7 research outputs found

    Basin tectonic history and paleo-physiography of the pelagian platform, northern Tunisia, using vitrinite reflectance data

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    Constraining the thermal, burial and uplift/exhumation history of sedimentary basins is crucial in the understanding of upper crustal strain evolution and also has implications for understanding the nature and timing of hydrocarbon maturation and migration. In this study, we use Vitrinite Reflectance (VR) data to elucidate the paleo‐physiography and thermal history of an inverted basin in the foreland of the Atlasic orogeny in Northern Tunisia. In doing so, it is the primary aim of this study to demonstrate how VR techniques may be applied to unravel basin subsidence/uplift history of structural domains and provide valuable insights into the kinematic evolution of sedimentary basins. VR measurements of both the onshore Pelagian Platform and the Tunisian Furrow in Northern Tunisia are used to impose constraints on the deformation history of a long‐lived structural feature in the studied region, namely the Zaghouan Fault. Previous work has shown that this fault was active as an extensional structure in Lower Jurassic to Aptian times, before subsequently being inverted during the Late Cretaceous Eocene Atlas I tectonic event and Upper Miocene Atlas II tectonic event. Quantifying and constraining this latter inversion stage, and shedding light on the roles of structural inheritance and the basin thermal history, are secondary aims of this study. The results of this study show that the Atlas II WNW‐ESE compressive event deformed both the Pelagian Platform and the Tunisian Furrow during Tortonian‐Messinian times. Maximum burial depth for the Pelagian Platform was reached during the Middle to Upper Miocene, i.e. prior to the Atlas II folding event. VR measurements indicate that the Cretaceous to Ypresian section of the Pelagian Platform was buried to a maximum burial depth of ~3 km, using a geothermal gradient of 30°C/km. Cretaceous rock samples VR values show that the hanging wall of the Zaghouan Fault was buried to a maximum depth of <2 km. This suggests that a vertical km‐scale throw along the Zaghouan Fault pre‐dated the Atlas II shortening, and also proves that the fault controlled the subsidence of the Pelagian Platform during the Oligo‐Miocene. Mean exhumation rates of the Pelagian Platform throughout the Messinian to Quaternary were in the order of 0.3 mm/year. However, when the additional effect of Tortonian‐Messinian folding is accounted for, exhumation rates could have reached 0.6-0.7 mm/year

    Health-related quality of life associated with trifluridine/tipiracil in heavily pretreated metastatic gastric cancer: results from TAGS

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    Background In TAGS, an international, double-blind, phase 3 trial, trifluridine/tipiracil significantly improved overall survival and progression-free survival compared with placebo in heavily pretreated metastatic gastric cancer patients. This paper reports pre-specified quality of life (QoL) outcomes for TAGS. Methods Patients were randomized 2:1 to trifluridine/tipiracil (35 mg/m2 twice daily on days 1–5 and 8–12 of each 28-day cycle) plus best supportive care (BSC) or placebo plus BSC. QoL was evaluated at baseline and at each treatment cycle, using the EORTC QLQ-C30 and EORTC QLQ-STO22 questionnaires; results were considered valid for analysis only if ≄ 10% of patients completed the questionnaires. Key QoL outcomes were mean changes from baseline and time to deterioration in QoL. A post hoc analysis assessed the association between QoL and time to deterioration of Eastern Cooperative Oncology Group performance score (ECOG PS) to ≄ 2. Results Of 507 randomized patients, 496 had baseline QoL data available. The analysis cut-off was 6 cycles for trifluridine/tipiracil and 3 cycles for placebo. In both treatment groups, there were no clinically significant deteriorations in the mean QLQ-C30 Global Health Status (GHS) score, or in most subscale scores. In a sensitivity analysis including death and disease progression as events, there was a trend towards trifluridine/tipiracil reducing the risk of deterioration of QoL scores compared with placebo. Deterioration in the GHS score was associated with deterioration in ECOG PS. Conclusion QoL was maintained in TAGS, and there was a trend towards trifluridine/tipiracil reducing the risk of QoL deterioration compared with placebo

    From sewer to saviour-targeting the lymphatic system to promote drug exposure and activity

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    The lymphatic system serves an integral role in fluid homeostasis, lipid metabolism and immune control. In cancer, the lymph nodes that drain solid tumours are a primary site of metastasis, and recent studies have suggested intrinsic links between lymphatic function, lipid deposition, obesity and atherosclerosis. Advances in the current understanding of the role of the lymphatics in pathological change and immunity have driven the recognition that lymph-targeted delivery has the potential to transform disease treatment and vaccination. In addition, the design of lymphatic delivery systems has progressed from simple systems that rely on passive lymphatic access to sophisticated structures that use nanotechnology to mimic endogenous macromolecules and lipid conjugates that 'hitchhike' onto lipid transport processes. Here, we briefly summarize the lymphatic system in health and disease and the varying mechanisms of lymphatic entry and transport, as well as discussing examples of lymphatic delivery that have enhanced therapeutic utility. We also outline future challenges to effective lymph-directed therapy

    From sewer to saviour — targeting the lymphatic system to promote drug exposure and activity

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