30,000 YEARS OF GROUND SURFACE TEMPERATURE AND HEAT FLUX CHANGES IN KARELIA RECONSTRUCTED FROM BOREHOLE TEMPERATURE DATA

Analyses of temperature-depth profiles logged in deep boreholes (> 1 km) permit the reconstruction of ground surface temperature (GST) and surface heat flux (SHF) histories in the period of global climate change at the border of the Pleistocene and the Holocene. We reconstructed past GST and SHF histories using data obtained from the 3.5-km-deep Onega borehole (Karelia, north-west Russia). The resulting reconstructions include information on the basal thermal regime of the Scandinavian Ice Sheet, which covered the region in the Last Glacial Maximum (LGM). The surface temperature history reveals a high amplitude of Pleistocene/ Holocene warming equal to 18–20 K. The heat flux changes precede the surface temperature changes and are close to the variations of insolation at a latitude of 60°N. A comparison of the reconstructed GST and SHF histories with the records of carbon dioxide contents in Antarctic ice cores shows that CO2 changes are much closer to temperature changes than they are to heat flux changes

Autoresonance in a Dissipative System

We study the autoresonant solution of Duffing's equation in the presence of dissipation. This solution is proved to be an attracting set. We evaluate the maximal amplitude of the autoresonant solution and the time of transition from autoresonant growth of the amplitude to the mode of fast oscillations. Analytical results are illustrated by numerical simulations.Comment: 22 pages, 3 figure

Asymptotics for a special solution to the second member of the Painleve I hierarchy

We study the asymptotic behavior of a special smooth solution y(x,t) to the second member of the Painleve I hierarchy. This solution arises in random matrix theory and in the study of Hamiltonian perturbations of hyperbolic equations. The asymptotic behavior of y(x,t) if x\to \pm\infty (for fixed t) is known and relatively simple, but it turns out to be more subtle when x and t tend to infinity simultaneously. We distinguish a region of algebraic asymptotic behavior and a region of elliptic asymptotic behavior, and we obtain rigorous asymptotics in both regions. We also discuss two critical transitional asymptotic regimes.Comment: 19 page

Benign and malignant paragangliomas: clinical presentation and treatment outcomes in 38 patients

Paragangliomas are tumors of neuroendocrine system. Tumors are characterized by a wide variety of localizations. The article presents an analysis of 38 cases of benign and malignant paragangliomas detected between 2010 and 2019 at the Sverdlovsk Regional Oncology Center.Параганглиомы - опухоли нейроэндокринного происхождения, характеризующиеся широким разнообразием локализаций. В статье представлен анализ 38 случаев доброкачественных и злокачественных параганглиом, выявленных за период с 2010 г. по 2019 г. на базе Свердловского областного онкологического диспансера

Lenvatinib Therapy in Patients with Unresectable Hepatocellular Carcinoma in Real Clinical Practice

Aim. To determine lenvatinib treatment outcomes in patients with advanced unresectable hepatocellular carcinoma (uHCC) in real clinical practice.Patients and methods. A multicenter retrospective observational study included 58 patients with a confirmed uHCC diagnosis receiving lenvatinib. At baseline, ECOG, Child-Pugh and BCLC scores were assessed. The objective response rate (ORR), disease control rate (DCR), median overall survival (OS) and median progression-free survival (PFS) rates were assessed. In addition, adverse effects (AE) during treatment were monitored.Results. The median OS and PFS comprised 14.6 (95 % CI 10.6–18.6) and 11.1 months (95 % CI 8.31–13.8), respectively. The ORR amounted to 32.8 %, while DCR reached the level of 79.3 %. The levels of ORR and DCR were not statistically significantly different between the patients with stages B and C according to the BCLC staging system, with grades 0 and 1 according to ECOG, with classes A and B according to the Child-Pugh score, with viral and non-viral HCC etiology, with and without extrahepatic spread, and with and without portal vein invasion. Patients with alpha-fetoprotein (AFP) blood levels <200 ng/mL showed significantly higher ORR and DCR compared to those with AFP levels >200 ng/mL (44.4 % vs. 13.6 %, p = 0.015; and 88.9 % vs. 63.6 %, p = 0.021, respectively). The uHCC stage according to BCLC, ECOG functional status, Child-Pugh class, presence or absence of extrahepatic spread and viral etiology had no effect on the OS and PFS median levels. Patients with macroscopic portal vein invasion had a significantly lower PFS compared with those lacking this complication: 3.97 (0.00-8.07) vs. 11.1 (8.46-13.7), p = 0.053. AFP levels ≥200 ng/mL adversely affected survival rates: median OS comprised 12.0 (5.95-18.9) months in the group of patients with AFP ≥200 ng/mL vs. 16.1 (8.73-23.5) months in the group of patients having AFP <200 ng/mL, p = 0.020. AEs were registered in 81.0% (n = 47) of patients. Among the most common AEs were arterial hypertension (32.8 %), weakness (24.1 %), weight loss (12.1 %) and appetite loss (10.3 %). Due to AEs, Lenvatinib was withdrawn in 5 (8.6 %) patients.Conclusion. Lenvatinib confirmed its efficacy and safety in patients with uHCC in real clinical practice. The treatment outcome might be affected by AFP levels and the presence of macroscopic portal vein invasion. Further comparative studies into treatment regimens applied in real clinical practice are required

Влияние мультидисциплинарного подхода и маршрутизации пациентов на результаты лечения больных гепатоцеллюлярным раком

Introduction: Hepatocellular cancer (HCC) is the sixth most common form of cancer worldwide and the third most common cause of cancer death. The long-term results of treatment are influenced by organizational decisions aimed at increasing the availability of specialized care. The purpose of our study is to evaluate the impact of rerouting and the introduction of a multidisciplinary approach on overall survival (OS) of patients with HCC.Materials and methods. A retrospective study was conducted to study the treatment tactics and results of treatment in all patients with HCC registered in the Sverdlovsk Regional Oncological Cancer Registry with a diagnosis of HCC from 2015 to 2021. A comparative analysis was carried out in 3 groups of patients: the control group, before changes, group of patients after changes in routing, and a group of patients with multidisciplinary approach involving a gastroenterologist / hepatologist and an interventional oncologist.Results: There is an increase in the number of patients who received advice from an oncologist and referred for specialized treatment: 12.0 %, 19.5 % and 34.9 %, respectively (p < 0.001). Median OS increased significantly only in the multidisciplinary approach group of 3.1 versus 2.2 months (p = 0.002). Low overall survival rates are associated with a large proportion of late stages. A significant increase in OS was registered in the group of patients with BCLC C stage: from 3.4 months to 12.5 months (p = 0.046).Conclusions: Simplifying the patient’s route from a gastroenterologist to an oncologist shortens the time to treatment start, increases the number of patients who receive advisory assistance in an oncological dispensary, but does not affect OS. A multidisciplinary approach allows more patients to receive specialized care. At the same time, the maximum effect on OS is noted at the BCLC C stage.Введение: Гепатоцеллюлярный рак (ГЦР) является шестой наиболее распространенной формой рака во всем мире и третьей наиболее распространенной причиной смертности от рака. На отдаленные результаты лечения влияют организационные решения, направленные на повышение доступности специализированной помощи. Цель нашего исследования — оценка влияния изменения маршрутизации и внедрения мультидисциплинарного подхода на общую выживаемость (ОВ) пациентов с ГЦР.Материалы и методы: Проведено ретроспективное исследование по изучению лечебной тактики и результатов лечения у всех пациентов с ГЦР, поставленных на учет в Свердловский областной онкологический канцер-регистр с диагнозом ГЦР с 2015 г. по 2021 г. Проведен сравнительный анализ в 3 группах пациентов: группа контроля (до изменений в маршрутизации), группа пациентов после изменений в маршрутизации и группа больных с мультидисциплинарным подходом с подключением гастроэнтеролога / гепатолога и интервенционного онколога.Результаты: Отмечается увеличение числа пациентов, получивших консультацию онколога и направленных на специализированное лечение: 12,0 %, 19,5 % и 34,9 % соответственно (р < 0,001). Медиана ОВ статистически значимо выросла только в группе с мультидисциплинарным подходом — 3,1 мес. против 2,2 мес. (р = 0,002). Низкие показатели общей выживаемости связаны с большим удельным весом поздних стадий. Значимое увеличение ОВ было в группе пациентов со стадией BCLC C: с 3,4 мес. до 12,5 мес. (р = 0,046).Выводы. Упрощение маршрута пациента от гастроэнтеролога до онколога сокращает сроки до начала лечения, увеличивает число больных, которые получают консультативную помощь в онкологическом диспансере, но не влияет на ОВ. Мультидисциплинарный подход позволяет большему числу больных получить специализированную помощь. При этом максимальное влияние на ОВ отмечается при стадии BCLC C.

Properties of field functionals and characterization of local functionals

Functionals (i.e. functions of functions) are widely used in quantum field theory and solid-state physics. In this paper, functionals are given a rigorous mathematical framework and their main properties are described. The choice of the proper space of test functions (smooth functions) and of the relevant concept of differential (Bastiani differential) are discussed. The relation between the multiple derivatives of a functional and the corresponding distributions is described in detail. It is proved that, in a neighborhood of every test function, the support of a smooth functional is uniformly compactly supported and the order of the corresponding distribution is uniformly bounded. Relying on a recent work by Yoann Dabrowski, several spaces of functionals are furnished with a complete and nuclear topology. In view of physical applications, it is shown that most formal manipulations can be given a rigorous meaning. A new concept of local functionals is proposed and two characterizations of them are given: the first one uses the additivity (or Hammerstein) property, the second one is a variant of Peetre's theorem. Finally, the first step of a cohomological approach to quantum field theory is carried out by proving a global Poincar\'e lemma and defining multi-vector fields and graded functionals within our framework.Comment: 32 pages, no figur