Is cancer incidence modified by SGLT2 inhibitors?

One of the most important achievements of diabetology in the second decade of the 21st century is undoubtedly the introduction of sodium-glucose cotransporter (SGLT2) inhibitors into clinical practice as a new class of glucose-lowering agents for type 2 diabetes. In addition to the glucosuria induced by these agents, which is their main pathway for achieving ‘antidiabetic recovery’, other consequences accompany the intake of SGLT2 inhibitors. These pathways, particularly in oncology, have not been extensively studied. Considering the analysis of the previous studies, this report demonstrates, although not significantly, that cancer morbidity in patients with T2DM treated with SGLT2 inhibitors may be organ-specific. In addition, agents within the class of SGLT-2 inhibitors may be useful in several variants of antitumor therapy, but this theory requires further study

ЭНДОКРИННЫЕ И СОПРЯЖЕННЫЕ С НИМИ ПОСЛЕДСТВИЯ КОНСЕРВАТИВНОГО / ХИМИОГОРМОНОТЕРАПЕВТИЧЕСКОГО / ЛЕЧЕНИЯ ОНКОЛОГИЧЕСКИХ БОЛЬНЫХ: ВОЗМОЖНОСТИ И СТЕПЕНЬ ЦЕЛЕСООБРАЗНОСТИ КОРРЕКЦИИ

Treatment of patients with malignant tumors, largely involves the use of chemotherapy, targeted therapy and endocrine therapy (anti-hormonal and hormonal drugs). Depending on the location and nature of the tumor, surgical interventions aiming to remove some endocrine organs (in particular, ovarian, testicular, thyroid and endocrine portion of the pancreas, etc.) can lead to disruption of their function. The objective of presented study is to focus our attention mainly on the effects (including the steroid and non-steroidal components) of anticancer treatment in the endocrine system and in the outcomes associated with hormonal and metabolic changes, clinical and phenotypic features. These effects are manifested not only by changes of laboratory and instrumental parameters, but also accompanied by changes in the clinical manifestations of the disease and the patient's subjective feelings. The therapy often has adverse effects, as the anticipated final results of influence of such processes as weight gain, dyslipidemia, impaired glucose tolerance, lack of ovarian, adrenal, growth hormone and testicular function, osteopenia, hot flushes, chronic fatigue e.t.c., which often limits the success of treatment. Passive registration of such violations, and the silent watching them – is only one side of the problem rather frequent enough, the other side - are the questions about modern approaches of their correction and its feasibility. In part, this problem has a genetic basis, which, along with other indicators, can determine not only the response to anti-tumor therapy, but the severity of endocrine changes, their potential prognostic role, as well as the indications for their prevention and elimination. There are many clinically significant situations that are need to be analysed and discussed, such as: complete androgen blockade in prostate cancer patients, endocrine effects of adjuvant chemotherapy and hormonal therapy in breast cancer patients of reproductive and postmenopausal age, the expected increase of the frequency of performing of preventive salpingoovariectomies in carriers of mutations in BRCA1 and BRCA2 genes, thyroid (in particular) and adrenocortical tropism of targeted therapy, consequences of high doses of corticosteroid support therapy, etc., that demonstrate the importance of this problem, considering these facts in clinical practice and the establishment of standards for the management of patients with these problems.Лечение больных, страдающих злокачественными новообразованиями, в значительной мере включает в себя применение химиотерапии, таргетной терапии и эндокринотерапии. (антигормональных и гормональных препаратов). В зависимости от локализации и природы опухолевого процесса, хирургические вмешательства, сводящихся к удалению некоторых эндокринных органов (в частности, яичников, тестикул, щитовидной и внутрисекреторной части поджелудочной железы и т. д.), могут приводить к нарушению их функции. Задача представленной работы состоит в том, чтобы, сконцентрировать наше внимание, преимущественно, на последствиях противоопухолевого лечения оказываемую на эндокринную систему (включая ее стероидный и нестероидный компоненты) и, главное, — на исходы, сопряженные с гормонально-метаболическими сдвигами, клиническими и фенотипическими особенностями. Такие последствия, проявляются не только изменениями лабораторных и инструментальных показателей, но и сопровождаются изменениями клинической картины заболевания, субъективных ощущений пациента. Проводимая терапия нередко оказываются «палкой о двух концах», поскольку на ожидаемые итоговые результаты влияют процессы такого рода, как прибавка массы тела, дислипидемия, нарушение толерантности к глюкозе, недостаточность овариальной, надпочечниковой, соматотропной и тестикулярной функции, остеопения, приливы, хроническая усталость т. д., что нередко ограничивает успех лечения. Пассивная регистрация подобных нарушений и молчаливое наблюдение за ними — лишь одна и достаточно нередкая сторона проблемы, другая — это вопросы о современных подходах их коррекции и целесообразности последних. Частично эта проблема имеет генетическое основание, которая, наряду с другими показателями, может определять не только реакцию на противоопухолевую терапию, но и степень выраженности эндокринных изменений, их потенциальную прогностическую роль, равно как и показания к их предупреждению / устранению. Круг клинически значимых и нуждающихся в анализе и обсуждении ситуаций, таких как: полная андрогенная блокада при раке предстательной железы, эндокринные последствия адъювантной химиотерапии и гормонотерапии при раке молочной железы у больных репродуктивного и постменопаузального возраста, ожидаемый всплеск частоты выполнения превентивной сальпингоовариэктомии у носительниц мутаций генов BRCA1 и BRCA2; «тиреоидная (в особенности) и адренокортикальная тропность» таргетной терапии, следствия высокодозной кортико-стероидной поддержки химиотерапии и т. д., свидетельствует о важности данной проблематики, необходимости ее учета в клинической практике и создании стандартов для ведения пациентов с перечисленными проблемами

Nonlinear Integer Programming

Research efforts of the past fifty years have led to a development of linear integer programming as a mature discipline of mathematical optimization. Such a level of maturity has not been reached when one considers nonlinear systems subject to integrality requirements for the variables. This chapter is dedicated to this topic. The primary goal is a study of a simple version of general nonlinear integer problems, where all constraints are still linear. Our focus is on the computational complexity of the problem, which varies significantly with the type of nonlinear objective function in combination with the underlying combinatorial structure. Numerous boundary cases of complexity emerge, which sometimes surprisingly lead even to polynomial time algorithms. We also cover recent successful approaches for more general classes of problems. Though no positive theoretical efficiency results are available, nor are they likely to ever be available, these seem to be the currently most successful and interesting approaches for solving practical problems. It is our belief that the study of algorithms motivated by theoretical considerations and those motivated by our desire to solve practical instances should and do inform one another. So it is with this viewpoint that we present the subject, and it is in this direction that we hope to spark further research.Comment: 57 pages. To appear in: M. J\"unger, T. Liebling, D. Naddef, G. Nemhauser, W. Pulleyblank, G. Reinelt, G. Rinaldi, and L. Wolsey (eds.), 50 Years of Integer Programming 1958--2008: The Early Years and State-of-the-Art Surveys, Springer-Verlag, 2009, ISBN 354068274

Stay calm! Regulating emotional responses by implementation intentions: assessing the impact on physiological and subjective arousal

Implementation intention (IMP) has recently been highlighted as an effective emotion regulatory strategy (Schweiger Gallo et al., 2009). Most studies examining the effectiveness of IMPs to regulate emotion have relied on self-report measures of emotional change. In two studies we employed electrodermal activity (EDA) and heart rate (HR) in addition to arousal ratings (AR) to assess the impact of an IMP on emotional responses. In Study 1, 60 participants viewed neutral and two types of negative pictures (weapon vs. non-weapon) under the IMP “If I see a weapon, then I will stay calm and relaxed!” or no self-regulatory instructions (Control). In Study 2, additionally to the Control and IMP conditions, participants completed the picture task either under goal intention (GI) to stay calm and relaxed or warning instructions highlighting that some pictures contain weapons. In both studies, participants showed lower EDA, reduced HR deceleration and lower AR to the weapon pictures compared to the non-weapon pictures. In Study 2, the IMP was associated with lower EDA compared to the GI condition for the weapon pictures, but not compared to the weapon pictures in the Warning condition. AR were lower for IMP compared to GI and Warning conditions for the weapon pictures

On the unitarization of linear representations of primitive partially ordered sets

We describe all weights which are appropriated for the unitarization of linear representations of primitive partially ordered sets of finite type

Elements of mathematics in problems. Through olympiads and circles to profession

This is a collection of teaching materials used in several Russian universities, schools, and mathematical circles. Most problems are chosen in such a way that in the course of the solution and discussion a reader learns important mathematical ideas and theories. The materials can be used by pupils and students for self-study, and by teachers. This is an abridged pre-copyedit version of the published book submitted with the permission of the publisher. Each included individual material is self-contained and ready-for-use. Solutions to problems are not included intentionally. This collection consolidates updates of several arXiv submissions, e.g., arXiv:1305.2598.Comment: Edited by A. Skopenkov, M. Skopenkov, A. Zaslavsky. In Russian. Optimized for printing on A5 paper. Moscow Center for Continuous Mathematical Education, 2018, 592pp (in Russian

Implementation of a quantum algorithm to solve Bernstein-Vazirani's parity problem without entanglement on an ensemble quantum computer

Bernstein and Varizani have given the first quantum algorithm to solve parity problem in which a strong violation of the classical imformation theoritic bound comes about. In this paper, we refine this algorithm with fewer resource and implement a two qubits algorithm in a single query on an ensemble quantum computer for the first time