Neo-Atlantis: The Netherlands under a 5-m sea level rise

What could happen to the Netherlands if, in 2030, the sea level starts to rise and eventually, after 100 years, a sea level of 5 m above current level would be reached? This question is addressed by studying literature, by interviewing experts in widely differing fields, and by holding an expert workshop on this question. Although most experts believe that geomorphology and current engineering skills would enable the country to largely maintain its territorial integrity, there are reasons to assume that this is not likely to happen. Social processes that precede important political decisions - such as the growth of the belief in the reality of sea level rise and the framing of such decisions in a proper political context (policy window) - evolve slowly. A flood disaster would speed up the decision-making process. The shared opinion of the experts surveyed is that eventually part of the Netherlands would be abandoned. © 2008 The Author(s)

A prebiotic intervention study in children with autism spectrum disorders (ASDs)

Different dietary approaches, such as gluten and casein free diets, or the use of probiotics and prebiotics have been suggested in autistic spectrum disorders in order to reduce gastrointestinal (GI) disturbances. GI symptoms are of particular interest in this population due to prevalence and correlation with the severity of behavioural traits. Nowadays, there is lack of strong evidence about the effect of dietary interventions on these problems, particularly prebiotics. Therefore, we assessed the impact of exclusion diets and a 6-week Bimuno® galactooligosaccharide (B-GOS®) prebiotic intervention in 30 autistic children. RESULTS: The results showed that children on exclusion diets reported significantly lower scores of abdominal pain and bowel movement, as well as lower abundance of Bifidobacterium spp. and Veillonellaceae family, but higher presence of Faecalibacterium prausnitzii and Bacteroides spp. In addition, significant correlations were found between bacterial populations and faecal amino acids in this group, compared to children following an unrestricted diet. Following B-GOS® intervention, we observed improvements in anti-social behaviour, significant increase of Lachnospiraceae family, and significant changes in faecal and urine metabolites. CONCLUSIONS: To our knowledge, this is the first study where the effect of exclusion diets and prebiotics has been evaluated in autism, showing potential beneficial effects. A combined dietary approach resulted in significant changes in gut microbiota composition and metabolism suggesting that multiple interventions might be more relevant for the improvement of these aspects as well as psychological traits

The inference of gray whale (Eschrichtius robustus) historical population attributes from whole-genome sequences

Commercial whaling caused extensive demographic declines in many great whale species, including gray whales that were extirpated from the Atlantic Ocean and dramatically reduced in the Pacific Ocean. The Eastern Pacific gray whale has recovered since the 1982 ban on commercial whaling, but the Western Pacific gray whale-once considered possibly extinct-consists of only about 200 individuals and is considered critically endangered by some international authorities. Herein, we use whole-genome sequencing to investigate the demographic history of gray whales from the Pacific and use environmental niche modelling to make predictions about future gene flow.Our sequencing efforts and habitat niche modelling indicate that: i) western gray whale effective population sizes have declined since the last glacial maximum; ii) contemporary gray whale genomes, both eastern and western, harbor less autosomal nucleotide diversity than most other marine mammals and megafauna; iii) the extent of inbreeding, as measured by autozygosity, is greater in the Western Pacific than in the Eastern Pacific populations; and iv) future climate change is expected to open new migratory routes for gray whales.Our results indicate that gray whale genomes contain low nucleotide diversity and have been subject to both historical and recent inbreeding. Population sizes over the last million years likely peaked about 25,000 years before present and have declined since then. Our niche modelling suggests that novel migratory routes may develop within the next century and if so this could help retain overall genetic diversity, which is essential for adaption and successful recovery in light of global environmental change and past exploitation

Randomized Phase II trial assessing estramustine and vinblastine combination chemotherapy vs estramustine alone in patients with progressive hormone-escaped metastatic prostate cancer

Abstract Based on the results of combined data from three North American Phase II studies, a randomised Phase II study in the same patient population was performed, using combination chemotherapy with estramustine phosphate (EMP) and vinblastine (VBL) in hormone refractory prostate cancer patients. In all, 92 patients were randomised into a Phase II study of oral EMP (10 mg kg day continuously) or oral EMP in combination with intravenous VBL (4 mg m(2) week for 6 weeks, followed by 2 weeks rest). The end points were toxicity and PSA response in both groups, with the option to continue the trial as a Phase III study with time to progression and survival as end points, if sufficient responses were observed. Toxicity was unexpectedly high in both treatment arms and led to treatment withdrawal or refusal in 49% of all patients, predominantly already during the first treatment cycle. The mean treatment duration was 10 and 14 weeks, median time to PSA progression was 27.2 and 30.8 weeks, median survival time was 44 and 50.9 weeks, and PSA response rate was only 24.6 and 28.9% in the EMP/VBL and EMP arms, respectively. There was no correlation between PSA response and survival. While the PSA response in the patients tested was less than half that recorded in the North American studies, the toxicity of EMP monotherapy or in combination with VBL was much higher than expected. Further research on more effective and less toxic treatment strategies for hormone refractory prostate cancer is mandatory

Development of a questionnaire specifically for patients with Ileal Orthotopic Neobladder (IONB)

The ileal orthotopic neobladder (IONB) is often used in patients undergoing radical cystectomy. The IONB allows to void avoiding the disadvantages of the external urinary diversion.In IONB patients the quality of life (QoL) appears compromised by the need to urinate voluntarily. The patients need to wake up at night interrupting the sleep-wake rhythm with consequences on social and emotional life.At present the QoL in IONB patients is evaluated by generic questionnaires. These are useful when IONB patients are compared with patients with different urinary diversions but they are less effective when only IONB patients are evaluated. To address this problem a specific questionnaire-the IONB-PRO-was developed. METHODS: A) Based on a conceptual framework, narrative-based interviews were conducted on 35 IONB patients. A basic pool of 43 items was produced and organized throughout two clinical and four QoL dimensions. An additional 15 IONB patients were interviewed for face validity testing.B) Psychometric testing was conducted on 145 IONB patients. Both classic test strategy and Rasch analysis were applied. Psychometric properties of the resulting scales were comparatively tested against other QoL-validated scales. RESULTS: The IONB-PRO questionnaire includes two sections: one on the QoL and a second section on the capability of the patient to manage the IONB. For evaluation of the QoL, three versions were delivered: 1) a basic 23-item QoL version (3 domains 23-items; alpha 0.86÷ 9.69), 2) a short-form 12-item QoL scale (alpha = 0.947), and 3) a short-form 15-item Rasch QoL scale (alpha = 0.967). Correlations of the long version scales with the corresponding dimensions of the EORTC-QLQ C30 and the EORTC-BLM30 were significant. The short forms exhibited significant correlations with the global health dimension of the EORTC-QLQ and with the urinary subscales of the EORTC-BLM30. The effect size was approximately 1.00 between patients at the 1-year follow-up period and those with 3, 5, and > 5-year follow-up periods for all scales. No relevant differences were observed between the 12-item short-form and the Rasch scale. CONCLUSIONS: The IONB-PRO long and short-forms demonstrated a high level of internal consistency and reliability with an excellent discriminanting validity

Proteomes of Extracellular Vesicles From Pancreatic Cancer Cells and Cancer-Associated Fibroblasts

OBJECTIVES: Extracellular vesicles (EVs) are lipid bound vesicles secreted by cells into the extracellular environment. Studies have implicated EVs in cell proliferation, epithelial-mesenchymal transition, metastasis, angiogenesis, and mediating the interaction of tumor cells and microenvironment. A systematic characterization of EVs from pancreatic cancer cells and cancer-associated fibroblasts (CAFs) would be valuable for studying the roles of EV proteins in pancreatic tumorigenesis. METHODS: Proteomic and functional analyses were applied to characterize the proteomes of EVs released from 5 pancreatic cancer lines, 2 CAF cell lines, and a normal pancreatic epithelial cell line (HPDE). RESULTS: More than 1400 nonredundant proteins were identified in each EV derived from the cell lines. The majority of the proteins identified in the EVs from the cancer cells, CAFs, and HPDE were detected in all 3 groups, highly enriched in the biological processes of vesicle-mediated transport and exocytosis. Protein networks relevant to pancreatic tumorigenesis, including epithelial-mesenchymal transition, complement, and coagulation components, were significantly enriched in the EVs from cancer cells or CAFs. CONCLUSIONS: These findings support the roles of EVs as a potential mediator in transmitting epithelial-mesenchymal transition signals and complement response in the tumor microenvironment and possibly contributing to coagulation defects related to cancer development