The evolution of central securities depositaries in Europe: stable functions in a changing environment

Settlement-delivery (S&D) operations of CSDs or ICSDs are the second last stage of the securities treatment procedure, the last stage being the delivery of securities into the accounts of the final holders by their account managers/custodians. As for national transfers, the organisation is fairly simple since regional depositors are directly connected to the central securities depositary which fulfils two overriding functions on their behalf:- ensuring the final custody of securities and testifying to their authenticity ;- ensuring the circulation of securities within the market through one or several S&D systems.Central Securities Depositaries ; Europe

The reform of European securities settlement systems : Towards an integrated financial market

The European Central Bank (ECB) will offer to banks in 2013 an european shared platform for securities settlement, named TARGET 2 Securities (T2S), in order to open the national financial markets. The financial crisis did not change the ECB agenda. This paper develops a spatial competition model to understand the impact of this new organisation on european post-trading services. We analyse the incentives of the Central Securities Depositaries (CSD) to move to T2S when they become competitors in the market for settlement services and remain in a monopoly position for depository services. Settlement and depository services are complementary goods, because banks have to pay for these two services to buy or sell a security. We show that such a reform should induce a decrease in the settlement price and more generally in post-trading prices, but that prices depend strongly on market organisation. Under certain conditions, partial adhesion would make prices increase. This configuration appears as a Nash equilibrium. As CSDs are free to adhere to T2S, the ECB might be forced to regulate.Post-trading organisation; securities settlement; depositary services; compatibility

L'évolution des dépositaires centraux de titres en Europe: des fonctions stables dans un espace mouvant

National audienceLes dépositaires centraux (CSD) remplissent deux fonctions dans un cadre national : la conservation ultime de titres et l'administration des systèmes de règlement livraison. Or, le passage d'une espace nationale à un espace domestique européen, met en évidence des surcapacités et des interférences entre les acteurs (CSD, ICSD, global-custodians) de ce marché. Cet article précise leurs fonctions actuelles et la façon dont elles doivent s'exercer dans un espace élargi. Nous insistons particulièrement sur la fonction de « conservateur/authentificateur », fondement de la confiance dans les marchés et posons la question de l'institution la plus apte à la tenir dans le nouvel espace domestique. Nous constatons que quelle que soit la solution retenue, une affirmation forte de la dimension européenne sera nécessaire, soit à travers un CSD unique, soit à travers un organisme réglementaire européen

The reform of European securities settlement systems : Towards an integrated financial market

Working paper du GATE 2011-29The European Central Bank (ECB) will offer to banks in 2013 an european shared platform for securities settlement, named TARGET 2 Securities (T2S), in order to open the national financial markets. The financial crisis did not change the ECB agenda. This paper develops a spatial competition model to understand the impact of this new organisation on european post-trading services. We analyse the incentives of the Central Securities Depositaries (CSD) to move to T2S when they become competitors in the market for settlement services and remain in a monopoly position for depository services. Settlement and depository services are complementary goods, because banks have to pay for these two services to buy or sell a security. We show that such a reform should induce a decrease in the settlement price and more generally in post-trading prices, but that prices depend strongly on market organisation. Under certain conditions, partial adhesion would make prices increase. This configuration appears as a Nash equilibrium. As CSDs are free to adhere to T2S, the ECB might be forced to regulate

Thrombolytic therapy of pulmonary embolism A meta-analysis

AbstractObjectivesWe sought to assess the efficacy and safety of thrombolytic therapy in patients with an acute pulmonary embolism (PE).BackgroundThrombolytic therapy is approved for the treatment of acute PE; however, the safety and efficacy of this therapy remain debated.MethodsA meta-analysis of randomized, controlled trials comparing thrombolytic agents with intravenous heparin in patients with acute PE was performed. Trials were identified through a combined search of the MEDLINE, EMBASE, and Current Contents databases. Three outcome measures were assessed: 1) mortality, 2) recurrence of PE, and 3) major hemorrhage.ResultsNine trials including 461 patients were identified. Compared with intravenous heparin, thrombolytic therapy had no significant effect on mortality (relative risk [RR] 0.63, 95% confidence interval [CI] 0.32 to 1.23) or the recurrence of PE (RR 0.59, 95% CI 0.30 to 1.18), but was associated with an increased risk of major hemorrhage (RR 1.76, 95% CI 1.04 to 2.98). These results were homogeneous and largely unaffected by the formulation of thrombolytic agent, the clinical severity of PE, the extent of vascular obstruction determined radiologically, or the methodologic quality of the included trials.ConclusionsCompared with intravenous heparin, thrombolytic therapy does not appear to have therapeutic benefit in unselected patients with acute PE, but it is associated with an increased risk of major hemorrhage. Given the small number of patients included in the randomized trials thus far, the negative results in terms of the efficacy outcomes should be interpreted with caution. Definitive evidence of the utility of thrombolytic therapy in this setting requires a large, randomized, controlled trial

Multivariate analysis identifies the estradiol level at ovulation triggering as an independent predictor of the first trimester pregnancy-associated plasma protein-A level in IVF/ICSI pregnancies

STUDY QUESTION: Can independent predictors of pregnancy-associated plasma protein-A (PAPP-A) levels be identified in a group of women who conceived following IVF/ICSI? SUMMARY ANSWER: The significantly decreased PAPP-A level in IVF and ICSI pregnancies compared with non-IVF/ICSI pregnancies was correlated strongly with the serum estradiol (E2) level at ovulation triggering. WHAT IS KNOWN ALREADY: The first trimester prenatal combined screening test for fetal aneuploidies in pregnancies conceived following assisted reproduction techniques (ART) is complicated by an alteration of the maternal biomarkers free β-hCG and PAPP-A, causing a higher false-positive rate compared with pregnancies which are conceived naturally. The use of controlled ovarian stimulation prior to IVF/ICSI is suggested to be the principle reason for these alterations of biomarkers in ART pregnancies. STUDY DESIGN, SIZE, DURATION: Between January 2010 and December 2011, 1474 women who conceived naturally and 374 women who conceived following IVF (n = 89), ICSI (n = 204) or intrauterine insemination (IUI, n = 81) were included in this retrospective study. Only singleton pregnancies were eligible for this study. For all women, serum analysis was performed in the same clinical laboratory. Measurement of nuchal translucency (NT) thickness was performed by four physicians belonging to the same infertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: First-trimester combined screening test of aneuploidy parameters (maternal age, PAPP-A and free β-hCG, NT thickness) were compared between non-ART and ART (IVF, ICSI and IUI) singleton pregnancies. Next, a minimal threshold E2 level at ovulation triggering was suggested for IVF/ICSI pregnancies above which the PAPP-A levels were significantly decreased compared with non-ART pregnancies. Finally, a multivariate analysis was performed to reveal independent predictors of PAPP-A level in IVF/ICSI pregnancies. MAIN RESULTS AND THE ROLE OF CHANCE: We showed a decrease of the multiple of the median (MoM) PAPP-A level in IVF and ICSI singleton pregnancies compared with non-ART singleton pregnancies (P < 0.001), with MoM values of 0.74 (0.16-3.16) and 0.81 (0.12-4.61) versus 0.98 (0.14-5.76), respectively. Analysis of variance of the overall model was highly significant (Fisher test 3.76, P = 0.01), indicating that the model explains a significant portion of the variation in the data. No difference in PAPP-A level was found between non-ART and IUI pregnancies. The free β-hCG level and NT thickness did not differ between ART and non-ART pregnancies. PAPP-A levels in IVF and ICSI pregnancies were strongly correlated with the E2 level at ovulation triggering. We showed by multivariate analysis that an E2 cut-off level of 1300 pg/ml at the time of ovulation could predict a significantly lower PAPP-A level at first trimester combined screening (β -0.239 ± 0.088, P < 0.005). LIMITATION, REASONS FOR CAUTION: The measures of biochemical markers can differ between laboratories and with the used equipment; therefore, extrapolation of the E2 cut-off level to other infertility centres should be undertaken with caution. WIDER IMPLICATIONS OF THE FINDINGS: One should be careful when using correction factors for ART patients undergoing the first trimester combined screening test. The proposed E2 cut-off level may help to identify a subgroup of women within the population of ART patients for whom use of a correction factor is justified. STUDY FUNDING/COMPETING INTEREST(S): None

Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator

Although many genetic variants are known for obesity, their function remains largely unknown. Here, in a weight-loss intervention cohort, the authors identify protein quantitative trait loci associated with BMI at baseline and after weight loss and find FAM46A to be a regulator of leptin in adipocytes

A Chemical Proteomics Approach to Phosphatidylinositol 3-Kinase Signaling in Macrophages

Prior work using lipid-based affinity matrices has been done to investigate distinct sets of lipid-binding proteins, and one series of experiments has proven successful in mammalian cells for the proteome-wide identification of lipid-binding proteins. However, most lipid-based proteomics screens require scaled up sample preparation, are often composed of multiple cell types, and are not adapted for simultaneous signal transduction studies. Herein we provide a chemical proteomics strategy that uses cleavable lipid "baits" with broad applicability to diverse biological samples. The novel baits were designed to avoid preparative steps to allow functional proteomics studies when the biological source is a limiting factor. Validation of the chemical baits was first confirmed by the selective isolation of several known endogenous phosphatidylinositol 3-kinase signaling proteins using primary bone marrow-derived macrophages. The use of this technique for cellular proteomics and MS/MS analysis was then demonstrated by the identification of known and potential novel lipid-binding proteins that was confirmed in vitro for several proteins by direct lipid-protein interactions. Further to the identification, the method is also compatible with subsequent signal transduction studies, notably for protein kinase profiling of the isolated lipid-bound protein complexes. Taken together, this integration of minimal scale proteomics, lipid chemistry, and activity-based readouts provides a significant advancement in the ability to identify and study the lipid proteome of single, relevant cell types

Assessing the health status of managed honeybee colonies (HEALTHY-B): a toolbox to facilitate harmonised data collection

Tools are provided to assess the health status of managed honeybee colonies by facilitating further harmonisation of data collection and reporting, design of field surveys across the European Union (EU) and analysis of data on bee health. The toolbox is based on characteristics of a healthy managed honeybee colony: an adequate size, demographic structure and behaviour; an adequate production of bee products (both in relation to the annual life cycle of the colony and the geographical location); and provision of pollination services. The attributes ‘queen presence and performance’, ‘demography of the colony’, ‘in-hive products’ and ‘disease, infection and infestation’ could be directly measured in field conditions across the EU, whereas ‘behaviour and physiology’ is mainly assessed through experimental studies. Analysing the resource providing unit, in particular land cover/use, of a honeybee colony is very important when assessing its health status, but tools are currently lacking that could be used at apiary level in field surveys across the EU. Data on ‘beekeeping management practices’ and ‘environmental drivers’ can be collected via questionnaires and available databases, respectively. The capacity to provide pollination services is regarded as an indication of a healthy colony, but it is assessed only in relation to the provision of honey because technical limitations hamper the assessment of pollination as regulating service (e.g. to pollinate wild plants) in field surveys across the EU. Integrating multiple attributes of honeybee health, for instance, via a Health Status Index, is required to support a holistic assessment. Examples are provided on how the toolbox could be used by different stakeholders. Continued interaction between the Member State organisations, the EU Reference Laboratory and EFSA is required to further validate methods and facilitate the efficient use of precise and accurate bee health data that are collected by many initiatives throughout the EU

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio