Overcoming obstacles to IPv6 on WLCG

The transition of the Worldwide Large Hadron Collider Computing Grid (WLCG) storage services to dual-stack IPv6/IPv4 is almost complete; all Tier-1 and 94% of Tier-2 storage are IPv6 enabled. While most data transfers now use IPv6, a significant number of IPv4 transfers still occur even when both endpoints support IPv6. This paper presents the ongoing efforts of the HEPiX IPv6 working group to steer WLCG toward IPv6-only services by investigating and fixing the obstacles to the use of IPv6 and identifying cases where IPv4 is used when IPv6 is available. Removing IPv4 use is essential for the long-term agreed goal of IPv6-only access to resources within WLCG, thus eliminating the complexity and security concerns associated with dual-stack services. We present our achievements and ongoing challenges as we navigate the final stages of the transition from IPv4 to IPv6 within WLCG

Polytomous response financial distress models: The role of accounting, market and macroeconomic variables

We apply polytomous response logit models to investigate financial distress and bankruptcy across three states for UK listed companies over a period exceeding 30 years and utilising around 20,000 company year observations. Results suggest combining accounting, market and macroeconomic variables enhances the performance, accuracy and timeliness of models of corporate credit risk. Models produced contribute to the prediction and early warning systems literature by investigating the distress/failure process with enhanced granularity. We employ marginal effects to assess individual covariates' impact on the probability of falling into each state. The new insights on individual risk factors are confirmed by analysis of vectors of changes in predicted probabilities of falling into a state of financial distress and corporate failure following changes in the level of individual covariates. Resulting models provide a better understanding of different risk factors and can help practitioners detect financial distress and failure in a timely fashion

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes