Neurosurgery in Ukraine: comparison with other countries of the world

The object is to determine the state and performance indicators of the bed density and workforce of the neurosurgical network of Ukraine. To conduct a comparative analysis of the data obtained with the data from other countries.Materials and methods. The work is based on the analysis of the results of a continuous study of the bed density, workforce, and medical work of neurosurgical departments of Ukraine in 2014-2019. The data on neurosurgical beds, workforce, and their work in other countries are taken from scientific articles or open Internet sources.The study did not include departments and physicians located on the non-controlled territory. When calculating the indicators, the population of the Crimea, Sevastopol, DPR, and LPR was not taken into account.Statistical data processing was performed using the analysis of dynamic series, using the median, arithmetic mean, weighted average, and quartiles. Microsoft Excel was used for calculations.Results. The density of neurosurgical beds in 2019 was 81 per 1 million population. This is a high level of density compared to Sweden, the Netherlands, Norway, and the UK (20-30), but lower than in the Russian Federation (90), the Czech Republic, Germany, and Greece (100).The density of neurosurgeons per 1 million population and the ratio of neurosurgeons to the total population in 2019 was 16.8 / 1 : 59,502, which corresponds to the indicator in the Russian Federation — 16.8 / 1 : 59,524, significantly lower than in Japan — 58.95 / 1 : 16962] and higher than in the USA — 15.2 / 1 : 65,580. When comparing the indicators of 2016, it was revealed that the density of neurosurgeons per 1 million population in Ukraine is higher than the average in Europe — 17.5 against 11.76.In 2019, 1,127 neurosurgical patients were operated in Ukraine per 1 million population, which is lower than the average level of neurosurgical care for the European population (1,642).The average stay of a patient in a bed in 2019 was 10.5 days, and the bed occupancy was 81 % (297 days of work per year), which meets the international standard for bed occupancy (80-85 % / 292-310 days).Conclusions. The regions of Ukraine differ in the density of neurosurgical beds and neurosurgeons, but the population of the country as a whole is provided with them at the level of European standards.The performance of the bed density and workforce of the neurosurgical network of Ukraine corresponds to this in several European countries, but, despite the positive dynamics, it is still less than the average European indicator and does not cover the annual demand of the country

The June 2016 Optical and Gamma-Ray Outburst and Optical Micro-Variability of the Blazar 3C454.3

The quasar 3C454.3 underwent a uniquely-structured multi-frequency outburst in June 2016. The blazar was observed in the optical $R$ band by several ground-based telescopes in photometric and polarimetric modes, at $\gamma$-ray frequencies by the \emph{Fermi}\ Large Area Telescope, and at 43 GHz with the Very Long Baseline Array. The maximum flux density was observed on 2016 June 24 at both optical and $\gamma$-ray frequencies, reaching $S^\mathrm{max}_\mathrm{opt}=18.91\pm0.08$ mJy and $S_\gamma^\mathrm{max} =22.20\pm0.18\times10^{-6}$ ph cm$^{-2}$ s$^{-1}$, respectively. The June 2016 outburst possessed a precipitous decay at both $\gamma$-ray and optical frequencies, with the source decreasing in flux density by a factor of 4 over a 24-hour period in $R$ band. Intraday variability was observed throughout the outburst, with flux density changes between 1 and 5 mJy over the course of a night. The precipitous decay featured statistically significant quasi-periodic micro-variability oscillations with an amplitude of $\sim 2$-$3\%$ about the mean trend and a characteristic period of 36 minutes. The optical degree of polarization jumped from $\sim3\%$ to nearly 20\% during the outburst, while the position angle varied by \sim120\degr. A knot was ejected from the 43 GHz core on 2016 Feb 25, moving at an apparent speed $v_\mathrm{app}=20.3c\pm0.8c$. From the observed minimum timescale of variability $\tau_\mathrm{opt}^\mathrm{min}\approx2$ hr and derived Doppler factor $\delta=22.6$, we find a size of the emission region $r\lesssim2.6\times10^{15}$ cm. If the quasi-periodic micro-variability oscillations are caused by periodic variations of the Doppler factor of emission from a turbulent vortex, we derive a rotational speed of the vortex $\sim0.2c$.Comment: 19 pages, 13 figures, 3 tables, accepted to the Astrophysical Journal 2019 March

Emission-line Variability during a Nonthermal Outburst in the Gamma-Ray Bright Quasar 1156+295

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.We present multi-epoch optical spectra of the γ-ray bright blazar 1156+295 (4C +29.45, Ton 599) obtained with the 4.3 m Lowell Discovery Telescope. During a multiwavelength outburst in late 2017, when the γ-ray flux increased to 2.5 × 10−6 phot cm−2 s−1 and the quasar was first detected at energies ≥100 GeV, the flux of the Mg ii λ2798 emission line changed, as did that of the Fe emission complex at shorter wavelengths. These emission-line fluxes increased along with the highly polarized optical continuum flux, which is presumably synchrotron radiation from the relativistic jet, with a relative time delay of ≲2 weeks. This implies that the line-emitting clouds lie near the jet, which points almost directly toward the line of sight. The emission-line radiation from such clouds, which are located outside the canonical accretion-disk related broad-line region, may be a primary source of seed photons that are up-scattered to γ-ray energies by relativistic electrons in the jet. © 2022. The Author(s). Published by the American Astronomical Society.This research was supported in part by NASA Fermi guest investigator program grants 80NSSC19K1504 and 80NSSC20K1565. We thank A. Tchekhovskoy for discussion of possible origins of the variable line-emitting clouds. These results made use of the Lowell Discovery Telescope (LDT) at Lowell Observatory. Lowell Observatory is a private, non-profit institution dedicated to astrophysical research and public appreciation of astronomy, and operates the LDT in partnership with Boston University, the University of Maryland, the University of Toledo, Northern Arizona University and Yale University. This study was based in part on observations conducted using the 1.8 m Perkins Telescope Observatory (PTO) in Arizona, which is owned and operated by Boston University. I.A. acknowledges financial support from the Spanish "Ministerio de Ciencia e Innovación" (MCINN) through the "Center of Excellence Severo Ochoa" award for the Instituto de Astrofísica de Andalucía-CSIC (SEV-2017-0709). Acquisition and reduction of the MAPCAT data were supported in part by MICINN through grants AYA2016-80889-P and PID2019-107847RB-C44. The MAPCAT observations were carried out at the German-Spanish Calar Alto Observatory, which is jointly operated by Junta de Andalucía and Consejo Superior de Investigaciones Científicas. Data from the Steward Observatory spectropolarimetric monitoring project were used; this program was supported by Fermi Guest Investigator grants NNX08AW56G, NNX09AU10G, NNX12AO93G, and NNX15AU81G. C.C. acknowledges support from the European Research Council (ERC) under the European Union Horizon 2020 research and innovation program under the grant agreement No. 771282.Peer reviewe

The Variant rs1867277 in FOXE1 Gene Confers Thyroid Cancer Susceptibility through the Recruitment of USF1/USF2 Transcription Factors

In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30–1.70; P = 5.9×10−9). Functional assays of rs1867277 (NM_004473.3:c.−283G>A) within the FOXE1 5′ UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/αCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era

Europe-wide expansion and eradication of multidrug-resistant Neisseria gonorrhoeae lineages: a genomic surveillance study

Centre for Genomic Pathogen Surveillance and the Euro-GASP study group: Sonja Pleininger, Alexander Indra, Irith De Baetselier, Wim Vanden Berghe, Blaženka Hunjak, Tatjana Nemeth Blažić, Panayiota Maikanti-Charalambous, Despo Pieridou, Hana Zákoucká, Helena Žemličková, Steen Hoffmann, Susan Cowan, Lasse Jessen Schwartz, Rita Peetso, Jevgenia Epstein, Jelena Viktorova, Ndeindo Ndeikoundam, Beatrice Bercot, Cécile Bébéar, Florence Lot, Susanne Buder, Klaus Jansen, Vivi Miriagou, Georgios Rigakos, Vasilios Raftopoulos, Eszter Balla, Mária Dudás, Lena Rós Ásmundsdóttir, Guðrún Sigmundsdóttir, Guðrún Svanborg Hauksdóttir, Thorolfur Gudnason, Aoife Colgan, Brendan Crowley, Sinéad Saab, Paola Stefanelli, Anna Carannante, Patrizia Parodi, Gatis Pakarna, Raina Nikiforova, Antra Bormane, Elina Dimina, Monique Perrin, Tamir Abdelrahman, Joël Mossong, Jean-Claude Schmit, Friedrich Mühlschlegel, Christopher Barbara, Francesca Mifsud, Alje Van Dam, Birgit Van Benthem, Maartje Visser, Ineke Linde, Hilde Kløvstad, Dominique Caugant, Beata Młynarczyk-Bonikowska, Jacinta Azevedo, Maria-José Borrego, Marina Lurdes Ramos Nascimento, Peter Pavlik, Irena Klavs, Andreja Murnik, Samo Jeverica, Tanja Kustec, Julio Vázquez Moreno, Asuncion Diaz, Raquel Abad, Inga Velicko, Magnus Unemo, Helen Fifer, Jill Shepherd, Lynsey PattersonBackground: Genomic surveillance using quality-assured whole-genome sequencing (WGS) together with epidemiological and antimicrobial resistance (AMR) data is essential to characterise the circulating Neisseria gonorrhoeae lineages and their association to patient groups (defined by demographic and epidemiological factors). In 2013, the European gonococcal population was characterised genomically for the first time. We describe the European gonococcal population in 2018 and identify emerging or vanishing lineages associated with AMR and epidemiological characteristics of patients, to elucidate recent changes in AMR and gonorrhoea epidemiology in Europe. Methods: We did WGS on 2375 gonococcal isolates from 2018 (mainly Sept 1-Nov 30) in 26 EU and EEA countries. Molecular typing and AMR determinants were extracted from quality-checked genomic data. Association analyses identified links between genomic lineages, AMR, and epidemiological data. Findings: Azithromycin-resistant N gonorrhoeae (8·0% [191/2375] in 2018) is rising in Europe due to the introduction or emergence and subsequent expansion of a novel N gonorrhoeae multi-antigen sequence typing (NG-MAST) genogroup, G12302 (132 [5·6%] of 2375; N gonorrhoeae sequence typing for antimicrobial resistance [NG-STAR] clonal complex [CC]168/63), carrying a mosaic mtrR promoter and mtrD sequence and found in 24 countries in 2018. CC63 was associated with pharyngeal infections in men who have sex with men. Susceptibility to ceftriaxone and cefixime is increasing, as the resistance-associated lineage, NG-MAST G1407 (51 [2·1%] of 2375), is progressively vanishing since 2009-10. Interpretation: Enhanced gonococcal AMR surveillance is imperative worldwide. WGS, linked to epidemiological and AMR data, is essential to elucidate the dynamics in gonorrhoea epidemiology and gonococcal populations as well as to predict AMR. When feasible, WGS should supplement the national and international AMR surveillance programmes to elucidate AMR changes over time. In the EU and EEA, increasing low-level azithromycin resistance could threaten the recommended ceftriaxone-azithromycin dual therapy, and an evidence-based clinical azithromycin resistance breakpoint is needed. Nevertheless, increasing ceftriaxone susceptibility, declining cefixime resistance, and absence of known resistance mutations for new treatments (zoliflodacin, gepotidacin) are promising.This study was supported by the European Centre for Disease Prevention and Control, the Centre for Genomic Pathogen Surveillance, the Li Ka Shing Foundation (Big Data Institute, University of Oxford), the Wellcome Genome Campus, the Foundation for Medical Research at Örebro University Hospital, and grants from Wellcome (098051 and 099202). LSB was funded by Conselleria de Sanitat Universal i Salut Pública, Generalitat Valenciana (Plan GenT CDEI-06/20-B), Valencia, Spain, and Ministry of Science, Innovation and Universities (PID2020–120113RA-I00), Spain, at the time of analysing and writing this manuscript.info:eu-repo/semantics/publishedVersio

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Prevalence of chronic HCV infection in EU/EEA countries in 2019 using multiparameter evidence synthesis

Publisher Copyright: © 2023 The Author(s)Background: Epidemiological data are crucial to monitoring progress towards the 2030 Hepatitis C Virus (HCV) elimination targets. Our aim was to estimate the prevalence of chronic HCV infection (cHCV) in the European Union (EU)/European Economic Area (EEA) countries in 2019. Methods: Multi-parameter evidence synthesis (MPES) was used to produce national estimates of cHCV defined as: π = πrecρrec + πexρex + πnonρnon; πrec, πex, and πnon represent cHCV prevalence among recent people who inject drugs (PWID), ex-PWID, and non-PWID, respectively, while ρrec, ρex, and ρnon represent the proportions of these groups in the population. Information sources included the European Centre for Disease Prevention and Control (ECDC) national operational contact points (NCPs) and prevalence database, the European Monitoring Centre for Drugs and Drug Addiction databases, and the published literature. Findings: The cHCV prevalence in 29 of 30 EU/EEA countries in 2019 was 0.50% [95% Credible Interval (CrI): 0.46%, 0.55%]. The highest cHCV prevalence was observed in the eastern EU/EEA (0.88%; 95% CrI: 0.81%, 0.94%). At least 35.76% (95% CrI: 33.07%, 38.60%) of the overall cHCV prevalence in EU/EEA countries was associated with injecting drugs. Interpretation: Using MPES and collaborating with ECDC NCPs, we estimated the prevalence of cHCV in the EU/EEA to be low. Some areas experience higher cHCV prevalence while a third of prevalent cHCV infections was attributed to PWID. Further efforts are needed to scale up prevention measures and the diagnosis and treatment of infected individuals, especially in the east of the EU/EEA and among PWID. Funding: ECDC.Peer reviewe

Modelling of the Process of Regional systems’ Development Imbalances Aligning with the Use of Tax Levers Моделирование процесса выравнивания диспропорций развития региональных систем с использованием налоговых рычагов

The article is devoted to the question of social-economic development regions disproportions. The complex of economic-mathematical models of disproportions development leveling of regions, based on tax levers, was provided.В статье рассмотрены вопросы диспропорций социально-экономического развития регионов. Предложен комплекс экономико-математических моделей выравнивания диспропорций развития региональных систем на базе налоговых рычагов

Нейрохірургічна служба України: порівняння з іншими країнами світу

The object is to determine the state and performance indicators of the bed density and workforce of the neurosurgical network of Ukraine. To conduct a comparative analysis of the data obtained with the data from other countries.Materials and methods. The work is based on the analysis of the results of a continuous study of the bed density, workforce, and medical work of neurosurgical departments of Ukraine in 2014-2019. The data on neurosurgical beds, workforce, and their work in other countries are taken from scientific articles or open Internet sources.The study did not include departments and physicians located on the non-controlled territory. When calculating the indicators, the population of the Crimea, Sevastopol, DPR, and LPR was not taken into account.Statistical data processing was performed using the analysis of dynamic series, using the median, arithmetic mean, weighted average, and quartiles. Microsoft Excel was used for calculations.Results. The density of neurosurgical beds in 2019 was 81 per 1 million population. This is a high level of density compared to Sweden, the Netherlands, Norway, and the UK (20-30), but lower than in the Russian Federation (90), the Czech Republic, Germany, and Greece (100).The density of neurosurgeons per 1 million population and the ratio of neurosurgeons to the total population in 2019 was 16.8 / 1 : 59,502, which corresponds to the indicator in the Russian Federation — 16.8 / 1 : 59,524, significantly lower than in Japan — 58.95 / 1 : 16962] and higher than in the USA — 15.2 / 1 : 65,580. When comparing the indicators of 2016, it was revealed that the density of neurosurgeons per 1 million population in Ukraine is higher than the average in Europe — 17.5 against 11.76.In 2019, 1,127 neurosurgical patients were operated in Ukraine per 1 million population, which is lower than the average level of neurosurgical care for the European population (1,642).The average stay of a patient in a bed in 2019 was 10.5 days, and the bed occupancy was 81 % (297 days of work per year), which meets the international standard for bed occupancy (80-85 % / 292-310 days).Conclusions. The regions of Ukraine differ in the density of neurosurgical beds and neurosurgeons, but the population of the country as a whole is provided with them at the level of European standards.The performance of the bed density and workforce of the neurosurgical network of Ukraine corresponds to this in several European countries, but, despite the positive dynamics, it is still less than the average European indicator and does not cover the annual demand of the country.Цель: определить состояние и показатели деятельности коечного фонда и кадровых ресурсов нейрохирургической сети Украины. Провести сравнительный анализ полученных данных с данными других стран.Материалы и методы. Проанализированы показатели коечного фонда, кадрового состава, лечебной работы нейрохирургических отделений Украины  и других стран. В исследование не включали отделения, врачей и население, находящиеся на неподконтрольной территории Украины. Применили анализ динамических рядов, использовали медиану, среднюю арифметическую, среднюю взвешенную, квартили.Результаты. Обеспеченность нейрохирургическими койками в 2019 г. составила 81 на 1 млн населения. Это высокий уровень обеспеченности по сравнению со Швецией, Нидерландами, Норвегией и Великобританией (20‒30), но ниже, чем в РФ (90), Чехии, Германии и Греции (100).Обеспеченность нейрохирургами на 1 млн населения и отношение количества нейрохирургов к общей численности населения в 2019 г. составили 16,8 и 1:59502, что соответствует показателю в РФ (16,8 и 1:59524), но значительно ниже, чем в Японии (58,95 и 1:16 962), и выше, чем в США (15,2 и 1:65 580). При сравнении показателей 2016 г. установлено, что обеспеченность нейрохирургами на 1 млн населения в Украине выше, чем в среднем по Европе, ‒ 17,50 и 11,76 соответственно.В 2019 г. в Украине в расчете на 1 млн населения прооперировано 1127 нейрохирургических больных, что ниже среднего уровня нейрохирургической помощи населению Европы (1642).Средняя продолжительность пребывания больного на койке в 2019 г. составила 10,5 дня, загруженность койки ‒ 81% (297 дней работы в год), что соответствует международному стандарту уровня занятости койки (80‒85% (292‒310 дней)).Выводы. Регионы Украины отличаются по обеспеченности нейрохирургическими койками и нейрохирургами, но население страны в целом обеспечено ими на уровне европейских стандартов.Показатели работы коечного фонда и кадровые ресурсы нейрохирургической сети Украины соответствуют таковым ряда европейских стран, но, несмотря на положительную динамику, меньше среднеевропейского показателя и не обеспечивают ежегодную потребность страны.Мета: визначити стан і показники діяльності ліжкового фонду та кадрових ресурсів нейрохірургічної мережі України. Провести порівняльний аналіз отриманих даних з даними інших країн.Матеріали і методи. Проаналізовано показники ліжкового фонду, кадрового складу, лікувальної роботи нейрохірургічних відділень України та інших країн. У дослідження не включали відділення, лікарів і населення, що знаходяться на непідконтрольній території України. Застосували аналіз динамічних рядів, використовували медіану, середню арифметичну, середню зважену, квартилі.Результати. Забезпеченість нейрохірургічними ліжками в 2019 р. становила 81 на 1 млн населення. Це високий рівень забезпеченості порівняно зі Швецією, Нідерландами, Норвегією та Великою Британією (20‒30), але нижче, ніж у РФ (90), Чехії, Німеччині та Греції (100).Забезпеченість нейрохірургами на 1 млн населення і відношення кількості нейрохірургів до загальної чисельності населення в 2019 р. становило 16,8 та 1:59 502, що відповідає показнику в РФ (16,8 і 1:59 524), значно нижче, ніж в Японії (58,95 і 1:16 962, та вище, ніж у США (15,2 і 1:65 580). При порівнянні показників 2016 р. установлено, що забезпеченість нейрохірургами на 1 млн населення в Україні вище, ніж в середньому в Європі, ‒ 17,5 та 11,76.У 2019 р. в Україні в розрахунку на 1 млн населення прооперовано 1127 нейрохірургічних хворих, що нижче за середній рівень нейрохірургічної допомоги населенню Європи (1642).Середня тривалість перебування хворого на ліжку в 2019 р. становила 10,5 дня, завантаженість ліжка ‒ 81% (297 днів роботи на рік), що відповідає міжнародному стандарту рівня зайнятості ліжка (80‒85% (292‒310 днів)).Висновки. Регіони України відрізняються за забезпеченістю нейрохірургічними ліжками і нейрохірургами, але населення країни в цілому забезпечено ними на рівні європейських стандартів.Показники роботи ліжкового фонду та кадрові ресурси нейрохірургічної мережі України відповідають таким низки європейських країн, але, незважаючи на позитивну динаміку, менше середньоєвропейського показника і не задовольняють щорічну потребу країни