A hybrid GCM paleo ice-sheet model, ANICE2.1 – [email protected]: set up and benchmark experiments

Fully coupled ice-sheet-climate modelling over 10,000 – 100,000-year time scales on high spatial and temporal resolution remains beyond the capability of current computational systems. Hybrid GCM-ice-sheet modelling offers a middle ground, balancing the need to accurately capture both long-term processes, in particular circulation driven changes in precipitation, and processes requiring a high spatial resolution like ablation. Here, we present and evaluate a model set-up that forces the ANICE 3D thermodynamic ice-sheet-shelf model calculating the four large continental ice-sheets (Antarctica, Greenland, North America and Eurasia), with pre-calculated output from two steady-state simulations with the HadCM3 general circulation model (GCM), using a so-called matrix method of coupling both components, where simulations with various levels of pCO2 and ice-sheet configuration are combined to form a time-continuous transient climate forcing consistent with the modelled ice-sheets. We address the difficulties in downscaling low-resolution GCM output to the higher-resolution grid of an ice-sheet model, and account for differences between GCM and ice-sheet model surface topography ranging from interglacial to glacial conditions. Although the approach presented here can be applied to a matrix with any number of GCM snapshots, we limited our experiments to a matrix of only two snapshots. As a benchmark experiment to assess the validity of this model set-up, we perform a simulation of the entire last glacial cycle, from 120 kyr ago to present-day. The simulated eustatic sea-level drop at the Last Glacial maximum (LGM) for the combined Antarctic, Greenland, Eurasian and North-American ice-sheets amounts to 100 m, in line with many other studies. The simulated ice-sheets at LGM agree well with the ICE-5G reconstruction and the more recent DATED-1 reconstruction in terms of total volume and geographical location of the ice sheets. Moreover, modelled benthic oxygen isotope abundance and the relative contributions from global ice volume and deep-water temperature agree well with available data, as do surface temperature histories for the Greenland and Antarctic ice-sheets. This model strategy can be used to create time-continuous ice-sheet distribution and sea-level reconstructions for geological periods up to several millions of years in duration, capturing climate model driven variations in the mass balance of the ice sheet

Broedsucces van kustbroedvogels in de Waddenzee in 2007 en 2008

Voor het derde en vierde opeenvolgende jaar werd het broedsucces van een aantal kustbroedvogels in de Waddenzee bepaald. Van Eider, Scholekster, Kluut, Kokmeeuw, Zilvermeeuw en Visdief, alsmede van Kleine Mantelmeeuw en Noordse Stern werd informatie verzamelen over het nestsucces en uitvliegsucces (het uiteindelijke broedsucces). Kennis over de jaarlijkse variatie in broedresultaten bij de verschillende soorten is van belang als een early warning systeem om de 'kwaliteit' (het reproducerend vermogen) van de vogelpopulaties in de Waddenzee te volgen en de achterliggende processen van populatieveranderingen te doorgronden. Directe aanleiding voor het project vormde de evaluatie van de effectiviteit van het nieuwe schelpdiervisserijbeleid en de mogelijke gevolgen voor de voedselvoorziening van schelpdieretende vogels

Cardiovascular mortality in women in their forties after hypertensive disorders of pregnancy in the Netherlands : a national cohort study

Peer reviewedPublisher PD

In-medium relativistic kinetic theory and nucleon-meson systems

Within the $\sigma-\omega$ model of coupled nucleon-meson systems, a generalized relativistic Lenard--Balescu--equation is presented resulting from a relativistic random phase approximation (RRPA). This provides a systematic derivation of relativistic transport equations in the frame of nonequilibrium Green's function technique including medium effects as well as flucuation effects. It contains all possible processes due to one meson exchange and special attention is kept to the off--shell character of the particles. As a new feature of many particle effects, processes are possible which can be interpreted as particle creation and annihilation due to in-medium one meson exchange. In-medium cross sections are obtained from the generalized derivation of collision integrals, which possess complete crossing symmetries.Comment: See nucl-th/9310032 for revised version which the authors incompetently resubmitted rather than correctly replacing thi

Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in metastatic malignant melanoma

The results of cytostatic therapy in metastatic melanoma are very disappointing. In phase II studies with high-dose cisplatin regimens, a remarkably high response rate was observed. In a phase I study with a short course of weekly cisplatin, combined with oral etoposide, we were able to reach, in most patients, a cisplatin dose intensity of 60 mg/m2/week. We performed a phase II study with this schedule in metastatic malignant melanoma. 15 consecutive patients were entered in the study. Treatment consisted of cisplatin 70 mg/m2 on days 1, 8, 15 and days 29, 36, 43 combined with oral etoposide 50 mg daily, days 1-15 and days 29-43. Patients with a response or stable disease continued treatment with oral etoposide 50 mg/m2 daily, days 1-21 every 4 weeks. All patients were evaluable for response and toxicity. The majority of the patients received six cycles of cisplatin with the planned cisplatin dose intensity of 60 mg/m2/week. A partial response was observed in 2 patients (13%; 95% confidence interval (CI) 2-44%) of, respectively, 22 and 12 weeks; stable disease was observed in 6 patients. Toxicity consisted mainly of alopecia and bone marrow suppression. 4 patients had tinnitus, one patient had neurotoxicity grade 1. The regimen studied has only limited activity in metastatic melanoma in spite of the high-dose intensity of cisplatin reached with this schedule

Diagnostic Capability of Peripapillary Retinal Volume Measurements in Glaucoma

Purpose: To determine the diagnostic capability of spectral domain optical coherence tomography peripapillary retinal volume (RV) measurements. Materials and Methods: A total of 156 patients, 89 primary open-angle glaucoma and 67 normal subjects, were recruited. Spectral domain optical coherence tomography peripapillary RV was calculated for 4 quadrants using 3 annuli of varying scan circle diameters: outer circumpapillary annuli of circular grids 1, 2, and 3 (OCA1, OCA2, OCA3). Area under the receiver operating characteristic curves and pairwise comparisons of receiver operating characteristic (ROC) curves were performed to determine which quadrants were best for diagnosing primary open-angle glaucoma. The pairwise comparisons of the best ROC curves for RV and retinal nerve fiber layer (RNFL) were performed. The artifact rates were analyzed. Results: Pairwise comparisons showed that the smaller annuli OCA1 and OCA2 had better diagnostic performance than the largest annulus OCA3 (P<0.05 for all quadrants). OCA1 and OCA2 had similar diagnostic performance, except for the inferior quadrant which was better for OCA1 (P=0.0033). The pairwise comparisons of the best ROC curves for RV and RNFL were not statistically significant. RV measurements had lower rates of artifacts at 7.4% while RNFL measurements had higher rates at 42.9%. Conclusions: Peripapillary RV measurements have excellent ability for diagnosing not only glaucoma patients but also a subset of early glaucoma patients. The inferior quadrant of peripapillary annulus OCA1 demonstrated the best diagnostic capability for both glaucoma and early glaucoma. The diagnostic ability of RV is comparable with that of RNFL parameters in glaucoma but with lower artifact rates. © 2017 Wolters Kluwer Health, Inc. All rights reserved

Limited added value of laboratory monitoring in thiopurine maintenance monotherapy in inflammatory bowel disease patients

Background: To timely detect myelotoxicity and hepatotoxicity, laboratory monitoring at 3-month intervals is advised throughout thiopurine maintenance treatment for IBD. However, reported incidence rates of myelotoxicity and hepatotoxicity in maintenance treatment are low. Aim: To assess incidence rates and clinical consequences of myelotoxicity and hepatotoxicity in thiopurine maintenance therapy after at least 1 year of thiopurine treatment. Methods: Retrospective analysis of therapy adjustment for laboratory toxicity in adult IBD patients after 12 consecutive months of azathioprine (AZA) or mercaptopurine monotherapy (ie baseline) between 2000 and 2016. Incidence rates of laboratory toxicity (ie myelotoxicity [leucocyte count <4.0 × 10e9/L, and/or platelet count <150 × 10e9/L] and/or hepatotoxicity (gamma-glutamyltransferase [GGT], alkaline phosphatase [AP], ALT and/or AST above ULN, excluding isolated increased AST/AP]) and associated diagnostic procedures and complications were assessed. Results: In total, 12.391 laboratory assessments were performed on 1132 patients (56% female, AZA 74%) during 3.3 years of median follow-up. Median monitoring frequency was 3.1 assessments/treatment year. Only 83/12.391 (0.7%) assessments resulted in therapy adjustment, dose reduction in 46 patients, cessation in 28 and allopurinol initiation in nine; risk of therapy adjustment was 1.9% per treatment year. Incidence rates of myelotoxicity were 7.1% (5.1% mild/1.8% moderate/0.1% severe) and hepatotoxicity 5.1% (3.8% mild/1.1% moderate/0.2% severe) per treatment year. Treatment-related complications with concurrent laboratory toxicity occurred in 12 patients (1.1%) and would not have been prevented by monitoring. Conclusion: Severe laboratory toxicity is uncommon after 1 year of thiopurine monotherapy at 4-month monitoring intervals. Therapy adjustments are rare after detection of laboratory toxicity. After 1 year of thiopurine monotherapy, laboratory monitoring may be lowered to less than a 4-month interval

Treatment planning evaluation and experimental validation of the magnetic resonance-based intrafraction drift correction

Background and purpose: MRI-guided online adaptive treatments can account for interfractional variations, however intrafraction motion reduces treatment accuracy. Intrafraction plan adaptation methods, such as the Intrafraction Drift Correction (IDC) or sub-fractionation, are needed. IDC uses real-time automatic monitoring of the tumor position to initiate plan adaptations by repositioning segments. IDC is a fast adaptation method that occurs only when necessary and this method could enable margin reduction. This research provides a treatment planning evaluation and experimental validation of the IDC. Materials and methods: An in silico treatment planning evaluation was performed for 13 prostate patients mid-treatment without and with intrafraction plan adaptation (IDC and sub-fractionation). The adaptation methods were evaluated using dose volume histogram (DVH) metrics. To experimentally verify IDC a treatment was mimicked whereby a motion phantom containing an EBT3 film moved mid-treatment, followed by repositioning of segments. In addition, the delivered treatment was irradiated on a diode array phantom for plan quality assurance purposes. Results: The planning study showed benefits for using intrafraction adaptation methods relative to no adaptation, where the IDC and sub-fractionation showed consistently improved target coverage with median target coverages of 100.0%. The experimental results verified the IDC with high minimum gamma passing rates of 99.1% and small mean dose deviations of maximum 0.3%. Conclusion: The straightforward and fast IDC technique showed DVH metrics consistent with the sub-fractionation method using segment weight re-optimization for prostate patients. The dosimetric and geometric accuracy was shown for a full IDC workflow using film and diode array dosimetry