rhuMAb VEGF was safely administered without dose-limiting toxicity at doses ranging up to 10 mg/kg. Multiple doses of rhuMAb VEGF were well tolerated, and pharmacokinetic studies indicate that doses of > or = 0.3 mg/kg have a half-life similar to that of other humanized antibodies. Subsequent trials will explore rhuMAb VEGF alone and in combination chemotherapy.

We formally derive the standard deterministic linear program (LP) for bid-price control by making an affine functional approximation to the optimal dynamic programming value function. This affine functional approximation gives rise to a new LP that yields tighter bounds than the standard LP. Whereas the standard LP computes static bid prices, our LP computes a time trajectory of bid prices. We show that there exist dynamic bid prices, optimal for the LP, that are individually monotone with respect to time. We provide a column generation procedure for solving the LP within a desired optimality tolerance, and present numerical results on computational and economic performance.

W e consider a network revenue management problem where customers choose among open fare products according to some prespecified choice model. Starting with a Markov decision process (MDP) formulation, we approximate the value function with an affine function of the state vector. We show that the resulting problem provides a tighter bound for the MDP value than the choice-based linear program. We develop a column generation algorithm to solve the problem for a multinomial logit choice model with disjoint consideration sets (MNLD). We also derive a bound as a by-product of a decomposition heuristic. Our numerical study shows the policies from our solution approach can significantly outperform heuristics from the choice-based linear program.

BACKGROUNDPeanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS Randomization and BlindingEligible participants were randomly assigned, in a 3:1 ratio, to receive either AR101, a peanut-derived pharmaceutical product that was manufactured

We consider a broad class of stochastic dynamic programming problems that are amenable to relaxation via decomposition. These problems comprise multiple subproblems that are independent of each other except for a collection of coupling constraints on the action space. We fit an additively separable value function approximation using two techniques, namely, Lagrangian relaxation and the linear programming (LP) approach to approximate dynamic programming. We prove various results comparing the relaxations to each other and to the optimal problem value. We also provide a column generation algorithm for solving the LP-based relaxation to any desired optimality tolerance, and we report on numerical experiments on bandit-like problems. Our results provide insight into the complexity versus quality trade-off when choosing which of these relaxations to implement.

Allergic reactions to the beta-lactam antibiotics (penicillins, cephalosporins, carbapenems, and monobactams) are a major factor limiting their use. Immediate hypersensitivity reactions to penicillins depend on the presence of preformed allergic (IgE) antibodies to several penicillin determinants. These materials can be used in in-vivo skin testing to exclude those patients at risk for immediate or accelerated allergic reactions. The cephalosporins have not had their relevant determinants defined as related to allergic reactions. The results of in-vivo challenges of patients with IgE to penicillin suggest the incidence of reactivity of cephalosporins in patients allergic to penicillin is less than generally appreciated. The monocyclic beta-lactam antibiotic, aztreonam (a monobactam), failed to show cross-reactivity with penicillin antibodies, because immune reactivity toward the monobactam was directed against side chain rather than nuclear determinants. On the other hand, the new bicyclic carbapenem beta-lactam drugs, represented by imipenem, showed extensive in-vivo cross-reactivity with penicillins.

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rhuMAbVEGF can be safely combined with chemotherapy at doses associated with VEGF blockade and without apparent synergistic toxicity. Its contribution to the treatment of advanced solid tumors should be evaluated in randomized treatment trials.