Dutch Research Research Articles

Empirical legal studies in the law school curriculum in the Netherlands: what is the state of the art and where do we go from here?

ABSTRACT This paper describes and discusses the portfolio of courses in which empirical legal research skills are currently taught to law students in the Netherlands. It results from an in-depth country-wide study we undertook as part of a project supported by the Dutch Research Council (NWO) in view of the growing attention to empirical legal studies (ELS). The paper concludes with a reflection on the future of ELS education in the Netherlands.

Implementation of Big Imaging Data Pipeline Adhering to FAIR Principles for Federated Machine Learning in Oncology

Cancer is a fatal disease and one of the leading causes of death worldwide. The cure rate in cancer treatment remains low; hence cancer treatment is gradually shifting towards personalized treatment. AI and radiomics have been recognized as one of the potential areas of research in personalized medicine in oncology. Several researchers have identified the capabilities of AI and radiomics to characterize phenotype and there by predict the outcome of treatment in oncology. Although AI and radiomics have shown promising initial results in diagnosis and treatment in oncology, these technologies are also facing challenges of standardization and scalability. In the last few years, researchers have been trying to develop research infrastructure for federated machine learning that increases usability of Big Data for clinical research. These research infrastructures are based on the Findable, Accessible, Interoperable and Reusable (i.e., FAIR) data principles. The India-Dutch “Big Imaging data approach for Oncology in a Netherlands India Collaboration” (BIONIC) is a jointly funded initiative by the Dutch Research Council (NWO) and the Indian Ministry of Electronics and Information Technology (MeitY), aiming to introduce radiomic-based research into clinical environments using federated machine learning on geographically dispersed collections of FAIR data. This paper described a prototype end-to-end research infrastructure implemented through the BIONIC partnership into a leading cancer care public hospital in India.

Confl icting Threads. Technological Innovation and the Socio-technical Ensemble of Weaving

This paper refers to two new approaches to conceive the relationship between technological innovation and society as one of anchoring: The TASC concept (Technologies as Anchors for Societal Conflicts) aims to show how societal conflicts are anchored in technologies that, as such, are not responsible for the conflict. The ‘Anchoring Innovation’ research program of the Dutch Research School in Classical Studies (OIKOS) aims to explain how technological in- novations were anchored in ancient society. Our paper trials these concepts along the threads that connect the social and the technical in the weaving of contemporary India and archaic Greece. The first part of the paper examines the Indian government’s efforts to provide technological upgradation to a community of weavers who insist on their loin loom that is embedded in their local ecology, making them appear backward and ignorant of innovation. In the second part, we examine how innovation in ancient Greece was anchored in the socially ubiquitous technology of weaving. In both cases, the social turns out to be an essential part of (the technology of) weaving. Conflicts arise where technology claims to be ahead of a society that must constantly adapt to it.

1H-NMR metabolomics-based surrogates to impute common clinical risk factors and endpoints.

SummaryBackgroundMissing or incomplete phenotypic information can severely deteriorate the statistical power in epidemiological studies. High-throughput quantification of small-molecules in bio-samples, i.e. ‘metabolomics’, is steadily gaining popularity, as it is highly informative for various phenotypical characteristics. Here we aim to leverage metabolomics to impute missing data in clinical variables routinely assessed in large epidemiological and clinical studies.MethodsTo this end, we have employed ∼26,000 1H-NMR metabolomics samples from 28 Dutch cohorts collected within the BBMRI-NL consortium, to create 19 metabolomics-based predictors for clinical variables, including diabetes status (AUC5-Fold CV = 0·94) and lipid medication usage (AUC5-Fold CV = 0·90).FindingsSubsequent application in independent cohorts confirmed that our metabolomics-based predictors can indeed be used to impute a wide array of missing clinical variables from a single metabolomics data resource. In addition, application highlighted the potential use of our predictors to explore the effects of totally unobserved confounders in omics association studies. Finally, we show that our predictors can be used to explore risk factor profiles contributing to mortality in older participants.InterpretationTo conclude, we provide 1H-NMR metabolomics-based models to impute clinical variables routinely assessed in epidemiological studies and illustrate their merit in scenarios when phenotypic variables are partially incomplete or totally unobserved.FundingBBMRI-NL, X-omics, VOILA, Medical Delta and the Dutch Research Council (NWO-VENI).

Dutch research into the country house and its landscape

One of the unmistakable trends in current country house research is the growing interest in the landscape context of country houses. The unquestioned emphasis on the main house and the garden is increasingly giving way to an approach that includes or focuses on the wider setting: village, nature, town, infrastructure, farms, churches, and other country houses. This article sketches the rise of this approach and offers an overview of the various perspectives. Among the aspects covered by landscape studies are country house regions, choice of location, the productive landscape, infrastructure, the political landscape and the mental landscape. Although this growing interest in the landscape setting is one of the most important recent developments in country house research, most of these studies are predominantly descriptive. This article calls for the establishment of a firmer methodological and theoretical underpinning – a task to which it is to be hoped that future researchers will devote themselves.

Filling a Theater During the COVID-19 Pandemic

In the summer of 2020, Music Building Eindhoven (MBE) had to deal with the economic consequences of the COVID-19 pandemic for theater halls because governmental regulations were having a severe impact on the occupancy. In particular, MBE faced the challenge of determining how to maximize the number of guests in a theater hall while respecting social distancing rules. We have developed and implemented an optimization model based on trapezoid packings to address this challenge. The model showed that up to 40% of the normal capacity can be realized for a single show setting and up to 70% in cases where artists opt for two consecutive performances per evening without reusing seats. The solution was adopted by MBE with significant monetary and managerial benefits. History: This paper was refereed. This article has been selected for inclusion in the Special Issue on Analytics Remedies to COVID-19. Funding: The research of F. Spieksma is supported by Dutch Research Council (NWO) Gravitation Project NETWORKS [Grant 024.002.003].

Safety and Efficiency of Diagnostic Strategies for Ruling Out Pulmonary Embolism in Clinically Relevant Patient Subgroups : A Systematic Review and Individual-Patient Data Meta-analysis.

How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown. To evaluate the safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds, as well as the YEARS algorithm, for ruling out acute PE in these subgroups. MEDLINE from 1 January 1995 until 1 January 2021. 16 studies assessing at least 1 diagnostic strategy. Individual-patient data from 20553 patients. Safety was defined as the diagnostic failure rate (the predicted 3-month VTE incidence after exclusion of PE without imaging at baseline). Efficiency was defined as the proportion of individuals classified by the strategy as "PE considered excluded" without imaging tests. Across all strategies, efficiency was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80 years or older (6.0% to 23%) or patients with cancer (9.6% to 26%). However, efficiency improved considerably in these subgroups when pretest probability-dependent D-dimer thresholds were applied. Predicted failure rates were highest for strategies with adapted D-dimer thresholds, with failure rates varying between 2% and 4% in the predefined patient subgroups. Between-study differences in scoring predictor items and D-dimer assays, as well as the presence of differential verification bias, in particular for classifying fatal events and subsegmental PE cases, all of which may have led to an overestimation of the predicted failure rates of adapted D-dimer thresholds. Overall, all strategies showed acceptable safety, with pretest probability-dependent D-dimer thresholds having not only the highest efficiency but also the highest predicted failure rate. From an efficiency perspective, this individual-patient data meta-analysis supports application of adapted D-dimer thresholds. Dutch Research Council. (PROSPERO: CRD42018089366).

Digital Dutch Archaeology: Future perspectives

Digital archaeology in the Netherlands is connected with investments in a new large-scale and innovative Dutch research infrastructure for the next 10 years. Priorities are set to combine forces at a national level in order to contribute to the international position of the Netherlands as a 'knowledge country'. Researchers need to coordinate and collaborate even more to set up a FAIR enabling data infrastructure with limited resources. Regarding the archaeological discipline, the use of formal quality standards and legislation that certifies archaeological organisations to carry out archaeological work improves national collaboration and stimulates the digital workflow. DANS is the dedicated national repository for archaeology in the Netherlands and is launching the Data Station Archaeology, a repository meeting the latest technological standards. Finding and sharing data of high quality facilitates knowledge of archaeological discoveries; a flourishing open access trend in Dutch archaeology stimulates a strong growth in the use of data. To keep up with innovative developments, a growing community of archaeologists and other specialists are working together in international projects to secure the future of European Archaeology.

International law from the outside: Insights from the Dutch Research Council (NWO)

International law from the outside: Insights from the Dutch Research Council (NWO)

Making care fit manifesto

Funding: This work was supported by the Royal Netherlands Academy of Arts and Sciences (KNAW) & Dutch Research Council (NWO) The Netherlands Organisation for Health Research and Development (ZonMw) (016.196.138).

Making Room for Everyone’s Talent

See RECORDING. Current societal challenges demand more cooperation and a multidisciplinary approach from scientists. Putting into practice the shared ambition in Dutch academia requires a modernisation of the system of Recognition & Rewards. The modernisation should improve the quality of each of the key areas in academia: education, research, impact, leadership and (for university medical centres) patient care. Why do we think a change in recognition and rewards is needed? We see a mismatch between what we deem important in academic work and what we reward academic staff for. Careers depend heavily on research performance, which is measured by a limited number of criteria. We need a better balance in how we recognize and reward academics to help us achieve excellent education, research, impact, and leadership, as well as the highest level of patient care in our university medical centres. We want to make Room for everyone’s talent! In the Dutch Recognition & Rewards programme we work in cooperation with all Dutch research universities, university medical centres, reputable research institutes, the Royal Academy, and research funders. We aim for a healthy and inspiring environment for all our staff, where all talents are valued. In this presentation I will explain what we want to change in academic career assessment in the Netherlands, and how we hope to initiate the desired cultural change. This change is a fundamental change of beliefs, not just a change in the rules of the game. To achieve this, a broad dialogue in academia is needed. We think that sharing best practices and experimenting will initiate the desired movement. Every university and research organisation in the Netherlands has set up a high-level Recognition & Rewards committee. The various committees are working enthusiastically to stimulate the intended culture change at an institutional level. There is a great and inspiring diversity of approaches. Experimenting, inspiring, co-creating, sharing best practices, and learning from each other are central in the joint programme. At a national level, we also monitor the commonality and ensure connections between the developments at the universities, university medical centres, research institutes, and research funders. We are aware that the Netherlands is only a very small country. We cannot change academic career assessment on our own. We need to work together all over the world to change the recognition and rewards of academics. We hope you are curious, critical, and open about your concerns and become involved!

“An Official Conscience and Warranting Agency”: Institutional Isomorphism and the Rise of Dutch Ethics Review in the 1970s and 1980s

Abstract Why did medical research involving human subjects, a practice that is arguably as old as medicine itself, come to be regulated by research ethics committees in the late twentieth century? In this essay, I answer this question for the Netherlands, by querying the rise of ethics review in the 1970s and 1980s through the lens of “institutional isomorphism”. Drawing on the classic work of Paul Dimaggio and Walter Powell, I argue that extra-national changes to funding and publishing requirements in this period were identifiably more important for the emergence of ethics review in the Netherlands than were ethical concerns for research misconduct – a process that was marked by definitive elements of internationally coercive, and perhaps also of mimetic isomorphism. In addition, I detail how, as a consequence of these developments, those involved in Dutch ethics review came to consider “variation and inconsistency” as one of the system’s biggest problems in the late 1980s. To remedy this, numerous normative isomorphic attempts were undertaken in the late twentieth century to make all Dutch research ethics committees act in the same way. This emphasis on institutional homogeneity has been borne out in the Netherlands, even though it has repeatedly been criticized for hampering democratic and ethical decision-making.

Conspiracy beliefs prospectively predict health behavior and well-being during a pandemic.

Conspiracy beliefs are associated with detrimental health attitudes during the coronavirus disease 2019 (Covid-19) pandemic. Most prior research on these issues was cross-sectional, however, and restricted to attitudes or behavioral intentions. The current research was designed to examine to what extent conspiracy beliefs predict health behavior and well-being over a longer period of time. In this preregistered multi-wave study on a large Dutch research panel (weighted to provide nationally representative population estimates), we examined if conspiracy beliefs early in the pandemic (April 2020) would predict a range of concrete health and well-being outcomes eight months later (December 2020; N = 5745). The results revealed that Covid-19 conspiracy beliefs prospectively predicted a decreased likelihood of getting tested for corona; if tested, an increased likelihood of the test coming out positive; and, an increased likelihood of having violated corona regulations, deteriorated economic outcomes (job loss; reduced income), experiences of social rejection, and decreased overall well-being. Most of these effects generalized to a broader susceptibility to conspiracy theories (i.e. conspiracy mentality). These findings suggest that conspiracy beliefs are associated with a myriad of negative life outcomes in the long run. Conspiracy beliefs predict how well people have coped with the pandemic over a period of eight months, as reflected in their health behavior, and their economic and social well-being.

Interferon gamma immunotherapy in five critically ill COVID-19 patients with impaired cellular immunity: A case series

BackgroundProlonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding has been described in immunocompromised coronavirus disease 2019 (COVID-19) patients, resulting in protracted disease and poor outcome. Specific therapy to improve viral clearance and outcome for this group of patients is currently unavailable.MethodsFive critically ill COVID-19 patients with severe defects in cellular immune responses, high SARS-CoV-2 viral RNA loads, and no respiratory improvement were treated with interferon gamma, 100 μg subcutaneously, thrice weekly. Bronchial secretion was collected every 48 h for routine diagnostic SARS-CoV-2 RT-PCR and viral culture.FindingsInterferon gamma administration was followed by a rapid decline in SARS-CoV-2 load and a positive-to-negative viral culture conversion. Four patients recovered, and no signs of hyperinflammation were observed.ConclusionsInterferon gamma may be considered as adjuvant immunotherapy in a subset of immunocompromised COVID-19 patients.FundingA.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781). G.J.O. and R.P.v.R. are supported by a VICI grant (016.VICI.170.090) from the Dutch Research Council (NWO). W.F.A. is supported by a clinical fellowship grant (9071561) of Netherlands Organization for Health Research and Development. M.G.N. is supported by an ERC advanced grant (833247) and a Spinoza grant of the Netherlands Organization for Scientific Research.

Untargeted metabolomics and infrared ion spectroscopy identify biomarkers for pyridoxine-dependent epilepsy.

BackgroundPyridoxine-dependent epilepsy (PDE-ALDH7A1) is an inborn error of lysine catabolism that presents with refractory epilepsy in newborns. Biallelic ALDH7A1 variants lead to deficiency of α-aminoadipic semialdehyde dehydrogenase/antiquitin, resulting in accumulation of piperideine-6-carboxylate (P6C), and secondary deficiency of the important cofactor pyridoxal-5'-phosphate (PLP, active vitamin B6) through its complexation with P6C. Vitamin B6 supplementation resolves epilepsy in patients, but intellectual disability may still develop. Early diagnosis and treatment, preferably based on newborn screening, could optimize long-term clinical outcome. However, no suitable PDE-ALDH7A1 newborn screening biomarkers are currently available.MethodsWe combined the innovative analytical methods untargeted metabolomics and infrared ion spectroscopy to discover and identify biomarkers in plasma that would allow for PDE-ALDH7A1 diagnosis in newborn screening.ResultsWe identified 2S,6S-/2S,6R-oxopropylpiperidine-2-carboxylic acid (2-OPP) as a PDE-ALDH7A1 biomarker, and confirmed 6-oxopiperidine-2-carboxylic acid (6-oxoPIP) as a biomarker. The suitability of 2-OPP as a potential PDE-ALDH7A1 newborn screening biomarker in dried bloodspots was shown. Additionally, we found that 2-OPP accumulates in brain tissue of patients and Aldh7a1-knockout mice, and induced epilepsy-like behavior in a zebrafish model system.ConclusionThis study has opened the way to newborn screening for PDE-ALDH7A1. We speculate that 2-OPP may contribute to ongoing neurotoxicity, also in treated PDE-ALDH7A1 patients. As 2-OPP formation appears to increase upon ketosis, we emphasize the importance of avoiding catabolism in PDE-ALDH7A1 patients.FundingSociety for Inborn Errors of Metabolism for Netherlands and Belgium (ESN), United for Metabolic Diseases (UMD), Stofwisselkracht, Radboud University, Canadian Institutes of Health Research, Dutch Research Council (NWO), and the European Research Council (ERC).

Perioperative pharmacokinetic-guided factor VIII concentrate dosing in haemophilia (OPTI-CLOT trial): an open-label, multicentre, randomised, controlled trial

Dosing of replacement therapy with factor VIII concentrate in patients with haemophilia A in the perioperative setting is challenging. Underdosing and overdosing of factor VIII concentrate should be avoided to minimise risk of perioperative bleeding and treatment costs. We hypothesised that dosing of factor VIII concentrate on the basis of a patient's pharmacokinetic profile instead of bodyweight, which is standard treatment, would reduce factor VIII consumption and improve the accuracy of attained factor VIII levels. In this open-label, multicentre, randomised, controlled trial (OPTI-CLOT), patients were recruited from nine centres in Rotterdam, Groningen, Utrecht, Nijmegen, The Hague, Leiden, Amsterdam, Eindhoven, and Maastricht in The Netherlands. Eligible patients were aged 12 years or older with severe or moderate haemophilia A (severe haemophilia was defined as factor VIII concentrations of <0·01 IU/mL, and moderate haemophilia as 0·01-0·05 IU/mL), without factor VIII inhibitors, and planned for elective low or medium risk surgery as defined by surgical risk score. Patients were randomly assigned (1:1) using a web-based randomisation system and treatment minimisation, stratified by method of administration of factor VIII concentrate (continuous infusion vs bolus administration) and risk level of surgery (low and medium risk surgery), to the pharmacokinetic-guided or standard treatment group. The primary endpoint was total amount of infused factor VIII concentrate (IU per kg bodyweight) during perioperative period (from day of surgery up to 14 days after surgery). Analysis was by intention to treat and the safety analysis population comprised all participants who underwent surgery with factor VIII concentrate. This study is registered with the Netherlands Trial Registry, NL3955, and is now closed to accrual. Between May 1, 2014, and March 1, 2020, 98 patients were assessed for eligibility and 66 were enrolled in the trial and randomly assigned to the pharmacokinetic-guided treatment group (34 [52%]) or the standard treatment group (32 [48%]). Median age was 49·1 years (IQR 35·0 to 62·1) and all participants were male. No difference was seen in consumption of factor VIII concentrate during the perioperative period between groups (mean consumption of 365 IU/kg [SD 202] in pharmacokinetic-guided treatment group vs 379 IU/kg [202] in standard treatment group; adjusted difference -6 IU/kg [95% CI -88 to 100]). Postoperative bleeding occurred in six (18%) of 34 patients in the pharmacokinetic-guided treatment group and three (9%) of 32 in the standard treatment group. One grade 4 postoperative bleeding event occurred, which was in one (3%) patient in the standard treatment group. No treatment-related deaths occurred. Although perioperative pharmacokinetic-guided dosing is safe, it leads to similar perioperative factor VIII consumption when compared with standard treatment. However, pharmacokinetic-guided dosing showed an improvement in obtaining factor VIII concentrations within the desired perioperative factor VIII range. These findings provide support to further investigation of pharmacokinetic-guided dosing in perioperative haemophilia care. Dutch Research Council (NWO)-ZonMw and Takeda.

Implementation of a diagnostic decision aid for people with memory complaints and their general practitioners: a protocol of a before and after pilot trial

IntroductionResearchers, policy-makers and healthcare professionals often stress the importance of an early dementia diagnosis. Empirical evidence, however, is scarce leading to a lack of consensus on the necessity of diagnosing...

When do academics patent outside their university? An in-depth case study

A central theme of university entrepreneurship—including the generation and commercialization of university-invented research—is academic patenting (referring to patenting by university scientists). This study explores organizational-, individual- and patent-level factors and their respective relationship with academic patenting. Based on a thorough investigation of all academic patents (that have at least one university scientist involved) from one of the largest Dutch research universities during the period 2000–2009, and further building on first-hand qualitative and quantitative data, the results show that Technology Transfer Offices (TTOs) are instrumental in generating more academic patents. However, this effect is predominantly manifested by the increase in the number of patents patented under the name (solely or jointly) of the university (university-owned patents), far more than the increase in the absolute volume of patents invented by the university (university-invented patents). Further, regarding individual academic inventors, our study shows that, in general, male researchers and lead-inventors with higher academic rankings are less likely to abide by the TTOs, resulting in more patents being filed outside the university. Regarding the academic invention, the value of the patent itself does not seem to be related to the choice of the ownership (e.g., university-owned or not) of the patent.

Bridging the gap from hospital discharge to cardiac rehabilitation using the intervention mapping approach (BRIDGE2CARE)

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Dutch Research Council INTRODUCTION Cardiac rehabilitation (CR) is the cornerstone of secondary prevention. After hospital discharge, patients have to wait for participation in CR while often feeling overwhelmed by their cardiac event and in need of tailored information and support. PURPOSE The objective of this study was to develop a remote (digital) intervention to bridge the gap from hospital discharge to CR. METHODS We developed an intervention by completing the first three steps of the intervention mapping protocol. Step 1: identification of information- and support needs from the literature and semi-structured interviews. Step 2: Describing performance objectives for the intervention and selecting determinants. Step 3: Generation of program themes and theory based change methods. RESULTS (Step 1) The following Information- and support needs were identified from the literature (n = 33) and semi structured interviews (n = 22): information about pathology and intervention, medication and side effects, daily physical activities, psychological distress, body signals and social support. Advanced communication and pedagogical skills of the health care provider and the ability to build trust were described as important prerequisites for the intervention. (Step 2) The following performance objectives were formulated: (1) Patients gain knowledge on how their cardiac illness and procedure affects their bodies and health, (2) Patients gain knowledge about medication and side effects, (3) Patients know which daily physical activities they can and can’t do after hospital discharge and are physically active, (4) Patients and informal caregivers can deal with psychological distress and know how to discriminate between harmful and harmless body signals. Objectives were described per determinant (knowledge, skill, attitude, social influence, self-efficacy and outcome expectation). (Step 3) A comprehensive remote intervention was developed using theory based coaching strategies, a digital patient platform and information videoclips. CONCLUSION This study describes the information and support needs of patients after cardiac hospitalization and offers a remote intervention that bridges the gap form hospital discharge to CR. Abstract Figure. BRIDGE2CARE

Interview with Geert Booij

Geert Booij (1947) is professor emeritus of linguistics at the University of Leiden where he worked from 2005-2012. From 1981-2005 he was professor of General Linguistics at the Vrije Universiteit Amsterdam, and from 1971-1981 assistant / associate professor at the University of Amsterdam, where he also obtained his Ph.D. degree in linguistics in 1977. He studied Dutch and general linguistics at the University of Groningen (1965-1971) where he obtained his MA degree (cum laude). He was dean of the Faculty of Letters at the Vrije Universiteit (1988-1991, 1998-2002), conrector of the Vrije Universiteit (1999-2002), dean of the Faculty of Letters of the University of Leiden (September 2005- October 2007), and member (1997-2002) and chair (2002-2004) of the Dutch Research Council for the Humanities of NWO (the Dutch organization for scientific research). He served on a number of national and international committees for the assessment of linguistic research achievements, and on audit committees for the quality of language programs at various universities in the Netherlands. Geert Booij also taught at the University of Canterbury in Christchurch, New Zealand (Erskine Fellow) in 2002, the Linguistic Society of America Institute at the University of Berkeley in 2009, at Harvard University (Erasmus professor of Dutch language and culture) in 2010, and at the Freie Universitat Berlin (Germanic Department, section Dutch) in 2011. In 2011 he received the Alexander von Humboldt Research Award for his overall achievements in linguistic research. He is an honorary member of the Linguistic Society of America . Geert Booij is one of the two founders and editors of the book series Yearbook of Morphology (1988-2005), which is, as of 2006, continued as the journal Morphology , of which he was one of the three editors until 2014. He is the author of a number of Dutch textbooks on grammar, morphology, and phonology, and of four English monographs: The Phonology of Dutch (1995), The Morphology of Dutch (2002, 2019 2 ), The Grammar of Words (2005, 2012), and Construction Morphology (2010), all published by Oxford University Press. He has published linguistic articles in a wide range of Dutch and international journals and volumes (see https://geert.booij.com for a list of, mostly downloadable, publications).