In this paper, the agent-based simulation model of sexual selection and pair formation mechanisms is proposed. Sexual selection is a mechanism that occurs when the numbers of individuals of both sexes are almost identical, while reproduction costs for one of the sexes are much higher. The mechanism of creating pairs allows individuals to form stable, reproducing pairs. Simulation experiments carried out using the proposed agent-based model, and several fitness landscapes were aimed at verifying whether sexual selection and the mechanism of pair formation can trigger sympatric speciation and whether they can promote and maintain population diversity. Experiments were mainly focused on the mechanism of pair formation and its impact on speciation and population diversity. Results of conducted experiments show that sexual selection can start speciation processes and maintain the population diversity. The mechanism of creating pairs, when it occurs along with sexual selection, has a significant impact on the course of speciation and maintenance of population diversity. Multi-agent systems ,2,3 and agent and multi-agent system are not strictly defined and they are used by researchers to name various approaches and systems, sometimes very distant from real agent-based systems. In this paper, we will use notions and definitions proposed by Ferber [agent is a physical or virtual entity, capable of operating in the environment and able to communicate with other agents.An In its activities, it strives to achieve its own goals.It may possess some resources.It may observe the environment, but only locally.It possesses only partial knowledge about the environment.It has some skills and can offer some services.It can also be able to reproduce.Concepts of y Ferber :An agentmulti-agent system is composed of [an environment,objects—passive elements of the system,agents—active elements of the system,relations between the environment, objects and agents,operations that allow agents to observe and interact with other system components,operators that represent the reactions of other system components to agents’ activities.A posed of :an envirOn the other hand, biologically and socially inspired artificial intelligence techniques are becoming more and more popular. Such techniques and algorithms include evolutionary algorithms, artificial neural networks, deep neural networks and deep learning, artificial immune systems, ant colony optimization algorithms or swarm algorithms ,9,10. ThA connection between the agent-based approach and modeling and simulation can be twofold. First of all, we can create an agent-based model of phenomena of interest, and thus describe them using concepts of agents, environment, and relations. In such a case, we are dealing with agent-based modeling and simulation (ABMS). The second option is to use simulation as a technique supporting the functioning of multi-agent system .The agent-based approach to modeling and simulation provides all fundamental notions and tools that allow creating simulation models of complex real-world phenomena in a very natural way. The agent-based approach allows describing real-world entities and relations using the concepts of autonomous agents, passive objects, environment, and relations between them ,14,15,16The ABMS approach is particularly effective in the case of biological mechanisms and phenomena ,6,13, soThe ABMS approach can be used when a real-world phenomena result from interactions between autonomous and active entities (agents), passive objects and environment . UsuallyThe agent-based approach allows modeling of such phenomena in a very natural way and does not require too many simplifications when preparing a simulation model. The ABMS approach enables modeling of entities (agents) with different characteristics and features, taking into account an intelligent behavior of agents and their adaptation to changing environmental conditions. It is also possible to model emergence and disappearance of social relations between agents, emergence and disappearance of organizations and teams , emergence and disappearance of social roles and hierarchies, and shaping and evolution of behavioral norms. Spatial relations are also relatively easy to model because agents and objects are located in an environment with a particular topography and physical dimensions. The agent-based approach also ensures scalability of a simulation model—it is quite easy to extend our model, adding new types of agents, relations, interactions, and resources.Along with the growing interest in agent-based modeling and simulation, some tools supporting, simplifying and accelerating the process of implementing agent-based simulations appeared. Of considerable importance was the fact that the ABMS approach is often used by researchers from fields far removed from computer science, such as biology, sociology, economics or political science. As a result, systems, programming libraries and tools of varying degrees of sophistication, complexity and putting different requirements regarding the computer science knowledge before the future users were created. The examples of such libraries and systems include NetLogo , Repast The agent-based approach combined with biologically inspired artificial intelligence algorithms can also be used as a computational system. An example of such an approach can be the concept of the evolutionary multi-agent system (EMAS), proposed for the first time in . The EMAA selection process is carried out thanks to the limited resources, which agents acquire from the environment and each other. These resources are necessary for agents to perform all activities in the system, such as reproduction and migration in the environment in search of better conditions . The resources are obtained from the environment or other agents, in such a way that agents that perform particular tasks better than other agents or are close to achieving a specific goal set for the population acquire more resources. Resources are consumed during the existence of an agent in the system because it executes various types of actions, which, in turn, is associated with the loss of a certain amount of resources. As a result, an agent with low fitness/adaptation rarely reproduces (because a minimum amount of resource is needed for this action), and may even lose the entire resource, which will cause removal of it from the system. In turn, agents with high fitness/adaptation gain many resources, thanks to which they can reproduce more often, and their features (encoded in the genotype) spread with time in the population. The resources are also used to limit the excessive growth of the population—the total amount of resources in the system is constant, and it limits the number of individuals that can exist in the system in a particular moment of time .Recombination and mutation operators are usually identical to those of classical evolutionary algorithms. The main difference from classical evolutionary algorithms is the decentralized selection process  and the fact that agents independently make decisions about executed actions, guided by the level of resources.The basic EMAS model  has beenThe model of the multi-agent system with biological and social mechanisms (BSMAS)  is a refAllopatric models—the speciation takes place as a result of the geographic separation of subpopulations, which reduces the flow of genes between subpopulations and ultimately leads to reproductive isolation and emergence of new species.Parapatric models—subpopulations of primary species live in habitats that only partially overlap, which limits the flow of genes. Such limitation potentially leads to the reproductive isolation and emergence of new species.Sympatric models—the speciation takes place within the population of primary species only as a result of co-evolutionary interactions with another species or as a result of sexual selection. The selective pressure caused by interactions between co-evolving species or sexes (within a single species) potentially leads to reproductive isolation and emergence of a new species. The space of environment, in which a population is located, does not play any role in the sympatric speciation.In this paper, we focus on agent-based modeling and simulation of sexual selection and pair formation mechanisms and their impact on the species formation processes and increasing and maintaining the population diversity. The speciation models in evolutionary biology can be divided into three groups ,45:Allopa cost of reproduction for one of the sexes  is much higher than for the other,proportions of both sexes in the population are almost equal.The existence of sexual selection results from two phenomena that occur in natural populations ,45,46:a The above phenomena cause there always being more males than females that are ready for reproduction. As a result, females can choose males based on their particular traits. The males’ traits, which females select, and preferences of females are genetically determined and are inherited by children and further reinforced. As a result, one of the sexes  evolves towards keeping the reproduction rate at an optimal level, and the sex  evolves towards increasing the reproduction rate. Such phenomenon leads to “arms races” and co-evolution of sexes.The authors of  proposedThe agent-based model proposed in this paper also includes a sexual selection mechanism, female costs of searching for a partner and carrying capacity of an ecosystem, which is modeled with the use of limited resources that are needed by agents to perform all of their actions. Additionally, the proposed simulation model includes mechanisms that affect the realism of the simulation, which include male costs of searching for a partner, the mechanism of forming reproducing pairs of agents that live and reproduce together for some time and a spatial structure of an environment. The mechanism of creating reproducing pairs, which significantly reduces the costs of searching for a new partner, was not examined in our previous works ,48. The The proposed agent-based simulation model shows that sexual selection together with the pair formation mechanism not only maintains population diversity but also leads to speciation—even in small or medium-sized populations, which tend to lose genetic diversity due to genetic drift much quicker than large populations—and thus increases the diversity of ecosystems.In this section, a review of entropy-based measures of population diversity is presented. In addition, entropy-based measures used during experiments are introduced below.The diversity is one of the fundamental concepts in biology and ecology. As a result of ongoing research, many indicators were proposed to measure the diversity. Unfortunately, the proposed indicators quite often give conflicting and inconsistent results. This fact has prompted some researchers to negate the usefulness of the whole concept of diversity .However, Jost  claims nS is the number of species and Jost  claims tcosystem .D equally common species should be calculated, then the resulting expression should be equated to the actual value of the diversity indicator, and the resulting equation should be solved for D. The calculated value of D would be the “effective number of species”, the “true diversity” of the ecosystem.Of course, it does not mean that Shannon entropy is a weak indicator of diversity—in fact, it is the most insightful and useful of all diversity indicators . It is oWhen the above procedure is applied to commonly used diversity indicators, the following equations for true diversities will be obtained . The speq goes to one [Most non-parametric diversity indicators—these include species richness, Shannon entropy, Simpson measures, Renyi entropies ,55, and s to one . All of s to one ,56:(1)D≡q is called the “order of diversity”. The order of diversity affects the sensitivity of the indicator to common and rare species. When Variable ndicator :(2)D0=∑iFor  follows :(3)D0.5=For For obtained :(5)D2=1/The four defined above diversity indicators f1f2f3f4 and actions that are used to realize the goals. There are two different sexes within the population: females and males see —they difThe genotype of on range .In the proposed model, the genotype of type see .genetic space  between female preferences (encoded as two independent variables), and male displayed traits .The role of the two independent variables depends on the sex of a given agent. For male agents, the two variables encode displayed traits based on which females make their choice regarding a partner for reproduction. In the case of female agents, the two independent variables encode preferences. A decision of choosing a partner for reproduction is based on a distance in An agent, which is ready for reproduction , starts looking for a partner. A female agent chooses a partner from male agents that are ready for reproduction and that are located within the same node of the environment as a given female agent (because agents can see each other only within a given node of the environment)—compare A female agent chooses a partner based on a degree of compliance of preferences (which are encoded in its genotype as two independent variables) with a male agent’s features, which are also encoded in its genotype as two independent variables. The more female’s preferences match male’s features, the higher the probability of selecting a given male agent.After the selection of a partner is completed, a female agent and a chosen male agent form a pair, and since then they migrate together within the environment and reproduce see . The paiWhen reproduction occurs, two offspring are created from two parents. During the reproduction, the intermediate recombination  and the i-th value of vector In the proposed model, the intermediate recombination is used . In the given by :(10)xiali-th value of vector i-th value of vector i-th value of vector In Equation , xiaj isThe intermediate recombination operator is also applied in the case of → vector :(11)σiali-th value of vector During the reproduction, the mutation operator with a mechanism of self-adaptation of its range is also used. Mutation takes place in two stages. First, the parameters of the mutation operator are mutated, and then vector  follows :(12)σi′=i-th value of vector In Equation , ξNRecommended values of  follows :(13)τ0=1In our experiments, In the second place, the mutation of the vector of independent variables  formula :(15)xi′=In this section, the results of simulation experiments carried out using the proposed agent-based model of sexual selection with pair formation mechanism are presented. The primary goal of these experiments was to study an impact of the proposed mechanism of pair formation on speciation processes and population diversity. In addition, the ability of sexual selection to initiate speciation processes and maintain population diversity was studied during the experiments.In all experiments, the developed and implemented multi-agent simulation system based on the proposed spBSMAS model see  was usedmaximum age of pair probability of mutation: probability of recombination: coefficient determining the minimal level of resource that is required for reproduction: coefficient determining how much of the resource is given to offspring by a coefficient determining how much of the resource is given to offspring by a coefficient determining how much of the resource is given back to the environment during migration to another node: The values of parameters of spBSMAS model, which were used during the experiments, were as follows:The above parameters’ values were obtained during preliminary experiments, which results are not shown in this paper. In the paper, these parameters were set to values that give reasonable results, which are in accordance with real processes taking place in ecosystems. For the sake of clarity of the experimental results, only the values of selected parameters that influence speciation and population diversity are changed during experiments.The first group of experimental results shows the phenomenon of speciation resulting from sexual selection and pair formation. In D indicator for Below each figure, the following information is shown: total number of agents in the population and values of In The process of evolution without sexual selection and pair formation mechanisms is shown in In the case of evolution process without sexual selection but with the pair formation mechanism turned on, we can observe that speciation does not take place. However, the individuals are dispersed throughout the whole fitness landscape see . The mecIn all experiments with sexual selection turned on, the value of parameter responsible for time of existence of reproducing pairs was set to Age=5000 . The maxThe phenomenon of disappearance of species results from the fact that, when pairs are dissolved (when they are older than In the case of Michalewicz fitness landscape , only onAlso in the case of Rastrigin fitness landscape, formed species can be observed in step 500 of the simulation b. The spA very similar situation occurred in the case of Schwefel fitness landscape. Species were formed before step 500 of the simulation b and theIn the case of Waves fitness landscape, processes of speciation are visible in step 500 b. ReprodThe second group of results  shows thIn The results show that in the case of periment . Such reIn the case of  similar . When paIn the case of Rastrigin fitness landscape, , the resMuch more interesting is the case of Schwefel fitness landscape. It can be clearly observed  that in The second series of experiments is even more interesting b. For maIn the case of Waves fitness landscape, the results are also very interesting . In the es again a. HoweveEven more interesting phenomena can be observed for eriments b for maxSympatric speciation can be triggered by sexual selection.The pair formation mechanism is necessary for a stable existence of species. It reduces the energetic effort necessary for finding a partner for reproduction greatly.In the cases when reproduction partners can be found in the nearest neighborhood and the energetic effort needed to find them is not very high, dissolution of existing pairs of agents can intensify speciation processes and increase the population diversity. Such phenomenon occurs because female agents are forced to choose male partners that do not fit their preferences perfectly—simply because there are no other partners in the nearest neighborhood. In such a case, children have much more diverse preferences and features because their parents differ significantly in genetic terms. Such situation can lead to forming new sub-populations, and possibly also new species.From presented results of experiments carried out with the use of the proposed agent-based simulation model, the following conclusions can be drawn:In this paper, the agent-based simulation model of sexual selection was proposed. In the proposed model, two types of agents exist: In the proposed model, agents live within the environment, which distributes resources among agents in proportion to their fitness value. The agents, on the other hand, lose resources while executing actions, such as reproduction and migration. The total amount of resource in the system is constant because it prevents an excessive increase in the number of agents. The model includes the pair formation mechanism, which allows agents from opposite sexes to form pairs. Individuals belonging to a pair can reproduce and move together in the environment.The primary goal of experiments conducted using the proposed agent-based model was to verify whether sexual selection can trigger sympatric speciation in a population and thus contribute to increasing the population diversity. The second goal was to verify whether the proposed pair formation mechanism can influence somehow the course of speciation processes.The results of simulation experiments show that, in the proposed agent-based model, sexual selection can start sympatric speciation. Species were formed quite quickly and stably existed during the simulation experiments. The existence of pair formation mechanism had an entirely positive influence on species formation, their stable existence and also on the population diversity. It turned out that the stable existence of species depends strongly on the maximal time of pairs existence (However, the second group of results—in which the population diversity was measured as an average distance of agents from the population centroid—showed a very interesting phenomenon. It turned out that in some experiments with Thus, the conclusions from experiments carried out with the proposed agent-based model can be summarized as follows. Sexual selection can trigger sympatric speciation processes in the population. The mechanism of creating pairs is crucial for the stable existence of species because agents do not have to search for new partners and lose their resources steadily. However, when pairs are stable for a long time, there is almost no change in the diversity of the ecosystem. In this case, stagnation can be observed—the diversity is stably maintained. However, new species do not appear. The dissolution of pairs gives a chance that something new and innovative may appear in the population. Pairs are created in new configurations, which eventually results in the emergence of new species and the increase of ecosystem diversity.The proposed agent-based model can be easily extended with new biological and social mechanisms and interactions. In future research, such mechanisms will be incorporated into the proposed model to make it more realistic and allow the emergence of new phenomena. In addition, based on BSMAS approach, new agent-based models of ecosystems will be proposed, which will include more complex biological and social relationships between species, sexes, and groups of agents.


Exchange-traded funds (ETFs) are one of the most rapidly expanding categories of financial products in Europe. One of the key yet still unanswered questions is whether European ETF markets have reached the size at which they could affect the financial systems. In our study, we examine 13 European countries during the period 2004–2017 in order to trace whether the share of ETFs in the total assets of investment funds has reached the ‘critical’ level that makes possible their further growth and can be associated with an influence on the financial system. We use a novel methodological approach that identifies the ‘critical mass’ along diffusion trajectories. Our results show that, in 10 countries, the share of ETFs in assets of investment funds increased. Still, in most countries, the share of ETFs did not exceed 1%. Estimates of the diffusion models indicate that the process of growing shares of ETFs was most dynamic and relatively most stable in Switzerland and United Kingdom. Results of the critical mass analysis imply that its achievement may be forecasted exclusively in these two cases. However, even in such cases there is no substantial evidence for a possible significant influence of ETFs on the local financial systems. Investment funds are a vital part of the modern financial system as they participate in operations made in other segments of the financial sector such as capital markets or banking. Over the last three decades, the investment funds industry has experienced substantial changes resulting from, among other factors, the adoption of new technologies in the financial system. Another partially linked development was the launch and surging popularity of new types of funds, among them exchange-traded funds (ETFs) as the most notable example .Referring to the explanation of the similar concept (‘investment company’) used by the US Investment Company Institute , investmIn our research, we focus on the European investment funds industry for two main reasons. First, it is one of the most developed in the world as, in terms of assets, as of late 2018, the combined European market accounted for ca. 40% of the global investment funds’ assets, only behind the markets in North and South America  whose share was at approximately 50% )The paper is divided into five sections, beginning with the introduction. The second section presents the basic features of ETFs, compares them to the mutual funds, and discusses their denotation as financial innovations and the potential impact on financial systems. The third section outlines data sources and the empirical setting. The paper is a substantially expanded version of the paper entitled “Exchange-traded funds in Europe: diffusion in investment funds industries” that was presented during 10th International Conference on Currency, Banking and International Finance.This section begins with the presentation of the main features of ETFs. Next, they are compared to the mutual funds. We also present the selected concepts of their inclusion in the financial innovations category. Finally, we discuss their possible role in the financial systems, both positive and negative.Exchange-traded funds (ETFs) represent one of the most recent types of investment product offered in the financial sector (in comparison to other categories of investment funds whose history is much longer) and the first such funds were launched in Canada and the United States in the early 1990s . ETFs maThe objective of the first ETFs available to investors was to track (follow) the returns on their benchmarks, in that case defined as selected equity market indexes, minimizing any possible tracking errors. ETFs were, therefore, a passive type of investment fund. Passive equity ETFs are still the largest category in all possible dimensions of the market development . However, over the years the global ETF industry has become much more diversified and currently many different types of ETFs are available, with various investment aims in relation to their benchmark , modified returns  and, above all, with exposure to various types of assets—not only equities but also bonds, commodities and other ,12,13,14One fundamental feature of ETFs is the duality of the transactions in their shares which occur on two basic types of markets: primary and secondary ,16,17. OIn contrast with ETFs, mutual funds may be considered to be a much more broadly recognized type of investment fund; on a global scale they are the largest category group in terms of assets or number of products offered by financial corporations. Moreover, in many countries they are the only category available for local investors. There are some discrepancies between various regions with regard to the terms used to label this group. We use ‘mutual funds’ throughout the paper as it underlines clearly the distinction between this category and ETFs. The other terms, such as ‘open-end funds’, despite their broad usage, can blur the main differences  while further ones, such as ‘unit trusts’ are too country-specific and/or focused on the legal aspects. In our research we utilize the definition of mutual funds provided by The International Investment Funds Association  which defines them as an investment company (we use the term investment fund) that buys a portfolio of assets  in order to meet a specified investment objective; mutual fund is ready to buy back (redeem) its shares on demand by investor; the issuance of new shares is continuous in most mutual funds .In order to fully understand the advantages offered by ETFs in comparison to the mutual funds, it is necessary to present a comparison of their attributes. The main differences, which may be regarded as relative advantages of ETFs, are summarized in For the reasons presented in the preceding paragraphs, ETFs may be regarded as a category of investment funds with applications similar to the conventional, well-established group, namely mutual funds. However, their features  make them more beneficial for many users. Consequently, ETFs may be considered to be an example of financial innovations. Another rather obvious reason for such denotation of ETFs is their much shorter history yet almost thirty years in case of the oldest North American markets may be perceived as rather long period, especially bearing in mind the high dynamics of the financial system. In order to more fully justify our approach to the analysis of the ETF markets, which requires assuming that they are innovative in comparison to other investment funds, we refer to the selected  publications whish use such a designation see . As it mGrowing assets of ETFs in many countries have resulted in the recent years in intensification of the discussion concerning their possible positive and negative impact on the financial system. Probably the most frequently analyzed event in the global economy during the early years of the XXI century is the 2008 financial crisis. Nonetheless, the size of the ETF markets, even the biggest ones such as the United States, had been rather small up to 2008 so the possible influence of ETFs on the emergence and spread of the financial turmoil was marginal. However, since 2008, ETF markets have grown rapidly in some of the most advanced countries, such as the USA, Japan, or the United Kingdom. This has led to a growing interest of researchers as well as various supervisory national and international institutions in the possible consequences of the broader adoption of innovative funds. This attention was magnified by various changes in the ETF industry  fund structures in Europe—their popularity peaked in 2008–2010) or events such as the first and second Flash Crashes on the US capital markets in 2010 and 2015 , with a -extension of the group of investors accessing financial markets, attracted by the features of ETFs such as their diversity or other benefits in relation to the conventional funds . HowThis section outlines the sources of data and methodological setting of our research. First, we present the details of our dataset, including the applied indicators and time period of the analysis. Second, we discuss the research methods: diffusion model and critical mass framework. Our analysis covers 13 European countries with ETFs listed on local exchanges : France, Germany, Greece, Hungary, Ireland, Italy, Norway, Poland, Spain, Sweden, Switzerland, Turkey, and United Kingdom. It means that we evaluate most European ETF markets. We do not study the markets with complicated structure which hinders their evaluation such as Baltic states with joint stock exchange or Luxembourg where many ETFs are domiciled but only a few are actually traded. Another exception is the Russian Federation due to lack of data on the investment funds consistent with data obtained for other countries; the size of the Russian ETF market is, though, rather small. Additional explanation is required for France where the stock exchange in Paris is part of the Euronext Group. Hence, due to the prevalence of the French segment, we classify all ETFs on Euronext as part of the French ETF market. A core indicator applied to reach the aims of our research is net assets (assets minus liabilities) of investment funds in the selected European countries (henceforth: ‘assets’), expressed in USD millions for comparability purposes. Here, we use end-of-quarter values. ‘Total assets’ are aggregated assets in particular country. In the case of ETFs, we use data on the funds which are primary listed (and traded) on the stock exchanges in the particular country—this serves as the basis for our classification . ‘Investment funds’ are all categories of funds included in this category by the data providers (see below), above all, various types of mutual funds and ETFs.The database used in this research is combined from two datasets. The first dataset includes quarterly observations of the total market for investment funds extracted from the statistical releases of the European Fund and Asset Management Association’s (EFAMA). The second dataset, which covers exclusively ETFs, is derived from the Lipper database provided by Refinitiv (formerly Thomson Reuters). Country-level quarterly estimates were calculated based on individual funds’ data (as of end of each consecutive quarter). Our database covers more than two thousand European ETFs. All individual observations were verified (by checking for missing data or inputting errors). To the best of our knowledge, it is one of the first research on the European investment funds (and ETFs in particular) in which fund-level observations were aggregated into country-level indicators.The time span of the analysis is subject to data availability, as a dataset on the assets of investment funds was acquirable for the period from second quarter of 2004 to the third quarter of 2017, i.e., 54 consecutive quarters. Moreover, in most countries in our sample, there were no ETFs before 2004.In our research, referring to the widespread perception in the relevant literature see , we claiIt may be stated, in the context of the theoretical concepts of the diffusion, that gradually increasing adoption of ETFs among investors can occur due to ‘word of mouth’ and emerging network effects . We assuBearing in mind the above-mentioned clarifications, and to achieve the main research goals of this work, we use a methodological framework that allows identifying the process of diffusion of ETFs. Therefore, we use not only elementary descriptive statistics but also innovation diffusion models  is pre-defined as exponential, without growth limits imposed, which potentially may lead to unrealistic projections, as different systems are usually constrained and hence do not grow infinitely. To challenge the latter, we add the ‘resistance’ parameter in Equation (1), imposing an upper ‘limit’ to the logistic growth , which aκ is the imposed upper asymptote that limits the growth of The modified version of Equation (1) follows:κ—upper asymptote that determines the limit of growth;The 3-parameter logistic differential equation can be re-written as a logistic growth function that takes only non-negative values throughout its whole path:to Satoh , NLS yieto Satoh . The keyκ to 90%κ. To facilitate interpretation of the diffusion pattern, a ‘specific duration’ parameter that shows the time needed for In our research we use the Equation (3) to estimate the parameters of country-specific patterns of diffusion of ETFs, and with this aim we define:Moreover, in our research, we assume that the process of the diffusion of ETFs is to a large extent analogous to the process of diffusion of innovations . Hence, to enrich this study we use the novel methodological approach developed and presented in Lechman ,57 that To calculate critical mass, first we define the replication coefficient If for a given country Referring to Equation (5), if  Lechman  discusse1.If 2.If 3.If Two defined coefficients—Determining ‘critical mass’ is possible when observing the in-time behaviour of respective coefficients—tern see .Initially, during the early diffusion phase, when the growth rates are low, replication coefficient tends to be higher than marginal growth If If critical mass is not reported, this means that during the early diffusion phase, the replication lacked the strength to ensure gradual increases in Profound analysis of In our research, we use the above-presented method to identify the critical mass along the trajectory of the diffusion of ETFs. Our aim is to trace whether, across examined economies, the ETFs share in total net assets of investment funds has reached the ‘critical’ level that ensures their further expansion in the investment industry.The main topic of the current section is the presentation of the results of our study. We begin with the discussion of the preliminary evidence on the assets of investment funds in Europe. In the second part we present the empirical results obtained with the application of diffusion models. In the third and final section we outline the results of the critical mass analysis, accompanied by an evaluation of the possible impact of ETFs on the financial system in the countries in scope of our research.At the end of the third quarter of 2017, the combined assets of investment funds in the 13 analyzed countries reached more than $11 trillion, i.e., the highest value in the history . Assets of ETFs were also at the historically highest level ($690 billion according to Lipper database) yet they constituted only approximately 6.2% of the entire investment industry. It was, though, the maximum market share of the innovative funds . However, examination of the country-level summary statistics shows very deep differences between the analyzed European markets, in terms of both total assets of investment funds or ETFs and shares of the innovative funds see .The four largest European markets for investment funds  are France, Germany, Ireland and the United Kingdom. For comparison, the four smallest are Greece, Hungary, Poland, and Turkey, and the inclusion of the two last countries in that group proves that the assets of investment funds are not necessarily fully explained by the size of the local economy. In the dynamic perspective, i.e., when observed changes are considered, it may be noticed that only in case of two countries total growth rate was negative, namely Greece and, to lesser extent, Italy . According to the 2017 data some of the largest ETFs which are primary listed in the examined countries included ‘iShares Core S & P 500 UCITS ETF USD (Acc)’ (the largest fund in the United Kingdom), ‘iShares EURO STOXX 50 UCITS (DE) ETF’ (the largest in Germany), ‘Lyxor Euro Stoxx 50 (DR) UCITS ETF D-EUR‘ (the biggest in France), ‘iShares Core EURO STOXX 50 UCITS ETF EUR (Acc)’ (the leader of the Swiss market), and ‘Lyxor FTSE Italia Mid Cap PIR (DR) UCITS ETF D-EUR’ . Generally, the funds with most assets track the US, regional or local equity market indexes. For a more detailed discussion about the structure of the European ETF markets, see .Analysis of the dynamic indicators regarding the European markets shows that in all but three countries the assets or shares of ETFs have increased since 2004 . The three exceptions are Greece, Hungary and Poland. In terms of the ETFs’ share, the decline in Poland was most substantial. The strongest increases in the values of assets can be noticed for Italy and Spain . The highest level of 2) and Germany with 7.4%. Estimates of the midpoint, 2 are 0.84 and 0.45 accordingly. For the remaining nine countries, in cases of seven economies, estimated country-wise diffusion models returned negative parameters  the financial systems of European countries or to exert such influence in the upcoming few years. Effects of the ETFs diffusion, presented in the This paper was designed to contribute to the present state of knowledge on the process of ETFs diffusion across the European financial markets. With this aim, we have selected 13 financial markets, for which balanced time series on the total assets of both ETFs and investment funds were available. Our analysis spans between 2004 and 2017, and within this time period we examine quarterly data on total assets of investment funds, total assets of ETFs, and share of ETFs in total assets of investment funds. The main focus of our research concentrates on the last variable. Our major target was two-fold. First, we aimed to develop country-wise ETFs diffusion patters, and to complete the latter we applied innovation diffusion models. Such an approach, still rare in this area of research, was used to unveil specific features of the ETFs diffusion paths and to demonstrate in-time dynamics of this process. Second, we used a novel methodological approach to calculate the ‘critical mass’ that provided more profound insight into the dynamic of the process of ETFs diffusion. Examination of the critical mass along ETFs diffusion trajectories for each individual country made it possible to determine the time and ETFs share in total assets of investment funds that enhanced the process of logistic growth of ETFs. Our research leads to several conclusions. First, we have shown that, during analyzed period, in 10 economies the total growth of the share of ETFs in assets of investment funds was observed, while the highest dynamics of the process was reported in Italy, United Kingdom and Germany. Only in Greece, Hungary, and Poland have we observed drops in ETFs share. The highest ETFs share in assets of investment funds was demonstrated for the United Kingdom, Switzerland, Germany, and France, with some significant between-country differences. In the remaining nine countries (except Sweden), the maximum observed ETFs shares did not exceed 1%, suggesting that in these financial markets the role of ETFs was still negligible between 2004 and 2017. A closer look at the estimates of diffusion models shows that, only for Germany, Italy, Spain, Switzerland, and the United Kingdom, the returned parameters are conclusive. Estimated parameters show that the highest intrinsic growth rates are reported for Spain and Switzerland, with the highest ceiling (upper asymptote) for the United Kingdom and Switzerland, suggesting that in these two countries the process of growing share of ETFs in assets of investment funds is most dynamic and follows relatively stable development path. Unreliable estimates of the diffusion models in the remaining cases are due to two main reasons, namely an indecently low share of ETFs and/or very unstable diffusion paths that are marked by sudden ups and downs; both heavily violate model estimates. As for the critical mass identification, results of the analysis imply that the achievement of the critical mass can convincingly be predicted exclusively for Switzerland and United Kingdom. These results coincide with the diffusion models estimates, and demonstrate that only in these two cases the process of increasing share of ETFs in assets of investment funds is stable enough so that entering logistic growth phase along development paths is possible.The results of our study show that, despite the substantial growth of both assets of ETFs and their share in the aggregate market for the investment funds in most of the analyzed countries, their role in the financial systems  remains immaterial. Moreover, even in the case of the two countries for which reaching the critical mass level of market share of ETFs seems plausible (assuming the continuation of the current diffusion trend), it would be an overstatement to conclude that they may significantly influence the local financial systems, either currently or in the near future. Further research could address the issue of the factors that boost or limit the diffusion of ETFs, in particular in the context of reaching the critical mass, and explanation of the between-country differences in the discussed processes. Furthermore, the results of our analysis have a number of potentially important implications that can be identified both at the level of investors and the entire economy. The still limited development of the ETF markets in most analyzed European countries means that investors have limited access to financial products that in many aspects are usually more beneficial than the conventional investment funds  and can be used to reach various aims due to their broad range of applications. In terms of the local economies, the identified problems of the ETF markets to reach the critical mass levels mean that the systemic benefits of ETFs remain to be gained, including growth of the accessibility of the financial markets  and increased financial openness through the cross-listing of ETFs and activities of ETFs with non-domestic holdings which may contribute positively to, e.g., diversification opportunities of investors or capital-raising possibilities for the enterprises.


Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials.Trypanosoma CD in the chronic phase will be recruited in four different countries . Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018.MULTIBENZ is a phase II, randomized, superiority, double-blind, multicenter international clinical trial. A total of 240 patients with This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood.NCT03191162. Registered on 19 June 2017.ClinicalTrials.gov,  Trypanosoma cruzi. It is endemic in the American continent, and according to the latest estimates, it affects around 6 million people. Thirteen percent of the Latin American population remains at risk of contracting the infection, which is transmitted to humans by Triatominae insects ). For this purpose, DNA is extracted using DNA Elution Solution reagent , and the concentration and quality are evaluated by measuring the absorbance at 260 and 280 nm using the Colibri microvolume spectrometer . The characterization of the HLA-B alleles is carried out by PCR sequence-specific oligonucleotide (SSO) , following the instructions of the Lifecodes HLA typing kit . Briefly, the PCR-SSO/Luminex consists of amplification with biotinylated primers of the most polymorphic regions of the HLA-B gene, followed by hybridization of the amplified product with specific probes for each allele located on the surface of Luminex microspheres and revealed with conjugated streptavidin with phycoerythrin. Finally, it is analyzed using an xMAP100 fluoroanalyzer (Luminex Corp.).Quantification of BNZ is done from dried blood samples on paper (DBS). The quantification is performed by liquid chromatography  coupled to triple-quadrupole mass spectrophotometry .Recruitment sitesThe MULTIBENZ study network includes four countries and seven centers, with the Spanish coordinating center located at Vall d’Hebron University Hospital in Barcelona, Spain. The study contemplates a total of three stages, which are outlined below.2.Selection phaseCountries involved in the recruitment will be Spain , Argentina , Brazil , and Colombia (Fundación Cardioinfantil – Instituto de Cardiología).T. cruzi will be withdrawn from the study. The screening procedure must occur up to 90 days or less before the initiation of treatment. Serology and DNA determination by PCR will be accepted as valid and will not need to be repeated if a positive result was obtained in a previous period of 3 months.Patients with CD in the chronic phase who come to the study centers will be evaluated in order to assess if they meet the inclusion criteria. For those who agree to participate and sign the informed consent, detection of parasitic DNA by PCR in peripheral blood will be performed. Patients with a PCR result negative for 3.Treatment phaseAll patients will undergo a clinical history and physical examination. Peripheral blood extraction will be performed for analysis: hemogram, biochemistry assays, and HLA study, and a negative pregnancy test (either in urine or blood) is mandatory in case of women in childbearing age. The evaluation of the visceral involvement of CD will be completed with a chest x-ray and electrocardiogram. The performance of other complementary tests will be carried out according to the clinical investigator’s decision, but they will not be considered necessary for the inclusion of the patient.In this phase, the patient will be randomized to one of the three arms of treatment, whose duration will be 60 days independently of the arm assigned. Initially, a baseline visit will be performed in which the patient will be trained on how to take the drug and identify AEs. After that, a total of four scheduled visits will occur during the treatment period, at 7, 15, 28, and 60 days after treatment initiation. A summary of these visits is presented in Table 4.Follow-up phaseDuring this phase, any patient may consult spontaneously for the eventual occurrence of any AE. The decision to interrupt the treatment will be according to the discretion of the clinical researcher treating the patient, taking into account the severity, intensity, and extent of these AEs. In addition, the patient may decide unilaterally to suspend or not the medication at any time during the treatment period.Once the patient has taken the last dose of treatment, which may be at the end of the therapeutic scheme (day 60), when a severe AE that obliges the patient to suspend the medication occurs, or when the patient unilaterally decides to suspend the medication, this phase will begin, and it will last up to 12 months after randomization. The visit schedule of this phase is presented in Table All AEs and other study outcomes in the randomization, treatment, and follow-up periods will have to be reported. In case of mild or moderate AEs, the administration of BNZ will be suspended temporarily according to the clinical researcher’s decision. Symptomatic treatment will be provided to the patient according to the treating physician.It will be considered that a patient has finished the study when he or she has completed the treatment and follow-up phase (per-protocol principle). The study may be interrupted in case of voluntary decision of the patient at any time if an AE forces interruption of the treatment, if significant protocol violations occur, or if the treating physician deems it would benefit the patient (intention-to-treat principle).The protocol has been approved by national regulatory agencies , by the institutional review boards for clinical research of all participating institutions, and by the national ethics review committees of the countries involved in the study (when applicable). All patients provide written informed consent, whereby the researcher will explain to each patient the nature of the study; its purposes, procedures, expected duration, and the potential risks and benefits related to participating; and any inconvenience that may occur.T. cruzi DNA in peripheral blood samples after treatment end is considered a therapeutic failure [CD continues to be an infectious disease with one of the highest disease burdens worldwide. Despite the modest cure rates in adult chronic patients and its safety profile, BNZ remains the best treatment option against the disease due to the lack of therapeutic alternatives . Convent failure .The currently used dose of BNZ is based on nonrandomized studies that were carried out more than 50 years ago, and they have never been analyzed in clinical trials. Moreover, there are no data regarding the relationship between dose and efficacy, because the great majority of published experience  has been with the standard dose.Recent studies have brought to light interesting results that point out different possibilities of treatment schemes. On the basis of two PK studies, authors suggested that current treatment regimens could be overdosed , 20. OneAt the same time, there is evidence of the opposite. According to mechanism of action of BNZ, it seems that the efficacy of the drug  is concentration-dependent. To include an arm with higher dose in a clinical trial could pose an increased risk of toxicity. The clinical experience obtained through clinical trials with higher doses of BNZ (400 mg/day) led to the belief that higher dose is not associated with higher frequency of AEs , 24.In addition, the mechanisms underlying BNZ toxicity are still not well understood. The production of several metabolites in the enzymatic reduction of the drug, their accumulation, and their interactions with cellular constituents could be the main reasons for producing these AEs , 33. SomAccording to the duration of the treatment, two approaches were considered. Taking into account the cure rates of patients with CD treated with shorter courses of BNZ (those who had to interrupt the treatment because of AEs), a shortened regimen has been incorporated. Finally, researchers explored the possibility of including a new arm with prolonged exposure. Unfortunately, due to the lack of clinical published experience and the potential risk of gonadal toxicity and its effect over the pituitary–testicular axis, that treatment arm was discarded , 35.Another aspect that will be assessed is the genetic variability of the parasite over the treatment response. The great majority of randomized clinical trials have been conducted in Argentinean or Bolivian patients, and scarce information is available in other geographical regions. In any case, the few existing data suggest an important effect of parasitic diversity in the treatment efficacy and response , 36.Therefore, this clinical trial will evaluate the efficacy and safety of different dosing regimens of BNZ compared with the standard treatment scheme. Experimental dosing regimens have been chosen on the basis of evidence derived from previous studies, in which it has been found that shorter-duration schemes and/or lower dose with the same duration could achieve the same cure rate. Moreover, higher doses could be used without entailing a higher rate of AEs. The results of this clinical trial will help to better identify the most adequate BNZ regimen in terms of efficacy and safety for the treatment of CD in the chronic phase.The MULTIBENZ study is included within the Berenice Project, founded by the European Commission and initiated in September 2012. The aim of the Berenice Project is to provide a new and cost-effective solution to treat patients with CD in chronic phase and to develop new drug formulations with trypanocidal activity. Its main objective is to obtain a more effective, better tolerated, and cheaper treatment to cure CD. The results obtained in the Berenice Project will upgrade European competitiveness through the transformation of research in the field of neglected infectious diseases.Recruitment was started in April 2018, and it is estimated to be completed in all countries by August 2020. Protocol version V1/ 05-12-2016.


In-country postgraduate training programme in low and middle income countries are widely considered to strengthen institutional and national capacity. There exists dearth of research about how new training initiatives in public health training institutions come about. This paper examines a south-south collaborative initiative wherein three universities based in Ethiopia, Rwanda and Mozambique set out to develop a local based postgraduate programme on health workforce development/management through partnership with a university in South Africa.We used a qualitative case study design. We conducted semi-structured interviews with 36 key informants, who were purposively recruited based on their association or proximity to the programme, and their involvement in the development, review, approval and implementation of the programme. We gathered supplementary data through document reviews and observation. Thematic analysis was used and themes were generated inductively from the data and deductively from literature on capacity development.University A successfully initiated a postgraduate training programme in health workforce development/management. University B and C faced multiple challenges to embed the programme. It was evident that multiple actors underpin programme introduction across institutions, characterized by contestations over issues of programme feasibility, relevance, or need. A daunting challenge in this regard is establishing coherence between health ministries’ expectation to roll out training programmes that meet national health priorities and ensure sustainability, and universities and academics’ expectations for investment or financial incentive. Programme champions, located in the universities, can be key actors in building such coherence, if they are committed and received sustained support. The south-south initiative also suffers from lack of long term and adequate support.Against the background of very limited human capacity and competition for this capacity, initiating the postgraduate programme on health workforce development/management proved to be a political as much as a technical undertaking influenced by multiple actors vying for recognition or benefits, and influence over issues of programme feasibility, relevance or need. Critical in the success of the initiative was alignment and coherence among actors, health ministries and universities in particular, and how well programme champions are able to garner support for and ownership of programme locally. The paper argues that coherence and alignment are crucial to embed programmes, yet hard to achieve when capacity and resources are limited and contested. This paper is part of broader study that explores a multi-faceted south-south collaboration among four academic institutions in sub-Saharan Africa, to strengthen national capacity towards generating much-needed leaders to spearhead workforce development/management –3. The pShortages of human resources for health (HRH) are particularly pronounced in sub-Saharan Africa. Weaknesses in planning for HRH needs contribute to this situation. The lack of leadership capacity for HRH and the absence of local leadership development programmes in the region partly underlie this crisis –7. LiterNeufeld and Johnson 2004) in their review of supply side studies noted the lack of leadership development training programmes in the Global South, and the dominance of institutions in the Global North in the few leadership development programmes in/for LMICs. The authors further highlighted the disproportionate emphasis given to developing individual capacity as opposed to institutional capacity such as infrastructure, curriculum and teaching capacity development, and incentives for staff retention and motivation  in their–13.Operating under such circumstances, training institutions have become contested spaces in the globalization (and marketization) of health professions education since programme development in the South becomes commercially interesting for higher education institutions in the North, with large sums of money available. Such contestation around programme priorities, and the competition for financial and very scarce human resources plays out in different ways, and in complex relations between northern and southern academic institutions in this regard .A growing body of literature on capacity development emphasizes its complexity, as it often involves ill-defined non-linear processes that bring into interaction multiple actors with diverse interests and priorities –22. It iPartnership, through its multiple variants, is recognised as one of the mechanisms to bring about development. South-south cooperation is one form of development partnership among a wide range of actors located in LMICs , 32.In year 2009 three of the universities  set out to develop a postgraduate programme focusing on health workforce development/management with technical support from the South African university. The support included providing educators from these universities a masters level training in health workforce development/management, development and adaptation of teaching resources, and sharing experience through workshops on delivery of open and distance teaching modalities. Funded by the World Health Organization (WHO) the initiative sought to respond to the twin challenges facing public health training universities of ‘building human resources capacity in ministries and health services while alleviating and improving their own capacity constraints’  right away. But we responded that we wouldn’t start in a rush, before clarifying how it is going to be operationalized. Is it a regular programme, or what? If it is regular, the registration is done through the university. If it is to be done as special… then you organize special classes, Saturdays, Sundays, or evening. If it is going to be special, then we need to make provision for staff, you can’t just ask them to teach. Time is precious.In the case of University C both regular and special models are common ways of introducing postgraduate programmes. In University B the regular model is the most common, and the special arrangement happens often for certificate or short courses. In University A all postgraduate programmes have a special status.Prior to introducing a programme, training institutions have to fulfil curriculum requirements, which vary across institutions, with some more protracted than others. With the growing number of programmes and in the context of shortage of capacity in the institutions, stringent curriculum approval processes are put in place to ensure introduction of only priority programmes, e.g. Generic MPH and Field Epidemiology.With respect to the new training programme on health workforce development/management, none of the three universities had such a programme, which is also distinct from the generic MPH running in all the universities at the time .The three public health training universities interact and collaborate with a range of external development and training partners, as well as local actors who influence the nature, scope, and success of their own engagement in the countries and beyond, all in the course of implementing their mandate, which encompasses teaching and learning, research, and extension/community outreach service. Table These actors that exert distinct influence to enable or constrain the process  include academics who assume the role of championing the programme, the training institution, relevant government institutions namely health ministry, and external development or training partners.Any of the aforementioned actors can initiate programme introduction, but the success of the initiative and its sustainability require support from all or most of these actors, which depends on alignment of their respective agendas. The following part of this section describes these actors and their roles and relationships in the context of introducing postgraduate programmes.The health ministry is a custodian of the health sector and prescribes strategic direction and programmes to public health training universities. The health ministry defines which training programmes are relevant to address national health priority, and outlines core competencies. Even though universities are under the governance of the education ministry, the health ministry assumes the above roles due to its superior expertise of the needs and resources in the sector.The health ministry often leads the role of initiating new public health postgraduate programmes in the institutions, by working with/through the three institutions, academics, or external partners. The ministry also initiates programmes particularly when those programmes are considered basic in the context of national health priorities such as Masters in Public Health, or Masters in Field Epidemiology.… Our [University B’s] training should contribute to resolve a given problem in [the country] or in the region…. We are free when we identify the need, we can also suggest the introduction of a given programme. But … we are [not] able to start a programme without the approval of the Ministry [of Health].While in theory academics, training institution, or external partners could initiate a training programme in the three universities, key informants made it clear that successful introduction or sustainability relies on the buy-in and ownership from the health ministry. One senior academic staff explained,The role of the health ministry in initiating the curriculum varied across the countries, with the ministry playing a more active role in University B and University C than in University A. In the case of University B and University C, it was reported that the ministry is the main stakeholder in training needs assessment and providing a required list of competencies.In the course of introducing the training programme on health workforce development/management, health ministries in each country endorsed the proposed programme as relevant and expressed support in the early stage of the collaboration in 2009. However, none of the universities received any tangible support from the ministries during the course of the collaboration (2009–2015), which undermined programme introduction particularly in the University B and University C. University A had somewhat better leverage of introducing programme, possibly due to the relative autonomy the university has in its relation to the health ministry.… It [health ministry] did have enough information [about programme]. … We [the local project team] have tried to communicate this with the ministry of health. But since the first communication …there has been a turnover of three ministers.The lack of support from ministry of health in University B and University C can be attributed to multiple factors. One of the factors is turnover of programme champions based in the universities or turnover of leadership at ministry of health, which resulted in the loss of implementation momentum or loss in institutional memory.This was further complicated by the advent of parallel processes in the two universities to introduce similar programmes by the health ministries with the backing of other external partners from the North.Like other academic institutions, the three universities have the mandate to train the next generation of public health professionals to meet national health priorities, but rely on ministries of health for strategic guidance and support when it comes to the programmes they offer.[The postgraduate programmes] emerged in a decentralized [fashion]. Faculties came up with the proposal, waited for approval and started the programme. Neither administrative nor academic management [of the programme] is centralized.While all the three universities had complex relationship with the health ministry, these complexities presented differently and impacted on project outcomes in different ways. University A has a relatively high level of autonomy from ministry of health when it comes to introduction of new postgraduate programmes. The programmes are open to private applicants and students working in non-government organizations while staff of the health ministry remain the main clients.When we started this school [in 2001], it was with the objective … to produce the health professionals for Ministry of Health [which] pays their tuition fees. … [Currently] Most of our students are from Ministry of Health.In University B the health ministry exerts a great deal of influence when it comes to programme introduction, and sends most of the trainees.[I] can't really say the support from MOH to university is high or strategic. Because it changes when there is turnover. It also gives you the programme, and does not give you anything [else]. Except for [giving us the] go ahead. No financing.University C has very close relation with MOH. Students mainly comprise ministry staff and academics from other universities. Lack of alignment in the interests of the health ministry on one hand, and the university and academics on the other hand (over issues of funding or selection of trainees) put a strain on their relationship. This was evident with two prominent but parallel processes of programme introduction prevailing in the university, regular and special. Key informants in University C reported that lately MOH is pushing for regular programmes, as it considers special programmes as unsustainable, as special programmes require additional financial incentives, on top of salaries, for those academics involved in teaching or coordinating the programme. The opportunity cost for academics who participate in new programmes without additional remuneration, as described in a related publication, is time away from engagement in external multiple job holding practice, which offers financial and professional benefits . The tra… If it [training programme] is project based [special], … it turns teachers into rent seekers [and] … it won’t have sustainability. It should be part of the [regular] system and integrated, and necessary capacity building, equipment, books should be fulfilled like offering training to teachers. That is when capacity building becomes sustainable.Conversely, MOH representatives contend that the training institution is performing below capacity and should accommodate new programmes that would meet the health workforce need of the sector. One government official described the practice of running special programmes or providing incentives to staff associated with the programme as perverse:The initiative to introduce the new programme on health workforce development/management had designated programme champions, who were senior academics in the training institutions. In University A the programme champion, a senior academic of the training institution, engaged with MOH about the programme, and was committed to spearhead the implementation of the programme in the university. The university initiated the health workforce development/management programme, with the programme champion ensuring that curriculum approval within and outside the institution was accomplished. Curriculum approval went through various processes at multiple levels  and external training partners  were influential in one or more of the universities.Engagement of the three universities with external partners can generally be characterized as fragmented. The lack of coordination has led to competition, duplication, and loss of capacity gains, whereby academic institutions or the health ministry choose one initiative over another, or allow both to co-exist, instead of seeking synergy or harnessing partnerships and support around similar initiatives.Northern training partners dominate the partnership space in the three universities and with MOH (in terms of resource or influence) compared to Southern training partners. In the case of University B and University C, there were reports of parallel processes to introduce a similar programme in human resources management in the institutions in collaboration with Northern external collaborates and led by different academic programme champions within the universities. In the two countries, there were inclinations towards collaborating with Northern external training partners, which are well resourced.… I can see that [this south-south] programme is the first [to be initiated]. … How do we go about it? Do we merge [it with a similar programme initiated with northern partners]? … were we supposed to accept [just this programme] … or did we do the right thing [to choose the programme supported by northern partners]?A key informant expressed exasperation about proliferation of similar initiatives often led by Northern external training partners as a case of, “…. the funder tail wagging the capacity development dog.” [P22] Recounting the ambivalence surrounding the scenario in University C in relation to decision about the choice of partners or programmes, a key informant stated,The figure below summarizes the aforementioned analysis, and highlights the prominent actors, processes and mechanisms that influenced the introduction of the postgraduate programme in public health in the three universities Fig. .Fig. 2MThe above figure shows the link between intervention, and associated resources and expertise, towards introduction of a postgraduate programme, and state of curriculum integration and training rollout in the target universities, and future changes in terms of development of critical mass of leaders, and improved national leadership and training capacity. It is evident in the above analysis that this transition is mediated by dynamic set of factors associated with multiple actors  and contextual factors within the university and beyond. Hence, curriculum integration or training roll out is contingent on seniority, role and motivation of programme champions, and opportunities and support at their disposal. Factors associated with the target universities and health ministries including recognition and support of programme or its champions, and incentive arrangements impact on motivation and opportunities of programme champions to spearhead integration of programme. Contextual factors such as national policies and procedures have a bearing on successful implementation of intervention. Interaction across these individual, institutional and context level factors further determine retention of programme champions in the target universities. Overall, the degree of alignment across these multiple actors and processes enable or constrain the success of the capacity development intervention resulting in the short-term outcomes of partial or non- integration in two universities (B and C), and full integration in University A.Baser and Morgan (2008) in their report entitled “Capacity, Change and Performance” emphasized the need for coherence in the context of complex capacity development initiatives that are characterized by multiple interrelated causes and potentiality of unintended outcomes . The autEvident in our analysis and discussed further in the sections below is the differential and dynamic experience of implementing the initiative across contexts owing much to the unpredictable interaction among multiple actors that is embedded in contestations over issues of programme relevance, feasibility, and actors’ roles.When it comes to programme introduction, the study established that success of initiatives depends on the degree of alignment achieved among the agendas and expectations of the various actors within and outside the institutions, who have varying influence on availability of resources for programmes, their legitimacy, implementation, and sustainability. The process is embedded in contestations over issues of programme feasibility, relevance, and need. The financial feasibility of programmes is contested between institutions and MOHs, institution and external partners, or institution and academics. The issues include academics’ workload and financial incentives, the training institution’s capacity to rollout the programme, or resources at the MOH’s disposal to support the initiative in the institutions.With respect to programme relevance and need, in all the three countries MOH has the discretion in deciding whether a programme meets a national priority, which is also influenced by the national and international priorities and interests, through the roles played by external partners. Future research needs to examine more closely the perception about global or local orientation of existing programmes, and practice of priority setting within the health ministries with respect to core competencies or training programmes.Cancedda et al. (2015), based on assessment of training initiatives originating through North-South collaboration in sub-Saharan Africa, recognized the confluence of factors influencing such initiatives and underlined the importance of, among others, adaptability, local ownership and funding, coherence between training and country health priorities, long term engagement, and integration and continuity of programmes . Our anaOne of the challenges observed, in the case of University B and University C, which undermine programme introduction or sustainability was the lack of coordination of efforts, and the resulting presence of parallel initiatives. There were reported instances of local and external partners of public health training institutions working in silos in their respective collaborations with the in the case of University B and C, which pose challenges of competition, duplication, and resource wastage. On the same note, a study drawing from four major initiatives in LMICs, highlighted the barriers in on-going practices of training initiatives for health professionals. In the face of poor coordination and communication about these training initiatives among stakeholders, including MOH and regulatory bodies, ‘low-income countries have been on the receiving end of a disorderly patchwork of small-scale, insufficient quality, short-term, and unsustainable health professional training initiatives … created unnecessary gaps or overlaps in resources, and failed to help meet long-term national health workforce needs’ . The autThe exclusive focus of universities on so called basic programmes, a common pattern in MOH’s programme selection, can be detrimental to the needed mix in the range of public health professionals, in the context wherein only a few public health programmes and training institutions exist in the countries. This can also undermine internationalization of academic institutions with respect to the diversity of global programmes in public health. What is evident in this study is that universities or academics lack autonomy in this regard.Contestation between health ministries and universities over issues of quality, relevance or alignment of training programmes with national priorities can be located in the debate about internationalization of higher education in Africa, wherein institutions engage in exchange of global knowledge and know-how towards executing their academic and research mandates , 45. AcaDespite the increasing demands put on universities to meet national health workforce needs, it was apparent in this research that there was not enough input to strengthen capacity of the public health training universities regarding personnel and infrastructure. The institutions are often expected to seek and get by with short-term solutions.The findings of this investigation complement those of earlier studies that attributed the lack of diversity in training programmes in LMICs to the multifaceted shortage of resources facing training institutions including faculty and support staff, funding, capacity to develop teaching material and curriculum, and teaching spaces , 47, 48.The successful introduction of the postgraduate programme on human resource management in University A suggests the important contribution that a south-south partnership can make. Literature on south-south cooperation reports on the fragile nature of such partnerships due to overreliance on funding from the North and capacity challenges to sustain partnership  despite Literature emphasizes the value of backing programme champions if they are to make progress in fulfilling their roles, and that they need to have qualities like seniority, credibility, personality, and leadership –54. LiteProgramme champion’s role is as much political as technical. Their responsibility requires more than meeting curriculum approval standards, as they need to work towards securing endorsement from health ministries and other stakeholders to give the new programme legitimacy and required resources.Taken together, the experiences of the three public health training universities resonate with other studies that recognize partnership and collaboration as key strategies for tackling complex challenges such as fostering innovation or improving performance , 54, 56.The findings from this study cannot be extrapolated to all public health training universities within the countries or the sub-Saharan region. The limited evidence suggests that universities within countries and in the region work with different set of actors, and have quite distinct experiences and relationships.The study has two main limitations. First, determining impact and sustainability of new programmes, which are key but long-term aspects of capacity development, was not feasible within the limited period of this research. The focus of the research was thus limited to investigating processes, and short and medium-term outcomes of the intervention. Second, due to social desirability bias , and tenAgainst the background of very limited human capacity and competition for this capacity, the process of introducing postgraduate programme in the three universities is a political as much as a technical undertaking influenced by multiple actors and agendas. The research shows that public health training universities are contested grounds among multiple actors  vying for recognition or benefits, and influence over issues of programme feasibility, relevance or need. A successful introduction and further sustainability depend on alignment of interests and coherence in contribution of most of the actors, health ministries and universities in particular. Critical in the success of this south-south cooperation is support available to such initiatives; and how well programme champions are able to garner support for and ownership of programme locally. The paper argues that coherence and alignment are crucial to embed programmes, yet hard to achieve when capacity and resources are limited and contested.


Mycobacterium bovis and is characterized by the development of granulomatous lesions in the lymph nodes, lungs and other tissues. It poses serious public health impacts and food security challenges to the agricultural sector in terms of dairy and meat productions. In Ethiopia, BTB has been considered as a priority disease because of its high prevalence in urban and peri-urban dairy farms. However, there has not been any national control program in the country. Thus, in order to initiate BTB control program in the country, information on control options is needed to tailor the best option for the Ethiopian situation. The objective of this study was to identify, evaluate and rank various BTB control options in Ethiopia using a multi-criteria decision analysis based on preference ranking organization method for enrichment evaluations (PROMETHEE) approach while accounting for the stakeholders' preferences. Control options were evaluated under two scenarios: with (scenario 1) and without (scenario 2) bacillus Calmette–Guérin (BCG) vaccination. Nine potential control options were identified that include combinations of three control options (1) test and slaughter with or without government support, (2) test and segregation, and (3) BCG vaccination. Under scenario 1, BCG vaccination, BCG vaccination and test and slaughter with partial compensation by government, and BCG vaccination and test and slaughter with full compensation by government were the top three ranked control options. Under scenario 2, test and slaughter with full compensation by government was the preferred control option, followed by test and segregation supported by test and slaughter with full government compensation, and test and slaughter with half compensation by government. Irrespective of the variability in the weighting by the stakeholders, the sensitivity analysis showed the robustness of the ranking method. In conclusion, the study demonstrated that BCG vaccination, and test and slaughter with full compensation by government were the two most preferred control options under scenarios 1 and 2, respectively. National level discussions were strongly recommended for further concretization and implementation of these control measures.Bovine tuberculosis (BTB) is a zoonotic bacterial infection caused by  M. bovis, a member of the Mycobacterium tuberculosis complex  from various pertinent organizations in Ethiopia were invited. Out of the 15 stakeholders invited, 10 of them agreed to participate in the MCDA process  software 1.4 was used to perform pair-wise comparisons of the performance of control options using the preferences of the stakeholders to compute the overall outranking scores .Based on the scores, the identified control options were listed from the most to the least preferred option. For ranking of the control options and visual display of the analysis results, the Geometrical analysis for interactive aid (GAIA) with two dimension (U-V) views and PROMETHEE table were used. The action profiles of the control options were performed for the top ranked control options to evaluate their relative performance on each criterion. The GAIA and sensitivity analysis were performed for scenario 1. GAIA walking weights were run to conduct sensitivity analysis to see the effect of weighing the evaluation criteria by stakeholders on the group ranking when the weights of the criterion were changed and to assess the robustness of the results.From the 10 stakeholders participate in the MCDA process (S1–S10), nine were from the government organization and one stakeholder represented an association of privately owned dairy farmers . The staAll stakeholders generated a specific weighting scheme based on their perceived relative importance of each criterion as defined for the intended decision-making process. For this, each stakeholder was provided 100 points, and was asked to distribute the points to all specified criteria. The weighting of the stakeholders varied among the clusters and within the cluster criteria. Three stakeholders  gave the highest weight for the economic criteria, while the other seven stakeholders gave the highest weight to the epidemiologic cluster: reduction of BTB prevalence. The social ethics cluster and criteria generally received the least weight by all stakeholders . Under sTo the best of our knowledge this is the first study to identify, evaluate and rank different BTB control options using MCDA tool based on the stakeholders' opinions and preferences in Ethiopia. Despite high prevalence of the disease in dairy cattle in the country, currently there is no BTB control and /or eradication program. The participation of stakeholders to achieve the purpose and use of participatory approaches such as MCDA are helpful to identify and evaluate BTB control options. In the present study, we generated the desired data from stakeholders who represented organizations with direct responsibilities or had specific interests in BTB prevention and control in Ethiopia.In addition to identifying, evaluating and ranking of BTB control options, the stakeholders also identified various pre-requisite measures such as legal framework for the implementation and allied issues as an integral part of a control program prior to its application. Similarly, these measures were identified and their implications on the future prevention and control of BTB in Ethiopia were mentioned as daunting tasks by Dibaba et al. . In agreM. bovis infected animals from BCG-vaccinated animals   . The expVA role) . HoweverAccording to the stakeholders, BCG vaccination poorly reduces the prevalence of BTB in cattle. This is likely influenced by the role of BCG in sensitizing cattle to respond to the conventional BTB diagnostic test, combined with the low level of protection of BCG vaccine in cattle compared to its relative effectiveness in humans . To overThe second and the third control options involve prior application of BCG vaccination to reduce the number of positive cattle followed by test and slaughter with half and full compensation by the government, respectively. In high income countries, test and slaughter is the most preferred and a widely applied approach to control and eventually eradicate BTB, since the prevalence is low , 7, 10. Alternatively, as revealed by the present study, applying BCG vaccination to reduce the prevalence and progression of BTB and subsequent integration with other control options such as test and slaughter, could be a novel approach for Ethiopia which can also be adopted by other low and middle income countries where BTB is endemic and implementation of test and slaughter policy is practically challenging. To that end, the availability and accessibility of commercial BCG vaccine is critically needed. In addition, mutual understanding, acceptability and cooperation between dairy cattle owners and the government are profoundly needed particularly regarding cost recovery scheme for the implementation of the approach.Under scenario 2 (which did not consider BCG vaccination as a feasible option), test and slaughter with full compensation by the government ranked the number one preferred control option. Indeed, this could be the most preferred and acceptable option for the cattle owner from the perespective of relatively practical applicability and lower socio-economic impacts. However, this might not be acceptable to the government, as it would be too costly vis-a-vis to other priorities of the government . BesidesM. bovis is killed at pasteurization temperature and holding time  and third (test and slaughter with cost sharing) options, would be the preferred options in developing countries. There are compelling evidences that test and segregation method significantly reduced the incidence of BTB , 31. Theing time . Use of n = 10) of the stakeholders gave the highest weight to the epidemiologic criterion  in evaluating the identified control options, while the social ethics criteria generally received the least weight. The epidemiologic criterion is practically important for the control and eradication of BTB. For instance, the application of test and slaughter policy is challenged mainly due to economic and animal welfare reasons, and this impact is lower when the prevalence of BTB is low . Third, it is necessary to critically evaluate the outcomes of the control program in the selected areas and then extend the best practices to scale up the program to other regions of the country. Finally, conducting persistent surveillance and monitoring of the status of BTB across the country will be needed to develop a national database that would help in periodic evaluation of the effectiveness of the control measures put in place and taking timely corrective actions as needed. An effective and safe BCG vaccine for use in cattle is critical for this approach.In conclusion, the study used an MCDA tool in identifying and evaluating BTB control options in Ethiopia. According to the stakeholders' preferences, calf vaccination and test and slaughter with full cost compensation by government are the best control options under a scenario that included BCG vaccination and a scenario with no BCG vaccination, respectively. Moreover, the study showed that integrating calf BCG vaccination with other potential control options, in minimizing the number of test positive cattle thereby decreasing the cost of compensation for culled/slaughtered cattle and maintain animal welfare as the most suitable BTB control option in Ethiopia that can also be used by other countries, especially low income countries.The original contributions generated for the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.FG, GEA, KM, TB, MM, and GA designed the study. FG, SL, TT, ZA, BU, and GA collected and summarized the data during multi-criteria decision process. FG analyzed the data. FG wrote the manuscript. FG, GEA, KM, TB, TT, MM, RS, SL, ZA, BU, and GA critically revised and edited the manuscript and approved its submission.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.