Pricing in Social Networks with Negative Externalities

We study the problems of pricing an indivisible product to consumers who are embedded in a given social network. The goal is to maximize the revenue of the seller. We assume impatient consumers who buy the product as soon as the seller posts a price not greater than their values of the product. The product's value for a consumer is determined by two factors: a fixed consumer-specified intrinsic value and a variable externality that is exerted from the consumer's neighbors in a linear way. We study the scenario of negative externalities, which captures many interesting situations, but is much less understood in comparison with its positive externality counterpart. We assume complete information about the network, consumers' intrinsic values, and the negative externalities. The maximum revenue is in general achieved by iterative pricing, which offers impatient consumers a sequence of prices over time. We prove that it is NP-hard to find an optimal iterative pricing, even for unweighted tree networks with uniform intrinsic values. Complementary to the hardness result, we design a 2-approximation algorithm for finding iterative pricing in general weighted networks with (possibly) nonuniform intrinsic values. We show that, as an approximation to optimal iterative pricing, single pricing can work rather well for many interesting cases, but theoretically it can behave arbitrarily bad

SHORT COMMUNICATION: Complementary tumor induction in neural grafts exposed to N-ethyl-N-nitrosourea and an activated myc gene

Using a combination of transplacental carcinogen exposure and retrovirus-mediated oncogene transfer into fetal brain transplants, we have studied complementary transformation by N-ethyl-N-nitrosourea (NEU) and the v-myc oncogene in the nervous system. Previous experiments had demonstrated that both agents will not induce tumors independently whereas simultaneous expression of v-H-ras and v-gag/myc exerted a powerful transforming potential in neural grafts. In order to identify other genetic alterations that co-operate with an activated myc gene, the neurotropic carcinogen NEU was used to generate mutations of cellular genes. On embryonic day 14 (ED14), pregnant donor animals (F344 rats) received a single i.v. dose of NEU (50 mg/kg). Twenty-four hours later (ED15), the fetal brains were removed, triturated and incubated with a retroviral vector carrying the v-gag/myc oncogene. Subsequently, these primary cell suspensions were transplanted stereotactically into the caudate-putamen of syngenic adult recipients. After latency periods of 3-6 months, 5 of 10 recipients harboring ED15 fetal brain transplants developed malignant, poorly differentiated neuroectodermal tumors in the grafts. No tumor development was observed in seven recipients harboring ED16 neural grafts. Cell lines were established from three tumors and the 110 kd gag/myc fusion protein encoded by the retroviral construct was identified in the tumors by Western blotting. Several candidate genes for mutational activation by NEU including the H-ras, K-ras and neu oncogenes were analyzed for specific point mutations by polymerase chain reaction (PCR) and direct DNA sequencing of the PCR products. However, no mutations were found in any of these genes. These findings lend further support to the multistep hypothesis of neoplastic transformation in the brain. The tumors induced in this model provide an interesting tool for the identification of genes that co-operate with an activated myc gene in neurocarcinogenesi

Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids

SummaryBackgroundA recent case-controlled study reported an increased risk of diabetes mellitus in patients treated with inhaled corticosteroids for asthma or COPD, versus age-matched controls.ObjectiveThe purpose of the current study was to evaluate whether there was an increased risk of new onset diabetes mellitus or hyperglycaemia among patients with asthma or COPD treated with inhaled corticosteroids.MethodsA retrospective analysis evaluated all double-blind, placebo-controlled, trials in patients ≥4 years of age involving budesonide or budesonide/formoterol in asthma (26 trials; budesonide: n = 9067; placebo: n = 5926), and in COPD (8 trials; budesonide: n = 4616; non-ICS: n = 3643). A secondary dataset evaluated all double-blind, controlled trials in asthma involving the use of inhaled corticosteroids (60 trials; budesonide: n = 33,496; fluticasone: n = 2773).ResultsIn the primary asthma dataset, the occurrence of diabetes mellitus/hyperglycaemia adverse events (AEs) was 0.13% for budesonide and 0.13% for placebo (HR 0.98 [95% CI: 0.38–2.50], p = 0.96) and serious adverse events (SAEs) was 0% for budesonide and 0.05% for placebo. In the secondary dataset, the occurrence of diabetes/hyperglycaemia as AE and SAE was 0.19% and 0.03%, respectively. In the COPD dataset, the occurrence of diabetes mellitus/hyperglycaemia AEs was 1.3% for budesonide and 1.2% for non-ICS (HR 0.99 [95% CI: 0.67–1.46], p = 0.96) and SAEs was 0.1% for budesonide and 0.03% for non-ICS.Conclusion and clinical relevanceTreatment with inhaled corticosteroids in patients with asthma or COPD was not associated with increased risk of new onset diabetes mellitus or hyperglycaemia

Comorbidity burden in axial spondyloarthritis: a cluster analysis

Objectives To examine how comorbidities cluster in axial spondyloarthritis (axSpA) and whether these clusters are associated with quality of life, global health and other outcome measures. Methods We conducted a cross-sectional study of consecutive patients meeting ASAS criteria for axSpA in Liverpool, UK. Outcome measures included quality of life (EQ5D), global health and disease activity (BASDAI). We used hierarchical cluster analysis to group patients according to 38 pre-specified comorbidities. In multivariable linear models, the associations between distinct comorbidity clusters and each outcome measure were compared, using axSpA patients with no comorbidities as the reference group. Analyses were adjusted for age, gender, symptom duration, BMI, deprivation, NSAID-use and smoking. Results We studied 419 patients (69% male, mean age 46 years). 255 patients (61%) had at least one comorbidity, among whom the median number was 1 (range 1–6). Common comorbidities were hypertension (19%) and depression (16%). Of 15 clusters identified, the most prevalent clusters were hypertension-coronary heart disease and depression-anxiety. Compared with patients with no comorbidities, the fibromyalgia-irritable bowel syndrome cluster was associated with adverse patient-reported outcome measures; these patients reported 1.5-unit poorer global health (95%CI 0.01, 2.9), reduced quality of life (0.25-unit lower EQ5D; 95%CI −0.37, −0.12) and 1.8-unit higher BASDAI (95% CI 0.4, 3.3). Similar effect estimates were found for patients in the depression-anxiety cluster. Conclusion Comorbidity is common among axSpA patients. The two most common comorbidities were hypertension and depression. Patients in the depression-anxiety and fibromyalgia-IBS clusters reported poorer health and increased axSpA severity

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects

Museu Militar de Bragança: fundação, práticas museológicas

O objecto de estudo decidido para este trabalho centra-se na reflexão sobre o Museu Militar de Bragança hoje, e as suas potencialidades enquanto gerador de desenvolvimento social. Para fazer esta reflexão consideramos pertinente a pesquisa histórica do museu, desde a sua fundação, atendendo à função e os objectivos propostos inicialmente pela instituição, bem como aos procedimentos museológicos actualmente observados. O museu militar de Bragança surge no primeiro quartel do século XX como um espaço de salvaguarda das memórias dos feitos bélicos das forças militares sedeadas em Bragança. Após a erradicação da última unidade militar de Bragança, em 1958, o museu é temporariamente encerrado e trasladado o acervo para o Museu Militar de Lisboa. Já na década de 80 do século XX o museu volta a ser instalado no local de origem, a torre de menagem do castelo, e impõe-se como espaço \ memória das vivências militares da cidade. No entanto, cremos que, para que o Museu Militar potencie as suas ferramentas enquanto gerador de desenvolvimento social, seria desejável consumar alguns procedimentos museológicos, actualmente já impostos na Lei Quadro dos museus. Neste sentido, na segunda parte do presente trabalho propomo-nos estabelecer um plano geral de práticas museológicas adaptado ao caso concreto do Museu Militar de Bragança. O presente trabalho aspira assim: a caracterizar sucintamente o conceito actual de Museu; a descrever o edifício onde está instalado o Museu Militar de Bragança, que constitui parte integrante da sua valência enquanto gerador de desenvolvimento local; a pesquisar o processo de fundação do museu, os seus objectivos e funções enquanto parte integrante de um maior complexo militar como era o quartel. (...