Second, But Not Last: Competition with Positive Spillovers

This paper extends the traditional rent-seeking model to consider contests in which the effects of the contestants’ efforts are externally unproductive (i.e., redistributive) but internally productive (i.e., with positive spillover effects on other contestants). Our results show that when players act sequentially, the presence of positive spillovers on other contestants may reduce, or even reverse, the first-mover’s advantage. A second-mover advantage is very likely to arise. Notably, in contests with multiple players, the second-mover advantage does not unravel into a last-mover advantage. Players want to be second, but not last. The comparative statics analysis shows how the strength of positive spillovers affects contestants’ equilibrium expenditures and payoffs, and aggregate rent dissipation

Injurers versus Victims: (A)Symmetric Reactions to Symmetric Risks

Tort models assume symmetry in the behavior of injurers and victims when faced by a threat of liability and a risk of harm without compensation, respectively. This assumption has never been empirically validated. Using a novel experimental design, we study the behavior of injurers and victims when facing symmetric accident risks. Experimental results provide qualified support for the symmetric behavior hypothesis

Sharing Residual Liability: ‘Cheapest Cost Avoider’ Revisited

Economic models of tort law evaluate the efficiency of liability rules in terms of care and activity levels. A liability regime is optimal when it creates incentives to maximize the value of risky activities at the net of accident and precaution costs. The allocation of primary and residual liability allows policymakers to induce parties to undertake socially desirable care and activity levels. Traditionally, tort law systems have assigned residual liability either entirely on the tortfeasor or entirely on the victim. In this paper, we unpack the cheapest cost-avoider principle (Calabresi, 1970) to consider the virtues and the limits of loss-sharing rules in generating optimal (second-best) incentives and allocations of risk. We find that loss-sharing may be optimal in the presence of countervailing policy objectives, of homogeneous risk avoiders and of subadditive risk, potentially offering a valuable tool for policymakers and courts in awarding damages in a large number of real-world accident cases

Accuracy of Verdicts under Different Jury Sizes and Voting Rules

Juries are a fundamental element of the criminal justice system. In this article, we model jury decision making as a function of two institutional variables: jury size and voting requirement. We expose the critical interdependence of these two elements in minimizing the probabilities of wrongful convictions, of wrongful acquittals, and of hung juries. We find that the use of either large nonunanimous juries or small unanimous juries offers alternative ways to maximize the accuracy of verdicts while preserving the functionality of juries. Our framework, which lends support to the elimination of the unanimity requirement in the presence of large juries, helps appraise US Supreme Court decisions and state legal reforms that have transformed the structure of American juries

Integrated approach to the study of mantle cell lymphoma

Il linfoma a cellule del mantello (MCL) \ue8 un linfoma non Hodgkin B caratterizzato dalla proliferazione di linfociti \u201cmaturi\u201d che esprimono CD5, con uno spettro morfologico e fenotipico pi\uf9 ampio di quanto inizialmente descritto quando fu riconosciuto come entit\ue0. Sebbene alcuni pazienti abbiano un decorso clinico indolente, in molti il comportamento \ue8 aggressivo con scarsa risposta ai convenzionali regimi chemioterapici. La caratteristica genetica tipica \ue8 la traslocazione t(11;14)(q13;q32) che comporta l\u2019iper-espressione della Ciclina D1, considerato l\u2019evento oncogenico iniziale. Il MCL pu\uf2 inoltre avere alterazioni cromosomiche e molecolari secondarie che alterano ad esempio il funzionamento del controllo del ciclo cellulare, della senescenza cellulare, della risposta al danno del DNA e molte altre. La conoscenza di questi meccanismi e del loro ruolo nella crescita tumorale \ue8 fondamentale per individuare modelli prognostici dell\u2019evoluzione clinica della malattia, nonch\ue9 per lo sviluppo di nuove terapie che abbiamo come bersaglio mirato proprio le vie alterate nei MCL. Il nostro progetto si \ue8 svolto in due fasi, una di raccolta dati da analisi del profilo proteico e fosfoproteico delle linee cellulari di MCL e una seconda di validazione su tessuto umano fissato in formalina e di sviluppo di modelli murini.Mantle cell lymphoma (MCL) is a well-defined lymphoid neoplasm characterized by a proliferation of mature B lymphocytes expressing CD5 that may show a spectrum of morphological and phenotypic features broader than initially described. Although some patients may follow an indolent clinical evolution, in most of them the tumour has an aggressive behaviour with poor response to conventional chemotherapy. The genetic hallmark is the t(11;14)(q13;q32) translocation leading to the overexpression of cyclin D1, which is considered the initial oncogenic event. In addition to this translocation, MCL may carry a high number of secondary chromosomal and molecular alterations that target regulatory elements of the cell cycle machinery and senescence (BMI1/INK4/ARF/CDK4/RB1), DNA damage response pathways (ATM/CHK2/p53), and cell survival signals. The knowledge of these mechanisms and their influence on the behaviour of the tumour are facilitating the development of prognostic models with a more precise prediction of the clinical evolution of the patients. This information coupled with the availability of a new generation of innovative drugs targeting basic molecular process of the tumour cells, should facilitate the design of new therapeutic protocols able to overcome the resistance of this aggressive lymphoma to conventional treatments and improve the life expectancy of the patients. The goal of our project has been to integrate information from high-throughput techniques (proteomic approach), find good candidate \u201cdrivers\u201d of MCL pathogenesis and validate them by independent techniques, especially by testing their functional importance in model systems, hopefully findings novel biomarkers that could be used in diagnostic practice. PhosphoScan analysis identified 421 unique peptides, corresponding to 341 proteins. Among these, several activated protein kinases were found. Interestingly, several identified proteins mapped to cytogenetic loci that have been reported to be altered in MCL by previous literature. Our data support a pro-survival role of BCR signaling in MCL and suggest that this pathway might be a candidate for therapy. Our findings also suggest that Syk activation patterns might be different in MCL compared to other lymphoma subtypes. For validation on tissues we characterised 40 MCL cases according to most recent criteria in order to recognize biological and prognostic variants; several proteins recognized by proteomics studies were also studied in tissues by means of immunohistochemistry. The final part of the project was focused on the attempt to establish experimental models by tumor xenografts. NOD/SCID mice were first injected by several ways with primary MCL cell in an effort to establish a model for further experimental work, but they developed GVHD and died. Then we\u2019ve found that injecting MCL cell lines into Rag -/- \u3b3 -/- mice we were able to grow big tumoral masses

Is triple-positive serology for Epstein-Barr virus (VCA-IgG, VCA-IgM, EBNA-IgG) a specific feature of angioimmunoblastic T-cell lymphoma?

Purpose: We assessed the frequency of triple-positive serology (viral capsid antigen [VCA]-immunoglobulin G [IgG], VCA-immunoglobulin M, Epstein-Barr nuclear antigen-IgG) for Epstein-Barr virus (EBV) in a small number of patients with angioimmunoblastic T-cell lymphoma (AITL) at disease onset. Methods: Nine patients with newly diagnosed AITL were retrospectively enrolled in the present study. For all of them, EBV serology data were available. Results: Of 9 patients, 7 (77.7%) had a triple-positive serology (VCA-IgG, VCA-IgM, EBNA-IgG ) for EBV. These patients were characterized by bone marrow involvement, high incidence of thrombocytopenia, and poor prognosis according to Revised International Prognostic Index and Prognostic Index for Angioimmunoblastic T-cell Lymphoma scores. Conclusion: Assessment of both viremia and serology for EBV could be useful in patients with clinical and laboratory data suggesting lymphoma diagnosis; furthermore, although our data need to be validated in a larger cohort of patients, triple positivity for EBV serology might help to direct the diagnosis toward AITL

Two cases of angioimmunoblastic T-cell lymphoma with concomitant positive serology for acute Epstein-Barr virus infection

TL) is a rare type of peripheral T-celllymphoma. Epstein-Barr virus (EBV) isknown to be associated with pathogenesisand histological progression of AITL andthe onset of the disease often mimics aninfectious process. Here we describe twocases of patients with serology for acuteEBV infection at the onset of AITL.IntroductionAngioimmunoblastic T-cell lymphom

Case Report: Microangiopathic Hemolytic Anemia With Normal ADAMTS13 Activity

Thrombotic microangiopathies (TMAs) include a heterogeneous group of diseases characterized by abnormalities in the vessel walls of arterioles and capillaries resulting in microvascular thrombosis that typically presents with a microangiopathic hemolytic anemia (MAHA) and severe thrombocytopenia. We describe here the case of an 82-year-old woman, who came to our attention for a clinical condition consistent with thrombotic microangiopathy. Even if initially highly suggestive for a thrombotic thrombocytopenic purpura (TTP), the elevated ADAMTS13 activity together with the alteration of the main coagulation parameters (D-dimer elevation, fibrinogen consumption, slightly prolonged prothrombin time), induced us to consider several other diseases in the differential diagnostic process. The case evolved toward a suspected overlapped secondary hemophagocytic syndrome, though the hyperferritinemia was finally interpreted within the frame of a cytokine storm. After a complex diagnostic workup, the clinical and biochemical parameters guided us toward the diagnosis of a cancer-related microangiopathic hemolytic anemia (CR-MAHA) secondary to a relapsing breast cancer with multiple metastatic localizations. Prednisone 1 mg/kg body weight was started, and several units of fresh frozen plasma were infused, obtaining a good control of the hemolysis. No specific oncological therapies were, however, possible, due to the older age and the critically compromised general condition of the patient; therefore, after clinical stabilization, the patient was discharged for treatment in a palliative care Hospital

Specific pattern of cell cycle during limb fetal myogenesis

AbstractTight regulation of cell proliferation and differentiation is required to ensure proper growth during development and post-natal life. The source and nature of signals regulating cell proliferation are not well identified in vivo. We investigated the specific pattern of proliferating cells in mouse limbs, using the Fluorescent ubiquitynation-based cell-cycle indicator (Fucci) system, which allowed the visualization of the G1, G1/S transition and S/G2/M phases of the cell cycle in red, yellow or green fluorescent colors, respectively. We also used the retroviral RCAS system to express a Fucci cassette in chick embryos. We performed a comprehensive analysis of the cell cycle state of myogenic cells in fetal limb muscles, adult myoblast primary cultures and isolated muscle fiber cultures using the Fucci transgenic mice. We found that myonuclei of terminally differentiated muscle fibers displayed Fucci red fluorescence during mouse and chick fetal development, in adult isolated muscle fiber (ex vivo) and adult myoblast (in vitro) mouse cultures. This indicated that myonuclei exited from the cell cycle in the G1 phase and are maintained in a blocked G1-like state. We also found that cycling muscle progenitors and myoblasts in G1 phase were not completely covered by the Fucci system. During mouse fetal myogenesis, Pax7+ cells labeled with the Fucci system were observed mostly in S/G2/M phases. Proliferating cells in S/G2/M phases displayed a specific pattern in mouse fetal limbs, delineating individualized muscles. In addition, we observed more Pax7+ cells in S/G2/M phases at muscle tips, compared to the middle of muscles. These results highlight a specific spatial regionalization of cycling cells at the muscle borders and muscle–tendon interface during fetal development