For many students, algebraic formulas are abracadabra: they lack symbol sense. Symbol sense includes identifying the structure of algebraic formulas, giving meaning to them, and reasoning with and... Show moreFor many students, algebraic formulas are abracadabra: they lack symbol sense. Symbol sense includes identifying the structure of algebraic formulas, giving meaning to them, and reasoning with and about formulas. Besides basic skills, symbol sense is needed to solve algebraic problems and it is not known how to teach symbol sense systematically.In this research we have studied how teaching graphing formulas by hand (i.e. sketching a graph of a formula) could promote grade 11- and 12-students’ symbol sense. Our GQR-design (Graphing formulas through recognition and qualitative reasoning) is based on expert research and pays explicit attention to recognition of basic function families and features, and to qualitative reasoning, that focuses on the global shape of a graph, with global descriptions and ignoring what is not relevant. These aspects get little attention in regular education, that often focuses on algebraic manipulation.We found that students improved their insight into formulas and found a positive correlation between students’ abilities to graph formulas and their abilities to solve non-routine algebra problems with symbol sense. The students were able to use essential aspects of symbol sense, learned in the context of graphing formulas, such as taking a global view for recognition, qualitative reasoning, and questioning a formula, when solving algebra problems.In the future, when technology will take over the manipulation of algebraic formulas, symbol sense will become even more important. Graphing formulas could promote students’ symbol sense in upper secondary school, and therefore deserves a prominent place in mathematics curriculum. Show less
The term “cardiometabolic disease” describes a cluster of sub-clinical disorders that are shared by cardiovascular diseases and type 2 diabetes, including dyslipidaemia, and glucose intolerance. In... Show moreThe term “cardiometabolic disease” describes a cluster of sub-clinical disorders that are shared by cardiovascular diseases and type 2 diabetes, including dyslipidaemia, and glucose intolerance. In clinical settings, fasting measurement is still the gold standard for the diagnosis of hyperglycemia and dyslipidaemia. However, due to irregular meal intake, we spend the majority of our waking hours in a non-fasting state. The non-fasting state is a dynamic condition that is affected by many factors, including diet, lifestyle, physiological factors, pathological conditions, and genetics. Thus far, the genes and genetic loci that affect postprandial glucose and lipid metabolism have not been fully understood. By using the data from the Netherlands Epidemiology of Obesity study, we found 1) postprandial measures after a liquid mixed meal were as robust as fasting measures by repeated measures; 2) to stratify pre-diabetic individuals into high- and low-risk of developing to type 2 diabetes, the model performance by using postprandial metabolites was similar to the model performance using fasting metabolites; 3) the genetics of fasting and postprandial metabolite levels are highly overlapped. All the findings suggest that postprandial measures after a liquid meal are as reliable and clinically relevant as fasting measures for cardiometabolic disease research and diagnosis. Show less
This dissertation presents methodological advances in the field of frailty models. Time to event data is very common in biomedical applications. Multivariate data, such as recurrent event... Show moreThis dissertation presents methodological advances in the field of frailty models. Time to event data is very common in biomedical applications. Multivariate data, such as recurrent event histories or clustered failures, typically require special modeling techniques. Frailty models extend the proportional hazards models by employing random effects. In this book, the first chapter represents an introduction to the field of frailty models. The second chapter studies the small sample properties of such models in more depth. In particular, it addresses the questions of identifiability of frailty models. The third chapter describes a score test that may be used to test whether a recurrent events process is associated with a terminal event. The fourth chapter studies the problem of event-dependent selection in the context of recurrent events data. This problem is relevant when the data are collected from registries. The fifth chapter introduces a novel R package and presents an overview of available software for estimating frailty models. Show less
The majority of platelet transfusions are given to patients with a hematological malignancy to prevent or treat bleeding complications. The adhered transfusion trigger for patients with an... Show moreThe majority of platelet transfusions are given to patients with a hematological malignancy to prevent or treat bleeding complications. The adhered transfusion trigger for patients with an increased risk of bleeding varies among hematologists. Although almost 20.000 donors are HLA typed in the Netherlands, adequate transfusion support cannot be guaranteed for all immunized patients, especially not for patients from a non-Caucasian background. From a clinical perspective, major hemorrhage is the most relevant outcome to measure effectiveness of platelet transfusions. We developed a model consisting of drop in hemoglobin, transfusion support, and CT-brain to enable the identification of major hemorrhage among leukemic patients in routinely recorded data. In the Netherlands, the standard platelet concentrate is derived from buffy coats and resuspended in plasma or platelet additive solution (PAS) and can be stored for seven days. Storage has a negative effect on safety and efficacy of platelet transfusions. Using routinely collected health care data, we demonstrated a lower risk of a positive blood culture after transfusion of platelet concentrates stored for five to seven days. Using the database of TRIP, we showed an increased risk of transfusion transmitted bacterial infections for platelet concentrates stored in PAS compared to those stored in plasma. Show less
The dissertation consists of research in three subjects in two themes—Bayes and networks: The first studies the posterior contraction rates for the Dirichlet-Laplace mixtures in a deconvolution... Show moreThe dissertation consists of research in three subjects in two themes—Bayes and networks: The first studies the posterior contraction rates for the Dirichlet-Laplace mixtures in a deconvolution setting (Chapter 1). The second subject regards the statistical inference in preferential attachment networks, in three different but related settings: for the general sublinear preferential attachment functions, we develop the empirical estimation (Chapter 3); in the case of affine preferential attachment model with random initial degrees, we employ the maximum likelihood estimation on the affine parameter with results on the estimator's asymptotic normality (Chapter 4); and for the parametric sublinear preferential attachment functions, we apply again the maximum likelihood estimation (Chapter 5). The last subject is about the modeling and inference of the movie-actor network with preferential attachment models (Chapter 6), and based on the data made publicly available by the internet movie database. Show less
This dissertation focuses on the Middle Dutch text the ‘Dialogue between Eckhart and the Layman’, an enigmatic spiritual piece of writing from the mid-fourteenth century. A layman and a master... Show moreThis dissertation focuses on the Middle Dutch text the ‘Dialogue between Eckhart and the Layman’, an enigmatic spiritual piece of writing from the mid-fourteenth century. A layman and a master converse about a broad range of religious and social subjects. The student remains anonymous, as the title suggests, and the master is named after Meister Eckhart, the famous German theologian and mystic. In this book I argue that the Dialogue can be considered as a text which sits neatly atop the fault line between the world and its monasteries and convents, between a worldly and a religious experience of faith. The text may well be our most important witness to the beginnings of a process of socioreligious changes, in which ordinary laymen, too, wanted to expand the spirituality they had previously internalized. I provide a reconstruction of the original text, an analysis of the dialectical interplay between the two protagonists and between the different levels of high and low, contemplative and practical theology and a contextualization of this dialogue within the broader intellectual culture of the Low Countries. In particular, I show how the text can be connected to the ideas of Jan van Ruusbroec and Jan van Leeuwen. Show less
Cardiac tachyarrhythmias are a vast contributor to morbidity and mortality worldwide. Still, the mechanisms underlying these arrhythmias are incompletely understood. As a result, many of the... Show moreCardiac tachyarrhythmias are a vast contributor to morbidity and mortality worldwide. Still, the mechanisms underlying these arrhythmias are incompletely understood. As a result, many of the treatment options available for these arrhythmias rely on sole alleviation of symptoms or prevention of complications secondary to the arrhythmia, or are associated with non-trivial adverse effects. An increased understanding of the mechanisms underlying cardiac tachyarrhythmias as well as the means to reverse them is a critical prerequisite if we are to shift towards more specific, more effective and less harmful arrhythmia treatment. Therefore, the research described in this thesis investigates the molecular and cellular determinants of cardiac tachyarrhythmias in ex vivo and in vitro models of cardiac hypertropfy/fibrosis, ventricular fibrillation and atrial fibrillation using state of the art electrophysiological and genetic tools. Show less
Cinema and society interact. This given becomes fascinating when socio-politically sensitive issues are adapted in films that confront spectators with the frames of reference they use to make sense... Show moreCinema and society interact. This given becomes fascinating when socio-politically sensitive issues are adapted in films that confront spectators with the frames of reference they use to make sense of society. This thesis studies how North-American and European films depict political torture in the context of the ‘War on Terror’. It starts from the debate that was held in the political and public domain concerning the actual torture of suspects of terrorist activities, and analyses political torture in film as a fictionalised, stylised form of such violence. In this way, it shows how public debates, politics, and art convene in cinema to engage with contemporary realities we, as societies, find difficult to witness and process. The analyses focus on War on Terror films made between 2004 and 2012. They incorporate ethical, political, and moral questions about the use of political torture, while addressing the West’s share in the geopolitics of the War on Terror. Ultimately, contributions are made to the fields of film narratology and cultural theory, as well as to current debates about the role of cinema in society: cinema as art object, as commercial artifice, and as commentary on socio- politically sensitive issues. Show less
This thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain... Show moreThis thesis describes the evaluation of pain perception in acute and chronic pain patients and the strength of the endogenous pain modulation system in chronic pain patients. Additionally, pain phenotypes are determined in patients with chronic pain. The ability of patients with acute pain after surgery and patients with fibromyalgia to consistently score random painful stimuli on a numerical rating scale is assessed, and the influence of opioids on this ability is evaluated. In patients with fibromyalgia, the offset analgesia paradigm is also evaluated. Offset analgesia is defined as the reduction in pain perception after a small decrease in a nociceptive heat stimulus, that is larger than would be expected from the magnitude of the stimulus decrease. This paradigm can be used to assess the endogenous ability to modulate incoming pain signals. Another manifestation of endogenous pain modulation is conditioned pain modulation (CPM). This is the reduction of pain perception of a nociceptive stimulus by the application of a second nociceptive stimulus on a remote area on the body. In this thesis the ability of a new device specifically developed to induce CPM is evaluated. In the last 2 chapters, the signs and symptoms of chronic pain patients with fibromyalgia, diabetes and sarcoidosis are used to construct 4 pain phenotypes. These phenotypes represent groups with more homogeneous patterns of signs and symptoms, which may be important to identify and evaluate targeted drug therapy. Show less
Public enforcement of competition law is in the hands of the Netherlands Authority for Consumers & Markets (ACM). The ACM has a wide variety of instruments at its disposal to combat unfair... Show morePublic enforcement of competition law is in the hands of the Netherlands Authority for Consumers & Markets (ACM). The ACM has a wide variety of instruments at its disposal to combat unfair competition. The increasing attention to administrative fines, the qualification of the administrative fine as a form of criminal prosecution and the introduction of more informal types of settlement have led to the question whether public enforcement procedures satisfy fundamental procedural rights. The research studies the various public enforcement procedures of Dutch competition law and compares them to fundamental procedural rights as stipulated in Article 6 ECHR and European law. The analysis brings to light the tension between safeguarding a fair trial on the one hand and the effectiveness of the enforcement of competition law on the other. Based on the concept of the right to a fair decision process, this thesis puts forward specific recommendations which will eliminate this tension. These recommendations are aimed at procedurally enhancing the administrative decision-making – for example by questioning witnesses – and at offering adequate judicial assessment. Show less
The aim of the research described in this thesis entitled ‘The use of transcriptomics data in detecting non-genotoxic carcinogens’ was to develop in vitro tests to improve testing strategies for... Show moreThe aim of the research described in this thesis entitled ‘The use of transcriptomics data in detecting non-genotoxic carcinogens’ was to develop in vitro tests to improve testing strategies for cancer hazard assessment of chemicals, to reduce the use of in vivo experiments. The scope of this thesis was twofold. First, an improved in vitro approach to assess genotoxicity was developed, with the intention to reduce the number of misleading positive test results. The emphasis was on characterization of the cell system, primary hepatocytes derived from transgenic mice. Results showed that this cell system will be of added value in genotoxicity testing. In the second part of this thesis, the focus was on the development of a ‘trancriptomics’-based approach to detect modes of action of non-genotoxic carcinogens. It has been demonstrated that the described comparison approach is promising in recognizing gene expression patterns, which can be related to modes of action. In addition, the approach is also suitable to detect toxicity of chemicals in general. In conclusion, through the development of in vitro approaches, as described within this thesis, an important contribution in the improvement of testing strategies for cancer hazard assessment of chemicals has been delivered. Show less
Schistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most... Show moreSchistosomiasis is a tropical disease affecting over 230 million people worldwide. Although effective drug treatment is available, reinfections are common, and development of immunity is slow. Most antibodies raised during schistosome infection are directed against glycans, some of which are thought to be protective. Developing schistosomula are considered most vulnerable to immune attack, and better understanding of local antibody responses raised against glycans expressed by this life stage might reveal possible glycan vaccine candidates for future vaccine research. In this tehsis we adressed the spatial and temporal expression of glycans expressed during the critical larval stages of schistosome development and we studied the (protective) antibody responses against these glycans in animals and infected human populations. Together these studies thereby contribute to an important basis for the understanding of the anti-glycan antibody responses towards Schistosoma in general and towards the vulnerable schistosomulum in particular. Show less
This thesis describes the synthesis of various teichoic acid (TA)-fragments, capsular polysaccharide (CPS)-mimics and a toolbox of glycerol phosphate probes. Most of these molecules feature one or... Show moreThis thesis describes the synthesis of various teichoic acid (TA)-fragments, capsular polysaccharide (CPS)-mimics and a toolbox of glycerol phosphate probes. Most of these molecules feature one or more phosphodiester functions, the introduction of which has been accomplished with phosphoramidite chemistry. The versatility of glycerol- and carbohydrate building blocks provided with a 2-cyanoethyl-protected phosphoramidite is illustrated by their application both in solution and in automated solid phase syntheses of TA and CPS oligomers as well as probes. The CPS-mimics are based on a polysaccharide present in the capsule of the gram negative bacterium Neisseria meningitidis, the pathogen that is the major cause of bacterial meningitis. The TA-fragments described in this thesis correspond to lipoteichoic acids (LTA) and wall teichoic acids (WTA) from Enterococcus faecalis and Enterococcus faecium, two commensal Gram-positive bacteria inhabiting the gastrointestinal tract. In both these bacterial families multi-drug-resistant strains have evolved and they are responsible for the majority of hospital-acquired infections. Enterococcal LTA generally consists of sn-glycerol-1-phosphate repeating units that can be decorated with carbohydrate- or D-alanyl appendages on the 2-OH of the glycerol moieties. The biosynthetic machinery of WTA is more complicated and can result in completely different structures. Show less
According to different diagnoses, the advent of democracy in Chile was characterised by a fragmentation of and crisis within social movements, due to the lack of demonstrations by civilian society... Show moreAccording to different diagnoses, the advent of democracy in Chile was characterised by a fragmentation of and crisis within social movements, due to the lack of demonstrations by civilian society and even due to an absence of civilians. The aim of this study is to examine and open up debate on activation processes and the deactivation of Chilean civil society in particular, paying special attention to the period of democratic reconstruction during the four Concertación governments as a time of social demobilisation. In the same way, this study goes into more depth and broadens academic discussion on the factors that influenced this deactivation. It poses that social demobilisation between 1990 and 2010 was heavily influenced by traumatic post-dictatorial memories, by civil society’s relationship with the state and the paradigm of governability and, finally, by the market and logic of neoliberal modernity. The influence of political, psychological and economic factors as important inhibitors of eventual mobilising actions in the transition become, at the same time, components of this new socio-political mould. With this, new identities became possible and were also brought to light during the 2011 cycle of demonstrations. Show less
Focusing on state and peace building in Kosovo, this research brings a new, more local perspective to the established literature. State and peace building is analyzed by using the methodology of... Show moreFocusing on state and peace building in Kosovo, this research brings a new, more local perspective to the established literature. State and peace building is analyzed by using the methodology of life stories, looking at the biographies of individuals whose life experiences reveal new aspects about the processes of state and peace building. Show less
