The treatment of choice for glomus jugulare tumors is still controversial. High rates of morbidity, incomplete resection, and the aggressive behavior of these tumors are the main arguments for advocates of primary radiotherapy. However, constant refinements in skull base techniques have made complete resection of these lesions a realistic goal. The high probability of achieving local control of these tumors by surgery has convinced us to support this option strongly. Between 1993 and 2000 we diagnosed 52 glomus tumors of the temporal bone. Of these patients, only 42 had a class C lesion (glomus jugulare) and were included in this study; 37 of these patients underwent surgery, 10 of whom had intracranial extension of the disease. The overall resection rate was 96%. Facial nerve function at 1 year was House-Brackmann grade I to II in 52% of patients and grade III or better in 84% of patients. Hospitalization was shorter than 14 days in 33 patients (89%). All patients with pharyngolaryngeal palsy had sufficient compensation at discharge. Twelve vocal chord Teflon injections were performed after surgery to reduce hoarseness and aspiration. No patient died. No relapse was observed (mean follow-up, 4.9 years).

No abstract

Glioblastoma multiforme (GBM) is the most common and lethal brain tumor characterized by a strongly immunosuppressive tumor microenvironment (TME) that represents a barrier also for the development of effective immunotherapies. The possibility to revert this hostile TME by immunoactivating cytokines is hampered by the severe toxicity associated with their systemic administration. Here, we exploited a lentiviral vector–based platform to engineer hematopoietic stem cells ex vivo with the aim of releasing, via their tumor-infiltrating monocyte/macrophage progeny, interferon-α (IFN-α) or interleukin-12 (IL-12) at the tumor site with spatial and temporal selectivity. Taking advantage of a syngeneic GBM mouse model, we showed that inducible release of IFN-α within the TME achieved robust tumor inhibition up to eradication and outperformed systemic treatment with the recombinant protein in terms of efficacy, tolerability, and specificity. Single-cell RNA sequencing of the tumor immune infiltrate revealed reprogramming of the immune microenvironment toward a proinflammatory and antitumoral state associated with loss of a macrophage subpopulation shown to be associated with poor prognosis in human GBM. The spatial and temporal control of IL-12 release was critical to overcome an otherwise lethal hematopoietic toxicity while allowing to fully exploit its antitumor activity. Overall, our findings demonstrate a potential therapeutic approach for GBM and set the bases for a recently launched first-in-human clinical trial in patients with GBM.

This paper analyses an optimal two‐part licensing scheme based on ad valorem royalties within a differentiated Bertrand duopoly where the innovator is also the downstream producer, and compares it with the optimal two‐part per‐unit royalty mechanism. After showing that the optimal two‐part ad valorem licensing scheme reduces to a pure ad valorem royalty scheme, we show that per‐unit contracts are typically preferred to ad valorem contracts by the patentee, as, under price competition, the per‐unit royalty has a stronger strategic effect than the ad valorem royalty. In contrast, welfare is higher under the ad valorem contract than under the per‐unit mechanism.

In this article, we develop a model encompassing behavior-based discriminatory pricing as a limit case of a more general framework where firms have incomplete information about consumers' purchase histories. We show that information accuracy has a nonmonotonic impact on profits and the worst situation for firms is when information accuracy is intermediate. We also discuss welfare and consumer surplus implications of information accuracy. Although welfare monotonically decreases with the level of information accuracy, there is an inverse U-shape relationship between consumers surplus and information accuracy.

We develop a model of behavior-and characteristic-based discriminatory pricing where consumers are heterogeneous both in tastes and in price sensitivity. Each firm is able to distinguish between the consumers that have bought from it and those that have bought from the rival. Furthermore, each firm learns the price sensitivity of their own consumers. We show that using this additional information may yield higher profits than uniform pricing provided that consumers are heterogeneous enough with respect to price sensitivity. We also discuss consumer surplus implications of such behaviorand characteristic-based price discrimination, and we show that the impact of price discrimination depends on both the consumer type and the level of consumers' heterogeneity.

No abstract

No abstract