NCA Annual Report 2015 and september 2009-2014 by Vrije Universiteit Amsterdam

Table of contents Word from the director ...................................................................................................................................... 3

Section I: Self-evaluation based on Annual Reports 2009-2014 .............................................................. 4 Introduction........................................................................................................................................................ 5 Part 1. Research description............................................................................................................................... 5 1.1 Organisation, composition and funding .................................................................................................. 5 1.2 Description of research programmes...................................................................................................... 6 1.2.1 Brain Imaging Technology ....................................................................................................................... 6 1.2.2 Brain Mechanisms in Health & Disease ................................................................................................... 7 1.2.3 Neurodegeneration ................................................................................................................................. 8 1.2.4 Neuroinflammation ................................................................................................................................. 9 1.2.5 Neurobiology of Mental Health ............................................................................................................ 10 1.3 Strategy and targets .............................................................................................................................. 10 1.4 Performance indicators ......................................................................................................................... 11 1.5 Results ................................................................................................................................................... 12 1.6 Own assessment of quality, relevance and viability ............................................................................. 13 1.7 Relevant environmental factors and future developments .................................................................. 14 1.8 SWOT analysis ....................................................................................................................................... 15 Part 2. PhD program ......................................................................................................................................... 16 2.1 Context, supervision and quality assurance .......................................................................................... 16 2.2 Participation in the Graduate School, courses for PhD students .......................................................... 17 2.3 Selection and admission ........................................................................................................................ 17 2.4 Supervision of PhD candidates, and guidance to labour market .......................................................... 17 2.5 The future of graduates in various sections .......................................................................................... 17 2.6 Duration and success rates ................................................................................................................... 18 2.7 Analysis and future strategy.................................................................................................................. 18 Part 3. Research integrity ................................................................................................................................. 19 3.1 General reflection on research integrity and culture............................................................................ 19 3.2 Data storage .......................................................................................................................................... 20 3.3 Quality control committees .................................................................................................................. 20 Part 4. Appendices............................................................................................................................................ 22 4.1 Research ................................................................................................................................................ 22 4.1.1 Research Organization .......................................................................................................................... 22 4.1.2 Research Staff Composition .................................................................................................................. 24 4.2 Funding.................................................................................................................................................. 24 4.3 Output indicators .................................................................................................................................. 26 4.4 Citation analysis .................................................................................................................................... 28 4.5 Length and success rates of PhD program ............................................................................................ 30 4.6 Key scientific publications in past six years ........................................................................................... 31 4.7 Conclusions and mission statements at the start of the institute ........................................................ 34 4.8 Midterm assessment 2008-2010........................................................................................................... 35

Section II: Annual Report 2015 .................................................................................................................... 37 1a. 1b. 2a. 2b. 3. 4.

Composition (input data) ...................................................................................................................... 38 Participating researchers ...................................................................................................................... 40 Quality and scientific relevance ............................................................................................................ 41 Quality control ...................................................................................................................................... 43 Output ................................................................................................................................................... 44 Earning capacity – NCA ......................................................................................................................... 46

Section III: Site Visit Report (February 2016)............................................................................................. 48 1. 1.1 1.2 1.3 1.4

Introduction .......................................................................................................................................... 49 Background ........................................................................................................................................... 49 Members of the assessment committee .............................................................................................. 49 Procedures followed ............................................................................................................................. 50 Research unit under assessment: Neuroscience Campus Amsterdam ................................................. 50

2. 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8

Qualitative and quantitative assessments of NCA research ................................................................. 52 NCA’s strategy and targets .................................................................................................................... 52 Assessment Neuroscience Campus Amsterdam as a whole ................................................................. 52 Assessment Brain imaging technology programme .............................................................................. 53 Assessment Brain mechanisms in health & disease programme .......................................................... 54 Assessment Neurodegeneration programme ....................................................................................... 54 Assessment Neuroinflammation programme ....................................................................................... 55 Assessment Neurobiology of mental health programme ..................................................................... 56 Summary in numerical scores ............................................................................................................... 56

3. 3.1 3.2

Qualitative assessment of PhD programme and research integrity policy ........................................... 57 Quality and organisation of PhD programme ....................................................................................... 57 Research integrity policy ....................................................................................................................... 58

4. 4.1 4.2 4.3

Recommendations ................................................................................................................................ 59 Quality of the research unit .................................................................................................................. 59 PhD programme .................................................................................................................................... 61 Research integrity ................................................................................................................................. 62

Appendices 1. Short CVs of the members of the assessment committee .................................................................... 63 2. Site visit programme ............................................................................................................................. 65 3. Quantitative data on NCA’s composition and financing ....................................................................... 67 4. Explanation of the categories utilised ................................................................................................... 70

Section IV: Response of Board of Deans (March 2016) ........................................................................... 71 Response of Board of Deans (March 14, 2016) ................................................................................................ 72

Section V: Transition to Amsterdam Neuroscience (2016) ..................................................................... 73 Transition to Amsterdam Neuroscience (2016) ............................................................................................... 74

Word from the director On behalf of all partners of the Neuroscience Campus Amsterdam (NCA), i.e. staff, coworkers and graduate students, we present the Annual Report of 2015. However in 2015 the Neuroscience Campus Amsterdam was also officially evaluated according to the socalled Standard Evaluation Protocol (SEP) under the authority of the Association of Universities in the Netherlands (VSNU), the Netherlands Organisation for Scientific Research (NWO), and the Royal Netherlands Academy of Arts and Sciences (KNAW). In preparation of the SEP protocol and Site Visit by the international evaluation committee, we produced a socalled Selfevalution of NCA 2009-2014, which is now published in Section I of this booklet. In section II, we give a short overview by way of extension for the year 2015. It is clear that the solid impact of our research output remains based primarily on both a quality-oriented, a curiosity- and also a strong purpose-driven research strategy. There are numerous examples of multidisciplinary studies that made it into high impact journals. With a total of more 600 peer reviewed papers and with more than 100 papers in the top 5% of the international journals, we maintain an excellent standard. In section III and IV, the SEP Report and Position of the Deans respectively are published. We are generally very content with the assessment and recommendations outlined in these sections. They also form the prelude to the intended transition from Neuroscience Campus Amsterdam (NCA with VU and VUmc partners only) to “Amsterdam Neuroscience”, now also including our alliance partners of the Amsterdam Medical Center (AMC), and the Swammerdam Institute for Life Sciences (SILS) of the University of Amsterdam (UvA). In section V, we give a short overview of the way in which the transition to Amsterdam Neuroscience will take place during 2016. Last but not least, as in previous years, we have continued to put much of our time and efforts in shifting NCA’s acquisition strategy towards a more biotech and pharma-industry-oriented position (www.iao-neuroscience.com). Under our guidance, the Industry Alliance Office (IAO) will continue to serve the Neuroscience research community of Amsterdam in line with the launch of Amsterdam Neuroscience, as described in Section V. Prof. dr. Arjen B. Brussaard Scientific Director of Neuroscience Campus Amsterdam & Chief Scientific Officer of the Industry Alliance Office

Section I â&#x20AC;&#x201C; Self-evaluation 2009-2014

Introduction The mission of the NCA is to study the brain and its disease mechanisms through an integrative approach running from molecule-to-bedside. We apply a systems biology approach of the brain where clinicians and clinical researchers are working side-by-side with neuroscientists, geneticists, psychologists, epidemiologists, biophysicists and statisticians. The NCA currently is the largest neuroscience research community gathered on one campus in the Netherlands. We strongly focus on molecular neurobiology, going all the way from biophysics, genetics, genomics and systems biology of the synapse, to heritability and genetic basis of brain function. In the present so-called self assessment 1 we present the facts and figures of our institute and provide an evaluation over the period 2009-2014. This document comprises three parts: (1) description of the research being performed at NCA, (2) documentation regarding the PhD program at NCA (3) description of research integrity at NCA, and several appendices, including documentation of input and output of the research.

Part 1. Research description 1.1 Organisation, composition and funding NCA is a research institute at the VU University Medical Center (VUmc) and VU University Amsterdam (VU). Built upon a rich, but scattered, neuroscience research history, it was founded in 2008 to create a research network organisation where scientists, students, medical professionals, and visiting scientists collaborate in the field of Translational Neuroscience to an extent that is quite unique in the Netherlands. All research activities are interdisciplinary and incorporate recent theoretical, methodological and application paradigms, always with the patient in mind. Our strongholds and international reputation build on our work in understanding the human brain, on our clinical studies of its major diseases, on development of advanced technologies and on a long tradition of behavioural genetics. NCA has a mission to produce innovative research and technology leading to scientific discoveries in Neuroscience. However, Neuroscience is valuable not only for the advancement of science but also because the results may greatly impact our society and economy. Over the last three decades Neuroscience has become a truly integrative science, from the molecule to the systems level and the patient, encompassing normal human brain function as well as the clinical expertise to diagnose and address the biological mechanisms underlying brain diseases. NCA aims to train national and international brain researchers by creating an environment of scientific excellence that will integrate various intellectual disciplines. From that convergence, we try to find solutions that will ultimately benefit society in the realms of medicine, engineering, alliance with biotech and pharma industry, and for graduate education. NCA is truly translational in nature, and explicitly links basic science and clinical science. In this sense, NCA functions as a network organisation where patient-centres, such as the Alzheimer Center, the MS Center, the Movement Disorder Clinic, the Center for Childhood White Matter Disorders and the GGZ inGeest clinic for Anxiety and Depression are the major â&#x20AC;&#x2DC;hubsâ&#x20AC;&#x2122; in our network. 1

Research evaluation at the universities and university medical centres in the Netherlands is organised by the respective boards. The present self-evaluation of the research institute Neuroscience Campus Amsterdam (NCA) covers the years 2009-2014. The procedures for this evaluation are carried out as outlined in the Standard Evaluation Protocol (SEP) 2015-2021 and further specified by the VU University Amsterdam (VU) and the VU University Medical Center Amsterdam (VUmc). This report was written under the responsibility of Hans Brug, dean of VUmc (chair of the Board of deans of NCA), Karen Maex, dean of the Beta-cluster Faculties, Peter Beek, dean of the Faculty of Psychology & Pedagogy, Arjen Brussaard, scientific director of NCA, and further in cooperation with the program leaders of the five NCA research programs and the management team of NCA. 5

Section I – Self-evaluation 2009-2014

As outlined in appendices 4.1.1, 4.7 and 4.8 at the start of NCA we launched this institute because of a sense of urgency and need to further integrate across the various Neuroscience disciplines. The composition of the research staff is given in section 4.1.2. Details on funding & finances are outlined in section 4.2. NCA has a lean management structure consisting of a scientific director, a management team and a supervisory board of deans. NCA is advised by an external, independent scientific committee, consisting of five scientists from the Netherlands, now chaired by Van Ommen. 1.2 Description of research programs At the start of NCA, a total of 10 research programs was launched (see Figure I-1). At midterm in 2011-2012 we decided that in view of a much wanted focus - and also with a keen eye on future collaborations in Amsterdam (i.e. in view of collaboration – a reduction of the total number of research programs at NCA was required. During the last 3 years, research at NCA has been organised in five research programs (see Figure I-2). A program Committee, with two Program Leaders and usually a dozen (or more) Program Members (Faculty), coordinates each research program. Program leaders of each program (often one with a clinical back ground and one with a more preclinical background) have the authority to organise and guide the program committee with respect to appointments, strategy of the research, and prioritisation of propositions to the director and the management team. With respect to leadership, the program leaders represent their program committee when it comes to decision making at the level of NCA as an entity.. 1.2.1 Brain Imaging Technology – Frederik Barkhof (VUmc) & Huibert Mansvelder (VU) Rationale and common goals: The field of brain imaging provides novel insights into brain function and disease mechanisms from the molecular level to the whole-brain network. Brain imaging is a rapidly developing field, and even for large centres it is increasingly challenging to keep up acrossthe-board research programs. At NCA we have excellent infrastructure and expertise on MRI, PET (including a local cyclotron), EEG/MEG. In addition Optical Coherence Tomography (OCT) of the human retina and Laser Scanning Microscopy (LSM) imaging technology of the cortex and deeper structures of the brain is implemented in this research program. Using the latter technology, we aim to study a) fundamental network functions in the brain and pathophysiological mechanisms of disease by collecting intraoperative data on neuronal activity by microrecordings, and combining this with anatomical data from Laser Scanning Microscopy and connectivity data from advanced MRI methods (under supervision of Frederik Barkhof and Huibert Mansvelder) and b) to further develop the techniques and clinical applications of optical coherence tomography and laser scanning microscopy (under supervision of Johannes de Boer in collaboration with Frederik Barkhof), studying the retinal manifestations of neurodegenerative disorders. Assets: The brain-imaging program has an extensive infrastructure including all available imaging modalities for cellular imaging (including fluorescence microscopy, electron microscopy, flow cytometry as part of the core facility cellular Imaging), magnetic resonance imaging (including 7T MR imaging), nuclear imaging techniques (including PET/MRI), magneto-electro-encephalography (MEG), and cutting edge in house developed optical imaging techniques. This ‘expensive infrastructure’ comes with advanced technical expertise to support data acquisition, data management and development of advanced data analysis tools (e.g., through Institute Quantivision, EATRIS), as well as statistical analysis. We provide services to other fields of medicine too, but the brain remains the main focus, at least for modalities such as MEG and highfield MRI.

Section I – Self-evaluation 2009-2014

Translational links: At NCA we wish to leverage on a fully translational Brain Imaging program, which focuses on multi-modal imaging and minimally invasive brain imaging techniques suitable for drug targeting strategies, and individualisation of treatment strategies. Improved profiling in human brain studies is provided by [a] fully translational brain imaging capacities (enhance weak points like micro PET/SPECT/MRI); [b] multi-modal imaging capacities (improve new technologies: high-field MRI, PET-MRI, OCT, in addition to real-time fMRI/EEG and improve close integration with physics and mathematics for receptor mapping, pharmaco-fMRI and network analysis); [c] minimally invasive programs suitable for ‘personalised medicine’ and drug-targeting strategies (focus on network analysis, defining new physiological parameters such as pharmaco-fMRI and other inventive receptor imaging strategies, neurofeedback, real-time fMRI/EEG). 1.2.2 Brain Mechanisms in Health & Disease – Matthijs Verhage (VU & VUmc) & Marjo van der Knaap (VUmc) Rationale and common goals: The objective of this research program is to find causal relationships in brain mechanisms of the healthy brain (under supervision of Matthijs Verhage) and the origin of disease (under supervision of Marjo van der Knaap). We investigate not only molecular processes but also integrate such processes at higher levels of organisation (organelles, cells, networks, the whole brain). In order to treat brain pathologies, we need to improve our understanding of basic brain functions and assess which molecular and physiological mechanisms are involved in those functions. The strength of this theme is its uniform importance for all specific brain disease indications and its links to all other programs. Moreover it includes cutting edge technology and the experts that are needed to implement this. In addition NCA applies complex trait genetics (under supervision of Danielle Posthuma). In the past decade we have seen major advances in technology (e.g. microarrays, next generation sequencing, brain imaging, induced pluripotent stem cells) in a number of fields, which have led to unprecedented advances in our knowledge of the genetic architecture of brain disorders. Advances in genotyping technology have been accompanied by a lowering of costs and an increase of datasets and sample sizes available for research. Thanks to sophisticated software tools, results from large-scale genetic studies have provided novel insights and keys for functional and pharmaceutical follow-up. In the next couple of years sample sizes for genetic association discovery analyses are expected to increase and will yield an increasing amount of reliable genetic discoveries. Interpreting these ‘hits’ in their polygenic context and using them to guide functional experiments is a major focus of our research program. Assets: This research program provides (i) cutting edge technology and infrastructure (quantitative proteomics, life cell imaging, FACS, laser capture dissection, brain organoid culture, in utero electroporation, in vivo multi-unit recordings and optogenetics, cellomics, computational modelling); (ii) the availability of numerous essential animal models systems; (iii) the Genetics Cluster Computer (http://www.geneticcluster.org) (Dept. Complex Trait Genetics, VUmc) which provides storage capacity and processing power for genetic research, available for massive calculations on big data; (iv) the genomics facility of AMC and VUmc (i.e. the merged departments of clinical genetics) which delivers services for large scale genome analyses (e.g. whole exome sequencing; in collaboration with the foundation HMF whole genome sequencing), RNA sequencing, and epigenic analyses; (v) the ‘Klinische Genetica Balie’ (Clinical Genetics Desk) which provides a platform where clinicians and scientists meet on a monthly basis to discuss patient cases and possibilities for follow-up research; (vi) the Center for Childhood White Matter Disorders which integrates research and clinical care, and creates a perfect setting for translational research (having a unique cohort of patients with White Matter Disorders, imaging and patient samples, including MRIs, DNA, cell lines and brain tissue); (vii) The stem cell lab

Section I â&#x20AC;&#x201C; Self-evaluation 2009-2014

(http://www.ipscenter.nl) (of the Center for Childhood White Matter disorders and Dept. Paediatrics & Dept. Complex Trait Genetics, under supervision of Dr Vivi Heine) which provides induced pluripotent stem (IPS) cell lines for patients and controls, which can be differentiated into glial or neuronal cell types; and (viii) access to cohorts of patients with Mendelian inherited diseases (such as with mental retardation with unknown cause after whole exome sequencing) due to high-risk alleles serving as a source to dissect complex traits. In addition investigators of this NCA program participate in NESCOG (Netherlands Study of Cognition which provides a population based control cohort with information on a wide range of phenotypes and genotypic information) and in several international consortia that provide data (raw genotypic data or summary statistics) such as the international Psychiatric Genomics Consortium. Translational links: As mentioned above, this theme nurtures all clinical themes of NCA (under supervision of Marjo van der Knaap) and maintains good connections to industry (biotech, pharma), incl. spin-offs and is able to stimulate new initiatives due to its strong scientific and innovative nature. This program further aims to build a bridge between clinicians and scientists: clinicians provide diagnostic expertise and patient material, which is analysed and interpreted in close collaboration with the scientists. One of the examples of actively working on translational science is the Klinische Genetica Balie (under supervision of Hanne Meijers). Identification of new disease genes or alleles is of relevance to patients and their families. Prognosis can be more precisely predicted in patients with a known genetic cause of their disease, and genotype based (risk reducing) interventions and therapies may be or become available. Further, identification of the genetic cause of the disease facilitates risk assessment and reproductive choices in couples concerned, e.g. offers the opportunity of prenatal diagnostics or Preimplantation Genetic Diagnostics in future pregnancies. The essence of this research program is the high quality-driven research with strong team spirit and availability of involved experts on all topics; the ability to bridge the gap between genome information and neurobiological processes and behavioural phenotypes; and the use of cutting edge technology and availability of unique animal models to solve complex questions the implementation of human embryonic stem cell - and patient derived induced pluripotent stem cell (iPSC) strategies in order to generate new models that connect fundamental brain research towards clinical relevant questions. 1.2.3 Neurodegeneration - Wiesje van der Flier (VUmc) & August Smit (VU) Rationale and common goals: Neurodegenerative disorders share a profound pathophysiological and clinical complexity; for the majority of patients, multiple causes in concert lead to the development of disease, which unfolds over the course of years, probably decades. A careful clinical evaluation is the corner stone for a valid diagnosis of any neurodegenerative disorder. Moreover, it provides fundamental insight into the basic mechanisms that are critical for the development and validation of animal models and biomarkers. To date, treatment is limited to alleviation of symptoms, but our ultimate goal is to recognise disease before it manifests clinically, understand disease mechanisms and subsequently modify the disease process to prevent progression to a full blown disease state. This goal can only be achieved by improving early diagnostics, understanding clinical heterogeneity and mixed pathologies, and unravelling underlying mechanisms in patients and relevant model systems. We are in an excellent position to execute an integrative research program tailored to these aims. New technologies and in-house assets are the necessary prerequisites for success.

Section I â&#x20AC;&#x201C; Self-evaluation 2009-2014

Assets: Our major assets are large and unique patient cohorts (Amsterdam Dementia Cohort: ~n=5000 under supervision of Ph. Scheltens and Wiesje van der Flier; Netherlands Parkinson cohort: ~n=1000 under supervision of Henk Berendse), large biobanks (under supervision of Charlotte Teunissen), extensive (multi-modal) brain imaging facilities and clinical trials. We have a strong tradition in translational research with excellent facilities. We have a longstanding and close collaboration with the Dutch Brain Bank and a history of research on post mortem tissue. Furthermore, we have ample experience in executing both complex, high-end clinical trials and large nationwide clinical trials. There is extensive expertise in clinical research, generation of wellcharacterised patient cohorts, clinical (endo)phenotyping (including advanced imaging using MRI, PET, EEG/MEG), as well as studies of (novel) biomarkers, neuroanatomy, neuropathology, transcriptomics, proteomics, gene finding, functional characterisation, cellular and animal models. A major challenge of the program will be to further emphasise synergistic approaches that can lead to breakthrough findings. The combined availability of Netherlands Brain Bank, the Normal Aging Brain Collection Amsterdam (NABCA) and the 100+ studies at the Alzheimer Center in collaboration with the Department of Clinic Genetics is unique worldwide. Translational links: The program Neurodegeneration is truly translational. Our starting point and inspiration are careful clinical observation of our patients by passionate clinicians. Clinical data collected in the patient setting form the basis for our clinical research activities, and they also form the inspiration for bedside to bench translation, i.e. for basic science aiming to unravel the underlying brain disease mechanisms (under supervision of August Smit). In turn, state of the art basic science aims to provide and test targets for the better diagnostic and prognostic biomarkers, and the development of novel or improved treatment (bench to bedside). Use of patient biomaterial and developing new approaches in employing patient-derived cells will boost this effort. We are fully equipped to test novel treatments (infrastructure for Phase 1, 2, 3, 4 studies are available). 1.2.4 Neuroinflammation â&#x20AC;&#x201C; Elga de Vries (VUmc) & Joep Killestein (VUmc) Rationale and common goals: The focus of the Neuroinflammation program is on multiple sclerosis. In these areas, VUmc/VU (MS Center Amsterdam) has a leading role in the Netherlands and beyond, both from a clinical and a research perspective. Research on the blood-brain-barrier (under supervision of Elga de Vries) as crucial dominator of multiple sclerosis will be encouraged. We will perform translational research through an integrative approach running from bedside to molecule and vice versa. Assets: Our major assets are large and unique patient cohorts, together with a strong translational link to basic sciences. About 50 percent of all newly diagnosed MS patients in the Netherlands visit the MS Center Amsterdam (under supervision of Bernard Uitdehaag & Joep Killestein) for a consultation. This has resulted in internationally unequalled biobanks on MS. Another major asset of this program is the strong translational link combining clinical and experimental research. Previous results have been quickly translated into patient care. Translational Links: Neuroinflammation is considered crucial in multiple sclerosis, but the concept of neuroinflammation is also important in many other neurological diseases, i.e., neurodegenerative disease. In these areas, we perform prospective clinical cohort studies, randomised clinical trials, and experimental research, combining our clinical expertise with ground-breaking, translational approaches using clinical data, human samples, next generation sequencing, in vitro techniques, and mouse models. By using unique in vitro and in vivo disease models new targets for therapies can be tested. Subsequently, we undertake a broad range of

Section I – Self-evaluation 2009-2014

clinical research from first-in-man studies to large national and international multicentre clinical trials. 1.2.5 Neurobiology of Mental Health – Brenda Penninx (VUmc) & Sabine Spijker (VU) Rationale and common goals: Psychiatric disorders share common neurobiological characteristics both in development and in clinical symptoms. This is especially true for psychiatric disorders that involve severe emotional disturbances, such as disorders that affect mood, attention/impulsivity and addiction/compulsivity. Translational, cross-disorder studies with a life span perspective (from early vulnerability to late disease chronicity) may enhance our knowledge and treatment possibilities for these disorders, which constitute a huge burden to patients but also to the society as a whole. The focus of this research program is to identify neurobiological mechanisms (e.g. pathophysiological mechanisms and genomic regions and gene variants) that mediate vulnerability to these most common psychiatric disorders. Our vision is to gain knowledge that can then be applied towards development of new treatments through collaborative efforts. Our aims are a) to identify neurobiological mechanisms (e.g. at the synaptic and brain systems level) that mediate vulnerability to and progression of psychiatric disorders, b) to determine the interaction with age, sex and environmental challenges, and c) to test innovative pharmacological, behavioural or neuromodulatory interventions that can help normalise psychiatric symptoms and endophenotypes in translational approaches. Assets: The presence of large patient cohorts related to common mood disorders (e.g. unipolar, bipolar depression, OCD) via a large-scale ongoing cohort studies, i.e. the Netherlands Study of Depression and Anxiety (NESDA under supervision of Brenda Penninx) are a typical stronghold of this program. In addition, we are able to study the normal variation in emotional states as mood and anxiety using general cohort databases such as the Netherlands Twin Registry (NTR). Another strength is the presence of animal models with face, predictive and etiological validity for psychiatric disorders (mood and anxiety, addiction, and attention & impulsivity) to bridge the gap between clinical (genetics, pathophysiological, brain imaging) and pre-clinical studies (molecular, cellular) (under supervision of Sabine Spijker). These models are essential in bridging the gap between human genetic, pathophysiological and brain imaging studies and pre-clinical studies at the molecular and cellular level. There is extensive expertise in implementing broad clinical (endo)phenotyping (including advanced imaging using MRI, PET, EEG/MEG), as well as studies of (novel) biomarkers, neuroanatomy, neuropathology, transcriptomics, proteomics, gene finding, functional characterisation, cellular and animal models. Translational links: In the near future we want to expand our links with the AMC and UvA, since the emotional states that are topic of our research interests are highly comorbid conditions, and may have partly a shared underlying pathophysiology. In addition, collaborative interventions and research projects with other research programs should be facilitated, in particular also in view of the partly shared neuro-immunological and neurotransmitter imbalance aetiology of psychiatric disorders 1.3 Strategy and targets At the launch of NCA in 2008, the Board of Deans took a strong position on the fact that the Neuroscience community on the VU/VUmc needed to ‘transcend the disciplinary boundaries, from physics via life sciences, and from there, all the way to medicine – and back – have been partially limited due to organisational boundaries until then’. Also through the start of NCA, the deans wanted to further resolve potential barriers for campus-wide collaborations. Hence we have then begun to invest in ‘building new bridges’ between different neuroscience research

Section I – Self-evaluation 2009-2014

support facilities by providing two strategies: a) concerted funding of research support facilities and investments in advanced technology programs, b) financial support for novel initiatives with the objective to ‘explore’ and ‘execute’ common research interests with a potential campus-wide impact. In addition valorisation, technology transfer, fund-raising and European collaboration were to be used as instruments to strengthen NCA’s core business. 1.4 Performance indicators According to the SEP protocol (and following the output indicators of D1), the research unit selects specific output indicators for each of six quality domains. The indicators that correspond with the profile and strategic decisions of the NCA research institute are listed below. Scientific indicators 1. Research products for peers. NCA aims at scientific research publications in particular in refereed journals. As the research has a relatively broad focus ranging from clinical neurological and psychiatric practice to fundamental medical biological issues, research is published both in clinical journals and in general medical-biological literature see for instance the key publication in Appendix 4.6 (pages 31-34). Given the fact that we have currently employed 160 PhD students, also in the coming year we aim for 40 dissertations to be published. 2. Use of research products by peers. The most important item in this respect is the number of citations. In section 4.4 a citation analysis is given both for NCA in general and for the NCA research program that were active until 2012. Another way in use of research products by peers is accounted for in appendices 5 of the annual reports of NCA. 3. Indicators of recognition from peers. Several NCA investigators have been awarded with nationally recognised prestigious grants from the National Research Council, including the socalled Spinoza Prize and by ERC grants (all highlighted in the annual reports of NCA), invited lectures at scientific meetings, memberships of editorial boards, memberships of scientific committees and organisation of scientific meetings. Another way the use of research products by peers is accounted for, is in the appendices 4 of the annual reports of NCA. Societal indicators 4. Research products for societal target groups. The main targets for NCA are students (training), the general public, patients (organisations) and industry (see section on public private partnerships). 5. Use of research products by societal groups. Many NCA scientists aim at performing collaborative contract research sponsored with industrial partners, in particular due to the intense strategy around the launch of the so-called Industry Alliance Office (www.iaoneuroscience.com). In 2013-2014 NCA has acquired a contract portfolio of in total more than 10 M€, though IAO. 6. Marks of recognition by societal groups. Full professors and PhD students are sometimes endowed by foundations and societies, indicating the increasing interest of the society to fund research at NCA.

Section I – Self-evaluation 2009-2014

1.5 Results Scientific Impact: The aggregated result output is shown in Table I-4 of section 4.3 (output indicators) and section 4.4 (citation analysis). The number of articles published per year and the total number of citations each year to these papers published shows the solid growth in output and relevance of their output in recent years, despite a relative constant input in fte of (non)tenured scientific personnel (see Table I-1 and Table I-3). At the onset of the new era in which the NCA became operational (i.e. during 2008-2009) the yearly output amounted to ~ 400 research papers per year. In recent years the total number of reports has settled to > 600. Of this total, 560 were peer reviewed reports (see Table I-4), with 77% being published in a top 25% journal and 45% being in the top-10% journals (see Annual Report 2014). Another way of benchmarking the output of NCA is to score the absolute impact factors: in all years between 2009-2014, we had 15-20 % of these papers (i.e. ~ 100 papers out of ~ 500 peer reviewed) in the highest impact journals (i.e. IF ~ 9 or higher. In the Annual Reports the relative impact and the number of high impact papers is further subcategorised per research program. The number of PhD projects is remarkably constant over the 6 year period (see Annual Report 2014), despite the gradual reduction in (non-)tenured scientific staff from 156 to 126 coworkers. In 2009-2011 a total of 116 PhD students entered the program, in the period 2012-2014 this amounted to 120. In the same period, the number of post docs fluctuates between 140-160 per year. Currently we have 181 PhD student employed and 144 postdocs (see Table I-1). In Table I-4 also the research output of the five NCA Research Programs is shown. The output is shown for the years 2013-2014; for the output in earlier years was categorised to more and other research programs and can be reviewed on the NCA-website. Other research output in non-refereed journals and for book chapters is rather limited. In section 4.4 three citations analyses are summarised. It is fair to conclude that NCA has a most prominent position in scientific research compared to their peers with both high output and the highest numbers of citations compared nationwide and up to 3.5 x world average MCNS. In section 4.6 for each NCA Research Program, at least 1 key publication per year is listed. Relevance to society: Neuroscience, neurology and psychiatry research has a considerable societal impact. This includes the impact of research findings in teaching and training professionals, educating care takers and communicating to society in general and external stakeholders (patient organisations and industry, see below) in particular. The most important aspects are described below. More detailed information can be found in the NCA Annual Reports. NCA aims to train national and international brain researchers by creating an environment of scientific excellence that will integrate various intellectual disciplines and, from that convergence, find solutions that will ultimately benefit society in the realms of medicine, engineering, business, and education. NCA is further set up to lend significant support to the inhouse patient-clinics of the VU University campus. In this sense, NCA functions as a network organisation where patient-centres, such as the Alzheimer Center, the MS Center, the Childhood Center for White Matter Disorders and the GGZ inGeest clinic for Anxiety and Depression are the major ‘hubs’ in our network. Both the Alzheimer Center and the MS Center have extensive ‘outreach’ activities. In addition, the outreach activities have been further formalised in recent years through active memberships of our staff in the Royal Netherlands Academy of Sciences, including Dorret Boomsma and Philip Scheltens and in ‘De Jong Akademie (DJA)’ (The Young Academy) of the Royal Netherlands Academy of Sciences, including Huibert Mansvelder, Danielle Posthuma, and Ysbrand van der Werf. Jeroen Geurts was the chair of the DJA. In this -and other – roles, Geurts’ contribution to outreach activities are numerous and include weekly radio programs, and lectures

Section I – Self-evaluation 2009-2014

for the ‘Universiteit van Nederland’ (www.universiteitvannederland.nl). In addition, he is leading ‘Stichting Brein in Beeld’ (www.breininbeeld.org). Public Private Partnership & Industry Alliance Office: NCA focuses on creating partnerships with small and large enterprises in order to capitalise on the research assets and create new models of joint funding. In order to make this happen we created a business model to facilitate public-private partnerships, i.e. commercially driven joint projects To this end we have set up a dedicated front-office, called the Industry Alliance Office, representing the NCA as a whole and offering internal scientific expertise, knowledge and network to external (commercial) partners. The main focus of the Industry Alliance Office is to become the preferred partner for the development of treatments and diagnostic tools for neurologic and neuropsychiatric diseases by investing in viable strategic alliances, creating a translational link between scientists and industrial partners The aim is to deliver value for the industry by offering tailor-made services in neurosciences, to build sustainable relationships with clients and to generate external revenues. The latter is an integral part of the business model, since new funding can be allocated to invest and further expand in the scientific excellence of the NCA regarding disease-orientated brain research. The Industry Alliance Office manages, coordinates and initiates commercial activities of the NCA, and stimulates public private partnerships with external stakeholders. The organisation has a lean structure consisting of a management team supported by NCA and under direction of the CEO of the institute, in addition to project management and business consultancy dedicated on a project-basis. This organisational structure will be scaled up to a next level in 2015. The internal value of the Alliance Office is to structure collective approaches for attracting means of funding to further support scientific research. Due to this approach it is believed that a shift can be established from single-based projects to long-term collaborations, whereby funding on a systematic basis and with higher gain can be achieved, and scientific objectives and challenges can still be met. Furthermore, the Industry Alliance Office will manage the coordination of collaborative projects with Industry. The NCA has the scientific expertise, infrastructure and commercial potential to offer and serve the industry. We do this through an integrated approach as illustrated by the so-called NCA Matrix. Commercial validation indicated that the business propositions of NCA are welcomed and the several assets of the institute generated considerable interest. 1.6 Own assessment of quality, relevance and viability Quality: The solid impact of our research output remains based primarily on a quality-oriented and purpose-driven research strategy. There are numerous examples of multidisciplinary studies that made it into high impact journals. With an annual total of more than 550 peer reviewed papers and each year with more than 100 papers in the top 5% of the international journals, in the period 2009-2014 we sustained an excellent standard. We recently celebrated the seventh anniversary of NCA. Being the playground for many graduates, and graduates-to-be, and working towards full integration in the field of Translational Neurosciences, we have succeeded in creating an appealing workplace for many and great perspectives on a sustainable future. Relevance: NCA has a mission to produce innovative research and technology leading to scientific discoveries in Neuroscience. However, Neuroscience is valuable not only for the advancement of science but also because it can greatly impact our society and economy. Over the last three decades Neuroscience has become a truly integrative science, from the molecule to the systems level and beyond, encompassing normal human brain function as well as the clinical expertise to diagnose – and address the biological mechanisms underlying - brain diseases. In the coming

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years, our efforts are expected to gather widespread interest, evolving into a new translational neuroscience, which further integrates basic and applied research, and may hold the key to solving many of society's problems. Viability: Since 2008 we have appointed 3 new heads of departments (i.e. Huibert Mansvelder, Jeroen Geurts and Danielle Posthuma) and at least 12 new research leaders (i.e. Henk Berendse, Wiesje van der Flier, Elga de Vries, Sabine Spijker, Bart van Berckel, Eus van Someren, Dick Veltman, Meike Bartels, Ronald Boellaard, John van Swieten, Jacqueline Vink and Odile van den Heuvel). Moreover we have an excellent line-up of younger staff which are or will be promoted to the level of associate professor (at least 6 candidates currently being prioritised). With the current scientific staff volume (of around ~ 125 co-workers) this appears a ‘viable’ ratio. 1.7 Relevant environmental factors and future developments Making the difference? Our academic reputation, and the quality and quantity of our graduate programs are accredited by formal organisations and NCA continues to coordinate and run the research MSc Neuroscience program as well as the PhD Neuroscience program (ONWAR), and in the ENC-Network (www.enc-network.eu), one of our European programs for graduate education. In addition, the societal relevance has been formalised in recent years, amongst others via active memberships of our staff in DJA of the Royal Academy of Sciences. Business strategy: We have also put efforts in shifting our attention towards a more biotech and pharma-industry-oriented position, since we have launched the Industry Alliance Office (http://www.iao-neuroscience.com/). The Industry Alliance Office operates as a one-stop-shop to external partners and was able to successfully offer integrated propositions around a dozen outside stakeholders. To further facilitate the growth of this business model and in order to also be able to involve additional 3rd party capacity, we have started to launch the Industry Alliance Office as a corporation (private limited company under incorporation). Merging of two Medical Centres in Amsterdam: Commissioned by the Board of the Medical Centres in Amsterdam, the VU University Medical Center (VUmc, being affiliated with the VU University Amsterdam) and the Amsterdam Medical Center (affiliated with the University of Amsterdam), the director of NCA was asked to file a project plan to merge NCA into a new truly Amsterdam-wide research network organisation, entitled Amsterdam Neuroscience. In doing so, we have thus outlined the feasibility and possible implementation of such new network research organisation on the basis of consensus meetings with heads of departments and research leaders, most lately during a so-called Open Forum symposium on 19 March 2015. The scale of the research organisation would make Amsterdam Neuroscience amongst one of the largest Neuroscience research communities in Europe. With the alliance program of Amsterdam Neuroscience we could add value to the Neuroscience research agenda in the upcoming years. Although there is no simple recipe for success, major characteristics for building a strong partner organisation - irrespective of laboratory or clinical housing - can be delineated. These include a consensus on shared leadership in the various research programs, a strong strategic and complementary research agenda, a shared, excellent graduate- and medical-training program, shared infrastructure and service facilities (including a clinical trial unit) for large-scale (investigator-initiated and sponsored) investigations. A strong embedded business development aims at adding new industry alliance programs. At NCA – through our experience over the last 6 years – we have a practice model of how to organise Amsterdam Neuroscience. If the project plan finds support from the Board of deans and

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during evaluation – among others during the Audit Evaluation of NCA - working from a shared vision towards a shared implementation plan in 2016 and beyond could create an appropriate follow-up-action in the establishment of the new network organisation. Amsterdam Academic Alliance: The Amsterdam Brain and Mind Project (www.abmp.eu) is a new 3 M€ initiative of UvA‐VUA Amsterdam Academic Alliance. As a joint venture of the UvA and the VUA, the project aims to build sustainable bridges between Amsterdam’s top research groups in the fields of neuroscientific and cognitive research. This will allow both universities in the city of Amsterdam to build a strong and prominent centre for the study of the brain and mind. Research within the Amsterdam Brain and Mind Project aims to jointly understand the biological underpinnings of the mind. To this end, we will initiate 10 joint postdoc projects on five interrelated themes. The Amsterdam Brain & Mind Project is coordinated by Agneta Fischer and Arjen Brussaard, and meanwhile launched the first call for joint research proposals in the spring of 2015. 1.8 SWOT analysis Strengths: • NCA has built a strong translational neuroscience organisation with five well focussed research programs, community oriented leadership and excellent publication records. In doing so we have managed to link the preclinical and the clinical research in an endurable manner. • All research programs are truly translational, ranging from basic science to intervention studies, with the ultimate aim to understand the etiology of – and interfere with neurodegenerative, neuroinflammatory and/or neuropsychiatric disorders, and to reduce the burden of these brain diseases for society at large. The research in our faculties perfectly matches the clinical research of the medical center, but also enables and/or initiates innovative and unique developments. • In recent years we have also built on alliances and more collaborations with industry, through the launch of our so-called Industry Alliance Office (IAO, www.iao-neuroscience.com). The management of NCA and the board of deans of NCA have facilitated this strategy by seeding conditional funding for dedicated Proof-of-Concept projects. Through the IAO, NCA organises guidance in (phase I/II) clinical trials, sets up collaborative (risk sharing) programs with industry and provides research services to external stakeholders, both in the field of (target) discovery, target validation and in the realms of biomarker research. The fact that the IAO has acquired a substantial deal flow generates interest both on campus and beyond. • Overall the way in which we organised NCA has been instrumental as best practice model for other institutes, in particular also in the alliance program with the University of Amsterdam and the Amsterdam Medical Center. Weaknesses: • The huge scope of research at NCA is one of its strengths but at the same time poses substantial ‘challenges’: there are (almost) too many ‘opportunities’ that could lead to further strengthening of the common ideas and strong cooperation. Our mid-career staff is essential when new internal translational collaborations need to be set up. However while in the period 2009-2014 NCA was in a solid position to financially support such translational projects by midcareer staff on campus, for 2015 and beyond the perspective on endurable funding (thus far) is limited. We try to overcome this by generating sufficient profit margin through project acquired via the IAO. • Scattering of infrastructure, core facilities and know-how could be regarded as a weakness, with many different types of expertise on various locations. Although VUmc has started to

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build its new centralized VUmc Imaging Center and other core facilities like ICT and biobanking also have constant attention, it is increasingly difficult to keep up across-the-board research programs and keep up with new developments. Opportunities: • A better link between brain and mind studies, such as recently started in a collaboration between NCA with a partner institute (Amsterdam Brain Cognition) from the University of Amsterdam in the so-called Amsterdam Brain & Mind Project (www.abmp.eu) is the first step towards taking better advantage of the unique setting of Amsterdam. • With the opportunity to expand NCA into Amsterdam Neuroscience and the frontier position that the latter can fill, it is imperative that we start building from our current unique expertise combinations and reinforce our translational line. This way, the organisation will be less vulnerable to single experts leaving (and leaving key research positions empty). • Joint research programs between VUmc and AMC will increase the need for central core facilities such as a facility for genomics, for brain imaging, for biobanking and ICT systems. The joint research programs are also going to increase the ‘catch-area’ of patients in the two academic hospitals, thereby facilitating clinical translational research. The implementation of a shared clinical trial unit might ensure continuous inclusion of patient in clinical trials and cohort-studies. In such collaboration both medical centers could also take advance of the opportunities of doing more investigator driven as well as industry sponsored clinical trials. Threats: • To sustain a full fletched matrix organization on campus is a challenge. Organizing core facilities and centralized support systems in the discipline oriented faculties versus the translational research organization that is NCA requires more balanced investments and governance. • The ambition of the boards of both universities and medical centers to launch Amsterdam Neuroscience, has great potential, but at the same time puts a huge governance issues on the agenda of the management (and the deans) of such an institute. • Also with the launch of Amsterdam Neuroscience we may encounter the potential pitfall that our organization becomes too big. We will try to prevent such from happening by stimulating collaborations within research programs more firmly. • Currently a ‘legal’ fire-wall is being set up between the VU University Amsterdam and the VU Medical Center - in order to allow for the merger of the two Medical Centers in Amsterdam. This is complicating since it may jeopardize the coherence (sense of belonging) of the current organization (i.e. of NCA, which is 65% VUmc and 35% VU Amsterdam, but more and more without feeling this ‘border’).

Part 2. PhD program 2.1 Context, supervision and quality assurance The central objective of graduate education at NCA is to train the next generation of excellent researchers. In doing so - both at the VU University Medical Center and at the VU University Amsterdam - we follow a set of so-called PhD regulations, that were agreed upon as per 1 January 2015. At the start of each PhD project the head of department, or one of its team members appoints a main (co-)supervisor to instruct the PhD candidate on the standard operating procedures which are outlined in a Quality Checklist. Part of this protocol is also that at the start of each project, the PhD student files a mandatory Training and Supervision Plan (TSP; that each

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PhD candidate should file at the beginning of his/her project) to be evaluated and monitored by the PhD supervisors up the moment of graduation. 2.2 Participation in the Graduate School, courses for PhD students NCA participates in the Graduate School Neurosciences Amsterdam Rotterdam, led by August Smit (www.onwar.nl). As such, each PhD student in NCA adheres to a centralised protocol with instructions. The VU and VUmc regulations can be found on the following portals; VU: http://www.vu.nl/en/research/taking-phd/index.asp, or VUmc: http://www.vumc.com/branch/phd/

2.3 Selection and admission Most PhD students are appointed on externally funded projects (EU, NWO, ZonMw, STW, NIH). In the recent past (2012) there also was a limited NCA funding for so-called Young Talent positions. For such ‘direct funded’ NCA positions the five programs were invited to submit applications whereby the proposed research projects were to bridge pre-clinical and clinical research. Applications were reviewed by a panel of scientists of both programs and the highest scoring projects were chosen. Next to these students, NCA, by working with the European Neuroscience Campus Network (www.enc-network.eu) in the period 2009-2013, had the possibility to introduce the possibility for excellent students to apply for so-called joint PhD positions. These latter students were invited to work on their own research plans, being a subject closely related to one of the main programs of the participating ENC-Network labs. In the time period 2009-2013, NCA being the coordinator of the ENC-Network, funded over 40 PhD positions. Selection of the PhD students, either for NCA or for externally funded projects, is performed by three to four members from NCA, usually mainly coming from the supervisor’s lab. Candidates are chosen because of their motivation, knowledge, experience, and enthusiasm. Depending on the subject and the research sections involved in the project, candidates differ from background. A more clinical oriented project is likely to be fulfilled by an MD whereas a (molecular) biologist/biochemist or a psychologist is more likely to be chosen for a fundamental oriented project. 2.4 Supervision of PhD candidates, and guidance to labour market Each PhD student has a team of dedicated supervisors supervising the research and which give guidance in approaching the labour market. More lately, this is done under supervision of a NCA’s PhD committee, chaired by the director of NCA with four additional members: the director of the Graduate School Neurosciences Amsterdam Rotterdam (ONWAR), the head of research of the VUmc Alzheimer Center, a representative of the VUmc MS Center and a representative of GGZ inGeest, partner of VUmc (Psychiatry). 2.5 The future of graduates in various sectors In the years 2008-2014 more than 267 PhD students started their four-year internship in one of the NCA laboratories. Of the NCA students that started their project before 2011, 65% meanwhile defended their thesis successfully, and 29% are underway (having a delay either because they already started in a new position, or since they combine their PhD training with a medical training as resident). NCA has an early dropout of only 6%. Of those that graduate 8 out 10 pursue a research career, mainly in academia, some after a few years going to industry (biotech or pharma). The remainder pursue another career, either in consultancy, management or business development.

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2.6 Duration and success rates The success rates in shown in Section 4.5 and Table I-5. In the years of this evaluation, a total of 127 standard PhD students were taken into account. Eight students (6.3%) discontinued the program. The mean duration for completing the thesis of the 90 individuals who completed the thesis in these years was 4.98 years (with a standard deviation of less than 8 months). We have not corrected these for part-time appointment and/or maternity or other leave of absence. 2.7 Analysis and future strategy Strengths • At NCA we have good link between the Master of Neuroscience program and the continuation of solid candidates in our PhD program. Moreover we have a very international community with many graduate students from abroad and from outside Europe. • Over last 6 years we have run two MSC ITNs (BrainTrain and CognitionNet) as coordinator and one Erasmus Mundus Joint Doctorate program (ENC-Network, with Arjen Brussaard as director/coordinator). • Due to a favourable ratio of staff versus PhD candidates, an optimal individual supervision and training can be accomplished. • The mean time of less than 5 years between start and defence of the thesis is shorter than the mean duration of PhD theses in research schools in the Netherlands of 5.1 years. • Over the years, more than 90% of all PhD students in NCA complete their thesis. This percentage is substantially higher than the mean percentage of 75% of PhD students who finish their thesis in Dutch research schools. • PhD students at NCA receive a relatively broad view on bio-medical science by participation in courses, lectures and congresses on both fundamental and clinical subjects in a wide variety of disciplines. • NCA has a number of good employment benefits for PhD students, such as resources for congresses, courses and printing of the thesis. Weaknesses • Due to the heterogeneous background of PhD students and their research subjects, it is difficult to organise a scientific training program for the whole group. The number of compulsory courses is relatively low. We have tried to solve this by customizing the NCA PhD regulations to the needs of the investigators being trained either in the preclinical domain or in the clinical domain. One other way in which we substitute for general training is by organizing obligatory in-house Annual Meetings, with review and feedback elements. Opportunities • Both the University of Amsterdam and the VU University Amsterdam have made new regulations for the PhD program, with more attention for the training and guidance plan, and in particular also scientific integrity. A total of 30 ECTS points should be included in each individual program. This will enable the establishment of a more focused PhD training program. Threats • An important threat is the reduction of direct funding for research. We hope to reverse this trend by generating (free) profit in Industry Alliance projects; see success rate in recent years in appendix 4.2, Table I-2.

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The ONWAR PhD program was officially accredited by the KNAW (Royal Academy of Sciences by external review committees, every 5 years since 1992, most recently in 2012. The following improvements were made: • The research institute has started a procedure for the allocation of new PhD positions for high quality projects which focus at the integration of fundamental and clinical science, through different initiatives. This strategy will hopefully be continued further, concentrating on the five main research programs. • Very talented students were invited to apply for a PhD position at NCA. In 2009 the first candidates were appointed (through ENC-Network funding), in 2010 ibid, 2011 ibid (and also with extra funding from NCA), and 2012 and 2013 this was repeated. This policy will be continued as funding allows. • According to the PhD regulations of both universities the course program will be formalised with 30 ECTS points and examinations. • The collaboration with other graduate schools will be intensified. • Due to the new NCA PhD regulations, the integration between the PhD training program and the post-graduate clinical training programs for neurological and psychiatry specialisations will be intensified.

Part 3. Research integrity 3.1 General reflection on research integrity and culture NCA adheres to the Research Guide of the VU University Medical Center. Specific other regulations (or adjustments) may apply for different NCA departments (in particular for those residing in other faculties). For NCA investigators, the Quality Checklist needs to be used for execution of projects run by PhD students, post docs and other affiliated co-workers. The VUmc Research Guide provides a valuable overview of the available support for conducting research at VUmc. Examples: Law and regulations i.e. the medical ethical review committee, grants desk, juridical support, obtaining of (special) research materials or equipment, and documenting research projects. In addition, human resource issues such as reimbursements and obtaining permits for non-EU scientist are indexed in the Research Guide. For all departments of NCA, proper labjournal-, clinical record form-, and other data-management are essential: • Good guidance in in research data management is given here: labjournal. This hyperlink also contains ‘tips and tricks’ for data mining. • Instruction on clinical research form management can be obtained on the job in the clinic directly and follows standard operating protocols established per department. • Research with data, information and support is given here: Research with data. This hyperlink also contains supporting links to biostatistical methodology. • Intellectual property and. Information is given here: Patenting and Valorization. You can also simply contact the Industry Alliance Office (preferably via a team leader of NCA), see www.iaoneuroscience.com. • Finalizing a project (in particular for PhD students and post docs leaving the department). Information and guidelines are given: Finalizing a project. • Archiving at the end of a project. Leaving data available and accessible for others. Information and guidelines are given here: Archiving.

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In order to consistently promote, facilitate and ensure conduction of scientific research according to the principles of conduct for research integrity in and across the University Medical Centers in Amsterdam, a joint research code was established. The joint research code was established on behalf of the Executive Boards of the Academic Medical Center (AMC) and VU University Medical Center (VUmc). The research code applies to all units operating with the VU/VUmc organisation. Every scientific practitioner - from principal investigators to junior researchers, as well as research support staff should know of this code and be familiar with its content. This research code is, however, not a research handbook, nor a 'cookbook' covering all regulations in detail. Instead, and because the process of evolving possibilities and questions is crucial in scientific research, the code provides a framework to guide researchers in living up to the values of independence and integrity. It provides and introduces the main issues on the different topics, and where useful or necessary refers to further readings. By making clear which conduct is expected and considered effective, this code hopes to contribute to an atmosphere of openness and a culture where doing research is an enjoyable and productive experience. The contents of this code can be found on the page of the Research Code VUmc-AMC. On this website one can also download a pdf of the code. 3.2 Data storage The proper storage of data is a crucial issue for NCA. This holds true for all types of research, but in particular for imaging and for complex trait genetics. For the imaging, we have installed a socalled NCA-grid facility in 2013-2014, a central grid computing system, that is available to all imaging experts of NCA. For big data analysis in clinical research VUmc has installed an Electronic Patient Dossier (EPD-) system (using the EPIC software) which can be further coupled via Data Ware House to software used for hospital initiated studies (like OpenClinica or Castor). In addition, NCA has access to the Genetics Cluster Computer (http://www.geneticcluster.org) (set up in the Dept. of Complex Trait Genetics, VUmc) which provides storage capacity and processing power for genetic research, available for massive calculations on big data. Additional data storage for sequence data (by investigators of the Netherlands Twin Register) is (too) limited and needs be insourced from external stakeholders. Data storage is also crucial from the preclinical research. In most of the laboratories official (electronic) laboratory journals are used. These journals contain all the information of the experiments performed. Patient data are stored digitally in protected directories according to the regulations for good clinical practice. In the near future this will be followed up by protection of the storage of all digital data. This protected data storage will be used for both experimental and patient-related data. A campus license on data storage software is available since the end of 2014. 3.3 Quality control committees Quality control of medical research projects is an important issue in the Neuroscience Campus Amsterdam. NCA has three research committees that provide an independent review of the scientific quality of research protocols brought forward by investigators. The purpose of the review is to ensure the highest quality of research and to support researchers affiliated to NCA. In addition, the Clinical Research Committee lead by Henk Berendse provides the director and management team with (solicited and unsolicited) advice on matters directly related to the institute's science policy. Hence a primary task of each research committee is to lend approval of any project within NCA before evaluation of a project by either the Medical Ethical Committee of the VU University Medical Center or the Animal Ethical Committee of the VU University. Since projects are executed

Section I â&#x20AC;&#x201C; Self-evaluation 2009-2014

in distinct faculties on campus, each faculty has an independent research committee dedicated to NCA. A secondary task of the Clinical Research Committee (VUmc) is to advise the director on the eligibility and methodological quality of all new research proposals (after grant award) brought forward by researchers for inclusion in the NCA research programs. Only after approval of the director of NCA, advised by the research committee, a project will be labelled within NCA. Only NCA-labelled projects are accountable for output-administrative and financial administration. Quality control of preclinical and biomedical research projects is under responsibility of the Biomedical Research Committee lead by August Smit (chair), also member of the management team of NCA. Quality control of biopsychology research projects is under responsibility of A.H.M. Willemsen (chair).

Section I – Self-evaluation 2009-2014

Part 4. Appendices 4.1

Research

4.1.1 Research Organization In Figure I-1 illustrates the organization Neuroscience Campus Amsterdam (NCA) as it was implemented from the start of the institute in 2008 until the summer of 2012. Investigators were grouped in one (or more) research programs. As shown, the ten research programs were categorized in three main research themes and further supported by research experts and infrastructure. As outlined below above, the total number of research programs was later-on reduced – during the reorganization of 2011-2012 upon advise of an internal evaluation – from ten to five research programs.

Figure I-1: Neuroscience Campus Amsterdam in period 2008-2011

In figure I-2, the current research organisation of the Neuroscience Campus Amsterdam (NCA) as it emerged after an extensive midterm review and being executed during reorganization of 20112012. As shown - of the ten previous research programs - only five new research program emerged, that were of a better comparable group size and that were also more translational and

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less oriented towards dominating disciplines. In short the reorganization can be summarized as follows (compare figure I-1 and I-2): The previous Brain Imaging and Photonics & Life Cell Imaging were merged into one new program entitled Brain Imaging Technology, Drug Screening was discontinued, the previous Integrative Analysis & Modelling program was merged with System Biology of the Synapse and Childhood White Matter Disorders into one new program entitled Brain Mechanisms in Health & Disease. Finally the previous studies of Addictive Behavior and the human studies of Attention and Cognition, were merged with previous Anxiety & Depression, into one new program entitled Neurobiology of Mental Health. Neurodegeneration was continued as before, and White Matter Disease was focussed on Multiple Sclerosis per se. Figure I-2: Neuroscience Campus Amsterdam in period 2012-present.

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4.1.2 Research Staff Composition An overview of the research staff of NCA is listed in Table I-1. For the five Research Programs that emerged from the reorganization in 2011-2012, the research staff is only give for the years 20132014. Upon request the research staff tables from earlier years are also available. Table I-1: Research staff at NCA in numbers coworkers employed and in full time equivalents (fte)

Footnote: For the analysis in this section in the category PhD-students, only coworkers that had an employee status as such and conducting research with a primary aim/obligation to graduate were included. External PhD students and MD research staff that also perform PhD thesis research without the obligation to graduate are not included.

4.2 Funding An overview of the financial budgets for research at NCA in â&#x201A;Źs is listed in Table I-2. An overview of the financial expenditure in fte (full time equivalents) is given in Table I-3. The fte support staff (laboratory technicians, nurses, support staff, animal care takers, etc.) is not given. For the five Research Programs that emerged from the reorganization in 2012, the research staff is only give for the years 2013-2014.

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Table I-2: Financial budgets of NCA research in €.

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Table I-3: Financial expenditure in fte research staff for NCA over the years 2009-2014, and for the research programs over the years 2013-2014.

4.3 Output indicators In Table I-4 an overview is given of the total scientific output of NCA. For the five Research Programs only for the years 2013-2014. Upon request the research staff tables from prior years are available.

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Table I-4: Aggregated research output of NCA

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4.4 Citation analysis Part of the academic reputation of scientist can be deduced from citation analyses. We report here on two citation analyses that have been performed recently for NCA. In the spring of 2015, the CWTS (Centre for Science and Technology Studies, University of Leiden) has performed a bibliometric analysis of the total number of NCA scientific publications over the years 2009-2012. A similar analysis was performed for VU University and for the VUmc. The latter showed that VUmc – both in general, but also in particular disciplines – scores amongst the best in the Netherlands and beyond. The NCA citation scores are shown below, in Figure I-3 and Figure I-4. Figure I-3: Distribution of NCA publications 2009-2012 over the web of science subject categories and their corresponding Mean Normalized Citation Scores (MNCS). World average of the MNCS is indicated by the dotted line.

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Figure I-4: Mean Normalized Citation Scores of NCA compared to VUmc and other Medical Centers in the Netherlands. NCA scores are aggregated for VUmc and VU University, VUmc scores exclude VU, and are further averaged MNCS scores also including also the citations scores on papers from other research institutes (CCA, ICaRVU, Move and EMGO). World average of the MNCS is indicated by the dotted line.

Section I – Self-evaluation 2009-2014

Figure I-5: Distribution of NCA publications 2009-2012 over the web of science subject categories but here per NCA research program and their corresponding Mean Normalized Citation Scores (MNCS). World average is indicated by the dotted line. As outlined above for Figure I-2, the total number of research programs was reduced – during the reorganization of 2011-2012 – from ten to five research programs. World average of the MNCS is indicated by the dotted line.

4.5 Length and success rates of PhD program For the starting year, the years 2008-2010 were chosen: In 2008 NCA was founded and PhD students and students that have started their project in 2011 or later, cannot have finished their thesis at the time of the audit of NCA, in the fall of 2015. In the Netherlands the research time of PhD project is typically 4 years. Including writing of the thesis and reviewing by the PhD reading committee (and waiting ~ on average 3-6 months for the availability of the time slot eligible for the formal graduation), this implies that typically a PhD project lasts more than 4 years. For the analysis in this section only PhD-students that had an employee status as such and conducting research with a primary aim/obligation to graduate were included. External PhD students and MD research staff that also perform PhD thesis research without the obligation to graduate are not included.

Section I – Self-evaluation 2009-2014

The success rates are shown in Table I-5. In the years of this evaluation, a total of 127 standard PhD students were taken into account. Eight students (6.3%) discontinued from the program. The mean duration for completing the thesis of the 90 individuals who completed the thesis in these years was 4.98 years (with a standard deviation of less than 8 months). We have not corrected for part-time appointment and/or maternity or other leave of absence. Table I-5: Success rates of PhD students of NCA started after the start in 2008 up to the last month of 2010.

4.6 Key scientific publications in past six years Below per review year five key publications are listed. Key publications of 2009: • Douw, L., Klein, M., Fagel, S.S.A.A., Heuvel, J. van den, Taphoorn, M.J.B., Aaronson, N.K., Postma, T.J., Vandertop, W.P., Mooij, J.J., Boerman, R.H., Beute, G.N., Sluimer, J.D., Slotman, B.J., Reijneveld, J.C. & Heimans, J.J. (2009). Cognitive and radiological effects of radiotherapy in patients with low-grade glioma: long-term follow-up. Lancet Neurology, 8(9), 810-818. (IF 14.3) • Wit, H. de, Walter, A.M., Milosevic, I., Gulyas-Kovacs, A., Riedel, D., Sorensen, J.B. & Verhage, M. (2009). Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes. Cell, 138(5), 935-946. (IF 31.3) • Koten, J.W., Wood, G., Hagoort, P., Goebel, R., Propping, P., Wilmes, K. & Boomsma, D.I. (2009). Genetic Contribution to Variation in Cognitive Function: An fMRI Study in Twins. Science 323, 1737-1740. (IF = 32) • Bochdanovits, Z., Verhage, M., Smit, A.B., Geus, E.J.C. de, Posthuma, D., Boomsma, D.I., Penninx, B.W.J.H., Hoogendijk, W.J.G. & Heutink, P. (2009). Joint reanalysis of 29 correlated SNPs supports the role of PCLO/Piccolo as a causal risk factor for major depressive disorder. Molecular Psychiatry, 14(7), 650-652. (IF = 12.5) • Montez, T., Poil, S.S., Jones, B.F., Manshanden, I., Verbunt, J.P.A., Dijk, B.W. van, Brussaard, A.B., Ooyen, A. van, Stam, C.J., Scheltens, P. & Linkenkaer-Hansen, K. (2009). Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America, 106(5), 1614-1619. (IF = 9.6) Key publications of 2010: • Furberg, H., Kim, Y.J., Dackor, J., Boerwinkle, E., Franceschini, N., Ardissino, D., Bernardinelli, L., Mannucci, P.M., Mauri, F., Merlini, P.A., Penninx, B.W.J.H., Smit, J.H., Vogelzangs, N., Boomsma, D.I., Geus, E.J.C. de, Vink, J.M., Willemsen, G., Tiemeier, H., Uitterlinden, A.G., Duijn, C.M. van, Maes, H.H., Audrain-McGovern, J., Posthuma, D., Thornton, L.M., Lerman, C., Kaprio, J., Rose, J.E., Ioannidis, J.P.A., Kraft, P., Lin, D.-Y. & Sullivan, P.F. (2010) Genome-wide meta-

Section I – Self-evaluation 2009-2014

•

analyses identify multiple loci associated with smoking behavior. Nature Genetics, 42(5), 441447 (IF = 34.3) Ruano, D., Abecasis, G.R., Glaser, B., Lips, E.S., Cornelisse, L.N., Jong, A.P.H. de, Evans, D.M., Smith, D.G., Thimpson, N.J., Smit, A.B., Heutink, P., Verhage, M. & Posthuma, D. (2010). Functional Gene Group Analysis Reveals a Role of Synaptic Heterotrimeric G Proteins in Cognitive Ability. American Journal of Human Genetics, 86(2), 113-125. (IF = 12.3) Dubois, B, Feldman, H.H., Jacova, C., Cummings, J.L., Dekosky, S.T., Barberger-Gateau, P., Delacourte, A., Frisoni, G., Fox, N.C., Galasko, D., Gauthier, S., Hampel, H., Jicha, G.A., Meguro, K., O'Brien, J., Pasquier, F., Robert, P., Rossor, M., Salloway, S., Sarazin, M., Souza, L.C. de, Stern, Y., Visser, P.J. & Scheltens, P. (2010). Revising the definition of Alzheimer's disease: a new lexicon. Lancet Neurology, 9(11), 1118-1127 (IF = 18.12) Kranendijk M, Struys EA, van Schaftingen E, Gibson KM, Kanhai WA, van der Knaap MS, Amiel J, Buist NR, Das AM, de Klerk JB, Feigenbaum AS, Grange DK, Hofstede FC, Holme E, Kirk EP, Korman SH, Morava E, Morris A, Smeitink J, Sukhai RN, Vallance H, Jakobs C, Salomons GS (2010) IDH2 mutations in patients with D-2-hydroxyglutaric aciduria. Science 330: 336 (IF 29.7) Groffen, A.J., Martens, S., Diez Arazola, R., Cornelisse, L.N., Lozovaya, N., Jong, A.P.H. de, Goriounova, N.A., Habets, R.L., Takai, Y., Borst, J.G., Brose, N., McMahon, H.T. & Verhage, M. (2010). Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release. Science, 327(5973), 1614-1618 (IF = 29.74)

Key publications of 2011: • Khatri, B., Barkhof, F., Comi, G., Hartung, H.P., Kappos, L., Montalban, X., Pelletier, J., Stites, T., Wu, S., Holdbrook, F., Zhang-Auberson, L., Francis, G. & Cohen, J.A. (2011). Comparison of fingolimod with interferon beta-1a in relapsing remitting multiple sclerosis: a randomized extension of the TRANSFORMS study. Lancet Neurology, 10(6), 520-529 (IF = 18.2) • Counotte, D.S., Goriounova, N.A., Li, K.W., Loos, M., Schors, R.C. van der, Schetters, D., Schoffelmeer, A.N.M., Smit, A.B., Mansvelder, H.D., Pattij, T. & Spijker, S. (2011). Lasting synaptic changes underlie attention deficits caused by nicotine exposure during adolescence. Nature Neuroscience, 14(4), 417-419. (IF = 14.2) • Flier, W.M. van der, Pijnenburg, Y.A.L., Fox, N.C. & Scheltens, P. (2011). Early-onset versus lateonset Alzheimer's disease: the case of the missing APOE epsilon 4 allele. Lancet Neurology, 10(3), 280-288. (IF = 33.6) • Alvarez, J.I., Dodelet-Devillers, A., Kebir, H., Ifergan, I, Fabre, P.J., Terouz, S., Sabbagh, M., Wosik, K., Bourbonniere, L., Bernard, M., Horssen, J. van, Vries, H.E. de, Charron, F. & Prat, A. (2011). The Hedgehog Pathway Promotes Blood-Brain Barrier Integrity and CNS Immune Quiescence. Science, 334(6063), 1727-1731. (IF = 31.4) • Demirkan et al. & Middeldorp, C.M. (2011). Genetic risk profiles for depression and anxiety in adult and elderly cohorts. Molecular Psychiatry, 16(7), 773-783 (IF = 15.5) Key publications of 2012: • Bis et al (group of Prof. Eco de Geus and Dorret Boomsma). Common variants at 12q14 and 12q24 are associated with hippocampal volume. Nat Genet. 2012 Apr 15;44(5):545-51. doi: 10.1038/ng.2237 & Stein et al (group of Prof. Eco de Geus and Dorret Boomsma); Enhancing Neuro Imaging Genetics through Meta-Analysis Consortium. Identification of common variants associated with human hippocampal and intracranial volumes. Nat Genet. 2012 Apr 15;44(5):552-61. doi: 10.1038/ng.2250. (IF = 34.3) • Knaap MS van der, Boor I, Estévez R. Megalencephalic leukoencephalopathy with subcortical cysts: chronic white matter oedema due to a defect in brain ion and water homoeostasis. Lancet Neurology 2012; 11: 973-985. (IF = 23.9)

Section I – Self-evaluation 2009-2014

• Vlies AE van der, Goos JD, Barkhof F, Scheltens P, van der Flier WM. Microbleeds do not affect rate of cognitive decline in Alzheimer disease. Neurology. 2012 Aug 21;79(8):763-9. (IF = 8.2) • Bugiani M, Postma N, Polder E, Dieleman N, Scheffer PG, Sim FJ, van der Knaap MS, Boor I. Hyaluronan accumulation and arrested oligodendrocyte progenitor maturation in vanishing white matter disease. Brain. 2013 Jan;136(Pt 1):209-22. doi: 10.1093/brain/aws320. PubMed PMID: 23365098. (IF = 9.9) • Lubke GH, Hottenga JJ, Walters R, Laurin C, de Geus EJ, Willemsen G, Smit JH, Middeldorp CM, Penninx BW, Vink JM, Boomsma DI. Estimating the genetic variance of major depressive disorder due to all single nucleotide polymorphisms. Biological psychiatry 2012;72(8):707-9. (IF = 9.2) Key publications of 2013: • Schmaal, L., Joos, L., Koeleman, M., Veltman, D.J., Brink, W. van den & Goudriaan, A.E. (2013). Effects of Modafinil on Neural Correlates of Response Inhibition in Alcohol-Dependent Patients. Biological Psychiatry, 73(3), 211-218. (IF = 9.5) • Bugiani, M.*, Depienne, C.*, Dupuits, C., Galanaud, D., Touitou, V., Postma, N.L., Berkel, C.G.M. van, Polder, E., Tollard, E., Darios, F., Brice, A., Die-Smulders, C.E. de, Vles, J.S., Vanderver, A., Uziel, G., Yalcinkaya, C., Frints, S.G., Kalscheuer, V.M., Klooster, J., Kamermans, M., Abbink, T.E.M., Wolf, N.I., Sedel, F.** & Knaap, M.S. van der** (2013). Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study. Lancet Neurology, 12(7), 659-668. *Shared first authors, **shared senior authors. (IF = 21.8) • Ossenkoppele, R., Prins, N.D., Pijnenburg, Y.A.L., Lemstra, A.W., Flier, W.M. van der, Adriaanse, S.F., Windhorst, A.D., Handels, R.L.H., Wolfs, C.A.G., Aalten, P., Verhey, F. R. J., Verbeek, M.M., Buchem, M.A. van, Hoekstra, O.S., Lammertsma, A.A., Scheltens, P. & Berckel, B.N.M. van (2013). Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers & Dementia, 9(4), 414-421. (IF = 17.4) • Doorn, R.P. van, Nijland, P.G., Dekker, N., Witte, M.E., Lopes Pinheiro, M.A., Hof, B. van het, Kooij, G., Reijerkerk, A., Dijkstra, C.D., Valk, P. van der, Horssen, J. van & Vries, H.E. de (2012). Fingolimod attenuates ceramide-induced blood-brain barrier dysfunction in multiple sclerosis by targeting reactive astrocytes. Acta Neuropathologica, 124(3), 397-410. (IF = 9.8) • Smoller, J.W., Ripke, S., Lee, P.H., et al (including Boomsma DI, de Geus EJ, Penninx B, Posthuma D, Smit JH) (2013). Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet, 381(9875), 1371-1379. (IF = 39.2) Key publications of 2014: • Tewarie, P., Steenwijk, M.D., Tijms, B.M., Daams, M., Balk, L.J., Stam, C.J., Uitdehaag, B.M.J., Polman, C.H., Geurts, J.J.G., Barkhof, F., Pouwels, P.J.W., Vrenken, H. & Hillebrand, A. (2014). Disruption of Structural and Functional Networks in Long-Standing Multiple Sclerosis. Human Brain Mapping, 35(12), 5946-5961. (IF = 6.9) • Aarts, E., Verhage, M., Veenvliet, J.V., Dolan, C.V. & Sluis, S. van der (2014). A solution to dependency: using multilevel analysis to accommodate nested data. Nature Neuroscience 17(4):491-496. (IF = 15.0) • Duits, F.H., Teunissen, C.E., Bouwman, F.H., Visser, P.J., Mattsson, N., Zetterberg, H., Blennow, K., Hansson, O., Minthon, L., Andreasen, N., Marcusson, J., Wallin, A., Rikkert, M.O., Tsolaki, M., Parnetti, L., Herukka, S.K., Hampel, H., Leon, M.J. de, Schroder, J., Aarsland, D., Blankenstein, M.A., Scheltens, P. & Flier, W.M. van der (2014). The cerebrospinal fluid "Alzheimer profile": Easily said, but what does it mean? Alzheimers & Dementia, 10(6), 713723. (IF = 17.5)

Section I – Self-evaluation 2009-2014

• Nijland, P.G., Witte, M.E., Hof, B. van het, Pol, S.M.A. van der, Bauer, J., Lassmann, H., Valk, P. van der, Vries, H.E. de & Horssen, J. van (2014). Astroglial PGC-1alpha increases mitochondrial antioxidant capacity and suppresses inflammation: implications for multiple sclerosis. Acta Neuropathologica Communinications, 2, 170. (IF = 10.8) • Wright, F.A., Sullivan, P.F., Brooks, A.I., Zou, F., Sun, W., Xia, K., Madar, V., Jansen, R., Chung, W., Zhou, Y.H., Abdellaoui, A., Batista, S., Butler, C., Chen, G., Chen, T.H., D’Ambrosio, D., Gallins, P., Ha, M.J., Hottenga, J.J., Huang, S., Kattenberg, V.M., Kochar, J., Middeldorp, C.M., Qu, A., Shabalin, A., Tischfield, J., Todd, L., Tzeng, J.Y., Grootheest, G., Vink, J.M., Wang, Q., Wang, W., Wang, W., Willemsen, G., Smit, J.H., Geus, E.J.C. de, Yin, Z., Penninx, B.W.J.H. & Boomsma, D.I. (2014). Heritability and genomics of gene expression in peripheral blood. Nature Genetics, 46(5), 430-437. (IF = 29.4) 4.7 Conclusions and mission statements at the start of the institute Rationale for starting the Neuroscience Campus Amsterdam: “Up to 2008 many different research programs in Neurosciences have been developed at the VUA/VUmc campus. However, efforts to transcend the disciplinary boundaries, from physics via life sciences, and from there, all the way to medicine – and back – have been partially limited due to organizational boundaries. Through the start of Neuroscience Campus Amsterdam we are trying to further resolve potential barriers. Hence we invest in ‘building new bridges’ between different neuroscience research support facilities by providing two strategies: a) concerted funding of research support facilities and investments in advanced technology programs in parallel to b) financial support for novel initiatives with the objective to ‘explore’ and ‘execute’ common research interests with a potential campus-wide impact. In addition valorization, technology transfer, funding-raising and European collaboration will be used as instruments to strengthen our core business.” Formulation of Mission of the Neuroscience Campus Amsterdam – 2008: “Our mission is to study the brain and its disease mechanisms through an integrative approach running from molecule-to-bedside. We apply a systems biology approach of the brain where clinicians and clinical researchers are working side-by-side with neuroscientist, geneticists, psychologists, biophysicists and tatisticians. Through this collaboration we aim at delivering proofof-concept for radically new approaches in the early diagnosis of brain disease, the elucidation of its underlying mechanisms and thus providing new perspectives on therapy”. (Quotes from Director & MT of the Neuroscience Campus Amsterdam – Start document). Quote/Executive Summary from the Business Plan – 2008: “At present, Neuroscience research is no longer one discipline, in which scientists can target – and solve – a research problem, from start to end. Instead, many disciplines are being developed, such that collaboration of experts from these different disciplines have a surplus value, and in view of the international competition, even becomes inevitable. As described in this Business Plan of the interfaculty Neuroscience institute, we are investing to make collaboration of neuroscientists from different disciplines, and we directing towards rewarding in particular the quality of the research. Collaboration should be initiated by formation of interdisciplinary teams focussed on a limited number of research themes. However at the same time, the organisation should be such that there is one research interfaculty institute, that is accountable for all Neuroscience research on campus, both in the preclinical and in the clinical domain. In addition to a focus on quality of research, we should focus on young talent. In the context of the Netherlands situation, it is necessary that senior investigators give way to novel

Section I – Self-evaluation 2009-2014

generations of researchers. With financial support of the College van Bestuur (Board of the University) and the science faculties involved, we target ‘quality of research’ and ‘viability’ of the institute as main targets to sustain and improve the fine quality reported by the different founding entities and research units, that now emerge into one new Neuroscience institute (Quote from Deans & Provost of the VU University Amsterdam & VU Medical Center – Business Plan of the Neuroscience Campus Amsterdam). 4.8 Midterm assessment 2008-2010 (by internal Scientific Advisory Board of NCA) Shown below is the main ‘general’ section written by the Scientific Advisory Board of the Neuroscience Campus Amsterdam based on discussions with the Management & Interview-days with all Research Program Leaders of the Neuroscience Campus Amsterdam on 20 and 21 June 2011: The Scientific Advisory Board from 2008-2014 consisted of: Prof. Dr MF Niermeijer, clinical geneticist, UMCN, Nijmegen (chair from 2008-2012); Prof. Dr GJB van Ommen, Human geneticist, UMCL, Leiden (chair from 2012-2014); Prof. Dr CI de Zeeuw, neuroscientist, ErasmusMC, Rotterdam; Prof. Dr F Verhulst, child psychiatrist, ErasmusMC, Rotterdam; and Prof. Dr G Padberg, Neurologist, UMCN, Nijmegen. General Impression & Concluding Remarks in the Midterm Report “The Neuroscience Campus Amsterdam is a high potential top neuroscience institute, which is on the steep part of its growth curve. The major research programs and the advanced technology programs outperform expectations: after three years of integrative functioning in Neuroscience Campus Amsterdam, there is a high volume and high-to-top-level scientific quality of publications and PhD theses, placing the Neuroscience Campus Amsterdam between the leading institutes in their field, as evidenced by all performance indicators. All major research program-leaders at Neuroscience Campus Amsterdam expressively stated the positive effects of integration. Moreover, as the Human Genome Project neared the completion of its first goal (i.e. mapping of genes), Neuroscience Campus Amsterdam departments successfully participated in the search of genes for common (i.e. multifactorial) diseases and for genes related to synapse function, neurodevelopmental disorders and neurodegeneration. The clinical departments continued their prominence among the world leaders in neuroinflammatory diseases, like Multiple sclerosis, and neurodegenerative diseases like Alzheimer- and Parkinson disease. The focused clinical approaches connect well with new basic research areas, from intraoperative functional microscopy (including imaging and electrophysiological recording) to searching new inroads across the blood-brain barrier and using patient stem cells as models for deciphering and treating his disease. Program-leaders successfully obtained a number of big international and national individual-, program- or technology grants, based upon their scientific track record and the added value of robust interdisciplinary cooperation and available technology. In the current period of shrinking funds, the Neuroscience Campus Amsterdam and the VU-campus as a whole should cherish its' earning power. Training young scientists in a Neuroscience curriculum and organizing PhD programs shows a high PhD productivity among the participating institutes. The high level of interdisciplinary subjects and techniques characterizes their quality. The director of the Neuroscience Campus Amsterdam succeeded in forming an international European Neuroscience Campus Network of seven high-level neuroscience centers (the ENC-Network) with a collaborative Joint Master and a joint PhD program both funded by Erasmus Mundus.

Section I â&#x20AC;&#x201C; Self-evaluation 2009-2014

The Neuroscience Campus Amsterdam has developed a high quality reporting on a complex organization, giving evidence of its scientific and financial health in terms of fundraising power, bibliometric performance and societal impact monitoring. The director of the Neuroscience Campus Amsterdam was acknowledged for his effective implementation during the various phases of the integration process since the start of the research institute. However in the SWOT analysis and during the Midterm Review on 20-21 June of 2011 by the Scientific Advisory Board, it was stipulated repeatedly that NCA has to make a position shift towards more public-private collaboration. To this end, starting in the fall of 2011, several strategic and business development initiatives should be undertaken by the management of the Neuroscience Campus Amsterdam, in order to define the contours of a so-called Industry Alliance Office dedicated to the institute.â&#x20AC;? (Quote from (vice-) chairs of the Scientific Advisory Board, Prof. Dr M.(Martinus) F. Niermeijer and Prof. Dr GJ van Ommen, in writting to Board of Deans of the Neuroscience Campus Amsterdam).

Section II - Annual Report 2015

Section II â&#x20AC;&#x201C; Annual Report 2015

1a) Composition (input data) Total fte research (including PhD students) Type of funding gs 1

gs 2

gs 3

gs 4

gs 5

Total

Total - 2015

60,6

37,5

91,1

5,5

N.A.

194,6

Total - 2014

64,6

38,7

77,5

6,6

N.A.

187,5

Total - 2013

63,5

41,3

69,2

7,7

N.A.

181,8

Total - 2012

63,8

48,4

70,2

0,1

190,4

Total - 2011

72,6

46,7

81,1

8,6

N.A.

208,9

Total - 2010

11,4

N.A.

189,4

Total - 2009

62,5

14,7

N.A.

179,2

Total - 2008

56,8

23,2

2,1

13,5

142,6

Total fte research PhD students Type of funding gs 1

gs 2

gs 3

gs 4

gs 5

Total

Total - 2015

8,8

24,3

64,4

3,3

N.A.

100,7

Total - 2014

10,2

24,3

55,3

5,3

N.A.

95,2

Total - 2013

13,3

26,8

N.A.

92.1

Total - 2012

13,7

29,3

42,4

5,9

0,1

91,4

Total - 2011

18,6

32,8

44,3

N.A.

98,7

Total - 2010

14,6

25,9

32,2

5,6

N.A.

78,2

Tables II-1. Total of appointed research time. Numbers are excluding support- and technical staff and only give FTE quota spent on research. The research time per research program is split in Table II-6. In this overview, gs 2 is NWO funded research, gs 3 is project funding from non-profit organizations, ministries, FES & EU and gs 4 is based on a mix of contract-research (for a major part on the basis of for-profit/industrial funding and minor part on the basis of donations/ philanthropy; gs5: funds that do not fit the other categories).

Section II â&#x20AC;&#x201C; Annual Report 2015

PhD projects

2008

2009

2010

2011

2012

2013

2014

2015

newly started

Table II-2. Newly started PhD projects in recent years. See appendix 2 at the website for a full list. fte per type of funding (incl PhD students)

Research program Brain Imaging Technology Brain Mechanisms in Health & Disease Neurodegeneration Neuroinflammation Neurobiology of Mental Health Total

2014

2013

gs 1

gs 2

gs 3

gs 4

Total

6,7 19,9 11,5 8,3 14,1 60,6

3,0 19,4 3,0 4,8 7,5 37,5

5,3 22,1 33,5 17,6 12,5 91,1

1,0 1,3 0,9 0,6 1,6 5,5

16,0 62,7 48,9 31,3 35,7 194,6

15,9 60,4 40,2 34,7 36,4 187,5

17,4 57,7 39,7 36,6 30,4 181,8

2015

2014

2013

fte PhD students per type of funding

Research program Brain Imaging Technology Brain Mechanisms in Health & Disease Neurodegeneration Neuroinflammation Neurobiology of Mental Health Total

2015

gs 1

gs 2

gs 3

gs 4

Total

0,3 5,0 0,2 0,0 3,2 8,8

1,7 12,5 2,7 3,8 3,7 24,3

4,3 19,6 20,9 11,7 7,9 64,4

0,8 0,4 0,5 0,0 1,6 3,3

7,0 37,5 24,3 15,5 16,5 100,7

6,8 35,3 20,7 15,1 17,4 95,2

7,5 35,4 20,1 15,4 13,7 92,1

Tables II-3. Input in fte (research time, not total number of appointments) per Research Program. A full list of coworkers is outlined in appendix 1 at the website. In this overview, gs2 is NWO funded research, gs3 is project funding from non-profit organizations, ministries, FES & EU and gs4 is based on a mix of contractresearch (for a major part on the basis of for-profit/industrial funding) and donations/philanthropy.

Section II â&#x20AC;&#x201C; Annual Report 2015

1b) Participating researchers A complete list of investigators, categorized by research program, is shown in the appendix. Participation in the NCA is according to rules set by the campus authorities. PhD students, team leaders and group leaders (with a few exceptions, being Prof. Brenda Penninx and Prof. Dorret Boomsma (also appointed in EMGO) and Prof. Johannes de Boer (also being director of LaserLab) can participate only in one research institute. See also appendix 1 at the website.

Section II â&#x20AC;&#x201C; Annual Report 2015

2a) Quality and scientific relevance In section I an overview of the research strategy, the recent developments and a selection of key publications per research program, are outlined. A check on scientific relevance is executed by the various research program committees listed. Here we further outline a short statistical analysis of the scientific relevance of the NCA program as an Institute (Table II-4) for 2015. The number of articles published per year and the total number of citations each year to these papers published shows the solid growth in output and relevance of their output in recent years. At the onset of the new era in which the NCA became operational (i.e. during 2008-2009) the yearly output amounted to ~ 400 research papers per year. In recent years the total number of reports has settled to 550-600 publications per year. In 2015, 600 papers were peer reviewed reports (see Table II-6), with 77% being published in a top 25% journal and 42% being in the top10% journals (see Table II-4). Another way of benchmarking the output of NCA is to score the absolute impact factors: in 2014, we had > 20 % of these papers (i.e. 120 papers out of 600 peer reviewed) in the highest impact journals (i.e. IF ~ 9 or higher). In Table II-5, the relative impact and the number of high impact papers is further subcategorized per research program.

5 4 3 2 1

top 10% 11-25% 26-50% 51-75% 76-100%

sc or e til e

er s 42 34 18 5 1

pe r

qu ar

ll p ap of a %

til e ua r Q

Re la

tiv

C at eg

or y

Fa c

to r

)

Quality of total research output

Table II-4. Percentage of papers categorized according to the relative impact factors scores for 2015.

Section II â&#x20AC;&#x201C; Annual Report 2015

pa ct im pa

fh ig

be ro

ro fp

m be

nu m

er s

1 of

2 RI F ith w er s ap

44%

33%

17%

Brain Mechanisms in Health & Disease

42%

25%

20%

11%

117

Neurodegeneration

44%

36%

16%

125

Neuroinflammation

42%

37%

17%

Neurobiology of Mental Health

44%

34%

17%

183

to ta l

of p

er s

ith

RI F

3 of

4 RI F

of of p

Brain Imaging Technology

of p

er s

ith

RI F ith w

er s ap

of p

er s

ith

RI F

Quality of research output per research program

Table II-5. Quality of the different Research Programs in 2015. Shown are the percentiles of papers categorized according Relative Impact Factor (RIF), the total number of papers and the number of papers published in the highest impact journals.

Section II â&#x20AC;&#x201C; Annual Report 2015

2b) Quality control Also in 2015, NCA had three Research Committees (the Clinical, the Biomedical and the Psychology Research Committee) that provide an independent review of the scientific quality of research protocols brought forward by investigators. The purpose of the review is to ensure the highest quality of research and to support researchers affiliated to NCA. In addition, the Clinical Research Committee lead by Prof. Henk Berendse, provides the Director and Management Team with (solicited and unsolicited) advice on matters directly related to the Institute's science policy. A primary task of each Research Committee is to lend approval to any project within NCA before evaluation of a project by either the Medical Ethical Committee of the VU University Medical Center or the Animal Ethical Committee of the VU University. Since projects are executed in distinct faculties on campus, each faculty has an independent Research Committee dedicated to NCA. A secondary task of the Clinical Research Committee (VUmc) is to advise the director on the eligibility and methodological quality of all new research proposals (after grant award) brought forward by researchers for inclusion in the NCA research programs. Only after approval of the director of NCA, advised by the Research Committee, a project will be NCA-labeled. Only NCAlabeled projects are accountable for output-administrative and financial administration. NCA adheres to the Research Guide of the VU Medical Center. Specific other regulations (or adjustments) may apply for different NCA departments (in particular for those residing in other faculties). For NCA investigators, the Quality Checklist needs to be used for execution of project run by PhD students, post docs and other affiliated coworkers. The VUmc Research Guide provides a valuable overview of the available support for conducting research at VUmc. Examples: Law and regulations i.e. the medical ethical review committee, grants desk, juridical support, obtaining of (special) research materials or equipment, and documenting research projects. In addition, human resource issues such as reimbursements and obtaining permits for non-EU scientist are indexed in the Research Guide.

Section II â&#x20AC;&#x201C; Annual Report 2015

3) Output Theses DissA DissB DissC

Scientific papers Wp WpREF

DissD

WpNR

Rest VP

Total

Books Chapters Total - 2015

600

685

Total - 2014

560

648

Total - 2013

510

609

Total - 2012

606

683

Total - 2011

508

572

Total - 2010

453

508

Total - 2009

424

490

Total - 2008

413

533

Table II-6. Aggregate of the output of NCA as an 'Institute'. A full list of publications is outlined in the 2 appendices at the website. See footnote for abbreviations.

Abbreviations table II-6 and table II-7: Theses A: Promotion VU/VUmc PhD-student at VU Theses B: Promotion external PhD-student at VU Theses C: Promotion VU/VUmc PhD-student at other university Theses D: Promotion external PhD-student at other university (promotor, co-promotor) Wp: Books/monographs/book chapters/proceedings WpRef: Scientific Papers refereed WpNR: Scientific Papers non-refereed VP: Professional publication

Section II â&#x20AC;&#x201C; Annual Report 2015

Theses

Scientific Output DissA

Brain Imaging Technology Brain Mechanisms in Health & Disease

DissC

Scientific papers

DissB

DissD

WpREF WpNR

Wp Books

Chapters

Rest

2015

2014

2013

Total

108

126

154

185

183

Neurodegeneration

133

160

152

150

Neuroinflammation

103

111

134

Neurobiology of Mental Health

188

203

139

198

2012

2011

2010

2009

Total

Integrative Analysis & Modeling

Photonics & Life Cell Imaging

Scientific Output

Advanced Technology Brain Imaging Drugs Screening & Therapy Design

Genes & the Brain Attention & Cognition Addictive Behavior

Systems Biology of the Synaps

Brain Disease Mechanisms Anxiety and Depression Neurodegeneration

201

157

151

180

White Matter Disease

209

181

144

136

Affiliated research

Table II-7. Output per Research Program of the NCA. A full list of publications is outlined in appendices at the website. See footnote on previous page for abbreviations. WpREF statistics contains also reports that were categorized in more than one NCA research program. In Table II-6 only unique (i.e. individual) items were scored.

Section II – Annual Report 2015

4) Earning capacity – NCA The collective and aggregate acquisition of external funding in 2015 amounted to a consolidation of the number and amount of awarded grants, including the number of personalized grants (see appendices at the website) and a cumulative of > 29 M€ of external grant support (see II- 8). The breakup grant acquisitions per research program are given in Table II-9.

External Funding - Neuroscience Campus Amsterdam gs 3

gs 2

gs 4 (mix)

Total

Total - 2015

€ 8.250.647

€ 12.707.163

€ 6.126.487

€ 27.084.297

Total - 2014

€ 14.147.550

€ 8.216.186

€ 11.750.880

€ 34.114.616

Total - 2013

€ 10.896.213

€ 10.343.102

€ 2.321.406

€ 23.560.721

Total - 2012

€ 11.092.777

€ 5.741.757

€ 416.324

€ 17.250.858

Total - 2011

€ 13.182.708

€ 11.819.720

€ 3.376.520

€ 28.378.948

Total - 2010

€ 7.939.262

€ 18.172.132

€ 3.534.291

€ 29.645.685

Total - 2009

€ 6.594.300

€ 13.580.420

€ 2.576.000

€ 22.750.720

Total - 2008

€ 3.533.146

€ 6.449.689

€ 926.165

€ 10.909.000

Table II-8. Acquisition of grants by collaborative efforts of the NCA - started in 2015 – and compared to 2008-2014 acquisitions. For further information, on acquisition per research program, see appendix 6 at the website. In this overview, gs 2 is NWO funded research (plus ERC funding), gs 3 is project funding from nonprofit, ministries, FES & EU and gs 4 is based on a mix of contract-research (for profit/industry) and donations/philanthropy.

Section II – Annual Report 2015

External Funding per Research Program in 2015 gs 3

gs 2 Brain Imaging Technology

gs 4 (mix)

Total

€ 1.553.000

€ 465.873

€ 1.372.822

€ 3.391.695

€ 468.645

€ 5.674.495

€ 1.141.164

€ 7.284.304

Neurodegeneration

€ 2.595.000

€ 1.471.828

€ 3.385.941

€ 7.452.769

Neuroinflammation

€ 250.000

€ 3.401.984

€ 150.000

€ 3.801.984

€ 3.384.002

€ 1.692.983

€ 76.560

€ 5.153.545

Brain Mechanisms in Health & Disease

Neurobiology of Mental Health

Table II-9. Grant acquisition per Research Program of 2015. Acquisition in 2015 is split in types of funding. A full list of acquired external funding is outlined in appendix 6 at the website. In this overview, gs2 is NWO-funded research (plus ERC funding from EU), gs3 is project funding from nonprofit, ministries, FES & EU and gs4 is based on a mix of contract-research (for profit/industry) and donations or philanthropy.

Section III â&#x20AC;&#x201C; Assessment of Research Quality 2009-2014 (Site visit report February 2016)

Section III – Site Visit Report

1. Introduction

1.1 Background This report describes the assessment of research conducted at the Neuroscience Campus Amsterdam (NCA) in the period 2009-2014. NCA is a research institute at the VU University Medical Center (VUmc) and VU University (VU) in Amsterdam, the Netherlands. The assessment was performed by an external assessment committee using the Standard Evaluation Protocol (SEP) 2015-2021. 3 The primary aim of SEP assessments is to evaluate the quality and societal relevance of research and to provide advice to improve these where necessary. SEP assessments focus on the strategic choices and future prospects of research groups. Target groups that are served by this assessment include: • NCA’s researchers and group leaders: they need to know how the quality of NCA research, its societal relevance, and its strategy are perceived by independent experts and how these elements can be improved; • Board of deans of VU and VUmc: they wish to track the impact of their research policy; • Dutch government: they want to know the outcomes of assessments in connection with the institution’s accountability for expenditure and its own efforts to support an outstanding research system; • Society and the private sector: they seek to solve a variety of problems using the knowledge that NCA research delivers. 1.2 Members of the assessment committee The board of deans of VU and VUmc has appointed as members of the assessment committee: • Professor Paul Matthews, chair (Imperial College London), • Professor Jonathan Flint (University of California, Los Angeles), • Professor Jean Marc Fritschy (University of Zurich), • Professor Catherine Lubetzki (Pierre and Marie Curie University), • Professor Andreas Meyer-Lindenberg (Central Insitute of Mental Health, Mannheim; University of Heidelberg), • Professor Trevor Smart (University College London), • Professor Reisa Sperling (Harvard Medical School). Professor Lubetzki could not attend the site visit due to personal circumstances, so she withdrew from the assessment committee. Dr Linda van den Berg (Washoe Life Science Communications) served as the secretary to the assessment committee. Short CVs of the committee members are provided in Appendix 1.

The SEP was drawn up and adopted by the Association of Universities in the Netherlands (VSNU), the Netherlands Organisation for Scientific Research (NWO), and the Royal Netherlands Academy of Arts and Sciences (KNAW). All research conducted at Dutch universities, university medical centres, and NWO or KNAW institutes is assessed once every six years in accordance with the SEP. 49

Section III – Site Visit Report

1.3 Procedures followed The assessment committee evaluated NCA research based on NCA’s self-assessment, its annual reports, and interviews with NCA representatives that were conducted during a site visit in November 2015. The site visit programme is provided in Appendix 2. The committee took into account international trends and developments in science and society as it formed its judgement. In addition, the committee bore in mind NCA’s strategy while assessing the quality and relevance of the research. Qualitative and quantitative assessment of NCA research The assessment committee based its judgement on three assessment criteria: 1. research quality, i.e., contribution to scientific knowledge, scale of research results (scientific publications, instruments, and infrastructure produced and other contributions to science); 2. relevance to society, i.e., quality, scale, and relevance of contributions (advisory reports for policy, contributions to public debates, etc.) targeting groups that NCA has itself designated as target groups (patients, the general public, students, and industry); 3. viability, i.e., the strategy that NCA intends to pursue in the future and the extent to which it can meet its targets in research and society during this period, the governance and leadership skills of NCA’s management. The qualitative assessments were supplemented by numerical scores (1–4) for each of the criteria. Assessment of NCA’s PhD programme The assessment committee also considered the supervision and instruction of PhD candidates at NCA. The assessment committee interviewed six PhD students during the site visit. The committee assumed that these individuals provided opinions that are representative of the group at large. In a separate session, the committee interviewed the PhD committee. The following topics were considered: • institutional context of the PhD programme, • selection and admission procedure, • quality assurance, • programme content and structure, • supervision and the effectiveness of supervision plans, • duration, success rate, and exit numbers, • career prospects and guidance of PhD candidates to the job market. Assessment of the NCA research integrity policy The committee also considered NCA’s policy on research integrity and the way in which violations of such integrity are prevented. This was discussed during the site visit. The committee was interested in how NCA deals with research data (i.e., data stewardship) and the extent to which a critical pursuit of science occurs at NCA. 1.4 Research unit under assessment: Neuroscience Campus Amsterdam NCA is a research institute at the VUmc and VU. Built upon a rich but scattered neuroscience history, NCA was founded in 2008 to create a research network organisation where scientists, students, and medical professionals collaborate in the field of translational neuroscience. NCA currently is the largest neuroscience research community gathered on one campus in the Netherlands. In 2014, NCA employed 451 researchers (181 PhD students, 144 post-docs, and 126 senior staff members, see Appendix 3 - Table III-1 for further details).

Section III – Site Visit Report

NCA is a virtual organisation on top of traditional departments within several VU and VUmc faculties. It functions as a network organisation. Patient centres such as the Alzheimer Centre, the MS Centre, the Movement Disorder Clinic, the Centre for Childhood White Matter Disorders, and the GGZ inGeest clinic for Anxiety and Depression are major hubs in the NCA network. NCA’s employees are appointed in VU or VUmc departments and they perform their research within NCA. Details about NCA’s financing are provided in Appendix 3 (Tables III-2 and III-3). All NCA research activities are interdisciplinary, i.e., clinicians and clinical researchers are working side by side with neuroscientists, geneticists, psychologists, epidemiologists, biophysicists, and statisticians. NCA’s strongholds and international reputation rely on its work in understanding the human brain, clinical studies of its major diseases, development of advanced technologies, and a long tradition of behavioural genetics. Research at NCA is organised into five research programmes that collaborate intensively: 1. Brain imaging technology, 2. Brain mechanisms in health and disease, 3. Neurodegeneration, 4. Neuroinflammation, 5. Neurobiology of mental health.

Section III – Site Visit Report

2. Qualitative and quantitative assessment of NCA research

2.1 NCA’s strategy and targets NCA’s mission is to study the brain and its diseases through an integrative approach, i.e., from molecule to bedside. NCA is translational and explicitly links basic science and clinical science. There is a strong focus on molecular neurobiology, including biophysics, genomics, systems biology of the synapse, and the genetic basis of brain function. NCA aims to advance neuroscience through innovative research and technology. In addition, NCA tries to find solutions that will benefit society through medicine and engineering. NCA’s graduate programme offers training for national and international brain researchers in an environment of scientific excellence. NCA was launched in 2008 to resolve disciplinary boundaries and to promote campus-wide collaborations. Hence, NCA has invested in building bridges by applying two strategies: 1) concerted funding of research support facilities and investments in advanced technology programmes and 2) financial support for novel initiatives to explore common research interests with campus-wide impact. In addition, valorisation, technology transfer, fund-raising, and European collaboration were used as instruments to strengthen NCA’s core business. NCA started off with ten research programmes. In 2011-2012, NCA research was reorganised into five research programmes to achieve greater focus. Each of these research programmes is coordinated by two programme leaders, often one with a clinical background and one with a more preclinical background. NCA has set up an Industry Alliance Office (IAO) to facilitate public-private partnerships, i.e. commercially driven joint projects in the fields of target discovery, target validation, and biomarker research. The IAO is a dedicated front-office that offers NCA’s scientific expertise, knowledge, and network to external commercial partners. Through the IAO, NCA organises guidance in clinical trials, collaborative programs with industry, and other research services to external stakeholders. The internal value of the IAO is to structure approaches to attract funding to support scientific research. 2.2 Assessment Neuroscience Campus Amsterdam as a whole Research quality The committee rates NCA’s overall research quality as excellent. NCA performs research of international quality across several areas of neuroscience. It also hosts many deeply phenotyped cohorts that promise a continuing contribution to the scientific mission. The institute has published an impressive number of articles in top scientific journals: 15-20% of NCA’s peer reviewed papers were published in journals with an average impact factor of at least 9 in the period 2009-2014. In addition, several NCA investigators have been awarded prestigious grants, including the national Spinoza Prize and ERC grants. Relevance to society NCA’s research is highly relevant to society, in particular for the following societal groups:

Section III – Site Visit Report

•

• •

Patients: NCA research addresses severely debilitating neurodegenerative diseases and mental disorders. Its translational nature provides a strategy to best ensure that results are relevant to patients. The Industry Alliance Office contributes to bringing new discoveries to the bedside. General public: NCA’s focus on prevention and early detection of brain diseases makes its research highly relevant to the general public. In addition, NCA engages in sharing its knowledge with the general public through outreach activities. Both the Alzheimer Center and the MS Center have extensive outreach programmes and several NCA staff members are involved in public outreach through the ‘De Jonge Akademie’ of the Royal Academy of Sciences. Students: NCA offers an excellent PhD training programme (see Chapter 3). Industry: The Industry Alliance Office (IAO) offers NCA’s scientific expertise, knowledge, and network to external commercial partners. The committee thinks the IAO adds exceptional value to the university.

• Viability Overall, NCA has many assets and the committee rates its viability as very good. The committee praised the outstanding leadership of NCA, especially noting the dynamic work attitude of the Director Arjen Brussaard who was seen as a key driver for collaboration across the NCA. The committee praised the extraordinary vertical integration of NCA research, i.e., the integration of basic science with clinical research, which is very successful. In addition, the committee praised NCA’s collaborative spirit, both internally (i.e., between the five research programmes) and externally (i.e., in international research consortia).

The committee was impressed by the young ages and by the equal gender distribution of NCA staff. NCA offers a strong platform to support researchers for interaction and sharing of infrastructure in ways that extend their scientific capabilities. There is a collaborative spirit, which is promoted by the geographical proximity and the theme-based coordination of the research groups. The cohesive culture and the diversity in age and gender are very important to NCA’s viability. In addition, the institute benefits from its integration with clinical care in hosting several world-class cohorts. However, the committee also identified potential threats to the long-term sustainability of NCA, with the most important being: • NCA’s ability to recruit and retain the most talented researchers seems limited; • Although NCA’s team spirit is admirable, the institute structure seems slightly monolithic; • Funding to support or develop important, larger elements of NCA’s research infrastructure seems uncertain. The committee will provide recommendations on how to deal with these concerns in Chapter 4. 2.3 Assessment Brain imaging technology programme Research quality The committee rates the research quality of this programme in the period 2009-2014 as very good. While some parts of this programme are world class, others have fallen behind the very high standards they themselves set for these areas 3-4 years ago. In particular, multimodal imaging approaches, optogenetics, computational neuroscience, molecular imaging, and animal imaging were noted as potential areas for further expertise development.

Section III – Site Visit Report

Relevance to society The programme is highly relevant to society because its approach is truly translational. For instance, the group is developing minimally invasive programmes suitable for personalised medicine and drug targeting strategies. Early imaging markers of Alzheimer’s disease and multiple sclerosis that can be utilized in prevention trials are also highly relevant. Viability Overall, the committee rates the viability of this programme as very good. The programme has some great resources derived particularly from its close clinical links, but there are some concerns, with the most important being staff renewal. Recently, one key staff member left NCA and another senior staff member became part-time. NCA’s management team acknowledges that this needs attention. In addition, the programme may need to consider new recruitment or partnerships to bring in additional expertise in areas potentially complementary with existing efforts that currently are under-represented, such as computational neuroscience and multimodality molecular neuroimaging. 2.4 Assessment Brain mechanisms in health & disease programme Research quality The quality of NCA’s research on brain mechanisms in health & disease is excellent. The programme has an outstanding publication record and its work has international impact. For instance, the research on white matter disorders is recognised as seminal and is responsible for contributing several fundamental new insights into the classification and aetiologies of this group of diseases. Other research groups within this programme provide cutting edge technology or contribute to research infrastructure, in some cases providing key support to international efforts (e.g., the Genetics Cluster Computer of the Complex Trait Genetics group provides storage and nodes for the Psychiatric Genomics Consortium). Relevance to society The work of this programme is highly relevant to patients. To provide an example, the Center for Childhood White Matter Disorders has made crucial contributions to the genetic diagnosis of patients with white matter disorders worldwide. In thirty years, the percentage of patients with white matter disease who have a DNA-confirmed diagnosis has increased from 60% to 90%. Viability This programme’s viability is rated as excellent. The research leaders are young and the programme is very focused. The programme has good connections with industry. The committee had the impression that some advanced research techniques may be somewhat confined to use in this group, so the committee encourages the researchers to share their techniques with the other NCA programmes where they might offer benefits. 2.5 Assessment Neurodegeneration programme Research quality The committee rates the research quality of the Neurodegeneration programme as excellent. Research in this programme is conventional in approach, but is nonetheless very strong internationally. The programme hosts exceptional patient cohorts and large biobanks (e.g., Amsterdam Dementia cohort and Netherlands Parkinson cohort). In addition, the researchers study general population cohorts (e.g., Netherlands Twin Register and the impressive, unique

Section III â&#x20AC;&#x201C; Site Visit Report

100+ study). There is good use of animal models and there are clear plans for developing new and useful lines. The committee praised the innovation of the genetic study of cognitively healthy ageing in the 100+ study and the strong research focus on proteomics of the synapse, linking basic and clinical science. Relevance to society The Neurodegeneration programme is highly relevant to society because it addresses major public health problems such as Alzheimerâ&#x20AC;&#x2122;s disease and Parkinsonâ&#x20AC;&#x2122;s disease. The researchers aim at understanding the mechanisms of neurodegeneration and preventing disease progression through early recognition. The basic science in this programme serves to develop diagnostic and prognostic biomarkers as well as new early treatments. The programme has an infrastructure for clinical trials. The patient cohorts have active public outreach programmes. Viability The viability of this research programme is considered excellent, especially because of the strong cohort resources. The committee expects that the researchers will be able to capitalize on their large data sets. The programme has convincingly demonstrated its ability to attract external funding in a sustained way (see Appendix 3, Table III-2) and it attracts fruitful collaborations. 2.6 Assessment Neuroinflammation programme Research quality The Neuroinflammation programme is rated as very good. The basic science in this programme is good and the scientists have access to unique resources, e.g., large patient cohorts, post-mortem tissue, and research tools. Approximately 50% of all Dutch multiple sclerosis (MS) patients visit the VUmc MS center at least once. However, the committee believes that the programme currently risks having too little critical mass in strategically key areas to maintain its historically world-class efforts. Relevance to society This programme is relevant to society as it contributes to the insight into the aetiology of a severely debilitating disease (MS). The researchers are working on methods to restore deficiencies in the blood-brain barrier in patients and they are involved in clinical trials, though clinical evaluation needs further development. In addition, the neuroimaging work has led in the development of current criteria for the diagnosis of multiple sclerosis used internationally. However, the committee thinks that the broader relevance of the focus on astrocytes presented to the committee needs to be made more explicit, e.g., through links to other disease processes and the definition of clear pathways to impact. Viability The viability of this programme is rated as very good. The programme has potential for excellence, but may be limited by the loss of one of its major leaders, who has not been replaced over the last six year period. The assessment committee believes that there is a strong case for integration of greater immunology expertise into the programme. The committee also believes that the researchers could enhance their connections with the other NCA programmes and other departments even further.

Section III â&#x20AC;&#x201C; Site Visit Report

2.7 Assessment Neurobiology of mental health programme Research quality The committee considers this programme excellent. NCAâ&#x20AC;&#x2122;s mental health research is outstanding: the programme has an impressive publication list, innovative ideas, valuable cohorts, and excellent tools. It hosts top scientists. The researchers study innovative phenotypes, e.g., the exploration of the genetic basis of happiness in the Netherlands Twin Register. They have successfully engaged in large international collaborations such as the ENIGMA neuroimaging genetics study. Their studies have considerable impact in the field of psychiatry, e.g., they have revealed a distinction between melancholic and immuno-metabolic subtypes of depression and clarified neurostructural bases of affective disorders. Relevance to society This programme is highly relevant to society because mental health disorders pose enormous personal, family and economic burdens by causing mental disability, and by their often chronic course. The programme has contributed significantly to our understanding of the mechanisms mediating vulnerability to mental diseases. For instance, NCA studies have added to the body of knowledge about adolescence as a vulnerable period for nicotine exposure. The programme is also studying interventions, e.g., the MOTAR study on the effect of combined treatment with antidepressants and running therapy in patients with anxiety or depression. The cohorts have active public outreach programmes, including newsletters and annual patient days. Viability The mental health programme at NCA is strong. Clinicians and researchers work together seamlessly in this programme. There is a good foundation for clinical research and there are excellent resources, e.g., the patient cohorts such as NESDA and a general population cohort (Netherlands Twin Register) with extensive phenotyping available. 2.8 Summary in numerical scores The four possible categories are excellent (=1), very good (=2), good (=3), and unsatisfactory (=4). See Appendix 4 for an explanation of these scores.

NCA as a whole Brain imaging technology programme Brain mechanisms in health & disease programme Neurodegeneration programme Neuroinflammation programme Neurobiology of mental health programme

Research quality 1 2 1

Relevance to society 1 1 1

Viability

1 2 1

2 2 1

Section III – Site Visit Report

3. Qualitative assessment of PhD programme and research integrity policy

3.1 Quality and organisation of NCA’s PhD programme Overall, the committee was impressed by NCA’s very strong PhD training programme. The programme is well structured and well financed. Institutional context of the PhD programme NCA clearly considers graduate training a very important task. At the start of 2015, NCA hosted ~180 PhD students. The committee learned that NCA has a PhD committee, which is chaired by the director of NCA and has four members: the director of the Graduate School Neurosciences Amsterdam-Rotterdam (ONWAR) and representatives of the VUmc Alzheimer Center, the VUmc MS Center, and GGZ inGeest. Selection and admission procedure The recruitment procedure for PhD students usually proceeds via a normal open call. Selection is performed by three to four NCA members. Candidates are chosen because of their motivation, knowledge, experience, and enthusiasm. The committee inferred that the selection procedure must be working well because the early drop-out percentage is very low (~6%). Quality assurance The committee learned that NCA has implemented campus-wide PhD regulations. These regulations demand, in part, that at the start of each project the PhD students: • receive instructions on the standard operating procedures for their studies, as outlined in a quality checklist; • receive an NCA-specific protocol of instructions and list of courses to be followed; • file a mandatory training and supervision plan for their PhD, which will be monitored by the supervisors. Programme content and structure NCA has a 30 ECTS points training plan, which is partly incorporated into the Graduate School Neurosciences Amsterdam Rotterdam (ONWAR). Each PhD student selects courses based on a personal profile. Students are encouraged to select courses that broaden their horizons. On average, roughly half of the training plan is completed at ONWAR, with the remainder followed elsewhere, i.e., training of general skills (e.g., scientific writing) and participating in national and international conferences. NCA holds the chair of ONWAR and is thus taking the lead in organising PhD student training in neuroscience in Amsterdam (VU, VUmc, NIN, UvA, and AMC) and Rotterdam (Erasmus MC). The committee strongly praised the outstanding leadership of ONWAR by August Smit. ONWAR’s course programme is continuously being improved using feedback from the students. There is an annual PhD student retreat that is organised by the students. This helps them to build their own network and inculcates other skills, such as how to organise a conference. The PhD committee of NCA did note one weakness of their PhD programme: due to the heterogeneous background of PhD students and their research subjects, it is difficult to organise a

Section III – Site Visit Report

scientific training programme for the whole group. They have tried to solve this by customizing the NCA PhD regulations to the needs of clinical and pre-clinical scientists. In addition, they organise an obligatory yearly NCA meeting with review and feedback elements. Supervision and the effectiveness of supervision plans Each student at NCA has a team of supervisors. The students’ progress is monitored every year using a progress form. In addition, there is a mentoring system within ONWAR, which functions as a back-up for the supervision teams in case of difficulties. Success rate, duration, and exit numbers Over the years, more than 90% of all PhD students at NCA complete their thesis. This percentage is substantially higher than the mean of 75% in Dutch research schools and the committee was impressed by this high success rate. In the years of this evaluation, the mean duration for completing the thesis was 4.98 years (with a standard deviation of less than 8 months). These numbers were not corrected for part-time appointments, maternity leaves, or other leaves of absence. The regular duration of a PhD project is four years in the Netherlands. Guidance of PhD candidates to the job market and career prospects The team of supervisors guide the students in approaching the labour market. In addition, NCA organises career events and there is an alumni programme that helps to keep track of where the students end up. Of those that graduate, 8 out of 10 pursue a research career, mainly in academia and some in industry (biotech or pharma). The remainder pursue other careers, e.g., consultancy, management, business development. Three years after PhD graduation, around 25% of the graduates are still in science, so the largest drop-out is among early post-docs. 3.2 Research integrity policy The assessment committee considered NCA’s research integrity policy and the way in which violations of such integrity are prevented. NCA’s research integrity policy looks outstanding and is an asset to be proud of. NCA adheres to the Research Guide of the VUmc and the joint research code of the VUmc and Academic Medical Center (AMC; this is the second academic hospital in Amsterdam). The committee had the impression that NCA’s culture is very open and as a result, certainly allows for an independent and critical pursuit of science. The VUmc Research Guide can be found on the NCA website. It provides an overview of the available support for conducting research at VUmc as well as guidelines for adequate data stewardship (including proper data storage). In the majority of NCA laboratories, official laboratory journals are used. Patient data are stored digitally in protected directories according to the regulations for good clinical practice. The committee learned that in the near future, this will be followed by protection of the storage of all digital data. This protected data storage will be used for both experimental and patient-related data. NCA has three research committees that provide an independent review of the scientific quality of research proposals of investigators. The purpose of this review is to ensure the highest quality of research and to support researchers affiliated to NCA.

Section III – Site Visit Report

4. Recommendations

4.1 Quality of the research unit 1) Strategy in general The committee recommends that NCA strategically assesses where it wants to be at the time of the next evaluation and beyond. In the past six years, NCA’s strategy was focused on promoting interdisciplinary collaboration and translational research. This has been extremely successful. However, other than the focus on translational research, NCA’s strategy is driven by the interests of individual researchers and groups. The committee recognised that NCA’s overall excellent research quality and much of its success in innovation can be attributed in part to an inspiring culture, in which scientists are encouraged to take risks and have the intellectual freedom to influence the direction of their research. However, a potential limitation of this may be that the NCA lacks enough of a top-down research strategy to maintain programmes at an internationally leading level, and to be able to move rapidly to develop important new areas of research that have not featured in the past at NCA. Looking to the future, the committee believes that NCA will need to manage longer-term research strategies for the whole institute. The committee encourages NCA to consider which research will be innovative, outstanding, sustainable, and achieve high impact. From this, a more granular ‘vision statement’ could be distilled that will help guide research groups in setting common objectives. This also will be useful as a guide for planning increased collaboration with the University of Amsterdam (see recommendation 2). As part of this exercise, the committee recommends that NCA also evaluates the balance between fundamental research and translational research to ensure that it contributes best to long term growth. The committee felt that there may be too little focus on basic science at the moment. 2) Amsterdam-wide initiatives The board of deans of VU and VUmc has asked the assessment committee to comment on the plans to intensify neuroscience collaborations with the University of Amsterdam (UvA). However, other than to note that there are areas that could usefully be strengthened (mentioned above), the committee feels it is not possible to comment on these plans because it does not have a comprehensive and informed view of UvA research. 3) External advisory board The committee recommends that NCA establishes an external scientific advisory board. The committee greatly admired the cohesive spirit of the NCA community. However, the committee also feared that this could make NCA somewhat monolithic unless explicit efforts were made for periodic renewal of ideas and staff from the outside. The committee learned that NCA was formerly advised by an independent external scientific committee, but that the board is currently inactive. The committee recommends reviving the advisory board. This board should meet to review progress at least once a year and provide input. Crucially, the board should be encouraged to help NCA identify new opportunities and areas for development. This will help NCA to stay at the forefront of neuroscience by proactively seizing opportunities and embracing technological and field changes quickly.

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4) Recruiting and retaining top scientists The committee recommends that the NCA management takes specific steps to increase the recruitment of international, world-leading scientists. A more general, important concern of the committee is the institute’s ability to recruit and retain the most talented scientists, as well as employees with specific skills. The committee feels this constitutes a threat to NCA’s viability. This was extensively discussed with NCA’s management team during the site visit. The committee recognised a number of challenges (not uncommon to other institutions), but encourages creative approaches to addressing them: • The number of staff positions is limited, certainly for non-clinical scientists. As a result, the institute has limited funds to recruit and retain world leaders. Most of NCA’s talents are funded with personal grants (e.g., ERC) or excellence programmes. • It is difficult to retain talented postdocs. NCA tries to keep the most talented postdocs on soft money, but this is often not sufficient to keep them long enough to enable them to grow into mature postdocs. A career progression strategy is needed for early-career scientists as they progress to full independence. • It is difficult for clinical researchers to stay active in research. Although the translational focus of the programmes encourages early research exposure, the demands of combined clinical training and care are high. Many of them perform a medical residency after or while finishing their PhD or, subsequently, need to take on substantial clinical care responsibilities, leaving them very little time for research. This makes it hard to stay at the forefront of science and limits incentives for a clinical academic career. Recruiting and retaining strong clinical researchers to expand the research with the extremely valuable clinical cohorts is essential. • Non-clinical staff members often have to spend a substantial part of their time on teaching. In some cases, this could risk compromising the ability to compete with international research groups, although some staff members have indicated that teaching is also a great method to recruit talented students. The balance needs to be monitored closely on an individual level. • Finally, while being impressed by the research quality, the committee also was surprised by the ‘Dutch dominance’ in NCA’s staff, i.e., almost all principal investigators have Dutch nationality. This was discussed with NCA’s management team. While there are clear drivers for this, e.g., language barriers particularly for medical doctors who need to speak Dutch, the committee encourages NCA to consider ways of more actively recruiting international scientists. Diversity of backgrounds and outlook will significantly contribute to future strength. 5) Structural funding for infrastructure The committee recommends that NCA explores ways of funding its infrastructure and support staff across programmes to enable long term support for some common advanced infrastructure and staff. The committee learned that it is difficult for NCA to obtain structural funding to maintain its infrastructure (e.g., for maintaining the cohorts, renewal of equipment, and computational facilities). In addition, it is difficult to obtain funding for personnel to support data acquisition, data analysis, and data management. More generally, it appeared sometimes difficult for the institute to retain the so-called ‘solid middle group’ of key advanced research support staff. 6) Industry Alliance Office (IAO) The committee encourages the IAO to explore possibilities to broaden its own potential. The IAO is unique and it is doing an outstanding job in attracting research funding. In 2013-2014, NCA has

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acquired a contract portfolio of more than EUR 10 M through the IAO (see Appendix 3, Table III2). The committee strongly praised this initiative, which constitutes a creative solution to the steadily declining amount of direct research funding. However, the committee had the impression that the IAO is self-limiting, in the sense that there ultimately is a limited potential demand from the traditional industry sources being pursued, e.g., the number of phase II trials is limited. The committee encourages the IAO to explore additional possibilities, for instance through exploiting intellectual property rights generated by the patient cohorts or expanding the scope of industry outreach, e.g., for healthcare technology companies. The committee has also discussed issues of data ownership and intellectual property rights with the IAO. The committee thinks it is important to ensure that the value generated from data and intellectual property rights contributes to support of NCA. 7) Outreach activities The committee encourages NCA to make a strong, coordinated effort to sell the ‘brand’ of excellence at NCA and to involve the public in its activities and support. Although the cohorts associated with NCA are continuously reaching out to the general public, the NCA institute per se seems to perform relatively fewer outreach activities. This might involve recruiting a press officer. Such an effort will help NCA to reach succeeding generations of talented researchers. In addition, involving the whole city of Amsterdam in NCA’s mission can help fund raising, recruiting study participants, and getting citizens involved in other ways. 8) Therapeutic development The committee encourages NCA to further promote the translation of its innovative findings in clinical practice. Although the committee praised NCA’s outstanding integration of basic science and clinical research, it noticed a relative lack of focus on the development of treatments (i.e., there is more focus on prevention and early detection). Possible initiatives could include: • a drug discovery programme in specific areas; • development of a broader range of clinical trial units; • promoting investigator-initiated trials; • developing new treatments based on experiences in related disease areas. 4.2 PhD programme 1) The committee recommends taking advantage of the unique situation in the Netherlands to market the PhD programme more internationally. This can be used as part of an explicit strategy for growth and renewal. The assessment committee learned that PhD students are employees instead of students in the Netherlands. This should make Dutch PhD programmes highly internationally competitive. NCA has a number of what appear to be particularly good employment benefits for PhD students, such as resources for conferences, courses, thesis printing, and an outstanding training environment. English is spoken throughout the research environment, which should attract non-English speakers who want to gain language proficiency in the course of their research training. In this sense, the PhD programme seems to be a hidden gem. 2) The committee recommends that the university management explores ways of continuing or enhancing the direct funding for PhD supervision. The NCA management team has expressed concerns about the ongoing reduction of direct funding for supervising PhD students. The PhD programme is not completely financially supported by the faculties at the moment. However, as

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noted above, the committee believes that this training programme should be viewed as a fundamentally important part of the plan for sustainability and growth of NCA. 3) The committee learned that in the first month of a PhD project, an ONWAR introduction course includes a visit to various ONWAR-associated research labs, so that students get acquainted with the landscape of neuroscience in Amsterdam and Rotterdam. The committee thinks it would be useful for students to actually work in multiple laboratories, so it might be good to consider lab rotations. 4.3 Research integrity No recommendations were deemed necessary.

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Appendix 1. Short CVs of the members of the assessment committee

Professor Paul Matthews (chairman) Paul Matthews is head of the Division of Brain Sciences in the Department of Medicine of Imperial College, London. His research is noted for innovative translational applications of clinical imaging for the neurosciences. He was the founding Director of two internationally leading research imaging centres, the University of Oxford Centre for Functional Magnetic Resonance Imaging of the Brain and GlaxoSmithKline’s Clinical Imaging Centre. From 2005 - 2014 he was a Vice President of GlaxoSmithKline Medicines Discovery and Development. Amongst many external commitments, Professor Matthews has served two terms on the MRC Neuroscience and Mental Health Board and remains active on several committees. He was a member of the UK HEFCE REF Neuroscience Subcommittee for assessment of Neurosciences, Psychology and related areas; and is a member of the Steering Committees for UK Biobank and for the UK Dementias Platform. Professor Matthews was awarded an OBE in 2008 for services to neuroscience. He was elected to the Academy of Medical Sciences in 2014. Professor Jonathan Flint Jonathan Flint is Professor of Molecular Psychiatry, Wellcome Trust Principal Fellow, Group Head / PI, and Consultant Physician at the Wellcome Trust Centre for Human Genetics, University of Oxford. His laboratory is investigating the genetic basis of psychiatric disorders, in particular the origins of stress related conditions, such as anxiety and depression. Knowing more about the biological basis of these very common disorders could help develop better therapies, and use more efficiently those we already have. His group has studied neuroticism, a personality trait that is a major genetic mediator of depression, in over 900 human families using a personality questionnaire. In addition, they use mice behaviour to help investigate human anxiety and depression. Professor Flint has published numerous publications, and has garnered a significant amount of grant support for his pioneering work. He is moving to a post at UCLA to run a large study of the genetic basis of depression. Professor Jean Marc Fritschy Jean Marc Fritschy is Professor for Neuropharmacology at the Institute of Pharmacology and Toxicology, University of Zurich and Director of the Neuroscience Center Zurich. Since August 2015, he is Deputy Dean of the Faculty of Medicine of the University of Zurich. A major topic of his research is the functional organization and plasticity of the GABAergic system, using a multidisciplinary approach ranging from molecular and cell biology to immunoelectron microscopy. His research group works with primary neuronal cultures and transgenic mice. Animal models are essential tools for investigating cellular and molecular alterations contributing to neurological and psychiatric disorders. To this end, they are working with mouse models of temporal lobe epilepsy and neurodegenerative diseases (Alzheimer’s and Parkinson), with a specific focus on neuro-immune interactions and the contribution of inflammation to pathophysiology of these brain diseases. He has been co-chief editor of the European Journal of Neuroscience, the official journal of the Federation of European Neuroscience Societies, in the period 2008-2014. Professor Andreas Meyer-Lindenberg Andreas Meyer-Lindenberg is Director of the Central Institute of Mental Health, as well as the Medical Director of the Department of Psychiatry and Psychotherapy at the Institute, based in

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Mannheim, Germany. He is also Professor and Chairman of Psychiatry and Psychotherapy at the University of Heidelberg in Heidelberg, Germany. In addition, he is board certified in psychiatry, psychotherapy, and neurology. His research interests focus on the development of novel treatments for severe psychiatric disorders through an application of multimodal neuroimaging, genetics and enviromics to characterize brain circuits underlying the risk for mental illness and cognitive dysfunction. Professor Trevor Smart Trevor Smart is the Schild Professor of Pharmacology at University College London and Head of the Department of Neuroscience, Physiology & Pharmacology. He chairs the UCL Neuroscience Research Domain that encompasses ~500 PIs in basic and clinical neuroscience. In 2000, he became an FRPharmS and in 2006 he was made a Fellow of the Academy of Medical Sciences. He is internationally recognised for his contributions to our understanding of the GABAA receptor. His research is focussed on the cellular and molecular physiology and pharmacology of GABAA, glycine and NMDA receptors, which are major inhibitory and excitatory neurotransmitter receptors in the brain, pivotally involved in controlling nerve cell excitability. These receptors feature prominently in neurological diseases, with the GABA receptor being a target for several therapeutic classes of drugs. In addition to his outstanding research record, he has been an editor of Journal of Physiology and Neuropharmacology and Senior Editor of Brit. J. Pharmacology. He has served on the MRC Neurosciences and Mental Health Board and currently sits on the Royal Society Newton Fellowships Panel. He has been previously awarded the Sandoz prize in Pharmacology, the Lilly Award for Pharmaceutical Sciences, the RSPGB Conference Science Medal and in 2012 delivered the biennial Gaddum Memorial Award Lecture. Professor Reisa Sperling Reisa Sperling is the Director of the Center for Alzheimer Research and Treatment at Brigham and Women’s Hospital and the Co-Director of the Neuroimaging Core and the Outreach Core of the Massachusetts Alzheimer's Disease Research Center at Massachusetts General Hospital. In addition, she is a Professor of Neurology at Harvard Medical School. Her research is focused on the early diagnosis and treatment of Alzheimer’s disease. Dr Sperling has overseen a number of clinical trials of potential disease-modifying therapeutics in early Alzheimer’s disease, and currently leads the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s disease (A4) Study, the first of its kind prevention trial in clinically normal older individuals with evidence of amyloid accumulation. She is the Principal Investigator of the Harvard Aging Brain Study, and has published over 120 peer-reviewed research articles on memory, aging, and early AD. Dr Sperling is a co-recipient of the 2015 American Academy of Neurology Potamkin Award. Dr Linda van den Berg Linda van den Berg assisted the committee as an external independent secretary. She is a selfemployed science writer and communications consultant with a background in biomedical sciences. Her company Washoe Life Science Communications offers a variety of communication services to academic institutes and commercial companies.

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Appendix 2. NCA site visit programme 16&17 November 2015

Time

Day 1: 16 November 2015

Activity

08:30-09:00

Breakfast meeting

Meet & Greet with assessment committee

Guests: Management Team members: Arjen Brussaard, Philip Scheltens, Brenda Penninx, Dorret Boomsma, August Smit, Johannes de Boer

Science writer (Linda van den Berg) attending

Opening session with Scientific Director & Management Team

Introduction Meeting

Guests: Management Team members: Arjen Brussaard, Philip Scheltens, Brenda Penninx, Dorret Boomsma, August Smit, Johannes de Boer

Science writer attending

9:00

1: Arjen Brussaard

15 minute kick-off

9:15

2: Management Team

Discussion: Q&As

10:00-12:00

Meeting with the Research Programme Leaders

Presentation & Discussion

Guests: Hugo Vrenken, Johannes de Boer, Huibert Mansvelder, Marjo van der Knaap, Matthijs Verhage, Wiesje van der Flier, August Smit, Joep Killestein, Elga de Vries, Brenda Penninx, Sabine Spijker

Science writer attending

1: Hugo Vrenken, Huibert Mansvelder, Johannes de Boer

10 minute presentation

09:00-10:00

10:00 10:15

2: Matthijs Verhage, Marjo van der Knaap

10 minute presentation

10:30

3: Wiesje van der Flier, August Smit

10 minute presentation

10:45

4: Elga de Vries, Joep Killestein

10 minute presentation

11:00

5: Sabine Spijker, Brenda Penninx

10 minute presentation

11:15

6: All

Discussion

12:00-13:00

Lunch Break / First Impressions

Closed Meeting

Only members of External Evaluation Committee

Science writer attending

Interview Sessions with individual Mid-Career Investigators and selected Group Leaders

Presentations & Discussion

13:00-14:45

Science writer attending