'Gardez-vous-en bien … de la brochure' : pamfletgebruik en politieke cultuur in de historiografie over de Brabantse Omwenteling, 1787-1789

At the end of the eighteenth century, the Austrian Netherlands were plagued by political turmoil and social upheaval, brought forth by a reaction against the reformatory movement set up by the Habsburg government. The contestation of Joseph II’s reformist policy was performed in public, as the region was flooded with polemical pamphlets, ideological treatises and many other types of popular writings during (but also before and after) the period of the Brabant Revolution (1787-1789). Pamphlets have stood at the centre of attention for the historiography of Belgian political culture at the end of the ancien régime, yet this wide employment of the source material has not led to a comparative overview of the way these writings have been used in historical research. This article will attempt to fill this gap, by first providing a methodological typology of several historiographical uses of a particular pamphlet, the Manifeste du Peuple Brabançon, written at the end of 1789, and signed by the leader of the conservative opposition, Hendrik Van der Noot. Secondly, I will attempt to show how eighteenth-century pamphleteers used a multitude of discourses at their disposal, by briefly discussing another set of (pre-revolutionary) pamphlets. This has immediate consequences for the current understanding of eighteenth-century Brabant political culture, which, so I argue, should not be considered discursively monolithic (containing one political language) but pluralist (containing multiple political languages)

Modelled glacier dynamics over the last quarter of a century at Jakobshavn Isbræ

Observations over the past 2 decades show substantial ice loss associated with the speed-up of marine-terminating glaciers in Greenland. Here we use a regional three-dimensional outlet glacier model to simulate the behaviour of Jakobshavn Isbræ (JI) located in western Greenland. Our approach is to model and understand the recent behaviour of JI with a physical process-based model. Using atmospheric forcing and an ocean parametrization we tune our model to reproduce observed frontal changes of JI during 1990–2014. In our simulations, most of the JI retreat during 1990–2014 is driven by the ocean parametrization used and the glacier's subsequent response, which is largely governed by bed geometry. In general, the study shows significant progress in modelling the temporal variability of the flow at JI. Our results suggest that the overall variability in modelled horizontal velocities is a response to variations in terminus position. The model simulates two major accelerations that are consistent with observations of changes in glacier terminus. The first event occurred in 1998 and was triggered by a retreat of the front and moderate thinning of JI prior to 1998. The second event, which started in 2003 and peaked in the summer 2004, was triggered by the final break-up of the floating tongue. This break-up reduced the buttressing at the JI terminus that resulted in further thinning. As the terminus retreated over a reverse bed slope into deeper water, sustained high velocities over the last decade have been observed at JI. Our model provides evidence that the 1998 and 2003 flow accelerations are most likely initiated by the ocean parametrization used but JI's subsequent dynamic response was governed by its own bed geometry. We are unable to reproduce the observed 2010–2012 terminus retreat in our simulations. We attribute this limitation to either inaccuracies in basal topography or to misrepresentations of the climatic forcings that were applied. Nevertheless, the model is able to simulate the previously observed increase in mass loss through 2014

Glacier dynamics at Helheim and Kangerdlugssuaq glaciers, southeast Greenland, since the Little Ice Age

Observations over the past decade show significant ice loss associated with the speed-up of glaciers in southeast Greenland from 2003, followed by a deceleration from 2006. These short-term, episodic, dynamic perturbations have a major impact on the mass balance on the decadal scale. To improve the projection of future sea level rise, a long-term data record that reveals the mass balance beyond such episodic events is required. Here, we extend the observational record of marginal thinning of Helheim and Kangerdlugssuaq glaciers from 10 to more than 80 years. We show that, although the frontal portion of Helheim Glacier thinned by more than 100m between 2003 and 2006, it thickened by more than 50m during the previous two decades. In contrast, Kangerdlugssuaq Glacier underwent minor thinning of 40-50m from 1981 to 1998 and major thinning of more than 100m after 2003. Extending the record back to the end of the Little Ice Age (prior to 1930) shows no thinning of Helheim Glacier from its maximum extent during the Little Ice Age to 1981, while Kangerdlugssuaq Glacier underwent substantial thinning of 230 to 265 m. Comparison of sub-surface water temperature anomalies and variations in air temperature to records of thickness and velocity change suggest that both glaciers are highly sensitive to short-term atmospheric and ocean forcing, and respond very quickly to small fluctuations. On century timescales, however, multiple external parameters (e. g. outlet glacier shape) may dominate the mass change. These findings suggest that special care must be taken in the projection of future dynamic ice loss

Research on increasing the enrolment in mathematics, physics, chemistry and computer science teacher education

Dit rapport geeft de resultaten weer van een onderzoek dat is uitgevoerd door drie universiteiten naar de vergroting van de instroom in de eerstegraads lerarenopleiding bij de bètavakken wiskunde, informatica, natuurkunde en scheikunde. Het onderzoek is tot stand gekomen in samenwerking met de decanen van de bètafaculteiten vanwege de zorgen over de lage instroom in universitaire lerarenopleidingen. Het onderzoek maakt deel uit van een project tot versterking van de bètadidactiek waaraan ook de Universiteit Twente en de Universiteit Utrecht deelnemen, en is mogelijk gemaakt door subsidie van het ministerie van Onderwijs, Cultuur en Wetenschap.In dit rapport worden de deelonderzoeken weergegeven in verschillende hoofdstukken:• Universiteit Leiden (dr. ir. Alma Kuijpers, dr. Michiel Dam, prof. r. ir. Fred Janssen): hoofdstukken 2 en 6.• Technische Universiteit Delft (dr. Begüm Coskun, prof. dr. Marc de Vries): hoofdstuk 4.• Rijksuniversiteit Groningen (dr. Els van Rooij, dr. Marjon Fokkens-Bruinsma, prof. dr. Martin Goedhart): hoofdstukken 3 en 5

TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer

Purpose: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from patients with metastatic castration-resistant prostate cancer (mCRPC) starting a new line of AR signaling inhibitors (ARSi). Experimental Design: Between March 2014 and April 2017, we recruited patients with mCRPC (n = 168) prior to ARSi in a cohort study encompassing 10 European centers. Blood samples were collected for comprehensive profiling of Cell Search-enriched circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Targeted CTC RNA sequencing (RNA-seq) allowed the detection of eight AR splice variants (ARV). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss of heterozygosity, mutations, and structural rearrangements in ctDNA. Clinical or radiologic progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox regression models. Results: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumor burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value [HR 1.88; 95% confidence interval (CI), 1.18-3.00; P = 0.008], and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs. 7.51 vs. 2.62 months; P < 0.0001), which was validated in an independent mCRPC cohort (n = 202) starting first-line ARSi (median, 14.3 vs. 6.39 vs. 2.23 months; P < 0.0001). Conclusions: In an all-comer cohort, tumor burden estimates and TP53 outperform any AR perturbation to infer prognosis. See related commentary by Rebello et al., p. 169

Accelerating changes in ice mass within Greenland, and the ice sheet's sensitivity to atmospheric forcing

The recent deglaciation of Greenland is a response to both oceanic and atmospheric forcings. From 2000 to 2010, ice loss was concentrated in the southeast and northwest margins of the ice sheet, in large part due to the increasing discharge of marine-terminating outlet glaciers, emphasizing the importance of oceanic forcing. However, the largest sustained (∼10 years) acceleration detected by Gravity Recovery and Climate Experiment (GRACE) occurred in southwest Greenland, an area largely devoid of such glaciers. The sustained acceleration and the subsequent, abrupt, and even stronger deceleration were mostly driven by changes in air temperature and solar radiation. Continued atmospheric warming will lead to southwest Greenland becoming a major contributor to sea level rise

Prognostic value of total tumor volume in patients with colorectal liver metastases:A secondary analysis of the randomized CAIRO5 trial with external cohort validation

Background:This study aimed to assess the prognostic value of total tumor volume (TTV) for early recurrence (within 6 months) and overall survival (OS) in patients with colorectal liver metastases (CRLM), treated with induction systemic therapy followed by complete local treatment.Methods: Patients with initially unresectable CRLM from the multicenter randomized phase 3 CAIRO5 trial (NCT02162563) who received induction systemic therapy followed by local treatment were included. Baseline TTV and change in TTV as response to systemic therapy were calculated using the CT scan before and the first after systemic treatment, and were assessed for their added prognostic value. The findings were validated in an external cohort of patients treated at a tertiary center. Results:In total, 215 CAIRO5 patients were included. Baseline TTV and absolute change in TTV were significantly associated with early recurrence (P = 0.005 and P = 0.040, respectively) and OS in multivariable analyses (P = 0.024 and P = 0.006, respectively), whereas RECIST1.1 was not prognostic for early recurrence (P = 0.88) and OS (P = 0.35). In the validation cohort (n = 85), baseline TTV and absolute change in TTV remained prognostic for early recurrence (P = 0.041 and P = 0.021, respectively) and OS in multivariable analyses (P &lt; 0.0001 and P = 0.012, respectively), and showed added prognostic value over conventional clinicopathological variables (increase C-statistic, 0.06; 95 % CI, 0.02 to 0.14; P = 0.008). Conclusion: Total tumor volume is strongly prognostic for early recurrence and OS in patients who underwent complete local treatment of initially unresectable CRLM, both in the CAIRO5 trial and the validation cohort. In contrast, RECIST1.1 did not show prognostic value for neither early recurrence nor OS.</p