Population genomics of post-glacial western Eurasia.

Western Eurasia witnessed several large-scale human migrations during the Holocene <sup>1-5</sup> . Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes-mainly from the Mesolithic and Neolithic periods-from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a 'great divide' genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 BP, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a 'Neolithic steppe' cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

The formation of human populations in South and Central Asia

By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization’s decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Популяционный иммунитет к SARS-COV-2 населения Калиниградской области в эпидемический сезон COVID-19

Introduction. The COVID-19 pandemic was announced by WHO in February 2020. In the Kaliningrad region, the first case (imported) was registered in early March 2020, the beginning of the epidemic increase fell on the 14th week. 2020, and the peak incidence was reached in the 22nd week of the year, after which there was a steady decrease in the number of cases. The study of population immunity was carried out at the 32nd week during the period of the lowest level of intensity of the epidemic process.Purpose of the study. Assessment of the assessment of the level of population immunity to the SARS-CoV-2 virus among the population of the Kaliningrad region during the period of the epidemic incidence of the population of COVID-19.Materials and methods. The study was carried out as part of the first stage of the Rospotrebnadzor program to assess population immunity to SARS-CoV-2 among the population of the Russian Federation. The selection of volunteers for the study was carried out by a questionnaire survey and subsequent randomization. The analysis includes the results of a survey of 2675 people. The number of volunteers in age groups ranged from 314 to 493 people. The results obtained were processed by the methods of variation statistics.Results. The results obtained showed that the average seroprevalence in the population was 50.2%, while the highest seroprevalence was found in the child age group 1-17 years (66.9%) and among persons aged 18-29 (57.0). No significant gender differences were found (men – 48,3 ± 1,6%, women – 51,1 ± 1,1%). The distribution of the proportion of seropositive people in the settlements of the region varied from 33,9% to 59.6%. The largest share of seroprevalence in the representative samples was found among people engaged in art / creativity (55,3%), the smallest – among educational workers (42,0%). Among COVID-19 convalescents, the level of humoral immunity reached 94,6%. Most of the seropositive volunteers (95,2%) did not have any symptoms of COVID-19, that is, they belonged to the category of asymptomatic carriers.Output. The results of a survey of a representative cohort of volunteers in the Kaliningrad region showed that they are characterized by a high level of population immunity, which makes it possible to expect a decrease in.Введение. Пандемия COVID-19 была объявлена Всемирная организация здравоохранения в феврале 2020 г. В Калининградской области первый случай (завозной) зарегистрировали в начале марта 2020 г., начало эпидемического нарастания пришлось на 14-ю неделю 2020 г., а пик заболеваемости был достигнут на 22-й неделе года, после чего отмечалось устойчивое снижение количества заболевший. Исследование популяционного иммунитета было проведено на 32-й неделе в период самого низкого уровня напряженности эпидемического процесса.Цель. Оценка уровня популяционного иммунитета к вирусу SARS-CoV-2 среди населения Калининградской области в период эпидемической заболеваемости населения COVID-19.Материалы и методы. Исследование проведено в рамках первого этапа программы Роспотребнадзора по оценке популяционного иммунитета к SARS-CoV-2 среди населения Российской Федерации. Отбор волонтеров для исследования проводили методом анкетирования и последующей рандомизации. В анализ включены результаты обследования 2675 человек. Количество волонтеров в возрастных группах варьировало от 314 до 493 человек. Полученные результаты обрабатывали методами вариационной статистики.Результаты. Полученные результаты показали, что средняя серопревалентность по популяции составила 50,2%, при этом набольшая серопревалентность была выявлена в детской возрастной группе 1–17 лет (66,9%) и среди лиц в возрасте 18–29 лет (57,0). Достоверных половых различий не установлено (мужчины – 48,3±1,6%, женщины – 51,1±1,1%). Распределение доли серопозитивных по населенным пунктам области варьировало от 33,9% до 59,6%. Наибольшая доля серопревалентных в репрезентативных выборках выявлена среди лиц, занятых искусством/творчеством (55,3%), наименьшая – среди работников образования (42,0%). Среди реконвалесцентов COVID-19 уровень гуморального иммунитета достиг 94,6%. Большая часть серопозитивных волонтеров (95,2%) не имела каких-либо симптомов COVID-19, то есть относилась к категории бессимптомных носителей.Выводы. Результаты обследования репрезентативной когорты волонтеров Калининградской области показали, что для них характерен высокий уровень популяционного иммунитета, позволяющий ожидать снижения напряженности эпидемического процесса.

The Peculiarities of the Internal Position of Younger Schoolchildren with the Various Orientation of the Personality

The article submits some psychological features of the internal position of younger schoolchildren with various orientations of the personality. The basic directions of psychological support of the internal position of the personality of younger schoolchildren are proved in the article