PEARL - THE NEW REGIONAL FORECASTING MODEL OF THE NETHERLANDS

The Netherlands has a rather long history of developing models in the field of regional forecasts. Among othter things, these forecasts are used as an instrument for planning of house-building. In 2004 Statistics Netherlands and the Spatial Planning Bureau started with the development of a new model, called PEARL (which stands for 'Population Extrapolations At Regional Level'). It is an integrated model for the forecast of the population (by ethnic group) and households. PEARL will be used to regionalize the official forecasts of population (by ethnic group) and households at the national level, which are compiled by Statistics Netherlands. The lowest level of the regional forecasts will be the municipal level, which permits the aggregation to larger NUTS regions, such as 'COROP' and 'province'. The forecast-horizon of the regional forecasts will be 15 to 20 years, although computations for a longer period are possible. An important objective of PEARL is to be considered as the official regional forecast, from 2007 onwards. Assumptions on demographic (growth) components (fertility, mortality, internal and external migration) and transition rates (with respect to the life course) will be formulated at the municipal level. These assumptions are used as input for PEARL. In this way transparency of the outcomes of the model is promoted. In order to achieve consistency between population and households, PEARL consists of both a macro- and a micro-layer. At the macro-layer (the municipal level) the assumptions are applied, while in the micro-layer (individual level) the resulting events are administrated. In this way the micro-layer consists of approximately 16 million persons and approximately 7 million households. In switching between the macro- and the micro-layer PEARL distinguishes itself from more conventional models. The primary goal is to use PEARL as a (robust) instrument for forecasting. However, it may also be used as a tool for compiling scenarios. This can be done at the macro level (by formulating alternative assumptions at the municipal level), but also at the micro level (by using alternative figures on risks). In the last application PEARL is used as a micro-simulation model. The software program PEARL is written in Delphi-5. The intention is to publish first outcomes (with a limited scope) in the second half of 2005

Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects

The purpose of this double-blind, randomized, placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria. Subjects (mean age 51 years, 63% male) were randomized to pravastatin 40 mg or matching placebo and to fosinopril 20 mg or matching placebo. Using high resolution ultrasound, flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) was assessed at baseline and after 4 years of treatment in a total of 276 subjects. At baseline, mean +/- standard error FMD was 4.73 +/- 0.49% and NID was 10.86 +/- 0.67%. Pravastatin significantly reduced total cholesterol and LDL cholesterol (p <0.01) and randomization to pravastatin was associated with a non-significant improvement of 18.9% in FMD (+0.80 +/- 0.95, p = 0.09), without a significant change in NID. Interestingly, pravastatin significantly increased FMD by 34.9% in men (+1.23, p = 0.04), but only 1.1 % in women (+0.06, p = 0.95). Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion, systolic and diastolic blood pressure (all p <0.01). In conclusion, after 4 years Of follow-up, pravastatin treatment tended to increase FMD, and this effect was predominantly present in men. Fosinopril treatment did not modify FMD during long-term follow-up. (C) 2006 Elsevier Ireland Ltd. All rights reserved

84 tomato accessions - Exploring genetic variation in the tomato (Solanum section Lycopersicon) clade by whole-genome sequencing

84 tomato accessions - Genetic variation in the tomato clade was explored by sequencing a selection of 84 tomato accessions and related wild species representative for the Lycopersicon, Arcanum, Eriopersicon and Neolycopersicon group. In addition, we present a reconstruction of three new reference genomes in support of our comparative genome analyses. This comparative analysis elucidates species specific chromosome structural differences. Furthermore, sequence diversity in commercial breeding lines appears extremely low, indicating the dramatic genetic erosion of crop tomatoes. For wild species the SNP frequency increases 20 folds to more than 10 million SNPs. Our study unequivocally illustrates the need for multiple reference genomes in support of tomato comparative genomics and Solanum genome evolution studies. Comparative sequence alignment reveals group, species, and accession specific polymorphisms within domestication syndrome genes, which are explanatory for characteristic fruit traits and growth habit in tomato accessions. Using gene models from the annotated Heinz reference genome, we observe a bias in dN/dS ratio in domestication syndrome genes compared to a random set of genes which probably is the result of a positive selection. Based on whole genome SNP information, we unambiguously resolved the phylogenetic placement for each accession in the four main groups in the Lycopersicon clade using Maximum Likelihood analyses. Phylogenetic relationships appear correlated with habitat and mating type and point to the occurrence of geographical races within these groups and thus are of practical importance for introgressive hybridization breeding

84 tomato accessions - Exploring genetic variation in the tomato (Solanum section Lycopersicon) clade by whole-genome sequencing

84 tomato accessions - Genetic variation in the tomato clade was explored by sequencing a selection of 84 tomato accessions and related wild species representative for the Lycopersicon, Arcanum, Eriopersicon and Neolycopersicon group. In addition, we present a reconstruction of three new reference genomes in support of our comparative genome analyses. This comparative analysis elucidates species specific chromosome structural differences. Furthermore, sequence diversity in commercial breeding lines appears extremely low, indicating the dramatic genetic erosion of crop tomatoes. For wild species the SNP frequency increases 20 folds to more than 10 million SNPs. Our study unequivocally illustrates the need for multiple reference genomes in support of tomato comparative genomics and Solanum genome evolution studies. Comparative sequence alignment reveals group, species, and accession specific polymorphisms within domestication syndrome genes, which are explanatory for characteristic fruit traits and growth habit in tomato accessions. Using gene models from the annotated Heinz reference genome, we observe a bias in dN/dS ratio in domestication syndrome genes compared to a random set of genes which probably is the result of a positive selection. Based on whole genome SNP information, we unambiguously resolved the phylogenetic placement for each accession in the four main groups in the Lycopersicon clade using Maximum Likelihood analyses. Phylogenetic relationships appear correlated with habitat and mating type and point to the occurrence of geographical races within these groups and thus are of practical importance for introgressive hybridization breeding

Urinary albumin excretion is related to cardiovascular risk indicators, not to flow-mediated vasodilation, in apparently healthy subjects

Based on studies in diabetic and hypertensive populations it has been postulated that early endothelial dysfunction is the mechanism responsible for the increased cardiovascular risk in microalbuminuric Subjects. We evaluated the relation between microalbuminuria and endothelial dysfunction, assessed as flow-mediated dilation of the brachial artery, in an apparently healthy population. Within the framework of the PREVEND Intervention Trial non-hypertensive and non-hypercholesterolemic subjects were recruited on the basis of reproducible microalbuminuria. Using high-resolution ultrasound, flow-mediated dilation and nitroglycerin-mediated dilation of the brachial artery was assessed to measure endothelium-dependent and endothelium-independent responses, respectively. For the current study subjects with diabetes mellitus, clinical atherosclerosis, and macroalbuminuria were excluded from the analyses. We studied 421 men and 233 women (mean age (SD) 50 (12)). Increasing levels of urinary albumin excretion were accompanied by a significant increase in age, percentage men, systolic and diastolic blood pressure, body mass index. and serum triglycerides, whereas there was no decrease of flow-mediated vasodilation or nitroglycerin-mediated vasodilation. Adjusted for age and sex, urinary albumin excretion was significantly related to systolic (r=0.19, P <0.001) and diastolic (r=0.16, P <0.001) blood pressure, body mass index (r=0.18, P <0.001), and triglycerides (r=0.13, P=0.001), but not to flow-mediated vasodilation (r= -0.01, P=0.8). In contrast to blood pressure, body mass index, and triglycerides, there was no relation between urinary albumin excretion and flow-mediated vasodilation in apparently healthy subjects. These data suggest that the presence of atherogenic risk factors precedes the development of endothelial dysfunction in microalbuminuric, but otherwise healthy subjects. (C) 2002 Elsevier Science Ireland Ltd. All rights reserve

Enzalutamide as a Fourth- or Fifth-Line Treatment Option for Metastatic Castration-Resistant Prostate Cancer

Objective: To evaluate the efficacy of enzalutamide (Enz) as fourth- or fifth-line treatment in men with metastasized castration-resistant prostate cancer (mCRPC), by analyzing a retrospective cohort of heavily pretreated patients. Methods: We evaluated toxicity, overall survival (OS), progression-free survival (PFS) and time to prostate-specific antigen (PSA) progression data from 47 CRPC patients treated with fourth-or fifth-line Enz. Results: All patients were treated with docetaxel and abiraterone acetate and 42 patients (89%) with cabazitaxel. The median age of the patients was 69 years (IQR, 63-73.5), 79% had bone metastases, 55% had lymph node metastases, and 17% had visceral metastases. The median duration of Enz treatment was 12.0 weeks (IQR, 8.3-20.4), and 11 patients (23%) responded to Enz (maximum PSA decline >= 50%). In general, Enz was well tolerated, with the most frequently reported adverse events being fatigue and nausea. The median OS was 40.1 weeks (95% CI, 25.4-61.4), the median PFS was 12.1 weeks (95% CI, 9.9-14.0) and the median time to PSA progression was 15.7 weeks (95% CI, 14.0-28.7). Conclusions: Analysis of this retrospective cohort suggests that Enz is well tolerated and that there is a 23% response rate in heavily pretreated CRPC patients, which is comparable with third-line treatment outcomes. (C) 2016 S. Karger AG, Base