Electricity markets: Designing auctions where suppliers have uncertain costs

We analyse how the market design influences the bidding behaviour in multi-unit auctions, such as wholesale electricity markets. It is shown that competition improves for increased market transparency and we identify circumstances where the auctioneer prefers uniform to discriminatory pricing. We note that political risks could significantly worsen competition in hydro-dominated markets. It would be beneficial for such markets to have clearly defined contingency plans for extreme market situations.market transparenc

The compelling arguments for the need of medical vascular physicians in Europe

<b></b> The burden of vascular diseases is growing worldwide, as the population ages, prompting a call to action not only in terms of awareness but also and most urgently in recognizing the need for vascular physicians, also called angiologists. Vascular medicine views the vascular system (arteries, veins, and lymphatics) as a whole, unique, and independent entity requiring specialized competencies. Vascular physicians offer a holistic and comprehensive approach to vascular patients including provision of interventional procedures, management of a heterogeneous group of multi-morbid and frail patients affected by multi-vessel diseases, and connecting different specialists in a multidisciplinary effort. Vascular medicine practise varies across European countries. While it is a firmly accepted medical speciality in many European countries it is not formally recognized by the European Union limiting adoption in the other countries. The lack of vascular physicians likely accounts for inequality of care of vascular patients as compared for example to patients with heart disease and might contribute to adverse outcomes and healthcare costs associated with vascular diseases. To move forward in the struggle to provide efficient care for multimorbid poly-vascular patients, it is essential to establish vascular medicine programs in Europe and worldwide. Important steps to achieve this goal include improving public awareness of vascular diseases, attain formal recognition by the EU of angiology/vascular medicine as a medical specialty, creating specialized treatment guidelines, and to harmonize vascular care in Europe

Blood sampling methodology is crucial for precise measurement of plasma catecholamines concentrations in mice

Epinephrine (E) and norepinephrine (NE) play a major role in regulating metabolism and cardiovascular physiology. Both are secreted in response to stress and their measurement in plasma allows the study of sympathoadrenal function. Several studies investigating sympathoadrenal physiology are conducted using mice. Review of the literature revealed that basal mouse NE and E plasma concentrations range within 4-140nM depending on the blood sampling method. Such variability doesn't allow study comparison and may conceal catecholamine variations in response to stress. Therefore, our aim was to determine a reliable sampling method to measure mouse plasma catecholamine concentrations. Results showed that arterial catheterization is the most accurate sampling method: E and NE basal levels were similar to those found in humans (1.1±0.3nM and 4.1±0.5nM, respectively). Retro-orbital bleeding led to analogous results. On the contrary, decapitation was stressful for mice and consequently NE and E concentrations were high (24.6±2.7nM and 27.3±3.8nM, respectively). These different bleeding methods were compared in terms of their ability to detect sympathoadrenal system stimulation (cold-pressure test). With catheter and retro-orbital samplings the expected increase in NE and E levels was easily perceived. In contrast, with decapitation no significant change in E was detected. In conclusion, arterial-catheter and retro-orbital blood sampling methods appear to be the most accurate procedures for studying the sympathetic nervous system in mice in both unstressed and stressed condition

An angiotensin II- and NF-κB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension

Aims Connexins (Cxs) play a role in the contractility of the aorta wall. We investigated how connexins of the endothelial cells (ECs; Cx37, Cx40) and smooth muscle cells (SMCs; Cx43, Cx45) of the aorta change during renin-dependent and -independent hypertension. Methods and results We subjected both wild-type (WT) mice and mice lacking Cx40 (Cx40−/−), to either a two-kidney, one-clip procedure or to N-nitro-l-arginine-methyl-ester treatment, which induce renin-dependent and -independent hypertension, respectively. All hypertensive mice featured a thickened aortic wall, increased levels of Cx37 and Cx45 in SMC, and of Cx40 in EC (except in Cx40−/− mice). Cx43 was up-regulated, with no effect on its S368 phosphorylation, only in the SMCs of renin-dependent models of hypertension. Blockade of the renin-angiotensin system of Cx40−/− mice normalized blood pressure and prevented both aortic thickening and Cx alterations. Ex vivo exposure of WT aortas, carotids, and mesenteric arteries to physiologically relevant levels of angiotensin II (AngII) increased the levels of Cx43, but not of other Cx. In the aortic SMC line of A7r5 cells, AngII activated kinase-dependent pathways and induced binding of the nuclear factor-kappa B (NF-κB) to the Cx43 gene promoter, increasing Cx43 expression. Conclusion In both large and small arteries, hypertension differently regulates Cx expression in SMC and EC layers. Cx43 is selectively increased in renin-dependent hypertension via an AngII activation of the extracellular signal-regulated kinase and NF-κB pathway

Interaction between widening of diameter of abdominal aorta and cardiovascular risk factors and atherosclerosis burden

The aim of this study was to investigate influence of traditional cardiovascular risk factors (CVRF) and subclinical atherosclerosis (ATS) burden on early stages of abdominal aortic diameter (AAD) widening among adults. 2,052 consecutive patients (P) (39% women), mean age 52±13years, were prospectively screened for CVRF, ATS, and AAD. B-mode ultrasound was used to evaluate the largest AAD and to detect carotid and femoral atherosclerotic plaques. Mean AAD was 15.2±2.8mm. Atherosclerotic plaques were detected in 71% of patients. Significant univariate correlation between AAD, traditional CVRF, and ABS was found. However, multiple regression analysis showed that only seven of them were significantly and weakly correlated with AAD (R²=0.27, p<0.001). On the other hand, a multivariate logistic analysis was used to evaluate CVRF impact on enlarged AAD≥25mm (EAAD) as compared to those with AAD<25mm. These factors did not account for more than 30% of interaction (R²=0.30, p=0.001). Furthermore, despite a large proportion of patients with high number of CVRF, and subclinical ATS, rate of patients with AAD≥25mm was low (1%) and scattered regardless their CHD risk score or ATS burden. In conclusion, these results suggest that although some traditional CVRF and presence of ATS are associated with early stages of EAAD, other determinants still need to be identified for a better understanding of abdominal aortic aneurysm pathogenesis

Assessment of angiotensin II receptor blockade in humans using a standardized angiotensin II receptor-binding assay

An in vitro angiotensin II (AngII) receptor-binding assay was developed to monitor the degree of receptor blockade in standardized conditions. This in vitro method was validated by comparing its results with those obtained in vivo with the injection of exogenous AngII and the measurement of the AngII-induced changes in systolic blood pressure. For this purpose, 12 normotensive subjects were enrolled in a double-blind, four-way cross-over study comparing the AngII receptor blockade induced by a single oral dose of losartan (50 mg), valsartan (80 mg), irbesartan (150 mg), and placebo. A significant linear relationship between the two methods was found (r = 0.723, n = 191, P < .001). However, there exists a wide scatter of the in vivo data in the absence of active AngII receptor blockade. Thus, the relationship between the two methods is markedly improved (r = 0.87, n = 47, P < .001) when only measurements done 4 h after administration of the drugs are considered (maximal antagonist activity observed in vivo) suggesting that the two methods are equally effective in assessing the degree of AT-1 receptor blockade, but with a greatly reduced variability in the in vitro assay. In addition, the pharmacokinetic/pharmacodynamic analysis performed with the three antagonists suggest that the AT-1 receptor-binding assay works as a bioassay that integrates the antagonistic property of all active drug components of the plasma. This standardized in vitro-binding assay represents a simple, reproducible, and precise tool to characterize the pharmacodynamic profile of AngII receptor antagonists in human

Supervised exercise training in patients with lower extremity peripheral artery disease

The optimal first line management of patients with symptomatic chronic lower extremity peripheral artery disease (PAD) includes secondary prevention of cardiovascular risk factors, pharmacological treatment, and supervised exercise therapy (SET). SET programs have shown to be effective in improving walking performance, functional performance, and quality of life. However, despite a large body of evidence, and despite national and international guidelines recommending SET as first line therapy, SET remains largely underused in patients with chronic PAD. This position paper aims to describe how SET is perceived, its accessibility and structure through Europe. An anonymous web-based survey was used. It comprised 21 questions developed in conjunction with an angiologist and a clinical exercise physiologist specialist in vascular rehabilitation. We had 131 responders from 17 countries. For patients with PAD, SET programs exist only in 59% of European countries. SET reimbursement is available in 41% of countries. SET programs showed to be heterogeneous across countries. Thirty-four percent of the SET programs are PAD-dedicated, while 23% are part of a cardiac rehabilitation program. In addition, among existing SET programs, 65% are dedicated to symptomatic patients with PAD only, 9% to both asymptomatic and symptomatic, 8% to post-revascularized patients only, and 1% to asymptomatic patients with PAD only. Finally, 17% reported not knowing which patients are eligible for enrolment in a SET program. Duration, frequency, and modality of SET also varied from country to country. Overall, these data indicate that a large variability of SET availability and characteristics exists across Europe. Therefore, there is an urgent need to provide detailed guidance to deliver optimal exercise therapeutic care in patients with PAD

Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease

Aims A hallmark of Fabry disease is the concomitant development of left-ventricular hypertrophy and arterial intima-media thickening, the pathogenesis of which is thought to be related to the presence of a plasmatic circulating growth-promoting factor. We therefore characterized the plasma of patients with Fabry disease in order to identify this factor. Methods and results Using a classical biochemical strategy, we isolated and identified sphingosine-1 phosphate (S1P) as a proliferative factor present in the plasma of patients with Fabry disease. Plasma S1P levels were significantly higher in 17 patients with Fabry disease compared with 17 healthy controls (225 ± 40 vs. 164 ± 17 ng/mL; P = 0.005). There was a positive correlation between plasma S1P levels and both common carotid artery intima-media thickness and left-ventricular mass index (r2 = 0.47; P = 0.006 and r2 = 0.53; P = 0.0007, respectively). In an experimental model, mice treated with S1P developed cardiovascular remodelling similar to that observed in patients with Fabry disease. Conclusion Sphingosine-1 phosphate participates in cardiovascular remodelling in Fabry disease. Our findings have implications for the treatment of cardiovascular involvement in Fabry diseas

The year in cardiology 2014: peripheral circulation

In 2014, the debate on the indication of revascularization in case of asymptomatic carotid disease continued, while another one regarding the use of surgery vs. stenting addressed some new issues regarding the long-term cardiac risk of these patients. Renal arteries interventions trials were disappointing, as neither renal denervation nor renal artery stenting was found associated with better blood pressure management or outcome. In contrast, in lower-extremities artery disease, the endovascular techniques represent in 2014 major alternatives to surgery, even in distal arteries, with new insights regarding the interest of drug-eluting balloons. Regarding the aorta, the ESC published its first guidelines document on the entire vessel, emphasizing on the role of every cardiologist for screening abdominal aorta aneurysm during echocardiography. Among vascular wall biomarkers, the aorta stiffness is of increasing interest with new data and meta-analysis confirming its ability to stratify risk, whereas carotid intima-media thickness showed poor performances in terms of reclassifying patients into risk categories beyond risk scores. Regarding the veins, new data suggest the interest of D-dimers and residual venous thrombosis to help the decision of anti-coagulation prolongation or discontinuation after the initial period of treatment for deep vein thrombosi

Outcome during and after anticoagulant therapy in cancer patients with incidentally found pulmonary embolism

Publisher Copyright: Copyright © 2016 ERS.Current guidelines suggest treating cancer patients with incidental pulmonary embolism comparably to patients with symptomatic pulmonary embolism. We used the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) registry to compare the rate of major bleeding and symptomatic pulmonary embolism during the course of anticoagulation and after its discontinuation in cancer patients with incidental pulmonary embolism. As of March 2016, 715 cancer patients with incidental pulmonary embolism had been enrolled in RIETE. During the course of anticoagulant therapy (mean 235 days), the rate of major bleeding was higher than the rate of symptomatic pulmonary embolism (10.1 (95% CI 7.48-13.4) versus 3.17 (95% CI 1.80-5.19) events per 100 patient-years, respectively), and the rate of fatal bleeding was higher than the rate of fatal pulmonary embolism (2.66 (95% CI 1.44-4.52) versus 0.66 (95% CI 0.17-1.81) deaths per 100 patient-years, respectively). After discontinuing anticoagulation (mean follow-up 117 days), the rate of major bleeding was lower than the rate of symptomatic pulmonary embolism (3.00 (95% CI 1.10-6.65) versus 8.37 (95% CI 4.76-13.7) events per 100 patient-years, respectively); however, there were no differences in the rate of fatal events at one death each. The risk/benefit ratio of anticoagulant therapy in cancer patients with incidental pulmonary embolism is uncertain and must be evaluated in further studies.publishersversionPeer reviewe