Edge effects in game theoretic dynamics of spatially structured tumours

Background: Analysing tumour architecture for metastatic potential usually focuses on phenotypic differences due to cellular morphology or specific genetic mutations, but often ignore the cell's position within the heterogeneous substructure. Similar disregard for local neighborhood structure is common in mathematical models. Methods: We view the dynamics of disease progression as an evolutionary game between cellular phenotypes. A typical assumption in this modeling paradigm is that the probability of a given phenotypic strategy interacting with another depends exclusively on the abundance of those strategies without regard local heterogeneities. We address this limitation by using the Ohtsuki-Nowak transform to introduce spatial structure to the go vs. grow game. Results: We show that spatial structure can promote the invasive (go) strategy. By considering the change in neighbourhood size at a static boundary -- such as a blood-vessel, organ capsule, or basement membrane -- we show an edge effect that allows a tumour without invasive phenotypes in the bulk to have a polyclonal boundary with invasive cells. We present an example of this promotion of invasive (EMT positive) cells in a metastatic colony of prostate adenocarcinoma in bone marrow. Interpretation: Pathologic analyses that do not distinguish between cells in the bulk and cells at a static edge of a tumour can underestimate the number of invasive cells. We expect our approach to extend to other evolutionary game models where interaction neighborhoods change at fixed system boundaries.Comment: 14 pages, 3 figures; restructured abstract, added histology to fig. 1, added fig. 3, discussion of EMT introduced and cancer biology expande

An Assessment of Poverty Studies in India with Special Reference to Economic Reforms

As it is well-known, the study of poverty is extremely important on moral and philosophical and also, political grounds. Further, evidences are available to show that poverty affects growth adversely. We, therefore, have made an attempt to review some of the important studies on poverty in India. The concept of poverty relates to socially perceived deprivation with respect to basic minimum needs. In the Indian context, poverty is measured in terms of a specified normative poverty line reflecting the minimum living standard of the people. Defining a poverty line is, therefore, the first step in estimating poverty. According to the Expert Group (1993), a poverty line, dividing the poor from the non-poor, is used by putting a price on the minimum required consumption levels of food, clothing, shelter, fuel and health care, etc. In equal practice however, the poverty lines are normative only in terms of calorie requirements of the diet. Since the beginning of sixties a number of studies have been conducted to estimate the incidence of poverty and to find out the determinants of poverty. Different methods have been used to estimate the incidence. All these are, however, based on the use of poverty lines and the distribution of expenditure of households. These lines have been updated by using alternative price index numbers, and, expectedly, it has resulted in different estimates. Even the base year poverty lines, used by various authors, are different. Various measures of poverty to know its severity and depth have also been estimated by the researchers. The relationships between the incidence of poverty and its determinants have been estimated by using different variables and models.

The Impact of Trade Liberalization on Household Welfare and Poverty in India

A 28-sector, 3-factor and 9-household group Computable General Equilibrium (CGE) model for India is constructed to analyze the impacts of Tariffs and Non-tariff Barriers (NTBs) on the welfare and poverty of socio-economic household groups. A general cut in tariffs leads to a decrease in overall welfare and reduction in poverty, which urban households are in a relatively better position to address. The choice of a fiscal compensatory mechanism with indirect tax on domestic consumption does not substantially change the pattern of impact except that it increases overall poverty in the economy. On the other hand, quota reductions on agriculture and food products result in a gain in welfare and a bigger reduction of poverty, with rural households doing better than urban households.Computable general equilibrium (CGE) model, microsimulations, International trade, poverty, India

Constituent Quark Scaling of Strangeness Enhancement in Heavy-Ion Collisions

In the frame work of a nuclear overlap model, we estimate the number of nucleon and quark participants in proton-proton, proton-nucleus and nucleus-nucleus collisions. We observe the number of nucleon ($N_{N-part}$)-normalized enhancement of multi-strange particles which show a monotonic increase with centrality, turns out to be a centrality independent scaling behavior when normalized to number of constituent quarks participating in the collision ($N_{q-part}$). In addition, we observe that the $N_{q-part}$-normalized enhancement, when further normalized to the strangeness content, shows a strangeness independent scaling behavior. This holds good at top RHIC energy. However, the corresponding SPS data show a weak $N_{q-part}$-scaling with strangeness scaling being violated at top SPS energy. This scaling at RHIC indicates that the partonic degrees of freedom playing an important role in the production of multi-strange particles. Top SPS energy, in view of the above observations, shows a co-existence of hadronic and partonic phases. We give a comparison of data with HIJING, AMPT and UrQMD models to understand the particle production dynamics at different energies.Comment: 9 pages, 17 figure

The Macro-Economic and Sectoral Impacts of HIV and AIDS in India

The adverse economic impact of HIV and AIDS occurs at three levels : the individual/household, sector, and national or macro-levels. In the early phase of the epidemic, the impacts at the sector and macro-levels are rather mild and, hence, not easily measurable or quantifiable. So far in India, given the low overall prevalence, the focus has been on the effects at the level of the individual and the household. The enlisted study, by Pradhan, Sundar and Singh (2006)1 also focuses on the impact of HIV and AIDS on affected households, which it finds to be seriously adverse, and, therefore, a matter of acute concern. At the same time, the study underplays the adverse economywide impact of AIDS. Given the current prevalence rate, the extrapolation of the household-level impact to the level of the state or the national economy does not reveal a large macro-economic impact. But, this is because the survey, on which the study is based, captures the snapshot of the economy at a given point of time, while the question of the macroeconomic impact of AIDS is essentially a dynamic one. As the HIV epidemic unfolds, its impacts are bound to be deeply compounded. These impacts cannot be assessed in their totality by a mere extrapolation of the household level impact. Furthermore, in 2005, the number of HIV-infected persons exceeds 5 million, and this number is expected to quintuple to between 20 million and 25 million by 2010. With that kind of a jump in the number of HIV cases in the next 5-10 years, there is bound to be a visible impact on the national economy. At present, little or nothing is known about the potential macro-economic impact of HIV and AIDS on the Indian economy. The rough-and-ready estimates of the macro-economic costs of AIDS that are available are of no help in guiding and accelerating the response of the Government of India to the potential threat to the economy imposed by this epidemic. A quantitative assessment of the macro-economic impact of AIDS on the Indian economy, therefore, needs to be undertaken urgently to assist the policy makers. Keeping this in mind, the study analyses the macro-economic and sectoral impacts of HIV and AIDS in India, using a fivesector computable general equilibrium (CGE) model.HIV, AIDS, macroeconomic impact of AIDS, computable general equilibrium

Exploiting evolution to treat drug resistance: Combination therapy and the double bind

Although many anti cancer therapies are successful in killing a large percentage of tumour cells when initially administered, the evolutionary dynamics underpinning tumour progression mean that often resistance is an inevitable outcome, allowing for new tumour phenotypes to emerge that are unhindered by the therapy. Research in the field of ecology suggests that an evolutionary double bind could be an effective way to treat tumours. In an evolutionary double bind two therapies are used in combination such that evolving resistance to one leaves individuals more susceptible to the other. In this paper we present a general evolutionary game theory model of a double bind to study the effect that such approach would have in cancer. Furthermore we use this mathematical framework to understand recent experimental results that suggest a synergistic effect between a p53 cancer vaccine and chemotherapy. Our model recapitulates the experimental data and provides an explanation for its effectiveness based on the commensalistic relationship between the tumour phenotypes