Raltitrexed (Tomudex) administration in patients with relapsed metastatic colorectal cancer after weekly irinotecan/5-Fluorouracil/Leucovorin chemotherapy

PURPOSE: The present study aimed at evaluating the efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) in relapse (>8 weeks) after a prior response or disease stabilization to first-line chemotherapy combination with lrinotecan+5-Fluorouracil (5-FU)+Leucovorin (LV). METHODS: Twenty-five patients with metastatic ACC entered; 17 males/8 females, median age 61 (range: 47–70), median Karnovsky PS: 80 (70–90), and sites of metastases; liver: 21, lung: 4, lymph nodes: 7, peritoneal: 5 and a life expectancy of at least 3 months, were entered in the present pilot study. All patients had progressed after prior chemotherapy with lrinotecan+5-FU+LV. Raltitrexed was administered at a dose of 3 mg/m(2) i.v. every 21 days. RESULTS: Three patients (12%) achieved a partial response (PR), 8 (32%) had stable disease (SD), and the remaining 14 (56%) developed progressive disease (PD). Median time-to-progression (TTP) was 5.5 months (range, 2–8.5), and median overall survival (OS) 8 months (range, 4.0–12.5). Toxicity was generally mild; it consisted mainly of myelosuppression; neutropenia grade 1–2: 52%-grade 3: 28%, and anemia grade 1–2 only: 36%. Mild mucositis grade 1–2 occured in 13.5% of patients and was the principal non-hematologic toxicity. CONCLUSION: Response to treatment with Raltitrexed is limited in patients with ACC failing after an initial response or non-progression to the weekly lrinotecan+5-FU+LV combination. However, it appears that a limited number of patients with PR/SD may derive clinical benefit, but final proof would require a randomized study

Gel stability in waves : breakage, behaviour, and implications for oil spill remediation

While oil spills are becoming less common, they are an ever-present threat associated with use of petroleum. New developments in chemistry have brought gellants back into the spotlight as a promising spill remediation technique. These chemicals change the material properties of spilled oil, making it more solid. This could help prevent the spreading or weathering of spilled oil, extending the window-of-opportunity available for remediation. While oil-gelling technology shows great promise, the behaviour of surface gels subject to linear ocean waves has not yet been investigated. Determining what wave conditions result in the breakup of a gel layer could help predict the utility of these technologies in the field. This study adopts an experimental perspective to provide insight into the behaviour of gels subjected to wave action, specifically addressing the stretching induced by spatially-variable velocity gradients. Bottom-of-tank experiments were designed to allow the isolation of wave-induced stretching effects from wave-induced bending. In these experiments, a dense gel (gelatin) was placed on the bottom of a wave tank and constrained vertically. As particle orbits in a shallow-water wave decay vertically with depth, this is an effective means of applying the same spatial velocity gradients that would be observed on the water surface. Analytical models were developed to describe the response of a viscoelastic gel to periodic, spatially-variable velocity gradients for Maxwell and Kelvin-Voigt materials. The analytical models matched experimental data in terms of trend, but under-predicted strain by a constant factor. Ultimately, gel breakage was determined to be related to peak stress across the gel’s cross-section. By connecting breaking criteria in monochromatic, linear waves from tank tests to real-world conditions, this project provides an initial perspective on when wave-induced stretching alone could cause the fracture of a marine surface gel.Applied Science, Faculty ofCivil Engineering, Department ofGraduat

Observed and simulated estimates of the meridional overturning circulation at 26.5° N in the Atlantic

Daily timeseries of the meridional overturning circulation (MOC) estimated from the UK/US RAPID/MOCHA array at 26.5° N in the Atlantic are used to evaluate the MOC as simulated in two global circulation models: (I) an 8-member ensemble of the coupled climate model ECHAM5/MPI-OM, and (II) the ECCO-GODAE state estimate. In ECHAM5/MPI-OM, we find that the observed and simulated MOC have a similar variability and time-mean within the 99% confidence interval. In ECCO-GODAE, we find that the observed and simulated MOC show a significant correlation within the 99% confidence interval. To investigate the contribution of the different transport components, the MOC is decomposed into Florida Current, Ekman and mid-ocean transports. In both models, the mid-ocean transport is closely approximated by the residual of the MOC minus Florida Current and Ekman transports. As the models conserve volume by definition, future comparisons of the RAPID/MOCHA mid-ocean transport should be done against the residual transport in the models. The similarity in the variance and the correlation between the RAPID/MOCHA, and respectively ECHAM5/MPI-OM and ECCO-GODAE MOC estimates at 26.5° N is encouraging in the context of estimating (natural) variability in climate simulations and its use in climate change signal-to-noise detection analyses. Enhanced confidence in simulated hydrographic and transport variability will require longer observational time series

Practical Issues in prototyping a national, public transport journey-planning system using the JourneyWeb protocol

This research examined the requirements for multiple travelers to request a local, medium-distance, national, or international itinerary plan from any node of a public transport journey planner system using timetable or schedule data from numerous public transport companies and modes. It was resolved that a four-tier, client-server architecture and a distributed data service would best meet these requirements, using the Internet to exchange trip schedule data according to an agreed JourneyWeb protocol based on extended markup language. The JourneyWeb protocol is explained, and the field characteristics and attributes used in mutual data interrogation between itinerary planning services, allowing the web of services to expand, are defined. Successive iterations of a prototype system, first between two counties and then expanded to include a larger geographic area, demonstrate progress to date using real schedule data

De Novo Treatment of Diffuse Large B-Cell Lymphoma With Rituximab, Cyclophosphamide, Vincristine, Gemcitabine, and Prednisolone in Patients With Cardiac Comorbidity:A United Kingdom National Cancer Research Institute Trial

Purpose The treatment of patients with diffuse large B-cell lymphoma (DLBCL) with cardiac comorbidity is problematic, because this group may not be able to receive anthracycline-containing chemoimmunotherapy. We designed a single-arm phase II multicenter trial of rituximab, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) in patients considered unfit for anthracycline-containing chemoimmunotherapy because of cardiac comorbidity. Patients and Methods Sixty-one of 62 patients received R-GCVP, administered on day 1 with gemcitabine repeated on day 8 of a 21-day cycle. Median age was 76.5 years. All patients had advanced disease; 27 (43.5%) had left ventricular ejection fraction of 50%, and 35 (56.5%) had borderline ejection fraction of > 50% but 55% and comorbid cardiac risk factors such as ischemic heart disease, diabetes mellitus, or hypertension. Primary end point was overall response rate at the end of treatment. Results Thirty-eight patients (61.3%; 95% CI, 49.2 to 73.4) achieved disease response (complete response [CR], n = 18; undocumented/unconfirmed CR, n = 6; partial response, n = 14). Two-year progression-free survival for all patients was 49.8% (95% CI, 37.3 to 62.3), and 2-year overall survival was 55.8% (95% CI, 43.3 to 68.4). Thirty-four patients experienced grade 3 hematologic toxicity. There were 15 cardiac events, of which seven were grade 1 to 2, five were grade 3 to 4, and three were fatal, reflecting the poor cardiac status of the study population. Conclusion Our phase II multicenter trial showed that the R-GCVP regimen is an active, reasonably well-tolerated treatment for patients with DLBCL for whom anthracycline-containing immunochemotherapy was considered unsuitable because of coexisting cardiac disease