Prevalence of BRCA1 in a hospital-based population of Dutch breast cancer patients

The prevalence of disease-related BRCA1 mutations was investigated in 642 Dutch breast cancer patients not selected for family history or age at diagnosis. They were tested for germline mutations in the BRCA1 gene using an assay which detects small deletions and insertions (DSDI), as well as the two major genomic founder deletions present in the Dutch population. Data on family history and bilateral breast cancer were obtained retrospectively. Ten protein truncating mutations were detected and one in-frame deletion with an unknown relation to disease risk. Four patients carried the Dutch founder deletion of exon 22. Based on these results the estimated prevalence of breast cancer in the general population in the Netherlands attributable to BRCA1 mutations is 2.1%. Under 40 years-of-age and under 50 years-of-age this prevalence is 9.5% and 6.4%, respectively. All mutation carriers were under 50 years-of-age at diagnosis of the first breast cancer, and five did not have any relative with breast cancer. The proportions of bilateral breast cancer in the mutation carriers and non-carriers did not differ from each other. These data indicate that in the general Dutch breast cancer population the great majority of BRCA1 mutations will be found in women diagnosed under 50 years-of-age. © 2000 Cancer Research Campaig

Building global water use scenarios

The Water Future and Solutions Initiative (WFaS) develops consistent, multi-model global water scenaros with the aim to analyze the water-food-energy-climate- environment nexus and identify future hotspots of water insecurity and related impacts on food and energy security. WFaS coordinates its work with on-going scenario development in the fifth assessment review of the Intergovernmental Panel on Climate Change (IPCC), which has developed climate scenarios based on the Representative Concentration pathways (RCPs) and alternative futures of societal developments described in the Shared Socio-economic Pathways (SSPs). In its 'fast-track' scenario assessment WFaS applies available multi-model ensembles of RCP climate scenarios and population, urbanization, and economic development quantifications of the SSPs. Here we interpret SSP narratives to indicate direct or indirect consequences for key water dimensions. Criical scenario assumptions are assessed for different conditions in terms of a country or regions ability to cope with water-related risks and its exposure to complex hydrologcal conditions. For this purpose a classification of hydro-economic challenges across countries has been developed. Scenario assumptions were developed for defined categories of hyro-economic development challenges and relevant features of SSPs. In this way we systematically assess qualitatively key scenario drivers required for global water models We then provide quantifications of assumptions for technological and structural changes for the industry and domestic sector. For the quantification of global scenarios of future water demand, we applied an ensemble of three global water models (H08, PCR-GLOBWB, WaterGAP). Ensemble results of global industrial water withdrawal highlight a steep increase in almost all SSP scenarios. Global amounts across the three models show a wide spread with the highest amounts reaching almost 2000 km^3 yr^-1 by 2050, more than doubled compared to the present industrial water use intensity (850 km^3 yr^-1). Increases in world population result in global domestic water withdrawals by 2050 reaching 700-1500 km^3 yr^-1 depending on scenario and water model. This is an increase of up to 250% compared to the present domestic water use intensity (400-450 km^3 yr^-1). We finally suggest improvements for future water use modelling

Anomalous Transient Current in Nonuniform Semiconductors

Nonequilibrium processes in semiconductors are considered with highly nonuniform initial densities of charge carriers. It is shown that there exist such distributions of charge densities under which the electric current through a sample displays quite abnormal behaviour flowing against the applied voltage. The appearance of this negative electric current is a transient phenomenon occurring at the initial stage of the process. After this anomalous negative fluctuation, the electric current becomes normal, i.e. positive as soon as the charge density becomes more uniform. Several possibilities for the practical usage of this effect are suggested.Comment: 1 file, 11 pages, RevTex, no figure

Cornetto: A Combinatorial Lexical Semantic Database for Dutch

One of the goals of the STEVIN programme is the realisation of a digital infrastructure that will enforce the position of the Dutch language in the modern information and communication technology.A semantic database makes it possible to go from words to concepts and consequently, to develop technologies that access and use knowledge rather than textual representations

Conceptual framework for scenarios development in the Water futures and Solutions project

The major purpose of the Water Futures & Solutions (WFaS) initiative is to develop a set of adaptable resilient and robust solutions and a framework to facilitate access to and guidance through them by decision makers facing a variety of water-related challenges to sustainable evelopment, and a set of optional pathways to achieve plausible sustainable development goals by 2050. The WFaS Initiative addresses the multidimensional aspects of the water system and is guided by stakeholders representing these various aspects. The Initiative views freshwater systems as being strongly interweaved with human activities (Economy, Society) and Nature as a whole. Dynamics and health of freshwater systems is critical to human well- being. The Initiative will go beyond scenario production and model comparisons and will focus on exploring solutions and necessary innovations to address the growing water challenges. Solutions can be combinations of technological innovations, regulatory approaches, manageent or institutional changes that improve the balance of water supply and demand, improve water quality, or reduce water-related risks for society. Solutions will often be embedded in and cut across all sectors of social and economic activities. In order to represent the aspirations and interdependencies as described above, the conceptual framework has been developed, to communicate project results to the target audiences. This document describes this conceptual framework that will be used: -to support development of qualitative water scenarios -to identify and select critical dimensions of the water scenarios -to guide integration of scenarios with quantitative models -to guide integration of information from various data sources into the scenarios -to support development and assessment of solutions -to support collaboration between project and stakeholder groups -to facilitate presentation of results to target audiences The WFaS conceptual framework is developed using the 'concept maps' technique (Caqas and Carff, 2005; Novak and Caqas, 2006b). Concept maps method was develop to represent knowledge in an organized way. It allows practitioners to represent concepts and specific relationships between concepts. It is flexible enough to adapt to different knowledge domains to support better understanding and communication between individuals and groups from different backgrounds

Simulations of lattice animals and trees

The scaling behaviour of randomly branched polymers in a good solvent is studied in two to nine dimensions, using as microscopic models lattice animals and lattice trees on simple hypercubic lattices. As a stochastic sampling method we use a biased sequential sampling algorithm with re-sampling, similar to the pruned-enriched Rosenbluth method (PERM) used extensively for linear polymers. Essentially we start simulating percolation clusters (either site or bond), re-weigh them according to the animal (tree) ensemble, and prune or branch the further growth according to a heuristic fitness function. In contrast to previous applications of PERM, this fitness function is {\it not} the weight with which the actual configuration would contribute to the partition sum, but is closely related to it. We obtain high statistics of animals with up to several thousand sites in all dimension 2 <= d <= 9. In addition to the partition sum (number of different animals) we estimate gyration radii and numbers of perimeter sites. In all dimensions we verify the Parisi-Sourlas prediction, and we verify all exactly known critical exponents in dimensions 2, 3, 4, and >= 8. In addition, we present the hitherto most precise estimates for growth constants in d >= 3. For clusters with one site attached to an attractive surface, we verify the superuniversality of the cross-over exponent at the adsorption transition predicted by Janssen and Lyssy. Finally, we discuss the collapse of animals and trees, arguing that our present version of the algorithm is also efficient for some of the models studied in this context, but showing that it is {\it not} very efficient for the `classical' model for collapsing animals.Comment: 17 pages RevTeX, 29 figures include

Towards Innovative Solutions through Integrative Futures Analysis - Preliminary qualitative scenarios

This report presents preliminary results of developing qualitative global water scenarios. The water scenarios are developed to be consistent with the underlying Shared Socio- Economic Pathways (SSPs). In this way different stakeholders in different contexts (climate, water) can be presented with consistent set of scenarios avoiding confusion and increasing policy impact. Water scenarios are based on the conceptual framework that has been developd specifically for this effort. The framework provides clear representation of important dimensions in the areas of Nature, Economy and Society and Water dimensions that are embedded in them. These critical dimensions are used to describe future changes in a consistent way for all scenarios. Three scenarios are presented based on SSP1, SSP2 and SSP3 respectively. Hydro-economic classes are introduced to further differentiate within scenarios based on economic and water conditions for specific regions and/or countries. In the process of building these preliminary water scenarios assumptions that are presented in this report, the number of challenges have been met. In the conclusions section these challenges are summarized and possible ways of tackling them are described

Detection of distant metastases in patients with oesophageal or gastric cardia cancer: a diagnostic decision analysis

Computed tomography (CT) is presently a standard procedure for the detection of distant metastases in patients with oesophageal or gastric cardia cancer. We aimed to determine the additional diagnostic value of alternative staging investigations. We included 569 oesophageal or gastric cardia cancer patients who had undergone CT neck/thorax/abdomen, ultrasound (US) abdomen, US neck, endoscopic ultrasonography (EUS), and/or chest X-ray for staging. Sensitivity and specificity were first determined at an organ level (results of investigations, i.e., CT, US abdomen, US neck, EUS, and chest X-ray, per organ), and then at a patient level (results for combinations of investigations), considering that the detection of distant metastases is a contraindication to surgery. For this, we compared three strategies for each organ: CT alone, CT plus another investigation if CT was negative for metastases (one-positive scenario), and CT plus another investigation if CT was positive, but requiring that both were positive for a final positive result (two-positive scenario). In addition, costs, life expectancy and quality adjusted life years (QALYs) were compared between different diagnostic strategies. CT showed sensitivities for detecting metastases in celiac lymph nodes, liver and lung of 69, 73, and 90%, respectively, which was higher than the sensitivities of US abdomen (44% for celiac lymph nodes and 65% for liver metastases), EUS (38% for celiac lymph nodes), and chest X-ray (68% for lung metastases). In contrast, US neck showed a higher sensitivity for the detection of malignant supraclavicular lymph nodes than CT (85 vs 28%). At a patient level, sensitivity for detecting distant metastases was 66% and specificity was 95% if only CT was performed. A higher sensitivity (86%) was achieved when US neck was added to CT (one-positive scenario), at the same specificity (95%). This strategy resulted in lower costs compared to CT only, at an almost similar (quality adjusted) life expectancy. Slightly higher specificities (97–99%) were achieved if liver and/or lung metastases found on CT, were confirmed by US abdomen or chest X-ray, respectively (two-positive scenario). These strategies had only slightly higher QALYs, but substantially higher costs. The combination of CT neck/thorax/abdomen and US neck was most cost-effective for the detection of metastases in patients with oesophageal or gastric cardia cancer, whereas the performance of CT only had a lower sensitivity for metastases detection and higher costs. The role of EUS seems limited, which may be due to the low number of M1b celiac lymph nodes detected in this series. It remains to be determined whether the application of positron emission tomography will further increase sensitivities and specificities of metastases detection without jeopardising costs and QALYs