Mapping an unknown large-scale marine area by a side-scan sonar onboard a marine vehicle as quickly as possible is often of great importance. It is also important that a-priori unknown interesting parts of the area are scanned in more detail, i.e. with the removal of sonic shadows. In contrast to the standard overlap-all-sonar-ranges lawnmower pattern, which is an offline static coverage problem solution for side-scan sonar missions, here a novel online side-scan sonar data-driven coverage solution is proposed. The proposed coverage algorithm provides a coverage solution based on local information gain from side-scan sonar data. At the same time, the solution is generated in such a way that coverage path length is minimized while covering the same area as the standard lawnmower. Upper and lower bounds of the proposed algorithm's improvement compared to the overlap-all-sonar-ranges lawnmower method are estimated analytically and validated through extensive mission parameters variation simulations. Simulation results show that our approach can cut down coverage path length significantly compared to the standard lawnmower method in most application cases.

Analysis of electric power system reliability presented in this paper, refers to complex (composite) systems. General issue of assessment of complex electric power system reliability is how to implement and solve mathematical system equivalents and their possible states, taking into account as many possible effects, impacts and conditions of their real functions. Number of possible states of the system in real conditions can be very big, so it is extremely difficult to explore all cases of assessing the reliability of such systems. In this paper, the methods of determining possible states of the system, as well as the methods of determining system deficit, are presented and analysed. For calculations of electric power system reliability, in order to carry out a complete analysis and calculation of characteristic system reliability parameters, it is necessary to determine deficit of electricity. The paper also presents the concrete results obtained using the developed mathematical model and software program developed on its basis.

Introduction: Prior to the 1990s, the most common sources of HCV infections were blood transfusions, unsafe injections and I.V drug use. Screening of blood products for HCV has eradicated transfusion-transmitted hepatitis C in most countries since 1992–in Bosnia and Herzegovina, however, since 1995, due to the war. Aim: To investigate the impact of the source of HCV infection on the therapeutic response in patients treated for chronic HCV infection with dual combined therapy. Methods: We diagnosed chronic HCV infections amongst 246 patients over a period of five years and selected them according to the reported source of infection. Pegylated interferon alfa 2a or alfa 2b with ribavirin was administered during the time that was genotype-dependent. HCV RNA levels in sera were measured by real time PCR. Liver histology was evaluated in accordance with the level of necroinflammation activity and the stadium of fibrosis. Results: Regardless of the genotype of the virus and the source of infection, SVR was achieved in 67% of the patients. Therapeutic response (ETR) was not achieved in 25% of the patients who were infected with an untested blood transfusion and 6% of the patients who had had wartime surgery. Amongst the different sources of infections, patients with a war-surgery source of infection responded better to therapy than those with a blood transfusion source of infection (p = 0.023). A blood transfusion source of infection implies a larger fibrosis stage than in blood donors; (g = 1.177; s2 = 0.577). A blood transfusion source of infection implies a significantly larger necroinflammatory activity than in blood donors; (g = 1.456; s2 = 0.618). Conclusions: An untested blood transfusion was a significant risk factor for more advanced liver diseases in regards to necroinflammatory activity and the fibrosis stage. This source of infection was also a risk factor for low responses to antiviral therapy. At the same time, I.V. drug users had more progressive necroinflammatory activity, but a high therapeutic response to antiviral therapy.

Abstract Between 1974 and 1975, Zoran Popović, a conceptual artist from Belgrade, Yugoslavia, and his wife Jasna Tijardović, an art historian, spent a year in New York. During that time they engaged closely with the New York Art and Language group. This friendship and collaboration resulted in a rare instance of East-West exchange in Conceptual art: Popović and Tijardović published both co-authored and individual articles in the US journal The Fox, and members of Art and Language (Mel Ramsden, Michael Corris, and Jill Breakstone) gave a seminar in Belgrade's Student Cultural Center in the fall of 1975. One of the most important outcomes of this exchange is Zoran Popović's film Struggle in New York—Борба у Њујорку, which he made on his return visit to New York in the fall of 1976, and which features the members of New York Art and Language and other artists and activists from the downtown Manhattan art scene of the mid-1970s. This essay argues that in this film, Popović uses documentary techniques to establish a space for the display of radical artistic practices that engaged in a vigorous critique of art institutions. In so doing this film marks a limit position of institutional critique that approaches the idea of the abolishment and abandonment of art practice altogether. Further, the essay explores some differences between Conceptual art practice in Yugoslavia and the United States, arguing that Popović uses the crisis that tore the New York Art and Language group apart to address the unraveling of politicized Conceptual art practice in Belgrade's Student Cultural Center.

OBJECTIVES Irrational use of antibiotics is a major driver of antimicrobial resistance (AMR), exacerbated by dispensing of antibiotics without a prescription especially for typically viral infections. Such dispensing is common despite legislation. Pharmacists play a key role in advising on medicines, especially in countries where most patients seek pharmacist help as they cannot afford both physician fees and medicines. Consequently, our objective was to ascertain pharmacists' skills and knowledge regarding antibiotics when patients present to them with typically viral infections. METHODS This was a qualitative cross-sectional survey among 370 community pharmacists in Albania, with carefully selected and validated topics. The main outcome measure was knowledge of antibiotics and current legislation. RESULTS Variable knowledge regarding antibiotics among community pharmacists. 55% knew colds are caused by viruses and 93% that antibiotics are ineffective against influenza. However, 18% believed if colds last >4 days an antibiotic can bring a patient back to work, and only 13% stated antibiotics are ineffective against viruses. Encouragingly, 93% knew penicillins can cause anaphylactic shock, 74% that antibiotics kill bacteria causing infections, and only 7% that antibiotic misuse cannot cause AMR. However, 13% stated the main disadvantage of antibiotics is that they are ineffective against viruses and 93% admitted they had no treatment protocols to consult in their daily work to direct patient care. CONCLUSION Encouraging signs regarding pharmacists' knowledge of antibiotics in Albania; however, concerns. Instigating educational programmes among patients and pharmacists and greater enforcement of legislation should reduce AMR rates in Albania and across countries.

Aim: The aim of this paper was to present a 65 year old female patient with chronic heart disease, surgically treated for congenital heart defect type Tetralogy of Fallot. Case report: In the sixth year of life the patient underwent palliative Potts anastomosis surgery which created an anastomosis between the left pulmonary artery and the descending aorta. Total correction was made in 34 years of life, six months after catheterization, which indicated malignant pulmonary hypertension. She is regularly followed up by the cardiologists and receives daily therapy. The present state of the patient is satisfactory with cardiomegaly, light left ventricular dysfunction, moderate mitral and tricuspid regurgitation, pulmonary arterial hypertension, and aneurysmatic dilatation of left pulmonary artery as well as atrial fibrillation. Conclusion: The intense development of cardiology and cardiac surgery in the USA in children and adults over the last fifty years has led to the extension and improvement of the quality of life.

Abstract The aim of this study was to analyze the values of biochemical parameters in patients with diabetic ketoacidosis and ketonuria. In this prospective comparative study conducted at the Clinical Center of the University of Sarajevo, hundred patients of both genders with diabetes mellitus were enrolled. Newly diagnosed diabetic patients with complications like acute ketoacidosis (n = 50) and ketonuria (n = 50) were included in this study and compared. The values of biochemical parameters in these patients were analyzed. We found that mean values of pH, base excess, hydrogencarbonate, sodium, glucose, urea and creatinine concentrations in patients with ketoacidosis were significantly different compared to patients with ketonuria. The values of potassium and calcium serum concentrations were not significantly different. Also, values of pH, base excess, as well as concentrations of hydrogencarbonate, sodium, potassium, calcium, glucose, urea and creatinine were not significantly different between male and female patients with diabetic ketoacidosis. In patients with diabetic ketonuria we found a correlation between admission glucose concentration and acid-base balance.

Karst is a terrain with special hydrogeology and relief forms, and it develops in rocks that are relatively soluble in water. Quaternary deposits in karst areas of the Dinarides occupy relatively smaller areas, in poljes and beds of a small number of karst rivers. The subject of the study is the Quaternary formations in the Trebižat riverbed. Although the river has carved its bed through Quaternary limestones, occurrences of major water losses or sinking are not registered due to relatively thick, fine‐grained and clayey alluvium that has been deposited in the canyon. Their depth is relatively large and in places it is over 20 m. Tufa in the form fragments of different sizes is very often present. It has a high holey porosity that is partly due to the decomposition of water plant tissues, and partly due to the dissolution or releasing of organic tissue. Despite the high porosity, tufa does not have a high permeability because the pores are not well interconnected and are often filled with fine‐grained particles. The subject of the paper is geomechanical and hydrogeological properties of these sediments.

In this work we present a complex systems science analysis of the Self Organized Time Division Multiple Access (SOTDMA) algorithm. We translate the interaction among member nodes into a functional topology graph in order to measure the effect of each individual node’s adaptability on the global performance. The functional complexity metric corresponding to the functional topology is shown to have substantial correlation with important Key Performance Indicators (KPIs), namely probability of collision and probability of correct packet detection. We further use the functional complexity metric to analyze the trade-off between the two aforementioned KPIs in terms of system parameters. We finally show that the results obtained using this approach satisfy the predefined KPI constraints imposed on the algorithm and thus is successful in capturing the system behavior.

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.

Background Immune checkpoint inhibitors (CPI) against lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) are a novel therapeutic breakthrough in an increasing number of malignancies. CPI induced acute liver injury (ALI) is the second most frequently encountered organ toxicity occurring in up to 30% patients. There are no reported data on ALI disease pathogenesis, clinical evolution and outcome of patients treated with CPI therapy. Our multicentre cohort study evaluated clinico-pathological aspects of CPI-induced ALI. Method A retrospective analysis was performed of patients with CPI induced ALI presenting to 6 UK oncology centres between 2013 and 2017. Indices of acute liver injury, treatment related complications and outcome were recorded. Severity scoring of liver injury was based on Common Terminology Criteria for Adverse Events (ALI grade 1–4). Results 65% (36/57) patients received ipilimumab +pembrolizumab or nivolumab (combo group) and 35% (21/57) pembrolizumab or nivolumab alone (mono group). Median treatment duration to development of ALI was 96 days in the mono and 22 days in the combo group. All patients presented with acute elevations in transaminases (ALT 325 [155–543], ALP 111 [72–250]). Immungolulins and autoantibodies were normal. One patient developed acute synthetic dysfunction with no encephalopathy (Bilirubin 64, INR 1.5). 79% received steriods (mean dose:1.3 mg/kg); 34% MMF. Steroid refractory ALI was treated with anti-thymocyte globulin (ATG) in 4 patients. Pathological findings (n=6 liver biopsies) revealed lobular hepatitis and myelo-lymphoid cell infiltrate/aggregates (CD3+,CD8+,CD68+). Patients with severe, refractory (grade 4) ALI had signifcant reductions in circulating lymphocytes/monocytes. 63% (n=35) had a temporal association between recent infection and ALI. 15% (n=8) had colitis prior to onset of ALI. Anti-TNF-a administration for colitis was not associated with more severe ALI. 21% (n=11) developed bacterial infections. Fungal sepsis (aspergillus) occurred in all ATG (n=4) treated patients. Overall 14 patients died with 93% (n=13) due to disease progression and 7% (n=1) due to immunotherapy related neuropathy. All deaths due to progressive disease were in patients with grade 3–4 ALI. Acturial median survival was significantly lower in grade 3–4 (14.5 months) vs grade 1–2 (25 months) liver injury. Conclusion Our data report on the largest cohort of CPI induced ALI identifying disease evolution, markers of disease severity and strong correlation with increased morbidity and mortality. Further research is required to delineate triggers and pathogenesis of CPI induced ALI in order to develop calibrated therapies to ameliorate liver injury.

Background Immune checkpoint inhibitors (ICIs) including anti-CLTA-4 (e.g. ipilimumab (ipi)) and anti-PD-1 antibodies (e.g. nivolumab (nivo)) have improved outcomes in many cancers. However their use is complicated by ICI-related diarrhoea/colitis (irD/C), a common cause of morbidity and ICI discontinuation. The National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) has been used to grade irD/C according to frequency of bowel movements over baseline. Grade 1–2 represents mild-moderate disease, grade 3–4 severe disease and grade 5 represents death. In clinical trials diarrhoea/colitis is more common in regimes using anti-CTLA-4 agents.1 There are few real world data reported in the UK. Methods Electronic medical records were reviewed for melanoma patients (pts) at The Royal Marsden Hospital (RMH) and melanoma, renal and lung cancer pts Guy’s and St Thomas’ Hospital (GSTT), receiving at least one ICI dose between 2011–2016. Clinical outcome data included class of ICI therapy and CTCAE grade of diarrhoea. Results 651 ICI treatment courses were administered mostly for melanoma (100% RMH, 53% GSTT). 285 (44%) received anti-CTLA-4 monotherapy, 288 (44%) anti-PD-1 monotherapy, and 77 (12%) combination ipi +nivo. The incidence of all-grade irD/C was 27% for anti-CTLA-4 therapy, 12% for anti-PD-1%–34% for ipi +nivo. The incidence of severe irD/C (grade 3–5) was 12% in anti-CTLA-4 monotherapy, 4% in anti-PD-1 therapy and 26% in combination therapy (figure 1). There was one only death reported in a pt who developed colitis following treatment with anti-CTLA-4 monotherapy.Abstract PTU-006 Figure 1 Conclusion This is the largest cohort of data reporting the incidence of irD/C involving real-world patients. Compared to trial data, the incidence of all-grade diarrhoea was slightly lower but the incidence of severe disease was higher in all treatment groups, particularly with ipi +nivo. Given the expansion of ICIs in other cancer types and use as an adjuvant therapy, there is an urgent need to engage gastroenterology services and to develop evidence-based management algorithms for treatment of irD/C. Reference . Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev2016;44:51–60.

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.