With its broad antimicrobial spectrum and non-specific mode of action via membrane disruption, any resistance to octenidine (OCT) seems unlikely and has not been observed in clinical settings so far. In this study, we aimed to investigate the efficacy of OCT against Escherichia coli and mutants lacking specific lipid head groups which, due to altered membrane properties, might be the root cause for resistance development of membrane-active compounds. Furthermore, we aimed to test its efficacy under different experimental conditions including different solvents for OCT, bacterial concentration and methods for analysis. Our primary goal was to estimate how many OCT molecules are needed to kill one bacterium. We performed susceptibility assays by observing bacterial growth behavior, using a Bioscreen in an analogous manner for every condition. The growth curves were recorded for 20 h at 420–580 nm in presence of different OCT concentrations and were used to assess the inhibitory concentrations (IC100%) for OCT. Bacterial concentrations given in cell numbers were determined, followed by Bioscreen measurement by manual colony counting on agar plates and QUANTOMTM cell staining. This indicated a significant variance between both methods, which influenced IC100% of OCT, especially when used at low doses. The binding capacity of OCT to E. coli was investigated by measuring UV-absorbance of OCT exposed to bacteria and a common thermodynamic framework based on Bioscreen measurements. Results showed that OCT’s antimicrobial activity in E. coli is not affected by changes at the membrane level but strongly dependent on experimental settings in respect to solvents and applied bacterial counts. More OCT was required when the active was dissolved in phosphate or Hepes buffers instead of water and when higher bacterial concentration was used. Furthermore, binding studies revealed that 107–108 OCT molecules bind to bacteria, which is necessary for the saturation of the bacterial surface to initiate the killing cascade. Our results clearly demonstrate that in vitro data, depending on the applied materials and the methods for determination of IC100%, can easily be misinterpreted as reduced bacterial susceptibility towards OCT.
The human papillomavirus (HPV) is a non-enveloped double-stranded DNA virus capable of infecting skin and mucosa epithelial cells. Commonly, HPV infection is associated with sexually transmitted diseases and is considered the leading cause of cervical cancer and other carcinomas of the anogenital tract. However, several studies reported their involvement in cancers of non-sexual regions, including colorectal, head and neck, and breast cancers. There are several studies from the Middle East and North Africa (MENA) regions on the potential association between high-risk HPVs and cancer; nevertheless, there are limited studies that address the significance of HPV vaccination as a potential guard against these cancers. In the current review, we present a comprehensive description of the current HPV-associated cancers prevalence rates in the MENA region, demonstrating their steady increase with time, especially in African regions. Moreover, we discuss the potential impact of vaccination against HPV infections and its outcome on human health in this region.
Background and objectives: the aim of this study was to analyse the utilisation of proton pump inhibitors (PPIs) during a 12-year period and to show the characteristics and patterns of their prescribing. Materials and methods: firstly, in the pharmacoepidemiological analyses the ATC/DDD methodology was used to assess the utilisation of PPIs in the Republic of Srpska. The annual PPI utilisation was expressed as a number of DDD/1000 inhabitants/year. Secondly, the cross-sectional surveys were used to reveal the characteristics of PPIs prescribing and medicines use, namely the dose, duration and indication, and possible adverse reactions. For the purposes of the surveys, the adapted version of questionnaires related to physicians’ and patients’ perspectives of medicines prescribing and use were performed. Results: the utilisation of medicines for alimentary tract and metabolism (group A/ATC classification) increased by almost threefold in a 12-year period, which was consistent with the total medicine utilisation. Pantoprazole was the most prescribed medicine among the PPIs. With the exclusion of PPIs in the therapy of Helicobacter pylori eradication, more than half of family physicians prescribed PPIs with antibiotics, and only 53/239 physicians, noticed some adverse reactions of PPIs in their patients. Most of the patients knew how to use PPIs and were taking these medicines in recommended daily doses, but approximately 45% of them were using PPIs for a long period of time (>6 months). Conclusions: the overuse of PPIs is a major concern due to potential serious adverse reactions, especially in elderly patients and in a case of prolonged exposure.
Background: Iron deficiency (ID) and anemia in patients with Inflammatory Bowel Disease (IBD) are associated with a reduced quality of life. We assessed the prevalence of ID and anemia in Dutch outpatients with IBD and compared routine ID(A) management among medical professionals to the European Crohn’s and Colitis Organisation (ECCO) treatment guidelines. Methods: Between January and November 2021, consecutive adult outpatients with IBD were included in this study across 16 Dutch hospitals. Clinical and biochemical data were extracted from medical records. Additionally, medical professionals filled out questionnaires regarding routine ID(A) management. Results: In total, 2197 patients (1271 Crohn’s Disease, 849 Ulcerative Colitis, and 77 IBD-unclassified) were included. Iron parameters were available in 59.3% of cases. The overall prevalence of anemia, ID, and IDA was: 18.0%, 43.4%, and 12.2%, respectively. The prevalence of all three conditions did not differ between IBD subtypes. ID(A) was observed more frequently in patients with biochemically active IBD than in quiescent IBD (ID: 70.8% versus 23.9%; p < 0.001). Contrary to the guidelines, most respondents prescribed standard doses of intravenous or oral iron regardless of biochemical parameters or inflammation. Lastly, 25% of respondents reported not treating non-anemic ID. Conclusions: One in five patients with IBD suffers from anemia that—despite inconsistently measured iron parameters—is primarily caused by ID. Most medical professionals treat IDA with oral iron or standard doses of intravenous iron regardless of biochemical inflammation; however, non-anemic ID is often overlooked. Raising awareness about the management of ID(A) is needed to optimize and personalize routine care.
This paper uses a mutual-information maximization paradigm to optimize the voltage levels written to cells in a Flash memory. To enable low-latency, each page of Flash memory stores only one coded bit in each Flash memory cell. For example, three-level cell (TL) Flash has three bit channels, one for each of three pages, that together determine which of eight voltage levels are written to each cell. Each Flash page is required to store the same number of data bits, but the various bits stored in the cell typically do not have to provide the same mutual information. A modified version of dynamic-assignment Blahut-Arimoto (DAB) moves the constellation points and adjusts the probability mass function for each bit channel to increase the mutual information of a worst bit channel with the goal of each bit channel providing the same mutual information. The resulting constellation provides essentially the same mutual information to each page while negligibly reducing the mutual information of the overall constellation. The optimized constellations feature points that are neither equally spaced nor equally likely. However, modern shaping techniques such as probabilistic amplitude shaping can provide coded modulations that support such constellations.
At the beginning of the 20th century, more than a thousand mosques originating from the Ottoman period (1463-1878) were recorded in Bosnia and Herzegovina. Some estimates point that the number currently is much smaller. The goal of this study is to establish a typological classification of historical forms that were developed in more than four centuries. The diversity of patterns comes from the mixed influences ranging from the developed Ottoman style to the local material conditions and regional building traditions. This study used a qualitative evaluation of many characteristic examples to identify prevalent features that point to different types and subtypes of mosques. The evaluation of various examples used both firsthand observation and the written sources that are readily available. Thirty-six historical domed mosques were founded in Bosnia and Herzegovina, and their architecture is essentially a reflection of the architectural pattern predominantly from the 16th-century classical repertoire. However, a significantly higher proportion of mosques have sloping roofs where they strongly suggest domestic influences. The paper defines distinctive roofed mosque types where common characteristics predominate. Certain variations from the standard show a clear need for flexibility, adaptability, or improvisation. The study shows that the fundamental concept of the Turkish single-unit mosque, which was developed in Anatolia beginning in the 12th century, underwent a broad interpretation in Bosnia and Herzegovina throughout the Ottoman period, as evidenced by a variety of distinct types of roofed mosques.
Faculty of Technology, University of Tuzla, Tuzla, Bosnia and Herzegovina, Department of Chemical Engineering, Carnegie Mellon University, Pittsburgh, PA, United States, Faculty of Chemistry and Chemical Engineering, University of Maribor, Maribor, Slovenia, Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland, Sustainable Process Integration Laboratory—SPIL, NETME Centre, Faculty of Mechanical Engineering, Brno University of Technology—VUT BRNO, Brno, Czechia, CanmetENERGY, Natural Resources Canada, Varennes, QC, Canada, School of Chemical Engineering, Dalian University of Technology, Dalian, China
Increasing demands for logistics services cause several challenges related to total costs and meeting global environmental requirements. Logistic operators make efforts to improve all logistic processes and the distribution chain system by optimizing distribution networks and transport routes. Also, using clean or renewable energy help to meet the above-mentioned requirements by using environmentally friendly means of transportation such as electric and hybrid vehicles. The replacement of conventional with electric vehicles provides numerous benefits for improving the efficiency of the distribution chain system. This process is part of the concept known as Green Logistics, which strives to minimize the environmental impact of the logistics network and delivery. This paper focuses on identification of indicators for evaluating the acceptability of replacing conventional vehicles with electric vehicles in the fleet of logistics operators. We propose an evaluation matrix based on key indicators such as total costs, eco score fleet rating, and range and energy supply of vehicles. We use these indicators to determine the advantages, challenges, and possibilities of introducing electric vehicles in the logistics operator’s fleet. Also, we conducted a multi-criteria analysis of replacing conventional with electric vehicles in the fleet of one logistics operator.
Interactive Imitation Learning (IIL) is a branch of Imitation Learning (IL) where human feedback is provided intermittently during robot execution allowing an online improvement of the robot's behavior. In recent years, IIL has increasingly started to carve out its own space as a promising data-driven alternative for solving complex robotic tasks. The advantages of IIL are its data-efficient, as the human feedback guides the robot directly towards an improved behavior, and its robustness, as the distribution mismatch between the teacher and learner trajectories is minimized by providing feedback directly over the learner's trajectories. Nevertheless, despite the opportunities that IIL presents, its terminology, structure, and applicability are not clear nor unified in the literature, slowing down its development and, therefore, the research of innovative formulations and discoveries. In this article, we attempt to facilitate research in IIL and lower entry barriers for new practitioners by providing a survey of the field that unifies and structures it. In addition, we aim to raise awareness of its potential, what has been accomplished and what are still open research questions. We organize the most relevant works in IIL in terms of human-robot interaction (i.e., types of feedback), interfaces (i.e., means of providing feedback), learning (i.e., models learned from feedback and function approximators), user experience (i.e., human perception about the learning process), applications, and benchmarks. Furthermore, we analyze similarities and differences between IIL and RL, providing a discussion on how the concepts offline, online, off-policy and on-policy learning should be transferred to IIL from the RL literature. We particularly focus on robotic applications in the real world and discuss their implications, limitations, and promising future areas of research.
The Covid-19 pandemic has a direct impact on the social, economic, political, and other segments of society through a large number of lockdowns in 2020 and 2021. The largest postal and logistics companies as an integral part of the supply chain have been directly affected by the Covid 19 pandemic. Disruption in the supply chain significantly affects the movement of goods and the economic development of countries. This paper investigates the impact of the covid-19 pandemic on the logistics sector, with special emphasis on public postal operators (PPO) in some countries of the Western Balkans (Bosnia and Herzegovina, Croatia, and Serbia). The paper analyzes the movement of express shipments in domestic transport, as well as imports and exports for 2020. There is almost no research on the implications of the covid-19 pandemic on the postal and logistics sectors of Bosnia and Herzegovina, Croatia, and Serbia. The aim of this research is to understand the impact of the pandemic on this sector.
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