Nearshore wave forecasting and hindcasting by dynamical and statistical downscaling

A high-resolution nested WAM/SWAN wave model suite aimed at rapidly establishing nearshore wave forecasts as well as a climatology and return values of the local wave conditions with Rapid Enviromental Assessment (REA) in mind is described. The system is targeted at regions where local wave growth and partial exposure to complex open-ocean wave conditions makes diagnostic wave modelling difficult. SWAN is set up on 500 m resolution and is nested in a 10 km version of WAM. A model integration of more than one year is carried out to map the spatial distribution of the wave field. The model correlates well with wave buoy observations (0.96) but overestimates the wave height somewhat (18%, bias 0.29 m). To estimate wave height return values a much longer time series is required and running SWAN for such a period is unrealistic in a REA setting. Instead we establish a direction-dependent transfer function between an already existing coarse open-ocean hindcast dataset and the high-resolution nested SWAN model. Return values are estimated using ensemble estimates of two different extreme-value distributions based on the full 52 years of statistically downscaled hindcast data. We find good agreement between downscaled wave height and wave buoy observations. The cost of generating the statistically downscaled hindcast time series is negligible and can be redone for arbitrary locations within the SWAN domain, although the sectors must be carefully chosen for each new location. The method is found to be well suited to rapidly providing detailed wave forecasts as well as hindcasts and return values estimates of partly sheltered coastal regions.Comment: 20 pages, 7 figures and 2 tables, MREA07 special issue on Marine rapid environmental assessmen

Treatment with anti-TNF alpha protects against the neuropathy induced by the proteasome inhibitor bortezomib in a mouse model

Bortezomib (BTZ), a proteasome inhibitor, is an effective anti-neoplastic drug used in the treatment of multiple myeloma and mantle cell lymphoma. However, it can induce a reversible peripheral neuropathy that may lead to treatment discontinuation. The mechanism through which BTZ exerts toxic effects in peripheral neurons is not clear. Release of proinflammatory cytokines after nerve damage can induce neurodegeneration, but the effects of BTZ on cytokine expression in neurons are unknown, although BTZ modulates the expression of cytokines, such as TNF-α and IL-6, in tumor cells. The aim of this study was to evaluate the expression and the role of these cytokines on the course of BTZ induced neuropathy in mice. IL-6, TNF-α, TGF-β1 and IL-1β were up-regulated in dorsal root ganglia but TNF-α and IL-6 increased faster and higher. Then, we studied the potential neuroprotective effect of selective antibodies anti-TNF-α and anti-IL-6 on the evolution of the neuropathy. Treatment with anti-TNF-α but not with anti-IL-6 significantly prevented the decrease of sensory nerve action potentials amplitude and the loss of myelinated and unmyelinated fibers. We conclude that monoclonal antibodies directed against TNF-α may be a suitable neuroprotective therapy against the neurotoxicity induced by BTZ. © 2013 Elsevier Inc

Dispositie van 8-methoxypsoraleen bij dier en mens /

Diss. doct. farmaceutische wetenschappe

REDUCTION OF THE PRODRUG LOPERAMIDE OXIDE TO ITS ACTIVE DRUG LOPERAMIDE IN THE GUT OF RATS, DOGS, AND HUMANS

ABSTRACT: Loperamide oxide (LOPOX) is a prodrug of loperamide (LOP)

Combined liver-thoracic transplantation: single-center experience with introduction of the "Liver-first' principle

Combined liver/thoracic transplantation(cLiThTx) is a complex procedure for end-stage/advanced liver and heart(H)/lung(Lu) disease. To avoid futile use of multiple organs in single recipients, results should be scrutinously analysed. Single-center cLiThTx (04/2000-12/2015) were reviewed for: demographics, indications, surgical technique, complications, rejection, five-year patient survival. Results are reported as median(range). Fourteen consecutive patients underwent cLiThTx: 3 cLiHTx, 10 cLiLuTx, 1 cLiHLuTx. Recipient age was 42years (17-63years). Most frequent indications were cystic fibrosis (n=5), hepatopulmonary fibrosis (n=2), amyloidosis (n=2) and epithelioid hemangio-endothelioma (n=2). Thoracic organs were transplanted first, except in three where LiTx preceded LuTx. In the latter, lungs were preserved by normothermic ex-vivo lung perfusion. Stenting was performed for stenosis of bile-duct (n=4), hepatic artery (n=2) and bronchus (n=2). Abdominal interventions were required for bleeding (n=3), evisceration (n=1) and adhesiolysis (n=1). One liver (cLiLuTx) was lost to hepatic artery thrombosis 3 months posttransplant and successfully re-transplanted. One patient (cLiHTx) died 4 months posttransplant (myocardial infarction). Follow-up was 4years (2months - 16years). One liver and 5 pulmonary rejections occurred, all mild and reversible. Two patients developed bronchiolitis obliterans, one is clinically well 16years posttransplant, the other successfully retransplanted. Estimated five-year patient survival is 90%. CLiThTx is safe with excellent short-/long-term surgical and immunological results. This article is protected by copyright. All rights reserved.status: publishe