IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate.

Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions. IgM but not IgD is downregulated on autoreactive B cells. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. IgD-only Lyn-/- B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1+ SLPC responses to T-dependent immunization. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells

The case for surgical skills centres in Sub Saharan Africa: The benefits and the challenges.

The purpose of this paper is to describe the educational and practice utilities of establishing Surgical Skills Centres. The paper also defines significant obstacles to the establishment of such centres in Sub- Saharan Africa. In 1996, the Royal College of Physicians and Surgeons Canada responded to the evolving roles and obligations of medical specialists by implementing a framework of core competencies called the “CanMEDS Roles” which define surgeons as medical experts, communicators, collaborators, managers, health advocates, scholars and professionals. A key competency expected of the medical expert is the demonstration of proficiency in procedural skills2

Fixed Price Approximability of the Optimal Gain From Trade

Bilateral trade is a fundamental economic scenario comprising a strategically acting buyer and seller, each holding valuations for the item, drawn from publicly known distributions. A mechanism is supposed to facilitate trade between these agents, if such trade is beneficial. It was recently shown that the only mechanisms that are simultaneously DSIC, SBB, and ex-post IR, are fixed price mechanisms, i.e., mechanisms that are parametrised by a price p, and trade occurs if and only if the valuation of the buyer is at least p and the valuation of the seller is at most p. The gain from trade is the increase in welfare that results from applying a mechanism; here we study the gain from trade achievable by fixed price mechanisms. We explore this question for both the bilateral trade setting, and a double auction setting where there are multiple buyers and sellers. We first identify a fixed price mechanism that achieves a gain from trade of at least 2/r times the optimum, where r is the probability that the seller's valuation does not exceed the buyer's valuation. This extends a previous result by McAfee. Subsequently, we improve this approximation factor in an asymptotic sense, by showing that a more sophisticated rule for setting the fixed price results in an expected gain from trade within a factor O(log(1/r)) of the optimal gain from trade. This is asymptotically the best approximation factor possible. Lastly, we extend our study of fixed price mechanisms to the double auction setting defined by a set of multiple i.i.d. unit demand buyers, and i.i.d. unit supply sellers. We present a fixed price mechanism that achieves a gain from trade that achieves for all epsilon > 0 a gain from trade of at least (1-epsilon) times the expected optimal gain from trade with probability 1 - 2/e^{#T epsilon^2 /2}, where #T is the expected number of trades resulting from the double auction

The allocative effectiveness of market protocols under intelligent trading

Abstract. We study the performance of four market protocols that lead to allocative ef-ficiency: batch auction, continuous double auction, specialist dealership, and a hybrid of these last two. In a former study, we compared them with respect to several additional performance criteria under the assumption of zero intelligence. This paper analyzes three performance criteria under different ways to remove the assumption of zero intelligence. The following conclusions are robust. The number of wasteful transaction is minimized by the batch auction and the dealership. Moreover, the former minimizes price dispersion and the latter minimizes time to convergence

Allocation mechanisms, incentives, and endemic institutional externalities

Whether an economic agent’s decision creates an externality often depends on the institutional context in which the decision was made. Indeed, in orthodox economics, a technological or exogenous externality occurs just in case one agent’s economic welfare or production possibilities are directly affected by the market decisions of other agents. A pecuniary externality occurs just in case one consumer’s economic welfare or producer’s profit is affected indirectly by price changes caused by changes in other agents’ decisions. Similarly, an institutional or endogenous externality may arise whenever allocations are determined by a mechanism that is not strategy proof for some agent. Then even a resource balance constraint creates an institutional externality except in special cases such as when no individual agent’s action can affect market clearing prices — i.e., there are no pecuniary externalities