Застосування зворотних залежностей у математичних моделях складних об’єктів та систем

Представлено метод побудови апроксимуючих поліноміальних функцій багатьох змінних, який засновано на використанні в поліномах від’ємних степенів та застосуванні до поліномів обмеження на сумарну величину ступеня добутку змінних. Запропоновано використання штрафної функції на кількість членів полінома. Експериментальним шляхом отримано оптимальну величину коефіцієнта запропонованої штрафної функції.Представлен метод построения аппроксимирующих полиномиальных функций многих переменных, основанный на использовании в полиномах отрицательных степеней и применении к полиномам ограничения на суммарную величину степени произведения переменных. Предложено использование штрафной функции на количество членов полинома. Экспериментальным путем получена оптимальная величина коэффициента предложенной штрафной функции.A method of constructing approximating polynomials functions of many variables, based on the use of the negative degrees in polynomials and the application of the limitation on the total value of the product variable to polynoms is presented. The usage of the penalty function for the number of polynomial members is suggested. The optimum value of the proposed penalty functions coefficient is experimentally obtained

Fatigue in children and adolescents with inflammatory bowel disease

AIM To identify factors other than active disease and anemia that contribute to fatigue in pediatric inflammatory bowel disease (IBD). METHODS We performed an electronic search in Medline and EMBASE from their inception to May 2017 using the search term "fatigue" or the related keywords "physical impairment" and "inflammatory bowel disease" with the filter "child" (age 0-18 years). Cross-sectional and case-control studies were included. We restricted our search to studies published in English. We used the PRISMA checklist and flow diagram. Duplicate articles were manually deleted in End Note. To identify further relevant studies, we checked the reference lists of the selected articles. RESULTS We identified 149 papers, of which 19 were retrieved for full text review. Eleven studies were subsequently excluded because fatigue was not evaluated as an outcome measure. Eight papers focused on the desired topic and were discussed in the final analysis. A lack of uniformity of outcome measures made the pooling of data impossible. In all but one study, questionnaires were used to evaluate fatigue. In the remaining study, an accelerometer was used to measure daily activities, sleeping time and their relationships with fatigue in a more quantifiable manner. Adolescents with IBD are significantly more fatigued than healthy controls. In addition to active disease, increased anxiety or depression and disturbed family relationships were frequently reported predictors of fatigue. Quantitative measurement of physical activity in patients with Crohn's disease showed a reduction in the number of steps per day, and patients with ulcerative colitis had a shorter duration of physical activity during the day. CONCLUSION Fatigue in pediatric IBD is related to a combination of biological, functional and behavioral factors, which should all be taken into account when managing fatigue

Autoimmune enteropathy : clinical and molecular aspects

Auto-immuun enteropathie (AIE) is een zeldzame oorzaak voor immunologisch gemedieerde chronische diarree op de kinderleeftijd. Kenmerkend voor de aandoening zijn circulerende autoantistoffen en verwoesting van de darmwand. Naast het darmlijden kunnen bij AIE ook andere uitingen van auto-immuniteit bestaan, zoals diabetes mellitus, auto-immuun thyreoïdie en auto-immuun anemie of trombocytopenie. Het is een zeer ernstige ziekte waaraan patiënten vaak op jonge leeftijd overlijden. Meer duidelijkheid over de pathofysiologie van AIE is van belang voor een gerichtere diagnostiek en verbetering van therapeutische mogelijkheden. Bovendien geeft het belangrijke informatie over de normale immunologische werking van de darm. Dit proefschrift levert hieraan een bijdrage door dieper in te gaan op de moleculaire achtergrond van AIE. De studies tonen aan dat regulerende T-cel (Treg)-functie een zeer belangrijke rol speelt in het ontstaan van AIE, echter de resultaten suggereren ook een rol voor andere factoren. Bij sommige patiënten ligt een mutatie in het FOXP3-gen ten grondslag aan de ziekte, bij andere patiënten is de oorzaak onduidelijk. Verder is duidelijk geworden dat Treg-functie beïnvloed kan worden door omgevingsfactoren. Dit heeft belangrijke consequenties voor de manier waarop de cellen werken en schept ook nieuwe therapeutische mogelijkheden. In het proefschrift wordt een veel grotere variatie in klinische presentatie van de ziekte beschreven dan tot op heden bekend was. Het is daarom een aanbeveling dat AIE bij een groter aantal patiënten moet worden overwogen. Tot slot gaat het proefschrift nader in op de huidige immunosuppressieve behandeling van AIE:Een moleculaire studie ondersteunt het gebruik van sirolimus bij deze aandoening. Autoimmune enteropathy (AIE) is a rare cause of immunologically mediated chronic diarrhea in childhood. Characteristic of the disorder are circulating autoantibodies and destruction of the intestinal wall. Besides affecting the bowel, the disease comprises other manifestations of autoimmunity, such as diabetes mellitus, autoimmune thyreoïdia and autoimmune anemia or thrombocytopenia. AIE is a very serious disease, often leading to mortality at a young age. More clarity about the pathophysiology of AIE is important for a better diagnosis and targeted therapeutic options. Additionally, more knowledge of the pathofysiology of AIE and intestinal regulatory T-cell (Treg)- function provides important information on normal immune function of the intestine. This thesis focusses on the undestanding of the disease by investigating the molecular background of AIE. The studies in this thesis show that Treg-dysfunction is very important in the pathophysiology of AIE, however the results also suggest that it is not the only disease-causing mechanism. In some patients a mutation in the FOXP3-gene is at the basis of disease, in others the cause is unclear. The results in this thesis support the hypothesis that environmental factors can affect Treg- function. This has important implications for the way these cells work and creates new opportunities for therapeutic intervention. This thesis describes a large variation in clinical presentation of AIE, which implicates that the disease should be considered in a much larger number of patients. Finally, the thesis examines the current immunosuppressive treatment in this disease, presenting molecular evidence for the use of sirolimus.

Evaluation of a Europe-wide Survey on Paediatric Nutrition Training

Commissioned by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), we investigated how European physicians training in these fields are educated in nutrition. A survey on time spent in nutrition training, composition of multidisciplinary nutrition teams, and topics covered during training enrolled 50 participants. A median of 20% of training time was spent on nutrition training during fellowship. Fourteen (28%) had regular nutrition teaching. Thirty-four (68%) were part of a multidisciplinary nutrition team. Twelve (24%) used the ESPGHAN syllabus. Most frequent topics during nutrition training were diagnosis/investigation of failure to thrive, indications/contraindications for enteral feeds, and benefits/risks of enteral/parenteral nutrition. Twenty-seven (54%) had taken a formal nutrition course. Nutrition training in Europe varies and the ESPGHAN training syllabus is not yet implemented Europe-wide. ESPGHAN nutrition summer schools, and Web-based learning may provide appropriate training. We suggest that all patients necessitating nutritional care be treated by multidisciplinary nutrition teams

IL-15 Renders Conventional Lymphocytes Resistant to Suppressive Functions of Regulatory T Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway

International audienceIL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to investigate the impact of IL-15 on the de novo generation and function of regulatory T cells in humans. Our data indicate that IL-15 does not counteract, but rather promotes the effect of TGF-beta on the de novo generation of regulatory T cells (Treg). Thus, in the presence of TGF-beta, IL-15 enhanced the acquisition of regulatory functions by CD4(+)CD25(-) T cells stimulated by anti-CD3 and anti-CD28 Abs. In contrast, IL-15 impaired the functions of Tregs by acting on effector CD4 and CD8 T cells. Accordingly, in the presence of IL-15, proliferation and IFN-gamma production by peripheral CD4 and CD8 T cells could not be efficiently inhibited by Tregs. IL-15-induced resistance of effector T cells to Tregs resulted from activation of the PI3K signaling pathway but did not involve the rescue of effector T cells from apoptosis. Altogether, these data point to the ambiguous role of EL-15 in the control of Treg functions. This dual role may be instrumental to mount rapid but transient proinflammatory immune responses against pathogens but may become deleterious in situations associated with protracted IL-15 over-expression. The Journal of Immunology, 2009, 182: 6763-6770