The evolution of clearing and central counterparty services for exchange-traded derivatives in the United States and Europe - a comparison

This paper is organised as follows. Section 1 explains why issues concerning central counterparty clearing houses are of direct concern to central banks and why a comparison of the European and the US situation is of interest. Section 2 provides a comparative overview of the organisation of derivatives exchanges in the United States and in Europe. Section 3 focuses on the organisation of clearing, covering a broad range of aspects. Section 4 analyses operational developments in international risk management practices and arrangements. Section 5 discusses various forms of structural consolidation in the clearing and settlement infrastructure by highlighting the different approaches taken in the United States and in Europe. Section 6 is devoted to the roles of central banks and financial market regulators regarding clearing and to the challenges they face as a result of current innovations in clearing arrangements. Finally, Section 7 summarises some of the main findings.

Governance of securities clearing and settlement systems

In the context of securities clearing and settlement systems, the nature of governance arrangements acquires a dimension that goes beyond their traditional function in corporate law. They constitute a tool for regulators and central banks to achieve their respective policy goals relating to market operation, market integrity, and systemic stability. In the light of the analysis of this paper, and pending a further evolution in the regulation of securities clearing and settlement in the Community, the following conclusions can be drawn. Whatever the model of corporate governance used in a jurisdiction, securities clearing and settlement systems should adopt and ensure effective implementation of the highest corporate governance standards or best practices adopted or recommended for companies in the jurisdiction in which it operates as such standards or practices evolve over time. Generally, this would imply that securities clearing and settlement systems at minimum should adopt and implement the best practices recommended for listed companies. Additionally, a securities clearing or settlement system should adopt corporate governance mechanisms adequate to address the interests of users and the public in the operation of the system. Such mechanisms should be organized so that the criteria followed to select participants on the board or on specialized committees are established ex ante. Board members should also take into account the interests of users and the public in board decisions, in particular, those relating to qualifications for system access, fair pricing, the integrity of the risk management system, innovation and efficiency, and the achievement of the policy objectives of competent authorities. Securities clearing and settlement systems should make adequate disclosures regarding their corporate governance arrangements so that users and the public can ascertain the manner in which conflicts of interest among owners, the board, users and the public interest are prevented, resolved or mitigated. Corporate governance arrangements of securities clearing and settlement systems should be the subject of adequate regulation and oversight to ensure that services are provided at fair prices to users under fair and equitable conditions of access; that the risk management programs of system operators are effective; that risk management decisions are not affected by considerations extraneous to the risk management function; and that, to the maximum extent possible, functional service providers compete in equivalent conditions of competition. Looking forward, the adoption of a harmonized regulatory regime for securities clearing and settlement systems should be considered to complete the internal market within the Community and to better achieve the policy goals identified in this paper relating to the governance of those systems.clearing, settlement, governance, risk management, oversight.

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

Arterial oxygen content is precisely maintained by graded erythrocytotic responses in settings of high/normal serum iron levels, and predicts exercise capacity: an observational study of hypoxaemic patients with pulmonary arteriovenous malformations.

Oxygen, haemoglobin and cardiac output are integrated components of oxygen transport: each gram of haemoglobin transports 1.34 mls of oxygen in the blood. Low arterial partial pressure of oxygen (PaO2), and haemoglobin saturation (SaO2), are the indices used in clinical assessments, and usually result from low inspired oxygen concentrations, or alveolar/airways disease. Our objective was to examine low blood oxygen/haemoglobin relationships in chronically compensated states without concurrent hypoxic pulmonary vasoreactivity.165 consecutive unselected patients with pulmonary arteriovenous malformations were studied, in 98 cases, pre/post embolisation treatment. 159 (96%) had hereditary haemorrhagic telangiectasia. Arterial oxygen content was calculated by SaO2 x haemoglobin x 1.34/100.There was wide variation in SaO2 on air (78.5-99, median 95)% but due to secondary erythrocytosis and resultant polycythaemia, SaO2 explained only 0.1% of the variance in arterial oxygen content per unit blood volume. Secondary erythrocytosis was achievable with low iron stores, but only if serum iron was high-normal: Low serum iron levels were associated with reduced haemoglobin per erythrocyte, and overall arterial oxygen content was lower in iron deficient patients (median 16.0 [IQR 14.9, 17.4]mls/dL compared to 18.8 [IQR 17.4, 20.1]mls/dL, p<0.0001). Exercise tolerance appeared unrelated to SaO2 but was significantly worse in patients with lower oxygen content (p<0.0001). A pre-defined athletic group had higher Hb:SaO2 and serum iron:ferritin ratios than non-athletes with normal exercise capacity. PAVM embolisation increased SaO2, but arterial oxygen content was precisely restored by a subsequent fall in haemoglobin: 86 (87.8%) patients reported no change in exercise tolerance at post-embolisation follow-up.Haemoglobin and oxygen measurements in isolation do not indicate the more physiologically relevant oxygen content per unit blood volume. This can be maintained for SaO2 ≥78.5%, and resets to the same arterial oxygen content after correction of hypoxaemia. Serum iron concentrations, not ferritin, seem to predict more successful polycythaemic responses

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Supported online self-management versus care as usual for symptoms of fatigue, pain and urgency/incontinence in adults with inflammatory bowel disease (IBD-BOOST): study protocol for a randomised controlled trial.

BACKGROUND: Despite being in clinical remission, many people with inflammatory bowel disease (IBD) live with fatigue, chronic abdominal pain and bowel urgency or incontinence that limit their quality of life. We aim to test the effectiveness of an online self-management programme (BOOST), developed using cognitive behavioural principles and a theoretically informed logic model, and delivered with facilitator support. PRIMARY RESEARCH QUESTION: In people with IBD who report symptoms of fatigue, pain or urgency and express a desire for intervention, does a facilitator-supported tailored (to patient needs) online self-management programme for fatigue, pain and faecal urgency/incontinence improve IBD-related quality of life (measured using the UK-IBDQ) and global rating of symptom relief (0-10 scale) compared with care as usual? METHODS: A pragmatic two-arm, parallel group randomised controlled trial (RCT), of a 12-session facilitator-supported online cognitive behavioural self-management programme versus care as usual to manage symptoms of fatigue, pain and faecal urgency/incontinence in IBD. Patients will be recruited through a previous large-scale survey of unselected people with inflammatory bowel disease. The UK Inflammatory Bowel Disease Questionnaire and global rating of symptom relief at 6 months are the co-primary outcomes, with multiple secondary outcomes measured also at 6 and 12 months post randomisation to assess maintenance. The RCT has an embedded pilot study, health economics evaluation and process evaluation. We will randomise 680 patients, 340 in each group. Demographic characteristics and outcome measures will be presented for both study groups at baseline. The UK-IBDQ and global rating of symptom relief at 6 and 12 months post randomisation will be compared between the study groups. DISCUSSION: The BOOST online self-management programme for people with IBD-related symptoms of fatigue, pain and urgency has been designed to be easily scalable and implemented. If it is shown to improve patients' quality of life, this trial will enable clinicians and patients to make informed management decisions. This is the first trial, to our knowledge, focused on multiple symptoms prioritised by both people with IBD and health professionals. TRIAL REGISTRATION: ISRCTN71618461 . Registered on 9 September 2019

Single view silhouette fitting techniques for estimating tennis racket position

Stereo camera systems have been used to track markers attached to a racket, allowing its position to be obtained in three-dimensional (3D) space. Typically, markers are manually selected on the image plane, but this can be time-consuming. A markerless system based on one stationary camera estimating 3D racket position data is desirable for research and play. The markerless method presented in this paper relies on a set of racket silhouette views in a common reference frame captured with a calibrated camera and a silhouette of a racket captured with a camera whose relative pose is outside the common reference frame. The aim of this paper is to provide validation of these single view fitting techniques to estimate the pose of a tennis racket. This includes the development of a calibration method to provide the relative pose of a stationary camera with respect to a racket. Mean static racket position was reconstructed to within ±2 mm. Computer generated camera poses and silhouette views of a full size racket model were used to demonstrate the potential of the method to estimate 3D racket position during a simplified serve scenario. From a camera distance of 14 m, 3D racket position was estimated providing a spatial accuracy of 1.9 ± 0.14 mm, similar to recent 3D video marker tracking studies of tennis

Returning to work after stroke: perspectives of employer stakeholders, a qualitative study.

Purpose: More than 40 % of working age adults with stroke fail to return to work. The work context is a key factor in return to work, but little is known about the experiences of employers in supporting employees with stroke. The aim of this study was to explore return to work after stroke from the employer perspective, to identify key features associated with success and to seek participants’ views regarding the role of healthcare in return to work. Methods: Data was gathered through 18 semi-structured interviews with employer stakeholders and included small business owners, line managers, human resources and occupational health staff. Data was analysed thematically. Results: The main themes identified were: the impact of stroke on the employer, characteristics of the employee, communication, knowledge and information, experience of other stakeholders, integrating healthcare in return to work. Conclusion: Employers face complex emotional and practical issues when helping an employee return to work after stroke, for which many lack knowledge and experience. The range and quality of support networks that they access is variable and advice and support from clinicians is welcomed. Further research is necessary to investigate how such support could be funded and integrated within existing service provision

Expression of RHOGTPase regulators in human myometrium

<p>Abstract</p> <p>Background</p> <p>RHOGTPases play a significant role in modulating myometrial contractility in uterine smooth muscle. They are regulated by at least three families of proteins, RHO guanine nucleotide exchange factors (RHOGEFs), RHOGTPase-activating proteins (RHOGAPs) and RHO guanine nucleotide inhibitors (RHOGDIs). RHOGEFs activate RHOGTPases from the inactive GDP-bound to the active GTP-bound form. RHOGAPs deactivate RHOGTPases by accelerating the intrinsic GTPase activity of the RHOGTPases, converting them from the active to the inactive form. RHOGDIs bind to GDP-bound RHOGTPases and sequester them in the cytosol, thereby inhibiting their activity. Ezrin-Radixin-Moesin (ERM) proteins regulate the cortical actin cytoskeleton, and an ERM protein, moesin (MSN), is activated by and can also activate RHOGTPases.</p> <p>Methods</p> <p>We therefore investigated the expression of various RHOGEFs, RHOGAPs, a RHOGDI and MSN in human myometrium, by semi-quantitative reverse transcription PCR, real-time fluorescence RT-PCR, western blotting and immunofluorescence microscopy. Expression of these molecules was also examined in myometrial smooth muscle cells.</p> <p>Results</p> <p>ARHGEF1, ARHGEF11, ARHGEF12, ARHGAP5, ARHGAP24, ARHGDIA and MSN mRNA and protein expression was confirmed in human myometrium at term pregnancy, at labour and in the non-pregnant state. Furthermore, their expression was detected in myometrial smooth muscle cells. It was determined that ARHGAP24 mRNA expression significantly increased at labour in comparison to the non-labour state.</p> <p>Conclusion</p> <p>This study demonstrated for the first time the expression of the RHOGTPase regulators ARHGEF1, ARHGEF11, ARHGEF12, ARHGAP5, ARHGAP24, ARHGDIA and MSN in human myometrium, at term pregnancy, at labour, in the non-pregnant state and also in myometrial smooth muscle cells. ARHGAP24 mRNA expression significantly increased at labour in comparison to the non-labouring state. Further investigation of these molecules may enable us to further our knowledge of RHOGTPase regulation in human myometrium during pregnancy and labour.</p