Correction: Individual-based model highlights the importance of trade-offs for virus-host population dynamics and long-term co-existence.

[This corrects the article DOI: 10.1371/journal.pcbi.1010228.].

Individual-based model highlights the importance of trade-offs for virus-host population dynamics and long-term co-existence.

Viruses play diverse and important roles in ecosystems. In recent years, trade-offs between host and virus traits have gained increasing attention in viral ecology and evolution. However, microbial organism traits, and viral population parameters in particular, are challenging to monitor. Mathematical and individual-based models are useful tools for predicting virus-host dynamics. We have developed an individual-based evolutionary model to study ecological interactions and evolution between bacteria and viruses, with emphasis on the impacts of trade-offs between competitive and defensive host traits on bacteria-phage population dynamics and trait diversification. Host dynamics are validated with lab results for different initial virus to host ratios (VHR). We show that trade-off based, as opposed to random bacteria-virus interactions, result in biologically plausible evolutionary outcomes, thus highlighting the importance of trade-offs in shaping biodiversity. The effects of nutrient concentration and other environmental and organismal parameters on the virus-host dynamics are also investigated. Despite its simplicity, our model serves as a powerful tool to study bacteria-phage interactions and mechanisms for evolutionary diversification under various environmental conditions.

Study of Knowledge, Attitudes, and Practices Toward Risk Factors and Early Detection of Noncommunicable Diseases Among Rural Women in India.

PURPOSE: In recognition of the growing burden of noncommunicable diseases (NCDs), including cancer, we assessed the knowledge, attitudes, and practices of rural women in low-resourced countries toward common NCDs and the barriers they face in receiving NCD early detection services. PATIENTS AND METHODS: The study was conducted in a rural block of India using the Rapid Assessment and Response Evaluation ethnographic assessment, which included in-depth interviews of key health officials; focus group discussions with women, men, teachers, and health workers from the block; and a knowledge, attitudes, and practices questionnaire survey. The home-based survey was conducted among 1,192 women selected from 50 villages of the block using a two-stage randomization process and stratified to 30- to 44-year and 45- to 60-year age-groups. RESULTS: Our study revealed low awareness among women with regard to tobacco as a risk factor; hypertension, diabetes, and cancer as major health threats; and the importance of their early detection. Only 4.8% of women reported to have ever consumed tobacco, and many others consumed smokeless tobacco without knowing that the preparations contained tobacco. Only 27.3% and 11.5% of women had any knowledge about breast and cervical cancer, respectively, and only a few could describe at least one common symptom of either cancer. Self-reported diagnosis of hypertension and diabetes was significantly lower than the reported national prevalence. Only 0.9% and 1.3% of women reported having had a breast examination or gynecologic checkup, respectively, in the past 5 years. Low female empowerment and misconceptions were major barriers. CONCLUSION: Barriers need to be addressed to improve uptake of NCD early detection services.

A pilot study to evaluate home-based screening for the common non-communicable diseases by a dedicated cadre of community health workers in a rural setting in India.

BACKGROUND: Population-based screening for the common non-communicable diseases (NCD) is recommended but is difficult to implement in the hard-to-reach areas of low resourced countries. The objective of our pilot study was to evaluate the feasibility and the efficacy of delivering NCD screening services at home by trained community health workers (CHWs). Men and women aged 30-60 years residing in rural areas of India were targeted for screening. METHODS: The CHWs made home visits to educate the participants about healthy lifestyles and symptoms of common cancers and counsel the tobacco/alcohol users to quit. They measured height, weight, blood pressure (BP) and random blood sugar for all and performed oral visual examination (OVE) to screen the tobacco/alcohol users for oral cancer. For cervical cancer screening, the women themselves provided self-collected vaginal samples that the CHWs delivered to the laboratory for high-risk Human Papillomavirus (HPV) detection. The women were not screened for breast cancer but were made aware of the common symptoms and the importance of early diagnosis. Further assessment of the screen-positive individuals and the women with breast symptoms was arranged at the nearest primary health center (PHC). RESULTS: The CHWs screened 1998 men and 4997 women from 20 villages within 6 months; the refusal rate was less than 10%. High BP and sugar were detected in 32.6% and 7.5% participants respectively; hypertension and diabetes were confirmed in 42.3% and 35% respectively among those undergoing follow-up. Obesity prevalence was only 2.4%. More than 50% men were tobacco chewers. Of the total participants, 2.6% were positive on OVE, though no oral cancer was detected among them. HPV test was positive in 8.6% women and they were triaged with visual inspection after application of acetic acid (VIA) test for treatment either by thermal ablation (same visit) or by loop excision. VIA was positive in 14% of the HPV-positive women and 56.5% of them received same day ablative treatment. The VIA-negative women were advised follow up after 1 year. No breast cancer was detected among the 0.6% women complaining of breast symptoms. CONCLUSIONS: Delivery of NCD screening services at home by trained CHWs is feasible and well-accepted by our study population.

Evolution of Cooperation in Social Dilemmas on Complex Networks.

Cooperation in social dilemmas is essential for the functioning of systems at multiple levels of complexity, from the simplest biological organisms to the most sophisticated human societies. Cooperation, although widespread, is fundamentally challenging to explain evolutionarily, since natural selection typically favors selfish behavior which is not socially optimal. Here we study the evolution of cooperation in three exemplars of key social dilemmas, representing the prisoner's dilemma, hawk-dove and coordination classes of games, in structured populations defined by complex networks. Using individual-based simulations of the games on model and empirical networks, we give a detailed comparative study of the effects of the structural properties of a network, such as its average degree, variance in degree distribution, clustering coefficient, and assortativity coefficient, on the promotion of cooperative behavior in all three classes of games.

Evolutionary dynamics of a smoothed war of attrition game.

In evolutionary game theory the War of Attrition game is intended to model animal contests which are decided by non-aggressive behavior, such as the length of time that a participant will persist in the contest. The classical War of Attrition game assumes that no errors are made in the implementation of an animal׳s strategy. However, it is inevitable in reality that such errors must sometimes occur. Here we introduce an extension of the classical War of Attrition game which includes the effect of errors in the implementation of an individual׳s strategy. This extension of the classical game has the important feature that the payoff is continuous, and as a consequence admits evolutionary behavior that is fundamentally different from that possible in the original game. We study the evolutionary dynamics of this new game in well-mixed populations both analytically using adaptive dynamics and through individual-based simulations, and show that there are a variety of possible outcomes, including simple monomorphic or dimorphic configurations which are evolutionarily stable and cannot occur in the classical War of Attrition game. In addition, we study the evolutionary dynamics of this extended game in a variety of spatially and socially structured populations, as represented by different complex network topologies, and show that similar outcomes can also occur in these situations.

The importance of delineating networks by activity type in bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida.

Network analysis has proved to be a valuable tool for studying the behavioural patterns of complex social animals. Often such studies either do not distinguish between different behavioural states of the organisms or simply focus attention on a single behavioural state to the exclusion of all others. In either of these approaches it is impossible to ascertain how the behavioural patterns of individuals depend on the type of activity they are engaged in. Here we report on a network-based analysis of the behavioural associations in a population of bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida. We consider three distinct behavioural states-socializing, travelling and foraging-and analyse the association networks corresponding to each activity. Moreover, in constructing the different activity networks we do not simply record a spatial association between two individuals as being either present or absent, but rather quantify the degree of any association, thus allowing us to construct weighted networks describing each activity. The results of these weighted activity networks indicate that networks can reveal detailed patterns of bottlenose dolphins at the population level; dolphins socialize in large groups with preferential associations; travel in small groups with preferential associates; and spread out to forage in very small, weakly connected groups. There is some overlap in the socialize and travel networks but little overlap between the forage and other networks. This indicates that the social bonds maintained in other activities are less important as they forage on dispersed, solitary prey. The overall network, not sorted by activity, does not accurately represent any of these patterns.

Evolutionary dynamics of the traveler's dilemma and minimum-effort coordination games on complex networks.

The traveler's dilemma game and the minimum-effort coordination game are social dilemmas that have received significant attention resulting from the fact that the predictions of classical game theory are inconsistent with the results found when the games are studied experimentally. Moreover, both the traveler's dilemma and the minimum-effort coordination games have potentially important applications in evolutionary biology. Interestingly, standard deterministic evolutionary game theory, as represented by the replicator dynamics in a well-mixed population, is also inadequate to account for the behavior observed in these games. Here we study the evolutionary dynamics of both these games in populations with interaction patterns described by a variety of complex network topologies. We investigate the evolutionary dynamics of these games through agent-based simulations on both model and empirical networks. In particular, we study the effects of network clustering and assortativity on the evolutionary dynamics of both games. In general, we show that the evolutionary behavior of the traveler's dilemma and minimum-effort coordination games on complex networks is in good agreement with that observed experimentally. Thus, formulating the traveler's dilemma and the minimum-effort coordination games on complex networks neatly resolves the paradoxical aspects of these games.

An application of evolutionary game theory to social dilemmas: the traveler's dilemma and the minimum effort coordination game.

The Traveler's Dilemma game and the Minimum Effort Coordination game are two social dilemmas that have attracted considerable attention due to the fact that the predictions of classical game theory are at odds with the results found when the games are studied experimentally. Moreover, a direct application of deterministic evolutionary game theory, as embodied in the replicator dynamics, to these games does not explain the observed behavior. In this work, we formulate natural variants of these two games as smoothed continuous-strategy games. We study the evolutionary dynamics of these continuous-strategy games, both analytically and through agent-based simulations, and show that the behavior predicted theoretically is in accord with that observed experimentally. Thus, these variants of the Traveler's Dilemma and the Minimum Effort Coordination games provide a simple resolution of the paradoxical behavior associated with the original games.

Attack robustness and centrality of complex networks.

Many complex systems can be described by networks, in which the constituent components are represented by vertices and the connections between the components are represented by edges between the corresponding vertices. A fundamental issue concerning complex networked systems is the robustness of the overall system to the failure of its constituent parts. Since the degree to which a networked system continues to function, as its component parts are degraded, typically depends on the integrity of the underlying network, the question of system robustness can be addressed by analyzing how the network structure changes as vertices are removed. Previous work has considered how the structure of complex networks change as vertices are removed uniformly at random, in decreasing order of their degree, or in decreasing order of their betweenness centrality. Here we extend these studies by investigating the effect on network structure of targeting vertices for removal based on a wider range of non-local measures of potential importance than simply degree or betweenness. We consider the effect of such targeted vertex removal on model networks with different degree distributions, clustering coefficients and assortativity coefficients, and for a variety of empirical networks.

Pharmacokinetic study of omacetaxine mepesuccinate administered subcutaneously to patients with advanced solid and hematologic tumors.

PURPOSE: Omacetaxine mepesuccinate is a first-in-class cephalotaxine demonstrating clinical activity in chronic myeloid leukemia. A subcutaneous (SC) formulation demonstrated efficacy and safety in phase 1/2 trials in patients previously treated with ≥1 tyrosine kinase inhibitor. This study assessed pharmacokinetics and safety of SC omacetaxine in patients with advanced cancers. METHODS: Omacetaxine 1.25 mg/m(2) SC was administered BID, days 1-14 every 28 days for 2 cycles, until disease progression or unacceptable toxicity. Blood and urine were collected to measure omacetaxine concentrations and inactive metabolites. Adverse events, including QT interval prolongation, were recorded. Tumor response was assessed at cycle 2 completion. RESULTS: Pharmacokinetic parameters were estimated from cycle 1, day 1 data in 21 patients with solid tumors or hematologic malignancies and cycle 1, day 11 data in 10 patients. Omacetaxine was rapidly absorbed, with mean peak plasma concentrations observed within 1 h, and widely distributed, as evidenced by an apparent volume of distribution of 126.8 L/m(2). Plasma concentration versus time data demonstrated biexponential decay; mean steady-state terminal half-life was 7 h. Concentrations of inactive metabolites 4'-DMHHT and cephalotaxine were approximately 10 % of omacetaxine and undetectable in most patients, respectively. Urinary excretion of unchanged omacetaxine accounted for <15 % of the dose. Grade 3/4 drug-related adverse events included thrombocytopenia (48 %) and neutropenia (33 %). Two grade 2 increases in QTc interval (>470 ms) were observed and were not correlated with omacetaxine plasma concentration. No objective responses were observed. CONCLUSIONS: Omacetaxine is well absorbed after SC administration. Therapeutic plasma concentrations were achieved with 1.25 mg/m(2) BID, supporting clinical development of this dose and schedule.

Bridging the gap in hematological malignancies.

After the success of the BTG Series in Singapore in 2010 and 2011, meeting organizers held the 3rd International Hematologic Malignancies Conference in Hong Kong. Held on 23-25 February, the BTG meeting provided an opportunity to further scientific discourse in the Asia-Pacific region. Featuring the world-renowned medical faculty and an abundance of discussion forums, the conference provided attendees the opportunity to interact with field leaders and exposed them to the latest research. The BTG conferences focus on hematologic malignancies, especially leukemia, lymphoma and myeloma. The BTG series provides an exceptional platform for the exchange of ideas for the Asia-Pacific hematology oncology healthcare community. It offers many novel opportunities for practicing physicians as well as fellows in training to meet with the world thought leaders. The annual conference brings together key opinion leaders from the Asia-Pacific region, the USA and Europe. The underlying motto is to bring the continents together and generate a global community in the quest against cancer. BTG recognizes the contributions of the Asia-Pacific physicians who are among the world leaders and gives the younger generation opportunities to present their work in a world arena.