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

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

Optimal network topologies for local search with congestion

The problem of searchability in decentralized complex networks is of great importance in computer science, economy and sociology. We present a formalism that is able to cope simultaneously with the problem of search and the congestion effects that arise when parallel searches are performed, and obtain expressions for the average search cost--written in terms of the search algorithm and the topological properties of the network--both in presence and abscence of congestion. This formalism is used to obtain optimal network structures for a system using a local search algorithm. It is found that only two classes of networks can be optimal: star-like configurations, when the number of parallel searches is small, and homogeneous-isotropic configurations, when the number of parallel searches is large.Comment: 4 pages. Final version accepted in PR

Effect of nocturnal Temperature-controlled Laminar Airflow on the reduction of severe exacerbations in patients with severe allergic asthma: a meta-analysis

Background: Allergen avoidance is important in allergic asthma management. Nocturnal treatment with Temperature-controlled Laminar Airflow (TLA) has been shown to provide a significant reduction in the exposure to allergens in the breathing zone, leading to a long-term reduction in airway inflammation and improvement in Quality of life (QoL). Allergic asthma patients symptomatic on Global Initiative for Asthma (GINA) step 4/5 were found to benefit the most as measured by Asthma Quality of Life Questionnaire (AQLQ). However, the effect of TLA on severe asthma exacerbations is uncertain and therefore a meta-analysis was performed. Methods: Patients with severe allergic asthma (GINA 4/5) were extracted from two 1-year randomised, double-blind, placebo-controlled trials conducted with TLA. A meta-analysis of the effect on severe exacerbations was performed by negative binomial regression in a sequential manner, defined by baseline markers of asthma control (symptoms and QoL scores). Results: The pooled dataset included 364patients. Patients with more symptoms at baseline (ACT3; N=179), had a significant mean 41% reduction in severe exacerbations (RR=0.59 (0.38-0.90); p=0.015) in favour of TLA. Higher ACQ7 cut-points of 3.5-4.5 resulted in significant reductions of 48-59%.More uncontrolled patients based on AQLQ total and symptom domains ≤3.0 at baseline also showed a significant reduction in severe exacerbations for TLA vs. placebo ((47% (p=0.037) and 53% (p=0.011), respectively). The meta-analysis also confirmed a significant difference in AQLQ-responders ((Minimal Clinically Important Difference)≥0.5; 74% vs. 43%, p=0.04). Conclusion: This meta-analysis of individual patient data shows a beneficial effect on severe exacerbations and quality of life for TLA over placebo in more symptomatic patients with severe allergic asthma. These outcomes support the national management recommendations for patients with symptomatic severe allergic asthma. The actual effect of TLA on severe exacerbations should be confirmed in a prospective study with larger numbers of patients

Stem cells as a therapeutic tool for the blind: biology and future prospects

Retinal degeneration due to genetic, diabetic and age-related disease is the most common cause of blindness in the developed world. Blindness occurs through the loss of the light-sensing photoreceptors; to restore vision, it would be necessary to introduce alternative photosensitive components into the eye. The recent development of an electronic prosthesis placed beneath the severely diseased retina has shown that subretinal stimulation may restore some visual function in blind patients. This proves that residual retinal circuits can be reawakened after photoreceptor loss and defines a goal for stem-cell-based therapy to replace photoreceptors. Advances in reprogramming adult cells have shown how it may be possible to generate autologous stem cells for transplantation without the need for an embryo donor. The recent success in culturing a whole optic cup in vitro has shown how large numbers of photoreceptors might be generated from embryonic stem cells. Taken together, these threads of discovery provide the basis for optimism for the development of a stem-cell-based strategy for the treatment of retinal blindness

Skin Barrier Development Depends on CGI-58 Protein Expression during Late-Stage Keratinocyte Differentiation

Adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) are limiting in cellular triglyceride catabolism. Although ATGL deficiency is compatible with normal skin development, mice globally lacking CGI-58 die postnatally and exhibit a severe epidermal permeability barrier defect, which may originate from epidermal and/or peripheral changes in lipid and energy metabolism. Here, we show that epidermis-specific disruption of CGI-58 is sufficient to provoke a defect in the formation of a functional corneocyte lipid envelope linked to impaired ω-O-acylceramide synthesis. As a result, epidermis-specific CGI-58-deficient mice show severe skin dysfunction, arguing for a tissue autonomous cause of disease development. Defective skin permeability barrier formation in global CGI-58-deficient mice could be reversed via transgenic restoration of CGI-58 expression in differentiated but not basal keratinocytes suggesting that CGI-58 is essential for lipid metabolism in suprabasal epidermal layers. The compatibility of ATGL deficiency with normal epidermal function indicated that CGI-58 may stimulate an epidermal triglyceride lipase beyond ATGL required for the adequate provision of fatty acids as a substrate for ω-O-acylceramide synthesis. Pharmacological inhibition of ATGL enzyme activity similarly reduced triglyceride-hydrolytic activities in wild-type and CGI-58 overexpressing epidermis implicating that CGI-58 participates in ω-O-acylceramide biogenesis independent of its role as a coactivator of epidermal triglyceride catabolism

Development and initial validation of the Bristol Impact of Hypermobility questionnaire

© 2016 Chartered Society of Physiotherapy Objectives Stage 1 – to identify the impact of joint hypermobility syndrome (JHS) on adults; Stage 2 – to develop a questionnaire to assess the impact of JHS; and Stage 3 – to undertake item reduction and establish the questionnaire's concurrent validity. Design A mixed methods study employing qualitative focus groups and interviews (Stage 1); a working group of patients, clinicians and researchers, and ‘think aloud’ interviews (Stage 2); and quantitative analysis of questionnaire responses (Stage 3). Setting Stages 1 and 2 took place in one secondary care hospital in the UK. Members of a UK-wide patient organisation were recruited in Stage 3. Participants In total, 15, four and 615 participants took part in Stages 1, 2 and 3, respectively. Inclusion criteria were: age ≥18 years; diagnosis of JHS; no other conditions affecting physical function; able to give informed consent; and able to understand and communicate in English. Interventions None. Main outcome measures The development of a questionnaire to assess the impact of JHS. Results Stage 1 identified a wide range of impairments, activity limitations and participation restrictions In Stage 2, a draft questionnaire was developed and refined following ‘think aloud’ analysis, leaving 94 scored items. In Stage 3, items were removed on the basis of low severity and/or high correlation with other items. The final Bristol Impact of Hypermobility (BIoH) questionnaire had 55 scored items, and correlated well with the physical component score of the Short Form 36 health questionnaire (r=−0.725). Conclusions The BIoH questionnaire demonstrated good concurrent validity. Further psychometric properties need to be established

Smoke gets in your eyes: re-reading gender in the "nostalgia film"

Upon its release, American Graffiti (George Lucas, 1973) was much admired by critics and audiences alike. Yet, in subsequent years, the film became known for its supposed “flattening of history,” and celebration of patriarchal values. This article demonstrates that such a judgement owes much to Fredric Jameson’s historically contingent work on postmodernism, which argues that American Graffiti constitutes the paradigmatic nostalgia film. In contrast, using close textual analysis, I demonstrate that American Graffiti provides a more complex construction of the past, and of gender, than has hitherto been acknowledged. Far from blindly idealising the early 1960s, the film interrogates the processes through which the period and its gender relations come to be idealised. This article has consequences not only for our understanding of Lucas’ seminal film, but also for the American New Wave, and the “nostalgia” text

Incomplete financial markets and jumps in asset prices

For incomplete financial markets, jumps in both prices and consumption can be unavoidable. We consider pure-exchange economies with infinite horizon, discrete time, uncertainty with a continuum of possible shocks at every date. The evolution of shocks follows a Markov process, and fundamentals depend continuously on shocks. It is shown that: (1) equilibria exist; (2) for effectively complete financial markets, asset prices depend continuously on shocks; and (3) for incomplete financial markets, there is an open set of economies U such that for every equilibrium of every economy in U, asset prices at every date depend discontinuously on the shock at that date