Background Immune check point inhibitors (ICPis) have transformed the treatment landscape for several cancers, but at the cost of triggering ICPi-induced colitis which resembles some aspects of IBD. Diagnosis is often made by symptoms, or by identifying endoscopic features of colitis. Little is known about histological findings in the absence of macroscopic disease. Furthermore, first-line management strategies beyond the use of systemic corticosteroids have not been explored. Our aim was to assess the incidence of microscopic inflammation in patients with ICPi-diarrhoea, and report our experience of treating two such patients with beclomethasone diproprionate (Clipper). Methods Electronic records of patients with advanced melanoma and ICPi- diarrhoea/colitis at the Royal Marsden Hospital (RMH) and Guy’s and St Thomas’ Hospital (GSTT) between 2011–2016, were retrospectively reviewed. Endoscopic, histological and clinical outcome data was recorded for patients who underwent flexible sigmoidoscopy and had colonic biopsies taken regardless of macroscopic findings. Two symptomatic patients (one treated with anti-PD-1, and another on combination -anti-PD-1/anti-CTLA-4 therapy) with isolated microscopic disease were managed with 5 mg Clipper, once a day, for 4 weeks. Endoscopic, histological and clinical outcomes were recorded 6 weeks after completion of therapy. Results A total of 63 flexible sigmoidoscopies were performed in 59 patients with ICPi diarrhoea/colitis. Microscopic inflammation with normal macroscopic appearances were recorded in 22% of cases. 6 patients were prescribed anti-CTLA-4, 4 anti-PD-1, and 4 combination therapy. Histological features that were distinct from conventional microscopic colitis were recorded in the majority of patients (10/14), which included acute and chronic inflammation, architectural distortion, crypt abscess formation and neutrophil infiltration. Four patients had changes consistent with conventional microscopic colitis (2 lymphocytic colitis, 2 collagenous colitis). Clipper induced clinical remission within 7 days, and histological remission by week 6 in both patients with ICPi-induced microscopic inflammation. There was no treatment associated adverse events. Conclusion Microscopic inflammation in the absence of macroscopic features of colitis is a common finding in ICPi-induced diarrhoea, justifying the routine practice of performing colonic biopsies even when endoscopy is normal. Our favourable clinical experience of using Clipper in 2 patients with microscopic inflammation merit further investigation in appropriately controlled clinical trials.

Power system stabilizers are controllers which damp power oscillations in electrical networks. They typically reside in the automation system of the power plant. Their design and structure are typically fixed in the design of the power plant. Optimal design and tuning of these decentralized controllers such that power oscillations are avoided is a challenging task. In the first part of the paper, we outline this problem and transform it into a so called structured controller synthesis problem where the control structure is fixed and optimal controller parameters need to be found. Based on this formulation, which preserves the real controller parameters, we propose a coordinate descent method to solve the controller design and tuning problem. To this end, we consider additional steady-state constraints in the system. We show the effectiveness of the proposed approach by detailed simulations of an established power system benchmark.

A variety of LQR-RRT kinodynamic motion planners are built on the idea of solving a two point boundary value problem in an LQR manner for affine systems. These planners can also be used for controllable nonlinear systems only if its linearized model at the equilibrium state is also controllable, and the cost function reflects only a time/control trade-off. We propose a class of RRT planners based on the SDRE (State Dependent Riccati Equation) control paradigm. The SDRE control is used both for finding the nearest state in the tree and for the tree expansion. By solving an LQR tracking problem for nonlinear systems within the SDRE framework, instead of a two point boundary value problem, the proposed planners deal with a wider range of controllable nonlinear systems and cost functions. We compare the proposed planners with LQR-RRT-like algorithms by observing the results obtained from the three specific benchmark examples.

Abstract The investigation of fish parasites in Bosnia and Herzegovina in recent years became significant, and therefore new records of parasitic trematodes and their hosts are important for better understanding of fish parasitology and pathology. In this study 41 parasitic specimens were collected and the basic taxonomical characters were measured (body length and width, diameter of oral and ventral sucker, length and width of pharynx, ovary length and width, testes length and width and eggs length and width). After the sampling of the parasites, they were collected and conserved in 70% ethanol. After that procedure the aforementioned characters were measured using Digimizer Image Analyzer Version 4.1. After all measurements, the trematode parasite Azygia robusta was confirmed for the first time on brown trout Salmo trutta. This first record was found in the Vrbas River near Banja Luka, Bosnia and Herzegovina (Sava River Basin). Former records of this parasite in Europe were observed on other salmonid fish species, as huchen Hucho hucho. This new record should be very important part of data of fish parasitology in Bosnia and Herzegovina.

This paper addresses the issue of modeling meanfield behavior in heterogeneous populations of linear timeinvariant SISO systems. Our analysis is conducted in the frequency domain, where the heterogeneity of input-output mappings (transfer functions) is modeled as a complex-valued Gaussian process. The mean-field model of diffusively coupled agents is obtained as a Gaussian approximation of averaged input-output behavior. It is shown that the strong coupling and the large number of agents reduce the population variance.

Abstract This paper uses a DEA-VRS methodology for the estimation of municipal efficiency to provide empirical evidence of the impact of decentralization in BiH under the Dayton Peace Agreement (DPA) on overall municipal efficiency. In particular, the paper focuses on the analysis of the overall efficiency of 33 new municipalities established under DPA. The findings suggest that the average municipal efficiency in BiH is rather low, and only 23 or 16% of municipalities in BiH are efficient. The average efficiency achieved is around 0.71. This means that with the same level of inputs (budget revenue) outputs may be increased by almost 30%, on average. The results of DEA-VRS efficiency estimation suggest that new municipalities have lower average efficiency (0.60) in comparison to “older” municipalities (0.74). In our sample, only six percent of newly created municipalities are efficient, 12% exhibit some level of efficiency, while the remaining 82% are inefficient, with significant share (39%) of very inefficient municipalities

We address a cooling energy management problem in a multi-building setting where buildings need to maintain comfort conditions for the occupants by keeping their zones temperature within a certain range. To this purpose, each one of them has its own chiller and is connected to a shared cooling network. The goal is to minimize the overall district electricity cost over some finite time horizon by optimally setting the temperature set-points in the buildings and the energy exchange with the cooling network, compatibly with comfort and actuation constraints, while accounting for uncertainty, mainly due to outside temperature, people occupancy, and solar radiation. To this purpose, a distributed version of the scenario approach to stochastic constrained optimization is adopted, which allows to guarantee by design a predefined robustness level of the obtained solution against uncertainty.

Introduction: Neuropathic pain resulting from injury to the nervous system. Up to 7% to 8% of the European population is affected. A number of different treatments for neuropathic pain have been studied including antiepileptic. Pregabalin and gabapentin are often considered first-line treatments. Pregabalin provides equivalent efficacy to gabapentin, showing greater potency at much lower doses and is considered as cost-effective intervention. In Federation of Bosnia and Herzegovina (FB&H), gabapentin is fully reimbursed, while pregabalin is enlisted on list B with copayment. Aim: To develop simple budget impact (BI) model and assess BI of introducing pregabalin into full reimbursement in FB&H. Material and methods: Budget impact model was developed using Microsoft Excel 2010. Local epidemiology data and data on drug consumption from government reports in 2016 were used. Two scenarios with three-year time horizon have been developed: 1) without and 2) with pregabalin reimbursed at the same level as gabapentin. Two developed scenarios have been compared from health insurance fund (HIF) perspective. Results: In scenario 1 consider both drugs fully reimbursement and without patient switch among alternatives the total cost would be increased for 780,025 KM; 852,027 KM and 943,830 KM over a 3-year period. In scenario 2 considering both drugs fully reimbursed but with patient switch topregabalin total annual cost would be increased for 732,241 KM; 742,395 KM and 751,761 KM. Comparing scenario 1 and 2 it is found that scenario 2 is more favorable from HIF perspective. Conclusion: Implementation of pharmacoeconomic principles in reimbursement decisions in Bosnia and Herzegovina would improve access to medicines and contribute rationale resource consumption.

The effect of the aqueous extract of Achillea millefolium L . (AM) on the electrochemical behaviour of iron in a simulated acid rain solution (pH 4.5) was studied by electrochemical techniques cyclic voltammetry, potentiodynamic polarization and electrochemical impedance spectroscopy. Experiments were carried out over a wide range of AM concentrations. The results of all techniques showed that AM extract contributes to iron passivation. The films formed in the presence of AM extract were thinner and more resistive then the films formed in pure simulated acid rain solution. The AM extract adsorbed on the iron according to the Freundlich isotherm. The thermodynamic data indicated physical adsorption of the AM extracts on the iron surface. The concentration of the metallic ions released into solution, measured by atomic absorption spectroscopy, was in accordance with the results obtained from the electrochemical techniques.

Background: The gene for 5,10-methylenetetrahydrofolate reductase (NAD(P)H) or MTHFR gene encodes protein methylenetetrahydrofolate reductase (MTHFR), an enzyme important in folate metabolism. Aim: The aim of this study was to determine the frequencies of 677C>T and 1298A>C polymorphisms in the MTHFR gene of healthy subjects from the population. Material and methods: The blood samples were collected from 164 unrelated and healthy donors from population consisted of 98 females and 66 males. Both the MTHFR 677C>T and 1298A>C single nucleotide polymorphisms (SNPs) were analyzed by Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium (LD) between pair of SNPs was calculated through Haploview analysis. Results: The frequency of MTHFR 677T allele in the population (32.62%) was in agreement with the frequency of this allele in most other populations, however, the frequency of MTHFR 1298C allele (38.41%) was higher than that reported for most other populations in the world. Haploview analysis showed a relatively strong LD between 677C>T and 1298A>C SNPs with D′ values of 0.87. Conclusion: Regarding the two MTHFR polymorphisms, three of the nine combined genotypes were present in 87.2% of the population. 33.54% subjects were complex heterozygous (677CT/1298AC genotype), 34.15% subjects had 677CC/1298AC and 19.51% of 677CT/1298AA genotype. The subjects with 677TT genotype had a 1298AA or 1298AC genotype while subjects with 1298CC genotype had only 677CC genotype. The subjects with 677CC/1298AA genotype were only 3.05%. We were not found triple 677CT/1298CC and quadruple 677TT/1298CC mutation suggesting decreased viability of embryos with increased numbers of mutant alleles.

Aim To compare individual case safety reports (ICSR) rates and characteristics between Croatia, Serbia, Montenegro, and Bosnia and Herzegovina (B&H). Methods This retrospective pharmacoepidemiological study used the data from ICSR received by the Agency for Medicines and Medical Devices in B&H in 2011-2016. The number, characteristics, and sources of reports, suspected drugs, and patient characteristics were analyzed. The results were compared with the publicly available data from Croatia, Serbia, and Montenegro. Results The number of reported adverse drug reactions per one million of inhabitants was lowest in B&H and highest in Croatia. There were significant differences in reporter characteristics, sources of reports, and the percentage of missing data in ICSR, while the Anatomical Therapeutic Chemical product classes, patient’s sex, and adverse drug reaction System Organ Classes were similar. Conclusion Despite the historical and geographical vicinity of B&H and its neighboring countries, there were significant differences in indicators of pharmacovigilance development.

Phasor estimation is an essential task in power system since the voltage angle and voltage RMS determine the available active power and its flow. This paper proposes fast and simple algorithm for harmonic phasor estimation in a three-phase system. Harmonics are considered the most serious power quality (PQ) problem in the emerging scenario with a growing proportion of power electronic based devices in the power system. The algorithm is based on well-known mathematical transform and recommendations given in relevant IEC and IEEE standards. The presented algorithm can be used to generate input data for Harmonic State Estimation.

The paper describes a photovoltaic system (PVS) composed of a group of photovoltaic (PV) panels and presents the initial evaluation of power quality (PQ) in the low-power microgrid connected to these PV panels. This PVS is called solar tree and it is built as a research platform at our faculty to conduct teaching and research on renewable energy sources. The solar tree can operate in two modes: on-grid and off-grid (autonomous operation). An off-grid mode was analysed and experiments were carried out in order to determine the maximum power that can be delivered to the load connected to this autonomous photovoltaic system (APVS). Also, the various consumer's responses to a sudden load changes in this APVS were analysed. The experiments were carried out by using modern power quality monitoring devices and PQ of this single-phase APVS with energy storage is examined in terms of compatibility with the relevant international standards.