“May the evidence be with you …”

“The autoreactive B cell response in myasthenia gravis”

“Europeanization through Framing?”

How to account for the spectacular investment and growth of childcare facilities in the Netherlands as of 1995 onwards, and what is the role of the EU therein? The thesis examines the implementation of one European Union (EU) guideline in the Netherlands: the reconciliation between work and private life guideline, and the attached Barcelona quantitative target on childcare facilities coverage rate. The study traces the transformations in Dutch childcare policy since WWII and the underlying political dynamics. It is revealed that the observed policy outcomes are result of activities undertaken by the domestic pro-childcare coalition, and cannot be attributed to the European level of governance. The EU’s influence is discovered (rather indirectly) at the level of strategic policy framing.

Key words:

child care facilities, Netherlands, EU

“Eijsden, een vrijheid met Luikse stadsrechten; Een rechtshistorische schets van de ontwikkeling van een Minderstad in de regio tussen Maas en Rijn (ca. 1300-ca. 1550)”

Was Eijsden in the utmost south-west corner of the Dutch province Limburg a town, a village of neither? That question is at the centre of this law historical study of the development of Eijsden in the period 1300 – 1550. On the basis of legal rules and legal practice in combination with territorial, demographic and socio-economic aspects, Van Hall concludes that in the studied era Eijsden can be regarded as a small town, a Minderstadt. Eijsden received privileges from the prince bishop of Liège that were derived from the city rights of Liège. Eijsden is exemplary for numerous small towns that were established in the Late Middle Ages by various sovereign lords in the politically fiercely contested area on both sides of the Maas. Hans van Hall (1949) is attached as archivist to the Regional Historic Centre Limburg and the Social Historic Centre for Limburg, both co-financers of this research. 

Key words: 

urban history, Late Middle Ages, Eijsden, Liège

“The true mystery of the world is the visible, not the invisible”

“Team Adaptation; A cognitive perspective”

To face the ever increasing dynamics, complexity and insecurity of their environment, it is crucial that teams learn to adapt. This dissertation studies the role of team cognitive structures (the knowledge teams have of their task and team) and cognitive processes in team adaptation. In earlier studies the focus was often on overlap in knowledge structures among team members, but flexibility and complexity of these structures turn out to be at least as important. Team adaptation is positively related to the degree to which team members adapt their knowledge structures in line with changes in their environment. Moreover, well performing teams spend relatively much time on structuring and sharing information in the start phase of a crisis and subsequently take decisions faster than less well performing teams.

Key words:

team cognitive structures, team adaptation

“CD 36; a target to restore cardiac function in type 2 diabetes”

Today in the Netherlands 50% of the people are overweight and half of them will develop diabetes type 2. The risk that these people develop cardiovascular diseases is twice as high. The healthy heart uses both sugars and fats for fuel, but the heart of diabetic patients uses mainly fats. This dissertation studied promising new target proteins for the development of new heart metabolic treatments and tested these in in vitro and in vivo models for insulin resistance. Hopefully these new insights will help people in the process of lifestyle change that are also necessary for the prevention and treatment of heart metabolic diseases.

Key words:

diabetes, cardiovascular diseases, target proteins

“Van genen, golven en gestalten”

“The nutritional anti-inflammatory reflex: From rodents to man”

“Detection of developmental toxicity using differentiating embryonic stem cells; a transcriptomic approach”

The use of test animals is more than ever on the social agenda. There are many actions by test animal activists against the use of test animals and at the same time there is a programme going on to detect the toxicity of substances that are on the market. In this PhD research a test method was developed that uses stem cells instead of test animals. The researchers have shown that with the help of this test method the harmfulness of a substance for the embryonic development can be identified.

Key words:

test animals, alternatives, stem cells

“De Doos van Pandora, vooronder-stellingen over de ontwikkeling van het volkenrecht”

“Integrating pre-clinical skills training in skills laboratory and primary health care centers to prepare medical students for their clerkships”

Indonesian medical students encounter problems when transitioning from the preclinical to the clinical phase of the undergraduate curriculum. Many students feel ill prepared for training in the clinical environment. This thesis explores the transition problems of students of the Faculty of Medicine – Gadjah Mada University (FM-GMU), Indonesia, and describes the implementation of early clinical experiences (ECE) as a possible solution. Students who participated in ECE in Primary Health Care Centers learn more efficiently during their first clerkship(s) and take more opportunities to perform skills, compared to students who did not take part in ECE. Considering the limitations of clerkships in duration and learning opportunities, this difference clearly enhances the effectiveness of the clinical phase.

Key words:

clinical skills training, undergraduate, ECE, primary health care 

“Interactions between ET-1 and CGRP in resistance arteries”

“The use of personal developments plans in the Workplace. Effects, purposes and supporting conditions”

Despite the popularity of Personal Development Plans (PDPs) in the workplace, little is known about the actual use of the tool and its impact on the employee’s learning and development. Therefore this PhD project researched the effectiveness of the PDP practice for the undertaking of learning activities, expertise-growth and performance. It showed that it is not the PDP that makes employees develop; it is the way it is implemented and used that make the PDP practice work. HRD departments should focus on the supporting conditions within those practices and implement PDPs as learning and development tools especially, since their real power lies in that purpose.

Key words:

Personal Development Plans (PDPs), professional development, workplace

“In pursuit of corporate sustainability and responsibility: past cracking perceptions and creating codes”

“Corporate responsibility, beyond Voluntarism. Regulatory options to reinforce the license to operate”

“Molecular profiling of ovarian serous neoplasms: defining the borderline”

Ovarian cancer is the main cause of death in women with a tumour in the female genitalia. The high death rate can be explained by the fact that the disease is often only diagnosed in an advanced stage, because usually these women don’t have any complaints. The objective of this dissertation is to discover better tumour classification and diagnosis options for two types of tumours (carcinomas and borderline tumours). The distinction between these tumours is clinically very relevant because treatment and prognosis are considerably different. The researchers indeed found several markers that can distinguish borderline tumour and carcinoma. It also turned out that the markers that underwent genetic or epigenetic changes are mainly involved in invasion (the spreading of tumour cells to surrounding tissue). Hopefully in the future the identified markers can be used in the clinic as a diagnostic tool.

Key words:

eierstokkanker, borderline tumor, carcinoom, invasie

“Developmental changes in the pulmonary circulation: role of the nitric oxide / soluble guanylate cyclase / cyclic GMP and the isoprostane pathways”

“Novel pharmacological strategies to reduce acute radiation injury”

After nuclear disasters such as accidents in nuclear plants, but also during cancer treatment with radiotherapy/x-ray treatment, people are exposed to high doses of ionizing radiation. In both cases the radiation exposure can lead to intestinal damage. Given the serious consequences of this damage, it is necessary to develop medicines that prevent and/or decrease this radiation injury. This dissertation presents two new medicines that decrease radiation injury in mice. Not only is shown that these medicines work, but also how they work. Special is that one of these medicines decreases the injury, even when it is not administered until two days after the radiation.

Key words:

radiation injury, medication

“Essays on Financial Market Instability”

This doctoral thesis encompasses a range of topics in empirical finance. The researcher employed new statistical methods to investigate the linkages between international stock markets. He found that stock markets move more closely together during financial crises, limiting the benefits for investors from investing in equity markets abroad. He also found that financial shocks are transmitted across borders through changes in the market's attitude towards risk and financial panic rather than through global macroeconomic developments. This research has practical consequences for portfolio managers who seek to rebalance a well-diversified asset portfolio in response to adverse developments in financial markets, and to central bankers who must combat systemic risks and instability in financial markets.

Key words:

finance, (internationale) effectenmarkt

“Disability and Employment; A Contemporary Disability Human Rights Approach Applied to Danish, Swedish and EU Law and Policy”

This thesis examines the evolving principles of disability human rights law in the field of employment and applies them to Danish, Swedish and EU law and policy. Based on an analysis of the newly-adopted UN Convention on the Rights of Persons with Disabilities and present-day interpretations of international and European human rights instruments, four key characteristics of a contemporary disability human rights approach are identified. The comparison of laws, policies and statistics shows that the main explanation for the extreme difference in employment rates for persons with disabilities and reduced working capacity in Denmark and Sweden lies in the level of employers’ obligations (secured in law and policy) towards these employees. These obligations ensure that working conditions and working tasks are adjusted to the capacity of the employee in question.

Key words:

human rights law, disability, Denmark, Sweden, EU

“The European Public Prosecutor’s Office – Analysis of a Multilevel Criminal Justice System”

Since 2009, the EU is allowed to establish a European Public Prosecutor’s Office. This EPPO would prosecute EU fraud, as well as heavy cross-border criminality. The EPPO would strongly limit the autonomy of the member states. This dissertation makes propositions for the practical realization of the EPPO. It proposes the form of a European prosecutor’s office that settles the most important cases and relies on the national public prosecutor’s offices for all other cases. The EPPO must constitutionally be well embedded. The preference goes to a semi-independent European public prosecutor’s office that is under the general control of the EU Council of Ministers. The EPPO will render account to the Council of Ministers as well as to the European Parliament, the European Commission and the national parliaments.

Key words:

European Public Prosecutor’s Office (EPPO), European criminal law, European constitutional law, public prosecutor’s office

“Free gathering and movement of evidence in criminal matters in the EU”

“Assessment of injury in reperfused acute myocardial infarction using cardiovascular magnetic resonance imaging”

Accurate research into different characteristics of the myocardial infarct leads to a better understanding of underlying mechanisms. Magnetic resonance imaging (MRI) shows that de-spite successful opening of coronary arteries half of the patients have a declined blood circulation in capillaries and haematoceles in heart muscle tissue. Of all measured characteristics especially the infarct size is determinant for heart function repair after three months. Thirty minutes after a Dotter procedure the electrocardiogram can already show if a patient has an increased risk of declined function repair. For determination of the extensiveness of threat-ened heart muscle tissue during an acute coronary artery closure, MRI is more effective than angiographic and electrocardiographic methods. 

Key words:

myocardial infarct, MRI, function repair

“Debating Europe: Reflections on EU Affairs in the Public Sphere”

Since its inception, the European Union (EU) has grown in size and its competences have increased. These developments have been accompanied by growing worries about the democratic legitimacy of the Union and its policies. One of the core manifestations of this so-called ‘democratic deficit’ is a European public deficit.
Following a qualitative analysis of Dutch and German newspaper coverage of the debates on the future of Europe and EU air quality legislation, this thesis argues that this public deficit mainly represents a qualitative problem, reflected by mismatches in the timing and content of national debates vis-à-vis European policymaking in Brussels. In terms of democracy, this decreases opportunities to timely influence decision-making and hold the right people accountable.

Key words:

European Union, democratic legacy, public sphere

“Understanding consumers’ attitudes toward novel food technologies”

“HLA antibodies: detection and clinical relevance”

“Regulatory ubiquitylation in DNA repair: a multi-faceted role in maintaining genomic integrity”

"Memory distrust in the legal context"

So far, in the context of criminal law memory distrust has only been described on het basis of casuistic. This dissertation is a first attempt to empirically study memory distrust. Memory distrust can be defined as a situation in which people have little trust in their memories, which makes them extra vulnerable for external suggestions. Especially in the forensic practice memory distrust can have radical consequences. The results show that providing negative information usually leads to people starting to distrust their memory. And the more people distrust their memory, the more inclined they are to accept misleading information. Moreover, memory distrust incites more false confessions of the type that people believe in themselves.

Key words:

memory distrust, pseudo memories, false confessions

“Kupffer cells in fatty liver disease: does size really matter?”

“The role of the council secretariat and the European Commission in EU Foreign Policy”

For years, foreign policy was the exclusive domain of the individual European member states. This research shows that recently, however, they have handed over many tasks to Brussels. The reason is that European institutions can execute certain matters more efficiently than the member states. But the member states take no risks. They carefully weigh the pros and cons of delegation. This research also studies the consequences of delegation. It shows that the member state have lost sovereignty to a limited extent. Brussels has especially much influence when it concerns sending European police and justice missions to for example Kosovo.

Key words:

European Union, foreign policy, member states

“Pelvic physiotherapy in faecal incontinence”

This dissertation studies different aspects of the management of patients with faecal incontinence. Among those affected are young mothers. It appeared that a third- or fourth-degree sphincter rupture (prevalence 27%) was associated with postpartum faecal incontinence. 
If treatment by means of medication and dietary adaptations fails, pelvic physiotherapy is recommended as an early intervention given the low associated morbidity and reported improvement rates. A randomised controlled trial provided no evidence for an add-on effect of rectal balloon training to pelvic floor muscle training. This result will not change the existing recommendations as yet. Offer advice, information and pelvic floor muscle training at first, followed by the use of various elements of biofeedback in case of insufficient symptom relief. The use of constipating medication, any obstetric factor, and experiencing minor embarrassment predicted a favourable outcome of pelvic physiotherapy treatment. In the evaluation of patients with faecal incontinence, it is suggested that the Wexner score is most suitable for severity assessment and the Fecal Incontinence Quality of Life Scale for evaluating quality of life.

Key words:

feacal incontinence, pelvic physiotherapy

“Strategic Decision Making in Complex Games”

“Work and Pain: complaints of the arms, neck and shoulders among computer office workers. A study in Sudan and the Netherlands”

“Return of the narrative. Studies on transportation in social media”

These days, consumers write their negative experiences on Facebook and in blogs and have therefore considerable influence on the public opinion; this dissertation studied how companies can best react to negative reviews. The businesslike way in which the majority of the companies react causes a tremendous clash. Companies are used to communicate with their customers by means of statements and arguments. One of the conclusions of the research is that companies should always start with an apology and after that tell their side of the story. Moreover, this works better when the story is not told by the company spokesman, but by someone from the work floor. Social media are all about human contact. Van Laer developed a method that activates the empathic part of the brain by means of brain games. As a result, employees don’t only focus on financial results, but they also put themselves in the position of the customer. 

Key words:

consumer behaviour, social media, communication

“Who’s left behind? Social dimensions of health transition and utilization of medical care in Poland”

“Challenging the patient centred paradigm: designing feasible guidelines for doctor patient communication”​

“Innovation in Healthy Nutrition: every advantage has a disadvantage”

“Succesfully Managing Alliance Portfolios: an alliance capability view”

“Studies of the Affective and Developmental Domains of Psychopathology in Psychosis”

“Malaria Rapid Diagnostic Tests: Laboratory aspects in the diagnostic setting”

“Platelets in atherothrombosis - roles of CD36 and P2Y12 receptors”

“Parietal cortex and spatial cognition combining evidence from neuroimaging and functional brain stimulation”

The parietal cortex appears to be a mediator and regulator for the integration of all kinds of spatial functions, such as directing attention, comparing angles or combining sensory input from various sources. Damage to the parietal cortex leads to defects in the spatial cognition such as Neglect and Extinction, where one half of the visual field is neglected. Often spontaneous recovery occurs by reorganization, but the underlying mechanisms thereof are still unknown. Combining the imaging techniques (fMRI, EEG) with magnetic brain stimulation (TMS) made it possible to visualize for the first time how the brains can compensate TMS induced disorders. Follow-up research may ultimately lead to a treatment that stimulates spontaneous recovery. 

Key words:

parietal cortex, spatial cognition, fMRI, EEG, TMS 

“Some genetic polymorphisms and their impact on head and neck cancer susceptibility”

“HIV prevention and education among young people in Yemen”

This dissertation studies the impact of peer education and life-skills for HIV prevention among 6221 Yemeni young people. The findings revealed that the interventions have succeeded in improving HIV knowledge and risk perception; decreasing levels of stigma and discrimination; and in promoting less risky practices and behaviours related to HIV infection. Enabling elements had been the culturally sensitive messages, advocacy with decision makers and parents, participation and capacity building of peer educators and all existing stakeholders at school and community level.  The results from this evaluation could be useful in implementing future peer education interventions in similar conservative Muslim settings.

Key words:

Peer education, HIV education, Yemeni Young People 

“Building a common state or deepening divisions: Bosnian constitutional ethno federalism and its consequences”

The research shows the impact of the Bosnian constitutional system on the political development in the country. The main argument is that the constitutional system is beneficial to the nationalistic political parties. Therefore, the country lacks necessary reforms, as there is no cooperation between fractions representing particular ethno-political groups. 
There are several ‘constitutional’ explanations of this situation. The divisions within the country compel political actors to seek its support within one national group. The second reason is an overgrown administration in Bosnia and Herzegovina, which provides plenty of employment opportunities for the groups linked to the political elites. The engagement of international actors in the political life in Bosnia allows the political leaders to throw the blame on ‘the foreigners’.
A solution of this problem would be separation of ethnic questions from these of general, political or economic character, as well as new arrangements regarding territorial and institutional set up of the country.

Key words:

Constitutional system of Bosnia and Herzegovina, consociational democracy, power sharing, ethnic conflicts, Balkans, post-conflict settlement

“Material versus psychosocial explanations of socioeconomic differences in health-related functioning in older people”

The connection between socioeconomic status and health has often been studied. Frequently, unhealthy behaviour is put forward as an important explanation, but interventions in this field don’t appear to reduce the health differences between poor and rich. This dissertation studied the more fundamental explanations of socioeconomic health differences in older people. One of the conclusions is that factors related to how people look at life are even more important than living in relative poverty. The feeling of being in control of life is an important explanation for the fact that people from the higher socioeconomic classes feel healthier than people from the lower classes. These findings can contribute to the development of an effective strategy to reduce health differences.

Key words:

socioeconomic status, health differences, older people 

“Een besef van eigen kracht. Limburgse provinciale politiek in de periode 1962-2007”

In the period 1962-2007, the Limburg Provincial Government grew from a waiting public body that submissively implemented the state policy into an initiating political player in Limburg society. This development happened step by step, and there were four moments when the Provincial Government fundamentally changed its course. Three elements were involved: external urgent circumstances, the alliances between persons and the space that was offered by the central government and which the Provincial Government used to develop its own initiatives. The moment these three elements came together, the Provincial Government changed its general policy in a relatively short period of two to three years.

Key words:

provincial politics, Limburg, province, public administration, agenda-making

“Stakeholder Theory in Finance; on the Financial Relevance of Nonfinancial Stakeholders”

“Experimental Spinal Cord Stimulation in Neuropathic Pain Models”

“Het onzichtbare zichtbaar maken”

“Time in teams: methodological issues in the study of temporal dynamics”

“The role of neuroimaging phenotypes in ecogenetic studies of psychotic disorder”

Schizophrenia occurs in 1 of 100 persons and is a serious psychological disorder that involves severely disturbed contact with reality. Genetic and environmental influences play a role in the development of schizophrenia. The studies in this thesis delivered proof of associations between changes in the brain in individuals with an increased risk of schizophrenia and environmental factors such as cannabis use, childhood trauma and daily stress. In spite of the fact that the exact underlying mechanisms are not known yet, it is possible to speculate that differences in sensitivity to the environment are manifested in structural changes in the brain, which results in the development of psychotic symptoms.

Key words:

schizophrenia, brain changes, gene-environment interaction, stress, cannabis, childhood trauma, genetic risk

“The antioxidant flavonoid 7-mono-O (B-hydroxyethyl)- Rutoside: from clinic to concept”

Flavonoids are antioxidants that make an important contribution to the good effects of vegetables and fruit on health. Research was conducted into the flavonoid monoHER, a promising substance that can be applied to prevent heart damage as a result of chemotherapy.  MonoHER turns out to be an extremely good antioxidant, which explains its positive effects. It also turns out that substances our body makes from monoHER, so-called metabolites, are important for the health effect of monoHER; they can contribute to keeping heart and vessels in good condition and to inhibiting disturbed inflammation processes that play a damaging role in many diseases, ranging from diabetes and lung and liver diseases to ageing. These metabolites are possibly even more powerful than monoHER itself. This research has showed how monoHER works and allows us to apply monoHER more effectively. 

Key words:

monoHER, flavonoid, antioxidant, metabolites, health

“Managing work-based postgraduate medical education in clinical departments”

“Vascular Calcifications and Matrix Gla Protein in Hypertensive Subjects”

People with calcified vessels have an increased risk of developing cardiovascular diseases compared to people without calcifications. This dissertation describes research into vascular calcification in people with hypertension. Matrix Gla protein inhibits, if activated by vitamin K, the development of vascular calcifications. With more calcification we found lower vitamin K levels and a relation between Matrix Gla protein and stiffness of blood vessels. And finally, patients who take vitamin K inhibiting medicines long-term also have more vessel calcifications. Administering vitamin K turned out to inhibit calcification in test animals. Whether this also applies to humans and if the risk of cardiovascular diseases decreases then needs further investigation. 

Key words:

vascular calcification, vitamin K, cardiovascular risk matrix Gla protein

“Parietal Matters in Early Alzheimer's Disease: evidence from structural and functional MRI”

Presently, imaging techniques, such as MRI, enable early diagnosis of brain diseases. Up to now, early diagnostics of Alzheimer mainly focused on areas in the temporal lobe, but this lacks precision. This dissertation investigated if studying an area connected to the temporal lobe, the parietal lobe, can improve the reliability of the diagnosis. The results show that changes in the structure and function of parietal areas can support early detection of Alzheimer. The research offers new insights about possible underlying causes of this disorder, such as a reduced connectivity between the temporal lobe and the parietal lobe. 

Key words:

brains, Alzheimer, early diagnostics, MRI

“Vestibular Exploration on advanced diagnostics and Therapy”

Studies of the vestibular system with advanced diagnostic instruments show that the perception of tilts mainly depends on emotional information and less on vestibular (inner ear) information. This creates the possibility to help patients with a serious vestibular disability improve their postural balance by replacing the vestibular information by sensory information. For that purpose an advanced vibratory belt was developed that transfers information about body tilts via the tactile sense around the waist. In these disabled patients, this vibratory belt shows a significant improvement in balance, self-confidence and independence.

Key words:

vestibular system, emotional information, vestibular information

“Frail elderly; identification and disability prevention in primary care”

Frail elderly run an increased risk of developing disabilities in activities. How can we identify frail elderly who live in their own homes, and which interventions support them in doing (and continuing to do) the activities that are meaningful to them? This dissertation concludes that existing screening instruments for frailty have potential, but still insufficiently select the right target group. Frail elderly show satisfaction with an innovative interdisciplinary intervention programme (‘Care out of Precaution’), focused on self-management of meaningful activities. Primary care professionals are also positive and find the programme manageable; it stimulates interdisciplinary and preventive work. A few adjustments are still needed for successful implementation in primary care.

Key words:

frail elderly, prevention, screening, intervention

“The Welfare Effects of Integrating AIDS Treatment with Food Transfers: evidence from Zambia”

Many HIV/AIDS treatment programmes now combine free provision of medication with food assistance for patients threatened by hunger and malnutrition. This study evaluates the health and economic effects from this combined aid. The study is based on data collected from 400 families in Zambia after 6 months of food aid distribution. The main findings of the study are that it improves adherence to AIDS medication (i.e. the patient takes it regular) but has no effect on the patient’s weight gain. Food aid appears to encourage male non-patient adults to increase their work or in cases where they were unemployed, to return to work, while for female non-patient adults they only return to work when the patient has taken medicine for a long time. However, food aid appears to be discouraging AIDS patients from working or returning to work. The main conclusion of the thesis is that food transfers in the form of food aid generally have a beneficial impact on the recipients, but food aid providers need to facilitate a gentle transition from food aid to self sustenance, through linking up patients with job training or access to micro-credit.

Key words:

AIDS treatment, food aid

“Childhood overweight: parents in control? On the Influence of parents in maintaining children’s weight problems”

This dissertation studies the role of parents in children’s overweight. The first part focuses on the influence of restriction on eating behaviour. The assumption is that using too much control can lead to undesired eating behaviour and overweight.  Two studies confirm this hypothesis: prohibiting both attractive and less attractive food leads to a greater desire and a larger intake of this forbidden food. The second part focuses on the role of parents in treating overweight. Results show that an intervention which is only aimed at parents is effective in reducing overweight. 

Key words:

childhood overweight, parents, influence eating behaviour

“Evaluating Clinical Teaching through Cognitive Apprenticeship”

Supervision of medical students is the key to successful learning during apprenticeships. However, this supervision is often carried out by doctors who are experts in their professional field, but who have often received too little additional training to fulfil their role of supervisor. To help doctors improve their supervising skills this dissertation presents an instrument (the Maastricht Clinical Teaching Questionnaire) that was developed to allow students to give feedback to their supervisors, as well as a model that can structure supervision during the apprenticeships. Research has shown the usability and practical relevance of the instrument and the model, which allows optimizing supervision during apprenticeships.  

Key words:

research medical education, apprenticeship, supervision

“Exploratory Pathway Analysis”

“Nieuwe wijnen in oude vaten”

“Kinetics and effects of orally administered ATP”

“VEGF and NOTCH in Blood Vessels, an Intricate and Fascinating Interplay”

The NOTCH pathway comprises a highly conserved intercellular signaling mechanism. In vertebrates, NOTCH pathway components are expressed in various organs including blood vessels, where they play essential roles in neovascularization and atherosclerosis. Our studies provide a detailed molecular analysis of Notch-signaling interaction with Vascular Endothelial Growth Factor (VEGF) in Endothelial Cells and the role of metalloproteinase ADAM10 in this process.  
The new insights in VEGF and Notch signaling and their instructive role in blood vessel growth can be used to improve the efficacy of current cardiovascular therapies.  By targeting these molecules growth of blood vessels (tissue revascularization) can be stimulated or blocked, as for instance in tumor growth or atherosclerosis.  

Key words:

NOTCH pathway, molecular analysis, VEGF, vascular biology

“Regional Sustainable Development: Barriers in Practice; Findings from policy, citizens, practitioners and monitoring”

This research into the implementation problems of sustainability policy has found an important barrier: the frequent lack of vision on the desired future.  This also turns out to be the opinion of the interviewed Limburg citizens. A central characteristic of sustainable development is in fact an integral vision and the authorities should be leading there. Limburg citizens also see a role for business, education and research, as well as for the citizens themselves. The research also showed that Limburg citizens are not yet sustainable, whereas almost 80% of the interviewed people claim to find sustainability important. This difference between thinking and doing is among others a result of the fact that people don’t know what they should pay attention to and that they don’t have concrete examples. 

Key words:

policy for sustainability, sustainable development, Limburg, authorities

“Vitamine D as an immune modulator in multiple sclerosis”

Multiple Sclerosis (MS) is an incurable, invalidating inflammatory disease of the brains that especially affects young adults. At the beginning of the disease process there is an important role for specific immune cells (T cells) that attack the brain. In experimental research vitamin D inhibits these bad T cells which could possibly be favourable for MS patients. This dissertation shows that MS patients who suffer from many MS attacks have lower vitamin D levels in their blood, as well as patients with a more disturbed balance between good and bad T cells. Giving extra vitamin D to a small group of patients was safe and showed subtle indications for an improvement of this balance. To further study this effect the SOLAR study was developed. In this first large-scale clinical study into the effects of vitamin D in MS 348 European MS patients are administered high doses of vitamin D or placebo. The results of the SOLAR study may lead to an expansion of the up to now limited treatment arsenal in MS.

Key words:

vitamin D, multiple sclerosis, immune system, therapy

“Werken naar vermogen: vermogen om te werken”

“Teaching and assessment of professional behaviour: Rhetoric and Reality”

Training in professional behaviour and the assessment thereof in medical programmes increasingly gains interest, among others as a result of the new Higher Education and Research Act. This Act establishes that students who don’t function well (in this case show unprofessional behaviour) in some cases have to quite their study programme. Professional behaviour can be described as behaviour that shows and expresses the standards and values of the professional practice. This is expressed by dealing with ‘tasks and work’, with ‘others’ and with ‘the personal functioning’. This dissertation describes the theoretical and practical aspects of learning from and dealing with (un)professional behaviour in the (basic and continued) medical programme and as a practitioner. It also describes how professional behaviour can contribute to patient safety and quality of care, for example by means of a complaints analysis.

Key words:

(un)professional behaviour, medical programme, physicians

“Risk for psychosis: A Life Span Perspective”

Schizophrenia is a disease of all ages, but it usually originates at the young adult age. We studied differences in vulnerabilities for schizophrenia throughout the life span. Although the incidence of schizophrenia strongly decreases with age, the risk continues to exist at a very late age. Patients, who developed a first psychosis at an early age have a more serious type of the disease, with more serious symptoms and more memory and attention problems. Men run a risk that is twice as high as women’s to develop this serious early generated schizophrenia. From middle age, however, women run a relatively higher risk. Defective hearing is one of the environmental factors that contribute to the development of psychosis in younger people. Although vulnerability for psychosis originates already early in the developing brain, the timing is further determined by a complex mix of environmental factors, hormonal and age-related changes.

Key words:

psychosis, life span, risk factors

“Revalideren is goed schakelen”

“Intracellular glycation and endothelial dysfunction; role of methylglyoxal”

People with diabetes have an increased risk of developing cardiovascular diseases. The mechanisms as a result of which the high glucose levels in their blood can cause this damage are still largely unknown, but the formation of glycated proteins appears to play an important role here. This research shows that the substance methylglyoxal, a waste product in the decomposition of glucose, is an important precursor of glycation, and that accumulation of methylglyoxal in the cell can cause a decreased blood vessel function in diabetic rats. Furthermore it turns out that the detoxification of methylglyoxal by means of the enzyme glyoxalasis leads to less glycated proteins, an improved blood vessel function and even to reduced kidney damage. As a result of this finding a reduction of methylglyoxal formation may even become a therapeutic intervention in the future, which can combat the diabetes induced cardiovascular diseases.

Key words:

diabetes, vascular complications

“Elaboration during problem-based, small group discussion; a new approach to study collaborative learning”

“Currency crises and their Early Warning Systems”

“Indicators of energy balance and risk of epigenetic instability in colorectal cancer”

“Macrophages and modified lipoproteins: modulation of inflammation?”

“Imaging imagination; a Multi-method investigation into the brain dynamics of visual mental imagery”

Why is one person much better at visualizing the way home or his partner’s face than the other? The studies in this dissertation show that an area in the most anterior part of the brain functions as a police officer that directs other areas, for example areas that encode faces or the spatial environment, and integrates information.  It also turns out that all these areas communicate with each other in a specific order and that this communication takes place by certain patters of brain waves. This information can help us better understand the interaction between our imagination, the perception of reality and our memory.  

Key words:

fMRI, EEG, connectiviteit, voorstellingsvermogen

“Prevention of long-term sickness absence and major depression through early intervention”

Treatment and reintegration of employees that are absent and also suffer from psychological complaints still turn out complicated.  In this project the effectiveness of a preventive strategy, consisting of a screening and early intervention, was investigated for the prevention of long-term sickness absence and depression. The studied group consisted of employees with a high risk of future sickness absence and mild depressive complaints. The results show that the preventive strategy is effective in both preventing long-term sickness absence and reducing depressive complaints. Therefore, this strategy is a good starting point for applying a more proactive approach in occupational health care.

Key words:

prevention, long-term sickness absence, depressive complaints, intervention

“Strategic asset allocation; The effect of uncertainty on portfolio choice”

Long term investors (such as pension funds) use an econometric forecasting model for future share returns to determine their portfolios.  Such a forecasting model shows that shares are less risky and therefore more appealing to long term investors than to short term investors. However, my dissertation shows that in fact there is much uncertainty for the long term whether (i) the used forecasting model is the right model, (ii) if the used model parameters are correct, and (iii) if the model is stable over time. That is why shares often turn out more risky and unappealing for the long term than for the short term.

Key words:

Long-term investment, forecasting of shares, financing, econometrics 

“The role of private actors in the provision of public goods with applications to infrastructure and financial stability; accounting and financial approaches to assess macroeconomic perspectives”

“Selective Search in Games of Different Complexity”

Since computers emerged computer scientists have used board games as pilots for artificial intelligence. Their programmes use a virtual tree to find a move. In this tree each side-branch represents a choice made by a player during the game. This dissertation studies how selective search methods can find the best move in a faster way. Selective search methods are intended to explore only the important parts of the tree, but they take the risk of overlooking the best move.  The selective search methods we developed solved that the African board game Fanorona, broke the record in the game SameGame – a version of BubbleBreaker – and realized that computers play more strongly in Stratego and Halma.

Key words:

artificial intelligence, board games

“Cannulation practice and complications in hemodialysis vascular access”

The condition for a good hemodialysis treatment is a good vascular access. There are 2 types of internal vascular access, namely the autogenous arteriovenous fistula (AVF; connection between artery and vein) and the arteriovenous graft (AVG; a plastic vessel prosthesis that is inserted between an artery and a vein). In the course of one year the vascular access undergoes cannulation 312 times on average. There are few data about the damage this does to the vascular wall of a vascular access. This study shows that faulty cannulation of a newly placed AVF occurs twice as often as that of a prosthesis vascular access. Research into the two different cannulation techniques, namely the rope-ladder cannulation technique (the entire length of the vascular access is used for cannulation) and the buttonhole cannulation technique (repeatedly cannulating in the same place which generates a channel of scar tissue to the vascular access, comparable with an earring hole) showed that despite more faulty cannulations hypodermic hematomas and aneurysmata occurred significantly less often in the buttonhole group. However, the risk of infection is greater with the buttonhole technique. 

Key words:

hemodialysis, vascular access, cannulation

“Midwives, obstetrics, fear and trust. A four-part invention”

“Empirical studies on audit quality in the Belgian market for audit services”

This dissertation studies the influence of various factors on the audit quality. Based on data from the Belgian audit services market this research comes to the following conclusions.  Firstly, it turns out that accountants’ offices use the experience of partners to control risks that are attached to audits. Secondly, the research shows that accountant fees can lead to economic dependence between accountants and customers, which has negative consequences for the audit quality. Finally, the research shows that competition on the market for audit services contributes to a higher quality of these audits.

Key words:

Belgian audit services, audit quality

“Staphylococcus aureus prevalence, antibiotic resistance and genetic background in different patient populations in the Netherlands”

“Venous thromboembolism, cancer and inflammation: an update. The Good, the Bad and the Ugly”

“Ecologische psychiatrie: De context van ervaren”

“Persistent Risk Factors in Financial Markets”

Many risk factors in financial markets, such as the short-term interest rate, the yield spread, the rent to price ratio, or conditional stock market volatilities, exhibit strong temporal dependence. Financial theory suggests that investors care about risk and adjust their return expectations accordingly. Hence, it is important for market participants to understand the duration of shock impacts, as it determines the length of the time period during which expected returns remain low (or high) on average. We focus on the implications of persistence in financial risk factors on empirical asset pricing. Capturing the strong temporal dependence in risk factors with long-memory models, we develop a generalized model for bond yields and find that risk premiums of excess bond returns are very persistent and that positive news about the short-term interest rate imply a negative adjustment of expected excess returns. We further investigate the consequences of persistent risk factors in the real-estate and the stock market. We show that when properly accounting for this temporal dependence, one can find strong evidence in favor of return predictability, a positive risk-return trade-off, and the present-value relation of prices and fundamentals.

Key words:

financial risk and return, time-series persistence

“The Nε- (Carboxymethyl)lysine-RAGE axis; Implications for the pathogenesis of obesity-related complications”

As the number of people with obesity increases, the number of people with type 2 diabetes and diabetic complications, such as cardiovascular diseases, also rises.  An important mechanism that explains the increased risk of type 2 diabetes and cardiovascular diseases in obese people is the release of inflammatory substances from the fatty tissue, which subsequently causes chronic inflammation reactions. An important question is which factors provoke the fat cells to produce these inflammatory substances. This research shows that the glycated protein N-(Carboxymethyl)lysine (CML) accumulates in the fatty tissue of obese people and stimulates the fat cells to produce inflammatory substances. The discovery that CML plays an important role in the development of inflammatory substances in the fatty tissue offers new perspectives for the development of therapeutic interventions that can prevent the emergence of type 2 diabetes and cardiovascular diseases in obese people. 

Key words:

obesity, type 2 diabetes, cardiovascular diseases, CML, treatment

“Working Together: Theories and Thoughts on Collaborative Capital”

“De drie musketiers zijn inmiddels meer geworden”

“Dietary interventions and intestinal defence to protect against salmonella infection”

Intestinal infections are still a world-wide problem, also due to the increase of antibiotics resistance in the pathogenic agents. This dissertation describes how the defence against one of the main pathogens, Salmonella, can be increased with certain food components. A supplement of di-peptide cystine or a polyphenol turned out to inhibit infection induced diarrhoea and to lower the intestinal permeability during a Salmonella infection in pre-clinical studies. Possibly these food components also increase the defence of people, but this should be further investigated. Moreover, a new and promising biomarker, the protein PAP, was identified. By means of measurements in a faeces sample this allows to monitor the intestinal defence in man. 
This PhD research was conducted at NIZO food research, commissioned by TI Food and Nutrition.

Key words:

intestinal infection, intestinal defence, nutrition, polyphenol, cystine, biomarker

“Cold and diet induced thermogenesis in humans; Implications for obesity”

Both exposure to cold and an increased food intake lead to an increase of the energy use, the so-called adaptive thermogenesis.  After exposure to cold, this mechanism effects that a person becomes hypothermic less quickly and after overnutrition it brings about that less food substances are stored in the body. However, there are important differences between persons in this response. Some do not, or hardly, increase their energy use, others even up to 15 per cent. Persons with a healthy weight averagely increase their energy use, whereas people with obesity don’t. This metabolic reaction to cold is connected with the reaction to overnutrition: someone who increases his energy use when he is exposed to cold, also does this in the case of overnutrition. The difference in this response is explained by mitochondrial disconnection in the skeleton muscle: in not obese people the available energy in the mitochondria (energy stations) is not only used for the cellular metabolism (turnover of ADP into ATP), but also for the production of warmth. Obese people use less energy and therefore produce less warmth. The not used energy is stored as fat. 

Key words: 

energy use, thermogenesis, obesity

“Triggers for energy expenditure: thermogenic ingredients & circadian aspects”

The current increase in overweight and obesity are the consequence of an imbalance in energy expenditure and energy intake. This dissertation shows that besides limitation of the food intake it is necessary to stimulate the energy expenditure with natural ingredients. These ingredients (such as green tea blended with a little caffeine, protein diets, caffeine and capsaicin) can be part of the daily nutrition. The results show that green tea blended with a little caffeine raises the energy use and the fat oxidation and can be used to realize weight loss and weight maintenance. Protein diets also increase the energy expenditure, particularly proteins with a higher concentration of essential amino acids. These proteins also realize a stronger effect of hunger suppression. When green tea/caffeine and protein are administered at the same time, there is no amplified effect. The dissertation also shows that after fragmented sleep the carbohydrate oxidation is raised and the fat oxidation lowered, and the first signs of decreased insulin sensitivity became visible. This means that too little or disturbed sleep can underlie overweight because of a disturbed homeostasis. 

Key words:

obesity, energy expenditure, green tea/caffeine blend, protein, fat oxidation, sleep

“Clinical and molecular genetic studies in hereditary cutaneous leiomyomatosis”

“Over een zoete ziekte en vette jaren”

“Tuberculosis in India; a case of innovation and control”

India is the country with the highest number of Tuberculosis patients. This thesis draws on innovation studies and Science and Technology Studies to examine innovation dynamics in organizational, strategic, technological and service delivery aspects of public Tuberculosis control in India. The results reveal that the dynamics of innovation and control in coping with Tuberculosis in India are a complex interplay of mutual influence and requirement. This is often disregarded by actors in the field. Controlling for example every aspect of a diagnostic process through standardization can exclude local scientific and non-scientific expertise and as a result face challenges in the field. Yet, innovating a diagnostic test without standardizing operational processes is not feasible for the TB programme and will fail to be taken into consideration by the decision-makers. The mechanism that would need to be fostered to strengthen innovation capacities are situated assessments of the relation between different practices of innovation and control.

Key words:

Tuberculosis, healthcare innovation, India

“Modulation of the neuroinflammatory response after spinal cord injury”

“Optimal experimental designs for functional magnetic resonance imaging”

Before performing a functional magnetic resonance imaging (fMRI) experiment, a researcher needs to decide on the number of persons (subjects) to be scanned and on the duration of their scanner sessions. Furthermore, the order and timing of the considered stimulus types have to be chosen to present them during the subject’s scanner session. This thesis evaluates the influence of several experimental factors on the efficiency and costs of fMRI experiments. One major result is a method to determine the optimal number of subjects and optimal scanner session length for a certain type of fMRI experiments, i.e. blocked designs. It is seen that commonly employed numbers of subjects (10-20) are too low in certain cases. Another interesting result is that the optimal length of stimulus blocks in a blocked design is slightly shorter than previous recommendations.

Key words:

functional magnetic resonance imaging (fMRI), optimal design

“Constructing Agrarian Alternatives; how a creative dissent project engages with the vulnerable livelihood of marginal farmers in South India”

“Uncoupling protein 3 and the protection of skeletal muscle mitochondrial function; a transgenic approach”

Mitochondria are the power stations of the cell.  They make energy out of carbohydrates and fats from nutrition and are therefore essential for life.  However, mitochondria also make oxygen radicals that can lead to damage to DNA, proteins and fats, and are involved in the ageing process and the possible development of diabetes and cardiovascular diseases. In this dissertation we studied if the mitochondrial uncoupling protein 3 (UCP3), mainly  present in the skeletal muscle and the heart, plays a role in the protection of mitochondria against these oxygen radicals. The results from the studies described in this dissertation provide independent and convergent evidence that UCP3 does indeed play a role in the regulation of the mitochondrial oxygen radical production. Further research will be necessary to show the involvement of UCP3 in the ageing process and the development of diabetes and cardiovascular diseases.

Key words:

mitochondria, oxygen radicals, UCP3

“Was het maar zo makkelijk”

“Beter in Beweging”

“Capital Allocation and Non-Cooperative Behavior in Diversified Firms”

Diversified firms that comprise several business activities play a central role in all major economies across the world. An important issue among these firms is how to allocate capital among their distinct businesses for large-scale investments, e.g. the construction of a new production site. This dissertation analyzes these internal capital allocation processes, how inefficiencies can arise through non-cooperative behavior of managers and how these inefficiencies can be resolved. More specifically, this dissertation provides evidence that firms can improve the efficiency of their internal capital allocations either by adjusting the compensation contracts of these managers or alternatively by rearranging the organizational design of their business units. Furthermore, it is examined how delegating authority over investment projects within the firm affects the way in which managers renegotiate the initially requested capital budget to their own advantage. Apart from extending academic knowledge about internal capital allocations, this dissertation provides important insights for practitioners who seek to improve capital allocations or who need to evaluate the allocation efficiency of diversified firms, for instance during mergers and acquisitions.

Key words:

diversified firms, capital allocations, behavior of managers 

“Redesigning dementia care; an evaluation of small-scale, homelike care environments”

Small-scale residential homes are strongly emerging in nursing home care for elderly people with dementia. Experiences are mostly positive compared to traditional nursing home care. The present dissertation, however, shows a differentiated picture of the effects of small-scale living on the residents, their caretakers and employees. Contrary to expectation the quality of life of residents in small-scale residential homes does not differ from that of comparable residents in traditional nursing homes with wards of at least 24 persons. Between both groups no differences were found in neuropsychiatric symptoms and turbulence. The work satisfaction and motivation of employees don’t show differences either. The involvement of family members of residents in small-scale residential homes does not differ from traditional wards.  Family members of residents from small-scale residential homes show a lower care load and are more satisfied with the care. A complete change to small-scale residential homes is therefore not obvious.

Key words:

dementia, nursing home care, small-scale residential homes 

“Visual Vestibular Mismatch: A poorly understood presentation of balance system disease”

The inner ear balance system stabilizes the eyes and the body in space.  Vision also analyzes environmental movement. Balance system disease or injury can cause disagreement or “mismatch” between the balance system information and environmental visual information. If the brain then relies on visual information, this can cause unsteadiness, but a copy of the mismatch is also sent to the nausea and anxiety centers of the brain. This mismatch (i.e. not the disease itself) can in some patients cause severe symptoms (nausea, vomiting, anxiety, newly developed motion sickness, panic disorder and sweating), which are genuine and do not suggest psychiatric disease.   Astronauts also have similar symptoms during and just after spaceflight, because the balance system is confused by the lack of gravity in space.  

Key words:

ziekte van het evenwichtssysteem, visuele informatie over de omgeving

“Cardiovascular prevention; nurses and doctors working together”

Prevention of cardiovascular diseases is very important. High-risk patients need to be traced and guided. The GP practice is the primary place for that, in cases of complicating problems patients are referred to the specialist. The prevention of cardiovascular diseases will be improved when practice nurses in the GP practice carry out the regular protocol check in patients. Almost all patients are satisfied about this; smokers form an exception; they experience less understanding for their situation and feel corrected more often than non-smokers. Motivating talks, self-management programmes and automated risk profiles could further improve the prevention by practice nurses. That also applies to the after-care track by special-ised nurses in the hospital.

Key words:

cardiovascular diseases, prevention, practice nurses

“Nuclear Structure at the Crossroad of Premature Aging and Lipodystrophy”

“Food intake meeting ENERGY AND REWARD HOMEOSTASIS”

The current obesity epidemic is mainly caused by a strong increase in the food consumption. Examples of factors that influence the food intake are changes in concentrations of hormones related to appetite and satiation, meal pattern, ‘reward homeostasis’ of food, and stress. Results of the studies described in this dissertation show that the relation between hormone concentration changes and appetite/satiation is too limited (30-70%) to give the hormone concentration changes the predicate ‘biomarker’ for satiation.  It also turns out that the control of the food intake should be bigger when the meal lasts longer; the increased food intake of going out for dinner should therefore be attributed to environmental factors. People often appear to eat while they are not hungry; people eat to experience the ‘reward homeostasis’ afterwards. This is reinforced in conditions of acute stress. Acute stress stimulates food and energy intake, particularly in obese persons with an ‘apple’ figure. Possible functional food that could influence the stress response has not been found yet. On the contrary, stress even appeared to dominate for example the very satiating effect of protein.

Key words:

obesity, food intake, appetite, hormones, reward homeostatis, stress

“Circulating Matrix Gla-protein: a biomarker for vascular disease”

MGP is a protein that protects the vessel wall against arteriosclerosis. Vitamin K is necessary to activate it. This dissertation describes the development of test methods to measure MGP in blood, and we show that these tests can be used for the diagnosis of cardiovascular diseases. With one test (t-ucMGP) you can quickly identify patients with calcified blood vessels. Another test (dp-ucMGP) can be used to estimate the vitamin K status of the blood vessel wall and consequently the risk of arteriosclerosis. Vitamin K supplement scan positively influence this test and possibly also inhibit the development of arteriosclerosis. 

Key words:

Vascular disease, vitamin K, arteriosclerosis

“Perception and action in nicotine addiction; fMRI and behavioral studies of sensorimotor and multisensory processes in smokers and non-smokers”

The present thesis employs functional magnetic resonance imaging (fMRI) and behavioral experiments to explore perceptual and action-related processes in nicotine addiction. Due to smokers’ experience with the sensorimotor and multisensory activities of seeing, reaching for and acting upon smoking paraphernalia, the corresponding perceptual and action representations are particularly enhanced on the neural and behavioral level. The correlations between smoking-related automatized behavior, test scores indicating the individual severity of nicotine addiction and the response of smokers’ action-related brain regions to smoking cues demonstrate the relevance of these findings for both future research and clinical practice. The behavioral and brain responses to smoking cues studied in this thesis can initiate the development of a marker for the degree of nicotine addiction, therapy success or relapse risk for smokers trying to quit smoking.

Key words:

fMRI, behavorial experiments, nicotine addiction

“Nutritional Modulation of Intestinal Inflammation”

Millions of people throughout the world suffer from a chronic intestinal inflammation: Crohn’s disease & colitis ulcerosa). This dissertation studies if certain nutrients can influence the intestinal inflammation. The most important finding is that addition of calcium to food can decrease the inflammation in rats. Calcium inhibits the diarrhoea, lowers the intestinal permeability, and relieves certain inflammatory processes in the intestinal wall of the rats.  Possibly also influence on the intestinal mucus layer and intestinal bacteria plays a role in this protective effect of calcium. Since the same mechanisms can also work in humans, calcium supplements can be promising as an additional therapy for patients with chronic intestinal inflammation.

This PhD research was conducted within TI Food and Nutrition.

Key words:

intestinal inflammation, food, calcium

“Polymorphisms in interstitial lung diseases; Friend or foe ?”

Besides known lung diseases, such as asthma and COPD, there are also so-called diffuse or interstitial lung diseases. Possible causes for the development of interstitial lung diseases are genetic factors and contact with xenobiotic substances via inhaled air or the blood stream. In that way, medicine can have a damaging effect on the lungs. This dissertation shows a.o. that preliminary determination of certain genetic features is very valuable to prevent medicine toxicity. In the future, this information can be recorded in the form of a ‘medical passport’ so that individual tailor-made care can be provided.  

Key words:

interstitial lung diseases, genetic features, medicine toxicity

“Can we account for individual productivity differences in scientific research? An illustrative analysis of publication records of French university and CNRS physicists”

“Modulators of bleeding tendency in severe factor V deficiency”

“The origins, evolution and functions of p53”

“Beyond Booms: Fundamentals and Mechanisms of Housing Markets in Decline”

Housing markets are more risky than they appear to be. When the first lines of this dissertation were written, residential real estate seemed to be a safe asset class, characterized by steady positive returns and low risk. The following years proved this perception to be wrong – and so does this research. Mispricings of homes are found to occur often and to persist for long periods of time. Real options amplify these deviations from fundamentals and thereby increase house price volatility. Demographics ultimately determine the demand for housing services. Against common belief, an aging society does not necessarily demand less housing. Human capital is the key demand factor, not age. Finally, drops in aggregate house prices increase the inequalities within cities with declining population numbers, which is a discomforting result, given Europe’s challenging demographic outlook.

Key words:

housing markets, mispricings of homes, human capital

“Prevention of anxiety disorders; Is screening and offering a child-or-parent-focused intervention (cost-)effective?”

This study shows that preventive interventions in anxiety disorders are effective as well as cost-effective. Applying a screening procedure followed by offering an intervention also turns out useful and cost-effective. Applying the screening procedure and offering the parent intervention appears the most cost-effective if at least one of the parents suffered from anxiety. However, the strength of these findings was modest, and the results need to be corroborated and further supported by future longitudinal anxiety prevention research that studies the effects during longer periods of time.

"From settings limits to shaping practices; Trust and accountability in health care for older people”

This dissertation studied the role of age as a value judgement in the medical decision making process. The debate about the role of age forms the basis for this study.  The objective was not to draw lines, but to promote elderly-sensitive medicine, recognizing that more health care is not always better. The discussion was also taken to a societal level. With the formation of health care practices, we do not want to force the results of an ethical debate on doctors, but on the contrary, use their practices and insights. That’s why we have studied both the decision-making processes and the arguments. The most important question is whether we can trust doctors and whether their decisions can pass the test. That’s why we developed a framework based on ‘accountability’ of and ‘trust’ in doctors in the care for the elderly.

Key words:

care for the elderly, age discrimination, trust, elderly-sensitive medicine

“ARE YOU BEING SERVED?”

“Connectivity and Growth in Sub-Saharan Africa: the role of communication satellites”

The thesis explores the importance of the strategic application of Information and Communication Technologies (ICTs) to Sub Saharan African (SSA) economies to enhance growth opportunities in the region.  
We conclude that in order for ICTs to make a meaningful contribution to economic growth in Africa, there is a need to contain and reinvest resources in the sector on the continent. African service providers need to curb the drain of meager resources to foreign satellite and fibre optic providers, so that they can compete favorably in international telephony pricing and extend their services to hard-to-reach rural areas as well, where services like telemedicine have failed to take root and contribute positively partly because of high connectivity charges.

Key words:

information and communication technologies, economic growth, Sub Saharan Africa

“Deciphering mitochondrial and molecular pathology in Type 2 Diabetes Mellitus”

Type 2 Diabetes Mellitus (T2DM) is caused by disturbed energy management.  Mitochondria are the energy factories of a cell and badly functioning mitochondria are considered the cause of the development of insulin resistance, but publications on this subject are contradictory.  This dissertation describes the mitochondrial and molecular changes in muscle and fat tissue of T2DM patients. It is shown that the decreased mitochondrial function in muscle tissue has no causal role, but is a consequence of T2DM and can be improved by an adjusted training programme. Also changes in molecular processes in preadipocytes of T2DM patients were recorded and more insight was gained in the functions of two genes hat are involved in the development of T2DM. This knowledge of the disease process contributes to a better treatment of T2DM. 

Key words:

type 2 Diabetes Mellitus, mitochondria, gene expression

“On fertile ground? New perspectives on gonadal function in classic galactosemia”

​

Key words:

hereditary metabolic disease, fertility, early ovarian failure 

“Innovation in Finance to Finance Innovation: Supporting pro-poor entrepreneur-based innovation”

This thesis proposes a new way of conceptualising financing of inclusive innovation in rural areas by focusing on pro-poor entrepreneur-based innovation (PEBI) and by considering the knowledge flows in different parts of the financial system. Inclusive innovation refers to innovation that provides the poor with better goods, services or livelihood opportunities. Empirically, the thesis found that the Indian banking system does not efficiently support rural PEBI. Instead an alternative financing sector has emerged recently, in which there are three broad categories of organisations: micro venture capital firms, small-scale finance providers, and grassroots innovators and incubators. They are complementary, forming an ecosystem of finance for different types of rural PEBI. What these organisations have in common is an integrated approach to support; an emphasis on partnerships and networks to provide better services and acquire expertise; continuous involvement in the investees; and a dual bottom line.

Key words:

finance innovation, entrepreneurship, rural 

“Dynamic Cooperation”

Cooperation is essential in many aspects of our life and in many situations in economics. We decide to make friends, get married, work together and to form more complex partnerships like defensive alliances, trade-corporations, international agreements on environmental issues, common exploitation policies in the European Union, labor unions or cartels. Game theory attempts to enhance our understanding of people's behavior in such situations mathematically.

We show for instance that - just like extreme endowments lead to exchanges in a market - bad initial allocations facilitate cooperation, or that market structure plays a crucial role in the agreements agents might have. Our model can also be used to assess the stability and sustainability of an agreement in a stochastic environment.

Key words:

game theory, cooperation, behavior

“Pharmacological characterization of wnt/frizzled signaling”

“Understanding HIV-related stigma”

“Clinical evaluation of the surgical and endoscopic treatment of morbid obesity”

Morbid obesity (a BMI of > 40 kg/m2 or > 35 kg/m2), is a worldwide and rapidly growing health problem. Diet, exercise and behaviour therapy appear not successful in the long run. Surgical interventions, such as the laparoscopic adjustable gastric band and the vertical gastric sleeve, are in fact successful. However, the number of necessary reoperations due to the occurrence of complications after the vertical gastric sleeve amounts to 65% after 7 years, and after a laparoscopic adjustable gastric band to 44%. The best option after failed gastric sleeve surgery is the conversion into a Roux-en-Y gastric bypass. This shows good long-term results with regard to weight loss, improvement of gastrointestinal complaints and has a low figure of reoperations. Also the duodenal-jejunal bypass sleeve, and endoscopically placed plastic sleeve in the duodenum shows promising results with 19% overweight loss after 3 months without serious side-effects. Moreover, the bypass effect of the duodenum has a very favourable effect on type 2 diabetes mellitus. This will need to be further investigated in the future.

Key words:

morbid obesity, surgery, Roux-en-Y gastric bypass, duodenal-jejunal bypass sleeve

“Vision and Audition in Motion”

“At risk for psychosis; exploring cognition as intermediate phenotype”

This dissertation studies how cognition as a vulnerability marker is connected with specific symptoms of psychosis, and which influence a delayed cognition has on the development of psychotic symptoms when a person has experienced a traumatic event in childhood.  It turns out that a traumatic event in childhood leads to positive symptoms of psychosis (for example delusions) when there is a higher genetic vulnerability to psychosis. Furthermore, it is shown that the subjective experience of cognitive errors can be a risk factor for the development of negative symptoms of psychosis (or example lack of motivation). It also turns out that patients, and to a lesser degree family members, show an abnormal processing of words (for example incoherent speech), but that this is not connected with the so-called symptoms of disorganization. The conclusion is that cognition is connected with psychotic symptoms, but no direct connection with specific symptoms of psychosis was found.

Key words:

psychosis, cognition, risk factors

“Predicting outcome for lung cancer patients: towards individualized treatment in Radiotherapy”

“Cross-cultural intelligence amid intricate cultural webs; a tale of the UnDutchables in the Land of 1001 Smiles”

This study probes the cross-cultural work life of real Dutch and Thai individuals at five Dutch firms in Thailand. Besides the well-known clashing effect of cross-cultural interaction, on which the academic attention and public awareness have concentrated heavily, this study uncovers three other, more subtle, consequences of cross-cultural life – those of reciprocal, unification, and variation. To deal with and thrive in such complex conditions, we need more than our IQ and EQ and must resort to a unique kind of social intelligence: cross-cultural intelligence or XCQ. XCQ is a learning-by-doing execution of the ability to practice cross-cultural heuristic effectively and offers a new framework for examination. Most importantly, to balance the popular and dominant view of cross-cultural life as a war, inevitably fraught with differences, clashes, and fault lines, this study propounds the less celebrated yet intriguing view of cross-cultural life as a dance, constantly searching for complements, unison and contact lines

Key words:

Dutch culture, Thai culture, cross-cultural interaction, cross-cultural intelligence (XCQ)

“Government Spending in Dynamic General Equilibrium Models”

Empirical evidence shows that government spending raises private consumption. This contrasts with the prescriptions of current economic models, where government spending only has a mediocre role as it primarily takes resources from consumption and investment. This dissertation analyzes the channels through which government spending affects the macroeconomic equilibrium. It shows that when temporary shocks have long run consequences, the immediate reaction of the economy to the shock also changes since households are forward looking. Taking this into account, the dissertation shows that government spending can increase demand enough to increase consumption.

Key words:

government spending, private consumption

“Diabetes self-management; strategies to support patients and health care professionals”

The number of people with diabetes has strongly increased in the past decades and will continue to increase considerably. As a result, there is a greater need for interventions aimed at the improvement of self-management. This research describes the evaluation of a counselling strategy for patients and health care professionals. The educational website (www.diep.info) is positively evaluated by users and turns out effective in the improvement of knowledge about diabetes. Using the website and having motivating talks appears difficult in daily practice for health care professionals. In care, there should be more emphasis on education and counselling of patients as a quality aspect of diabetes care. 

Key words:

diabetes, zelfmanagement, counseling

“Individuals’ Path to retirement”

This dissertation covers financial decisions of individuals with regard to their retirement. We look at how people in Germany and the Netherlands are actually making, as well as how they should be making, these decisions. We provide evidence that people are getting a lot of decisions right on average. Young people in Germany for instance seem to be aware of the implications from the pension reforms in the 1990s and early 2000, which decrease their return to the public state pension for them.  Few people in the Netherlands participate in the Levensloopregeling. Our empirical research shows that it becomes more likely for individuals to join the older they become. Given uncertain wages and investment returns, a preference for leisure and reasonable impatience we also show that this pattern is optimal . Thus, individuals make some decisions very well in line with life-cycle theory. However, not always. When it comes to complex financial products such as a life-cycle fund our results imply that individuals do not understand  everything and are reducing the weight of this fund in their portfolio the older they become.

Key words:

Retirement, individual financial decision making

“Lifestyle factors and risk of pancreatic cancer”

Survival chances for pancreatic cancer are amongst the worst of all types of cancer. Prevention could therefore have an important influence on the mortality. Results on the basis of the Dutch Cohort Study of nutrition and cancer, which started in 1986 among over 120.000 persons, show that excessive alcohol intake and smoking increases the risk of pancreatic cancer, whereas quitting smoking decreases the risk.  Research persons that practised sports in the past had a lower risk of pancreatic cancer in comparison to research persons who never practised sports. There turned out to be no connection with the other studied nutrition factors, among which glycaemic index, energy restriction, meat intake, fruit, vegetables and vitamins.

Key words:

pancreatic cancer, risk factors, nutrition, lifestyle

“White Collars Green Sleeves; an Interorganizational Comparison of Determinants of Energy-Related Behaviors among Office Workers”

Energy-saving behaviour contributes to a better environment. This thesis evaluates to what extent and through which mechanisms the organisational context influences energy-saving behaviour of office workers. Four organisations (profit and non-profit) in the Dutch provinces Zuid-Holland and Limburg participated in the empirical study. Previous research has shown that habits, attitudes, social norms and perceived control over one’s own behaviour are the most important general influences at the individual level. As expected, organisational aspects primarily had an indirect influence through the known individual factors. However, the finding that the influence of habits and social norms could differ substantially between organisations was remarkable. In contrast, attitudes and perceived control played a relatively constant role. Interventions in organisations should therefore be preceded by a pilot study on the role of habits and social norms in energy-saving behaviour. 

Key words:

energy consumption, organisations, influences on behaviour

“Context dependent face selection in a visual and semantic perspective”

In everyday life, we often engage in a conversation with someone we did not see for long time, in the context of other people. The crucial elements for a successful interaction with that person are the recognition of his/her face and the retrieval of some background information (e.g. profession). The goal of our research was to understand whether both these cognitive processes are influenced by the presence of surrounding (irrelevant) people. We found that in order to recognize a relevant face the brain filters all the other faces out. However, it uses contextual faces’ information to make the face-profession association.

Key words:

brain, recognition, face selection

“The role of NF-kB activation I fatty acid-induced insulin resistance in skeletal muscle”

“Idiopathic cardiomyopathies: the role of virus persistence and immune-mediated disease”

“Evaluation of self-help computerized cognitive behavioural therapy for depression; Integrating clinical, economic and patient perspectives”

Depression is a very common disorder that leads to a lower quality of life and high costs. Yet, many people with depression remain untreated. This dissertation shows that low-threshold online self-help without professional guidance is no adequate solution. The therapy is less expensive than other therapies, but the improvement of depressive complaints is not very good and the therapy compliance is low. This dissertation mainly shows limitations and possible improvements of online therapy. Adding personal guidance, adjusting the therapy to the individual patient, and giving attention to required computer skills, equipment and location can optimize the treatment by realizing better therapy compliance, therapy outcomes and patient experiences. 

Key words:

depression, online self-help therapy

“Essays on individual decision making; with special references to Agribusiness and food markets”

This thesis develops economic models that reveal how Dutch producers-investors desire to co-operate and how consumers react in crisis situations. The decision contexts that used for testing these models were the Dutch, American and German agribusiness and food retailing markets. If we understand the decision-making process, then we may be able not only to predict, but also to explain economic behavior in turbulent and dynamic markets. The results of this study demonstrate: a) that Dutch producer-investors are in favor for participating in “strategic” co-op alliances; b) that the heterogeneity among food producers (members of co-op firms) should be taken into account for designing the governance structure and marketing services that these firms provide to their stakeholders; and c) whether the solution to a crisis lies in more effective communication efforts through the media or in more drastic measures with respect to product supply, such as recalls or product elimination.
The models produced could be applied to future crisis situations and other areas of economy as well, such as food product-harm crisis (bird flu, etc), financial crisis, etc. 

Key words:

economic models, decision-making, risk situations, agribusiness, food retail

“Stimulating fits”

Epilepsy is a very common neurodegenerative disorder that is difficult to treat.  25% of the patients keep having seizures in spite of medicine use. These therapy resistant epilepsy patients can benefit from nervus vagus stimulation (NVS). How it works and why these patients benefit can have from this treatment is unknown. We have developed a new epilepsy model that studies the effects of NVS. First results show that NVS decreases the seriousness and duration of epileptic seizures and that changes occur at the level of the brain stem, where the signals from the nervus vagus enter the brains. These results can be translationally converted (from the laboratory to the clinical practice) which can enable a better treatment of epilepsy in the future. 

Key words:

epilepsy, treatment, therapy resistant, nervus vagus stimulation

“Renewable Energy Tax Incentives and WTO law: Irreconcilably Incompatible”

In light of Kyoto Protocol obligations, this thesis examines  wether direct corporate tax incentives for the development of renewable energy sources, currently in place in six coutries  (Ireland, the UK, the Netherlands, Belgium, Canada and New Zealand) are in line with EU and WTO rules on subsidies. From a parallel examination of the EU legal regime it is discovered that the EU legal environment provides inspiration for the WTO regime. The WTO regime is void of environmental exceptions which would provide a safety-net for environmentally-motivated subsidies. In this thesis, suggestions are made for positive changes to be made to the current WTO legal environment to create room for environmentally-motivated subsidies such as those in place in the case-study countries for the development of renewable energy.

Key words:

tax incentives, renewable energy, WTO law

“Roken in Nederland. De keerzijde van de tolerantie”

“Local space and economic success; the role of spatial Segregation of migrants in the Netherlands”

Many non-western migrants have little to spend and live in disadvantaged neighbourhoods. The main conclusion in this dissertation is that their local space determines their economic success, both in employment and as independent entrepreneurs. This is not only influenced by the composition of the local population, but als by the built-up environment. It makes a difference whether a business is conducted in a pre-war or post-war neighbourhood. Interesting is, however, that the business success of entrepreneurs in the four main cities is not per se bigger than elsewhere in the Netherlands. Moreover, second generation migrant entrepreneurs are not more successful than their parents’ generation. Finally, it turns out that non-western migrants living in migrant neighbourhoods perform less successfully on the labour market than those who live elsewhere. This is however not due to the concentration of allochthonous inhabitants in these neighbourhoods, but due to the concentration of poverty. The concentration of people with a migration background can in fact enhance the labour market integration of newcomers.

Trefwoorden:

non-western immigrants, residential environment, economic success, 

“Chronic oxidative stress and telomere shortening”

“Surgical revascularisation in patients with left ventricular dysfunction, management and predictors of outcome”

As shown in earlier studies, patients with a decreased left ventricular function benefit more from bypass surgery than from treatment with medication or a dotter procedure.  Left ventricular dysfunction Nevertheless, left ventricular dysfunction remains one of the main risk factors for early and late death after bypass surgery. This dissertation mainly describes the predictive factors of both the short-term and the long-term results after bypass surgery in patients with a decreased heart function. In addition to the earlier described risk factors, it turns out that anaemia and disturbed kidney function are important predictors for early death in this patient population. Patients with a normal ventricular function, who underwent bypass surgery, have a long-term survival comparable to and even better than the regular Dutch population. The use of a special pacemaker (biventricular, for both ventricles) improves the blood circulation and lowers the need for supporting medication. 

Key words:

Bypass surgery, left ventricle, dysfunction, result

“The role of technological advances in sodium prescription and adequacy assessment during hemodialysis”

During the dialysis treatment various options can be used that are available on the dialysis machine. This dissertation describes, tests and validates several of these options.  
The ‘online’ measured plasma conductivity appears to match plasma natrium. That provides insight into the fact that the use of the standard dialysis fluid sodium (most used in the Netherlands) can lead to an increase of plasma sodium as a consequence of the dialysis treatment. This dissertation therefore advocates individualized dialysis fluid sodium. Also, the ‘online’ effectiveness of the dialysis treatment can be measured, which can secure good quality control. 

Key words:

dialysis, dialysis fluid conductivity, sodium, dialysis effectiveness

“Constraints to Human Capital Investment in Developing Countries: Using the Asian Financial Crisis
in Indonesia as a Natural Experiment”

Families in developing countries invest less in education than would be expected. This dissertation investigates whether families have a low preference for education, are confronted with low market returns or they face actual constraints in investing in their children’s human capital. Parents in Indonesia face two main constraints to fully investing in their children aged 6 - 15. The first constraint is low family income and this is given that families have to finance up to 60% of their children’s entire education. The second constraint is inadequate state provision of basic school building facilities particularly in underdeveloped areas across the Indonesian archipelago. The challenge is for policymakers to remove these two constraints and create incentives for parents to choose to keep investing in their children at higher schooling levels. 

Key words:

investment in education, developing countries

“Impact Evaluation of a Job-Training Programme for Disadvantaged Youths: The Case of Projoven”

This dissertation evaluates the effects of Projoven, a job-training programme targeting economically disadvantaged youths in Peru. This study suggests that training could be an effective policy intervention. However, to enhance training potential it should be taken into account that the programme works differently for different people (depending on their poverty status and prior work experience); that not all the trainees receive the same doses of training (in terms of quality and quantity); and that precarious internship conditions could lead them to drop out of the programme. Since the behaviour of trainees, training providers and training firms are affected by the set of rules and incentives under which the programme is carried out, the analysis of the institutional framework must be also taken into consideration when evaluating Projoven’s effectiveness.

Key words:

job-training programme, disadvantaged youths

“Lamin interA/Ctors: from the premature to senescence”

Progeria patients age approximately ten times faster than normal and die on average at the age of 13. Genetic defects in the lamin-A gene cause Progeria via mainly unknown mechanisms. This dissertations shows that Progeria-associated lamin-A binds other proteins and DNA than healthy lamin-A, and among others looses binding with the NURD protein complex. This loss leads to irreparable genetic damage, which is an important cause of ageing, and it also appears to underlie the normal ageing process in healthy persons. The discovery of this new ageing mechanism has contributed to the set-up of a screening for new medication against senescence symptoms.

Key words:

Progeria, senescence, lamin-A  

“Transparency of Transferability; diagnosing International aspects of economic evaluations of health care technologies”

Economic evaluations are increasingly used in the decision making process about reimbursing new medical treatments. Judging to which extent results from economic evaluations are usable in another country is known as judging the transferability. Because of the growing demand for economic evaluations and the limited research capacity it is not efficient to conduct all studies personally. This dissertation studies this transferability, so that policymakers can determine if foreign data can be used and which data should possibly be gathered in the own country. The conclusion is that transferability-related problems are partly the consequence of differences in national guidelines. It also turns out that national methods to assess patients’ quality of life lead to considerable differences between countries in terms of cost effectiveness of interventions. This leads to two recommendations, namely the development of an international guideline for economic evaluations and the development of an instrument to adjust data to another country.  

Key words:

economic evaluations, transferability, health care technologies

“Essays on Economies with Heterogenous Interacting Consumers”

The current thesis is concerned with the importance of including consumer interaction in theoretical models for deriving aggregate implications. 
Applications discussed include advertising and R&D policies. The thesis demonstrates that changes in structure and intensity of consumer interaction can drastically change the behaviour of demand. 

Key words:

consumer interaction, theoretical models, advertising, R&D policies

“Barrett’s esophagus and esophageal and gastric cancer subtypes: an epidemiologic perspective”

Esophageal cancer occurs more and more, but what are the risk factors for this disease? Results on the basis of the Dutch Cohort Study on nutrition and cancer that has been conducted since 1986 among over 120.000 persons show that smoking increases the risk of esophageal and gastric cancer. Alcoholic beverages are a risk for one type of esophageal cancer (squamous cell carcinoma), while overweight increases the risk of another type of esophageal cancer (adenocarcinoma). The study once again confirmed that eating many vegetables and fruits is healthy: it lowers the risk of esophageal and gastric cancer. Furthermore, the micro-nutrient selenium may possibly protect against esophageal cancer and one type of gastric cancer (cardia cancer).

Key words:

esophageal cancer, risk factors, nutrition, alcohol

“Risk attitudes in a social environment”

This dissertation studies by means of economic experiments the effect of the social environment on the risk behaviour of individuals in risky situations, such as pandemia outbreaks, receiving or not receiving a donor liver, terrorism threat, but also for example participating in a lottery. The social environment in itself appears not to have a great influence on the risk behaviour of an individual. However, it this person fulfils the role of social planner and has to decide how risks will be dispersed over the social environment (for example determining who is entitled to a donor liver, or who is or isn’t admitted to a medical study programme), he has a strong preference for procedures that apply to everyone and where fate determines the allocation. But as soon as the level of the risk is determined by a social environment they can choose themselves, people will sooner make risky, but efficient choices that ultimately decrease the risk. An example of this is the proposition by Chancellor Angela Merkel to place countries with an unhealthy national financial system out of the European Union. The threat of exclusion will force the EU countries to better watch over their financial system, which lowers the risk of another Euro crisis. 

Key words:

economic experiment, risk behaviour, social environment, choice behaviour

“Recidive in België en Nederland. Een analyse van 200 jaar rechtspraak en rechtsleer”

“Between family and friends: understanding the interdependence of private transfers”

“The adolescent brain: neurocognitive development and subject-related factors”

This dissertation studies how the brain functioning develops during thinking functions in adolescents. Adolescents of respectively 13, 17 and 21 years old largely activate the same brain areas when, for example they make decisions. However, the degree to which de brain areas are active increases when the young person grows older. These brain changes occur dispersed in the brains and they are not specific for a certain thinking function. They indicate a general development principle in the functioning of the brains. Moreover, this research shows considerable individual changes between adolescents; gender and the experienced stress in the scanner influence thinking functions and brain activity. These research findings are important for the way we look at adolescents. In the educational system, for example, it is assumed that high-school students are quite capable of independent working, whereas this PhD research shows that this ability is still in development during adolescence.  

Key words:

adolescents, development, brains

“Gastrointestinal targets to modulate satiety and food intake”

Diets that contain a relatively high level of proteins are regarded an effective treatment for weight control. Particularly for the prevention of weight increase after a period of weight loss. So far, it is not known whether it makes a difference which specific proteins are used in these diets. This dissertation studies which proteins have the greatest effect on a feeling of hunger and food intake. It turns out that proteins from peas have the greatest effect. It also turned out that inhibition of the decomposition of this protein in the stomach even increases the effect. Obese men ate less after they had been administered pea protein directly in the intestines, than after they had eaten this protein. These results can contribute to new perspectives in the treatment of overweight and obesity.

Key words:

diets, proteins, feeling of hunger, food intake 

“Exploiting tumour and lung heterogeneity with radiotherapy”

In the current lung cancer treatment with radiotherapy, the entire tumour is treated with the same quantity of radiation. However, there are indications that certain parts of a tumour are more aggressive and need a higher radiation dose to be cured than other parts.  This dissertation studied the possibilities of focusing the radiation dose more specifically on the most aggressive part of the lung tumour. The research shows that the effectiveness of the treatment could increase with 30% without increasing the side-effects. The dissertation also shows how can be determine how much radiation dose the aggressive  parts need and how can be monitored if the radiation dose is administered to the right location. It also turns out that some parts of the normal lungs are extra sensitive for radiation and that the dose to specifically these parts should be limited as much as possible. It is emphasised that the results should be confirmed in further research.

Key words:

lung cancer, radiotherapy, dose of radiation

“Celbiologie van thrombose en hemostase: de trombus”

“To buy or not to buy: Empirical studies on Buyer-Supplier Collaboration”

Buying companies that want to have a better access to a supplier’s critical resources than competition need to develop close social relationships with this supplier’s employees. This is the outcome of a study by Agnieszka Blonska. This research is one of the first to demonstrate a close social relationship between buyer and supplier companies’ employees has a positive influence on supplier allocation of preferences among buyers, supplier and buyer customization, and cross-functional information sharing behavior of buyers and suppliers. The research was conducted from both, supplier and buyer perspectives.

Key words:

social relationship employees, customization

“Neurophatic pain: glial responses and plasticity in the spinal nociceptive network”

“Physical activity recognition using a wearable accelerometer. New perspectives for energy expenditure assessment and health promotion”

A physically active lifestyle is important for living a healthy life. However, defining how much physical activity is necessary for promoting health requires objective and valid instruments for monitoring physical activity and the related physiological outcomes. This thesis showed that accurate recognition of physical activity types, like walking, cycling, and running was feasible using a wearable accelerometer. This method improved daily estimations of energy-expenditure, and it showed that the cycling-, walking- and sitting daily duration determined the subjective activity level. Furthermore, specific activity types characterizing the behavior of obese subjects played a key role for protecting against cardiovascular diseases.

Key words:

physical activity, accelerometer

“Algebraic polynomial system solving and applications”

The problem of calculating the solutions of a system of polynomial contrasts can be approached by means of an algebraic method that remodels the problem into a large eigenvalue problem. This method is the starting point for the development of computational procedures for the two applications that are at the centre of this dissertation:
(i)  The global optimization of a polynomial function in several variables, and
(ii) the model-order reduction problem for reductions of size one, two or three.

Key words:

polynomial contrasts

“Mood and Motivation in Parkinson’s disease”

“Genetic background and impact of Staphylococcus aureus in a cross-border region”

MRSA (the hospital bacteria) occurs more in Belgian and German hospitals in the Euregion Meuse-Rhine than in Dutch hospitals. The ‘Search & Destroy’ policy of the Dutch government has – in spite of the high cost – realized containment of the MRSA contaminations in hospitals. Via genetic research this dissertation shows that several MSRA variants have dispersed to the Dutch patient population. Because there are many cross-border movements by patients between hospitals, and new ‘variants’ of the MRSA bacteria occur, the MRSA containment policy between the hospitals in the Euregion Meuse-Rhine should be matched to prevent transfer of MRSA between patients. 

Key words:

MRSA, cross-border, Euregion Meuse-Rhine

“MR Imaging of coronary atherosclerosis”​

“Risks and recommendations in WRULD”

Mouse arms, currently no longer called RSI, but WRULD (work-related upper limb disorders), still occur frequently and involve high costs. Physiotherapy and posture therapy show insufficient results, even in the case of incipient complaints. At the origin of WRULD stressful situations and a perfectionist are important factors. When the complaints persist, the way a person experiences his complaints and perceives them as a psychological burden plays an important role. Risk factors such as a perfectionist mentality and anxiety, among others pain anxiety causing the avoidance of activities deserve more attention. 
Therefore, in the treatment of WRULD, guidance by a psychologist (for perfectionist persons) and a behaviour therapist (for people with anxiety) should be included. Moreover, sports are important for WRULD patients. Fit persons experience fewer complaints. 

Key words:

mouse arm, WRULD, treatment

“Coronary heart disease in the Netherlands: Incidence, etiology and risk prediction”

Diseases of the coronaries, such as a heart infarct, cause a high disease burden in the Netherlands. This dissertation describes how often these diseases occur and how they are connected to various risk factors. Also, a risk score was developed that can predict the risk that a person will have a heart disease with fatal or not-fatal effect within the next ten years. This risk is calculated on the basis of his or her risk factors. Based on such a score can be decided to give lifestyle advice or start a treatment in order to lower the risk of a heart disease for this person.

Key words:

diseases of the coronaries, incidence, risk factors, risk score

“Veni, Vidi, da Vinci”

“Imaging of carotid atherosclerosis”

“Pax6 in Mammalian degenerative retina”

“Paratonia enlightened; definition, diagnosis, course, riskfactors and treatment”

“Polyethylene Wear in Total Hip Arthroplasty”

“Surgery for knee osteoarthritis: outcome measurements and their clinimetric implications”

 "Solving Difficult Game Positions"

"New horizons in lymph node imaging in head and neck cancer"

“Toxicogenomic Responses to N-Nitroso Compound Exposure in Relation to Human Colorectal Cancer Risk”

This research shows that a diet with much red meat leads to changes in the gene activities in the intestines that can increase the risk of colorectal cancer. This can explain why the intake of red meat has been connected with the development of colorectal cancer for years already. Assumed was that red meat would increase a Group of substances, called nitrosamines, in the intestines and that these substances would subsequently influence the gene activity. This turns out not to be the case: red meat does not increase the formation. The present nitrosamines, however, did cause carcinogenic changes in the gene activity, but these changes can not directly be attributed to eating red meat. 

Key words:

cancer, colorectal cancer, red meat, nitrosamines, N-nitroso compounds

"Perceived cognitive problems in Young-old adults: contextual factors, assessment and intervention"

“Molecular imaging of biologic characteristics and drug uptake”

“Veneuze Pathologie in Beeld”

“An inconvenient deliberation: The Precautionary Principle’s Contribution to the Uncertainties Surrounding Climate Change Liability”

The thesis’ focus is on a legal perspective on the interdisciplinary problem of Climate Change in terms of the responsibility and the liability for damage, which results from the activities of multiple actors. In an integrative, problem‐oriented manner, the book scrutinizes how scientific uncertainties translate into legal uncertainties in a liability claim over the damaging consequences of Climate Change. In this context, it analyzes how the Precautionary Principle, a principle aimed at making uncertainty manageable, can help to overcome some of the legal obstacles in such a claim, whilst, at the same time, potentially creating new liabilities. The book advocates for a consistent application of the principle, taking due account of its flexible interpretation in both public and private decision-making, and in judicial appreciation in Climate Change liability cases.

Key words:

climate change, liability, uncertainty, precautionary principle

“The role of the skeletal muscle in early-stage metabolic syndrome”

The muscle plays an important role in the development of the metabolic syndrome (metabolic disease due to an imbalance between eating and exercising). The worldwide increase of the metabolic syndrome is caused by high-fat food. This dissertation describes the effect of high-fat food on the muscle by molecular changes at the gene, protein and fat metabolite level. High-fat food causes molecular changes in the muscle that indicate an increase of the capacity of the fat metabolism. By actually measuring the fat metabolism the molecular changes were confirmed. These findings show how molecular research can be successfully integrated with more applied research.

Key words:

metabolic syndrome, muscle, high-fat food

“The role of dairy products and constituents in metabolic risk management”

The metabolic syndrome is a combination of various risk factors for cardiovascular diseases. In this project, we studied the effects of dairy products on these risk factors in test persons with overweight.  In the long term, it turns out that consumption of semi-skimmed dairy products lowers the systolic blood pressure, but has no positive effects on other risk factors. In the long term, milk has negative effects on the fat content in the blood directly after a meal, but positive effects on the glucose level. Further research will have to show if these findings also apply to other dairy products, other quantities, or other populations.

Key words:

dairy products, metabolic risk factors, metabolic syndrome

“Het persoonlijke genoom: het begin van een nieuw tijdperk in de gezondheidszorg”

“Manipulability, Decomposability, and Rationalizability”

Social choice theory, as the name suggests, deals with techniques for finding an alternative for a society respecting their preferences over the set of alternatives. Of course, such a technique must satisfy some desirable properties such as strategy-proofness and unanimity. Strategy-proofness ensures that the individuals can not be better off by misrepresenting their true preferences, whereas unanimity implies that if all agents report the same preference, then the rule selects the top of that common preference. However, the classic results of Gibbard (1973) and Satterthwaite (1975) have shown that if we allow for all possible preferences of the individuals then the only rule that satisfies these properties is the dictatorial one. As all the non-dictatorial rules are manipulable, the natural question arises, which one is least manipulable, i.e., manipulable at minimum number of profiles. Furthermore, this impossibility result leaves another question open as to whether in a more restricted context rules other than dictatorships can be strategy-proof. We address these two fundamental questions in this research.

Key words:

social choice theory, strategy-proofness

“Paternal Exposure to benzo(a)pyrene; a genetic risk in offspring?”

Each day we are exposed to substances that are dangerous for the environment that influence our health and possibly the health of our offspring.  Benzo(a)pyrene, for example, is formed by the combustion of organic materials, such as wood, diesel and tobacco. Research has already shown that benzo(a)pyrene can cause DNA mutations and consequently cancer. This dissertation describes the DNA-damaging effects of benzo(a)pyrene in testes and male reproductive cells of mice and shows that benzo(a)pyrene can cause germinal line mutations in spermatogonial stem cells of mice. Transferral of these mutations on the offspring may increase the risk of diseases, such as cancer, at a young age. Future research will have to show whether benzo(a)pyrene causes germinal line mutations in humans.

Key words:

benzo(a)pyrene, DNA damage, mutations, germinal line

“The Institutional Transformation of social policy in east central Europe: Poland and Hungary in comparative and historical perspective”

“Human resource management practices and learning for innovation in developing countries: Pharmaceutical firms in Mexico”

“There’s something in the air. Volatile organic compounds in exhaled air as biomarker in inflammatory lung diseases. Development and validation”

This dissertation describes the development and application of a method in which by measuring volatile organic compounds (VOCs) in exhaled breath various inflammation-related pulmonary diseases can be determined and studied. The exhaled breath of people with diseases such as cystic fibrosis and COPD (chronic obstructive pulmonary disease) turns out to differ from that of healthy people. By means of advanced classification models (support vector machines) it is possible to select a limited number of VOCs that can subsequently be used to diagnose. Diagnoses by means of the exhaled breath turned out correct in over 90% of the cases. 

Key words:

VOCs, diagnosis, pulmonary diseases

“‘Eating too much or too little’. An FMRI food reward study of (ab)normal eating behaviour”

This research studied by means of functional magnetic resonance imaging (fMRI) which influence the factors caloric density, hunger, attention and cognitive control have on the activity in the reward system. Attention and cognitive control appeared to have the greatest influence. When the participants were shown tasty food and for example aimed their attention at a neutral aspect, the activity in the reward circuit disappeared. When they thought about the tastiness of the food, the activity raised. If you want to change eating behaviour, it’s important that you learn to think differently about eating. Finally, the results showed that Anorexia Nervosa (AN) patients had serious disorders in the reward circuit: as opposed to healthy participants the AN patients showed hardly any activity in the reward circuit when they saw tasty food. Therefore, it is important that future treatments are focused on repairing this reward circuit. 

Key words:

fMRI, attraction of food, reward system, Anorexia Nervosa.

“Microeconometric Evidence of Financing Frictions and Innovative Activity”

“Data Integration with Biological Pathways”

Biological experiments generate many data, but unfortunately these are not always optimally used. That is why BiGCaT, the Bio-informatics department of UM, has developed new software in collaboration with the Gladstone institute in San Francisco. This new software can link these data to dozens of online databases. Moreover, the data are attractively presented on illustrations that represent the processes in the cell, the so-called biological pathways. These illustrations are made by means of a specially developed wiki. With our software, two earlier studies into long-term food shortage were joined together. This reanalysis has led to new insights, without the need for an expensive experiment. The results will contribute to a better treatment of patients that have problems absorbing food due to illness. 

Key words:

food shortage biological data, software

“Improving the quality and cost-effectiveness of breast cancer follow-up”

In the Netherlands, annually almost 13.000 women get breast cancer. After completion of the treatments, the patient remains under observation for a long time, also called the follow-up. The guideline in the Netherlands is a three-monthly hospital check in the first year after the treatment, but there are doubts whether these frequent checks provide optimum care.  Studies among 320 breast cancer patients from seven hospitals in the Netherlands show that a number of hospital checks in the first year can be replaced by telephone checks by the mammacare nurse, maintaining quality of life, high patient satisfaction and no increase of anxiety feelings. Moreover, the combination of telephone follow-up and an educational group programme appears to be a cost-effective strategy. Based on these results, it is advised to critically examine the guideline for follow-up for the first year after breast cancer and to implement telephone follow-up and the educational group programme in the guideline.

Key words:

breast cancer, check, follow-up

“Combinatoric Innovation; Environmentsfor sharing and creating Intellectual capital”

“Living with Less: Prospects for Sustainability”

In spite of the growing awareness that a more sustainable way of living is necessary, consuming less is still a very difficult option. This dissertation studies the impact of spending less money on the way of living in a post-modern consumer society. Besides a theoretical analysis of 150 years of consumer studies, the dissertation describes the development of thinking about economy from ancient times until now. Qualitative and quantitative empirical research results among other in the consumption behaviour model”: the Transformation Model Living with Less. Furthermore, a socio-economic profile of Dutch downshifters is presented. Based on the so-called Triple G of a sustainable lifestyle (Money, Green, Health) the results for sustainability are discussed. Finally, the dissertation presents recommendations for a marketing strategy to promote a sustainable lifestyle. 

Key words:

sustainability, lifestyle, consumption

“Bewegingsstoornissen bij psychosen So what”

“The Wealth of Nations: Global imbalances and adjustments in a financially integrated world”

The dissertation pursues the question of how increasing financial integration impacts real economic activity, for instance aggregate consumption and investment or the trade balance of a country. We find that countries which are well integrated in international equity markets, as measured by the amount and geography of foreign equity holdings, are better able to maintain consumption relatively stable while GDP varies. We also find that for some countries (US and UK) price movements in equity and housing markets are more important than the exchange rate in explaining trade balance movements. Finally we analyze by means of a portfolio-balance model how huge US current account deficits lead to a continued accumulation of US net foreign debt and concomitant surpluses in Asian and oil-exporting countries. In a similar way we analyze the external imbalances between Northern and Southern Europe.

Key words:

economische activiteit, handelsbalans, financiële (wan)verhoudingen

“Experimental studies on innate immune regulatory proteins during non-infectious tissue damage”

“Doorwerking van de beginselen van behoorlijke rechtspleging in de bestuurlijke voorprocedures”

A citizen who disagrees with a decision of an administrative authority must first of all object to this decision at the administrative authority that took the decision. If he is put in the wrong after a re-judgement of the administrative authority, he can go to court.   Because the appeal procedure as an administrative pre-procedure is an important element of the safeguarding of citizens’ legal rights against the administrative authority, this dissertation compares the appeal procedure at the administrative authority with the judicial procedure. Studied is whether the principles of procedural due process that apply to the judge also apply to the administration. Although not all principles of procedural due process apply to the same extent to the administrative pre-procedures, the conclusion is that largely comparable demands apply with the same ratio as in the judicial procedure. Violation of the demands that apply to the administration must therefore not too easily be overlooked and left without consequences.

Key words:

appeal procedure, administrative authority, judicial procedure

“Resynchronization of the ischemic asynchronous heart”

“May I have your attention please? A neuroscientific study into message attention for health information”

Realizing behaviour changes through health information is a difficult and complex task. This complexity is partly due to the way that people process health information. Aim of the research was to gain more insight into the underlying action mechanisms of various forms of health information, such as personally relevant and threatening health information.  Attention processes for these two different messages were studied by measuring brain activity (EEG and fMRI), eye movements and reaction times during the processing of the information.  The conclusion is that personally relevant health information can raise the attention, whereas presenting threatening health information can evoke defensive reactions.

Key words:

health information, method, information processing, attention

“Influence of micro-environments on pre-school children’s energy balance-related behaviours and weight status”

Based on the KOALA Birth Cohort Study and child-care observations, the home and child-care environment were examined as potential determinants of overweight in young children (age 0-7). Breast-feeding protected against overweight, probably through affecting later snacking. Parental stimulation of children’s healthy behaviours was more effective than restriction of unhealthy behaviours. Furthermore, diet and physical activity already clustered (co-occurred) at a young age. Children attending child-care appeared to be more often overweight. Observations showed the importance of child-care staff and physical environmental factors regarding diet and physical activity. The findings can be used to inform future childhood overweight prevention interventions.

Key words:

child-care; childhood overweight; dietary intake; environment; parent; physical activity

“Sence and Simplicity’: Dilemma’s en Parallellen in de perioperatieve zorg”

“Conflicting demands in ethnically diverse societies: Ethnopolitical contention and identity values in Europe”

“Defining, Measuring and Addressing Vulnerability: The Case of Post Conflict Environments”

“Piracy and P2P File-sharing Networks”

We find that the producers of digital goods suffer not as much from piracy as the consumers benefit from it. The society as a whole benefits from piracy. A consumer’s surplus is the value of the consumption of a product minus the price, and the producer's surplus is the price minus costs (roughly speaking, profit). The total welfare is then the sum of all consumers’ and producer’s surplus  (value minus costs).
It may be welfare decreasing if authorities overemphasize the protection of intellectual property rights. Comparing year 2003 to 1999, according to our estimates, the American music industry suffered from a $1.6 billion forgone annual profit. Total annual welfare increased by $13.1 billion. In 2008, annual profit has dropped by another $1.4 billion, while annual welfare soared by another $12.4 billion. By 2020, annual welfare will have improved by a whopping $29.7 billion since 1999.

Key words:

digital goods, piracy

“Competing and Complementary Perspectives on the EU as a Crisis Management Actor: An Examination of the Common Security and Defence Policy through the Lenses of Idealism and Realism”

In this dissertation policy analysis is applied to the Common Security and Defence Policy (CSDP) in order to explain the actions of the European Union (EU) as an international crisis management actor. It contributes to a more detailed perception of the motivations behind EU crisis management missions. Twenty-three CSDP missions are examined. A synthesis of the findings suggests that the EU pursues crisis management based on an evenly balanced mix of realist and idealist influences. CSDP missions are as much about satisfying vital self-interests as advancing universal value interests. Responses are based on realist perceptions of the security environment and tailored to address statecentric threats in the neighbourhood of the EU or in former colonies of Member States. These actions are guided by idealist principles, often involving non-coercive measures. Responses tend to provide assistance through civilian instruments rather than military force.

Key words:

International Crisismanagement, EU safety, CSDP

“Exploring exposure in vivo in chronic pain”

Pijngerelateerde angst levert bij chronische pijnpatiënten een  In chronic pain patients, pain related fear considerably contributes to the maintenance of the experienced functional limitations. Pain related fear is fear of moving and/or fear of  (renewed) injury, or fear of pain or other types of physical sensations, or fear of the future (for example of becoming restrained to a wheelchair, not being able to work anymore, or no longer being the person you always wanted to be).  An exposure in vivo treatment (GEXP), in which patients are exposed step by step to the situations, activities or movements they are afraid of appears to be an effective treatment. Patients experience in various situations, both short and long term, fewer functional limitations and even less pain, and changes on the tissue level. Where traditional pain treatments often do not lead to the desired result, GEXP appears the appropriate treatment.

Key words:

chronic pain, pain related fear, exposure in vivo treatment

“Towards strategies to stimulate First time trial of unfamiliar healthful food products”

To lower the risk of cardiovascular diseases the Dutch are recommended to limit the intake of saturated fat and to eat sufficient vegetables and fruit. This can already be achieved by replacing the daily consumed products by healthier alternatives, for example by replacing full cheese by skim-milk cheese. Trying an unknown product is an important step towards integration of such a product in the daily eating pattern.  In the framework of this PhD track various strategies were developed to promote trying healthy alternatives for the first time. Results from two experimental studies show among others that offering a test sample and giving a flavour description in which a healthy unknown alternative product is compared to the taste of a well-known product are simple, but effective ways of getting the Dutch to try an unknown product for the first time.

Key words:

health, healthy food, change eating pattern

“Richtlijnen in de spreekkamer. Van dogma naar dans”

“Private Law 2.0: on the Role of Private Actors in a Post-National Society”