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Toby Kiers E.,VU University Amsterdam | Palmer T.M.,University of Florida | Ives A.R.,University of Wisconsin - Madison | Bruno J.F.,University of North Carolina at Chapel Hill | Bronstein J.L.,University of Arizona
Ecology Letters | Year: 2010

There is growing concern that rapid environmental degradation threatens mutualistic interactions. Because mutualisms can bind species to a common fate, mutualism breakdown has the potential to expand and accelerate effects of global change on biodiversity loss and ecosystem disruption. The current focus on the ecological dynamics of mutualism under global change has skirted fundamental evolutionary issues. Here, we develop an evolutionary perspective on mutualism breakdown to complement the ecological perspective, by focusing on three processes: (1) shifts from mutualism to antagonism, (2) switches to novel partners and (3) mutualism abandonment. We then identify the evolutionary factors that may make particular classes of mutualisms especially susceptible or resistant to breakdown and discuss how communities harbouring mutualisms may be affected by these evolutionary responses. We propose a template for evolutionary research on mutualism resilience and identify conservation approaches that may help conserve targeted mutualisms in the face of environmental change. © 2010 Blackwell Publishing Ltd/CNRS.


Nanning A.M.,VU University Amsterdam
Journal of the International Academy of Periodontology | Year: 2011

To compare the effectiveness of an oral irrigator (OI) with a prototype jet tip or a standard jet tip to floss as adjunct to daily toothbrushing on gingival bleeding. In this single masked, 3-group parallel, 4-week home use experiment, 108 subjects were randomly assigned to one of three groups: 1) 01 with a prototype jet tip; 2) OI with a standard jet tip; 3) waxed dental floss. All groups used their assigned product once a day as adjunct to twice daily toothbrushing for two minutes with a standard ADA reference toothbrush. Professional instructions were given by a dental hygienist in 01 use or floss use according to written instructions. All subjects also received a toothbrush instruction leaflet (Bass technique). Subjects were assessed for both bleeding and plaque at baseline and after two weeks and four weeks and were instructed to brush their teeth approximately 2 to 3 hours prior to their assessment. With respect to mean bleeding scores the ANCOVA analysis with baseline as covariate and week 4 as dependent variable showed a significant difference between groups in favor of both the oral irrigator groups. For plaque, however, no significant difference among groups was observed. When combined with manual toothbrushing the daily use of an oral irrigator, either with prototype or standard jet tip, is significantly more effective in reducing gingival bleeding scores than is the use of dental floss, as determined within the limits of this 4-week study design.


Meynen G.,VU University Amsterdam
Theoretical Medicine and Bioethics | Year: 2011

Competent decision-making is required for informed consent. In this paper, I aim, from a phenomenological perspective, to identify the specific facets of competent decision-making that may form a challenge to depressed patients. On a phenomenological account, mood and emotions are crucial to the way in which human beings encounter the world. More precisely, mood is intimately related to the options and future possibilities we perceive in the world around us. I examine how possibilities should be understood in this context, and how, in depression, decision-making might be compromised. I suggest that, based on this analysis, a specific emphasis and alertness in assessments of competence in depressed patients is called for. In fact, close attention should be paid to the range of future possibilities depressed patients are able to perceive. In addition, providing environmental cues to these patients might be one way of enhancing their decision-making capacity. The practical suggestions arrived at are open to empirical research. © 2011 The Author(s).


Garaude J.,Mount Sinai School of Medicine | Garaude J.,French Institute of Health and Medical Research | Kent A.,Mount Sinai School of Medicine | Van Rooijen N.,VU University Amsterdam | Blander J.M.,Mount Sinai School of Medicine
Science Translational Medicine | Year: 2012

Toll-like receptor (TLR) ligands are increasingly being used as adjuvants in cancer vaccine trials to harness innate immunity and prime effective antitumor immune responses. Despite some success, enhancing tumor antigen presentation, promoting a protective antitumor response, and overcoming the immunosuppressive tumor microenvironment pose considerable challenges that necessitate further improvements in vaccine design. Here, we show that expression of the TLR ligand flagellin within tumor cells constitutes an effective antitumor vaccination strategy that relies on simultaneous engagement of TLR5 and the Nod-like receptors (NLRs) NLRC4/NAIP5 (neuronal apoptosis inhibitory protein 5) by flagellin along with associative recognition of tumor antigen for optimal antigen presentation to T cells. Although TLR5 signaling was critical for mediating rapid macrophage-dependent clearance of flagellin-expressing tumor cells in vivo, TLR5 and NLRC4/NAIP5 were equally important for priming antitumor CD4 + and CD8 + T cells and suppressing tumor growth. Vaccination with irradiated flagellin-expressing tumor cells prevented tumor development, and disrupting flagellin recognition by TLR5 or NLRC4/NAIP5 impaired protective immunization against an existing or subsequent tumor. Our findings delineate a new strategy to induce anticancer immune responses consisting of introducing microbial structures with dual TLR and NLR stimulatory activity into tumor cells. This ensures recognition of tumor-derived antigen within the inflammatory context of microbial recognition and additionally activates both the phagocytic and the cytosolic pathways of innate immune defense against the tumor.


Kooi B.W.,VU University Amsterdam
Journal of Mathematical Biology | Year: 2015

We study the dynamics of a predator–prey system where predators fight for captured prey besides searching for and handling (and digestion) of the prey. Fighting for prey is modelled by a continuous time hawk–dove game dynamics where the gain depends on the amount of disputed prey while the costs for fighting is constant per fighting event. The strategy of the predator-population is quantified by a trait being the proportion of the number of predator-individuals playing hawk tactics. The dynamics of the trait is described by two models of adaptation: the replicator dynamics (RD) and the adaptive dynamics (AD). In the RD-approach a variant individual with an adapted trait value changes the population’s strategy, and consequently its trait value, only when its payoff is larger than the population average. In the AD-approach successful replacement of the resident population after invasion of a rare variant population with an adapted trait value is a step in a sequence changing the population’s strategy, and hence its trait value. The main aim is to compare the consequences of the two adaptation models. In an equilibrium predator–prey system this will lead to convergence to a neutral singular strategy, while in the oscillatory system to a continuous singular strategy where in this endpoint the resident population is not invasible by any variant population. In equilibrium (low prey carrying capacity) RD and AD-approach give the same results, however not always in a periodically oscillating system (high prey carrying-capacity) where the trait is density-dependent. For low costs the predator population is monomorphic (only hawks) while for high costs dimorphic (hawks and doves). These results illustrate that intra-specific trait dynamics matters in predator–prey dynamics. © 2015, The Author(s).


Radua J.,Kings College London | Van Den Heuvel O.A.,VU University Amsterdam | Surguladze S.,Kings College London | Mataix-Cols D.,Kings College London
Archives of General Psychiatry | Year: 2010

Context: Whether obsessive-compulsive disorder (OCD) is adequately classified as an anxiety disorder is a matter of considerable debate. Objectives: To quantitatively compare structural brain changes in OCD and other anxiety disorders using novel voxel-based meta-analytical methods and to generate an online database to facilitate replication and further analyses by other researchers. Data Sources: The PubMed, ScienceDirect, and Scopus databases were searched between 2001 (the date of the first voxel-based morphometry study in any anxiety disorder) and 2009. All voxel-based morphometry studies comparing patients with any anxiety disorder and healthy controls were retrieved. Manual searches were also conducted. Authors were contacted soliciting additional data. Study Selection: Thirty-seven data sets were identified, of which 26 (including 639 patients with anxiety disorders and 737 healthy controls) met inclusion criteria. Data Extraction: Coordinates were extracted from clusters of significant gray matter difference between patients patients and controls. Demographic, clinical, and methodological variables were extracted from each study or obtained from the authors. Data Synthesis: Patients with anxiety disorders (including OCD) showed decreased bilateral gray matter volumes in the dorsomedial frontal/anterior cingulate gyri. Individuals with OCD had increased bilateral gray matter volumes (vs healthy controls and vs individuals with other anxiety disorders) in the lenticular/caudate nuclei, while patients with other anxiety disorders (mainly panic and posttraumatic stress disorders) had decreased gray matter volumes in the left lenticular nucleus. The findings remained largely unchanged in quartile and jackknife sensitivity analyses. Controlling for potential confounders such as age or antidepressant medication had little impact on the results. Conclusions: The meta-analysis consistently revealed common as well as distinct neural substrates in OCD and other anxiety disorders. These results have implications for the current debate surrounding the classification of OCD in the DSM-V. ©2010 American Medical Association. All rights reserved.


Maliepaard M.,Rotterdam University | Mathijssen I.M.J.,Rotterdam University | Oosterlaan J.,VU University Amsterdam | Okkerse J.M.E.,Rotterdam University
Pediatrics | Year: 2014

OBJECTIVES: To examine intellectual, behavioral, and emotional functioning of children who have syndromic craniosynostosis and to explore differences between diagnostic subgroups. METHODS: A national sample of children who have syndromic craniosynostosis participated in this study. Intellectual, behavioral, and emotional outcomes were assessed by using standardized measures: Wechsler Intelligence Scale for Children, Third Edition, Child Behavior Checklist (CBCL)/6-18, Disruptive Behavior Disorder rating scale (DBD), and the National Institute of Mental Health Diagnostic Interview Schedule for Children. RESULTS: We included 82 children (39 boys) aged 6 to 13 years who have syndromic craniosynostosis. Mean Full-Scale IQ (FSIQ) was in the normal range (M = 96.6; SD = 21.6). However, children who have syndromic craniosynostosis had a 1.9 times higher risk for developing intellectual disability (FSIQ <85) compared with the normative population (P <.001) and had more behavioral and emotional problems compared with the normative population, including higher scores on the CBCL/6-18, DBD Total Problems (P < .001), Internalizing (P < .01), social problems (P < .001), attention problems (P < .001), and the DBD Inattention (P < .001). Children who have Apert syndrome had lower FSIQs (M = 76.7; SD = 13.3) and children who have Muenke syndrome had more social problems (P < .01), attention problems (P < .05), and inattention problems (P < .01) than normative population and with other diagnostic subgroups. CONCLUSIONS: Although children who have syndromic craniosynostosis have FSIQs similar to the normative population, they are at increased risk for developing intellectual disability, internalizing, social, and attention problems. Higher levels of behavioral and emotional problems were related to lower levels of intellectual functioning. Copyright © 2014 by the American Academy of Pediatrics.


Janssen M.H.M.,VU University Amsterdam | Powis I.,University of Nottingham
Physical Chemistry Chemical Physics | Year: 2014

In this Perspective we discuss photoelectron circular dichroism (PECD), a relatively novel technique that can detect chiral molecules with high sensitivity. PECD has an enantiomeric sensitivity of typically 1-10%, which is two to three orders of magnitude larger than that of the widely employed technique of circular dichroism (CD). In PECD a chiral molecule is photoionized with circular polarized light, and the photoelectron angular scattering distribution is detected using particle imaging techniques. We present the general physical principles of photoelectron circular dichroism and we address both single- and multiphoton excitation. PECD has been measured with synchrotron radiation in single-photon ionization as well as, very recently, with femtosecond laser radiation in multiphoton ionization. We discuss the experimental implementation of PECD, focusing on velocity map coincidence imaging where the momentum distribution of both the electron and the coincident ion is measured. The coincident detection of the mass and momentum of the ion adds very powerful mass-correlated information to the PECD measurement of the chiral molecule. We illustrate the capabilities and the potential of PECD with various experimental examples and introduce computational methods that are able to model quantitatively experimental PECD results. We conclude with an outlook on novel developments and (analytical) implementations of PECD that may further broaden the application of PECD for the sensitive detection of chirality in molecules. © 2014 the Owner Societies.


Fernandez I.,Complutense University of Madrid | Bickelhaupt F.M.,VU University Amsterdam | Bickelhaupt F.M.,Radboud University Nijmegen
Chemical Society Reviews | Year: 2014

In this Tutorial Review, we make the point that a true understanding of trends in reactivity (as opposed to measuring or simply computing them) requires a causal reactivity model. To this end, we present and discuss the Activation Strain Model (ASM). The ASM establishes the desired causal relationship between reaction barriers, on one hand, and the properties of reactants and characteristics of reaction mechanisms, on the other hand. In the ASM, the potential energy surface ΔE(ζ) along the reaction coordinate ζ is decomposed into the strain ΔEstrain(ζ) of the reactants that become increasingly deformed as the reaction proceeds, plus the interaction ΔEint(ζ) between these deformed reactants, i.e., ΔE(ζ) = ΔEstrain(ζ) + ΔE int(ζ). The ASM can be used in conjunction with any quantum chemical program. An analysis of the method and its application to problems in organic and organometallic chemistry illustrate the power of the ASM as a unifying concept and a tool for rational design of reactants and catalysts. This journal is © the Partner Organisations 2014.


Van Weering J.R.T.,VU University Amsterdam | Cullen P.J.,University of Bristol
Seminars in Cell and Developmental Biology | Year: 2014

The endosome system is a collection of organelles that sort membrane-associated proteins and lipids for lysosomal degradation or recycling back to their target organelle. Recycling cargo is captured in a network of membrane tubules emanating from endosomes where tubular carriers pinch off. These tubules are formed and stabilized through the scaffolding properties of cytosolic Bin/Amphiphysin/Rvs (BAR) proteins that comprise phosphoinositide-detecting moieties, recruiting these proteins to specific endosomal membrane areas. These include the protein family of sorting nexins that remodel endosome membrane into tubules by an evolutionary conserved mechanism of dimerization, local membrane curvature detection/induction and oligomerization. How the formation of such a tubular membrane carrier is coordinated with cargo capture is largely unknown. The tubular structure of the membrane carriers could sequester membrane-bound cargo through an iterative mechanism of geometric sorting. Furthermore, the recent identification of cargo adaptors for the endosome protein sorting complex retromer has expanded the sorting signals that retrieve specific sets of cargo away from lysosomal degradation through distinct membrane trafficking pathways. © 2014 Elsevier Ltd.


Boer D.,University of Groningen | Den Dunnen W.J.,VU University Amsterdam
Physical Review Letters | Year: 2010

The W boson can obtain a small right-handed coupling to quarks and leptons through mixing with a hypothetical W′ boson that appears in many extensions of the standard model. Measuring or even bounding this coupling to the light quarks is very challenging. Only one model independent bound on the absolute value of the complex mixing parameter has been obtained to date. Here we discuss a method sensitive to both the real and CP-violating imaginary parts of the coupling, independent of assumptions on the new physics, and demonstrate quantitatively the feasibility of its measurement at RHIC. © 2010 The American Physical Society.


Johnson N.C.,Northern Arizona University | Angelard C.,University of Lausanne | Sanders I.R.,University of Lausanne | Kiers E.T.,VU University Amsterdam
Ecology Letters | Year: 2013

Mycorrhizal symbioses link the biosphere with the lithosphere by mediating nutrient cycles and energy flow though terrestrial ecosystems. A more mechanistic understanding of these plant-fungal associations may help ameliorate anthropogenic changes to C and N cycles and biotic communities. We explore three interacting principles: (1) optimal allocation, (2) biotic context and (3) fungal adaptability that may help predict mycorrhizal responses to carbon dioxide enrichment, nitrogen eutrophication, invasive species and land-use changes. Plant-microbial feedbacks and thresholds are discussed in light of these principles with the goal of generating testable hypotheses. Ideas to develop large-scale collaborative research efforts are presented. It is our hope that mycorrhizal symbioses can be effectively integrated into global change models and eventually their ecology will be understood well enough so that they can be managed to help offset some of the detrimental effects of anthropogenic environmental change. © 2013 John Wiley & Sons Ltd/CNRS.


Fischer D.,VU University Amsterdam
Current Opinion in Neurology | Year: 2016

PURPOSE OF REVIEW: In this update, we describe recent findings on imaging techniques used for the analysis and quantification of affected muscles, advances in pattern recognition, and quantitative muscle imaging in clinical studies. RECENT FINDINGS: Whole-body muscle MRI and meta-analytical approaches, so-called (hierarchical) heat maps of affected muscles are promising advances compared with commonly applied lower leg pattern recognition approaches. Muscle fat fraction assessments measuring chemical shift differences and T2-relaxation times of separated fat and water components in skeletal muscle are currently the most reliable quantitative muscle imaging techniques. Quantitative muscle MRI detects subclinical disease progression in muscular dystrophies and is a powerful surrogate outcome measure in clinical trials. SUMMARY: Diagnostic and quantitative muscular imaging techniques are increasingly important for diagnostic workup and for interventional studies in patients with inherited myopathies. Copyright © 2016 Wolters Kluwer Health, Inc. All rights resereved.


Full recovery after gynecological surgery takes much longer than expected regardless of surgical technique or the level of invasiveness. After discharge, detailed convalescence recommendations are not provided to patients typically, and postoperative care is fragmented, poorly coordinated, and given only on demand. For patients, this contributes to irrational beliefs and avoidance of resumption of activities and can result in a prolonged sick leave. To develop an eHealth intervention that empowers gynecological patients during the perioperative period to obtain timely return to work (RTW) and prevent work disability. The intervention mapping (IM) protocol was used to develop the eHealth intervention. A literature search about behavioral and environmental conditions of prolonged sick leave and delayed RTW in patients was performed. Patients' needs, attitudes, and beliefs regarding postoperative recovery and resumption of work were identified through focus group discussions. Additionally, a literature search was performed to obtain determinants, methods, and strategies for the development of a suitable interactive eHealth intervention to empower patients to return to normal activities after gynecological surgery, including work. Finally, the eHealth intervention was evaluated by focus group participants, medical doctors, and eHealth specialists through questionnaires. Twenty-one patients participated in the focus group discussions. Sufficient, uniform, and tailored information regarding surgical procedures, complications, and resumption of activities and work were considered most essential. Knowing who to contact in case of mental or physical complaints, and counseling and tools for work reintegration were also considered important. Finally, opportunities to exchange experiences with other patients were a major issue. Considering the determinants of the Attitude-Social influence-self-Efficacy (ASE) model, various strategies based on a combination of theory and evidence were used, resulting in an eHealth intervention with different interactive functionalities including tailored convalescence recommendations and a video to communicate the most common pitfalls during the perioperative period to patients and employers. Fifteen patients in the focus groups, 11 physicians, and 3 eHealth specialists suggested points for improvement to optimize the usability of the eHealth intervention and judged it an approachable, appropriate, and attractive eHealth intervention to empower gynecological patients. The IM protocol was a useful method to develop an eHealth intervention based on both theory and evidence. All patients and stakeholders judged the eHealth intervention to be a promising tool to empower gynecological patients during the perioperative period and to help them to return to normal activities and work.


Van Der Vaart A.,VU University Amsterdam | Van Zanten H.,TU Eindhoven
Journal of Machine Learning Research | Year: 2011

We consider the quality of learning a response function by a nonparametric Bayesian approach using a Gaussian process (GP) prior on the response function. We upper bound the quadratic risk of the learning procedure, which in turn is an upper bound on the Kullback-Leibler information between the predictive and true data distribution. The upper bound is expressed in small ball probabilities and concentration measures of the GP prior. We illustrate the computation of the upper bound for the Matérn and squared exponential kernels. For these priors the risk, and hence the information criterion, tends to zero for all continuous response functions. However, the rate at which this happens depends on the combination of true response function and Gaussian prior, and is expressible in a certain concentration function. In particular, the results show that for good performance, the regularity of the GP prior should match the regularity of the unknown response function. © 2011 Aad van der Vaart and Harry van Zanten.


Butz M.,Julich Research Center | van Ooyen A.,VU University Amsterdam
PLoS Computational Biology | Year: 2013

Lasting alterations in sensory input trigger massive structural and functional adaptations in cortical networks. The principles governing these experience-dependent changes are, however, poorly understood. Here, we examine whether a simple rule based on the neurons' need for homeostasis in electrical activity may serve as driving force for cortical reorganization. According to this rule, a neuron creates new spines and boutons when its level of electrical activity is below a homeostatic set-point and decreases the number of spines and boutons when its activity exceeds this set-point. In addition, neurons need a minimum level of activity to form spines and boutons. Spine and bouton formation depends solely on the neuron's own activity level, and synapses are formed by merging spines and boutons independently of activity. Using a novel computational model, we show that this simple growth rule produces neuron and network changes as observed in the visual cortex after focal retinal lesions. In the model, as in the cortex, the turnover of dendritic spines was increased strongest in the center of the lesion projection zone, while axonal boutons displayed a marked overshoot followed by pruning. Moreover, the decrease in external input was compensated for by the formation of new horizontal connections, which caused a retinotopic remapping. Homeostatic regulation may provide a unifying framework for understanding cortical reorganization, including network repair in degenerative diseases or following focal stroke. © 2013 Butz, van Ooyen.


Kerkhof A.J.F.M.,VU University Amsterdam | Molenberghs G.,Interuniversity Institute for Biostatistics and Statistical Bioinformatics oStat
Social Psychiatry and Psychiatric Epidemiology | Year: 2014

Purpose: Accessibility and availability of mental health care services are necessary but not sufficient for people to seek help for psychological problems. Attitudes and stigma related to help seeking also determine help seeking intentions. The aim of this study is to investigate how cross-national differences in attitudes and stigma within the general population are related to professional and informal help seeking intentions in low and high suicide rate regions. Methods: By means of a postal structured questionnaire, data of 2999 Dutch and Flemish respondents between 18 and 65 years were gathered. Attitudes toward help seeking, perceived stigma, self-stigma, shame and intention to seek help were assessed. Results: People in the Netherlands, where suicide rates are low, have more positive attitudes toward help seeking and experience less self stigma and shame compared to the people in Flanders, where suicide rates are relatively high. These attitudinal factors predicted professional as well as informal help seeking intentions. Perceived stigma was negatively associated with informal help seeking. Shame was positively associated with higher intention to use psychotropic drugs and perceived stigma was negatively associated with the intention to seek help from a psychotherapist in Flanders but not in the Netherlands. Conclusion: Help seeking for psychological problems prevent these problems to aggravate and it is assumed to be a protective factor for suicide. Our results stress the importance of the promotion of positive attitudes and the reduction of stigma within the general population to facilitate help seeking from professional providers and informal networks. Focusing on these attitudinal factors is believed to be a key aspect of universal mental health and suicide prevention policies. © 2013 Springer-Verlag Berlin Heidelberg.


Nieuwenhuis S.,Leiden University | De Geus E.J.,VU University Amsterdam | Aston-Jones G.,Medical University of South Carolina
Psychophysiology | Year: 2011

Many psychophysiologists have noted the striking similarities between the antecedent conditions for the P3 component of the event-related potential and the orienting response: both are typically elicited by salient, unexpected, novel, task-relevant, and other motivationally significant stimuli. Although the close coupling of the P3 and orienting response has been well documented, the neural basis and functional role of this relationship is still poorly understood. Here we propose that the simultaneous occurrence of the P3 and autonomic components of the orienting response reflects the co-activation of the locus coeruleus-norepinephrine system and the peripheral sympathetic nervous system by their common major afferent: the rostral ventrolateral medulla, a key sympathoexcitatory region. A comparison of the functional significance of the locus coeruleus-norepinephrine system and the peripheral sympathetic nervous system suggests that the P3 and orienting response reflect complementary cognitive and physical contributions to the mobilization for action following motivationally significant stimuli. Copyright © 2010 Society for Psychophysiological Research.


Groeneveld A.B.J.,VU University Amsterdam | Navickis R.J.,Hygeia Associates | Wilkes M.M.,Hygeia Associates
Annals of Surgery | Year: 2011

Objective: To provide an updated systematic review on the comparative safety of colloids based on recent clinical studies. Background: Recent investigations, including large-scale randomized trials and meta-analyses, have sought to determine the effects of colloids on mortality and morbidity. Hypothesized differences in safety profile between hydroxyethyl starch (HES) solutions have also been evaluated in randomized trials. Methods: Clinical studies reported since 2002 with safety data for acutely ill patients receiving HES, gelatin, dextran, or albumin were sought by computer searches and other methods. Safety endpoints included mortality, morbidity, bleeding and impaired coagulation, and acute kidney injury (AKI). Data extracted from the included study reports were qualitatively summarized. Results:: Sixty-nine clinical studies were included. Of those, 42 were randomized controlled trials (RCTs) with 10,382 total patients. New safety data, since 2002, predominantly concerned albumin or HES. A large RCT of intensive care unit patients showed that albumin does not adversely affect survival. Acute kidney injury and a dose-dependent increase in mortality were observed in a large RCT of patients with severe sepsis or septic shock receiving HES. Impaired coagulation and clinical bleeding were frequently reported after HES infusion, especially in cardiac surgery. In head-to-head randomized comparisons of different HES solutions, observed effects on coagulation and renal function were similar. Gelatin showed less impairment of coagulation than HES. Very few safety data related to dextran were identified. Conclusions: Albumin displayed a more favorable safety profile than HES. Available evidence does not support the existence of consistent safety differences between HES solutions. Copyright © 2011 by Lippincott Williams & Wilkins.


Jager T.,VU University Amsterdam
Ecotoxicology | Year: 2014

In dose-response analysis, regression analysis and hypothesis testing are the main tools of choice. These methods, however, have specific requirements for the design of acute toxicity experiments. To produce meaningful results, both approaches require a constant exposure concentration over the duration of the test, and regression analysis makes an additional demand for at least two doses with partial mortality at the end of the test. These requirements, however, result from the limitations of the statistical techniques, which only use the observations at the end of the test. In practice, most standard protocols for acute testing prescribe that observations are made at several points in time (often daily). In this contribution, I demonstrate how dynamic modelling can make use of this information to produce robust estimates of LC50 as function of time, with confidence intervals, from data sets that violate the requirements for standard dose-response analysis. This form of modelling invites an entirely different, more flexible, view on experimental design, which could lead to a more efficient use of test animals and, at the same time, a stronger support for environmental risk assessment as well as the science of ecotoxicology. © 2013 Springer Science+Business Media New York.


Cuijpers P.,VU University Amsterdam
Current Opinion in Psychiatry | Year: 2015

Purpose: of review Much has been learned from the 400 randomized trials on psychotherapies for adult depression that have been conducted, but much is also still unknown. In this study some recent attempts to further reduce the disease burden of depression through psychotherapies are reviewed.Recent findings :In the past, many new psychotherapies have promised to be more effective than existing treatments, usually without success. We describe recent research on two new therapies, acceptance and commitment therapy and cognitive bias modification, and conclude that both have also not shown to be more effective than existing therapies. A growing number of studies have also focused on therapies that may be successful in further reducing the disease burden, such as treatments for chronic depression and relapse prevention. Other studies are aimed at scaling up psychological services, such as the training of lay health counselors in low-income and middle-income countries, telephone-based, and internet-based therapies.Summary: Psychotherapies are essential tools in the treatment of adult depression. Randomized trials have shown that these treatments are effective, and by focusing on key issues, such as chronic depression, relapse, and scaling them up, psychotherapies contribute more and more to the reduction of the disease burden of depression. © Lippincott Williams & Wilkins.


Bos-Brouwers H.E.J.,VU University Amsterdam
Business Strategy and the Environment | Year: 2010

Recently, innovation processes towards sustainable development have received increasing attention in academic literature. This research introduces the combination of insights from innovation theory, sustainable development practice and small business characteristics to unlock new knowledge on factors that influence the translation of sustainable innovation within small and medium-sized enterprises (SMEs) into practice. The sustainability themes and activities as described for large companies (i.e. in the sustainability reporting and management literature) were used as starting point in this study. It presents empiric results of the PRIMA Project conducted within the rubber and plastics industry (RPI) on sustainable innovation activities.It will show that many sustainable innovations are directed at the improvement of technological processes (eco-efficiency) and to lower costs of production. These innovations can be seen as incremental. Companies with sustainability integrated in their orientation and innovation processes show value creation: the development of products new to the market (radical innovations) and cooperation with stakeholders. The PRIMA project shows that more insight in SME innovative characteristics and (e)valuation of sustainable innovation efforts provides opportunities to improve the sustainability performance of SMEs. © 2009 John Wiley & Sons, Ltd and ERP Environment.


Roberts J.A.,QIMR Berghofer Medical Research Institute | Boonstra T.W.,University of New South Wales | Boonstra T.W.,Black Dog Institute | Boonstra T.W.,VU University Amsterdam | Breakspear M.,QIMR Berghofer Medical Research Institute
Current Opinion in Neurobiology | Year: 2015

Fluctuating oscillations are a ubiquitous feature of neurophysiology. Are the amplitude fluctuations of neural oscillations chance excursions drawn randomly from a normal distribution, or do they tell us more? Recent empirical research suggests that the occurrence of 'anomalous' (high amplitude) oscillations imbues their probability distributions with a heavier tail than the standard normal distribution. However, not all heavy tails are the same. We provide canonical examples of different heavy-tailed distributions in cortical oscillations and discuss the corresponding mechanisms that each suggest, ranging from criticality to multistability, memory, bifurcations, and multiplicative noise. Their existence suggests that the brain is a strongly correlated complex system that employs many different functional mechanisms, and that likewise, we as scientists should refrain from methodological monism. © 2014 Elsevier Ltd.


Novoderezhkin V.,Moscow State University | Van Grondelle R.,VU University Amsterdam
Journal of Physical Chemistry B | Year: 2013

We model the spectra (absorption and circular dichroism) and excitation dynamics in the B800 ring of the LH2 antenna complex from Rs. molischianum using different theoretical approaches, i.e., Förster theory, standard and modified versions of the Redfield theory, and the more versatile nonperturbative approach based on hierarchically coupled equations for the reduced density operator. We demonstrate that, although excitations in the B800 ring are localized due to disorder, thermal effects, and phonons, there are still sizable excitonic effects producing shift, narrowing, and asymmetry of the spectra. Moreover, the excitation dynamics reveals the presence of long-lived (up to 1 ps) non-oscillatory coherences between the exciton states maintained due to nonsecular population-to-coherence transfers. The sub-ps decay of the coherences is followed by slow motion of the excitation around the ring, producing equilibration of the site populations with a time constant of about 3-4 ps, which is slower than the B800 → B850 transfer. The exact solution obtained with the hierarchical equations is compared with other approaches, thus illustrating limitations of the Förster and Redfield pictures. © 2013 American Chemical Society.


Lika K.,University of Crete | Kooijman S.A.L.M.,VU University Amsterdam
Journal of Sea Research | Year: 2011

The standard Dynamic Energy Budget (DEB) model assumes that assimilates of an isomorphic individual are first added to reserve, a fraction κ of mobilised reserve is allocated to soma (somatic maintenance plus growth of structure), and the rest to maturity maintenance and maturation or reproduction. Food, reserve and structure have constant chemical composition. We here discuss all possible topological alternatives to the standard DEB model, and compare them on the basis of seven properties: the ability to capture weak homeostasis and general empirical growth and reproduction patterns. We selected a reserve dynamics such that reserve mobilisation rate is independent of assimilation, somatic maintenance is proportional to the amount of structure, maturity maintenance to the level of maturity, and assimilation to the surface area. The alternatives only differ from the standard DEB model in topology, but we drop the κ-rule and allow κ to vary with the amount of structure. For this purpose we introduce the concept 'generalised von Bertalanffy growth rate' and study how it behaves as a function of the ultimate structural length, both intra- and inter-specifically. The 21 derived topological alternatives of the standard DEB are classified into five classes of models, depending on the first allocation event for the assimilation flux. The possibilities of the first allocation event for the assimilation flux are: splitting (κ-models), storing (A-models), both maintenance fluxes simultaneously (P-models), somatic maintenance (S-models) or maturity maintenance (J-models). We conclude that the standard DEB model with constant κ is the only one that passes all our tests successfully. Only assimilation (A) models can naturally accommodate embryo development. The κ-models, which after splitting the fraction 1-κ of assimilates is allocated to maturity maintenance and maturity/reproduction while the fraction κ of assimilates is first stored in reserve or allocated to somatic maintenance, pass most tests, but have maturation and reproduction directly from food. So, embryos have to do this differently and reproduction is prohibited during starvation in these models. © 2011.


Shapira A.,Russell Berrie Nanotechnology Institute | Livney Y.D.,Russell Berrie Nanotechnology Institute | Livney Y.D.,Technion - Israel Institute of Technology | Broxterman H.J.,VU University Amsterdam | Assaraf Y.G.,Technion - Israel Institute of Technology
Drug Resistance Updates | Year: 2011

Anticancer drug resistance almost invariably emerges and poses major obstacles towards curative therapy of various human malignancies. In the current review we will distinguish between mechanisms of chemoresistance that are predominantly mediated by ATP-driven multidrug resistance (MDR) efflux transporters, typically of the ATP-binding cassette (ABC) superfamily, and those that are independent of such drug efflux pumps. In recent years, multiple nanoparticle (NP)-based therapeutic systems have been developed that were rationally designed to overcome drug resistance by neutralizing, evading or exploiting various drug efflux pumps and other resistance mechanisms. NPs are being exploited for selective drug delivery to tumor cells, to cancer stem/tumor initiating cells and/or to the supportive cancer cell microenvironment, i.e. stroma or tumor vasculature. Some of these NPs are currently undergoing preclinical in vivo studies as well as advanced stages of clinical evaluation with promising results. Nanovehicles harboring a payload of therapeutic drug combinations for the selective targeting and elimination of tumor cells as well as the simultaneous overcoming of mechanisms of drug resistance are a subject of intense research efforts, some of which are expected to enter clinical trials in the near future. In the present review we highlight novel approaches to selectively target cancer cells and overcome drug resistance phenomena, through the use of various nanometric drug delivery systems. In the near future, it is anticipated that innovative theragnostic nanovehicles will be developed which will harbor four major components: (1) a selective targeting moiety, (2) a diagnostic imaging aid for the localization of the malignant tumor and its micro- or macrometastases, (3) a cytotoxic, small molecule drug(s) or novel therapeutic biological(s), and (4) a chemosensitizing agent aimed at neutralizing a resistance mechanism, or exploiting a molecular "Achilles hill" of drug resistant cells. We propose to name these envisioned four element-containing nanovehicle platform, "quadrugnostic" nanomedicine. This targeted strategy holds promise in paving the way for the introduction of highly effective nanoscopic vehicles for cancer therapeutics while overcoming drug resistance. © 2011 Elsevier Ltd. All rights reserved.


Boers M.,VU University Amsterdam
Clinical and Experimental Rheumatology | Year: 2011

This article provides a perspective on the immediate and follow-up results of the COBRA trial that compared the combination of step-down prednisolone, methotrexate and sulfasalazine with sulfasalazine monotherapy in early rheumatoid arthritis (RA). The combination provided immediate relief of symptoms and signs of RA, but the clinical benefit compared to monotherapy appeared mostly dependent on low-dose glucocorticoid therapy that was mandatorily discontinued after 28 weeks. Strong benefit was apparent in the slowing of joint damage progression, and this effect persisted for over JO years despite uncontrolled therapy after the trial period. In the trial toxicity of COBRA was less than monotherapy, and long-term safety of the regimen was comparable to regimens that do not include glucocorticoids. COBRA was the first study to validate the 'reverse-pyramid' concept in RA, and helped to establish the idea of a window of opportunity where the prognosis of RA may be altered with early and intensive therapy. Subsequent studies have shown COBRA is feasible in practice, acceptable to patients, and has efficacy similar to the combination of TNF inhibition and high-dose methotrexate, at a fraction of the cost. © CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2011.


Klein M.,VU University Amsterdam
Advances and technical standards in neurosurgery | Year: 2010

Standard therapeutic options for brain tumors include surgery, radiotherapy, and chemotherapy. Unfortunately, these same therapies pose risks of neurotoxicity, the most common long-term complications being radiation necrosis, chemotherapy-associated leukoencephalopathy, and cognitive deficits. Currently, there is no consensus on the treatment strategy for these tumors. Because of the relatively slow growth rate of low-grade gliomas, patients have a relatively long expected survival. Compared to traditional outcome measures like (progression-free) survival, evaluation of health-related quality of life may be time-consuming and burdensome for both the patient and the doctor. Besides, given the relatively low incidence of brain tumors and the ultimately fatal outcome of the disease, the interest in HRQOL emerged relatively late in these patients. Moreover, the notion that the disease itself may affect the patient's ability to judge his or her own functioning may hinder the use of patient self-reported measures. The studies presented in this chapter describe outcomes of both single dimensional and multidimensional methods of studying HRQOL. Although only few studies incorporated HRQOL as outcome measure, most studies have embraced the notion that an accurate assessment of HRQOL must be based on patient self-report. HRQOL instruments from other cancer groups are adapted for use with brain tumor patients. The multidimensional scales used to study changes in HRQOL studies in brain tumor patients provide a more comprehensive view of what is important to the patient concerning living with their disease and receiving treatment. In future trials, more sensitive measures of long-term cognitive, functional, and HRQOL outcomes on LGG patients at important time points over the disease trajectory are needed to better understand the changing needs that take place over time.


Noordhof D.A.,VU University Amsterdam
Sports medicine (Auckland, N.Z.) | Year: 2010

The maximal accumulated oxygen deficit (MAOD) method has been extensively, but unfortunately not very methodically, used; the procedure used to determine the MAOD varies considerably. Therefore, this review evaluates the effect of different numbers and durations of submaximal exercise bouts on the linear power output (PO)-oxygen uptake ((.)VO2) relationship and thus the MAOD. Changing the number and duration of the submaximal exercise bouts substantially influences the calculated MAOD when relatively long submaximal exercise bouts are used and no fixed value of the y-intercept is forced into the linear regression line. This is most likely due to non-linearity of the PO-(.)VO2 relationship for exercise intensities above the lactate threshold (LT). Non-linearity of the PO-(.)VO2 relationship is probably caused by the development of a slow component in (.)VO2 during submaximal exercise at intensities above the LT. Thus, it is important to standardize the number, duration and intensity of submaximal exercise bouts necessary to establish the PO-(.)VO2 relationship. Beyond changing the number and duration of the submaximal exercise bouts, the effect of different supramaximal exercise bouts on the calculated MAOD has been investigated. While it has become clear that different exercise protocols result in relatively similar values of the MAOD, a closer look at individual data suggests that it may be important to choose an exercise protocol that is representative of the athlete's event. The validity of the MAOD method was studied by different authors comparing the MAOD with metabolic measurements of anaerobic adenosine triphosphate (ATP) production. The main limitation with the metabolic measurements of anaerobic ATP production from muscle biopsy data is that the active muscle mass is unknown, which makes it hard to accurately study the validity of the MAOD method. From the studies that evaluated the reliability of the MAOD method it is clear that the MAOD method may not be a reliable measure of anaerobic capacity. From these findings it can be concluded that the MAOD method may have limitations as a valid and reliable measure of anaerobic capacity and needs to be further improved. We suggest the use of 10 x 4 minute submaximal exercise bouts and a fixed value of the y-intercept for the construction of the linear PO-(.)VO2 relationship, after which the MAOD can be determined during a supramaximal exercise protocol specific for the athlete's event. This method will lead to a more robust PO-(.)VO2 relationship and will therefore result in more valid and reliable results.


Many initiatives are undertaken to improve the empowerment of people with disabilities in developing countries. However, an overview of adequate measurement tools to evaluate such activities is not available to date. This systematic literature review aims to describe and assess the available tools to measure empowerment in people with disability, suitable for use in developing countries. A systematic literature review was conducted. Articles were eligible when they described the development, validation, translation or the use of an instrument measuring empowerment in the context of disability. The instruments were assessed on their psychometric properties and on equivalence properties when they were translated. Thirty-six articles were found in which 17 questionnaires were developed, validated, translated or used. The questionnaires varied in the construct of empowerment, the target population and the psychometric properties. None of the questionnaires were developed or validated in a developing country. The psychometric properties and equivalence criteria were not adequately described and measured in any article. The Empowerment Scale (ES) of Rogers was the most often validated, translated and used questionnaire, receiving the highest number of positive ratings for the psychometric properties. The ES is the tool most widely used to measure empowerment, but adequate validation in a developing country context is still lacking. Cultural validity should be assessed in any culture before it is used. Further research is needed to develop empowerment instruments for developing countries and to assess the equivalence criteria, including psychometric properties of such questionnaires.


de Boer J.,VU University Amsterdam | Wardekker J.A.,Copernicus Institute for Sustainable Development and Innovation | van der Sluijs J.P.,Copernicus Institute for Sustainable Development and Innovation
Global Environmental Change | Year: 2010

The present paper describes a frame-based approach to situated-decision-making on climate change. Building on the multidisciplinary literature on the relationship between frames and decision-making, it argues that decision-makers may gain from making frames more explicit and using them for generating different visions about the central issues. Frames act as organizing principles that shape in a " hidden" and taken-for-granted way how people conceptualize an issue. Science-related issues, such as climate change, are often linked to only a few frames, which consistently appear across different policy areas. Indeed, it appears that there are some very contrasting ways in which climate change may be framed. These frames can be characterized in terms of a simple framework that highlights specific interpretations of climate issues. A second framework clarifies the built-in frames of decision tools. Using Thompson's two basic dimensions of decision, it identifies the main uncertainties that should be considered in developing a decision strategy. The paper characterizes four types of decision strategy, focusing on (1) computation, (2) compromise, (3) judgment, or (4) inspiration, and links each strategy to the appropriate methods and tools, as well as the appropriate social structures. Our experiences show that the frame-based guide can work as an eye-opener for decision-makers, particularly where it demonstrates how to add more perspectives to the decision. © 2010 Elsevier Ltd.


Verburg P.H.,VU University Amsterdam | Neumann K.,Wageningen University | Nol L.,CAH Vilentum University of Applied Sciences
Global Change Biology | Year: 2011

Land use and land cover data play a central role in climate change assessments. These data originate from different sources and inventory techniques. Each source of land use/cover data has its own domain of applicability and quality standards. Often data are selected without explicitly considering the suitability of the data for the specific application, the bias originating from data inventory and aggregation, and the effects of the uncertainty in the data on the results of the assessment. Uncertainties due to data selection and handling can be in the same order of magnitude as uncertainties related to the representation of the processes under investigation. While acknowledging the differences in data sources and the causes of inconsistencies, several methods have been developed to optimally extract information from the data and document the uncertainties. These methods include data integration, improved validation techniques and harmonization of classification systems. Based on the data needs of global change studies and the data availability, recommendations are formulated aimed at optimal use of current data and focused efforts for additional data collection. These include: improved documentation using classification systems for land use/cover data; careful selection of data given the specific application and the use of appropriate scaling and aggregation methods. In addition, the data availability may be improved by the combination of different data sources to optimize information content while collection of additional data must focus on validation of available data sets and improved coverage of regions and land cover types with a high level of uncertainty. Specific attention in data collection should be given to the representation of land management (systems) and mosaic landscapes. © 2010 Blackwell Publishing Ltd.


van der Veldt A.A.,VU University Amsterdam
Discovery medicine | Year: 2010

In the past 5 years, the introduction of targeted therapy has dramatically changed the outcome of patients with metastatic renal cell cancer (mRCC). In particular, drugs that inhibit signaling of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) have significantly improved the perspectives of patients with this chemoresistant disease. Here, we review the currently approved targeted drugs for the treatment of mRCC. We describe the anti-VEGF monoclonal antibody bevacizumab, the receptor tyrosine kinase inhibitors sunitinib, sorafenib and pazopanib as well as the mTOR inhibitors temsirolimus and everolimus and discuss their role in the contemporary management of patients with mRCC.


Bouwer L.M.,VU University Amsterdam
Bulletin of the American Meteorological Society | Year: 2011

A number of studies were conducted to demonstrate the best way to assess the potential influence of climate change on disaster losses was to analyze future projections in place of historical data. These studies showed that increases in exposure and wealth were the most important drivers for growing disaster losses. Most of these studies also showed that disaster losses remained constant after normalization, including losses from earthquakes They found that increases after normalization did not fully correct for wealth and population increases, or they identified other sources of exposure increases or vulnerability changes or changing environmental conditions. The analysis of these disaster loss studies showed that economic losses from various weather-related natural hazards, such as storms, tropical cyclones, floods, and small-scale weather events had increased around the globe.


Boellaard R.,VU University Amsterdam | Quick H.H.,University of Duisburg - Essen
Seminars in Nuclear Medicine | Year: 2015

Whole-body PET/MR hybrid imaging combines excellent soft tissue contrast and various functional imaging parameters provided by MR with high sensitivity and quantification of radiotracer uptake provided by PET. Although clinical evaluation now is under way, PET/MR demands for new technologies and innovative solutions, currently subject to interdisciplinary research. Attenuation correction (AC) of human soft tissues and of hardware components has to be MR based to maintain quantification of PET imaging as CT attenuation information is missing. MR-based AC is inherently associated with the following challenges: patient tissues are segmented into only few tissue classes, providing discrete attenuation coefficients; bone is substituted as soft tissue in MR-based AC; the limited field of view in MRI leads to truncations in body imaging and, consequently, in MR-based AC; and correct segmentation of lung tissue may be hampered by breathing artifacts. Use of time of flight during PET image acquisition and reconstruction, however, may improve the accuracy of AC. This article provides a status of current image acquisition options in PET/MR hybrid imaging. © 2015 Elsevier Inc.


Jakobsdottir S.,VU University Amsterdam
International Journal of Obesity | Year: 2016

OBJECTIVE:Early anthropometric and metabolic changes during a caloric-restricted diet in obese postmenopausal women and correlations between these factors with activity in brain areas involved in processing of visual food related stimuli were investigated.SUBJECTS AND METHODS:An 8-week prospective intervention study of 18 healthy postmenopausal women, with a body mass index of 30–35 kg m-2. The first 2 weeks subjects were on an isocaloric diet and 4 weeks on a 1000 kcal restricted diet followed by 2 weeks on an isocaloric diet. Anthropometric and laboratory analyses were performed weekly during the isocaloric diet and three times a week during the caloric-restricted diet. Functional magnetic resonance imaging scans were obtained before and after the caloric restriction in four separate sessions (fasting or sated). Generalized Estimating Equations analysis was used for data analysis.RESULTS:A mean weight loss of 4.2±0.5 kg (4.8%) and a 4.2±0.4 cm decline in waist circumference were achieved. In the first week of caloric restriction, triglyceride, leptin, resistin and adiponectin levels as well as systolic blood pressure decreased and insulin-like growth factor-binding protein 1 levels increased. During and after weight loss, a significant increase in ghrelin levels was observed. Before weight loss, increased activation of the right amygdala was seen in response to food stimuli, and free fatty acids and glucose correlated with activity in various areas involved in food reward processing. After weight loss, fasting ghrelin and sated leptin levels correlated with activity in these areas.Conclusions:Already in the first week of caloric restriction in obese postmenopausal women, various favourable metabolic changes occur before clinically relevant weight loss is achieved. Activity in the amygdala region and correlations of metabolic factors with activity in brain areas involved in food reward processing differ substantially before and after weight loss.International Journal of Obesity advance online publication, 21 June 2016; doi:10.1038/ijo.2016.103. © 2016 Macmillan Publishers Limited


Katan M.B.,VU University Amsterdam
Beneficial Microbes | Year: 2012

Probiotics are microbes that are claimed to promote health and well-being when added to foods. However, the European Food Safety Authority (EFSA) has so far advised negatively about health claims for probiotics. Companies and scientists have protested against these rejections, sometimes in vigorous language. I argue that EFSA could not have acted differently, given EU regulations and the lack of convincing evidence for some of the claimed effects of probiotics on human health and well-being. One EU regulation that makes it hard to demonstrate the benefits of probiotics is the prohibition of medical claims, i.e. claims that a food prevents or cures a disease. If this prohibition did not exist, manufacturers of nutritional treatments might circumvent the costly procedures required for drugs, and market their products to ill people without thorough proof that they are effective and safe. However, the prohibition is also a legal fiction, because promotion of health and prevention of disease is largely the same thing. EFSA has recently indicated that it will allow health claims based on the ability of probiotics to reduce infections. To a certain extent, this abolishes the distinction between health claims and medical claims. It remains to be seen if probiotics producers can convince EFSA that their products prevent or cure infections and other diseases in humans. © 2012 Wageningen Academic Publishers.


Anthoff D.,Irish Economic and Social Research Institute | Tol R.S.J.,Irish Economic and Social Research Institute | Tol R.S.J.,VU University Amsterdam
Journal of Environmental Economics and Management | Year: 2010

Estimates of the marginal damage costs of carbon dioxide emissions require the aggregation of monetised impacts of climate change over people with different incomes and in different jurisdictions. Implicitly or explicitly, such estimates assume a social welfare function and hence a particular attitude towards equity and justice. We show that previous approaches to equity weighting are inappropriate from a national decision maker's point of view, because domestic impacts are not valued at domestic values. We propose four alternatives (sovereignty, altruism, good neighbour, and compensation) with different views on concern for and liability towards foreigners. The four alternatives imply radically different estimates of the social cost of carbon and hence the optimal intensity of climate policy. © 2010 Elsevier Inc.


Dijk J.,VU University Amsterdam | Willems B.,University of Tilburg
Energy Policy | Year: 2011

In a competitive electricity market, nodal pricing is the most efficient way to manage congestion. Counter-trading is inefficient as it gives the wrong long term signals for entry and exit of power plants. However, in a non-competitive market, additional entry will improve the competitiveness of the market, and will increase social benefit by reducing price-cost margins. This paper studies whether the potential pro-competitive entry effects could make counter-trading more efficient than nodal pricing. We find that this is unlikely to be the case, and expect counter-trading to have a negative effect on overall welfare. The potential benefits of additional competition (more competitive prices and lower production cost) do not outweigh the distortions (additional investment cost for the entrant, and socialization of the congestion cost to final consumers). © 2011 Elsevier Ltd.


Cloetingh S.,VU University Amsterdam | Burov E.,University Pierre and Marie Curie
Basin Research | Year: 2011

Lithospheric folding is an important mode of basin formation in compressional intraplate settings. Basins formed by lithospheric folding are characterized by distinct features in subsidence history. A comparison with extensional basins, foreland basins, intracratonic basins and pull-apart basins provides criteria for the discrimination between these modes of basin formation. These findings are important in deciphering the feedbacks between tectonics and surface processes. In addition, inferences on accommodation space and thermal regime have important consequences for hydrocarbon maturity. Lithospheric folding is coupled to compressional reactivation of basins and faults, and therefore, strongly affects reservoir characteristics of sedimentary basins. © 2010 The Authors. Basin Research © 2010 Blackwell Publishing Ltd, European Association of Geoscientists & Engineers and International Association of Sedimentologists.


Connectivity and network analysis in neuroscience has been applied to multiple spatial scales, but the links between these different scales have rarely been investigated. In tumor-related epilepsy, altered network topology is related to behavior, but the molecular basis of these observations is unknown. We elucidate the associations between microscopic features of brain tumors, local network topology, and functional patient status. We hypothesize that expression of proteins related to tumor-related epilepsy is directly correlated with network characteristics of the tumor area. Glioma patients underwent magnetoencephalography, and functional network topology of the tumor area was used to predict tissue protein expression patterns of tumor tissue collected during neurosurgery. Protein expression and network topology were interdependent; in particular between-module connectivity was selectively associated with two epilepsy-related proteins. Total number of seizures was related to both the role of the tumor area in the functional network and to protein expression. Importantly, classification of protein expression was predicted by between-module connectivity with up to 100% accuracy. Thus, network topology may serve as an intermediate level between molecular features of tumor tissue and symptomatology in brain tumor patients, and can potentially be used as a non-invasive marker for microscopic tissue characteristics. Copyright © 2013 Elsevier Inc. All rights reserved.


Buijck M.,VU University Amsterdam
Journal of Pediatric Gastroenterology and Nutrition | Year: 2016

ABSTRACT: The diagnostic work-up and follow-up of paediatric functional gastrointestinal disorders and organicconditions usually includes invasive tests, carrying a high burden on patients. There is a place, therefore, for novel, noninvasive disease-specific biomarkers. Volatile organic compounds (VOCs), originating from (patho)physiological metabolic processes in the human body, are excreted as waste products through all conceivable bodily excrements. The spectrum of VOCs harbours a magnificent source of information, with the potential to serve as noninvasive diagnostic biomarkers and to monitor disease activity. VOC analysishas been studied in children and infants with a variety ofgastro-intestinal diseases, including inflammatory bowel disease, liver diseases, irritable bowel syndrome, necrotising enterocolitis and infectious diarrhoea. Most of these studies, although limited in sample size, show that patients can be discriminated from controls based on their VOC profiles, underscoring the potential of VOC analysis in diagnosis and follow-up. Currently, however, the application of VOC analysis in clinical practice is limited; substantial challenges, including methodological, biological and analytical problems, still need to be met. In this review we provide an overview of the available literature on the potential of VOCs as biomarkers for paediatric gastro-intestinal diseases. We discuss the available techniques to analyse VOCs and provide topics for VOC-related research which need to be addressed before VOC diagnostics can be implemented in daily clinical practice. © 2016 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,


Schuengel C.,VU University Amsterdam
Attachment and Human Development | Year: 2012

Teacher-child relationships may be a developmental issue in its own right, instead of an aspect of wider developmental issues such as attachment or adaptation to school. This paper discusses research findings on teacher-child relationships to argue that teacher-child relationships are important for carrying forward the experiences represented in the attachment behavioral system, although it is not clear whether teacher-child relationships themselves add to the attachment behavioral system or to the sociability behavioral system. The research demonstrates that attachment theory offers a useful template for understanding the role of teacher-child relationships in development. Listing teacher-child relationships among main developmental issues for today's children puts the spotlight on avenues for improving teacher-child relationships. © 2012 Copyright Taylor and Francis Group, LLC.


Rietveld P.,VU University Amsterdam
Environmental Innovation and Societal Transitions | Year: 2011

Policies to reduce congestion and energy use in transport have been rather ineffective in most countries during the last decades, partly due to rebound effects. Telework has been proposed as a promising way to reduce energy use in transport. Experiences with telework indicate that this is not as widespread as is often thought and that various rebound effects exist. A transition towards a large scale introduction of telework would involve the overcoming of various barriers by changes in the internal organization of firms, changes in the social responsibility of firms, and changes in life styles and activity patterns of workers. © 2010 Elsevier B.V. All rights reserved.


Berkhout F.,VU University Amsterdam
Global Environmental Change | Year: 2010

In this article I argue that the climate controversies of 2009 and 2010 should be seen as a contest about the boundaries of science; a contest which sociologists argue has long been important in establishing claims about the nature and authority of science. This boundary typically comes under pressure where science is asked to contribute to public policy. Three changes appear to have brought pressure on this boundary, and therefore on the authority of science, in the domain climate change: public scrutiny of practices in science, such as peer review; the intensification of climate politics, especially around the 2009 Copenhagen climate summit; and the opportunities provided by new media for dissident opinions to play a role in the international public discourse about climate change. These changes explain the intensity of the recent climate controversies. They seem to confront climate science and science generally with uncomfortable questions about its own procedures, about the status of scientific knowledge claims in the public realm and about the role of expertise. At the end of the article I speculate about how to reconstruct a more open and interactive boundary between science and public discourse as a basis for more reasoned debate about climate change. © 2010 Elsevier Ltd.


Krabbendam L.,VU University Amsterdam | Hooker C.I.,Harvard University | Aleman A.,University of Groningen
Schizophrenia Bulletin | Year: 2014

Epidemiological studies have suggested that the association between city upbringing and minority status with risk for schizophrenia can be explained by social mechanisms. Neuroimaging approaches hold promise for investigating this claim. Recent studies have shown that in healthy individuals, city upbringing and minority status are associated with increased activity in brain circuits involved in emotion regulation during social evaluative processing. These findings support the hypothesis that changes in the ability to regulate social stress contribute to the mechanism of risk. This is in accordance with a body of evidence demonstrating the sensitivity of the human brain to social stress, based on observational studies investigating the neurological sequelae of interpersonal trauma and experimental studies manipulating exposure to interpersonal distress. In this report, we summarize these initial findings, discuss methodological and conceptual challenges of pursuing this line of inquiry in schizophrenia, and suggest an outline for future research. © 2014 The Author. Published by Oxford University Press.


Vast areas of (sub)arctic tundra are dominated by the ericoid dwarf shrub Empetrum hermaphroditum. Recent experimental and observational data have shown that Empetrum can be damaged heavily by recurrent extreme winter warming. In addition, summer warming leads to increased soil N availability in tundra ecosystems. In a 7-year experiment, I investigated the recovery of subarctic Empetrum-dominated tundra vegetation using a factorial combination of various degrees of aboveground Empetrum removal (simulating the damaging effects of extreme winter warming) and N addition (simulating one of the effects of summer warming). After 7 years no new species had established in the plots. The growth of planted Betula nana seedlings was stimulated by Empetrum removal and reduced by N addition. This Empetrum-dominated tundra ecosystem was resilient against severe disturbances. Only when Empetrum was 100% removed did it fail to recover, and only in combination with high N supply the subordinate species (notably Eriophorum vaginatum and Rubus chamaemorus, a graminoid and a forb) could benefit. In the 50% removal treatment Empetrum recovered in 7 years when no N was supplied and the cover of the subordinate species did not change. However, when N was added Empetrum recovered faster (in 4 years) and the subordinates decreased. When Empetrum was not removed and N was added, Empetrum even increased in abundance at the expense of the subordinate species. Thus, profound changes in tundra ecosystems can only be expected when Empetrum is very heavily damaged as a result of recurrent extreme winter warming and when soil N availability is increased as a result of summer warming. These changes in species composition upon extreme disturbance events may lead to a wide variety of ecosystem feedbacks and cascade processes as this tundra system is relatively species-poor, and can be hypothesized to have low functional redundancy. © 2009 Blackwell Publishing Ltd.


Berkhout M.J.,VU University Amsterdam
Journal of Hand Surgery: European Volume | Year: 2010

Radioscapholunate arthrodesis is a salvage procedure indicated for osteoarthritis of the radiocarpal joint involving the lunate facet of the radius. This cadaver study examines changes in wrist motion resulting from radioscapholunate arthrodesis, and the effects of surgical techniques to improve the range of motion. Simulated radioscapholunate arthrodesis, distal scaphoidectomy and triquetrectomy were carried out sequentially on six cadaver forearms and measurements (maximum flexion/extension and radial/ulnar deviation) were taken in the intact situation and after each surgical step using a magnetic tracking device. Radioscapholunate arthrodesis diminishes the amplitudes of movements of the wrist in all directions, but range of motion in the radioscapholunate fused wrist improves after scaphoidectomy and improves further after triquetrectomy (88% of original flexion/extension and 98% of original radial/ulnar deviation). Radioscapholunate arthrodesis causes a significant change in kinematics between the hamate and the triquetrum in flexion/extension. © 2010 The Author(s).


Manfredini D.,University of Padua | Lobbezoo F.,VU University Amsterdam
Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology | Year: 2010

Objectives: The present paper aims to systematically review the literature on the temporomandibular disorders (TMD)-bruxism relationship published from 1998 to 2008. Study design: A systematic search in the National Library of Medicine's PubMed database was performed to identify all studies on humans assessing the relationship between TMD symptoms and bruxism diagnosed with any different approach. The selected articles were assessed independently by the 2 authors according to a structured reading of articles format (PICO). Results: A total of 46 articles were included for discussion in the review and grouped into questionnaire/self-report (n = 21), clinical assessment (n = 7), experimental (n = 7), tooth wear (n = 5), polysomnographic (n = 4), or electromyographic (n = 2) studies. In several studies, the level of evidence was negatively influenced by a low level of specificity for the assessment of the bruxism-TMD relationship, because of the low prevalence of severe TMD patients in the studied samples and because of the use of self-report diagnosis of bruxism with some potential diagnostic bias. Conclusions: Investigations based on self-report or clinical bruxism diagnosis showed a positive association with TMD pain, but they are characterized by some potential bias and confounders at the diagnostic level (eg, pain as a criterion for bruxism diagnosis). Studies based on more quantitative and specific methods to diagnose bruxism showed much lower association with TMD symptoms. Anterior tooth wear was not found to be a major risk factor for TMD. Experimental sustained jaw clenching may provoke acute muscle tenderness, but it is not analogous to myogenous TMD pain, so such studies may not help clarify the clinical relationship between bruxism and TMD. © 2010 Mosby, Inc. All rights reserved.


de Groot P.W.J.,University of Castilla - La Mancha | Brandt B.W.,VU University Amsterdam
Fungal Genetics and Biology | Year: 2012

Surface proteins, such as those located in the cell wall of fungi, play an important role in the interaction with the surrounding environment. For instance, they mediate primary host-pathogen interactions and are crucial to the establishment of biofilms and fungal infections. Surface localization of proteins is determined by specific sequence features and can be predicted by combining different freely available web servers. However, user-friendly tools that allow rapid analysis of large datasets (whole proteomes or larger) in subsequent analyses were not yet available. Here, we present the web tool ProFASTA, which integrates multiple tools for rapid scanning of protein sequence properties in large datasets and returns sequences in FASTA format. ProFASTA also allows for pipeline filtering of proteins with cell surface characteristics by analysis of the output created with SignalP, TMHMM and big-PI. In addition, it provides keyword, iso-electric point, composition and pattern scanning. Furthermore, ProFASTA contains all fungal protein sequences present in the NCBI Protein database. As the full fungal NCBI Taxonomy is included, sequence subsets can be selected by supplying a taxon name. The usefulness of ProFASTA is demonstrated here with a few examples; in the recent past, ProFASTA has already been applied successfully to the annotation of covalently-bound fungal wall proteins as part of community-wide genome annotation programs. ProFASTA is available at: http://www.bioinformatics.nl/tools/profasta/. © 2012 Elsevier Inc.


A lack of empirical evidence impedes assessment of the spatial and temporal extent of critical conditions for recurring high turbidity in large wind-exposed shallow lakes. Here spatiotemporal variation in total suspended matter (TSM) concentration was captured by processing 30 Envisat Medium Resolution Imaging Spectrometer (MERIS) images of a shallow lake (Markermeer) with a spectral matching algorithm. The TSM maps showed elevated downwind concentrations for moderate winds (from 4 to 9 m s -1), which occur 68% of the time. Regressions confirmed the relationship between hourly averaged wind speed and TSM. To explore critical conditions for resuspension, wind speed, linear fetch, and water depth were combined in a spatial model based on simplified linear wave equations. Remotely sensed TSM patterns matched predicted areas of resuspension from these wave equations. On average, over 70% of cells were true positive or negative, with elevated TSM matching the predicted resuspending bottom area and background TSM matching no resuspension. Images acquired during moderate winds register local resuspension. This implies that under these conditions, a critical shear stress threshold for resuspension is passed, followed by upward mixing over the few meters of water column. Images acquired during low wind speeds (≤3 m s -1) either do not show a TSM pattern or display settling because it takes several hours of low wind before all particles are removed from the visible top layer. Because of the good spatial matching, the resuspension model can also be used for future verification of the retrieval capacity of the spectral matching algorithm.


Since the end of the Cold War, two parallel developments took place in global governance: fragmentation in social/environmental legislations across countries, and an increasing uniformity (or 'globalisation') of economic/financial legislations. In the liberal democratic context of global governance, both of these developments are embodied in partnerships for sustainable development. Studying these partnerships in the context of private environmental governance and tracing the origin of the concept in business and law, can reveal the implications of 'privatisation of governance' on sovereignty, authority, and global governance. Focusing on partnerships in the United Nations context, this paper examines the private environmental governance institutions in their historical economic context. © 2012 The White Horse Press.


Pattberg P.,VU University Amsterdam
Environment and Planning C: Government and Policy | Year: 2012

Climate change is widely acknowledged as a key business risk. Companies around the globe are taking action to mitigate their carbon emissions, develop climate-friendly products and services, and prepare for the negative impacts of climate change for their operations. Financial investors, on their part, are becoming more concerned about business responses to climate change and begin to demand concrete risk management strategies. In this context an increasing number of private initiatives are seeking to change business behaviour in a more sustainable direction. Key instruments used are governance by disclosure. This paper explores the agency of nonstate actors in manufacturing climate change into a key business risk, a development that enabled the use of disclosure-based governance mechanisms in global climate politics. © 2012 Pion and its Licensors.


Garcia-Santos G.,VU University Amsterdam
Journal of Hydrology | Year: 2012

Laurel forests in the Canary Islands (Spain) survive where humid conditions are guaranteed throughout the year. On peaks and ridges, laurel forest gives way to mixed evergreen tree-heath/beech forest of low stature (" fayal-brezal" ) that has to cope with rapidly changing light, temperature and humidity conditions due to the occurrence of intermittent sunny and foggy periods during the mostly rainless summer. These conditions are poorly understood and there is a lack of information on the interrelations between tree physiological behavior and ambient climatic and soil water conditions in fayal-brezal. In this study sap velocities were measured for 2years in two dominant tree species (Myrica faya and Erica arborea) in a ridge-top forest in the National Park of Garajonay on the island of La Gomera. The resulted average daily stand transpiration was 1.2±0.12mm (416mmyear -1). However, the narrow-leaved E. arborea exhibited higher sap velocities than the broad-leaved M. faya. Also, sap velocity increased with stem diameter in E. arborea but not in M. faya. Nocturnal flow activity was observed throughout the year and reflected ambient conditions on some occasions, and stem water storage recovery on others. Strong stomatal control in response to increases in vapor pressure deficit was seen in both species. Fog reduced sap velocity from 10% up to 90% but no consistent pattern was found. Soil water uptake during the dry summer (246mm) was much larger than atmospheric water inputs (41mm, rain and fog). The low moisture levels in the top 0.3m of the soil had limited influence on transpiration rates indicating that vegetation must have had access to moisture in deeper layers. © 2011 Elsevier B.V.


Bronkhorst A.W.,TNO | Bronkhorst A.W.,VU University Amsterdam
Attention, Perception, and Psychophysics | Year: 2015

How do we recognize what one person is saying when others are speaking at the same time? This review summarizes widespread research in psychoacoustics, auditory scene analysis, and attention, all dealing with early processing and selection of speech, which has been stimulated by this question. Important effects occurring at the peripheral and brainstem levels are mutual masking of sounds and “unmasking” resulting from binaural listening. Psychoacoustic models have been developed that can predict these effects accurately, albeit using computational approaches rather than approximations of neural processing. Grouping—the segregation and streaming of sounds—represents a subsequent processing stage that interacts closely with attention. Sounds can be easily grouped—and subsequently selected—using primitive features such as spatial location and fundamental frequency. More complex processing is required when lexical, syntactic, or semantic information is used. Whereas it is now clear that such processing can take place preattentively, there also is evidence that the processing depth depends on the task-relevancy of the sound. This is consistent with the presence of a feedback loop in attentional control, triggering enhancement of to-be-selected input. Despite recent progress, there are still many unresolved issues: there is a need for integrative models that are neurophysiologically plausible, for research into grouping based on other than spatial or voice-related cues, for studies explicitly addressing endogenous and exogenous attention, for an explanation of the remarkable sluggishness of attention focused on dynamically changing sounds, and for research elucidating the distinction between binaural speech perception and sound localization. © 2015, The Author(s).


Steenweg M.E.,VU University Amsterdam
Archives of neurology | Year: 2012

To describe a novel pattern of magnetic resonance imaging (MRI) abnormalities as well as the associated clinical and laboratory findings. The MRIs of more than 3000 patients with an unclassified leukoencephalopathy were systematically reviewed.Clinical and laboratory data were retrospectively collected.Setting: University hospital. Seven patients (3 male) shared similar MRI abnormalities and clinical features. Pattern of MRI abnormalities and clinical and laboratory findings. The MRIs showed signal abnormalities of the deep cerebral white matter, corpus callosum, thalamus, basal ganglia,brainstem, and cerebellar white matter between the ages of 9 months and 2 years. On follow-up, abnormalities gradually improved. Clinical regression occurred in the second half-year of life with spasticity and loss of milestones.From the second year on, clinical improvement occurred.So far, no second episode of regression has happened.Lactate levels were elevated during clinical regression. These patients represent a single novel leukoencephalopathy,probably caused by a mitochondrial defect.


Peters E.J.,VU University Amsterdam
The Medical clinics of North America | Year: 2013

Foot infections are common in persons with diabetes mellitus. Most diabetic foot infections occur in a foot ulcer, which serves as a point of entry for pathogens. Unchecked, infection can spread contiguously to involve underlying tissues, including bone. A diabetic foot infection is often the pivotal event leading to lower extremity amputation, which account for about 60% of all amputations in developed countries. Given the crucial role infections play in the cascade toward amputation, all clinicians who see diabetic patients should have at least a basic understanding of how to diagnose and treat this problem. Copyright © 2013 Elsevier Inc. All rights reserved.


De Leeuw S.,VU University Amsterdam | Van Den Berg J.P.,Jeroen Van Den Berg Consulting
Journal of Operations Management | Year: 2011

It is generally believed that companies applying performance management practices outperform those that do not measure and manage their performance. Studies examining the link between performance management and performance improvement implicitly assume that performance management affects behavior of individuals in an organization, which then facilitates the achievement of organizational goals. This study takes a step towards understanding this implicit assumption. We investigate how performance management practices relate to improvement in performance by influencing behavior of individuals. We focus on operational performance management, i.e. the definition and use of performance measures on the shopfloor in production and distribution. We use a survey among 102 companies to identify the relations between performance management practices, shopfloor behavior and improvement in performance. We identified three independent clusters of operator behavior that positively correlate with performance improvement: "Understanding", "Motivation" and "Focus on Improvement". We show that 17 out of the 20 performance management practices found in literature have a significant and positive relation with one or more clusters of operator behavior. We furthermore found that there is a positive correlation between the number of performance management practices applied and performance improvement, suggesting that it is not only which practices are applied but also how many. Recommendations emerging from this study enable managers to identify which behavioral changes are desired to improve performance and to select those performance management practices that positively influence the desired behavior. © 2011 Elsevier B.V. All rights reserved.


Ten Kate L.P.,VU University Amsterdam
Journal of Community Genetics | Year: 2012

In this paper I will review different aspects of genetic risk in the context of preconception care. I restrict myself to the knowledge of risk which is relevant for care and/or enables reproductive choice. The paper deals with chromosomes, genes and the genetic classification of diseases, and it explains why Mendelian disorders frequently do not show the expected pattern of occurrence in families. Factors that amplify genetic risk are also discussed. Of the two methods of genetic risk assessment-history taking and genetic screening-the former method is examined to some extent, and the consequences of an inadequate family history are illustrated in a case report. The paper ends with a review of the sparse literature available on the frequency of a positive family history and an outline of the challenges and rewards faced by professionals when confronted with a positive history. © The Author(s) 2011.


Verhagen E.,VU University Amsterdam | Verhagen E.,University of Ballarat | Bolling C.,Minas Tenis Clube
British Journal of Sports Medicine | Year: 2015

Online technology dominates our era and eHealth has become a reality for sports clinicians and researchers. Contemporary online platforms enable self-monitoring and provide tailored feedback to the different stakeholders who play a role in the health and care of athletes. Innovations such as digital monitoring, mobile applications and connected hardware provide the critical tools to solve current enigmas in sports medicine research, and to streamline and facilitate injury prevention, management and rehabilitation. eHealth is not an emerging future of sports medicine-the technology to move our field forward in terms of research and practice is already available. This Analysis is based on Evert Verhagen's keynote presentation at the IOC World Conference on Injury and Illness Prevention in Sport (Monaco, 12 April 2014). It outlines the use of eHealth in research, implementation and practice, and provides an overview of possibilities and opportunities that existing and emerging eHealth solutions provide for sports and exercise medicine and physiotherapy.


Petzold A.,VU University Amsterdam | Petzold A.,University College London
Journal of Neuroimmunology | Year: 2013

The diagnosis of multiple sclerosis is based on dissemination in time and space. Before 2010 lack of evidence for dissemination in space could be substituted by a paraclinical test, cerebrospinal fluid (CSF) oligoclonal bands (OCBs). The present meta-analysis (13,467 patients) shows that the diagnostic specificity of OCB drops from 94% to 61% if inflammatory etiologies are considered. Importantly, this was not caused by poor laboratory practice. This review on CSF OCB further illustrates the conceptional problem of substituting dissemination in space with a biomarker. The potential prognostic value of intrathecal OCB will need to be tested prospectively. © 2013 Elsevier B.V.


Gooren L.J.,VU University Amsterdam
Asian Journal of Andrology | Year: 2010

Many signs of aging, such as sexual dysfunction, visceral obesity, impaired bone and muscle strength, bear a close resemblance to features of hypogonadism in younger men. The statistical decline of serum testosterone in aging men is solidly documented. It has been presumed that the above features of aging are related to the concurrent decline of androgens, and that correction of the lower-than-normal circulating levels of testosterone will lead to improvement of symptoms of aging. But in essence, the pivotal question whether the age-related decline of testosterone must be viewed as hypogonadism, in the best case reversed by testosterone treatment, has not been definitively resolved. Studies in elderly men with lower-than-normal testosterone report improvement of features of the metabolic syndrome, bone mineral density, of mood and of sexual functioning. But as yet there is no definitive proof of the beneficial effects of restoring testosterone levels to normal in elderly men on clinical parameters. Few of these studies meet as yet rigorous standards of scientific enquiry: double-blind, placebo-controlled design of the study. The above applies also to the assessment of safety of testosterone administration to elderly men. There is so far no convincing evidence that testosterone is a main factor in the development of prostate cancer in elderly men and guidelines for monitoring the development of prostate disease have been developed. It is of note that there are presently no long-term safety data with regard to the prostate. Polycythemia is another potential complication of testosterone treatment. It is dose dependent and can be managed with dose adjustment. © 2010 AJA, SIMM & SJTU All rights reserved.


Baumeister R.F.,Florida State University | Baumeister R.F.,King Abdulaziz University | Baumeister R.F.,VU University Amsterdam
Neuropsychologia | Year: 2014

Inhibition is a major form of self-regulation. As such, it depends on self-awareness and comparing oneself to standards and is also susceptible to fluctuations in willpower resources. Ego depletion is the state of reduced willpower caused by prior exertion of self-control. Ego depletion undermines inhibition both because restraints are weaker and because urges are felt more intensely than usual. Conscious inhibition of desires is a pervasive feature of everyday life and may be a requirement of life in civilized, cultural society, and in that sense it goes to the evolved core of human nature. Intentional inhibition not only restrains antisocial impulses but can also facilitate optimal performance, such as during test taking. Self-regulation and ego depletion- may also affect less intentional forms of inhibition, even chronic tendencies to inhibit. Broadly stated, inhibition is necessary for human social life and nearly all societies encourage and enforce it. © 2014 Elsevier Ltd.


Van Der Heijden M.G.A.,ART Agroscope Reckenholz Tanikon | Van Der Heijden M.G.A.,VU University Amsterdam
Ecology | Year: 2010

Nutrient loss from ecosystems is among the top environmental threats to ecosystems worldwide, leading to reduced plant productivity in nutrient-poor ecosystems and eutrophication of surface water near nutrient-rich ecosystems. Hence, it is of pivotal importance to understand which factors influence nutrient loss. Here it is demonstrated that arbuscular mycorrhizal (AM) fungi, widespread soil fungi that form mutualistic relationships with the majority of land plants, reduce nutrient loss from grassland microcosms during raininduced leaching events. Grassland microcosms with AM fungi lost 60% less phosphorus and 7.5% less ammonium compared to control microcosms without AM fungi. Similar results were obtained for microcosms planted with each of three different grass species. In contrast, nitrate leaching was not affected by AM. fungi but depended on the amount of nutrients supplied to the microcosms. Moreover, fertilization of the microcosms reduced the abundance of AM fungi and their ability to reduce phosphorus leaching losses. Extrapolation of these results suggests that the disruption of the mycorrhizal symbiosis is one of the reasons for enhanced phosphorus loss from fertilized ecosystems. The microcosms contained a sandy soil, a soil type vulnerable to leaching losses. The reduction of phosphorus leaching by AM fungi may, therefore, represent an upper limit. Advantages and limitations of the experimental setup for assessing the impact of AM fungi on nutrient cycling are discussed. The results indicate that AM fungi contribute to ecosystem sustainability by promoting a closed phosphorus cycle and reducing phosphorus leaching losses. © 2010 by the Ecological Society of America.


Polman C.H.,VU University Amsterdam | Rudick R.A.,Cleveland Clinic
Neurology | Year: 2010

Background: The Multiple Sclerosis Functional Composite (MSFC) provides a focused and sensi-tive evaluation of disability in patients with multiple sclerosis (MS) that may be more responsive to change than that provided by the Expanded Disability Status Scale. Expert Clinical Opinion: The MSFC is a 3-part quantitative instrument that measures arm, leg, and cognitive function with the 9-Hole Peg Test (arm/hand dexterity), the Timed 25-Foot Walk (leg function), and the Paced Auditory Serial Addition Test (3-second version, PASAT3; cognition). The MSFC has excellent test-retest reliability. Construct validity was supported by expected differ-ences in scores between patients with primary or secondary progressive MS compared with relapsing-remitting MS. Concurrent validity was demonstrated by significant correlations with the Expanded Disability Status Scale, the Sickness Impact Profile, and the Short Form-36, partic-ularly on the physical components of the latter 2 scales. MSFC scores also correlate with MRI changes. Limitations of the MSFC include practice effects with the PASAT and to a lesser extent the 9-Hole Peg Test, variations in the reference populations used to calculate Z-scores, and the lack of an accepted definition of a clinically meaningful change. Future Directions: Future research should be directed at adding a test that measures visual func-tion (e.g., contrast acuity), at replacing the PASAT by a cognition test that has better measurement characteristics, and at developing methods to better understand the clinical relevance of changes in MSFC scores. Copyright © 2010 by AAN Enterprises, Inc. All rights reserved.


Kaspers G.,VU University Amsterdam
British Journal of Haematology | Year: 2014

The prognosis of paediatric acute myeloid leukaemia (AML) has improved significantly over the recent decades, but still about one-third of patients relapse. These patients have a relatively poor prognosis, with a probability of long-term survival from relapse of about 35%. This can only be achieved with very intensive chemotherapy and, usually, allogeneic stem cell transplantation, leading to very significant toxicity and even treatment-related mortality. Major improvements in the treatment of paediatric relapsed AML thus are required still, and several possibilities are discussed. In case of a suspected relapse, a comprehensive diagnostic work-up has to be undertaken, because significant changes in the biological features of the AML cells may have occurred between initial diagnosis and relapse. This review discusses many practical issues that one encounters in the treatment of children with relapsed AML. It will also be of interest for those involved in translational research in AML. © 2014 John Wiley & Sons Ltd.


Fuchs R.,Wageningen University | Herold M.,Wageningen University | Verburg P.H.,VU University Amsterdam | Clevers J.G.P.W.,Wageningen University
Biogeosciences | Year: 2013

Human-induced land use changes are nowadays the second largest contributor to atmospheric carbon dioxide after fossil fuel combustion. Existing historic land change reconstructions on the European scale do not sufficiently meet the requirements of greenhouse gas (GHG) and climate assessments, due to insufficient spatial and thematic detail and the consideration of various land change types. This paper investigates if the combination of different data sources, more detailed modelling techniques, and the integration of land conversion types allow us to create accurate, high-resolution historic land change data for Europe suited for the needs of GHG and climate assessments. We validated our reconstruction with historic aerial photographs from 1950 and 1990 for 73 sample sites across Europe and compared it with other land reconstructions like Klein Goldewijk et al. (2010, 2011), Ramankutty and Foley (1999), Pongratz et al. (2008) and Hurtt et al. (2006). The results indicate that almost 700 000 km2 (15.5 %) of land cover in Europe has changed over the period 1950-2010, an area similar to France. In Southern Europe the relative amount was almost 3.5% higher than average (19 %). Based on the results the specific types of conversion, hot-spots of change and their relation to political decisions and socio-economic transitions were studied. The analysis indicates that the main drivers of land change over the studied period were urbanization, the reforestation program resulting from the timber shortage after the Second World War, the fall of the Iron Curtain, the Common Agricultural Policy and accompanying afforestation actions of the EU. Compared to existing land cover reconstructions, the new method considers the harmonization of different datasets by achieving a high spatial resolution and regional detail with a full coverage of different land categories. These characteristics allow the data to be used to support and improve ongoing GHG inventories and climate research. © Author(s) 2013. CC Attribution 3.0 License.


Rabinovich G.A.,CONICET | Rabinovich G.A.,University of Buenos Aires | van Kooyk Y.,VU University Amsterdam | Cobb B.A.,Case Western Reserve University
Annals of the New York Academy of Sciences | Year: 2012

Unlike their protein "roommates" and their nucleic acid "cousins," carbohydrates remain an enigmatic arm of biology. The central reason for the difficulty in fully understanding how carbohydrate structure and biological function are tied is the nontemplate nature of their synthesis and the resulting heterogeneity. The goal of this collection of expert reviews is to highlight what is known about how carbohydrates and their binding partners-the microbial (non-self), tumor (altered-self), and host (self)-cooperate within the immune system, while also identifying areas of opportunity to those willing to take up the challenge of understanding more about how carbohydrates influence immune responses. In the end, these reviews will serve as specific examples of how carbohydrates are as integral to biology as are proteins, nucleic acids, and lipids. Here, we attempt to summarize general concepts on glycans and glycan-binding proteins (mainly C-type lectins, siglecs, and galectins) and their contributions to the biology of immune responses in physiologic and pathologic settings. © 2012 New York Academy of Sciences.


van de Grift T.C.,VU University Amsterdam
Academic Medicine | Year: 2016

PROBLEM: Grappling with complex structural health care issues requires medical professionals to have training in skills and knowledge that go beyond the basic and clinical sciences. It is also crucial for health care professionals to be able to work collaboratively. However, medical education has only limitedly institutionalized the teaching of these skills. APPROACH: In fall 2014, a one-semester crossover course called Hacking Healthcare was developed by the University of Amsterdam in cooperation with the Gerrit Rietveld Academie of Fine Arts and six health care institutions in the greater Amsterdam area. The course comprised one or two weekly three-hour evening sessions consisting of a lecture, workshop, and group work. It was structured using the three stages of the design thinking process—inspiration, ideation, and implementation. Twenty-seven medicine, psychology, other science disciplines, and art students participated, working in interdisciplinary groups on an assigned case study. OUTCOMES: The course yielded both unconventional and holistic key insights and a wide range of tangible outcomes, which were also considered to be relevant by the patient. Among university (i.e., nonart) students (n = 14), the average overall score of the course was 8.5 out of 10, with 10 being the highest rating. Aspects of the course that were mentioned as positive points were the activating teaching environment, academic development, and development of collaboration skills and creative capabilities. NEXT STEPS: This approach could be applied in other fields, such as medical education on a larger scale, clinical practice, and the design of scientific research. © 2016 by the Association of American Medical Colleges


Rhebergen D.,VU University Amsterdam | Graham R.,University of Sydney
Current Opinion in Psychiatry | Year: 2014

PURPOSE OF REVIEW: Dysthymic disorder and other chronic depressive disorders have recently been merged in DSM-5 into a 'persistent depressive disorder' category. As its introduction in DSM-III, the validity of dysthymic disorder has long been challenged, posing concerns regarding the validity of its successor - persistent depressive disorder. This review aims to present recent findings regarding the validity and utility of dysthymic disorder. RECENT FINDINGS: Several recent studies raise questions regarding the validity of dysthymic disorder, namely, results indicating a significant overlap between dysthymic disorder and other mood and/or anxiety disorders, failure of such a diagnosis to predict illness outcome and the lack of any validation strategy identifying that it is a depressive entity or subtype. SUMMARY: Research findings indicate that dysthymic disorder is a heterogeneous diagnosis encompassing many different depressive (and anxiety or personality weighted) conditions, and without clear evidence of its validity as a diagnostic entity. As dysthymic disorder is a key component of DSM-defined persistent depressive disorder - the latter is at similar risk of providing a heterogeneous domain diagnosis, and thus limiting identification of specific causative factors and preferential treatment modality. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Min R.,University of Bern | Di Marzo V.,National Research Council Italy | Mansvelder H.D.,VU University Amsterdam
Neuroscientist | Year: 2010

Hippocampal depolarization-induced suppression of inhibition (DSI) is a robust form of short-term synaptic plasticity. DSI is mediated by endocannabinoid signaling. Since this discovery, pinning down the endogenous cannabinoid receptor ligand that mediates DSI has been problematic. Blocking degradation of the endocannabinoid 2-arachidonoyl glycerol (2-AG) lengthens DSI, which seems to indicate that 2-AG mediates DSI. In contrast, pharmacological inhibition of the 2-AG-synthesizing enzyme diacylglycerol lipase (DAGL) has yielded conflicting results: DAGL inhibitors often fail to block hippocampal DSI. Recently, 2 studies seem to have cornered this problem using DAGL knockout mice. Hippocampal DSI is absent in DAGL-α knockout mice, pointing to a key role for 2-AG in DSI. However, these studies do not reconcile the discrepancy with pharmacological experiments. Here, we argue that the seeming contradiction between results from pharmacological and genetic approaches may be explained in several ways. We suggest that the contradiction may be resolved by taking a different perspective on endocannabinoid signaling: in some forms of endocannabinoid-mediated signaling endocannabinoids might not be necessarily produced "on demand" but presynthesized and stored until needed. © The Author(s) 2010.


Bakker S.T.,Netherlands Cancer Institute | De Winter J.P.,VU University Amsterdam | Te Riele H.,Netherlands Cancer Institute
DMM Disease Models and Mechanisms | Year: 2013

Fanconi anaemia (FA) is a rare autosomal recessive or X-linked inherited disease characterised by an increased incidence of bone marrow failure (BMF), haematological malignancies and solid tumours. Cells from individuals with FA show a pronounced sensitivity to DNA interstrand crosslink (ICL)-inducing agents, which manifests as G2-M arrest, chromosomal aberrations and reduced cellular survival. To date, mutations in at least 15 different genes have been identified that cause FA; the products of all of these genes are thought to function together in the FA pathway, which is essential for ICL repair. Rapidly following the discovery of FA genes, mutant mice were generated to study the disease and the affected pathway. These mutant mice all show the characteristic cellular ICL-inducing agent sensitivity, but only partially recapitulate the developmental abnormalities, anaemia and cancer predisposition seen in individuals with FA. Therefore, the usefulness of modelling FA in mice has been questioned. In this Review, we argue that such scepticism is unjustified. We outline that haematopoietic defects and cancer predisposition are manifestations of FA gene defects in mice, albeit only in certain genetic backgrounds and under certain conditions. Most importantly, recent work has shown that developmental defects in FA mice also arise with concomitant inactivation of acetaldehyde metabolism, giving a strong clue about the nature of the endogenous lesion that must be repaired by the functional FA pathway. This body of work provides an excellent example of a paradox in FA research: that the dissimilarity, rather than the similarity, between mice and humans can provide insight into human disease. We expect that further study of mouse models of FA will help to uncover the mechanistic background of FA, ultimately leading to better treatment options for the disease.


Nurmohamed M.T.,VU University Amsterdam | Heslinga M.,Amsterdam Rheumatology and Immunology Center | Kitas G.D.,Dudley Group NHS Foundation Trust
Nature Reviews Rheumatology | Year: 2015

Patients with rheumatoid arthritis (RA) and other inflammatory joint diseases (IJDs) have an increased risk of premature death compared with the general population, mainly because of the risk of cardiovascular disease, which is similar in patients with RA and in those with diabetes mellitus. Pathogenic mechanisms and clinical expression of cardiovascular comorbidities vary greatly between different rheumatic diseases, but atherosclerosis seems to be associated with all IJDs. Traditional risk factors such as age, gender, dyslipidaemia, hypertension, smoking, obesity and diabetes mellitus, together with inflammation, are the main contributors to the increased cardiovascular risk in patients with IJDs. Although cardiovascular risk assessment should be part of routine care in such patients, no disease-specific models are currently available for this purpose. The main pillars of cardiovascular risk reduction are pharmacological and nonpharmacological management of cardiovascular risk factors, as well as tight control of disease activity. © 2015 Macmillan Publishers Limited.


Sitters G.,VU University Amsterdam
Nature Methods | Year: 2014

Force spectroscopy has become an indispensable tool to unravel the structural and mechanochemical properties of biomolecules. Here we extend the force spectroscopy toolbox with an acoustic manipulation device that can exert forces from subpiconewtons to hundreds of piconewtons on thousands of biomolecules in parallel, with submillisecond response time and inherent stability. This method can be readily integrated in lab-on-a-chip devices, allowing for cost-effective and massively parallel applications. © 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.


Kearney M.R.,University of Melbourne | Simpson S.J.,University of Sydney | Raubenheimer D.,Massey University | Kooijman S.A.L.M.,VU University Amsterdam
Functional Ecology | Year: 2013

Models of the regulatory behaviour of organisms are fundamental to a strong physiologically-based understanding of species' responses to global environmental change. Biophysical models of heat and water exchange in organisms (biophysical ecology) and nutritionally-explicit models for understanding feeding behaviour and its fitness consequences (the Geometric Framework of nutrition, GF) are providing such an underpinning. However, temperature, water and nutrition interact in fundamental ways in influencing the responses of the organism to their environment, and a priority is to develop an integrated approach for conceptualising and measuring these interactions. Ideally, such an approach would be based on a thermodynamically-formalized energy and mass budgeting approach that is sparsely parameterised and sufficiently general to apply across a range of situations and organisms. Here we illustrate how mass-balance aspects of Dynamic Energy Budget theory can be applied to obtain first-principles estimates of fluxes of O2, CO2, H2O and nitrogenous waste. Then, using an herbivorous lizard (Egernia cunninghami) as a case study, we demonstrate how these estimates can be integrated with heat/water exchange models and environmental data to provide a holistic understanding of how foraging strategy, food availability, habitat and weather interact with heat, water and nutrient/energy budgets across the life-cycle. The analysis shows the potential importance of the water balance in affecting the energy budgets of ' dry skinned' ectotherms, especially early in ontogeny, and highlights a significant gap in our knowledge of the physiological and behavioural traits that affect water balance when compared with our knowledge of thermal traits. In general, the modelling approach we describe can provide the thermodynamically-constrained stage on which other evolutionary and ecological interactions play out; the 'thermodynamic niche'. This in turn provides a solid foundation from which to tackle key questions about organismal responses to environmental change. © 2012 British Ecological Society.


Kooijman S.A.L.M.,VU University Amsterdam | Lika K.,University of Crete
Journal of Sea Research | Year: 2014

The eco-physiology of taxa in an evolutionary context can best be studied by a comparison of parameter values of the energy budget that accounts for the inter-relationships of all endpoints of energy allocation. To this end, the parameters of the standard Dynamic Energy Budget (DEB) model have been estimated for 64 fish species from all 5 fish classes. The values are compared with those of the whole collection of over 300 species from most large animal phyla. The goodness of fit was very high, but the data were rather incomplete, compared with the energy balance for full life cycles. Metabolic acceleration, where maximum specific assimilation and energy conductance increase with length between birth and metabolic metamorphosis, seems to be confined, among fish, to some species of ray-finned fish and seems to have evolved independently several times in this taxon. We introduce a new altriciality index, i.e. the ratio of the maturity levels at puberty and birth, and conclude that ray-finned fish are more altricial, and cartilaginous fish are more precocial than typical animals. Fish allocate more to reproduction than typical animals. Parameter estimates show that 66% of the fish species considered invest less in reproduction than the value that would maximize the reproduction rate of fully grown individuals. By comparison, 85% of all the animal species in the collection do so. Consistent with theoretical expectations, allocation to reproduction and maturity at birth increase with cubed (ultimate structural) length, and reserve capacity with length for non-ray-finned fish, with the consequence that reproduction rate decreases with length. Ray-finned fish, however, have a maturity at birth and a reserve capacity almost independent of length, and a reproduction rate that increases with cubed length. Reserve capacity tends to increase with ultimate length for non-accelerating ray-finned fish, but not for accelerating species. Reproduction rate decreases inter-specifically with length in non-ray-finned fish, as expected, but increases with cubed length in ray-finned fish. This pattern follows naturally from the patterns of size at birth and reserve capacity and can be seen as adaptation to the predation of prey of ray-finned fish on their tiny neonates. Both the von Bertalanffy growth rate and the specific allocation to reproduction in fully grown adults correlate positively with specific somatic maintenance among fish species. These observations support the recently proposed waste-to-hurry hypothesis. Determinatesness increases in the sequence: fish, amphibians, reptiles, mammals and birds. © 2014 Elsevier B.V. All rights reserved.


Bobbert M.F.,VU University Amsterdam
Medicine and Science in Sports and Exercise | Year: 2014

PURPOSE: In the literature, substantial decreases in power output in jumping have been described for both unloading and loading, and these have been attributed to the intrinsic force-velocity-power relationship of muscle. The purpose of this study was to gain a solid understanding of how and why unloading and loading affect power output during jumping. METHODS: Vertical jumps were simulated with a model of the musculoskeletal system, consisting of four rigid segments actuated by six muscles. Muscle stimulation over time was optimized to ensure maximal performance in each loading condition. RESULTS: It was found that, in contrast to what is reported in the literature, unloading by an extra vertical force of -60% of body weight caused a small increase in the peak of the rate of change of the effective energy of the center of mass (dEeff/dt). Loading by an extra vertical force of +60% of body weight caused a decrease in peak dEeff/dt, but this decrease was much smaller than that described in the literature. The small variations in peak dEeff/dt among loading conditions in the simulated jumps were only in part due to the intrinsic force-velocity-power relationship of muscle. Why did the effects of unloading and loading in the simulation model deviate from effects reported in subjects? One possible explanation is that subjects tend to make a smaller countermovement when loaded; in the simulation model, making a smaller countermovement caused a major reduction in peak dEeff/dt. A second possible explanation is that subjects cannot quickly optimize their control and therefore produce submaximal power output in unfamiliar loading conditions. CONCLUSION: The effects of unloading and loading are due only in part to the intrinsic force-velocity-power relationship of muscle. © 2014 by the American College of Sports Medicine.


Oscillations in electrical activity are a characteristic feature of many brain networks and display a wide variety of temporal patterns. A network may express a single oscillation frequency, alternate between two or more distinct frequencies, or continually express multiple frequencies. In addition, oscillation amplitude may fluctuate over time. The origin of this complex repertoire of activity remains unclear. Different cortical layers often produce distinct oscillation frequencies. To investigate whether interactions between different networks could contribute to the variety of oscillation patterns, we created two model networks, one generating on its own a relatively slow frequency (20 Hz; slow network) and one generating a fast frequency (32 Hz; fast network). Taking either the slow or the fast network as source network projecting connections to the other, or target, network, we systematically investigated how type and strength of inter-network connections affected target network activity. For high inter-network connection strengths, we found that the slow network was more effective at completely imposing its rhythm on the fast network than the other way around. The strongest entrainment occurred when excitatory cells of the slow network projected to excitatory or inhibitory cells of the fast network. The fast network most strongly imposed its rhythm on the slow network when its excitatory cells projected to excitatory cells of the slow network. Interestingly, for lower inter-network connection strengths, multiple frequencies coexisted in the target network. Just as observed in rat prefrontal cortex, the target network could express multiple frequencies at the same time, alternate between two distinct oscillation frequencies, or express a single frequency with alternating episodes of high and low amplitude. Together, our results suggest that input from other oscillating networks may markedly alter a network's frequency spectrum and may partly be responsible for the rich repertoire of temporal oscillation patterns observed in the brain.


The progressing discovery of genetic variants associated with drug-related adverse events has raised expectations for pharmacogenetic tests to improve drug efficacy and safety. To further the use of pharmacogenetics in health care, tests with sufficient potential to improve efficacy and safety, as reflected by good clinical validity and population impact, need to be identified. The potential benefit of pharmacogenetic tests is often concluded from the strength of the association between the variant and the adverse event; measures of clinical validity are generally not reported. This paper describes measures of clinical validity and potential population health impact that can be calculated from association studies. We explain how these measures are influenced by the strength of the association and by the frequencies of the variant and the adverse event. The measures are illustrated using examples of testing for HLA-B*5701 associated with abacavir-induced hypersensitivity and SLCO1B1 c.521T>C (*5) associated with simvastatin-induced adverse events.The Pharmacogenomics Journal advance online publication, 10 May 2016; doi:10.1038/tpj.2016.34. © 2016 Macmillan Publishers Limited


Kooijman S.A.L.M.,VU University Amsterdam
Journal of Sea Research | Year: 2014

Acceleration of metabolism is defined as a long-term increase of respiration, that is faster than the typical trajectory during the life cycle of an individual, from embryo to adult. The Dynamic Energy Budget (DEB) model is used to quantify the typical trajectory. All DEB parameters were estimated for over 300 animal species from most large phyla and all chordate classes. The goodness of fit is generally excellent, including embryo development (embryo weight, respiration, amount of yolk). Although many species match predictions for metabolic rates, particular taxa, including all those with larval development, but also ones with less clear larval stages, deviated and have a lower metabolic rate as embryo, compared to late juvenile and adult stages: they accelerate their metabolism during the life cycle. Five different types of acceleration are identified, examples are given, and methods are presented to recognise these different types. Associated life history traits are discussed in an evolutionary and ecological context. Arguments are presented for why accelerating species have an extra slow start of metabolism and why parental care evolved in endotherms. © 2014 Elsevier B.V. All rights reserved.


Plomp H.N.,VU University Amsterdam
Occupational medicine (Oxford, England) | Year: 2010

The effectiveness of health care intervention depends heavily on the extent to which people trust the health care professionals with whom they come into contact. Therefore, to ensure effective health care, it is important to establish what factors influence patient perceptions of the trustworthiness of health care professionals. To explore the relation between trust and vulnerability in the occupational doctor-patient relationship by considering two opposing hypotheses on factors influencing perceptions of trustworthiness. An explorative, cross-sectional study design in which trust and vulnerability were measured quantitatively (questionnaire) as well as qualitatively (semi-structured interview) in a stratified sample (N = 68; response rate 24%). The 'urgency' or threat of vulnerability (current reported poor health, high workload and high absenteeism) was found to be important in explaining the relationship between trust and vulnerability. The first hypothesis of vulnerability leading to lower level trust appeared only to apply to patients with good health and low workload. Although trust levels were higher among patients with poor health and high workload, the second hypothesis (the more vulnerable, the higher the trust level) could not be confirmed for highly vulnerable patients because distrust was hard to overcome if physicians' independency, agency or expertise was questioned. Trust and the need for trust vary with the character and severity of ill health. Studies on trust in doctor-patient relationships are more worthwhile if they are directed at specific groups and situations.


Cohen C.I.,SUNY Downstate Medical Center | Meesters P.D.,VU University Amsterdam | Zhao J.,SUNY Downstate Medical Center
The Lancet Psychiatry | Year: 2015

Worldwide, in the past few decades, the demographics of older people (ie, people 55 years and over) with schizophrenia have changed completely with respect to absolute numbers of people affected, the proportion of all people with the disorder, life expectancy, and residential status. The ageing schizophrenia population has created vast health-care needs and their medical comorbidity contributes to higher mortality than in the general population. Proposals to classify schizophrenia into early-onset, late-onset, and very-late-onset subtypes now should be tempered by the recognition that comorbid medical and neurological disorders can contribute to psychotic symptoms in later life. The concept of outcome has become more nuanced with an appreciation that various outcomes can occur, largely independent of each other, that need different treatment approaches. Data show that schizophrenia in later life is not a stable end-state but one of fluctuation in symptoms and level of functioning, and show that pathways to improvement and recovery exist. Several novel non-pharmacological treatment strategies have been devised that can augment the clinical options used to address the specific needs of older adults with schizophrenia. © 2015 Elsevier Ltd.


De Koning J.J.,VU University Amsterdam
International Journal of Sports Physiology and Performance | Year: 2010

The quality of performance during international competitions such as the Olympic Games and various world championships is often judged by the number of world records attained. The simple fact that world records continue to improve is evidence that sports performance is progressing. Does this also mean that athletes are improving? Is the continual progression of world-record performances evidence that contemporary athletes are superior to the athletes who performed in the past? Technological developments may obscure insight into the athletic enhancement made by athletes over the years. This commentary tries to separate technological and athletic enhancement in the progression of world records by the use of a power balance model.Copyrighjt©Human Kinetics, Inc.


Millo D.,VU University Amsterdam
Biochemical Society Transactions | Year: 2012

Understanding the mechanism of ET (electron transfer) through electroactivemicrobial biofilms is a challenge in the field of fundamental and applied life sciences. To date, electrochemical techniques such as CV (cyclic voltammetry) have been applied successfully to study the ET process in intact microbial biofilms on electrodes, providing important insight into their redox properties. However, CV as such does not provide any structural information about the species involved in the redox process. This shortcoming may limit the understanding of the ET process in microbial biofilms. To overcome this restriction, spectroelectrochemical techniques have been designed consisting of a spectroscopic technique performed in combination with electrochemical methods on the same electrode sample. These analytical approaches allow in vivo measurements of microbial biofilms under physiologically relevant conditions and controlled applied potential. The present review describes these spectroelectrochemical methodologies and critically addresses their impact on the understanding of the ET through biofilms. ©The Authors Journal compilation ©2012 Biochemical Society.


Borlaug B.A.,Mayo Medical School | Paulus W.J.,VU University Amsterdam
European Heart Journal | Year: 2011

Half of patients with heart failure (HF) have a preserved left ventricular ejection fraction (HFpEF). Morbidity and mortality in HFpEF are similar to values observed in patients with HF and reduced EF, yet no effective treatment has been identified. While early research focused on the importance of diastolic dysfunction in the pathophysiology of HFpEF, recent studies have revealed that multiple non-diastolic abnormalities in cardiovascular function also contribute. Diagnosis of HFpEF is frequently challenging and relies upon careful clinical evaluation, echo-Doppler cardiography, and invasive haemodynamic assessment. In this review, the principal mechanisms, diagnostic approaches, and clinical trials are reviewed, along with a discussion of novel treatment strategies that are currently under investigation or hold promise for the future. © 2010 The Author.


Steenweg M.E.,VU University Amsterdam
Human mutation | Year: 2010

L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship. (c) 2010 Wiley-Liss, Inc.


van der Waal I.,VU University Amsterdam
Oral Oncology | Year: 2010

In spite of tremendous progress in the field of molecular biology there is yet no single marker that reliably predicts malignant transformation of a potentially malignant disorder of the oral mucosa. Therefore, it is recommended to excise or laser any oral of oropharyngeal leukoplakia/erythroplakia, if feasible, irrespective of the presence or absence of dysplasia. However, it is actually unknown whether such removal truly prevents the possible development of a squamous cell carcinoma. Therefore, lifelong follow-up is recommended at intervals of no more than 6 months. At present, oral lichen planus is more or less accepted as being a potentially malignant disorder. There are no means to prevent such event. The efficacy of follow-up of oral lichen planus is questionable. © 2010 Elsevier Ltd. All rights reserved.


Teunissen C.E.,VU University Amsterdam | Khalil M.,Medical University of Graz
Multiple Sclerosis Journal | Year: 2012

Neurodegeneration is the correlate of disease progression in multiple sclerosis (MS) and thus biological biomarkers that sensitively reflect this process are much needed. Neurofilament protein subunits are potential cerebrospinal fluid (CSF) biomarkers for disease progression in MS. We argue that the neurofilament light subunit can reflect acute axonal damage mediated by inflammatory mechanisms and can imply prognostic value for conversion from clinically isolated syndrome (CIS) to definite MS. The neurofilament heavy subunit may rather reflect chronic irreversible damage and has prognostic value for disease progression or disability. The neurofilament intermediate subunit has not yet been studied. Recent studies showing higher neurofilament light or heavy subunit levels to be altered upon treatment regimes indicate their potential clinical value in monitoring treatment or side effects. Future studies should be aimed at the optimisation, standardisation and interlaboratory implementation of the assays and address the predictive value of these biomarkers. © The Author(s) 2012.


van der Waal I.,VU University Amsterdam
Medicina Oral, Patologia Oral y Cirugia Bucal | Year: 2013

Oral cancer makes up 1%-2% of all cancers that may arise in the body. The majority of oral cancers consists of squamous cell carcinomas. Oral cancer carries a considerable mortality rate, being mainly dependent on the stage of the disease at admission. Worldwide some 50% of the patients with oral cancer present with advanced disease. There are several ways of trying to diagnose oral cancer in a lower tumor stage, being 1) mass screening or screening in selected patients, 2) reduction of patients' delay, and 3) reduction of doctors' delay. Oral cancer population-based screening ("mass screening") programs do not meet the guidelines for a successful outcome. There may be some benefit when focusing on high-risk groups, such as heavy smokers and heavy drinkers. Reported reasons for patients' delay range from fear of a diagnosis of cancer, limited accessibility of primary health care, to unawareness of the possibility of malignant oral diseases. Apparently, information campaigns in news programs and TV have little effect on patients' delay. Mouth self-examination may have some value in reducing patients' delay. Doctors' delay includes dentists' delay and diagnostic delay caused by other medical and dental health care professionals. Doctors' delay may vary from almost zero days upto more than six months. Usually, morbidity of cancer treatment is measured by quality of life (QoL) questionnaires. In the past decades this topic has drawn a lot of attention worldwide. It is a challenge to decrease the morbidity that is associated with the various treatment modalities that are used in oral cancer without substantially compromising the survival rate. Smoking cessation contributes to reducing the risk of oral cancers, with a 50% reduction in risk within five years. Indeed, risk factor reduction seems to be the most effective tool in an attempt to decrease the morbidity and mortality of oral cancer. © Medicina Oral S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946.


Gooren L.,Emeritus Medical Center | Lips P.,VU University Amsterdam
Journal of Sexual Medicine | Year: 2014

Introduction: Guidelines for cross-sex hormone treatment of transsexual people are now in place. However, little attention has been paid to the issue of treatment suitability for older people. Does existing treatment need to be adapted as subjects age, and does it make a difference if treatment is only started when the subject is already older? Aim: To assess the necessity of adapting cross-sex hormone administration for elderly transsexual people. Main Outcome Measures: Risks/benefits of continued use of cross-sex hormones with regard to bone health, cardiovascular risks, and malignancies. Methods: Due to lack of data on the subject population, sex hormone treatment of other conditions in older non-transsexual people has been taken as the best available analogy to determine the extent to which these might be applicable to comparable transsexual persons. Findings in transsexual people receiving cross-sex hormone treatment sometimes modified the above approach of applying guidelines for the elderly to the aging transsexual population. Results: Testosterone administration to female-to-male transsexual persons (FtoM) carries little risk with regard to cardiovascular disease and cancer. For those with high hematocrit or cardiac insufficiency the dose can be reduced. Administration of estrogens to male-to-female transsexual persons (MtoF), particularly when combined with progestins, does significantly increase the risk of developing cardiovascular disease (almost a twofold incidence compared with the general population). This may require dose adjustment or changing from oral to safer transdermal estrogens. Tumors of the breasts, prostate and pituitary may occur. In FtoM, breast cancer can occur even after breast ablation. Older subjects can commence cross-sex hormone treatment without disproportionate risks. Conclusion: Cross-sex hormones may be continued into old age but monitoring for cardiovascular disease and malignancies, both of the old and new sex, is recommended. MtoF will have more health complications in old age than FtoM requiring adaptations of treatment. Gooren L and Lips P. Conjectures concerning cross-sex hormone treatment of aging transsexual persons. J Sex Med 2014;11:2012-2019. © 2014 International Society for Sexual Medicine.


Anna J.M.,University of Toronto | Scholes G.D.,University of Toronto | Van Grondelle R.,VU University Amsterdam
BioScience | Year: 2014

How could quantum mechanics possibly be important in biology We will discuss this question in the light of recent experiments that suggest that quantum mechanics - or at least coherence - is at play after photosynthesis is initiated by light. First, we give a brief description of light harvesting in photosynthesis. We follow this with an introduction to two-dimensional electronic spectroscopy, in which we demonstrate how this spectroscopic technique can be used to indicate coherent contributions to energy transfer dynamics. As a final point, we focus on the possible role that coherence may play in photosynthetic biological systems. © 2013 The Author(s) 2013. Published by Oxford University Press on behalf of the American Institute of Biological Sciences. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.


To evaluate the cost effectiveness, cost utility, and cost-benefit of an integrated care programme compared with usual care for sick listed patients with chronic low back pain. Economic evaluation alongside a randomised controlled trial with 12 months' follow-up. Primary care (10 physiotherapy practices, one occupational health service, one occupational therapy practice) and secondary care (five hospitals) in the Netherlands, 2005-9. 134 adults aged 18-65 sick listed because of chronic low back pain: 66 were randomised to integrated care and 68 to usual care. Integrated care consisted of a workplace intervention based on participatory ergonomics, with involvement of a supervisor, and a graded activity programme based on cognitive behavioural principles. Usual care was provided by general practitioners and occupational physicians according to Dutch guidelines. The primary outcome was duration until sustainable return to work. The secondary outcome was quality adjusted life years (QALYs), measured using EuroQol. Total costs in the integrated care group (£13165, SD £13600) were significantly lower than in the usual care group (£18475, SD £13616). Cost effectiveness planes and acceptability curves showed that integrated care was cost effective compared with usual care for return to work and QALYs gained. The cost-benefit analyses showed that every £1 invested in integrated care would return an estimated £26. The net societal benefit of integrated care compared with usual care was £5744. Implementation of an integrated care programme for patients sick listed with chronic low back pain has a large potential to significantly reduce societal costs, increase effectiveness of care, improve quality of life, and improve function on a broad scale. Integrated care therefore has large gains for patients and society as well as for employers.


Cohen-Kettenis P.T.,VU University Amsterdam
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2010

Psychosocial aspects of the treatment of disorders of sex development (DSDs) concern gender assignment, information management and communication, timing of medical interventions, consequences of surgery, and sexuality. Although outcome is often satisfactory, a variety of medical and psychosocial factors may jeopardise the psychological development of children with DSDs. This sometimes results in the desire to change gender later in life. The clinical management of gender dysphoria in individuals with DSD may profit from methods and insights that have been developed for gender dysphoric individuals without DSD. In DSD care, clinical decisions are often made with long-lasting effects on quality of life and should be based on empirical evidence. Yet, such evidence (e.g., regarding gender assignment, information management and timing of surgery) is largely non-existent. DSD-specific protocols and educational materials need to be developed to standardise and evaluate interventions in order to facilitate decision making of professionals and individuals with DSD and enhance psychosocial care in this area. © 2009 Elsevier Ltd. All rights reserved.


The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen’s d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen’s d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen’s d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen’s d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen’s d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.Molecular Psychiatry advance online publication, 30 June 2015; doi:10.1038/mp.2015.69. © 2015 Macmillan Publishers Limited


Desoye G.,Medical University of Graz | Van Poppel M.,VU University Amsterdam
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2015

Recent studies have established that the neonate born to a pregnancy with maternal diabetes or obesity ('diabesity') is characterized by increased fat accumulation. The neonatal fat is the result of triglyceride synthesis and deposition stimulated by elevated fetal insulin levels combined with insulin's mitogenic activity directly stimulating the growth of the white adipocytes. Fetal insulin levels are determined by fetal glucose and some amino acids such as arginine. Although the placenta plays a key role in providing maternally derived nutrients to the growing fetus, there is currently no evidence that it actively contributes to an excessive maternal-to-fetal glucose flux at the end of gestation. Early in gestation, the maternal environment in diabesity, and in particular the glucose-insulin axis, can modify placental growth and development, which may contribute to an enhanced glucose flux to the fetus already early in pregnancy. This may have long-lasting effects on the fetal pancreas and accelerate beta-cell maturation. The association of fetal and neonatal insulin levels and the proportion of body fat with obesity later in the offspring's life calls for interventions during pregnancy to prevent or reduce fetal hyperinsulinaemia. Dietary and/or physical activity interventions initiated before or in early pregnancy would likely be most effective. Results from the very few studies with fetal insulin as the outcome are inconsistent. However, there is a major lack of randomized intervention trials on this topic. © 2014 Elsevier Ltd. All rights reserved.


Koelemeij J.C.J.,VU University Amsterdam
Physical Chemistry Chemical Physics | Year: 2011

A calculation of dynamic polarizabilities of rovibrational states with vibrational quantum number v = 0-7 and rotational quantum number J = 0,1 in the 1sσg ground-state potential of HD+ is presented. Polarizability contributions by transitions involving other 1sσ g rovibrational states are explicitly calculated, whereas contributions by electronic transitions are treated quasi-statically and partially derived from existing data [R. E. Moss and L. Valenzano, Mol. Phys., 2002, 100, 1527]. Our model is valid for wavelengths >4 μm and is used to assess level shifts due to the blackbody radiation (BBR) electric field encountered in experimental high-resolution laser spectroscopy of trapped HD+ ions. Polarizabilities of 1sσg rovibrational states obtained here agree with available existing accurate ab initio results. It is shown that the Stark effect due to BBR is dynamic and cannot be treated quasi-statically, as is often done in the case of atomic ions. Furthermore it is pointed out that the dynamic Stark shifts have tensorial character and depend strongly on the polarization state of the electric field. Numerical results of BBR-induced Stark shifts are presented, showing that Lamb-Dicke spectroscopy of narrow vibrational optical lines (∼10 Hz natural linewidth) in HD + will become affected by BBR shifts only at the 10-16 level. © the Owner Societies 2011.


Solnes Miltenburg A.,VU University Amsterdam
Systematic reviews | Year: 2013

One of the effective strategies for reducing the number of maternal deaths is delivery by a skilled birth attendant. Low utilization of skilled birth attendants has been attributed to delay in seeking care, delay in reaching a health facility and delay in receiving adequate care. Health workers could play a role in helping women prepare for birth and anticipate complications, in order to reduce delays. There is little evidence to support these birth preparedness and complication readiness (BP/CR) programs; however, BP/CR programs are frequently implemented. The objective of this review is to assess the effect of BP/CR programs on increasing skilled birth attendance in low-resource settings. Due to the complexity of BP/CR programs and the need to understand why certain programs are more effective than others, we will combine both quantitative and qualitative studies in this systematic review. Search terms were selected with the assistance of a health information specialist. Three reviewers will independently select and assess studies for quality. Data will be extracted by one reviewer and checked for accuracy and completeness by a second reviewer. Discussion between the reviewers will resolve disagreements. If disagreements remain, a third party will be consulted. Data analysis will be carried out in accordance with the BP/CR matrix, developed by the Johns Hopkins Program for International Education in Gynecology and Obstetrics (JHPIEGO). Study data will be grouped and analyzed by quality and study design and regrouped according to type of intervention strategy. This review will provide: 1) an insight into existing BP/CR programs, 2) recommendations on effective elements of the different approaches, 3) proposals for concrete action plans for health professionals in the field of reproductive health in resource-poor settings and 4) an overview of existing knowledge gaps requiring further research. PROSPERO registration no.: CRD42012003124.


The neuro-anatomical substrates of major depressive disorder (MDD) are still not well understood, despite many neuroimaging studies over the past few decades. Here we present the largest ever worldwide study by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Major Depressive Disorder Working Group on cortical structural alterations in MDD. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2148 MDD patients and 7957 healthy controls were analysed with harmonized protocols at 20 sites around the world. To detect consistent effects of MDD and its modulators on cortical thickness and surface area estimates derived from MRI, statistical effects from sites were meta-analysed separately for adults and adolescents. Adults with MDD had thinner cortical gray matter than controls in the orbitofrontal cortex (OFC), anterior and posterior cingulate, insula and temporal lobes (Cohen’s d effect sizes: −0.10 to −0.14). These effects were most pronounced in first episode and adult-onset patients (>21 years). Compared to matched controls, adolescents with MDD had lower total surface area (but no differences in cortical thickness) and regional reductions in frontal regions (medial OFC and superior frontal gyrus) and primary and higher-order visual, somatosensory and motor areas (d: −0.26 to −0.57). The strongest effects were found in recurrent adolescent patients. This highly powered global effort to identify consistent brain abnormalities showed widespread cortical alterations in MDD patients as compared to controls and suggests that MDD may impact brain structure in a highly dynamic way, with different patterns of alterations at different stages of life.Molecular Psychiatry advance online publication, 3 May 2016; doi:10.1038/mp.2016.60. © 2016 Macmillan Publishers Limited


To assess the prevalence of normal weight, overweight and obesity among 10-18-year-old Czech Republic adolescents and to assess the association between energy balance-related behaviours and overweight/obesity. Cross-sectional data from 'The 6th Nation-wide Anthropological Survey of Children and Adolescents 2001 Czech Republic' have been used. Height and weight were objectively measured. Data on adolescents' behaviours were assessed with self-reported questionnaires. Background variables were assessed by means of a parental questionnaire. Multi-level logistic regression analyses were conducted to assess behavioural risk factors of being overweight/obese. Data on 31,228 adolescents aged 10-18 years were included in the present study. The highest prevalence of being overweight or obese was found among boys and younger adolescents. Boys were more physically active, watched more television (TV) and used the computer more often than did girls. Being on a diet and skipping meals were positively associated with being overweight/obese, independent of gender. In boys (10-14 years old), inverse associations with being overweight/obese were found when being more physically active. Monitoring weight showed inverse relations with being overweight/obese in 15-18-year-old girls. Watching TV more than 7 h a week was positively associated with being overweight/obese in 15-18-year-old girls, and was found to be negatively associated in boys of the same age group. These behaviours should be targeted when preventing overweight and obesity among Czech Republic adolescents. Studies using better measures of energy balance-related behaviours are needed.


The positron emitter zirconium-89 ((89)Zr) has very attractive properties for positron emission tomography (PET) imaging of intact monoclonal antibodies (mAbs) using immuno-PET. This protocol describes the step-by-step procedure for the facile radiolabeling of mAbs or other proteins with (89)Zr using p-isothiocyanatobenzyl-desferrioxamine (Df-Bz-NCS). First, Df-Bz-NCS is coupled to the lysine-NH(2) groups of a mAb at pH 9.0 (pre-modification), followed by purification using gel filtration. Next, the pre-modified mAb is labeled at room temperature by the addition of [(89)Zr]Zr-oxalic acid solution followed by purification using gel filtration. The entire process of pre-modification, radiolabeling and purification steps will take about 2.5 h.


van den Kommer T.N.,VU University Amsterdam
Dementia and Geriatric Cognitive Disorders | Year: 2010

Aim: To evaluate previously developed classification models to make implementation in primary care possible and aid early identification of persons at risk for dementia. Methods: Data were drawn from the OCTO-Twin study. At baseline, 521 persons ≥80 years of age were nondemented, and for 387 a blood sample was available. Predictors of dementia were collected and analyzed in initially nondemented persons using generalized estimating equations and Cox survival analyses. Results: In the basic model using predictors already known or easily obtained (basic set), the mean 2-year predictive value increased from 6.9 to 28.8% in persons with memory complaints and an MMSE score ≤25. In the extended model, using both the basic set and an extended set of predictors requiring further assessment, the 8-year predictive value increased from 15.0 to 45.8% in persons with low cholesterol and an MMSE score ≤24. Conclusion: Both models can contribute to an improved early identification of persons at risk for dementia in primary care. Copyright © 2010 S. Karger AG, Basel.


Badalian A.M.,Institute of Theoretical and Experimental Physics | Bakker B.L.G.,VU University Amsterdam
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

The masses of higher D(nL) and Ds(nL) excitations are shown to decrease due to the string contribution, originating from the rotation of the QCD string itself: it lowers the masses by 45 MeV for L=2 (n=1) and by 65 MeV for L=3 (n=1). An additional decrease ∼100 MeV takes place if the current mass of the light (strange) quark is used in a relativistic model. For D s(1D33) and Ds(2P1H) the calculated masses agree with the experimental values for Ds(2860) and Ds(3040), and the masses of D(2S01), D(2S13), D(1D33), and D(1D2) are in agreement with the new BABAR data. For the yet undiscovered resonances we predict the masses M(D(2P23))=2965 MeV, M(D(2P03))=2880 MeV, M(D(1F43))=3030 MeV, and M(D s(1F23))=3090 MeV. We show that for L=2, 3 the states with j q=l+1/2 and jq=l-1/2 (J=l) are almost completely unmixed ( -1°), which implies that the mixing angles θ between the states with S=1 and S=0 (J=L) are θ≈40°for L=2 and ≈42°for L=3. © 2011 American Physical Society.


Zant W.,VU University Amsterdam
Food Policy | Year: 2012

We investigate how food-aid affects price and production of staple food, with a partial equilibrium model with non-separable production and consumption. The model captures the key characteristics of sub-Saharan Africa subsistence economies. Simulations generate negative but also positive food-aid elasticities of production. Conditions are identified which mitigate the negative impact and support a positive impact. The share of domestic food production in total staple food demand (+) and the share of income from staple food production in total household income (-) are key determinants. Price and production equations, estimated with a panel of district data of the Malawi maize market for the period 1999-2010, show a small positive impact of food-aid. Large negative impacts of food-aid are not likely given production and income shares and behavioural responses. © 2011 Elsevier Ltd.


Ettema E.J.,VU University Amsterdam
Theoretical medicine and bioethics | Year: 2010

Patients with a life-threatening illness can be confronted with various types of loneliness, one of which is existential loneliness (EL). Since the experience of EL is extremely disruptive, the issue of EL is relevant for the practice of end-of-life care. Still, the literature on EL has generated little discussion and empirical substantiation and has never been systematically reviewed. In order to systematically review the literature, we (1) identified the existential loneliness literature; (2) established an organising framework for the review; (3) conducted a conceptual analysis of existential loneliness; and (4) discussed its relevance for end-of-life care. We found that the EL concept is profoundly unclear. Distinguishing between three dimensions of EL-as a condition, as an experience, and as a process of inner growth-leads to some conceptual clarification. Analysis of these dimensions on the basis of their respective key notions-everpresent, feeling, defence; death, awareness, difficult communication; and inner growth, giving meaning, authenticity-further clarifies the concept. Although none of the key notions are unambiguous, they may function as a starting point for the development of care strategies on EL at the end of life.


Van Burg E.,VU University Amsterdam
Journal of Product Innovation Management | Year: 2012

Previous studies show that resource constraints have mixed effects on innovation and opportunity identification by entrepreneurs. Sometimes, resource constraints lead to identifying more opportunities, whereas in other cases, entrepreneurs see fewer opportunities. This study explores a new approach to reconcile this inconsistency. Using a sample of 219 small- and medium-sized enterprises (SMEs), we explore relationships between supply and demand constraints, on the one hand, and identifying supply and demand opportunities, on the other hand. The results show that supply constraints have a positive effect on identifying supply opportunities but a negative effect on identifying demand opportunities. Similarly, demand constraints have a positive effect on identifying demand opportunities but a negative effect on identifying supply opportunities. Thus, this study shows that resource constraints direct the entrepreneur's attention toward opportunities inside the constrained domain rather than outside the constrained domain. An important consequence for theory is that a complete explanation of the mixed effects of resource constraints should consider different types of resource constraints and different sources of opportunities simultaneously. For practicing entrepreneurs, being aware of this mechanism can prevent missing out on promising opportunities outside the constrained domains. © 2012 Product Development & Management Association.


Wurdinger T.,VU University Amsterdam
Journal of the National Cancer Institute | Year: 2013

Background Glioblastomas exhibit a high level of chemotherapeutic resistance, including to the antimitotic agents vincristine and taxol. During the mitotic agent-induced arrest, glioblastoma cells are able to perform damage-control and self-repair to continue proliferation. Monopolar spindle 1 (MPS1/TTK) is a checkpoint kinase and a gatekeeper of the mitotic arrest. Methods We used glioblastoma cells to determine the expression of MPS1 and to determine the effects of MPS1 inhibition on mitotic errors and cell viability in combination with vincristine and taxol. The effect of MPS1 inhibition was assessed in different orthotopic glioblastoma mouse models (n = 3-7 mice/group). MPS1 expression levels were examined in relation to patient survival. Results Using publicly available gene expression data, we determined that MPS1 overexpression corresponds positively with tumor grade and negatively with patient survival (two-sided t test, P < .001). Patients with high MPS1 expression (n = 203) had a median and mean survival of 487 and 913 days (95% confidence intervals [CI] = 751 to 1075), respectively, and a 2-year survival rate of 35%, whereas patients with intermediate MPS1 expression (n = 140) had a median and mean survival of 858 and 1183 days (95% CI = 1177 to 1189), respectively, and a 2-year survival rate of 56%. We demonstrate that MPS1 inhibition by RNAi results in sensitization to antimitotic agents. We developed a selective small-molecule inhibitor of MPS1, MPS1-IN-3, which caused mitotic aberrancies in glioblastoma cells and, in combination with vincristine, induced mitotic checkpoint override, increased aneuploidy, and augmented cell death. MPS1-IN-3 sensitizes glioblastoma cells to vincristine in orthotopic mouse models (two-sided log-rank test, P < .01), resulting in prolonged survival without toxicity. Conclusions Our results collectively demonstrate that MPS1, a putative therapeutic target in glioblastoma, can be selectively inhibited by MPS1-IN-3 sensitizing glioblastoma cells to antimitotic drugs. © The Author 2013. Published by Oxford University Press. All rights reserved.


Hensen E.F.,VU University Amsterdam | Bayley J.-P.,Leiden University
Familial Cancer | Year: 2011

The last 10 years have seen enormous progress in the field of paraganglioma and pheochromocytoma genetics. The identification of the first gene related to paraganglioma, SDHD, encoding a subunit of mitochondrial succinate dehydrogenase (SDH), was quickly followed by the identification of mutations in SDHC and SDHB. Very recently several new SDH-related genes have been discovered. The SDHAF2 gene encodes an SDH co-factor related to the function of the SDHA subunit, and is currently exclusively associated with head and neck paragangliomas. SDHA itself has now also been identified as a paraganglioma gene, with the recent identification of the first mutation in a patient with extra-adrenal paraganglioma. Another SDH-related co-factor, SDHAF1, is not currently known to be a tumor suppressor, but may shed some light on the mechanisms of tumorigenesis. An entirely novel gene associated with adrenal pheochromocytoma, TMEM127, suggests that other new paraganglioma susceptibility genes may await discovery. In addition to these recent discoveries, new techniques related to mutation analysis, including genetic analysis algorithms, SDHB immunohistochemistry, and deletion analysis by MLPA have improved the efficiency and accuracy of genetic analysis. However, many intriguing questions remain, such as the striking differences in the clinical phenotype of genes that encode proteins with an apparently very close functional relationship, and the lack of expression of SDHD and SDHAF2 mutations when inherited via the maternal line. Little is still known of the origins and causes of truly sporadic tumors, and the role of oxygen in the relationships between high-altitude, familial and truly sporadic paragangliomas remains to be elucidated. © 2010 The Author(s).


Verweij K.J.,VU University Amsterdam
Psychological medicine | Year: 2013

Various studies support the inclusion of cannabis withdrawal in the diagnosis of cannabis use disorder (CUD) in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (criterion B), (2) estimate the role of genetic and environmental influences on individual differences in cannabis withdrawal and (3) determine the extent to which genetic and environmental influences on cannabis withdrawal overlap with those on DSM-IV-defined abuse/dependence. The sample included 2276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined in accordance with criterion B of the proposed DSM-5 revisions. Cannabis abuse/dependence was defined as endorsing one or more DSM-IV criteria of abuse or three or more dependence criteria. The classical twin model was used to estimate the genetic and environmental influences on variation in cannabis withdrawal, along with its covariation with abuse/dependence. Of all the cannabis users, 11.9% met criteria for cannabis withdrawal. Around 50% of between-individual variation in withdrawal could be attributed to additive genetic variation, and the rest of the variation was mostly due to non-shared environmental influences. Importantly, the genetic influences on cannabis withdrawal almost completely (99%) overlapped with those on abuse/dependence. We have shown that cannabis withdrawal symptoms exist among cannabis users, and that cannabis withdrawal is moderately heritable. Genetic influences on cannabis withdrawal are the same as those affecting abuse/dependence. These results add to the wealth of literature that recommends the addition of cannabis withdrawal to the diagnosis of DSM-5 CUD.


Terluin B.,VU University Amsterdam
Journal of Clinical Epidemiology | Year: 2012

A number of studies have demonstrated a correlation between baseline severity and minimally important change (MIC) values. However, Browne et al. stated that these studies failed to account for "mathematical coupling," and that, therefore, the correlation between baseline severity and MIC values may be spurious. The present article demonstrates that on the level of individual scores, mathematical coupling causes the observed baseline and change scores to correlate even in the absence of any true correlation between these variables. This phenomenon is because of the fact that change scores can only be estimated by subtracting the baseline score from the follow-up score, causing the baseline and change scores to share a common piece of error variance. However, MIC values are always determined on group level, and mathematical coupling does not affect group-level statistics or the correlation of these statistics across groups. Therefore, mathematical coupling does not account for the association between baseline severity and MIC values as suggested by Browne et al. © 2012 Elsevier Inc. All rights reserved.


Detterbeck F.C.,Yale University | Postmus P.E.,VU University Amsterdam | Tanoue L.T.,Yale University
Chest | Year: 2013

The current Lung Cancer Stage Classification system is the seventh edition, which took effect in January 2010. This article reviews the definitions for the TNM descriptors and the stage grouping in this system. Copyright © by the American College of Chest Physicians 2013.


O'Higgins T.G.,Scottish Association for Marine Science | Gilbert A.J.,VU University Amsterdam
Estuarine, Coastal and Shelf Science | Year: 2014

The introduction of the Marine Strategy Framework Directive (MSFD) with its focus on an Ecosystem Approach places an emphasis on the human dimensions of environmental problems. Human activities may be the source of marine degradation, but may also be adversely affected should degradation compromise the provision of ecosystem services. The MSFD marks a shift away from management aiming to restore past, undegraded states toward management for Good Environmental Status (GEnS) based on delivery of marine goods and services. An example relating ecosystem services to criteria for Good Environmental Status is presented for eutrophication, a long recognised problem in many parts of Europe's seas and specifically targeted by descriptors for GEnS. Taking the North Sea as a case study the relationships between the eutrophication criteria of the MSFD and final and intermediate marine ecosystem services are examined. Ecosystem services are valued, where possible in monetary terms, in order to illustrate how eutrophication affects human welfare (economic externalities) through its multiple effects on ecosystem services. © 2013 Elsevier Ltd.


Groth P.,VU University Amsterdam | Moreau L.,University of Southampton
Future Generation Computer Systems | Year: 2011

From the World Wide Web to supply chains and scientific simulations, distributed systems are a widely used and important approach to building computational systems. Tracking provenance within these systems is crucial for determining the trustworthiness of data they produce, troubleshooting problems, assigning responsibility for decisions, and improving performance. To facilitate such tracking, the Open Provenance Model (OPM) has been created to enable the interchange of provenance between a distributed system's components. However, to date, the ability of OPM to represent distributed systems has not been verified. In this work, we show how OPM can be used to represent a set of distributed systems' patterns. We present a profile that shows that these patterns are a specialisation of OPM. Finally, we define a contract that enables participants in a distributed system to ensure that their provenance can be integrated cohesively. © 2011 Elsevier B.V. All rights reserved.


Berking M.,University of Marburg | Ebert D.,University of Marburg | Cuijpers P.,VU University Amsterdam | Hofmann S.G.,Boston University
Psychotherapy and Psychosomatics | Year: 2013

Background: Deficits in emotion regulation skills are possible factors maintaining major depressive disorder (MDD). Therefore, the aim of the study was to test whether integrating a systematic emotion regulation training (ERT) enhances the efficacy of routine inpatient cognitive behavioral therapy (CBT) for MDD. Methods: In a prospective randomized controlled trial, 432 inpatients meeting criteria for MDD were assigned to receive either routine CBT or CBT enriched with an intense emotion regulation skills training (CBT-ERT). Results: Participants in the CBT-ERT condition demonstrated a significantly greater reduction in depression (response rates-CBT: 75.5%, CBT-ERT: 84.9%; remission rates-CBT: 51.1%, CBT-ERT: 65.1%). Moreover, CBT-ERT participants demonstrated a significantly greater reduction of negative affect, as well as a greater increase of well-being and emotion regulation skills particularly relevant for mental health. Conclusions: Integrating strategies that target emotion regulation skills improves the efficacy of CBT for MDD. © 2013 S. Karger AG, Basel.


OBJECTIVES: The Health-promotion through Obesity Prevention across Europe (HOPE) project aims to bring the European scientific knowledge on overweight, obesity and their determinants together and use the expertise of researchers across Europe to contribute to tackling the obesity epidemic. DESIGN/SUBJECTS/RESULTS: This special issue of Public Health Nutrition presents important results from one of the work packages of the HOPE project that aims at gaining and integrating knowledge on the determinants of nutrition, physical activity and obesity among schoolchildren and adolescents (aged 10-18 years) in different European regions. It includes contributions from Northern Europe (Norway), Central and Eastern Europe (Germany, Poland and the Czech Republic), Southern Europe (Greece) and Western Europe (Belgium and The Netherlands), as well as an overview of the availability of good-quality data on prevalence rates and trends in overweight (including obesity) among adolescents in European Union (EU) countries. The studies that are included report prevalence differences, data on relevant nutrition and physical activity behaviours, as well as potential physical and environmental behavioural determinants. CONCLUSION: These papers provide further evidence on differences in obesity and overweight prevalence among different EU regions and countries, and contribute to the further exploration of risk factors that may or should be addressed in obesity prevention efforts for school-aged children and adolescents in EU countries.


Web-based questionnaires have become increasingly popular in health research. However, reported response rates vary and response bias may be introduced. The aim of this study was to evaluate whether sending a mixed invitation (paper-based together with Web-based questionnaire) rather than a Web-only invitation (Web-based questionnaire only) results in higher response and participation rates for female childhood cancer survivors filling out a questionnaire on fertility issues. In addition, differences in type of response and characteristics of the responders and nonresponders were investigated. Moreover, factors influencing preferences for either the Web- or paper-based version of the questionnaire were examined. This study is part of a nationwide study on reproductive function, ovarian reserve, and risk of premature menopause in female childhood cancer survivors. The Web-based version of the questionnaire was available for participants through the Internet by means of a personalized user name and password. Participants were randomly selected to receive either a mixed invitation (paper-based questionnaire together with log-in details for Web-based questionnaire, n = 137) or a Web-only invitation (log-in details only, n = 140). Furthermore, the latter group could request a paper-based version of the questionnaire by filling out a form. Overall response rates were comparable in both randomization groups (83% mixed invitation group vs 89% in Web-only invitation group, P = .20). In addition, participation rates appeared not to differ (66% or 90/137, mixed invitation group vs 59% or 83/140, Web-only invitation group, P =.27). However, in the mixed invitation group, significantly more respondents filled out the paper-based questionnaire compared with the Web-only invitation group (83% or 75/90 and 65% or 54/83, respectively, P = .01). The 44 women who filled out the Web-based version of the questionnaire had a higher educational level than the 129 women who filled out the paper-based version (P = .01). Furthermore, the probability of filling out the Web-based questionnaire appeared to be greater for women who were allocated to the Web-only invitation group (OR = 2.85, 95% CI 1.31-6.21), were older (OR = 1.08, 95% CI 1.02-1.15), had a higher educational level (OR high vs low = 0.06, 95% CI 0.01-0.52), or were students (OR employed vs student = 3.25, 95% CI 1.00-10.56). Although overall response as well as participation rates to both types of invitations were similar, adding a paper version of a questionnaire to a Web-only invitation resulted in more respondents filling out the paper-based version. In addition, women who were older, had a higher level of education, or were students, were more likely to have filled out the Web-based version of the questionnaire. Given the many advantages of Web-based over paper-based questionnaires, researchers should strongly consider using Web-based questionnaires, although possible response bias when using these types of questionnaires should be taken into account. Nederlands Trial Register NTR2922; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2922 (Archived by WebCite at http://www.webcitation.org/5zRRdMrDv).


Schaafsma F.G.,VU University Amsterdam
The Cochrane database of systematic reviews | Year: 2013

Physical conditioning as part of a return to work strategy aims to improve work status for workers on sick leave due to back pain. This is the second update of a Cochrane Review (originally titled 'Work conditioning, work hardening and functional restoration for workers with back and neck pain') first published in 2003, updated in 2010, and updated again in 2013. To assess the effectiveness of physical conditioning as part of a return to work strategy in reducing time lost from work and improving work status for workers with back pain. Further, to assess which aspects of physical conditioning are related to a faster return to work for workers with back pain. We searched the following databases to March 2012: CENTRAL, MEDLINE (from 1966), EMBASE (from 1980), CINAHL (from 1982), PsycINFO (from 1967), and PEDro. Randomized controlled trials (RCTs) and cluster RCTs that studied workers with work disability related to back pain and who were included in physical conditioning programmes. Two review authors independently extracted data and assessed risk of bias. We used standard methodological procedures expected by The Cochrane Collaboration. We included 41 articles reporting on 25 RCTs with 4404 participants. Risk of bias was low in 16 studies.Three studies involved workers with acute back pain, eight studies workers with subacute back pain, and 14 studies workers with chronic back pain.In 14 studies, physical conditioning as part of a return to work strategy was compared to usual care. The physical conditioning mostly consisted of graded activity with work-related exercises aimed at increasing back strength and flexibility, together with a set date for return to work. The programmes were divided into a light version with a maximum of five sessions, or an intense version with more than five sessions up to full time or as inpatient treatment.For acute back pain, there was low quality evidence that both light and intense physical conditioning programmes made little or no difference in sickness absence duration compared with care as usual at three to 12 months follow-up (3 studies with 340 workers).For subacute back pain, the evidence on the effectiveness of intense physical conditioning combined with care as usual compared to usual care alone was conflicting (four studies with 395 workers). However, subgroup analysis showed low quality evidence that if the intervention was executed at the workplace, or included a workplace visit, it may have reduced sickness absence duration at 12 months follow-up (3 studies with 283 workers; SMD -0.42, 95% CI -0.65 to -0.18).For chronic back pain, there was low quality evidence that physical conditioning as part of integrated care management in addition to usual care may have reduced sickness absence days compared to usual care at 12 months follow-up (1 study, 134 workers; SMD -4.42, 95% CI -5.06 to -3.79). What part of the integrated care management was most effective remained unclear. There was moderate quality evidence that intense physical conditioning probably reduced sickness absence duration only slightly compared with usual care at 12 months follow-up (5 studies, 1093 workers; SMD -0.23, 95% CI -0.42 to -0.03).Physical conditioning compared to exercise therapy showed conflicting results for workers with subacute and chronic back pain. Cognitive behavioural therapy was probably not superior to physical conditioning as an alternative or in addition to physical conditioning. The effectiveness of physical conditioning as part of a return to work strategy in reducing sick leave for workers with back pain, compared to usual care or exercise therapy, remains uncertain. For workers with acute back pain, physical conditioning may have no effect on sickness absence duration. There is conflicting evidence regarding the reduction of sickness absence duration with intense physical conditioning versus usual care for workers with subacute back pain. It may be that including workplace visits or execution of the intervention at the workplace is the component that renders a physical conditioning programme effective. For workers with chronic back pain physical conditioning has a small effect on reducing sick leave compared to care as usual after 12 months follow-up. To what extent physical conditioning as part of integrated care management may alter the effect on sick leave for workers with chronic back pain needs further research.


Eleveld M.A.,VU University Amsterdam | Van der Wal D.,Netherlands Institute for Sea Research | Van Kessel T.,Deltares
Remote Sensing of Environment | Year: 2014

Optical data from a sun-synchronous satellite were used to investigate how large-scale estuarine suspended particulate matter (SPM) concentrations were affected by tidal and bulk meteorological drivers, and how retrieved SPM is biased by tidal aliasing and sampling under clear sky conditions. Local absorption and scattering properties were used to derive surface SPM maps from 84 cloud-free ENVISAT MERIS FR reflectance images of the Westerschelde estuary (51° 30' N, 3° 30' E) for the period 2006-2008, and validated with in situ SPM at fixed stations (r. = 0.89 for geometric means). The distinctly different SPM maps were categorized for different tidal and seasonal conditions. Resulting composites reveal spatial patterns in SPM as a function of semi-diurnal tidal phase, fortnightly tidal phase, or season. For the estuary proper, tidal and seasonal effects on the variation of SPM are similar in magnitude. Observed controls for surface SPM are distance to shallow source area, tidal current velocity, and advection of North Sea and estuarine surface waters. Turbidity maxima appear only during favourable tidal and meteorological conditions. For the Westerschelde, the bias introduced by sun-synchronous sampling causes low water image acquisitions to uniquely coincide with spring tides, and high water images with neap tides. Cloud-free images were associated with low wind velocities. Simulations from a mud transport model confirmed the overestimation of geometric mean SPM from the tidal aliasing, and underestimation from fair weather. This resulted in a net relative error of -. 8% at the wave-exposed mouth, but biases cancelled out in the upper estuary. We argue that local biases should be considered when interpreting water quality products for estuaries and coasts around the world. © 2014 Elsevier Inc.


This study of outcomes after either surgery or stereotactic ablative radiotherapy for patients with early-stage non-small cell lung cancer found that overall survival was correlated only with the Charlson Comorbidity Index, and that only tumor diameter was correlated with locoregional tumor control. These findings will increase clinical equipoise and facilitate patient inclusion into ongoing trials comparing both treatments. Copyright © 2013 American Cancer Society.


We investigated the development of the brain's functional connectivity throughout the life span (ages 5 through 71 years) by measuring EEG activity in a large population-based sample. Connectivity was established with Synchronization Likelihood. Relative randomness of the connectivity patterns was established with Watts and Strogatz' (1998) graph parameters C (local clustering) and L (global path length) for alpha (~10 Hz), beta (~20 Hz), and theta (~4 Hz) oscillation networks. From childhood to adolescence large increases in connectivity in alpha, theta and beta frequency bands were found that continued at a slower pace into adulthood (peaking at ~50 yrs). Connectivity changes were accompanied by increases in L and C reflecting decreases in network randomness or increased order (peak levels reached at ~18 yrs). Older age (55+) was associated with weakened connectivity. Semi-automatically segmented T1 weighted MRI images of 104 young adults revealed that connectivity was significantly correlated to cerebral white matter volume (alpha oscillations: r = 33, p<01; theta: r = 22, p<05), while path length was related to both white matter (alpha: max. r = 38, p<001) and gray matter (alpha: max. r = 36, p<001; theta: max. r = 36, p<001) volumes. In conclusion, EEG connectivity and graph theoretical network analysis may be used to trace structural and functional development of the brain.


Van Den Berg D.P.G.,Parnassia Psychiatric Institute | Van Der Gaag M.,Parnassia Psychiatric Institute | Van Der Gaag M.,VU University Amsterdam
Journal of Behavior Therapy and Experimental Psychiatry | Year: 2012

Background: Initial studies have shown that posttraumatic stress disorder (PTSD) can be effectivelytreated in patients with a psychotic disorder. These studies however used adapted treatment protocols, avoided direct exposure to trauma related stimuli or preceded treatment with stabilizing techniques making treatment considerably longer in duration. Method: An open trial in which adult subjects with a psychotic disorder and a comorbid PTSD (n = 27) received a maximum of six Eye Movement Desensitization and Reprocessing (EMDR) therapy sessions. PTSD symptoms, psychotic symptoms and additional symptoms were assessed at baseline and end-of-treatment. Results: The dropout rate was 18.5 percent (five subjects). Only five of the twenty-two completers (22.7%) still met criteria for PTSD after treatment. PTSD symptoms, auditory verbal hallucinations, delusions, anxiety, depression, and self-esteem all improved significantly. Paranoid ideation and feelings of hopelessness did not improve significantly. Treatment did not lead to symptom exacerbation in subjects. There were no adverse events, such as suicide attempts, self-mutilation, aggressive behavior or admission to a general or psychiatric hospital. Conclusions: This pilot study shows that a short EMDR therapy is effective and safe in the treatment of PTSD in subjects with a psychotic disorder. Treatment of PTSD has a positive effect on auditory verbal hallucinations, delusions, anxiety symptoms, depression symptoms, and self-esteem. EMDR can be applied to this group of patients without adapting the treatment protocol or delaying treatment by preceding it with stabilizing interventions. © 2011 Elsevier Ltd. All rights reserved.


Westerhof N.,VU University Amsterdam | Westerhof B.E.,BMEYE Inc | Westerhof B.E.,Heart Failure Research Center
Journal of Hypertension | Year: 2013

Objectives: In treatment of hypertension not only the pressure response is of interest, but also the effect on arterial parameters, for example, stiffness and resistance, is essential. We therefore reviewed what quantitative information on arterial stiffness can be obtained from pressure wave analysis. Methods: Using data from published large cohort studies, we derived relations between stiffness and the pressure-derived variables systolic pressure, pulse pressure, augmentation index (AIx), return time of reflected wave and reflection magnitude. Results: All pressure-derived variables give limited information on arterial function in terms of stiffness and resistance, except AIx (in low stiffness range only). Input impedance as a comprehensive description of the arterial system is too complex to derive and interpret in practice, but is accurately described by three parameters: systemic vascular resistance, total arterial stiffness, and aortic characteristic impedance (outflow tract size and proximal aortic stiffness). These parameters predict aortic pressure well in terms of magnitude and shape: with measured flow the predicted (p) and measured (m) systolic, Ps, and diastolic, Pd pressures relate as P sp = 0.997Psm- 1.63 and Pd, p = 1.03P dm-3.12mmHg (n=17). Therefore, methods should be developed to determine, preferably noninvasively, these three arterial parameters. Conclusion: Variables derived from pressure wave shape alone (e.g. inflection point, AIx among others), and wave separation (e.g. reflection magnitude), while predicting cardiovascular events, give little information on arterial function. We propose to develop new, and improve existing, noninvasive methods to determine systemic vascular resistance, total arterial stiffness, and aortic characteristic impedance. This will allow quantifying the response of arterial function to treatment. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.


As nation-state leaders age they increasingly engage in inter-state militarized disputes yet in industrialized societies a steady decrease in testosterone associated with aging is observed - which suggests a decrease in dominance behavior. The current paper points out that from modern societies to Old World monkeys increasing both in age and social status encourages dominant strategies to maintain acquired rank. Moreover, it is argued this consistency has shaped an implicit prototype causing followers to associate older age with dominance leadership. It is shown that (i) faces of older leaders are preferred during intergroup conflict and (ii) morphing U.S. Presidential candidates to appear older or younger has an overriding effect on actual election outcomes. This indicates that democratic voting can be systematically adjusted by activating innate biases. These findings appear to create a new line of research regarding the biology of leadership and contextual cues of age. © 2012 Spisak.


McDonald M.M.,Michigan State University | Navarrete C.D.,Michigan State University | van Vugt M.,VU University Amsterdam | van Vugt M.,University of Oxford
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2012

The social science literature contains numerous examples of human tribalism and parochialism-the tendency to categorize individuals on the basis of their group membership, and treat ingroup members benevolently and outgroup members malevolently. We hypothesize that this tribal inclination is an adaptive response to the threat of coalitional aggression and intergroup conflict perpetrated by 'warrior males' in both ancestral and modern human environments. Here, we describe how male coalitional aggression could have affected the social psychologies of men and women differently and present preliminary evidence from experimental social psychological studies testing various predictions from the 'male warrior' hypothesis. Finally, we discuss the theoretical implications of our research for studying intergroup relations both in humans and non-humans and discuss some practical implications.


Boer D.,University of Groningen | Brodsky S.J.,SLAC | Brodsky S.J.,University of Southern Denmark | Mulders P.J.,VU University Amsterdam | Pisano C.,University of Cagliari
Physical Review Letters | Year: 2011

We show that linearly polarized gluons inside unpolarized hadrons can be directly probed in jet or heavy quark pair production in electron-hadron collisions. We discuss the simplest cos2 asymmetries and estimate their maximal value, concluding that measurements of the unknown linearly polarized gluon distribution in the proton should be feasible in future Electron-Ion Collider or Large Hadron electron Collider experiments. Analogous asymmetries in hadron-hadron collisions suffer from factorization breaking contributions and would allow us to quantify the importance of initial- and final-state interactions. © 2011 American Physical Society.


For many instructors in higher education, use of a learning management system (LMS) is de facto mandatory. Nevertheless, instructors often have much freedom in deciding which functionalities of the LMS they use; that is, whether they perform each individual instructor task using the LMS. Alternatively, they may perform one specific instructor task using alternative means, or, quite often, not perform it at all. The current Technology Acceptance model (TAM) fails to describe this decision process accurately, as TAM (1) does not focus on the level of the individual task; (2) does not make a distinction between not performing a task and performing a task using alternative means; and (3) does not recognize one important factor that affects the performance of a specific task - task importance. A test of three different models shows that the decision process is best represented as a two-step process. First, influenced by task importance, a choice is made to either perform a specific task or not. Second, after the decision has been made to perform the task, and influenced by the usefulness and ease of use of the LMS, a choice is made between performing the task using the LMS and using alternative means. © 2012 Elsevier Ltd. All rights reserved.


Van Uden-Kraan C.F.,VU University Amsterdam
Journal of medical Internet research | Year: 2011

Although peer-to-peer contact might empower patients in various ways, studies show that only a few patients actually engage in support groups. The objective of our study was to explore factors that facilitate or impede engagement in face-to-face and online peer support, using the theory of planned behavior (TPB). A questionnaire was completed by 679 patients being treated for arthritis, breast cancer, or fibromyalgia at two Dutch regional hospitals. Our results showed that only a minority of the patients engaged in organized forms of peer support. In total 10% (65/679) of the respondents had engaged in face-to-face meetings for patients in the past year. Only 4% (30/679) of the respondents had contact with peers via the Internet in the past year. Patients were more positive about face-to-face peer support than about online peer support (P < .001). In accordance with the TPB, having a more positive attitude (P < .01) and feeling more supported by people in the social environment (P < .001) increased the intention to participate in both kinds of peer support. In addition, perceived behavioral control (P = .01) influenced the intention to participate in online peer support. Nevertheless, the intention to engage in face-to-face and online peer support was only modestly predicted by the TPB variables (R(2) = .33 for face-to-face contact and R(2) = .26 for online contact). Although Health 2.0 Internet technology has significantly increased opportunities for having contact with fellow patients, only a minority seem to be interested in organized forms of peer contact (either online or face-to-face). Patients seem somewhat more positive about face-to-face contact than about online contact.


De Jager D.J.,Leiden University | Vervloet M.G.,VU University Amsterdam | Dekker F.W.,Leiden University
Nature Reviews Nephrology | Year: 2014

Patients with chronic kidney disease (CKD) have increased risk of all-cause mortality; the elevated cardiovascular mortality in patients with end-stage renal disease is particularly well documented. Lately, the increased noncardiovascular mortality in these patients has gained particular attention. In this article, both cardiovascular and noncardiovascular mortality in CKD are discussed, with specific attention paid to studies that provide details of noncardiovascular causes of death. Examples are provided of several cardiovascular risk factors that also seem to be associated with noncardiovascular mortality, including levels of fetuin-A, troponin T, and C-reactive protein, as well as vitamin D deficiency and proteinuria. Potential pathophysiological mechanisms (such as inflammatory reactions and the uraemic milieu) that might explain the increased cardiovascular and noncardiovascular mortality in CKD are also discussed. Future research should not only focus on preventing cardiovascular mortality, but also on studying noncardiovascular mortality and the potential link between causal pathways of cardiovascular mortality and noncardiovascular mortality in CKD. © 2014 Macmillan Publishers Limited. All rights reserved.


Pandit A.,VU University Amsterdam | De Groot H.J.M.,Leiden University
Photosynthesis Research | Year: 2012

This short review describes how solid-state NMR has provided a mechanistic and electronic picture of pigment-protein and pigment-pigment interactions in photosynthetic antenna complexes. NMR results on purple bacterial antenna complexes show how the packing of the protein and the pigments inside the light-harvesting oligomers induces mutual conformational stress. The protein scaffold produces deformation and electrostatic polarization of the BChl macrocycles and leads to a partial electronic charge transfer between the BChls and their coordinating histidines, which can tune the light-harvesting function. In chlorosome antennae assemblies, the NMR template structure reveals how the chromophores can direct their self-assembly into higher macrostructures which, in turn, tune the light-harvesting properties of the individual molecules by controlling their disorder, structural deformation, and electronic polarization without the need for a protein scaffold. These results pave the way for addressing the next challenge, which is to resolve the functional conformational dynamics of the lhc antennae of oxygenic species that allows them to switch between light-emitting and light-energy dissipating states. © 2011 The Author(s).


Blacquiere T.,Wageningen University | Smagghe G.,Ghent University | Van Gestel C.A.M.,VU University Amsterdam | Mommaerts V.,Ghent University
Ecotoxicology | Year: 2012

Neonicotinoid insecticides are successfully applied to control pests in a variety of agricultural crops; however, they may not only affect pest insects but also non-target organisms such as pollinators. This review summarizes, for the first time, 15 years of research on the hazards of neonicotinoids to bees including honey bees, bumble bees and solitary bees. The focus of the paper is on three different key aspects determining the risks of neonicotinoid field concentrations for bee populations: (1) the environmental neonicotinoid residue levels in plants, bees and bee products in relation to pesticide application, (2) the reported side-effects with special attention for sublethal effects, and (3) the usefulness for the evaluation of neonicotinoids of an already existing risk assessment scheme for systemic compounds. Although environmental residue levels of neonicotinoids were found to be lower than acute/chronic toxicity levels, there is still a lack of reliable data as most analyses were conducted near the detection limit and for only few crops. Many laboratory studies described lethal and sublethal effects of neonicotinoids on the foraging behavior, and learning and memory abilities of bees, while no effects were observed in field studies at field-realistic dosages. The proposed risk assessment scheme for systemic compounds was shown to be applicable to assess the risk for side-effects of neonicotinoids as it considers the effect on different life stages and different levels of biological organization (organism versus colony). Future research studies should be conducted with field-realistic concentrations, relevant exposure and evaluation durations. Molecular markers may be used to improve risk assessment by a better understanding of the mode of action (interaction with receptors) of neonicotinoids in bees leading to the identification of environmentally safer compounds. © Springer Science+Business Media, LLC 2012.


We present new evidence that changes in sector structure explain a considerable and increasing part of Manufacturing energy intensity trends across 19 OECD countries. We show that cross-country convergence of Manufacturing energy intensity levels is caused by efficiency improvements in lagging countries, while undermined by increasing international differences in sector structure. Particularly, we find that efficiency-driven catching-up processes only began to dominate the diverging impact of structural changes after 1995, reversing gradual crosscountry divergence of Manufacturing energy intensity levels into rapid convergence. Subsequently, we link sector structure dynamics to changing global production patterns under influence of international trade and specialization. We conclude that increasing trade and market integration helped reducing energy productivity gaps across countries, despite the contribution of increasing specialization to growing cross-country variation in sector structure. These trends are mainly driven by energy-intensive sectors, while various countries specialize in sectors for which they do not have a comparative energy productivity advantage. Copyright © 2015 by the IAEE. All rights reserved.


Kaspers G.J.L.,VU University Amsterdam
Expert Review of Anticancer Therapy | Year: 2012

Pediatric acute myeloid leukemia (AML) is currently associated with survival rates as high as 70%. However, many events still occur, side effects are significant, and late effects occur and can even be life-threatening. Thus, the treatment of pediatric AML still needs further improvement. While most study groups agree on several principles of AML treatment, many unanswered questions and even controversies remain, which will be the topic of this review. Relapsed AML, the most frequent event in children, will also be discussed. The controversies justify future clinical studies. Fortunately, biotechnical developments provide novel treatment targets and targeted drugs, and will enable minimal residual disease-driven tailored therapy. Moreover, a wide range of new drugs is being developed. International collaboration is required to perform randomized, or even single-arm clinical studies, in this setting of subgroup-directed therapy, and fortunately is being accomplished. Therefore, optimism is justified and the treatment of pediatric AML will continue to improve. © 2012 Expert Reviews Ltd.


Current data on the prevalence of overweight and energy-balance behaviors among European children is necessary to inform overweight prevention interventions. A school-based survey among 10-12 year old children was conducted in seven European countries using a standardized protocol. Weight, height, and waist circumference were measured; Engagement in physical activity, sedentary and dietary behaviors, and sleep duration were self-reported. Descriptive analyses were conducted, looking at differences according to country, gender, and parental education. 7234 children (52%girls; 11.6 ± 0.7 years) participated. 25.8% and 5.4% of boys, and 21.8% and 4.1% of girls were overweight (including obese) and obese (according to International Obesity Task Force criteria), respectively. Higher prevalence of overweight/obesity was observed in Greece, Hungary, Slovenia and Spain than in Belgium, Netherlands and Norway. Large differences between countries were found in intakes of sugar-sweetened beverages, breakfast, active transport, TV and computer time. More favorable overweight status and behavior patterns were found in girls than boys and in children of higher educated parents than in children of lower educated parents. High levels and striking differences in overweight status and potential risk behaviors were found among schoolchildren across Europe.


Kruijver M.,VU University Amsterdam
Forensic Science International: Genetics | Year: 2015

What is the probability that the likelihood ratio exceeds a threshold t, if a specified hypothesis is true? This question is asked, for instance, when performing power calculations for kinship testing, when computing true and false positive rates for familial searching and when computing the power of discrimination of a complex mixture. Answering this question is not straightforward, since there is are a huge number of possible genotypic combinations to consider. Different solutions are found in the literature. Several authors estimate the threshold exceedance probability using simulation. Corradi and Ricciardi [1] propose a discrete approximation to the likelihood ratio distribution which yields a lower and upper bound on the probability. Nothnagel et al. [2] use the normal distribution as an approximation to the likelihood ratio distribution. Dørum et al. [3] introduce an algorithm that can be used for exact computation, but this algorithm is computationally intensive, unless the threshold t is very large. We present three new approaches to the problem. Firstly, we show how importance sampling can be used to make the simulation approach significantly more efficient. Importance sampling is a statistical technique that turns out to work well in the current context. Secondly, we present a novel algorithm for computing exceedance probabilities. The algorithm is exact, fast and can handle relatively large problems. Thirdly, we introduce an approach that combines the novel algorithm with the discrete approximation of Corradi and Ricciardi. This last approach can be applied to very large problems and yields a lower and upper bound on the exceedance probability. The use of the different approaches is illustrated with examples from forensic genetics, such as kinship testing, familial searching and mixture interpretation. The algorithms are implemented in an R-package called DNAprofiles, which is freely available from CRAN. © 2014 Elsevier Ireland Ltd. All rights reserved.


Van Ulsen P.,VU University Amsterdam
Advances in Experimental Medicine and Biology | Year: 2011

Bacterial adhesins mediate the attachment of bacteria to their niches, such as the tissue of an infected host. Adhesins have to be transported across the cell envelope to become active and during this secretion process they fold into their final conformation. This chapter focuses on the biogenesis of the classical monomeric autotransporter proteins, which are the most ubiquitous class of secreted proteins in Gram-negative bacteria. They may function as adhesins, but other functions are also known. Autotransporter proteins have a modular structure and consist of an N-terminal signal peptide and a C-terminal translocator domain with in between the secreted passenger domain that harbours the functions. The signal peptide directs the transport across the inner membrane to the periplasm via the Sec machinery. The translocator domain inserts into the outer membrane and facilitates the transport of the passenger to the cell surface. In this chapter, I will review our current knowledge of the secretion of classical monomeric autotransporters and the methods that have been used to assess their folding during the translocation, both in vitro and in vivo. © 2011 Springer Science+Business Media B.V.


Galue H.A.,University of Amsterdam | Galue H.A.,VU University Amsterdam
Chemical Science | Year: 2014

In fullerenization chemistry, the whittling of carbon units from graphenic all-hexagon systems drives the local structural transformation from a sp 2-hybridized composition into a pyramidal-like carbon composition. This chemical process recently observed in real time is believed to involve the self-sculpting action of local strain forces leading to fullerene growth. Here, an atomistic structural representation of this process is elaborated and correlated with spectral simulations of graphenic molecular models in varied curvature-strain stages that allows uncovering the fingerprint of fullerenization. Application of this fingerprint to Infrared Space Observatory data reveals that interstellar graphenic matter undergoes fullerenization, leading to the formation of strained fullerene-like 3D species. This suggests an evolutionary chemical interrelation between forms of strained molecular nanostructures, and includes bowls, cones and cages. These results offer a valuable platform in all-carbon chemistry useful to advance our understanding of both experimental and interstellar sp2-carbon nanostructures. © 2014 the Partner Organisations.


Henschke N.,VU University Amsterdam
Cochrane database of systematic reviews (Online) | Year: 2010

BACKGROUND: Behavioural treatment is commonly used in the management of chronic low-back pain (CLBP) to reduce disability through modification of maladaptive pain behaviours and cognitive processes. Three behavioural approaches are generally distinguished: operant, cognitive, and respondent; but are often combined as a treatment package. OBJECTIVES: To determine the effects of behavioural therapy for CLBP and the most effective behavioural approach. SEARCH STRATEGY: The Cochrane Back Review Group Trials Register, CENTRAL, MEDLINE, EMBASE, and PsycINFO were searched up to February 2009. Reference lists and citations of identified trials and relevant systematic reviews were screened. SELECTION CRITERIA: Randomised trials on behavioural treatments for non-specific CLBP were included. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the risk of bias in each study and extracted the data. If sufficient homogeneity existed among studies in the pre-defined comparisons, a meta-analysis was performed. We determined the quality of the evidence for each comparison with the GRADE approach. MAIN RESULTS: We included 30 randomised trials (3438 participants) in this review, up 11 from the previous version. Fourteen trials (47%) had low risk of bias. For most comparisons, there was only low or very low quality evidence to support the results. There was moderate quality evidence that:i) operant therapy was more effective than waiting list (SMD -0.43; 95%CI -0.75 to -0.11) for short-term pain relief;ii) little or no difference exists between operant, cognitive, or combined behavioural therapy for short- to intermediate-term pain relief;iii) behavioural treatment was more effective than usual care for short-term pain relief (MD -5.18; 95%CI -9.79 to -0.57), but there were no differences in the intermediate- to long-term, or on functional status;iv) there was little or no difference between behavioural treatment and group exercise for pain relief or depressive symptoms over the intermediate- to long-term;v) adding behavioural therapy to inpatient rehabilitation was no more effective than inpatient rehabilitation alone. AUTHORS' CONCLUSIONS: For patients with CLBP, there is moderate quality evidence that in the short-term, operant therapy is more effective than waiting list and behavioural therapy is more effective than usual care for pain relief, but no specific type of behavioural therapy is more effective than another. In the intermediate- to long-term, there is little or no difference between behavioural therapy and group exercises for pain or depressive symptoms. Further research is likely to have an important impact on our confidence in the estimates of effect and may change the estimates.


Braam K.I.,VU University Amsterdam
The Cochrane database of systematic reviews | Year: 2013

A decreased physical fitness and impaired social functioning has been reported in patients and survivors of childhood cancer. This is influenced by the negative effects of disease and treatment of childhood cancer and by behavioural and social elements. Exercise training for was studied by the use of the nine-minute run-walk test, the timed up-and-down stairs test, and the 20-m shuttle run test. Only the up-and-down stairs test showed significant differences between the intervention and the control group, in favour of the intervention group (P value = 0.05, no further information available).Bone mineral density was assessed in one study, in which a statistically significant difference in favour of the exercise group was identified (standardised mean difference (SMD) 1.07; 95% confidence interval (CI) 0.48 to 1.66; P value < 0.001). Body mass index was assessed in two studies. The pooled data on this item did not show a statistically significant difference between the intervention and control study group.Flexibility was assessed in three studies. In one study the active ankle dorsiflexion method was used to assess flexibility and the second study they used the passive ankle dorsiflexion test. No statistically significant difference between the intervention and control group was identified with the active ankle dorsiflexion test, whereas with the passive test method a statistically significant difference in favour of the exercise group was found (SMD 0.69; 95% CI 0.12 to 1.25; P value = 0.02). The third study assessed body flexibility by the use of the sit-and-reach distance test; no statistically significant difference between the intervention and control group was identified.One study assessed the effects of an inspiratory muscle training programme aimed to train the lung muscles and increase physical fitness. This study reported no significant effect on either inspiratory or expiratory muscle strength. Two other studies using either knee and ankle strength changes by hand-held dynamometry or the number of completed push-ups (with knees on the ground) and a peripheral quantitative computed tomography of the tibia to determine the muscle mass did not identify statistically significant differences in muscle strength/endurance.The level of daily activity, health-related quality of life, fatigue, and adverse events were assessed in one study only; for all these items no statistically significant differences between the intervention and control group were found.None of the included studies evaluated the outcomes activity energy expenditure, time spent exercising, anxiety and depression, or self efficacy. The effects of physical exercise training interventions for childhood cancer participants are not yet convincing due to small numbers of participants and insufficient study methodology. Despite that, first results show a trend towards an improved physical fitness in the intervention group compared to the control group. Changes in physical fitness were seen by improved body composition, flexibility, and cardiorespiratory fitness. However, the evidence is limited and these positive effects were not found for the other assessed outcomes, such as muscle strength/endurance, the level of daily activity, health-related quality of life, and fatigue. There is a need for more studies with comparable aims and interventions, using higher numbers of participants and for studies with another childhood cancer population than ALL only.


Moghimi M.,VU University Amsterdam
Quintessence international (Berlin, Germany : 1985) | Year: 2013

To provide an empirical description of the relationship between the spread of head and neck infections, and the causal tooth. The hospital records of 155 patients presenting with odontogenic head and neck infections due to a single identifiable tooth from January 2000 to August 2011 were reviewed. The following data were collected: age, sex, clinical presentation, etiology, location, and spread of infection. The causal tooth and location of infection were subsequently compared to the literature. In the present study population, the causal tooth most frequently (47.1%) consisted of the third mandibular molar. Infection of maxillary teeth most commonly spread to the buccal space, whereas infection originating in the mandible mostly spread to the submandibular, pterygomandibular, and buccal spaces. The literature search provided 18 usable articles. Fourteen studies discriminated between mandibular and maxillary origin of infection, and three articles elaborated on the direct relationship between causal tooth and location of infection. Spaces most frequently affected in the literature are the submandibular, masticator, lateral pharyngeal, buccal, and sublingual spaces. A large amount of discrepancy was found between studies. When describing the location of infection, most studies do not discriminate between maxillary and mandibular origin. Although the literature seems to be unambiguous about the predetermined spread, this article demonstrates that it is more difficult to predict the spread of an infected tooth than previously expected. Large studies with clearly noted causal teeth in relation to location of spread should shed more light on the discrepancies found in this review.


In the present paper the effects of rapid, high-amplitude base-level changes during the last glacial-interglacial transition were studied for the Ain River in eastern France. During the Würm glacial maximum (MIS 2) rapid aggradation by deep-water Gilbert-type deltas and shallow-water fan deltas occurred at the margins of a 20 to 50m deep proglacial lake. A temporal high-amplitude lake-level fall of 60m resulted in gravel deposition by forced-regressive deltas, followed by rapid lake-level rise and fine-grained glaciolacustrine deposition. During the final deglaciation, a rapid base-level fall of 40m resulted in a complex fluvial response. Knickpoint formation and headward incision of the highstand deltas and concomitant deposition of gravel sheets by forced-regressive deltas and braided systems occurred in several depocentres on the former glacial lake floor. Preservation of highstand and falling-stage deposits and terrace formation in the incised valley depended on vertical incision and lateral channel migration. Terraces are well developed in the former lake-floor depressions, whereas vertical incision was dominant in the higher lake-floor areas. The Ain terrace staircase was likely formed by autogenic processes during a single allogenic base-level fall. This case study possibly offers an analogue for the preservation of interglacial highstand coastal deltas during sea-level fall at warm-to-cold climate transitions, although the rates of base-level fall are different. © 2013 Collegium Boreas. Published by John Wiley & Sons Ltd.


de Vet H.C.,VU University Amsterdam
BMJ (Clinical research ed.) | Year: 2013

Clinicians are interested in observer variation in terms of the probability of other raters (interobserver) or themselves (intraobserver) obtaining the same answer. Cohen's κ is commonly used in the medical literature to express such agreement in categorical outcomes. The value of Cohen's κ, however, is not sufficiently informative because it is a relative measure, while the clinician's question of observer variation calls for an absolute measure. Using an example in which the observed agreement and κ lead to different conclusions, we illustrate that percentage agreement is an absolute measure (a measure of agreement) and that κ is a relative measure (a measure of reliability). For the data to be useful for clinicians, measures of agreement should be used. The proportion of specific agreement, expressing the agreement separately for the positive and the negative ratings, is the most appropriate measure for conveying the relevant information in a 2 × 2 table and is most informative for clinicians.


This experiment examines how far extraversion of the target (self-generated information), extraversion of the target's friends (friends-generated information), and number of friends (system-generated information) influence the perceived popularity, communal orientation, and social attractiveness of the target. The warranting principle states that judgments rely more heavily on other-generated than self-generated information because the former is more immune to manipulation. It is argued that the warranting principle becomes more important when more interpersonal traits have to be judged. In line with the expectations, other-generated information had only weak impact on the popularity judgments. With regard to communal orientation, other-generated information had stronger effects and qualified the effects of self-generated information. Only other-generated information had an impact on perceived social attraction. © 2010 International Communication Association.


Samoocha D.,VU University Amsterdam
Journal of medical Internet research | Year: 2010

BACKGROUND: Patient empowerment is growing in popularity and application. Due to the increasing possibilities of the Internet and eHealth, many initiatives that are aimed at empowering patients are delivered online. OBJECTIVE: Our objective was to evaluate whether Web-based interventions are effective in increasing patient empowerment compared with usual care or face-to-face interventions. METHODS: We performed a systematic review by searching the MEDLINE, EMBASE, and PsycINFO databases from January 1985 to January 2009 for relevant citations. From the 7096 unique citations retrieved from the search strategy, we included 14 randomized controlled trials (RCTs) that met all inclusion criteria. Pairs of review authors assessed the methodological quality of the obtained studies using the Downs and Black checklist. A meta-analysis was performed on studies that measured comparable outcomes. The GRADE approach was used to determine the level of evidence for each outcome. RESULTS: In comparison with usual care or no care, Web-based interventions had a significant positive effect on empowerment measured with the Diabetes Empowerment Scale (2 studies, standardized mean difference [SMD] = 0.61, 95% confidence interval [CI] 0.29 - 0.94]), on self-efficacy measured with disease-specific self-efficacy scales (9 studies, SMD = 0.23, 95% CI 0.12 - 0.33), and on mastery measured with the Pearlin Mastery Scale (1 study, mean difference [MD] = 2.95, 95% CI 1.66 - 4.24). No effects were found for self-efficacy measured with general self-efficacy scales (3 studies, SMD = 0.05, 95% CI -0.25 to 0.35) or for self-esteem measured with the Rosenberg Self-Esteem Scale (1 study, MD = -0.38, 95% CI -2.45 to 1.69). Furthermore, when comparing Web-based interventions with face-to-face deliveries of the same interventions, no significant (beneficial or harmful) effects were found for mastery (1 study, MD = 1.20, 95% CI -1.73 to 4.13) and self-esteem (1 study, MD = -0.10, 95% CI -0.45 to 0.25). CONCLUSIONS: Web-based interventions showed positive effects on empowerment measured with the Diabetes Empowerment Scale, disease-specific self-efficacy scales and the Pearlin Mastery Scale. Because of the low quality of evidence we found, the results should be interpreted with caution. The clinical relevance of the findings can be questioned because the significant effects we found were, in general, small.


van Meerloo J.,VU University Amsterdam
Methods in molecular biology (Clifton, N.J.) | Year: 2011

The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay is based on the conversion of MTT into formazan crystals by living cells, which determines mitochondrial activity. Since for most cell populations the total mitochondrial activity is related to the number of viable cells, this assay is broadly used to measure the in vitro cytotoxic effects of drugs on cell lines or primary patient cells. In this chapter the protocol of the assay is described including important considerations relevant for each step of the assay as well as its limitations and possible applications.


Hoen A.,PBL Netherlands Environmental Assessment Agency | Koetse M.J.,VU University Amsterdam
Transportation Research Part A: Policy and Practice | Year: 2014

This paper presents results of an online stated choice experiment on preferences of Dutch private car owners for alternative fuel vehicles (AFVs) and their characteristics. Results show that negative preferences for alternative fuel vehicles are large, especially for the electric and fuel cell car, mostly as a result of their limited driving range and considerable refueling times. Preference for AFVs increases considerably with improvements on driving range, refueling time and fuel availability. Negative AFV preferences remain, however, also with substantial improvements in AFV characteristics; the remaining willingness to accept is on average € 10,000-€ 20,000 per AFV. Results from a mixed logit model show that consumer preferences for AFVs and AFV characteristics are heterogeneous to a large extent, in particular for the electric car, additional detour time and fuel time for the electric and fuel cell car. An interaction model reveals that annual mileage is by far the most important factor that determines heterogeneity in preferences for the electric and fuel cell car. When annual mileage increases, the preference for electric and fuel cell cars decreases substantially, whilst the willingness to pay for driving range increases substantially. Other variables such as using the car for holidays abroad and the daily commute also appear to be relevant for car choice. © 2014 Elsevier Ltd.


van Poppel M.N.,VU University Amsterdam
Sports medicine (Auckland, N.Z.) | Year: 2010

Many questionnaires have been developed to measure physical activity (PA), but an overview of the measurement properties of PA questionnaires is lacking. A summary of this information is useful for choosing the best questionnaire available. Therefore, the objective of this study was to evaluate and compare measurement properties of self-administered questionnaires assessing PA in adults. We searched MEDLINE, EMBASE and SportDiscus, using 'exercise', 'physical activity', 'motor activity' and 'questionnaire' as keywords. We included studies that evaluated the measurement properties of self-report questionnaires assessing PA. Article selection, data extraction and quality assessment were performed by two independent reviewers. The quality and results of the studies were evaluated using the Quality Assessment of Physical Activity Questionnaires (QAPAQ) checklist. Construct validity, reliability and responsiveness were rated as positive, negative or indeterminate, depending on the methods and results. We included 85 (versions of) questionnaires. Overall, the quality of the studies assessing measurement properties of PA questionnaires was rather poor. Information on content validity was mostly lacking. Construct validity was assessed in 76 of the questionnaires, mostly by correlations with accelerometer data, maximal oxygen uptake or activity diaries. Fifty-one questionnaires were tested for reliability. Only a few questionnaires had sufficient construct validity and reliability, but these need to be further validated. Responsiveness was studied for only two questionnaires and was poor. There is a clear lack of standardization of PA questionnaires, resulting in many variations of questionnaires. No questionnaire or type of questionnaire for assessing PA was superior and therefore could not be strongly recommended above others. In the future, more attention should be paid to the methodology of studies assessing measurement properties of PA questionnaires and the quality of reporting.


Weijerman M.E.,VU University Amsterdam | De Winter J.P.,Spaarne Hospital
European Journal of Pediatrics | Year: 2010

Down syndrome (DS) is one of the most common chromosomal abnormalities. Because of medical advances and improvements in overall medical care, the median survival of individuals with DS has increased considerably. This longer life expectancy requires giving the necessary care to the individual with DS over their total longer lifespan. DS medical guidelines are designed for the optimal care of the child in whom a diagnosis of DS has been confirmed. We present an overview of the most important issues related to children with DS based on the most relevant literature currently available. © 2010 The Author(s).


van der Sluis S.,Medical Center | Posthuma D.,Medical Center | Posthuma D.,Erasmus Medical Center | Dolan C.V.,University of Amsterdam | Dolan C.V.,VU University Amsterdam
PLoS Genetics | Year: 2013

To date, the genome-wide association study (GWAS) is the primary tool to identify genetic variants that cause phenotypic variation. As GWAS analyses are generally univariate in nature, multivariate phenotypic information is usually reduced to a single composite score. This practice often results in loss of statistical power to detect causal variants. Multivariate genotype-phenotype methods do exist but attain maximal power only in special circumstances. Here, we present a new multivariate method that we refer to as TATES (Trait-based Association Test that uses Extended Simes procedure), inspired by the GATES procedure proposed by Li et al (2011). For each component of a multivariate trait, TATES combines p-values obtained in standard univariate GWAS to acquire one trait-based p-value, while correcting for correlations between components. Extensive simulations, probing a wide variety of genotype-phenotype models, show that TATES's false positive rate is correct, and that TATES's statistical power to detect causal variants explaining 0.5% of the variance can be 2.5-9 times higher than the power of univariate tests based on composite scores and 1.5-2 times higher than the power of the standard MANOVA. Unlike other multivariate methods, TATES detects both genetic variants that are common to multiple phenotypes and genetic variants that are specific to a single phenotype, i.e. TATES provides a more complete view of the genetic architecture of complex traits. As the actual causal genotype-phenotype model is usually unknown and probably phenotypically and genetically complex, TATES, available as an open source program, constitutes a powerful new multivariate strategy that allows researchers to identify novel causal variants, while the complexity of traits is no longer a limiting factor. © 2013 van der Sluis et al.


OBJECTIVE:: The authors first examined the influence of moderate to severe congenital hearing impairment (CHI) on the correctness of samples of elicited spoken language. Then, the authors used this measure as an indicator of linguistic proficiency and examined its effect on performance in language reception, independent of bottom-up auditory processing. DESIGN:: In groups of adults with normal hearing (NH, n = 22), acquired hearing impairment (AHI, n = 22), and moderate to severe CHI (n = 21), the authors assessed linguistic proficiency by analyzing the morphosyntactic correctness of their spoken language production. Language reception skills were examined with a task for masked sentence recognition in the visual domain (text), at a readability level of 50%, using grammatically correct sentences and sentences with distorted morphosyntactic cues. The actual performance on the tasks was compared between groups. RESULTS:: Adults with CHI made more morphosyntactic errors in spoken language production than adults with NH, while no differences were observed between the AHI and NH group. This outcome pattern sustained when comparisons were restricted to subgroups of AHI and CHI adults, matched for current auditory speech reception abilities. The data yielded no differences between groups in performance in masked text recognition of grammatically correct sentences in a test condition in which subjects could fully take advantage of their linguistic knowledge. Also, no difference between groups was found in the sensitivity to morphosyntactic distortions when processing short masked sentences, presented visually. CONCLUSIONS:: These data showed that problems with the correct use of specific morphosyntactic knowledge in spoken language production are a long-term effect of moderate to severe CHI, independent of current auditory processing abilities. However, moderate to severe CHI generally does not impede performance in masked language reception in the visual modality, as measured in this study with short, degraded sentences. Aspects of linguistic proficiency that are affected by CHI thus do not seem to play a role in masked sentence recognition in the visual modality. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Kroeze R.J.,VU University Amsterdam
Methods in molecular biology (Clifton, N.J.) | Year: 2011

Adipose stem cell preparations, either obtained as a freshly isolated so-called stromal vascular fraction (SVF) or as cells cultured to homogeneity and then referred to as adipose stem cells (ASCs), have found widespread use in a broad variety of studies on tissue engineering and regenerative medicine applications, including bone repair.For newcomers within the field, but also for established research laboratories having up to 10 years of expertise in this research area, it may be convenient to strive for, and use consensus protocols (1) for studying the osteogenic differentiation potential of ASC preparations in vitro, and (2) for osteogenic induction regimes for in vivo implementation. To assist in achieving this goal, this chapter describes various step-by-step osteogenic differentiation protocols for adipose-derived stem cell populations (SVF as well as ASCs) currently applied within our laboratory, with particular emphasis on protocols aimed at intra-operative use. The protocols describe the use of inducing compounds, including the bone morphogenetic proteins (BMPs), 1,25-dihydroxyvitamin-D3, and polyamines, as well as methods and parameters for evaluating the level of differentiation achieved.We would appreciate receiving feedback on the protocols described; this will facilitate the development of consensus protocols, which in turn will allow better comparison of data sets generated by different research groups. This continuing standardization, which might be reported on at international meetings like those of IFATS ( http://www.IFATS.org ), might be of benefit for the whole ASC research community.


Instructors in higher education perform some instructional tasks much more often using a learning management system (LMS) tool than other tasks. In studies that aim to explain these differences, the Technology Acceptance Model (TAM) perspective is missing. In this study, an adapted, task-level TAM questionnaire was used to measure task importance, task performance, LMS usefulness, LMS ease of use, and intention to use an LMS for 18 different instructional tasks among 180 instructors at a Dutch research university. The results show that low intention to use an LMS can be explained by (1) low task importance or performance, and/or (2) low LMS usefulness, and/or (3) low LMS ease of use level. The LMS tools and tasks within each of the three groups were not related substantively. This raises a question regarding whether an instructor's LMS intention level can best be explained by the combination of a specific tool, a specific instructional task, and a specific user interface. © 2013 Elsevier Ltd. All rights reserved.


Relapses after initial successful treatment in acute myeloid leukemia are thought to originate from the outgrowth of leukemic stem cells. Their flow cytometrically assessed frequency is of importance for relapse prediction and is therefore assumed to be implemented in future risk group profiling. Since current detection methods are complex, time- and bone marrow consuming (multiple-tubes approach), it would be advantageous to have a broadly applicable approach that enables to quantify leukemia stem cells both at diagnosis and follow-up. We compared 15 markers in 131 patients concerning their prevalence, usefulness and stability in CD34+CD38- leukemic stem cell detection in healthy controls, acute myeloid leukemia diagnosis and follow-up samples. Ultimately, we designed a single 8-color detection tube including common markers CD45, CD34 and CD38, and specific markers CD45RA, CD123, CD33, CD44 and a marker cocktail (CLL-1/TIM-3/CD7/CD11b/CD22/CD56) in one fluorescence channel. Validation analyses in 31 patients showed that the single tube approach was as good as the multiple-tube approach. Our approach requires the least possible amounts of bone marrow, and is suitable for multi-institutional studies. Moreover, it enables detection of leukemic stem cells both at time of diagnosis and follow-up, thereby including initially low-frequency populations emerging under therapy pressure.Leukemia advance online publication, 6 October 2015; doi:10.1038/leu.2015.252. © 2015 Macmillan Publishers Limited


As relapses are common in acute myeloid leukemia (AML), early relapse prediction is of high importance. Although conventional minimal residual disease (MRD) measurement is carried out in bone marrow (BM), peripheral blood (PB) would be an advantageous alternative source. This study aims to investigate the specificity of leukemia-associated immunophenotypes used for MRD detection in blood samples. Consistency of PB MRD as compared with BM MRD was determined in flow cytometric data of 205 paired BM and PB samples of 114 AML patients. A significant correlation was found between PB and BM MRD (r=0.67, P<0.001), while median PB MRD percentage was factor 4-5 lower compared with BM MRD. Primitive blast (CD34+/CD117+/CD133+) frequency was significantly lower in PB (median factor 23.7), indicating that PB MRD detection is more specific than BM. Cumulative incidence of relapse 1 year after induction therapy was 29% for PB MRD-negative and 89% for PB MRD-positive patients (P<0.001). Three-year OS was 52% for MRD-negative and 15% for MRD-positive patients (P=0.034). Similar differences were found after consolidation therapy. As PB MRD appeared to be an independent predictor for response duration, the highly specific PB MRD assay may have a prominent role in future MRD assessment in AML.Leukemia advance online publication, 6 October 2015; doi:10.1038/leu.2015.255. © 2015 Macmillan Publishers Limited


Lago P.,VU University Amsterdam
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

Carbon emission of IT is an issue. ICT energy consumption is expected to grow by 73% (instead of the originally targeted 26%) until 2020, and the service sector alone counts for 70% of the European economy. Energy consumption is a combination of what we use, and how we use it. Most green initiatives look at what types of devices do consume energy, and try to optimize their up-time as such. Few initiatives, though, measure how do software systems actually use these devices, with the goal of optimizing consumption of devices and computing resources. Basic research is needed to address this software optimization problem. The proposed approach is to make visible the environmental impact of software services by measuring it. In this way, we will become aware of the amount of energy needed by our software, and hence learn how to target software optimization where it is mostly needed. As a first step in this direction, in this paper we define three main problem areas to realize green service-based applications, and propose a service-oriented approach to address them. Thanks to that we can bring clarity in what entails managing and developing green software according to environmental strategies. © 2011 Springer-Verlag.


Sitter R.,VU University Amsterdam
SIAM Journal on Computing | Year: 2014

The generalized 2-server problem is an online optimization problem where a sequence of requests has to be served at minimal cost. Requests arrive one by one and need to be served instantly by at least one of two servers. We consider the general model where the cost function of the two servers may be different. Formally, each server moves in its own metric space and a request consists of one point in each metric space. It is served by moving one of the two servers to its request point. Requests have to be served without knowledge of future requests. The objective is to minimize the total traveled distance. The special case where both servers move on the real line is known as the CNN problem. We show that the generalized work function algorithm, WFA?, is constant competitive for the generalized 2-server problem. Further, we give an outline for a possible extension to k ≥ 2 servers and discuss the applicability of our techniques and of the work function algorithm in general. We conclude with a discussion on several open problems in online optimization. © 2014 Society for Industrial and Applied Mathematics.


Tastepe C.S.,VU University Amsterdam
The International journal of oral & maxillofacial implants | Year: 2012

To evaluate the air powder abrasive treatment as an implant surface cleaning method for peri-implantitis based on the existing literature. A PubMed search was conducted to find articles that reported on air powder abrasive treatment as an implant surface cleaning method for peri-implantitis. The studies evaluated cleaning efficiency and surface change as a result of the method. Furthermore, cell response toward the air powder abrasive-treated discs, reosseointegration, and clinical outcome after treatment is also reported. The PubMed search resulted in 27 articles meeting the inclusion criteria. In vitro cleaning efficiency of the method is reported to be high. The method resulted in minor surface changes on titanium specimens. Although the air powder abrasive-treated specimens showed sufficient levels of cell attachment and cell viability, the cell response decreased compared with sterile discs. Considerable reosseointegration between 39% and 46% and improved clinical parameters were reported after treatment when applied in combination with surgical treatment. The results of the treatment are influenced by the powder type used, the application time, and whether powder was applied surgically or nonsurgically. The in vivo data on air powder abrasive treatment as an implant surface cleaning method is not sufficient to draw definitive conclusions. However, in vitro results allow the clinician to consider the method as a promising option for implant surface cleaning in peri-implantitis treatment.


Bakker B.L.G.,VU University Amsterdam | Ji C.-R.,North Carolina State University
Progress in Particle and Nuclear Physics | Year: 2014

With the acceptance of QCD as the fundamental theory of strong interactions, one of the basic problems in the analysis of nuclear phenomena became how to consistently account for the effects of the underlying quark/gluon structure of nucleons and nuclei. Besides providing more detailed understanding of conventional nuclear physics, QCD may also point to novel phenomena accessible by new or upgraded nuclear experimental facilities. We review several interesting applications of QCD to nuclear physics. © 2013 Elsevier B.V. All rights reserved.


Kluytmans J.A.J.W.,VU University Amsterdam
Clinical Microbiology and Infection | Year: 2010

The widespread use of antimicrobial agents, in combination with insufficient infection control measures, is the main driver of the current pandemic of antimicrobial resistance in human pathogens. The use of antimicrobials in food animal production also contributes, because resistant organisms and resistance genes can spread from animals to humans by direct contact or through the food chain. An important, traditionally human, pathogen, methicillin-resistant Staphylococcus aureus (MRSA), is currently endemic in many hospitals around the world and has also emerged in the community. Recently, a new reservoir of MRSA has been identified in food production animals and people in contact with these animals. This involves a specific clone, multilocus sequence type 398 (ST398), which has spread extensively among animals. ST398 has also been found in up to 11.9% of retail meat samples in several surveys from different parts of the world, posing a potential threat to human health. © 2009 The Author. Journal Compilation © 2009 European Society of Clinical Microbiology and Infectious Diseases.


Van Hooff J.C.,VU University Amsterdam | Ford R.M.,Griffith University
Brain Research | Year: 2011

The present study examined the electrophysiological correlates of intentional forgetting using the item-method directed forgetting paradigm. Participants (N = 23) studied a series of words each followed by either a "remember" cue (TBR) or a "forget" cue (TBF) and then undertook an old/new recognition memory test for which they were requested to endorse studied items regardless of original remember/forget status. Event-related potentials time locked to the cues were examined as a function of subsequent recognition-memory accuracy. Results showed that TBR and TBF cues elicited Dm or subsequent memory effects that differed in scalp distribution and polarity, suggesting activation of fundamentally different encoding operations for the respective sets of items. Additionally, analyses that examined the processes underlying successful implementations of intentions to forget (i.e., TBF-miss vs. TBR-miss) and intentions to remember (i.e., TBR-hit vs. TBF-hit) revealed that in case of unwanted information a frontal inhibition mechanism is engaged to stop processes associated with intentional memory formation. These results counter the possibility that directed forgetting reflects only the more elaborate encoding of TBR than TBF words and, instead, implicate the existence of an active inhibitory mechanism directed at TBF words once the forget cue is presented. © 2011 Elsevier B.V.


Batenburg A.,VU University Amsterdam | Das E.,Radboud University Nijmegen
Journal of Medical Internet Research | Year: 2014

Background: Due to mixed findings in research on the effect of online peer-to-peer support on psychological well-being, there is a need for studies explaining why and when online support communities are beneficial for cancer patients. Objective: Previous studies have typically not taken into account individual coping differences, despite the fact that patients have different strategies to cope with cancer-related emotions. In the current study, it was predicted that the effects of online support group participation would partly depend on patients' ability to cope with thoughts and emotions regarding the illness. Methods: For this study, 184 Dutch breast cancer patients filled out a questionnaire assessing activity within a peer-led online support community, coping with emotions and thoughts regarding the illness (cognitive avoidance, emotional processing, and expression) and psychological well-being (depression, breast cancer-related concerns, and emotional well-being). Of these, 163 patients were visiting an online peer-led support community. Results: Results showed interactions of the intensity of support group participation and coping style on psychological well-being. Specifically, we found an interaction of online activity and emotional expression on depression (beta=-.17, P=.030), a marginally significant interaction of online activity and emotional expression on emotional well-being (beta=.14, P=.089), and an interaction of online activity and cognitive avoidance on breast cancer-related concerns (beta=.15, P=.027). For patients who actively dealt with their emotions and thoughts, active online support group participation was positively related to psychological well-being. For patients high on avoidance of illness-related thoughts or low on emotional expression, active participation was negatively related to measures of well-being. Conclusions: The current study revealed the role of individual differences in coping in online support group participation. Results suggest that breast cancer patients' ability to cope with emotions and thoughts regarding the illness influence the relationship between online support group participation and psychological well-being.


van Wilgen C.P.,University of Groningen | Verhagen E.A.L.M.,VU University Amsterdam
Journal of Science and Medicine in Sport | Year: 2012

Objectives: Preventive approaches for overuse injuries in sports will be more successful when synchronised with athletes' and coaches' beliefs. We interviewed athletes and coaches in order to better characterize their beliefs about the definition of an overuse injury, as well as the intrinsic and extrinsic risk factors that underlie overuse injuries. Design: Qualitative study using in-depth interviews in athletes and coaches of different sports. Methods: Athletes who had experienced overuse injuries and coaches who trained athletes who had sustained overuse injuries from sports clubs were invited to participate through interview. We explored each participant's individual definition of an overuse injury and the beliefs concerning the intrinsic and extrinsic risk factors concerning overuse injuries were explored. Results: After nine athletes and nine coaches, sample size saturation was confirmed. Athletes and coaches integrate somatic as well as psychological and sociological factors into the definition of and risk factors for overuse injuries. Intrinsic factors for an overuse injury were related to physical factors, technique, psychological factors and heredity. The extrinsic factors were related to situational, social and training factors, as well as the individual coach. Conclusions: Athletes and coaches have a holistic view on the definition of overuse injuries, and the intrinsic and extrinsic risk factors for overuse injuries. If preventive approaches for overuse injuries are developed and implemented, they should incorporate physical factors, as well as incorporate psychological and social factors. Based on the input of coaches and athletes, the latter are important risk factors for overuse injuries. © 2011 Sports Medicine Australia.


Background: Most registration trials in rheumatoid arthritis (RA) include a placebo arm in the setting of an incomplete response to disease-modifying antirheumatic treatment (DMARD-IR). A minimum duration of 6 months is required despite serious methodological and ethical shortcomings. Objective: To study whether a 3-month placebo period is sufficient to prove efficacy. Methods: Meta-analysis of placebo- or active control trials of biological agents in DMARD-IR RA, comparing the contrast in ACR response between experimental and control groups at 3 and 6 months. Results: Twenty trials yielded 15 placebo and 18 active control contrasts (>10 000 patients). At 3 months active treatment showed a highly significant contrast with placebo for ACR20 and ACR50 in every instance. As all groups improved further the mean contrast at 6 months was unchanged. For ACR70 the contrast was clearly greater at 6 months owing to further improvement only in the experimental groups. In active control trials contrasts were smaller, and for ACR50 and ACR70 these decreased somewhat owing to "catch-up" responses in the control groups. Conclusion: The placebo phase of registration trials for RA can be limited to 3 months. An accompanying viewpoint proposes that patients receiving placebo should then be switched to standard of care, allowing a more valid and comprehensive assessment, including safety.


Ansink E.,VU University Amsterdam
Ecological Economics | Year: 2010

Using the Heckscher-Ohlin trade model, I refute two prominent but incorrect claims on virtual water trade. These claims are that virtual water trade (i) levels uneven water distribution, and (ii) reduces the potential for water conflict. Both claims are based on an incorrect understanding of comparative advantage in the production of water-intensive goods. The results show that both claims only hold under certain conditions, but do not necessarily follow from the Heckscher-Ohlin trade model. © 2010 Elsevier B.V.


Proper function of the neurovasculature is required for optimal brain function and preventing neuroinflammation and neurodegeneration. Within this review, we discuss alterations of the function of the blood-brain barrier in neurologic disorders such as multiple sclerosis, epilepsy, and Alzheimer's disease and address potential underlying mechanisms. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.


Lindau D.,Nijmegen Center for Molecular Life science | Gielen P.,Nijmegen Center for Molecular Life science | Kroesen M.,Nijmegen Center for Molecular Life science | Wesseling P.,Radboud University Nijmegen | And 2 more authors.
Immunology | Year: 2013

Myeloid-derived suppressor cells (MDSC) and regulatory T (Treg) cells are major components of the immune suppressive tumour microenvironment (TME). Both cell types expand systematically in preclinical tumour models and promote T-cell dysfunction that in turn favours tumour progression. Clinical reports show a positive correlation between elevated levels of both suppressors and tumour burden. Recent studies further revealed that MDSCs can modulate the de novo development and induction of Treg cells. The overlapping target cell population of Treg cells and MDSCs is indicative for the importance and flexibility of immune suppression under pathological conditions. It also suggests the existence of common pathways that can be used for clinical interventions aiming to manipulate the TME. Elimination or reprogramming of the immune suppressive TME is one of the major current challenges in immunotherapy of cancer. Interestingly, recent findings suggest that natural killer T (NKT) cells can acquire the ability to convert immunosuppressive MDSCs into immunity-promoting antigen-presenting cells. Here we will review the cross-talk between MDSCs and other immune cells, focusing on Treg cells and NKT cells. We will consider its impact on basic and applied cancer research and discuss how targeting MDSCs may pave the way for future immunocombination therapies. © 2012 Nijmegen Centre for Molecular Life Sciences Immunology © 2012 Blackwell Publishing Ltd.


Peters G.J.,VU University Amsterdam
Therapeutic Advances in Medical Oncology | Year: 2015

Fluoropyrimidines form the mainstay in treatment of gastrointestinal malignancies. For decades 5-fluorouracil (5FU), was the major fluoropyrimidine. Currently it is usually given in a combination with leucovorin and oxaliplatin, i.e. FOLFOX, or irinotecan, i.e. FOLFIRI, or all three, i.e. FOLFIRINOX, but gradually it has been replaced by oral fluoropyrimidine prodrug formulations, such as tegafur-uracil and S-1 (both contain ftorafur), and capecitabine (Xeloda®). Novel drugs such as the antivascular endothelial growth factor antibody, bevacizumab, and the anti-epidermal growth factor receptor antibody, cetuximab, are often combined with one of these treatment options. However, when resistance emerged, no alternatives were available. TAS-102, a combination of trifluorothymidine and the thymidine phosphorylase inhibitor TPI in a 1:0.5 ratio, is a novel oral formulation, which is active in 5FU-resistant models, both in vitro and in xenograft models. In addition to inhibition of thymidylate synthase, the major mechanism of action of classical fluoropyrimidines, TAS-102's major mechanism of action is incorporation into DNA, thereby causing DNA damage. TAS-102 also follows an alternative activation pathway via thymidine kinase, and is not a substrate for dihydropyrimidine dehydrogenase. All together this explains the efficacy in 5FU-resistant models. In early clinical studies, the twice-daily schedule (5 days on, 2 days rest) for 2 weeks every 4 weeks, led to a significant disease control rate in various malignancies. This schedule showed consistent activity in two randomized trials on fluoropyrimidine refractory colorectal cancer patients, reflected by an increase of 2-3 months in overall survival in the TAS-102 group compared with placebo. Considering the impressive preclinical potential of various combinations TAS-102 has the promise to become an alternative for 5FU-resistant cancer. © SAGE Publications.


Vermeulen L.,Center for Experimental Molecular Medicine | Meijer G.A.,VU University Amsterdam
Nature Reviews Gastroenterology and Hepatology | Year: 2015

Colorectal cancer (CRC) is considered a heterogeneous disease, both regarding pathogenesis and clinical behaviour. Four decades ago, the adenoma-carcinoma pathway was presented as the main pathway towards CRC, a conclusion that was largely based on evidence from observational morphological studies. This concept was later substantiated at the genomic level. Over the past decade, evidence has been generated for alternative routes in which CRC might develop, in particular the serrated neoplasia pathway. Providing indisputable evidence for the neoplastic potential of serrated polyps has been difficult. Reasons include the absence of reliable longitudinal observations on individual serrated lesions that progress to cancer, a shortage of available animal models for serrated lesions and challenging culture conditions when generating organoids of serrated lesions for in vitro studies. However, a growing body of circumstantial evidence has been accumulated, which indicates that ≥ 15% of CRCs might arise through the serrated neoplasia pathway. An even larger amount of post-colonoscopy colorectal carcinomas (carcinomas occurring within the surveillance interval after a complete colonoscopy) have been suggested to originate from serrated polyps. The aim of this Review is to assess the current status of the serrated neoplasia pathway in CRC and highlight clinical implications. © 2015 Macmillan Publishers Limited.


Wattjes M.P.,VU University Amsterdam
International psychogeriatrics / IPA | Year: 2011

Clinical neuroimaging is increasingly being used in the diagnosis of neurodegenerative diseases and has become one of the most important paraclinical tools in the diagnosis of dementia. According to current guidelines, neuroimaging, preferably magnetic resonance imaging (MRI), should be performed at least once during the diagnostic work-up of patients with suspected or definite dementia. MRI is helpful in identifying or excluding potentially treatable causes of dementia; however, these account only for a small proportion of dementias. In addition, MRI is able to support the clinical diagnosis in a memory clinic setting by identifying certain patterns of atrophy and vascular damage. Visual rating scales are well-established methods in the clinical routine for the assessment and quantification of regional/global cortical atrophy, hippocampal atrophy and vascular damage. In addition, MRI is able to detect certain aspects of pathology associated with dementia, such as cerebral microbleeds which are related to cerebral amyloid angiopathy and Alzheimer pathology. This review paper aims to give an overview of the application of structural MRI in the diagnostic procedure for memory clinic patients in terms of excluding and supporting the diagnosis of various diseases associated with dementia.


Poater J.,VU University Amsterdam | Sola M.,University of Girona | Vinas C.,Institute Of Ciencies Dels Materials Of Barcelona | Teixidor F.,Institute Of Ciencies Dels Materials Of Barcelona
Angewandte Chemie - International Edition | Year: 2014

A bridge between classical organic polycyclic aromatic hydrocarbons (PAH) and closo borohydride clusters is established by showing that they share a common origin regulated by the number of valence electrons in an electronic confined space. Application of the proposed electronic confined space analogy (ECSA) method to archetypal PAHs leads to the conclusion that the 4n+2 Wade-Mingos rule for three-dimensional closo boranes is equivalent to the (4n+2)π Hückel rule for two-dimensional PAHs. More importantly, use of ECSA allows design of new interesting fused closo boranes which can be a source of inspiration for synthetic chemists. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Barkhof F.,VU University Amsterdam | Haller S.,University of Geneva | Rombouts S.A.R.B.,Leiden University
Radiology | Year: 2014

Resting-state (RS) functional magnetic resonance (MR) imaging constitutes a novel paradigm that examines spontaneous brain function by using blood oxygen level-dependent contrast in the absence of a task. Spatially distributed networks of temporal synchronization can be detected that can characterize RS networks (RSNs). With a short acquisition time of less than 10 minutes, RS functional MR imaging can be applied in special populations such as children and patients with dementia. Some RSNs are already present in utero, while others mature in childhood. Around 10 major RSNs are consistently found in adults, but their exact spatial extent and strength of coherence are affected by physiologic parameters and drugs. Though the acquisition and analysis methods are still evolving, new disease insights are emerging in a variety of neurologic and psychiatric disorders. The default mode network is affected in Alzheimer disease and various other diseases of cognitive impairment. Alterations in RSNs have been identified in many diseases, in the absence of evident structural modifications, indicating a high sensitivity of the method. Moreover, there is evidence of correlation between RSN alterations and disease progression and severity. However, different diseases often affect the same RSN, illustrating the limited specificity of the findings. This suggests that neurologic and psychiatric diseases are characterized by altered interactions between RSNs and therefore the whole brain should be examined as an integral network (with subnetworks), for example, using graph analysis. A challenge for clinical applications of RS functional MR imaging is the potentially confounding effect of aging, concomitant vascular diseases, or medication on the neurovascular coupling and consequently the functional MR imaging response. Current investigation combines RS functional MR imaging and other methods such as electroencephalography or magnetoencephalography to better understand the vascular and neuronal contributions to alterations in functional connectivity. © RSNA, 2014.


Schlager W.,VU University Amsterdam | Purkis S.,Nova Southeastern University
Sedimentology | Year: 2015

Reticulate ridges of reefs and sediment in Holocene lagoons are usually interpreted as an inheritance of antecedent karst topography. Satellite imagery served as a template for integrating plan-view geometry with published data from coring, drilling and seismic surveys to test the antecedent-karst hypothesis. The link between karst morphology and overlying reef patterns can be demonstrated convincingly for a rather limited number of examples, particularly those on a substrate of tower karst with high relief. On very young limestones, doline karst with reticulate patterns develops very slowly because of the high porosity. Moreover, karst control can be ruled out for the significant number of reticulate reefs that are founded on terrigenous sediment or on demonstrably flat pre-Holocene rock surfaces. One likely cause of reticulate patterns is biotic self-organization that has been shown to generate reticulate and labyrinthic patterns of mussel beds on tidal flats and tree cover of arid ecosystems. Another pathway to reticulate reefs may be the colonization of reticulate hydrodynamic bedforms by reef builders. Thus, reticulate patterns of Holocene reef-sediment ridges are highly ambiguous indicators of antecedent karst. © 2014 International Association of Sedimentologists.


Pang X.,Technical University of Delft | Visser T.D.,Technical University of Delft | Visser T.D.,VU University Amsterdam
Optics Express | Year: 2013

The Gouy phase, sometimes called the focal phase anomaly, is the curious effect that in the vicinity of its focus a diffracted field, compared to a non-diffracted, converging spherical wave of the same frequency, undergoes a rapid phase change by an amount of π . We theoretically investigate the phase behavior and the polarization ellipse of a strongly focused, radially polarized beam. We find that the significant variation of the state of polarization in the focal region, is a manifestation of the different Gouy phases that the two electric field components undergo. © 2013 Optical Society of America.


Romero E.,VU University Amsterdam
Nature Physics | Year: 2014

The crucial step in the conversion of solar to chemical energy in photosynthesis takes place in the reaction centre, where the absorbed excitation energy is converted into a stable charge-separated state by ultrafast electron transfer events. However, the fundamental mechanism responsible for the near-unity quantum efficiency of this process is unknown. Here we elucidate the role of coherence in determining the efficiency of charge separation in the plant photosystem II reaction centre by comprehensively combining experiment (two-dimensional electronic spectroscopy) and theory (Redfield theory). We reveal the presence of electronic coherence between excitons as well as between exciton and charge-transfer states that we argue to be maintained by vibrational modes. Furthermore, we present evidence for the strong correlation between the degree of electronic coherence and efficient and ultrafast charge separation. We propose that this coherent mechanism will inspire the development of new energy technologies.


Van Der Steen J.T.,VU University Amsterdam
Journal of Alzheimer's Disease | Year: 2010

Death with dementia is increasingly common. Although prognostication is difficult, it is an incurable life-limiting illness for which palliative care for the patient is often appropriate. Dementia patients are otherwise at risk of overtreatment with burdensome and possibly non-beneficial interventions and undertreatment of symptoms. Although recent studies indicate encouraging trends of improved palliative care, little evidence supports effectiveness of specific treatments. As of January 2010, at least 45 studies, almost all performed after 2000, have reported on treatment, comfort, symptom burden, and families' satisfaction with care. Over half (25; 56%) of these studies were in US settings, and most were small or retrospective. Few randomized trials and prospective observational studies have been performed so far, but several promising studies have been completed recently or are underway in various countries. Guidelines for care and treatment, still mostly consensus-based, support the benefits of advance care planning, continuity of care, and family and practitioner education. Assessment tools for pain, prognosis, and family evaluations of care have been developed and some have been shown to be effective in clinical practice. With increasing numbers of well-designed, large-scale studies, research in the next decade may result in better evidence-based guidelines and practice. © 2010 IOS Press and the authors. All rights reserved.


Koole G.,VU University Amsterdam | Pot A.,CCmath
Operations Research | Year: 2011

We consider an inbound call center with a fixed reward per call and communication and agent costs. By controlling the number of lines and the number of agents, we can maximize the profit. Abandonments are included in our performance model. Monotonicity results for the maximization problem are obtained, which lead to an efficient optimization procedure. We give a counterexample to the concavity in the number of agents, which is equivalent to saying that the law of diminishing returns does not hold. Numerical results are given. Subject classifications: call centers; monotonicity. Area of review: Manufacturing, Service, and Supply Chain Operations. History: Received July 2008; revisions received January 2009, August 2009; accepted October 2009. © 2011 INFORMS.


Rubinstein S.M.,VU University Amsterdam
Cochrane database of systematic reviews (Online) | Year: 2011

Many therapies exist for the treatment of low-back pain including spinal manipulative therapy (SMT), which is a worldwide, extensively practiced intervention. To assess the effects of SMT for chronic low-back pain. An updated search was conducted by an experienced librarian to June 2009 for randomised controlled trials (RCTs) in CENTRAL (The Cochrane Library 2009, issue 2), MEDLINE, EMBASE, CINAHL, PEDro, and the Index to Chiropractic Literature.   RCTs which examined the effectiveness of spinal manipulation or mobilisation in adults with chronic low-back pain were included. No restrictions were placed on the setting or type of pain; studies which exclusively examined sciatica were excluded. The primary outcomes were pain, functional status and perceived recovery. Secondary outcomes were return-to-work and quality of life. Two review authors independently conducted the study selection, risk of bias assessment and data extraction. GRADE was used to assess the quality of the evidence. Sensitivity analyses and investigation of heterogeneity were performed, where possible, for the meta-analyses. We included 26 RCTs (total participants = 6070), nine of which had a low risk of bias. Approximately two-thirds of the included studies (N = 18) were not evaluated in the previous review. In general, there is high quality evidence that SMT has a small, statistically significant but not clinically relevant, short-term effect on pain relief (MD: -4.16, 95% CI -6.97 to -1.36) and functional status (SMD: -0.22, 95% CI -0.36 to -0.07) compared to other interventions. Sensitivity analyses confirmed the robustness of these findings. There is varying quality of evidence (ranging from low to high) that SMT has a statistically significant short-term effect on pain relief and functional status when added to another intervention. There is very low quality evidence that SMT is not statistically significantly more effective than inert interventions or sham SMT for short-term pain relief or functional status. Data were particularly sparse for recovery, return-to-work, quality of life, and costs of care. No serious complications were observed with SMT. High quality evidence suggests that there is no clinically relevant difference between SMT and other interventions for reducing pain and improving function in patients with chronic low-back pain. Determining cost-effectiveness of care has high priority. Further research is likely to have an important impact on our confidence in the estimate of effect in relation to inert interventions and sham SMT, and data related to recovery.


Van Der Burg L.R.A.,Maastricht University | Ter Wee M.M.,VU University Amsterdam | Boonen A.,Maastricht University
Annals of the Rheumatic Diseases | Year: 2012

Objectives: To review systematically the effect of biological treatment in patients with ankylosing spondylitis (AS) on three work outcomes: work status, absence from paid work and at-work productivity. Methods: A systematic literature search was performed (Pubmed, Embase, Cochrane Library) to identify relevant articles. Risk of bias of included studies was assessed using the Cochrane guidelines for cohorts and randomised controlled trials (RCTs). Data were extracted using a self-composed data extraction form. Owing to extensive interstudy heterogeneity, narrative summaries were used to present the data. Results: Nine studies were included (six uncontrolled cohorts, one population-controlled cohort and two RCTs) that reported on 39 comparisons. Overall, 961 patients were treated with three different tumour necrosis factor α inhibitors (etanercept, infliximab, adalimumab). For presenteeism and absence from work, most comparisons showed improvement in favour of biological agents, but not all comparisons were statistically significant and they usually concerned before-after analyses. For work status, changes were less often positive, but studies dealt with patients with longstanding AS, lacked power and had a relatively short follow-up. Conclusions: Although trends towards beneficial effects of biological agents in longstanding AS were seen on all work outcomes, the methodological limitations in the studies included hampers clear conclusions. Since the majority of studies were (extensions of) controlled trials, the generalisability of the effect of biological agents on work participation in real life should be further studied in larger (population-controlled) studies. The effect of biological agents in patients with early disease has not yet been examined.


Stam C.J.,VU University Amsterdam
Nature Reviews Neuroscience | Year: 2014

Modern network science has revealed fundamental aspects of normal brain-network organization, such as small-world and scale-free patterns, hierarchical modularity, hubs and rich clubs. The next challenge is to use this knowledge to gain a better understanding of brain disease. Recent developments in the application of network science to conditions such as Alzheimer's disease, multiple sclerosis, traumatic brain injury and epilepsy have challenged the classical concept of neurological disorders being either 'local' or 'global', and have pointed to the overload and failure of hubs as a possible final common pathway in neurological disorders. © 2014 Macmillan Publishers Limited. All rights reserved.


Ang C.W.,VU University Amsterdam
Pediatric Infectious Disease Journal | Year: 2016

We describe an 8 month old girl with diarrhea, urosepsis and hemolytic uremic syndrome caused by E. coli. Typing of cultured E. coli strains from urine and blood revealed the presence of virulence factors from multiple pathotypes of E. coli. This case exemplifies the genome plasticity of E. coli and the resulting heteropathogenic strains. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Langer C.J.,University of Pennsylvania | Mok T.,Chinese University of Hong Kong | Postmus P.E.,VU University Amsterdam
Cancer Treatment Reviews | Year: 2013

The prognosis for patients with relapsed/progressive non-small cell lung cancer (NSCLC) remains poor. For first-line therapy, a number of platinum-based regimens are standard; second-line therapies include single-agent docetaxel, pemetrexed, and erlotinib. Treatment options for patients whose tumors have failed to respond to two or more conventional chemotherapy regimens are limited, with erlotinib, which targets the epidermal growth factor receptor, and crizotinib, which targets EML4/ALK, the only agents currently approved in the United States as third-line therapy for patients with advanced/metastatic NSCLC. Among the targeted agents that have undergone evaluation for third-line therapy and beyond are afatinib, apatinib, axitinib, AUY922, pazopanib, sorafenib, sunitinib, and vandetanib. Agents that affect multiple pathways have the potential to provide significant clinical benefits. Identifying molecular characteristics that make tumors more likely to respond to a targeted therapy is crucial. This article reviews the hypotheses and data that provide the rationale for the development of targeted agents for third- and fourth-line treatment of patients with relapsed/refractory NSCLC. © 2012 Elsevier Ltd.


Huisman W.,VU University Amsterdam
British Journal of Criminology | Year: 2013

Recently, Situational Crime Prevention Theory (SCPT) has been proposed as an alternative to offender-based theories of white-collar crime. This paper uses the results of a cross-case analysis of 23 criminal investigations of environmental crime in the Netherlands to explore the fruitfulness of SCPT as a method of scientific study of environmental crime and the development of prevention strategies. This analysis shows that most environmental crimes are crimes of omission, while SCPT is designed for predatory crimes of commission. In addition, while it is concluded that SCPT is helpful in analysing opportunities for environmental crime, it is difficult to draw innovative prevention strategies on the basis of SCPT, since most suggestions have already been covered in contemporary models for environmental regulation. © The Author 2013. Published by Oxford University Press on behalf of the Centre for Crime and Justice Studies (ISTD). All rights reserved.


Korolnek T.,University of Maryland University College | Zhang J.,University of Maryland University College | Beardsley S.,University of Maryland University College | Scheffer G.L.,VU University Amsterdam | Hamza I.,University of Maryland University College
Cell Metabolism | Year: 2014

Several lines of evidence predict that specific pathways must exist in metazoans for the escorted movement of heme, an essential but cytotoxic iron-containing organic ring, within and between cells and tissues, but these pathways remain obscure. In Caenorhabditis elegans, embryonic development is inextricably dependent on both maternally derived heme and environmentally acquired heme. Here, we show that the multidrug resistance protein MRP-5/ABCC5 likely acts as a heme exporter, and targeted depletion of mrp-5 in the intestine causes embryonic lethality. Transient knockdown of mrp5 in zebrafish leads to morphological defects and failure to hemoglobinize red blood cells. MRP5 resides on the plasma membrane and endosomal compartments and regulates export of cytosolic heme. Together, our genetic studies in worms, yeast, zebrafish, and mammalian cells identify a conserved, physiological role for a multidrug resistance protein in regulating systemic heme homeostasis. We envision other MRP family members may play similar unanticipated physiological roles in animal development. © 2014 Elsevier Inc.


Kamphuis P.J.G.H.,Danone Research | Scheltens P.,VU University Amsterdam
Journal of Alzheimer's Disease | Year: 2010

Age-related changes in nutritional status can play an important role in brain functioning. Specific nutrient deficiencies in the elderly, including omega-3 fatty acids, B-vitamins, and antioxidants among others, may exacerbate pathological processes in the brain. Consequently, the potential of nutritional intervention to prevent or delay cognitive impairment and the development of Alzheimer's disease (AD) is a topic of growing scientific interest. This review summarizes epidemiological studies linking specific nutritional deficiencies to mild cognitive impairment (MCI), as well as completed and ongoing nutritional studies in prevention of MCI and AD. Processes that underlie AD pathogenesis include: membrane/synaptic degeneration, abnormal protein processing (amyloid-β, tau), vascular risk factors (hypertension, hypercholesterolemia), inflammation, and oxidative stress. Consideration of mechanistic evidence to date suggests that several nutritional components can effectively counteract these processes, e.g., by promoting membrane formation and synaptogenesis, enhancing memory/behavior, improving endothelial function, and cerebrovascular health. The literature reinforces the need for early intervention in AD and suggests that multi-nutritional intervention, targeting multiple aspects of the neurodegenerative process during the earliest possible phase in the development of the disease, is likely to have the greatest therapeutic potential. © 2010 - IOS Press and the authors.


The prognosis of myelodysplastic syndromes (MDS) is currently estimated by using the revised International Prognostic Scoring System (IPSS-R). Several studies have shown that further refinement of prognostication for MDS can be achieved by adding flow cytometric parameters. However, widespread implementation of flow cytometry for the prognosis of MDS is hampered by complexity of the analysis. Therefore, the aim of this study was to construct a robust and practical flow cytometric score that could be implemented as a routine procedure. To achieve this, bone marrow aspirates of 109 MDS patients were analyzed by flow cytometry. A second cohort consisting of 103 MDS patients was used to validate the MDS flow cytometric score (MFS). The parameters forming the MFS were sideward light scatter and CD117 expression of myeloid progenitor cells and CD13 expression on monocytes. Three MFS risk categories were formed. Patients with MDS and intermediate MFS scores had significantly better overall survival (OS) compared with the patients with high MFS scores. The MFS further refined prognostication within the IPSS-R low-risk category, by identifying patients with worse OS in case of high MFS. In conclusion, a practical three parameter flow cytometric prognostic score was constructed enabling further refinement of prognostication of MDS.Leukemia advance online publication, 4 December 2015; doi:10.1038/leu.2015.295. © 2015 Macmillan Publishers Limited


Figgen D.,Massey University | Koers A.,VU University Amsterdam | Schwerdtfeger P.,Massey University
Angewandte Chemie - International Edition | Year: 2010

(Figure Presented) Small but mighty: An unprecedented large parity-violation energy difference of 0.7 Hz for the N-W stretching frequency of N≡WHCII, which conveniently lies in the CO 2 laser frequency range, is predicted from relativistic density functional theory. This result could lead to the first successful detection of such effects in chiral molecules. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Meredith R.M.,VU University Amsterdam
Neuroscience and Biobehavioral Reviews | Year: 2015

During sensitive and critical periods, the brain undergoes significant plasticity from the level of individual synapses and neuronal networks up to the level of behaviour. Both sensitive and critical periods during neurotypical development of the young animal provide a framework to the early temporally-regulated modifications that occur in the nervous system.In neurodevelopmental disorders (NDD), notably autistic syndromes and intellectual disability, children exhibit developmental delays in motor, social and sensory processes and often miss key developmental milestones. In corresponding genetic NDD mouse models, recent data reveal temporally-regulated and in some cases, transient impairments in many neuronal and behavioural phenotypes during development. However, the mechanisms underlying these impairments in NDDs and their potential links with neurobiological mechanisms governing neurotypical development are not fully investigated. This article highlights the potential for the use of known critical and sensitive periods during vertebrate development to investigate and advance our understanding of the neural bases underlying impairments in these developmental disorders of the nervous system. © 2014 Elsevier Ltd.


Edens B.,Statistics Netherlands | Edens B.,VU University Amsterdam | Hein L.,Wageningen University
Ecological Economics | Year: 2013

In spite of an increasing interest in environmental economic accounting, there is still very limited experience with the integration of ecosystem services and ecosystem capital in national accounts. This paper identifies four key methodological challenges in developing ecosystem accounts: the definition of ecosystem services in the context of accounting, their allocation to institutional sectors; the treatment of degradation and rehabilitation, and valuing ecosystem services consistent with SNA principles. We analyze the different perspectives taken on these challenges and present a number of proposals to deal with the challenges in developing ecosystem accounts. These proposals comprise several novel aspects, including (i) presenting an accounting approach that recognizes that most ecosystems are strongly influenced by people and that ecosystem services depend on natural processes as well as human ecosystem management; and, (ii) recording ecosystem services as either contributions of a private land owner or as generated by a sector 'Ecosystems' depending on the type of ecosystem service. We also present a consistent approach for recording degradation, and for applying monetary valuation approaches in the context of accounting. © 2013 Elsevier B.V.


de Kraker A.,VU University Amsterdam
Environment and History | Year: 2013

This paper looks into the historic storms of coastal Flanders and the south-western part of the Netherlands between 1390 and 1725. High quality information about these weather extremes has been retrieved from administrative documents concerning the annual maintenance of sea walls. Because the period under study deals with non-instrumental storm data, a method has been applied to assess this information, from which a picture emerges of annual storminess and of changing storminess throughout this long time period. Thus, periods of increasing and declining storm frequency can be distinguished. These fluctuations are compared with the storminess of the present period and some consideration is also given to possible links between historic storm frequency and temperature. Finally, attention is paid to the second decade of the eighteenth century, with its unusually high number of gales, and options for further research are explored. © 2013 The White Horse Press.


Rubinstein S.M.,VU University Amsterdam
Cochrane database of systematic reviews (Online) | Year: 2012

Many therapies exist for the treatment of low-back pain including spinal manipulative therapy (SMT), which is a worldwide, extensively practised intervention. This report is an update of the earlier Cochrane review, first published in January 2004 with the last search for studies up to January 2000. To examine the effects of SMT for acute low-back pain, which is defined as pain of less than six weeks duration. A comprehensive search was conducted on 31 March 2011 in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PEDro, and the Index to Chiropractic Literature. Other search strategies were employed for completeness. No limitations were placed on language or publication status. Randomized controlled trials (RCTs) which examined the effectiveness of spinal manipulation or mobilization in adults with acute low-back pain were included. In addition, studies were included if the pain was predominantly in the lower back but the study allowed mixed populations, including participants with radiation of pain into the buttocks and legs. Studies which exclusively evaluated sciatica were excluded. No other restrictions were placed on the setting nor the type of pain. The primary outcomes were back pain, back-pain specific functional status, and perceived recovery. Secondary outcomes were return-to-work and quality of life. SMT was defined as any hands-on therapy directed towards the spine, which includes both manipulation and mobilization, and includes studies from chiropractors, manual therapists, and osteopaths. Two review authors independently conducted the study selection and risk of bias (RoB) assessment. Data extraction was checked by the second review author. The effects were examined in the following comparisons: SMT versus 1) inert interventions, 2) sham SMT, 3) other interventions, and 4) SMT as an additional therapy. In addition, we examined the effects of different SMT techniques compared to one another. GRADE was used to assess the quality of the evidence. Authors were contacted, where possible, for missing or unclear data. Outcomes were evaluated at the following time intervals: short-term (one week and one month), intermediate (three to six months), and long-term (12 months or longer). Clinical relevance was defined as: 1) small, mean difference (MD) < 10% of the scale or standardized mean difference (SMD) < 0.4; 2) medium, MD = 10% to 20% of the scale or SMD = 0.41 to 0.7; and 3) large, MD > 20% of the scale or SMD > 0.7. We identified 20 RCTs (total number of participants = 2674), 12 (60%) of which were not included in the previous review. Sample sizes ranged from 36 to 323 (median (IQR) = 108 (61 to 189)). In total, six trials (30% of all included studies) had a low RoB. At most, three RCTs could be identified per comparison, outcome, and time interval; therefore, the amount of data should not be considered robust. In general, for the primary outcomes, there is low to very low quality evidence suggesting no difference in effect for SMT when compared to inert interventions, sham SMT, or when added to another intervention. There was varying quality of evidence (from very low to moderate) suggesting no difference in effect for SMT when compared with other interventions, with the exception of low quality evidence from one trial demonstrating a significant and moderately clinically relevant short-term effect of SMT on pain relief when compared to inert interventions, as well as low quality evidence demonstrating a significant short-term and moderately clinically relevant effect of SMT on functional status when added to another intervention. In general, side-lying and supine thrust SMT techniques demonstrate a short-term significant difference when compared to non-thrust SMT techniques for the outcomes of pain, functional status, and recovery. SMT is no more effective in participants with acute low-back pain than inert interventions, sham SMT, or when added to another intervention. SMT also appears to be no better than other recommended therapies. Our evaluation is limited by the small number of studies per comparison, outcome, and time interval. Therefore, future research is likely to have an important impact on these estimates. The decision to refer patients for SMT should be based upon costs, preferences of the patients and providers, and relative safety of SMT compared to other treatment options. Future RCTs should examine specific subgroups and include an economic evaluation.


Huitema D.,VU University Amsterdam | Meijerink S.,Radboud University Nijmegen
Ecology and Society | Year: 2010

This special feature aims to further our understanding of the way in which transitions occur in water management. We contend that if we want to understand such transitions, we need to understand policy change and its opposite, policy stability. These issues have attracted considerable academic attention. Our interest is, however, very specific and thereby unique: we review the role that (groups of) individuals play in the process of preparing, instigating, and implementing policy change. In this article, a review of the literature on policy change provides the basis from which we extract a set of strategies which are available to policy entrepreneurs. The questions for the rest of this special feature are first, can we detect the influence of policy entrepreneurs in actual cases of major policy change, and second, which strategies have they actually used to affect policy change? © 2010 by the author(s).


van Marwijk H.,VU University Amsterdam
Cochrane database of systematic reviews (Online) | Year: 2012

The 'off-label' effect of alprazolam on depression has not been systematically evaluated. To determine the antidepressant effect, including tolerability and acceptability, of alprazolam as monotherapy for major depression, when compared to placebo and conventional antidepressants in outpatients and patients in primary care. We searched the Cochrane Central Register of Controlled Trials and the Cochrane Depression, Anxiety and Neurosis Group Register, which includes relevant randomised controlled trials from the following bibliographic databases: The Cochrane Library (all years to February 2012); EMBASE (1970 to February 2012); MEDLINE (1950 to February 2012) and PsycINFO (1960 to February 2012). Two review authors identified relevant trials by assessing the abstracts of all possible studies. We applied no language restrictions. We selected randomised controlled trials (RCTs) of alprazolam versus placebo or conventional antidepressants for depression in adults, excluding studies with inpatients only. Two review authors performed the data extraction and 'Risk of bias' assessment independently with disagreements resolved through discussion with a third review author. Primary outcomes included the mean difference (MD) in reduction of depression on a continuous measure of depression symptoms, and the risk ratio (RR) of the clinical response based on a dichotomous measure, with 95% confidence intervals (CI). We identified 21 alprazolam studies (22 reports) with a total of 2693 participants. Seven studies used a placebo (n = 771) and 20 used cyclic antidepressants (n = 1765). The typical duration of the studies was four to six weeks. We considered six studies to have a high risk of bias.When alprazolam was compared with placebo for reduction in symptoms all estimates indicated a positive effect for alprazolam. Pooled estimates of efficacy data showed a moderately large continuous mean difference (MD) at the end of trial (-5.34, 95% CI -7.48 to -3.20; I(2) = 68%). The risk difference (RD) for the dichotomous measure of clinical response (50% improvement) was 0.32 in favour of alprazolam (95% CI 0.22 to 0.42; I(2) = 0%), with a number needed to treat to benefit (NNTB) of 3 (95% CI 2 to 5). The RD of all-cause withdrawals did not differ between alprazolam and placebo.When depression severity was measured as a continuum the effect of alprazolam did not differ statistically or clinically from the effects of any of the conventional antidepressants combined (MD 0.25, 95% CI -0.93 to 1.43; I(2) = 55%). However, for dichotomised depression severity, alprazolam had less effect than antidepressants (RR 0.86, 95% CI 0.75 to 0.99; I(2) = 37%; RD -0.11, 95% CI -0.24 to 0.01; I(2) = 58%; NNTB 9, 95% CI 4 to 100). The RD of all-cause withdrawals was -0.04 (95% CI -0.07 to 0.00; I(2) = 35%), in favour of alprazolam. Alprazolam appears to reduce depressive symptoms more effectively than placebo and as effectively as tricyclic antidepressants. However, the studies included in the review were heterogeneous, of poor quality and only addressed short-term effects, thus limiting our confidence in the findings. Whilst the rate of all-cause withdrawals did not appear to differ between alprazolam and placebo, and withdrawals were less frequent in the alprazolam group than in any of the conventional antidepressants combined group, these findings should be interpreted with caution, given the dependency properties of benzodiazepines.


Voelkel N.F.,Virginia Commonwealth University | Gomez-Arroyo J.,Virginia Commonwealth University | Abbate A.,Virginia Commonwealth University | Bogaard H.J.,VU University Amsterdam | Nicolls M.R.,Stanford University
European Respiratory Journal | Year: 2012

Pulmonary arterial hypertension (PAH) is no longer an orphan disease. There are three different classes of drugs for the treatment of PAH that are currently being used and an increasing number of patients are being treated with a single drug or combination therapy. During the last 25 yrs, new insights into the pathobiology of PAH have been gained. The classical mechanical concepts of pressure, flow, shear stress, right ventricle wall stress and impedance have been complemented with the new concepts of cell injury and repair and interactions of complex multicellular systems. Integrating these concepts will become critical as we design new medical therapies in order to change the prognosis of patients with these fatal diseases. This review intends to summarise recent pathobiological concepts of PAH and right ventricle failure mainly derived from human studies, which reflect the progress made in the understanding of this complex group of pulmonary vascular diseases. Copyright©ERS 2012.


Hickey C.,University of Trento | Hickey C.,VU University Amsterdam | Kaiser D.,University of Trento | Peelen M.V.,University of Trento
Journal of Experimental Psychology: General | Year: 2015

Reward is thought to motivate animal-approach behavior in part by automatically facilitating the perceptual processing of reward-associated visual stimuli. Studies have demonstrated this effect for low-level visual features such as color and orientation. However, outside of the laboratory, it is rare that low-level features uniquely characterize objects relevant for behavior. Here, we test whether reward can prime representations at the level of object category. Participants detected category exemplars (cars, trees, people) in briefly presented photographs of real-world scenes. On a subset of trials, successful target detection was rewarded and the effect of this reward was measured on the subsequent trial. Results show that rewarded selection of a category exemplar caused other members of this category to become visually salient, disrupting search when subsequently presented as distractors. It is important to note that this occurred even when there was little opportunity for the repetition of visual features between examples, with the rewarded selection of a human body increasing the salience of a subsequently presented face. Thus, selection of a category example appears to activate representations of prototypical category characteristics even when these are not present in the stimulus. In this way, reward can guide attention to categories of stimuli even when individual examples share no visual characteristics. © 2015 American Psychological Association.


Vandenberghe J.,VU University Amsterdam
Geologie en Mijnbouw/Netherlands Journal of Geosciences | Year: 2012

Multi-disciplinarity and multi-proxy approaches are necessary to understand the processes in complex earth systems. However, unlimited and uncontrolled multi-proxy-correlations may be risky. A number of case studies illustrate the potential pitfalls when the processes that drive the individual proxies have no common causal significance or dating is not precise enough. Crossing thresholds at different levels and delay times may also be factors that hamper direct correlations of proxies. Multi-proxy analysis of the intrinsic relationships between proxies in a system is the primary task before any correlation should be made.


Beunk F.F.,VU University Amsterdam | Kuipers G.,Stroom 171
Precambrian Research | Year: 2012

We have revisited and re-interpreted deformation structures in the classical ore province of west Bergslagen, part of the ∼1.9-1.8Ga old Svecofennian orogen in south-central Sweden. Four successive phases and styles of deformation reflect (1) continental rifting associated with bimodal magmatism in continental back-arc basins (D 1), (2) closure of the rift(s) by upright tight to isoclinal folds on any scale (D 2), (3) renewed rifting (D 3) with deposition of argillites, conglomerates and submarine basalts in restricted rift basins, and (4) intense buckling and folding of west Bergslagen along variably but generally steeply plunging folds (D 4). Strain localization during D 4 initiated a network of conjugate retrogressive shear zones and closely related large scale vertical drag folds, with the southwest-northeast striking West Bergslagen Boundary Zone system acting as the main tectonic boundary along which west Bergslagen slipped relative to the central part of the province. D 4 transpression and variably oblique D 4 shear may have caused the preservation of a low grade domain in west Bergslagen as well as the exhumation of a granulite facies domain near the hinge of the orocline. D 4 structures include a regional scale oroclinal bend of 135° in southwest Bergslagen, connecting common southwest-northeast strikes in west Bergslagen to east-west strikes to the south and east. In central Bergslagen, the oroclinal bend tightens to 180°. To the south, it lines up with another orocline, the two forming an S-shaped pair of large-scale buckle folds. The orocline finds expression in the regional patterns of form lines and magnetic anomalies, and in the spatial distribution of specific intrusive rock suites. The northern structural boundary of the province is known as an east-west striking zone of dip slip movement and local wrenching, which we also interpret as a D 4 effect. The D 4 structures imply the evolution of a separate ribbon-like Bergslagen micro-continent, at least 700km long, rifted from the former active continental margin during the D 3 event, and finally accreted, slightly obliquely, to pre-existing Fennoscandia to the present north. By correlating D 4 deformation structures with the areal distribution and previously determined radiometric ages of 'late orogenic' anatectic granites, we derive a provisional estimate, 1.83-1.82Ga, as the lower age limit to the initiation of terrane accretion. D 4 accretion is Svecofennian orogeny proper in this part of the belt, younger than the currently preferred estimate of ∼1.86Ga. West Bergslagen's synsedimentary hydrothermal ore deposits, originating from 1.91 to 1.89Ga old volcanism and rifting, have been remobilized to various extent during the 'late-orogenic' D 4 phase, and show pronounced concentration along D 4 shear zones. © 2012 Elsevier B.V.


Leonardi P.M.,Northwestern University | Huysman M.,VU University Amsterdam | Steinfield C.,Michigan State University
Journal of Computer-Mediated Communication | Year: 2013

Social media are increasingly implemented in work organizations as tools for communication among employees. It is important that we develop an understanding of how they enable and constrain the communicative activities through which work is accomplished because it is these very dynamics that constitute and perpetuate organizations. We begin by offering a definition of enterprise social media and providing a rough historical account of the various avenues through which these technologies have entered and continue to enter the workplace. We also review areas of research covered by papers in this special issue and papers on enterprise social media published elsewhere to take stock of the current state of out knowledge and to propose directions for future research. © 2013 International Communication Association.


Hedlund-De Witt A.,VU University Amsterdam
Environmental Ethics | Year: 2013

Insight into worldviews is essential for approaches aiming to design and support (more) sustainable pathways for society, both locally and globally. However, the nature of worldviews remains controversial, and it is still unclear how the concept can best be operationalized in the context of research and practice. One way may be by developing a framework for the understanding and operationalization worldviews by investigating various conceptualizations of the term in the history of philosophy. Worldviews can be understood as inescapable, overarching systems of meaning and meaning making that to a substantial extent inform how humans interpret, enact, and co-create reality. Moreover, worldviews are profoundly historically and developmentally situated. An Integrative Worldview Framework (IWF) can operationalize worldviews by differentiating five interrelated aspects: ontology, epistemology, axiology, anthropology, and societal vision. The evolution of the worldview concept is suggestive of an increasing reflexivity, creativity, responsibility, and inclusiveness-each of which are qualities that appear to be crucial for the global sustainable development debate.


de Jong Gierveld J.,Netherlands Interdisciplinary Demographic Institute NIDI | van Tilburg T.,VU University Amsterdam
European Journal of Ageing | Year: 2010

Loneliness concerns the subjective evaluation of the situation individuals are involved in, characterized either by a number of relationships with friends and colleagues which is smaller than is considered desirable (social loneliness), as well as situations where the intimacy in confidant relationships one wishes for has not been realized (emotional loneliness). To identify people who are lonely direct questions are not sufficient; loneliness scales are preferred. In this article, the quality of the three-item scale for emotional loneliness and the three-item scale for social loneliness has been investigated for use in the following countries participating in the United Nations "Generations and Gender Surveys": France, Germany, the Netherlands, Russia, Bulgaria, Georgia, and Japan. Sample sizes for the 7 countries varied between 8,158 and 12,828. Translations of the De Jong Gierveld loneliness scale have been tested using reliability and validity tests including a confirmatory factor analysis to test the two-dimensional structure of loneliness. Test outcomes indicated for each of the countries under investigation reliable and valid scales for emotional and social loneliness, respectively. © 2010 The Author(s).


Smeulers A.,VU University Amsterdam
British Journal of Criminology | Year: 2010

The genocide in Rwanda in 1994 stands out for the enormous number of people killed in a relatively short period of time; the mass involvement of the civilian population and the extreme and violent nature of the killings: victims were hunted down, beaten, raped and mutilated before being killed by machetes. This article describes how, within a politically explosive situation, many otherwise non-violent and law-abiding citizens became involved in genocide. It also explains how it was social interaction - rather than pure ethnic hatred - between various types of perpetrators and group dynamics, in which some fanatics managed to induce and force many others to join in, that were instrumental in the genocidal process in Rwanda.


van den Besselaar P.,VU University Amsterdam
Journal of Informetrics | Year: 2012

Project funding is an increasingly important mode of research funding. The rationale is that through project funding new fields and new themes can be supported more effectively. Furthermore, project funding improves competition, which is expected to select the better research projects and researchers. However, project funding has a price, as it requires researchers to invest time in reviewing proposals, and to participate in selection committees. In that perspective, selection committee membership can be seen as a service to the scholarly community.However, what do committee members themselves get from membership? In this paper we show that committee members in average are more successful in grant applications than other principle investigators, and this is not explained by performance differences. The findings suggest that committee membership is not only service, but also self-service. © 2012 Elsevier Ltd.


Gordijn M.S.,VU University Amsterdam
Cochrane database of systematic reviews (Online) | Year: 2012

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate host defence against infections, which remains a cause of morbidity and death. The exact occurrence and duration of HPA axis suppression after glucocorticoid therapy for childhood ALL are unclear. To examine the occurrence and duration of HPA axis suppression after (each cycle of) glucocorticoid therapy for childhood ALL. We searched the Cochrane Central Register of Controlled Trials (in The Cochrane Library, issue 3, 2010), MEDLINE/PubMed (from 1945 to July 2010) and EMBASE/Ovid (from 1980 to July 2010). In addition, we searched reference lists of relevant articles, conference proceedings and ongoing trial databases. All study designs, except case reports and patient series with fewer than 10 patients, examining the effect of glucocorticoid therapy for childhood ALL on the HPA axis function. Two review authors independently performed the study selection. One review author performed the data extraction and 'Risk of bias' assessment, which was checked by another review author. We identified seven studies (total number of participants = 189), including one randomised controlled trial (RCT), which assessed the adrenal function. None of the studies assessed the HPA axis at the level of the hypothalamus, pituitary, or both. Due to substantial differences between studies, results could not be pooled. All studies had some methodological limitations. The included studies demonstrated that adrenal insufficiency occurs in nearly all patients in the first days after cessation of glucocorticoid treatment for childhood ALL. The majority of patients recovered within a few weeks, but a small amount of patients had ongoing adrenal insufficiency lasting up to 34 weeks. In the RCT, the occurrence and duration of adrenal insufficiency did not differ between the prednisolone and dexamethasone arms. In one study included in the review it appeared that treatment with fluconazole prolonged the duration of adrenal insufficiency. Based on the available evidence, we conclude that adrenal insufficiency commonly occurs in the first days after cessation of glucocorticoid therapy for childhood ALL, but the exact duration is unclear. Since no data on the level of the hypothalamus and the pituitary were available we cannot make any conclusions regarding those outcomes. Clinicians should consider prescribing glucocorticoid replacement therapy during periods of serious stress in the first weeks after cessation of glucocorticoid therapy for childhood ALL, to reduce the risk of life-threatening complications. However, more high-quality research is needed for evidence-based guidelines for glucocorticoid replacement therapy.Special attention should be paid to patients receiving fluconazole therapy, and perhaps similar antifungal drugs, as this may prolong the duration of adrenal insufficiency.


Klomp T.,VU University Amsterdam
Cochrane database of systematic reviews (Online) | Year: 2012

Many women would like to have a choice in pain relief during labour and also would like to avoid invasive methods of pain management in labour. Inhaled analgesia during labour involves the self-administered inhalation of sub-anaesthetic concentrations of agents while the mother remains awake and her protective laryngeal reflexes remain intact. Most of the agents are easy to administer, can be started in less than a minute and become effective within a minute. To examine the effects of all modalities of inhaled analgesia on the mother and the newborn for mothers who planned to have a vaginal delivery. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2012), ClinicalTrials.gov, and Current Controlled Trials (2 June 2012), handsearched conference proceedings from the American Society of Clinical Anesthesia (from 1990 to 2011), contacted content experts and trialists and searched reference lists of retrieved studies. Randomised controlled trials comparing inhaled analgesia with other inhaled analgesia or placebo or no treatment or other methods of non-pharmacological pain management in labour. Review authors independently assessed trials for eligibility, methodological quality and extracted all data. Data were double checked for accuracy. Twenty-six studies, randomising 2959 women, were included in this review.Inhaled analgesia versus a different type of inhaled analgesia Pain relief was measured using a Visual Analogue Scale (VAS) from 0 to 100 mm where 100 corresponds to the most relief. Pain intensity was measured using a VAS from 0 to 100 mm, where 0 corresponds to no pain at all and 100 corresponds to the worst pain. The highest score for pain relief is the most positive in contrast to 'pain intensity' in which the higher score is more negative. Flurane derivatives were found to offer better pain relief than nitrous oxide in first stage of labour as measured by a lower pain intensity score (average mean difference (MD) 14.39, 95% confidence interval (CI) 4.41 to 24.37, three studies, 70 women), also a higher pain relief score for flurane derivatives compared with nitrous oxide (average MD -16.32, 95% CI -26.85 to -5.79, two studies, 70 women). Substantial heterogeneity was found in the analyses of pain intensity (P = 0.003) and in the analysis of pain relief (P = 0.002).These findings should be considered with caution because of the questionable design of the included cross-over trials. More nausea was found in the nitrous oxide group compared with the flurane derivatives group (risk ratio (RR) 6.60 95% CI 1.85 to 23.52, two studies, 98 women).Inhaled analgesia versus placebo or no treatment Placebo or no treatment was found to offer less pain relief compared to nitrous oxide (average RR 0.06, 95% CI 0.01 to 0.34, two studies, 310 women; MD -3.50, 95% CI -3.75 to -3.25, one study, 509 women). However, nitrous oxide resulted in more side effects for women such as nausea (RR 43.10, 95% CI 2.63 to 706.74, one study, 509 women), vomiting (RR 9.05, 95% CI 1.18 to 69.32, two studies, 619 women), dizziness (RR 113.98, 95% CI 7.09 to 1833.69, one study, 509 women) and drowsiness (RR 77.59, 95% CI 4.80 to 1254.96, one study, 509 women) when compared with placebo or no treatment.There were no significant differences found for any of the outcomes in the studies comparing one strength versus a different strength of inhaled analgesia, in studies comparing different delivery systems or in the study comparing inhaled analgesia with TENS.Due to lack of data, the following outcomes were not analysed within the review: sense of control; satisfaction with childbirth experience; effect on mother/baby interaction; breastfeeding; admission to special care baby unit; poor infant outcomes at long-term follow-up; or costs. Inhaled analgesia appears to be effective in reducing pain intensity and in giving pain relief in labour. However, substantial heterogeneity was detected for pain intensity. Furthermore, nitrous oxide appears to result in more side effects compared with flurane derivatives. Flurane derivatives result in more drowsiness when compared with nitrous oxide. When inhaled analgesia is compared with no treatment or placebo, nitrous oxide appears to result in even more side effects such as nausea, vomiting, dizziness and drowsiness. There is no evidence for differences for any of the outcomes comparing one strength verus a different strength of inhaled analgesia, comparing different delivery systems or comparing inhaled analgesia with TENS.


Kiers E.T.,VU University Amsterdam | Denison R.F.,University of Minnesota
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2014

Trade-offs between individual fitness and the collective performance of crop and below-ground symbiont communities are common in agriculture. Plant competitiveness for light and soil resources is key to individual fitness, but higher investments in stems and roots by a plant community to compete for those resources ultimately reduce crop yields. Similarly, rhizobia and mycorrhizal fungi may increase their individual fitness by diverting resources to their own reproduction, even if they could have benefited collectively by providing their shared crop host with more nitrogen and phosphorus, respectively. Past selection for inclusive fitness (benefits to others, weighted by their relatedness) is unlikely to have favoured community performance over individual fitness. The limited evidence for kin recognition in plants and microbes changes this conclusion only slightly. We therefore argue that there is still ample opportunity for human-imposed selection to improve cooperation among crop plants and their symbionts so that they use limited resources more efficiently. This evolutionarily informed approach will require a better understanding of how interactions among crops, and interactions with their symbionts, affected their inclusive fitness in the past and what that implies for current interactions. © 2014 The Author(s) Published by the Royal Society. All rights reserved.


Den Haan J.M.M.,VU University Amsterdam | Martinez-Pomares L.,University of Nottingham
Seminars in Immunopathology | Year: 2013

Macrophages in lymphoid organs exhibit a wide variety of phenotypes and functions. These cells excel in the removal of apoptotic cells that arise during the generation of immune cells and are thereby essential for the prevention of auto-immune responses. In addition to this macrophages in the secondary lymphoid organs form an important barrier for spreading of infections by phagocytosis of pathogens and the activation of both innate and adaptive immune responses. Thus, the remarkable ability of macrophages to phagocytose and handle a wide range of self and non-self material and to produce immunomediators is effectively exploited within lymphoid organs to regulate immune activation. © 2013 Springer-Verlag Berlin Heidelberg.


Chinapaw M.J.,VU University Amsterdam
Sports medicine (Auckland, N.Z.) | Year: 2010

Because of the diversity in available questionnaires, it is not easy for researchers to decide which instrument is most suitable for his or her specific demands. Therefore, we systematically summarized and appraised studies examining measurement properties of self-administered and proxy-reported physical activity (PA) questionnaires in youth. Literature was identified through searching electronic databases (PubMed, EMBASE using 'EMBASE only' and SportDiscus) until May 2009. Studies were included if they reported on the measurement properties of self-administered and proxy-reported PA questionnaires in youth (mean age <18 years) and were published in the English language. Methodological quality and results of included studies was appraised using a standardized checklist (qualitative attributes and measurement properties of PA questionnaires [QAPAQ]). We included 54 manuscripts examining 61 versions of questionnaires. None of the included questionnaires showed both acceptable reliability and validity. Only seven questionnaires received a positive rating for reliability. Reported validity varied, with correlations between PA questionnaires and accelerometers ranging from very low to high (previous day PA recall: correlation coefficient [r] = 0.77). In general, PA questionnaires for adolescents correlated better with accelerometer scores than did those for children. From this systematic review, we conclude that no questionnaires were available with both acceptable reliability and validity. Considerably more high-quality research is required to examine the validity and reliability of promising PA questionnaires for youth.


Smits N.,VU University Amsterdam | Finkelman M.D.,Tufts University
Statistics in Medicine | Year: 2014

Health questionnaires are often built up from sets of questions that are totaled to obtain a sum score. An important consideration in designing questionnaires is to minimize respondent burden. An increasingly popular method for efficient measurement is computerized adaptive testing; unfortunately, many health questionnaires do not meet the requirements for this method. In this paper, a new sequential method for efficiently obtaining sum scores via the computer is introduced, which does not have such requirements and is based on the ordinal regression model. In the assessment, future scores are predicted from past responses, and when an acceptable level of uncertainty is achieved, the procedure is terminated. Two simulation studies were performed to illustrate the usefulness of the procedure. The first used artificially generated symptom scores, and the second was a post hoc simulation using real responses on the Center for Epidemiologic Studies Depression scale. In both studies, the sequential method substantially reduced the respondent burden while maintaining a high sum score quality. Benefits and limitations of this new methodology are discussed. © 2013 John Wiley & Sons, Ltd.


Braam A.W.,VU University Amsterdam
Journal of palliative medicine | Year: 2011

Although religiousness may, to a certain extent, be expected to alleviate emotional suffering in the last week of life, some religious beliefs might also provoke emotional distress. For the current study, after-death interviews with proxy respondents of deceased sample members of the Longitudinal Aging Study Amsterdam provided information on depressive mood and anxiety in the last week of life, as well as on the presence of a sense of peace at the approaching end of life. Proxy respondents also were asked about serious physical symptoms in the last week of life of the respondent, the respondent's cognitive decline, and their estimate of the salience of religion for the sample member. Other characteristics were derived from the last interviews with the sample members when still alive: depressive symptoms, chronic diseases, religious affiliation, church attendance, belief in Heaven, belief in Hell, and salience of religion. None of the characteristics of religiousness was significantly associated with depressive mood or anxiety, as estimated by the proxy respondent. A sense of peace, however, was predicted by higher church attendance, belief in Hell (among church-members), and the proxy's estimate of the salience of religion. It can be concluded that religiousness did not affect depressive mood or anxiety in the last week of life in the current sample. It is possible that religiousness supports a sense of peace, which may be a more-existential facet of mood and is discussed as relevant in the last phase of life and in palliative care.


Driessen E.,VU University Amsterdam | Hollon S.D.,Vanderbilt University
Psychiatric Clinics of North America | Year: 2010

Cognitive behavioral therapy (CBT) is efficacious in the acute treatment of depression and may provide a viable alternative to antidepressant medication (ADM) for even more severely depressed unipolar patients when implemented in a competent fashion. CBT also may be of use as an adjunct to medication treatment of bipolar patients, although there have been few studies and they are not wholly consistent. CBT does seem to have an enduring effect that protects against subsequent relapse and recurrence following the end of active treatment, which is not the case for medications. Single studies that require replication suggest that patients who are married or unemployed or who have more antecedent life events may do better in CBT than in ADM, as might patients who are free from comorbid Axis II disorders, whereas patients with comorbid Axis II disorders seem to do better in ADM than in CBT. There also are indications that CBT may work through processes specified by theory to produce change in cognition that in turn mediate subsequent change in depression and freedom from relapse following treatment termination, although evidence in that regard is not yet conclusive. © 2010 Elsevier Inc.


Bosch L.J.W.,VU University Amsterdam
Current Colorectal Cancer Reports | Year: 2011

Detection of molecular markers for colorectal neoplasia in feces has the potential to improve performance of simple noninvasive screening tests for colorectal cancer. Most research has explored the value of DNA-based, RNA-based, and protein-based markers. In all cases there has been a trend to move from a single marker to a panel of markers to improve sensitivity. Unfortunately, no type of molecular marker has proved specific for neoplasia. DNA tests have been improved by combining mutation detection with assessment of DNA integrity plus epigenetic markers of neoplasia. RNA-based approaches are just beginning to explore the full power of transcriptomics. So far, no protein-based fecal test has proved better than fecal immunochemical tests for hemoglobin. Finally, no marker or panel of markers has yet been developed to the point where it has been evaluated in large unbiased population studies to assess performance across all stages of neoplasia and in all practical environments. © 2011 The Author(s).


Kruijver M.,VU University Amsterdam
Forensic Science International: Genetics | Year: 2016

Several problems in forensic genetics require a representative model of a forensic DNA database. Obtaining an accurate representation of the offender database can be difficult, since databases typically contain groups of persons with unregistered ethnic origins in unknown proportions. We propose to estimate the allele frequencies of the subpopulations comprising the offender database and their proportions from the database itself using a latent variable approach. We present a model for which parameters can be estimated using the expectation maximization (EM) algorithm. This approach does not rely on relatively small and possibly unrepresentative population surveys, but is driven by the actual genetic composition of the database only. We fit the model to a snapshot of the Dutch offender database (2014), which contains close to 180,000 profiles, and find that three subpopulations suffice to describe a large fraction of the heterogeneity in the database. We demonstrate the utility and reliability of the approach with three applications. First, we use the model to predict the number of false leads obtained in database searches. We assess how well the model predicts the number of false leads obtained in mock searches in the Dutch offender database, both for the case of familial searching for first degree relatives of a donor and searching for contributors to three-person mixtures. Second, we study the degree of partial matching between all pairs of profiles in the Dutch database and compare this to what is predicted using the latent variable approach. Third, we use the model to provide evidence to support that the Dutch practice of estimating match probabilities using the Balding-Nichols formula with a native Dutch reference database and θ = 0.03 is conservative. © 2016 Elsevier Ireland Ltd. All rights reserved.


van Asselt H.,VU University Amsterdam | Brewer T.,Georgetown University
Energy Policy | Year: 2010

The implementation of climate policies in the US and EU in light of uncertainties about future international climate policy has shifted attention to two interrelated concerns, namely competitiveness and carbon leakage. Although various policy measures are available to address these concerns, there has been much discussion about one such measure in particular: the use of offsetting measures at the border. This article compares policy discussions in the US and the EU on how to address competitiveness and carbon leakage concerns, with a focus on the role of import-related border adjustment measures. It analyses the kinds of measures that so far have been put forward with a view to addressing competitiveness and carbon leakage; compares the approaches to the problems in the US and the EU; and provides a preliminary discussion of international cooperation on border adjustment measures. It concludes that two kinds of cooperation are needed between the EU and the US - not only cooperation through formal international negotiations, but also cooperation through international learning processes, in which the EU and the US learn from each other about design and implementation issues as they develop their respective cap-and-trade systems. © 2009 Elsevier Ltd. All rights reserved.


Glioblastoma (GBM) is a malignant brain tumor with dismal prognosis. GBM patients have a median survival of less than 2 years. GBM is characterized by fast cell proliferation, infiltrative migration, and by the induction of angiogenesis. MicroRNAs and polycomb group (PcG) proteins have emerged as important regulators of gene expression. Here we determined that miR-101 is down-regulated in GBM, resulting in overexpression of the miR-101 target PcG protein EZH2, a histone methyltransferase affecting gene expression profiles in an epigenetic manner. Inhibition of EZH2 in vitro by pre-miR-101, EZH2 siRNA, or small molecule DZNep, attenuated GBM cell growth, migration/invasion, and GBM-induced endothelial tubule formation. In addition, for each biological process we identified ontology-associated transcripts that significantly correlate with EZH2 expression. Inhibition of EZH2 in vivo by systemic DZNep administration in a U87-Fluc-mCherry GBM xenograft mouse imaging model resulted in reduced tumor growth. Our results indicate that EZH2 has a versatile function in GBM progression and that its overexpression is at least partly due to decreased miR-101 expression. Inhibition of EZH2 may be a potential therapeutic strategy to target GBM proliferation, migration, and angiogenesis.


Rheumatoid arthritis (RA) is the most common chronic inflammatory disorder of the musculoskeletal system that may cause permanent joint damage. The disease has a major impact on the quality of life of affected individuals, costs for the health care system, and society. Currently, no curative treatment is available, and patients are subjected to a prolonged course of treatment. Due to their role in the pathogenesis of RA, B cells have become an attractive target for therapy. Rituximab (Mabthera®/Rituxan®) is a therapeutic monoclonal antibody against CD20 expressed on B cells, which is effective in depleting B cells and approved worldwide for the treatment of RA. Rituximab was shown to be highly beneficial in decreasing clinical symptoms, safe, and well tolerated. However, clinical experience revealed that approximately 30-40% of RA patients do not respond to it. Given the destructive nature of RA, the risk of adverse effects, and considerable costs for therapy, there is a strong need to make predictions on the clinical outcome before the start of therapy. Since nearly all treated patients experience an effective depletion of circulating B cells, questions have been raised concerning the mechanism of action. In this review, novel developments, in particular the findings on the role of the interferon system, will be highlighted. This may add new and important information to our understanding of the mechanism that underlies the clinical outcome of rituximab treatment and may lead to the identification of biomarkers to predict the response.


Tanenbaum A.S.,VU University Amsterdam
Communications of the ACM | Year: 2016

MINIX shows even an operating system can be made to be self-healing.


Verhagen T.,VU University Amsterdam | Van Dolen W.,University of Amsterdam
Information and Management | Year: 2011

Our study provides insight into the relationships between online store beliefs and consumer online impulse buying behavior. Drawing upon cognitive emotion theory, we developed a model and showed how beliefs about functional convenience (online store merchandise attractiveness and ease of use) and about representational delight (enjoyment and website communication style) related to online impulse buying. The model was tested using survey data from 532 customers of a Dutch online store. Our results showed significant effects of merchandise attractiveness, enjoyment, and online store communication style, mediated by consumers' emotions. The study should enhance our understanding of online impulse buying and, by assessing the impact of the online store, of beliefs in non-rational decision-making settings. © 2011 Elsevier B.V.


Amor S.,VU University Amsterdam | Amor S.,Queen Mary, University of London | Woodroofe M.N.,Sheffield Hallam University
Immunology | Year: 2014

Emerging evidence suggests important roles of the innate and adaptive immune responses in the central nervous system (CNS) in neurodegenerative diseases. In this special review issue, five leading researchers discuss the evidence for the beneficial as well as the detrimental impact of the immune system in the CNS in disorders including Alzheimer's disease, multiple sclerosis and CNS injury. Several common pathological mechanisms emerge indicating that these pathways could provide important targets for manipulating the immune reposes in neurodegenerative disorders. The articles highlight the role of the traditional resident immune cell of the CNS - the microglia - as well as the role of other glia astrocytes and oligodendrocytes in immune responses and their interplay with other immune cells including, mast cells, T cells and B cells. Future research should lead to new discoveries which highlight targets for therapeutic interventions which may be applicable to a range of neurodegenerative diseases. © 2013 John Wiley & Sons Ltd.


Philippon M.,VU University Amsterdam | Brun J.-P.,University of Rennes 1 | Gueydan F.,Montpellier University
Tectonophysics | Year: 2012

The Cycladic Blueschist Unit (CBU) represents the northern passive margin of the Adria continental block and ophiolites that are the remnants of the Pindos Ocean, which were affected by high pressure-low temperature metamorphism in the blueschist and eclogite facies during the Eocene. Prior to the Lutetian, the ophiolitic and margin units were thrust towards the SW inside a NE-dipping subduction zone. Two subsequent exhumation stages are characterized by top-to-the-NE senses of shear: i) from mantle depths to lower crustal levels, before 37. Ma, which was accommodated by an extensional inversion of the Vardar suture zone, and ii) from deep crustal levels to the near-surface, between 30 and 20. Ma, which was accommodated by the North Cycladic Detachment. It is during this late stage of ductile exhumation that the central Cyclades Core Complex was exhumed. Segmentation of the CBU by normal faults started at 12. Ma, as recorded by the low temperature thermochronometers, and was coeval with block rotation and folding with NS-trending axes, which were predominantly controlled by the Myrthes-Ikaria strike-slip fault in the centre of the Cyclades. A map restoration of the CBU geometry, prior to segmentation, has been carried out using available structural and paleomagnetic data. The restoration shows that, following the CBU exhumation from mantle depths to crustal levels, a single core complex was exhumed along a single NE dipping detachment. © 2011 Elsevier B.V.


Magliacane S.,VU University Amsterdam
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

Provenance is an increasingly important aspect of data management that is often underestimated and neglected by practitioners. In our work, we target the problem of reconstructing provenance of files in a shared folder setting, assuming that only standard filesystem metadata are available. We propose a content-based approach that is able to reconstruct provenance automatically, leveraging several similarity measures and edit distance algorithms, adapting and integrating them into a multi-signal pipeline. We discuss our research methodology and show some promising preliminary results. © 2012 Springer-Verlag Berlin Heidelberg.


The aim of this study was to assess the association between the proportions of penumbra-visualized by late gadolinium enhanced cardiovascular magnetic resonance imaging (LGE-CMR)-after acute myocardial infarction (AMI) and the prevalence of ventricular tachycardia (VT). One-hundred and sixty-two AMI patients, successfully, treated by primary percutaneous coronary intervention (PCI) underwent LGE-CMR after a median of 3 days (3-4) and 24-h Holter monitoring after 1 month. With LGE-CMR, the total amount of enhanced myocardium was quantified and divided into an infarct core (>50% of maximal signal intensity) and penumbra (25-50% of maximal signal intensity). With Holter monitoring, the number of VTs (≥4 successive PVCs) per 24 h was measured. The mean total enhanced myocardium was 31 ± 11% of the left ventricular mass. The % penumbra accounted for 39 ± 11% of the total enhanced area. In 29 (18%) patients, Holter monitoring showed VT, with a median of 1 episode (1-3) in 24 h. A larger proportion of penumbra within the enhanced area increased the risk of VTs [OR: 1.06 (95% CI: 1.02-1.10), P = 0.003]. After multivariate logistic regression analysis, the presence of ventricular fibrillation before primary PCI [OR: 5.60 (95% CI: 1.54-20.29), P = 0.01] and the proportional amount of penumbra within the enhanced myocardium [OR: 1.06 (95% CI: 1.02-1.10), P = 0.04] were independently associated with VT on Holter monitoring. Larger proportions of penumbra in the subacute phase after AMI are associated with increased risk of developing VTs. Quantification of penumbra size may become a useful future tool for risk stratification and ultimately for the prevention of ventricular arrhythmias.


Temme A.J.A.M.,Wageningen University | Verburg P.H.,VU University Amsterdam
Agriculture, Ecosystems and Environment | Year: 2011

Spatial maps of agricultural intensity are needed for analyses of environmental issues, including biodiversity changes. We present a method to produce such maps for Europe. While most studies beyond farm level focus on land cover change only, this paper focuses on spatial variation in land use intensity and its dynamics.Our method defines agricultural land use intensity in terms of nitrogen input. For arable land, it combines field observations with administrative-level statistics to assess probability of occurrence for three land use intensity classes. For grassland, it uses maps of livestock density to assess probability of occurrence for two intensity classes. Agricultural land is spatially allocated to intensity classes using an algorithm that downscales intensity changes simulated with an agricultural economic model.Our results are 1km2 resolution maps of classified agricultural land use intensity in the year 2000. We illustrate the method by exploring changes in the spatial pattern of land use intensity for a financial policy reform scenario in the year 2025. Results indicate spatial heterogeneity in land use intensity across European countries, including large differences in intensity between countries, between regions, but also within regions.Our method could be improved with smaller-resolution agricultural statistics and broader intensity indicators. © 2010 Elsevier B.V.


Zhou J.,VU University Amsterdam
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2015

We study the transverse single spin asymmetry in Drell-Yan production in pA collisions with incoming protons being transversely polarized. We carry out the calculation using a newly developed hybrid approach. The polarized cross section computed in the hybrid approach is consistent with that obtained from the usual TMD factorization at low transverse momentum as expected, whereas at high transverse momentum, color entanglement effect is found to play a role in contributing to the spin asymmetry of Drell-Yan production, though it is a 1/Nc2 suppressed effect. © 2015 American Physical Society.


Conti M.,University of Padua | Willemsen J.,VU University Amsterdam | Crispo B.,University of Trento