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BACKGROUND AND AIM: Implementation science (IS) has emerged as an important approach to achieving scale-up and policy adoption of evidence-based research. The majority of IS approaches have been in...

Taenia solium is an important cause of acquired epilepsy worldwide and remains endemic in Asia, Africa, and Latin America. Transmission of this parasite is still poorly understood despite the design of infection experiments to improve our knowledge of the disease, with estimates for critical epidemiological parameters, such as the probability of human-to-pig infection after exposure to eggs, still lacking. In this paper, a systematic review was carried out and eight pig infection experiments were analyzed to describe the probability of developing cysts. These experiments included different pathways of inoculation: with ingestion of proglottids, eggs, and beetles that ingested eggs, and direct injection of activated oncospheres into the carotid artery. In these experiments, different infective doses were used, and the numbers of viable and degenerated cysts in the body and brain of each pig were registered. Five alternative dose-response models (exponential, logistic, log-logistic, and exact and approximate beta-Poisson) were assessed for their accuracy in describing the observed probabilities of cyst development as a function of the inoculation dose. Dose-response models were developed separately for the presence of three types of cysts (any, viable only, and cysts in the brain) and considered for each of the four inoculation methods (“Proglottids”, “Eggs”, “Beetles” and “Carotid”). The exact beta-Poisson model best fit the data for the three types of cysts and all relevant exposure pathways. However, observations for some exposure pathways were too scarce to reliably define a dose-response curve with any model. A wide enough range of doses and sufficient sample sizes was only found for the “Eggs” pathway and a merged “Oral” pathway combining the “Proglottids”, “Eggs” and “Beetles” pathways. Estimated parameter values from this model suggest that a low infective dose is sufficient to result in a 50% probability for the development of any cyst or for viable cyst infections. Although this is a preliminary model reliant on a limited dataset, the parameters described in this manuscript should contribute to the design of future experimental infections related to T. solium transmission, as well as the parameterization of simulation models of transmission aimed at informing control.

Like many other oceanic islands around the globe, environmental conditions, social circumstances and forces of globalization combine to challenge the sustainability of the Galapagos Archipelago of Ecuador. This paper describes a food-supply system in Galapagos that is mainly controlled by population growth, weak local agriculture, imports from mainland Ecuador and the influence of a growing tourism industry. We use system dynamics (SD) as a modeling technique in this paper to identify the main driving forces operating on the Galapagos food system to create a series of future scenarios and to examine the subsequent implications across the supply system structures. We model the supply side of the food system using secondary data collected from governmental and non-governmental sources. We find that the consumption profile of the local inhabitants of the Galapagos is on average higher than consumption in the Ecuadorian mainland. This fact, plus rapid growth of the local population fueled by the tourism industry, has created a decrease in per capita local food production and an increase on food import dependence that now, challenges the sustainability of the archipelago. Imports are the largest source of food in the archipelago. Approximately 75% of the agricultural food supply was transported from the mainland in 2017. Our model projects that this fraction will increase to 95% by 2037 with no changes in food policy. Moreover, any plan to increase tourism arrivals must be accompanied by a plan to address the subsistence needs of the new population that the tourism industry attracts. Policies to promote local agricultural growth should be central to the development strategy implemented in the Galapagos.

This paper presents a decision-support system based on a system dynamics model designed to examine tourism management in the Galapagos Islands. A participatory approach was used to integrate the views of multiple stakeholders in the Galapagos Islands and to build an understandable, graphical representation of the impacts of tourism and residential population growth. Each subsystem is examined through hypotheses involving three scenarios of tourism growth that are associated with different residential population expansions. A number of integrative and linked social-ecological effects in our model have been shown to severely shock the natural environment of the Galapagos and saturate the capacity of several socio-economic subsystems. Major concerns of the expanding human dimension in the Galapagos are represented by (1) the growing number of introduced species that threaten the Islands’ unique natural environment, and (2) the rapid saturation of the Galapagos National Park's tourism reception capaci...

Biodiversity of island ecosystems has made them very attractive to develop tourism activities. Nature tourism is considered a potential sustainable economic opportunity that could encourage environmental protection while improving local livelihoods. Nevertheless, given the complexity of social and ecological multi-scale interactions, a systemic assessment of the implications of tourism on island’s sustainability deserves a holistic perspective to assure that social and ecological goals are reached given the irreversibility that some impacts have on islands habitats with high natural values. This research develops a system dynamics model-based approach to understand and assess the dynamics of tourism sustainability in island ecosystems taking as a case study the Galapagos Islands. The modeling approach provides valuable insights into the mechanisms through which tourism influences and is influenced by demographic dynamics and exerts social and ecological pressures on the Islands. The relevance of scale in the tourism activity is highlighted given that the major constraints to improve social and environmental goals were associated with tourism and population growth. This study presents a significant attempt to build a model useful to study tourism strategies taking into account the complexities to improve tourism sustainability in island’s ecosystems arising from strong reinforcing and balancing feedback. Further research may look at strengthening the model-based approach to capture the perspective of relevant stakeholders, particularly with regard to the indicators to assess tourism sustainability.

Background Despite relatively successful control campaigns, malaria remains a relevant public health problem in the Peruvian Amazon. Several studies suggest that malaria persistence in the area can be connected with a high prevalence of asymptomatic infections, which were subsequently shown to be connected with work-related exposure in areas of hyperendemic transmission. In this study, we tested the hypothesis that the infection reservoir represented by asymptomatic carriers in the northern Peruvian Amazon, combined with circular human movement to and from hyperendemic working areas, can capture the observed hypoendemic malaria transmission. Methods We designed a set of agent-based models that represent local-scale malaria transmission in a typical riverine community in the northern Peruvian Amazon. The models include asymptomatic individuals as well as a full representation of human movements within the community and between the community and external hyperendemic working places. Several theoretical scenarios are explored to verify if and how malaria clinical immunity prevalence and human work-related movements influence the malaria morbidity registered in the community. Results Agent-based simulations suggest that malaria incidence observed through passive case detection can be reproduced as exclusively generated by the asymptomatic infection reservoir. Scenarios analysis also show that, even if asymptomatic infections are completely eliminated, human movements to and from hyperendemic working areas generate a flow of imported cases that is enough to permit the persistence of transmission in the community. Simulation results were verified over a wide range of clinical immunity prevalence values and over a wide range of percentages of people working in remote hyperendemic areas. This context of unstable malaria transmission is observed to be vulnerable to severe outbreaks. Conclusions Asymptomatic malaria infection and occupational circular human movement to hyperendemic transmission areas are designated by agent-based models as possible exclusive causes of residual hypoendemic malaria transmission observed in the Peruvian Amazon. Control strategies are proposed to decrease asymptomatic infection prevalence and to block transmission from asymptomatic individuals to the malaria susceptible population.

Though malaria control initiatives have markedly reduced malaria prevalence in recent decades, global eradication is far from actuality. Recent studies show that environmental and social heterogeneities in low-transmission settings have an increased weight in shaping malaria micro-epidemiology. New integrated and more localized control strategies should be developed and tested. Here we present a set of agent-based models designed to study the influence of local scale human movements on local scale malaria transmission in a typical Amazon environment, where malaria is transmission is low and strongly connected with seasonal riverine flooding. The agent-based simulations show that the overall malaria incidence is essentially not influenced by local scale human movements. In contrast, the locations of malaria high risk spatial hotspots heavily depend on human movements because simulated malaria hotspots are mainly centered on farms, were laborers work during the day. The agent-based models are then used to test the effectiveness of two different malaria control strategies both designed to reduce local scale malaria incidence by targeting hotspots. The first control scenario consists in treat against mosquito bites people that, during the simulation, enter at least once inside hotspots revealed considering the actual sites where human individuals were infected. The second scenario involves the treatment of people entering in hotspots calculated assuming that the infection sites of every infected individual is located in the household where the individual lives. Simulations show that both considered scenarios perform better in controlling malaria than a randomized treatment, although targeting household hotspots shows slightly better performance.

This study is concerned with the development and test of a coarse-grained representation specifically constructed for proteins and peptides, where each amino acid of the sequence is represented by a charged dipolar sphere. The model was parametrized from the physical properties of individual amino acids and applied to the study of the interaction between solvated proteins. Using an implicit solvent approach and our coarse-grained model, we computed the potential of mean force for the association of well-known proteins, such as the Cu-Zn superoxide dismutase, lysozyme, and basic pancreatic trypsin inhibitor, and a peptide, Aβ7. The coarse-grained potentials of mean force were systematically compared with their all-atoms counterpart. For both the polar and nonpolar contributions to this potential, the results of our calculations show that the coarse-grained model provides a good approximation of the all-atoms potential when the distance between the molecule surfaces is greater than a solvent molecular diameter. For shorter distances and for specific interactions, like those found between the SOD monomers, the electrostatic desolvation effect appears to be underestimated by our coarse-grained representation. The possibility of a very short range all-atom refinement to better describe the interaction at close contact is explored. We find also that the most important contribution to the association free-energy comes from the hydrophobic solvent accessible surface area term, which is well reproduced by our coarse-grained approach.

BACKGROUND: The Amazon environment has been exposed in the last decades to radical changes that have been accompanied by a remarkable rise of both Plasmodium falciparum and Plasmodium vivax malaria. The malaria transmission process is highly influenced by factors such as spatial and temporal heterogeneities of the environment and individual-based characteristics of mosquitoes and humans populations. All these determinant factors can be simulated effectively trough agent-based models. METHODS: This paper presents a validated agent-based model of local-scale malaria transmission. The model reproduces the environment of a typical riverine village in the northern Peruvian Amazon, where the malaria transmission is highly seasonal and apparently associated with flooding of large areas caused by the neighbouring river. Agents representing humans, mosquitoes and the two species of Plasmodium (P. falciparum and P. vivax) are simulated in a spatially explicit representation of the environment around the village. The model environment includes: climate, people houses positions and elevation. A representation of changes in the mosquito breeding areas extension caused by the river flooding is also included in the simulation environment. RESULTS: A calibration process was carried out to reproduce the variations of the malaria monthly incidence over a period of 3 years. The calibrated model is also able to reproduce the spatial heterogeneities of local scale malaria transmission. A "what if" eradication strategy scenario is proposed: if the mosquito breeding sites are eliminated through mosquito larva habitat management in a buffer area extended at least 200 m around the village, the malaria transmission is eradicated from the village. CONCLUSIONS: The use of agent-based models can reproduce effectively the spatiotemporal variations of the malaria transmission in a low endemicity environment dominated by river floodings like in the Amazon.

Water around biomolecules slows down with respect to pure water, and both rotation and translation exhibit anomalous time dependence in the hydration shell. The origin of such behavior remains elusive. We use molecular dynamics simulations of water dynamics around several designed protein models to establish the connection between the appearance of the anomalous dynamics and water-protein interactions. For the first time we quantify the separate effect of protein topological and energetic disorder on the hydration water dynamics. When a static protein structure is simulated, we show that both types of disorder contribute to slow down water diffusion, and that allowing for protein motion, increasing the spatial dimensionality of the interface, reduces the anomalous character of hydration water. The rotation of water is, instead, altered by the energetic disorder only; indeed, when electrostatic interactions between the protein and water are switched off, water reorients even faster than in the bulk. The dynamics of water is also related to the collective structure--à voir the hydrogen bond (H-bond) network--formed by the solvent enclosing the protein surface. We show that, as expected for a full hydrated protein, when the protein surface offers pinning sites (charged or polar sites), the superficial water-water H-bond network percolates throughout the whole surface, hindering the water diffusion, whereas it does not when the protein surface lacks electrostatic interactions with water and the water diffusion is enhanced.

Currently tourism is the main driver of change in the Galapagos Islands, affecting the social, terrestrial, and marine sub-systems. Tourism also has direct and indirect consequences for the unique archipelago��������s natural habitats and for the human well-being. Describing the mechanisms that drive and affect most the tourism development in Galapagos is a preliminary condition to developing a better understanding of the interaction structure of factors that shape the Galapagos archipelago as a social-ecological complex system. In this paper, we present a first attempt to represent the touristic market in Galapagos trough an Agent Based Model (ABM) of touristic activity, focusing on touristic offers, reservations, and touristic activities. The model is based on an individual-based representation of tourists�������� consumption preferences and touristic accommodation offers in the Galapagos Islands. Tourist agents are created to mimic the real world by assigning average characteristics of individuals who visit the Galapagos Archipelago of Ecuador. The accommodation offers (i.e., hotels and cruises) are generated in accordance with actual conditions derived from data collected through field surveys. The model includes a market agent that can change the prices, create and delete accommodation offers following an evolutionary algorithm. We carried out preliminary simulations that show a close agreement between real world data and model outputs. Furthermore we used the model to generate three �������what if����� scenarios in order to study how emergent patterns in the touristic market in Galapagos are affected by changes in the archipelago environment. In this way we illustrate how the model can be used as a useful tool to help public policy makers to explore the consequences of their decisions.

Biological experiments were combined with molecular dynamics simulations to understand the importance of amino acidic residues present in the bromodomain of the yeast histone acetyltransferase Gcn5p. It was found that residue Pro371 plays an important role in the molecular recognition of the acetylated histone H4 tail by Gcn5p bromodomain. Crystallographic analysis of the complex showed that this residue does not directly interact with the histone substrate. It has been demonstrated that a double mutation Pro371Thr and Met372Ala in the Gcn5p bromodomain impairs chromatin remodeling activity. It is demonstrated here that, in this double mutant and in the fully deleted bromodomain strain, there is lower growth under amino acid deprivation conditions. By in vitro surface plasmon resonance (Biacore) experiments it is shown that the binding affinity of the double mutation to acetyl lysine 16 histone H4 peptide decreases. Molecular dynamics simulations were used to explain this loss in acetyl lysine-Gcn5p bromodomain affinity, in the double mutant. By comparing nanosecond molecular dynamics trajectories of the native as well as the single and doubly mutated bromodomain, it is concluded that the presence of Pro371 is important to the functionality of the Gcn5p bromodomain. In the simulation a point mutation involving this highly conserved residue induced an increase in the flexibility of the ZA loop, which in turn modulated the exposure of the binding pocket to the acetyl lysine. The combined double mutations (Pro371Thr-Met372Ala) not only markedly perturb the motion of the ZA loop but also destabilize the entire structure of the bromodomain.

This paper reports on extensive molecular dynamics simulations (about 40 ns in total) in both the reduced and the oxidized states of Ferredoxin from Cyanobacterium Anabaena PCC7119. These calculations have provided us with the free energy profile of the phi(47) backbone angle which controls the "CO in" to "CO out" transition of Cys46 in the reduced and oxidized Fd7119. Our main motivation has been to identify the time scales involved in the reduction of Fd and single out the amino acid residues crucially affecting the conformational change and, thus, electron transfer. The free energy profiles obtained in this study are relevant to electron transfers in the PSI/Fd7119 and Fd7119/FNR complexes. Our findings based on hydrated ferredoxin simulations are that activated processes are to occur in the protein during electron transfer to and from ferredoxin. The relative stability and the activation barrier of the "CO in" to "CO out" transition can be modulated by the distance between the Ser47 and the Glu94 residues. In our calculations, for short distances, the "CO in" state is favored in the reduced form, whereas for large distances, the "CO out" state becomes increasingly favored. Accordingly, conformational changes in Fd7119 when bound to PSI or FNR can have crucial effects on the kinetics of the electron transfer. Our simulations also show that the hydrogen bond between between Ser47(OG) and Cys46(O) is essential to lock in the "CO out" state. This finding explains why only the Ser47Thr Fd7119 mutant sustains electron transfer activity, as only residues serine and threonine can form a specific hydrogen bond with Cys46(O). Finally, our simulations predict that Phe65 has a large probability of being in close contact with the Cys46(O) at the top of the conformational free energy barrier. This carbonyl/phenyl ring interaction can then facilitate the de-localization of the Fd's electron toward the Pi orbitals of Phe65 aromatic ring which is thought to be crucial to the Fd7119/FNR electron transfer