A complementary emissions test for light-duty vehicles: Assessing the technical feasibility of candidate procedures

Light-duty diesel vehicles emit on the road substantially more nitrogen oxides than permitted by regulatory emissions standards. The European Commission addresses this problem by developing a complementary emissions test procedure for the type approval and in-service conformity testing of these vehicles. To facilitate the technical development, the European Commission established in January 2011 the Real-Driving Emissions - Light-Duty Vehicles (RDE-LDV) working group that is open to all stakeholders. This report presents the results of the technical assessment that was carried out by the RDE-LDV working group for two candidate procedures: (i) emissions testing with random driving cycles in the laboratory and (ii) on-road emissions testing with Portable Emissions Measurement Systems (PEMS). Both procedures are technically feasible. However, PEMS on-road testing appears to be more effective than random-cycle testing in limiting the pollutant emissions of light-duty vehicles because it (i) allows a wider range of driving conditions to be covered and (ii) might more effectively prevent the detection of emissions tests and the use of defeat strategies. Nonetheless, PEMS on-road testing faces practical challenges, including open safety issues, the currently limited availability of PEMS equipment, and potential climatic, geographical, and seasonal constraints for the execution of emissions tests. Random-cycle testing presents advantages over PEMS on-road testing in that already established laboratory equipment and know-how to be used. The present assessment is subject to uncertainty because the implementation and running costs as well as the overall effectiveness of the two candidate procedures depend on the definition of concrete boundary conditions (e.g., permitted test temperatures, severity of driving patterns). These definitions are not yet agreed. Accounting for the resulting uncertainty, it has been decided that the JRC will develop a PEMS-based test procedure. Vehicle manufacturers are given the opportunity to develop a random cycle-based test procedure. A decision will be made regarding the implementation for type approval and in-service conformity testing based on a comparison of the two fully developed test procedures by the end of 2013.JRC.F.8-Sustainable Transpor

A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC.</p> <p>Methods/Design</p> <p>The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 2^1/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating.</p> <p>Discussion</p> <p>If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC.</p> <p>Trial Register</p> <p>Trial registered at <url>http://www.clinicaltrials.gov</url>: NCT00355862</p> <p>(EudraCT Number: 2005-005362-36)</p

A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma

Peer reviewe

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma : A Randomized, Multicenter, Open-Label Phase 3 Trial

Background We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). Methods In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. Results Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age 60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). Conclusions Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.Peer reviewe

Does the reason for discontinuation of a first TNF inhibitor influence the effectiveness of a second TNF inhibitor in axial spondyloarthritis? Results from the Swiss Clinical Quality Management Cohort

BACKGROUND: With regard to switching tumor necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA), conflicting results have been reported as to whether the effectiveness of a second TNFi depends on the reason for discontinuation of the first TNFi. METHODS: Patients with a clinical diagnosis of axSpA starting a second TNFi in the Swiss Clinical Quality Management cohort were included. Effectiveness of treatment at 1 year, as well as drug survival, was compared between subgroups having discontinued the first TNFi because of lack of response, adverse events (AEs), or other reasons. Lack of response was further divided into primary or secondary lack of response (PLR or SLR, respectively), depending on whether the first TNFi was stopped before or after 6 months of treatment. RESULTS: Among 632 patients with axSpA, median survival of a second TNFi was 1.1 years after PLR and 3.8 years after SLR (p = 0.003). At least moderate disease activity as defined by an Ankylosing Spondylitis Disease Activity Score using the erythrocyte sedimentation rate (ASDAS-ESR) <2.1 was achieved after 12 months by 11 %, 39 %, 26 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). Only 4 % of patients achieved an ASDAS-ESR inactive disease state after PLR, in comparison to 22 % of those after SLR. Similar results were demonstrated in patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axSpA (n = 488): ASDAS-ESR <2.1 was achieved after 12 months by 9 %, 41 %, 29 %, and 39 % of patients who discontinued their first TNFi because of PLR, SLR, AEs, and other reasons, respectively (p = 0.01). CONCLUSIONS: The effectiveness of a second TNFi is significantly impaired in patients with axSpA after PLR to a first TNFi compared with SLR

Biostratigraphische Gliederung und Korrelation : Zentrale und westliche Paratethys, Rhône-Tal und mediterraner Raum

Discussion of biostratigraphic results obtained so far. Possibilities of correlations by means of various groups of fossils. Evidence for possible markers.Discussion des résultats biostratigraphiques obtenus jusqu'ici. Possibilités de corrélations au moyen de divers groupes de fossiles. Mise en évidence d'éventuels marqueurs.Steininger Fritz F., Rögl Fred, Carbonnel Gilles, Jĭrĭcek Rudolf, Hugueney Marguerite. Biostratigraphische Gliederung und Korrelation : Zentrale und westliche Paratethys, Rhône-Tal und mediterraner Raum. In: Documents des Laboratoires de Géologie, Lyon. Hors-série n°7, 1982. Nouveaux résultats biostratigraphiques dans le bassin molassique, depuis le Vorarlberg jusqu’en Haute-Savoie. Projet P.I.C.G. 73/I/25, section 5. pp. 87-91