Targeting leisure and business passengers with unsegmented pricing

We analyse the fare setting strategy of a leading European low-cost carrier, Ryanair, which, until recently, adopted an unsegmented pricing policy (all tickets belong to a single fare class). We show that, to account for different demand characteristics, the company adjusts the two main components governing the dynamics of posted fares, namely time (the number of days before departure) and capacity (the current number of available seats). We find that: 1) in routes with a strong presence of leisure (business) traffic, fares are set to be less (more) responsive to the time component; 2) in schedules more suitable for leisure (business) travellers, fares are set to be less (more) responsive to the capacity component

Do "clean hands" ensure healthy growth? Theory and Practice in the Battle against corruption

This paper analyzes the existing relationship between economic growth and the monitoring of corruption and examines the possible outcome of the implementation of a State reform in order to weed out corruption. Growth is always higher when monitoring is high and therefore corruption eradicated. But growth declines when monitoring against corruption is not too high, say intermediate, so much that it makes an equilibrium with corruption and little monitoring a more growth-enhancing solution. It is also stressed that when reforms to combat corruption appear to be implausible, they tend to curb most productive investments. The model is estimated using a dynamic panel data approach for Italy. Italy has been plagued by corruption and in the late 80s and early 90s several scandals erupted which led to the well-known "Clean Hands" (Mani pulite) inquiries. Empirical results support the theoretical model. Pubblicazione referata; ISSN: 1605-799

An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes

The Endoplasmatic Reticulum Aminopeptidases ERAP1 and ERAP2 are implicated in a variety of immune and non-immune functions. Most studies however have focused on their role in shaping the HLA class I peptidome by trimming peptides to the optimal size. Genome Wide Association Studies highlighted non-synonymous polymorphisms in their coding regions as associated with several immune mediated diseases. The two genes lie contiguous and oppositely oriented on the 5q15 chromosomal region. Very little is known about the transcriptional regulation and the quantitative variations of these enzymes. Here, we correlated the level of transcripts and proteins of the two aminopeptidases in B-lymphoblastoid cell lines from 44 donors harbouring allelic variants in the intergenic region between ERAP1 and ERAP2. We found that the presence of a G instead of an A at SNP rs75862629 in the ERAP2 gene promoter strongly influences the expression of the two ERAPs with a down-modulation of ERAP2 coupled with a significant higher expression of ERAP1. We therefore show here for the first time a coordinated quantitative regulation of the two ERAP genes, which can be relevant for the setting of specific therapeutic approaches

Direct learning ofLPVcontrollers from data

In many control applications, it is attractive to describe nonlinear (NL) and time-varying (TV) plants by linear parametervarying (LPV) models and design controllers based on such representations to regulate the behaviour of the system. The LPV system class offers the representation of NL and TV phenomena as a linear dynamic relationship between input and output signals, which relationship is dependent on some measurable signals, e.g., operating conditions, often called as scheduling variables. For such models, powerful control synthesis tools are available, but the way how to systematically convert available first principles models to LPV descriptions of the plant, to efficiently identify LPV models for control from data and to understand how modeling errors affect the control performance are still subject of undergoing research. Therefore, it is attractive to synthesize the controller directly from data without the need of modeling the plant and addressing the underlying difficulties. Hence, in this paper, a novel data-driven synthesis scheme is proposed in a stochastic framework to provide a practically applicable solution for synthesizing LPV controllers directly from data. Both the cases of fixed order controller tuning and controller structure learning are discussed and two different design approaches are provided. The effectiveness of the proposed methods is also illustrated by means of an academic example and a real application based simulation case study

Prognostic impact of coronary microcirculation abnormalities in systemic sclerosis: a prospective study to evaluate the role of non-invasive tests

INTRODUCTION: Microcirculation dysfunction is a typical feature of systemic sclerosis (SSc) and represents the earliest abnormality of primary myocardial involvement. We assessed coronary microcirculation status by combining two functional tests in SSc patients and estimating its impact on disease outcome. METHODS: Forty-one SSc patients, asymptomatic for coronary artery disease, were tested for coronary flow velocity reserve (CFR) by transthoracic-echo-Doppler with adenosine infusion (A-TTE) and for left ventricular wall motion abnormalities (WMA) by dobutamine stress echocardiography (DSE). Myocardial multi-detector computed tomography (MDCT) enabled the presence of epicardial stenosis, which could interfere with the accuracy of the tests, to be excluded. Patient survival rate was assessed over a 6.7- ± 3.5-year follow-up. RESULTS: Nineteen out of 41 (46%) SSc patients had a reduced CFR (≤2.5) and in 16/41 (39%) a WMA was observed during DSE. Furthermore, 13/41 (32%) patients showed pathological CFR and WMA. An inverse correlation between wall motion score index (WMSI) during DSE and CFR value (r = -0.57, P <0.0001) was observed; in addition, CFR was significantly reduced (2.21 ± 0.38) in patients with WMA as compared to those without (2.94 ± 0.60) (P <0.0001). In 12 patients with abnormal DSE, MDCT was used to exclude macrovasculopathy. During a 6.7- ± 3.5-year follow-up seven patients with abnormal coronary functional tests died of disease-related causes, compared to only one patient with normal tests. CONCLUSIONS: A-TTE and DSE tests are useful tools to detect non-invasively pre-clinical microcirculation abnormalities in SSc patients; moreover, abnormal CFR and WMA might be related to a worse disease outcome suggesting a prognostic value of these tests, similar to other myocardial diseases

Direct data-driven control of linear parameter-varying systems

In many control applications, nonlinear plants can be modeled as linear parameter-varying (LPV) systems, by which the dynamic behavior is assumed to be linear, but also dependent on some measurable signals, e.g., operating conditions. When a measured data set is available, LPV model identification can provide low complexity linear models that can embed the underlying nonlinear dynamic behavior of the plant. For such models, powerful control synthesis tools are available, but the way the modeling error and the conservativeness of the embedding affect the control performance is still largely unknown. Therefore, it appears to be attractive to directly synthesize the controller from data without modeling the plant. In this paper, a novel data-driven synthesis scheme is proposed to lay the basic foundations of future research on this challenging problem. The effectiveness of the proposed approach is illustrated by a numerical example

Targeted Therapies in Axial Psoriatic Arthritis

Specific and high-quality evidence on the efficacy of the current targeted therapies for axial disease in psoriatic arthritis (axPsA) is still scarce. Indeed, almost all the cohorts investigated in clinical trials on PsA consisted of patients with peripheral arthritis, where a small number of them also had axial involvement. Only one randomized controlled trial was so far specifically designed to assess the efficacy of a biological disease-modifying antirheumatic drug (DMARD) in axPsA. For other biological and synthetic targeted DMARDs, the most specific evidence for treatment in axPsA is extrapolated from post-hoc analyses based on PsA patients with concomitant peripheral and axial manifestations. Furthermore, the current trials and post-hoc analysis on axPsA are affected by major limitations, including the lack of a widely accepted definition of axPsA and the lack of specific and validated outcome measures. Finally, poor data are available on the genetics of axPsA, although alleles differentially expressed in different patterns of axPsA might offer advantages in the prospective of personalized medicine in axPsA patients. Overall, this review suggests that there is an urgent need for more reliable evidence derived from studies specifically designed for axPsA and based on a validated definition of axPsA and on specific outcome measures

Expression analysis of HLA-E and NKG2A and NKG2C receptors points at a role for natural killer function in ankylosing spondylitis

Background. Ankylosing Spondylitis (AS) is a complex chronic inflammatory disease strongly associated with the majority of HLA-B27 alleles. HLA-E are non-classical MHC class I molecules that specifically interact with the natural killer receptors NKG2A (inhibitory) and NKG2C (activating), and have been recently proposed to be involved in AS pathogenesis. Objectives: To analyze the expression of HLA-E and the CD94/NKG2 pair of receptors in HLA-B27 positive AS patients and healthy controls (HC) bearing the AS-associated, B*2705 and the non-AS-associated, B*2709 allele. Methods: The level of surface expression of HLA-E molecules on CD14 positive peripheral blood mononuclear cell was evaluated in 21 HLA-B*2705 patients with AS, 12 HLA-B*2705 HC, 12 HLA-B*2709 HC and 6 HLA-B27 negative HC, using the monoclonal antibody MEM-E/08 by quantitative cytofluorimetric analysis. The percentage and density of expression of HLA-E ligands NKG2A and NKG2C were also measured on CD3-CD56+ NK cells. Results. HLA-E expression in CD14 positive cells was significantly higher in AS patients (587.0 IQR 424-830) compared to B*2705 HC (389 IQR 251.3-440.5, p=0.0007), B*2709 HC (294.5 IQR 209.5-422, p=0.0004) and HLA-B27 negative HC (380 IQR 197.3-515.0, p=0.01). A higher number of NK cells expressing NKG2A compared to NKG2C was found in all cohort analysed as well as a higher cell surface density. Conclusion: The higher surface level of HLA-E molecules in AS patients compared to HC, concurrently with a prevalent expression of NKG2A, suggests that the crosstalk between these two molecules might play a role in AS pathogenesis accounting for the previously reported association between HLA-E and AS