Ki67 proliferation in core biopsies versus surgical samples - a model for neo-adjuvant breast cancer studies

Background: An increasing number of neo-adjuvant breast cancer studies are being conducted and a novel model for tumor biological studies, the "window-of-opportunity" model, has revealed several advantages. Change in tumor cell proliferation, estimated by Ki67-expression in pre-therapeutic core biopsies versus post-therapeutic surgical samples is often the primary end-point. The aim of the present study was to investigate potential differences in proliferation scores between core biopsies and surgical samples when patients have not received any intervening anti-cancer treatment. Also, a lack of consensus concerning Ki67 assessment may raise problems in the comparison of neo-adjuvant studies. Thus, the secondary aim was to present a novel model for Ki67 assessment. Methods: Fifty consecutive breast cancer cases with both a core biopsy and a surgical sample available, without intervening neo-adjuvant therapy, were collected and tumor proliferation (Ki67, MIB1 antibody) was assessed immunohistochemically. A theoretical model for the assessment of Ki67 was constructed based on sequential testing of the null hypothesis 20% Ki67-positive cells versus the two-sided alternative more or less than 20% positive cells.. Results: Assessment of Ki67 in 200 tumor cells showed an absolute average proliferation difference of 3.9% between core biopsies and surgical samples (p = 0.046, paired t-test) with the core biopsies being the more proliferative sample type. A corresponding analysis on the log-scale showed the average relative decrease from the biopsy to the surgical specimen to be 19% (p = 0.063, paired t-test on the log-scale). The difference was significant when using the more robust Wilcoxon matched-pairs signed-ranks test (p = 0.029). After dichotomization at 20%, 12 of the 50 sample pairs had discrepant proliferation status, 10 showed high Ki67 in the core biopsy compared to two in the surgical specimen (p = 0.039, McNemar's test). None of the corresponding results for 1000 tumor cells were significant - average absolute difference 2.2% and geometric mean of the ratios 0.85 (p = 0.19 and p = 0.18, respectively, paired t-tests, p = 0.057, Wilcoxon's test) and an equal number of discordant cases after dichotomization. Comparing proliferation values for the initial 200 versus the final 800 cancer cells showed significant absolute differences for both core biopsies and surgical samples 5.3% and 3.2%, respectively (p < 0.0001, paired t-test). Conclusions: A significant difference between core biopsy and surgical sample proliferation values was observed despite no intervening therapy. Future neo-adjuvant breast cancer studies may have to take this into consideration

Hotelling Was Right About Snob/Congestion Goods (Asymptotically)

We add congestion/snobbery to the Hotelling model of spatial competition. For any firm locations on opposite sides of the midpoint, a pure strategy price equilibrium exists and is unique if congestion costs are strong enough relative to transportation costs. The maximum distance between firms in any pure strategy symmetric location equilibrium declines toward zero as congestion costs increase relative to transportation costs. For any non-zero minimum distance between firms, high enough congestion costs relative to transportation costs guarantee that the unique pure strategy symmetric location equilibrium involves minimum differentiation. In this sense Hotelling was right about differentiation of snob/congestion goods.Hotelling, spatial competition, differentiation, congestion, snobbery

Matching for Credit: Risk and Diversification in Thai Microcredit Groups

How has the microcredit movement managed to push financial frontiers? In a context in which borrowers vary in unobservable risk, Ghatak (1999, 2000) shows that group-based, joint liability contracts price for risk more accurately than individual contracts, provided that borrowers match homogeneously by risk-type. This more accurate risk-pricing can attract safe borrowers and rouse an otherwise dormant credit market. We extend the theory to include correlated risk, and show that borrowers will anti-diversify risk within groups, in order to lower chances of facing liability for group members. We directly test risk-matching and intra-group diversification of risk using data on Thai microcredit borrowing groups. We propose a non-parametric univariate methodology for assessing homogeneity of matching; structural multivariate analysis is carried out using Fox's (2008) matching maximum score estimator. We find evidence of a) homogeneous sorting by risk and b) risk anti-diversification within groups, though not along occupational lines. Thus there is evidence that group lending improves risk-pricing in this context and is part of the explanation of the rise in financial intermediation among the poor. However, the anti-diversification results reveal a potentially negative aspect of voluntary group formation and point to limitations of microcredit groups as risk-sharing mechanisms.[Working Paper No. 251]microcredit, matching, credit markets, adverse selection, risk-sharing

Comment on "A note on the Hotelling principle of minimum differentiation: Imitation and crowd"

We argue that the minimum differentiation firm location equilibrium and the pure strategy pricing equilibrium in Di Cintio's [Di Cintio, M., 2007. A note on the Hotelling principle of minimum differentiation: Imitation and crowd. Research in Economics 61 (3), 122-129] "Note" need not exist under the conditions claimed.

A conditional Gini: measure, estimation, and application

The Gini measure of inequality can be written as the ratio of means. By extension, we define the conditional Gini as the ratio of conditional means. This conditional Gini shows how inequality varies with population characteristics, both levels and differences, and creates novel opportunities to trace inequality as differences in observables vary across the population. We propose a regression-based method for estimating the conditional Gini, and a method for inference using recent techniques for clustered data. The conditional Gini is estimated using a large, nationally representative household survey from Thailand. We find that wealth differences are associated with significantly less income inequality among households that use the financial sector than among those that do not, consistent with the idea that financial access relaxes self-financing constraints and broadens economic opportunity.N

Corruption: Political Determinants and Macroeconomic Effects

Two aspects of corruption are examined theoretically: its effect on macroeconomic variables, and its determination from the political environment. Corruption is defined in an occupational choice model as the extra fees or bribes that must be paid by some entrepreneurs. Even in an environment of perfect information and well-defined property rights, wages and total output decrease with the level of corruption. Inverted-U relationships of income inequality with both corruption and output are calculated. Second, two types of decentralization, regional and bureaucratic, are analyzed. The effects depend crucially on agents' mobility across regions. Under imperfect mobility assumptions, corruption decreases with regional decentralization and increases with bureaucratic decentralization. Two methods of controlling corruption are analyzed in this setting: democratic accountability and incentive payments. The same factor that makes bureaucratic decentralization more corrupt makes it more resistant to efforts to rein in corruption; the reverse is true for regional decentralization. This model matches emerging stylized facts relating corruption to output, inequality, and decentralization, and reinterprets findings linking bureaucratic wage levels and corruption.Corruption, decentralization, electoral accountability, optimal wage policy

Optimal Pricing Under Stochastic Inflation: State:Dependent (s,S) Policies

A model of firm-level optimal pricing under stochastic inflation and fixed costs of adjusting prices is solved and characterized. In this model, inflation alternates stochastically between some positive rate g and zero inflation. We find that a single (s,S) band is not optimal for the firm, as was claimed in the earlier literature. Rather, the firm will set a different (s,S) band for each state of the world, with the zero-inflation band wholly contained in the positive-inflation band. A numerical example is then presented, showing that a higher variance of aggregate price changes increases price dispersion in the positive-inflation state and decreases price dispersion in the zero-inflation state.Inflation, inflation variability, menu costs, price dispersion, state-dependent pricing