The intestine under stress : effects of chemotherapy on the intestinal epithelium

In studying the effects of cytostatic drugs on intestinal function, the use of experimental animals is indispensable. Only they permit a detailed analysis of the entire organ in time, allowing each study of each phase of the disease. This would be both unethical and technically very difficult to perform in biopsies of human patients, especially in cancer patients who are already suffering from both disease and treatment. In our studies, the rat was chosen as a model, because of the similarities to humans in intestinal physiology and the availability of techniques and tools. In this thesis, attention was focussed on the absorptive and defensive functions of the intestine during damage and regeneration induced by the cytostatic drug methotrexate (MTX). MTX was chosen among the various cytostatic drugs available, because of the considerable knowledge about its pharmacology and its way of action in humans and animal species. As folic acid analogue, MTX directly seizes the proliferative machinery of the intestine, thereby disturbing the normal cell turnover of the epithelium

An Altered Derivatives Marketplace: Clearing Swaps Under Dodd-Frank

Though over a year has passed, the impact of the Dodd Frank Act remains unclear. This Note examines the provisions of the Act that relate to swap transactions within the context of pre-reform and postreform markets. In order to reduce the uncertainties inherent in unregulated swap transactions, the Act employs a comprehensive framework, which includes mandatory clearing through derivative clearing organizations, extensive reporting requirements, margin requirements, and position limits. This Note argues that, in doing so, the Dodd Frank Act addresses the fundamental failures of pre-reform derivative markets. However, the importance of the role for derivative clearing organizations under this framework creates a risk that these organizations will become systemically significant, mirroring problems with under-capitalized and over-exposed financial institutions in the downturn

Omineca Herald, December, 26, 1913

De afgelopen jaren is het bewustzijn voor de kwaliteit van zorg bij belanghebbenden gegroeid. De hoge kosten voor IC-zorg leiden ertoe dat een groot deel van het budget voor de gezondheidszorg wordt uitgegeven aan IC's. Dit maakt de IC een interessant onderdeel van het ziekenhuis om efficiëntie en effectiviteit van de geleverde zorg te monitoren, te vergelijken en te verbeteren. De behandelduur op de IC kan een belangrijke rol spelen bij onderzoek naar de efficiëntie van de geleverde IC-zorg. Onder experts bestaat weinig consensus met betrekking tot de beste methode om de IC-behandelduur te voorspellen. Het eerste deel van dit proefschrift behandelde de ontwikkeling en het voorspellend vermogen van prognostische modellen voor IC-behandelduur. Het tweede deel van dit proefschrift behandelde de presentatie van de waarden van kwaliteitsindicatoren. Een enkele kwaliteitsindicator kan niet alle aspecten van zorgkwaliteit en efficiëntie zuiver meten. Vaak wordt gebruik gemaakt van een set kwaliteitsindicatoren om ruimte voor verbetering in zorgkwaliteit te kunnen identificeren en hiermee beleidsbeslissingen te ondersteunen. In dit proefschrift hebben we de associatie tussen de kwaliteitsindicatoren voor ziekenhuissterfte; heropname op de IC binnen 48 uur na IC-ontslag; en IC-behandelduur als uitkomstmaat behandeld. Tevens werden in dit proefschrift ranglijsten en funnel plots geïntroduceerd als methoden om de waarden van kwaliteitsindicatoren grafisch weer te geven

A high-resolution and harmonized model approach for reconstructing and analyzing historic land changes in Europe

Human-induced land use changes are nowadays the second largest contributor to atmospheric carbon dioxide after fossil fuel combustion. Existing historic land change reconstructions on the European scale do not sufficiently meet the requirements of greenhouse gas (GHG) and climate assessments, due to insufficient spatial and thematic detail and the consideration of various land change types. This paper investigates if the combination of different data sources, more detailed modelling techniques, and the integration of land conversion types allow us to create accurate, high-resolution historic land change data for Europe suited for the needs of GHG and climate assessments. We validated our reconstruction with historic aerial photographs from 1950 and 1990 for 73 sample sites across Europe and compared it with other land reconstructions like Klein Goldewijk et al. (2010, 2011), Ramankutty and Foley (1999), Pongratz et al. (2008) and Hurtt et al. (2006). The results indicate that almost 700 000 km² (15.5%) of land cover in Europe has changed over the period 1950–2010, an area similar to France. In Southern Europe the relative amount was almost 3.5% higher than average (19%). Based on the results the specific types of conversion, hot-spots of change and their relation to political decisions and socio-economic transitions were studied. The analysis indicates that the main drivers of land change over the studied period were urbanization, the reforestation program resulting from the timber shortage after the Second World War, the fall of the Iron Curtain, the Common Agricultural Policy and accompanying afforestation actions of the EU. Compared to existing land cover reconstructions, the new method considers the harmonization of different datasets by achieving a high spatial resolution and regional detail with a full coverage of different land categories. These characteristics allow the data to be used to support and improve ongoing GHG inventories and climate research

Expanding the toolbox : Assessing methods for local outdoor recreation planning

Peer reviewedPublisher PD

Venom immunotherapy in patients with clonal mast cell disorders: IgG4 correlates with protection

BackgroundPatients with clonal mast cell disorders (cMCD), systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS), represent an increased risk for Hymenoptera venom anaphylaxis (HVA). Lifelong venom immunotherapy (VIT) is recommended; however, its efficacy and safety are controversial. Hence, we sought to evaluate the efficacy and safety of VIT in HVA patients with cMCD.MethodsA retrospective study was conducted among 46 patients with Vespula venom allergy who had experienced severe HVA, 32 cMCD (22 with SM and 10 with MMAS) and 14 controls. There were no differences between cMCD patients and controls in age (58 vs 66) and duration of VIT (47 vs 48 months), respectively.ResultsDuring VIT, 11 (34%) cMCD patients experienced adverse reactions (ARs) (7% in controls), including 1 anaphylaxis. There were 23 re‐stings in 17 (53%) patients during VIT. Of episodes, four (17%) presented with anaphylaxis, 14 (60%) presented with local reaction, and five (23%) were asymptomatic. In 11 episodes (48%), the patient did not take epinephrine, of these 8 (73%) presented with local reaction, and 3 (27%) were asymptomatic. Patient‐based protection from anaphylaxis was 76% (4/17) in cMCD vs. 100% in controls during VIT. The venom‐specific IgG4 concentrations increased during VIT (P < .001) although tryptase and IgE were unaltered.ConclusionBoth safety and efficacy of VIT in cMCD patients were slightly reduced than controls. Severe ARs were rare. The elevated IgG4 levels may be a biomarker for efficacy of VIT in cMCD patients, as it correlates with protection from re‐stings.Patients with clonal mast cell disorders (cMCD) convey increased risk for venom‐induced anaphylaxis and lifelong venom‐immunotherapy (VIT) is recommended, when appropriate. VIT appears to be rather safe and effective in cMCD patients, as the risk of severe adverse reactions are rare. Elevated levels of venom‐specific IgG4 correlates with protection from re‐sting anaphylaxis in cMCD patients during VIT.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153084/1/all13980.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153084/2/all13980_am.pd

Beyond the urban-rural dichotomy:Towards a more nuanced analysis of changes in built-up land

Urban land and rural land are typically represented as homogenous and mutually exclusive classes in land change analyses. As a result, differences in urban land use intensity, as well as mosaic landscapes combining urban and rural land uses are not represented. In this study we explore the distribution of urban land and urban land use intensity in Europe and the changes therein. Specifically, we analyze the distribution of built-up land within pixels of 1 km2. At that resolution we find that most built-up land is distributed over predominantly non-built-up pixels. Consistently, we find that most urban land use changes between 2000 and 2014 come in small incremental changes, rather than sudden large-scale conversions from rural to urban land. Using urban population densities, we find that urban land use intensity varies strongly across 1 km2 pixels in Europe, as illustrated by a coefficient of variation of 85%. We found a similarly high variation between urban population densities for most individual countries and within areas with the same share of built-up land. Population changes have led to different combinations of urban land expansion and urban intensity changes in different study periods (1975–1990, 1990–2000, and 2000–2015) and countries. These findings suggest that land use change models could be improved by more nuanced representations of urban land, including mosaic classes and different urban land use intensities