 d [SC: 2907 μg d/ml (CV: 32%) versus IV: 3328 μg d/ml (CV: 20%); GMR, 0.87 (90% CI 0.83-0.92)]. Progression-free survival [hazard ratio 1.08 (95% CI 0.82-1.41)], objective response rate (SC: 12% versus IV: 10%), and incidence of anti-atezolizumab antibodies (SC: 19.5% versus IV: 13.9%) were similar between arms. No new safety concerns were identified. Ctrough and AUC0-21 d for atezolizumab SC were consistent with the other approved atezolizumab IV indications. Conclusions Compared with IV, atezolizumab SC demonstrated noninferior drug exposure at cycle 1. Efficacy, safety, and immunogenicity were similar between arms and consistent with the known profile for atezolizumab IV. Similar drug exposure and clinical outcomes following SC and IV administration support the use of atezolizumab SC as an alternative to atezolizumab IV.This work was supported by F. Hoffmann-La Roche Ltd (no grant number)

ХРОНИЧЕСКАЯ ИНТОКСИКАЦИЯ «ВЕСЕЛЯЩИМ ГАЗОМ» (ЗАКИСЬЮ АЗОТА) – ПРИЧИНА В12 -ДЕФИЦИТНОЙ МИЕЛОПОЛИНЕЙРОПАТИИ У ЛИЦ МОЛОДОГО ВОЗРАСТА

The problem of using nitrous oxide (“laughing gas”) is now important because young people often prefer this kind of entertainment. Regular short-term inhalation of nitrous oxide increases the risk of developing vitamin B12 deficiency, which is an essential cofactor of important  metabolic processes. This article describes 2 clinical cases of neurological disorders in young adults who had used nitrous oxide. We demonstrate difficulties in the diagnosis, therapeutic tactics and prognosis. В настоящее время проблема злоупотребления закисью азота («веселящим газом») приобрела актуальность, так как среди лиц молодого возраста выросла популярность данного вида «развлечения». Регулярное даже краткосрочное вдыхание закиси азота  повышает вероятность развития дефицита витамина В12 – незаменимого кофактора важных процессов метаболизма. В статье приводятся 2 клинических наблюдения развития неврологических нарушений у молодых людей, злоупотребляющих закисью азота.Рассмотрены трудности диагностики подобных состояний, терапевтическая тактика и прогноз.

Мутации в геноме вирусов гриппа птиц подтипов Н1 и Н5, ответственные за адаптацию к млекопитающим

Avian influenza viruses of H1 and H5 subtypes were involved in the formation of highly pathogenic viruses that caused pandemics and panzootics in the 20th–21st centuries. In order to assess the zoonotic potential of viruses of these subtypes, two viruses of H1N1 and H5N3 have been isolated from wild ducks in Moscow and adapted to growth in mouse lungs. Their phenotypic properties were studied, and the genetic changes that occurred during adaptation were identified. The original A/duck/Moscow/4970/2013 (H1N1) and A/duck/Moscow/4182-C/2010 (H5N3) viruses were apathogenic for mice but became pathogenic after 7–10 passages in mouse lungs. Complete genome sequencing revealed 2 amino acid substitutions in the proteins of the H1N1 mouse-adapted variant (Glu627Lys in PB2 and Asp35Asn in hemagglutinin (HA) – numbering according to H3) and 6 mutations in the proteins of H5N3 virus (Glu627lys in PB2, Val113Ala in PB1, Ser82Pro in PB1-F2, Lys52Arg in HA2, Arg65Lys in NP, and Ser59Ile in NA). The increase in virulence is most likely due to a common substitution in the protein PB2 Glu627Lys as revealed in both viruses. The replacement of Asp35Asn in HA of the mouse-adapted H1N1 virus is associated with an increase in the pH value of the HA transition from 5.0 for 5.5 in comparison to the HA of parent virus. The found mutations in HA, NA, and PB1-F2 proteins of the adapted H5N3 variant are unique. The mutations Glu627Lys in PB2, Arg65Lys in NP, and Val113Ala in PB1 are most likely host adaptive.Вирусы гриппа птиц подтипов Н1 и Н5 участвовали в формировании высокопатогенных вариантов вирусов, вызвавших пандемии и  панзоотии в  XX–XXI  веках. С  целью оценки зоонозного потенциала вирусов этих подтипов, выделенных от диких уток в черте Москвы, была проведена адаптация вирусов к размножению в легких мышей, изучены их фенотипические свойства и идентифицированы генетические изменения, возникшие при адаптации. Изначально апатогенные для мышей вирусы A/duck/Moscow/4970/2013 (H1N1) и A/duck/Moscow/4182‑C/2010 (H5N3) после 7–10 пассажей через легкие мышей изменили фенотип на патогенный. Полногеномное секвенирование выявило в адаптированных к мышам вирусах 2 аминокислотные замены в вирусе гриппа H1N1 (Glu627Lys в белке PB2 и Asp35Asn в гемагглютинине (HA) — нумерация по H3) и 6 мутаций в белках вируса H5N3 (Glu627Lys в PB2, Val113Ala в PB1, Ser82Pro в PB1‑F2, Lys52Arg в HA2, Arg65Lys в NP и Ser59Ile в NA). Возрастание вирулентности для мышей, скорее всего, обусловлено общей для обоих вирусов заменой – Glu627Lys в  белке PB2. Замена Asp35Asn в  HA адаптированного к  мышам вируса гриппа H1N1  ассоциирована с возрастанием значения рН конформационного перехода HA с 5.0 до 5.5 относительно HA дикого вируса. Обнаруженные в адаптированном варианте H5N3 мутации в белках НА, NA и PB1‑F2 — уникальные. Мутации Glu627Lys в PB2, Arg65Lys в NP и Val113Ala в PB1, скорее всего, носят адаптационный характер

Extensive Mammalian Ancestry of Pandemic (H1N1) 2009 Virus

We demonstrate that the novel pandemic influenza (H1N1) viruses have human virus–like receptor specificity and can no longer replicate in aquatic waterfowl, their historic natural reservoir. The biological properties of these viruses are consistent with those of their phylogenetic progenitors, indicating longstanding adaptation to mammals

Mutations in the genome of avian influenza viruses of the H1 and H5 subtypes responsible for adaptation to mammals

Avian influenza viruses of the H1 and H5 subtypes were involved in the formation of highly pathogenic viruses that caused pandemics and panzootics in the 20th–21st centuries. In order to assess the zoonotic potential of viruses of these subtypes, two viruses of the H1N1 and H5N3 subtypes have been isolated from wild ducks in Moscow and adapted for growth in mouse lungs. Their phenotypic properties were studied, and the genetic changes that occurred during adaptation were identified. The original A/duck/Moscow/4970/2013 (H1N1) and A/duck/Moscow/4182-C/2010 (H5N3) viruses were apathogenic for mice but became pathogenic after 7–10 passages in mouse lungs. Complete genome sequencing revealed 2 amino acid substitutions in the proteins of the H1N1 mouse-adapted variant (Glu627Lys in PB2 and Asp35Asn in hemagglutinin (HA) – numbering according to H3) and 6 mutations in the proteins of H5N3 virus (Glu627lys in PB2, Val113Ala in PB1, Ser82Pro in PB1-F2, Lys52Arg in HA2, Arg65Lys in NP, and Ser-59Ile in NA). The increase in virulence is most likely due to a Glu627Lys substitution in the protein PB2 found in both viruses. The replacement Asp35Asn in HA of the mouse-adapted H1N1 virus is associated with an increase in the pH value of the HA transition to 5.5 versus 5.0 for that of the wild virus. The mutations found in the HA, NA, and PB1-F2 proteins of the adapted H5N3 variant are unique. The mutations Glu627Lys in PB2, Arg65Lys in NP, and Val113Ala in PB1 are most likely host adaptive

Frequency of D222G and Q223R Hemagglutinin Mutants of Pandemic (H1N1) 2009 Influenza Virus in Japan between 2009 and 2010

BACKGROUND: In April 2009, a novel swine-derived influenza A virus (H1N1pdm) emerged and rapidly spread around the world, including Japan. It has been suggested that the virus can bind to both 2,3- and 2,6-linked sialic acid receptors in infected mammals, in contrast to contemporary seasonal H1N1 viruses, which have a predilection for 2,6-linked sialic acid. METHODS/RESULTS: To elucidate the existence and transmissibility of α2,3 sialic acid-specific viruses in H1N1pdm, amino acid substitutions within viral hemagglutinin molecules were investigated, especially D187E, D222G, and Q223R, which are related to a shift from human to avian receptor specificity. Samples from individuals infected during the first and second waves of the outbreak in Japan were examined using a high-throughput sequencing approach. In May 2009, three specimens from mild cases showed D222G and/or Q223R substitutions in a minor subpopulation of viruses infecting these individuals. However, the substitutions almost disappeared in the samples from five mild cases in December 2010. The D187E substitution was not widespread in specimens, even in May 2009. CONCLUSIONS: These results suggest that α2,3 sialic acid-specific viruses, including G222 and R223, existed in humans as a minor population in the early phase of the pandemic, and that D222 and Q223 became more dominant through human-to-human transmission during the first and second waves of the epidemic. These results are consistent with the low substitution rates identified in seasonal H1N1 viruses in 2008

Dataware for cost-oriented environmental management of the enterprise

В статье охарактеризованы сущность стоимость-ориентированного экологического менеджмента и особенности обеспечения его информационной поддержки путём формирования сбалансированной системы эколого-экономических показателей предприятия. Предлагается авторский алгоритм стоимость-ориентированного экологического менеджмента при использовании сбалансированной системы эколого-экономических показателей предприятия.The article characterizes the essence of cost-oriented environmental management and peculiarities of its information support by means of creating a balanced system of enterprise ecological-economic indicators. The author suggests her own cost-oriented environmental management algorithm on the base of a balanced system of enterprise ecological-economic indicators

Innovative tools for management of social-ecological-economical sustainability of industrial enterprise

В статье рассматривается проблема устойчивого развития промышленных предприятий. Для ее решения автором предлагается внедрение интегральных технологических и нетехнологических (организационно-управленческих) инноваций, способствующих поддержанию одновременно и социальной, и экологической, и экономической устойчивости предприятий.This paper is consecrated to problem concerned sustainable development of industrial enterprise. The author proposes an application of the cumulative technological and nontechnological (organizational and management) innovations which make for ensuring of social and ecological and economical sustainability of enterprises consentaneously

Management of Ecological Cost of the Enterprise

The author approach to the realization of conception of management of cost enterprise in the sphere of ecological management is described. The meaning of ecological cost is characterized. And methodological approaches to the increasing of this cost mainly by management of its financial and not financial factors are considered.В статье описывается авторский подход к реализации концепции управления стоимостью бизнеса (предприятия) в сфере экологического менеджмента. В частности, характеризуется понятие «экологическая стоимость», а также рассматриваются методические подходы к повышению данной стоимости, главным образом посредством управления ее финансовыми и нефинансовыми факторами