Wordt stedelijk waterbeheer steeds duurzamer?

De kennis over stedelijk waterbeheer heeft de afgelopen decennia een grote vlucht genomen. Maar dat dit nog geen garantie voor duurzaam stedelijk waterbeheer biedt, was goed terug te zien op het congres over dit onderwerp in Porto Alegre (Brazilië). Inzicht hebben in de effecten van klimaatverandering is nog maar een eerste stap naar steden, die voldoende beschermd zijn voor overstromingen, en gezond water bieden aan hun inwoners. Ervaringsuitwisseling van stedelijk waterdeskundigen van over de hele wereld helpt daar in ieder geval bij

Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat

Introduction. A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods. Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg j1 of fluvoxamine. Analysis. With increasing dose a disproportional increase in brain concentrations was observed. Th

Spisulosine (ES-285) given as a weekly three-hour intravenous infusion: results of a phase I dose-escalating study in patients with advanced solid malignancies

Spisulosine is a marine compound that showed antitumor activity in preclinical studies. We report results of a phase I trial performed in patients with advanced solid tumors with the marine compound, with the aim to determine the maximum tolerated dose (MTD) of a weekly 3-h intravenous (iv.) infusion, and to evaluate the safety, efficacy, and pharmacokinetics (PK) of the compound. Two centers contributed 25 patients to the trial, and 7 dose levels were explored. In dose levels ranging from 4 to 128 mg/mA(2)/day, no dose-limiting toxicities (DLT) were observed. One patient had DLT at 200 mg/mA(2), a reversible grade 3 ALT increase. The MTD was not reached due to early termination of the Spisulosine trial program but is considered to be likely in the range of 200 mg/mA(2) for this schedule. Drug-related adverse reactions included mild to moderate nausea, pyrexia, injection site reactions, and vomiting. One case of grade 4 peripheral motor and sensory neuropathy associated with general weakness and pain was observed during treatment cycle 4 and possibly contributed to the death of the patient. Grade 3 laboratory abnormalities included anemia and lymphopenia and increases in liver enzymes (alkaline phosphatase, transaminases, and bilirubin). Objective responses were not observed, and only four patients had short-lasting stable disease (< 3 months). The PK data indicated a wide distribution, a long residence time, and dose proportionality of the agent. Hepato- and neuro-toxicity are schedule independent dose-limiting adverse events for this marine compound, as illustrated by this and other early clinical trials

Conversation in the museum: experiments in dynamic hypermedia with the intelligent labelling explorer

We outline experience with the Intelligent Labelling Explorer, a dynamic hypertext system developed at the University of Edinburgh, in collaboration with the National Museums of Scotland. First, we indicate a number of ways in which labels on museum objects ought to be tuned to take into account types of visit, the interests of visitors, and their evolving knowledge during a visit. Secondly, we sketch the general architecture of our system, and then focus on the conversational effects which the system can create. We then briefly indicate future directions of research, before critically discussing the applicability (or otherwise) of the spatial metaphor to flexible hypertexts. Keywords: adaptive museum hypermedia, natural language techniques for dynamic hypertext generation, content adaptation in hypertext and hypermedia, web-based museum hypermedia, navigation design 1. Introduction We take dynamic hypertext to be that variety of flexible hypertext which relies upon techniques from th..

Transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND-study)

Background: Recent non-randomized studies suggest that extended endoscopic mucosal resection (EMR) is equally effective in removing large rectal adenomas as transanal endoscopic microsurgery (TEM). If equally effective, EMR might be a more cost-effective approach as this strategy does not require expensive equipment, general anesthesia and hospital admission. Furthermore, EMR appears to be associated with fewer complications. The aim of this study is to compare the cost-effectiveness and cost-utility of TEM and EMR for the resection of large rectal adenomas. Methods/design. Multicenter randomized trial among 15 hospitals in the Netherlands. Patients with a rectal adenoma 3 cm, located between 115 cm ab ano, will be randomized to a TEM- or EMR-treatment strategy. For TEM, patients will be treated under general anesthesia, adenomas will be dissected en-bloc by a full-thickness excision, and patients will be admitted to the hospital. For EMR, no or conscious sedation is used, lesions will be resected through the submucosal plane i

Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers.

Few studies have assessed visuo-spatial working memory and inhibition in attention-deficit/hyperactivity disorder (ADHD) by recording saccades and consequently little additional knowledge has been gathered on oculomotor functioning in ADHD. Moreover, this is the first study to report the performance of non-affected siblings of children with ADHD, which may shed light on the familiality of deficits. A total of 14 boys with ADHD, 18 non-affected brothers, and 15 control boys aged 7-14 years, were administered a memory-guided saccade task with delays of three and seven seconds. Familial deficits were found in accuracy of visuo-spatial working memory, percentage of anticipatory saccades, and tendency to overshoot saccades relative to controls. These findings suggest memory-guided saccade deficits may relate to a familial predisposition for ADHD

Societal Innovation: between dream and reality lies complexity

Jan Rotmans (1961) is one of the founders of Integrated Assessment (IA), and has outstanding experience in IA modeling, scenario-building, uncertainty management and transition management. During the past twenty years he has led a diversity of innovative projects in the field of climate change, global change, sustainable development and transitions and system innovations. He is founder and director of the International Centre for Integrative Studies (ICIS) (1998) at Maastricht University. Since 2004 he is a full professor in Transitions and Transition Management at Erasmus University Rotterdam in the Netherlands, where he founded the DRIFT-institute: Dutch Research Institute For Transitions. He is vice-president of The Integrated Assessment Society (TIAS), and founder and director of the Dutch Knowledge Network on System Innovations and Transitions (KSI). Jan Rotmans is founder of two scientific journals, Environmental Modeling and Assessment and Integrated Assessment, and has published ten books and more than 150 peer-reviewed scientific articles in journals and books in the fields of environment, sustainability, governance, transitions and system innovations.There are no easy, off-the-shelf solutions for persistent societal problems, because these are caused by fundamental flaws in our societal systems. Such systemic errors demand radical changes in our thinking and actions, i.e. transitions and system innovations. Transitions require a long period (one to two generations), and take time, patience, money, confidence, but also courage, daring and perseverance to gain the upper hand over various types of resistance. Research into transitions is by definition multidisciplinary and interdisciplinary. For this we need knowledge and experience from systems analysis, social administration, history, innovation science, economics, business administration and technology. The nature of research into transitions is fundamental, explorative, creative and practical. A conceptual framework for research into transitions is presented that consists of four interlinked conceptual building blocks, which in turn provide an outline of a transition theory in its embryonic stages. These concepts are rooted in common notions from complexity theory, new forms of governance and social theory. Central here is the concept of transition management, for which a new management framework is developed. Transition management is an attempt to tackle persistent stubborn problems by steering them in a more sustainable direction, through a visionary, cyclical process of putting issues on the agenda, learning, orchestrating and experimenting. Not based on management and control but through clever, subtle changes and adjustments at several levels concurrently. Transition management is a very promising management concept that can initially be applied to a wide range of complex societal problems: from health care to energy provision, and from social security to mobility. Transition management can also be applied to complex processes of change in a business context.Voor hardnekkige maatschappelijke problemen bestaan geen pasklare oplossingen. Deze zijn het gevolg van weeffouten in onze maatschappelijke stelsels. Deze systeemfouten vergen radicale veranderingen in ons denken en handelen: transities en systeeminnovaties. Transities vergen een lange periode (1 à 2 generaties), en kosten tijd, geduld, geld, vertrouwen, maar ook moed, durf en doorzettingsvermogen om verschillende soorten weerstand te overwinnen. Onderzoek naar transities is per definitie multi-en interdisciplinair, waarbij kennis nodig is vanuit de systeemkunde, bestuurskunde, geschiedenis, innovatiewetenschappen, economie, bedrijfskunde en techniek. Transitieonderzoek is zowel fundamenteel, exploratief, ontwerpend en praktisch van aard. Een conceptueel kader voor transitieonderzoek wordt gepresenteerd, dat bestaat uit een viertal samenhangende conceptuele bouwstenen, die de contouren vormen van een transitietheorie in wording. Deze concepten zijn geworteld in gemeenschappelijke noties uit de complexiteitstheorie, nieuwe vormen van governance en de sociale theorie. Centraal hierin staat het concept van transitiemanagement, waarvoor een nieuw sturingsraamwerk is ontwikkeld. Transitiemanagement beoogt hardnekkige problemen bij te sturen in een meer duurzame richting, via een visionair, cyclisch proces van agenderen, leren, instrumenteren en experimenteren. Niet op basis van controle en beheersing, maar via slim, subtiel schakelen en bijsturen op meerdere niveaus. Transitiemanagement is een veelbelovend sturingsconcept wat in beginsel toepasbaar is op tal van complexe maatschappelijke problemen: van gezondheidszorg tot energievoorziening, en van sociale zekerheid tot mobiliteit. Ook in de bedrijfscontext kan transitiemanagement worden toegepast op complexe veranderingsprocessen

Neurotrophic factors in prostate and prostatic cancer

Recent progress in growth factor research has led to a reexamination of the involvement of neurotrophic factors outside their classical domain of the nervous system. These last few years have seen a substantial accumulation of data concerning Nerve Growth Factor (NGF)'s prevalence within the prostate. NGF and its receptors were reported from the normal prostatic tissue, benign hyperplasia and prostatic cancer. Divergent ideas about the biological role of this factor, its specific distribution pattern within the tissue and its implication in the progression of carcinogenesis have been proposed. Especially the role of NGF in the metastatic process bears direct clinical relevance for research in this area. Many questions remain to be solved like the one on the prevalence of other neurotrophic factors. It is now increasingly becoming clear that neurotrophic factors do play a role in normal physiology and pathology of prostatic cells, opening up new prospects for diagnosis and treatment