Cooperation and Competition in a Duopoly R&D Market

In a general setting with uncertainty and spillovers in R&D activity, we consider the incentive to cooperate among firms at any or all of the following three stages. Firms can jointly agree on the level of R&D expenditures, they can set up joint research facilities, and/or they can engage in an information sharing agreements, by which they agree to share any findings with the other firm. We compare expenditures on R&D, profit levels, and welfare levels across the different possible cooperative and competitive setups and offer antitrust implications. Our model differs from previous analyses in three important ways. First, most studies consider only research aimed at lowering production costs, and therefore consider only situations where total profits fall as spillovers increase. We allow for the possibility of product innovation, and define the concepts of offsetting spillovers (falling total profits) and incremental spillovers (when total profits increase as spillovers increase). Second, we consider a wider variety of cooperation possibilities than do most prior studies. Finally, we use far more general functional forms than is usual in the literature.

Secondary analysis of an RCT on Emergency Department-Initiated Tobacco Control: Repeatedly assessed point-prevalence abstinence up to 12 months and extension of results through a 10-year follow-up.

INTRODUCTION:Emergency departments (EDs) are opportune places for tobacco control interventions. The 'Tobacco Control in an Urban Emergency Department' (TED) study, ISRCTN41527831, originally evaluated the effect of motivational interviewing on-site plus up to four booster telephone calls on 12-month abstinence. This study's aim was to evaluate the effect of the intervention on 7-day point-prevalence abstinence at 10 years follow-up (primary outcome) as well as on repeated point-prevalence abstinence at 1, 3, 6, 12 months and at 10 years (continual smoking abstinence, secondary outcome). METHODS:At the 10 years follow-up and after informed consent, study participants responded to a mailed questionnaire. The primary outcome was analyzed in observed-only and in all-cases analyses. The secondary outcomes were analyzed using a multiple adjusted GLMM for binary outcomes. RESULTS:Out of 1012 TED-study participants, 986 (97.4%) were alive and 231 (23.4% of 986) responded to the follow-up at 10 years. For observed-only and all-cases analyses, the effect of the baseline intervention on 7-day point-prevalence abstinence at the 10 years follow-up was statistically non-significant. However, when taking into account all repeated measures, the intervention significantly influenced continual abstinence with odds ratio 1.32 (95% CI: 1.01-1.73; p=0.042). Baseline motivation, perceived self-efficacy to stop smoking, and nicotine dependency were independently associated with long-term continual smoking abstinence (all p<0.05). CONCLUSIONS:A conventional analysis failed to confirm a significant effect of the ED-initiated tobacco control intervention on the point-prevalence abstinence at 10 years. Results from a more integrative analysis nonetheless indicated an enduring intervention effect on continual abstinence among smokers first encountered in the emergency department setting 10 years earlier

Adjoint algebraic entropy

The new notion of adjoint algebraic entropy of endomorphisms of Abelian groups is introduced. Various examples and basic properties are provided. It is proved that the adjoint algebraic entropy of an endomorphism equals the algebraic entropy of the adjoint endomorphism of the Pontryagin dual. As applications, we compute the adjoint algebraic entropy of the shift endomorphisms of direct sums, and we prove an Addition Theorem for the adjoint algebraic entropy of bounded Abelian groups. A dichotomy is established, stating that the adjoint algebraic entropy of any endomorphism can take only values zero or infinity. As a consequence, we obtain the following surprising discontinuity criterion for endomorphisms: every endomorphism of a compact abelian group, having finite positive algebraic entropy, is discontinuous.Comment: 27 page

Resolutions of surfaces with big cotangent bundle and A_2 singularities

Neste trabalho obtemos um novo critério para garantir que a resolução duma superfície de tipo geral com singularidades canónicas tem o fibrado cotangente grande, e um novo limite inferior para os valores de d para os quais existem superfícies lisas com o fibrado cotangente grande que são equivalentes por deformação a uma hipersuperfície lisa em P^3 de grau d

Development of A Micro-CT Scanner with Dual-Energy Option and Endovascular Contrast Agent Administration Protocol for Fetal and Neonatal Virtual Autopsy

The rate of parental consent for fetal and perinatal autopsy is decreasing, whereas parents are more likely to agree to virtual autopsy by non-invasive imaging methods. Fetal and perinatal virtual autopsy needs high-resolution and good soft-tissue contrast for investigation of the cause of death and underlying trauma or pathology in fetuses and stillborn infants. This is offered by micro-computed tomography (CT), as opposed to the limited resolution provided by clinical CT scanners, and this is one of the most promising tools for non-invasive perinatal postmortem imaging. We developed and optimized a micro-CT scanner with a dual-energy imaging option. It is dedicated to post-mortem CT angiography and virtual autopsy of fetuses and stillborn infants in that the chamber can be cooled down to around 5 °C; this increases tissue rigidity and slows decomposition of the native specimen. This, together with the dedicated gantry-based architecture, attempts to reduce potential motion artifacts. The developed methodology is based on prior endovascular injection of a BaSO4-based contrast agent. We explain the design choices and considerations for this scanner prototype. We give details of the treatment of the optimization of the dual-energy and virtual mono-energetic imaging option that has been based on minimizing noise propagation and maximizing the contrast-to-noise ratio for vascular features. We demonstrate the scanner capabilities with proof-of-concept experiments on phantoms and stillborn piglets

Sustained increase of alpha7 nicotinic receptors and choline-induced improvement of learning deficit in STOP knock-out mice.

International audienceMice deficient in the microtubule stabilizing protein STOP (stable tubule only polypeptide) show synaptic plasticity anomalies in hippocampus, dopamine hyper-reactivity in the limbic system and severe behavioral deficits. Some of these disturbances are alleviated by long-term antipsychotic treatment. Therefore, this mouse line represents a pertinent model for some aspects of schizophrenia symptomatology. Numerous data support dysfunction of nicotinic neurotransmission in schizophrenia and epidemiological studies show increased tobacco use in schizophrenic patients, in whom nicotine has been reported to improve cognitive deficits and impairment in sensory gating. In this study, we examined potential alterations in cholinergic (ACh) and nicotinic components and functions in STOP mutant mice. STOP KO mice displayed no variation of the density of ACh esterase and beta2* nicotinic receptors (nAChRs), large reductions in the density of vesicular ACh transporter and alpha6* nAChRs and marked increases in the density of alpha7 nAChRs, in some brain areas. STOP KO mice were hypersensitive to the stimulating locomotor effect of nicotine and, interestingly, their impaired performance in learning the cued version of the water maze were improved by administration of the preferential alpha7 nAChR agonist choline. Altogether, our data show that the deletion of the ubiquitous STOP protein elicited restricted alterations in ACh components. They also suggest that nicotinic neurotransmission can be deficient in STOP KO mice and that mutant mice can represent a meaningful model to study some nicotinic dysfunctions and therapeutic treatments

X-ray magneto-optics of lanthanide materials: principles and applications

Lanthanide metals are a particular class of magnetic materials in which the magnetic moments are carried mainly by the localized electrons of the 4f shell. They are frequently found in technically relevant systems, to achieve, e.g., high magnetic anisotropy. Magneto-optical methods in the x-ray range are well suited to study complex magnetic materials in an element-specific way. In this work, we report on recent progress on the quantitative determination of magneto-optical constants of several lanthanides in the soft x-ray region and we show some examples of applications of magneto-optics to hard-magnetic interfaces and exchange-coupled layered structures containing lanthanide elements.Comment: 7 pages, 6 figures, invited contribution to the Symposium "X-ray magneto-optics" of the Spring Meeting of the German Physical Society held in Regensburg, Germany, 8-12 March 2004. Revised version, minor change

Tumor and circulating biomarkers in patients with second-line hepatocellular carcinoma from the randomized phase II study with tivantinib

ARQ 197-215 was a randomized placebo-controlled phase II study testing the MET inhibitor tivantinib in second-line hepatocellular carcinoma (HCC) patients. It identified tumor MET as a key biomarker in HCC. Aim of this research was to study the prognostic and predictive value of tumor (MET, the receptor tyrosine kinase encoded by the homonymous MNNG-HOS transforming gene) and circulating (MET, hepatocyte growth factor [HGF], alpha-fetoprotein [AFP], vascular endothelial growth factor [VEGF]) biomarkers in second-line HCC. Tumor MET-High status was centrally assessed by immunohistochemistry. Circulating biomarkers were centrally analyzed on serum samples collected at baseline and every 4-8 weeks, using medians as cut-off to determine High/Low status. Tumor MET, tested in 77 patients, was more frequently High after (82%) versus before (40%) sorafenib. A significant interaction (p = 0.04) between tivantinib and baseline tumor MET in terms of survival was observed. Baseline circulating MET and HGF (102 patients) High status correlated with shorter survival (HR 0.61, p = 0.03, and HR 0.60, p = 0.02, respectively), while the association between AFP (104 patients) or VEGF (103 patients) status and survival was non-significant. Conclusions: Tumor MET levels were higher in patients treated with sorafenib. Circulating biomarkers such as MET and HGF may be prognostic in second-line HCC. These results need to be confirmed in larger randomized clinical trials

Routine frailty assessment predicts postoperative complications in elderly patients across surgical disciplines – a retrospective observational study

BACKGROUND: Frailty is a frequent and underdiagnosed functional syndrome involving reduced physiological reserves and an increased vulnerability against stressors, with severe individual and socioeconomic consequences. A routine frailty assessment was implemented at our preoperative anaesthesia clinic to identify patients at risk. OBJECTIVE: This study examines the relationship between frailty status and the incidence of in-hospital postoperative complications in elderly surgical patients across several surgical disciplines. DESIGN: Retrospective observational analysis. SETTING: Single center, major tertiary care university hospital. Data collection took place between June 2016 and March 2017. PATIENTS: Patients 65 years old or older were evaluated for frailty using Fried's 5-point frailty assessment prior to elective non-cardiac surgery. Patients were classified into non-frail (0 criteria, reference group), pre-frail (1-2 positive criteria) and frail (3-5 positive criteria) groups. MAIN OUTCOME MEASURES: The incidence of postoperative complications was assessed until discharge from the hospital, using the roster from the National VA Surgical Quality Improvement Program. Propensity score matching and logistic regression analysis were performed. RESULTS: From 1186 elderly patients, 46.9% were classified as pre-frail (n = 556), and 11.4% as frail (n = 135). The rate of complications were significantly higher in the pre-frail (34.7%) and frail groups (47.4%), as compared to the non-frail group (27.5%). Similarly, length of stay (non-frail: 5.0 [3.0;7.0], pre-frail: 7.0 [3.0;9.0], frail 8.0 [4.5;12.0]; p < 0.001) and discharges to care facilities (non-frail:1.6%, pre-frail: 7.4%, frail: 17.8%); p < 0.001) were significantly associated with frailty status. After propensity score matching and logistic regression analysis, the risk for developing postoperative complications was approximately two-fold for pre-frail (OR 1.78; 95% CI 1.04-3.05) and frail (OR 2.08; 95% CI 1.21-3.60) patients. CONCLUSIONS: The preoperative frailty assessment of elderly patients identified pre-frail and frail subgroups to have the highest rate of postoperative complications, regardless of age, surgical discipline, and surgical risk. Significantly increased length of hospitalisation and discharges to care facilities were also observed. Implementation of routine frailty assessments appear to be an effective tool in identifying patients with increased risk. Now future studies are needed to investigate whether patients benefit from optimization of patient counselling, process planning, and risk reduction protocols based on the application of risk stratification