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

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.

A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144

A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages

A type III secretion system (T3SS) in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJKIM) has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJKIM in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJKIM were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJCO92, YopJKIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJKIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJCO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways

Surgical treatment of patients with lesions of the spinal column (solitary plasmacytoma th1), with spondylolisthesis C7 (III). Clinical case

The article presents a case report of surgical treatment of patients with secondary of the lesion of the spinal column (solitary plasmacytoma in the body of vertebrae Th1) complicated compression fracture and spondylolisthesis C7 3 degrees. In order to achieve the conditions of radical removal of the bulk of education, as well as the elimination of coarse listez in segment of the spine, surgery will be held in three stages. In the postoperative period marked by a partial regression of weakness in the limbs, numbness regression, regression of pain syndrome. Achieve adequate anatomical restoration of vertebral column with sufficient fixation of unstable segment.В статье представлен клинический случай хирургического лечения пациента с вторичным очагом поражения позвоночного столба (солитарной плазмоцитомой в теле Th1 позвонка), осложненной компрессионным переломом и спондилолистезом С7 3 степени. Для достижения условий радикального удаления объемного образования, а также устранения грубого листеза в заинтересованнм сегменте позвоночника, оперативное лечение решено провести в три этапа. В послеоперационном периоде отмечен частичный регресс слабости в конечностях, регресс онемения, регресс болевого синдрома. Достигнуто адекватное анатомическое восстановление позвоночного столба с достаточной фиксацией нестабильного сегмента

Assessment of frequency of the medical and diagnostic surgeries which are carried out concerning metastatic damage of the spine column, and also identification of groups of interest for carrying out additional researches in the specified group of patients

Work is devoted to identification and definition of tactics of maintaining patients with metastatic damage of a backbone. The assessment of frequency of carrying out the medical and diagnostic surgeries which are carried out concerning metastatic damage of a spine column, and also identification of groups of interest and justification of expediency of carrying out additional researches in the specified group of patients is made. During work relevance of carrying out additional researches concerning metastatic from the primary and undetected centers, group of patients with metastatic of a cancer of kidney, specification of histologi options of tumors of patients with the subsequent specification of frequency of occurrence of various morphological options is shown.Работа посвящена проблеме выявления и определения тактики ведения пациентов с метастатическим поражением позвоночника. Произведена оценка частоты проведения лечебных и диагностических оперативных вмешательств, выполняемых по поводу метастатического поражения позвоночного столба, а также выявление групп интереса и обоснование целесообразности проведения дополнительных исследований в указанной группе пациентов. В ходе работы показана актуальность проведения дополнительных исследований в отношении метастазов из первично-невыявленных очагов, группы пациентов с метастазами рака почки, уточнения гистологических вариантов опухолей пациентов с последующим уточнением частоты встречаемости различных морфологических вариантов