A Markovian event-based framework for stochastic spiking neural networks

In spiking neural networks, the information is conveyed by the spike times, that depend on the intrinsic dynamics of each neuron, the input they receive and on the connections between neurons. In this article we study the Markovian nature of the sequence of spike times in stochastic neural networks, and in particular the ability to deduce from a spike train the next spike time, and therefore produce a description of the network activity only based on the spike times regardless of the membrane potential process. To study this question in a rigorous manner, we introduce and study an event-based description of networks of noisy integrate-and-fire neurons, i.e. that is based on the computation of the spike times. We show that the firing times of the neurons in the networks constitute a Markov chain, whose transition probability is related to the probability distribution of the interspike interval of the neurons in the network. In the cases where the Markovian model can be developed, the transition probability is explicitly derived in such classical cases of neural networks as the linear integrate-and-fire neuron models with excitatory and inhibitory interactions, for different types of synapses, possibly featuring noisy synaptic integration, transmission delays and absolute and relative refractory period. This covers most of the cases that have been investigated in the event-based description of spiking deterministic neural networks

Crystalline bis(η5-cyclopentadienyl)bis(benzoato/carboxylato)titanium(IV) precursordirected route to functional titanium dioxide nanomaterials

Five titanocene(IV) carboxylates of the general formula Cp2Ti(O2CR)2 viz., [Ti(η5-C5H5)2(O2CC6H5-4-CH3)2] (1), [Ti(η5 -C5H5)2(O2CC4H3-2-O)2] (2), [Ti(η5-C5H5)2(O2CC4H3-3-O)2] (3), [Ti(η5-C5H5)2(O2CC(CH3)3)2] (4) and [Ti(η5-C5H5)2(O2C(CH)C(CH3)3)2] (5) have been synthesized. All the titanocene(IV) carboxylates have been characterized by IR, 1H and 13C NMR spectroscopic techniques, and the crystal and molecular structures of 1-5 have been determined by single crystal X-ray crystallography. The structures present similar features with monodentate carboxylate ligands and tetrahedral Ti centres, assuming the each Cp ring occupies one position only. The differences in the structures relate primarily to the relative orientations of the carboxylate ligands. In the molecular packing, non-conventional Cp-C–H …O(carbonyl) hydrogen bonds are observed in each case and lead to supramolecular chains in each of 1, 4 and 5. In 2, the 2-furyl-O atoms also participate in C–H …O interactions leading to a two-dimensional array. Finally, in 3, a two-dimensional array arises as a result of Cp-C–H …O(carbonyl) and 3-furyl-C–H …O(carbonyl) interactions. As representative example, compound 3 was used as starting material for the synthesis of TiO2 nanoparticles

Длительная регионарная анальгезия в комплексной терапии обширных гнойно-некротических ран на фоне декомпенсированной артериальной и венозной недостаточности (клиническое наблюдение)

Objective: to demonstrate the successful complex treatment of a shin circular wound in a patient with intense pain due to critical limb ischemia and wound infection, which became possible against the background of prolonged peripheral blockade. Materials and methods. A 72-year-old patient with critical ischemia of the right lower extremity was treated for a circular purulent-necrotic wound of the shin leg from November 2016 to April 2017 at the Wounds and Wound Infections Department of FSBI “A. V. Vishnevsky NRC of Surgery” Ministry of Health of Russia. An examination revealed the impossibility of right lower limb arterial insufficiency surgical correction. The patient refused amputation of the lower limb. For the relief of pain, a long-term blockage of the sciatic nerve was used (infusion of ropivacaine 6.0–8.0 mg / hr into the perineural catheter, additional 100 mg ropivacaine boluses were used before performing traumatic daily dressings). The intensity of pain was evaluated on a visual analogue scale (VAS), sought to achieve a pain intensity of not more than 3 points at rest and not more than 4 points on – when moving. Results. Blockade of the sciatic nerve reduced the intensity of pain from 8–10 to 0–3 points, which made it possible to continue treatment. In total, the duration of sciatic nerve catheterization at the stages of treatment was 115 days (18 + 41 + 23 + 32), the maximum duration of one of the peripheral nerve catheterizations was 41 days. Complications associated with nerve catheterization were not observed in the patient. The pain syndrome is stopped, the area of the wound defect is reduced in size. Discharged for outpatient treatment. Conclusion. Long-term peripheral analgesia made it possible to gain time necessary for cleansing the wound surface from necrotic tissues, therapy with drugs that improve arterial blood supply to the limbs, as well as for performing reconstructive and reconstructive operations after the wound process has passed to the reparative stage. Long-term peripheral blockade is a prerequisite for the successful treatment of extensive wounds of the lower extremities caused by insufficient arterial blood supply at the stage of critical limb ischemia, accompanied by intense pain. Цель исследования: демонстрация опыта успешного комплексного лечения циркулярной раны голени у пациентки с интенсивным болевым синдромом, обусловленным критической ишемией конечности и раневой инфекцией, которое стало возможным на фоне пролонгированной периферической блокады. Материалы и методы исследования. Пациентка 72 лет с критической ишемией правой нижней конечности лечилась по поводу циркулярной гнойно-некротической раны голени с ноября 2016 по апрель 2017 года в Отделе ран и раневых инфекций ФГБУ «НМИЦ хирургии им. А. В. Вишневского» Минздрава России. При обследовании выявлена невозможность хирургической коррекции артериальной недостаточности правой нижней конечности. От ампутации нижней конечности больная отказалась. Для купирования болевого синдрома использовали длительную блокаду седалищного нерва (инфузия ропивакаина 6,0–8,0 мг/ч в периневральный катетер, до выполнения травматичных ежедневных перевязок применяли дополнительно болюсы ропивакаина по 100 мг). Интенсивность боли оценивали по визуальной аналоговой шкале (ВАШ), стремились к достижению интенсивности боли не более 3 баллов в покое и не более 4 баллов по ВАШ при движении. Результаты исследования. Блокада седалищного нерва уменьшила интенсивность боли по ВАШ от 8–10 до 0–3 баллов, что обеспечило возможность продолжать лечение. В сумме продолжительность катетеризации седалищного нерва на этапах лечения составила 114 суток (18 + 41 + 23 + 32), максимальная продолжительность одной из катетеризаций периферического нерва – 41 сутки. Осложнений, связанных с катетеризацией нерва, у больной не наблюдали. Болевой синдром купирован, площадь раневого дефекта уменьшена в размерах. Выписана на амбулаторное лечение. Заключение. Длительная периферическая анальгезия позволила выиграть время, необходимое для очищения поверхности раны от некротических тканей, терапии препаратами, улучшающими артериальное кровоснабжение конечности, и выполнения реконструктивных и восстановительных операций после перехода раневого процесса в репаративную стадию. Длительная периферическая блокада является необходимым условием успешного лечения обширных ран нижних конечностей, обусловленных недостаточностью артериального кровоснабжения в стадии критической ишемии, сопровождающихся интенсивным болевым синдромом.

СПОСОБ ХИРУРГИЧЕСКОГО ЛЕЧЕНИЯ ДИАБЕТИЧЕСКОЙ ОСТЕОАРТРОПАТИИ ПРИ ПОЛНОЙ ПОТЕРЕ ОПОРОСПОСОБНОСТИ КОНЕЧНОСТИ ВСЛЕДСТВИЕ ГНОЙНЫХ ОСЛОЖНЕНИЙ

The article presents a method of surgical treatment that may be used for therapy of diabetic osteoarthropathy in the cases of complete loss of support ability of limbs due to purulent complications: total purulent destructive osteoarthritis of the ankle joint, panflegmona involving the middle and posterior skeletal sections of the foot (patent application No. 2014142790 dated 23.10.2014). The method is in two-stage surgical treatment of this category of patients. The 1st stage is guillotine amputation of the lower third of the shin that allows removing the purulent center, which causes severe intoxication in patients and determines, in particular, the severity of their condition, radically, completely and quickly (within 5–7 min), and significantly reducing intraoperative blood loss and "energy loss" through the wound in the postoperative period (the small size of the wound with guillotine amputation), which leads to rapid recovery in the postoperative period; as well as stopping swelling of the leg as soon as possible and creating the conditions for reamputation with saving of the knee joint. The 2nd stage is reamputation of the affected extremity on the border of the upper and the middle third of the shin with the fasciomyoplastic method as a scheduled surgery. Due to application of the two-staged surgical, it is possible to prevent development of generalization of the infection and death, save the knee joint, reduce the rehabilitation period, and significantly improve the quality of life of patients. В статье представлен способ хирургического лечения, который может быть использован для лечения диабетической остеоартропатии в случаях полной потери опороспособности конечности вследствие гнойных осложнений: тотальный гнойно-деструк- тивный остеоартрит голеностопного сустава, панфлегмона с вовлечением скелета среднего и заднего отделов стопы (патент- ная заявка № 2 014 142 790 от 23.10.2014). Способ заключается в двухэтапном хирургическом лечении данной категории больных. На 1-м этапе проводится гильотинная ампутация в нижней трети голени, позволяющая радикально, полно и быстро (в течение 5–7 мин) удалить гнойный очаг, вызывающий сильнейшую интоксикацию у больных и определяющий, в частности, тяжесть их состояния; значительно уменьшить интраоперационную кровопотерю и «энергетические потери» через рану в послеопераци- онном периоде (небольшой размер раны при гильотинной ампутации), что приводит к быстрому восстановлению в послеоперационном периоде; в кратчайшие сроки купировать отек голени и создать условия для реампутации с сохранением коленного сустава. На 2-м этапе проводится реампутация пораженной конечности на границе верхней и средней трети голени фасциомиопластическим способом в плановом порядке. Благодаря применению двухэтапного хирургического лечения у больных удается предотвратить развитие генерализации инфекции и летальный исход, сохранить коленный сустав, уменьшить сроки реабилитации и значительно улучшить качество жизни.

Опыт успешного комплексного лечения пациента с диабетической нейроостеоартропатией среднего отдела стопы в стадии гнойных осложнений

The article presents a clinical case of the successful complex treatment of a patient L., 58 years old, with diabetic neuroosteoarthropathy in the middle part of the foot (Charcot's foot), complicated by a deep plantar phlegmon. The strategy of complex treatment, perioperative management and rehabilitation is described in detail. The long-term relapse-free observation period for a patient is more than 5 years.В статье представлено клиническое наблюдение успешного комплексного лечения пациента Л., 58 лет, с диабетической нейроостеоартропатией среднего отдела стопы (стопа Шарко), осложненной глубокой флегмоной подошвенной поверхности. Подробно описана стратегия комплексного лечения, периоперационное ведение и реабилитация. Отдаленный безрецидивный период наблюдения за больным составляет более 5 лет

Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Analysis of biased competition and cooperation for attention in the cerebral cortex

A new approach to understanding the interaction between cortical areas is provided by a mathematical analysis of biased competition, which describes many interactions between cortical areas, including those involved in top-down attention. The analysis helps to elucidate the principles of operation of such cortical systems, and in particular the parameter values within which biased competition operates. The analytic results are supported by simulations that illustrate the operation of the system with parameters selected from the analysis. The findings provide a detailed mathematical analysis of the operation of these neural systems with nodes connected by feedforward (bottom-up) and feedback (top-down) connections. The analysis provides the critical value of the top-down attentional bias that enables biased competition to operate for a range of input values to the network, and derives this as a function of all the parameters in the model. The critical value of the top-down bias depends linearly on the value of the other inputs, but the coefficients in the function reveal non-linear relations between the remaining parameters. The results provide reasons why the backprojections should not be very much weaker than the forward connections between two cortical areas. The major advantage of the analytical approach is that it discloses relations between all the parameters of the model