Suchergebnisse

Background: Efforts to control STI/HIV in sub-Saharan Africa has met with difficulties. Although the epidemic seems to be levelling off, prevalence and incidence are still high in many parts. In spite of 20 years of HIV control activities little or no behavioural change has been reported in Tanzania. Reasons for this could be that determinants of transmission have not been properly addressed or that changing sexual behavioural patterns is difficult and demands long-term interventions to succeed. It could also be that the balance between prevention and care is not optimal or that implementation has not been efficient. In my studies I have focused on the health system and how interventions are planned and implemented. Objective : The overall objective is to identify and characterise major obstacles to the control of sexually transmitted infections and HIV in Zambia and Tanzania, respectively. Methods : In papers I and II we determined treatment efficacy and the quality of STI care through participant observation and patient interviews. The main method in papers III and IV-VI was participant observation including interviews and the study of grey and published literature. In paper VII the capacity for antiretroviral treatment (ART) was estimated through a scenario analysis. Main findings : Paper I showed that the Zambian STI treatment algorithms for genital ulcers were not efficacious as the treatment for chancroid lacked efficacy; paper II demonstrated that the health education part of syndromic management including condom promotion was poor and that vaginal examinations were rarely carried out. Paper III has two components. One is on health sector reform including effects of integration of HIV control activities into horizontal functions and the other on management aspects of STI/HIV control in Tanzania - also the subject of papers IV-VI. There are large differences in prevalence within Tanzania. The limited analysis of disease determinants and the little efforts at explaining these have resulted in plans that do not forcefully tackle the core problems surrounding sexual behaviour and the probability for transmission. Furthermore, since policies in many HIV related areas, such as ART, are linked to international politics, there is a large gap between policies and national and local resources. This has often led to the formulation of unrealistic plans, which are poorly adapted to the resource limitations and therefore rarely fully implemented. Instead they are outlined to attract funding. This has increased drastically during the last few years, but the human resources have remained limited. Although better funding opens up for improvements, over-financing will not increase service output much. The ongoing health sector reform has had to consider a situation of limited resources and how these should be allocated. The short-term interest of effective HIV control has stood against the long-term needs to strengthen the whole system - a dilemma not yet resolved, and now further complicated by over-funding for ART. Paper VII shows that international plans for an ART scale up are unrealistic and that only part of the treatment targets set in the national plan are likely to be met mainly due to the lack of qualified staff. Conclusions : Disease determinants need to be further researched and analysed. Country specific plans are needed. Current plans for HIV control are neither realistic nor adapted to actual resources causing distortion to how these are used. Plans have to aim at an optimal balance between prevention and care, and focus on the core of the problem: determinants of new infections. Operational issues have to be tackled. Neither STI case management nor ARV treatment currently contribute much directly to a reduction of HIV incidence, but may, if reinforced, add to the effect of prevention efforts. A multi-component prevention programme, if prioritised and scaled up, might - through synergistic interaction have a major effect of the epidemic and significantly reduce HIV incidence.

Selenium (Se) is a trace element of great ecological importance whose environmental distribution is highly impacted by anthropogenic activity. In the 1980s, selenium was recognized as a major aquatic contaminant following widespread deformities and mortality among waterfowl hatchlings near the agricultural drainage evaporation ponds of the Kesterson Reservoir (CA, USA). Today, 400,000 km 2 in the Western United States are threatened by agricultural selenium contamination, as are parts of Canada, Egypt, Israel, and Mexico. From the soil aggregate to the watershed, from the soils of the Central Valley to the sediments of the Salton Sea, and from Environmental Science to Policy and Management, in this dissertation I explore agricultural selenium contamination across scales, ecosystems, and disciplines. I begin with a review of the science, policy, and management of irrigation-induced selenium contamination in California, the heart of worldwide research on the issue. I then delve into the physical and biogeochemical mechanisms that control selenium reduction and mobility within the structured surface soils that are the source of contamination, using an aggregate-scale combined experimental and reactive transport modeling approach. Finally, I present a diagenetic model for selenium incorporation into the sediment of the Salton Sea, which has been receiving seleniferous agricultural drainage over the last 100 years.To extract lessons from the last 30 years of seleniferous drainage management and water quality regulation in California, I reviewed the history and current developments in science, policy, and management of irrigation-induced selenium contamination in California. Specifically, I evaluated improvements in the design of local attenuation methods and the development of programs for selenium load reductions at the regional scale. On the policy side, I assessed the site-specific water quality criteria under development for the San Francisco Bay-Delta in the context of previous regulation. This approach may be a landmark for future legislation on selenium in natural water bodies and I discussed challenges and opportunities in expanding it to other locations such as the Salton Sea. By combining proven management tools with the novel, site-specific policy approach, it may be possible to avoid future events of irrigation-induced selenium contamination. However, the majority of regional selenium load reductions in California were achieved by decreasing drainage volume rather than selenium concentrations. Thus, there appear to be opportunities for additional improvements through management practices that enhance selenium retention in source soils.Soil aggregates are the basic structural units of soil. They are mm- to cm-sized microporous assemblages of loosely bound soil particles, separated from one another by macropores. To elucidate how aggregate-scale transport and microbial reduction affect selenium retention in surface soils, I conducted a series of flow-through experiments utilizing artificial aggregate systems. These systems mimic the dual porosity of structured soils with an artificial soil aggregate (ID 2.5 cm) contained in a flow-through reactor cell. Aggregates were composed of either pure quartz sand or ferrihydrite-coated quartz sand inoculated with selenium reducing bacteria ( Thauera selenatis or Enterobacter cloacae SLD1a-1). Oxic and anoxic conditions were compared, as well as various selenate (0.25-0.8 mM) and carbon source (0.3 and 1.2 mM) input concentrations. The presence of oxygen in the input solution significantly decreased selenium reduction, however, the detection of selenite in effluent samples indicates the occurrence of anoxic microzones within aggregates. Furthermore, I found that solid phase concentrations of reduced selenium increased towards the core of aggregates across all experimental conditions. A bulk model, ignoring intra-aggregate heterogeneity in reactions and transport, misrepresented the dynamics of the aggregate systems.To quantify the likely implications of these experimental results for soils with different degrees of aggregation, I formulated a general mechanistic framework for aggregate scale heterogeneity in selenium reduction. Specifically, I constructed a dynamic 2D model of selenium fate in single idealized aggregates, in which reactions were implemented with double-Monod rate equations coupled to the transport of pyruvate, O 2 , and Se-species (selenate, selenite, and elemental selenium). The spatial and temporal dynamics of the model were validated with the experimental data and predictive simulations were performed covering aggregate sizes between 1 and 2.5 cm diameters. Simulations predict that selenium retention scales with aggregate size. Depending on aeration conditions and the input concentrations of selenate and pyruvate, selenium retention was predicted to be 4-23 times higher in 2.5-cm-aggregates compared to 1-cm-aggregates. Under oxic conditions, aggregate size and pyruvate-concentrations were found to have a positive synergistic effect on selenium retention. Promoting soil aggregation on seleniferous agricultural soils may thus help decrease the impacts of selenium contaminated drainage on downstream aquatic ecosystems receiving it.One such ecosystem is California's largest inland water body, the Salton Sea, which is maintained entirely by agricultural runoff. Whereas elevated selenium concentrations are detected in the rivers feeding the lake, the lake's concentrations of dissolved selenium are low since most selenium entering the lake is sequestered in its sediment through microbial reduction. To predict the distribution profiles of selenium within the sediment and evaluate the factors driving them, I constructed a diagenetic model for reductive incorporation of selenate into Salton Sea sediment. The model predicts near surface (2 cm) sediment concentrations of solid phase selenium between 0.024 and 0.272 µmol/g depending on local reduction kinetics, and dissolved concentrations in the water column. This is in good agreement with the literature when considered in conjunction with the potential impact of bioturbation which according to exploratory simulations may lower near surface concentrations by around 25%. The range of modeled selenium concentrations in surface sediment crosses threshold values for which negative impacts on fish and waterfowl have been predicted or observed at other sites, suggesting that ecological impacts of selenium in the Salton Sea may depend locally on variation in the diagenetic factors here explored.This work presents agricultural selenium contamination as a complex problem that crosses ecosystems, scales, and disciplines. From a management perspective, the tension between dispersed non-point sources and hotspots where elevated selenium concentrations and sensitive aquatic ecosystems converge is difficult to address. Differences in biogeochemical conditions and trophic transfer within food webs render traditional regulatory approaches ineffective and force regulators to engage with the science of site-specific selenium transfer between ecological compartments. At the same time, gaps still exist in our mechanistic understanding of selenium's environmental cycling and in our integration of scientific knowledge across different ecosystems and scales. Centimeter scale heterogeneity in the biogeochemical conditions within source soils may fundamentally control selenium emissions across large agricultural areas and thus determine the selenium loading of rivers, lakes, and estuaries. Within aquatic environments receiving seleniferous drainage, the first few centimeters of surface sediment may control selenium exposure for entire food webs. Improved understanding at this level holds the potential to simultaneously reduce selenium emissions and respond more effectively to pollution where it occurs. In order to preserve sensitive habitat while also meeting agricultural drainage needs in seleniferous regions we must bridge the gaps between ecosystems, scales, and disciplines.

This Thesis has been mainly developed in the laboratories of IMAES research group in the Chemical Engineering Department at the University of Castilla-La Mancha (UCLM). It is a part of a research line dealing with the elimination of emerging contaminants in wastewater using advanced oxidation processes. It has been supported by the "Ministerio de Economia y Competitividad" (MINECO, Spanish Government) through the project CTM2013-44317-R entitled "Tratamiento en planta piloto de efluentes acuosos industriales mediante sonofotocatálisis UV/solar" and UCLM funding GI20142907. In addition, some parts of this research were carried out at the Department of Chemical Engineering of the University of Bath (United Kingdom), thanks to University of Bath International Research Fund Future Research Leaders Incubator Scheme, and at the School of Engineering of the University of Edinburgh, through a research visit supported by MINECO. Over the past 15 years, increasing numbers of studies have identified numerous different water sources containing trace, but accumulating, toxic chemicals. Many of such chemicals are thought to be recalcitrant, inhibitory or toxic to biological treatment in both wastewater treatment works and in the environment and so may be able to enter our water cycle. Photocatalysis is a promising degradation technology for such compounds, however due to inefficient and costly reactor systems, it has not yet been widely taken up by Industry. This project seeks to rectify this, by comparing a wide range of photocatalytic reactor technologies that have been integrated with further intensification technologies to increase the efficiency and effectiveness of the pollutant degradation. This includes: different reactor configurations (falling film photoreactor, solar compound parabolic collectors (CPC), a spinning disc reactor.) and intensifications processes (use of ultrasound (US), ferrioxalate and sulfate radicals-based advanced oxidation processes). This Thesis is focussed on comparing and optimizing the key parameters controlling the reaction kinetics and mechanisms of the reactors to determine the optimal degree of treatment of these types of accumulating toxic biologically recalcitrant chemicals in wastewaters, using antipyrine and carmamazepine as model compounds. The treatment efficiency and effectiveness, neural network optimization as well as technoeconomic analysis were used to determine the optimal intensification technology of photocatalytic process. Finally, real industrial effluents were also tested to prove the validity of studied processes. Overall, the main novelty of this work will be the first extensive study comparing a wide range of photocatalytic process intensification technologies. ANTIPIRINE The removal of antipyrine (AP) was evaluated under a sono-photo-Fenton system (UV/H2O2/Fe/US) in a synthetic wastewater reaching 79% of mineralization in 50 minutes in optimal conditions ([H2O2]0 = 500 mg/L; [Fe2+]0 = 27 mg/L; Amplitude = 20% and Pulse length = 1). The radical reaction in the bulk solution was found be the primary mineralization pathway (94.8%), followed by photolysis (3.65%), direct reaction with H2O2 (0.86%) and reaction by ultrasonically generated oxidative species (0.64%). Complete mineralization of reaction intermediates refractory towards hydroxyl radical was attained using persulfate anions simultaneously activated by heat energy (thermally, ultrasound) and UV-C light. The SO·4-based mineralization process enables another reaction pathway generating more easy degradable derivatives reaching more than 99% of total organic carbon (TOC) removal in 120 min under selected optimal operating conditions ([S2O82-]0 = 1200 mg/L; Temperature = 50 ªC; Amplitude = 10%; pH = 2.8). This demonstrated that activated persulfate-based oxidation system is a potential alternative to degrade intermediate compounds, which are refractory to hydroxyl radicals. The degradation of AP in aqueous solution using UV-A-LED (365 nm) photo-Fenton reaction intensified with ferrioxalate complexes and with the addition of persultate was also studied. A complete degradation of AP and 93% of mineralization of AP solution was reached in 2.5 and 60 min, respectively. In the last step of reaction, different intermediates difficult to be degraded such as 2-butenedioic acid, butanedioic acid, 4-oxo-pentanoic acid, acetate and formate may be generated. Finally, the photodegradation of AP solutions was also studied and optimized in a novel photocatalytic spinning disc reactor (SDR). A heterogeneous process (UV/H2O2/TiO2) was selected. TiO2 was immobilized on the surface of a glass disc using the sol-gel method. AP was completely degraded under the optimal conditions: pH = 4; [H2O2]0 = 1500 mg/L; Disc speed = 500 rpm; Flowrate = 25 mL/s. In addition, regeneration of the disc (up to 10 cycles) was performed with no loss in efficiency. The value of the apparent volumetric rate constant was found to be 6.9·10^4 s-1 with no apparent mass transfer limitation. Based on the main identified intermediates, a reaction mechanism was proposed for antipyrine photodegradation: firstly, cleavage of the N-N bond of penta-heterocycle leads to the formation of two aromatic acids and N-phenylpropanamide. An attack to the C-N bond in the latter compound produced bencenamina. Finally, the phenyl ring of the aromatic intermediates was opened and molecular organic acids were formed. CARBAMAZEPINE Different sytems including UV/H2O2/Fe/US, UV/H2O2/US and UV/H2O2 were used to study the photodegradation process of the antiepileptic drug carbamazepine (CBZ). An important synergistic effect between sonolysis and UV irradiation of 27.7% was quantified using the pseudo-first-order rate constants for carbamazepine degradation. An empirical model that includes the scavenger effect was applied and satisfactorily reproduced both degradation and mineralization of CBZ. It was found that the carbamazepine photodegradation occured mainly through a radical mechanism in two steps: during the first 10–15 min, CBZ was completely degraded, whereas TOC barely changed, confirming that intermediates were not easy to mineralize. From that moment, intermediates were formed and HO· radicals were responsible for increased mineralization rate with a gradual decrease in the scavenger effect (kscv = 0.0004 min^-1 mM^-1). 93% of mineralization in 35 minutes was reached when the initial conditions were [Fe2+]0 = 15 mg/L and [H2O2]0 = 680 mg/L. A study of the flow pattern inside the reactor showed that improvement in mineralization rate with US radiation cannot be attributed to a positive effect in mixing. On the other hand, \textit{in situ} chemical oxidation of CBZ was also performed using persulfate anions simultaneously activated by heat energy (thermal, ultrasound), UV-C light, Fe2+ ions and hydrogen peroxide. Nearly complete mineralization (99%) was reached in 90 min. The mineralization process of carbamazepine solutions can be described using pseudo-second-order kinetics in the studied system. A lab thin film reactor was tested to remove CBZ in a photo-Fenton system assisted with ultrasound radiation (UV/H2O2/Fe/US) achieving 89% of mineralization in 35 min. The synergism between the UV process and the sonolytic one was quantified as 55.2%. The sono-photodegradation of CBZ was also tested in a thin film pilot plant reactor and compared with a 28-L UV-C conventional pilot plant and with a solar Collector Parabolic Compound (CPC). At pilot plant scale, a UV/H2O2/Fe/US process reaching 60% of mineralization would cost 2.1 and 3.8 €/m^3 for the conventional and thin film plant, respectively. In the solar process, electric consumption accounts for a maximum of 33% of total costs. Thus, for 80% TOC removal, the cost of this treatment was about 1.36 €/m^3. However, the efficiency of the solar installation decreases in cloudy days and cannot be used during night, so that a limited flow rate can be treated. REAL WASTEWATER FROM BEVERAGE INDUSTRY Real industrial wastewater from beverage industry was studied during solar photo-Fenton system intensified with ferrioxalates complexes in a CPC plant. 70.6% and 96.6% of TOC was removed after 55 and 125 min, respectively, under optimal conditions (H2O2 flowrate = 460 mL/h}; (COOH)2 flowrate = 2100 mL/h}; [Fe2+]0 = 150 mg/L;} pH = 2.79; Medium solar power = 35.8 Wh). It was found that solar power was the main factor affecting mineralization during the first 60 Wh of accumulated solar energy due to the generation of hydroxyl radicals. However, solar power is unimportant at the end of the process (150 Wh of accumulated energy), when the molecular reaction mechanism between H2O2 and the intermediates was predominant. The overall mineralization process (k = 0.0096 min^-1) occured due to the contributions of the photo-Fenton process (k = 0.0044 min^-1) and the ferrioxalate photochemistry (k = 0.003 min^-1)}. The synergism between both processes was 22.9% based on the pseudo-first-order rate constants for TOC removal. A wastewater with similar characteristics was treated in a conventional UV-C pilot plant using a photo-Fenton process intensified with persulfate. Under optimal conditions (pH = 2.9; [H2O2]0 = 4000 mg/L}; [Fe2+]0 = 375 mg/L), 53% of mineralization was achieved after two hours. The remaining TOC was mainly composed of acetate and formate, whose decarboxylation was limited via hydroxyl radical reactions. Thus, persulfate was added to the system after 2 h to obtain a more efficient decarboxylation by sulfate radicals. The combined treatment with UV-C irradiation and thermally activated persulfate enhanced the mineralization efficiency. Under the best conditions, 76% mineralization was achieved in 4 h: first 2 h under photo-Fenton reaction (UV-C/H2O2/Fe) and UV-C/H2O2/Fe/S2O82-/Thermal process in the second two hours (65 ªC; [S2O82-]0 = 1500 mg/L). WASTEWATER EFFLUENT FROM PHARMACEUTICAL INDUSTRY Finally, a ferrioxalate-assited photo-Fenton process was used to treat an industrial wastewater effluent from a pharmaceutical laboratory in a CPC semi-industrial plant. More than 79% of TOC was removed in 2 h when the aquous effluent containing up to 400 mg/L of organic carbon concentration. It could be seen that most of TOC removal occurs early in the first hour of reaction. Then the degradation shows a slower rate due to the generation of acetates which are more difficult to eliminate.

It is advisable to consider informatization of education from different sides with the application of knowledge of various sciences. The content of the theoretical and methodological foundations constitute the terms of those sciences which are able to justify the most general fundamental, essential characteristics of information, not the individual aspects of it but those which relate to the definition of methods, techniques, ways of knowledge of this complex phenomenon and its transformation. General scientific approaches: systematic, synergistic, historical-logical, cultural, cyber, being refracted to the problems of informatization of education allow to solve a specific set of tasks. There are such tasks among them as: establishment of the cause-and-effect relationships of processes related to information; identification of strategic partnerships and networks and consideration of the information process from the standpoint of integrity; definition of the boundaries of self-organization processes related to information; consideration of mechanisms of management of the process of informatization of education.The practice of cognition of objective reality shows that the true regularities of the origin and development of various phenomena and processes may be possibly established only by long observation of them. Informatization of military education, as an element of objective reality, isn't an exception of this rule. The definition of laws is possible only by analysis of real experience, which has accumulated to date enough as the research has shown.Analysis of the development of informatization of education showed that the informatization level was mainly determined by the capabilities of existing techniques and technologies (technological level), staff qualification in information technology (level information of training), the quality of information educational resources (scientific and methodological level) at the different historical stages. ; Информатизацию образования целесообразно рассматривать с разных сторон с применением знаний различных наук. Содержание теоретических и методологических основ составляют положения тех наук, которые способны обосновать наиболее общие фундаментальные, сущностные характеристики информатизации, причем не отдельные ее аспекты, а те, которые связаны с определением методов, способов, путей познания этого сложного явления и его преобразования. Общенаучные подходы: системный, синергетический, историко-логический, культурологический, кибернетический, будучи преломленными к проблемам информатизации образования, позволяют решить определенный круг задач. Среди решаемых задач такие как: установление причинно-следственных связей процессов, связанных с информатизацией; выявление системообразующих связей и отношений, рассмотрение процесса информатизации с позиций целостности; установление границ самоорганизации процессов, связанных с информатизацией; рассмотрение механизмов управления процессом информатизации образования.При этом практика познания объективной реальности показывает, что установить истинные закономерности происхождения и развития различных явлений, процессов можно только путем длительного наблюдения за ними. Не является исключением из этого правила и информатизация военного образования, как элемент объективной реальности. Установление закономерностей возможно только анализом реального опыта, а его, как показало исследование, к настоящему времени накоплено достаточно.Анализ развития информатизации образования показал, что на различных исторических этапах уровень информатизации определялся, прежде всего, возможностями имеющейся техники и технологии (технологический уровень), квалификацией персонала в области информационных технологий (уровень информационной подготовки), качеством созданных информационных образовательных ресурсов (научно-методический уровень).

Structural and Dynamical Properties of Atactic Polystyrene in the Interface and Interphase Region Surrounding Grafted and Ungrafted Silica Nanoparticles The composite industry has long achieved enhanced material properties by mixing micro sized inorganic filler particles with a polymer matrix1,2. This is because the combination of two or more different materials can have a synergistic effect on the overall composite material properties imparting advantages that are absent in the individual constituents. A well-known example is that of adding carbon black as reinforcing material to increase tire strength, toughness, and resistance to tear and abrasion3,4. To achieve improved materials performance, the design of conventional composites has typically focused on reducing the dimensions of the filler particles. This is done in order to increase the filler surface area to enable greater interaction with the polymer matrix. Consequently, these efforts have received a significant boost with the dawn of the 'nano era'. Wherein experimental methods and tools are now used to synthesize, characterize, and investigate matter at the nano-scale level [10-9 m] which is close to molecular and atomic dimensions. The advent of such methods is exciting as it suddenly offers new possibilities of creating novel materials that can be tailored at very small dimensions. This expectation has been derived from the notion that the behavior of materials at their nanoscale level directly influences their microscopic properties and consequently their bulk macroscopic characteristics. As is typical in any emerging field, the challenge is to understand the fundamental aspects that control the final observable properties of these composite materials. In contrast to the behavior of materials in conventional composites, recent experimental observations of polymer nanocomposites have demonstrated multifunctional changes in their properties. Examples include - but are not limited to - the decrease in the polymer viscosity5, shifts in the polymer glass transition temperature6,7, and changes in the composite material's thermo-mechanical8,9 properties. However, what is still lacking and remains unclear are the fundamental explanations for the differences in the behavior between conventional composites and nanocomposites. In order to address questions pertaining to these differences, this PhD work was part of a large European Union consortium of universities and industrial partners, NanoModel. The aim of the group was to develop a unified scientific understanding from both experimentalists and theoreticians on the behavior of polymers in the presence of a surface. Such understanding of the important controlling parameters would ultimately support the design of industrial polymer nanocomposite materials. Therefore, both the structural and dynamical investigations always sought to address some of several important open questions that necessitated this work. These questions include among other things: (1) Does a nanoparticle influence the behavior of the surrounding polymer? (2) Since the dispersion state of the nanoparticles is known to control the resulting nanocomposite properties, which controlling parameters are important in obtaining a well-mixed polymer nanocomposite? (3) What role does the size/dimension of the nanoparticle play? (4) Is it necessary to graft or attach polymers to the filler particles, in other words, functionalizing the nanoparticles to facilitate their dispersion in the polymer melt? (5) How long should the grafted polymer chains be relative to the bulk polymer and which grafting density is optimal to achieve a good dispersion state? (6) To what extent are the polymer properties in the interface (next to the surface) and interphase (where grafted and bulk free polymer chains mix) region changed if they are at all? (7) Which parameters influence the width or extent of both the interface and interphase region? (8) Can we observe the same phenomena or changes by employing both experimental and theoretical approaches? Therefore, the contribution of this PhD thesis within the NanoModel framework was to investigate the structural and dynamical properties of atactic polystyrene in the vicinity of a silica nanoparticle as a model system for polymer nanocomposites at the atomistic level (see Figure 1.1 for a simulation snapshot). This model system was chosen because of its importance to the NanoModel partners since bulk polystyrene is an important, largely used, and well characterized polymer while silica is a typical traditional filler particle. Naturally, consortium partners like BASF would find it invaluable to produce new tailored plastics with superior properties to the traditional ones. At the same time, partners like BOSCH and CRP-FIAT would benefit from knowing the nanoparticle effect on the mechanical properties and the processing of the nanocomposite which directly impacts their injection molding processes for example. On the experimental front, Fribourg University, Juelich, and Epidoris were involved in nanocomposite sample preparation and characterization. These experimental results validated those obtained from computational studies from TU Darmstadt, National University of Athens, Trieste University, and BASF. Therefore, the influence of the nanoparticles of various diameters (3.0, 4.0, and 5.0 nm) and grafting states (0.0, 0.5, and 1.0 chains/nm2) on atactic polystyrene was studied. To perform this work, a computer molecular dynamics (MD) simulation tool, YASP10, was employed. This tool numerically solves Newton's equations of motion for a system of interacting atoms to generate a trajectory of their movements. Following this, the resulting trajectories can be analyzed for different properties that characterize the structure, dynamics, and thermodynamics of the system. The use of atomistic MD simulations has the advantage of being able to investigate both static and dynamic properties of a system in fine detail. The ensuing results have the benefit of being related to experimental observations such as those probed by nuclear magnetic resonance11 (NMR) and dielectric spectroscopy12 (DS) studies. Additionally, other experimental techniques like neutron, x-ray, and light scattering now allow the determination of the atomistic structure of a material. Thus, computer modeling techniques interface with and complement experimental methods in understanding the link between structural and dynamical properties of polymers. While many experimental5,6,9,13-20 investigations have been performed to study the behavior of polymers at surfaces, very few atomistic21-25 computer modeling studies have been done. This necessitates the development a unified theoretical and experimental understanding of the polymer static and dynamic modifications in the presence of a surface. This is important because such changes determine in part the overall material properties. Examples of these material properties include their mechanical strength, appearance, how well they can be processed, and the duration of the polymer aging process. Additionally, this work sets a foundation for coarse-grained simulations, which investigate longer polymer chains and bigger systems. Static and dynamic properties of polymers determine whether nanoparticles form clusters or are well dispersed in a polymer melt. This is a pivotal challenge in experimental techniques because it is difficult to control the dispersion of nanoparticles, which finally determines the resulting material properties. Parameters that influence the static, dynamic, and nanoparticle dispersion state include - but are not limited to - the nanoparticle size, grafting density, the ratio of the length of grafted to free chains, and surface-polymer interactions. Therefore, developing an understanding of how these parameters interplay with each other will aid in the control and tailoring of the final nanoparticle dispersion state. The first half of this cumulative PhD thesis, chapter 2, presents results of the atactic polystyrene structure around the nanoparticle. The quantities of interest were the polymer density, radius of gyration, and its orientation relative to the nanoparticle surface. The analysis of the computer simulation output trajectory files resolved these polymer properties as a function of distance from the nanoparticle surface to quantify the surface effect. Varying both the polymer grafting density and the nanoparticle surface curvature enabled the understanding of how these two parameters interplay and influence the polymer's structural properties. For instance, the extents of the polymer density modifications under the influence of the nanoparticle surface indicate the wettability of the surface by the polymer. This is important in mitigating adhesive failure and mechanical stress distribution in the nanocomposite material. At the same time, the density changes directly influence the polymer dynamical properties like the glass transition temperature and polymer aging processes. Therefore, understanding and being able to control these changes is vital since polymer properties like the elastic modulus and conductivity amongst many other physical properties change significantly around the polymer glass transition. These observations underscore not only the importance of the polymer in the interface region but also the width of the interphase region. The latter is influenced by the nanoparticle grafting state and the nanoparticle curvature as investigated in this work but also on the length ratio between the grafted and free polymer chains. While changes in the polymer radius of gyration give a measure of how stretched a polymer coil is, this has the effect of directly influencing the packing of polymer chains and their orientation. Additionally, the induced orientation of the polymer and its segments is important in processes that depend on transport properties such as electrical and thermal conductivity. Therefore, the different polymer structural properties are interlinked and understanding their cause-and-effect gives tuning parameters in the design of polymer nanocomposites. Complementary to structural properties discussed in chapter 2, chapter 3 forms the second half of this thesis and discusses the dynamical properties of the polymer. These included the mean-squared displacement (MSD) of the polymer chain center-of-mass and reorientational dynamics of intramolecular segment vectors. These quantities were also calculated under different nanoparticle grafting states and surface curvature. Changes in the polymer chain MSD and the reorientation of its end-to-end vector have given a measure of the global polymer mobility. To understand the local dynamics at the monomer level, the reorientation of a three-monomer and the C-Cpara segment vector as well as the backbone C-H bond vector was investigated (see Figure 1.2). The advantage of obtaining such a local resolution is that it allows for comparison with experimental NMR and DS studies which probe the C-H bond vector and the C-Cpara segment vectors, respectively. To develop a unified understanding, explanations of the dynamical property changes were linked to the previously observed structural properties either in the interface or interphase region, see chapter 2. The objectives to this thesis were to use the molecular dynamics simulation tool (YASP), setup the model system under investigation, perform the simulations, and write analysis programs to determine the different polymer properties. Therefore, I interpreted, understood, and explained my results in light of their interconnectedness as well as results from other simulations and experimental work on polymer nanocomposite systems. Finally, this work ends with chapter four which encompasses the conclusions and an outlook for further investigations.

Информатизацию образования целесообразно рассматривать с разных сторон с применением знаний различных наук. Содержание теоретических и методологических основ составляют положения тех наук, которые способны обосновать наиболее общие фундаментальные, сущностные характеристики информатизации, причем не отдельные ее аспекты, а те, которые связаны с определением методов, способов, путей познания этого сложного явления и его преобразования. Общенаучные подходы: системный, синергетический, историко-логический, культурологический, кибернетический, будучи преломленными к проблемам информатизации образования, позволяют решить определенный круг задач. Среди решаемых задач такие как: установление причинно-следственных связей процессов, связанных с информатизацией; выявление системообразующих связей и отношений, рассмотрение процесса информатизации с позиций целостности; установление границ самоорганизации процессов, связанных с информатизацией; рассмотрение механизмов управления процессом информатизации образования. При этом практика познания объективной реальности показывает, что установить истинные закономерности происхождения и развития различных явлений, процессов можно только путем длительного наблюдения за ними. Не является исключением из этого правила и информатизация военного образования, как элемент объективной реальности. Установление закономерностей возможно только анализом реального опыта, а его, как показало исследование, к настоящему времени накоплено достаточно. Анализ развития информатизации образования показал, что на различных исторических этапах уровень информатизации определялся, прежде всего, возможностями имеющейся техники и технологии (технологический уровень), квалификацией персонала в области информационных технологий (уровень информационной подготовки), качеством созданных информационных образовательных ресурсов (научно-методический уровень). ; It is advisable to consider informatization of education from different sides with the application of knowledge of various sciences. The content of the theoretical and methodological foundations constitute the terms of those sciences which are able to justify the most general fundamental, essential characteristics of information, not the individual aspects of it but those which relate to the definition of methods, techniques, ways of knowledge of this complex phenomenon and its transformation. General scientific approaches: systematic, synergistic, historical-logical, cultural, cyber, being refracted to the problems of informatization of education allow to solve a specific set of tasks. There are such tasks among them as: establishment of the cause-and-effect relationships of processes related to information; identification of strategic partnerships and networks and consideration of the information process from the standpoint of integrity; definition of the boundaries of self-organization processes related to information; consideration of mechanisms of management of the process of informatization of education. The practice of cognition of objective reality shows that the true regularities of the origin and development of various phenomena and processes may be possibly established only by long observation of them. Informatization of military education, as an element of objective reality, isn't an exception of this rule. The definition of laws is possible only by analysis of real experience, which has accumulated to date enough as the research has shown. Analysis of the development of informatization of education showed that the informatization level was mainly determined by the capabilities of existing techniques and technologies (technological level), staff qualification in information technology (level information of training), the quality of information educational resources (scientific and methodological level) at the different historical stages.

Политико-географическая дискретность трансграничья, которую обозначает государственная граница, может преодолеваться за счёт гуманитарно-географических (транспортно-географическая, эколого-географическая, культурно-географическая) форм дополнительности как однородных приграничных территориальных структур, которые проявляют трансграничную континуальность, подобно естественно-географической континуальности, игнорирующей политические границы; так и разнородных, обнаруживающих трансграничную дискретность. Континуальная транспортно-географическая дополнительность периферийных сопредельных сторон, обладающих древовидным географическим рисунком транспортных сетей, открывает новые вариативные возможности по перевозке грузов в формате международной трансграничной территории, переводя её на более высокий уровень, как у центральных регионов стран. Синергетический трансграничный эффект континуальной эколого-географической дополнительности проявляется в обмене инновационными методами наблюдения за природой в формате трансграничных особо охраняемых территорий, превращая их в места внедрения инноваций. Таким образом, меняется география внедрения инновационного развития не от центральных мест крупных городов (от центра к периферии), а от периферии к центру. Континуальная культурно-географическая дополнительность имеет свои особенности: наличие трансграничных памятников и мемориалов, которые выступают в качестве трансграничных аттракторов, способствующих культурной интеграции приграничных территорий. Возможна трансграничная дополнительность и неоднородных гуманитарно-географических структур, возникающая при их трансграничной дискретности, однако, она не обеспечивает трансграничного синергетического эффекта. Дискретность приграничных территориальных структур не позволяет скоординировано решать возникающие трансграничные проблемы. Континуальные формы дополнительности приграничных структур обеспечивают более эффективное трансграничное взаимодействие, его атрибутом является трансграничная симметрия, которая прослеживается во взаимной территориальной организации городов, транспортных путей, особо охраняемых территорий. ; Political and geographic discontinuity of Trans-border area, which the frontier represents, can be overcome through the humanitarian and geographical (transportgeographical, ecological and geographical, cultural and geographical) forms of additionality as homogeneous border territorial structures that perform cross-border continuity, like the natural geographic continuity, ignoring political boundaries and heterogeneous, revealing cross-border discontinuity. Continual transport and geographical additionality of peripheral adjacent parts with the arbuscular geographical pattern of transport networks opens new possibilities for the freight in the format of international cross-border area, transferring it to a higher level, as it is in the central regions of the country. Synergistic cross-border effects of the continual eco-geographical additionality is manifested in the exchange of innovative methods of nature observing in the format of trans-border protected areas, turning them into places of innovation introduction. Thus, the geography of the innovative development introduction, not from central places big cities (from the center to the periphery), but from the periphery to the center, is changing. Continual cultural and geographical additionality has its own characteristics: the presence of cross-border monuments and memorials, which act as trans-border attractors, promoting cultural integration of border areas. The trans-border and non-uniform humanitarian-geographical structures additionality is possible, arising in their cross-border discontinuity, however, it does not provide the cross-border synergy. Discontinuity of trans-border structures does not allow the coordinated solving of emerging trans-border problems. Continuity forms of additionality of cross-border structures provide more effective cross-border cooperation; its attribute is cross-border symmetry, which is apparent in the mutual territorial organization of cities, transport ways, protected areas.

BACKGROUND Tobacco smoking is the cause of many preventable diseases and premature deaths in the UK and around the world. It poses enormous health- and non-health-related costs to the affected individuals, employers, and the society at large. The World Health Organization (WHO) estimates that, globally, smoking causes over US$500 billion in economic damage each year. OBJECTIVES This paper examines global and UK evidence on the economic impact of smoking prevalence and evaluates the effectiveness and cost effectiveness of smoking cessation measures. STUDY SELECTION Search methods We used two major health care/economic research databases, namely PubMed and the National Institute for Health Research (NIHR) database that contains the British National Health Service (NHS) Economic Evaluation Database; Cochrane Library of systematic reviews in health care and health policy; and other health-care-related bibliographic sources. We also performed hand searching of relevant articles, health reports, and white papers issued by government bodies, international health organizations, and health intervention campaign agencies. Selection criteria The paper includes cost-effectiveness studies from medical journals, health reports, and white papers published between 1992 and July 2014, but included only eight relevant studies before 1992. Most of the papers reviewed reported outcomes on smoking prevalence, as well as the direct and indirect costs of smoking and the costs and benefits of smoking cessation interventions. We excluded papers that merely described the effectiveness of an intervention without including economic or cost considerations. We also excluded papers that combine smoking cessation with the reduction in the risk of other diseases. Data collection and analysis The included studies were assessed against criteria indicated in the Cochrane Reviewers Handbook version 5.0.0. Outcomes assessed in the review Primary outcomes of the selected studies are smoking prevalence, direct and indirect costs of smoking, and the costs and benefits of smoking cessation interventions (eg, "cost per quitter", "cost per life year saved", "cost per quality-adjusted life year gained," "present value" or "net benefits" from smoking cessation, and "cost savings" from personal health care expenditure). MAIN RESULTS The main findings of this study are as follows: The costs of smoking can be classified into direct, indirect, and intangible costs. About 15% of the aggregate health care expenditure in high-income countries can be attributed to smoking. In the US, the proportion of health care expenditure attributable to smoking ranges between 6% and 18% across different states. In the UK, the direct costs of smoking to the NHS have been estimated at between £2.7 billion and £5.2 billion, which is equivalent to around 5% of the total NHS budget each year. The economic burden of smoking estimated in terms of GDP reveals that smoking accounts for approximately 0.7% of China's GDP and approximately 1% of US GDP. As part of the indirect (non-health-related) costs of smoking, the total productivity losses caused by smoking each year in the US have been estimated at US$151 billion. The costs of smoking notwithstanding, it produces some potential economic benefits. The economic activities generated from the production and consumption of tobacco provides economic stimulus. It also produces huge tax revenues for most governments, especially in high-income countries, as well as employment in the tobacco industry. Income from the tobacco industry accounts for up to 7.4% of centrally collected government revenue in China. Smoking also yields cost savings in pension payments from the premature death of smokers. Smoking cessation measures could range from pharmacological treatment interventions to policy-based measures, community-based interventions, telecoms, media, and technology (TMT)-based interventions, school-based interventions, and workplace interventions. The cost per life year saved from the use of pharmacological treatment interventions ranged between US$128 and US$1,450 and up to US$4,400 per quality-adjusted life years (QALYs) saved. The use of pharmacotherapies such as varenicline, NRT, and Bupropion, when combined with GP counseling or other behavioral treatment interventions (such as proactive telephone counseling and Web-based delivery), is both clinically effective and cost effective to primary health care providers. Price-based policy measures such as increase in tobacco taxes are unarguably the most effective means of reducing the consumption of tobacco. A 10% tax-induced cigarette price increase anywhere in the world reduces smoking prevalence by between 4% and 8%. Net public benefits from tobacco tax, however, remain positive only when tax rates are between 42.9% and 91.1%. The cost effectiveness ratio of implementing non-price-based smoking cessation legislations (such as smoking restrictions in work places, public places, bans on tobacco advertisement, and raising the legal age of smokers) range from US$2 to US$112 per life year gained (LYG) while reducing smoking prevalence by up to 30%–82% in the long term (over a 50-year period). Smoking cessation classes are known to be most effective among community-based measures, as they could lead to a quit rate of up to 35%, but they usually incur higher costs than other measures such as self-help quit-smoking kits. On average, community pharmacist-based smoking cessation programs yield cost savings to the health system of between US$500 and US$614 per LYG. Advertising media, telecommunications, and other technology-based interventions (such as TV, radio, print, telephone, the Internet, PC, and other electronic media) usually have positive synergistic effects in reducing smoking prevalence especially when combined to deliver smoking cessation messages and counseling support. However, the outcomes on the cost effectiveness of TMT-based measures have been inconsistent, and this made it difficult to attribute results to specific media. The differences in reported cost effectiveness may be partly attributed to varying methodological approaches including varying parametric inputs, differences in national contexts, differences in advertising campaigns tested on different media, and disparate levels of resourcing between campaigns. Due to its universal reach and low implementation costs, online campaign appears to be substantially more cost effective than other media, though it may not be as effective in reducing smoking prevalence. School-based smoking prevalence programs tend to reduce short-term smoking prevalence by between 30% and 70%. Total intervention costs could range from US$16,400 to US$580,000 depending on the scale and scope of intervention. The cost effectiveness of school-based programs show that one could expect a saving of approximately between US$2,000 and US$20,000 per QALY saved due to averted smoking after 2–4 years of follow-up. Workplace-based interventions could represent a sound economic investment to both employers and the society at large, achieving a benefit–cost ratio of up to 8.75 and generating 12-month employer cost savings of between $150 and $540 per nonsmoking employee. Implementing smoke-free workplaces would also produce myriads of new quitters and reduce the amount of cigarette consumption, leading to cost savings in direct medical costs to primary health care providers. Workplace interventions are, however, likely to yield far greater economic benefits over the long term, as reduced prevalence will lead to a healthier and more productive workforce. CONCLUSIONS We conclude that the direct costs and externalities to society of smoking far outweigh any benefits that might be accruable at least when considered from the perspective of socially desirable outcomes (ie, in terms of a healthy population and a productive workforce). There are enormous differences in the application and economic measurement of smoking cessation measures across various types of interventions, methodologies, countries, economic settings, and health care systems, and these may have affected the comparability of the results of the studies reviewed. However, on the balance of probabilities, most of the cessation measures reviewed have not only proved effective but also cost effective in delivering the much desired cost savings and net gains to individuals and primary health care providers.

Background: Tobacco smoking is the cause of many preventable diseases and premature deaths in the UK and around the world. It poses enormous health- and non-health-related costs to the affected individuals, employers, and the society at large. The World Health Organization (WHO) estimates that, globally, smoking causes over US$500 billion in economic damage each year. Objectives: This paper examines global and UK evidence on the economic impact of smoking prevalence and evaluates the effectiveness and cost effectiveness of smoking cessation measures. Study selection Search methods: We used two major health care/economic research databases, namely PubMed and the National Institute for Health Research (NIHR) database that contains the British National Health Service (NHS) Economic Evaluation Database; Cochrane Library of systematic reviews in health care and health policy; and other health-care-related bibliographic sources. We also performed hand searching of relevant articles, health reports, and white papers issued by government bodies, international health organizations, and health intervention campaign agencies. Selection criteria: The paper includes cost-effectiveness studies from medical journals, health reports, and white papers published between 1992 and July 2014, but included only eight relevant studies before 1992. Most of the papers reviewed reported outcomes on smoking prevalence, as well as the direct and indirect costs of smoking and the costs and benefits of smoking cessation interventions. We excluded papers that merely described the effectiveness of an intervention without including economic or cost considerations. We also excluded papers that combine smoking cessation with the reduction in the risk of other diseases. Data collection and analysis: The included studies were assessed against criteria indicated in the Cochrane Reviewers Handbook version 5.0.0. Outcomes assessed in the review: Primary outcomes of the selected studies are smoking prevalence, direct and indirect costs of smoking, and the costs and benefits of smoking cessation interventions (eg, "cost per quitter", "cost per life year saved", "cost per quality-adjusted life year gained," "present value" or "net benefits" from smoking cessation, and "cost savings" from personal health care expenditure). Main results: The main findings of this study are as follows: 1. The costs of smoking can be classified into direct, indirect, and intangible costs. About 15% of the aggregate health care expenditure in high-income countries can be attributed to smoking. In the US, the proportion of health care expenditure attributable to smoking ranges between 6% and 18% across different states. In the UK, the direct costs of smoking to the NHS have been estimated at between £2.7 billion and £5.2 billion, which is equivalent to around 5% of the total NHS budget each year. The economic burden of smoking estimated in terms of GDP reveals that smoking accounts for approximately 0.7% of China's GDP and approximately 1% of US GDP. As part of the indirect (non-health-related) costs of smoking, the total productivity losses caused by smoking each year in the US have been estimated at US$151 billion. 2.The costs of smoking notwithstanding, it produces some potential economic benefits. The economic activities generated from the production and consumption of tobacco provides economic stimulus. It also produces huge tax revenues for most governments, especially in high-income countries, as well as employment in the tobacco industry. Income from the tobacco industry accounts for up to 7.4% of centrally collected government revenue in China. Smoking also yields cost savings in pension payments from the premature death of smokers. 3. Smoking cessation measures could range from pharmacological treatment interventions to policy-based measures, community-based interventions, telecoms, media, and technology (TMT)-based interventions, school-based interventions, and workplace interventions. 4. The cost per life year saved from the use of pharmacological treatment interventions ranged between US$128 and US$1,450 and up to US$4,400 per quality-adjusted life years (QALYs) saved. The use of pharmacotherapies such as varenicline, NRT, and Bupropion, when combined with GP counseling or other behavioral treatment interventions (such as proactive telephone counseling and Web-based delivery), is both clinically effective and cost effective to primary health care providers. 5. Price-based policy measures such as increase in tobacco taxes are unarguably the most effective means of reducing the consumption of tobacco. A 10% tax-induced cigarette price increase anywhere in the world reduces smoking prevalence by between 4% and 8%. Net public benefits from tobacco tax, however, remain positive only when tax rates are between 42.9% and 91.1%. The cost effectiveness ratio of implementing non-price-based smoking cessation legislations (such as smoking restrictions in work places, public places, bans on tobacco advertisement, and raising the legal age of smokers) range from US$2 to US$112 per life year gained (LYG) while reducing smoking prevalence by up to 30%–82% in the long term (over a 50-year period). 6. Smoking cessation classes are known to be most effective among community-based measures, as they could lead to a quit rate of up to 35%, but they usually incur higher costs than other measures such as self-help quit-smoking kits. On average, community pharmacist-based smoking cessation programs yield cost savings to the health system of between US$500 and US$614 per LYG. 7. Advertising media, telecommunications, and other technology-based interventions (such as TV, radio, print, telephone, the Internet, PC, and other electronic media) usually have positive synergistic effects in reducing smoking prevalence especially when combined to deliver smoking cessation messages and counseling support. However, the outcomes on the cost effectiveness of TMT-based measures have been inconsistent, and this made it difficult to attribute results to specific media. The differences in reported cost effectiveness may be partly attributed to varying methodological approaches including varying parametric inputs, differences in national contexts, differences in advertising campaigns tested on different media, and disparate levels of resourcing between campaigns. Due to its universal reach and low implementation costs, online campaign appears to be substantially more cost effective than other media, though it may not be as effective in reducing smoking prevalence. 8. School-based smoking prevalence programs tend to reduce short-term smoking prevalence by between 30% and 70%. Total intervention costs could range from US$16,400 to US$580,000 depending on the scale and scope of intervention. The cost effectiveness of school-based programs show that one could expect a saving of approximately between US$2,000 and US$20,000 per QALY saved due to averted smoking after 2–4 years of follow-up. 9. Workplace-based interventions could represent a sound economic investment to both employers and the society at large, achieving a benefit–cost ratio of up to 8.75 and generating 12-month employer cost savings of between $150 and $540 per nonsmoking employee. Implementing smoke-free workplaces would also produce myriads of new quitters and reduce the amount of cigarette consumption, leading to cost savings in direct medical costs to primary health care providers. Workplace interventions are, however, likely to yield far greater economic benefits over the long term, as reduced prevalence will lead to a healthier and more productive workforce. Conclusions: We conclude that the direct costs and externalities to society of smoking far outweigh any benefits that might be accruable at least when considered from the perspective of socially desirable outcomes (ie, in terms of a healthy population and a productive workforce). There are enormous differences in the application and economic measurement of smoking cessation measures across various types of interventions, methodologies, countries, economic settings, and health care systems, and these may have affected the comparability of the results of the studies reviewed. However, on the balance of probabilities, most of the cessation measures reviewed have not only proved effective but also cost effective in delivering the much desired cost savings and net gains to individuals and primary health care providers.

Die klassische Literatur über die Nahrungskonkurrenz unterscheidet zwischen zwei Hauptformen des Wettbewerbs: Interferenzkonkurrenz und Ausbeutungskonkurrenz. Interferenzkonkurrenz ist eine direkte Form des Wettbewerbs, die von gruppierten, verteidigbaren Ressourcen hervorgerufen wird und eine ungleiche Verteilung der Ressourcen zur Folge hat. Ausbeutungskonkurrenz ist eine indirekte Art des Wettbewerbs, die eine gleiche Verteilung der Ressourcen zu Folge hat, aber sich die Menge, die jeder bekommt, mit erhöhter Gruppengröße verringert. Sozioökologische Modelle über Primaten bieten eindeutige Vorhersagen für Verhaltensantworten und die Energiebilanz abhängig von den Eigenschaften der Ressource. Die sozialen Auswirkungen beschreiben das Wettbewerbssystem innerhalb von Gruppen und zwischen Gruppen, wie Charakteristika der Dominanzbeziehungen und den Grad von Toleranz unter Weibchen. Die zwei Arten in der Gattung Pan, Schimpansen (P. troglodytes) und Bonobos (P. paniscus), haben einige soziale Eigenschaften gemeinsam, darunter die Abwanderung von Weibchen und starke Fission-Fusion-Dynamiken. Jedoch unterscheiden sich weibliche Bonobos von Schimpansen durch ihren hohen Grad an Geselligkeit, größere Toleranz und ihre sozio-sexuellen Verhaltensweisen. Bisher wurden die proximaten Mechanismen, die diesen Eigenschaften zugrunde liegen, noch nicht gründlich untersucht. Meine Doktorarbeit hatte zum Ziel die Voraussagen, die von der sozioökologischen Theorie abgeleitet werden können, zu untersuchen. Diese stellt wiederholte soziale Interaktionen an Orten wo Nahrung vorkommt mit unterschiedlichen Energiebilanzen und allostatischer Belastung von weiblichen Bonobos in Bezug. Insbesondere war mein Ziel aufzuklären, ob diese Unterschiede durchweg mit der Position in der Rangordnung zusammenhängen. Mit meiner Studie konnte ich außerdem einen formalen Test der sozioökologischen Hypothese durchführen. Diese schlägt vor, dass Unterschiede in der Geselligkeit zwischen weiblichen Schimpansen und Bonobos durch die Verfügbarkeit üppiger Nahrungsressourcen im Lebensraum der Bonobos zustande kommen. Des Weiteren untersuchte ich zwei alternative Hypothesen, welche besonders die erhöhte Geselligkeit von Bonobos erklären sollen. Um dies zu tun, beschrieb ich die proximaten Mechanismen der Nahrungskonkurrenz weiblicher Bonobos innerhalb von Gruppen, indem ich die relativen Auswirkungen sozialer und ökologischer Parameter auf die Effizienz bei der Nahrungsaufnahme, die Energiebilanz und die allostatische Belastung maß. Über zweimal neun Monate sammelte ich Daten von 14 weiblichen Bonobos der Bompusa-Gruppe am Studienstandort LuiKotale in der Demokratischen Republik Kongo. Mit der Fokusbaum-Methode (focal tree method) sammelte ich Daten über die Eigenschaften von Nahrungsressourcen, auf einer für Bonobos relevanten Skala, an 683 Orten an denen Nahrung vorkam. Ich erfasste die Rate der Nahrungsaufnahme und Bewegungen im Fokus stehenden Baum, um die Effizienz bei der Nahrungsaufnahme festzustellen. Ich sammelte nicht-invasive Urinproben, um die Energiebilanz von Weibchen anhand der C-Peptidmenge und der allostatischen Belastung (Menge der Kortisolmetaboliten) abzuschätzen. Ich sammelte Scan-Daten über die Zusammensetzung der Gruppe und das Fressen am Boden wachsender krautiger Vegetation und nutzte diese um mögliche unterschiedliche Strategien der Nahrungsaufnahme bei den Weibchen abzuleiten. Um zu untersuchen, ob Weibchen Koalitionen gegen andere Weibchen oder Männchen bilden, analysierte ich Daten über das Vorkommen agonistischer Interaktionen. Meine erste Studie untersuchte die relativen Beiträge ökologischer und sozialer Faktoren zur erfolgreichen Nahrungsaufnahme, dem zur Nahrungsaufnahme nötigen Aufwand und der Energiebilanz bei Weibchen. Basierend auf dem Zusammenspiel geringerer Nahrungsaufnahme und erhöhter Bewegung innerhalb des Nahrungsvorkommens, konnte ich feststellen, dass Bonobos ihre Nahrungsressourcen erschöpfen, was eine Grundvoraussetzung für das Vorkommen von Nahrungskonkurrenz ist. Ich fand heraus, dass hochrangige Weibchen eine höhere Effizienz bei der Nahrungsaufnahme hatten als niedrigrangige Weibchen, da ein hoher Rang mit höheren Raten der Nahrungsaufnahme in Kombination mit einer geringeren Wahrscheinlichkeit der Bewegung innerhalb des Nahrungsvorkommens zusammenhing. Ich fand heraus, dass Unterschiede in der Energiebilanz bei Weibchen durch die monatliche Verfügbarkeit von Früchten erklärt werden konnte, aber nicht mit der Position in der Rangordnung zusammenhingen. Ich zeigte, dass niedrigrangige Weibchen die niedrigere Effizienz bei der Nahrungsaufnahme weder dadurch kompensierten, dass sie krautige Vegetation am Boden fraßen, noch, dass sie in kleineren Gruppen auf Nahrungssuche gingen als höherrangige Weibchen. Ich konnte zeigen, dass Interferenzkonkurrenz ein Teil des Kokurrenzsystems von Bonobos ist. Dies kommt wahrscheinlich dadurch zustande, dass hochrangige Weibchen bessere Positionen für die Nahrungsaufnahme im Nahrungsvorkommen einnehmen und von niedrigrangigen Weibchen gemieden werden. Zusammen mit der Erschöpfung des Nahrungsvorkommens und in Ermangelung von Hinweisen darauf, dass niedrigrangige Weibchen alternative Strategien zur Nahrungsaufnahme wählen, habe ich gezeigt, dass die Hypothese des Überflusses an Ressourcen eine unwahrscheinliche Erklärung für die Unterschiede in der Geselligkeit zwischen weiblichen Schimpanse und Bonobos ist. So unterstützt meine Studie die Hypothese, dass sich die Geselligkeit und Duldung von Weibchen bei Bonobos evolutionär entwickelt hat, da größtenteils nicht-verwandte Weibchen flexible Koalitionen bilden müssen, um Nahrungsressourcen gegen Männchen zu verteidigen und Schikanen durch Männchen abzuwehren. In meiner zweiten Studie untersuchte ich die Vorrausagen des Konzeptes der allostatischen Belastung, um die Wirkungen des energetischen Zustandes, der Position in der Rangordnung und des reproduktiven Zustandes auf die Menge an Kortisolmetaboliten bei den Weibchen, ein Maß für die allostatische Belastung, zu untersuchen. Ich stellte fest, dass es keine Beziehung zwischen der Energiebilanz und der in derselben Urinprobe gemessenen Kortisolmenge gab. Ich fand heraus, dass Weibchen in der frühen Phase der Milchbildung höhere Kortisolmengen hatten als sich im Zyklus befindende Weibchen und Weibchen in einer späteren Phase der Milchbildung. Ich fand auch heraus, dass die drei höchstrangigen Weibchen höhere Kortisolmengen aufwiesen, als die 11 Weibchen auf den anderen Positionen in der Rangordnung. Ich zeigte, dass Weibchen in den höheren Positionen in der Rangordnung einer größeren allostatischen Belastung ausgesetzt sind. Auch zeigte ich, dass die frühe Phase der Milchbildung die allostatische Belastung der Weibchen, unabhängig von der Position in der Rangfolge, erhöht. Zusammengenommen verbessern die Ergebnisse meiner Studie unser Verständnis der sozialen Beziehungen zwischen Weibchen, bei einer Art, die allgemein als friedfertig und tolerant angesehen wird. Niedrigranginge Bonoboweibchen haben nur beschränkt Nachteile durch Nahrungskonkurrenz, da ihre Energiebilanzen ähnlich derer der hochrangingen Weibchen waren. Die höchstrangigen Weibchen sind durch die Sozialität benachteiligt. Dies scheint mehr durch soziale Ursachen, als durch Nachteile bei der Nahrungsaufnahme begründet. Die erhöhten Nachteile der Sozialität für weibliche Bonobos, könnten einerseits in der Erhaltung der Position in der Rangordnung und des Erlangens von Rang bei gleichzeitigem Fehlen von weiblichen Verwandten begründet liegen und andererseits durch ihre Beteiligung an Konflikten zwischen den Geschlechtern hervorgerufen werden, ins besonders wenn Unterstützung ihrer Söhne in Konflikten dabei eine Rolle spielt. ; Social interactions with conspecifics have fitness consequences for individuals. Socio-ecology is a subdiscipline of behavioral ecology. Socio-ecology integrates ecology, sexual selection, inclusive fitness theory, and evolutionary optimality modelling to advance our understanding of how social strategies evolve. Social strategies are sets of repeated individual behavioural decisions from which social systems eventually arise. A successful strategy maximizes an individuals' inclusive fitness. Behavioural decisions are constrained by several factors, many of which stem from the surrounding ecological and social environment. Group living comes with the costs of within-group competition for resources and increased disease transmission risk, which needs to balance out against the benefits of sociality for group living to evolve. Benefits of group living include reduced risk of predation, increased access to mates, defense of resources, and enhanced foraging success, among others. Social strategies are modulated by sex, because male and female fitness are limited by different resources. In mammals, female fitness is limited by access to food resources due to the energetic costs of gestation and lactation. Therefore, feeding competition tends to pose a greater cost of sociality for females than for males. Primate socio-ecology has focused on how food resource characteristics affect the distribution of females and their social strategies, which in turn defines the social strategies of males. Male coercion, infanticide risk, and predation risk are also key factors which shape female strategies. Classical literature on resource competition makes a distinction between two main forms of competition, contest and scramble. Contest competition is a direct form of competition induced by clumped, defendable resources, and it results in a skewed distribution of resources among group members. Scramble is an indirect form of competition that results in equal resource distribution among group members but the amount received by everyone decreases with increasing group size. Primate socio-ecological models have been central in providing distinct predictions for the behavioural responses and net energy intake depending on the resource characteristics. The social outcomes describe the competitive regimes within and betw een groups, including characteristics of dominance relationships and degree of tolerance among females. The two species in genus Pan, chimpanzees (P. troglodytes) and bonobos (P. paniscus), share several social traits, including female dispersal and a high degree of fission-fusion dynamics. However, female bonobos are distinct due to their high gregariousness (i.e. high ratio of attendance in mix-sex parties and female cohesiveness), increased social tolerance and socio-sexual behaviours. The proximate mechanisms underlying these traits have not been studied rigorously thus far. Several hypotheses have been proposed to explain the species difference within the Genus Pan, however a formal test with the appropriate parameters has been lacking. As our closest living relatives together with the chimpanzees, studying bonobos in their natural habitat can also enhance our understanding of human evolution. My thesis aim was test predictions derived from socio-ecological theory, which link repeated social interactions in feeding patches to variation in female energy balance and glucocorticoid levels reflecting allostatic load (i.e. the cumulative burden on the body due to environmental challenges) in female bonobos. In particular, my aim was to elucidate, whether the variation is consistently associated with female dominance rank position such that the costs of feeding competition are skewed. With my study, I was also able to comprehensively test a socio-ecological hypothesis, the Resource Abundance hypothesis, which proposes that differences in gregariousness between female chimpanzees and bonobos are due to the differences in the availability of abundant food resources. In addition, I tested two alternative hypotheses, the Cooperative Defence and Priority of Access hypotheses, proposed to explain the increased gregariousness in female bonobos specifically. The former proposes female defence of food resources against males as the main driver of female sociality in bonobos, while the latter invokes female defence of food resources against other females, respectively. To test the predictions for these hypotheses, I characterized the proximate mechanisms of within-group feeding competition in female bonobos by assessing the relative effects of social and ecological parameters on female feeding efficiency, energy balance and allostatic load. I collected data on 14 adult female bonobos of the Bompusa community at the study site of LuiKotale in Democratic Republic of Congo during two nine-month field seasons. I obtained data on food resource characteristics on a scale relevant to the bonobos from 683 feeding patches using the focal tree method. I recorded food intake rates and movement in focal trees to assess female feeding efficiency. I collected non-invasive urine samples to assess female energy balance based on C-peptide levels and allostatic load based on cortisol metabolite levels. I collected scan data on party composition and terrestrial herbaceous vegetation feeding, and used it to infer potential alternative female feeding strategies. To examine whether females predominantly formed coalitions against other females or against males, I analysed all occurrence data on agonistic interactions. My first study evaluated the relative contributions of ecological and social factors on female feeding success, feeding effort and energy balance. Based on the combined effects of decreasing food intake and increasing movement in feeding patches, I established that bonobos depleted their food resources, which is a condition for feeding competition to occur. I found that high-ranking females had higher feeding efficiency than low-ranking females, because high dominance rank was associated with higher food intake rates in combination with lower probability of moving in feeding patches. This finding is consistent with within-group contest competition and most likely results from high-ranking females attaining better feeding positions in food patches and avoidance of high-ranking females by low-ranking females. I found that variation in female energy balance was explained by monthly availability of fruits (positive association between energy balance and fruit availability), but not by female dominance rank. I demonstrated that low-ranking females did not compensate for the lower feeding efficiency by feeding in terrestrial herbaceous vegetation patches or by foraging in smaller parties than high-ranked females. I also found that female-female coalitions mainly targeted males. In combination with the patch depletion and lack of support for lower-ranking females using alternative feeding strategies, I have shown that the Resource Abundance hypothesis is an unlikely explanation for the differences in female gregariousness between chimpanzees and bonobos. My study lends stronger support for the Cooperative Defence hypothesis, suggesting that female gregariousness and tolerance in bonobos evolved due to the need of flexible coalition formation among the mostly unrelated females in defense of food resources against males and to deter harassment by males. In my second study, I tested the predictions of the allostatic load framework to asses the effects of energetic condition, dominance status, and reproductive state on female cortisol metabolite levels as a proxy of allostatic load. I established, that there was no relationship between energy balance and cortisol levels measured from the same urine sample. I found that females in early lactation state had higher cortisol levels compared to females in cycling or late lactation state. I also found that the three highest-ranked females had higher cortisol levels compared to the 11 females on all other dominance rank positions. I also showed that females at the highest dominance rank position face increased allostatic load. Moreover, I found that early lactation increases allostatic load of females independent of dominance rank position. The combined results of my study refine our understanding of female social relationships in a species that is peaceful and tolerant according to the widely held notion. Lower-ranking female bonobos suffer only limited costs of within-group feeding competition. Despite having lower feeding efficiency compared to high-ranking females, the energy balance of low-ranking females is similar to those of higher-ranked females. I did not find indication that low-ranked females used compensatory feeding strategies of feeding away from the main party or feeding more on terrestrial herbs. Another possibility is that lower-ranking females feed longer, which I did not test for. However, I did find that highest-ranking females face costs of sociality that seem to be driven by social effects rather than by nutritional challenges. The increased costs of sociality to the highest-ranked female bonobos may be due to dominance rank maintenance and acquisition in the absence of support from female relatives on the one hand. Moreover, there may be additional energetic costs for those high-ranking females who provide agonistic support for their son(s). My study therefore consolidates the modulating effect of male strategies on female social relationships, and the importance of considering the synergistic effects of male and female strategies on sociality.

Keynote address: Revaluing the orbital prefrontal cortex / R.J. Dolan -- Specialized elements of orbitofrontal cortex in primates / H. Barbas -- The orbitofrontal cortex: Novelty, deviation from expectation, and memory / M. Petrides -- Definition of the orbital cortex in relation to specific connections with limbic and visceral structures and other cortical regions / J.L. Price -- Role of orbitofrontal cortex connections in emotion / N.L. Rempel-Clower -- Perspectives on olfactory processing, conscious perception, and orbitofrontal cortex / G.M. Shepherd -- What can an orbitofrontal cortex-endowed animal do with smells? / J.A. Gottfried -- Taste in the medial orbitofrontal cortex of the macaque / T.C. Pritchard, G.J. Schwartz, T.R. Scott. -- The role of the human orbitofrontal cortex in taste and flavor processing / D.M. Small ... [et al.] -- The role of the orbitofrontal cortex in sensory-specific encoding of associations in Pavlovian and instrumental conditioning / A.R. Delamater -- The contribution of orbitofrontal cortex to action selection / S.B. Ostlund, B.W. Balleine -- Neural encoding in the orbitofrontal cortex related to goal-directed behavior / T. Furuyashiki, M. Gallagher -- Interactions between the orbitofrontal cortex and the hippocampal memory system during the storage of long-term memory / S.J. Ramus ... [et al.] -- Orbitofrontal cortex and the computation of economic value / C. Padoa-Schioppa -- Lights, camembert, action! The role of human orbitofrontal cortex in encoding stimuli, rewards, and choices / J.P. O'Doherty -- Orbitofrontal cortex and amygdala contributions to affect and action in primates / E.A. Murray, A. Izquierdo -- Synergistic and regulatory effects of orbitofrontal cortex on amygdala-dependent appetitive behavior / A.C. Roberts, K. Reekie, K. Braesicle -- Reconciling the roles of orbitofrontal cortex in reversal learning and the encoding of outcome expectancies / G. Schoenbaum ... [et al.] -- Flexible neural representations of value in the primate brain / C.D. Salzman ... [et al.] -- The contribution of the medial prefrontal cortex, orbitofrontal cortex, and dorsomedial striatum to behavioral flexibility / M.E. Ragozzino -- A comparison of reward-contingent neuronal activity in monkey orbitofrontal cortex and ventral striatum. Guiding actions toward rewards / J.M. Simmons ... [et al.] -- Orbital versus dorsolateral prefrontal cortex. Anatomical insights into content versus process differentiation models of the prefrontal cortex / D.H. Zald -- Difficulty overcoming learned non-reward during reversal learning in rats with ibotenic acid lesions of orbital prefrontal cortex / D.S. Tait, V.J. Brown -- The role of orbitofrontal cortex in decision making. A component process account / L.K. Fellows -- Neuronal activity related to anticipated reward in frontal cortex. Does it represent value or reflect motivation? / M.R. Roesch, C.R. Olson -- Neuronal mechanisms in prefrontal cortex underlying adaptive choice behavior / J.D. Wallis -- Dysfunctions of medial and lateral orbitofrontal cortex in psychopathy / R.J.R. Blair -- The orbitofrontal cortex, real-world decision making, and normal aging / N.L. Denburg ... [et al.] -- Orbitofrontal cortex function and structure in depression / W.C. Drevets -- Symptoms of frontotemporal dementia provide insights into orbitofrontal cortex function and social behavior / I.V. Viskontas, K.L. Possin, B.L. Miller -- The role of the orbitofrontal cortex in anxiety disorders / M.R. Milad, S.L. Rauch -- Vulnerability of the orbitofrontal cortex to age-associated structural and functional brain changes / S.M. Resnick ... [et al.] -- The orbital prefrontal cortex and drug addiction in laboratory animals and humans / B.J. Everitt ... [et al.] -- Neural correlates of inflexible behavior in the orbitofrontal-amygdalar circuit after cocaine exposure / T.A. Stalnaker ... [et al.] -- Orbitofrontal cortex and cognitive-motivational impairments in psychostimulant addiction. Evidence from experiments in the non-human primate / P. Olausson ... [et al.] -- The orbitofrontal cortex, impulsivity, and addiction. Probing orbitofrontal dysfunction at the neural, neurochemical, and molecular level / C.A. Winstanley

Problem and Purpose Innovative solutions in national defense are needed to respond to national security threats in our uncertain environment. Leader attitudes and behaviors have a substantial impact on innovation. Unfortunately we did not completely understand the effect of leader attitudes and behaviors on innovation and the team dynamics that lead to innovation, especially in the military. The purpose of this study was to determine how leadership attitudes and behaviors contribute to product innovation within the U.S. Navy and how leadership emerges within this complex adaptive system of innovation. Method The research was a qualitative design based on a multiple or comparative case study. A theoretical/conceptual framework of complexity leadership theory was used as a meso model to understand adaptive innovative processes at work in the context of bureaucratic forms of organizing. Three teams based on three product innovations were selected because they demonstrated breakthrough innovation with disruptive technology and successfully fielded their capabilities within cost and schedule thresholds. Data from three project teams were collected using interviews, focus groups, and program documentation. Eighteen individuals participated in interviews and focus groups. The attitudes and behaviors of nine formal leaders and several emerging leaders were analyzed and evaluated. The results were summarized in six different themes that were apparent across all three projects and multiple leaders. Results These six themes were a combination of leader attitudes and behaviors that contributed to the success of the three projects. These attitudes and behaviors were observed at all levels of the organization from the program manager, to the IPT leaders, to the engineers getting the job done. The first theme was urgency driven by a heartfelt need. The second theme was that these leaders would listen and were open to ideas. The third theme was to know the process and challenge the process while managing risk and ensuring it is good enough. The fourth theme was vision, passion, assertive, persistence, and moderating setbacks. The fifth theme was trusted leader with credibility, integrity, and was professional. The last theme was collaboration, teamwork, and recognition. Communication was apparent throughout all the themes and links them together. Conclusions The attitudes and behaviors of the leaders in this study contributed to the innovation by keeping the polarity within these themes in creative tension. The leaders established a strong sense of urgency based on a heartfelt need while also creating an atmosphere and practice of making sure everyone had a voice and their voice counted. The leaders were professional with credibility and integrity. They knew the process, but also challenged the process, managed risk, and encouraged a solution that was good enough. The leaders were passionate about the vision and were assertive and persistent in removing obstacles. But they also encouraged collaboration and teamwork. They moderated setbacks and prevented the team from getting discouraged and took opportunities to recognize the team both informally and formally. These leader attitudes and behaviors contributed toward leaders emerging in the organization. A wheel of innovation is proposed that demonstrates the themes in a synergistic and balanced approach. While this improved our understanding of how leader attitudes and behaviors drive innovation, there are still significant areas for further study. Further case studies are needed to determine if this wheel of innovation is applicable outside of the U.S. Navy. Quantitative studies based on these findings are needed to expand the understanding and generalizability of the model.

Brieuc Van Nieuwenhuyse1, Dimitri Van der Linden1,2, Olga Chatzis2, Cédric Lood3,4, Jeroen Wagemans3, Rob Lavigne4, Catherine de Magnée5, Étienne Sokal1,6, Hector Rodriguez-Villalobos7, Sarah Djebara8, Maya Merabishvili9, Patrick Soentjens8, Jean-Paul Pirnay9. 1Institute of Experimental and Clinical Research's Pediatric department, UCLouvain, Brussels, Belgium; 2Pediatric Infectious Diseases, General Pediatrics Department, Cliniques universitaires Saint-Luc, Brussels, Belgium; 3Department of Biosystems, Laboratory of Gene Technology, KULeuven, Leuven, Belgium; 4Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KULeuven, Leuven, Belgium; 5Pediatric and Transplantation Surgery, Cliniques universitaires Saint-Luc, Brussels, Belgium; 6Pediatric Hepatology and Gastro-enterology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 7Department of Microbiology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 8Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium; 9Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium A 14-month old boy undergoes a first liver transplantation (LT) (Day 0), from an ABO-incompatible living donor. On D+20, we detect a fecal carriage of an extensively drug-resistant (XDR) Pseudomonas aeruginosa (Pa) strain. Besides intermediate susceptibility to aztreonam and colistin and susceptibility to gentamycin, the strain is resistant to all other antibiotics. On D+53, the child enters a severe septic state due to a bacteremia with the same Pa strain. New antibiogram suggests a resistance to colistin. Liver bilomas' drainage material is cultured and grows the same Pa strain. Admission to the pediatric intensive care unit and adjunction of intravenous (IV) aztreonam, gentamycin, and colistin led to no improvement on the microbiological or clinical levels during the next four days. By collaborating with Queen Astrid Military Hospital (Brussels, Belgium), we initiated phage therapy (PT) on D+57 in accordance to the Article 37 of the Declaration of Helsinki and with the patient's parents' consent. PT is the use of lytic bacteriophage viruses to achieve antibacterial effect. Phage cocktail BFC1 contains two anti-Pa phages (PNM and 14/1) and one anti-Staphylococcus aureus phage (ISP). BFC1 was administered in situ by instillations through biliary catheter during six days, and in IV for 86 days (72 days until 2nd LT, 14 days afterwards), the longest described duration for IV PT in a child. Previous antibiotic therapy was pursued all along. Intraoperative PT was performed during 2nd LT by bathing the peritoneal cavity in phage solution during the anhepatic phase. To further our understanding of the case, seven Pa isolates, both bloodborne and liver-borne, were sequenced. Serum samples obtained before, during, and after phage therapy were analyzed through double agar overlay method to search for phage immune neutralization (PIN). Phage-induced virulence tradeoffs (PIVT) assays were performed in a Galleria mellonella model. In vitro phage-antibiotic interactions were evaluated with OmniLog® system. PT initiation was followed by immediate (<24 h) eradication of Pa from blood cultures. Reappearance of Pa in blood cultures after four days of PT led to a doubling of the PT dose, which was followed by eradication of Pa from bloodstream until 2nd LT. The child has known no further infectious episode since then. Sequencing confirmed the emergence of bacterial phage resistance (BPR) in four isolates. Such BPR did not lead to therapeutic failure, possibly thanks to PIVT. PIN against phage ISP was detected, but not against any anti-Pa phage. OmniLog® assays suggested synergistic properties between phage PNM and three antibiotics administered concomitantly to the patient. In conclusion, prolonged IV phage therapy combined with antibiotics led to the durable eradication of an XDR Pa sepsis in an immunosuppressed 14-month old boy, eventually allowing for 2nd LT. This possibly relied on synergy between phages and antibiotics. This combined therapy was safe.

Brieuc Van Nieuwenhuyse1, Dimitri Van der Linden1,2, Olga Chatzis2, Cédric Lood3,4, Jeroen Wagemans3, Rob Lavigne4, Catherine de Magnée5, Étienne Sokal1,6, Hector Rodriguez-Villalobos7, Sarah Djebara8, Maya Merabishvili9, Patrick Soentjens8, Jean-Paul Pirnay9. 1Institute of Experimental and Clinical Research's Pediatric department, UCLouvain, Brussels, Belgium; 2Pediatric Infectious Diseases, General Pediatrics Department, Cliniques universitaires Saint-Luc, Brussels, Belgium; 3Department of Biosystems, Laboratory of Gene Technology, KULeuven, Leuven, Belgium; 4Department of Microbial and Molecular Systems, Centre of Microbial and Plant Genetics, KULeuven, Leuven, Belgium; 5Pediatric and Transplantation Surgery, Cliniques universitaires Saint-Luc, Brussels, Belgium; 6Pediatric Hepatology and Gastro-enterology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 7Department of Microbiology, Cliniques universitaires Saint-Luc, Brussels, Belgium; 8Center for Infectious Diseases, Queen Astrid Military Hospital, Brussels, Belgium; 9Laboratory for Molecular and Cellular Technology, Queen Astrid Military Hospital, Brussels, Belgium A 14-month old boy undergoes a first liver transplantation (LT) (Day 0), from an ABO-incompatible living donor. On D+20, we detect a fecal carriage of an extensively drug-resistant (XDR) Pseudomonas aeruginosa (Pa) strain. Besides intermediate susceptibility to aztreonam and colistin and susceptibility to gentamycin, the strain is resistant to all other antibiotics. On D+53, the child enters a severe septic state due to a bacteremia with the same Pa strain. New antibiogram suggests a resistance to colistin. Liver bilomas' drainage material is cultured and grows the same Pa strain. Admission to the pediatric intensive care unit and adjunction of intravenous (IV) aztreonam, gentamycin, and colistin led to no improvement on the microbiological or clinical levels during the next four days. By collaborating with Queen Astrid Military Hospital (Brussels, Belgium), we initiated phage therapy (PT) on D+57 in accordance to the Article 37 of the Declaration of Helsinki and with the patient's parents' consent. PT is the use of lytic bacteriophage viruses to achieve antibacterial effect. Phage cocktail BFC1 contains two anti-Pa phages (PNM and 14/1) and one anti-Staphylococcus aureus phage (ISP). BFC1 was administered in situ by instillations through biliary catheter during six days, and in IV for 86 days (72 days until 2nd LT, 14 days afterwards), the longest described duration for IV PT in a child. Previous antibiotic therapy was pursued all along. Intraoperative PT was performed during 2nd LT by bathing the peritoneal cavity in phage solution during the anhepatic phase. To further our understanding of the case, seven Pa isolates, both bloodborne and liver-borne, were sequenced. Serum samples obtained before, during, and after phage therapy were analyzed through double agar overlay method to search for phage immune neutralization (PIN). Phage-induced virulence tradeoffs (PIVT) assays were performed in a Galleria mellonella model. In vitro phage-antibiotic interactions were evaluated with OmniLog® system. PT initiation was followed by immediate (<24 h) eradication of Pa from blood cultures. Reappearance of Pa in blood cultures after four days of PT led to a doubling of the PT dose, which was followed by eradication of Pa from bloodstream until 2nd LT. The child has known no further infectious episode since then. Sequencing confirmed the emergence of bacterial phage resistance (BPR) in four isolates. Such BPR did not lead to therapeutic failure, possibly thanks to PIVT. PIN against phage ISP was detected, but not against any anti-Pa phage. OmniLog® assays suggested synergistic properties between phage PNM and three antibiotics administered concomitantly to the patient. In conclusion, prolonged IV phage therapy combined with antibiotics led to the durable eradication of an XDR Pa sepsis in an immunosuppressed 14-month old boy, eventually allowing for 2nd LT. This possibly relied on synergy between phages and antibiotics. This combined therapy was safe.

This paper analyzes the theoretical and methodological foundations of ethnic and regional entities and their relationships in the context of multi-ethnic society; The notion of ethnic and regional entities and their relationships in the context of multi-ethnic society; the essence and importance of the theory of ethnic and regional organizations in the context of system-structuralist, structural-functional, communication and synergistic approaches using the principles trialektyky and synergy. Comprehensive analysis of the theoretical and methodological foundations of the social and philosophical analysis of ethnic and regional entities and their relationships in the context of multi-ethnic society, forms of practical realization of detecting the impact of pan-European integration process of their development will help to build the logic of modern social process and serve as a basis for understanding how may develop post-crisis situation of the system. Treat any, including ethno-national and regional, relations in the humanities or social sciences can only be based on a clear understanding of the concept of relationships. The purpose of the article - to form the theoretical bases of theoretical and methodological foundations of ethnic and regional entities and their relationships in the context of multi-ethnic society. In our case, the ethno-national and regional relations and is the kind of social phenomenon, which combines attitude, disposition, motives and effects, causes and consequences, individual and social. Objective factors is the incentive that shapes all other forms and manifestations of inter-ethnic or inter-regional relations. National Ethnic and Regional Relations entering the political field of social an act combine rules and actions of political actors with the variability of situations. This social an act caused ethno-political and regional factors, which is implemented as a set of ethnic and regional relations, the driving force behind the development of multi-ethnic society. Interethnic dispositions are considered as some settings to interact (negatively or positively) with other ethnic groups in any area of life in any form - from personal interaction with people of other nationalities to perceive phenomena, elements of history, culture, nature and direction of social and economic development. Individuals who self-identification almost automatically excludes certain groups. In this group the signs Ethnic and Regional Relations increasing strength and stability, assuming the form of stereotypes. Psychologists generally believe that ethnic stereotypes occupy a key place among interethnic attitudes, but they are limited as the object of study individuals or mostly small groups - groups (often a student), or groups of subjects in a specially created environment. It should be noted that all the social and human sciences require a unifying methodological basis, which can only social philosophy, which allows you to combine individual, group and overall. ; В статье дается анализ теоретико-методологических основ этнонациональных и региональных образований и их отношений в контексте полиэтнического социума; раскрыто понятие этнонациональных и региональных образований и их отношений; обосновано сущность и значение теории этнонациональных и региональных образований и их отношений в контексте системно-структуралистского, структурно-функционального, коммуникативного и синергетического подходов с использованием принципов триалектики и синергетики. ; В статті дається аналіз теоретико-методологічних засад етнонаціональних та регіональних утворень та їх відносин в контексті поліетнічного соціуму; розкрито поняття етнонаціональних та регіональних утворень та їх відносин в контексті поліетнічного соціуму; обґрунтовано сутність і значення теорії етнонаціональних та регіональних утворень в контексті системно-структуралістського, структурно-функціонального, комунікаційного і синергетичного підходів з використанням принципів тріалектики и синергетики