A model study of tidal distributions in the Celtic and Irish Sea regions determined with finite volume and finite element models

An unstructured mesh model of the west coast of Britain, covering the same domain and using topography and open boundary forcing that are identical to a previous validated uniform grid finite difference model of the region, is used to compare the performance of a finite volume (FV) and a finite element (FE) model of the area in determining tide–surge interaction in the region. Initial calculations show that although qualitatively both models give comparable tidal solutions in the region, comparison with observations shows that the FV model tends to under-estimate tidal amplitudes and hence background tidal friction in the eastern Irish Sea. Storm surge elevations in the eastern Irish Sea due to westerly, northerly and southerly uniform wind stresses computed with the FV model tend to be slightly higher than those computed with the FE model, due to differences in background tidal friction. However, both models showed comparable non-linear tide–surge interaction effects for all wind directions, suggesting that they can reproduce the extensive tide–surge interaction processes that occur in the eastern Irish Sea. Following on from this model comparison study, the physical processes contributing to surge generation and tide–surge interaction in the region are examined. Calculations are performed with uniform wind stresses from a range of directions, and the balance of various terms in the hydrodynamic equations is examined. A detailed comparison of the spatial variability of time series of non-linear bottom friction and non-linear momentum advection terms at six adjacent nodes at two locations in water depths of 20 and 6 m showed some spatial variability from one node to another. This suggests that even in the near coastal region, where water depths are of the order of 6 m and the mesh is fine (of order 0.5 km), there is significant spatial variability in the non-linear terms. In addition, distributions of maximum bed stress due to tides and wind forcing in nearshore regions show appreciable spatial variability. This suggests that intensive measurement campaigns and very high-resolution mesh models are required to validate and reproduce the non-linear processes that occur in these regions and to predict extreme bed stresses that can give rise to sediment movement. High-resolution meshes will also be required in pollution transport problem

Review of experience over four decades in the management of carotid body tumours

Objective: To review the experience of the management of carotid body tumours in a major vascular centre in mainland China. Patients and methods: This was a retrospective review of 52 cases of carotid body tumour. There were 24 male and 28 female patients with an age range of 18-67 years; and 23 right-sided, 24 left-sided and five bilateral lesions. The modality of preoperative imaging was as follows: duplex scan and computed tomography in 40 cases, magnetic resonance imaging in 10 cases, carotid artery angiogram in 32 cases with selective embolization of the feeding vessel in 19. Operative treatment was carried out for 55 lesions and was summarized as follows: simple tumour excision for 44 lesions and en bloc tumour excision together with carotid bifurcation for 11 lesions; ICA reconstruction with interposition graft in three cases; and external to ICA anastomosis in two cases. Results: There were no operative mortalities. Postoperative complications included two ischaemic strokes, one case of vagus nerve damage and one case of hypoglossal nerve damage. Conclusion: Carotid body tumour is a rare neoplasm. Its special anatomical position imposes great difficulty during surgery. Adequate preoperative preparation and embolization of feeding arteries could reduce operative blood loss, improve tumour excision and preserve the ICA flow.link_to_subscribed_fulltex

Mechanisms of Resistance to EGFR Inhibition Reveal Metabolic Vulnerabilities in Human GBM.

Amplification of the epidermal growth factor receptor gene (EGFR) represents one of the most commonly observed genetic lesions in glioblastoma (GBM); however, therapies targeting this signaling pathway have failed clinically. Here, using human tumors, primary patient-derived xenografts (PDX), and a murine model for GBM, we demonstrate that EGFR inhibition leads to increased invasion of tumor cells. Further, EGFR inhibitor-treated GBM demonstrates altered oxidative stress, with increased lipid peroxidation, and generation of toxic lipid peroxidation products. A tumor cell subpopulation with elevated aldehyde dehydrogenase (ALDH) levels was determined to comprise a significant proportion of the invasive cells observed in EGFR inhibitor-treated GBM. Our analysis of the ALDH1A1 protein in newly diagnosed GBM revealed detectable ALDH1A1 expression in 69% (35/51) of the cases, but in relatively low percentages of tumor cells. Analysis of paired human GBM before and after EGFR inhibitor therapy showed an increase in ALDH1A1 expression in EGFR-amplified tumors (P < 0.05, n = 13 tumor pairs), and in murine GBM ALDH1A1-high clones were more resistant to EGFR inhibition than ALDH1A1-low clones. Our data identify ALDH levels as a biomarker of GBM cells with high invasive potential, altered oxidative stress, and resistance to EGFR inhibition, and reveal a therapeutic target whose inhibition should limit GBM invasion