Political Cycles : Issue Ownership and the Opposition Advantage

We propose a two dimensional infinite horizon model of public consumption in which investments are decided by a winner-take-all election. Investments in the two public goods create a linkage across periods. We follow the idea of issue ownership introduced by Petrocik (1996) in considering parties with different specialties. We show that the incumbent party vote share decreases the longer it stays in power. The median voter is generally not indifferent between the two parties and, when she is moderate enough, no party can maintain itself in power for ever. This result holds when the parties' main objective is to win the election and is compatible with a large range of candidates sub-objectives, that may change from one election to the next. Finally, the more parties are specialized and the more public policies have long-term effects, the more political cycles are likely to occur. ...French Abstract : Nous proposons un modèle de consommation publique à horizon infini. Les investissements engagés dans la fourniture de deux biens publics sont déterminés par les élections. Ces investissements créent un lien entre les élections successives. Nous suivons l'idée introduite par Petrocik (1996) selon laquelle les partis "possèdent" certains thèmes, en considérant qu'ils ont des spécialités différentes. Nous montrons que la part des voix du parti au pouvoir décroît entre deux élections. L'électeur médian n'est généralement pas indifférent entre les deux partis et, lorsqu'il est suffisamment modéré, aucun parti ne peut se maintenir indéfiniment au pouvoir. Ce résultat est valide lorsque l'objectif principal des partis est de gagner l'élection et est compatible avec un grand ensemble de sous objectifs, qui peuvent changer d'une élection à l'autre. Finalement, plus les partis sont spécialisés et plus les politiques ont des effets de long terme, plus les cycles politiques sont susceptibles d'apparaître.CYCLES; ALTERNATION; ISSUE OWNERSHIP; PUBLIC GOODS; OPPOSITION

Evolution of BCL-2/IgH hybrid gene RNA expression during treatment of T(14;18)-bearing follicular lymphomas

Bcl-2, the gene over-expressed in follicular lymphomas (FL), is able to block chemotherapy-induced apoptosis. Consequently, we wondered whether bcl-2/IgH expression variations during treatment of FL could predict the outcome of patients with t(14;18)-bearing FL. For this purpose, we used a reverse transcription polymerase chain reaction (RT-PCR) assay to analyse 180 serial peripheral blood samples (PBS) during 34 treatment phases in 25 patients with t(14;18)-bearing FL. In all patients but two, bcl-2/IgH gene expression was demonstrated in pre-treatment samples. During 16 out of the 34 treatment phases (47%), bcl-2/IgH expression became negative: all but one were responders to chemotherapy. This conversion was transient in six cases. In 18 treatment phases, bcl2/IgH expression remained detectable: eight were clinically considered as treatment failures, while eight others achieved PR and two achieved CR. We observed a significant correlation between treatment response and RNA PCR results (P = 0.002). Three-year overall survival of patients with stable bcl2/IgH-negative conversion was 100% compared to 54% for the remaining patients (P = 0.069); 3-year freedom from progression was respectively 87.5% and 13% (P = 0.005). These results indicate a correlation between bcl-2/IgH expression variations and both clinical response and outcome. Whether this might predict disease outcome early remains to be confirmed. © 1999 Cancer Research Campaig

Targeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma

Cancer cells activate stress-response mechanisms to adapt themselves to a variety of stressful conditions. Among these protective mechanisms, those controlled by the stress-induced nuclear protein 1 (NUPR1 ) belong to the most conserved ones. NUPR1 is an 82-residue-long, monomeric, basic and intrinsically disordered protein (IDP), which was found to be invariably overexpressed in some, if not all, cancer tissues. Remarkably, we and others have previously showed that genetic inactivation of the Nupr1 gene antagonizes the growth of pancreatic cancer as well as several other tumors. With the use of a multidisciplinary strategy by combining biophysical, biochemical, bioinformatic, and biological approaches, a trifluoperazine-derived compound, named ZZW-115, has been identified as an inhibitor of the NUPR1 functions. The anticancer activity of the ZZW-115 was first validated on a large panel of cancer cells. Furthermore, ZZW-115 produced a dose-dependent tumor regression of the tumor size in xenografted mice. Mechanistically, we have demonstrated that NUPR1 binds to several importins. Because ZZW-115 binds NUPR1 through the region around the amino acid Thr68, which is located into the nuclear location signal (NLS) region of the protein, we demonstrated that treatment with ZZW-115 inhibits completely the translocation of NUPR1 from the cytoplasm to the nucleus by competing with importins

Challenges of caring for older patients with multimorbidity including cancer

Introduction: As the population is ageing, the number of older patients with multimorbidity including cancer continues to increase. To improve care for these patients, the European Union-funded project "Streamlined Geriatric and Oncological evaluation based on IC Technology" (GERONTE) was initiated to develop a new, patientcentred, holistic care pathway. The aim of this paper is to analyse what challenges are encountered in everyday clinical practice according to patients, their informal caregivers, and healthcare professionals as a starting point for the development of the care pathway.Materials and Methods: An expert panel of cancer and geriatrics specialists participated in an online survey to answer what challenges they experience in caring for older patients with multimorbidity including cancer and what treatment outcomes could be improved. Furthermore, in-depth interviews with older patients and their informal caregivers were organised to assess what challenges they experience.Results: Healthcare professionals (n = 36) most frequently mentioned the challenge of choosing the best treatment in light of the lack of evidence in this population and how to handle interactions between the (cancer) treatment and multimorbidities. Twelve patients and caregivers participated, and they most frequently mentioned challenges related to treatment outcomes, such as how to deal with symptoms of disease or treatment and how to maintain quality of life. From the challenges, five main themes emerged that should be taken into account when developing a new care pathway for older patients with multimorbidity including cancer. Two themes focus on decision making aspects such as personalized treatment recommendations and inclusion of nononcologic information, two focus on patient support and monitoring to maintain quality of life and functioning, and one overarching theme addresses care coordination to prevent fragmentation of care.Discussion: In conclusion, the management of older patients with multimorbidity including cancer is complex and although progress has been made on improving aspects of their care, challenges remain and patients are at risk of receiving inappropriate, unnecessary, and potentially harmful treatment. A patient-centred care pathway that integrates solutions to the five main themes and that moves away from a single-disease centred approach is needed.Horizon 2020 (H2020

ZZW-115-dependent inhibition of NUPR1 nuclear translocation sensitizes cancer cells to genotoxic agents

Establishing the interactome of the cancer-associated stress protein Nuclear Protein 1 (NUPR1), we found that it binds to several hundreds of proteins, including proteins involved in nuclear translocation, DNA repair, and key factors of the SUMO pathway. We demonstrated that the NUPR1 inhibitor ZZW-115, an organic synthetic molecule, competes with importins for the binding to the NLS region of NUPR1, thereby inhibiting its nuclear translocation. We hypothesized, and then proved, that inhibition of NUPR1 by ZZW-115 sensitizes cancer cells to DNA damage induced by several genotoxic agents. Strikingly, we found that treatment with ZZW-115 reduced SUMOylation of several proteins involved in DNA damage response (DDR). We further report that the presence of recombinant NUPR1 improved the SUMOylation in a cell-free system, indicating that NUPR1 directly stimulates the SUMOylation machinery. We propose that ZZW-115 sensitizes cancer cells to genotoxic agents by inhibiting the nuclear translocation of NUPR1 and thereby decreasing the SUMOylation-dependent functions of key proteins involved in the DDR

Sabotage in Contests: A Survey

A contest is a situation in which individuals expend irretrievable resources to win valuable prize(s). ‘Sabotage’ is a deliberate and costly act of damaging a rival’s' likelihood of winning the contest. Sabotage can be observed in, e.g., sports, war, promotion tournaments, political or marketing campaigns. In this article, we provide a model and various perspectives on such sabotage activities and review the economics literature analyzing the act of sabotage in contests. We discuss the theories and evidence highlighting the means of sabotage, why sabotage occurs, and the effects of sabotage on individual players and on overall welfare, along with possible mechanisms to reduce sabotage. We note that most sabotage activities are aimed at the ablest player, the possibility of sabotage reduces productive effort exerted by the players, and sabotage may lessen the effectiveness of public policies, such as affirmative action, or information revelation in contests. We discuss various policies that a designer may employ to counteract sabotage activities. We conclude by pointing out some areas of future research

Follicular lymphoma international prognostic index.

The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992. Univariate and multivariate analyses were used to propose a PI. This index was then tested on 919 patients. Five adverse prognostic factors were selected: age (> 60 years vs or = 120 g/L), number of nodal areas (> 4 vs or = 3 adverse factors, 27% of patients, HR = 4.3). This Follicular Lymphoma International Prognostic Index (FLIPI) appeared more discriminant than the International Prognostic Index proposed for aggressive non-Hodgkin lymphomas. Results were very similar in the confirmation group. The FLIPI may be used for improving treatment choices, comparing clinical trials, and designing studies to evaluate new treatments