In vitro frequency analysis of spleen colony-forming and marrow-repopulating hemopoietic stem cells in the mouse

An assay is described for Day-12 spleen colony-forming cells (CFU-S-12) and hemopoietic stem cells with marrow-repopulating ability (MRA) in the mouse using a miniaturized stroma-dependent bone marrow culture assay in vitro. Bone marrow cells are grown in liquid culture in microtiter wells, and the resulting adherent stromal layers are depleted of all hemopoietic activity by 20 Gy gamma irradiation. Subsequently, single cell suspensions containing stem cells are overlaid in a range of concentrations, and the presence of one or more emerging phase nonrefractive cell clones (cobblestone areas) in a single well scored as positive. The frequencies of cobblestone area-forming cells (CAFC) are then calculated by employing Poisson statistics. It is shown that the CAFC Day-10 and CAFC Day-28 frequencies closely correlate with those of CFU-S-12 and MRA cells, respectively

Tool catalogue frame-based information tools

In the perception, knowledge production and policymaking on complex issues (‘wicked problems’), such as climate change, frames and framing play an important but often hidden role. Frames relate to one’s ‘schemas of interpretation’; the conceptual images, values, starting points, and mental models that one may have of an issue. This can include, for instance, one’s problem definition, perceptions of the cause-effect relationships in an issue, one’s primary goals, perception of one’s and others’ roles and responsibilities relating to the issue, and views on suitable strategies and interaction with (other) stakeholders (cf. Dewulf et al., 2005)

Defining Uncertainty: A Conceptual Basis for Uncertainty Management in Model-Based Decision Support

The aim of this paper is to provide a conceptual basis for the systematic treatment of uncertainty in model-based decision support activities such as policy analysis, integrated assessment and risk assessment. It focuses on the uncertainty perceived from the point of view of those providing information to support policy decisions (i.e., the modellers’ view on uncertainty) – uncertainty regarding the analytical outcomes and conclusions of the decision support exercise. Within the regulatory and management sciences, there is neither commonly shared terminology nor full agreement on a typology of uncertainties. Our aim is to synthesise a wide variety of contributions on uncertainty in model-based decision support in order to provide an interdisciplinary theoretical framework for systematic uncertainty analysis. To that end we adopt a general definition of uncertainty as being any deviation from the unachievable ideal of completely deterministic knowledge of the relevant system. We further propose to discriminate among three dimensions of uncertainty: location, level and nature of uncertainty, and we harmonise existing typologies to further detail the concepts behind these three dimensions of uncertainty.We propose an uncertainty matrix as a heuristic tool to classify and report the various dimensions of uncertainty, thereby providing a conceptual framework for better communication among analysts as well as between them and policymakers and stakeholders. Understanding the various dimensions of uncertainty helps in identifying, articulating, and prioritising critical uncertainties, which is a crucial step to more adequate acknowledgement and treatment of uncertainty in decision support endeavours and more focused research on complex, inherently uncertain, policy issues

Integraal waterbeheer : kritische zone en onzekerheden : integraal hoofdrapport

In het kader van het Nationaal Modellen- en Datacentrum (NMDC) is in 2011 het NMDC innovatieproject 'Integraal waterbeheer - van kritische zone tot kritische onzekerheden' gestart (www.nmdc.eu). Dit project heeft tot doel om de modellen voor bodem, water, vegetatie en klimaat(verandering) door samenwerking beter op elkaar aan te laten sluiten, daarbij beter geschikt te maken om effecten van klimaatverandering te berekenen en om de verschillende typen onzekerheden bij dit soort studies in beeld te brengen. Het project is uitgevoerd door Alterra, Deltares, KNMI, PBL en TNO. In twee cases (Baakse Beek en Walcheren) hebben zij hun state-of-the-art modellen voor meteo, gewasgroei, vegetatie-ontwikkeling, hydrologie en geologie ingezet en aan elkaar gekoppeld. Dit rapport behandelt integraal de resultaten van het innovatieproject. De resultaten van de case voor de Baakse Beek zijn specifiek opgenomen in een NMDC deelrapport (Van Ek et al., 2012). Voor de case Walcheren wordt verwezen naar een artikel in voorbereiding (Kroes, J. et al., 2013). De resultaten bieden nieuwe inzichten in de vocht- en zouthuishouding van de bodem, potenties voor grondwaterafhankelijke natuur en groei van landbouwgewassen in het huidige klimaat en projecties voor klimaatverandering rond 2050. In het project zijn verschillende methoden toegepast om inzicht te krijgen in verschillende onzekerheden, hetgeen voor dergelijke integrale (model)studies praktische aanknopingspunten biedt voor de analyse van onzekerheden en effectieve samenwerking tussen de instituten

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC