Radboud University Nijmegen Research Articles

Eradicating cancer cells: struggle with a chameleon

Eradication of cancer stem cells to abrogate tumor growth is a new treatment modality. However, like normal cells cancer cells show plasticity. Differentiated tumor stem cells can acquire stem cell properties when they gain access to the stem cell niche. This indicates that eradicating of stem cells (emptying of the niche) alone will not lead to eradication of the tumor. Treatment should be directed to cancer stem cells and more mature cancer cells.

Patients with cervical cancer: why did screening not prevent these cases?

The objective of the study was to assess the screening history of women with cervical cancer and review normal cervical smears 5 years preceding the diagnosis. Cytological and histological results of 401 women treated for invasive cervical cancer between 1991 and 2008 at the Radboud University Nijmegen Medical Center were studied. Ninety-eight normal smears were reviewed. Of the 401 women, 269 (67%) received at least 1 invitation for the national screening program for cervical cancer (NCSP). One- third fell outside the target age of the NCSP. Seventeen percent never responded to the invitation(s). Twenty-one percent had 1 or more normal smears within 5 years preceding the diagnosis. After review, only 39% of those smears were reviewed as a normal smear. Half of the women with cervical cancer were never screened because of the limited target age range or nonattendance. Twenty-one percent had a normal smear within 5 years preceding the diagnosis, caused by interpretation and/or sampling errors.

Influence of birth mode on early neurological outcome in infants with myelomeningocele

Objective The aim of the study was to determine whether route of birth affects early neurological outcome in infants with myelomeningocele. Study design In a retrospective cohort study, 95 neonates with myelomeningocele evaluated at the Radboud University Nijmegen Medical Centre between 1990 and 2006 were reviewed. The effect of delivery mode on early neurological outcome was assessed as the difference between the functional neurological level of the defect and the X-ray level (ΔFAX). Results Early neurological outcome was better in the vaginally delivered infants (ΔFAX 0.96 ± 2.1) than in those delivered by cesarean section (ΔFAX 0.20 ± 2.5). After correction for confounders, multiple regression analysis demonstrated that vaginal delivery was associated with significantly better early neurological outcome as compared to cesarean section ( β = 1.21; 95% CI 0.16; 2.27; p = 0.03) for infants in vertex and breech position combined. Subgroup analysis revealed a non-significant trend towards better outcome after vaginal delivery that was more pronounced in infants in breech position than in vertex position. Conclusion In infants with myelomeningocele, born in either vertex or breech position, there is no clinical evidence that early neurological outcome is improved by cesarean section.

Attention to gender in communication skills assessment instruments in medical education: a review

Gender is increasingly regarded as an important factor in doctor-patient communication education. This review aims to assess if and how gender is addressed by current assessment instruments for communication skills in medical education. In 2009 at Radboud University Nijmegen Medical Centre, an online search was conducted in the bibliographic databases PubMed, PsycINFO and ERIC for references about communication skills assessment instruments designed to be completed by trained faculty staff and used in medical education. The search strategy used the following search terms: 'consultation skills'; 'doctor-patient communication'; 'physician-patient relations'; 'medical education'; 'instruments'; 'measurement', and 'assessment'. Papers published between January 1999 and June 2009 were included. The assessment instruments identified were analysed for gender-specific content. The search yielded 21 communication skills assessment instruments. Only two of the 17 checklists obtained explicitly considered gender as a communication-related issue. Only six of 21 manuals considered gender in any way and none gave specific details to explain which aspects of communication behaviour should be assessed with regard to gender. Very few communication assessment instruments in medical education focus on gender. Nevertheless, interest exists in using gender in communication skills assessment. The criteria for and purpose of assessing gender in communication skills in medical education are yet to be clarified.

The effect of antecedent hypoglycaemia on β2-adrenergic sensitivity in healthy participants with the Arg16Gly polymorphism of the β2-adrenergic receptor

Aims/hypothesisHomozygosity for glycine at codon 16 (GlyGly) of the β2-adrenergic receptor may alter receptor sensitivity upon chronic stimulation and has been implicated in the pathogenesis of hypoglycaemia unawareness. We compared the effect of antecedent hypoglycaemia on β2-adrenergic receptor sensitivity between GlyGly participants and those with arginine 16 homozygosity (ArgArg) for the β2-adrenergic receptor.MethodsWe enrolled 16 healthy participants, who were either GlyGly (n = 8) or ArgArg (n = 8). They participated randomly in two 2 day experiments. Day 1 consisted of two 2-h hyperinsulinaemic hypoglycaemic (2.8 mmol/l) or euglycaemic (4.8 mmol/l) glucose clamps. On day 2, we measured the forearm vasodilator response to the β2-adrenergic receptor agonist salbutamol and the dose of isoprenaline required to increase the heart rate by 25 bpm (IC25).ResultsThe vasodilator response to salbutamol tended to be greater after antecedent hypoglycaemia than after euglycaemia (p = 0.078), consistent with increased β2-adrenergic receptor sensitivity. This effect was driven by a significant increase in β2-adrenergic receptor sensitivity following hypoglycaemia compared with euglycaemia in ArgArg participants (p = 0.019), whereas no such effect was observed in the GlyGly participants. Antecedent hypoglycaemia tended to decrease the IC25 in ArgArg participants, whereas the reverse occurred in the GlyGly participants (GlyGly vs ArgArg group p = 0.047).Conclusion/interpretationAntecedent hypoglycaemia did not affect β2-adrenergic receptor sensitivity in healthy GlyGly participants, but increased it in ArgArg participants. If these results also hold for participants with type 1 diabetes, such an increase in β2-adrenergic receptor sensitivity may potentially reduce the risk of repeated hypoglycaemia and the subsequent development of hypoglycaemia unawareness in ArgArg diabetic participants.Trial registrationClinicalTrials.gov NCT00160056FundingRadboud University Nijmegen Medical Centre.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2062-3) contains supplementary material, which is available to authorised users.

Endoscopic Endonasal Transsphenoidal Surgery Of Pituitary Tumors

Dr. van Lindert is Neurosurgeon, and Dr. Grotenhuis is Neurosurgeon, Department of Neurosurgery, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands; E-mail: [email protected]. All faculty and staff in a position to control the content of this CME activity and their spouses/life partners (if any) have disclosed that they have no financial relationships with, or financial interests in, any commercial organizations pertaining to this educational activity. Lippincott Continuing Medical Education Institute, Inc. is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Lippincott Continuing Medical Education Institute, Inc. designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity. To earn CME credit, you must read the CME article and complete the quiz and evaluation on the enclosed form, answering at least 70% of the quiz questions correctly. This activity expires on January 14, 2012. Category: Tumor

Plugin architecture for the INCF Scalable Brain Atlas: CoCoMac and beyond

Plugin architecture for the INCF Scalable Brain Atlas: CoCoMac and beyond

Striving to optimize behavior: performance monitoring and adaptive changes in brain activity

Event Abstract Back to Event Striving to optimize behavior: performance monitoring and adaptive changes in brain activity Markus Ullsperger1* 1 Radboud University Nijmegen, Netherlands For successful, goal-directed behavior it is necessary to continuously monitor for deviations of action outcomes from the intended goals and for situations associated with high likelihood to fail. This performance monitoring enables us to adaptively change our behavior, strategies, motivation and cognition in order to achieve optimal action outcomes. I will give an overview on the current knowledge about the functional neuroanatomy of performance monitoring. To elucidate the interactions between performance monitoring and adaptive changes in brain activity and behavior I will discuss findings demonstrating systematic trial-by-trial changes in EEG and fMRI signals prior to, on, and after errors. The presented data support the notion that the posterior mesial frontal cortex signals the need for adjustments and triggers diverse and independent adaptive mechanisms by interactions with other brain regions. Moreover, error-preceding changes in brain activity and our current understanding of maladaptive processes leading to erroneous behavior will be discussed. In the last part of the presentation, I will discuss the relationship of reinforcement learning and performance monitoring. By means of genetic and pharmacological data I will highlight the role of dopamine in this function. Keywords: erroneous behavior, Functional neuroanatomy, Performance monitoring, reinforcement learning Conference: XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011. Presentation Type: Keynote Lecture Topic: Keynote Lectures Citation: Ullsperger M (2011). Striving to optimize behavior: performance monitoring and adaptive changes in brain activity. Conference Abstract: XI International Conference on Cognitive Neuroscience (ICON XI). doi: 10.3389/conf.fnhum.2011.207.00003 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Nov 2011; Published Online: 08 Nov 2011. * Correspondence: Prof. Markus Ullsperger, Radboud University Nijmegen, Nijmegen, Netherlands, m.ullsperger@donders.ru.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Markus Ullsperger Google Markus Ullsperger Google Scholar Markus Ullsperger PubMed Markus Ullsperger Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Interareal directed interactions and their modulation by selective attention assessed with high density electrocorticography in monkey

Event Abstract Back to Event Interareal directed interactions and their modulation by selective attention assessed with high density electrocorticography in monkey Andre Bastos1, 2*, Pascal Fries2, 3, Robert Oostenveld2, Jan-Mathijs Schoffelen2 and Conrado A. Bosman2 1 University of California at Davis, United States 2 Donders Institute, Radboud University Nijmegen, Netherlands 3 Ernst Strüngmann Institute in Cooperation with Max Planck Society, Germany Behaviorally relevant stimuli are processed in visual cortex at the expense of irrelevant ones. The selection of relevant stimuli and the allocation of selective attention require parietal and frontal regions. Yet, it is not fully understood how these areas convey their selection to visual areas. The selection needs to flexibly implement appropriate patterns of interactions in visual cortex. Such flexible interactions might be subserved by flexible patterns of neuronal synchronization. To test this possibility, we trained two monkeys to perform a selective attention task. During fixation, two gratings were presented in the two hemifields. On a given trial, one of them was the behaviorally relevant target. We recorded local field potentials with a subdural electrocorticography (ECoG) grid that contained 252 electrodes, spaced at 2-3 mm, covering large expanses of the left hemisphere from V1 through V4, parietal and central cortex up to frontal eye field (FEF). Coherence and Granger Causality analyses revealed networks with spatially and spectrally distinct synchronization patterns. Areas V1 and V4 were synchronized in the gamma-frequency band (50-90 Hz) and this interaction was almost unidirectional from V1 to V4. Attention to a contralateral stimulus enhanced this feedforward gamma-band influence. Parietal cortex was synchronized with both V4 and with FEF in the beta frequency band. Between parietal cortex and V4, this interaction was predominantly from parietal to V4. For many V4-parietal electrode pairs, selective attention modulated and often enhanced the interaction. We propose that these two spatially and spectrally segregated networks interact to coordinate executive signals from the parietal and prefrontal cortices with perceptual processing in visual cortex Keywords: electrocorticography, neuronal oscillations Conference: XI International Conference on Cognitive Neuroscience (ICON XI), Palma, Mallorca, Spain, 25 Sep - 29 Sep, 2011. Presentation Type: Symposium: Oral Presentation Topic: Symposium 3: The role of neuronal oscillations in computation and communication in multi-scale brain networks Citation: Bastos A, Fries P, Oostenveld R, Schoffelen J and Bosman CA (2011). Interareal directed interactions and their modulation by selective attention assessed with high density electrocorticography in monkey. Conference Abstract: XI International Conference on Cognitive Neuroscience (ICON XI). doi: 10.3389/conf.fnhum.2011.207.00023 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 09 Nov 2011; Published Online: 15 Nov 2011. * Correspondence: Dr. Andre Bastos, University of California at Davis, Davis, United States, andrembastos@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Andre Bastos Pascal Fries Robert Oostenveld Jan-Mathijs Schoffelen Conrado A Bosman Google Andre Bastos Pascal Fries Robert Oostenveld Jan-Mathijs Schoffelen Conrado A Bosman Google Scholar Andre Bastos Pascal Fries Robert Oostenveld Jan-Mathijs Schoffelen Conrado A Bosman PubMed Andre Bastos Pascal Fries Robert Oostenveld Jan-Mathijs Schoffelen Conrado A Bosman Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Constrain your data: relating detailed animal studies to spatial templates in neuroimaging

Event Abstract Back to Event Constrain your data: relating detailed animal studies to spatial templates in neuroimaging Gleb Bezgin1* and Rembrandt Bakker2 1 Baycrest, Rotman Research Institute, Canada 2 Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behavior, Netherlands Techniques such as EEG, fMRI, PET and DTI are widely utilized to extract information on functional and anatomical connectivity in the human brain. For each analyzed brain, these methods provide a complete picture of the measured quantity at a limited resolution. This is in sharp contrast with invasive animal studies, carried out primarily in non-human primates. In particular, the most unambiguous information on long-range interareal connectivity is provided by axonal fibre tract tracing studies. Obtained data are precise up to axonal level, albeit typically apply only to a particular part of the analyzed brain. Hence, linking these two kinds of resources is mutually beneficial. We describe an approach for spatially registering all cortical brain regions from the textual database CoCoMac (K?tter, 2004). Currently, it contains 458 studies, mainly tract tracing experiments, many of which define their own cortical (sub)parcellation. Direct registration to a surface-based Macaque cortex is applied to 9 core parcellations using the tool Caret (Van Essen and Dierker, 2007). The rest of the database is semantically linked to these core parcellations using previously developed algebraic and machine learning techniques (Stephan et al., 2000; Bezgin et al., 2008; Bakker et al., ongoing work). For the translation to the human cortex we rely on Van Essen's landmark-based macaque to human warpings. As a result, one can query CoCoMac for a given spatial coordinate in any of the Caret-supported macaque and human cortical templates. Connectivity was analyzed using multiple graph-theoretical measures to capture global properties of the derived network using the new brain network visualization and analysis tool ConJUNGtion developed on the basis of JUNG software (Madadhain et al., 2005). As a next step, the spatial connectivity maps can be used either as a direct validation of neuroimaging data, or indirectly by constraining generative models of brain activity with a plausible anatomical connectivity assignment. References Bezgin G., Wanke E., Krumnack A., Kötter R. (2008) Deducing logical relationships between spatially registered cortical parcellations under conditions of uncertainty. Neural Networks 21(8): 1132-1145. K?tter R. (2004) Online retrieval, processing, and visualization of primate connectivity data from the CoCoMac database. Neuroinformatics 2(2), 127-44. Madadhain J., Fisher D., Smyth P., White S., Boey Y.B. (2005) Analysis and visualization of network data using JUNG. Journal of Statistical Software, Vol. 10, p. 1--35. Paxinos G., Huang X.-F., Petrides M. and Toga A.W. (2009) The Rhesus Monkey Brain in Stereotaxic Coordinates, 2nd Edition. Amsterdam: Elsevier Science. Stephan K.E., Zilles K., Kötter R. (2000) Coordinate-independent mapping of structural and functional data by objective relational transformation (ORT). Phil. Trans. R. Soc. Lond. B 355, 37-54. Van Essen D. C., Dierker D. L. (2007) Surface-based and probabilistic atlases of primate cerebral cortex. Neuron 56, 209–225. Figure 1 Keywords: digital atlasing Conference: 4th INCF Congress of Neuroinformatics, Boston, United States, 4 Sep - 6 Sep, 2011. Presentation Type: Poster Presentation Topic: Digital atlasing Citation: Bezgin G and Bakker R (2011). Constrain your data: relating detailed animal studies to spatial templates in neuroimaging. Front. Neuroinform. Conference Abstract: 4th INCF Congress of Neuroinformatics. doi: 10.3389/conf.fninf.2011.08.00070 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 17 Oct 2011; Published Online: 19 Oct 2011. * Correspondence: Dr. Gleb Bezgin, Baycrest, Rotman Research Institute, Toronto, Canada, gbezgin@rotman-baycrest.on.ca Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Gleb Bezgin Rembrandt Bakker Google Gleb Bezgin Rembrandt Bakker Google Scholar Gleb Bezgin Rembrandt Bakker PubMed Gleb Bezgin Rembrandt Bakker Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Long-term Results of the Neuroendoscopic Management of Colloid Cysts of the Third Ventricle: A Series of 90 Cases

The endoscopic removal of third ventricular colloid cysts has been developed as an alternative to microsurgical transcortical-transventricular and transcallosal approaches. To examine the value of endoscopic technique by reviewing the large number of endoscopically treated patients with long-term follow-up in 2 neurosurgical centers. A retrospective chart review was conducted for all patients admitted for resection of a third ventricular colloid cyst to the Radboud University Nijmegen Medical Centre (Nijmegen, The Netherlands) and the Hôpital Henri Mondor (Paris, France) between 1994 and 2007. Both clinical and radiological symptoms and operative results were evaluated. Postdischarge clinical follow-up was available for 85 patients over a mean period of 4 years 3 months. Permanent morbidity occurred in 1 patient (persisting preoperative memory deficit). Follow-up imaging of 80 evaluable patients showed that total or nearly total cyst removal was possible in 46 individuals (57.5%). Residual cyst was present in 34 patients (42.5%), and 6 required repeated endoscopic surgery for symptomatic regrowth. Recurrent cysts were mainly seen within the first 2 years after surgery. It is debatable whether the higher numbers of recurrent or residual cysts can be justified by the slightly lower complication rates achieved with endoscopic removal. However, results have been improving over the years. Moreover, the modifications observed on control magnetic resonance images justify the need for regular control imaging for at least the first 2 years postoperatively.

PP048-MON IMMUNE FUNCTION OF PATIENTS ON OLIVE OIL-BASED HOME PARENTERAL NUTRITION WITHOUT AN IMMUNE MODULATING UNDERLYING DISEASE

PP048-MON IMMUNE FUNCTION OF PATIENTS ON OLIVE OILBASED HOME PARENTERAL NUTRITION WITHOUT AN IMMUNE MODULATING UNDERLYING DISEASE E.D. Olthof1, H.M. Roelofs1, M.W. Versleijen1, R.H. te Morsche1, E.R. Simonetti2, P.W. Hermans2, G.J. Wanten1. 1Department of Gastroenterology and Hepatology, 2Laboratory of Pediatric Infectious Diseases, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands Rationale: It remains unclear whether the increased risk for infectious complications seen in patients on Home Parenteral Nutrition (HPN) results from impaired host defenses or from the presence of a venous access device. This study therefore compared immune function of patients on olive-oil based HPN and controls. Methods: Venous blood samples from 20 patients on oliveoil based HPN without an immune modulating underlying disease (Clinoleic®, 6 months; >3 times/ week), and 21 matched healthy controls were analyzed. Neutrophil function was assessed by evaluating neutrophil capacity to kill Streptococcus pneumonia, expression of markers for leukocyte adhesion (CD11b), -activation (CD62L) and -degranulation (CD66b) and stimulus induced oxygen radical production. Non-parametric statistical analysis was performed using the Mann-Whitney U test. Results: Neutrophils from HPN patients displayed a similar capacity to kill Streptococcus pneumoniae compared to controls (mean±SEM: 49±5% and 45±5% killing respectively, p = 0.513). Also, levels of CD66b (p = 0.725) in granulocytes and of CD11b and CD62L in granulocytes (p = 0.106 and p = 0.121 respectively) and monocytes (p = 0.958 and p = 0.211 respectively) were not different in patients and controls. Spontaneous, phorbol esterand zymosan-induced oxygen radical production was also not different in whole blood (p = 0.068, p = 0.835 and p = 0.167 respectively) or isolated neutrophils (p = 0.696, p = 0.784 and p = 0.835 respectively) of patients and controls. Conclusion: In conclusion, we found no evidence for the presence of compromised immune functions in patients on olive-oil based home parenteral nutrition without an immune modulating underlying disease to explain the increased susceptibility to infections seen in some of these patients. Disclosure of Interest: E. Olthof: None Declared, H. Roelofs: None Declared, M. Versleijen: None Declared, R. te Morsche: None Declared, E. Simonetti: None Declared, P. Hermans: None Declared, G. Wanten Grant/Research Support from: Baxter Netherlands BV

Strong in Biomaterials and Polymer Science

What was most interesting and important to our reader in 2010? Among the 270 articles published in the last two years the topics drug and gene delivery and tissue engineering could assemble the most citations in 2010, followed by more classical polymer topics such as biodegradable polymers, glycol- and biopolymers (Table 1). It's thus fair to say: Macromolecular Bioscience is strong in biomaterials and polymer science. What was most interesting to me? I have to admit that I was deeply impressed by the outstanding topical issues we published within the last year. In November, a special issue on “Instructive Materials for Functional Tissue Engineering” guest-edited by Anita Driessen-Mol, Carlijn V. C. Bouten, and Frank P. T. Baaijens (Eindhoven University of Technology, The Netherlands) highlighted topics such as cardiac repair, heart valves and blood vessel replacements, and in situ bone formation, just to name a few. Issue 9 was dedicated to “Polymers in Biomedicine” (guest-edited by Andreas Lendlein, GKSS Research Center Teltow, Germany). With the help of board member Jan C.M. van Hest (Radboud University Nijmegen, The Netherlands) we published an impressive issues on “Micro- and Nanocapsules for Biological and Biomedical Applications”. The renaissance of “Analytical Ultracentrifugation”, a topical issue organized by one of our newer board members, Helmut Cölfen (University of Konstanz, Germany) on the occasion of the 125th birthday of Theodor Svedberg, concentrated on a less classical, though not less interesting topic for Macromolecular Bioscience. All in all, the anniversary year of Macromolecular Bioscience was a year of great topical diversity, which has made it so exciting for me. A year of celebrations? Not only. It was also a year of hard work. Dealing with roughly 10% more submissions as compared to 2009, we were still able to reduce the average time to initial decision of all published articles to 35 days. But there is even more to be happy about. The number of article accesses (full-text downloads) and the number of total citations both increased by more than 20%. After one decade, Macromolecular Bioscience confirms its position among the top 5 biomaterials and the top 10 polymer journals with an ISI impact factor of 3.108. Finally, we welcome two new members to our international advisory board: We are looking forward to an intensified cooperation with Helmut Schlaad (MPI of Colloids and Interfaces, Golm, Germany) and Brent Sumerlin (Southern Methodist University, Dallas, USA). Not only our board members, but also our critical reviewers, our authors, and last but not least our readers contribute to the success of Macromolecular Bioscience. It's time to thank all of you for your commitment and your ongoing interest in our journal. Together, we are looking forward to the exciting second decade of Macromolecular Bioscience.

Risk of colorectal and endometrial cancers in EPCAM deletion-positive Lynch syndrome: a cohort study

Lynch syndrome is caused by germline mutations in MSH2, MLH1, MSH6, and PMS2 mismatch-repair genes and leads to a high risk of colorectal and endometrial cancer. We previously showed that constitutional 3' end deletions of EPCAM can cause Lynch syndrome through epigenetic silencing of MSH2 in EPCAM-expressing tissues, resulting in tissue-specific MSH2 deficiency. We aim to establish the risk of cancer associated with such EPCAM deletions. We obtained clinical data for 194 carriers of a 3' end EPCAM deletion from 41 families known to us at the Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands and compared cancer risk with data from a previously described cohort of 473 carriers from 91 families with mutations in MLH1, MSH2, MSH6, or a combined EPCAM-MSH2 deletion. 93 of the 194 EPCAM deletion carriers were diagnosed with colorectal cancer; three of the 92 women with EPCAM deletions were diagnosed with endometrial cancer. Carriers of an EPCAM deletion had a 75% (95% CI 65-85) cumulative risk of colorectal cancer before the age of 70 years (mean age at diagnosis 43 years [SD 12]), which did not differ significantly from that of carriers of combined EPCAM-MSH2 deletion (69% [95% CI 47-91], p=0·8609) or mutations in MSH2 (77% [64-90], p=0·5892) or MLH1 (79% [68-90], p=0·5492), but was higher than noted for carriers of MSH6 mutation (50% [38-62], p<0·0001). By contrast, women with EPCAM deletions had a 12% [0-27] cumulative risk of endometrial cancer, which was lower than was that noted for carriers of a combined EPCAM-MSH2 deletion (55% [20-90], p<0·0001) or of a mutation in MSH2 (51% [33-69], p=0·0006) or MSH6 (34% [20-48], p=0·0309), but did not differ significantly from that noted for MLH1 (33% [15-51], p=0·1193) mutation carriers. This risk seems to be restricted to deletions that extend close to the MSH2 gene promoter. Of 194 carriers of an EPCAM deletion, three had duodenal cancer and four had pancreatic cancer. EPCAM deletion carriers have a high risk of colorectal cancer; only those with deletions extending close to the MSH2 promoter have an increased risk of endometrial cancer. These results underscore the effect of mosaic MSH2 deficiency, leading to variable cancer risks, and could form the basis of an optimised protocol for the recognition and targeted prevention of cancer in EPCAM deletion carriers.

Selective amplification of the lower-frequency branch via stimulated super-radiance in a waveguided free electron laser oscillator driven by short electron bunches

In this letter, we propose a mechanism to extend the spectral range of a waveguided free electron laser (FEL) oscillator driven by a rf LINAC toward significantly longer wavelengths without changing the undulator or accelerator design parameters. This mechanism involves selective amplification of a lower-frequency branch supported in a FEL due to the waveguide dispersion. Based on simulations performed for the terahertz FEL under construction at the Radboud University Nijmegen, we conclude that these long wavelengths can be efficiently amplified via stimulated super-radiance as the electron bunches are shorter than the radiation wavelength.

Een goed begin van de dag: een experimentele studie naar imitatie-effecten van ontbijtgedrag

Social modeling effects on young women’s breakfast intake Numerous studies have shown that the presence of others influences young women’s food intake. They eat more when the other eats more, and eat less when the other eats less. However, most of these studies have focused on snack situations. The present study assesses the degree to which young women model the breakfast intake of a same-sex peer in a semi-naturalistic setting. The study took place in a laboratory setting at the Radboud University Nijmegen, the Netherlands, during the period January – April 2009. After completing three cover tasks, normal-weight participants (N=57) spent a 20-min break with a peer who ate a large amount or a small amount of breakfast or no breakfast at all. The participants’ total amount of energy consumed (in kilocalories) during the break was measured. An analysis of variance was used to examine whether young women modeled the breakfast intake of same-sex peers. Results indicate a main effect of breakfast condition, (F(2,54)=8.44, p<.01). Participants exposed to a peer eating nothing ate less than did participants exposed to peer eating a small (d=.85) or large amount of breakfast (d=1.23). Intake in the Small-Breakfast condition did not differ significantly from intake in the Large-Breakfast condition. The findings from the present study provide evidence for the assumption that modeling effects of food intake are weaker in eating contexts in which scripts or routines may guide an individual’s eating behavior.

Intraoperative Auditory Steady State Response Measurements During Vibrant Soundbridge Middle Ear Implantation in Patients With Mixed Hearing Loss

To optimize intraoperatively the coupling of the floating mass transducer (FMT) of the Vibrant Soundbridge middle ear implant to the round or oval cochlear window in patients with mixed hearing loss. Intraoperative measurement of objective hearing thresholds using auditory steady state responses (ASSRs). Radboud University Nijmegen Medical Centre, tertiary referral hospital. Four individuals with mixed hearing loss and, at least no incus, in need for a middle ear implant. Surgical placement of the Vibrant Soundbridge. ASSR thresholds were measured intraoperatively, whereas FMT coupling to the cochlea was manipulated to find the most effective coupling of the FMT. Differences in ASSR thresholds between different FMT coupling options within patients. With ASSR, we assessed placement of the FMT in the round window niche, loosely or tightly packed in the niche; creation of a mobile window in case of a fixed stapes footplate; and FMT position coupled to the stapes that afforded vibration in the natural vibration direction or perpendicular to it. Furthermore, test-retest variations in ASSR thresholds were studied. It was shown that differences in ASSR thresholds could be detected, while manipulating the FMT couplings, which were statistically significant. Intraoperative ASSR measurement is a good method to study different positions of the FMT and to determine the best position of the FMT for a patient.

Social Modeling Effects on Young Women's Breakfast Intake

Numerous studies have shown that the presence of others influences young women's food intake. They eat more when the other eats more, and eat less when the other eats less. However, most of these studies have focused on snack situations. The present study assesses the degree to which young women model the breakfast intake of a same-sex peer in a semi-naturalistic setting. The study took place in a laboratory setting at the Radboud University Nijmegen, the Netherlands, during the period January to April 2009. After completing three cover tasks, normal-weight participants (n=57) spent a 20-minute break with a peer who ate a large amount or a small amount of breakfast or no breakfast at all. The participants' total amount of energy consumed (in kilocalories) during the break was measured. An analysis of variance was used to examine whether young women modeled the breakfast intake of same-sex peers. Results indicate a main effect of breakfast condition, F(2,54)=8.44; P<0.01. Participants exposed to a peer eating nothing ate less than did participants exposed to a peer eating a small amount ( d=0.85) or large amount of breakfast ( d=1.23). Intake in the Small-Breakfast condition did not differ substantially from intake in the Large-Breakfast condition. The findings from the present study provide evidence that modeling effects of food intake are weaker in eating contexts in which scripts or routines guide an individual's eating behavior.

Tooth Agenesis Patterns in Bilateral Cleft Lip/Palate (BCLP) Indicate Possible Common Genetic Pathways

Tooth agenesis patterns in bilateral cleft lip and palate. Bartzela TN, Carels CEL, Bronkhorst EM, Ronning E, Rizell S, Kuijpers-Jagtman AM. Eur J Oral Sci 2010;118:47-52. Michael D. Martin, DMD, MSD, MPH, MA, PhD. Are there patterns of tooth agenesis in BCLP that may indicate genetic contributions common to tooth developmental anomalies and cleft lip/palate? Supported by the Department of Dentistry, Radboud University Nijmegen Medical Center, the Netherlands. Retrospective cohort. Level 2: Limited-quality, patient-oriented evidence. Not applicable.

Patterns of cortical degeneration in an elderly cohort with cerebral small vessel disease

Emerging noninvasive neuroimaging techniques allow for the morphometric analysis of patterns of gray and white matter degeneration in vivo, which may help explain and predict the occurrence of cognitive impairment and Alzheimer's disease. A single center prospective follow-up study (Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort study (RUN DMC)) was performed involving 503 nondemented elderly individuals (50-85 years) with a history of symptomatic cerebral small vessel disease (SVD). Age was associated with a global reduction in cortical thickness, and this relationship was strongest for ventrolateral prefrontal cortex, auditory cortex, Wernicke's area, superior temporal lobe, and primary visual cortex. Right and left hemispheres differed in the thickness of language-related areas. White matter (WM) lesions were generally negatively correlated with cortical thickness, primarily in individuals over the age of 60, with the notable exception of Brodmann areas 4 and 5, which were positively correlated in age groups 50-60 and 60-70, respectively. The observed pattern of age-related decline may explain problems in memory and executive functions, which are already well documented in individuals with SVD. The additional gray matter loss affecting visual and auditory cortex, and specifically the head region of primary motor cortex, may indicate morphological correlates of impaired sensory and motor functions. The paradoxical positive relationship between WM lesion volume and cortical thickness in some areas may reflect early compensatory hypertrophy. This study raises a further interest in the mechanisms underlying cerebral gray and white matter degeneration in association with SVD, which will require further investigation with diffusion weighted and longitudinal MR studies.